Organic Chemistry

Several sulfonyl chlorides are available to activate OH groups. The most common one

is para-toluenesulfonyl chloride.

Once the alcohol has been activated by being converted into a sulfonate ester, the

appropriate nucleophile is added, generally under conditions that favor reactions.

The reactions take place readily at room temperature because the leaving group is so

good. For example, a para-toluenesulfonate ion is about 100 times better than a chlo-

ride ion as a leaving group. Sulfonate esters react with a wide variety of nucleophiles,

so they can be used to synthesize a wide variety of compounds.

para-Toluenesulfonyl chloride is called tosyl chloride and is abbreviated TsCl; the

product of the reaction of para-toluenesulfonyl chloride and an alcohol is called an

alkyl tosylateand is abbreviated ROTs. The leaving group, therefore, is The

product of the reaction of trifluoromethanesulfonyl chloride and an alcohol is called

an alkyl triflateand is abbreviated ROTf.

PROBLEM 4 SOLVED

Explain why the ether obtained by treating an optically active alcohol with followed

by sodium methoxide has the same configuration as the alcohol, whereas the ether

obtained by treating the alcohol with tosyl chloride followed by sodium methoxide has a

configuration opposite that of the alcohol.

SOLUTION Conversion of the alcohol to the ether via the alkyl halide involves two

successive reactions: (1) attack of on the bromophosphite and (2) attack of

on the alkyl halide. Each reaction takes place with inversion of configura-

tion, so the final product has the same configuration as the starting material. In contrast,

CH 3 O- SN 2

SN 2 Br-

H

R OH

CH 3

H

R OCH 3

CH 3

1. PBr 3 /pyridine


2. CH 3 O−

H

R OH

CH 3

H

CH 3 O R

CH 3

1. TsCl/pyridine


2. CH 3 O−

PBr 3

an alkyl tosylate

CH 3 CH 2 CH 2 OTs + −C N CH 3 CH 2 CH 2 C N + −OTs

an alkyl triflate

CH 3 CH 2 CH 2 OTf + CH 3 NH 2 CH 3 CH 2 CH 2 NH 2 CH 3 + −OTf

+

• OTs.

SN 2

para-toluenesulfonyl

chloride

methanesulfonyl

chloride

H 3 CSCl

O

O

SCl

O

O

H 3 C

trifluoromethanesulfonyl

chloride

SCl

O

O

F 3 C

444 CHAPTER 12 Reactions of Alcohols, Ethers, Epoxides, and Sulfur-Containing Compounds

Tutorial:

Leaving groups

3-D Molecules:

Methanesulfonyl chloride;

Methanesulfonate

methyl ester

−

−

−OTs

CH 3 SCH 3 CH 2 CH 2 CH 2 O S

O

O

CH 3 CH 3 CH 2 CH 2 CH 2 SCH 3 −O S

O

O

+ + CH 3

CN CH 3 CH 2 CH 2 O S N

O

O

CH 3 CH 3 CH 2 CH 2 C −O S

O

O

+ + CH 3

−OTs

ROTs

ROTs

BRUI12-437_480r3 27-03-2003 11:51 AM Page 444