Improved synthesis of 5,5"-dibromo-2,2′:6′,2"-terpyridine

Article abstract of DOI:10.1055/s-2002-19767

5,5"-dibromo-2,2′:6′,2"-terpyridine has been synthesized in very good yield and on a multigram scale modifying the Stille cross-coupling strategy published by Schlüter and coworkers in a previous work.

Full text of DOI:10.1055/s-2002-19767

LETTER
271
Improved Synthesis of 5,5 -Dibromo-2,2 :6 ,2 -terpyridine
I
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Synt he
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dine t X. Colasson, Christiane Dietrich-Buchecker,* Jean-Pierre Sauvage
Laboratoire de Chimie Organo-Minérale, UMR 7513 du CNRS, Faculté de Chimie, Université Louis Pasteur, 4, rue Blaise Pascal,
67070 Strasbourg Cedex, France
Fax +33(390)241368; E-mail: dietrbuc@chimie.u-strasbg.fr
Received 1 November 2001
Abstract: 5,5 -dibromo-2,2 :6 ,2 -terpyridine has been synthe-
sized in very good yield and on a multigram scale modifying the
Stille cross-coupling strategy published by Schlüter and coworkers
in a previous work.
Key words: 5,5 -dibromo-2,2 :6 ,2 -terpyridine, Stille cross-cou-
pling, terpyridine derivatives
Terpyridine derivatives are of special interest as far as co-
ordination chemistry applied to electron transfer is
concerned1 as well as in the field of macrocyclic and lin-
ear receptors.2 A particularly promising starting com-
pound in view of preparing terpyridine-containing rings
Scheme 1
and multicomponent ligands is 5,5 -dibromo-2,2 :6 ,2 -
terpyridine. Only a few examples of 5,5’’-disubstituted-
2,2 :6 ,2 -terpyridines are known.3 Schlüter and cowork-
matographed on a short and wide alumina column without
any decomposition. 5 was obtained following the proce-
dure described in the literature.11 The yield of the latter
could be easily improved by controlling the time of reac-
tion. It appeared that after 7 hours of reflux the product
underwent a reduction process leading to plain pyridine.
The last step of the synthesis described here was per-
formed in the classical Stille cross-coupling conditions
and 6 was obtained in 90% yield on a multigram scale.12
The very good yield observed for this double Stille cross-
coupling reaction can be explained in two points: 1) this
step is performed with isolated and pure intermediates (in
this case, 3 and 5), 2) the high reactivity of a carbon-iodine
bond permitting almost quantitative and selective oxida-
tive addition on Pd in presence of a carbone-bromine
bond.
ers have first proposed the synthesis of diX-2,2 :6 ,2 -
terpyridine (X = Br or Cl) substituted in C-5 and C-5 po-
sitions,4 using the Stille cross-coupling methodology.5
The yield could be improved (from 26.5% to 50% for the
final step consisting of a Stille coupling using 2,6-bis(tri-
methylstannyl)pyridine) taking advantage of the selectiv-
ity between iodine and bromine.6
We would like to report that a new strategy leads to a very
efficient synthesis of 5,5 -dibromo-2,2 :6 ,2 -terpyridine,
in which the final coupling occurs with 90% yield. A po-
tential difficulty of Schlüter’s strategy is the preparation
and the use (in situ) of 2,6-bis(trimethylstannyl)pyridine.7
In order to avoid this intermediate, we envisaged a syn-
thetic way in which the stannyl functionality was brought
by the two external and disymmetric pyridines of the final
terpyridine and not by the central one.
1 was obtained following the procedure described in the
literature in 95% yield starting from the commercially
available 2-amino-5-bromopyridine.8 The transformation
of 1 into 2 occured in hydroiodic acid (57% in water) in
80% yield (Scheme).6 2-Trimethylstannyl-5-bromopyri-
dine 3 was easily obtained by reacting 2 with BuLi (1.4 M
in hexane) in toluene at –78 °C and then quenching the
lithium derivative with ClSnMe3.9 The iodo vs. bromo se-
lectivity in the interconversion with BuLi as well as the
nature of the solvent, which determines the regioselectiv-
ity,10 afforded 3 in quantitative yield. 3 could be chro-
Acknowledgement
We acknowledge the French Ministry of National Education for a
fellowship (for B. X. C.).
References
(1) Sauvage, J.-P.; Collin, J.-P.; Chambron, J.-C.; Guillerez, S.;
Coudret, C. Chem. Rev. 1994, 94, 993.
(2) (a) Constable, E. C. Comprehensive Supramolecular
Chemistry, 9; Pergamon: Oxford, 1996, 213. (b) Sauvage,
J.-P. Acc. Chem. Res. 1998, 31, 611.
(3) Cargill-Thompson, A. M. W. Coord. Chem. Rev. 1997, 160,
1.
(4) Lehmann, U.; Henze, O.; Schlüter, A. D. Chem.-Eur. J.
1999, 5, 854.
(5) Stille, J. K. Angew. Chem., Int. Ed. Engl. 1986, 25, 508;
Angew. Chem. 1986, 98, 504.
Synlett 2002, No. 2, 01 02 2002. Article Identifier:
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B. X. Colasson et al.
LETTER
(6) Lehmann, U.; Schlüter, A. D. Eur. J. Org. Chem. 2000,
3483.
(7) Yamamoto, Y.; Yanagi, A. Chem. Pharm. Bull. 1982, 30,
1731.
eluted with ether). This short purification afforded 3 in 97%
yield (6.39 g, yellow oil).
1H NMR (200 MHz, CDCl3): = 8.82 (d, 1 H, H6, 4J = 2.5
Hz); 7.68 (dd, 1 H, H4, 3J = 8.1 Hz, 4J = 2.5 Hz); 7.35 (d, 1
H, H3, 3J = 8.1 Hz); 0.32 (s with Sn satellites, 9 H, CH3,
J[1H-119Sn] = 54.4 Hz, J[1H-117Sn] = 51.2 Hz).
MS (EI): m/z = 321.0 ([M+] calcd 320.8).
(8) Case, F. H. J. Am. Chem. Soc. 1946, 68, 2574.
(9) 5-Bromo-2-iodopyridine (5.85 g, 20.5 mmol) was dissolved
in 200 mL of toluene. 16.2 mL BuLi (1.4 M in hexane, 22.5
mmol) were added dropwise onto the solution maintained at
–20 °C during the beginning of the addition (after the first
drops of BuLi, the solution became red) and progressively
the temperature was lowered to –76 °C. The solution was
then stirred at –76 °C for two hours after which a solution of
ClSnMe3 (4.92 g, 24.6 mmol) in toluene was added
carefully. At the end of the addition the yellow solution was
stirred for one additional hour at –76 °C and then allowed to
warm up to r.t. Toluene was evaporated and the crude
product taken up in CH2Cl2. Insoluble salts were filtered off
on a sintered glass. The filtrate was evaporated to dryness
and the resulting yellow oil was submitted to a very fast
chromatography (15 min, over 100 g of oven dried alumina,
(10) Wang, X.; Rabbat, P.; O’Shea, P.; Tillyer, R.; Grabowsky, E.
J. J.; Reider, P. J. Tetrahedron Lett. 2000, 41, 4335.
(11) Newkome, G. R.; Roper, J. M. J. Organomet. Chem. 1980,
186, 147.
(12) 5-Bromo-2-trimethylstannylpyridine 3 (6.4 g, 19.9 mmol)
and 2,6-diiodopyridine 5 (3.17 g, 9.5 mmol) were dissolved
in toluene (200 mL). The solution was degassed three times,
Pd(PPh3)4 (660 mg, 0.6 mmol) added, and the mixture was
degassed three times again. The solution was heated at reflux
for 18 h. Pd0 was filtered off and the solvent evaporated.
Filtration of the resulting solid on alumina with CH2Cl2 as
eluent yielded 6 in 90% yield (3.32 g, white solid, according
to 1H NMR, purity is 95%). All spectroscopic data are in
good agreement with literature.5
Synlett 2002, No. 2, 271–272 ISSN 0936-5214 © Thieme Stuttgart · New York