Palladium-catalyzed [5+2] oxidative annulation of N-Arylhydrazones with alkynes through C–H activation to synthesize Benzo[d][1,2]diazepines

Article abstract of DOI:10.1016/j.tet.2018.05.051

An efficient and novel method using palladium catalyst for the synthesis of benzo[d][1,2]diazepines by [5 + 2] annulation of N-arylhydrazones with alkynes has been developed. This methodology undergoes through eight membered palladacycle serving as a back

Full text of DOI:10.1016/j.tet.2018.05.051

Accepted Manuscript
Palladium-catalyzed [5+2] oxidative annulation of N-Arylhydrazones with alkynes
through C-H activation to synthesize Benzo[d][1,2]diazepines
Manjoorahmed Asamdi, Mohammedumar M. Shaikh, Prakashsingh M. Chauhan,
Kishor H. Chikhalia
PII:
S0040-4020(18)30599-4
10.1016/j.tet.2018.05.051
TET 29558
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 18 January 2018
Revised Date: 17 May 2018
Accepted Date: 18 May 2018
Please cite this article as: Asamdi M, Shaikh MM, Chauhan PM, Chikhalia KH, Palladium-catalyzed
[5+2] oxidative annulation of N-Arylhydrazones with alkynes through C-H activation to synthesize
Benzo[d][1,2]diazepines, Tetrahedron (2018), doi: 10.1016/j.tet.2018.05.051.
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ACCEPTED MANUSCRIPT
Palladium-Catalyzed [5+2] Oxidative Annulation of N-Arylhydrazones with
Alkynes through C-H Activation to Synthesize Benzo[d][1,2]diazepines.
Manjoorahmed Asamdia, Mohammedumar M. Shaikha, Prakashsingh M. Chauhana and Kishor H.
Chikhaliab*
a Department of chemistry, Gujarat University, Ahmedabad, 380009, Gujarat, India.
b Department of chemistry, Veer Narmad South Gujarat University, Surat, 395007, Gujarat, India. E-mail:
Chikhalia_kh@yahoo.com; Tel: +91 79 26300969
Abstract
An efficient and novel method using palladium catalyst for the synthesis of
benzo[d][1,2]diazepines by [5+2] annulation of N-arylhydrazones with alkynes has been
developed. This methodology undergoes through eight membered palladacycle serving as a
backbone for the formation of C-C/C-N bond to provide benzodiazepine derivatives in moderate
to good yield.
Keywords: Pd catalyst, [5+2] annulation, C-H activation, Alkyne, Palladacycle.
Graphical Abstract:
R
N
N
Pd(OAc)2 cat.
Cu(OAc)2
R1
N R2
R1
N R2
H
H
R
R
C-H activation
R
R and R2 = aryl
R1 = Various substituents
1.
Introduction
In the light of history N-Heterocyclic compounds have emerged as an important motif to
construct wide range of reactive intermediates, drugs, and bioactive molecules1a-c. Particularly,
benzodiazepines have been recognized as versatile scaffold due to their promising biological and
pharmacological activities2a-e. These moieties are found to be important tools in drug discovery
as well as they are potent antitumor3a-d, anti-HIV4a,b, anti inflammatory5a,b and central nervous
1

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system (CNS) agents6 (Figure 1). Moreover, 1,2-diazapine analogs are important scaffolds in
organic synthesis as it provides the pathway to synthesize other cyclic compounds7.
Figure 1 Potent biologically active Benzodiazepine core.
Over the past decades the synthetic community have witnessed the application of hydrazone in
organic synthesis to synthesize plethora of compounds8a-e. More conveniently they have been
emanated as powerful synthons for constructing diverge range of cyclic compounds through
transition metal catalyzed or transition metal free reactions. Some of the reaction of hydrazone
includes [3+2] cycloaddition with aryne or alkyne9a-c, intramolecular cycloaddition with internal
olefins10a,b, transition metal catalyzed intra- and inter- molecular annulation11a-d etc. Being an
effective precursor for the establishment of five and six membered N-heterocyclic compounds
the ease of constructing higher member ring still remain unexplored12a,b
.
Metal catalyzed annulation involving C-H activation as a key step has gained lot of interest
among researchers all over the world as it provide the elegant protocol to construct diverse range
of cyclic compounds as it overshadows the traditional pattern which requires prefunctionalized
substrate13a-i. The other credential to this strategy is that it offers the shortest possible route,
improve atom economy of organic synthesis14a-c
.
In context to this metal catalyzed C-H activation proves to be an efficient protocol in [3+2] or
[4+2] cycloaddition reaction to build up cyclic scaffolds which are difficult to synthesize by
conventional method15a-e. However, very few reports has been documented of [5+2]
cycloaddition to construct seven membered ring motif employing palladium catalyst. [5+2]
oxidative annulation of o-arylanilines with alkynes to synthesize imine-containing
dibenzo[b,d]azepines with high stereoselectivity through Pd(II) was disclosed by Luan and co-
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workers16 (Scheme 1A). Recently, Thikekar et al. described regioselective synthesis of 1,2-
fused-indole diazepines through [5+2] annulation of o-indolo anilines with alkynes employing
palladium catalyst17 (Scheme 1B).
. Leading from these examples and our continuing interest in
transition metal catalyzed C-H activation18a-f herein we report the first Pd(II) catalyzed [5+2]
annulations of N-arylhydrazones with alkyne to synthesize benzo[d][1,2]diazepines through C-H
activation under mild condition (Scheme 1C). To the best of our knowledge, no previous
synthesis of benzo[d][1,2]diazepines have been reported in the literature.
Scheme 1 Pd(II) catalyzed [5+2] annulation of alkynes.
2.
Results and discussion
In order to obtain optimized reaction condition N-phenylhydrazone 1a was treated with diphenyl
acetylene 2a in the presence of Pd(II) catalyst and Cu(II) as oxidant (Table 1). It was noted that
no desired transformation was observed on employing Ru(II) catalyst under different solvent
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system (Table 1, entries 1-3). However, switching over to PdCl2 catalyst afforded the product 3a
in 22% yield in THF and slight increased in yield was recorded when solvent system was
changed to 1,4-dioxane (Table 1, entries 4-5). Furthermore, investigation revealed that
replacement of PdCl2 with Pd(OAc)2 and using 1,4-dioxane as solvent gave remarkable yield
turning out to be optimized condition for the reaction: Pd(OAc)2 catalyst (10 mol %), Cu(OAc)2
oxidant (1 equiv.), at 100 °C in 1,4-dioxane for 12 h (Table 1, entry 6). Changing the solvent or
altering the reaction temperature doesn’t increase the yield (Table 1, entries 7-11). Moreover,
reasonable yield of the expected product was obtained when CuCl2 or dioxygen were used as
oxidant and no yield was obtained when the reaction was carried out without catalyst (Table 1,
entry 12-14).
Table 1 Optimization of the reaction conditions.a
Entry Catalyst
Solvent
Reaction
Yield of 3ab
Temperature (°C)
(%)
1
2
[Ru(p-cymene)Cl2]2 THF
[Ru(p-cymene)Cl2]2 MeCN
100
100
0
0
3
4
5
6
7
8
9
10
11
12c
13d
14
[Ru(p-cymene)Cl2]2 1,4-dioxane
100
100
100
100
100
100
100
rt
0
PdCl2
THF
22
31
76
62
56
48
19
53
44
57
0
PdCl2
1,4-dioxane
1,4-dioxane
THF
Toluene
DMF
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
-------
80
100
100
100
aReaction conditions: 1a (0.30 mmol, 1 equiv.), 2a (0.45 mmol, 1.5 equiv.), catalyst (10 mol%),
Cu(OAc)2 (0.30 mmol, 1 equiv.), in 3.0 mL of solvent for 12 h at 100 °C. bisolated yield. c oxidant
is CuCl2. doxidant is O2.
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With the optimized condition in hand for unusual [5+2] annulation, the substrate scope of the
reaction was explored by employing broad range of hydrazone (1a-1l) to react with symmetrical
alkyne 2a. It was observed that reaction proceeded smoothly to afford desired product in good to
moderate yield with both electron donating or electron withdrawing groups (Table 2, entries 1-
12). In particular, electron donating substituents at substrate 1 gave good yield as compared to
electron withdrawing substituents. Moreover, high electronegative atom fluorine on aromatic
ring was also well tolerated to give annulated product in 65% yield. The other symmetrical
alkyne 2b was also examined using hydrazone 1a, 1b, 1c and 1d which produce 3m, 3n, 3o and
3p product respectively.
Table 2 Substrate scope.
R
N
N
Pd(OAc)2, Cu(OAc)2
R1
N R2
N R2
R1
1,4-dioxane, 100 °C, 12h
H
H
R
R
R
1
2
3
Entry
Hydrazone
Alkyne
Product
Yield(%)
1
76
N
N
N
2a
HN
R = Ph
Ph
R1= H, R2= Ph
Ph
3a
1a
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8
58
2a
N
N
HN
N
R = Ph
O2N
O2N
Ph
R1= 4-NO2, R2= Ph
Ph
1h
3h
10
66
N
HN
N
N
2a
OMe
OMe
R = Ph
Ph
R1= 3-CH3, R2= 4-(OMe)C6H4
Ph
3j
1j
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14
1b
69
2b
N
N
R= 4-(OMe)C6H4
OMe
MeO
3n
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On the basis of above results and literature survey,11b,16,17,19a,b a possible mechanism is proposed
in scheme 2. Initially Pd-N adduct A is formed from the reaction of substrate 1a and Pd(II)
catalyst followed by C-H bond activation leading to the formation of six membered palladacycle
B. Coordination of 2a with palladacycle B resulting in the formation of Pd(II) intermediate C.
Eight membered palladacycle D is formed by migratory insertion of 2a into Pd-C bond of C.
Finally, desired product 3a is formed by C-N bond reductive elimination and Pd(II) catalyst is
regenerated by Cu(OAc)2 oxidant completing the catalytic cycle.
Scheme 2 Plausible mechanism for intermolecular [5+2] annulation.
3.
Conclusion:
In conclusion, we have developed an efficient and effective method to synthesize
benzo[ ][1,2]diazepines by [5+2] annulation of -arylhydrazones with alkyne via C–H
d
N
functionalization with a catalytic amount of palladium(II) acetate in the presence of
Cu(II) as oxidant. The reaction witnessed the formation of desired compound through
eight membered palladacycle as well as tolerance of wide range of functional group.
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Further, investigation to construct heterocyclic compounds through C-H functionalization
is going on in our laboratory.
4. Experimental Section:
4.1. General information:
All the reagents and solvents were purchased from Sigma-Aldrich and Merck and were used as
recieved without any further purification. The synthesized compounds were characterized by 1H
NMR, 13C NMR and elemental analysis. Melting points were determined in open capillaries on a
Veego electronic apparatus VMP-D (Veego Instrument Corporation, Mumbai, India) and are
uncorrected. 1H NMR and 13C NMR spectra were recorded on a 400 MHz FT NMR, Avance III
Bruker model spectrometer using DMSO-d6 as a solvent and TMS as internal standard. ESI mass
spectra were recorded on a Bruker Daltonics MicroTof. NMR chemical shifts are reported as
parts per million (ppm) downfield from TMS. The splitting patterns are designated as follows: s,
singlet; d, doublet; t, triplet; m, multiplet. Elemental analysis (C, H, N) were performed using a
Heraeus CarloErba 1180 CHN analyzer (Hanau, Germany).
4.2 General method for the synthesis of N-aryl hydrazone:
To the mixture of acetophenone A (3 g, 25 mmol, 1 equiv.), phenyl hydrazine B (2.70 g, 25
mmol, 1 equiv.) in 15 mL of ethanol was added acetic acid in catalytic amount. The mixture was
refluxed at 80 °C for 4 h and the progress of the reaction was monitored on TLC. The solvent
was evaporated in vacuo and crude was recrystallized from ethanol which afforded 1a and was
used directly for the annulation reaction. All the N-arylhydrazone 1b-1l were synthesized
following the same procedure.
4.3 General Procedure To Prepare Benzo[d][1,2]diazepines (3) from N-Arylhydrazones (1):
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To an oven-dried flat-bottomed flask previously equipped with magnetic stirrer bar was charged
with N-arylhydrazone 1 (63.0 mg, 0.30 mmol), Pd(OAc)2 (6.7 mg, 10 mol%), Cu(OAc)2 (54.4
mg, 0.30 mmol) in 1,4-dioxane (3.0 mL) followed by alkyne (80.2 mg, 0.45 mmol). The reaction
mixture was stirred at 100 °C for 12 h. Upon completion of reaction the mixture was cooled to
room temperature, poured into brine, and extracted with EtOAc. The combined extracts were
dried over MgSO4 and filtered through pad of Celite eluting with ethyl acetate. The filtrate was
concentrated under reduced pressure and was purified by column chromatography
(EtOAc/hexane) on silica gel to afford the benzo[d][1,2]diazepines 3.
4.3.1 1-Methyl-3,4,5-triphenyl-3H-benzo[d][1,2]diazepine (3a).
Yield: 76 %. yellow solid; mp: 164-166 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.83 (dd, J = 7.2,
2.4 Hz, 1H), 7.53 (dd, J = 7.4, 1.9 Hz, 1H), 7.40-7.45 (m, 8H), 7.24-7.26 (m, 6H), 7.10-7.14 (m,
3H), 2.56 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 165.9, 143.51, 142.28, 137.26, 136.62,
136.34, 131.25, 130.02, 129.74, 129.28, 129.18, 129.03, 128.85, 128.83, 128.78, 126.45, 126.35,
126.27, 121.78, 121.33, 120.34, 20.54. Anal. Calcd. For C28H22N2: C: 87.01; H: 5.74; N: 7.25.
Found: C: 87.05; H: 5.72; N: 7.21. MS-EI (m/z) 386.63.
4.3.2 1,8-Dimethyl-3,4,5-triphenyl-3H-benzo[d][1,2]diazepine (3b).
1
Yield: 68 %. yellow solid; mp: 143-145 °C; H NMR (400 MHz, DMSO-d6) δ, 7.80 (d, J = 6.1
Hz, 1H), 7.44-7.46 (m, 6H), 7.29-7.31 (m, 7H), 7.20 (dd, J = 7.2 , 2.4 Hz, 1H), 7.13-7.15 (m,
3H), 2.57 (s, 3H), 2.36 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 165.7, 143.76, 143.51, 137.83,
136.61, 136.34, 133.48, 132.59, 130.03, 129.75, 129.29, 129.14, 129.01, 128.85, 128.83, 128.77,
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126.47, 126.36, 122.38, 121.78, 120.36, 21.23, 20.57. Anal. Calcd. For C29H24N2: C: 86.97; H:
6.04; N: 6.99. Found: C: 86.11; H: 6.17; N: 6.81. MS-EI (m/z) 400.34.
4.3.3 8-Methoxy-1-methyl-3,4,5-triphenyl-3H-benzo[d][1,2]diazepine (3c).
1
Yield: 74 %. yellow solid; mp: 155-158 °C; H NMR (400 MHz, DMSO-d6) δ 7.76 (d, J = 6.1
Hz, 1H), 7.44-7.46 (m, 6H), 7.24-7.26 (m, 6H), 7.10- 7.13 (m, 4H), 6.91 (dd, J = 6.8 , 1.9 Hz,
1H), 3.79 (s, 3H), 2.58 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 164.9, 157.26, 146.20, 143.51,
136.61, 136.34, 132.21, 131.65, 130.02, 129.78, 129.18, 129.28, 129.02, 128.85, 128.83, 126.47,
126.33, 121.78, 120.33, 115.16, 107.35, 56.05, 20.55. Anal. Calcd. For C29H24N2O: C: 83.63; H:
5.81; N: 6.73; O: 3.84. Found: C: 83.34; H: 5.87; N: 6.83; O: 3.85. MS-EI (m/z) 416.46.
4.3.4 7-Methoxy-1-methyl-3,4,5-triphenyl-3H-benzo[d][1,2]diazepine (3d).
1
Yield: 70 %. yellow solid; mp: 187-191 °C; H NMR (400 MHz, DMSO-d6) δ 7.44-7.46 (m,
7H), 7.36 (m, 1H), 7.26-7.29 (m, 6H), 7.13-7.16 (m, 3H), 6.89 (dd, J = 7.2, 2.4 Hz, 1H), 3.80 (s,
3H), 2.56 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 166.01, 161.01, 143.56, 138.97, 138.74,
136.65, 136.32, 130.01, 129.73, 129.28, 129.16, 129.02, 128.86, 128.84, 126.49, 126.36, 123.27,
121.36, 120.71, 115.60, 114.24, 56.02, 20.53. Anal. Calcd. For C29H24N2O: C: 83.63; H: 5.81; N:
6.73; O: 3.84. Found: C: 83.65; H: 5.81; N: 6.80; O: 3.62. MS-EI (m/z) 416.55.
4.3.5 1,7-Dimethyl-3,4,5-triphenyl-3H-benzo[d][1,2]diazepine (3e).
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Yield: 67 %. yellow solid; mp: 102-105 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.63 (m, 1H) 7.49
(d, J = 6.1 Hz, 1H), 7.44-7.46 (m, 6H), 7.26-7.29 (m, 6H), 7.13-7.16 (m, 4H), 2.56 (s, 3H),2.36
(s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 164.87, 143.51, 142.23, 139.33, 137.12, 136.65,
136.31, 132.50, 130.04, 129.74, 129.25, 129.16, 129.02, 128.85, 128.83, 126.50, 126.32, 125.64,
121.51, 121.32, 120.68, 21.23, 20.56. Anal. Calcd. For C29H24N2: C: 86.97; H: 6.04; N: 6.99.
Found: C: 86.95; H: 6.01; N: 6.85. MS-EI (m/z) 400.64.
4.3.6 8-Fluoro-1-methyl-3,4,5-triphenyl-3H-benzo[d][1,2]diazepine (3f).
1
Yield: 65 %. yellow solid; mp: 194-197 °C; H NMR (400 MHz, DMSO-d6) δ 7.86 (m, 1H),
7.44-7.46 (m, 6H), 7.26-7.31 (m, 7H), 7.13-7.18 (m, 4H), 2.59 (s, 3H). 13C NMR (100 MHz,
DMSO-d6) δ 167.12, 163.24, 144.52, 143.51, 136.64, 136.32, 133.33, 132.58, 130.02, 129.71,
129.28, 129.13, 129.03, 128.83, 128.80, 126.46, 126.33, 121.79, 120.34, 114.61, 107.97, 20.54.
Anal. Calcd. For C28H21FN2: C: 83.14; H: 5.23; F: 4.70; N: 6.93. Found: C: 83.25; H: 5.21; F:
4.67; N: 6.86. MS-EI (m/z) 404.43.
4.3.7 1-Methyl-8-nitro-3,4,5-triphenyl-3H-benzo[d][1,2]diazepine (3g).
1
Yield: 60 %. yellow solid; mp: 206-208 °C; H NMR (400 MHz, DMSO-d6) δ 8.05 (m, 1H),
7.94 (dd, J = 6.8, 1.9 Hz, 1H), 7.63 (d, J = 6.0 Hz, 1H), 7.42-7.43 (m, 6H), 7.30-7.32 (m, 6H),
7.10-7.15 (m, 3H), 2.60 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 165.51, 144.31, 143.52,
143.50, 140.36, 136.65, 136.32, 130.04, 129.77, 129.28, 129.13, 129.11, 129.02, 128.87, 128.82,
126.47, 126.38, 124.91, 121.74, 120.34, 116.56, 20.54. Anal. Calcd. For C28H21N3O2: C: 77.94;
H: 4.91; N: 9.74; O: 7.42. Found: C: 77.90; H: 4.81; N: 9.80; O: 7.39. MS-EI (m/z) 431.61.
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4.3.8 1-Methyl-7-nitro-3,4,5-triphenyl-3H-benzo[d][1,2]diazepine (3h).
1
Yield: 58 %. yellow solid; mp: 137-140 °C; H NMR (400 MHz, DMSO-d6) δ 8.57 (m, 1H),
8.05 (dd, J = 7.2, 2.4 Hz, 1H), 7.81 (d, J = 6.1 Hz, 1H), 7.41-7.44 (m, 6H), 7.26-7.29 (m, 6H),
7.12-7.14 (m, 3H), 2.58 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 166.02, 147.55, 144.09,
143.52, 140.71, 136.65, 136.32, 130.02, 129.76, 129.28, 129.14, 129.03, 128.85, 128.82, 126.47,
126.32, 125.78, 121.39, 121.34, 120.72, 119.54, 20.55. Anal. Calcd. For C28H21N3O2: C: 77.94;
H: 4.91; N: 9.74; O: 7.42. Found: C: 77.89; H: 4.84; N: 9.74; O: 7.49. MS-EI (m/z) 431.44.
4.3.9 7-Methoxy-3-(4-methoxyphenyl)-1-methyl-4,5-diphenyl-3H-benzo[d][1,2]diazepine
(3i).
1
Yield: 71 %. yellow solid; mp: 166-167 °C; H NMR (400 MHz, DMSO-d6) δ 7.48 (m, 1H),
7.39-7.41 (m, 4H), 7.25-7.28 (m, 6H), 7.14 (m, 2H), 7.08 (m, 2H), 6.89 (dd, J = 7.2, 2.4 Hz, 1H),
6.77 (m, 1H), 3.80 (s, 3H), 3.76 (s, 3H), 2.59 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 165.11,
161.01, 159.47, 138.99, 138.74, 136.91, 136.67, 136.33, 130.02, 129.74, 129.24, 129.13, 129.02,
128.37, 126.34, 123.27, 121.35, 120.74, 115.57, 114.23, 113.81, 56.01, 20.54. Anal. Calcd. For
C30H26N2O2: C: 80.69; H: 5.87; N: 6.27; O: 7.17. Found: C: 80.65; H: 5.81; N: 6.24; O: 7.11.
MS-EI (m/z) 446.58.
4.3.10 3-(4-Methoxyphenyl)-1,8-dimethyl-4,5-diphenyl-3H-benzo[d][1,2]diazepine (3j).
13

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Yield: 66 %. yellow solid; mp: 89-92 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.80 (d, J = 6.1 Hz,
1H), 7.46 (m, 4H), 7.28-7.30 (m, 7H), 7.14-7.18 (m, 3H), 7.04 (m, 2H), 3.78 (s, 3H), 2.57 (s,
3H), 2.36 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ 165.42, 159.48, 143.74, 137.83,136.94,
136.62, 136.33, 133.46, 132.58, 130.02, 129.75, 129.28, 129.13, 129.02, 128.79, 128.35, 126.37,
122.38, 121.77, 120.32, 113.82, 56.01, 21.22, 20.54. Anal. Calcd. For C30H26N2O: C: 83.69; H:
6.09; N: 6.51; O: 3.72. Found: C: 83.64; H: 6.04; N: 6.50; O: 3.72. MS-EI (m/z) 430.58.
4.3.11 1-Methyl-7-nitro-3-(4-nitrophenyl)-4,5-diphenyl-3H-benzo[d][1,2]diazepine (3k).
1
Yield: 56 %. yellow solid; mp: 215-217 °C; H NMR (400 MHz, DMSO-d6) δ 8.55 (m, 1H),
8.34 (m, 2H), 8.05 (dd, J = 7.2, 2.4 Hz, 1H), 7.82 (d, J = 6.1 Hz, 1H), 7.54 (m, 2H), 7.45 (m,
4H), 7.26-7.28 (m, 4H), 7.13-7.15 (m 2H), 2.60 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ
168.01, 148.47, 147.55, 147.13, 144.09, 140.71, 136.64, 136.32, 130.02, 129.75, 129.26, 129.14,
129.03, 127.19, 126.32, 125.78, 123.64, 121.39, 121.34, 120.72, 119.54, 20.54. Anal. Calcd. For
C28H20N4O4: C: 70.58; H: 4.23; N: 11.76; O: 13.43. Found: C: 70.51; H: 4.22; N: 11.70; O:
13.49. MS-EI (m/z) 476.57.
4.3.12
(3l).
7-Methoxy-1-methyl-3-(4-nitrophenyl)-4,5-diphenyl-3H-benzo[d][1,2]diazepine
1
Yield: 63 %. yellow solid; mp: 176-178 °C; H NMR (400 MHz, DMSO-d6) δ 8.39 (m, 2H),
7.58 (m 2H), 7.51 (d, J = 6.1 Hz, 1H), 7.40-7.42 (m, 4H), 7.26-7.27 (m, 4H), 7.13-7.14 (m, 2H),
6.90 (dd, J = 6.8, 2.4 Hz, 1H), 6.79 (m, 1H), 3.76 (s, 3H), 2.60 (s, 3H). 13C NMR (100 MHz,
DMSO-d6) δ 165.24, 161.01, 148.47, 147.13, 138.99, 138.74, 136.67, 136.33, 130.02, 129.74,
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129.28, 129.13, 129.02, 127.17, 126.34, 123.67, 123.26, 121.35, 120.74, 115.57, 114.23, 56.01,
20.54. Anal. Calcd. For C29H23N3O3: C: 75.47; H: 5.02; N: 9.10; O: 10.40. Found: C: 75.44; H:
5.07; N: 9.12; O: 10.28. MS-EI (m/z) 461.47.
4.3.13 4,5-Bis(4-methoxyphenyl)-1-methyl-3-phenyl-3H-benzo[d][1,2]diazepine (3m).
1
Yield: 75 %. yellow solid; mp: 110-113 °C; H NMR (400 MHz, DMSO-d6) δ 7.75 (d, J = 7.2
Hz, 1H), 7.56 (d, J = 6.8 Hz, 1H), 7.43-7.45 (m, 8H), 7.28 (m, 2H), 7.10 (m, 1H), 6.87-6.89 (m,
4H), 3.78 (s, 6H), 2.55 (s, 3H). 13C NMR (100 MHz, DMSO-d6) δ164.33, 159.53, 159.27,
143.54, 142.29, 137.24, 131.92, 131.26, 130.32, 130.21, 129.31, 128.85, 128.83, 128.78, 126.47,
126.28, 121.76, 121.33, 120.37, 114.51, 114.27, 56.02, 20.54. Anal. Calcd. For C30H26N2O2: C:
80.69; H: 5.87; N: 6.27; O: 7.17. Found: C: 80.65; H: 5.88; N: 6.20; O: 7.25. MS-EI (m/z)
446.48.
4.3.14 4,5-Bis(4-methoxyphenyl)-1,8-dimethyl-3-phenyl-3H-benzo[d][1,2]diazepine (3n).
1
Yield: 69 %. yellow solid; mp: 211-213 °C; H NMR (400 MHz, DMSO-d6) δ 7.75 (d, J = 6.1
Hz, 1H), 7.43-7.44 (m, 6H), 7.30 (m, 1H), 7.26 (m, 2H), 7.19 (dd, J = 7.2, 2.4 Hz, 1H), 7.09 (m,
1H), 6.87-6.89 (m, 4H), 3.79-3.80 (s, 6H), 2.59 (s, 3H), 2.36 (s, 3H). 13C NMR (100 MHz,
DMSO-d6) δ 165.82, 159.51, 159.26, 143.78, 143.52, 137.80, 133.46, 132.58, 131.93, 130.35,
130.27, 129.30, 128.82, 128.80, 128.78, 126.50, 122.38, 121.78, 120.36, 114.51, 114.21, 56.03,
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21.20, 20.54. Anal. Calcd. For C31H28N2O2: C: 80.84; H: 6.13; N: 6.08; O: 6.95. Found: C:
80.80; H: 6.13; N: 6.06; O: 6.89. MS-EI (m/z) 460.55.
4.3.15 8-Methoxy-4,5-bis(4-methoxyphenyl)-1-methyl-3-phenyl-3H-benzo[d][1,2]diazepine
(3o).
1
Yield: 73 %. yellow solid; mp: 199-201 °C; H NMR (400 MHz, DMSO-d6) δ 7.69 (d, J = 6.1
Hz, 1H), 7.42 (m, 6H), 7.26 (m, 2H), 7.05-7.07 (m, 2H), 6.88-6.90 (m, 5H), 3.79-3.80 (s, 9H),
2.57 (m, 3H). 13C NMR (100 MHz, DMSO-d6) δ 165.15, 159.50, 159.25, 157.21, 146.13,
143.55, 132.26, 131.90, 131.62, 130.31, 130.24, 129.33, 128.84, 128.81, 126.46, 121.76, 120.34,
115.18, 114.49, 114.21, 107.34, 56.02, 20.54. Anal. Calcd. For C31H28N2O3: C: 78.13; H: 5.92;
N: 5.88; O: 10.07. Found: C: 78.22; H: 5.84; N: 5.90; O: 10.02. MS-EI (m/z) 476.64.
4.3.16 7-Methoxy-4,5-bis(4-methoxyphenyl)-1-methyl-3-phenyl-3H-benzo[d][1,2]diazepine
(3p).
N
N
MeO
OMe
MeO
1
Yield: 64 %. yellow solid; mp: 184-187 °C; H NMR (400 MHz, DMSO-d6) δ 7.43-7.44 (m,
7H), 7.35 (m, 1H), 7.26 (m, 2H), 7.09 (m, 1H), 6.87-6.89 (m, 5H), 3.79-3.80 (s, 9H), 2.58 (s,
3H). 13C NMR (100 MHz, DMSO-d6) δ 166.78, 161.01, 159.51, 159.26, 143.56, 138.97, 138.73,
131.94, 130.31, 130.25, 129.29, 128.87, 128.85, 126.45, 123.28, 121.36, 120.71, 115.58, 114.51,
114.24, 56.02, 20.54. Anal. Calcd. For C31H28N2O3: C: 78.13; H: 5.92; N: 5.88; O: 10.07. Found:
C: 78.08; H: 5.93; N: 5.86; O: 10.08. MS-EI (m/z) 476.51.
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Acknowledgements
Authors are thankful to Dr. N. K. Shah, Head, Department of Chemistry, Gujarat University for
lab facilities and NFDD Centre, Rajkot for spectral analysis.
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