S. P. Borikar et al. / Tetrahedron Letters 50 (2009) 1007–1009
1009
References and notes
Br
1. (a) Kuroboshi, M.; Waki, Y.; Tanaka, H. J. Org. Chem. 2003, 68, 3938; (b)
Qingwei, Y.; Elizabeth, P. K.; Zhi, Y. J. Org. Chem. 2003, 68, 7528.
2. (a) Gao, C.; Tao, X.; Qian, Y.; Huang, J. Chem. Commun. 2003, 1444; (b) Euzenat,
L.; Horhant, D.; Ribourdouille, Y.; Duriez, C.; Alcaraz, G.; Vaultier, M. Chem.
Commun. 2003, 2280.
3. Djerassi, C.; Scholz, C. R. J. Am. Chem. Soc. 1948, 70, 417.
4. Arcus, C. L.; Strauss, H. E. J. Chem. Soc. 1952, 2669.
5. (a) Reeves, W. P.; Lu, C. V.; Schulmeier, B.; Jonas, L.; Hatlevik, O. Synth. Commun.
1998, 28, 499; (b) Banks, R. E.; Hasszeldine, R. N.; Latham, J. V.; Young, I. M. J.
Chem. Soc. 1965, 594.
R
R
RT
CH3
Br3
CH3
Br
+ HBr
N
N
Br2
Bu
2
Bu
1
R = NH2, OH
6. Ali, S. I.; Nikalje, M. D.; Sudalai, A. Org. Lett. 1999, 1, 705.
7. (a) Tanaka, K.; Shiraishi, R.; Toda, F. J. Chem. Soc., Perkin Trans. 1 1999, 3069; (b)
Muathen, H. A. J. Org. Chem. 1992, 57, 2740; (c) Kajigaeshi, S.; Moriwaki, M.;
Tanaka, T.; Fujisaki, S.; Kakinami, T.; Okamoto, T. J. Chem. Soc., Perkin Trans. 1
1990, 897; (d) Avramoff, M.; Weiss, J.; Schaechter, O. J. J. Org. Chem. 1963, 28,
3256; (e) Buckles, R. E.; Popov, A. I.; Zelezny, W. F.; Smith, R. J. J. Am. Chem. Soc.
1951, 73, 4525.
8. Chiappe, C.; Capraro, D.; Conte, V.; Pieraccini, D. Org. Lett. 2001, 3, 1061.
9. Zhu, H.-P.; Yang, F.; Tang, J.; He, M.-Y. Green Chem. 2003, 5, 38.
10. Wu, H.-H.; Yang, F.; Pg, C.; Tang, J.; He, M.-Y. Tetrahedron Lett. 2004, 45, 4963.
11. Driver, G.; Johnson, K. E. Green Chem. 2003, 5, 163.
Scheme 2. Regioselective bromination of anilines and phenols with [BMPy]Br3
under mild conditions.
cule, took 45 min for monobromination (entry 12). Similarly, a
variety of substituted anilines underwent regioselective monobro-
mination (entries 1–10). Imidazole underwent monobromination
to afford 2-bromoimidazole in 5 min (entry 22).
All the reactions were quenched by adding water. This caused
precipitation of the products as solids or oils, which were readily
separated and washed with fresh portions of water, and then dried
(either with sodium sulfate or in vacuo). The aqueous phase con-
taining highly water soluble 1 was easily concentrated in vacuo
to recycle 1, which then could be used to regenerate RTIL 2 with
bromine (Scheme 2).
All the reactions were carried out in air at room temperature,
adding 1.0 equiv of IL 2 to an equimolar amount of substrate with-
out any solvent. Although the reactions were slightly exothermic,
no special precautions were taken for cooling. They were moni-
tored by TLC and were stopped after the disappearance of the
substrate.
In summary, a new room temperature ionic liquid bromine ana-
log, which is safer and easier to use, was synthesized and charac-
terized. It displayed improved selectivity and better reaction
conditions, as compared to current bromination techniques. This
new functional RTIL 2 may be classified as ‘green’ for the following
reasons: (1) it eliminates toxic bromine vapors, (2) the bromine
carrier 1 can be easily recovered and recycled, and (3) it avoids
the use of organic solvents. Furthermore, 2 afforded good-to-excel-
lent yields for a wide variety of anilines and phenols at room
temperature.
12. Bortolini, O.; Bottai, M.; Chiappe, C.; Conte, V.; Pieraccini, D. Green Chem. 2002,
4, 621.
13. Horvath, I. T.; Anastas, P. T. Chem. Rev. 2007, 107, 2169.
14. (a) Ranu, B. C.; Banerjee, S. J. J. Org. Chem. 2005, 70, 4517; (b) Noguera, G.;
Mostany, J.; Agrifoglio, G.; Dorta, R. Adv. Synth. Catal. 2005, 347, 231; (c) Davis,
J. H. Chem. Lett. 2004, 33, 1072; (d) Earle, M. J.; Katdare, S. P.; Seddon, K. R. Org.
Lett. 2004, 6, 707.
15. Qian, W.; Jin, E.; Bao, W.; Zhang, Y. Angew. Chem., Int. Ed. 2005, 44, 952.
16. (a) Chang-chun, L. Huaxue Shijie 2008, 49, 481; (b) Kaushik, M. P.;
Polshttiwar, V. Indian J. Chem., Sect. B Org. Med. Chem. 2006, 45, 2542; (c)
Iranpoor, N.; Firouzabadi, H.; Azadi, R. Tetrahedron Lett. 2006, 47, 5531; (d)
Zhang-Gao, L.; Zhen-Chu, C.; Yi, H. Chin. J. Chem. 2005, 23, 1537; (e) Le, Z.
G.; Chen, Z. C.; Hu, Y.; Zheng, Q. G. Synthesis 2004, 2809; (f) Salazar, J.;
Dorta, R. Synlett 2004, 1318; (g) Chiappe, C.; Leandri, E.; Pieraccini, D.
Chem. Commun. 2004, 2536.
17. Preparation of 1-butyl-3-methylpyridinium tribromide 2: In a fume cupboard,
molecular bromine (0.22 mL, 0.436 mmol) was added dropwise over 10 min to
1-butyl-3-methylpyridinium bromide (1, 1.0 g, 0.436 mmol) under stirring and
cooling in a ice-bath affording a deep red liquid IL 2, and stirring was continued
for 2 h. Under reduced pressure over 5 h at 60 °C, 1.62 g (95.4%) of the pure IL 2
was obtained as a red oil. 1H NMR (CDCl3, 200 MHz): d 0.72 (t, 3H, J = 7.33 Hz),
1.14 (m, 2H), 1.76 (m, 2H), 2.38 (s, 3H), 4.41 (t, 2H, J = 7.58 Hz), 7.74 (t, 1H,
J = 7.83 Hz), 8.07 (d, 1H, J = 8.09 Hz), 8.62 (d, 1H, J = 6.07 Hz), 8.66 (s, 1H); 13C
NMR (CDCl3, 300 MHz): d 12.86, 18.23, 18.76, 32.81, 61.36, 127.34, 139.41,
141.10, 143.35, 145.47; MS (ESI): 150 (MÀX3); Anal. Calcd for C10H16Br3N: C,
30.80; H, 4.14; N, 3.59. Found: C, 31.01; H, 4.13; N, 3.40.
18. Similar examples that demonstrate the complete elimination of residual vapor
pressure of strong acids in functional RTIL are: (a) Susan, M. A. B. H.; Noda, A.;
Mitsushima, S.; Watanabe, M. Chem. Commun. 2003, 938; (b) Cole, A. C.; Jensen,
J. L.; Ntai, I.; Tran, K. L. T.; Weaver, K. J.; Forbes, D. C.; Davis, J. H., Jr. J. Am. Chem.
Soc. 2002, 124, 5962.
19. Typical experimental procedure: To a stirred mixture of anilines or phenols
(3.3 mmol) was added 1-butyl-3-methylpyridinium tribromide (3.3 mmol) at
room temperature. After completion of the reaction as indicated by TLC, water
was added into the reaction mixture to quench the IL. The resulting reaction
mixture was extracted with diethyl ether, separated from the organic layer,
dried over sodium sulfate, and concentrated to afford pure monobromo
anilines or monobromo phenols.
Acknowledgments
The financial support from the DST, New Delhi (GAP264126) is
gratefully acknowledged. We are grateful to Dr. Ganesh Pandey for
his support and encouragement.