A Guidebook to Mechanism in Organic Chemistry

Electrophilic and Nucleophilic Substitution in Aromatic Systems *

and it is not possible to say, a priori, whether the overall effect on the

nucleus will be activation or de-activation. Here the direction and

magnitude of the dipole moment of Ph • Yean be some guide (see p. 119).

The overall electron-donating effect of OH and NH 2 , as compared

with the overall electron-withdrawing effect of CI, reflects the con­

siderably greater ease with which oxygen and nitrogen will release

their electron pairs as compared with chlorine; this is more than

sufficient to outweigh the inductive effect in the two former cases but

not in the latter. It should, however, be remembered that the moments

of a number of the composite groups, e.g. OH, are not collinear with

course, electrophilic reagents (e.g. KM11O4), on phenol, benzene and
nitrobenzene; phenol is extremely readily attacked with destruction
of the aromatic nucleus, while benzene is resistant to attack and
nitrobenzene even more so.
It is also reflected in the Friedel-Crafts reaction. Alkylation of
benzene leads to an initial product, Ph-R, which is more readily
attacked than benzene itself due to the electron-donating substituent
R. It is thus extremely difficult to stop the reaction at the mono-
alkylated stage and polyalkylation is the rule (p. 111). In acylation,
however, the initial product, Ph-CO-R, is less readily attacked
than is benzene itself and the reaction can readily be stopped at this
stage. It is indeed often preferable to synthesise a mono-alkyl benzene
by acylation followed by Clemmensen or other reduction, rather than
by direct alkylation, because of difficulties introduced during the
latter by polyalkylation and possible rearrangement of R. The presence
of an electron-withdrawing substituent is generally sufficient to
inhibit the Friedel-Crafts reaction and, for example, nitrobenzene is
often used as a solvent as it readily dissolves A1C1 3.
The overall electron-withdrawing effect is clear-cut with, for
example, N0 2 , for here inductive and mesomeric effects reinforce
each other, but with^e.g. NH 2 , these effects are in opposite directions