The combination of benzamides/NCS as nitrogen/halogen sources for aminohalogenation of β-nitrostyrenes resulting in dichlorinated haloamides

Article abstract of DOI:10.1007/s11426-010-4001-4

The combination of benzamide and NCS was found to be an efficient nitrogen/halogen source for aminohalogenation of β-nitrostyrenes. The reaction was convenient to carry out by using 4-dimethylaminopyridine as the catalyst, resulting in vicinal dichlorinat

Full text of DOI:10.1007/s11426-010-4001-4

SCIENCE CHINA
Chemistry
September 2010 Vol.53 No.9: 1946–1952
doi: 10.1007/s11426-010-4001-4
• ARTICLES •
The combination of benzamides/NCS as nitrogen/halogen sources
for aminohalogenation of β-nitrostyrenes resulting in
dichlorinated haloamides
ZHI SanJun1,2, MEI HaiBo1, ZHANG GuangQian1, SUN Hao1, HAN JianLin1*,
LI GuiGen4 & PAN Yi1,3*
1 School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, China
2 School of Chemistry and Chemical Engineering, Huaiyin Normal University, Huai’an 221003, China
3 State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, China
4 Department of Chemistry and Biochemistry, Texas Tech University, Texas 79409-1061, USA
Received March 30, 2010; accepted April 25, 2010
The combination of benzamide and NCS was found to be an efficient nitrogen/halogen source for aminohalogenation of
β-nitrostyrenes. The reaction was convenient to carry out by using 4-dimethylaminopyridine as the catalyst, resulting in vicinal
dichlorinated haloamino nitroalkanes with opposite regiochemistry to that generated from other electron-deficient olefins ob-
served previously. The reaction proceeded smoothly at room temperature with good yields and excellent regioselectivities. A
mechanism involving a chloronium intermediate was proposed to explain the resulting regiochemistry. The current system ex-
plored a new type of nitrogen sources for aminohalogenation of functionalized olefins.
aminohalogenation, benzamide, β-nitrostyrenes, DMAP, haloamides
ketones [13–15], vinylidenecyclopropanes [16], α,β-unsa-
turated nitriles [17] and β-nitrostyrenes [18, 19]. These
aminohalogenation processes are believed to proceed in-
volving aziridinium or chloronium ion intermediates [13–15,
18, 19].
Although several synthetic approaches to vicinal halo-
amine functionalities have been developed, the nitrogen
sources for the catalytic aminohalogenation of functional-
ized olefins remain great challenges [13–42]. Sulfonamides
are usually used as the most suitable nitrogen sources for
aminohalogenation of α,β-unsaturated olefins, including
TsNCl2 [13–15], TsNH2/NBS [31–35] and NsNCl2 [2,
40–42]. In our continuing study on this reaction, we tried to
employ benzamides as nitrogen sources to replace sulfona-
mides. The benzamides are new nitrogen sources for ami-
nohalogenation of α,β-unsaturated olefins, and the advan-
tage of such a replacement is that the N-benzoyl protecting
1 Introduction
The vicinal haloamines belong to a significant class of
building blocks in organic and medicinal chemistry, because
they can be easily converted into various synthetic interme-
diates by the replacement of the halogen in both intramo-
lecular and intermolecular reactions. Among all the meth-
odologies for preparation of vicinal haloamines, aminoha-
logenation and related reactions of alkenes can be used as
the most attractive tools, in which carbon-nitrogen bonds
and carbon-halogen bonds were formed at the same time
[1–12]. In the last decade, many new aminohalogenation
processes have been developed for several functionalized
olefins, including α,β-unsaturated carboxylic esters and
*Corresponding author (email: hanjl@nju.edu.cn; yipan@nju.edu.cn)
© Science China Press and Springer-Verlag Berlin Heidelberg 2010
chem.scichina.com
www.springerlink.com

ZHI SanJun, et al. Sci China Chem September (2010) Vol.53 No.9
1947
group of the resulting products can be easily cleaved [43–45]
compared with the N-sulfonyl protecting group. Herein, we
report a DMAP catalyzed aminohalogenation reaction of
β-nitrostyrenes (1) with benzamides as nitrogen sources and
N-chlorosuccinimide (NCS) as the halogen source, yielding
products of 1-aryl-1-arylformamino-2,2-dichloro-2-nitroe-
thanes (3) (Scheme 1). The new aminohalogenation system
provides an easy access to 1,2-vicinal diamino products that
are chemically and biologically significant [46].
was concentrated and purified via flash chromatography
with EtOAc and petroleum ether (v/v = 1:4) as the eluent to
yield the pure products 3.
Benzamido-2,2-dichloro-2-nitro-1-phenylethane (3a)
Colorless solid. mp 130–131 °C. IR (KBr): υ 3400, 1660,
1579, 1511, 1481, 1322 cm−1. 1H NMR (300 MHz, CDCl3) δ
7.78–7.81 (m, 2H), 7.43–7.58 (m, 8H), 7.18 (d, J = 9.9 Hz,
1H), 6.53 (d, J = 9.9 Hz, 1H) ppm. 13C NMR (75 MHz,
CDCl3) δ 166.2, 132.8, 132.4, 132.1, 129.5, 128.8, 128.5,
128.5, 126.9, 115.2, 61.9 ppm. ESI-MS m/z: 361.1 [M+Na]+.
1-Benzamido-2,2-dichloro-2-nitro-1-(p-tolylethyl)ethane (3b)
Colorless solid. mp 155–156 °C. IR (KBr) υ 3239, 2923,
1
1644, 1581, 1515, 1315 cm−1. H NMR (300 MHz, CDCl3)
δ 7.78–7.81 (m, 2H), 7.57–7.60 (m, 1H), 7.54–7.57 (m, 2H),
7.45–7.50 (m, 2H), 7.20–7.28 (m, 2H), 7.12 (d, J= 10.2 Hz,
1H), 6.48 (d, J = 10.2 Hz, 1H), 2.37 (s, 3H) ppm. 13C NMR
(75 MHz, CDCl3) δ 166.5, 140.0, 133.2, 132.3, 129.7, 129.5,
128.8, 128.7, 127.2, 115.7, 62.1, 21.2 ppm. MS (ESI) m/z:
375.1 [M+Na]+.
Scheme 1 Aminohalogenation with benzamides as nitrogen sources.
2 Experimental
2.1 General methods
All moisture-sensitive reactions were performed under ni-
trogen in glassware that had been flame-dried. Solvents
were dried and distilled prior to use. Flash chromatography
was performed on silica gel 60 (F-254) TCL plates (20 cm ×
20 cm). Melting points are uncorrected. IR spectra were
collected with a Bruker Vector 22 instrument (KBr pellets).
1H NMR (300 MHz) and 13C NMR (75 MHz) were acquired
in deuterated dimethylsulfoxide (CD3SOCD3), deuterated
acetone (CD3COCD3) and deuterated chloroform (CDCl3).
Elemental analyses were performed with a Perkin-Elmer
240 elemental analysis instrument. Mass spectra of new
compounds were measured with a Finnigan LCQ Electros-
pray Mass Spectrometer.
1-Benzamido-1-(4-chlorophenyl)-2,2-dichloro-2-nitroethane
(3c)
Colorless solid. mp 161–162 °C. IR (KBr) υ 3228, 1644,
1
1583, 1520, 1312, cm−1. H NMR (300 MHz, CDCl3): δ
7.76–7.79 (m, 2H), 7.37–7.57 (m, 7H), 7.16 (d, J = 9.9 Hz,
1H), 6.49 (d, J= 9.9 Hz, 1H) ppm. 13C NMR (75 MHz,
CDCl3) δ 166.2, 135.6, 132.5, 132.2, 130.9, 128.7, 128.5,
126.9, 114.9, 61.4 ppm. MS (ESI) m/z: 394.9 [M+Na]+.
1-Benzamido-2,2-dichloro-1-(4-fluorophenyl)-2-nitroethane
(3d)
Colorless solid. mp 133–134 °C. IR (KBr) υ 3262, 1644,
1
1590, 1529, 1510, 1336 cm−1. H NMR (300 MHz, CDCl3)
δ = 7.76–7.79 (m, 2H), 7.43–7.56 (m, 5H), 7.03–7.13 (m,
3H), 6.50 (d, J = 10.2 Hz, 1H) ppm. 13C NMR (75 MHz,
CDCl3) δ 166.5, 165.1, 161.7, 132.9, 132.5, 130.9, 130.8,
128.8, 128.7, 128.6, 127.2, 116.1, 115.8, 115.4, 61.7 ppm.
MS (ESI) m/z: 379.1 [M+Na]+.
2.2 Starting materials procedure
Starting materials β-Nitrostyrenes (1a–1h) were prepared
according to the reported methods [47–50].
1-Benzamido-1-(4-bromophenyl)-2,2-dichloro-2-nitroethane
(3e)
2.3 General procedure for aminohalogenation
Colorless solid. mp 150–151 °C. IR (KBr) υ 3322, 1649,
Into a dry vial was added 1 (1.0 mmol), benzamide (3.0
mmol), DMAP (0.2 mmol, 20 mol%) and freshly distilled
CH2Cl2 (5.0 mL) with nitrogen atmosphere. The mixture
was stirred at room temperature for 10 min before NCS (3.0
mmol) was added. The resulting mixture was stirred at room
temperature for 48 h in the capped vial nitrogen atmosphere
protection and the reaction was then quenched with satu-
rated aqueous Na2SO3 (2.0 mL) solution. The solid precipi-
tates were filtered off and washed with EtOAc (3 × 10 mL).
The combined organic phases were washed with brine and
dried with anhydrous sodium sulfate. The organic solution
1
1582, 1522, 1329, 1312, 1266 cm−1. H NMR (300 MHz,
CDCl3) δ 7.74–7.77 (m, 2H), 7.52–7.57 (m, 3H), 7.36–7.46
(m, 4H), 7.23 (d, J = 9.9 Hz, 1H), 6.47 (d, J = 9.9 Hz, 1H)
ppm. 13C NMR (75 MHz, CDCl3) δ 166.5, 132.8, 132.6,
132.0, 131.8, 130.5, 128.8, 127.2, 124.3, 115.1, 61.8 ppm.
MS (ESI) m/z: 438.9 [M+Na]+.
1-Benzamido-2,2-dichloro-1-(2-fluorophenyl)-2-nitroethane
(3f)
Colorless solid. mp 145–146 °C. IR (KBr) υ 3268, 1642,

1948
ZHI SanJun, et al. Sci China Chem September (2010) Vol.53 No.9
(d, J = 9.9 Hz, 1H), 6.44 (d, J= 9.9 Hz, 1H) ppm. 13C NMR
(75 MHz, CDCl3) δ 165.6, 136.1, 132.0, 131.5, 130.9, 130.1,
129.1, 128.6, 127.3, 114.9, 61.7 ppm. MS (ESI) m/z: 472.8
[M + Na]+.
1
1586, 1525, 1490, 1321 cm−1. H NMR (300 MHz, CDCl3)
δ 7.79–7.82 (m, 2H), 7.34–7.58(m, 6H), 7.25 (d, J= 9.9 Hz,
1H), 7.25–7.14 (m, 1H), 6.79 (d, J = 9.9 Hz, 1H) ppm. 13C
NMR (75 MHz, CDCl3) δ 166.3, 163.0, 159.6, 132.8, 132.5,
131.9, 131.8, 131.0, 131.0, 128.8, 127.2, 124.7, 127.7,
120.1, 120.0, 116.8, 116.5, 115.3, 59.0 ppm. MS (ESI) m/z:
379.1 [M+Na]+.
1-(4-Chlorophenyl)-2,2-dichloro-2-nitro-1-(4-nitrobenzamido)
ethane (3l)
Colorless solid. mp 187–189 °C. IR (KBr) υ 3304, 1667,
1
1581, 1528, 1332, 1291 cm−1. H NMR (300 MHz, CDCl3)
1-Benzamido-2,2-dichloro-1-(4-methoxyphenyl)-2-nitroethane
(3g)
δ 8.34–8.37 (m, 2H), 7.94–7.97 (m, 2H), 7.43 (m, 4H), 7.11
(d, J = 9.9 Hz, 1H), 6.45 (d, J= 9.9 Hz, 1H) ppm. 13C NMR
(75 MHz, d-DMSO) δ 166.5, 149.8, 139.2, 135.1, 132.1,
132.1, 130.0, 129.0, 124.0, 116.0, 62.0 ppm. MS (ESI) m/z:
439.9 [M+Na]+.
Colorless solid. mp 124–126 °C. IR (KBr) υ 3406, 1663,
1612, 1580, 1510, 1255, 1188, 1027 cm-1. H NMR (300
1
MHz, CDCl3) δ 7.77–7.80 (m, 2H), 7.40–7.58 (m, 5H), 7.12
(d, J = 10.2 Hz, 1H), 6.90–6.93 (m, 2H), 6.47 (d, J = 10.2
Hz, 1H), 3.82 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3) δ
166.5, 160.6, 133.2, 132.3, 130.1, 128.8, 127.2, 124.6,
115.8, 114.2, 61.8, 55.3 ppm. MS (ESI) m/z: 391.0
[M+Na]+.
1-(2-Bromobenzamido)-1-(4-chlorophenyl)-2,2-dichloro-2-
nitroethane (3m)
White solid. mp 170–171 °C. IR (KBr) υ 3300, 1658, 1583,
1
1519, 1493, 1336, 1317 cm−1. H NMR (300 MHz, CDCl3)
1-(4-Chlorobenzamido)-2,2-dichloro-2-nitro-1-phenylethane
δ 7.57–7.64 (m, 2H), 7.32–7.48 (m, 6H), 7.22 (d, J=9.9 Hz,
1H), 6.52 (d, J = 9.9 Hz, 1H) ppm. 13C NMR (75 MHz,
CDCl3) δ 166.2, 136.1, 135.5, 133.6, 132.2, 130.9, 130.5,
130.3, 129.0, 127.7, 119.1, 114.8, 61.8 ppm. MS (ESI) m/z:
472.8 [M+Na]+.
(3h)
Colorless solid. mp 132–133 °C. IR (KBr) υ 3406, 1668,
1590, 1573, 1506, 1478, 1315, 1249 cm−1. H NMR (300
1
MHz, CDCl3) δ 7.68–7.71 (m, 2H), 7.48–7.52 (m, 2H),
7.39–7.45 (m, 5H), 7.19 (d, J = 10.2 Hz, 1H), 6.49 (d, J =
10.2 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3) δ 165.9,
138.7, 132.5, 131.4, 130.0, 128.9, 128.9, 128.7, 115.5, 62.4
ppm. MS (ESI) m/z: 394.9 [M+Na]+.
1-(2-Chlorobenzamido)-1-(4-chlorophenyl)-2,2-dichloro-2-
nitroethane (3n)
Colorless solid. mp 171–172 °C. IR (KBr) υ 3300, 1657,
1
1583, 1521, 1493, 1338, 1319 cm−1. H NMR (300 MHz,
2,2-Dichloro-2-nitro-1-(4-nitrobenzamido)-1-phenylethane
CDCl3) δ 7.72–7.74 (d, J = 7.5 Hz, 1H), 7.53 (d, J= 9.9 Hz,
1H), 7.36–7.47 (m, 7H), 6.53 (d, J = 9.9 Hz, 1H) ppm. 13C
NMR (75 MHz, CDCl3): δ 165.0, 136.1, 132.6, 132.5, 131.1,
131.0, 130.6, 130.5, 130.4, 129.1, 127.4, 114.8, 61.9 ppm.
MS (ESI) m/z: 428.9 [M+Na]+.
(3i)
Colorless solid. mp 155–156 °C. IR (KBr) υ 3310, 1661,
1602, 1579, 1342, 1319, 1266 cm−1. H NMR (300 MHz,
1
CDCl3) δ 8.31–8.33 (d, J = 8.4 Hz, 2H), 7.93–7.96 (d, J =
8.4 Hz, 2H), 7.43–7.50 (m, 5H), 7.21 (d, J = 9.9 Hz, 1H),
6.49 (d, J = 9.9 Hz, 1H) ppm. 13C NMR (75 MHz, CDCl3)
δ 164.7, 150.0, 138.6, 132.1, 130.2, 129.0, 128.8, 128.5,
124.0, 115.2, 62.5 ppm. MS (ESI) m/z 406.1 [M+Na]+.
1-(4-Bromobenzamido)-2,2-dichloro-2-nitro-1-(p-tolyl)
ethane (3o)
Colorless solid. mp 162–163 °C. IR (KBr) υ 3301, 1663,
1
1602, 1578, 1525, 1338, 1318, 1296 cm−1. H NMR (300
1-(4-Chlorobenzamido)-1-(4-chlorophenyl)-2,2-dichloro-2-
MHz, CDCl3) δ 8.29–8.34 (m, 2H), 7.93–7.96 (m, 2H), 7.39
(d, J = 8.4 Hz, 2H), 7.25 (d, J= 8.4 Hz, 2H), 7.18 (d, J= 9.9
Hz, 1H), 6.44 (d, J = 9.9 Hz, 1H), 2.38 (s, 3H) ppm. 13C
NMR (75 MHz, CDCl3) δ 164.6, 149.9, 140.3, 138.5, 129.6,
129.0, 128.5, 128.4, 123.8, 115.2, 62.2, 21.1 ppm. MS (ESI)
m/z: 452.9 [M+Na]+.
nitroethane (3j)
Colorless solid. mp 159–160 °C. IR (KBr) υ 3312, 1653,
1580, 1524, 1487, 1328, 1311 cm−1. H NMR (300 MHz,
1
CDCl3) δ 7.74–7.70 (m, 2H), 7.38–7.49 (m, 6H), 7.01 (d,
J = 9.9 Hz, 1H), 6.45 (d, J=9.9 Hz, 1H) ppm. 13C NMR (75
MHz, CD3COCD3) δ 165.9, 137.5, 135.2, 132.1, 132.0,
131.3, 129.5, 128.6, 128.4, 115.7, 61.8 ppm. MS (ESI) m/z:
428.9 [M+Na]+.
2,2-Dichloro-1-(4-fluorophenyl)-2-nitro-1-(4-nitrobenzamido)
ethane (3p)
Colorless solid. mp 190–192 °C. IR (KBr) υ 3305, 1664,
1
1605, 1579, 1534, 1338, 1298, 1229 cm−1. H NMR (300
1-(4-Bromobenzamido)-1-(4-chlorophenyl)-2,2-dichloro-2-
nitroethane (3k)
MHz, CDCl3) δ 8.32–8.35 (m, 2H), 7.93–7.96 (m, 2H),
7.47–7.57 (m, 2H), 7.11–7.16 (m, 3H), 6.46 (d, J = 9.6 Hz,
1H) ppm. 13C NMR (75 MHz, CD3COCD3) δ 165.7, 165.6,
164.9, 161.6, 149.8, 139.8, 139.0, 139.0, 131.9, 131.8,
Colorless solid. mp 145–146 °C. IR (KBr) υ 3301, 1649,
1
1587, 1516, 1479, 1343, 1311, 1258 cm−1. H NMR (300
MHz, CDCl3) δ 7.60–7.64 (m, 4H), 7.38–7.45 (m, 4H), 7.03

ZHI SanJun, et al. Sci China Chem September (2010) Vol.53 No.9
1949
129.2, 129.1, 123.3, 115.8, 115.5, 115.2, 61.9, 61.8 ppm.
benzamide as the nitrogen source. As shown in Table 1,
DMAP was the most effective catalyst for the reaction, re-
sulting in product 3a with 44% chemical yield (Table 1,
entry 1). Besides DMAP, CuOTf could also catalyze the
reaction and 40% yield was obtained (Table 1, entry 9).
Other catalysts either resulted in no product or gave poor
chemical yields with most β-nitrostyrene remaining (Table
1, entries 2–8, 10–12).
To further optimize the reaction conditions, several or-
ganic solvents were used in the catalytic reaction. As shown
in Table 2, the desired products could be observed when
CH3CN, CHCl3, CCl4 or toluene were used as the solvent.
Dichloromethane was found to be the best solvent, and the
yield increased to 55% (Table 2, entry 2). No aminohaloge-
nation products were found at all when using DMF or THF
as the solvent (Table 2, entries 6 and 7). Increasing the
loading amount of NCS did not have much effect on the
yield (Table 2, entry 8). However, the use of 3.0 equiv of
benzamide could increase the chemical yield to 60% (Table
2, entry 9). The use of 20 mol% DMAP was necessary, and
the yield increased to 63% (Table 2, entry 10). Similar to
our previous aminohalogenation system, longer reaction
time and higher temperature did not show any apparent im-
provement on the current system (Table 2, entries 12 and
13).
MS (ESI) m/z: 423.9 [M+Na]+.
2,2-Dichloro-1-(4-methoxyphenyl)-2-nitro-1-(4-nitrobenza-
mido)ethane (3q)
Colorless solid. mp 170–171 °C. IR (KBr) υ 3339, 2971,
1
1651, 1604, 1582, 1523, 1346, 1311, 1256 cm−1. H NMR
(300 MHz, CDCl3) δ 8.30–8.33 (m, 2H), 7.92–7.97 (m, 2H),
7.38–7.42 (m, 2H), 7.15 (d, J = 9.6 Hz, 1H), 6.92–6.95 (m,
2H), 6.43 (d, J = 9.6 Hz, 1H), 3.83 (s, 3H) ppm. 13C NMR
(75 MHz, CDCl3) δ 164.5, 160.7, 149.9, 138.5, 129.9, 128.3,
123.9, 123.8, 115.3, 114.3, 62.0, 55.3 ppm. MS (ESI) m/z:
436.1 [M+Na]+.
1-(4-Chlorophenyl)-2,2-dichloro-1-(4-methoxybenzamido)-
2-nitroethane (3r)
Colorless solid. mp 120–121 °C. IR (KBr) υ 3442, 2963,
1
1637, 1608, 1580, 1505, 1317, 1252, 1179 cm−1. H NMR
(300 MHz, CDCl3) δ 7.73–7.77 (m, 2H), 7.36–7.45 (m, 4H),
7.01 (d, J = 10.2 Hz, 1H), 6.93–7.01 (m, 2H), 6.47 (d, J =
10.2 Hz, 1H), 3.87 (s, 3H) ppm. 13C NMR (75 MHz, CDCl3)
δ 165.8, 162.9, 135.9, 131.3, 130.1, 129.1, 128.9, 124.8,
115.2, 113.9, 61.6, 55.4 ppm. MS (ESI) m/z: 424.9
[M+Na]+.
After the reaction conditions have been optimized, a se-
ries of β-nitrostyrenes and benzamides were investigated
carefully. As listed in Table 3, a wide range of β-nitrosty-
renes can be employed as substrates for this reaction and
give useful to excellent chemical yields (36%–85%). The
reaction of β-nitro-4-methylstyrene gave a high yield, which
3 Results and discussion
Initially, β-nitrostyrene (1a) was subjected to the reaction as
a model substrate. The reaction of 1a with NCS and ben-
zamide (2a) was conducted under our previously reported
catalytic aminohalogenation condition with DMAP as the
catalyst in the presence of 4 Å molecular sieves in acetoni-
trile (Scheme 2) [18]. After 48 h, 1a was partly consumed
and the product was detected with 44% chemical yield. The
Table 1 Aminohalogenation of β-nitrostyrene using a range of catalystsa)
1
major product was carefully isolated and characterized. H
NMR analysis of this isolated product revealed that the
1
β-proton was not present in the H NMR spectrum, which
indicated that dichlorinated haloamide formed in the current
process.
Entry
1
Cat.
DMAP
Ph3P
Time (h)
48
Yield (%) b)
44
10
30
35
10
36
36
30
40
10
20
30
2
48
3
2,2’-Bpy
4,4’-Bpy
MnSO4
Ni(OAc)2
Mn(OAc)2
AgOAc
CuOTf
CuI
48
4
48
5
48
6
48
7
48
8
48
9
48
Scheme 2 DMAP catalyzed aminohalogenation reaction.
10
11
12
48
CuCl
48
In order to improve the chemical yields, several catalysts
including Ph3P, 2,2’-bpy, 4,4’-bpy, MnSO4, Ni(OAc)2,
Mn(OAc)2, AgOAc, CuOTf, CuI, CuCl and PdCl2 were
employed in the current aminohalogenation reaction with
PdCl2
48
a) Conditions: β-nitrostyrene (1.0 mmol), benzamide (2.0 mmol) and
NCS (3.0 mmol), catalysts (10 mol%) and 4 Å molecular sieves (500 mg)
in solvent (5.0 mL) under N2 at room temperature. b) Isolated yields.

1950
ZHI SanJun, et al. Sci China Chem September (2010) Vol.53 No.9
a)
Table 2 Optimization of reaction conditions for aminohalogenation of
β-nitrostyrenea)
Table 3 Aminohalogenation of 1 with benzamides/NCS in CH2Cl2
Entry
1
Ar1
Ph
Ar2
Ph
Time (h) Product b) Yield (%) c)
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
3a
3b
3c
3d
3e
3f
63
70
68
63
67
62
49
68
71
70
75
85
54
51
71
76
55
36
Cat.
(mol%)
Yield
(%) c)
44
55
Entry
Solvent Time (h)
T (°C)
Ratio b)
2
4-CH3-Ph
4-Cl-Ph
4-F-Ph
4-Br-Ph
2-F-Ph
4-CH3O-Ph
Ph
Ph
3
Ph
1
2
CH3CN
CH2Cl2
CHCl3
CCl4
48
48
48
48
48
48
48
48
48
48
72
48
10
10
10
10
10
10
10
10
10
20
20
10
25
25
25
25
25
25
25
25
25
25
25
50
1:2:3
1:2:3
1:2:3
1:2:3
1:2:3
1:2:3
1:2:3
1:2:4
1:3:3
1:3:3
1:3:3
1:3:3
4
Ph
5
Ph
3
40
6
Ph
4
30
7
Ph
3g
3h
3i
5
PhMe
35
8
4-Cl-Ph
4-NO2-Ph
4-Cl-Ph
4-Br-Ph
4-NO2-Ph
2-Br-Ph
2-Cl-Ph
4-Br-Ph
4-NO2-Ph
6
DMF
N.R.d)
N.R.d)
56
9
Ph
7
THF
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
10
11
12
13
14
15
16
17
18
4-Cl-Ph
4-Cl-Ph
4-Cl-Ph
4-Cl-Ph
4-Cl-Ph
4-CH3-Ph
4-F-Ph
3j
8
3k
3l
9
60
10
11
12
63
3m
3n
3o
3p
3q
3r
56
60
a) Conditions: β-nitrostyrene (1.0 mmol), benzamide and NCS, cata-
lyzed by DMAP, in the presence of 4 Å molecular sieves (500 mg) in sol-
vent (5.0 mL) under N2. b) The ratio is β-nitrostyrene:benzamide:NCS. c)
Isolated yields. d) No reaction was observed.
4-CH3O-Ph 4-NO2-Ph
4-Cl-Ph 4-CH3O-Ph
a) Conditions: β-nitrostyrenes (1.0 mmol), DMAP (20 mol%), ben-
zamides (3.0 mmol), NCS (3.0 mmol) and 4 Å molecular sieves (500 mg)
in CH2Cl2 (5.0 mL) under N2 at room temperature. b) As shown by 1H
NMR spectroscopic analysis of the crude product, there is no regioisomer
observed for each case. c) Isolated yields.
may due to the stabilization of the positively charged inter-
mediate with electron-donating methyl group (Table 3, en-
try 2). Other substituted groups on the aromatic ring of
β-nitrostyrenes did not show apparent effect on the chemi-
cal yields. Varieties of benzamides were found to be suit-
able nitrogen sources for the current system. In the case of
the nitrogen source with a strong electron-withdrawing
group (NO2) on the aromatic ring (Table 3, entries 12 and
16), the highest yields of aminochlorination products were
obtained. It is possibly due to that the electron-withdrawing
nature of nitro groups makes the deprotonation of aryl am-
ide become easier. As expected, the lowest yield was ob-
tained with the nitrogen source substituted by a strong elec-
tron-donating group (OCH3) on the aromatic ring (Table 3,
entry 18). The regioselectivities of the reaction were com-
pletely controlled, and solely one regio-isomer was ob-
Scheme 3 Possible mechanism.
1
served for all these cases. Careful H NMR analysis of the
‘Cl+’ from A to the C=C bond of β-nitrostyrenes to give the
chloronium intermediate B. The positively charged
chloronium intermediate B is opened by BzNH2 on the
β-position of β-nitrostyrenes, and regioselectively forms
intermediate C, which is a normal monohaloamino product.
The final dichlorinated product D is formed via deprotona-
tion/electrophilic chlorination of mono-haloamine precursor
C [47–50].
products revealed that the chlorine moiety was attached to
the α-carbon position of nitroalkane instead of the β-carbon
position as encountered in nearly all of the previous cases
where the electron-withdrawing olefins were employed
[32–38].
Based on the resulting regiochemistry, the chloronium
intermediate is believed to predominantly form during the
reaction process (Scheme 3), which is similar to our previ-
ous reported aminohalogenation of β-nitrostyrene with
TsNCl2 as the nitrogen source [18]. The first step involves
the DMAP-promoted dissociation of N−Cl bond of NCS, to
form intermediate A. The following step is the delivery of
4 Conclusions
In conclusion, a new regio- and stereoselective aminohalo-

ZHI SanJun, et al. Sci China Chem September (2010) Vol.53 No.9
1951
corresponding mechanistic studies. Org lett, 2006, 8: 625–628
genation of β-nitrostyrenes with DMAP as the catalyst and
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developed. The reaction is convenient to carry out at room
temperature, and provides an easy access to vicinal
haloamino nitroalkanes with opposite regiochemistry to that
of other electron-deficient olefins previously observed. Use-
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have been obtained. The advantage of this new type of nitro-
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