Chapter 11 1

CH3CH2CH2

CHH

Br OH

H

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 =>

Chapter 11 2

CH3CH2CH2

CHH

Br OH

H

Summary Table

=>

Chapter 11 3

CH3CH2CH2

CHH

Br OH

H

Oxidation States• Easy for inorganic saltsCrO4

2- 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=>

Chapter 11 4

CH3CH2CH2

CHH

Br OH

H1º, 2º, 3º Carbons

=>

Chapter 11 5

CH3CH2CH2

CHH

Br OH

H

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

=>

Chapter 11 6

CH3CH2CH2

CHH

Br OH

HOxidation 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

=>

Chapter 11 7

CH3CH2CH2

CHH

Br OH

H3° Alcohols Don’t Oxidize• Cannot lose 2 H’s• Basis for chromic acid test

=>

Chapter 11 8

CH3CH2CH2

CHH

Br OH

H

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 1alcohols to aldehydes. =>

Chapter 11 9

CH3CH2CH2

CHH

Br OH

HBiological 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.

=>

Chapter 11 10

CH3CH2CH2

CHH

Br OH

H

Alcohol as a Nucleophile

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

=>

COH

R X

Chapter 11 11

CH3CH2CH2

CHH

Br OH

HAlcohol 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)

=>

COH

+

C-Nuc bond forms, C-O bond breaks

Chapter 11 12

CH3CH2CH2

CHH

Br OH

H

Formation of Tosylate Ester

p-toluenesulfonyl chlorideTsCl, “tosyl chloride”

COH

CH3

S

Cl

OO N

CH3

S OO

OH

C

CH3

S

O

OO

C

ROTs,a tosylate ester

=>

Chapter 11 13

CH3CH2CH2

CHH

Br OH

H

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

=>

Chapter 11 14

CH3CH2CH2

CHH

Br OH

HSummary of Tosylate Reactions

=>

Chapter 11 15

CH3CH2CH2

CHH

Br OH

HReduction of Alcohols• Dehydrate with conc. H2SO4, then add H2

• Tosylate, then reduce with LiAlH4

CH3CHCH3

OHH2SO4

CH2 CHCH3H2

PtCH3CH2CH3

alcohol alkene alkane

alcoholCH3CHCH3

OHTsCl

CH3CHCH3

OTsLiAlH4

alkaneCH3CH2CH3

tosylate=>

Chapter 11 16

CH3CH2CH2

CHH

Br OH

HReaction 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

HR Br =>

Chapter 11 17

CH3CH2CH2

CHH

Br OH

HReaction 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. HCl1° alcohols react slowly or not at all.2 alcohols react in 1-5 minutes.3 alcohols react in less than 1 minute.

=>

Chapter 11 18

CH3CH2CH2

CHH

Br OH

H

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.

=>

Chapter 11 19

CH3CH2CH2

CHH

Br OH

HReactions 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)

=>

Chapter 11 20

CH3CH2CH2

CHH

Br OH

HMechanism with PBr3

• P bonds to -OH as Br- leaves• Br- attacks backside (SN2)• HOPBr2 leaves =>

Chapter 11 21

CH3CH2CH2

CHH

Br OH

HReaction 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

=>

Chapter 11 22

CH3CH2CH2

CHH

Br OH

H

Dehydration Reactions

• Conc. H2SO4 produces alkene• Carbocation intermediate• Saytzeff product• Bimolecular dehydration produces ether• Low temp, 140°C and below, favors ether• High temp, 180°C and above, favors

alkene =>

Chapter 11 23

CH3CH2CH2

CHH

Br OH

H

Dehydration Mechanisms

CH3CHCH3

OHH2SO4

alcoholCH3CHCH3

OHH

CH3CHCH3

CH2 CHCH3H2O

CH3OH

H3O+

CH3OH CH3 OH2 CH3 O

H

CH3

H2OCH3OCH3

=>

Chapter 11 24

CH3CH2CH2

CHH

Br OH

HEnergy Diagram, E1

=>

Chapter 11 25

CH3CH2CH2

CHH

Br OH

H

Unique Reactions of Diols

• Pinacol rearrangement• Periodic acid cleavage

=>

Chapter 11 26

CH3CH2CH2

CHH

Br OH

HPinacol 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

=>

Chapter 11 27

CH3CH2CH2

CHH

Br OH

HPeriodic Cleavage of Glycols

Same products formed as from ozonolysisof the corresponding alkene.

CH3 C

H

OH OH

CH3

C CH3HIO4

CH3 CH

O+ C

OCH3

CH3

C CH3C

H CH3

CH3

OsO4H2O2

O3(CH3)2S

=>

Chapter 11 28

CH3CH2CH2

CHH

Br OH

H

Esterification

• Fischer: alcohol + carboxylic acid• Tosylate esters• Sulfate esters• Nitrate esters• Phosphate esters

=>

Chapter 11 29

CH3CH2CH2

CHH

Br OH

H

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

=>

Chapter 11 30

CH3CH2CH2

CHH

Br OH

H

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+

=>

Chapter 11 31

CH3CH2CH2

CHH

Br OH

H

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

=>

Chapter 11 32

CH3CH2CH2

CHH

Br OH

H

Nitrate Esters

+ H O CH2CH3H+

N OHO

OOCH2CH3N

O

O

CH2

CH2

CH2

O H

O H

O H

+ 3 HO NO2

CH2

CH2

CH2

O NO2

O NO2

O NO2

nitroglycerineglycerine =>

Chapter 11 33

CH3CH2CH2

CHH

Br OH

H

Phosphate Esters

P

O

OH

OH

HO CH3OHP

O

OH

OH

CH3OCH3OH

P

O

OCH3

OH

CH3O

P

O

OCH3

OCH3

CH3O

CH3OH

=>

Chapter 11 34

CH3CH2CH2

CHH

Br OH

HPhosphate 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

Chapter 11 35

CH3CH2CH2

CHH

Br OH

H

Alkoxide Ions

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

ether synthesis)

CH3CH2CHCH3

OCH3CH2 Br+ CH2CH2CH

CH3

O CH2CH3

=>