1 15.1 15.1 Sources of Alcohols Sources of Alcohols Organic - - PDF document

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• Alcohols by reduction of aldehydes and ketones
• Metal hydride reagents
• Reduction of carboxylic acid derivatives with LiAlH4
• Alcohols by opening of epoxides
• Preparation of diols
• Reactions of alcohols

Chapter 15: Alcohols, Chapter 15: Alcohols, Diols Diols, and Ethers , and Ethers 15.1 15.1 – – Sources of Alcohols Sources of Alcohols 15.1 15.1 – – Sources of Alcohols Sources of Alcohols

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15.1 15.1 – – Sources of Alcohols Sources of Alcohols Organic Synthesis Organic Synthesis – – Molecular Engineering Molecular Engineering

Two main components : Carbon-Carbon bond formation – organometallics Functional group manipulation – e.g. R2CHOH to R2C=O

OH CH3CH2OH

15.2 15.2 – – Preparation of Alcohols by Reduction of RR Preparation of Alcohols by Reduction of RR’ ’C=O C=O

H X H H H M R O R' R O H R' XH3 R O H R' X(OCHRR')3

solvent (for NaBH4)

• r H3O+ (for LiAlH4)

R OH H R'

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15.3 15.3 – – Preparation of Alcohols by Reduction of RCO Preparation of Alcohols by Reduction of RCO2

2R

R’ ’

Mechanism analogous to Grignard-Ester Reaction

O OH

• 1. LiAlH4, THF
• 2. H3O+

OH H H O OCH3

• 1. LiAlH4, THF
• 2. H3O+

OH H H

15.4 15.4 – – Preparation of Alcohols from Preparation of Alcohols from Epoxides Epoxides

Nucleophilic ring-opening is an SN2 process governed by steric hindrance around the electrophilic carbon being attacked

O

m-CPBA

• 1. CH3MgBr
• 2. H3O+

OH CH3

• 1. m-CPBA
• 2. CH3MgBr
• 3. H3O+

OH CH3

15.5 15.5 – – Preparation of Preparation of Diols Diols

Cis-dihydroxylation via an osmate ester intermediate

O Os O O O

OsO4, ROOH, NaOH

OH OH O O Os O O

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15.6 15.6 – – Reactions of Alcohols Reactions of Alcohols – – Review Review

OH

TsCl pyridine

OTs X Cl

HI, HBr SOCl2

Br

PBr3

15.7 15.7 – – Conversion of Alcohols to Ethers Conversion of Alcohols to Ethers

OH ONa OCH3

NaH THF CH3Br

OH N O H OCH2CH3 N O H

• 1. NaH, THF
• 2. CH3CH2I

Phenacetin

• Acid-base reaction followed by SN2 reaction on alkyl halide
• Limited to primary alkyl halides (secondary give E2 in competition)

OH

H+, heat

O

(-H2O)

O H H HO O H

• H+

(-H2O)

• Acid-base reaction followed by SN2 reaction on alcohol
• Limited to primary alcohols (2o/3o give elimination products)

15.7 15.7 – – Conversion of Primary Alcohols to Ethers Conversion of Primary Alcohols to Ethers

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OH

H2SO4 ∆

O OH

H2SO4 ∆

O HO OH

H2SO4 ∆

O intermolecular intermolecular intramolecular

15.7 15.7 – – Conversion of Primary Alcohols to Ethers Conversion of Primary Alcohols to Ethers 15.8 15.8 – – Esterification Esterification of Alcohols

• f Alcohols

ROH + R' O OH

H+

R' O OR alcohol + carboxylic acid ester + water + H2O O OH CH3OH H2SO4 O OCH3 O OH H2SO4 HO O O

Examples Acyl chlorides Acetic anhydride

OH O R O Cl

pyridine

O R OH O O O O O pyridine

15.8 15.8 – – Other Methods of Other Methods of Esterification Esterification

Skip Section 15.9

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OH H H H O OH O OH R H R O OH R R

no reaction under normal conditions

primary secondary tertiary

15.10 15.10 – – Oxidation of Alcohols Oxidation of Alcohols 15.10 15.10 – – Oxidation of Alcohols Oxidation of Alcohols – – Mechanism 15.3 Mechanism 15.3

N H ClCrO3 N H 2 Cr2O7 2 Pyridinium chlorochromate (PCC) Pyridinium dichromate (PDC)

OH H H

PDC or PCC CH2Cl2

O H primary alcohol aldehyde

Also works for secondary alcohols to ketones

15.10 15.10 – – Oxidation of Alcohols Oxidation of Alcohols – – Stopping at the Stopping at the Aldehyde Aldehyde

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Structure of NAD+

Figure 15.2

OH H H NAD+ O H alcohol dehydrogenase

15.11 15.11 – – Oxidation of Alcohols Oxidation of Alcohols – – Biological Oxidation Biological Oxidation 15.11 15.11 – – Oxidation of Alcohols Oxidation of Alcohols – – Biological Oxidation Biological Oxidation

Uses:

R R OH OH R R

R R O O R R I O O O R R O O R R

OH OH

OsO4 t-BuOOH NaOH NaIO4

CHO CHO

H2O

Compare to ozonolysis:

• 1. O3

CHO CHO

• 2. Zn, Me2S

15.12 15.12 – – Oxidative Cleavage of Vicinal Oxidative Cleavage of Vicinal Diols Diols

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Important – more acidic than alcohols: pKa ~ 10

SH SH SH SH ethanethiol butanethiol thiophenol 3-methyl-1-butanethiol

15.13 15.13 – – Thiols Thiols