THE SELECTIVE CATALYTIC OXIDATION
OF D-GLUCONIC ACID TO 2-KETO - D-GLUCONIC ACID
OR D-GLUCARIC ACID
PROEFSCHRIFT
TER VERKRIJGING VAN DE GRAAD VAN DOCTOR IN DE TECHNISCHE WETENSCHAPPEN AAN DE TECHNISCHE HOGESCHOOL EINDHOVEN, OP GEZAG VAN DE RECTOR MAGNIFICUS, PROF. DR. S.T.M. ACKERMANS, VOOR EEN COMMISSIE AANGEWEZEN DOOR HET COLLEGE VAN DEKANEN IN HET OPENBAAR TE VERDEDIGEN OP
DINSDAG 24 APRIL 1984 TE 16.00 UUR
DOOR
PETER CAROLUS CORNELIS SMITS
GEBOREN TE URMOND
Dit proefschrift is goedgekeurd door de
promotoren: prof. drs. H.S. van der Baan
prof. dr. ir. K. van der Wiele
co-promotor: dr. ir. B.F.M. Kuster
Aan mijnouders
i
Page
1. Introduction 1.1. Carbohydrates as a chemical feedstock 1
1.2. Oxidation of monosaccharides 4
1.3. Properties and applications of the oxidation-
products of glucose 6
1.4. Aspects of phosphate reduction 10
1.5. Choice of oxidation system 11 1.6. Aim and outline of this thesis 12
References 15
2. Literature survey
2.1. Introduction 17
2.2. Oxidation of D-glucose to D-gluconic acid 21 2.2.1. Homogeneous oxidation 21
2.2.2. Biochemical oxidation 22
2.2.3. Heterogeneous catalytic oxidation 24
2.3. Oxidation of D-glucose or D-gluconic acid to D-glucaric acid 27 2.3.1. Homogeneous oxidation 27 2.3.2. Heterogeneous catalytic oxidation 27
2.4. Manufacture of 2-keto-D-gluconic acid 28 2.4.1. Oxidation of D-glucose or o-gluconic acid 28 2.4.2. Alternative oxidation methods 32
2.5. Oxidation of L-gulonic acid to 2-keto-L-gulonic acid 33
2.6. Discussion 33 References 34
3. Analysis
3.1. Introduction
3.2. Ion exchange chromatography
3.2.1. Introduction
3.2.2. Experimental
3.2.3. Typical results
3.3. Preparative ion exchange chromatography
3.3.1. Experimental
3.3.2. Typical results
3.4. l3c-nuclear magnetic resonance spectroscopy
3.4.1. Introduction
3.4.2. Experimental
3.4.3. Typical results
3.5. Isotachophoresis 3.5.1. Introduction
3.5.2. Experimental
3.5.3. Typical results 3.6. A specific detection method for a-keto
carboxylic acids 3.6.1. Introduction 3.6.2. Experimental
3.6.3. Typical results
References
4. Equipment and experimental methods
4.1. Introduction
4.2. The catalysts 4.2.1. The platinum on carbon catalyst 4.2.2. The lead platinum on carbon catalyst
4.3. Equipment 4.4. Experimental methods
4.5. Mass transfer in the stirred tank reactor
References
ii
43
44
44
45 46
52
52
53
55
55
55
56
60
60
61 61
65 65
65 66
67
69
69
69
71
74 75 76
76
iii
S. Selective catalytic production of D-glucaric acid
S.1. Introduction 77
S.2. Exploratory experiments of the oxidation of D-gluconic acid with Cu1II) and Co(!I) catalysts 81
S.3. Product distribution during the oxidation of D-gluconic acid with a Pt/C catalyst 82
S.4. Oxidation of D-gluconic acid in the presence
of borate 86 S.S. Oxidation of D-gluconic acid, partly in the
form of o-lacton 93 S.6. Addition of Pb(II) to the oxidation formulation 98
References 99
6. Characteristics and scope of the Pb/Pt/C catalyst in ·the oxidation of carbohydrates and their monocarboxylic ac~ds
6.1. Introduction 101
6.2. Experimental 102
6.3. The effect of lead on the Pt-catalyzed oxidation of D-gluconic acid 102
6.3.1. Addition of a heterogeneous lead compound to the Pt/C catalyst 102
6.3.2. Addition of a homogeneous lead compound to a Pt/C catalyst 106
6.3.3. Addition of Pb3 CP04 ) 2/c to a Pt/C catalyst 108
6.3.4. Addition of EDTA to a Pt/Pb/C catalyst 110
6.4. Influence of the Pb/Pt ratio 111
6.S. Metal ions other than Pb2+ llS 6.6. Other substrates than D-gluconic acid 6.7. Deactivation of the catalyst References
117 123
128
7. Selective catalytic production of 2-keto-D-gluconic
7 .1. Introduction
7.2. Influence of the catalyst concentration 7.3. Influence of the oxygen concentration 7.4. Influence of the pH 7.5. Influence of the temperature
7.6. Product distribution
8. Final discussion 8.1. Introduction 8.2. Coordination of Pb2+ with D-gluconic acid
acid
iv
129 129
134 140 143 146
153
153 8.3. Reaction mechanism 157 8.4. Kinetics of the D-gluconic acid oxidation with
a Pb/Pt/C catalyst 160 8.5. Applications of the Pb/Pt/C catalyst References
Appendix I: Structure formulas
Summary
Samenvatting
Dankwoord
Levensbericht
161 163
165
167
170
173
175
1
Chapter 1
Introduction
1.1. Carbohydrates as a chemicai feedstock
Carbohydrates are produced every year in large quantities
by photosynthesis, mainly in the form of the polysaccharides
cellulose and starch, and the disaccharide sucrose. All can
be hydrolyzed to monosaccharides, yielding glucose, while from
sucrose also fructose is obtained. Starch and sucrose are almost
exclusively used as food, while cellulose is mainly used for
the manufacture of paper and rayon and in the form of wood as
fuel and construction material. Only a very small part of
the available carbohydrates is used as a feedstock for the
chemical industry.
Since the publication of the first report of the Club of
Rome (1) the awareness has grown that the reserves of oil,
natural gas and coal are not unlimited, Therefore, it is
mandatory to look for alternative raw materials for the chemical
industry. In certain instances carbohydrates can offer such an
alternative, the more so because one can try to arrange that
the rate of production by agriculture remains in equilibrium
with the rate of conversion and consumption. Due to the
enormously increased price of oil also the economic attractiveness
of processes based on carbohydrates is improving.
The high oxygen content of the sugars makes it possible
to produce, for some chemicals used at present, substitutes,
that cause fewer environmental problems.
2
From the monosaccharides obtained by hydrolysis, glucose
is the most important raw-material for the chemical indus~ry.
The main products which are of industrial interest are
summarised in table 1.1. More detailed information is given
in the literature (2-7) •
Biocatalytic processes Catalytic processes
ethanol glucitol
acetic acid mannitol (via fructose)
lactic acid gluconic acid
vitamin C (via glucitol) glucaric acid
gluconic acid
fructose
Table 1.1. Produate and proaeesee of industrial
interest, starting from gluaose
The processes can broadly be divided into catalytic and
biochemical (biocatalytic) processes. In this thesis we will
call processes using man made, mainly, although not exclusi
vely, inorganic catalysts catalytic processes, and processes that use microorganisms or enzymes biocatalytic or enzymatic
processes. Their main features are compared in table 1.2.
Although catalytic processes offer more advantages than
disadvantages than biochemical processes, the former have
yet found little application in the carbohydrate-industry.
This is mainly caused by the fact that the selectivity of the
catalytic processes is not high enough. In general, inorganic
catalysts are less specific than biocatalysts, moreover a
characteristic property of carbohydrate molecules is their
rather high number of almost identical functional groups.
Combination of these two factors will generally lead to a
3
lower selectivity when an inorganic catalyst is substituted
for a biocatalyst in a carbohydrate process. This is especially
true for processes involving conversion of only one hydroxyl
group. Of these processes oxidation processes are commercially
by far the most important.
process type catalytic biocatalytic
reaction time + -concentration level of reactants + -reactor volume + -product separation from catalyst + -continuous operation + -reliability (resistance against poisoning) + -selectivity - +
product purification - +
+ : favourable less favourable
Table 1.2. Comparison between aataZytia and bioaataZytia
aarbohydrate proaesses.
Improvement of the selectivity would take away this
obstacle for the application of catalytic oxidation processes
in carbohydrate industry. Therefore the main aim of the
research work described in this thesis is the improvement
of the selectivity of the catalytic oxidation of D-glucose
to D-glucaric acid or 2-keto-D-gluconic acid.
0 II C-H I
H-C-OH I
HO-C,-H I
H-C-OH I
H-C-OH I CH
20H
D-glucose
TOOH
H-T-OH
HO-T-H
H-C-OH I
H-C-OH I CH 20H
D-gluconic acid
COOH I
H-C-OH I
HO-C-H I
H-C-OH I
H-T-OH
COOH
D-glucaric acid
COOH I c = 0 I
HO-C-H I
H-C-OH I
H-C-OH
tH2
0H
2-keto-D-gluconic acid
4
1.2. O~idation of monosaaaharides
Oxidation of monosaccharides is one of the main reactions
that can be applied to carbohydrates. A well~known industrial
example is the oxidation of L-sorbose to 2-keto-L-gulonic acid
from which vitamin C (L-ascorbic acid) can be readily obtained:
0
.9] HO-C II
HO-C I
H-C I
HO-C-H I CH 20H
L-sorbose 2-keto-L-gulonic acid
L-ascobic acid
Without precautions the oxidation step is accompanied by many
side reactions, so that a protection of the other, also
reactive OH-functions by means of e.g. acetone is necessary.
This oxidation requires therefore three reaction steps:
attachment of the protective groups, oxidation of the remaining
target group, and removal of the protective groups, as shown
below.
fH 20H
f 0 HO-f-H
H-f-OH
HO-f-H CH 20H
L-sorbose
2,3:4,6 d1-Disopropylidene 2-keto-L-gulonic acid
2,3:4,6 - d1-0-1sopropylidene -n-L-sorbofuranose
f OOH
r = o HO-C-H
I H-C-OH
I HO-C-H
I CH 20H
2-keto-L-gulonic acid
These three steps are part of the present industrial route
for the production of vitamin C and are based on the work
of Reichstein et al. (8) published in 1933 (!).It would be
economically attractive if one could manage to oxidize
L-sorbose without the need of the introduction and subsequent
removal of protective groups. In chapter 6 we will, on basis
of our findings, propose an alternative route for the manu
facture of vitamin c. Another industrial example is the, at present mainly
biochemical, oxidation of D-glucose to D-gluconic acid. In
5
The Netherlands D-gluconic acid is produced by Glucona, a
joint-venture of Akzo and AVEBE. At the moment they use two
processes, one based on the fungus Aspergillus niger, and the
other predicated the bacterium Gluconobacter oxydans. A logical
development in this field is the use of the immobilized enzyme
system glucose oxydase-catalase from e.g. Aspergillus niger
in a continuous process as described by Hartmeier and Tegge (9),
Richter and Heinecker (10) and Tramper (30).
An important competitor of this process consists of the
catalytic oxidation with palladium on carbon. An industrial
process (with a high selectivity) is currently in operation
in Japan. Dirkx (29) has found that this oxidation can be
carried out with a high selectivity ( > 95%) too, using a
trickle-bed reactor and (deactivated) platinum on carbon
(Pt/C) as catalyst.
The next step, the oxidation of D-gluconic acid to
D-glucaric acid, is much more difficult. There is no bio
catalyst known for this reaction, while for the aqueous
alkaline oxidation with oxygen and Pt/C as catalyst, the
highest productivity reported is 50-55 %. For commercial
application this is far from attractive. In this thesis we
will describe some preliminary experiments to improve this
productivity.
6
1. 3. Properties and appZiaations of the o:xidation-produats
of g"luaose
The main product property of the oxidation-products of
monosaccharides derives from their sequestering capacity,
i.e. their ability to form soluble complexes with certain
metal ions.
At a pH above 13 gluconic- , glucaric- , galactonic- ,
galactaric-, and xylaric acid are good sequestrants (12,13).
Gluconic acid is the only sugar acid which is at present
applied on a large commercial scale as a sequestrant. The sequestering capacity of glucaric acid is about a factor 5
higher than that of gluconic acid (3% NaOH, 25°C) (12).
However, the relative high cost of production of glucaric
acid by nitric acid oxidation of glucose has discouraged the
widespread use of glucaric acid as a metal ion sequestrant (14). In weak alkaline medium ( pH 8-13) the sequestering capa
city of the sugar acids is low, but on complexing the sugar
acids with boric acid the sequestering capacity in a weak
alkaline medium is much improved (15,16). For example, the
sequestering capacity of disodium glucarate increases by a
factor 9 by complexing it with 1 mol boric acid/mol glucarate
(pH= 9.5, 25°C) (15).
One of the main applications of sequestrants nowadays is
in the formulation of detergents. The most important sequestrants
used for this purpose are citric acid, ethylene diamine tetraacetic acid (EOTA), nitrilo tri-acetic acid (NTA), and scdium
tripolyphosphate.
The choice of the sequestrant for a specific application
depends, among other factors, upon the type of ion to be com
plexed, pH and temperature. Table 1.3. gives the sequestering
capacity (defined here as g Ca 2 + complexed per 100 g seques
trant) for a number of sugar acids and the four other se
questrants. The data are adopted from work described by Heesen
(16) and van der Steen (17).
sequestrant mol boric acid/ sequesterin9 capacity mol sequestran t 9 Ca 2
•;100 9 sequestrant (pH = 9.5, 25•c1
sodium gluconate 0 0.5
1 6.5 disodium glucarate 0 La
1 16.5 disodium galactarate 0 1.3
1 14.0 L(+) sodium tartrate 0 2.0
1 a.a trisodium citrate 0 5.5
1 5.2 Na-NTA 0 16.2 K4-EDTA 0 4.9 sodium tripolyphosphate 0 12.3
table 1.3. Sequestering aapaaity towards ca2 + for some sequestrants
7
From table 1.3. is concluded that the sequestering capa
city of the sugar acid/boric acid complexes can easily compete
with that of the more conventional sequestrants.
Sodium tripolyphosphate is used on a large scale in syn
thetic detergents, but it causes serious environmental pollu.
tion. Therefore, considerable research is carried out by various
industrial laboratories to find alternatives for sodium tri
polyphosphate (18-26). A computersurvey over the years 1971 -
1981 by International Research Service S.D.C. (20) showed
that no less than 400 patent applications were filed world-
wide by about 40 companies: detergent manufactures, oil-com
panies, chemical industries, and others.
8
To judge the potential alternatives, the following pro
perties have to be compared: sequestering capacity, bio
degradibility, toxicological- and cancerous properties and
of course the price.
From all the possibilities suggested in The Netherlands
only two serious candidates (20) remained: zeolite and NTA.
The zeolite used is a special sodium-aluminium-silicate.
It is a crystalline water-insoluble ion- exchanger that
exchanges its sodium ions with the metal-ions from the solution.
A more recent study at our laboratory (27), however,
showed that the oxidation mixture of D-glucose, prepared by
the use of Pt/C as catalyst and oxygen as oxydant, offers a
clear alternative. The main constituent of this mixture is
D-glucaric acid, which, in combination with boric acid, is a very good sequestrant (table 1.3.). The detergents in use
nowadays already contain borates, consequently they need not
to be added separately. According to this study the price of
the so-called "Glucombinaat" is as low as, or even lower than
the other alternatives.
Akzo successfully (21,26) introduced another alternative,
the so-called "washing-bag", in which a mixture of dicarboxylic
acids (succinic- , glutaric- and adipic acid) is used as
phosphate-substitute.
The sugar acids and their complexes with boric acid not
only are an alternative for sodium tripolyphosphate, but also
are potential alternatives for other sequestrants for other
applications, e.g. bottle washing, cleaning of metal-surfaces,
tanning in the leather industry, and as carrier of certain
metal ions in pharmaceutical applications.
The other oxidation reaction described in this work is
that leading to 2-keto-D-gluconic acid. This product is an
important intermediate. It can be converted into its ascorbic
acid analog D-a~aboascorbic acid (!so-vitamin C) (28) :
TOOH c = 0
HO-~-H I
H-C-OH I
H-C-OH I CH20H
2-keto-D-gluconic acid D-araboascorbic acid (!so-vitamin C)
9
This iso-vitamin C has only a very low anti-scorbutic activity,
but it is potentially a very good anti-oxydant in e.g. food.
The a-keto carboxylic acid can also be transformed into
a dicarboxylic acid. Thus 2-keto-D-gluconic acid reacts with
cyanide and hydrolysis of the product gives a 2-carboxy-D
gluconic acid.
2-keto-D-gluconic acid
f OOH HO-C-COOH
I HO-C-H
I H-C-OH
H-t-OH I CH20H
+
f OOH HOOC-C-OH
I HO-C-H
H-h-oH I
H-C-OH I CH20H
2-carboxy-D-gluconic acid
These two 2-carboxy-D-gluconic acids are poly-hydroxy-di-car
boxylic acids. Based on table 1.3. it can be expected that,
eventually in combination with boric acid, the product is a
10
good sequestrant too. The addition product is subject of
extensive industrial research.
1.4. Aspects of phosphate reduction
Phosphates can cause serious environmental pollution by
cutrofication of the surface-water. In The Netherlands the
situation around the phosphate-load of the surface-water is
rather complex (20). Only 52% of it results from activities
in The Netherlands. The rest comes into our country via the
big main rivers, especially the Rhine. From the internal
phosphate load 70% is from domestic origin. Half of it comes from feaces and urine and the other half from synthetic de
tergents. The latter quantity amounts to about 10 000 ton of
phosphate per year.
To reduce the phosphate content of the surface-water there
are three possibilities:
- replacement of the phosphates in the synthetic detergents
by other sequestrants
- obviation of the need for sequestrants by central water
softening
- or dephosphatation of the waste water
In the Netherlands at the moment the best solution for this
problem is still under discussion. From the above mentioned
percentages it is clear that the reduction of the phosphate
load, due to the complete replacement of phosphate in the
detergents in The Netherlands will only be about 18% of the total load. However, if the surrounding countries would take
the same measure, the reduction would be about 35%. From these
figures it is clear that replacement of the phosphates in the
detergents will alleviate the phosphate problem considerably.
It will be just a matter of price and policy which solution or
combination of solutions will be chosen. The phosphate substi-
tutes have in their favour the intention of the Dutch
government to completely eliminate the phosphates in the
detergents by 1987.
11
Any possible substitute of the polyphosphates must not
only have good sequestering properties, but must also be able
to compete pricewise. Therefore a process to manufacture such
a substitute must be as simple as possible.
1.5. Choice of oxidation system
We have investigated only catalytic oxidations of mono
saccharides, because the non-catalytic oxidations by chemical
oxidants are in general much slower, more costly, and less
selective than the catalytic oxidations. In section 1.1. we
already discussed the choice between an inorganic catalytic
and a biocatalytic process. We will now examine the economic
aspects of the inorganic catalytic processes in some detail,
First we have to consider the choice of the oxidizing
agent. In chapter 2 we will discuss some of the possibilities,
and show that there is no oxidizing agent that posseses a
higher selectivity than low pressure oxygen in combination
with a noble metal catalyst. Consequently the process can use
air, the cheapest oxidizing agent available.
The price of the catalyst is in general not so important,
at least when the catalyst losses are low and the catalyst does
not deactivate or can easily be recovered and regenerated. As already mentioned in section 1.3. it is for certain
applications not necessary to purify the oxidation mixture (27).
When a complexing agent has to be produced, the reaction mix
ture needs only little purification, because almost all of the
by-products act as a sequestrant too, although their sequestering
capacity i~ lower than that of the desired product. This is
one of the main reasons for us to investigate methods to im
prove the selectivity for the component with the highest
12
sequestering-capacity. A higher selectivity of course also
facilitates, in general, an eventual purification, thus making
the process cheaper.
The only by-product from our oxidation-mixtures that has
to be removed, if the mixture is to serve as a sequestrant, is
oxalate. This is easily removed by precipitation as calcium
oxalate convertable with sulphuric acid to oxalic acid. For
this oxalic acid, currently mostly imported from abroad, there
exists a good market in our country. The only product that may
have a negative value is calcium sulphate.
The utilization of 2-keto-D-gluconic acid as a source of
iso-vitamin C, applicable as a food anti-oxidant will necessi
tate extensive purification either of the keto acid or the
iso-vitamin c.
1.6. Aim and outiine of this thesis
Biocatalytic oxidation of monosaccharides have found
extensive applications in the carbohydrate industry, while the
(anorganic) catalytic oxidations have found as yet hardly any
application, although recently there is improvement in this
respect (11). The main reason why the catalytic processes, with their potential advantages, lag behind the enzymatic processes,
is the lower selectivity of the former processes. For this
reason we have investigated potential possibilities to improve
the selectivity of some of the catalytic oxidation processes.
Hardly any data are available in this respect. We have chosen
the oxidation of D-glucose, because it is very readily available
and because of its potential applicability of its oxidation
products. From the literature it is known that the first step
in the oxidation-process (D-glucose + D-gluconic acid) can be
carried out with a high selectivity ( > 95%) both catalytically
(29) and with the aid of enzymes (9,10).
This study will largely be devoted to the second step:
the oxidation of D-gluconic acid to D-glucaric acid or
2-keto-D-gluconic acid in aqueous solution with Pt/C and
modified Pt/C catalysts. Dirkx (29) also studied the
13
kinetics of the oxidation of D-gluconic acid to D-glucaric acid,
and the present thesis is in certain respect a continuation
of that work.
In chapter 2 a survey of the literature data on the pre
paration of D-glucaric acid and 2-keto-D-gluconic acid is given.
The analysis of the various reaction mixtures is described
in chapter 3. For this purpose mainly ion-exchange chromatography is used. At times isotachophoresis, 13c-nuclear magnetic
resonance and a specific detection method for a-keto-carboxylic
acids are used to help the identification and quantification of
the various components of the reaction mixtures. For identifica
tion purposes we have also made use of preparative liquid chro
matography for the isolation of certain components out of the
product mixtures.
In chapter 4 a description of the stirred tank reactor,
the preparation of a number of catalysts, and the basic experi
mental procedure is given.
Some explorative experiments to improve the selectivity
for D-glucaric acid are discussed in chapter 5. During one of
these experiments we discovered the selective catalytic produc
tion of 2-keto-D-gluconic acid with a lead modified Pt/C
catalyst. As this compound is of potential industrial interest,
we decided to study its manufacture more closely.
In chapter 6 we describe investigations into the potentials
of this oxidation reaction, e.g. with respect of the catalyst
preparation and also in respect to various monosaccharides as
substrate.
In chapter 7 we dis.cuss the experiments to improve the
selectivity of the reaction described in chapter 6 and experi
ments that are the basis of a reaction model.
Finally in chapter 8 an attempt will be made to give a
consistent description of the factors that determine the charac-
14
teristics of the Pb/Pt/C catalyst. The description will be based
on the results presented in chapter 6 and 7 and a literature
studie on the complexation of D-gluconic acid with Pb2+.
References
1. Rapport van de Club van Rome, Het Spectrum, Utrecht,
Au1a Pocket 500 (1972) 2. van Ling, G., Polytechnisch Tijdschrift, 386 (1970)
3. Dewar, E.T., Manuf. Chemist., 29, 458 (1958)
4. Machell, G., Manuf. Chemist., l!r 520 (1960)
5. Korf, D., Ph.D. thesis, University of Technology, Delft,
The Netherlands (1963)
6. Van Velthuijzen, J.A., Seminar on Sucrochem. (1973)
15
7. Van der Baan, H.S., Kuster, B.F.M~, Innovation study,
University of Technology, Eindhoven, The Netherlands (1982)
8. Reichstein, T.H., Griissner, A., Oppenauer, R., Helv. Chim.
Acta,~, 561/1019 (1933)
9. Hartmeier, w., Tegge, G., Starch, l!• 348 (1979)
10. Richter, G., Heinecker, H., Starch,;!_!, 418 (1979)
11. Kuster, B.F.M., private communication
12. Mehltretter, C.L., Alexander, B.H., Rist, C.E., Ind. Eng.
Chem., !2_, 2782 ( 1953)
13. Yufera, E.P., Easas, C.A., Carrasco, A.A., Rev. Agroquim.
Technol. Alimentos, !• 40 (1961) i C.A. 57, 16384g (1963)
14. Mustakas, G.C., Slatter, R.L., Zipf, R.L., Ind. Eng. Chem.,
46, 427 (1954)
15. Peters, H., Dutch Patent, 99,202 (1961)
16. Heesen, J., Dutch Patent, 7,215,180 (1972)
17. Van der Steen, H.C., Internal report, University of Techno-
logy, Eindhoven, The Netherlands (1974) 18. Chemisch Weekblad, 72 (24) , 1 ( 1976)
19.
20.
21.
22.
23.
24.
25.
Chemisch Weekblad, 73 (30/31), 1
Van Reede, D.' Chemisch Weekblad,
ibid., 77, 353 ( 1 981)
ibid.' 78, 139 ( 1 982)
ibid., 78, 214 (1982)
ibid. I 78, 330 ( 1982)
ibid., 79, 225 ( 1983)
( 1977)
77, 336 ( 1 981 )
16
26. ibid, 22..1 379 (1982)
27. "Glucombinaat", Internal report, University of Technology,
Eindhoven, The Netherlands (1982)
28. Maurer, K., Schiedt, B., Ber., 66, 1054 (1933)
29. Dirkx, J.M.H., Ph. D. thesis, University of Technology,
Eindhoven, The Netherlands (1977)
30. Tramper, J., Luyben, K.C.A.M., Van den Tweel, W.J.J.,
Eur. J. Appl. Microbiol. Biotechnol., ..12 1 13 (1983).
17
Chapter 2
Literature Survey
2.1. Introduation
In this chapter we present a survey of the literature
concerning the oxidation of D-glucose to D-gluconic acid and
of D-gluconic acid to D-glucaric acid or 2-keto-D-gluconic acid.
Furthermore we will pay attention to some other routes for the
production of 2-keto-D-gluconic acid. Because of the commercial
importance of L-ascorbic acid (vitamin C) we also present
literature data on the production of 2-keto-L-gulonic acid, a
precursor of vitamin c. In this literature survey we mainly review those methods
of preparation that are of potential industrial interest. As we
have already pointed out in chapter 1, processes will be only
of interest if they are not too costly. In our survey, therefore,
we pay special attention to the use of air and gaseous oxygen as
oxidizing agents and to the selectivity of the various processes.
The oxidation reactions can in general be grouped in three
main processes: homogeneous oxidation, heterogeneous catalytic
oxidation, and biochemical oxidation. Each of which we discuss
shortly below.
18
Homogeneous oxidation
In the group of homogeneous oxidation we have· gathered
the non-catalytic oxidation with oxidizing agents other than
oxygen and the electrochemical oxidations.
For the oxidation of a hemiacetal or an aldehyde to an acid or a lactone we have, besides oxygen, in general the
following oxidizing agents to our disposal:
- halogens
- nitric acid - Ag! - CuII
- Fe!II
For the homogeneous oxidation of a primary hydroxyl to a
carboxyl, nitric acid or NOx is often used (119,120). In this
reaction the corresponding aldehyde is formed as an intermediate.
In general this type of oxidation is not so very selective be
cause of concurring side- and consecutive reactions. E.g., with
D-gluconic acid the oxidation of the hydroxyls on c2 and c5 to
keto groups, followed by cleavage of the carbon chain causes
serious reduction of the selectivity towards L-guluronic acid.
The selective oxidation of one of the.secondary hydroxyl
groups of a hexose to a carboxyl group is rather difficult. The
aldehyde (or hemiacetal) function is almost always oxydized
first, the primary hydroxyl groups thereafter. To avoid this,
these groups have to be protected first e.g. by the formation
of glycosides or acetals. This also goes for those secundary
hydroxyls which we don't want to be oxidized.
Oxidizing agents other than oxygen have the disadvantage
that they are relatively expensive and their products have to
be removed from the reaction mixture.
19
Heterogeneous catalytic oxidation
This group of reactions mainly consists of the noble-metal
catalized oxidations with oxygen. This procedure offers, to
gether with the biochemical oxidation, the best possibilities
for application on a commercial scale. The selective oxidation of D-glucose to D-gluconic acid can be carried out with
palladium on a carrier in an aqueous solution. For the manu
facture of D-glucaric acid platinum on a carrier is to be
prefered. The oxidation of the a-hydroxyl of D-gluconic acid
can only be carried out selectively, with platinum on a carrier,
if the other hydroxyls are protected.
Biochemical oxidation
Aerobic microorganisms usually oxidize their organic
substrates completely to carbon dioxide and water. During this degradative process, energy and intermediary metabolites re
quired for biosynthesis are generated. Under special circum
stances, however, such as (i) an excess of carbon substrate in the growth medium, (ii) inhibition of certain metabolic path
ways by the presence of inhibitory compounds and (iii} abnormal
physiological conditions (e.g. extremes of pH or temperature), oxidation of the substrate may be incomplete, leading to the
accumulation of intermediate metabolite in the medium. This type
of incomplete oxidation is not genotypically determined, but
simply reflects a changed phenotypic expression of the organism, induced by environmental conditions.
Microorganisms have been described, which possess only a very limited capacity to oxidize certain substrates, more or
less independent of culture conditions. In many cases, these organisms are not even able to assimilate carbon from the sub
strates that they convert, and are able to grow only at the
expense of other organic nutrients present in the medium. Many of these so-called "microbial transformations" are
20
carried out by enzymes, that may be present constitutively
or induced by the substrate. On the other hand they may be
effected by other "essential" enzymes of intermediary meta
bolism acting non-specifically. A survey of the enormous
diversity in oxidative microbial transformations has been
published by Kieslich (1) in 1976.
An important group of aerobic bacteria, which are parti
cularly characterized by their ability to oxidize organic
substrates incompletely, are the acetic acid bacteria. These
organisms have been used since ancient times f.or the manu
facture of vinegar. In this connection especially members of
the genus Gluconobacter are known for their relatively rapid
and imcomplete oxidation of a wide range of organic compounds
and the near quantitative excretion of the oxidation products
into the reaction medium. Today, commercial biochemical
processes, such as the production of L-sorbose from D-glucitol
and D-gluconic acid from D-glucose, are carried out with mem
bers of this genus.
Besides bacteria, fungi are used for the selective oxidation
of monosaccharides. For the manufacture of D-gluconic acid from
D-glucose fungi of the genera Aspergillus and Penicillium are
used.
In general, biochemical oxidations take place in a narrow
pH-range at about 30°C in aerated substrate solutions containing mycelia together with a number of nutrient salts. The process
requires relatively long reaction times and is sensitive to
contamination. The isolation of the products is generally
rather complicated and expensive. This is the main reason why
at present much research is devoted to the immobilization of
the active enzyme species of the fungi and bacteria.
2.2. Oxidation of D-gZucose to D-gZuconic acid
The oxidation of aldoses to the corresponding aldonic
acids has been the subject of numerous publications (2-5),
some of which are related to preparative methods on a labo
ratory scale only.
2.2.1. Homogeneous oxidation
Considerable attention has been given to studying the
mechanism and kinetics of the oxidation by means of halogen
compounds. In acid solution the free halogen or hypohalous
acid is the active oxidant, whereas in alkaline media the
hypohalous anion plays the major role (6). The most widely
21
used homogeneous method is oxidation with bromine in aqueous
solution having been first used by Hlasiwetz in 1861 (7). The
hydrobromic acid formed as a by-product lowers the rate of
oxidation. To minimize this effect buffered solutions (pH 5-6),
are used, or barium carbonate or barium benzoate is added to
the system (8). According to Isbell and Pigman (9), the
primary oxidation product from the reaction of D-glucose with
bromine in the presence of barium carbonate is D-glucono-o
lactone. Grover and Mehrotra (10,11) found that the oxidation
of D-glucose to D-gluconic acid by means of bromine in a
strongly alkaline solution can be described as a bimolecular
second order reaction between the monosaccharide and the
hypobromite ion. From the influence of the pH on the reaction
rate, it is concluded that the hypobromite ion is the actual
oxidizing agent. Analogous conclusi9ns have been reported by
Ingles and Israel (12,13) for hypoiodite oxidations. More
recently, Perlmutter-Hayman and Persky (14) concluded from the
dependence of the reaction rate on the molecular bromine
concentration that this species is the oxidizing agent.
22
The dependence of the reaction rate on pH can be explained by
the assumption that the anionic form of glucose is more
reactive than the glucose molecule.
Extensive kinetic studies on the oxidation of D-glucose
in acidic chlorine solutions has been reported by Lichtin and
Saxe (15), Grillo (16), and Urquiza (17).
Processes have been patented in which glucose is oxidized
by bromine-bromate (181 and by bromic acid together with sodium
chlorate (19). Biniecki and Moll (20) reported the oxidation
by potassium chlorate.
The main drawback of the above processes is the difficulty
of separating the gluconate from the large amounts of salts
and the regeneration of the letter. This disadvantage is partly
overcome by indirect electrolytic oxidation in which bromine
or iodine is formed electrolytically from a small quantity of
the hydrohalic acid (20-28). Recently yields of 77% (29) and 70% (30) have been reported. 'l'he direct electrooxidation of
D-glucose to D-gluconic acid on Pt electrodes has been studied
by Rao and Drake (31) in neutral solution.
Besides the oxidation with halogens, other homogeneou~
methods have been described (2). As they are of no great
industrial importance, they will not be discussed here.
2.2.2. Biochemicai oxidation
This is nowadays one of the most widely applied industrial
procedures for manufacturing D-gluconic acid. This acid, the
simplest oxidation product of glucose, is produced by many
microorganisms, particularly by bacteria of the Acetobacter
and Pseudomonas genera and by molds of the Penicillium and
Aspergillus genera. Previous publications (32,33) have re
viewed some of these oxidations, which will not be discussed
in detail here.
As early as 1880, Boutroux (34) described a biochemical
process for the selective oxidation of D-glucose to D-gluconic
23
acid. The first technical processes were based on surface
techniques with fungi (35). A number of methods based on this
principle were patented about 1930 (36-40), and subsequently
other batch-wise liquid-phase processes have been developed,
that use rotary fermentors (41-45). Aspergillus niger is often
used as the biologically active material. Other processes make
use of a vertical fermentor for which the active mycelium is
cultivated separately in a prefermentor (46). Concentrated
D-glucose solutions can be converted if borax is added to the
reactor to prevent early precipitation of calcium gluconate
(47). A semicontinuous process has been developed in which the
mycelium is separately used (48): after the conversion of one
batch, the mycelium can be separated from the solution by
flotation, so that about 80% of the liquid can be removed
without appreciable loss of active material.
Another method is separation of the mycelium by filtration
or centrifugation, after which it can be added to a fresh
glucose solution (49). In 1959 a continuous process was pa~
tented to produce D-gluconic acid monohydrate (50). In this
field much attention has been devoted to the study of various
types of enzyme-producing bacteria, the isolation of the
enzymes and the mechanism and kinetics of the reaction (51-67).
The following reaction-scheme is a combination of the work of
Gibson et al.(68) and Tsukamoto et al. (69).
1. E0
x + D-glucose + Ered glucono-6-lactone + Ered + glucono-
6-lactone
3. glucono-6-lactone + u2o + gluconic acid
The enzyme in step 1 and 2 is glucose oxidase. This enzyme
catalyzes a dehydrogenation of the glucose through the
24
formation of an enzyme-substrate complex which splits into
glucono-o-lactone and a reduced form of the enzyme. The latter
is oxidized again by dissolved oxygen and hydrogen peroxide is
formed. This peroxide is decomposed by the second vital enzyme
catalase. Glucono-o-lactone can hydrolyze to gluconic acid
either spontaneously or catalyzed by the enzyme gluconolactonase.
The rate-determining step in the overall reaction is dependent
on several factors and can be e.g. the formation of the complex
or the hydrolysis of the lactone.
In enzyme catalysis where the reaction is run in a homo
geneous batch reactor, it is necessary to separate enzymes from
the reaction mixture at the end of the reaction, for example,
by ultrafiltration, affinity chromatography, etc. In order to
avoid these tedious recovery processes, increasing attention
has been given in recent years to the preparation, utilization,
and stability of immobilized enzymes (70-87). There are still
problems with the stability of the immobilized enzymes. n2o2 causes severe deactivation, and the intraparticle mass transfer
of oxygen can easily be rate-limiting, making the immobilized
enzymes less effective than the homogeneous enzymes. In general
the selectivity is very high (90-100%), but the reaction-rate
is rather low. Reactions still require at least several hours.
Another recent development in the field of biochemical
oxidation is the combined hydrolysis and oxidation of e.g.
sucrose (88), maltose (89), starch hydrolysate (90), molases
(90,91), and starch (92) for the manufacture of D-gluconic acid.
2.2.J. Heterogeneous catalytic oxidation
As early as 1861, von Gorup-Besanez (93) oxidized
mannitol in an aqueous alkaline solution in the presence of
platinum black to yield mannonic acid. In 1953 Heyns and co
workers initiated an very extensive research program on the
selective oxidation of carbohydrates with oxygen by means of
noble-metal catalysis in alkaline solution. This work is
Ref .no. Author Reaction Catalyst [Cat] [Glucose l Glucose Reaction Yield Notes temp pH type conversion time
•c g/l mmol/l· % hr
( 100) Acres et al. 45 1%Pd/o.-Al 2o 3 1000 92 a)
( 101) Asahi Chem. Ind. 70 Pt/C 57 2 49 b)
{ H.'2) Buckley et al. 25-55 e-11 2%Pd/C 45 1000-2500 7-10 80-90
(103) Dirkx 45-65 9-10.3 5%Pt/C 500-1000 60-90 es a) ( 104) Hattori et al. 45-55 9.3-9.7 5%Pt/C 1.5 650 99.2 1. 7 94 (105) Heyns et al. 22 B-9 5%Pt/C 20 100 5-10 70
(99) Johnson Matthey 40-60 7-14 1%Pd/Al 2o 3 50-2000 90-100 90 al (106) Kao Soap lo. 5%Pd/C 94 (107) !<awaken F.C. Pd:Pt=J,5:1,5 6 800 14 93 ( 108) 'Kimura et al 40 9-10 2%Pd/C 1600 2 96 ( 109) Kiyoura et al. 70 7,0-7,5 Pd/C 1. 5 94 { 110) Nakagawa et al. 35 10 2%Pd/C 2500 10,5 88 c) ( 111) Nakayama et al. 50 l?d/C 1. 7 95 d) (112 I Nishikido et al. 50 5%Pd/C 15 95 61 2 56 b)
( 113) Nishikido et al. 70 21%Pb0/5%Pd/C 40 200 98 83 bl ( 114) Okada et al. 40 7-14 0,5%Pd/BaS04 3-7 50-300 30 0,1-0,3 el (97) Poethke 20 e Pd/MgO:Pd/BaS04 2500
( 115) Saito et al. 75-85 ~7 ~,5%Pd+1,5%Pt)/C 94 15 85 (116) De Wilt et al. 25-65 8-12 10%Pt/C 0-1,6 50-250 100 1-2 90 (117) De Wit et al. 25 13-14 5%Pt/C 10 70 97 0,67 96 fl
al Continuous tricklebed reactor bl Non-aqueous solvent c)1,3% o 3 in air as oxidizing-agent d) Reactor with circulating pipe el Stirred tank reactor + continuous multistage contactor
fl oxygen free + hydrogen. production
Table 2. 1.: Literature aonaerning the heterogeneous aata'tytia oxidation of D-gluaose to D-g'tuconic a aid
26
sununarized in three comprehensive reviews (94-96). They have
given selectivity-rules, which we will discuss in detail in
chapter 5. A catalyst prepared by reduction of chloroplatinic
acid with formaldehyde is reconunended as the most effective
for oxidizing glucose. The produced acids impede the reaction,
because the oxidation proceeds fastest at a pH of about 9.
To avoid this, pH-control by buffers, or (stepwise) addition
of hydroxide are applied.
In general, the selectivity of the platinum catalyzed
oxidation is lower than of the enzymatic processes. According
to Poethke (97), the selectivity can be affected by a conse
cutive oxidative degradation of the produced D-gluconic acid -
probably by a Ruff mechanism. Furthermore, above pH 12 the
oxidative degradation of D-glucose becomes more important as
a non-platinum catalyzed side reaction. D-glucaric acid has been reported as an important consecutive reaction product depending
on the catalyst quality (98,99). For the selective production
of D-gluconic acid, this consecutive reaction has to be supres
sed, e.g. by using palladium instead of platinum. A schematic
survey of the literature concerning the heterogeneous catalytic
oxidation of D-glucose to D-gluconic acid is given in Tabel 2.1.
The selective manufacture of D-glucono-o-lactone requires
oxidation in non-aqueous media (101,112,113). In aqueous media
the lactone would hydrolize spontaneously.
Table 2.1. shows that the oxidation of D-glucose to
D-gluconic acid with oxygen can be carried out selectively and
fast by means of a Pd/C catalyst. The highest selectivities
reported approach the biochemical ones. This is substantiated
by the recent start in Japan of the industrial production of
D-gluconic acid by means of a palladium catalyst (118).
27
2.3. Oxidation of D-gluaose or D-gluaonia aaid to D-gluaaria aaid
For the manufacture of D-glucaric acid, only two methods
are known, viz. the homogeneous oxidation with nitric acid, and
the heterogeneous catalytic oxidation with noble-metal catalysts.
As far as we are aware, no selective biochemical method for the
preparation of D-glucaric acid exists yet.
2.3.1. Homogeneous oxidation
D-glucose can be oxidized to D-glucaric acid with nitric
acid (119,120). Mustakas et al. (121) studied this process on
a pilot plant scale and obtained a yield of 44% (as K-H-gluca
rate). According to Truchan (122), pretreatment of the glucose
with ammonia, followed by the oxidation with nitric acid, would
give a yield of 65%.
Another possible route for the manufacture of D-glucaric
acid is the oxidation of starch to polyglucuronic acid by N02 (123-125). Although glucuronic acid can be oxidized very selec
tive to D-glucaric acid, yields are low, due to the extensive
degradation during the hydrolysis of the polymer.
2.3.2. Heterogeneous aatalytia oxidation
Platinum and palladium are used as catalyst for the
oxidation of aqueous solutions of carbohydrates with oxygen.
The use of a palladium catalyst for the further oxidation of
D-gluconic acid in alkaline solution leads to many degradation
products, including D-arabinonic acid, D-erythronic acid, and
no D-glucaric acid is obtained at all (97).
Among others, de Wilt (116) has studied the oxidation of
D-glucose to D-gluconic acid with Pt/C as catalyst. The maximum
selectivity for D-gluconic acid was about 95%, which was
obtained at a low pH (8) and low temperature (30°C) (116).
28
At a somewhat higher pH (pH 9-10) and/or temperature (55°C),
attack on the primary hydroxyl group at C-6 of D-gluconic acid
results; thus, a 55% yield of D-glucaric acid is obtained from
D-glucose (98,103,126).
2.4. Manufaature of 2-keto-D-gluaonia aaid
From the literature various methods for the manufacture
of 2-keto-D-gluconic acid are known (127). Those with D-glucose
or D-gluconic acid as substrate will be discussed in section
2.4.1. Some alternative methods, starting from other mono
saccaride-derivatives, will briefly be discussed in section
2.4.2.
2.4.1. Oxidation of D-gluaoae or D-gluaonia aaid
Oxidizing-agents other than oxygen
Since the molecule of D-gluconic acid contains many
reactive groups, it is obvious that chemical oxydizing agents
must be highly selective in their action if they are to de
hydrogenate only the second carbon atom. D-gluconic acid or its
lactones can be oxidized with chlorates in the presence of
vanadium pentoxide and phosphoric acid (128-132) to produce
2-keto-D-gluconic acid. When the oxidation is carried out in a
mildly acidic aqueous medium (pH between 3 and 4) after 40
hours a yield of 50% is obtained (130). Improvement of the yield and a simpler recovery of the product is possible by
the addition of a water miscible organic solvent which is sub-•
stantially inert to the oxidizing action of the chlorates in
the presence of the vanadium catalyst. Thus, ammonium-D-gluconate
is converted in an aqueous methanol (50%) medium in 24 hours
to the methyl ester of 2-keto-D-gluconic acid with a yield of
72% (131).
29
The same authors also patented the specific oxidation with
chromic acid (133). The oxidation is catalyzed by the addition
of small amounts of substances such as nickel, cerium, iron,
platinum and their salts. According to this patent, the oxida
tion of D-gluconic acid with chromic acid in the presence of
feric sulphate at 0°C, yields 40% of 2-keto-D-gluconic acid
after 12 hours.
The electrochemical oxidation of D-glucose to D-gluconic
acid with bromide solution as the electrolyte, have been dis
cussed in section 2.2. There was no evidence that the 2-keto
acid was formed as a byproduct. However, Pasternack and Regna
(134) have found that an electrolytic process involving the
combined action of a halide, other than an iodide, and soluble
chromium compounds will convert the aldonic acid to the corres
ponding 2-keto-acid. The relatively small amount of chromium
required in this process compared to the above mentioned chromic
acid oxidation is of great advantage, because of the easier
purification of the product and the lower costs of the oxydizing
agent. Thus, the electrochemical oxidation of calcium-D-gluco
nate with calcium bromide and chromium trioxide at 20°C gave a
yield of 80% of calcium-2-keto-D-gluconate after about 6 hours.
Oxygen as oxidizing-agent
In their comprehensive review of the heterogeneous cata
lytic oxidation of carbohydrates with oxygen at a platinum
catalyst, Heyns et al. (96) conclude that for the oxidation of
the secondary hydroxyl groups of open-chain polyhydroxy mono
saccharide-deri vates, almost no selectivity is to be expected.
This is in agreement with our observations. D-gluconic acid must
suitably be protected to direct the platinum catalyzed oxidation
to 2-keto-D-gluconic acid. Some examples of the oxidation of
protected monosaccaride-derivatives will be given in section
2.4.2. In thi~ thesis, however, we will describe a catalytical
method with which it is possible to oxidize D-gluconic acid
w 0
Ref.no. author reaction pH type of biocatalyst Conv. time yield notes temp % hrs % •c
(135) Agapova et al. Pseudomonas ( 136) Banik et al. Bacillus firmus
B. circulans B. subtilis
(137) Bernhauer et al. Bacterium gluconicum 80 (138) Bernhauer et al. A. suboxydans ( 139) Blais ten Ps. fluorescens a)
Ps. fragi a) Ps. reptilivora a)
( 14 0) Bull et al. Serratia marcescens NRRL B-486 a) ( 141) F!!rber 27 Cyanococcus chromospirans 20 .. 100 ( 14 2) F!!rber et al. Ps. chromospirans
Ps. aeruginosa ( 143) F'ewster A. suboxydans ( 14 4) Ikeda Ps. fluorescens a)
Serratia marcescens (145) Knobloch et al. A. orleanense 720 56
A. ascendens 720 39 (146) Kozhobekova et al. 5 100 12 (147) Kulhanek Ps. aeruginosa 74 b) (148) Lockwood et al. 30 Ps. aeruginosa 192 70 a) ,c)
Ps. fluorescens 82 948 88 949 84 142 75
frag11 4973 86 graveolens 4683 77
4684 82
Ref.no. author reaction pH type of b1ocatalyst time yield notes
t<o~P hrs %
30 Ps. mil de nberg i1 795 192 100 al ,cl oval1s 950 55
pavonacea 951 77
putida 4359 85 schuylk1111ensis 82 vendrelli 7700 81
( 149) Misenheimer 30 Serratia marcescens NRRL B-486 16-32 100 al (1501 Neijssel et al. Klebsiella aerogenes NCTC-418 al (151) Norris et al. Ps. aerug1nosa
(152) Pfeifer et al. Ps. fluorescens al Ps. fragi a) Ps, reptilivora a)
(153) Stoutharner A. suboxydans
(154) Stubbs et al. 25 Bacterium gluconicurn 25 82 al (155) Vondrova-Hovezova et al. Ps. chrornospirans
(1561 Yamazaki 5 Ps. fluorescens 168 40 d) (1571 l:'okosawa Ps. fluorescens a)
a) glucose oxidation instead of gluconic acid oxidation c) the numbers in the column yield are selectivities b) 10 strains of Ps aeruginosa are examined d) simultaneous oxidation of D-gluconate and L-idonate
A,~ Acetobacter B.= Bacillus Ps. Pseudomonas
table 2.2. Literature concerning the biochemical oxidation of D-gZucose or D-gZuconic acid acid to 2-keto-D-gluconic
w ....
32
to 2-keto-D-gluconic acid selectively, obviating the use of
protective groups.
Biochemical oxidation
Special bacteria are cultivated for the fermentative
oxidation of D-glucose or D-gluconic acid to 2-keto-D-gluconic
acid. A schematic survey of the literature concerning this
oxidation is given in table 2.2. In this table we again
encounter the characteristics of a biochemical process: the
yields are generally high, but the processes are slow. In
section 1.1. we already discussed this matter.
2.4.2. Aiternative oxidation methoda
Besides the oxidation of D-glucose or D-gluconic acid,
there are some alternative methods for the manufacture of
2-keto-D-gluconic acid:
- Oxidation of D-glucosone (D-arabino-hexos-2-ulose) with
bromine in water under the influence of light (158,159).
After 3-4 days at room temperature the yield is 68%.
- Direct oxidation of D-fructose, with oxygen in an aqueous
alkaline medium. Heyns (160) describes this reaction u~ing platinum as catalyst.(The analogous oxidation of L-sorbose
to 2-keto-L-gulonic acid has been the subject of more
investigations, as this product is a precursor of vitamin C).
- Oxidation of a D-fructose derivative substituted in such a
way that only the neighbouring ce2oe group remains free.
Thus, 2,3-4,5-di-0-isopropylidene-D-fructopyranose
(S - diacetone-D-fructose) is oxidized with potassium
permanganate to the diacetone derivate of 2-keto-D-gluconic
acid (161-163). The same oxidation can also be carried out
with air in aqueous alcohol with Pt/C as catalyst with a
yield of more than 90% in 2-5 hours (164).
None of these routes is commercially attractive.
33
2.5. Oxidation of L-gulonia acid to 2-keto-L-gulonic acid
The lead/platinum/carbon catalyst is also active in the
oxidation of L-gulonic acid to 2-keto-L-gulonic acid. The latter
product is a direct precursor of vitamin C, and for this
reason this oxidation step can be of great industrial impor
tance. We want to find out whether our oxidation method can
compete with others. For comparison we will review the litera
ture concerning the oxidation of L-gulonic acid to 2-keto-Lgulonic acid shortly:
- Oxidation with chl?rate in the presence of vanadium pentoxide and phosphoric acid. After 20 hours the yield
is 68% if the reaction is carried out in an aqueous
solution (130).
- Oxidation with chromic acid. The yield for 2-keto-L
gulonic acid is 41% and the selectivity is about 70% after
24 hours of reaction (133).
- Electrochemical oxidation with a combination of mainly
bromide and a little chromium trioxide. No yield is
stated (134).
- Biochemical oxidation. Aerobic fermentation with Pseudo
monas aeruginosa leads to a conversion of 44% after 8
days (165) and with Xantomonas translucens a yield of
minimal 85% is achieved after more than 72 hours at
28-30°C (166).
2.6. Disaussion
In section 1.6 we have given our motivation for investiga
ting possibilities to improve the selectivity of the catalytic
oxidation of D-glucose to the commercially attractive products
34
D-glu~onic acid, D-glucaric acid and 2-keto-D-gluconic acid.
From the literature survey in this chapter it is clear that the
oxidation of D-glucose to D-gluconic acid can be carried out
with a high selectivity (~95%) either with the aid of enzymes
or with noble metal catalysts. Such a selectivity is not ob
tained for the oxidation of D-gluconic acid to D-glucaric acid
or to 2-keto-D-gluconic acid, with two exceptions: The micro
bial manufacture of 2-keto-D-gluconic acid and the electrochemi
cal oxidation of calcium-D-gluconate to calcium-2-keto-D-gluco
nate. We have already discussed the disadvantages of the bio
chemical process in section 1.1. The latter process is slow
and makes use of relatively expensive oxidants. Therefore we
have directed our efforts towards improving the selectivity
of the catalytic oxidation of D-gluconic acid to either
D-glucaric acid or to 2-keto-D-gluconic acid with air as
oxidizing agent.
References
1. Kieslich, K., "Microbial transformation of non-steroid
cyclic compounds", Thieme Stuttgart, (1976)
2. Stanek, J., Cerny, M. , Kocourek, J. , Pacak, J., "The Monosaccharides", p 657, Academic Press, New York (1963)
3. Mehltretter, c., Starch,_!.~_, 313 (1963) 4. de Wilt, H., Ind. Eng. Chem. Prod. Res. Develop., .l..!.1 370
( 1972) 5. Theander, o. , "Carbohydr.: Chem. Biochem. (2nd Ed.) , 1 B,
1013 Ed. Pigman, w., Horton, D., Academic Press, New
York (1980) 6. Green, J.W., "The Carbohydrates", p. 336, W. Pigman, Ed.,
Academic Press, New York (1957)
35
7. Hlasiwetz, H., Ann., 119, 281 (1861)
8. Hudson, c.s., Isbell, H.S., J. Am. Chem. Soc., i:!_, 2225
(1929); Isbell, H.S., Methods in Carbohyd. Chem.,~' 13
(1963)
9. Isbell, H.S., Pigman, W., Bur. Standards J. Res., 1Q, 337
(1933)
10. Grover, K.C., Mehrotra, R.C., z. Physik. Chem. (Frankfurt),
.li1 345 (1958)
11. Mehrotra, R.C., Grover, K.C., Vijana Parishad Anusandhan
Patrika, i• 255 (1961); C.A. 59, 6493e
12. Ingles, O.G., Israel, G.C., J. Chem. Soc., 810 (1948)
13. Ingles, O.G., Israel, G.C., ibid., 1949, 1213 (1949)
14. Perlmutter-Hayman, B., Persky, A., J. Am. Chem. Soc.,
82, 276 (1960)
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40
106. Kao Soap Co., Ltd., Belg. Patent 851,804 (Jun 16, 1977)
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63,12.1 (Jun 1, 1976)
109. Kiyoura, T., Kimura, T., Sugiura, T., Japan. Kokai 76
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120. Bose, R.J., Hullar, T.L., Lewis, B.A., Smith, F., J. Org.
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123. Graefe, G., Starch, ~, 205 (1953)
41
124. Heyns, K., Graefe, G., Chem. Ber., 86, 646 (1953)
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Carbohydr. Res., 59, 63 (1977)
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131.
132.
133.
134.
(Jan 30, 1940)
Ibid., U.S. Patent
Ibid., U.S. Patent
Ibid., U.S. Patent
Ibid., U.S. Patent
2,203,923
2,207,991
2,153,311
2,222,155
(Jun 11 I 1940)
(Jul 16 I 1940)
(Apr 4, 1939)
(Nov. 19, 1940)
135. Agapova, E.V., Goucharova, L.A., Kapterova, Yu. v., Kozhobekova, K.K., Rubtsov, I.A., Pomortseva, N.V.,
Tarnopol'skaya, I.P., Gofman, L.Kh., U.S.S.R. Patent
603,659 (Apr 25, 1978)
136. Banik, s., Dey, B.K., Indian Agric., 22, 93 (1978)
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582 (1958)
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7189
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~oncharova, L.A., Tarnopol'skaya, I.P., V'yunova, G.M.,
42
Deposited Doc. 1976, VINITI 3540-76; CA 89, 127 687x
147. Kulhanek, M., Chem. Listy, fl, 1071 (19531 ibid., 1081 (1953)
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42, 51 (1941)
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151. Norris, F.C., Campbell, J.R., Can. J. Res., 27C, 157 (1949)
Ibid. I 1 6 5 ( 1 9 4 9)
Ibid., 253 (1949)
Ibid., 28C, 203 (1950)
152. Pfeifer et al., Ind. Eng. Chem., 50, 1009 (1958)
153. $touthamer, A.H., Ph. D. thesis, University of Utrecht,
The Netherlands (1960)
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1954, 9469
156. Yamazaki, M., J. Fermentation Technol.,1J_, 86 (1953);
Ibid., 126 ( 1953)
Ibid., 230 (1953)
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158. Neuberg, c., Kitasato, T., Biochem. z., 183, 485 (1927)
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43
Chapter 3
Analysis
3.1. IntPoduction
For the study of the kinetics of a reaction, its reaction
network, and its selectivity, a fast and accurate analysis of
all the reaction products is a prerequisite. Because the oxi
dation of D-gluconic acid shows many ramifications, much
attention had to be paid to the analytical aspects of our
investigation. For the noble metal catalyzed oxidation of
D-glucose or D-gluconic acid in aqueous medium the following
products can be expected (1-4). (In Appendix I the structure
formulas are givenl:
(a) c1 , c6 oxidation products: D-gluconic acid, D-glucose
dialdehyde, L-guluronic acid, D-glucaric acid and
D-glucuronic acid
(b) keto carboxylic acids: especially 2- and 5-keto-D-gluconic
acid
(c) products of oxidative c-c bond rupture: c1-c5 monocarboxylic
acids, c2-c5 dicarboxylic acids and carbon dioxide
(d) isomerisation products ( pH ~ 12): D-fructose and D-mannose.
The analysis of the various products has received only
little attention in the literature. No suitable methods for
qualitative determination or separation are given, let alone
their quantification. Verhaar and De Wilt (1,5) developed a
useful gas liquid chromatographic procedure. However, this
procedure requires a very time consuming derivatization
44
(silylation) of the products and therefore can not be auto
mated. Moreove4D-glucaric acid could not be determined
properly. For these reasons this method was discarded.
Dirkx and Verhaar (2,6) developed a liquid chromatographic
procedure based on ion-exchange chromatography, allowing the
main oxidation products to be determined. We have used an
automated and modified procedure based on this procedure, as
described in section 3.2.
Occasionally we have used preparative liquid chromatography
(section 3 .. 3.) for the separation of certain components out of
the reaction mixture and 13c~nuclear magnetic resonance spec
troscopy (section 3.4.) for their identification.
Dirkx (2) also described an isotachophoretic procedure for
the separation of the oxidation products. Occasionally we used
a modification of this method to obtain additional information
(section 3.5.).
A specific detection method for u-keto acids (section 3.6.)
was applied to prove the presence and estimate the concentration
of various u-keto acids.
3.2. Ion-e~change chromatography
3.2.1. Introduction
A review of ion-exchange chromatography of carboxylic acids
is given by Jandera and Churacek (7).
In order to improve the separation we replaced Dirkx and
Verhaar's (6) single eluant, a sodium sulphate solution, by a
series of two eluants. The first was a sodium chloride solution,
which gives a good separation of the monocarboxylic acids, but
takes too much time for the dicarboxylic acid elution. For this
we switched, after the elution of the monocarboxylic acids, to
magnesium chloride, which gave a satisfactory separation and
elution time for the dicarboxylic acids, as suggested by Lee and Samuelson (8).
3.2.2. Experimental
45
Table 3.1. summarizes the apparatus and experimental
conditions used for the analysis of our reaction samples, and
fig. 3.1. shows a block-diagram of the liquid chromatograph.
eluant A eluant B eluant C
4-way valve
pump
static + dynamic mixer
r--I injection-valve
I I pre-column
I analytical
.., I
I I I I I column ___ J L ___
UV-detector
automatic sampler
column oven
integrator/ recorder
,_x_r_-_de_t_e~c_t_or __ _J --1 recorder
waste
Figure 3.1. Block diagram of the analytical chromatographic system
The columns were slurry-packed at room temperature with a sus
pension of the ion-exchange resin in a 0.125 M NaCl solution.
A strong basic anion exchange resin serves as column material
(type Aminex A-27 or Alltech Anion Exchange Resin BA-X8).
For pretreatment the samples only needed filtration over
a Millipore type HA filter (0.45 µ).Continuous UV-detection
at 212 nm and, occasionally, differential refractive index
(RI)-detection were used.
46
liquid chromatograph detectors
data-system pre-column dimensions separation-column dimensions:
column-material
column-temperature injection-volume eluant A eluant B eluant-degassing flow program
Spectra Physics type SP 8100
variable wavelength UV/VIS detector, Spectra Physics type SP 8400, detection at
212 nm. (Occasionally) differential refractive index detector, Waters type R 401 Spectra Physics type SP 4100 75 mm x ll 4.6 mm 250 mm x ll 4.6 mm
strong basic anion exchange resin, Biorad
type Arninex A-27 (particle diameter 12-15µ) or Alltech type Anion Exchange Resin BA-XS (particle diameter 7-10µ) as•c 10 µ1
0.125 M NaCl solution
0.0875 M Mgc1 2 solution helium method
time eluant
(min)
0-19 A 19-38 B 38-45 A
flow (ml/ min)
1.0 1.1
1.0
table 3.1. Apparatus and experimental conditions of the ahromatographia system
The. molecular UV response depends on the interaction of
various functional groups within tbe molecule, whereas the
molecular RI response is roughly proportional to the molecular
mass. Therefore, especially the ratio of the UV- and RI-signal
gives valuable information for the identification of the peaks
in the chromatograms.
The (off-line) analytical system operated automatically
and was programmed in such a way that after 5 reaction samples
2 calibration samples were introduced.
3.2.3. Typiaal results
Figure 3.2. shows a chromatogram of a calibration sample.
The upper curve shows the UV-signal and the lower one the RI
signal. A good separation of the components of the calibration
samples is obtained. Especially the dicarboxylic acids are very
well separated when compared to the results of Dirkx and
Verhaar (2,6).
5 4
6
1ii 7 c:: O> ·;;; 3 8 > ::::>
a:
0 10 20 30 40
time (min) --
figure 3.2. Chromatogram (UV- and RI-eignat) of a aatibration sampte
47
1: D-gtuaonia aaid, 2: D-gataaturonia aaid, 3: D-gtuauronia aaid, 4: 2-keto-L-gutonia aaid, 5: o~aiia aaid, 6: tartronia aaid, 7: D-giuaaria aaid, 8: tartaria aaid
The UV-signal shows some discontinuities denoted by arrows.
These are due to programmed baseline corrections. The baseline
drift is caused by the eluant- and flow programming.
The dicarboxylic acids could not be detected by the RI
detector, due to the difference in refractive index of the NaCl-
48
and the MgC1 2 solution, causing too much shift of the baseline.
In the calibration samples D-galacturonic acid is used
for the calibration of L-guluronic acid, because the latter was
not available in a pure form. We have identified L-guluronic
acid with the aid of a sample containing L-guluronic acid and
D-mannuronic acid, kindly supplied by Mr. Schols of the
Wageningen University of Agriculture.
For the calibration of 2-keto-D-gluconic acid (2KGOZ) and
5-keto-D-gluconic acid (SKGOZ) we used 2-keto-L-gulonic acid
(2KGUZ) to save costs. We have determined the ratios of the
molar responses of 2KGOZ to 2KGUZ and of SKGOZ to 2KGUZ. The
results are summarized in table 3.2.
2KGOZ SKGOZ 2KGUZ 2KGUZ
peak area 1.22 0.88
peak height 1. 20 0.86
table 3.1. Ratios of the peak heights and peak areas of 2-keto-D-gluconic acid to 2-keto-L-gulonic acid, and of 5-ketoD-gluconic acid to 2-keto-L-guZonic acid
Figure 3.3. shows the calibration curves (peak area versus
concentration) of 4 key components. As is seen in this figure,
a non-linear relationship between peak area and concentration
is obtained. The following relation is used to calculate the
concentration of the various components in a reaction sample:
where:
C = concent,ration, A peak area, and a and b are constants
The constants a and b (0.9 - 1.1) in the above formula are
calculated with the least-squares-method.
200
.::::: 0 1150 c: .2 100 i ... t: ~ c: 50
8
49
o D-Gluconic acid
~ 2-keto-D-Gluconic acid <> Oxalic acid a D-Glucaric acid
o.pc:::.:.......,...~-..~.._,,...-~..-~ ....... ~-..-_j. 0 80 160 240
peak area (arbitrary units)
figure 3.3. Calibration aurves of D-gluaonic acid, 2-keto-D-gluconic acid, oxalia acid, and D-glucaric acid
Figure 3.4. illustrates a chromatogram of a sample of the
oxidation of D-gluconic acid with Pt/C as catalyst. The identi
fication of the components in this - and following chromato
grams is based on three methods, i.e. liquid chromatography
(this section), preparative l~quid chromatografphy in combination with 13c-nuclear magn~tic resonance spectroscopy (section
3.3. and 3.4.), and isotachophoresis (section 3.5.)
Besides D-gluconic-, 4-guluronic- and D-glucaric acid, viz. the.reactant, the intermediate and the main oxidation product, the following by-products are identified: the monocarboxylic
acids with c 4 up to c 1 , viz. D-erythronic-, D-glyceric -gycolic- and formic acid, the dicarboxylic acids with c 4 up to c 2 , viz. tartaric-, tartronic- and oxalic acid, and the ketoacids 2- and 5-keto-D-gluconic acid. We have not determined the
stereochemistry of the mono- and dicarboxylic acids.
However, as we think that these products mainly arise from
oxidative cleavage of the carbon chain by which at both sides
of the cleavage a carboxylic acid group is formed, the monocarboxylic acids must have a stereo chemistry corresponding
50
-;;; c: Ol
"iii
> :::>
-;;; c: .Ql fl)
a:
2
0 10
8
10
9 11
! t
20 30 40
time (min)
figuPe J.4. ChPomatogPam (UV- and RI-signal) of a sample of the oxidation of D-gluoonio aoid ~ith a Pt/C aatalyst
1: D-gluoonio aoid, 2: L-guluPonio acid, J: 5-ketoD-gluconic acid + D-epythPonic acid + D-glycePio acid, 4: 2-keto-D-gluconic acid + glycolic acid, 5,8: not identified, ?: foPmic acid, 8: oxalic acid, 9: taPtPonic acid, 10: D-glucaPic acid, 11: taPtaPic acid
to D-gluconic acid.
Figure 3.5. illustrates a chromatogram of a reaction sample
of the oxidation of D-gluconic acid with a Pb/Pt/C catalyst.
Comparison of this chromatogram with the previous one shows a
Cii c: .2' <I)
> :::>
Cii c: .2' <I)
a:
51
4
10
0 10 20 30 40
time (min) -
figure J.5. Chromatogram (UV- and RI-signal) of a sample of the oxidation of D-gluconic acid with a Pb/Pt/C catalyst
1: D-gluoonio aoi~ 2: L-guluronio aoid, 3: 5-keto-Dgluoonio aoid, 4: 2-keto-D-gluoonio aoid, 5: not identified, 6: formio aoid, ?: oxaZio aoid, 8: tartronio aoid, 9: D-glucario acid, 10: a-keto-D-glucaric acid
marked difference in product composition. Here the main product
is 2-keto-D-gluconic acid and the by-products are L-guluronic-,
D-glucaric-, 5-keto-D-gluconic-, formic-, oxalic-, tartronic
and a-keto-D-glucaric acid.
52
3.3. Preparative ion exchange chromatography
3.3.1. Experimental
For preparative ion exchange chromatography a large injec
tion volume is used on a separation column with a high capacity.
The instrument and experimental conditions are described in
table 3.3.
pump
injection-valve
injection volume column-dimensions column-material
column-temperature
detection
eluant A eluant B flow-program
Orlita membrane pump type DMP/AE-10-4. 4
Rheodyne type 7010 2 ml
250 x ill 12 mm
stron9 basic anion exchange resin
Biorad type AG1-X8 {paricle diameter < 63 ~)
es•c UV-detection at 216 nm with a variable wavelength UV-detector Pye Unicam type LC3 0.25 M NaCl-solution 0.15 M MgC1 2-solution
time eluant flow {min) (ml/min)
0-50
50-80 80-100
A
B
A
3,3 3,3
3,3
table 3.3. Apparatus and experimental conditions of the self-assembled preparative liquid chromatographic system
The fractions containing the desired product are collected
from 5-10 injections. The product is then separated from the
excess of salt from the eluant by the following procedure:
Acidification with hydrochloric acid to pH 2, evaporation to
dryness in a film evaporator at 50°C and reduced pressure, ex
traction of the residue with methanol, filtration of the salt
residue, evaporation of the methanol to dryness in a film eva
porator, addition of water and adjusting the pH to 7. The
products in these solutions are identified by 13c-NMR.
53
S.S.2. Typical t>esuite
A reaction mixture of the oxidation of D-gluconic acid with
a Pb/Pt/C catalyst was first concentrated three 'fold in a film evaporator. From each of 5· injections of this concentrate
the last 70% of the peak containing the 2- and 5-keto-D-gluconic
acid was collected and worked up. Normal analysis (as described in section 3.2.) now produces the chromatogram of figure 3.6.
I I
a:
4
0 10 20 30 40
time (min) -
figure S.6. Chomatogram (UV- and RI-signal) of a fraction collected from a reaction mixture of the oxidation of D-gluconic acid with a Pb/Pt/C catalyst
1: D-gluconic acid, 2: L-guluronic acid, S: 5-keto-Dgluconic acid + D-glyceric acid + D-erythronic acid, 4: 2-keto-D-gluconic acid + glycolic acid, 5: not identified, 6: oxalic acid
54
Comparison with the chromatogram of the starting product
mixture (figure 3.7) clearly shows the effect of the chroma
tographic purification and improved peak resolution. The
refined sample was also analyzed with 13c-NMR (section 3.4.)
and isotachophoresis (section 3.5.).
iii c: Cl ·o;
a:: 4
0 10
7
20 30 40
time (min) -
figure 3.7. Chromatogram (UV- and RI-signal) of a sample of the oxidation of D-gluconic acid with a Pb/Pt/C catalyst
1: D-gluconic acid, 2: L-guluronic acid, 3: 5-ketoD-gluconic acid + D-glyceric acid + D-erythronic acid, 4: 2-keto-D-gluconic acid + glycolic acid, 5: not identified, 6: formic acid, 7: oxalic acid, 8: tartronic acid, 9: D-glucaric acid, 10: tartaric acid, 11: a-keto-D-glucaric acid
55
3.4. 13c- nuaiear magnetia resonanae epeatroeaopy
3.4.l, Introduation
Natural abundance carbon-13 nuclear magnetic resonance
c13c-NMR) spectroscopy is increasingly being utilized for the investigation of carpohydrates. Recent improvements in instru
mentation have successfully overcome the inherently low sensi
tivity of 13c-NMR experiments on non-enriched samples which contain, of all the carbon present, only about 1.1% carbon-13.
The present day experimental technique takes advantage of stable
spectrometers, wide-band proton decoupling and pulsed Fourier
transform techniques. A considerable advantage of 13c-NMR
spectroscopy is the large range of chemical shifts. Resonance
frequencies for most organic molecules, including carbohydrates,
are spread over 200 ppm. Additionally, with complete proton decoupling each magnetically non-equivalent carbon appears
as a sharp single line and individual lines are resolvable if
separated by only 0.1 ppm. such considerable resolving power
renders 13c-NMR an effective tool for investigating subtle structural differences and provides a convienient method for
the analysis of complex mixtures. These considerations made us apply this technique for the identification of certain reaction products in the complex reaction mixture.
3.4.2. Experimentai
Proton-decoupled, natural abundance-carbon-13, pulse Fourier
transform NMR spectra were recorded with a Bruker WM-250 ( 63 MHz) or a Bruker CXP-300 (75.6 MHz) spectrometer. Spectra were
recorded at ambient temperature by using the deuterium resonance
56
of acetone-D6 (external standard) as the lock signal and the
Me4Si (external standard) as reference signal. Sample tubes
of 10 nun diameter were used. Typical measurement conditions
were: number of scans 5000-6000, data points 16K zero-filled
to 32K before Fourier transformation, sweep width 20 KHz and
repetition time 10 s.
3.4.3. Typical re8ults
In figure 3.8. the 13c-NMR spectrum is given for the sample
used for the chromatogram of figure 3.6. (section 3.3.2.). This
spectrum is rather complex, mainly due to the various tautomeric
forms of two of the components of the mixture. Using data
published by Crawford et al. (9) the chemical shifts arising
from the four tautomeric forms of 2-keto-D-gluconate and the
three tautomeric forms of 5-keto-D-gluconate could be identi
fied and with the aid of a spectrum of D-gluconate (10) also
the chemical shifts of this component could be assigned. Of the
remaining 13 smaller signals, 3 further signals could be assigned, as their integrals were of the same order of magnitude,
and at least a factor 2 higher than those of the remainder.
These 3 signals can be ascribed to a -COOH group, a ~ CHOH
group and a -cu2oH group. Combination of this information with our postulate of the oxidative cleavage of the reaction products (section 3.2.3.) leads us to the conclusion that these three
signals belong to D-glyceric acid.
The remaining signals all are rather small and of the
same order of magnitude, so that no further assignments could
be made. These signals are supposed to represent by-products
with a relatively low concentration. This is in agreement with
our isotachophoretic analysis of this sample. Below the various tautomeric forms of 2- and 5-keto-D
gluconic are shown and in table 3.4. a survey of the chemical
shifts of the components of the above described sample is given.
84 60
8 (ppm)
180 160 140 120 100 BO 60
8 (ppm)
figure 3.8. 13
C-NMR spectrum of a fraction of a sample of the oxidation of D-gZuconic acid with a Pb/Pt/C-cataZyst
58
Tautomeric forms of 2-keto-D-gluconic acid:
! ~ a-pyranose B-pyranose
HOH2V0~ooli
~µOH OH H
HOH2v .. O-~ OH
H~COOH OH H
! a-furanose e-furanose
Tautomeric forms of 5-keto-D-gluconic acid:
Hv.O~ooH HOH2~µH
Oil H
§. a-furanose
COOH I
H-C-OH I
HO-C-H I
H-C-OH
' C=O I
CH 20H
l open chain form
HOH2v.O~H HOµCOOH
OH H
i B-furanose
The D-gluconate ion only exists in the open chain form.
59
Compound chemical shift (ppm)
c, c2 c3 c4 cs c6
D-gluconic acid open chain form 178;3 73.9 72.6 71.1 71.6 62.9
2-keto-D-gluconic acid
a-pyranose 174 .6 97.3 69.5 70 .1 69.4 64.44 6-f uranose 175.3 99.9 78.5 74.8 81.2 62.3 a-f uranose 174.3 104.2 83.0 76.0 62.5 61.5 a-pyranose a a 11.2b 72.4b 67.0b 64.36
5-keto-D-gluconic acid 6-furanose 175.7 79.3 76,6C 76 .sc 103.1 64.0 a-furanose 176.1 62.9 60.1d 76.9d 106.9 62.7 open chain form 178.1 a 72.4e 73.2e a 66.2
I
D-glyceric acid i
open chain form 176.6 75.5 63.1 I
table 3.4. Chemical shifts of D-gluconic-, 2- and 5-keto-D-gluconic- and D-glyceric acid. a: Peaks not assigned. b,c,d and e: Assignments may be interchanged.
To understand the stereochemistry and the stability of the two
keto acids it is nescessary to know the tautomeric equilibria.
From our spectrum we have calculated the following equilibrium
composition:
2-keto-D-gluconate in water
ratio of the average integrals of c3-c6 ~:i:~:l
ratio of the heights of c2 (method of Crawford)
Crawfords data (D20 as solvent)
5-keto-D-gluconate in water
ratio of the average integral of C and 6. 2., 3, 4 ratio of the heigths of c
5
Crawfords data (D2o as solvent)
69:23:4}:3}
76:20:4:traces
80:17:3:traces
6:5:7 70:12:18
79:14:?
79:10:11
60
Our data agree rather well with those of Crawford. We were not able to fully calculate the ratio of the tautomeric forms of
5-keto-D-gluconic acid according to the method of Crawford, because the chemical shift of c5 of the open chain form is
213.4 ppm (9), but unfortunately the spectrum is recorded only up to 206 ppm.
3.5. Iaotaohophoreaia
3.5.1. Introduotion
Isotachophoresis is a useful technique for the separation
of ionic compounds. The principles and theoretical backgrounds
of isotachophoresis have been described by Everaerts et al.
(11-13). The use of isotachophoresis for the analysis of the oxidation products of D-gluconic acid has been described by Dirkx (2). However at the conditions they have used, D-gluconic-,
L-guluronic and 2- and 5-keto-D-gluconic acid can not be separated. To achieve a good separation of these important components of our reaction samples, we have modified their method by lowering the pH of the electrolyte. Dirkx used an electrolyte system of pH = 6. At this pH all the above mentioned reaction
products are fully dissociated, so their average electric charge is identical. Also the shapes of the products are almost identical. Therefore the separation can only be caused by the minor variations in structure. These variations were obviously not big enough to cause sufficient differences in effective mobilities for a good separation under Dirkx's conditions. By lowering the
pH of the electrolyte system to 2.95, a value representing
about the average pKa of these acids, greater differences in the degree of dissociation are obtained. This led to a good separa
tion of the above mentioned sugar acids, and also to an improved separation of the other reaction products.
61
3.5.2. Ezperimental
The analyses were carried out with an apparatus manufac
tured by THE's department of Instrumental Analysis of professor Everaerts. A conductivity detector, as described by
Everaerts and Verheggen (14) was used. In table 3.5. the
apparatus characteristics and experimental conditions are
sununerized.
leading electrolyte
counter-ion
pH additive
terminator
counter-ion
pH
capillary current strength
injection volume
time for analysis
0.01 M Cl
B-alanine
2.95
0.2% hydroxy ethyl cellulose
0.05 M propionate sodium
7-8
teflon, 200x ~ 0.45 mm 80 µA
2 µl (after diluting 1:11)
16-17 minutes
table 3.5. Apparatus characteristics and ezperimental conditions of the isotachophoretic analysis
3.5.3. Typical results
Below some typical isotachopherograms of reaction samples of the catalytic oxidation of D-gluconic acid are given. TWo
signals are recorded: the electric resistance (R) of the
electrolyte passing the electrodes of the conductivity detector and the differentiated signal of the former (dR/dt). The
qualitative information of a zone is given by the level of its integr~l signal, while the quantitative information is given by
62
the distance between the two peaks in the differentiated
signal which correspond to the begin and end of the zone. In the
isotachopherograms the zone of .the leading electrolyte is
denoted by L and the zone of the terminating electrolyte by T.
dR dt
I 10 9 8 7 . I ~R
-- time
figure J.9. Isotachophero~ram of a sample of the oxidation of D-gluconic acid with a Pt/C catalyst
1: oxalic acid, 2: tartronic acid, J,4,5,8: not identified, 6: tartaric acid, ?: 2-keto-D-gZuconic acid, 9: formic acid, 10: D-gZucaric acid, 11: DgZyceric acid, 12: 5-keto-D-gluconic acid + Derythronic acid, lJ: glycolic acid, 14: L-guZuronic acid, 15: D-gZuconic acid
In figure 3.9. the isotachopherogram of a reaction sample
of the oxidation of D-gluconic acid with a Pt/C catalyst is
presented. The corresponding chromatogram is shown in figure
3.4. The product distribution was already discussed in section
3.2.3., but the identification of the peaks in this chromato
gram is, as in others, mainly based on isotachophoresis in
combination with 13c-NMR. The molar responses of all of the
63
identified oxidation products are, as opposed to the molar responses from the UV-signals of the liquid chromatograph,
equal within a variation of + 20%. Consequently an isotachopherogram gives a good fingerprint of the sample under investigation. Thus, the concentration of the not yet identified component corresponding to zone 8, is of the same order of magnitude of e.g. L-guluronic acid and must therefore be classified as a major byproduct. The less important byproducts corresponding to zones 3,4 and 5 are probably dicarboxylic
acids.
4
time
dR dt
R
figure 3.10. IBotachopherogram of a 8ampie of the oxidation of D-giuconic acid with a Pb/Pt/C cataiyBt
1: oxalic acid, 2: tartronic acid, 3: a-keto-D-gtucaric acid, 4: 2-keto-D-gluconic acid, 5: not identified, 6: formic acid, 7: D-gtucaric acid, 8: 5-keto-D-giuconic acid, 9: L-guturonic acid, 10: D-giuconic acid
In figure 3.10. the isotachopherogram of a reaction sample of the oxidation of D-gluconic acid with a Pb/Pt/C catalyst is presented. The corresponding chromatogram is given in figure
64
3.5. This isotachopherogram confirms that 2-keto-D-gluconic acid is the main oxidation product and that the byproducts are, compared to the oxidation with a Pt/C catalyst, present in low
concentrations. It confirms also that in this sample no glycolic
acid is present, as was already concluded from the ratiQ of the
UV- and the RI-signal of the peak of 2-keto-D-gluconic acid in
figure 3.5. In figure 3.11. the isotachopherogram is shown of the sample
used for the chromatogram of figure 3.6. and the 13c-NMR spectrum of figure 3.8. This confirms both the qualitative and quantita
tive results of 13c-NMR and illustrates that the interpretation of the chromatograms has to be carried out with care, as several components can not be separated.
1 11 1o9 e
4
dR dt
j
2 R 1
L
-- time
figure 3.11. Ieotachopherogram of a fraction collected from a reaction mixture of the oxidation of D-gtuconic acid with a Pb/Pt/C catalyst
1: oxalic acid, 2: tartronic acid, 3: tartaric acid 4: 2-keto-D-gZuconic acid, 5,6: not identified, 7: DgZyceric acid, 8: 5-keto-D-gZuconic acid, 9: Derythronic acid, 10: gZycoZia acid, 11: L-guZuronic acid, 12: D-gZuconia acid
J.6. A specific detection method for a.-keto carbozyZic acids
J.6.1. Introduction
0-phenylene diamine reacts with a.-keto carboxylic acids
to form 2-hydroxy quinoxalines.
o~c,,,oH
65
©("": I ------;> @(N'( + H20
NH2 ~c~
0 R ~
N R
o-phenylene a.-keto 2-hydroxy di amine carboxylic acid quinoxaline
This reaction is specific for a.-keto acids and has been used
to determine these acids in the presence of other keto carbo
xylic acids. Lanning and Cohen (15) have developed a specific
and quantitative spectrophotometric analysis of 2-keto-hexonic
acids based on this reaction. Moghimi et al. (16) have modified
this assay slightly and we have used this method after again
a small modification.
J.6.2. Ezperimentai
The reaction samples are diluted with water until the
(expected) concentration of 2-keto acid comes in the range of
25-250 µmol/l. To 2 ml of the diluted samples, contained in
thick-walled 5 ml test tubes, 1.5 ml of a freshly prepared
reagent solution (0.375 M hydrochloric acid containing 15 mg
of o-phenylene diamine per ml) is added. The closed tubes are
heated for 45 minutes at 100°C and allowed to cool (The reaction
'66
tak.es place during the heating period). With a double beam
spectrophotometer (Perkin Elmer type 124) the extinction of the
samples is recorded. A 2 ml volume of water to which 1.5 ml
of reagent is added and to which the same heat treatment is
applied serves as the blank reference.
3.6.3. TypicaZ resuZts.
Figure 3.12. shows the UV-spectrum of a reaction sample
of the oxidation of D-gluconic acid with a Pb/Pt/C catalyst,
to which the above detection method h~s been applied.
1.0 -------~
~ 2 ::I c: 0
.8
•t; .6
5 x ~
c: .g .4 (,)
.5 x "'
.2
300 400
wavelength (nm)
figure 3.12. UV-spectrum of a sampZe of the oxidation of D-gZuconic acid ~ith a Pb/Pt/C cataZyst, to ~hich the specific detection method has been appZied
In accordance with Lanning and Cohen (5) an absorption maximum
at 334 nm was found. In contrast with their results, however,
we did not find a constant ratio between the absorption at
334 nm and at 364 nm, neither in our product mixtures, nor in
67
our calibration samples.
The specificity of this reaction was found to be in agree
ment with the data of Lanning and Cohen. The contribution of
the byproducts to the total absorption is small. One should
keep in mind, however, that the method gives too high values
in the presence of other 2-keto-acids like a-keto-D-glucaric
acid and 2-keto-D-erythronic acid, which give comparable
absorption. Fortunately, the concentration of these products
is relatively low, and the method is therefore quite useful
to get a quick estimate of the 2-keto-D-gluconic acid concen
tration. We have used this method also to detect and estimate
the production of 2-keto-D-galactonic acid and 2-keto-D-arabi
nonic acid in the oxidation of D-galactose and D-arabinose,
respectively.
References
1. De Wilt, H.G.J., Ph.D. thesis, University of Technology,
Eindhoven, The Netherlands (1969)
2. Dirkx, J.M.H., Ph. D. thesis, University of Technology,
Eindhoven, The Netherlands (1977)
3. De Wilt, H.G.J., Kuster, B.F.M., Carbohydr. Res.~. 343
(1972) 4. Dirkx, J.M.H., Van der Baan, H.S., Van den Broek, J.M.A.J.J.,
Carbohyd. Res., 59, 6:3 (1977) 5. verhaar, L.A.Th., De Wilt, H.G.J., J. Chromatogr., !.!.1 168
(1969) 6. Dirkx, J.M.H., Verhaar, L.A.Th., Carbohydr. Res., 73, 287
( 1979) 1. Jandera, P., Churacek, J., J. Chromatogr., 86, 351 (1973)
8. Lee, K.S., Samuelson, Anal. Chim. Acta., 37, 359 (1967)
9. Crawford, T.C., Andrews, G.C., Faubl, tl., Chmurny, G.N.,
J. Am. Chem. Soc., 102, 2220 (1980)
10. sadtler Standard Carbon -13 NMR Spectra, Sadtler Research
Laboratories, Inc. (1976)
68
11. Everaerts, F.M., Ph.D. thesis, University of Technology,
Eindhoven, The Netherlands (1968)
12. Everaerts, F.M., Routs, R.J., J. Chromatogr., 58, 181 (1971)
13. Everaerts, F.M., Beckers, J.L., Verhe99en, Th. P.E.M.,
Isotachophoresis, J. of Chrom. Library, ~, Elsevier Sc.
Publ. Co. (1976)
14. Everaerts, F.M., Verhe9gen, Th. P.E.M., J. Chromato9r.,
11.1 193 (1972)
15. Lanning, M.C., Cohen, S.S., J. Biol. Chem., 189, 109 (1951)
16. Mo9himi, A., Tate, M.E., Oades, J.M., Soil Biol. Biochem.,
.!.Q., 283 ( 1978)
69
Chapter 4
Equipment and Experimental Methods
4.1. Introduction
The present investigations called for a reactor system in
which the temperature, pH and oxygen partial pressure can be
accurately controlled and easily changed from experiment to
experiment. It is also necessary that the catalyst can be
easily replaced. We have developed a stirred tank reactor, in
which the three phases - liquid substrate solution, gaseous oxygen or oxygen containing gas and solid catalyst - are well
mixed, meeting the above requirements.
In sections 4.3. and 4.4. the stirred tank reactor plus
its auxiliary equipment and its mode of operation are described.
The preparation and regeneration of the catalysts used shall
be discussed first.
4.2. The cataiysts
4.2.1. The piatinum on carbon cataiyst
The Pt/C catalysts are prepared according to Dirkx (1),
which is derived from the procedure of Zelinski! (2,3): The
active carbon (Norit PK 10 x 30 or Norit SX-2) is ground in a
mortar or a ball mill to a fine powder, from which the sieve-
70
fraction 50-105 µ is used. A solution of 10 g hexachloroplatinic
acid (H2PtC16 .6u2o) in 100 ml water is added to 72 g of the
sieved active carbon, and about 100 ml water is added to obtain
complete wetting of the carbon. During the adsorption of the
chloroplatinum complex on the active carbon, which takes place
at room temperature, nitrogen is bubbled through the suspension.
After 5 hours the adsorption equilibrium is reached, and the
suspension is cooled to 0°c. After adding 170 ml of 35% form
aldehyde solution, the platinum (IV) is reduced to Qlatinum
metal by addition of 90 ml 30% KOH solution over a period of
15 hours. The suspension is fi.ltered and the catalyst is washed
with distilled water until the filtrate is neutral. After
drying at 50°C at reduced pressure (about 10 2Pa) the catalyst
is ready for use.
The platinum content, which for this catalyst is about
5% by weight, is determined according to the method of Charlot
(4) and Ayres et al. (5,6): The platinum is dissolved in aqua
regia and converted to a complex with SnC12 followed by measu
ring the extinction of the solution of 403 nm.
Some platinum loss (10-20%) takes place during the pre
paration of the catalyst, probably caused by desorption of some
u 2PtC16 from the active carbon, at the start of the treatment.
This u 2PtC16 is then reduced in solution and not readsorbed.
The above procedure gives a catalyst with a reproducible acti
vity.
According to de Wilt (7) these catalysts have a platinum
dispersion of about 1.0. We did not determine the Pt-surface
by o2 or u 2 titration, as this technique, according to Dirkx
(2), does not give information on the metal surface used for
the oxidation reaction. De Wilt measured the Pt surface of a
number of Pt catalysts, and found large deviations (factor 2-3)
in activity for catalysts with almost the same Pt-surface. The
variation in activity/m2 Pt of catalysts with different Pt
contents was even much higher (factor 15-20)
Besides the home made Pt/C catalyst we have also
71
used a commercial 5% Pt/C catalyst from Degussa (type F 196
RA/W). This catalyst is supplied wet and used as such, because
drying causes a loss of activity. The quantity of catalyst is
always calculated on a dry basis.
After use the catalyst has to be regenerated for economic
reasons. This succeeded fairly well by washing it with about
2 1 hot water (90°C) per 10 gram of catalyst. If the catalyst
was used repeatedly, this procedure did not result in a complete
regeneration. The source of this irreversible deactivation is
not completely clear. In any way, it was not caused by Pt-loss
during prolonged use. A better, although still incomplete,
regeneration was obtained by washing the catalyst with 0.1 M HCl.
4.2.2. The Zead pZatinum on carbon catalyst
As a basis for a lead platinum on carbon (Pb/Pt/Cl catalyst
either a home made or a commercial Pt/C catalyst was used.
A solution containing the required amount of lead (II)
acetate in just enough water to obtain complete wetting is added to the Pt/C catalyst. To completely fill the pores of the catalyst with liquid, the suspension is heated until a small
part of the water is evaporated. The suspension is allowed to
cool and after 18 hours a solution containing 1.8 times the
amount of sodium hydroxide or trisodium phosphate, necessary to precipitate all the lead, is added under vigorous agitation.
After 18 hours the suspension is filtered and the catalyst is
washed with water until the filtrate is neutral. Initially the
catalyst was dried at 50°C at reduced pressure, but later the wet catalyst was used.
The lead content of the Pb(OH) 2/Pt/C or Pb3 (Po) 4) 2/Pt/C ca
talyst is according to Martens ( 8) determined gravimetrically as
, lead (II) chromate after dissolving the lead in 2 M .. nitric acid.
A used Pb/Pt/C catalyst is also regenerated by washing it
with hot water. This method is not succesful for a heavily deactivated catalyst, as discussed in more detail in chapter 6.
72
:
----€)
---@
figure 4.1. The stirred tank reactor
3, 21 f'langes
S gasket rings (teflon)
7 stirrer shaft
9 turbine stirrer, 12 blades Rushton type
10 baffle
11 0-ring
12 stud
15 : bottom plate
19 inner reactor wall (pyrex glass) diameter 110 mm/height 200 mm
20 outer reactor wall (pyre~ glass) diameter 130 mm/height 200 mm
73
11
13
figure 4.8. Flow sheet of the reactor and auxiliary equipment
List of symbols:
1: reactor
8: turbine-stirrer
J: polarographic oxygen analyser
4: thermostatbath
5: drain
e: sampling tubing
7: KOH burette
8: substrate supply vessel
9: condensor
10: gas circulation pump
11: bubble indicator
18: oxygen supply vessel
lJ: gas burette
14: contact manometer
74
4.3. Equipment
A schematic presentation of the stirred tank reactor is
given in figure 4.1. Unless otherwise mentioned, all parts are
made of stairless steel type AISI 321. A general flow sheet of
the reactor and auxiliary equipment is shown in figure 4.2.
The reaction temperature is regulated by circulating water
from a waterbath through the double-wall of the reactor. The
variation of the temperature in the reactor was + 0.5°C.
The pH of the reaction mixture is measured by a combined
glass-reference electrode (Radiometer GK 2402 B or C) attached
to a pH-meter/controller (Radiometer TTTld). Before each ex
periment the electrode is equilibrated at the operating temperature in a buffer solution (Merck Titrisol) of the experimental
pH for at least 3 hours. The pH is controlled by automatic
titration with .SN KOH. The alkali consumption is recorded by
measuring the level in the KOH burette.
The total system pressure is controlled at 0,1 MPa by
means of a contact manometer. The oxygen consumption is de
termined as a function of time by means of a gas burette system. In order to minimize the effect of accumulation of inert gases
from impurities in the oxygen or from the reaction (co2), the
oxygen supply vessel is included in the closed gas circulation
system. The oxygen concentration in the liquid phase is measured
by an oxygen-electrode (Beckman 39553 Oxygen Sensor) attached
to a polarographic oxygen analyzer (Beckman Fieldlab Oxygen
Analyzer) . The electrode is radially mounted in the reactor
wall at the level of the stirrer blades.
75
4.4. ExpePimentat methods
An experiment is prepared and started as follows: The
desired amount of catalyst, suspended in 400 ml of pure water,
is introduced into the stirred batch reactor. The concentrated
substrate solution, having the operating pH, is filled into its
supply vessel. Both reactor and supply vessel are then heated
to the reaction temperature. The reaction is started according
to one of the following two procedures:
StaPting pPoaeduPe A:
The catalyst suspension and the concentrated substrate
solution have been heated in the oxidation gas atmosphere, and
the experiment is started by introducing the concentrated sub
strate solution into the reactor.
StaPting pPoaeduPe A:
The catalyst suspension and .the concentrated substrate
solution have been heated in a nitrogen atmosphere. After intro
ducing the concentrated substrate solution into the reactor, the
suspension is kept in a nitrogen atmosphere for 10 minutes.
Thereafter the stirrer and the nitrogen flow are stopped. After
the gas circulation system has been quickly evacuated and refil
led with oxygen, the experiment is started by switching on
the stirrer.
During the run samples (5 ml) are taken with a syringe.
After sampling the catalyst is filtered off, and the clear
samples are stored in a refrigerator until analysis. The measu
red concentrations are corrected for the dilution with KOH
(and sampling).
76
4.5. Maas tPanafer in the atiPred tank reactor
In the three phase system gas-liquid-solid the following
mass transfer steps can influence the reaction rate:
1. Oxygen transfer from the gas- to the liquid phase
2. Diffusion of reactants from the bulk of the liquid phase
to the surface of the catalyst
3. Pore diffusion of the reactants
In case of the Pt/C catalyst the stirrer speed could easily be
chosen high enough to prevent mass transfer limitation at the
interface or in the liquid phase, while the particle size was
small enough to prevent pore diffusion effects. On the other
hand, most of the oxidations with a Pb/Pt/C catalyst (chapter
6 and 7) were carried out under conditions where the oxygen
transfer from the gas- to the liquid phase was limiting. This
was checked by measuring the oxygen concentration in the liquid
phase. A low oxygen concentration in the liquid phase was
necessary to prevent a fast deactivation of the lead containing
catalyst (section 7.6).
References
1. Dirkx, J.M.H., Ph.D. thesis, University of Technology,
Eindhoven, The Netherlands (1977) 2. Zelinskii, N.D., Turowa-Pollak, M.B., Ber., 58, 1298 (1925)
3. Liberman, A.L., Schnabel, K.H., Vasina, T.V., Kazanskki,
B.A., Kinet. Katal., ~. 446 (1961) 4. Charlot, C., Les methods de la chimique analitique, Masson,
Paris (1961) 5. Ayres, C.H., Meyer, A.S., Anal. Chem., .!1_, 299 (1951) 6. Ayres, C.H., Meyer, A.S., J. Am. Chem. Soc.,'!.]_, 2671 (1955)
7. De Wilt, H.G.J., Ph. D. thesis, University of Technology,
Eindhoven, The Netherlands (1969) 8. Martens, W.R.M., M.Sc. thesis, University of Technology,
Eindhoven, The Netherlands (1983)
77
Chapter 5
Selective Catalytic Production of D-Glucaric
Acid
5.1. Introduction
On basis of the present day state of the art of the
platinum catalyzed oxidation of D-gluconic acid to D-glucaric
acid, we will discuss some potential possibilities to improve
the selectivity of this reaction. some explorative experiments
are presented in sections 5.2.-5.6.
In 1953 Heyns and co-workers initiated a very extensive
research program on the selective oxidation of carbohydrates
with oxygen by means of noble metal catalysis in alkaline
solution, summarized in three comprehensive reviews (1-3).
The mechanism of the catalytic oxidation falls into two
extreme cases (4):
(1) A pure auto-oxidation can be postulated wherein the adsorbed
oxygen is activated by the platinum and a peroxide inter
mediate is formed, which decomposes to an aldehyde and
hydrogen peroxide.
RCH20H + Pt-02 + R-THOH + Pt
OOH
78
R-CHOH + R-CHO + H2o2 I OOH
Another possibility is the activation of the adsorbed
substrate
o2 + Pt-RCH20H + Pt-RCHOH I OOH
Pt-~CHOH + Pt-RCHO + H202 OOH
The hydrogen peroxide produced is rapidly decomposed by
the catalyst. Between these extremes intermediate path
ways, e.g. activation of both substrate and oxygen are
possible.
(2) A pure dehydrogenation can be depicted in which the platinum
abstracts hydrogen from the chemisorbed substrate alcohol.
In a second step the chemisorbed hydrogen is removed from
the metal by reaction with oxygen.
Pt + Pt-RCH20H + RCHO + 2 Pt-H
2 Pt-H + !02 + 2PT + H20
After extensive discussion of all possibilities Heyns
et al (3) concluded that most results of the various oxidation
reactions studied are in favour of a pure dehydrogenation
mechanism, especially for the reactions that take place in the
absence of oxygen. This is in agreement with the observations
of De Wit et al. (5). They have found that in alkaline medium
under ambient conditions in the presence of noble metals, aldoses
can be converted to their aldonic acids with concomitant pro-
79
duction of hydrogen gas. They also showed that this dehydrogena
tion is accomplished by ionization of the hexose followed by
hydride abstraction by the catalyst.
However, in the presence of oxygen, an alternative mechanism,
in which oxygen plays a role in the first reaction step, can-
not be excluded completely. Perhaps, dependent on the reaction
conditions and the kind of substrate, different mechanisms are
operative.
Heyns et al. (3) have postulated selectivity rules for the
catalytic oxidation of carbohydrates with oxygen by means of
platinum catalysis in alkaline solution. All these can be de
rived from a dehydrogenation mechanism. Both electronic and
steric effect determine which group or groups in a carbohydrate
molecule will be oxidized preferentially.
Due to electronic effects the oxidation rate decreases
in the series:
hemiacetal > primary hydroxyl > secondary hydroxyl
The steric effects can be understood by the assumption
that the platinum has to attack the hydrogen bonded to the
c-atom of th.e -CHOH- group to accomplish the dehydrogenation. This is evidenced by the observation that in all ring systems
investigated the preferentially oxidized ;:-cHOH group has the
hydrogen (on the c-atom) most exposed.
Application of these electronic- and steric effects to
the platinum catalyzed oxidation of D-gluconic acid with oxygen
in neutral or alkaline medium leads to the following considera
tions:
In neutral or alkaline medium D-gluconic acid is completely
dissociated (pKa = 3.6 at 25°C). The gluconate anion occurs
only in the open chain form (section 3.4.):
80
0 ~ c-o-
l H-C-OH
I HO-C-H
I H-C-OH
I H-C-OH
I CH 20H
D-gluconate anion
Due to electronic effects the primary hydroxyl group on
c6
will be oxidized with a higher reaction rate than the
secondary hydroxyl groups. To determine the steric hindrance
one has to examine the time averaged positions of the R1- and
R2 group of the R1 R2CHOH group to be oxidized. In the D-gluconate
anion the hydrogen bonded to the C-atom of the R1R2CHOH group
is shielded more in its approach to and contact with platinum.
According to this steric effect the primary hydroxyl group will
be oxidized with a higher reaction rate than the secondary
hydroxyl groups.
From the latter set of CHOH groups the secondary hydroxyl group
on c2 and c5 are expected to be more exposed than those on
c3 and c4 . Besides this steric effect, also the difference in
adjacent groups, e.g. COO- for c2
compared to CH20H for c5
,
will influence the reaction rate (electronic effect) . Also the
way of adsorption of the non-reacting part of the molecule on
the catalyst surface can accelerate or retard the oxidation of
a giveD CHOH group. Therefore it is rather difficult to pre
dict the resulting reaction rates. Consequently the following
series of (decreasing) oxidation selectivities must be viewed
as being a rough approximation only:
c6 primary hydroxyl > c5 and c 2 secondary hydroxyls >
c3 and c4 secondary hydroxyls
To improve the selectivity for D-glucaric acid, the oxi
dation must be accelerated at c6
or retarded at especially
81
c5
and c2
. We have tried to achieve the former by the use of
catalysts other than noble metals and by complexing part of the
molecule with cations (section 5.2.) and the latter by complex
ing the gluconate anion with borate (section 5.3.) and by con
verting the gluconate anion (partly) into D-glucono-o-lactone
(section 5.4.) .
5.2. Explo~ato~y expe~iments o f the oxidation of D-glueonio
acid with Cu(II) and Co (II) oatalysts
Unless otherwise stated, a standard set of reaction con
ditions as given in table 5.1., is used for the catalytic
oxidation of D-gluconic acid.
pH T
oc
8 55
[GOZ]O % 02 in the [cat] starting
mmol/1 oxidation gas g/1 procedure
200 100 40 B
tab le 5 .1. Standa~d ~eae ti on condi tio n s fo~ the oataly tio ox idation of D-g luco nie acid
A study of the literature with respect to an alternative
catalyst for the oxidation of D-gluconic acid to D-glucaric
acid in 1980 (6) did not yield much useful information. The most
promising leads were those articles (7-10) that reported on the
oxidation with oxyge n of both prima r y - a nd secondary alcohol
groups to aldehyde-, keto- and carboxylic acid groups with the
aid of copper and cobalt complexes. Therefore we have carried
out some explorative experiments with Cu(II)- and Co(II)- com
plexes as catalyst for the oxidation of both D-glucose and
82
and D-gluconic acid. The experiments were conducted at
70°C at pH 7-10 with a substrate concentrat1on of
200 mmol/l and a catalyst concentration of about 5% by weight
relative to the substrate. The following compounds and complexes
were tested:
Cu(II) and Co(II) sulphate, -glycinate, -glutaminate, -p-amino
benzoate, -acetyl acetonate, -hystidinate and -1,2-dimethyl-
4-nitro-imidazolate.
The complexes of both metal ions with glycinate and acetyl
acetonate were the most active catalysts. They catalyzed,
however, the degradation of D-glucose at a pH higher than 7.5,
and the degradation of D-gluconic acid at a pH higher than 9.5.
Within the pH range of 7-9 Cu(II)-glycinate accelerates the
degradation of D-glucose by a factor 3 compared to the noncatalytic oxidative degradation.
No L-guluronic acid or D-glucaric acid was found in the
reaction mixture. Only chain cleavage products like formic
acid., glycolic acid, glycerinic acid and oxalic acid, and not
yet identified products were formed. None of these products
were produced selectively enough to make these catalyst
industrially attractive.
5. 3. Pr>oduet distr>ibution during the oxidatio_n of D-glueonie
aeid with a Pt/C eatalyst
The product distribution of the platinum catalyzed oxi
dation of D-gluconic acid under standard conditions, applying
a standard 5% Pt/C catalyst from Degussa (type F 1961 RA/W) is
shown in figure 5.1. as a function of time for the main compo
nents, and in figure 5.2. for the identified side- and conse
cutive products. These figures illustrate that D-glucaric acid
is the main product and that L-guluronic acid is its precursor.
Besides oxidation on c6 also some oxidation on c2 and c5 takes
place, re·sul ting in the formation of 2- and 5-keto-D-gluconic
s ~ 150 E
0 , 1,5 time (ks)
o gluconic acid
A guluronic acid
CJ glucaric acid
83
figure 5.1. Main product distribution in the oxidation of D-gZuconic acid with a standard Pt/C cataZyst under standard conditions
.2 10
i ~ . 0 ...
0 ·• 1 Ui time (ks)
<> 5-lteto-O-gluconic acid
4 2-keto-O-gluconic acid
D oxalic acid
o tartronic acid
v tartaric acid
figure 5.2. By-product distribution in the oxidation of D-gZuconic aci¢ with a standard Pt/C cataZyst under standard conditions
84
acid, respectively (figure 5.2.).
In these figures the curves for 2- and 5-keto-D-gluconic
acid are partly dotted to indicate that their concentrations
are, at those times, not considered reliable anymore. This is
due to the formation of the chain cleavage products glycolic
acid and 0-erythronic acid which elute in our analytical system
at the same time as 2- and 5-keto-D-gluconic acid,· respectively
(see figure 3.4.). The concentration of the two keto-acids are
calculated, however, as if the two corresponding peaks in the
chromatograms represented only keto acid. However, from our
isotachophoretic analyses (see section 3.5.3.) can be conclu
ded that only after the two keto acids have reached their
maximum concentration the above two chain cleavage products
are formed in significant amounts. This agrees with the assump
tion that glycolic acid and D-erythronic acid are the chain cleavage products from 5- and 2-keto-D-gluconic acid, respec
tively (see section 7.6.). This makes the concentration of the
two keto acids reasonably reliable up to their maximum.
From the shape of the curves of the chain cleavage products
oxalic acid, tartronic acid and tartaric acid it can be con
cluded that D-gluconic acid is not their precursor, but possibly
L-guluronic acid, 5-keto-D-gluconic acid or 2-keto-D-gluconic
acid.
The difference in selectivity for oxidation at c6 , c5 and c2 is best illustrated by figure 5.3. The conversion and
selectivities used are defined as follows:
conversion
[C ] - [GOZ] 6total O [c J 6total 0
(5.1.)
selectivity c6 [GLZ] + [GAZ] (5.2.) [c6
) - [GOZ] total 0
85
selectivity c5 [5 KGOZ]
(5.3.) [C ] - [GOZ] 6total 0
selectivity c2 [2KGOZ]
(5.4.) [C ] - [GOZ] 6total 0
In these definitions we use the total concentration of material
present at time t = 0, expressed in c6 units ([c6totalJ 0), instead of the D-gluconic acid concentration at time t = O.
This is done, because at the time that we indicate with t = O,
under the conditions of starting procedure B, already some
D-gluconic acid is converted.
·• --------·- .. ~ . . 2 "-----...____----------' -
0 ·2 .4 .6 .. conversion i- i
o selectivity c6
'1 selectivity c5
o selectivity c2
figuPe 5.J. Seleativities c6 , C5 and C2 fop the
oxidation of D-gZuaonia aaid ~ith a stan
daPd Pt/C aatalyst undeP standaPd aonditions
In figure 5.3. only the reliable data on the selectivities
c5
and -c2 are taken into account. This figure demonstrates that
the order of decreasing selectivity is: selectivity c6 > selec
tivity c5 > selectivity c2 . This is in agreement with our
86
considerations in respect to electronic- and steric effects
discussed in section S.1. That the. (integral) selectivity
CS and -c2 decreases as a function of the conversion is due
to the oxidative cleavage of S- and 2-keto-D-gluconic acid,
respectively. Extrapolation of the selectivity curves to
conversion = 0 gives the following results:
selectivity c6 ~ O.S6
selectivity CS ~ 0.31
selectivity c2 ~ 0.12
This demonstrates that with a Pt/C catalyst D-gluconic acid
is mainly oxidized at c6 , CS and c2 .
5.4. Oxidation of D-gluconic acid in the presence of borate
A possible method to improve the selectivity of the oxi
dation of D-gluconic acid to D-glucaric acid involves the use
of protective groups. In the introduction (chapter 1) we have
already discussed the use protective groups is economically
not very attractive. This is true in so far as the introduction
and subsequent removal of the protective groups is not very
selective, difficult or slow. If, however, as for borate, the
above two steps are very fast, and would result in a high selec
tivity, some of these drawbacks are obviated. For the produc
tion of sequestering agents for laundering, it would not be
necessary to remove the borate from the product mixture.
If required for other purpose, however, the use of borate
immobilized on the catalyst will possibly offer a potential
alternative. However, before trying to find an answer to all
these questions, we first have carried out some explorative
experiments, to find out wether the addition of boLate to the
reaction medium has really a positive influence on the
selectivity for D-glucaric acid.
87
The oxidation of the secondary hydroxyl groups in the
D-gluconate anion probably follows a dehydrogenation mechanism
which includes 2 steps:
(a) The dissociation of the hydroxyl group.
(b) The hydride transfer to the catalyst.
A protective groups thus can have two functions:
(a) To prevent the dissociation of the hydroxyl group, and
thus to retard the transfer of the hydride ion.
(b) To hinder sterically the transfer of the hydride ion.
The formation of borate gluconate complexes has received
hardly any attention in the literature. Therefore we have
carried out some experiments in which gluconate solutions were
mixed with borate solutions of the same pH, whereafter the pH
was measured. In table 5.2. the results are summarized.
pH Borate/gluconate L\pH ratio
8 0.5 -1. 77
1 -1.55
2 -1.26
9 0.5 -1. 72
1 -1. 24
2 -0.85
10 0.5 -.1 .67
1 -0.96
2 -o. 72
11 0.5 -0.62
1 -0.53
2 -0.23
table 5.2. Change of the pH when a gluconate and a borate solution of the same pH are mixed
88
From this table one sees that the pH changes are rather
great. This suggest, according to Boeseken (11), that besides
a mono complex, spirane type of complexes could be formed:
mono complex spirane type complex
Recent results of van Duin et al. (12) indicate that indeed,
besides mono esters, a spirane type of complex is formed in
the analogous system glucarate-borate at molar ratio's of
borate/glucarate about 0.5 and pH above 9.
It is surprising that at pH 11 there is a pH effect when
gluconate solutions are mixed with borate solutions. At this
pH boric acid (pKa ~ 9) and D-gluconic acid (pKa = 3.6) are
completely dissociated and according to the reaction
B- + n GOZ- -----"'- B (GOZ) (n+ 1 ) - + n
the pH change cannot result from borate ester formation.
According to Weigel (13) the geometry and the rig~dity
of the molecule determine which combination of oxygen atoms of
the hydroxyl groups can approach the borate ion close enough, i.e. within a distance of 0.24 nm, to play a role in the complex
formation. For an acyclic compound like the gluconate anion, especially the oxygen atoms of a trans (Fischer projection)
vicinal diol can, in an eclipsed conformation of the molecule,
approach close enough for complex formation. This agrees with
van Duin's work (see above) which indicates that mainly 2,3
and/or 3,4 borate esters are formed with glucarate. Possibly
corresponding gluconate borate esters can be expected.
89
A home-prepared 5% Pt/C catalyst was used at pH's 8,9
and 10 with borate/gluconate ratio's of O, 1 and 2. The other
reaction conditions were standard. Figures S.4.-5.6. show that
the addition of borate to the substrate solution results in
a large decrease of the reaction rate with the decrease being
greater the more borate is added. This suggest the oxidation
rates of the borate-gluconate complexes to be lower than that
of the free gluconate. This is substantiated by the observations
that, although the oxidation rate of the free gluconate increases
with increasing pH, this rate decreases with increasing pH for
experiments with borate added and that the extent of complex
ation increases in this range with increasing pH (van Duin
et al. (12)). There is, however, one exception to this genera
lized statement, viz. the experiment at pH 9 and a borate/glu
conate ratio of 1 (figure S.S.). For this experiment the reac
tion rate is greater than for the corresponding experiment
at pH 8.
For the conversion and selectivity for these and subsequent
experiments in this chapter we have used other definitions than
before. These experiments are intended to improve the selec
tivity for D-glucaric acid and thus we use as selectivity the
one for D-glucaric acid. As L-guluronic acid is an intermediate
product, that still can be converted to the desired product,
it can for selectivity purposes be considered as being uncon
verted starting material. Consequently we have adjusted our
definitions for conversion and selectivity for D-glucaric acid
as follows:
conversion GAZ [C6tota1lo - [GOZ] -[GLZ]
[C6tota1lo
(S.S.)
90
pH 8 o (borate]/[glucooate] = 0
'ii 6 [borate)/(gluconate]
~ 10
• <> [borate]/[glucooate] = 2
N 0 Cl
40 80 time I k$)
120
figure 5.4. D-gZuaonia aaid aonaentration (logarithmia saale) as a function of 'time for
.§ 'a;
I N 0 C1
pH = 8 with the borate/gluaonate ratio as parameter
101 0 40 80 12()
time 1ks1
pf! 9 o[borato)/[gluconate] o
"[borate]/[gluconate]
<>[borate] I [gluconate]
= 1
figure 5.5. D-gluaonia acid concentration (logarithmic saale) as a funation of time for pH = 9 with the borate/gluconate ratio as parameter
time I ks)
pH 10 o (boratel/[gluconate] = O
t>[borate]/[gluconate] = l
o [borate) /[gluconate}
figure 5.6. D-gluconic aaid concentration (logarithmic saale) as a function of time for pH = 10 with the borate/gZuconate ratio as parameter
91
[GAZ] selectivity GAZ = [CGtotalJO - [GOZJ - [GLZ] (5.6.)
The chromatograms of the reaction samples of ~hese
experiments were influenced by the addition of borate. The glu
conic acid concentrations are at least initially, overestimated
by about 10% at the borate/gluconate ratio 1 and ~Y about 15%
at the borate/gluconate ratio 2. Therefore the calculated initial
selectivities and conversions are not very rialiable. This must
be considered in the interpretation of the figures 5.7.-5.9.
These figures show that at pH 8 the selectivity for D-glucaric
acid indeed has improved by the addition of borate to the
D-gluconic acid solution, but that it remained constant or
got worse at pH 9 and 10.
It will be clear that first more detailed insight is necessary
in the borate gluconate species present under the conditions
of the above experiments in order to be able to give a plausible
explanation for the observed differences in rates and selec
tivities. The highest selectivity obtained with borate at
pH 8 and a conversion of 0.7 is hardly higher than that found
at pH 9 and 10 without borate.
As the reaction rates for the latter are higher by a factor
10 or more, it can be concluded from these experiments that,
within the ranges examined, the addition of borate to the
D-gluconic acid solution does not result in an industrial
attractive process.
92
pH 8 O [borate]/[9luconate] 0
I .e A [borate]/[gluconate)
<> [borate]/[gluconate] • 2 N < C).6
.2
0 .2
figure 5.?.
,, ·& .9 conversion GAZ 1 - 1
SeZectivity for D-gZucaric acid oxidation of D-gZuconic acid at with the borate/gZuaonate ratio meter
f qr the pH = 8 as para-
pH 9 o [borate]/[gluconate)
"[borate]/[gluconate)
0
I .e <> [borate]/[gluconate) • 2
N < <!).6
. 2
~ ·~~· __..... ...
o+--..,.~-.---..~-.-~~-.--~~~~,----+
0 .2 .. ·8 .&
conversion GAZ 1 - 1
figure 5.8. Selectivity for D-glucaric acid for the oxidation of D-gluconic acid at pH = 9 with the borate/gluaonate ratio as para-
I .e
N .< C).6
meter
~ y ,,,_'·~
-~ . . . ...... I a
0 ,.2 .4 ·O .9 conversion GAZ ; - 1
pH 10 o [boratel/[gluconate] = 0
A {boratel/[gluconatel = 1
<> [borate]/[gluconate] = 2
figure 5.9. SeZectivity for D-glucaric acid for the oxidation of D-gluconic acid at pH = 10 with the borate/gZuconate ratio as parameter
5.5. Oxidation of D-gluconic acid, paPtly in the foPm of the
6-lactone
93
Another alternative to improve the selectivity for oglucaric acid could possibly be the transformation of the
D-gluconate anion into the D-glucono-6-lactone. On the analogy of methyl-a-D-glucoside (14) also D-glucono-o-l~cton~
could possibly be oxidized at c6 with a high selectivity.
HO
HO
H
Pt/C -->' 90%
methyl-a-D-glucoside
H
H
Pt/C
0 ~
D-glucono-6-lactone
H
ref ( 14)
methyl-a-D-glucuronide
H
HO
H
D-glucaro-6-lactone
! other lactones of D-glucaric
acid
Methyl-a-D-glucoside is oxidized at the c6 position
with a selectivity of 90% (14), because the possible side
reactions are less favourable, because all the other hydrogens that could be abstracted are either protected by acetal
formation, or in the for abstraction less favourable
94
axial position. The same is more or less true for the o-lactone
of D-gluconic acid. Due to the double bond between the c and o atoms of the carboxyl group this compound does not possess a
perfect chair form, but is in the vicinity of this group some
what more flattened. Nevertheless, also in this conformation
the hydrogens on c2-c5 are in a, for abstraction, less
favourable position.
In aqueous medium the following equilibrium exists:
0 II
H-~--:j TOOH coo -I
+ 820 H-C-OH
820 H-C..,.OH
I I HO-C-H 0 HO-C-H; HO-C-H + 820
H-f~ - 820 I -820 I e-cr-oe H-C-OH
I H-C H-C-OH e-1-oe I I
CH20H CH20H CH20H
D-glucono-o- D-gluconic D-gluconate lac tone acid anion
The relatively minor quantity of the y-lactone has been
kept out of the consideration for. simplicity reasons.
The c-lactone can hydrolyze to the free acid, which in its
turn can dissociate to the anion. The pKa of D-gluconic acid
+
at 25°C is about 3.6, so that at pH> 5 gluconic acid is largely
present in the form of the D-gluconate anion. At lower pH,
however, also the other species are present in more or less
significant amounts. After some time an equilibrium will be
established. According to Ansems (15) at pH 4 about 6% of the
total amount of the D-gluconic acid species will be present
in the form of the o-lactone. For pH 3 this figure is about
17%. This illustrates that even at a low pH where most of the
gluconic acid is not dissociated the amount of lactone is
still relatively low. This demonstrates that no big improve-
ments of the selectivity due to the presence of the lactone
are to be expected. Nevertheless we have carried out some
experiments to find out if at these pH's there is any
improvement in selectivity at all. If so, it would be worth
while to change the reaction medium to a less aqueous, or
non-aqueous composition in order to shift the equilibrium
further in the direction of the lactone. The experiments have been carried out with a home made
95
5% Pt/C catalyst. The only difference with the standard operating
procedure is the use of D-glucono-o-lactone instead of sodium
D-gluconate. This was done to approach the equilibrium compo
sition of the gluconic acid species from the lactone side in
order to maximize the presence of the o-lactone. Initially
four experiments were carried out at pH= 8, 7, 6 and 5, while the other conditions were standard. Figure 5.10. shows
::::: 0 E ' E '°
N 0 Cl
10 20 time (ks)
30 40
T • ss•c o pH S
t. pH 7
0 pH 6
o pH 5
figure 5.10. D-gluconic acid concentration (logarithmic scale) as a function of time with the pH as parameter
that the decrease of the oxidation rate at decreasing pH, which
was observed by Dirkx (16) for the pH range 11-8, is continued
in the pH range 8-5. As the rate determining step in the oxi
dation is not known with certainty the decrease in reaction
rate with decreasing pH cannot be explained as yet. Figure 5.11.
98
5.6. Addition of Pb(II) to the o~idation formulation
According to the patent literature (17), the use of a
Pt/C catalyst modified with Pb(OHl 2 for the oxidation of
D-glucose in non-aqueous media results in a high yield for
D-glucono-o-lactone. We have tested this modified catalyst
for the oxidation of D-gluconic acid in aqueous medium at a
pH of 8 and a temperature of 55°C. This, however, resulted
rather surprisingly in the formation of 2-keto-D-gluconic acid.
As this compound is of potential industrial interest, we de
cided to study its manufacture in more detail. The following
chapter of this thesis will be devoted to this study.
99
References
1. Heyns, K., Paulsen, H~, Angew. Chem., 69, 600 (1957)
2. Heyns, K., Paulsen, H., Adv. Carbohyd. Chem., 12 1 169 (1962)
3. Heyns, K., Paulsen, H., Ruediger, G., Weyer, J., Fortschr.
Chem. Forsch., .!...!. 1 285 (1969)
4. Rottenberg, M., Turkauf, M., Helv. Chim. Acta, 42, 226 (1959)
5. De Wit, G., De Vlieger, J.J., Kock-van Dalen, A.C., Kieboom,
A.P.G., van Bekkum, H., Tetrah. Lett.,~, 1327 (1978)
6. Schiffelers, F.X.M.G., M. Sc. thesis, University of
Technology, Eindhoven, The Netherlands (1981)
7. Tsuji, J., Tahayamagi, H., J. Arn. Chem. Soc., 96, 7349 (1974)
8. Tsuji, J., Tahayamagi, H., Sakai, I., Tetrah. Lett., 11. 1
1245 (1975)
9. Munakata, M., Nishibayashi, s., Sakamoto, H., J. Chem. Soc.
Chem. Comm., .11_, 829 (1980)
10. Nigh, W.G., Oxidation in Organic Chemistry, Part B, p.35,
(ed.) Trahanovski, w.s., Academic Press, New York (1973)
11. Boeseken, J., Adv. Carbohydr. Chem., ! 1 189 (1949)
12. van Duin, M., Kieboom, A.P.G., Van Bekkum, H., unpublished
results 13. Weigel, H., Adv. Carbohydr. Chem., ..l§_, 61 (1963) 14. Kremers, J.C.M., M. Sci. thesis, University of Technology,
Eindhoven, The Netherlands (i984) 15. Ansems, A.M.M., Internal Report, University of Technology,
Eindhoven, The Netherlands (1980) 16. Dirkx, J.M.H., Ph. D. thesis, University of Technology,
Eindhoven, The Netherlands (1977)
17. Nishikido, J., Tamura, N., Fukuoka, Y., Fuji, s., Ger.
Offen!. 2,936,652 (1980)
101
Chapter 6
Characteristics and Scope of the Pb/Pt/C Catalyst
in the Oxidation of Carbohydrates and their
monocarboxylic acids.
6~1. IntPoduation
The only literature data available on the oxidation of
carbohydrates with Pb/Pt/C catalyst is the patent (1) claiming
the selective oxidation of D-glucose to D-glucono-o-lactone in
non-aqueous media. Another patent (2), deals with the catalytic
oxidation of a-hydroxy-arylacetatic acids to arylglyoxylic acids
with molecular oxygen in aqueous alkaline medium. At this
process, however, yielding 2-keto-carboxylic acids, there is
no selectivity problem, because the substrate contains only
one oxidizable hydroxyl group.
In these patents no mention is made about the function of
lead in the catalysts. In section 6.3. we describe our investi
gations in this respect. The influence of the Pb/Pt ratio is
discussed in section 6.4. To determine the scope of our cata
lytic system we have investigated metal ions other than Pb2+
(section 6.5.) and oxidized substrates other than D-gluconic
acid (section 6.6.). The deactivation of the Pb/Pt/C catalyst
is discussed in section 6.7.
102
6.2. Experimental
Unless otherwise stated, a standard set of reaction condi
tions as given in table 6.1. is used for the catalytic oxidation
of D-gluconic acid and the other substrates.
pH T
•c
8 55
[substrateJ 0 mmol/l
200
~ o2 in
oxidation 9as
100
catalyst [cat)
9/l
40
Pb/Pt ratio I raol-basis
0.5
table 6.1. Standard reaction conditions for the catalytic oxidation of D-gluconic acid and other substrates
The rate of the non-catalytic oxidation of D-gluconic acid
is negligible under the above mentioned conditions (7). Unless
stated otherwise, starting procedure B (see section 4.4.) is
applied, and as basis for the standard Pb/Pt/C catalyst the 5%
Pt/C type F 196 RA/W from Degussa is used. The experiments are
carried out in reactors of different sizes, applying different
stirrer speeds (320-1500 rpm) to assure that oxygen transfer
limitation from the gas to the liquid phase will occur, keeping
the oxygen concentration in the solution low. This prevents rapid
deactivation of the catalyst, as is discussed in section 6.7.
6.3. The effect of lead on the Pt-catalyzed oxidation of
D-gluconic acid
6.3.1. Addition of a heterogeneous lead compound to the Pt/C
catalyst
Figure 6.1. and 6.2. give the concentrations of the main
components in the reaction mixture of the oxidation of D-glu-
200
~l!IO E E
c .g 100
I 8 !IO
0
0 ·5 1 1.6 time (ks)
o gluconic acid
A guluronic acid
a glucaric aciC
103
figure 6.1. Main product distribution in the oxidation of D-gZuconic acid with a standard Pt/C cataZyst under standard conditions
200
"ii 150 E E
c i 100
~ § 8 50
0
' ' I
0
\
f 1.5 time (kst
o gluconic acid
c 2-keto-D-gluconic acid
" oxalic acid
figure 6.2. Main product distribution in the o~idation of D-gZuconic acid with a standard Pb3(P04J2/ Pt/C catalyst under standard conditions
conic acid with a Pt/C and with a Pb/Pt/C catalyst respectively,
as a function of the reaction time. Comparison of these two
figures demonstrates, that after an initial period, in which
the oxygen transfer limits the reaction rate, the oxidation on
the Pb/Pt/C catalyst is faster. In section 8.3. we will return
to this observation. In the Pb/Pt/C catalyst the lead is added in the form of Pb 3 (P0412 •
The differences in selectivity of the above two catalysts is
best illustrated by figure 6.3. in which the (integral) selecti
vity for the oxidation at c6 (selectivity c6) and at c2 (selecti
vity c2) as a function of the conversion is given. The conversion
and the two selectivities are defined as:
104
conversion
[C ] - [GOZ] 6total 0 [C ] 6total 0
(6.1.)
selectivity c6 = [ GL Z ] + [GAZ ]
[C ] - [GOZ] 6total 0
(6.2.)
selectivity c2 [2 KGOZ] (6.3.) [C ] - [GOZ] 6total 0
We use as the initial concentration, [CGtotal]O' the total quantity of material present in the reactor calculated as an
average of the results from the analyses of the second, third
and fourth sample.
.a -.... -
.4 > 8 .$ conversion ( - I
selectivity c6
o Pt/C
<> Pb/Pt/C
selectivity c 2 a Pt/C
a Pb/Pt/C
figure 6.J. Comparison of the selectivities for the oxidation of D-gluconia acid at C2 and c6 with a standard Pt/C catalyst and a standard PbJ(P04J:;i!Pt/C catalyst under standard conditions
From table 6.2., in which the above defined selectivities
are summarized for a conversion of 0.5, it is clear that the
addition of the lead salt to the Pt/C catalyst changes the
ratio of its c2- and c6-oxidation selectivities with a factor of about 150.
Pt/C Pb 3 (P04) 2/Pt/C
selectivity c2 0.054 0.82
selectivity c6 0.63 0.066
selectivity c 2/selectivity c6 0.086 12.4
tabie 6.2. seiectivities in the D-giuconic acid oxidation with a Pt/C versus Pb 3 (P0 4J2/PT/C cataZyst at 50% conversion
105
I
The carbon balances of the experiments are initially too
low. This is probably caused by adsorption of D-gluconic acid
on the catalyst in a nitrogen atmosphere. The amount of material
missing is equal to or even higher than would correspond to the
adsorption of 1 mol of D-gluconic acid per mol platinum. This
acid is assumed to desorb slowly when the atmosphere is changed from nitrogen to oxygen. The adsorption results initially also
in an apparent very low selectivity for 2-keto-D-gluconic acid.
This selectivity is so low that even if the reaction would be
100% selective after the first sample is taken, one still could
not obtain the selectivities found for the subsequent samples.
This is another indication that initially a certain quantity of
acids is not noticeable in our analysis. Of course other compo
nents in the reaction mixture can also adsorb on the catalyst,
We have corrected for adsorption by multiplying the concen
~rations found for D-gluconic acid and its products in the first
sample by the ratio between the average of the total amount of
material found in the three following samples and the amount
found in the first sample.
The initial part of the curves of the D-gluconic acid concentration as a function of time are dotted to indicate the ob
served mass deficiency. In the first sample the concentration
of the products formed from D-gluconic acid are generally so
low that the correction hardly influences their concentration
curves and these are therefore generally not dotted.
It is evident that the above described correction also will
introduce uncertainties in derived figures, such as conversion
and selectivity. Therefore the initial part of their curves are
106
dotted also.
The oxidation with a Pb 3 (P04) 2/Pt/C catalyst system shows
that the addition of a heterogeneous lead compound to a Pt/C
catalyst changes its selectivity completely. To study the func
tion of lead in these catalysts we have carried out oxidation
,reactions in which the lead was added to the reacting system
in other forms.
6.3.2. Addition of a homogeneous lead compound to a Pt/C
catalyst
When an oxidation is carried out with a normal Pt/C cata
lyst and the same Pb/Pt and Pb/gluconic acid ratio as in the
previous experiments, but with a lead (II) acetate solution
added to D-gluconic acid in the substrate supplyvessel at
pH 7 applying starting procedure B, selective production of 2-keto-D-gluconic acid is also obtained (figure 6.4.). This
suggests that a lead (II) gluconate complex could possibly be
the active species in the selective oxidation.
.e
.4 .6 .9 conversion l - ~
selectivity c6
A 1st run
a 2nd run
selectivity c2
o 1st run
O 2nd run
figure 6.4. Selectivities for the o:cidation of Dgluconic acid at C2 and Ce with a Pt/C cataZyst after the addition of lead (II) acetate to the substrate soiution (lat run). In the second run 1/5 of the catalyst of the first run is used, without the addition of lead (II) acetate.
107
In the reaction liquid we found by atomic absorption at
the end of the run only 1.3% of the lead originally added. This
implies that almost all of the lead must be bound to the Pt/C
catalyst and that at the utmost a low concentration of lead (II)
(13 mg/l) in solution is required for the selective oxidation.
The "Pt/C" catalyst*> used in this experiment is washed
with hot water and 1/5 of it is used for a second experiment
under the same conditions as the first, except that no extra
lead is added. In this second experiment initially even a
higher selectivity for oxidation at c2 than in the first run
is observed (figure 6.4.), so that at least a part of the lead
that remained on the "Pt/C" catalyst after washing stayed there
and kept its ability to increase the selectivity for the oxi
dation at c2 • In fact we observed that it is possible to use
a Pb/Pt/C catalyst over and over again without serious loss
of activity or selectivity.
In the course of the first experiment with the lead (II)
acetate solution, the selectivity c2 is increasing at the ex
pense of the selectivity c6 . This is a strong indication that
during the experiment catalytic sites are formed that are active
for oxidation at c2 and that the number of these sites increases
during the experiment, possibly at the expense of platinum sites that are more active for oxidation at c6 . Washing of the catalyst
obviously does not result in the removal of the newly formed
sites .. The fact that hardly any lead was found in the reaction
liquid suggests that it probably is involved in the formation
of the new type of sites. The fact that also a Pb
3(P04) 2/Pt/C catalyst gives a high
selectivity c2 can be accomodated either by the assumption that
during the preparation of this catalyst the lead is preferen
tially adsorbed in the vicinity of the platinum or by a mechanism
*) We write "Pt/C" with quotation marks,. because this catalyst
is not a pure Pt/C catalyst anymore, but most probably con
taines a quantity of lead.
108
in which a part of the lead salt deposited on the catalyst is
dissolved by complex formation with D-gluconic acid and there
after the complex is transported to the platinum site. There
the following three processes are possible:
(a) The lead gluconate complex is oxidized on the platinum site
and the lead remains complexed with the product and can
subsequently be transferred to another gluconate ion.
(b) The lead gluconate complex is oxidized on the platinum site, whereafter a Pb-Pt ensemble is formed that is catalytically
active for the oxidation at c2 •
(c) The lead from the lead gluconate complex forms an ensemble
with platinum on which the oxidation of the gluconate ion
at c2 takes place. We will discuss these possibilities in the subsequent sections.
In order to check the hypothesis that some of the lead
is dissolved by complex formation and transported as a complex
to the platinum site, we have carried out an oxidation with a
normal Pt/C catalyst to which lead (II) phosphate precipitated
on a carbon carrier was added, after we had verified that
Pb3 (P04 ) 2/c alone is neither selective nor active. The Pb 3 (P04) 2 /c is priE>r to use washed with a sodium-D
gluconate solution (200 mmol/l, pH 8) and water to make sure
that no unadsorbed or easily disolvable lead was present in the Pb/C anymore. The Pb/Pt ratio in the reactor is 0.5. From the
high selectivity for oxidation at c2 as compared to c6 (figure
6.5.) it is clear that lead must take part in the oxidation
reaction, and that it must therefore be moved from its own carrier
to the platinum site on the other carrier. This is supported by
the observation that at the end of the reaction the concentration
of lead in the solution amounted 7 mg/l corresponding to 0.7% of the amount of lead originally present as Pb 3 (P04) 2;c. (This demon-
.2
.4 .a .a conversion l- I
selectivity c6
A 1st run
o 2nd run
selectivity c.2
o 1st run
O 2nd run
figure 6.5. Selectivities for the oxidation of D-gluconic acid at C2 and Ce with a combined Pb3(P04J2/C plus Pt/C catalyst system (1st and 2nd run)
109
strates the sequestering power of gluconate, because the solu
bility of Pb3 (Po4>2 in water is only 0.14 ppm).
The combined Pb/C plus Pt/C catalyst was washed with hot
water and used again in a second experiment. This gave once more
an improvement of the selectivity for oxidation at c2 as com-
O 1st run
A 2nd run
10•+0---,,.r----• ..-.---,,.-, --,..-.• --,-t.o
time I ks;
figure 6.6. First order presentation of D-gZuconic acid as a function of the time for the first and the second run of the oxidation of DgZuconic acid with a combined Pb3(P04J2/C and Pt/C catalyst system
110
pared to the first run of this section (figure 6.5.), and also
some enhancement of the rate of oxidation (figure 6.6.). This
confirms that lead transported from its own carrier to the
Pt/C is deposited on the latter.
6.3.4. Addition of EDTA to a Pb/Pt/C catalyst
As will be discussed in chapter 8 the selectivity for
oxidation at c2 is supposed to be caused by complex formation
between lead (probably from the lead platinum ensembles on the
catalyst) and the D-gluconate anion. In order to check this pos
tulate we have added to a suspension of a Pb 3 (P04 ) 2/Pt/C cata
lyst ethylenediamine tetraacetic acid (EDTA), which is a very
strong ligand for lead (II) (3), before the substate was
added and the reaction started.
There will be a competition between EDTA and D-gluconate to
form a complex with Pb 2+, that may result in one of the following
situations:
(a) EDTA extracts all lead from the catalyst system and from
the gluconate, leaving a clean Pt/C catalyst
(b) EDTA binds to lead on the Pb/Pt/C catalyst and thus hinders
adsorption of the gluconate
The quantification of the results of the HPLC analyses were
hindered by the addition of EDTA (EDTA/Pb = 2), making the ab
solute values not so accurate. The relative values, however,
are usable. Figure 6.7. illustrates that the selectivity for
c2 oxidation is relatively low whereas the selectivity for c6 oxidation is relatively high, and that the selectivity for c2 decreases and for c6 increases as a function of the conversion.
As both EDTA adsorption on the lead of the Pb/Pt/C catalyst and
attainment of the equilibrium distribution of Pb2+ in solution
between EDTA and gluconate will be fast, it seems that lead
extraction from the Pb/Pt/C catalyst is the process that is
actually happening.
.. I
!''6
·~ " .! .4
" "' .2
0 0
~
~·
~· .2 ..
conversion .6 .a I->
selectivity c6
6 Pt/C + EDTJ\
'1 Pb/Pt/C + EDTJ\
selectivity c2
o Pt/C + EDTA
0 Pb/ Pt/C + EDTA
111
figure 6.?. Comparison of the aeteativitiea for the oxidation of D-gtuconia aaid at C2 and C6 ~ith a Pt/C and Pb/Pt/C aatatyat after addition of EDTA to the aatatyat auapenaion
6.4. Inftuenae of the Pb/Pt ratio
In section 6.3. we have demonstrated the effect of lead in
the Pb/Pt/C catalyst with experiments in which the Pb/Pt ratio
was 0.5. In this section the results of experiment with different
Pb/Pt ratio's are discussed. For these experiments Pb 3 (Po4) 2/Pt/C
catalysts were prepared in the usual manner, except that the
lead content was varied. As the lead gluconate complex may be
the active species in the selective oxidation at c2 , we also
give the Pb/GOZ0 ratio's. In figure 6.8. and 6.9. the results of these experiments
are summarized. The curves for Pb/Pt = 0.5 are dotted because
the corresponding experiment was carried out in another reactor
at another stirrer speed. Therefore we cannot fully compare
the result of this experiment with the others, but from figure
6.8. the conclusion can be drawn that a Pb/Pt ratio of 0.2,
corresponding to a Pb/Goz0 ratio of 10-2 is sufficient for a
selective catalyst. We have also investigated Pb/Pt ratio's of
112
.s
·--~. 0 . 4 . 6 '8
conversion ( - I
. ....
6 Ph/Pt 0
• Pb/Pt 0.01
<> Pb/Pt 0.2
U Pb/Pt = 0. 5
figure 8.8. Seleativity for 2-keto-D-gtuaonia aaid as a funation of the aonversion of D-gtuaonia aaid with the Pb/Pt ratio of the Pb 3 (P0 4J2/Pt/C aatalysts as parameter
200
§ 16 :;, 100
ii g 0
" 50 N
8 0
' \ I I \ \ \
' \ .s !
time (kSJ
o Pb/Pt = 0
A Pb/Pt = 0.01
0 Pb/Pt 0.2
U Pb/Pt = 0.5
figure 6.9. D-gluaonia aaid aonaentration as a funation of time with the Pb/Pt ratio of the Pb3(P04)2/Pt/C aataZysts as parameter
0.5, 1 and 2. The results are not shown here, but they indicate
that the use of Pb/Pt ratio's higher than 0.5 result all in the
same high selectivity.
The fact that with a Pb/Pt/C catalyst with a Pb/Goz0 ratio
of 10-2 selectivities of 90% can be obtained shows clearly that
113
only catalytic amounts of lead are necessary. A Pb/Pt ratio of
0.01 (Pb/GOZ0
= 5.10-4 ) is not sufficient to achieve a
significant increase in selectivity. This can be understood as
follows: The reaction may be (pseudo) first order in the amount of
Pb2+ present for one of the two following reasons:
(a) The number of really active sites, 1.e. Pb/Pt sites is
proportional to the lead content.
(b) The concentration of Pb gluconate complex is proportional to the [Pb 2+J.
We find that with a ratio of lead/gluconate of 10-2 or a Pb/Pt
ratio of 0.2 already the maximal catalytic effect. It is diffi
cult to understand why the selectivity and activity would not
be further increased by raising the lead/gluconate ratio to
values higher than 10-2 • This makes it rather improbable that
the lead gluconate complex is the active intermediate. On the
other hand it may well be possible that with a Pb/Pt ratio of
0.2 the optimal lead platinum surface modification is already
attained. With a lead/gluconate ratio of 10-2 the ratio of Pb2+
complexed gluconate/non-complexed gluconate must be smaller than 10-2 , and possibly below 7.10-4 , because that is the ratio
between complexed and non-complexed gluconate that we found
at the end of the Pt/C + Pb/C experiment. This again makes it hard to understand how the dissolved Pb 2+-gluconate compl~x would be the catalytically active species. So also this argu
ment is in favour of the formation of lead-platinum surface ensembles as the catalytically active species.
Another indication for the assumption that these ensembles are
the catalytically active species is the following:
In the experiment with Pb/Pt = 0.2 the ratio of the selec-' tivity for oxidation at c2 to the selectivity for oxidation at
c6
is 0.9/0.05 = 18 (figure 6.10.). This means that the rate
for oxidation at c2 is a factor 18 higher than the rate for oxidation at c
6• A reduction of the lead content of the
catalyst by a factor 20 (Pb/Pt = 0.2 ~ Pb/Pt = 0.01) would
114
.s
l ?''e :~ .! ... .. .,
• 2
0
0
.,-~
/ .
.2 . 4 . e .a conversion I - !
selectJ.v1ty c6
~ Pb/Pt = 0.01
D Pb/Pt = 0.2
selectivity c2
o Pb/Pt = 0.01
o Pb/Pt = 0.2
figure 6.10. Comparison of the selectivities for the o~idation of D-giuconic acid at C2 and C6 with standard Pb3(P04)2/Pt/C catalysts with a Pb/Pt ratio of 0.01 and 0.2
reduce the amount of Pb-Pt ensembles by a factor 20, which, as
a rough approximation, would result in a ratio of the above
selectivities of about 1. This is initially indeed what we
have observed (figure 6.10.). That this ratio decreases during
the experiment could have two reasons:.
(a) Part of the lead-platinum ensembles deactivates, due to the
adsorption of some product
(b) Part of the lead is extracted from the catalyst by the
gluconate
The latter explanation does not seem very probable, because we
observed no strong loss of selectivity already at the beginning
of the experiment, although the catalyst has already been in
contact with the gluconate for about 1 ks (starting procedure B).
A deactivation of the Pb-Pt ensemble, due to the adsorption
of some product, however, is very well possible. The Pb/Goz 0
-4 ratio amounts 5.10 so only a very small amount of product
is necessary to cover all the lead present.
That Pb3 (P04) 2 really interacts with the platinum of the
catalyst follows from the subsequent experiments:
On 20 g of carbon carrier 1 gr of platinum was deposited
according to the standard procedure (section 4.2.1.). An equal
amount of carbon carrier was treated identically, except that
no H2Ptc16 was added. On both carriers 0.69 g Pb3 (P04 ) 2 (Pb/Pt= 0.5) was deposited in the usual way (section 4.2.2.).
When both lead containing products were exposed for 6 ks at
55oc to half a liter of a 200 mmol/l D-gluconic acid solution
115
at pH 8 in a nitrogen atmosphere, we found the lead concentration in the solution contacted with the Pt free Pb3 (Po4>2/c
product to be 1.5 mg/l, whereas for the Pb3 (P04) 2/Pt/C catalyst
the lead content was at or below the detection limit of 0.2 mg/l.
6.5. Metal ions other than Pb 2+
In chapter 8 it will be shown that the selective oxidation
of D-gluconic acid at c 2 is accomplished by complex formation of the Pb(II) on the Pb/Pt/C catalyst, with the D-gluconate
anion. The specificity is probably caused by the fact that
Pb(II) forms a bidentate complex with the carboxylate group
and the oxygen of the a-hydroxyl group. In this section we will describe the use of two other metal ions, which are reported
(4,5) to be able to form this kind of complexes also.
In figure 6.11. the results are summarized of the oxidation of D-gluconic acid with a Bi(OH) 3/Pt/C catalyst and with a
Pt/C catalyst (5% Pt/C, Degussa F 196 RA/W) to the suspension of which copper(II) acetate has been added. The Bi/Pt/C was
prepared from a home made 4% Pt/C catalyst according to an analogous method as for the Pb(OH) 2/Pt/C catalyst (section 4.2.2.).
116
.a
0
-.-
·• .e conversion (-1
.a
selectivity c6
"' Cu
C Bi
.. Pb
selectivity c2
0 Cu
•Bi
<> Pb
figure 6.11. Comparison of the seZectivities for the o~idation of D-gZuconic acid at C2 and C6 with a Pb3(P04)2/Pt/C aataZyst, a Bi(OH)3/ Pt/C cataZyst, and a Pt/C cataZyst to the suspension of which copper( II) acetate has been added
The catalyst concentrations were both 40 g/l, the Bi/Pt ratio
was 0.5, and the Cu/Pt ratio was 2.
A comparison of the reaction rates is not very informative,
because the experimental conditions and the Pt/C basis for both
experiments were different, but the rates were found to be in
the same order of magnitude as obtained with the Pb/Pt/C
catalysts. Also the same produbts were observed. Figure 6.11.
illustrates that the Bi(OH) 3/Pt/C catalyst was more selective
for c 2 oxidation than the cu2+ - Pt/C system, but that even the
Bi/Pt/C catalyst was not as selective as the Pb/Pt/C catalyst.
These exploratory experiments neither imply that it is impossible
to prepare better catalysts with copper or bismuth,nor that
by using different reaction conditions the selectivity can not
be increased. Certainly bismuth seems to be promissing as an
additive in the Pt-catalyzed oxidation.
11 7
6.6. Other substrates than D-gZuconic acid
The results obtained with a Pb/Pt/C catalyst, for the
selective oxidation of D-gluconic acid, led us to a study of
the oxidation of other substrates. We will first discuss the
oxidation of the following, commercially interesting carbohy
drates: D-glucose, D-galactose, D-arabinose and L-gulonic acid.
The reactions were all carried out in the same reactor. For
all experiments the same, for that reactor rather low~stirrer
speed (1000 rpm) was used, so that the Pb/Pt/C catalyst
(Pb/Pt 0.5) remained reasonably active, i.e. that the oxygen
concentration in the liquid was kept at a low value. This means
that the reaction rates that can be derived from the figures
6.12.-6.15. (showing the concentrations of the main products
as a function of time) are each influenced by an unknown oxygen
concentration that not necessarily has to be the same in the
four experiments.
The curves for 2-keto-D-galactonic acid and 2-keto-D-ara
binonic acid are dotted, because their concentration could
only be estimated, as no pure compounds were available for
calibration. Neither did we have mixtures containing the 2-keto
derivative of o~galactonic acid or D-arabinonic acid for
identification. Nevertheless, the peaks of these 2-keto acids
could be assigned, because the peak pattern in the chromato
grams from the reaction mixtures of all four substrates were
nearly identical. Moreove~with the specific detection method
described in section 3.6., the presence of 2-keto carboxylic
acids in the reaction mixtures was proved. The concentration
of both 2-keto-D-galactonic acid and 2-keto-D-arabinonic acid
in the final reaction mixtures estimated with this method were
about 25% higher than those estimated from the HPLC results. As we know from the oxidation of D-gluconic acid that these
deviations can be caused by smaller 2-keto-carboxylic acids,
that influence the outcome of the method specific for 2-keto
200
:::: ~ 150
E
c: 0 100
~ E "' " c: 0
" 50
0 0
200
~ 150
E
c: 0 100 -~
" "' " c: 0 50
"
0
I) glucose
c qluconic acid
A 2-keto-O-gluconic acid ~ n oxalic acid E
6. 12 c: 2 ~ E e c: 0 <.>
.5 1.5 time i ksl
<0iarabinose
A arabinonic acid
~ o 2-keto-o-arabinonic acid
o oxalic acid E
c: .g 6.14 ~
c .. <.> c: 0 <.>
.5 1.5 time ( ksl
200
150
100
50
0 0
200
' 150 ' ' '
100
50
0
.5 1.s time ( ksJ
.5 1.5 time (ks!
1:;9alactose
A qalactonic acid
ti 2-keto-D-qalacton ic acid
o oxalic acid
6. 13
o gulonic acid
"" 2-keto-1-gulonic acid
o oxalic acid
6. 15
figure 6.12.-6.15. Main product distribution in the oxidation of D-glucose, D-galactose, D-arabinose and L-gulonic acid with a standard Pb 3(P0 4J2 /Pt/C catalyst under standard conditions
acids, we preferred to use only concentrations estimated from
the HPLC results.
The 2-keto-D-galactonic acid concentration was estimated
11 9
by assuming that 2-keto-D-galacton·ic acid and D-galactonic acid
would have the same ratio between their molecular responses
as found between the molecular responses of 2-keto-D-gluconic
acid and D-gluconic acid. When applying this same method to
2-keto-D-arabinonic acid, a substantial surplus in the carbon
balance was found. Therefore we took a sample from the oxidation
of D-arabinose in which only small amounts of (detectable) by
products were .present. The deficit between the amount of star
ting material and the mass balance of this sample was ascribed
to 2-keto-D-arabinonic acid. This value. was used to determine
the molecular response for this compound. Consequently the
absolute values of the concentrations of the two 2-keto-carboxylic
acids may each contain a constant systematic deviation.
Figures 6.12.-6.14. show that when an aldose is oxidized
with a Pb3 (P04 l 2/Pt/C catalyst, first the hemiacetal group is
oxidized followed by reaction at c2 . This is caused by two
effects. In the first place the oxidation of an aldehyde group
is fast and secondly the complex formation with lead requires
the presence of a carboxylate group.
The selectivities c2 for these substrates are compared
with the results of the oxidation of D-gluconic acid in figure
6.16. As in the oxidation of D-glucose, D-galactose and
D-arabinose an intermediate is produced (D-gluconic acid, D-·
galactonjc acid, and D-arabinonic acid, respectively), that can
still be converted to the desired product, this intermediate
can for selectivity purposes be considered as being not conver
ted starting material. Consequently we have adjusted our
definitions. For e.g. the oxidation of D-glucose this leads to
the following expressions:
conversion
[ C ] - [ G] - [ GOZ] 6total 0 c 6total 0
(6. 4.)
120
selectivity c2 = [2 KGOZ] (C ] - [G] - (GOZJ 6total 0
.a
0
·- .... - ~ -----..... --·-- - --.... -D-...
-2 .• ·6 conversion (-)
..
• 0-qluconic acid
A O-qlucose
v O-galactose
c o-ara.bi.nose
~ L-qulon1c acid
(6. 5.)
figuPe 6.16. Selectivity foP a-keto-eaPboxylie aeid for the oxidation of D-glueoae, D-galaetose, D-arabinose, L-gulonie aeid and D-glueonie aeid with a atandard Pb~(P04 J2/Pt/C eatalyat at standard eondit~ons.
instead of the original relations (6-1) and (6-3).
For the oxidation of L-gulonic acid the original definitions for
conversion and selectivity c 2 are used. The curves corresponding
to D-galactose and D-arabinose are dotted to indicate the ad
herent uncertainties.
L-gulonic acid is oxidized with a very high selectivity
(0.97 at a conversion of about o.85), which is even higher than
that for D-gluconic acid. The selectivity for 2-keto-D-gluconic
acid starting from D-glucose, is almost the same as that for
the D-gluconic acid oxidation. Only at high conversions the
selectivity of the D-glucose oxidation is slightly higher than
the D-gluconic acid oxidation. This indicates that the oxidative
cleavage of 2-keto-D-gluconic acid to oxalic acid in the pre
sence of a little D-glucose is slower than in the absence of
121
D-glucose. This is to be expected if the oxidation of both
D-glucose and 2-keto-D-gluconic acid are competitive catalytic
reactions, but also if the oxygen concentration in th~ solution
is lower as long as D-glucose is present, as will be discussed
in section 6.7.
As discussed earlier, it is difficult to determine the
initial selectivity, but figure 6.16. illustrates that possibly
the initial selectivities c2 for the oxidation of the various
substrates are all relatively high. For a more accurate deter
mination the complex formation of the aldonic acids with Pb2+
has to be investigated.
The reaction rates of the oxidative splitting of the
a-keto-carboxylic acids can be derived from figure 6.16.
The differences in the slopes of the selectivity curves are
caused by the differences in the rates of cleavage of the
carbon chain. It is clear that these rates are not directly
proportional to the 2-keto acid concentration. Two effects play
a role, viz. the increased oxygen concentration in the liquid
phase as a result of the decreased oxygen consumption rate,
and the change in catalyst activity.
These reaction rates can be ranked as follows:
2-keto-L-gulonic acid < 2-keto-D-gluconic acid ~
2-keto-D-arabinonic acid ~ 2-keto-D-galactonic acid
In order to explain this sequence we will examine the main forms
in which the 2-keto-carboxylic acids are present under
reaction conditions:
H OH
H
OH H
B-pyranose form of 2-keto-Dgl uconate
a-pyranose form of 2-keto-D-galactonate
coo-
122
Vo~00-ii"t--{0H
OH OH
a-furanose form of 2-ketoD-arabinonate
HO
H H
a-pyranose form of 2-keto-L-gulonate
Tne 2-keto-carboxylic acids will exist preferentially in
conformation in which the COO- and OH groups are equatorially
positioned, as this represents energetically the most favourable
geometry. According to the above structure formules it is to be
expected that 2-keto-L-gulonic acid is most stable and there
fore perhaps most resistant towards oxidative cleavage. This
sequence is also in agreement with the observation that 2-keto
D-gluconic acid exists for about 75% in the 8-pyranose form
(section 3.4.2.) and 2-keto-L-gulonic acid for more than 97%
in the a-pyranose form (6).
These experiments show that with a Pb/Pt/C catalyst a
hemiacetal function is first oxidized to a carboxyl function,
whereafter the oxidation at c2 takes place. To obtain further
insight in the background of the observed selectivities we
also investigated the oxidation of D-glucuronic acid, D-fructose
and methyl-a-D-glucoside.
D-glucuronic acid has both a hemiacetal and a carboxyl group,
so it was used to see whether the hemiacetal group or the
a-carbon would react first. We found that the hemiacetal function
had to be oxidized first to a carboxyl function before oxi
dation at the a-position could occur. This seems to indicate that
only a free hydroxyl in the a-position of a polyhydroxy carbo
xylic acid is able to form the reactive complex with lead.
D-fructose gave cleavage of the carbon chain by which gly
colic acid and oxalic acid were produced, in accordance to what
has been reported by Dirkx (7) on the Pt/C catalyzed oxidation of L-sorbose.
For methyl-a-D-glucoside we expected oxidation towards
methyl-a-D-glucuronide, as happens on a Pt/C catalyst. We ob
served indeed this reaction, but it was very much slower (by
123
a factor 8} and about half as selective as on Pt/C. This indi
cates that the lead-platinum ensembles not only have a very
possitive influence on the c2 oxidation, but possibly also
have a negative influence on the rate of oxidation at c2 •
The results presented thus far are summarized in the
following selectivity rules for Pb/Pt/C catalysts:
An aldose is first oxidized to an aldonic acid, which is sub
sequently oxidized to a 2-keto-aldonic acid.
- The a-hydroxyl of an aldonic acid will be oxidized preferen
tially.
6. 7. Deactivation of the catalyst
Our experiments have mainly been carried out under such
conditions that the oxygen transfer from the gas to the liquid
phase limited the oxygen concentration in the liquid phase to
very low levels. If this is not done, a fast deactivation of the
catalyst occurs. This deactivation is a rather complex phenomenon,
as will be shown below. First the two starting procedures are
compared. The reactions were carried out under standard condi
tions using a standard Pb/Pt/C catalyst, but with such a high
stirrer speed that mass transfer limitation from the gas phase
to the liquid phase was avoided. In figure. 6.17. the influence
of the two starting procedures is given. It can be seen that after an initial period (about 25 s) the starting procedure B
(treatment of the catalyst with nitrogen before the start)
results in a much higher reaction rate than the starting pro
cedure A (catalyst saturated with oxygen before the start of
the experiment). Dirkx (7) has observed the same effect for a
Pt/C catalyst, but in his case the difference between the two
124
N 0 (.!)
10' .i----~-~--~--~---+ 0 1 1,5
time (ks>
o sta.rtinq procedure A
A starting procedure B
figure 6.1?. Influenae of the starting proaedure on the oxidation rate of D-gluaonia aaid with a standard Pb3(P04J2 /Pt/C aatalyst
10
time t kS I 20
o startinq pro~edure A
1> starting procedure B
figure 6.18. Influenae of the starting proaedure on the oxidation rate of D-gluaonia aaid with a 5% Pt/C aatalyst (Dirkx, (?))
starting procedures (figure 6.18.) was not so pronounced as in
our experiments. Moreover, Dirkx's catalyst could easily be re
activated by temporarily replacement of the oxygen in the reactor
by nitrogen. In our case, however, this method was not. succes
ful. We presume that this difference is caused by the one factor
that makes the catalysts different, viz. the lead present in our
125
catalyst. However, even with the starting procedure A we find
an initial activity (first 25 s) that is rather high and of the
same order of magnitude as starting procedure B.
This means that for the deactivation oxygen alone is not enough,
but that both oxygen and substrate are necessary. It is possible
that with this combination certain reaction products are formed
that transform the active sites in less active ones, either by
irreversible adsorption or by chemical reaction. As will be
shown below, indeed certain reaction products have a negative
influence on the catalyst activity. The difference in the deacti
vation process for the two starting procedures must then be
ascribed to the preferential formation of deactivating compounds
when starting procedure A is used. There is, however, also
another possibility, namely that during the reaction oxygen on
the catalyst is activated to form an inactive platinum oxygen
compound.
Figure 6.19. illustrates that the oxidation on the less
_a I
-2
·---
o-t--.---.~.....--,-~~-.-~~~~-+
• ·' . e .a conversion ( - l
<> starting procedure A
A startinq procedure 6
figure 6.19. Influence of the starting procedure on the selectivity for 2-keto-D-gluconic acid at the oxidation of D-gluconic acid with a standard Pb3(P04)2/Pt/C catalyst
active sites is not only slower, but also less selective. This
again shows that this deactivation has a specific influence on
the lead part of 'the catalyst, as this is the element that
126
causes the high selectivity for c2 oxidation.
To answer the question whether adsorption of certain reac
tion products or some other change of the catalyst is the main
cause of the deactivation,we have re-used the catalyst and the
reaction liquid resulting from an oxidation reaction in sub
sequent experiments according to the following scheme:
fresh catalyst """
fresh 0-gluconic acid fresh catalyst solution ""' /
,,__e_x_pe_n_· m_e_n_t_1~[
filtrate / ~ {GOZ] ~ 200 mmol/1 used catalyst
l .--------. e>eperiment 2
washed with hot water
l fresh D-gluconic /acid solution
,------''---,I e>eperiment 3 .
We used the standard conditions and starting procedure A which was modified as follows: Instead of heating the
catalyst suspension in the oxidation gas atmosphere, it was
heated in a nitrogen atmosphere, and after the suspension had
reached the operating temperature, it was treated with oxygen
for 0.9 ks. In experiment 1 fresh catalyst and a fresh D-glu
conic acid solution were used. After 0.65 ks the catalyst was
filtered off and washed with 3 1 hot water to remove adsorbed
reaction products as completely as possible. The filtrate was
concentrated in a film evaporator at 50°C and D-gluconic acid
was added to obtain again 0.5 1 with a concentration of 200 mmol/l. Thereafter two experiments were carried out: the
filtrate was contacted with fresh catalyst (experiment 2) and the
used catalyst was contacted with a fresh D-gluconic acid solution
(experiment 3).
For these three experiments the D-gluconic acid concentra
tion as a function of time is given in figure 6.20. Both ex
periments 2 and 3 show a lower reaction rate than experiment 1,
but the reduction in activity is much greater in experiment 2
5 2 oro E §.
N 0 l!l
10• -i----~-~-....... --...--..---t 0 d 4 d ~ • ~ ~
time (ksl
6. fresh catalyst +
fresh qluconate solution
o fresh catalyst +
filtrate of experiment l
~ used catalyst +
fresh gluconate solu~ion.
127
figure 6.20. InfZuenae of re-use of aataZyst and reaation mixture on the oxidation rate of D-gZuaonia aaid with a standard Pb 3(P04J2/Pt/C aataZyst
than in experiment 3. We therefore conclude that the deactivation
is mainly caused by adsorption of certain reaction products
specifically on the lead part of the catalyst. This is in agree
ment with the observed decrease in selectivity for oxidation at
c2 with decreasing activity (figure 6.21.)
_.a I
<3 .e ... j ti ~-· .. ..
.. ·• ·B ·8 conversion I- l
o fresh catalyst +
fresh gluconate solution
A fresh catalyst +
filtrate of experiment l
.0 used catalyst +
fresh qluconate solution
figure 6.21. InfZuenae of re-use of aatatyst and reaation mixture on the seZeativity for the oxidation at C2 of D-gZuaonia aaid with a standard Pb3(P04)2/Pt/C catalyst
128
References
1. Nishikido, J., Tamura, N., Fukuoka, Y., Fuji, s., Ger.
Offenl. 2,936,652 (1980)
2. Fiege, H., Wedemeyer, K., Bauer, K., Malleken, R., European
Patent 5,779 (1979)
3. Pecsok, R.L., Juvet, R.S., J. Am. Chem. Soc., 78, 3967 (1956)
4. Sawyer, D.T., Chem. Rev., 64, 633 (1964)
5. Sawyer, D.T., Brannan, J.R., Inorg. Chem.,~' 65 (1966)
6. Crawford, T.C., Andrews, G.C., Faubl, H., Chmurny, G.N.,
J. Am. Chem. Soc., 102, 2220 (1980)
7. Dirkx, J.M.H., Ph. D. thesis, University of Technology,
Einhoven, The Netherlands (1977)
129
Chapter 7
Selective Catalytic Production of 2-keto
D-Gluconic Acid
7.1. Introduction
In the preceding chapter we have discussed the characteris
tics and scope of the Pb/Pt/C catalyst. In this chapter we
present subsequent investigations that were aimed at improving
the selectivity of the production of 2-keto-D-gluconic acid from
D-gluconic acid with a Pb/Pt/C catalyst. For that reason we have
investigated the influence of the catalyst concentration (section
7.2.), the oxygen partial pressure (section 7.3.), the pH (sec
tion 7.4.) and the temperature (section 7.5.).
7.2. Influence of the catalyst concentration
The concentration of oxygen in the liquid phase is deter
mined on the one hand by the net rate of oxygen transfer from
the gas phase to the liquid phase, which is mainly governed by
the stirrer speed, and on the other hand by the rate of oxygen
consumption by the chemical reactions taking place in the
reaction suspension. As long as a reasonable active catalyst is
maintained, the conditions can be chosen so that the oxygen con
centration in the liquid is kept very low and the transfer of
oxygen from the liquid back to the gas phase can be neglected.
By changing the concentration of the catalyst at a constant
130
stirrer speed, one can change the rate of conversion per
unit of reaction volume, almost without influencing the mass
transfer from the gas phase to the bulk of the liquid and from
the bulk of the liquid to the outer surface of the catalyst
particles. With the stirrer speed selected (750 rpm) for the present series
of experiments we observed in the first 200 seconds of the
experiment with 40 g/l of catalyst a decrease in the oxygen gas
pressure in the reactor. In this period the oxygen pressure
regulating system could not cope with the oxygen demand of the reaction. This problem was not present during the two other ex
periments with 20 g/l and 10 g/l of catalyst, respectively.
As basis for the Pb/Pt/C catalyst used in this study a home
made Pt/C catalyst, containing 4,85% by weight platinum, is used. The usual standard reaction conditions were applied, except that the pH was adjusted to 9.
-s 0 E ~ 10'
.~ 1 ~ I i \
: •. \ time t ks;
[catalyst)
A 40 g/l
a 20 g/l
.. 10 g/l
figure 7.1. D-gZuconic acid concentration (Zogarithmic scaZe) as a function of time with the cataZyst concentration as parameter
In figure 7.1. a graph of the D-gluconic acid concentration
as a function of time is given for the three experiments. This illustrates that after an initial period of fast reaction the
131
reaction rate decreases markedly in each experiment (by a factor
4 or more) • If we define the initial activity as being proportional
to the quantity D-gluconic acid converted in the first 300
seconds, the initial activity is proportional to the catalyst
quantity as shown in figure 7.2. This indicates that in the presence of a fresh
-~ 150 E E
S,oo "' :;; ii N 60 g
figuPe 7.2. D-gluconic acid concentPation aftep 300 seconds convePsion as a function of the catalyst concentPation
catalyst the reaction behaves as being first order in
catalyst. This is a rather unexpected result. If we assume that
the oxygen mass transfer from the gas to the liquid is in the
three experiments governed by always the same mass transfer
coefficient and the same transfer area, then the difference
between the equilibrium oxygen saturation concentration and
the actual oxygen concentration in the liquid should be
proportional to the reaction rate:
(7-1)
132
In which:
r = reaction rate
11:,= mass transfer coefficient
a = exchange area
C*= equilibrium oxygen concentration
C = actual oxygen concentration
mol/m3 .s
m/s m2;m3
mol/m3
mol/m3
With C* estimated at 0.9 mol/m3 , and assuming that C is very
low for the experiment with 40 g/l catalyst, say below 0.01
mol/m3 , we would calculate the oxygen concentration for the
experiment with 20 g/l catalyst during the initial period to
be about 0.46 mol/m3 and for the experiment with 10 g/l
catalyst about 0.68 mol/m3 • The corresponding value for
kL·a= 0.25 s-1 , which is normal for the stirrer speed and
reactor geometry used. As we, nevertheless, find the proportio
nality depicted in figure 7.2., we must conclude that the
initial reaction rate is zero order in oxygen.
In the second part of the curves of figure 7.1. straight
lines are obtained that suggest that the reactions behave in
that part of the experiments as being first order in D-gluconic acid. However, if we accept this first order relation
and express the first order rate constants, that can be derived
from the data of the second part of the curves, per gram of
catalyst, the rate constant obtained for the experiment with
40 g/l of catalyst is 3.3 times higher than the rate constant
for the 20 g/l experiment and 4.8 times higher than the rate
constant for the 10 g/l experiment. This indicates that the
degree of deactivation of the catalyst is more or less inversely
proportional to the quantity of catalyst present. In section 6.7.
we have shown that certain products present in the reaction
mixture have a poisoning effect on the catalyst. Figure 7.2
illustrates that the initial conversion is proportional to the
133
amount of catalyst. This would, as a first approximation, mean
that the degree of deactivation for the three experiments should
be the same. As, however, the concentration of the products is
highest in the experiment with 40 g/l catalyst one would expect
the deactivation in this case also to be the highest. As the
opposite is found we must conclude that another factor is also
operative in the catalyst deactivation. The only variable left
over is the oxygen concentration in the liquid phase. This oxygen
concentration is highest in the experiment with the lowest quan
tity of catalyst. In accordance with the results of Dirkx (1) on
the oxidation of D-glucose and D-gluconic acid over Pt/C and of
Ostermaier et al. (2) on the low temperature oxidation of ammonia
over a Pt/Al2o3 catalyst, we assume that a surplus of oxygen can
also in our case be responsible for part of the deactivation of
our catalyst.
.&
l ?'.e :~ t; ~-4 .. .,
.2
0 0
. .......... ~--------' .... ---',,,~~ '\
~ -- _____ .,.. __ ............ .2 .4 ·• .&
conversion ( - I
selectivity c2
(catalyst]
0 40 9/l
<> 20 9/l
• I 0 9/ l
selectivity c6
[catalyst]
.. 40 9/ l
• 20 g/ 1
.. 10 9/l
figuPe 7.3. Influenae of the aatalyst aonaentPation on the selectivity c2
Figure 7.3. illustrates that the deactivation of the catalyst is accompanied by a decrease in the (integral) selectivity
c2 • This was already demonstrated in section 6.7. The selectivity
C6 , however, increases slightly. This again indicates that
134
at least a part of the deactivation is caused by the
adsorption of certain reaction products on that part of the
catalyst where lead and platinum interact. The graph of the
2-keto-D-gluconic acid concentration as a function of the
D-gluconate conversion (figure 7.4.) shows that the decrease
in the (integral) selectivity c2 is caused by oxidative cleavage of the target product. So it seems.that this reaction
does not need the presence of lead as a co-catalyst. Figure 7.4.
also shows that the oxalic acid is one of the products of the
oxidative cleavage. In section 7.6. the product distribution
will be discussed in more detail.
150
2-keto-D-gluconic acid //,..,.--.\ [catalyst]
s; / 0 40 g/l
~ 100 / .. 20 9/l /
E / " 10 g/l
c
/~/) oxalic acid 0
'i [catalyst] ~ 50
g • 40 9/ l
0 ~ 20 9/l u
a I 0 g/ l 0 /_ ..,,- -- --
0 .a .. .e .a conversion (-)
figure ?.4. 2-keto-D-gluaonia aaid - and o~alia aaid aonaentration with the aatalyst aonaentration as parameter
?.5. Influenae of the oxygen aonaentration
In the previous section and in section 6.7. we have demon
strated that the catalyst starts to deactivate when the oxygen
concentration in the liquid. phase becomes substantially above
zero and that the deactivation is accompanied by a decrease
in selectivity.
135
In order to postpone the onset of the deactivation we carried
out a standard experiment in which instead of pure oxygen air
was used as the oxidizing agent. In this way the oxygen concentration in the liquid phase must be reduced, compared
to the concentration when pure oxygen is used, and the deacti
vation delayed.
~ §_ ISO
" .!2 e i: 100 .. ll 0
" N 50 0 Cl
.. 1 1.&
time 1 ks I
o air
A pure oxygen
figure 7.5. D-gluconic acid concentration as a function of time with the o~ygen partial pressure as parameter
Figure 7.5. shows the D-gluconic acid concentration as a
function of time, when the oxidation is carried out with pure oxygen and with air. We see that for a large part of the experi
ment the conversions both are zero order in D-gluconic acid, but
that the reaction rate in the case of air as oxidant is about one fifth of the rate obtained with ~xygen. This demonstrates that
the reaction rates observed are governed by the oxygen transfer rate, and that the oxygen concentration in the liquid must be small compared to the equilibrium oxygen concentration. At these low oxygen concentrations the chemical reaction rate will be
controlled by the oxygen concentration in the liquid.
136
3
time lksl
o air
4 pure oxygen
figure ?.6. D-gluaonia aaid aonaentration (logarithmic saale) as a funation of time ~ith the o=ygen partial pressure as parameter
From the figure 7.6. where the D-gluconic acid concentration
is plotted on a logarithmic scale we can conclude that the re
lative deactivation proceeds slower for the oxidation with air
than with pure oxygen.
.e
.2
.2 ·• ·6 ·8 conversion l- I
selectivity c2
o air
o pure oxygen
selectivity c6
A air
g pure oxygen
figure?.?. Influence of the o=ygen partial pressure on the selectivity c2 for the o=idatiori of D-gluconie acid
137
As can be deduced from figure 7.7., where the selectivities are plotted as a function of the conversion, the selectivities c2 are (after an initial period where the data are not too reliable) essentially equal for both oxygen partial pressures. This indicates that under the conditions of these two experiments, which are for a large part of the experiment mass transfer limited,the selectivity c2 is more a function of the conversion than of the very low oxygen concentration. This, however, cannot be considered as a proof that the deactivation is purely caused by the products formed, because in both cases the oxygen concentration in the liquid is bound to increase when the conversion of D-gluconic acid approaches completeness. We further note that also the selectivities c6 are ~ore or less equal for both experiments. If we compare the rate of disappearance of 2-keto-D-gluconic acid from figures 6.2. and 7.8. we can see that with air as the oxidant t~e rate of conversion of the keto acid is about 60%
~ 'f50 E
0 3
time 1 ks) 4
air
o qluconic acid
A 2-keto~D-qluconic acid
ct oxalic acid
figure ?.8. Main products for the oxidation of Dgluconic acid with air as oxidizing agent
of the rate with pure oxygen. Thus here the proportionality between oxidation rates and oxygen gas phase pressure as was found for the D-gluconic acid conversion (figure 7.5.), is not present anymore. This either means that the rate of oxidative cleavage of 2-keto-D-gluconic acid has a low order in oxygen
138
or that the catalyst has changed differently for the two experi
ments. On the basis of the identical selectivities c2 we would
prefer the first explanation.
We further studied the influence of the oxygen concentra
tion on the catalyst deactivation by executing some experiments
with a high stirrer speed (550 rpm), a small quantity of cata
lyst (5 g/l), pure oxygen and with D-gluconic acid concentrations
of 100, 200 and 400 mmol/l, respectively. Under these conditions
the reaction rates are so low, that the oxygen concentration in
the liquid must be substantial and perhaps approaches the satura
tion concentration. We now observe, as is illustrated in figure
~ E E
N 0 Cl
,<J.
o'
"' ....
............_.
5 1 u; 2 2.s 3 time lksf
3.5
[9luconic acid) at t=O
<> 400 mmol/l
o 200 mmol/ l
~ I 00 mmol/l
figure ?.9. D~giuconic acid concentration (Zogarithmic scate) as a function of time with the starting gluconate concentration as parameter
7.9, that the catalyst is deactivated in a period of one or two
minutes. In that period always some 20% of the D-gluconic acid
has been converted, indicating that on a fresh catalyst the
reaction behaves as being first order in D-gluconic acid. At this
stage of our study we got at our disposal a polarographic oxygen
analyzer, to monitor the oxygen concentration in the liquid.
100
80 .. c " C> 60 > x 0
.t::
" ~ 40 c 0 ~~
" 20 10 "'
0
'?"
·' 'fime (ks i3 .4 .5
[gluconic acid] at t=O
• 400 mmol/l
A 200 mmol/ l
9 l 00 mmol/l
139
figuPe 7.10. Concentpation of oxygen in the Ziquid phase foP the oxidation of D-gZuconic acid at vaPious substPate concentPations
Figure 7.10. shows for the present three experiments the course
of the oxygen concentration. In the active period the oxygen concentration is indeed very low, well below the accuracy of
the instrument: 0.05 ppm. The 100% value in this scale corresponds to 29 ppm, viz. the saturation concentration when the solution is in contact with pure oxygen at 0.1 MPa and the reaction
temperature of 55°C. In figure 7.11 we have redrawn those curves from figures 7.9. and 7.10. that correspond to an initial D-gluconic acid concentration of 100 mmol/l. Taking into account that the 95% response time for the polarographic oxygen analyzer
is in the order of 10 seconds, then we must conclude that only at the very beginning of the reaction very low oxygen concen
trations exist and that quite a part of the deactivation takes place under oxygen concentrations that are near 5aturation.
140
100 100
-l .o
.--.. 80
c: .g15 •+:
j 60 H
0 El!
'! ~8 u so 40 .. c: -0 u .... N :zo "": 0 0 I!)
10 0 .o. .OB .12 time t ks 1
figuPe 7.11. D-gZuaonia acid aonaentPation and the o~ygen aonaentPation in the Ziquid phase fop the e~pePiment with the staPting aonaentPation of 100 mmoZ/Z
7.4. InfZuenae of the pH
The reactivity of carbohydrates is rather strongly influenced
by the pH of the reacting solution. As the pH influence on the
oxidation of D-gluconic acid to 2-keto-D-gluconic acid might be
different from the pH influence on all other unwanted reactions,
it is obvious that a study o~ the influence of the pH on the
course of the oxidation of D-gluconic acid is worthwile. As
carbohydrates generally become more unstable at pH > 9, we have
studied the pH range from 9 to 4. The other reaction conditions
were standard, except that catalysts, regenerated by prolonged
washing with hot water, were used. were used.
The pH of the reacting system was adjusted to the required
pH during the period that the system was still filled with
nitrogen. At the moment the nitrogen was replaced by oxygen a
rise in pH was noticed, that decreased slowly as a result of
the formation of the extra acids until the required pH was
reached and controlled thereafter by the alkali supply
141
system. We assume that in the presence of nitrogen some alkali
is adsorbed on the catalyst, which is desorbed again in an oxygen
atmosphere. As is to be expected, the initial increase of the pH
was most pronounced at the pH's around 7 and about 0.7 pH units at pH 7.
N 0 (!)
0 1 1.5 time (ks)
o pH 9
A pH 8
• pH 7
o pH 6
0 pH 5
V pH 4
figure 7.12. D-giuconic acid concentration riogarithmic ecaieJ ae a function of time with th• pH aa parameter
Figure 7.12. illustrates that for pH's below 7 the oxi
dation rate decreases with decreasing pH. The same is true for
the oxidation of D-gluconic acid without lead(1). As all the
experiments were carried out at the same stirrer speed, a slower reaction will, according to the foregoing discussion,
result in a deactivation of the catalyst at a lower conversion. This is illustrated for pH 4, 5 and 6 by figure 7.12. For the
higher pH's the intrinsic reaction rate is high enough to let
the oxygen transfer from the gas phase to the liquid phase limit
the overall reaction rate, and therefore the curves for pH 7, 8
and 9 more or less coincide. The selectivities at pH 4 and 5
(figure 7.13.) are low, possibly because of the deactivation of the catalyst. That the selectivity at pH 6 is still rather high
142
is caused by the fact that the deactivation started when a rather
high conversion was already attained.
_a I
o+-~~.----~--..~~-.-~~....-~--+
0 .2 .4 ·6 conversion I- )
o pH 9
A pH 8
• pH 7
D pH 6
<> pH 5
• pH 4
figure 7.13. InfZuenae of the pH on the seZeativity C2 for the oxidation of D-gZuaonia aaid with a Pb/Pt/C aatalyst
We find that at pH 7 the productivity for 2-keto-D-gluconic acid is highest. This is caused by the fact that the
high initial selectivity is maintained almost until all D-glu
conic acid is converted. The high initial selectivity presumably
results from the favourable conditions for complexation with leao{IIJ at that pH. The fact that the high selectivity is main
tained up to relatively high conversion derives from the obser
vation that the rate of the oxidative cleavage decreases with
decreasing pH. This is best illustrated by figure 7.14., in
which the oxygen consumption is given as a function of time. The
first part of the curves corresponds {mainly) to the oxi~ation
of D-gluconic acid to 2-keto-D-gluconic acid, and the second part
corresponds (mainly) to the oxidative splitting of 2-keto-D
gluconic acid. The difference in slope in the second part for the
various pH's demonstrates clearly that the rate of oxidative
cleavage decreases with decreasing pH.
eo
O'
" 60 E c 2 Q. E 40 :I II> c 0 u c ..
20 "' >-" 0
1 1.s time (kst
.. pll
o pa
a pa
143
9
B
7
figure 7.14. Inftuence of the pH on the oxygen consumption for the oxidation of D-gtuconic acid with a Pb/Pt/C catatyst
7.5. Inftuence of the temperature
As a number of competing reactions are involved that most
likely have different energies of activation, a study of the
influence of the temperature on the course of the oxidation of
D-gluconic acid may yield valuable information. Experiments were
carried out at pH 7 and in the temperature range from 36-65°c.
The other reaction conditions were standard. The same regenerated
Pb/Pt/C catalyst is used as in the previous experiments (section
7.4.). That the overall reaction rate increases with increasing
temperature can be derived from figure 7.15. In these experiments
again an active period is followed by a less active period. The
latter is, according to earlier findings, caused by a too high
oxygen concentration in the liquid phase. As the maximal oxygen
transfer rate was hardly temperature dependent within the range
examined, as follows from the data for the first 300 seconds of
figure 7.16., and as the oxidation of D-gluconic acid probably is
144
0 .2 ·• . e time ( ltst
.e
oT = 56.2_0 c
AT = 45.6°C
a T = 36. 2<>c
figure 7.15. D-gluaonic acid concentration (logarithmic saale) as a function of time with the temperature as parameter
g 30
E c ·8 a. 20 E " .. c: 0 u c: .. 10
"' ,.. .. 0
0 ·2 ... ·6
time ; ks 1 ·8
OT = 56.2°C
AT = 45,,6°C
gT = 36.2°C
figure 7.18. Influence of the temperature on the o~ygen consumption
first order in D-gluconic acid, a higher reaction rate constant per unit of reaction volwne will result in a lower concentration of D-gluconic acid at the moment that the oxygen concentration in the liquid phase deflects substantially from zero.
145
Or put in another way, as the reaction rates are initially
limited by oxygen mass transfer from the gas phase, and therefore
rather independent of the temperature, the higher values of
the reaction rate constants at the higher temperature are
compensated by corresponding lower oxygen concentrations in the
solutions. This lower oxygen concentration results in less de
activation as can be seen in figure 7.15., where the high acti
vity is maintained longest for the highest temperature.
.2 ·• .e .e conversion 1- l
OT = 56~2°C
AT = 45.6°C
a T = 36.2°C
figure ?.1?. Inftuenae of the temperature on the seteativity C2 for the oxidation of D-gtuaonia aaid with a Pb/Pt/C aatatyst
From the fact that the selectivity for oxidation at c2 is hardly temperature dependent (figure 7.17.) can be concluded
that the activation energies for the various oxidation reactions
of D-gluconic acid do not differ to an appreciable extent.
At high conversion the selectivity decrease is noticeable at
a slightly .lower conversion when the reaction temperature is
lower. This is in accordance with our observation that the
deactivation of the catalyst is accompanied with a decrease in
selectivity.
146
7.6. PPoduat distPibution
In chapter 6 and in the previous sections of this chapter
we have mainly discussed the two main components of the reaction
mixture, viz. D-gluconic acid, the reactant, and 2-keto~D-glu
conic acid, the main product, and to a lesser extent oxalic acid, a product of the oxidative cleavage. In figure 7.18. the
~ 15 E
1 1.5 time (ks>
4 9uluronic acid
°' S-keto-D-9luconic acid
o tartronic acid
D 9lucari~ acid
v ta Ttar ic acid
figuPe 7.18. By-pPoduat distPibution foP the o~idation of D-gluaonia acid with a standaPd Pb/Pt/C catalyst at standaPd Peaation conditions
concentrations of the identified products formed by side and
consecutive reactions are given as a function of time for an experiment under standard conditions applying a standard catalyst.
The corresponding information of the main components is given in
figure 6.2. These results illustrate that D-gluconic acid is
oxidized, not only at c2 , but also to a lesser extent at c6 ,
producing L-guluronic acid (GLZ) and D-glucaric acid (GAZ), and
at c5 , producing 5-keto-D-gluconic acid (SKGOZ). Besides these
products, also chain cleavage products other than oxalic acid,
like tartaric acid (TAA) and tartronic acid (TA) are formed.
147
In the concentration of L-guluronic acid, D-glucaric
acid and 5-keto-D-gluconic acid a maximum occurs. This means
that these components are oxidized further. L-guluronic acid
is transformed into D-glucaric acid. This is in agreement with
our results on the oxidation of D-glucuronic acid (section 6.6.).
D-glucaric acid most probably produces a-keto-D-glucaric acid.
In the chromatograms one finds indeed a peak that probably corresponds to this product. In order to check this, we have
oxidized D-glucaric acid with a standard Pb/Pt/C catalyst
under standard conditions. Liquid chromatography shows that D-glucaric acid is indeed the precursor of the product under
investigation. As this acid has two free a-hydroxyl groups and
the catalyst is selective for the oxidation of free a-hydroxyl
groups, it is most probable that indeed a-keto-D-glucaric acid is
this product. Further identification (by 13c-NMR) is in progress.
The 5-keto-D-gluconic acid can, in analogy to 2-keto-D
gluconic acid, be oxidized further by carbon chain cleavage,
producing glycolic acid and a c 4 uronic acid or dicarboxylic acid. Another possibility is the reaction to 5-keto-D-glucaric
acid or 2,5-diketo-D-gluconic acid. Indeed the presence of small amount of 2,5-diketo-D-gluconic acid, kindly supplied by
dr. T.C. Crawford of Pfizer Inc., Groton, Connecticut, were
demonstrated in the reaction samples, but these can also result
from 2-keto-D-gluconic acid. carbon dioxide is also a by-product formed. At the standard
operating pH, it is mainly present in the form of bicarbonate.
This is, however, not detected at our liquid chromatographic
analysis. Therefore we (occasionally) determined its concentration as follows: The reaction mixture is acidified, the carbon
dioxide formed is stripped from the solution. with nitrogen and
absorbed in a standard solution of sodium hydroxide. The concen
tration is determined by titration with hydrochloric acid. The oxidative cleavage of 2-keto-D-gluconic acid is always
accompanied by a systematic deficit in the mass balance. In the
previous sections we have seen that oxalic acid is one of the
148
products of the cleavage of the carbon chain. Besides this c2 fragment another fragment must be formed. In first instance this
most probably is a c4 fragment. The expected c4 fragment either
is D-erythrose or D-erythronic acid. As the latter can be detec
ted with our analytical system, but is hardly found in the
reaction samples, two possibilities arise:
(a) The c4 fragment is indeed D-erythrose, a product that is not
detected at our analytical system
(b) An intermediate product is (very) strongiy adsorbed on the
catalyst If possibility (a) is true, then the c6-balance must be constant
if oxalic acid is calculated as if it possesses 6 carbon atoms
instead of 2. In figure 7.19. this modified c6-balance is
250 +------'"---~.,...---"----'-----t
230
.... 0 ~ 210
~ ; 190
ii ~ 8 170
(c6
total] + a•(oxalic acid]
--=~~~~ ~ ----~- \
150 +---~,...--......----.---..---0 ·•
[ catalystl 40 g/l
o a = o A a = 2/3
(catalystl 10 9/l
<O a = O
o a • 2/3
figure 7.19. [Cs totail and [Cs totail + 2/3 [ox] as a funation of the aonversion with the aatalyst aonaentration as parameter
compared to the usual c6-balance for the experiments with 40 g/l
catalyst and 10 g/l catalyst (section 7.2.). These results in~
dicate that indeed, in certain cases, at the oxidative splitting
of 2-keto-D-gluconic acid., besides oxalic acid a C 4 fragment is
formed that is not detected. We tentatively assume this c4 frag
ment to be D-erythrose.
To study the above oxidative cleavage in more detail, we
149
have oxidized a purified reaction mixture, that almost exclusively
contained 2-keto-D-gluconic acid,with 40 g/l of fresh Pb/Pt/C
catalyst. In this experiment the ratio of the increase of the
oxalic acid concentration and the decrease of the 2-keto-D
gluconic acid concentration rose slightly from 1.7 initially
to 2.2 after a conversion of 76%. At the latter conversion the
mass deficit amounted about 19%. This is roughly in agreement
with the mass deficit from the reaction 1 c6 + 2.2 c2 • The fact
that the above described ratio is higher than 1 and increases
with the conversion, indicates that at the cleavage of the
carbon chain of 2-keto-D-gluconic acid between c2 and c3 most
probably an aldehydic c4 fragment is formed, that on its turn
is rather slowly oxidized and thereafter also split between
c2 and c3 at which oxalic acid and an aldehydic c2 fragment
is formed. That the above ratio reaches values higher than 2
means that the remaining aldehydic c2 fragment must also partly be oxidized to oxalic acid. This observation thus supports our
assumption that the mass deficit is caused by the formation of
non-acidic products that are not detected at our ana,lytical system. That the above ratio is initially higher than 1 means
that the oxidation of D-erythrose on a fresh catalyst is much
faster than on a deactivated catalyst. On the basis of the above considerations, and the assumption
that not yet identified products in our reaction samples are
D-erythronic acid and 2-keto-D-erythronic acid, the following
scheme for the cracking of 2-keto-D-gluconic acid is proposed:
1.?ott T""°
aor-H Hr-OH
H""';-Otl CH 20H
2-keto-oqluconic ac14
oxalic acid
1-~ H--C-OH
1i-~-OH
CH 20H
D-erythrose
,o 7-oH C-Ol! •o
f'~H H-('.-OH
H-f-oH CH 200
o-erythronic acid
. \
,o ~-()II c-u 'o
qlycoxilie acid
"° ~-OR
HJ:~ Cu2oa
2-keto .. l)oo erythronlc
acid
9lycolic acid
oxalic acid
.J· \ o,
150
This scheme shows that at the very end, l mol of 2-keto-D
gluconic acid is oxidatively degraded to 3 mol oxalic acid.
For 5-keto-D-gluconic acid an analogous chain cleavage
pattern can be formulated:
,,.0 C-OH
I H-C-OH
I HO-C-H
I H-C-OH
I C=O
' CH 20H
~-keto-ogluconic
acid
"'° C-OH I
H-C-OH I
HO-C-H I
C-H "o
'L-threuronic acid
+
glycolic acid
' H-C-OH I
OH-C-H I
<;;OH 'o
tartaric acid
It is evident that the resulting tartaric acid and gly
colic acid can be oxidized too, but as 5-keto-D-gluconic acid
is only formed in small amounts, these consecutive products
are of minor importance.
In chapter 3 we have discussed the analytical results
(figures 3.6., 3.8. and 3.11.) of a fraction collected from
a reaction mixture of the oxidation of D-gluconic acid with a
Pb/Pt/C catalyst applying starting procedure A (section 6.7.).
These results demonstrate that besides the usual products also
smaller monocarboxylic acids are formed: D-glyceric acid,
glycolic acid and possibly a small amount of D-erythronic acid.
This indicates that deactivation of the Pb/Pt/C catalyst makes
it less selective for oxidation at c2 in favour of chain
cleavage.
The above results are summarized in the following general reaction scheme:
,0 ~-OH
H-~-OH
HO-~-H
H-1-oH H-~-OH
CH20H
D-9 l ucon ic actd
<!.o '--oH
'i'"" HO-~-H
H-C-OH
H~-OH CH20H
2-keto-o-9luconic acid
,o <;-OH
H-~-OH
HO-~-H
H-~-OH
1""0 CH20H
:.-keto-D-9luconic
acid
J) ~-OH
H-~-OH
H0-1-H
H-<;-OH
H~-OH
C-H
' 0
L-guluronJ.c acid
<je,H
~"'° cha.in HO-c-H cleavage H~-oH ........,.. products
~=o CH20H
2, 5-di-keto-ogluconic acid
~~OH H•C-OH
00-~-H
u1-0H H-C-OH
C-oH 'o
D-qlucarJ.c acid
chain cleavage products
oxalic acid
1f0oH h-~-OH
tt-<;-OH
CH2ou
o-erythronic acid
,o ~-OH
u-q-oH HO-C-H
C~u
tartaric acid
glycolic add
.o ~-OH
~"'0 H-<;-OH
CH20H
2-keto-ocrythronic acid
chain cJ.eavaqe products
--[ ... : .. ,o 1-0H CH 20H
glycolic acid
,..... U1 ,.....
152
References
1. Dirkx, J.M.H., Ph. D. thesis, University of Technology,
Eindhoven, The Netherlands (1977) 2. Ostennaier, J.J., Katzer, J.R., Manogue, W.H., J. Catal.,
!!1 277 (1976) 3. Perry, R.H., Chilton, C.H., "Chemical Engineers's Handbook",
(5th ed.), Ch. 3, p. 98, Mc Graw-Hill Kogakusha, Ltd.,
Tokyo ( 1 9 7 3 )
153
Chapter 8
Final Discussion
8.1. Introduction
In chapter 6 and 7 we have presented our study on the
potential of a Pb3 (P04) 2/Pt/C system as a selective catalyst in
the oxidation of aldonic acids in aqueous media. This first study
had as main objective the delineation of the catalyst properties. In this chapter the characteristics of this system will be in
corporated in a tentative proposal for the reaction mechanism
(section 8.3). A literatury study concerning the complexation of
D-gluconic acid with lead(II), as presented in section 8.2,,
resulted in useful information for the deduction of the adsorp
tion of the substrate on the catalyst. In section 8.4. a discussion on the kinetics of the reaction is given. Potential appli
cations of the Pb/Pt/C catalyst are presented in section 8.5.
8.2. Coordination of Pb 2+ with D-gluaonia acid
In the preceeding two chapters we have discussed that in the
reaction mixtures the lead(II) of the Pb3 (P04) 2/Pt/C catalyst
system can occur as the following species:
a. adsorbed as lead(II)phosphate in the direct vicinity of the
platinum crystallites, and probably bound to the platinum part
154
of the catalyst (Pb-Pt ensembles) •
b. adsorbed as Pb3 (P04J 2 not in the direct vicinity of the
platinum. 2+
c. dissolved, either as coordinated or as free Pb •
The lead(II) species not in the direct vicinity of platinum
are catalytically not active (section 6.3.3.), and the concen
trations of the dissolved species are so low (sections 6.3.2.
and 6.3.3.) that it is unlikely that they play an important role
in the conversion. From the fact that Pt/C without lead (chapter
5) has a much different effect on the oxidation of D-gluconic
acid than the Pb3 (Po4 J2/Pt/C catalyst formulation, we concluded
that the lead-platinum ensembles are responsible for the charac
teristic properties of the modified Pt/C catalyst.
The substrate must be activated and positioned in such a way
in relation to the hydrogen abstracting platinum site of the
catalyst that this abstraction occurs preferentially at the
second carbon atom. We assume that this is caused by the specific
interaction between the substrate and the lead of the catalyst
system. The literature on the complexation of D-gluconic acid
with bivalent lead yields the followin9 information:
Pecsok and Juvet (1) have studied the gluconate complexes
with lead(II). With a combination of optical rotation and polaro
graphic measurements they proved the existence of a number of
lead-gluconate complexes. Both Pecsok and Juvet (1) and Coccioli
and Vicedomini (2,3) have determined the stability constants for
the various species present. According to them the following
species can occur: + *l A 1:1 species (PbGH4 ) and a 1:2 species (Pb(GH4> 2> are
present in the pH range 1-6. In the pH range 5-10 one solid lead
*) In this chapter we depict D-gluconic acid, in accordance with
the coordination chemistry literature, as HGH4 • The first H
refers to the hydrogen of the carboxyl function and the other
four H's refer to the hydrogens of the four secondary hydroxyl
groups.
gluconate complex or a mixture of. different solid complexes is
formed at a lead gluconate ratio of about 1. At a pH above 10
a 2:2 (Pb 2 (GH2 l 2- 2) and a 3:2 species. exist.
155
According to Carel! and Olin (4,5) lead(II) hydroxyl com
plex species can also be present. In acid solution the hydroxyl
ion concentration is too low for the formation of such species.
At higher pH's, however, the latter authors have demonstrated,
in the absence of gluconate, the existence of Pb(OH)x (2-x)
species in which x is the average number of hydroxyl ions
coordinated per Pb 2+ ion. This number rises from 0 (only
coordination with H2o) at about pH 6, to 3 at pH 13. Based on these results it is to be expected that, especially at higher
pH's, a competition will occur between the above two ligands,
viz. the gluconate ion and the hydroxyl ion. Indeed Coccioli 2- 2-and Vicedomini (3) have found Pb(GH 2) (OH) and PB 2 (GH) (OH) 2
species in strongly alkaline medium. Melsqn and Pickering (6)
have demonstrated that also at a lower pH hydroxyl functions can be incorporated into a lead gluconate species, by precipitating
the lead hydroxyl gluconate salt Pb 2 (GH4 ) 2 (0H) 2 by adding sodium
hydroxide slowly to a 1:1 lead gluconate solution until the pH reached 7.3.
The above data refer mainly to dissolved lead species. In
our experiments, however, the lead(II) is mainly deposited on
the catalyst surface. Therefore there might be geometric limitations to the interaction with the substrate. Nevertheless, one
might expect that the interactions that occur on the catalysts
will show types of bounding that are comparable to those found in
the complexes in homogeneous solution. As we have carried out our oxidations mainly in the pH range
of 5-9 we will examine the types of species present at these conditions in more detail. The authors mentioned (1-6),reported for
relatively high Pb 2+/gluconate ratio's the formation of a preci
pitate in neutral solution. However, we have found that if we 2+ add to the substrate solution, as Pb , the small amount of lead
present in our catalyst system, no precipitation occured. Based
on this observation, one would expect that the gluconate species
156
formed on the active sites of our catalyst are not irreversibly
adsorbed. This is in agreement with the results of our oxidations.
From the stability constants reported for the various lead
complexes it can be calculated that under the conditions of our
experiments, pH 5-9, lead(II) complexation with gluconate is
more likely than with hydroxyl.
Brannan and Sawyer (7,8) claim, on basis of unpublished NMR data, that in neutral solution the lead is bonded to the carboxy
late group and the a-oxygen. They have demonstrated that in alkaline medium (pH 11-13) also they-oxygen is involved. Isbell's
optical rotation measurements and Melson and Pickering's (6) infrared data in combination w:iith Littleton's (11) X-ray data of the lead alkali salt of D-gluconic acid support the conclusion that the a-oxygen is bonded to the lead ion. With respect to the Bi/Pt/C catalyst one might note that the above NMR study (7)
indicates that also in the 1:1 bismuth gluconate complex the bonding involves the carboxylate and the a-oxygen of the ligand and possibly, to a small extent, the carboxylate and $-oxygen.
Coccioli and Vicedomini (3) have determined the following dissociation equilibria for the D-gluconate anion at 25 °c in 1 M Nac104 solution:
+H2o GH 2- + - ____,,.
GH4 3 + H30 13.66 + 0.08
-H20
GH 2-+H20
GH 3- + H O+ 3 2 3 14.06 + 0.10
-H20
The fact that, at a pH as low as 10.5 (1,9), the hydroxyl functions involved in complex formation already start to dissociate, indicates that complex formation facilitates this dis
sociation. The information presented above can be accomodated by the
following structure of a dissolved lead gluconate species, that
157
could occur at our reaction conditions:
fl gO c-o ~
H-d-o ~Pb ----bo I 'H I 'H
HO-C-H HO-C-H I I
H-C-OH H-C-OH I I
H-C-OH H-C-OH I I
CH20H CH20H
As mentioned earlier, such a 1:2 lead gluconate complex is,
because of geometric limitations, rather unlikely at the cata
lyst surface, but one might perhaps expect an adsorbed species of
the following kind:
HOHH H 0'\\ I I I I
,c-~-9-9-9-cH2oH 0 0 H OHCE \ I \·
\ I H \I
0 Pb 0
I /\ I O-P-0 O-P-0
JI
0 II
0
8.S. Reaation meahanism
The experimental evidence presented in this thesis is
insufficient to decide unequivocally for one special reaction mechanism. To that end further studies are required. It is clear
that these investigations will not be easy, because we have as
yet not been able to maintain an. active catalyst under conditions where oxygen transfer from the gas phase is not limiting. The
following discussion regarding the reaction mechanism must there
fore be considered as a first approximation only.
158
In section 5.1. we came to the conclusion that the oxidation
of D:-gluconic acid on a Pt/C catalyst probably follows a dehydrogenation mechanism. We would suggest that the oxidation of the
same substrate on a Pb/Pt/C catalyst is also a dehydrogenation
reaction. De Wit et al. (11,12) have shown that the reaction of
reducing sugars, e.g. D-glucose, on a Pt/C catalyst in an alkaline
medium (pH 12-13) and in the absence of oxygen is a dehydrogena
tion reaction that can be depicted as:
The reaction proceeds via the glucose anion, and the rupture of
the carbon-hydrogen bond on c1 is the rate-determining step. In section 8.2. we have already discussed the existance of
lead-platinum ensembles. In the molecular model shown below it
is suggested that, on the analogy of the model of the Delft group
(12), in our case gluconate can complex with the lead in such a way that the hydrogen on c2 is located favourably for abstraction. Moreover.the coordination with Pb(II) is considered to enhance
the ability of the H at c2 to be transferred as a hydride ion.
As has been pointed out in the previous section the hydroxyl
group on c2 is probably not yet dissociated, but due to complex formation the hydrogen oxygen bond is weakened. Therefore we prefer a mechanism in which the dissociation and the hydride
transfer are concerted processes, as is depicted below.
We further suggest that, on the analogy of the D-glucose
oxidation, here these two concerted reactions determine together
the rate of the oxidation of D-gluconic acid. This is in agreement
with our observations that in the active period of the catalyst
159
e --~r 9--;;? x H :Z:-.0 ,,,- ' (' r
.. KJ ~.
.. I
Pb Pt
the reaction rate is probably first order in catalyst (section
7.2.) and in gluconate (section 7.2.), and zero order in oxygen ~xcept at very low oxygen concentrations (section 7.2.) • In the
latter case the catalyst may become covered with hydrogen, which
will stop further dehydrogenation. The reaction rate then will
be determined by the oxygen supply and presumably be first order
in the oxygen gas pressure. This is in agreement with the results of the experiments with air and pure oxygen (section 7.3.).
The driving force for the dehydrogenation is probably the enhancement of the hydroxyl dissociation which activates the c2-H bond, in combination with the favoured position of the c2 hydrogen towards the platinum site. This explaines the high selectivity for oxidation at c 2 and also ~he observation that the reaction rate on a Pb/Pt/C catalyst is higher than on a Pt/C
catalyst with the same platinum content.
After reaction the product (2-keto-D-gluconic acid) will
desorb and the hemiacetal ring will be formed. Unfortunately we
have no data on the coordination of 2-keto-D-gluconic acid with
160
Pb(II) to predict the competition between the main product and
the substrate in the coordination with the lead(I1) on the catalyst and in the solution.
The influence of the pH on the reaction rate (section 7.4.) can possibly be explained by the increase in degree of dis
sociation of the hydroxyl group at c2 with increasing pH, thus
facilitating the hydride abstraction. However, it must be kept in mind that at relatively high pH's hydroxyl complexation of the lead on the catalyst can compete with the D-gluconic acid coordination.
The cause of the deactivation of the Pb/Pt/C catalyst is uncertain. There are strong indications that the deactivation starts when the oxygen concentration in the liquid phase rises significantly above zero (section 7.3.). This could result in a change of the lead site and/or the platinum site. A change of the platinum site could possibly be the chemisorption of oxygen on this site as suggested by Dirkx for the oxygen deactivation of
Pt/C catalysts in carbohydrate oxidation (13), or a real chemical reaction to a less active site. As was discussed in section 6.6.,
the adsorption of certain reaction products 6n especially the
lead-platinum ensembles is probably another cause of deactivation.
8.4. Kinetics of the D-~iuconic acid oxidation with a
Pb/Pt/C catatyet
As demonstrated in section 7.3. with three experiments at different substrate concentrations, it is not possible to determine the reaction rate constants in the normal way. This is due to the fast deactivation of the catalyst as soon as the oxygen concentration in the liquid phase rises substantially above zero. At the reaction conditions applied up to now, we have provided for
such low oxygen concentrations by limiting the oxygen transfer
from the gas- to the liquid phase. This, however, did also limit
161
the reaction rate, so the data obtained in this way cannot be
used to calculate reaction rate constants. It follows from these
considerations that it will only be possible to determine the
kinetics if either of the following two constraints are satis
fied:
1. The oxygen transfer from the gas- to the liquid phase must
not limit the overall reaction rate.
2a. The oxygen concentration in the liquid phase must be very
low, or
2b. Ways and means are to be found to maintain the activity of
the catalyst at near equilibrium oxygen concentration in the
solution.
As far as the first mentioned two constraints are concerned,
these seem at first sight to be contradictory, but a combination
with the second possibility may be feasible. If we would use a
low oxygen partial pressure of the oxidation gas mixture in
combination with a very high kL.a (see formula 7.1), i.e. a very
high stirrer speed, and with a low catalyst concentration, it
could be possible to fulfil the above constraints. A further
possibility lies in the search for more stable Pb/Pt/C catalysts.
To this end the deactivation mechanism must be studied in-detail.
8.5. Applications of the Pb/Pt/C catalyst
In the introduction (section 1.3.) we have already discussed
the use of the Pb/Pt/C cai:alyst in the manufacture of iso
vitamine C, a very good anti-oxidant in e.g. food, and 2-carboxy
D-gluconic acid, a potential phosphate substitute in detergent
formulations.
Besides these two appl:ications, there seems to be another
important industrial application, viz. an alternative route for
the manufacture of vitamin C, as proposed by Kuster and Godefroi
(14) :
162
starch
methyl-«-O-glucoside
<f H20H H-C-OH
I HO-C-H
I H-C-OH
I H-C-OH
I COCH
L-gulonic acid
L-ascorbic acid
(vitamin Cl
Pt/C
H I
CH 3o-c -----i H-~-OH I
HO-C-H 0
H-~-OH I H-C__j
I COOH
methyl-u-0-glucoronide
Pb/Pt/C
?H20H H-C-OH
I HO-C-H
I H-C-OH
I C=O I COCH
2-keto-L-gulonic acid
To underline the industrial interest for the method, described
in this thesis, for the manufacture of a-keto-carboxylic acids
with the aid of Pb/Pt/C catalysts, it may be mentioned that a
Dutch patent has been applied for this procedure by Akzo N.V.
References
1. Pecsok, R.L., Juvet, R.S., J.Am.Chem.Soc., 78, 3967 (1956)
2. Coccioli, F., Vicedomini, M., J.Inorg.Nucl.Chem., 40, 2103 (1978)
3. ibid., 40, 2106 (1978)
4. Olin, A., Acta Chem. Scand., 14, 126 (1960)
5. Carell, B., Olin, A., Acta Chem. Scand., .!!• 1999 (1960)
6. Melson, G.A.,Pickering, W.F., Aust.J.Chem., 3,! 1 2889 (1968)
7. Brannan, J.R., Sawyer, D.T., unpublished results
8. Sawyer, D.T., Chem.Rev., 64, 633 (1964)
Sawyer, D.T. I Brannan, J .R. I Inorg .Chem., ~I 65 (1966)
Isbell, H. s. I J.Res.Natl.Bur.Std., 14, 305 . (1935)
163
9.
10.
11. De Wit, G. I De Vlieger, J .J., Kock-van Dalen, A.C. I Kieboom,
12.
A.P.G., Van Bekkum, H. I Tetrahedron Lett., 15, 1327 (1978) De Wit, G., De Vlieger, J.J., Kock-van Dalen, A.C., l~eus, R. I
Laroy, R., Van Hengstum, A.J., Kieboom, A.P.G., van Bekkum,
H., Carbohydr.Res., 91, 125 (1981)
13. Dirkx, J.M.H., Ph.D.Thesis, Eindhoven University of Technology,
Eindhoven, The Netherlands {1977)
14. Kuster, B.F.M., Godefroi, E.F., Internal report, Eindhoven
University of Technology, Eindhoven, The Netherlands, {1982).
Appendix I: Structure formulas
-?o C-H I
HO-C-H I
H-C-OH I
H-C-OH I
H-C-OH . I
H
D-arabi-
nose
p C-OH I
H-C-OH I
HO-C-H I
HO-C-H I
H-C-OH I
H-C-OH I H
D-galacto
nic acid
,p C~H I
HO-C-H I
HO-C-H I
H-C-OH I
HO-C-H I C-OH
" L-guluro
nic acid
p C-OH I
HO-C-H I
H-C-OH I
H-C-OH I
H-C-OH I
H
D-arabi
nonic acid
0 c!oe I
H-C-OH I
HO-C-H I
H-C-OH I
H-C-OH I C-OH ~
D-glucaric
acid
0 c!oH I
H-C-OH I H
glycolic
acid
H I
H-C-OH I C=O I
HO-C-H I
H-C-OH I
H-C-OH
' H-C-OH I H
D-fructose
0 c!u I
H-C-OH I
HO-C-H I
H-C-OH I
H-C-OH I C-OH ~o
D-glucuro
nic acid
p C-OH I
H-C-OH I
HO-C-H I
H-C-OH I
H-C-OH I
H-C-OH I H
D-gluconic
acid
.P c!:.e I
H-C-OH I
HO-C-H I
HO-C-H I
H-C-OH I
H-C-OH I H
D-galactose.
p C-H I
H-C-OH I
HO-C-H I
H-C-OH I
H-C-OH I
H-C-OH I H
D-glucose
p Cloe I C=O I
H-C-OH I
H-C-OH I
H-C-OH I H
2-keto-D-
arabinonic
acid
165
166
~o C~OH
~o C~OH
~o C-oe
?o C-OH
I I I I C=O C=O H-C-OH C=O I I I I
HO-C-H HO-C-H HO-C-H HO-C-H I I I I
HO-C-H H-C-OH H-C-OH H-C-OH I I I I
H-C-OH H-C-OH C=O HO-C-H I I I I
H-C-OH H-C-OH H-C-OH H-C-OH I I I I
H H H H
2-keto-D- 2-keto-D- 5-keto-D- 2-keto-L-
galactonic gluconic gluconic gulonic acid
acid acid acid
c!0oe p I
HO-C-H ~o
C-OH I I
HO-C-H H-C-OH C~OH H-C-OH I ~ I I
H-C-OH C-OH C-OH I ~ ~ HO-C-H I
H-C-OH I H
L-gulonic formic oxalic tartronic
acid acid acid acid
COOH I
CHOH I
CHOH I
COOH
tartaric
acid
167
Summary
This thesis deals with the selective oxidation of D-glucose
and D-gluconic acid to 2-keto-D-gluconic acid with oxygen in
neutral or weak alkaline aqueous medium with the aid of a plati
num on carbon catalyst that has been modified by addition of an
ins.oluble lead (II) salt. We also report on our endeavours to
improve the manufacture of D-glucaric acid from D-gluconic acid.
D-Glucaric acid and 2-keto-D-gluconic acid are industrially
interesting products. The former and 2-carboxy-D-gluconic acid,
that can be made out of 2-keto-D-gluconic acid, are potential
alternatives for the polyphosphates in detergent formulations.
!so-vitamin C, another product that can be manufactured from
2-keto-D-gluconic acid, can serve as anti-oxidant in e.g. food.
Further a survey of the literature concerning the preparation of
D-gluconic acid, D-glucaric acid and 2-keto-D-gluconic acid is
presented.
Much attention has been directed to the analysis of the
substrates and their products. Ion-exchange chromatography was used successfully for this purpose. At times isothachophoresis, preparative liquid chromatography in combination with 13c-nuclear
magnetic resonance spectroscopy, and a specific detection method
for a-keto acids were applied to obtain additional information.
For the present investigations a batch-wise operated stirred
tank reactor is used. The copper(II) and cobalt(II) compounds and
complexes testes as catalyst for the oxidation of D-gluconic acid,
did not result in the production of D-glucaric acid, but some of
them did catalyze the degradation of D-gluconic acid. The oxida-
168
tion of borate. gluconate esters with a Pt/C catalyst at pH 8-10
and borate/gluconate ratios of land 2 did not result in an
industrially interesting approach for manufacturing D-glucaric
acid. In the Pt/C catalyzed oxidation of D-gluconic acid the selectivity for D-glucaric acid and the reaction rate decreases
with decreasing pH. However, below pH 3.5 the selectivity and reaction rate increases again. Both improvements are, however, not great.
More positive results are obtained by the deposition of a lead(II) compound (e.g. Pb 3 (P04) 2) on Pt/C. This results in a catalyst with which aldoses or aldonic acid can be oxidized with oxygen to the corresponding a-keto-aldonic acids with a high
selectivity (about 90%) • The ratio for oxidation of D-gluconic acid at c2 compared to c6 is about a factor 150 higher for the modified Pt/C catalyst than for the normal Pt/C catalyst. Leadplatinum ensembles are probably the catalytically active species
of the Pb/Pt/C catalyst. This modified catalyst is also more active than the normal Pt/C catalyst. A Pb/Pt ratio of about 0.2 is enough to obtain the maximal selectivity for 2-keto-D-gluconic acid, indicating that with this ratio the optimal lead platinum
surface modification is already obtained. The Pb/Pt/C catalyst deactivates very fast (within a few
minutes) when the oxygen concentration in the liquid phase rises substantially above zero. Adsorption of certain products, probably on the lead-platinum ensembles, also causes deactivation of the catalyst.
With the addition of copper(II) acetate and especially bismuth(III) hydroxyde to a Pt/C catalyst also an improved selectivity for oxidation at the a-carbon is found. As lead(II), copper(II) and bismuth(III) all form complexes with D-gluconic acid in which both the carboxylate function and the a-hydroxyl group are involved, the observations on Cu(II) and Bi(III) support our notion that such complexes also play a role in the catalysis of the Pb/Pt/C catalyst. This complex formation leads
to enhanced ionization of the hydroxyl function at c2 • Due to the
juxtaposition of the lead(II) and the platinum on the catalyst,
169
and the negative charge of the oxygen on c2 , hydride transfer
from this carbon atom to the platinum is facilitated. Based on the observations that the reaction is probably first order in catalyst and D-gluconate and zero-order in oxygen (except at very low oxygen concentrations), we postulate that the hydride abstraction and the ionization of the a-hydroxyl function determine together the rate of the reaction.
170
Samenvatting
Dit proefschrift beschrijft de selectieve oxydatie van
D-glucose en D-gluconzuur tot 2-keto-D-gluconzuur met zuurstof
in neutraal of zwak alkalisch waterig milieu met behulp van een
platina op kool katalysator die gemodificeerd is door toevoeging van een onoplosbaar lood(II) zout. We berichten ook over onze
inspanningen om de bereiding van D-glucaarzuur uit D-gluconzuur
te verbeteren.
D-Glucaarzuur en 2-keto-D-gluconzuur zijn industrieel
interessanteprodukten. De eerste en 2-carboxy-D-gluconzuur, dat
gemaakt kan worden uit 2-keto-D-gluconzuur, zijn potentiele
alternatieven voor de polyfosfaten in de wasmiddel formuleringen.
Iso-vitamine C, een ander produkt dat bereid kan worden uit
2-keto-D-gluconzuur, kan dienen als ant:L-oxydant in bijv. voedsel.
Verder is een overzicht van de literatuur betreffende de berei
ding van D-gluconzuur, D-glucaarzuur en 2-keto-D-gluconzuur gegeven.
Er is veel aandacht geschonken aan de analyse van zowel de substraten als hun produkten. Ionenwisselings-chromatografie werd met succes toegepast voor dit doel. Bij gelegenheid werden ook isotachoforese, preparatieve vloeistofchromatografie in
kombinatie met 13c-kernspin-resonantie spektroskopie en een specifieke detektie-methode voor a-keto zuren gebruikt voor het
verkrijgen van additionele informatie.
Voor het onderzoek werd een ladingsgewijs bedreven geroerde
tank reactor gebruikt. De als katalysator geteste koper(II) en
cobalt(!!} verbindingen en komplexen voor de oxidatie van
171
D-gluconzuur, resulteerden niet in de produktie van D-glucaar
zuur, maar enkele katalyseerden wel de degradatie. van D:-glucon
zuur. De oxidatie van boraat-gluconaat esters met een Pt/C
katalysator bij pH 8-10 en boraat/gluconaat·verhouding van 1 en
2 resulteerde niet in een industrieel interessante benadering
van de fabrikage van D-glucaarzuur. Bij de platina op kool
gekatalyseerde oxydatie van D-gluconzuur daalt de selektiviteit
voor D-glucaarzuur en de reaktiesnelheid met dalende pH. Echter
beneden pH 3,5 stijgen de selektiviteit en de reaktiesnelheid
weer. Beide verbeteringen zijn echter niet groot.
Positievere resultaten worden verkregen door het neerslaan
van een lood(II) verbinding (bijv. Pb 3 (P04 ) 2) op Pt/C. Dit levert
een katalysator waarmee aldoses en aldonzuren met een hoge selek-·
tiviteit (ongeveer 90%) met zuurstof geoxydeerd kunnen worden tot
de korresponderende a-keto-aldonzuren. De verhouding voor de oxydatie van D-gluconzuur op c2 ten opzichte van c6 is ongeveer
een faktor 150 hoger voor de gemodificeerde Pt/C katalysator dan
voor de normale Pt/C katalysator. Waarschijnlijk zijn lood
platina ensembles de katalytisch aktieve species van de Pb/Pt/C katalysator. Deze gemodificeerde katalysator is ook aktiever dan
de gewone Pt/C katalysator. Een Pb/Pt verhouding van ongeveer 0,2
is voldoende om de maximale selektiviteit voor 2-keto-D-glucon
zuur te verkrijgen, wat er op wijst dat. bij deze verhouding al de
optimale lood-platina oppervlakte-modifikatie is bereikt. De Pb/Pt/C deaktiveert erg snel (binnen enkele minuten) als
de zuurstofconcentratie in de vloeistoffase substantieel boven
nul stijgt. Adsorptie van bepaalde produkten, waarschijnlijk op
de lood-platina ensembles, veroorzaakt ook deaktivering van de
katalysator. Met de toevoeging van koper(II)acetaat en bismuth(III)
hydroxyde aan een Pt/C katalysator wordt ook een verbeterde
selektiviteit voor oxydatie op het a-koolstofatoom verkregen. Daar zowel lood(II) als koper{II) als bismuth(!!!) met D-glucon
zuur komplexeren, waarbij zowel de carboxylaat funktie als de
a-hydroxyl 'C}roep zijn betrokken, ondersteunen de waarnemingen aan
Cu(II) en Bi(III) ons denkbeeld dat zulke komplexen ook een rol
172
spelen bij de katalyse van de Pb/Pt/C katalysator. Deze komplexering leidt tot sterkere dissociatie. van de hydroxyl funktie op
c2 • Door de juiste positionering. van het lood(II) en het platina op de katalys-ator, en de negatieve lading van de zuurstof op c2 ,
wordt de hydride overdracht van dit koolstofatoom naar het
platina vergemakkelijkt. Gebaseerd op de waarnemingen dat de reaktie waarschijnlijk eerste orde is in katalysator en D-gluconaat en nulde orde in zuurstof (behalve voor erg lage zuurstofconcentraties) postuleren we dat de hydride abstraktie.en de ionisatie van de a-hydroxyl funktie samen de snelheid van de reactie bepalen.
173
Dankwoord
Bet onderzoek, beschreven in dit proefschrift, is tot stand gekomen dankzij de medewerking van velen. In het bijzonder geldt
dit voor de medewerkers en studenten van de vakgroep Chemische Technologie. Aan allen hiervoor mijn hartelijke dank.
Mijn hartelijke dank gaat uit naar mijn promotoren prof. H.S. van der Baan en prof. K. van der Wiele, alsmede naar mijn co-promotor B.F.M.Kuster, voor hun stimulerende en kritische discussies die mijn werk steeds zeer ten goede zijn gekomen.
In het bijzonder dank ik heel hartelijk de heer W.P.Th. Groenland, die met zeer grote toewijding en kennis van zaken heeft meegewerkt aan het onderzoek.
Vee! dank ben ik verschuldigd aan de afstudeerders F.X.M.G. Schiffelers, M.G.M.Wolfs, C.H.M.G.Krutzen, W.R.M.Martens, R. Reintjens en H.Naus, alsook W.Brouwer, die allen met veel inzet en enthousiasme hebben meegewerkt aan het onderzoek. Eveneens dank ik de vele praktikanten en stagiaires voor hun bijdragen.
Verder ben ik dank verschuldigd aan de heren W.Bol en L.A.Th. Verhaar van de werkgroep Koolhydraten voor hun collegialiteit en interessante discussies.
De heren D.Francois, M.P.A. van der Heyden, A.G.M.Manders, G.A. van de Put en R.J.M. van der Wey dank ik voor de goede technische ondersteuning. De heer J.M.A. van Hettema voor het altijd snel afhandelen van administratieve zaken en de heer W.C.G.Heugen voor zijn behulpzaamheid die de gang van zake vaak vergemakkelijkte.
De vakgroep Instrumentele Analyse en in het bijzonder de heren F.M.Everaerts, J.C.Reijenga en Th.P.E.M.Verheggen van de werkgroep Isotachoforese, de heer A.C.Schoots van de werkgroep Vloeistofchromatografie en de heren J.W. de Haan en L.J.M. van de Ven van de werkgroep Kernspin-resonantie spektroskopie dank ik heel hartelijk voor hun adviezen en daadwerkelijke analyses van
de monsters. De diskussies met de .heren Batelaan en de Kleyn van Akzo
hebben bijgedragen tot de praktische toepasbaarheid van het in
174
het proefschrift beschreven reaktiesysteem. Mijn hartelijke dank
hiervoor.
Prof.H. van Bekkum van de T.H.Delft en prof.E.F.Godefroi
dank ik voor het snelle en concientieuze corrigeren van het
manuscript van dit proefschrift.
Mijn dank gaat verder uit naar de heer R.J.M. van der Weij
voor het vele en uitstekende tekenwerk in dit proefschrift en de
dames A.M.A. van Bemmelen en C.Rovers voor de goede verzorging
van het vele typewerk.
Gaarne maak ik van deze gelegenheid gebruik om ook famlie,
vrienden en bekenden te danken voor hun indirekte bijdragen tot
de totstandkoming van dit proefschrift.
175
Levensbericht
Peter Carolus Cornelia Smits, .geboren op 26 april 1953 te
Urmond, began na zijn eindexamen MULO-B in 1969 met de studie
Chemische Techniek aan de Hogere Technische School te Heerlen en
behaalde zijn diploma op 28 juni 1974. Na het vervullen van de
militaire dienstplicht in de periode 1974-1975, studeerde hij
Scheikundige Technologie aan de Technische Hogeschool te Eind
hoven, alwaar hij op 31 oktober 1979 met lof afstudeerde. Zijn
afstudeerwerk betrof het opstellen van een model voor de kirietiek
van de heterogeen alkalische isomerisatie van lactose in een
buisreaktor. Per 1 november 1979 trad hij in dienst van de Technische
Hogeschool te Eindhoven als wetenschappelijk assistent bij de
vakgroep Chemische Technologie, waar, onder leiding van prof.drs.
H.S. van der Baan, het in dit proefschrift beschreven onderzoek
werd verricht.
STELLINGEN
behorende bij het proef sohrift van
P.c.c. Smits
24 april 1984
1. Bij de interpretatie van de experimentele resultaten van Schwartz
et al. voor de radiale gassnelheidsdistributie in gepakte bedden
heeft Schlunder ten onrechte de wrijving aan de wand verwaarloosd.
Sahwa!'tz, C.E., Smith, J.M., Ind. Eng. Chem., !E_, 1209
(1953)
Sahlunde!', E.U., Chem. Reaction Engng. Rev. Houston,
ACS Symposium'Se!'ies, !.,?_, 111 (19?8)
2. Het door carugati et al. voorgestelde mechanisme van de chloor
vorming aan co 3o 4 geaktiveerde titaan anodes in waterige NaCl
oplossing is onwaarschijnlijk.
Carugati,A., Lodi, G., Trasatti, s., Extended abstraats
ISE 34th meeting, EPlangen, 31? (1983)
3. De conclusie van Hikita et al., dat bij de chemisch versnelde
absorptie van co2 in waterige monoethanolamine-oplossingen de
fysische oplosbaarheid van co2 toeneemt met de amine-concentratie,
wordt door hun experimenten niet gestaafd.
Hikita, H., Asai, S., Katsu, Y., Ikumo, S., A.I.Ch.E.
Jou!'nal, 25, ?93 (19?9)
4. De door Bajaj et al. berekende reaktiviteitsverhoudingen voor
de copolymerisatie van acrylonitril met 3-chloor-2-hydroxypropyl
methacrylaat in waterig milieu zijn niet consistent met hun
experimentele resultaten.
Bajaj, P., Padmanaban, M., J. Pol. Sai.: Pol. Chem. Ed.,
~. 2261 (1983)
5. De door Hearon et al. geclaimde resultaten van de hydrogenolyse
van methyl-a-D-glucuronide tot L-gulono-y-lacton in een 1% zwavel
zuur oplossing (voorbeeld 3) zijn aanvechtbaar.
Hearon, W.M., Witte, J.F., U.S. Patent 4.33?.202
(29 juni 1982)
6. Door de oxidatie van D-glucono-o-lacton met behulp van een
platina op kool katalysator in een zodanig milieu uit te voeren,
dat het lacton veel langzamer gehydrolyseerd dan geoxideerd
wordt, kan een hoge selektiviteit voor D-glucaarzuur verkregen
worden.
Dit proefs~hrift, hoofdstuk 5
7. De bewering van Dautzenberg et al. dat de propagatie stap in de
Fischer Tropsch synthese over Ru/Al2o3 , snelheidsbepalend is
berust op een verkeerde veronderstelling gezien de hoge waarde
van de Schulz-Flory constarite (a= 0.95).
F.M. Dautzenberg, J.N. HeZZe, R.A. van Santen,
H. V2rbeek, J. CataZ. 8 (1977)
S. In het hedendaagse wetenschappelijk onderwijs, waarbij specialisten door specialisten worden opgeleid is de benaming
"universiteit" niet meer op zijn plaats.
9. Om weggebruikers direkter te confronteren met de betekenis van
s.rielheid voor de verkeersveiligheid verdient het aanbeveling de eenheid "km/uur" te vervangen door "m/s".