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838
J . Org. Chem. 2002, 67, 1838-1842
Electr och em ica l Hom ocou p lin g of 2-Br om om eth ylp yr id in es
Ca ta lyzed by Nick el Com p lexes
†
,†
‡
‡
Kelnner W. R. de Fran c¸ a, Marcelo Navarro,* EÄ ric L e´ onel, Muriel Durandetti, and
‡
J ean-Yves N e´ d e´ lec
Departamento de Qu ı´ mica Fundamental, Universidade Federal de Pernambuco, CCEN, 50670-901,
Recife, PE, Brasil, and Laboratoire d’Electrochimie, Catalyse et Synth e` se Organique,
UMR 7582 CNRS, 2, Rue Henri-Dunant, 94320 Thiais, France
Received November 13, 2001
2
,2′-Bipyridine (bpy) and a series of dimethyl-2,2′-bipyridines were synthesized from 2-bromopyridine
and 2-bromomethylpyridines, respectively, using an electrochemical process catalyzed by nickel
complexes. The method is simple and efficient, with isolated yields between 58 and 98% according
to the structure. We first studied the influence of the presence and the position of the methyl group
2
on the yield, using N,N-dimethylformamide (DMF) or acetonitrile (AN) as the solvent, NiBr bpy
as the catalyst, and Zn as the sacrificial anode, in an undivided cell and at ambient temperature.
On the basis of a better understanding of the reaction mechanism based on electroanalytical studies,
we could improve the dimerization both by substituting the catalyst ligand (bpy) by the reagent
itself, i.e., 2-bromomethylpyridine or 2-bromopyridine, and by using Fe instead of Zn as the sacrificial
anode.
In tr od u ction
The nickel-catalyzed homocoupling of aryl halides has
Sch em e 1
recently received considerable attention1 because the
reactions proceed under mild conditions, as compared to
the classical Ullmann reaction conditions, to give the
corresponding biaryls in good to high yields. The yield of
biaryls has notably been found to be dependent on a
suitable choice of the low-valent nickel complex and the
solvent. Iyoda and co-workers have thus reported an
precursor, DMF as the solvent, and Zn as the sacrificial
anode.
Because of the interest in substituted bipyridines as
6
precursors of chelates for transition-metal complexes, we
efficient homocoupling of aryl halides using Ni(PPh
3 2
)Br
decided to investigate this electrochemical route more
deeply in order to explore its scope and limitations. In
this paper we describe the influence on yield of the
methyl substituent position in 2-bromomethylpyridines,
using first the reaction conditions previously applied to
the synthesis of 6,6′-dimethylbipyridine. This study has
led us to a better understanding of the catalytic cycle and
to ways of improving the preparation of bipyridines.
as catalyst precursor, along with Zn as the reducing
agent, THF as the solvent, and in the presence of Et
NI.2
4
-
Nickel complexed to the ligand 2,2′-bipyridine (bpy) has
also been studied as a catalyst in the electroreductive
homocouplings and cross-couplings of aryl, alkenyl, and
alkyl halides.3 The electrochemical procedure is very
simple and efficient, giving notably very good yields of
the respective dimers in the homocoupling reactions. In
addition, the use of a sacrificial anode makes possible
the implementation of an undivided electrochemical cell.
Several anode metals may be used such as Mg, Al, Fe,
Resu lts a n d Discu ssion
We thus first conducted a series of experiments with
2
-bromopyridine and the various 2-bromomethylpy-
ridines with the reaction conditions previously used for
and Zn and are selected according to both the reduction
5
potential of the organic halide and the type of reaction.4
the dimerization of 2-bromo-6-methylpyridine: that is,
in DMF, at room temperature, with a current intensity
of 100 mA, and having a zinc rod as the sacrificial anode.
Results are given in Table 1.
Recently we reported the successful electrochemical
dimerization of 2-bromo-6-methylpyridine, yielding 75%
of the isolated product, 6,6′-dimethyl-2,2′-bipyridine
5
The reactions were run until the full consumption of
the starting reagent. There is clearly an influence of the
position of the methyl groups on the efficiency of the
dimerization. Thus, 3,3′-dimethyl-2,2′-bipyridine is ob-
tained in the same yield as bipyridine, while 4,4′- and
(
2
Scheme 1). The method uses NiBr bpy as the catalyst
†
Universidade Federal de Pernambuco.
‡
Laboratoire d′Electrochimie, Catalyze et Synth e` se Organique.
1) (a) J olly, P. W.; Wilke, G. The Organic Chemistry of Nickel;
(
Academic Press: New York, 1975; Vol. 2, p 246. (b) J olly, P. W. In
Nickel Catalysed Coupling of Organic Halides and Related Reactions;
Wilkinson, G., Ed.; Pergamon Press: Oxford, U.K., 1982; Vol. 8, p 713.
2) Iyoda, M.; Otsuka, H.; Sato, K.; Nisato, N.; Oda, M, Bull. Chem.
Soc. J pn. 1990, 63, 80
3) N e´ d e´ lec, J .-Y.; P e´ richon, J .; Troupel, M. Topics in Current
Chemistry; Springer-Verlag: Berlin, Heidelberg, 1997; p 185.
4) Chaussard, J .; Folest, J .-C.; N e´ d e´ lec, J .-Y.; P e´ richon, J .; Sibille,
S.; Troupel, M. Synthesis 1990, 370.
5
,5′-dimethyl-2,2′-bipyridines are obtained in a higher
yield, 45%, and 6,6′-dimethyl-2,2′-bipyridine gives the
highest yield, 75%.
(
(
(5) Cassol, T. M.; Demnitz, F. W. J .; Navarro, M.; De Neves, E. A.
Tetrahedron Lett. 2000, 41, 8203.
(6) Kaes, C.; Katz, A.; Housseini, M. W. Chem. Rev. 2000, 100, 3553.
(
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0.1021/jo016280y CCC: $22.00 © 2002 American Chemical Society
Published on Web 02/26/2002