our previous work,9 the product resulting from the O-arylation
of the pyridine derivative by the solvent was detected in small
quantity (8%).
Notes and references
1 S. Tasler, J. Mies and M. Lang, Adv. Synth. Catal., 2007, 349,
2286.
With this efficient system in hand we next extended the
scope of the reaction to various bromopyridine derivatives.
We found that the reaction was applicable to a broad range of
derivatives and was not strongly affected by electron-releasing
or electron-withdrawing groups (Table 5, entries 1, 2, 4 and 5).
The efficiency of the reaction was not sensitive to the steric
hindrance of an adjacent methyl group (Table 4, entry 2).
Similarly, the catalytic system was also found to be suitable for
the amination of 3-bromopyridine and 2-bromopyrimidine,
yielding 3-aminopyridine 7 and 2-aminopyrimidine 8 in high
yields (Table 2, entries 6 and 7).16 It is noteworthy that the
diamination of 2,6-dibromopyridine afforded 4 in good yield.
However, the use of 20 equiv. of NH3ÁH2O (10 equiv./Py–Br)
resulted in an incomplete reaction leading to a mixture of 2,6-
diaminopyridine and 2-bromo-6-aminopyridine. To ensure
good conversion and yield, 40 equiv. of NH3ÁH2O (20 equiv.
per Br) have to be used, then the diaminopyridine 4 was
isolated in 68% yield. Finally, as mentioned previously for
the amination of 2-bromopyridine, the synthesis of products 2,
5 and 8 were accompanied by the formation of O-arylation
products in 5%, 6% and 7%, respectively. Finally, the amination
reaction using 10 equiv. of NH3ÁH2O was still possible upon
longer reaction time. For instance the transformation of
6-bromo-2-picoline and 2-bromo-6-methoxypyridine were
performed over 24 h with high conversion (98%) providing 2
and 5 in 70 and 80% yield, respectively.
2 Y. Shirota and H. Kageyama, Chem. Rev., 2007, 107, 953.
3 (a) F. Ullmann, Ber. Dtsch. Chem. Ges., 1903, 36, 2382;
(b) I. Goldberg, Ber. Dtsch. Chem. Ges., 1906, 39, 1691. For recent
reviews on copper mediated coupling reactions, see: (c) F. Monnier
and M. Taillefer, Angew. Chem., Int. Ed., 2008, 47, 3096;
(d) G. Evano, N. Blanchard and M. Toumi, Chem. Rev., 2008,
108, 3054; (e) S. V. Ley and A. W. Thomas, Angew. Chem., Int.
Ed., 2003, 42, 5400; (f) D. Ma, Acc. Chem. Res., 2008, 41, 1450.
4 S. Guram, R. A. Rennels and S. L. Buchwald, Angew. Chem., Int.
Ed. Engl., 1995, 34, 1348.
5 J. Louie and J. F. Hartwig, Tetrahedron Lett., 1995, 36, 3609.
6 For reviews on palladium catalysed amination reactions, see:
(a) J. F. Hartwig, Acc. Chem. Res., 2008, 41, 1534;
(b) D. S. Surry and S. L. Buchwald, Angew. Chem., Int. Ed.,
2008, 47, 6338; (c) S. L. Buchwald, C. M. Auger, G. Mignani and
U. Scholz, Adv. Synth. Catal., 2006, 348, 23.
7 For recent publications on palladium catalyzed amination using
ammonia, see: (a) T. Schulz, C. Torborg, S. Enthaler, B. Schaffner,
¨
A. Dumrath, A. Spannenberg, H. Neumann, A. Borner and
¨
M. Beller, Chem.–Eur. J., 2009, 15, 4528; (b) G. D. Vo and
J. F. Hartwig, J. Am. Chem. Soc., 2009, 131, 11049; (c) Q. Shen
and J. F. Hartwig, J. Am. Chem. Soc., 2006, 128, 10028;
(d) D. S. Surry and S. L. Buchwald, J. Am. Chem. Soc., 2007,
129, 10354. For a review, see: (e) M. C. Willis, Angew. Chem., Int.
Ed., 2007, 46, 3402.
8 For a recent review on amination reactions including copper
catalysed reactions, see: M. Kienle, S. R. Dubbaka, K. Brade
and P. Knochel, Eur. J. Org. Chem., 2007, 4166.
9 S. Gaillard, M. K. Elmkaddem, C. Fischmeister, C. M. Thomas
and J.-L. Renaud, Tetrahedron Lett., 2008, 49, 3471.
10 For a recent example of copper catalyzed amination using
ammonia, see: R. Ntaganda, B. Dhudshia, C. L. B. Macdonald
and A. N. Thadani, Chem. Commun., 2008, 6200.
11 J. Kim and S. Chang, Chem. Commun., 2008, 3052.
12 (a) M. Taillefer and N. Xia, 2007, Fr 2007/06827; (b) N. Xia and
M. Taillefer, Angew. Chem., Int. Ed., 2009, 48, 337.
13 L. Jiang, X. Lu, H. Zhang, Y. Jiang and D. Ma, J. Org. Chem.,
2009, 74, 4542.
14 H. Xu and C. Wolf, Chem. Commun., 2009, 3035.
15 (a) F. Y. Kwong, A. Klapars and S. L. Buchwald, Org. Lett., 2002,
4, 581; (b) F. Lang, D. Zewge, I. N. Houpis and R. P. Volante,
Tetrahedron Lett., 2001, 42, 3251; (c) Z. Guo, J. Guo, Y. Song,
L. Wang and G. Zou, Appl. Organomet. Chem., 2009, 23, 150.
16 Pyrimidine derivatives are of potential interest for the treatment of
diseases associated with histamine H4 receptor activity. H. Sato,
K. Tanaka, M. Shimazaki, K. Urbahns, K. Sakai, F. Gantner and
K. Bacon, WO2005/054239, 2005.
In summary, we have presented an efficient catalytic system
for the amination of various bromopyridine and pyrimidine
derivatives. The reaction proceeds with high conversions and
yields under mild conditions regardless of the substitution by
electron-donating or -withdrawing groups. The interest of the
system is based on the use of a cheap copper complex and
aqueous ammonia as a cheap and easy to handle ammonia
source.
The authors are grateful to the Agence Nationale pour la
Recherche for its support through a ‘‘Jeunes Chercheurs-
Jeunes Chercheuses’’ grant (ANR-06-JCJC-0013).
ꢀc
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 925–927 | 927