LMZ/CHEM109A/ Winter 2010 Chapter 10: Reactions of alcohols, amines, ethers, epoxides and sulfur-containing compounds I. Nucleophilic substitution reactions for the conversion of alcohols to other functional groups A. Introduction:

B. Conversion of alcohol to alkyl halide (Reaction at C-O bond) (sec. 11.1): in-situ converting OH into good leaving groups 1. Conversion of alcohol to alkyl bromide by reaction with HBr (or NaBr, H2SO4) R* OH + HBr + H2O

racemic mixture

SN1R* Br

3R* OH + HBr + H2O

inversionSN2R* Br

1

Mechanism?

2. Conversion of alcohol to alkyl chloride by reaction with Lucas reagent (HCl, ZnCl2)

R* OH + HCl + H2Oracemic mixture

SN1R* Cl

3R* OH + HCl + H2O

inversionSN2R* Cl

1

ZnCl2ZnCl2

Mechanism?

3. Reaction of alcohols (especially 1 or 2) with thionyl chloride (Sec. 11.9) R

R'H

OH

RR'

HX

R' = H or alkyl or aryl stereochemistry??

SOCl2 (+ SO2 + HCl)

Mechanism?

4. Reaction of alcohols (especially 1 or 2) with phosphorus halide (Sec. 11.8)

RR' H

OH

RR'

HX

R' = H or alkyl or aryl inversion for 1 and 2 C

PCl3, PBr3, or PCl5 (+ HOPX2X= Br or Cl)

(Note: For the synthesis of alkyl chloride, thionyl chloride generally gives better yields than PCl3 or PCl5.)

Mechanism (for reaction with PBr3)?

H3CC

CH2CH3

H OHPBr3

e.g. 1

C. Conversion of alcohols to tosylate (Reaction at O-H bond) (Sec. 10.3)

RR'

HOH

RR'

OH

+ NEt3HCl(or pyridinumchloride)R' = H or alkyl or aryl retension

CH3SO

OCl

tosyl chlorideSO

OCH3

tosylate(p-TosCl)

NEt3 or pyridine

HC

Et

Me OH CH3SO

OCl

pyridine

e.g. 2

D. Conversion of alcohol to other functional groups via halides or tosylates: Stereochemical consequences (sec/ 10.3)

PCl3or PBr3

RR' H

O-H

RR'

OTosH + HCl

retension

CH3SO

OCl Nu e.g. N3

SN2

RR'

NuHinversion

retension + inversion : overall inversion

RR' H

OH

RR'

HX + H2O

inversion

Nu e.g. N3SN2

RR' H

Nuinversion

double inversion : overall retention

(p-TosCl)