LETTER
NBS/LiBr for the Bromination of C=C Bonds
1271
Soc. 1955, 77, 4883. (c) Skell, P. S.; Tlumak, R. L.;
Seshadri, S. J. Am. Chem. Soc. 1983, 105, 5125.
(d) Buckles, E.; Johnson, R. C.; Probst, W. J. J. Org. Chem.
1957, 22, 55.
Ross and co-workers investigated the true nature of the
brominating agent in a similar system, NBS and quaterna-
ry ammonium bromide, and its role in the dibromination
of olefins.13 They believed that molecular Br2 was the real
brominating agent for the dibromination of olefins in their
system and an equilibrium between the complex and mo-
lecular Br2 was postulated (Scheme 3).
(8) (a) Schmid, H. Helv. Chim. Acta 1946, 29, 1144.
(b) Braude, E. A.; Waight, E. S. J. Chem. Soc. 1952, 1116.
(c) Karunakaran, C.; Manimekalai, A. Pol. J. Chem. 1994,
68, 2065. (d) Huang, Z.-Z.; Wang, L.; Huang, X. Synth.
Commun. 2003, 33, 757. (e) Albert, J.; Koide, K. Org. Lett.
2004, 6, 3655. (f) McDermott, P. J.; Stockman, R. A. Org.
Lett. 2005, 7, 27. (g) Fan, C. A.; Tu, Y.-Q.; Song, Z.-L.;
Zhang, E.; Shi, L.; Wang, M.; Wang, B.-M.; Zhang, S.-Y.
Org. Lett. 2004, 6, 4691. (h) Mellegaard, S. R.; Tunge, J. A.
J. Org. Chem. 2004, 69, 8979. (i) Padwa, A.; Lee, H. I.;
Rashatasakhon, P.; Rose, M. J. Org. Chem. 2004, 69, 8209.
(9) Alkene 1a (0.2 mmol), LiBr (0.4 mmol), NBS (0.4 mmol),
and THF (2.0 mL) were added to a Schlenk tube
δ– δ+
Br Br
δ–
S–
SBr, Br–
Complex
Br2
+
N
A
SBr = N-bromosuccinimide
Scheme 3
successively under an ambient atmosphere. The mixture was
stirred at r.t. for the appropriate time. Sat. aq Na2S2O3 was
added to quench the reaction, the organic layer was washed,
then dried over anhyd Na2SO4. Flash column chromatogra-
phy gave the pure product 2a as a white solid. 1H NMR
(CDCl3, 300 MHz, TMS): d = 3.98–4.11 (m, 2 H), 5.14 (dd,
1 H, J = 5.4, 9.9 Hz), 7.34–7.42 (m, 5 H, Ar). 13C NMR
(CDCl3, 75 MHz, TMS): d = 34.99, 50.84, 127.62, 128.83,
129.15, 138.56. MS: m/z (%) = 262 (M+, 1), 185 (86), 183
(90), 104 (100).
In the present dibromination reaction, we believe that a
similar complex between NBS and LiBr might exist and
the equilibrium described by Ross could also be in-
volved.13–15 We also confirmed that the dibromination
reaction of 7a under the optimized conditions was un-
affected by the addition of the radical inhibitors such as
2,2,6,6-tetramethyl-1-piperidinyloxy
free
radical
(TEMPO) and 2,6-di-tert-butyl-4-methylphenol (BHT)
(0.1 equiv), rendering unlikely the intervention of a radi-
cal pathway.16
(10) For reviews, see: (a) Brandi, A.; Goti, A. Chem. Rev. 1998,
98, 598. (b) Nakamura, I.; Yamamoto, Y. Adv. Synth. Catal.
2002, 344, 111. (c) Brandi, A.; Cicchi, S.; Cordero, F. M.;
Goti, A. Chem. Rev. 2003, 103, 1213.
(11) For the dibromination of MCPs in the presence of TiBr4 and
DEAD/DIAD, or by molecular Br2, see: Shao, L.-X.; Zhao,
L.-J.; Shi, M. Eur. J. Org. Chem. 2004, 4894; and references
cited therein.
(12) MCP 1a (0.2 mmol), LiBr (0.4 mmol), and THF (2.0 mL)
were placed in a Schlenk tube under an ambient atmosphere
and the mixture was stirred for about 10 min at r.t. Then NBS
(0.4 mmol) was added and the mixture was stirred at r.t. for
the appropriate time. Sat. aq Na2S2O3 was added to quench
the reaction. The mixture was washed and dried over anhyd
Na2SO4. The solvent was removed under reduced pressure
and the residue was purified by flash column chromatogra-
phy to give product 8a as a colorless liquid. IR (CH2Cl2):
3933, 3054, 2985, 1486, 1443, 1265, 896, 746 cm–1.
1H NMR (CDCl3, 300 MHz, TMS): d = 3.07 (t, 2 H, J = 6.9
Hz), 3.62 (t, 2 H, J = 6.9 Hz), 7.20–7.32 (m, 10 H, Ar).
13C NMR (CDCl3, 75 MHz, TMS): d = 31.04, 40.76, 123.20,
127.42, 127.57, 128.06, 128.51, 128.72, 128.83, 140.31,
142.68, 144.87. MS: m/z (%) = 368 (29), 366 (60), 364 (M+,
34), 192 (100). HRMS: m/z calcd for C16H14Br2: 363.9457;
found: 363.9470.
In conclusion, we have found a convenient and efficient
method for the dibromination of substrates bearing car-
bon–carbon unsaturated bonds such as alkenes, alkynes,
allenes, and MCPs with NBS and LiBr. It is noteworthy
that the present method has provided a new route for the
dibromination reactions in the absence of molecular Br2
and that THF was used as the solvent to alleviate the prob-
lem of toxic organic solvents in traditional reactions. Fur-
ther studies are now under way to investigate the details
of the related reactions.
Acknowledgment
We thank the State Key Project of Basic Research (Project 973)
(No. G2000048007), Shanghai Municipal Committee of Science
and Technology, and the National Natural Science Foundation of
China for financial support (203900502, 20025206, and 20272069).
References and Notes
(1) Olah, G. A.; Laali, K. K.; Wang, Q.; Prakash, G. K. S. Onium
Ions; John Wiley & Sons: New York, 1998.
(2) The Merck Index, 12th ed.; Budavari, S.; O’Neil, M. J.;
Smith, A.; Heckelman, P. E.; Kinneary, J. F., Eds.; Merck:
Rahway, 1996.
(3) Goehring, R. R. In Encyclopaedia of Reagents for Organic
Synthesis; Paquette, L. A., Ed.; John Wiley & Sons: New
York, 1995, Vol. 1, 679–680.
(4) Braddock, D. C.; Cansell, G.; Hermitage, S. A. Synlett 2004,
461; and references cited therein.
(5) Chiappe, C.; Capraro, D.; Conte, V.; Pieraccini, D. Org. Lett.
2001, 3, 1061.
(13) Finkelstein, M.; Hart, S. A.; Moore, W. M.; Ross, S. D.;
Eberson, L. J. Org. Chem. 1986, 51, 3548; and references
cited therein.
(14) We found that the reaction mixture quickly changed from
colorless to deep orange as soon as NBS was added. After
the reaction was complete, the reaction solution changed to
pale yellow. When the reaction was quenched with a sat.
solution of aq Na2S2O3, the reaction mixture immediately
changed from pale yellow to colorless. These phenomena
suggest that molecular Br2 is involved in the equilibrium.
(15) We were unsuccessful in obtaining a crystal structure,
however, the white solid obtained from the reaction of NBS
and LiBr in THF decomposed to pyrrolidine-2,5-dione,
which was confirmed by X-ray diffraction.
(6) Salazar, J.; Dorta, R. Synlett 2004, 1318; and references
cited therein.
(7) (a) Dittmer, K.; Martin, R. P.; Herz, W.; Cristol, S. J. J. Am.
Chem. Soc. 1949, 71, 1201. (b) Wright, J. B. J. Am. Chem.
(16) The yields in the presence of TEMPO and BHT were 99%
and 96%, respectively.
Synlett 2006, No. 8, 1269–1271 © Thieme Stuttgart · New York