Li et al.
FIGURE 2. 81Br NMR spectrum of the rection mixture (externally referenced to a 10 mM NaBr solution).
7.91 (s, 1.6 Hz, 1H), 7.28-7.31 (m, 1H), 6.45 (d, J ) 16.0 Hz,
1H), 4.28 (q, J ) 7.0, 2H), 1.37 (t, J ) 7.0, 3H). 13C NMR
(CDCl3): δ 165.8, 151.3, 150.4, 138.8, 135.9, 129.6, 123.0, 122.8,
60.9, 14.2. LRMS (ES-MS) [(M + H)+]: for C10H10O2ClN 211.04,
found 212.1.
(E)-Ethyl 3-(6-Chloropyridin-3-yl)acrylate (Entry 2 in Table
2). H NMR (CDCl3): δ 8.68 (d, J ) 2.4 Hz, 1H), 7.80 (dd, J )
FIGURE 3. Byproducts (trace amounts in entry 1 of Table 1) detected
by LC-MS.
1
2.4, 5.6 Hz, 1H), 7.63 (d, J ) 16.2 Hz, 1H), 7.40 (d, J ) 5.6 Hz,
1H), 6.47 (d, J ) 16.4 Hz, 1H), 4.34 (q, J ) 7.2, 2H), 1.34 (t, J )
7.2, 3H). 13C NMR (CDCl3): δ 166.4, 153.4, 149.8, 139.6, 136.9,
129.6, 124.9, 121.5, 61.2, 14.6. LRMS (ES-MS) [(M + H)+]: for
C10H10O2ClN 211.04, found 212.1.
(E)-Ethyl 3-(2-Chloropyridin-4-yl)acrylate (Entry 3 in Table
2). 1H NMR (CDCl3, 300 MHz): δ 8.43(d, J ) 5.1 Hz, 1H), 7.53
(d, J ) 15.9 Hz, 1H), 7.40 (s, 1H), 7.12-7.30 (m, 1H), 6.58 (d, J
) 15.9 Hz, 1H), 4.29(q, J ) 7.2 Hz, 2H), 1.34 (t, J ) 7.2 Hz, 3H).
13C NMR (CDCl3): δ 165.6, 152.5, 150.3, 144.8, 140.0, 124.2,
122.5, 120.3, 61.1, 14.2.
1
(E)-Ethyl 3-(Pyridin-3-yl)acrylate (Entry 4 in Table 2). H
NMR (CDCl3, 300 MHz): δ 8.90 (s, 1H), 6.11 (t, J ) 3.3 Hz,
1H), 7.82-7.86 (m, 1H), 7.64-7.71 (m, 1H), 7.31-7.36 (m, 1H),
6.50-6.57 (m, 1H), 4.24-4.33 (m, 2H), 1.32-1.38 (m, 3H). 13C
NMR (CDCl3): δ 166.2, 150.7, 149.7, 140.8, 134.1, 130.2, 123.7,
120.5, 119.9, 60.7, 14.2.
(E)-1,2-Di(pyridin-3-yl)ethane (Entry 5 in Table 2). 1H NMR
(CDCl3): δ 8.62-8.63 (m, 2H), 7.43-7.70 (m, 4H), 7.42 (d, J )
5.6 Hz, 2H), 7.04-7.19 (m, 2H). 13C NMR (CDCl3): δ 155.5,
150.1, 137.0, 132.1, 124.5, 123.2.
FIGURE 4. Proposed reaction pathway.
The 1,2-dibromo compounds used in these studies were
prepared by addition of bromine in either carbon tetrachloride
or carbon disulfide according to literature procedures.17
In conclusion, we have demonstrated that DMSO alone
without a metal or an oxidant efficiently effects reductive
debromination pathways in a variety of substrates. The com-
bination of halogenation and reductive dehalogenation has been
used to temporarily protect double bonds,18 to purify olefins,19
and to introduce a new double bond in organic synthesis.20
Although reductive dehalogenation of 1,2-dihalo compounds
with other agents has been the subject of many reports,21 our
novel DMSO procedure reported here is the most facile, mild,
and convenient method for such a transformation.
(E)-N,N-Dimethyl-4-(2-(pyridin-4-yl)vinyl)aniline (Entry 6 in
1
Table 2). H NMR (CDCl3, 300z): δ 8.56 (d, J ) 4.8 Hz, 1H),
7.46-7.64 (m, 4H), 7.35 (d, J ) 8.1 Hz, 1H), 7.06-7.08 (m, 1H),
7.00 (d, J ) 12.3 Hz, 1H), 6.95 (d, J ) 8.7 Hz, 2H), 3.0 (s, 6H).
13C NMR (CDCl3): δ 156.5, 149.5, 136.3, 132.9, 128.3, 124.9,
121.3, 121.1, 122.2, 40.3.
(Z)-2-Bromo-3-(3-methylthiophen-2-yl)acrylic Acid Methyl
1
Ester (Entry 2 in Table 3). H NMR (CDCl3): δ 8.52 (s, 1H),
(20) (a) It is worth mentioning here that the following cited preparation
of a 14C-labeled dibenzosuberenone was made with a key step of the
reductive debromination. Such a reduction was carried out using copper
bronze in DMSO. As clearly stated in the paper, copper bronze was the
reducing agent, while the DMSO was used as the reaction solvent and was
not credited for the reduction. Apprearently, DMSO must have partially
contributed to the reduction. Nonetheless, this is a good example to illustrate
the synthetic value of the reductive debromination. Kendall, J. T. J. Labelled
Cpd. Radiopharm. 1999, 42, 477. (b) Allred, E. L.; Beck, B. R.; Voorhees,
K. J. J. Org. Chem. 1974, 39, 1426.
(21) (a) Khurana, J. M.; Maikap, G. C.; Sahoo, P. K. Synthesis 1991,
827 (Debromination at high temperature). (b) Vijayashree, N.; Samuelson,
A. G. Tetrahedron Lett. 1992, 33, 559 (Cu/Cu(II) mediated debromination
of activated vicinal dibromides). (c) Fukunaga, K.; Yamaguchi, H. Synthesis
1981, 879 (Debromination of Vic-dibromides with Na2S/DMF). (d) Na-
kayama, J.; Machida, H.; Hishino, M. Tetrahedron Lett. 1983, 24, 3001
(Debromination of vic-dibromides with Na2S/R3NMe+Cl-).
Experimental Section
(E)-Ethyl 3-(2-Chloropyridin-3-yl)acrylate (Entry 1 in Table
1
2). H NMR (CDCl3): δ 8.63 (s, 1H), 7.97 (d, J ) 16.0 Hz, 1H),
(17) (a) Cossy, J.; Pete, J. P. Bull. Soc. Chim. Fr. 1979, 559. (b) Sanchez
B. J.; Hernandez, M. D.; McPhee, D. J. Bol. Soc. Quim. Peru 1982, 48,
195.
(18) Solo, A. J.; Singh, B. J. J. Org. Chem. 1965, 30, 1658.
(19) Soday, F. J.; Boord, C. E. J. Am. Chem. Soc. 1933, 55, 3293.
6020 J. Org. Chem., Vol. 72, No. 16, 2007