Chapter 11. Alcohols from carbonyl compounds

(由羰基化合物制醇） .Oxidation-reduction and organometallic compounds

(氧化 -还原和有机金属化合物）11.1 IntroductionCarbonyl (羰基） compounds are a broad group of compounds that includes aldehydes, ketones, carboxylic acids, and esters.

O

The carbonyl group

R

H

O

R

R'

O

R

HO

O

R

R'O

O

An aldehyde A ketone A carboxylic acid A carboxylate ester

ôÊ»ù È© ͪ ôÈËá õ¥

11.1A Structure of the carbonyl group

O

120o

120o

120o

1. C-sp2 hybridization2. The bond angles is 120o.

3. It is a trigonal planar structure

4. The carbon-oxygen double bond

consists of sigma-a bond and a pi-bond

O

120o

120o

120oO O

O O

O-+

Polarization of the - bond Resonance structures

11.1B Reaction of carbonyl compounds with nucleophiles

O

Polarization of the - bond

+:Nu- O-Nu

O OH[ H ] Reduction

[ O ] Oxidation

O OH[ H ] Reduction

[ O ] Oxidation

NaBH4 or LiAlH4

KMnO4

R

H

O

R

H

O-

[ H ] Reduction

NaBH4 or LiAlH4+ H-

H

ROHRCH2OH

nucleophilic addition

11.2 Oxidation-Reduction reactions in organic chemistry

Reduction of an organic molecule usually corresponds to increasing its hydrogen

content or to decreasing its oxygen content.

R

O

OH[ H ]

ReductionR

O

H

Carboxylic acid Aldehyde

oxygen content decreases

R

O

H[ H ]

ReductionR CH2OH

Aldehyde Alcohol

oxygen content decreases

[ H ]

ReductionR CH3

Alcohol Alkanes

oxygen content decreases

R CH2OH

The opposite of reduction is oxidation. Thus, increasing the oxygen content of an organic molecule or decreasing its

hydrogen content is an oxidation.

oxygen content decreases

[ O ]R CH2OH

Alkanes Alcohols

oxygen content increases

R CH3

[ H ]

[ O ]

[ H ]RCHO

[ O ]

[ H ]RCOOH

[ O ]R CH2Cl

Alkanes

R CH3

[ H ]

[ O ]

[ H ]RCHCl2

[ O ]

[ H ]RCCl3

11.3 Alcohols by reduction of carbonyl compounds

R

O

OH[ H ]

ReductionR CH2OH

Carboxylic acid 1o Alcohols

R

O

OR'[ H ]

ReductionR CH2OH

1o Alcohols

+ R'OH

R

O

H[ H ]

ReductionR CH2OH

Aldehyde 1o Alcohols

R

O

R[ H ]

Reduction

RHC

Ketone2o Alcohols

OH

R

R

O

OH R CH2OH

Carboxylic acid 1o Alcohols

[ H- ]

ReductionLiAlH4+

Lithiumaluminum hydride

Et2O

H3C

O

OH H3C CH2OH

H3C

CH3

COOH

2,2-Dimethylpropanoic acid

1. LiAlH4 / Et2O

2. H2OAcetic acid Ethanol

CH3

1. LiAlH4 / Et2O

2. H2OH3C

CH3

CH2OH

CH3

Neopentyl alcohol ÐÂÎì´¼ (92%)

CH3CH2CH2CHO

Butanal 1-Butanol

[ H- ]

ReductionNaBH4

SodiumBorohydride

H2O

+ CH3CH2CH2CH2OH

CH3CH2CCH3

Butanone2-Butanol

[ H- ]

ReductionNaBH4

SodiumBorohydride

H2O

+ CH3CH2CHCH3

O

OH

The NaBH4 is also reduced reagent

The mechanism for the reduction of a ketone by sodium borohydride and Lithium aluminum hydride

OLiAlH4

NaBH4

[H-]

Hydride transfer

O-HHOH

OHH

Alcohols

nucleophile addition

Sodium borohydride (NaBH4) is a milder reducing agent than lithium aluminum hydride (LiAlH4). Lithium aluminum hydride will reduce acids. Esters, aldehydes, and ketones; but sodium borohydride will reduce only aldehydes and ketones.

11.4 Oxidation of alcohols

Primary alcohols can be oxidized to aldehydes and carboxylic acids.

R CH2OH[ O ]

R CHO R COOH

1o Alcohol Aldehyde Carboxylic acid

[ O ]

CH3CH2CH2CH2OH

1-Butanol

K2Cr2O7

H2SO4CH3CH2CH2CHO

Butanalbp, 117.7 oC bp, 75.7 oC 50%

CH3CH2OHCu

300 oCCH3CH2OH + H2

Dehydrogenation

CH3CH2CH2CH2OH

1-Butanol

CH3CH2CH2CHO

Butanal

PCC

25 oCCH2Cl2

CrO3 + HCl +

N N

CrO

O

O Cl-

H+

Pyridinium chlorochromate

ßÁà¤ÈýÑõ»¯¸õ

Pyridine

PCC Pyridinium chlorochromate ßÁà¤ÈýÑõ»¯¸õ

11.4B Oxidation of 1o Alcohols to carboxylic acids, Oxidation of 2o

alcohols to ketone.CH3CH2CH2CH2OH

1-Butanol

CH3CH2CH2COOKKMnO4, KOH HCl

CH3CH2CH2COOH

CH3CH2CHCH3

OH

2-Butanol

KMnO4, KOHCH3CH2CCH3

O

Butanone

OH

Cyclooctanol

H2CrO4

Acetone 35 oC

O

Cyclooctanone»·¹ï´¼ »·¹ïͪ

11.4D Mechanism of Chromate oxidations （铬酸氧化机理）

Step 1

RC

R

O H

H+

HO Cr

O

O

OH RC

R

O

H

Cr

O

O

OH+ H2O

Chromate ester (¸õËáõ¥£©

RC

R

O

H

Cr

O

O

OHR

R

O + HCrO3- + H3O+

Step 2

KetoneCr 6+ Cr4+

6+4+

H2O

Chromate ester (¸õËáõ¥£©

11.4E A Chemical test for primary and secondary alcohols

Primary alcohols 1o RCH2OH

Secondary alcohols 2o R2CHOH

Secondary alcohols 3o R3COH

+ CrO3 / aqueous H2SO4

Chromic oxide

greenish opaque

solution Cr3+

greenish opaque

solution Cr3+

No reaction

11.5 Organometallic compounds （有机金属化合物）

Compounds that contain carbon-metal bonds are called organometallic compounds. It include Carbon-lead, carbon-tin, carbon-thallium, carbon-mercury, carbon-lithium and carbon-magnesi

um bonds.

C:- M+

M = Na+ or K+

(Primarily ionic)

Alkylsodium and alkylpotassium compounds are highly reactive and are among the most powerful of base

C: M

M = Mg or Li

Organometallic compounds of lithiumand magnesium are of great importancein organic synthesis. They are relativly stable in ether solutions, but their carbon-metalbonds have considerable ionic character.

(Primarily covalent)

C M

M = Pb, Sn, Hg, or TI

Organomercury and organolead compounds are much less reactiv; they are often volatile and are stable in air. They are all poisonous. They are generally soluble in nonpolar solvents. Tetraethyllead, for example, has been used as an "antiknock" compound in gasoline.

11.6 Preparation of organolithium and organomagnesium compounds

11.6A Organolithium compounds (有机锂化合物）

Organolithium compounds are often prepared by the reaction of organic halides with lithium metal.

(Butyl bromide)

CH3CH2CH2CH2Br + 2 Li- 10oC

Et2OCH3CH2CH2CH2Li + LiBr

Butyllithium(80-90%)

R X

( or Ar X)

+ 2 Li RLi + LiX

(or ArLi)

The order of reactivity of halides is;

RI RBr RCl

11.6B Grignard reagents （格利雅试剂） ;

Organomagnesium halides were discovered by the French chemist Victor Grignard in 1900. Grignard received the Nobel Prize for his discovery in 1912, and organomagnesium halides are now called Grignard reagents in his honor. Grignard reagents hav

e great use in organic synthesis.

RX + Mg RMgXEt2O

or THF

ArX + MgEt2O

or THFArMgX

Grignard reagents

Grignard reagents are usually prepared by the reaction of an organic halides and magnesium metal in an ethe

r solvent

CH3I + Mg CH3MgIEt2O

or THF

C6H5Br + MgEt2O

or THFC6H5MgBr

Methylmagnesium iodide(95%)

Phenylmagnesium bromide(95%)

Grignard reagents

A Grignard reagent forms a complex with its ether solvent; the structure of the complex can be represe

nted as follows:

R

Mg

X

H3CH2C

O

H3CH2C

O

CH2CH3

CH2CH3

ComplexStability of Grignard reagentsThe solvent is a diethyl ether

R

Mg

X

O O

ComplexStability of Grignard reagents

The solvent is tetrahydrofuran (THF)

11.7 Reactions of organolithium and organomagnesium compounds11.7A Reactions with compounds contai

ning acidic hydrogen atomsCH3MgI

C6H5MgBr

Methylmagnesium iodide

Phenylmagnesium bromide

+ H2O CH4 + Mg

OH

I

+ H2O C6H6 + Mg

OH

Br

CH3MgI

C6H5MgBr

Methylmagnesium iodide

Phenylmagnesium bromide

+ HOCH3 CH4 + Mg

OCH3

I

+ HOCH2CH3 C6H6 + Mg

OCH2CH3

Br

Grignard reagents and organolithium compounds abstract protons that are

much less acidic than those of water and alcohols. They react with the termi

nal hydrogen atoms of 1-alkynes.

R C CH + R'MgX

Terminal alkyne Grignardreagent

R' H + R C CMgX

Alkynylmagnesium halide±»¯È²»ùþ

Alkanes

pKa = 50

R C CH + R'Li R' H + R C CLi

AlkynyllithiumAlkaneȲ»ùï®

Terminal alkyne Alkyl lithium

11.7B Reaction of Grignard reagents with oxiranes

(环氧乙烷与格利雅试剂反应）+RMgX

Grignardreagent

O

R CH2CH2OMgXH+

R CH2CH2OH

A primary alcoholOxirane

Et2O

H2O

+CH3CH2MgI

Grignardreagent

O

CH3CH2CH2CH2OMgIH+

CH3CH2CH2CH2OH

Butyl alcoholOxirane

Et2O

H2O

在合成上增加两个碳原子伯醇

+C6H5MgI

Grignardreagent

O

C6H5CH2CH2OMgI

H+

C6H5CH2CH2OH

phenylethanol

Oxirane

Et2O

H2O

±½»ùÒÒ´¼

+C6H5MgI

Grignardreagent

O

C6H5CH2CHOMgI

H+

C6H5CH2CHOH

phenylpropanol

Oxirane

Et2O

H2O

±½»ù-2-±û´¼

CH3

CH3

CH3

11.7C Reactions of Grignard reagents with Carbonyl Compounds（格利

雅试剂与羰基反应）

+RMgX

Grignardreagent

RCOMgXH+

RCOHEt2O

H2OO

Aldehyde or Ketone or ester

Nucleophile addition

Alcohols

11.8 Alcohols from Grignard reagents

1. A Grignard reagent reacts with formaldehyde to give a primary alcohol (伯醇） .

+CH3MgBr

Grignardreagent

CH3CH2OMgBrH+

CH3CH2OHEt2O

H2O

H

H

O

formaldehyde

Nucleophile addition

Ethyl Alcohols

+C6H5MgBr

Grignardreagent

C6H5CH2OMgBrH+

C6H5CH2OHEt2O

H2O

H

H

O

formaldehyde

Nucleophile addition

Benzyl Alcohol±½¼×́¼ Üлù´¼

2. Grignard reagent reacts with higher aldehydes to give seconda

ry alcohol (仲醇）

+CH3CH2MgBr

CH3CH2CHOMgBrH+

CH3CH2CHOHEt2O

H2O

H3C

H

O

AcetaldehydeÒÒÈ©

Nucleophile addition

2-Butanol

2o ´¼

CH3 CH3

Ethylmagnesium bromide ä廯ÒÒ»ùþ

+C6H5MgBr

Grignardreagent

C6H5CHOMgBrH+

C6H5CHOHEt2O

H2O

H3C

H

O

Acetaldehyde

Nucleophile addition

Phenyl ethanol±½»ùÒÒ´¼CH3

CH3

3. Grignard reagent reacts with ketones to give tertiary alcohol (叔醇）

+CH3CH2MgBr

CH3CH2COMgBrH+

CH3CH2COHEt2O

H2O

H3C

H3C

O

Acetone±ûͪ

Nucleophile addition

2-Methyl-2-butanol

3o ´¼ £¨Êå´¼£©

CH3 CH3

Ethylmagnesium bromide ä廯ÒÒ»ùþ

CH3 CH3

+C6H5MgBr

Grignardreagent

H+Et2O

H2O

cyclohexanone»·¼ºÍª

Nucleophile addition

O

OMgBrOH

4. A Grignard reagent also adds to the carbonyl group of an ester (酯） .

+RMgBr

Grignardreagent

RCEt2OR

R'O

O

esters

Nucleophile addition

OR'

R

Initial product(Unstable)

O MgBr

Br

Mg

OR'

R

R

O

-Ketones

H+

H2O

Tertiary alcohols

3o ´¼ £¨Êå´¼£©

RMgBrR C

R

R

OMgBr R C

R

R

OH

+CH3CH2MgBr

Grignardreagent

CH3CH3CEt2OH3C

H3CH2CO

O

Ethyl acetateÒÒËáÒÒõ¥

Nucleophile addition

OCH2CH3

CH3

Initial product(Unstable)

Br

Mg

OCH2CH3

H3C

H3CH2C

O

-2-Butone

O MgBr

H+

H2O

3-Methyl-3-pentanol

3o ´¼ £¨Êå´¼£©

CH3CH2MgBrH3CH2C C

CH2CH3

CH3

OMgBr H3CH2C C

CH2CH3

CH3

OH

12

345

11.8 Planning a Grignard synthesis

CH3CH2 C

C6H5

OH

CH2CH3

a

b

3-Phenly-3-pentanol

(3-±½»ù-3-Îì´¼£©

C6H5MgBr + CH3CH2CCH2CH3

O

a

CH3CH2MgBr + C6H5CCH2CH3

O

b

CH3CH2MgBr + C6H5COCH2CH3

O

2

Synthesis of 3-phenyl-3-pentanol

CH3CH2CCH2CH3

O

1.

Br

Mg

Et2O

1.

2. H3O+

CH3CH2 C

C6H5

OH

CH2CH3

3-Phenly-3-pentanol

(3-±½»ù-3-Îì´¼£©

MgBr

2. CH3CH2Br CH3CH2MgBrMg

Et2O

C6H5CCH2CH3

O

1.

2. H3O+CH3CH2 C

C6H5

OH

CH2CH3

3. 2 CH3CH2MgBrC6H5COCH2CH3

O

1.

2. H3O+CH3CH2 C

C6H5

OH

CH2CH3CH3CH2BrMg

Et2O

Illustrating a Multistep Synthesis (举例说明多步合成）

O

2,5-Dimethyl-3-hexanone2,5-¶þ¼×»ù-3-¼ºÍª

OH

2,5-Dimethyl-3-hexanol2,5-¶þ¼×»ù-3-¼º´¼

O

H

MgBr

O

H

Br MgBrMg

Et2O

OMgBr

2,5-Dimethyl-3-hexanone2,5-¶þ¼×»ù-3-¼ºÍª

H3O+

OH

H2CrO4

acetone

O

phenyl-acetaldehyde±½ÒÒÈ©

O

H

OH

H

2-Phenyl-ethanol

MgBr +O

Phenylmagnesium bromide Oxirane

Synthesis of phenyl-acetaldehyde

MgBrO

Phenylmagnesium bromide

BrMg

Et2O CH2CH2OMgBr

H3O+

CH2CH2OHPCC

CH2Cl2CH2CHO

11.8B Restrictions on the use of Grignard reactions

CH3MgBr + HOCH2CH2CCH3

O

HOCH2CH2C

OMgBr

CH3

CH3

OH, -NH2, -NHR, COOH, SO3H, SH, C CH

CHO, COR, COOR, CONH2, NO2, CN,O

Grignard reagents containing these groups cannot be prepared

CH3MgBr + HOCH2CH2CCH3

O

CH4 + BrMgOCH2CH2CCH3

O

11.8C The use of lithium reagents

Organolithium reagents (RLi) react with carbonyl compounds in the same way as Grignard reagents.

RLi + O

R C OLiH3O+

R C OH

Organolithiumreagent

aldehyde or ketones Lithium alkoxide Alcohol

CH3Li +H3C

H3C

O

H3C C

CH3

CH3

OLiH3O+

H3C C

CH3

CH3

OH

Organolithiumreagent

acetone Lithium alkoxide 2-Methyl-2-propanol

11.8D The use of sodium alkynides (炔化钠的使用）

Sodium alkynides also react with aldehydes and ketones to yield alcohols.

H3C C CH +NaNH2

H3C C CNa NH3

H3C C CNa +H3C

H3C

O H3C C C C

CH3

CH3

ONa

H3O+

H3C C C C

CH3

CH3

OH

HO

CH3

H3C C CNa

HO

CH3O

NaO

CH3

H3O+

nucleophile addition