SbCl3-Al2O3-catalyzed, solvent-free, one-pot synthesis of benzo[b]1,4-diazepines

Article abstract of DOI:10.1080/00397910500451456

This article explores the use of antimony(III) chloride adsorbed on neutral alumina as an efficient catalyst for the one-pot synthesis of benzo[b]1,4-diazepines (83-94%) under solvent-free conditions. The process is easy, efficient, ecofriendly, and econo

Full text of DOI:10.1080/00397910500451456

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SbCl3‐Al2O3–Catalyzed, Solvent‐Free, One‐Pot
Synthesis of Benzo[b]1,4‐diazepines
Bilal A. Ganai a , Satish Kumar a , Charanjeet S. Andotra a & Kamal K.
Kapoor a
a Department of Chemistry, University of Jammu, Jammu, India
Published online: 16 Aug 2006.
To cite this article: Bilal A. Ganai , Satish Kumar , Charanjeet S. Andotra & Kamal K. Kapoor (2006)
SbCl3‐Al2O3–Catalyzed, Solvent‐Free, One‐Pot Synthesis of Benzo[b]1,4‐diazepines, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 36:6, 803-807, DOI:
10.1080/00397910500451456
To link to this article: http://dx.doi.org/10.1080/00397910500451456
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Synthetic Communicationsw, 36: 803–807, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500451456
SbCl3-Al2O3–Catalyzed, Solvent-Free,
One-Pot Synthesis of Benzo[b]1,4-diazepines
Bilal A. Ganai, Satish Kumar, Charanjeet S. Andotra,
and Kamal K. Kapoor
Department of Chemistry, University of Jammu, Jammu, India
Abstract: This article explores the use of antimony(III) chloride adsorbed on neutral
alumina as an efficient catalyst for the one-pot synthesis of benzo[b]1,4-diazepines
(83–94%) under solvent-free conditions. The process is easy, efficient, ecofriendly,
and economical.
Keywords: Antimony(III) chloride, benzo[b]1,4-diazepines, solid-supported reagents,
sun rays
INTRODUCTION
Considerable interest has been focused on the synthesis of benzodiazepines
because of their wide range of biological activities and therapeutic
uses.[1a,1b] In addition to their well-known anxiolytic, anticonvulsant,
sedative, and muscle-relaxant activities found in therapeutics,[2] benzo-
diazepines also exhibit activities as antibiotics[3a,3b] anti-HIV agents,[4a,4b]
and farnesyltransferase inhibitors.[5] Because of their rich therapeutic value,
efficient methods for their preparation are continually being developed.
However, the most commonly employed methods involve the cyclocondensa-
tion of 1,2-diamines with ketones,[6] enones,[7] or b-haloketones[8] in the
presence of acid catalysts such as BF3-etherate,[9] NaBH4,[10] polyphosphroic
acid-SiO2,[11] MgO-POCl3,[12] Yb(OTf),[13] Al2O3-P2O5,[14] AcOH,[15]
SO242-ZrO2,[16] Ag3PW12 O40,[17] Zn [L-proline]2,[18] and ionic liquids.[19]
Received in India July 28, 2005
Address correspondence to Kamal K. Kapoor, Department of Chemistry, University
of Jammu, Jammu 180 006, India. Tel.: 91-191-2453969; Fax: 91-191-2450014;
E-mail: k2kapoor@yahoo.com
803

804
B. A. Ganai et al.
In our earlier communication,[20] SbCl3-Al2O3 was used as an efficient
catalyst for the synthesis of several dimeric quinazolines in solvent-free con-
ditions. In view of the advantages associated with solvent-free reactions[21]
such as easy handling, simple equipment, less environmentally hazardous
reactions, time and energy efficiency, and low capital outlay for scaling, we
thought to explore the usage of SbCl3-Al2O3 as a catalyst to synthesize
benzo[b]1,4-diazepines from o-phenylene diamine and benzylidene acetophe-
nones under solvent-free conditions. When a mixture of o-phenylene diamine
and various benzylidene acetophenones (Table 1) and 1.6 mol% of SbCl3 as
SbCl3-Al2O3 was heated at 608C in an oil bath under solvent-free conditions,
the formation of the desired products was observed, which was supported by
1
the spectroscopic data, particularly the H NMR spectra of 3a–g, by the
indicative appearance of the ABM–spin system with characteristic geminal
and vicinal coupling constant for the methylene group resonances (2J ¼ 9–
3
3
11 Hz, J ¼ 4–5.5 Hz, J ¼ 9–11 Hz) and the vicinal coupling constants for
methine resonances (3J ¼ 5–5.5 Hz, 3J ¼ 9–11 Hz). The IR spectra and
HRMS of compounds 3a–g are also in agreement with the structures
envisaged. Similar product formation was observed in about 45 min when
the previously mentioned mixture was exposed to sun rays. Although the
yields of the products were comparable to that in the oil bath at 608C, we
did not pursue it further, keeping in view the impracticality of the
procedure because the sun rays cannot be delivered/diverted to the reaction
place in the laboratory. However, when this reaction was carried out in the
dark at room temperature, only 30% conversion to the product benzo[b]1,4-
diazepine was noticed after 24 h. No formation of the products occured
Table 1. SbCl3-Al2O3–catalyzed solvent-free one-pot formation of benzo[b]1,4-dia-
zepines
Time
(min)
Yield
(%)
Entry
R1
R2
Product 3
1
2
3
4
5
6
7
H
Cl
H
H
H
Cl
H
H
H
a
b
c
d
e
f
120
90
94
92
85
90
88
83
84
OCH3
H
120
100
80
F
Br
110
70
CH3
g

Benzo[b]1,4-diazepines
805
when the reaction was carried out with SbCl3 or Al2O3 alone as catalysts either
in solvent-free conditions or in the presence of a solvent (CHCl3). Here the
role of sun rays seems to be providing the heat energy to the reaction.
The substrates benzylidene acetophenones 1a–1 g were prepared by
the well-known Claisen–Schmidt condensation process.[22] The substrates
1a–1 g were allowed to react with o-phenylene diamine using Sb(III)
chloride–Al2O3 as catalyst at 608C in an oil bath without any solvent. The
resulting products 3a–3 g were obtained in good yields (83–94%) after
simple workup followed by purification by column chromatography.
In conclusion, an efficient, simple, one-pot, solvent-free synthesis of
benzo[b]1,4-diazepines has been accomplished from o-phenylene diamine
and benzylidene acetophenones in the presence of SbCl3-Al2O3.
EXPERIMENTAL
Melting points were measured in open capillaries on a Perfit melting-point
apparatus and are uncorrected. IR spectra on KBr were recorded on Brucker-
1
4800 infrared spectrometer. H NMR and HRMS spectra were recorded on
Brucker Ac-200 (200-MHz) spectrometer and JEOL D-300 mass spectrometer
at 70 eV respectively. The progress of the reaction was monitored by TLC
(0.5-mm-thick plates using BDH silica gel G as adsorbent). The plates were
developed with ceric ammonium sulfate in H2SO4, and the compounds were
observed as black spots without heating. Development of plates with
Draggendroff reagent resulted in orange spots. All solvents were distilled
before use. Column chromatography was performed on silica gel (100–200
mesh), and compounds were eluted with graded solvent systems of
petroleum ether (40–60) and ethylacetate. Recrystallization was achieved
with a CHCl3–petroleum ether (40–60) solvent system.
Synthesis of Catalyst
The catalyst was prepared by the same procedure as described in our earlier
communication.[20]
General Procedure for Synthesis of 3a–3 g
The benzylidene acetophenone derivatives 1a–1 g (10 mmol), o-phenylene
diamine (10 mmol), and SbCl3-Al2O3 catalyst (3.17 g) were thoroughly
ground in a pestle-mortar and transferred to a round-bottom flask. This
round-bottom flask was heated in an oil bath at 608C until the completion
of the reaction (TLC). Ethylacetate (50 ml) was added to the reaction
mixture after cooling to room temperature, and the resultant heterogeneous
solution was stirred for 5 min and filtered to remove the insoluble materials.

806
B. A. Ganai et al.
The filterate was dried over anhydrous Na2SO4. The solvent was removed, and
the residue was column chromatographed to obtain solid products, which were
further recrystallized (83–94% yield).
2,4-Diphenyl-1H,2H,3H-benzo [b]1,4-diazepine 3a: Yellowish needles
(94%), mp 130–1318C. IR (n, cm21): 3440, 3350, 3067, 2890, 1604, 1508,
1466, 1210, 834, 770. H NMR (CDCl3): d 7.8–6.8 (m, 14H aromatic), 5.1
1
(dd, 1H, J ¼ 4 and 8 Hz), 3.9 (brs, 1 ꢀ NH, D2O exchangeable), 3.1 (dd,
1H, J ¼ 4 and 10 Hz), 3.0 (dd, 1H, J ¼ 8 and 10 Hz). HRMS: m/z at
298.3794 (Mþ) 100% (calc. for C21H18N2, 298.3896).
2-(4-Chlorophenyl)-4-phenyl-1H,2H,3H-benzo[b]1,4-diazepine 3b: Yellow
crystal (92%), mp 110–1128C. IR (n, cm21): 3455, 3367, 3045, 2900, 1609,
1516, 1470, 1204, 840, 777. 1H NMR (CDCl3): d 7.9– 6.75 (m, 13H
aromatic), 5.2 (dd, 1H, J ¼ 4.5 and 9 Hz), 3.6 (brs, 1 ꢀ NH, D2O exchange-
able), 3.2 (dd, 1H, J ¼ 4.5 and 11 Hz), 3.1 (dd, 1H, J ¼ 9 and 11 Hz). HRMS:
m/z at 332.8341 (Mþ) 100% (calc. for C21H17ClN2, 332.8344).
2-(4-Methoxyphenyl)-4-phenyl-1H,2H,3H-benzo[b]1,4-diazepine 3c:Yellow
solid (85%), mp 64–658C. IR (n, cm21): 3433, 3328, 2872, 1600, 1514, 1454,
1200, 872, 758. H NMR (CDCl3): d 7.8–6.7 (m, 13H aromatic) 5.3 (dd, 1H,
1
J ¼ 4.2 and 8 Hz), 3.8 (brs, 1 ꢀ NH, D2O exchangeable), 3.4 (s, 3H), 3.2 (dd,
1H, J ¼ 4.2 and 10Hz) 3.0 (dd, 1H, J ¼ 8 and 10Hz). HRMS: m/z at
328.4158 (Mþ) 100% (calc. for C22H20N2O, 328.4160).
2-(3-Chlorophenyl)-4-phenyl-1H,2H,3H-benzo[b]1,4-diazepine 3d: White
powder (90%), mp 112–1148C. IR (n, cm21): 3452, 3360, 3045, 2898,
1608, 1510, 1468, 1205, 840, 772. H NMR (CDCl3): d 7.9–6.7 (m, 13H
1
aromatic), 5.2 (dd, 1H, J ¼ 4.4 and 9.1 Hz), 3.4 (brs, 1 ꢀ NH, D2O exchange-
able), 3.2 (dd, 1H, J ¼ 4.4 and 11.2 Hz), 3.0 (dd, 1H, J ¼ 9.1 and 11.2 Hz).
HRMS: m/z at 332.8342 (Mþ) 100% (calc. for C21 H17 ClN2, 332.8344).
2-(4-Fluorophenyl)-4-phenyl-1H,2H,3H-benzo[b]1,4-diazepine 3e: Shining
light yellow crystals (88%), mp 84–858C. IR (n, cm21): 3461, 3362, 3074,
2904, 1610, 1508, 1470, 1210, 840, 774. H NMR (CDCl3): d 7.8–6.75
1
(m, 13H aromatic), 5.3 (dd, 1H, J ¼ 5 and 10 Hz), 3.9 (brs, 1 ꢀ NH, D2O
exchangeable), 3.2 (dd, 1H, J ¼ 5 and 12Hz), 3.3 (dd, 1H, J ¼ 10 and 12Hz).
HRMS: m/z at 316.3793 (Mþ) 100% (calc. for C21H17FN2, 316.3800).
2-(4-Bromophenyl)-4-phenyl-1H,2H,3H-benzo[b]1,4-diazepine 3f: White
Solid (83%), m.p. 103–1048C IR (n, cm21): 3432, 3340, 2872, 1602, 1504,
1450, 1202, 834, 766. H NMR (CDCl3): d 7.7–6.75 (m, 13H aromatic)
1
5.1 (dd, 1H, J ¼ 4 and 8 Hz), 3.8 (brs, 1 ꢀ NH, D2O exchangeable) 3.0
(dd, 1H, J ¼ 4 and 10 Hz), 2.9 (dd, 1H, 8 and 10 Hz) HRMS: m/z at
376.0424/378.0301 (Mþ) (calc. for C21H17BrN2, 376. 0569/378.0549).
2-(4-Methylphenyl)-4-phenyl-1H,2H,3H-benzo[b]1,4-diazepine 3 g: Yellow
crystals (84%), m.p. 78–808C. IR (n, cm21) 3452, 3358, 3040, 2892, 1602,

Benzo[b]1,4-diazepines
807
1502, 1466, 1212, 832, 756. 1H NMR (CDCl3): d 7.9–6.7 (m, 13H aromatic)
5.0 (dd, 1H, J ¼ 4.2 and 8 Hz), 3.6 (brs, 1 ꢀ NH, D2O exchangeable) 2.4
(s, 3H) 3.1 (dd, 1H, J ¼ 4.2 and 10.2 Hz), 3.0 (dd, 1H, J ¼ 8 and 10.2 Hz).
HRMS: m/z at 312.4164 (Mþ) 100% (calc. for C22H20N2, 312.4166).
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