Chapter 3
52
Chapter-3
SOCl2/β-Cyclodextrin: A New and Efficient
Catalytic System for Beckmann Rearrangement
and Dehydration of Aldoximes Under Aqueous
Condition
3.1 Introduction
3.2 Review of Literature
3.3 Present Work
3.4 Conclusion
3.5 Experimental Section
3.6 Spectral Data
3.7 References
Synthetic Communication 2013, 43 (1), 118-128.
Chapter 3
53
3.1 Introduction
The rearrangement of ketoximes to corresponding amides, known as
“Beckmann reaction or rearrangement”, is a common method in organic chemistry1
and is a topic of current interest. The Beckmann rearrangement, named after the
German chemist Ernst Otto Beckmann (1853–1923).1c
The Beckmann rearrangement
has been tremendous interest to all practicing organic chemist, as the reaction affects a
nitrogen insertion into a carbon framework. It generally proceeds through anti
migration. Beckmann rearrangement is industrially important for the manufacture of
Nylon-6 precursor, ε-caprolactum. The amide functionality is an important motif in
polymers, natural products, and pharmaceuticals.2 The amide bond is a key functional
group in organic and biological chemistry.3 Beyond conventional methods toward the
synthesis of amides,4 many alternative strategies have been reported.
5 In fact, the
development of new amide forming reactions till in demand with improvements by
the pharmaceutical industry.6
Amide has an immensely important due to its role as a privileged
pharmacophore and building block in a myriad of biomolecules as well as
pharmaceutically interesting compounds.7 The benzazepines having amide
functionality have been reported, which may be used in the treatment of certain
diabetic conditions.8 Amide derivative of Ibuprofen resulted in improved analgesic,
gastroprotective as well as anti-inflammatory activity.9 Ibuprofen heterocyclic amides
are also investigated for their analgesic and toxicological properties.10
A series of
5,5-diarylpenta-2,4-dienoicacids and their amides have been synthesized and
evaluated as antimalarial agents.11
The amides also act as precursors for the synthesis
of heterocycles like pyrimidine derivatives,12
δ-lactums,13
for the synthesis of
sulphenylated oxazolines, oxazines or tetrahydropyrroles,14
etc. Bioactive amides
moieties are shown in Figure 3.1.
Chapter 3
54
NH
NN
O
H2N
Antifungal20
HN
O
CH2OH
Amide derivative of Ibuprofen10
(Analgesic)
Cl CH CHCH CHCONH-iPr
Antimalerial11
Figure 3.1: Bioactive amide derivatives.
The nitrile functionality is a key constituent of numerous natural products and
also serves as an important synthetic intermediate for pharmaceuticals,15
agricultural
chemicals, dyes, material sciences16
and as intermediates in microbial metabolism.17
Nitriles are also products of the petrochemical industry and are widely used as
chemical solvents, recrystallizing agents. Nitriles are of important synthon in
preparative organic chemistry due to their conversion into carboxylic acids,
aldehydes, amides, amines and ketones15,18
. Nitrile compounds are viable precursors
for preparation of a variety of nitrogen-containing functional compounds,18
amino
acids by Strecker reaction,19
synthesis of bioactive heterocycles like
5-aminopyrazoles,20
aryl 2-oxazolines,21
tetrahydropyridinethione, pyridopyrimidines,
pyridotriazines dihydropyridines22
and oxazolines,23
etc.
3.2 Review of Literature
The most common methods for the preparation of amides are the reaction
between carboxylic acid derivatives particularly acid halides, acid anhydrides, and
esters with the amines. Despite their wide scope, limitations are associated with the
use of acid halides, anhydrides, and esters. Limitations are mostly due to the limited
stability of many acid chlorides, reactions with esters require strongly basic or acidic
catalysts.24
Conventional Beckmann rearrangement usually requires relatively high
temperature, large amount of strongly acidic and dehydrating media such as
concentrated H2SO4 (forms ammonium sulfate as byproduct),25a
polyphosphoric
acid,25b
P2O5-methanesulfonic acid,25c
that leads to the large waste products
(formation of inorganic salts caused by neutralization) and not applicative to sensitive
Chapter 3
55
substrate. Consequently research is being pursued to make the process mild and
catalytic. To avoid these requisite harsh conditions several methodologies in liquid
phase,26-28
supercritical water,29
ionic liquid,30
vapour phase31
have been developed.
Many catalytic systems such as boria hydroxyapatite, metal ilerite, supported oxide
and zeolite have been reported.31
However these processes require high reaction
temperature (300 0C), low selectivity and can suffer from rapid decay in the activity
of catalyst. Various inorganic catalyst such as terpyridine ruthenium,5e
AlCl3.6H2O/KI/H2O/CH3CN,28c
metal lewis acid- Ga(OTf)3,28d
[RhCl(cod)]2, Au/Ag
co-catalytic system,32
triphosphazene in HIIP or acetonitrile26a
also reported. The
other reagent includes cyanuric chloride/DMF,28a
anhydrous oxalic acid,31d
chlorosulfonic acid in toluene.26b
However some of these processes require hazardous
high cost solvents like DCM, DMF, acetonitrile, toluene, etc with high reaction time.
Therefore, the development of simple, highly efficient and selective Beckmann
rearrangement process is still highly demandable.
Furuya Y. et al. (2005)33
Furuya Y. et al. have reported the commercially available cyanuric chloride as
an effective organocatalyst for the Beckmann rearrangement of ketoximes into amides
in acetonitrile under refluxing condition (Scheme 3.1).
R1 R2
NOH
CH3CN, reflux
CNC (2 or 5 mol%), ZnCl2 (2 mol%)NH
O R2
R1
Scheme 3.1
Ramalingan C. et al. (2007)34
Ramalingan C. et al. has found an acetonitrile solution of mercury(II) chloride
as an efficient catalytic system for rearrangement of diverse range of ketoximes to
their corresponding amides/lactums (Scheme 3.2).
R' R
NOH
CH3CN, 80 0C, 8 h
NH
O R
R'HgCl2 (12-30%)
Scheme 3.2
Chapter 3
56
Li Z. et al. (2008)35
Li Z. et al. developed an efficient and rapid method for Beckmann
rearrangement of ketoximes by using recyclable and reusable silica-supported
phosphorus chloride as catalyst under microwave irradiation in anhydrous
tetrahydrofuran (Scheme 3.3).
R1
R2
NOH SiO2-OPCl2
THF, MW, 3-8 Min.
R1, R2 = alkyl, aryl
NH
O
R1R2
Scheme 3.3
Liu X. et al. (2009)36
Liu X. et al. reported a mild, efficient and eco-friendly procedure for
Beckmann rearrangement catalyzed by a series of novel Bronsted acidic ionic liquids
(ILs) consisting double SO3H cations mediated zinc chloride (ILs–ZnCl2) catalytic
system (Scheme 3.4). High yields of amides were achieved by using 5 mol % of
ILs–ZnCl2 catalysts. In addition, the catalyst system could be recycled and reused for
three times.
R1 R2
NOH
solvent
NH
O R2
R1Acidic ionic liquid- ZnCl2
Scheme 3.4
Yadav L. D. S. et al. (2010)37
Yadav L. D. S et al. have performed Bromodimethylsulfonium bromide
(BDMS)-catalyzed Beckmann rearrangement of a variety of ketoximes in the
imidazolium-based ionic liquid [bmim]PF6 under mild conditions without using any
additional co-catalyst or solvent to afford excellent conversion and selectivity
(Scheme 3.5). The ionic liquid is recovered and reused for up to three runs without
any loss of efficiency.
R1 R2
NOH
[bmim]PF6, 80 0C
NH
O R2
R1
S +Br
_Br
BDMS
R1, R2 = phenyl, alkyl, cycloalkyl
Scheme 3.5
Chapter 3
57
Yadav L. D. S. et al. (2010)38
Yadav L. D. S et al. has been shown Bromodimethylsulfonium bromide, in
combination with zinc chloride, an excellent catalytic system for liquid-phase
Beckmann rearrangement of various ketoximes into the corresponding amides/lactams
in acetonitrile at reflux temperature (Scheme 3.6) with good to excellent yields.
R1 R2
NOH
ZnCl2, MeCN, reflux
NH
O R2
R1
S +Br
_Br
BDMS
Scheme 3.6
Liu L. F. et al. (2011)39
Liu L. F. et al. invented aluminum chloride, an inexpensive and commercially
available lewis acid catalyst for Beckmann rearrangement. The stoichiometric
amounts of catalyst smoothly promote the Beckmann rearrangement of various
ketoximes to the corresponding amides in anhydrous acetonitrile under reflux
temperature (Scheme 3.7).
R1
R2
NOH AlCl3 (10 mole %)
CH3CN, reflux, 2 h NH
O
R1R2
R1, R2 = alkyl, aryl
Scheme 3.7
At the same time, dehydration of aldoximes to nitriles is also an important
transformation in organic synthesis and a number of methods have been developed.40
There are many methods using SOCl2 for dehydration of aldoximes to nitriles has
been reported like silica gel/SOCl2,41a
SOCl2-benztriazole,41b
Na2CO3/SOCl2.41c
Although the methods developed so far have their own limitations for example, the
use of extremely anhydrous reaction condition, toxic and hazardous chemicals and the
need of cumbersome work-up procedures.42
One of the most general methods for
synthesis of alkyl nitriles is direct nucleophilic substitution of alkyl halides with
inorganic cyanides, although the reaction is frequently accompanied by elimination of
hydrogen halides, especially with bulky alkyl halides.43
They were also usually
prepared by regenerating CN group via oxidation,44
rearrangement45
or elimination.
The direct preparation of nitriles from aldehydes was generally achieved by the
dehydration of the corresponding aldoximes using classical reagents46
or other new
Chapter 3
58
reagents like trichloroisocyanuric acid,47
trichloroacetyl chloride/triethylamine,
dicyclohexyl carbodiimide, phosphonitrilic chloride,40b
CuCl2,48
chlorosulfonyl
isocyanate, triphenylphosphine, Burgess reagent49
and also include the use of
expensive (2,4-dinitrophenyl hydroxylamine)50
, (hydroxylamine-o-sulfonic acid),51
hazardous (selenium dioxide)52
or corrosive (formic acid)53
reagents. Some other
method for synthesis of nitriles includes use of hypervalent iodine (III) reagent in
aqueous ammonium acetate,54
microwave reaction with catalytic amount of
pyridine,55
microwave mediated solvent free reaction in presence of TiO2,56
CuCl2 in
acetonitrile under ultrasound irradiation,57
etc.
Yang S. H. et al. (2001)58
Yang S. H. et al. performed catalytic dehydration of aldoximes with catalytic
system [RuCl2(p-cymene)]2/molecular sieves under essentially neutral and mild
conditions resulting into various types of cyano compounds with good to excellent
yields (Scheme 3.8).
N
H
ROH + [RuCl2(p-cymene)]2
(2 mol %)
MS 4 A0
CH3CN, 80 0C
10-60 min
R CN
Scheme 3.8
Lee K. et al. (2004)59
Lee K. et al. reported the various aliphatic, aromatic and heterocyclic aromatic
type of aldoximes conversion to corresponding nitriles in good to excellent yields
using 2-chloro-1-methylpyridiniun iodide (CMPI) as a dehydrating agent using
triethylamine in dichloromethane under Argon atmosphere (Scheme 3.9).
R
HN
OH CMPI, Et3N, CH2Cl2
rt, 1-2 h, ArR CN
R = aliphatic, aromatic, heterocyclic aromatic
Scheme 3.9
Saini A. et al. (2005)60
Saini A. et al. developed an efficient method for the transformation of
aldoximes to nitriles induced by zinc-iodine system in good to excellent yields in
acetonitrile at room temperature (Scheme 3.10).
Chapter 3
59
R
HN
OH Zn / I2
CH3CN, rtR CN
Scheme 3.10
Gucma M. et al. (2008)61
Gucma M. et al. have mentioned the transformation of benzaldehyde
aldoximes with electron donating group to corresponding nitriles with the help of
N-chlorosuccinimide and pyridine in acetonitrile (Scheme 3.11). In this method for
the simple benzaldehyde oxime and alkanal aldehyde oximes get deprotected into
corresponding benzaldehyde.
ArCH NOH + NCl
O
O
pyridine
MeCNArCN + NH
O
O
+ py.HCl
Scheme 3.11
Singh M. K. et al. (2009)62
Singh M. K. et al. have converted an easily synthesized aldoximes to the
corresponding nitriles by a reaction with 1H-benzotriazol-1-
yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP) and DBU in
CH2Cl2, THF, or DMF (Scheme 3.12). As an alternative reagent that eliminates the
formation of hexamethylphosphoramide as a byproduct, use of 1H-benzotriazol-1-yl-
4-methylbenzenesulfonate (Bt-OTs) and DBU was also investigated.
R
HN R CN
Ar orAr or
NN
N
x
DBU, CH2Cl2
BPO: x = OP+(NMe2)3PF6-
Bt-OTs: x = OTs
OH
Scheme 3.12
Saha D. et al. (2009)63
Saha D. et al. described a simple and convenient procedure for the synthesis of
nitriles by dehydration of aldoximes using an ionic liquid, 1-pentyl-3-
methylimidazolium tetrafluoroborate, [pmim]BF4 under organic solvent-free
condition (Scheme 3.13). A variety of aromatic, heteroaromatic and aliphatic
Chapter 3
60
aldoximes were converted to the corresponding nitriles. The ionic liquid was
recovered and reused for subsequent reactions.
RCH NOH RCN[pmim]BF4
90 0C
R = aryl, heteroaryl, alkyl
Scheme 3.13
Rad M. N. S. et al. (2010)64
Rad M. N. S. et al. reported a facile and efficient method for dehydration of
aldoximes into nitriles using N-(p-toluenesulfonyl) imidazole (TsIm) (Scheme 3.14).
In this method, aldoximes were refluxed with TsIm in the presence of
1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU) in dimethylformamide (DMF) to afford
the corresponding nitriles in good yields. This methodology is highly efficient for
various structurally diverse aldoximes including aromatic, heteroaromatic and
aliphatic oximes.
R
HN
OH Tslm/DBU
DMF, reflux 15-90 min.
R CN
H3C S
O
O
NN
Tslm =
Scheme 3.14
Li Y. T. et al. (2011)65
Li Y. T. et al. invented catalytic dehydration of aldoximes efficiently with
NiCl2 in acetonitrile under neutral condition and in N2 atmosphere. Under these
conditions, various functionalized aldoximes produce the corresponding nitriles in
good to excellent yields (Scheme 3.15).
N
H
ROH
NiCl2 (0.025 mmol)
MS 4 A0
CH3CN, reflux,
3 h
R CN
Scheme 3.15
Rad M. N. S. et al. (2012)66
Rad M. N. S. et al. developed a rapid and highly convenient synthesis of
nitriles from the corresponding aldoximes using 8-bromocaffeine (8-BC) (Scheme
3.16). In this protocol, aldoximes react with 8-BC in the presence of
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and N,N-dimethylformamide (DMF) to
Chapter 3
61
furnish the corresponding nitriles under both microwave-assisted and/or conventional
heating (reflux) conditions in short times and in good to excellent yields.
R
HN
OH 8-BC, DBU, DMF
Conventional heatingor Microwave
R CN
N
N
O
O N
NBr8-BC = DBU = N
N
Scheme 3.16
3.3 Present Work
In comparison with some inflammable and toxic organic solvents, water may
serve as superior solvent that is safe to use in organic reactions.67
The low cost of
water renders the chemical processes more economical. In many cases, water can be
recycled to improve the problem of solvent disposal. Furthermore, using water as a
solvent may also have advantages of simple operation and high efficiency in many
organic reactions. Synthetic chemists continue to explore new methods to carry out
chemical transformations. Herein we present our results on highly selective
SOCl2/β-cyclodextrin catalyzed Beckmann rearrangement and dehydration of
aldoximes to corresponding nitriles (Scheme 3.17). As the Beckmann rearrangement
usually requires electrophilic activation of oxime hydroxy group, we hypothesized
that β-CD facilate the transformation of ketoximes to amide or dehydration of
aldoximes by hydrogen bonding with β-CD hydroxyl groups by supramolecular
interaction. The hydrogen bonding with oxygen may also force up for departing of
leaving group and accelerate the rate of migration or rate of dehydration.
R
R'N
OHi. SOCl2 , Acetone
ii. -CD , H2OR
HN
O
R' ORR
C N
If R' = H80 0C5
6 a-g
7 a-m Scheme 3.17
In order to explore the best reaction condition the 4-bromoacetophenone
oxime was selected as a model molecule under various reaction conditions (Table
3.1).
Chapter 3
62
Table 3.1: Screen of reaction conditions.a
Br
NOH
Mei) SOCl2, Acetone
ii) Beta-CD (0.5 mmol),
H2O Br
NH
Br
O
Me+
Me
O
A B
Entry Temp. (0C) Time (h) Yield (%)
b
A B
1
2
3
4
Room temp.
40
60
80
12
2.45
0.5
0.41
30 68
38 53
47 50
85 -
a Reaction condition : To a solution of 4-bromoacetophenone oxime in acetone, SOCl2
added dropwise at 0-10 0C. Then clear solution of β-CD dissolved in distilled water
(10 mL) was added at room temperature and stir at given temperature. A mole ratio of
oxime: SOCl2: β-CD = 5: 6: 0.5 b Isolated yield.
Table 3.2: Transformation of ketoximes to amide using different amount of catalyst
at 80 0C.
a
i) SOCl2, Acetone
ii) Beta-CD, H2O, 80 0C
Br
NOH
Me
Br
NH Me
O
Entry Catalyst (mmol) Time (min.) Yield (%)
1 0.5 25 85
2 1 25 84
3 2 28 84
4 4 30 80
5 5 40 80
6 - 35 41
a A mole ratio of oxime: SOCl2 = 5: 6 was used.
The effect of temperature for above reaction has been studied and it was found
that at lower temperature (entry 1, Table 3.1), the rate of migration was very slow,
require high reaction time and leading to the side product identified as 4-bromo
acetophenone (by TLC comparison and Mp with authentic sample). Increase in
Chapter 3
63
temperature fevers the rate of migration and best result was found at 80 0C (entry 4,
85%, Table 3.1). The reactions were also carried out by varying amount of catalyst
(Table 3.2) at 80 0C. When we have increased the amount of catalyst from 0.5 to 5
mmol, no yield improvements were observed. When same reaction was carried out at
80 0C without β-CD catalyst, formation amide and starting carbonyl compound takes
place. The efficiency of catalyst have been studied for the structurally divers ketoxime
(Table 3.3). The reactions were found to be complete within 5 – 25 min. As per usual
migratory aptitude of Beckmann rearrangement, here only migration of aryl group
was observed. The naphthalene and diphenyl compounds also show good results
(entry 6d – 6g, Table 3.3). In our results the electronic effect of substituents on
aromatic ring was not more pronouns.
Table 3.3: Catalytic conversions of various ketoximes to amide using SOCl2/β-CD as
catalysta.
R
R'N
OHi. SOCl2 , Acetone
ii. -CD (0.5 mmol),
H2O, 80 0C
R
HN
O
R'
56 a-g
Entry Amide Time
(min.)
Yield b
(%)
Melting point (0C)
Measured Reported
6a HN
O
5 86 113 11470
6b HN
O
8 88 150 149-15169
6c HN
OBr
25 85 165-167 16770
6d
HN O
20 90 159-166 16070
6e HN
O
15 91 129-132 -
Chapter 3
64
6f HN
O
20 93 162 16270
6g HN
Cl
O
18 94 197-200 19470
a A molar ratio of ketoximes: SOCl2: β-CD = 5: 6: 0.5,
b Isolated yield after column
chromatography.
The starting oximes used in present study are mostly mixture of syn and
anti isomer, but we obtained majority of single amide isomer as the product which is
favored based on migratory aptitude (except entry 6g). The equilibrium among
involved isomer is faster than rearrangement so that the product composition is
determined by the relative rates of migration of involved groups. On prolonged
heating at 80 0C there was no further dehydration of amide to nitrile or hydrolysis of
amide to acid and amine occurs. The reaction was also carried out in absence of
SOCl2 for prolonged time but the starting oximes get isolated. The catalyst is
quantitatively recovered and reused up to three cycles (Table 3.4).
Table 3.4: Reuse of β-CD for 6c.
No. of use Yield (%) Recovery of β-CD (%)
1 85 96
2 85 90
3 83 85
Table 3.5: Catalytic dehydration of aldoximes to corresponding nitriles using SOCl2/
β-CD as a catalyst.a
RN
OH
H RC N
i. SOCl2 , Acetone
ii. -CD (0.5 mmol),
H2O, 80 0C7 a-m
Entry Nitrile Time
(min.)
Yield b
(%)
Melting point (0C)
Measured Reported
7a CN
15 90 190 (Bp) 19170
Chapter 3
65
7b CN
NO2
8 98 116-118 11870
7c CN
O2N
10 91 148 14970
7d CN
Cl
10 96 96 9670
7e CN
Br
15 91 112 11370
7f
NH
CN
20 94 180-182 179-18269
7g CN
HO
12 91 112 11369
7h CN
MeO
12 91 58 57-5970
7i CN
MeO
OMe
MeO
15 92 92-94 -
7j CN
Cl
15 94 44 43-4669
7k CN
Me
20 92 216-218 21870
(Bp)
7l CN
HO
OMe
25 93 84 85-8769
7m Me CN 10 89 96-98 9770
(Bp)
a A molar ratio of aldoximes: SOCl2: β-CD = 5: 6: 0.5.
b Isolated yield after column
chromatography.
Chapter 3
66
With promising results in hand for the formation of amide from ketoximes, we
next tested for the aldoximes to examine generality of this reaction under identical
condition. Aldoximes
were found to be undergoing dehydration furnishes the
corresponding nitriles in good to excellent yields and within short reaction time
(8 - 25 min, Table 3.5). On comparison of the overall reactivity of aldoximes and
ketoximes in our results with respect to time and yields, aldoximes were found to be
more reactive. The effect of substituent on aromatic ring like nitro, halide, hydroxyl,
methoxy, and methyl was found to be less on reaction efficiency and selectivity. The
same reaction proceeds much slowly when reaction carried out in acetonitrile at
similar condition affording side product (monitor by TLC). Not only aromatic
aldoximes were efficiently converted to aromatic cyano compounds but heterocyclic
(entry 7f) as well as aliphatic aldoxime (entry 7m) could also be employed as a good
substrate with similar selectivity to affords the corresponding nitriles. Compounds
entry 7a, 7d, 7h, 7k were isolated in 90, 96, 91 and 92% yields in shorter reaction time
while using a literature procedure60,68
these compounds were isolated in 82, 87, 82
and 85% yields in 1 h reaction time. Furthermore catalytic activity of recovered
catalyst (β-CD) was examined. As shown in Table 3.6, the yield of
3-nitrobenzonitrile in second and third use of catalyst not found to be decreasing
much more. In each case almost > 86% of β-CD was easily recovered by cooling of
aqueous layer. However when these reactions were carried out in presence of simple
oligosaccharides such as glucose or dextrose, the reaction was completed in 30 min.
and 20 min. with yields only 45% and 55% for 4-bromoacetophenone oxime and
4-nitrobenzaldehyde oxime respectively. It confirms that cyclodextrin may form
complex with oxime, thus yields of reaction increased to 85% and 91% respectively.
Glucose or dextrose also not recovered from aqueous layer quantitatively.
Table 3.6: Reuse of β-CD for 7b.
Number of use Yield (%) Recovery of β-CD
(%)
1 98 94
2 94 90
3 90 86
Chapter 3
67
3.4 Conclusion
In conclusion, we have described a highly efficient protocol for conversion of
ketoximes to amide and dehydration of aldoximes to nitrile using nontoxic and
inexpensive β-CD catalyst in water. The advantages of this protocol includes a simple
reaction set-up not requiring specialized equipment, mild reaction condition, high
product yields, very short reaction time, reusable catalyst and eliminating the use of
hazardous solvents.
3.5 Experimental Section
Chemicals required for the synthesis were obtained from Aldrich,
Spectrochem. Melting points were taken in open capillary tubes and are uncorrected.
IR spectra were recorded on Shimadzu FT-IR IRAffinity-1 using KBr. 1H NMR
spectra were recorded with a Varian Mercury at 300 MHz in CDCl3 with TMS as an
internal standard. Mass spectra were under ESI mode, on Thermo Finnigan (Model-
LCQ Advantage MAX) mass spectrometer.
Typical procedure for transformation of oximes into amide and nitriles
To a solution of oxime (5 mmol) in acetone (2 mL), SOCl2 (6 mmol) was
added dropwise with stirring at 0-10 0C. Then clear solution of β-CD (0.5 mmol) in
distilled water (10 mL) was added at room temperature and stir at 80 0C for
appropriate time (monitored by TLC, Hexane: Ethyl acetate 9:1). The organic
material was extracted in ethyl acetate (3 x 20 mL). The aqueous layer was cooled to
0 0C; in which β-CD reappeared as a white solid. The obtained white solid mass was
filtered, dried to recover β-CD and reused. The organic phase dried over anhydrous
Na2SO4, solvent was evaporated under reduced pressure, the crude product purified
by column chromatography using hexane-ethyl acetate (9:1) as eluent to afford pure
product.
The selected products were characterized by FTIR, NMR, Mass spectroscopy,
whereas the remaining products characterized by their physical constants,
comparative TLC and are found to be in good agreement with the authentic samples.
Chapter 3
68
3.6 Spectral Data
N-p-Tolyacetamide: H
N
O
Molecular formula: C9H11NO
Molecular weight : 149
Mp : 150 0C
IR (KBr, cm-1
) ν : 3300, 2922, 1664, 1602, 817 1H NMR (CDCl3, 300 MHz, ppm) δ : 7.36 (d, 2H, J = 8 Hz, Aromatic), 7.20
(brs, 1H, NH), 7.11 (d, 2H, J = 8Hz,
Aromatic), 2.30 (s, 3H, COCH3), 2.15
(s, 3H, CH3)
MS (m/e) : 150 [M+1]
N-(Naphthalene-6-yl) acetamide: HN
O
Molecular formula: C12H11NO
Molecular weight : 185
Mp : 129-132 0C
IR (KBr, cm-1
) ν : 3284, 2983, 1668, 1589 1H NMR (CDCl3, 300 MHz, ppm) δ : 8.17 (s, 1H, NH), 7.79 – 7.76 (m, 3H,
Aromatic), 7.45 – 7.39 (m, 4H,
Aromatic), 2.23 (s, 3H, COCH3)
MS (m/e) : 186 [M+1]
N-Phenylbenzamide: HN
O
Molecular formula: C13H11NO
Molecular weight : 197
Mp : 162 0C
IR (KBr, cm-1
) ν : 3344, 3053, 1654, 1598, 750 1H NMR (DMSO-d6,
300 MHz, ppm) δ :
10.2 (brs, 1H, NH), 7.96 – 7.07 (m, 10H,
Aromatic)
MS (m/e) : 198 [M+1]
4-Chloro-N-phenylbenzamide:
HN
O
Cl
Molecular formula: C13H10ClNO
Molecular weight : 231
Mp : 197-200 0C
IR (KBr, cm-1
) ν : 3350, 3057, 1653, 1598, 848 1H NMR (CDCl3, 300 MHz, ppm) δ : 7.85 – 7.16 (m, 9H, Aromatic), 7.74
(s, 1H, NH)
Chapter 3
69
MS (m/e) : 232 [M+1]
4-Nitrobenzonitrile: CN
O2N
Molecular formula: C7H4N2O2
Molecular weight : 148
Mp : 148 0C
IR (KBr, cm-1
) ν : 2223, 1600, 1348, 860 1H NMR (CDCl3, 300 MHz, ppm) δ : 8.36 (d, 2H, Aromatic), 7.90 (d, 2H,
Aromatic)
1H-Indole-3-carbonitrile:
NH
CN
Molecular formula: C9H6N2
Molecular weight : 142
Mp : 180-182 0C
IR (KBr, cm-1
) ν : 3230, 3122, 2227 1H NMR (CDCl3, 300 MHz, ppm) δ : 8.68 (brs, 1H, NH), 7.80 – 7.26 (m, 5H,
Aromatic)
MS (m/e) : 143 [M+1]
4-Hydroxybenzonitrile: CN
HO
Molecular formula: C7H5NO
Molecular weight : 119
Mp : 112 0C
IR (KBr, cm-1
) ν : 3275, 3169, 2233, 1610, 1166, 839 1H NMR (CDCl3, 300 MHz, ppm) δ : 7.56 (d, 2H, Aromatic), 6.93 (d, 2H,
Aromatic), 6.09 (s, 1H, OH)
MS (m/e) : 120 [M+1]
4-Methoxybenzonitrile: CN
MeO
Molecular formula: C8H7NO
Molecular weight : 133
Mp : 58 0C
IR (KBr, cm-1
) ν : 3024, 2843, 2218, 1604, 1024, 829 1H NMR (CDCl3, 300 MHz, ppm) δ : 7.60 (d, 2H, Aromatic), 6.98 (d, 2H,
Aromatic), 3.88 (s, 3H, OCH3)
MS (m/e) : 134 [M+1]
Chapter 3
70
2-Chlorobenzonitrile: CN
Cl
Molecular formula: C7H4ClN
Molecular weight : 137
Mp : 44 0C
IR (KBr, cm-1
) ν : 3093, 2229, 1591, 759 1H NMR (CDCl3, 300 MHz, ppm) δ : 7.69 – 7.34 (m, 4H, Aromatic)
4-Hydroxy-3-methoxybenzonitrile: CN
HO
OMe
Molecular formula: C8H7NO2
Molecular weight : 149
Mp : 84 0C
IR (KBr, cm-1
) ν : 3226, 3028, 2225, 1028 1H NMR (CDCl3, 300 MHz, ppm) δ : 7.26 – 6.95 (m, 3H, Aromatic), 6.06 (s,
1H, OH), 3.93 (s, 3H, OCH3)
MS (m/e) : 150 [M+1]
3.6.1 Spectra
Table 3.7: FTIR, 1H NMR and Mass spectra of selected compounds.
Sr.
No.
Spectra
1 FTIR of N-p-Tolyacetamide
2 1H NMR of N-p-Tolyacetamide
3 Mass of N-p-Tolyacetamide
4 FTIR of N-(Naphthalene-6-yl) acetamide
5 1H NMR of N-(Naphthalene-6-yl) acetamide
6 Mass of N-(Naphthalene-6-yl) acetamide
7 FTIR of 4-Hydroxy-3-methoxybenzonitrile
8 1H NMR of 4-Hydroxy-3-methoxybenzonitrile
9 Mass of 4-Hydroxy-3-methoxybenzonitrile
Chapter 3
71
Chapter 3
72
Chapter 3
73
Chapter 3
74
Chapter 3
75
Chapter 3
76
Chapter 3
77
Chapter 3
78
Chapter 3
79
Chapter 3
80
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