A Guidebook to Mechanism in Organic Chemistry

Nucleophilic Substitution at a Saturated Carbon Atom

Even if no stereochemical point is at issue, participation of neigh­

bouring groups can be of interest because of their possible effect on

the rate of reaction. Thus ClCHaCHaSEt may be hydrolysed

approximately 10,000 times as rapidly as ClCHa-CH 2 -OEt under

the same conditions. This is far too large a difference for it to be due to

inductive or steric effects in such simple molecules and is thought to

arise from the rate-determining formation of a cyclic sulphonium salt

(XV) which, being highly strained, undergoes extremely ready and

rapid hydrolysis:

EtS: T CHgJ-Cl > EtS—CH* > EtS: CH 2 —OH

\ / determining \ / verv N. /

CH 2 CH 2 rap,d CH 2 +He

®C1 (XV)

The oxygen in the ether, CICHaCHaOEt, being more electro­

negative, does not part with its unshared electrons so readily as

sulphur, hence no cyclic salt is formed and the chlorine undergoes

hydrolysis by a normal displacement reaction. Suitable nitrogen-

containing compounds also show such enhanced ease of hydrolysis

proceeding via ethyleneimmonium iorfs such as (XVI):

m

f\ ^ rate ffi EOH

Me 2 m * CHj-J-CI —• > Me 2 N—CH 2 > Me 2 N: CH 2 —OH

\^y/ determining rapid

CH 2 CH 2 CH 2

eCI (XVI)

Their hydrolysis normally proceeds less rapidly than that of similar
sulphur compounds, however, reflecting the greater stability of the
cyclic nitrogen, as compared with the cyclic sulphur, intermediates.
These features are of interest in relation to the classical vesicant
agents of chemical warfare such as mustard gas itself, S(CH 2 -CH 2 C1),
and the related nitrogen mustards such as MeN(CHa-CHaCl)a. The
cyclic immonium derivatives obtained as intermediates during the
hydrolytic destruction of the latter have the additional hazard of being
powerful neurotoxins.

'a

EFFECT OF ENTERING AND LEAVING GROUPS

Changing the nucleophilic reagent employed, i.e. the entering group,
is not going to alter the rate of an SN 1 displacement reaction, e.g. of a