TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4271–4273
Photochemical conversion of 4-chloroaniline into 4-alkylanilines†
Paolo Coppo, Maurizio Fagnoni and Angelo Albini*
Department of Organic Chemistry, University of Pavia, v. Taramelli 10, 27100 Pavia, Italy
Received 25 July 2000; revised 11 April 2001; accepted 27 April 2001
Abstract—Irradiation of 4-chloroanilines in the presence of alkenes gives 4-(2%-chloroalkyl)-anilines. When the irradiation is
carried out in the presence of NaBH4, 4-alkylanilines are obtained directly. The reaction appears to occur via the corresponding
phenyl cation. © 2001 Elsevier Science Ltd. All rights reserved.
Methods for the preparation of ring-alkylated anilines
are scarce. As for alkylation of anilines, the Friedel–
Crafts reaction has been applied only to some tertiary
derivatives1 and palladium-catalysed coupling occurs
only with amides.2 Other examples involve elaborate
procedures such as metallation of chromium carbonyl
complexes3 or reactions via N-sulfonium salts.4 Con-
versely, the seemingly appealing SRN1 amination of
alkylphenylhalides is restricted to a few applications.5
Therefore, entry to ring-alkylated anilines usually
involves multistep procedures, generally the nitration of
alkylbenzenes—with the associated problems of regiose-
lectivity and side-reactions—followed by reduction.6 As
an example, the reported synthesis of 4-alkylanilines, a
class of compounds active as strong and selective aro-
matase inhibitors, involves a low-yielding multi-step
procedure via the nitro derivative.7
We have recently reported8 that irradiation of 4-choro-
N,N-dimethylaniline (1a, Scheme 1) in the presence of
benzene, as well as some alkenes, results in substitution
of the chloro group by the phenyl or alkyl group (see
formula 2), whereas in the absence of such traps reduc-
tive dechlorination to give 3a and coupling to give the
monochloro diphenyldiamine 4a occur. This offered an
alternative entry to alkylanilines and we were eager to
explore whether the reaction could be extended and, in
particular, whether it also occurred with a primary
amine such as 1b.
In fact, we found that irradiation of 4-chloroaniline 1b
in neat acetonitrile proceeded in a manner similar to
that of 1a, yielding diamine 4b and aniline 3b. When
the reaction was carried out in the presence of alkenes
(1 M), the yield of products 3b and 4b was strongly
reduced and 4-(b-chloroalkyl)anilines were formed in
reasonable yields (55–73%). Thus, with both cyclopen-
tene (n=1) and cyclohexene (n=2) the corresponding
b-chloroalkylated compounds 5 and 6 were the main
products (trans stereochemistry, see Scheme 2, Table 1).
We then tested a non-symmetrically substituted olefin,
1-hexene, and found that the two regioisomeric adducts
7 (main product) and 8 were formed (ratio of 7/8 1.9).9
Our current rationalisation is that the initial step is
heterolytic photocleavage of the CꢀCl bond, followed
by the addition of the resulting phenyl cation (9, see
Scheme 3)—and then of chloride—onto the alkenes.
We carried out some experiments to test this mecha-
nism (versus an alternative hypothesis where homolytic
cleavage occurred and where the phenyl radical (10)
was involved). Thus, the photoreaction of chloroanili-
nes required a polar medium (e.g. both 1a and 1b were
ca. 20 times less photoreactive in cyclohexane than in
acetonitrile). 4-Iodoaniline, expected to undergo
Scheme 1.
Keywords: alkylation; photochemistry; alkyl halides; fragmentation
reaction.
* Corresponding author. Fax: 39-0382-507323; e-mail: albini@
chifis.unipv.it
†
Dedicated with gratitude to Professor Iacopo Degani on the occa-
sion of his 70th birthday.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00709-2
Coppo, Paolo
