Derivatives of 2,3-dihydro-1H-1,5-benzodiazepine from o-nitroanilines and chalcones induced by low-valent titanium

Article abstract of DOI:10.1081/SCC-120001997

2,3-Dihydro-1H-1,5-benzodiazepines have been prepared in good yield by reaction of o-nitroanilines with chalcones induced by the TiCl₄-Sm-THF system under mild reaction conditions.

Full text of DOI:10.1081/SCC-120001997

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DERIVATIVES OF 2,3-DIHYDRO-1H-1,5-
BENZODIAZEPINE FROM o-NITROANILINES AND
CHALCONES INDUCED BY LOW-VALENT TITANIUM
Yongmin Ma a & Yongmin Zhang b
a Department of Chemistry , Zhejiang University , XiXi Compus, Hangzhou, 310028, P. R.
China
b Department of Chemistry , Zhejiang University , XiXi Compus, Hangzhou, 310028, P. R.
China
Published online: 16 Aug 2006.
To cite this article: Yongmin Ma & Yongmin Zhang (2002) DERIVATIVES OF 2,3-DIHYDRO-1H-1,5-BENZODIAZEPINE FROM o-
NITROANILINES AND CHALCONES INDUCED BY LOW-VALENT TITANIUM, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 32:2, 165-169, DOI: 10.1081/SCC-120001997
To link to this article: http://dx.doi.org/10.1081/SCC-120001997
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SYNTHETIC COMMUNICATIONS, 32(2), 165–169 (2002)
DERIVATIVES OF 2,3-DIHYDRO-
1H-1,5-BENZODIAZEPINE FROM
o-NITROANILINES AND CHALCONES
INDUCED BY LOW-VALENT TITANIUM
Yongmin Ma and Yongmin Zhang*
Department of Chemistry, Zhejiang University,
XiXi Compus, Hangzhou, 310028, P. R. China
ABSTRACT
2,3-Dihydro-1H-1,5-benzodiazepines have been prepared in
good yield by reaction of o-nitroanilines with chalcones
induced by the TiCl4-Sm-THF system under mild reaction
conditions.
Low-valent titanium reagent has an exceedingly high ability in
promoting reductive coupling of carbonyl compound and its attracting
increasing interest in organic synthesis.1 A lot of other functional groups
can also be reduced.2 Recently, we reported the reduction of sulfoxides to
sulfides and reductive coupling of niltriles with nitro compounds using
TiCl4/Sm/THF system.3
*Corresponding author.
165
Copyright & 2002 by Marcel Dekker, Inc.
www.dekker.com

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166
MA AND ZHANG
Mishriky described that 2,3-dihydro-1H-1,5-benzodiazepine was
derived from o-phenylenediamine with chalcone by the effect of base
catalysis when the components are reacted at 120ꢀC.4 Here, we wish to
report that 2,3-dihydro-1H-1,5-benzodiazepine could be formed from
o-nitroanilines and chalones promoted by TiCl4/Sm in anhydrous THF
under a neutral, room temperature condition, and the reaction is very
quick. But, when a mixture of o-phenylenediamine and chalcone was
stirred under similar condition, the reaction could not happen even at
reflux temperature.
When o-nitroanilines 1 and chalcones 2 were treated with low-valent
titanium, prepared from titanium tetrachloride and samarium powder in
anhydrous tetrahydrofuran, the products 2,3-dihydro-1H-1,5-benzo-
diazepines 3 were obtained in good yields (Scheme 1). The results were
summarized in Table 1.
Scheme 1.
Table 1. Cross-Coupling Reactions of o-Nitroanilines and Chalcones
Induced by TiCl4/Sm System
Entry
X
R1
R2
Yield (%)*
a
b
c
d
e
f
g
h
i
H
H
H
H
H
Cl
Cl
Cl
Cl
Cl
H
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
90
92
92
88
85
79
84
88
86
81
72
p-CH3-C6H4
p-CH3O-C6H4
3,4-OCH2O-C6H4
p-Cl-C6H4
C6H5
p-CH3-C6H4
p-CH3O-C6H4
3,4-OCH2O-C6H4
p-Cl-C6H4
j
k
C6H5
C6H5CH¼CH
*Isolated Yield.

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o-NITROANILINES AND CHALCONES
167
In conclusion, the low-valent titanium, prepared by TiCl4/Sm system,
induced the reactions of o-nitrophenylamines and chalcones has been
studied. Further studies on other chemical transformation of this low-
valent reagent are now in progress.
EXPERIMENTAL
Tetrahydrofuran was distilled from sodium-benzophenone immedi-
ately prior to use. All reactions were conducted under a nitrogen atmos-
phere. Melting points were uncorrected. Infrared spectra were recorded on a
Perkin-Elmer 683 spectrometer in KBr with absorptions in cmÀ1. 1H-NMR
spectra were determined on a Brucker AC 300 and Brucker AC 80 spectro-
meter as CDCl3 solutions. Chemical shifts were expressed in ppm downfield
from internal standard tetramethylsilane. Mass spectra were recorded on
HP5989B Mass spectrometer. Elemental analyses were carried out on an
EA 1110 instrument.
General Procedure for the Synthesis of 2,3-Dihydro-1H-1,5-benzo-
diazepines 3a–k: TiCl4 (0.22 ml, 2 mmol) was added dropwise using syringe
to a stirred suspension of Sm powder (0.45 g, 2 mmol) in freshly distilled dry
THF (20 ml) at room temperature under a N2 atmosphere. After the com-
pletion of addition, the mixture was refluxed for 2 h. The suspension of the
low-valent titanium reagent formed was cooled to room temperature and a
solution of o-nitroanilines compounds 1a–k (1 mmol) and chalcones com-
pound 2a–k (1 mmol) in anhydrous THF (3 ml) was added. The mixture was
stirred at room temperature under N2 atmosphere. After the reaction com-
pleted, the reaction mixture was quenched with 0.1 N HCl (5 ml) and
extracted with diethyl ether (3 Â 15 ml). The combined extracts were
washed with a saturated solution of Na2S2O3 (15 ml) and a saturated
solution of NaCl (15 ml) and dried over anhydrous Na2SO4. After eva-
porating the solvent under reduced pressure, the crude product was purified
by preparative TLC on silica gel using ethyl acetate-cyclohexane (1: 8) as
eluent.
2,3-Dihydro-2,4-diphenyl-1H-1,5-benzodiazepine (3a): mp 126–128ꢀC
(lit.,5,6 129–129.5ꢀC). nmax (cmÀ1): 3360, 1620. dH (ppm) 3.00 (2H, d,
J ¼ 3.2 Hz, CH2), 3.70 (1H, br s, NH), 5.05 (1H, dd, J ¼ 4.8, 4.6 Hz, CH),
7.15–8.10 (14H, m, ArH).
2,3-Dihydro-2-(40-methylphenyl)-4-phenyl-1H-1,5-benzodiazepine (3b):
mp 125–127ꢀC. nmax (cmÀ1): 3380, 1610. dH (ppm) 2.20 (3H, s, CH3), 2.98
(2H, d, J ¼ 3.7 Hz, CH2), 3.47 (1H, br s, NH), 4.85 (1H, dd, J ¼ 4.6, 4.4 Hz,
CH), 6.92–7.94 (13H, m, ArH). m/z: 312 (Mþ, 13.67), 297 (9.82), 221 (40.86),

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168
MA AND ZHANG
195 (26.87), 194 (100), 118 (8.20), 77 (40.93). Anal. Calcd. For C22H20N2: C,
84.58; H, 6.45; N, 8.97. Found: C, 84.25; H, 6.42; N: 8.90.
2,3-Dihydro-2-(40-methoxyphenyl)-4-phenyl-1H-1,5-benzodiazepine(3c):
mp 143–145ꢀC. (lit.5,6 146–147ꢀC). nmax (cmÀ1): 3360, 1615. dH (ppm) 3.04
(2H, d, J ¼ 3.8 Hz, CH2), 3.60 (3H, s, OCH3), 3.75 (1H, br s, NH), 5.00 (1H,
dd, J ¼ 4.7, 4.6 Hz, CH), 6.60–7.80 (13H, m, ArH).
2,3-Dihydro-2-(30,40-methylenedioxyphenyl)-4-phenyl-1H-1,5-benzodia-
zepine (3d): mp 148–150ꢀC. nmax (cmÀ1): 3360, 1610. dH (ppm) 3.08 (2H, d,
J ¼ 3.3 Hz, CH2), 3.50 (1H, br s, NH), 4.90 (1H, dd, J ¼ 4.8, 4.8 Hz, CH),
5.72 (2H, s, OCH2O), 6.65–7.83 (12H, m, ArH). m/z: 342 (28.49), 327
(15.87), 265 (30.43), 195 (48.61), 194 (100), 148 (33.34), 77 (47.55). Anal.
Calcd. For C22H18N2O2: C, 77.17; H, 5.30; N, 8.18. Found: C, 77.43; H,
5.38; N, 8.10.
2,3-Dihydro-2-(40-chlorophenyl)-4-phenyl-1H-1,5-benzodiazepine (3e):
mp 140–142ꢀC. (lit.5 144–145ꢀC). nmax (cmÀ1): 3385, 1620. dH (ppm) 2.96
(2H, d, J ¼ 3.0 Hz, CH2), 3.45 (1H, br s, NH), 5.00 (1H, dd, J ¼ 4.5, 4.4 Hz,
CH), 6.80–7.80 (13H, m, ArH).
2,3-Dihydro-2,4-diphenyl-7-chloro-1H-1,5-benzodiazepine (3f ): mp
94–96ꢀC. nmax (cmÀ1): 3380, 1620. dH (ppm) 2.95 (2H, d, J ¼ 2.9 Hz,
CH2), 3.70 (1H, br s, NH), 4.80 (1H, dd, J ¼ 4.5, 4.3 Hz, CH), 6.87–7.65
(13H, m, ArH). m/z: 332 (Mþ, 30.54), 317 (16.20), 255 (20.76), 230 (34.30),
229 (26.27), 228 (100), 104 (16.41), 77 (35.16). Anal. Calcd. For C21H17ClN2:
C, 75.78; H, 5.15; N, 8.42. Found: C, 76.04; H, 5.09; N, 8.34.
2,3-Dihydro-2-(40-methylphenyl)-4-phenyl-7-chloro-1H-1,5-benzodiaze-
pine (3g): mp 136–138ꢀC. nmax (cmÀ1): 3380, 1610. dH (ppm) 2.22 (3H, s,
CH3), 3.10 (2H, d, J ¼ 3.9 Hz, CH2), 3.60 (1H, br s, NH), 4.80 (1H, dd,
J ¼ 4.7, 4.4 Hz, CH), 6.84–7.92 (12H, m, ArH). m/z: 346 (Mþ, 13.84), 331
(10.03), 269 (7.16), 230 (34.96), 229 (21.26), 228 (100), 118 (9.20), 77 (32.28).
Anal. Calcd. For C22H19ClN2: C, 76.18; H, 5.52; N, 8.08. Found: C, 75.93;
H, 5.51; N, 7.93.
2,3-Dihydro-2-(40-methoxyphenyl)-4-phenyl-7-chloro-1H-1,5-benzodia-
zepine (3h): mp 134–136ꢀC. nmax (cmÀ1): 3320, 1620. dH (ppm) 3.05 (2H, d,
J ¼ 4.2 Hz, CH2), 3.60 (1H, br s, NH), 3.63 (3H, s, OCH3), 4.85 (1H, dd,
J ¼ 4.6, 4.3 Hz, CH), 6.83–7.88 (12H, m, ArH). m/z: 362 (Mþ, 8.93), 347
(9.04), 285 (11.00), 230 (34.92), 229 (23.76), 228 (100), 134 (25.45), 77
(25.55). Anal. Calcd. For C22H19ClN2O: C, 72.82; H, 5.28; N, 7.72.
Found: C, 72.29; H, 5.24; N, 7.53.
2,3-Dihydro-2-(30,40-methylenedioxyphenyl)-4-phenyl-7-chloro-1H-1,5-
benzodiazepine (3i): mp 135–137ꢀC. nmax (cmÀ1): 3380, 1620. dH (ppm) 2.98
(2H, d, J ¼ 4.0 Hz, CH2), 3.55 (1H, br s, NH), 4.75 (1H, dd, J ¼ 4.3, 4.0 Hz,
CH), 5.72 (2H, s, OCH2O), 6.78–7.89 (11H, m, ArH). m/z: 376 (Mþ, 11.13),
361 (8.26), 299 (14.33), 230 (35.15), 229 (41.72), 228 (100), 148 (20.06), 77

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o-NITROANILINES AND CHALCONES
169
(18.14). Anal. Calcd. For C22H17ClN2O2: C, 70.12; H, 4.55; N, 7.43. Found:
C, 69.81; H, 4.58; N, 7.26.
2,3-Dihydro-2-(40-chlorophenyl)-4-phenyl-7-chloro-1H-1,5-benzodia-
zepine (3j): mp 108–110ꢀC. nmax (cmÀ1): 3360, 1610. dH (ppm) 3.15 (2H, d,
J ¼ 3.4 Hz, CH2), 3.70 (1H, br s, NH), 4.88 (1H, dd, J ¼ 4.3, 4.3 Hz, CH),
6.84–7.96 (12H, m, ArH). m/z: 366 (Mþ, 23.60), 351 (11.62), 289 (14.61). 230
(35.36), 229 (30.66), 228 (100), 138 (14.37), 77 (44.84). Anal. Calcd. For
C21H16Cl2N2: C, 68.68; H, 4.39; N, 7.63. Found: C, 68.49; H, 4.34; N, 7.41.
2,3-Dihydro-2-phenyl-4-(2-phenylethenyl)-1H-1,5-benzodiazepine (3k):
mp 134–136ꢀC. (lit.5,6 136–137ꢀC). nmax (cmÀ1): 3390, 1610. dH (ppm) 3.00
(2H, d, J ¼ 4.0 Hz, CH2), 3.55 (1H, br s, NH), 4.90 (1H, dd, J ¼ 4.8, 4.2 Hz,
CH), 6.55–7.45 (16H, m, ArH and CH¼CH).
ACKNOWLEDGMENT
We are grateful to the National Natural Science Foundation of China
(Project No. 29872010), the NSF of Zhejiang Province, China, and the
Laboratory of Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences for financial support.
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3. (a) Zhang, Y.M.; Yu, Y.P.; Bao, W.L. Synth. Commun. 1995, 25, 1825.
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Received in the Netherlands February 15, 2000

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