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

Chapter 15: Alcohols, Diols Chapter 15: Alcohols, Diols, and Ethers , and Ethers • Alcohols by reduction of aldehydes and ketones • Metal hydride reagents • Reduction of carboxylic acid derivatives with LiAlH 4 • Alcohols by opening of epoxides • Preparation of diols • Reactions of alcohols 15.1 – – Sources of Alcohols Sources of Alcohols 15.1 15.1 15.1 – – Sources of Alcohols Sources of Alcohols 1

15.1 15.1 – – Sources of Alcohols Sources of Alcohols Organic Synthesis – – Molecular Engineering Molecular Engineering Organic Synthesis Two main components : Carbon-Carbon bond formation – organometallics Functional group manipulation – e.g. R 2 CHOH to R 2 C=O OH CH 3 CH 2 OH 15.2 15.2 – – Preparation of Alcohols by Reduction of RR Preparation of Alcohols by Reduction of RR’ ’C=O C=O H O XH 3 O H X H M R R' R R' H H X(OCHRR') 3 OH O solvent (for NaBH 4 ) R R' R R' or H 3 O + (for LiAlH 4 ) H H 2

15.3 – – Preparation of Alcohols by Reduction of RCO Preparation of Alcohols by Reduction of RCO 2 R’ ’ 15.3 2 R O 1. LiAlH 4 , THF H H OH 2. H 3 O + OH O 1. LiAlH 4 , THF H H OCH 3 2. H 3 O + OH Mechanism analogous to Grignard-Ester Reaction 15.4 15.4 – – Preparation of Alcohols from Preparation of Alcohols from Epoxides Epoxides OH 1. CH 3 MgBr m -CPBA O 2. H 3 O + CH 3 OH 1. m -CPBA CH 3 2. CH 3 MgBr 3. H 3 O + Nucleophilic ring-opening is an S N 2 process governed by steric hindrance around the electrophilic carbon being attacked 15.5 – 15.5 – Preparation of Preparation of Diols Diols OH OsO 4 , ROOH, NaOH OH O O O O Os Os O O O O Cis-dihydroxylation via an osmate ester intermediate 3

15.6 – – Reactions of Alcohols Reactions of Alcohols – – Review Review 15.6 Br X Cl PBr 3 HI, HBr SOCl 2 OH OTs TsCl pyridine 15.7 15.7 – – Conversion of Alcohols to Ethers Conversion of Alcohols to Ethers NaH CH 3 Br OH ONa OCH 3 THF OCH 2 CH 3 OH 1. NaH, THF Phenacetin 2. CH 3 CH 2 I N N H H O O • Acid-base reaction followed by S N 2 reaction on alkyl halide • Limited to primary alkyl halides (secondary give E2 in competition) 15.7 15.7 – – Conversion of Primary Alcohols to Ethers Conversion of Primary Alcohols to Ethers H + , heat OH O (-H 2 O) - H + HO O H O (-H 2 O) H H • Acid-base reaction followed by S N 2 reaction on alcohol • Limited to primary alcohols (2 o /3 o give elimination products) 4

15.7 – – Conversion of Primary Alcohols to Ethers Conversion of Primary Alcohols to Ethers 15.7 H 2 SO 4 intermolecular OH O ∆ OH H 2 SO 4 O intermolecular ∆ H 2 SO 4 intramolecular HO OH ∆ O 15.8 15.8 – – Esterification Esterification of Alcohols of Alcohols O H + O ROH + + H 2 O R' OH R' OR alcohol + carboxylic acid ester + water O O CH 3 OH OCH 3 OH H 2 SO 4 Examples O O HO O OH H 2 SO 4 15.8 – 15.8 – Other Methods of Other Methods of Esterification Esterification O Acyl chlorides O R Cl OH O R pyridine Acetic anhydride O O O O OH O pyridine Skip Section 15.9 5

15.10 – – Oxidation of Alcohols Oxidation of Alcohols 15.10 H H H OH primary OH O O R H R secondary OH O R R tertiary no reaction under OH normal conditions 15.10 – – Oxidation of Alcohols Oxidation of Alcohols – – Mechanism 15.3 Mechanism 15.3 15.10 15.10 15.10 – – Oxidation of Alcohols Oxidation of Alcohols – – Stopping at the Stopping at the Aldehyde Aldehyde 2 Cr 2 O 7 N ClCrO 3 N H H 2 Pyridinium chlorochromate Pyridinium dichromate (PCC) (PDC) H H H PDC or PCC OH O CH 2 Cl 2 aldehyde primary alcohol Also works for secondary alcohols to ketones 6

15.11 – – Oxidation of Alcohols Oxidation of Alcohols – – Biological Oxidation Biological Oxidation 15.11 Structure of NAD + Figure 15.2 H H H NAD+ OH O alcohol dehydrogenase 15.11 – 15.11 – Oxidation of Alcohols Oxidation of Alcohols – – Biological Oxidation Biological Oxidation 15.12 15.12 – – Oxidative Cleavage of Vicinal Oxidative Cleavage of Vicinal Diols Diols R R R R O NaIO 4 R OH R O I O R OH R O O R O O R R R Uses: OH OsO 4 NaIO 4 CHO H 2 O CHO t -BuOOH OH NaOH Compare to ozonolysis: 1. O 3 CHO CHO 2. Zn, Me 2 S 7

15.13 – – Thiols Thiols 15.13 SH SH ethanethiol butanethiol SH SH thiophenol 3-methyl-1-butanethiol Important – more acidic than alcohols: pKa ~ 10 8