SHORT PAPER
Monobromination of Electron-Rich Aromatic Compounds
209
cess of lithium bromide was present in the reaction (entry Foundation of China (Project Y4080068, Y4100231) are greatly ap-
preciated.
1
2).
A proposed mechanism and catalytic cycle is shown in
Scheme 2, which included the transformation of the hy- References
pervalent iodine reagent (Koser’s reagent) to PhI(OTs)Br,
(1) (a) Diederich, F.; Stang, P. J. Metal Catalyzed Cross
and then an electrophilic substitution with anisole to form
the monobrominated product. The reduced by-product io-
dobenzene was again transformed into hypervalent iodine
reagent by the oxidation of m-chloroperoxybenzoic acid.
Coupling Reactions; Wiely-VCH: Weinheim, 1998.
(b) Miyaura, N.; Yamada, K.; Suginome, H.; Suzuki, A.
J. Am. Chem. Soc. 1985, 107, 972. (c) Taylor, R.
Electrophilic Aromatic Substitution; Wiley: New York,
1
990. (d) De La Mare, P. B. D. Electrophilic Halogenation;
Cambridge University Press: Cambridge, 1976, Chap. 5.
(2) (a) Dieter, R. K.; Nice, L. E.; Velu, S. E. Tetrahedron Lett.
996, 37, 2377. (b) Nair, V.; Panicker, S. B.; Augstine, A.;
OMe
Br
1
Ph
I
OMe
George, T. G.; Thomas, S.; Vairamani, M. Tetrahedron
2001, 57, 7417. (c) Dewkar, K. G.; Narina, V. S.; Sudalai,
A. Org. Lett. 2003, 5, 4501. (d) Ye, C.; Shreeve, M. J.
J. Org. Chem. 2004, 69, 8561. (e) Kumar, M. A.; Rohitha,
C. N.; Kulkarni, S. J.; Narender, N. Synlett 2010, 1629.
(3) (a) Khan, A. T.; Goswami, P.; Choudhury, L. H.
Tetrahedron Lett. 2006, 47, 2751. (b) Moriuchi, T.;
Yamaguchi, M.; Kikushima, K.; Hirao, T. Tetrahedron Lett.
LiBr
OTs
OTs
Br
Ph
I
PhI + H+ + –OTs
OH
2
007, 48, 2667. (c) Greb, M.; Hartung, J.; Kohler, F.;
Spehar, K.; Kluge, R.; Csuk, R. Eur. J. Org. Chem. 2004,
799. (d) Nica, S.; Pohlmann, A.; Plass, W. Eur. J. Inorg.
TsOH⋅H2O
3
Chem. 2005, 2032. (e) Crans, D. C.; Smee, J. J.;
Gaidamauskas, G.; Yang, L. Chem. Rev. 2004, 104, 849.
mCBA
mCPBA
(
f) Zhang, G.; Liu, R.; Xu, Q.; Ma, L.; Liang, X. Adv. Synth.
Scheme 2
Catal. 2006, 348, 862. (g) Podgorsek, A.; Eissen, M.;
Fleckenstein, J.; Stavber, S.; Zupan, M.; Iskra, J. Green
Chem. 2009, 11, 120. (h) Kikushima, K.; Moriuchi, T.;
Hirao, T. Tetrahedron Lett. 2010, 51, 340. (i) Yang, L.-J.;
Lu, Z.; Stahl, S. S. Chem. Commun. 2009, 6460.
In summary, we have developed an efficient and regiose-
lective bromination of electron-rich aromatic compounds
to give monobrominated compounds in good yields. This
method provides some advantages such as mild reaction
conditions, simple procedure, and good yields.
(
4) (a) Zhang, Y.; Shibatomi, K.; Yamamoto, H. Synlett 2005,
2
837. (b) Yadav, J. S.; Reddy, B. V. S.; Reddy, P. S. R.;
Basak, A. K.; Narsaiah, A. V. Adv. Synth. Catal. 2004, 346,
7. (c) Ganguly, N. C.; De, S.; Dutta, P. Synthesis 2005,
7
1
1103. (d) Kalyani, D.; Dick, A. R.; Anani, W. Q.; Sanford,
M. S. Org. Lett. 2006, 8, 2523. (e) Kalyani, D.; Dick, A. R.;
Anani, W. Q.; Sanford, M. S. Tetrahedron 2006, 62, 11483.
IR spectra were recorded on a Thermo-Nicolet 6700 instrument, H
NMR spectra were measured on a Bruker Avance III (500 M) spec-
trometer, and mass spectra were determined on Thermo-ITQ 1100
mass spectrometer. Iodobenzene, mCPBA, TsOH, LiBr, and all
aromatic compounds are commercially available.
(
f) Mo, F.-Y.; Yan, J. M.; Qiu, D.; Li, F.; Zhang, Y.; Wang,
J.-B. Angew. Chem. Int. Ed. 2010, 49, 2028.
(
5) (a) Varvoglis, A. Tetrahedron 1997, 53, 1179. (b) Stang, P.
J.; Zhdankin, V. V. Chem. Rev. 1996, 96, 1123.
Catalytic Bromination of Electron-Rich Aromatic Compounds;
Typical Procedure
Anisole (32 mg, 0.3 mmol), LiBr (26 mg, 0.3 mmol), mCPBA
(
2
c) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102,
523. (d) Kirschning, A. Eur. J. Org. Chem. 1998, 11, 2267.
(
(
(
e) Ochiai, M. J. Organomet. Chem. 2000, 611, 494.
f) Okuyama, T. Acc. Chem. Res. 2002, 35, 12.
g) Zhdankin, V. V.; Stang, P. J. Tetrahedron 1998, 54,
(
75%, 69 mg, 0.3 mmol), TsOH·H O (57 mg, 0.3 mmol), and iodo-
2
benzene (18 mg, 0.03 mmol) were mixed in THF (2 mL). The mix-
ture was stirred at r.t. for 1 h and then H O (5 mL), sat. aq Na S O
3
2
2
2
1
0927. (h) Grushin, V. V. Chem. Soc. Rev. 2000, 29, 315.
6) (a) Bovonsombat, P.; Angara, G. J.; McNelis, E. Synlett
992, 131. (b) Bovonsombat, P.; Elsa, D.; McNelis, E.
(
1 mL), and sat. aq Na CO (1 mL) were added. The mixture was
2 3
(
(
extracted with CH Cl (2 × 5 mL), the combined organic layers
2
2
1
were dried (MgSO ), filtered, and concentrated under reduced pres-
4
Tetrahedron Lett. 1994, 35, 2841. (c) Braddock, D. C.;
Cansell, G.; Hermitage, S. A. Synlett 2004, 461.
7) (a) Dohi, T.; Kita, Y. Kagaku 2006, 61, 68. (b) Richardson,
R. D.; Wirth, T. Angew. Chem. Int. Ed. 2006, 45, 4402.
(c) Dohi, T.; Minamitsuji, Y.; Maruyama, A.; Hirose, S.;
Kita, Y. Org. Lett. 2008, 10, 3559. (d) Ochiai, M. Chem.
Rec. 2007, 7, 13. (e) Uyanik, M.; Ishihara, K. Chem.
Commun. 2009, 2086. (f) Dohi, T.; Kita, Y. Chem.
Commun. 2009, 2073. (g) Liu, H.-G.; Tan, C.-H.
Tetrahedron Lett. 2007, 48, 8220.
sure. The residue was purified by chromatography on silica gel us-
ing (3:1 hexane–EtOAc) as eluent to give 4-bromoanisole; yield: 55
mg (98%); oil (Table 2).
1
H NMR (500 MHz, CDCl ): d = 7.37 (ddd, J = 10.0, 5.5, 3.0 Hz, 2
3
H), 6.78 (ddd, J = 10.0, 5.5, 3.0 Hz, 2 H), 3.78 (s, 3 H).
1
3
C NMR (125 MHz, CDCl ): d = 158.8, 137.5, 115.8, 112.9, 55.5.
3
MS (EI): m/z = 186, 188 [M+].
(
(
8) Zhou, Z.-S.; He, X.-H. Tetrahedron Lett. 2010, 51, 2480.
9) Srebnik, M.; Mechoulam, R.; Yona, I. J. Chem. Soc., Perkin
Trans. 1 1987, 1423.
Acknowledgment
Financial supports from the Natural Science Foundation of China
(Project 21072176) and the Zhejiang Province Natural Science
Synthesis 2011, No. 2, 207–209 © Thieme Stuttgart · New York