CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11Reactions of Alcohols

Jo BlackburnRichland College, Dallas, TX

Dallas County Community College District2006,Prentice Hall

Organic Chemistry, 6th EditionL. G. Wade, Jr.

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 2

Types of Alcohol Reactions

• Dehydration to alkene

• Oxidation to aldehyde, ketone

• Substitution to form alkyl halide

• Reduction to alkane

• Esterification

• Tosylation• Williamson synthesis of ether =>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 3

Summary Table

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 4

Oxidation States• Easy for inorganic salts

CrO42- reduced to Cr2O3

KMnO4 reduced to MnO2

• Oxidation: loss of H2, gain of O, O2, or X2

• Reduction: gain of H2 or H-, loss of O, O2, or X2

• Neither: gain or loss of H+, H2O, HX =>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 5

1º, 2º, 3º Carbons

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 6

Oxidation of 2° Alcohols• 2° alcohol becomes a ketone

• Reagent is Na2Cr2O7/H2SO4

• Active reagent probably H2CrO4

• Color change: orange to greenish-blue

CH3CHCH2CH3

OHNa2Cr2O7 / H2SO4

CH3CCH2CH3

O

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 7

Oxidation of 1° Alcohols• 1° alcohol to aldehyde to carboxylic acid

• Difficult to stop at aldehyde

• Use pyridinium chlorochromate (PCC) to limit the oxidation.

• PCC can also be used to oxidize 2° alcohols to ketones.

CH3CH2CH2CH2

OH N H CrO3Cl

CH3CH2CH2CH

O

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 8

3° Alcohols Don’t Oxidize

• Cannot lose 2 H’s

• Basis for chromic acid test

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 9

Other Oxidation Reagents• Collins reagent: Cr2O3 in pyridine• Jones reagent: chromic acid in acetone• KMnO4 (strong oxidizer)• Nitric acid (strong oxidizer)• CuO, 300°C (industrial dehydrogenation)• Swern oxidation: dimethylsulfoxide, with

oxalyl chloride and hindered base, oxidizes 2 alcohols to ketones and 1 alcohols to aldehydes. =>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 10

Biological Oxidation

• Catalyzed by ADH, alcohol dehydrogenase.• Oxidizing agent is NAD+, nicotinamide

adenine dinucleotide.• Ethanol oxidizes to acetaldehyde, then acetic

acid, a normal metabolite.• Methanol oxidizes to formaldehyde, then

formic acid, more toxic than methanol.• Ethylene glycol oxidizes to oxalic acid, toxic.• Treatment for poisoning is excess ethanol.

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 11

Alcohol as a Nucleophile

• ROH is weak nucleophile• RO- is strong nucleophile• New O-C bond forms, O-H bond breaks.

=>

CO

H

R X

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 12

Alcohol as an Electrophile• OH- is not a good

leaving group unless it is protonated, but most nucleophiles are strong bases which would remove H+.

• Convert to tosylate (good leaving group) to react with strong nucleophile (base). =>

CO

H

+

C-Nuc bond forms, C-O bond breaks

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 13

Formation of Tosylate Ester

p-toluenesulfonyl chlorideTsCl, “tosyl chloride”

CO

H

CH3

S

Cl

OO N

CH3

S OO

OH

C

CH3

S

O

OO

C

ROTs,a tosylate ester

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 14

SN2 Reactions of Tosylates

• With hydroxide produces alcohol

• With cyanide produces nitrile

• With halide ion produces alkyl halide

• With alkoxide ion produces ether

• With ammonia produces amine salt

• With LiAlH4 produces alkane =>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 15

Summary of Tosylate Reactions

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 16

Reduction of Alcohols

• Dehydrate with conc. H2SO4, then add H2

• Tosylate, then reduce with LiAlH4

CH3CHCH3

OHH2SO4

CH2 CHCH3H2

PtCH3CH2CH3

alcohol alkene alkane

alcohol

CH3CHCH3

OHTsCl

CH3CHCH3

OTsLiAlH4

alkane

CH3CH2CH3

tosylate

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 17

Reaction with HBr

• -OH of alcohol is protonated

• -OH2+ is good leaving group

• 3° and 2° alcohols react with Br- via SN1

• 1° alcohols react via SN2

H3O+

Br-

R O H R O H

H

R Br =>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 18

Reaction with HCl• Chloride is a weaker nucleophile than

bromide.• Add ZnCl2, which bonds strongly with

-OH, to promote the reaction.• The chloride product is insoluble.• Lucas test: ZnCl2 in conc. HCl

1° alcohols react slowly or not at all.2 alcohols react in 1-5 minutes.3 alcohols react in less than 1 minute.

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 19

Limitations of HX Reactions

• HI does not react• Poor yields of 1° and 2° chlorides• May get alkene instead of alkyl halide• Carbocation intermediate may rearrange.

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 20

Reactions with Phosphorus Halides

• Good yields with 1° and 2° alcohols

• PCl3 for alkyl chloride (but SOCl2 better)

• PBr3 for alkyl bromide

• P and I2 for alkyl iodide (PI3 not stable)

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 21

Mechanism with PBr3

• P bonds to -OH as Br- leaves

• Br- attacks backside (SN2)

• HOPBr2 leaves =>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 22

Reaction with Thionyl Chloride

• Produces alkyl chloride, SO2, HCl

• S bonds to -OH, Cl- leaves• Cl- abstracts H+ from OH

• C-O bond breaks as Cl- transferred to C =>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 23

Dehydration Reactions

• Conc. H2SO4 produces alkene

• Carbocation intermediate

• Zaitsev product

• Bimolecular dehydration produces ether

• Low temp, 140°C and below, favors ether• High temp, 180°C and above, favors

alkene =>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 24

Dehydration Mechanisms

CH3CHCH3

OHH2SO4

alcoholCH3CHCH3

OH

H

CH3CHCH3

CH2 CHCH3H2O

CH3OH

H3O+

CH3OH CH3 OH2 CH3 O

H

CH3

H2OCH3OCH3

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 25

Energy Diagram, E1

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 26

Unique Reactions of Diols

• Pinacol rearrangement• Periodic acid cleavage

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 27

Pinacol Rearrangement• Pinacol: 2,3-dimethyl-2,3-butanediol

• Dehydration with sulfuric acid

CH3 C

CH3

OH OH

CH3

C CH3H

+

CH3 C

CH3

OH OH

CH3

C CH3

H

CH3 C

CH3

OH

CCH3

CH3

CH3 C

CH3

OH

CCH3

CH3CH3 C

OH

CH3

C CH3

CH3

CH3 C

OH

CH3

C CH3

CH3

CH3 C

O

CH3

C CH3

CH3

pinacolone

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 28

Periodic Cleavage of Glycols

Same products formed as from ozonolysis of the corresponding alkene.

CH3 C

H

OH OH

CH3

C CH3

HIO4CH3 C

H

O+ C

OCH3

CH3

C CH3C

H CH3

CH3

OsO4

H2O2

O3

(CH3)2S

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 29

Esterification

• Fischer: alcohol + carboxylic acid

• Tosylate esters

• Sulfate esters

• Nitrate esters• Phosphate esters

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 30

Fischer Esterification• Acid + Alcohol yields Ester + Water

• Sulfuric acid is a catalyst.

• Each step is reversible.

CH3 C OH

O

+ CH2CH2CHCH3

CH3

OHH

+

CH3C

O

OCH2CH2CHCH3

CH3

+ HOH

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 31

Tosylate Esters• Alcohol + p-Toluenesulfonic acid, TsOH

• Acid chloride is actually used, TsCl

CH3CH2 O H + HO S

O

O

CH3

CH3CH2 O S

O

O

CH3

HOH+

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 32

Sulfate Esters

Alcohol + Sulfuric Acid

+HO S

O

O

OH H O CH2CH3H

+

OCH2CH3

O

O

SHO

CH3CH2O H + OCH2CH3

O

O

SHOH

+

CH3CH2O S

O

O

OCH2CH3

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 33

Nitrate Esters

+ H O CH2CH3H

+

N OH

O

OOCH2CH3N

O

O

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 34

Phosphate Esters

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 35

Phosphate Esters in DNA

=>

OCH2

HH

H

base

OP

O

O O

OCH2

HH

H

base

OP

O

O O

OCH2

HH

H

base

OP

O

O O

O

OCH2

HH

H

base

OP

O

O O

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 36

Alkoxide Ions

• ROH + Na (or NaH) yields sodium alkoxide• RO- + 1° alkyl halide yields ether (Williamson

ether synthesis)

CH3CH2CHCH3

O

CH3CH2 Br+ CH2CH2CH

CH3

O CH2CH3

=>

CH3CH2CH2

C

HH

Br OH

H

_

+

Chapter 11 37

End of Chapter 11