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Chapter 11Reactions of Alcohols

Jo BlackburnRichland College, Dallas, TX

Dallas County Community College District 2006, Prentice Hall

Organic ChemistryL. G. Wade, Jr.

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Types of Alcohol Reactions

• Dehydration to alkene

• Oxidation to aldehyde, ketone

• Substitution to form alkyl halide

• Reduction to alkane

• Esterification

• Williamson ether synthesis

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Summary Table

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Oxidation States

• For inorganics:

! CrO42- reduced to Cr2O3

! KMnO4 reduced to MnO2

• For organics

! 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

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1º, 2º, 3º Carbons

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

• Common reagent is Na2Cr2O7/H2SO4

• Active reagent probably H2CrO4

• Color change: orange to greenish-blue

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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.)

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Oxidation of 1°Alcohols

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3°Alcohols Don’t Oxidize

• Cannot lose 2 H’s

• Basis for chromic acid test

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Other Oxidation Reagents

• HOCl (NaOCl / H+)

• Collins reagent: Cr2O3 in pyridine

• Jones reagent: chromic acid in acetone

• KMnO4 (strong oxidizer)

• CuO, 300°C (industrial dehydrogenation)

• Various methods based on dimethylsulfoxide

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Chapter 11 11

Dehydrogenation:

Swern Oxidation

There are many other oxidation reagents. Here are two of them

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And the One You Did In the Lab

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Biological Oxidation

• Catalyzed by ADH, alcohol dehydrogenase.

• Oxidizing agent is NAD+, nicotinamideadenine 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.

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Product?

1. (CH3)2CHOH

2. (CH3)2C=O

3. CH3CH2COOH

4. No reaction

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Product?

1. CH3COOH

2. CH3CH2COOH

3. CH3CH2CHO

4. No reaction

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Product?

1. CH3COOH

2. CH3CH2COOH

3. CH3CH2CHO

4. No reaction

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Product?

1. (CH3)3COH

2. (CH3)2C=O

3. CH2=C(CH3)2

4. No reaction

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Alcohol as a Nucleophile

• ROH is weak nucleophile

• RO- is strong nucleophile

• New O-C bond forms, O-H bond breaks.

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Alcohol as an Electrophile

• OH- is very poor leaving group unless it is protonated

• Most nucleophiles are strong bases which would remove H+.

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

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∂ +

C-Nuc bond forms, C-O bond breaks

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Formation of Tosylate Ester

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p-toluenesulfonyl chlorideTsCl, “tosyl chloride”

ROTs,a tosylate ester

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(basically same as halides)

• 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

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SN2 Reactions of Tosylates

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Reduction of Alcohols

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Cannot just reduce off the oxygen of an alcohol

1. Dehydrate with conc. H2SO4, then add H2

or2. Tosylate, then reduce with LiAlH4

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Conversion to Alkyl Halides

• -OH of alcohol is protonated

• -OH2+ is good leaving group

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

• 1°alcohols react via SN2

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Reaction with HBr

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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.

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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.

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Reactions with Phosphorus Halides or Thionyl Chloride

• Good yields with 1°and 2°alcohols

• SOCl2 generally best for alkyl chlorides

• PBr3 for alkyl bromide

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

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Mechanism with PBr3

• P bonds to -OH as Br- leaves

• Br- attacks backside (SN2)

• HOPBr2 leaves Chapter 11 30

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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

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Product?

1. CH3CH2CH2OTs

2. CH3CH2CH2OCl

3. CH3CH2CH2Cl

4. CH3CH2CH2Ts

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Product?

1. CH3CH2CH2OSCl22. CH3CH2CH2Cl

3. CH3CH2CH2OCl

4. CH3CH2CH2SO2H

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Product?

1. CH3CH2CH2OPBr3

2. CH3CH2CH2OBr

3. CH3CH2CH2Br

4. CH3CH2CH2PBr2 0

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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

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Dehydration Mechanisms

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CH2 CHCH3

H

H2O CH2 CHCH3

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Energy Diagram, E1

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Unique Reactions of Diols

• Pinacol rearrangement

• Periodic acid cleavage

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Pinacol Rearrangement

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

• Dehydration with sulfuric acid

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Periodic Acid Cleavage of Glycols

Same products formed as from ozonolysis of the corresponding alkene.

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Esterification

• Fischer: alcohol + carboxylic acid

• Tosylate esters

• Sulfate esters

• Nitrate esters

• Phosphate esters

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Fischer Esterification

• Acid + Alcohol yields Ester + Water

• Sulfuric acid is a catalyst.

• Each step is reversible.

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Tosylate Esters

• Alcohol + p-Toluenesulfonic acid, TsOH

• Acid chloride is actually used, TsCl

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Why Tosylate Esters?

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Sulfate Esters

Alcohol + Sulfuric Acid

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Nitrate Esters

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Phosphate Esters

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Phosphate Esters in DNA

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Product?

1. CH3CH2COOCH3

2. CH3COOCH2CH3

3. CH3CH2COOCH2CH3

4. CH3COOCH3

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Product?

1. CH3OSO3H

2. CH3OSO3CH3

3. CH3OSO2CH3

4. CH3OSO2H

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Williamson Ether Synthesis

• ROH + Na (or NaH) yields sodium alkoxide

• RO- + 1°alkyl halide yields ether

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End of Chapter 11

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