The facile syntheses of 2,3-dihydro-1H-1,5-benzodiazepines and their ribofuranosides

Article abstract of DOI:10.1002/jhet.365

(Chemical Equation Presented) The facile syntheses of 2,3-dihydro-1H- benzodiazepines containing heterocyclic moieties and their ribofuranosides have been accomplished in ionic liquids at ambient temperature. The characterization of all these compounds ha

Full text of DOI:10.1002/jhet.365

May 2010
The Facile Syntheses of 2,3-Dihydro-1H-1,5-benzodiazepines and
Their Ribofuranosides
603
Renuka Jain, Tripti Yadav, Manoj Kumar, and Ashok K. Yadav*
Department of Chemistry, University of Rajasthan, Jaipur 302055, Rajasthan, India
*E-mail: drakyada@yahoo.co.in
Received May 8, 2009
DOI 10.1002/jhet.365
Published online 3 May 2010 in Wiley InterScience (www.interscience.wiley.com).
The facile syntheses of 2,3-dihydro-1H-benzodiazepines containing heterocyclic moieties and their
ribofuranosides have been accomplished in ionic liquids at ambient temperature. The characterization of
1
all these compounds has been done unambiguously by IR, H NMR, 13C NMR, GC-MS spectroscopy,
and elemental analysis.
J. Heterocyclic Chem., 47, 603 (2010).
INTRODUCTION
regard to the synthesis of 1,5-benzodiazepine derivatives
containing heterocyclic moieties, their spiro derivatives
[23] and nucleosides. Furthermore, the reported methods
are associated with several drawbacks, such as expen-
sive reagents, drastic reaction conditions, extended reac-
tion times, formation of the side products, unsatisfactory
yields, complex experimental procedures, and involving
the use of environmentally black listed solvents, e.g.
N,N-dimethylformamide, N-methylpyrrolidine, etc.
The 1,5-Benzodiazepines have attracted tremendous
attention due to their diversified medicinal properties [1–
4], e.g. analgesic, hypnotic, sedative, antianxiety, anticon-
vulsant, antidepressant, and anti-inflammatory activities.
These derivatives have also been used in viral infections
and cardiovasulcar disorders [5]. Commercial applica-
tions of this heterocyclic system as dyes for acrylic fibres
and in photography have also been reported [6].
In view of our continuous interest in the synthesis of
nucleosides [24] and the only report on ionic liquid pro-
moted lipase catalysed synthesis of nucleosides [25], we
have developed a facile synthesis of 2,3-dihydro-1H-
1,5-benzodiazepines containing heterocyclic moieties
and their spiro derivatives at ambient temperature in
environmentally benign ionic liquid (IL). These deriva-
tives could be subsequently transformed to their ribofur-
anosides in the same pot under mild conditions.
These derivatives also act as key intermediates for the
synthesis of fused ring derivatives [7], viz., triazolo-, oxa-
diazolo-, oxazino-, furano-, and pyrido- benzodiazepines.
A survey of the literature reveals that the synthesis of
1,5-benzodiazepines involves the condensation of o-
phenylenediamine with b-haloketones [8], a,b-unsatu-
rated carbonyl compounds [9] or ketones in the presence
of BF3-etherate [10], polyphosphoric acid or SiO2 [11],
NaBH4 [12], MgO-POCl3 [13], InBr3 [14], InCl3 [15],
ionic liquids [16], Amberlyst [17] or zinc montmorillon-
ite [18], etc.
RESULTS AND DISCUSSION
The chemistry of nucleosides has been an active area
of research in academia and in industry as it has demon-
strated significant importance in cancer and viral therapy
[19]. Also, protected nucleosides serve as building
blocks for the synthesis of oligonucleotides, which has
been used as probes for diagnostic purposes [20] and in
antisense therapeutics [21]. The antisense oligonucleo-
tides and siRNA have been extensively employed in
selective inhibition of gene expression [22]. To our
knowledge, only scanty information is available in
In our strategy, we first attempted the synthesis of
2,3-dihydro-1H-1,5-benzodiazepines containing hetero-
cyclic moieties/spiro derivatives from the reaction
between o-phenylenediamine and an heterocyclic
ketone(s) in an IL, viz. 1,3-di-n-butylimidazolium
bromide [BBIM]Br, 1,3-di-n-butylimidazolium tetra-
fluoroborate [BBIM]BF4, 1,3-di-n-butylimidazolium hex-
afluorophosphate [BBIM]PF6, 1-methoxyethyl-3-methyl-
imidazolium trifluoroacetate [MOEMIM]TFA, and 1-
C
V
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R. Jain, T. Yadav, M. Kumar, and A. K. Yadav
Vol 47
methoxyethyl-3-methylimidazolium mesylates [MOE-
MIM]Ms at ambient temperature (28 6 2ꢀ). The reac-
tion afforded 2,3-dihydro-1H-1,5-benzodiazepine con-
taining heterocyclic moieties or their spiro derivatives in
excellent yields (Table 1).
SUMMARY
In summary, a facile one pot synthesis of 2,3-dihy-
dro-1H-1,5-benzodiazepine derivatives containing heter-
ocyclic moieties, their spiro derivatives and their ribo-
furanosides have been developed at ambient temperature
in environmentally benign ionic liquids(s). [MOE-
MIM]TFA was found to be a better solvent for this pur-
pose. The simplicity of the procedure, easy recovery and
reuse of the reaction media viz. ionic liquid make this
methodology a convenient, efficient, economic, and
attractive.
The chracterization of the compounds 3a-k have been
1
carried out by IR, H NMR, 13C NMR, GC-MS spec-
troscopy and elemental analysis.
A plausible mechanism of the reaction appears to
involve nucleophilic attack of o-phenylenediamine on
the carbonyl carbon of the heterocyclic ketone to gener-
ate diaminoalcohol followed by loss of water to afford
diimine intermediate A. The latter may undergo 1,3-
hydrogen shift to yield isomeric imine-enamine interme-
diate B, which on cyclization affords 2,3-dihydro-1H-
1,5-benzodiazepines/spiro compounds via dipolar inter-
mediate (Scheme 1).
EXPERIMENTAL
Melting points were determined in open capillary tubes and
are uncorrected. IR spectra were recorded on a SHIMADZU
FT-IR spectrometer using KBr pellets. 1H NMR spectra were
recorded on a JEOL AL-300 MHz NMR spectrometer in
CDCl3 using TMS as an internal standard (chemical shift in d
ppm). 13C NMR spectra were recorded on a JEOL AL-75
MHz NMR spectrometer in CDCl3 using TMS as an internal
standard. Mass spectra were measured on HP 5890 GC-MS
(70eV.EI). The purity of the products was checked by TLC
using silica gel 60F 254 aluminium sheets and visualization
was accomplished by iodine/UV light. Ionic liquids were pre-
pared by reported methods [27,28]. All reagents were used as
obtained commercially.
Synthesis of 2,3-dihydro-1H-1,5-benzodiazepines (3a-k). o-
Phenylenediamine (0.005 mol) and heterocyclic ketone (0.010
mol) were added to IL (0.015 mol). The contents were stirred
magnetically at room temperature (28 6 2ꢀC). The progress of
the reaction was monitored by TLC using silica gel 60F 254
aluminum sheet in pet.ether/EtOAc 7:3. Upon completion of
the reaction, water (20 mL) was added to it. The organic com-
pound was then extracted with EtOAc (2 ꢁ 15 mL). The com-
bined organic layer was distilled under reduced pressure (10
mmHg) at 50ꢀC to afford compounds 3a-k. All these products
were further purified by column chromatography on silica gel
60–120 mesh by eluting with pet.ether-EtOAc (7:3).
2,4-Di(20-Furyl)-2-methyl-2,3-dihydro-1H-1,5-benzodiaze-
pine (3a). Solid, mp ¼ 152–153ꢀC; Rf ¼ 0.45 (pet.ether -
ethyl acetate ¼ 7:3); 1H NMR d : 1.69 (s, 3H, ACH3), 2.90
(d, J ¼ 13.2 Hz, 1H, methylene), 3.05 (d, J ¼ 13.2 Hz, 1H
methylene), 3.40 (s, 1H, NH), 6.46 (d, J ¼ 2.2 Hz, 1H, Furyl),
6.64 (d, J ¼ 3.0 Hz, 1H, Furyl), 6.90–7.03 (m, 2H, 1H furyl
and 1H phenyl), 7.10–7.15 (m, 1H, phenyl), 7.28 (d, J ¼ 2.8
Hz, 1H, phenyl), 7.40 (d, J ¼ 3.0 Hz, 1H, phenyl), 7.51 (d, J
¼ 1.4 Hz, 1H, furyl), 7.60 (d, J ¼ 3.0 Hz, 1H, Furyl), 7.78 (d,
J ¼ 1.4 Hz, 1H, Furyl); 13C NMR d : 28.80, 39.60, 71.40,
105.10, 110.62, 112.10, 113.72, 122.55, 123.15, 126.50,
128.45, 137.70, 141.30, 142.00, 146.10, 154.10, 158.50,
159.90; IR (KBr cm–1) m: 3320, 3040, 2970, 1640; GC-MS :
Mþ, 292.
To devise our goal of designing a one pot synthesis
of 2,3-dihydro-1H-1,5-benzodiazepiene ribofuranosides
4a-k, the solubility of the compounds 3a and 3j was
checked in ionic liquids by dissolving till saturation in 1
mL of IL. These data are summarized in Table 2.
The data presented in Table 2 suggest that the com-
pounds 3a and 3j show better solubility in [MOE-
MIM]Ms, [MOEMIM]TFA, which may therefore be
used for ribofuranosylation. This may be attributed due
to the ability of oxygenated cation to hydrogen bond
with -NH of the 1,5-benzodiazepine.
In a one-pot synthesis of 1,5-benzodiazepine ribofura-
nosides, o-phenylenediame (entry 1 Table 1) was first
reacted with heterocyclic ketone 2a in [MOEMIM]TFA,
the progress of the reaction being monitored by TLC.
After completion of the reaction, the sugar, viz., b-D-
ribofuranose-1-bromo-2,3,5-tribenzoate was added and
the contents were further stirred. After workup com-
pound 4a was obtained in 92% yield. On carrying out
this reaction in [MOEMIM]Ms, 4a was obtained in 80%
yield (Scheme 2).
These investigations suggest that [MOEMIM]TFA is
a better protocol for the synthesis of compounds 4a,
which is in consonance with the earlier report [26].
Same method was employed for the synthesis of ribofur-
anosides 4a-k.
The compounds 4a-k have been characterized on the
1
basis of IR, H NMR, 13C NMR, GC-MS spectroscopy,
and elemental analysis.
We also checked the recyclability of the ionic liquid
[MOEMIM]TFA for one pot synthesis of compound 4a
from o-phenylenediameine, and heterocyclic ketone 2a
as described earlier. The results of the recyclability are
shown in Table 3, which suggest that the yield of the
compound 4a decreases by 5.6 and 10%, respectively in
first and second recycling of [MOEMIM]TFA. However,
in the third cycle, the decrease in yield was significant.
2,4-Di(20-thiophenyl)-2-methyl-2,3-dihydro-1H,1,5-benzo-
diazepine (3b). Solid, mp ¼ 104–105ꢀC; Rf ¼ 0.48 (pet.ether
1
- ethyl acetate ¼ 7:3); H NMR d : 1.80 (s, 3H, CH3), 2.95 (d,
J ¼ 13.8 Hz, 1H, methylene), 3.05 (d, J ¼ 13.8 Hz, 1H, meth-
ylene), 3.60 (s, 1H, NH), 6.60–6.70 (m, 2H, 1H thiophenyl
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The Facile Syntheses of 2,3-Dihydro-1H-1,5-benzodiazepines
and Their Ribofuranosides
605
and 1H phenyl), 6.75 (dd, J ¼ 1.4 Hz, 1H, Phenyl), 6.80–6.85
(m, 2H, 1H thiophenyl and 1H phenyl), 6.92–6.98 (m, 2H, 1H
thiophenyl and 1H phenyl), 7.05 (dd, J ¼ 1.3 Hz, 1H, thio-
phenyl), 7.29 (d, J ¼ 1.5 Hz, 1H, thiophenyl), 7.37 (d, J ¼ 3.0
Hz, 1H, Thiophenyl); 13C NMR d : 31.10, 44.82, 73.10,
106.45, 111.20, 113.80, 114.60, 122.10, 124.20, 127.78,
Table 1
Synthesis of 2,3-dihydro-1H-1,5-benzodiazepines.
OPD
Yield of 1,5-bezodiazepines (%)/time (h)
[BBIM]Br [BBIM]BF4 [BBIM]PF6 [MOEMIM]TFA [MOEMIM]Ms
Entry Compd. R1 R2
R3
Product
1
2
3
4
3a
3b
3c
3d
H
H
H
H
H
H
H
H
85/7.5
80/7.0
78/6.5
80/7.0
87/6.5
85/6.0
83/6.0
82/6.5
90/5.5
87/5.5
85/5.5
86/6.0
92/4.5
90/5.0
94/5.0
92/5.0
80/4.5
90/5.5
90/5.5
88/5.5
5
6
3e
3f
H
H
H
82/7.0
78/7.0
85/6.5
83/6.5
85/6.0
86/6.0
94/5.0
90/5.0
90/5.5
88/5.5
Cl
7
3g
H NO2
73/7.0
79/6.5
82/6.0
85/5.0
80/5.5
(Continued)
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R. Jain, T. Yadav, M. Kumar, and A. K. Yadav
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Table 1
(Continued)
OPD
Entry Compd. R1 R2
Yield of 1,5-bezodiazepines (%)/time (h)
[BBIM]Br [BBIM]BF4 [BBIM]PF6 [MOEMIM]TFA [MOEMIM]Ms
R3
Product
8
9
3h
Cl Cl
63/7.5
67/7.5
69/7.0
72/7.0
72/6.5
75/6.5
79/5.5
80/5.5
75/6.5
3i
H NO2
76/6.5
76/6.0
85/6.0
10
3j
H
Cl
75/7.0
78/6.5
80/6.5
82/5.5
11
3k
H
H
75/7.5
77/6.5
82/6.5
90/5.0
128.20, 128.50, 130.48, 137.50, 141.40, 147.95, 153.78,
162.80; IR (KBr, cmꢂ1) m : 3325, 3040, 2970, 1625; GC-MS :
Mþ, 324.
7.55 (d, J ¼ 1.8 Hz, 1H, pyridyl), 7.80 (t, J ¼ 3.4 Hz, 1H, pyri-
dyl), 7.96 (s, 1H, pyridyl), 8.20 (d, J ¼ 7.0 Hz, 1H, pyridyl),
8.71 (d, J ¼ 1.8 Hz, 1H, pyridyl), 8.80 (d, J ¼ 1.8 Hz, 1H pyri-
dyl); 13C NMR d : 29.70, 42.70, 72.50, 121.45, 122.05, 122.95,
127.00, 128.80, 133.30, 133.45, 133.92, 134.10, 137.28, 139.40,
2,4-Di(20-pyridyl)-2-methyl-2,3-dihydro-1H-1,5-benzodiaze-
pine (3c). Solid, mp ¼ 162ꢀC; Rf ¼ 0.46 (pet.ether - ethyl ac-
1
etate ¼ 7:3); H NMR d : 1.82 (s, 3H, CH3), 2.91 (d, J ¼ 13.2
142.15, 147.35, 148.40, 150.45, 161.42, 164.60; IR (KBr, cmꢂ1
)
Hz, 1H, methylene), 3.05 (d, J ¼ 13.2 Hz, 1H, Mehtylene),
3.40 (s, 1H, NH), 6.80 (m, 1H, phenyl), 6.90 (m, 1H, phenyl),
6.95 (d, J ¼ 3.0 Hz, 1H, phenyl), 7.24 (dd, J ¼ 3.4 Hz, 1H,
pyridyl), 7.46 (d, J ¼ 3.0 Hz, 1H, phenyl), 7.55 (d, J ¼ 3.4
Hz, 1H, pyridyl), 7.66 (dd, J ¼ 3.4 Hz, 1H, pyridyl), 7.83 (t, J
¼ 4.9 Hz, 1H, pyridyl), 7.86 (dd, J ¼ 7.0 Hz, 1H, pyridyl),
8.63 (d, J ¼ 7.2 Hz, 1H, pyridyl), 8.68(d, J ¼ 4.6 Hz, 1H, pyr-
idyl), 8.80 (d, J ¼ 4.6 Hz, 1H, pyridyl); 13C NMR d : 31.15,
37.05, 73.25, 119.65, 120.68, 121.30, 123.95, 124.08, 126.56,
128.55, 128.80, 135.90, 136.00, 138.90, 139.15, 147.80,
148.26, 156.30, 165.15, 167.20; IR (KBr, cmꢂ1) m : 3315,
3015, 2970, 1635; GC-MS : Mþ, 314.
m : 3320, 3020, 2980, 1640; GC-MS : Mþ, 314.
2,4-Di(40-pyridyl)-2-methyl-2,3-dihydro-1H-1,5-benzodiaze-
pine (3e). Solid, mp ¼ 170ꢀC; Rf ¼ 0.44 (pet.ether - ethyl acetate
¼ 7:3); 1H NMR d : 1.89 (s, 3H, CH3), 2.90 (d, J ¼ 13.4 Hz, 1H,
methylene), 3.17 (d, J ¼ 13.4 Hz, 1H, methylene), 3.81 (s, 1H,
NH), 6.90 (dd, J ¼ 1.3 Hz, 1H, phenyl), 6.98 (dd, J ¼ 1.3 Hz, 1H,
Phenyl), 7.13 (d, J ¼ 1.3 Hz, 1H phenyl), 7.25 (d, J ¼ 1.3 Hz, 1H,
phenyl), 7.30 (d, J ¼ 1.75 Hz, 1H, pyridyl), 7.48 (d, J ¼ 2.10 Hz,
1H, pyridyl), 7.75 (d, J ¼ 2.4Hz, 1H, pyridyl), 7.98 (d, J ¼ 1.5 Hz,
1H, pyridyl), 8.10 (d, J ¼ 1.5 Hz, 1H, pyridyl), 8.28 (d, J ¼ 1.4
Hz, 1H, pyridyl), 8.70 (d, J ¼ 1.75 Hz, 1H, pyridyl), 8.80 (d, J ¼
2.15 Hz, 1H, pyridyl); 13C NMR d : 29.76, 42.80, 72.60, 121.40,
122.07, 122.90, 127.02, 128.75, 133.20, 133.40, 133.85, 134.10.
137.25, 139.40, 147.30, 148.10, 148.30, 150.40, 161.45, 164.60;
IR (KBr, cmꢂ1) m: 3310, 3010, 2965, 1630; GC-MS : Mþ, 314.
7-Chloro-2,4-di(20-pyridyl)-2-methyl-2,3-dihydro-1H-1,5-ben-
zodiazepine (3f). Solid, mp ¼ 161ꢀC; Rf ¼ 0.48 (pet.ether -
ethyl acetate ¼ 7:3); 1H NMR d : 1.82 (s, 3H, CH3), 2.83 (d, J ¼
13.0 Hz, 1H, methylene), 3.24 (d, J ¼ 13.0 Hz, 1H, methylene),
2,4-Di(30-pyridyl)-2-methyl-2,3-dihydro-1H-1,5-benzodiaze-
pine (3d). Solid, mp ¼ 168ꢀC; Rf ¼ 0.42 (pet.ether - ethylace-
1
tate ¼ 7:3); H NMR d : 1.82 (s, 3H, CH3), 2.98 (d, J ¼ 13.2
Hz, 1H, methylene), 3.08 (d, J ¼ 13.2 Hz, 1H, methylene), 3.50
(s, 1H, NH) 6.85–6.90 (m, 1H, phenyl), 6.95–6.98 (m, 1H, phe-
nyl), 7.30 (t, J ¼ 3.6 Hz, 1H, pyridyl), 7.35 (d, J ¼ 1.8 Hz, 1H,
phenyl), 7.40 (dd, J ¼ 3.0 Hz, 1H, phenyl), 7.50 (s, 1H, pyridyl),
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The Facile Syntheses of 2,3-Dihydro-1H-1,5-benzodiazepines
and Their Ribofuranosides
607
Scheme 1
Table 2
Solubility analysis of compounds in ionic liquids (mg mLꢂ1), room temperature (22ꢀC).
Solubility (mg mLꢂ1
[BBIM]PF6
)
Compounds
[BBIM]Br
[BBIM]BF4
[MOEMIM]TFA
[MOEMIM]MS
3a
3j
40
75
120
115
290
275
390
400
370
380
3.76 (s, 1H, NH), 7.02–7.06 (m, 2H, 1H pyridyl and 1H phenyl),
7.15–7.20 (m, 2H, 1H pyridyl and 1H phenyl), 7.28–7.30 (m,
2H, 1H pyridyl and 1H phenyl), 7.50 (t, J ¼ 2.8 Hz, 1H, pyri-
dyl), 7.86 (t, J ¼ 1.2 Hz, 1H, pyridyl), 8.60 (dd, J ¼ 1.65 Hz,
1H, pyridyl), 8.68 (d, J ¼ 1.8 Hz, 1H, pyridyl), 8.70 (d, J ¼ 2.10
Hz, 1, pyridyl); 13C NMR d : 31.28, 37.56, 73.50, 121.97,
122.46, 122.73, 124.38, 126.45, 127.14, 128.02, 130.45, 131.67,
136.46, 137.68, 140.21, 148.10, 148.31, 148.49, 156.31, 167.04;
IR (KBr, cmꢂ1) m : 3280, 3050, 2970, 1620; GC-MS : Mþ, 349.
7-Nitro-2,4-di(20-pyridyl)-2-methyl-2,3-dihydro-1H-1,5-ben-
zodiazepine (3g). Deep red solid, mp ¼ 141ꢀC; Rf ¼ 0.42
(pet.ether - ethyl acetate ¼ 7:3); 1H NMR d : 1.88 (s, 3H, CH3),
2.92 (d, J ¼ 13.8 Hz, 1H, methylene), 3.26 (d, J ¼ 13.8 Hz, 1H,
methylene), 3.28 (s, 1H, NH), 6.42 (s, 1H, phenyl), 6.56 (d, J ¼
1.8 Hz, 1H, phenyl), 7.10 (d, J ¼ 1.8 Hz, 1H, phenyl), 7.25 (dd,
J ¼ 1.3 Hz, 1H, pyridyl), 7.30–7.36 (m, 2H, pyridyl), 7.55 (d, J
¼ 1.9 Hz, 1H, pyridyl), 7.61 (dd, J ¼ 1.3 Hz, 1H, pyridyl), 8.16
(d, J ¼ 1.8 Hz, 1H, pyridyl), 8.65 (d, J ¼ 1.95 Hz, 1H, pyridyl),
8.70 (d, J ¼ 2.2 Hz, 1H, pyridyl); 13C NMR d : 32.10, 36.50,
75.10, 114.40, 117.20, 122.52, 124.10, 124.20, 125.90, 127.20,
129.10, 130.88, 135.70, 136.10, 138.40, 149.08, 149.90, 152.60,
163.38, 164.60; IR (KBr, cmꢂ1) m : 3325, 3140, 2940, 1620.
Anal. Calcd for C20H17N5O2 : C, 66.82; H, 4.77; N, 19.49.
Found : C, 66.85; H, 4.80; N, 19.47.
7,8-Dichloro-2,4-di(20-pyridyl)-2-methyl-2,3-dihydro-1H-1,5-
benzodiazepine (3h). Deep brown solid, mp ¼ 110ꢀC; Rf ¼
1
0.46 (pet.ether - ethyl acetate ¼ 7:3); H NMR d: 1.53 (s, 3H,
–CH3), 2.90 (d, J ¼ 13.2 Hz, 1H, methylene), 3.02 (d, J ¼
13.2 Hz, 1H, methylene), 4.10 (s, 1H, NH), 7.00 (s, 1H, phe-
nyl), 7.32 (d, J ¼ 1.70 Hz, 1H, pyridyl), 7.38 (d, J ¼ 2.9 Hz,
1H, pyridyl), 7.58 (d, J ¼ 2.8 Hz, 1H, pyridyl), 7.64 (d, J ¼
2.9 Hz, 1H, pyridyl), 7.77 (dd, J ¼ 1.70 Hz, 1H, pyridyl), 7.80
(s, 1H, phenyl), 8.63 (d, J ¼ 1.90 Hz, 1H, pyridyl), 8.84 (d, J
¼ 2.10 Hz, 1H, pyridyl), 8.90 (d, J ¼ 1.70 Hz, 1H, pyridyl);
13C NMR d : 31.52, 37.52, 77.10, 119.56, 123.40, 124.79,
129.51, 130.08, 130.21, 136.06, 136.57, 137.31, 138.53,
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R. Jain, T. Yadav, M. Kumar, and A. K. Yadav
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Scheme 2
Table 3
177.09. IR (KBr, cmꢂ1) m : 3520, 3410, 2910, 1640. Anal.
Calcd for C22H17N4Cl : C, 70.84; H, 4.59; N, 15.03. Found :
C, 70.87; H, 4.55; N, 15.05.
Recyclability studies of [MOEMIM]TFA for the synthesis of
compound 4a.
2-Spiro[5(3-methyl-1-phenylpyrazoline)]-300-methyl-100-phenyl
pyrazolino[4,5-c]-2,3-dihydro-1H-1,5-benzodiazepine (3k). Brown
solid, mp ¼ 142ꢀC; Rf ¼ 0.46 (pet.ether - ethyl acetate ¼
No. of cycles
Yield (%)/time (h)
1
0
1
2
3
90/3.0
85/3.0
81/3.0
78/3.5
7:3); H NMR d : 0.90 (s, 3H, CH3), 1.06 (s, 3H, CH3), 2.10
(s, 1H, methine), 2.60 (s, 2H, methylene), 3.70 (s, 1H, NH),
6.40–6.60 (m, 8H, phenyl), 6.90–7.02 (m, 3H, phenyl), 7.10–
7.18 (m, 3H, phenyl); 13C NMR d : 20.20, 21.50, 34.60,
42.40, 48.30, 54.30, 74.20, 110.90, 112.50, 113.60, 115.20,
116.10, 117.20, 122.20, 125.60, 127.60, 128.20, 129.10,
131.20, 132.80, 136.10 137.10, 141.20, 143.50, 146.70,
156.60; IR (KBr, cmꢂ1) m : 3520, 3400, 2905, 1640. Anal.
Calcd for C26H24N6 : C, 74.25; H, 5.75; N, 19.99. Found : C,
74.28, H, 5.72, N, 19.97.
Synthesis of 2,3,5-ꢀ-D-ribofuranose-1-bromo-2,3,5-tri-
benzoate. This has been synthesized by reported method [29].
Synthesis of 2,3-dihydro-1,5-benzodiazepine ribofurano-
sides (4a-k). After completion of the reaction between OPD
and heterocyclic ketone (monitored by TLC), 2,3,5-b-D-ribo-
furanose-1-bromo-2,3,5-tribenzoate equivalent to 1.1 mole of
compound 3 was added to the reaction mixture. The contents
were further stirred magnetically, till completion of the reac-
tion (checked by TLC). The ribofuranoside was extracted with
ethyl acetate (2 ꢁ 15 mL). The solvent was removed by distil-
lation under reduced pressure and the product 4 so obtained
was chromatographed over silica gel (60–120 mesh) column
by eluting with pet.ether-EtOAc (7:3) to afford pure
ribofuranosides.
138.97, 145.43, 148.33, 148.46, 156.10, 164.67, 168.53; IR
(KBr, cmꢂ1) m : 3310, 3050, 2940, 1620. Anal. Calcd for
C20H16N4Cl2 : C, 62.64; H, 4.20; N, 14.61. Found : C, 62.66;
H, 4.18; N, 14.64.
7-Nitro-2-spiro(20-chromane)-300,400-dihydrochromano[2,3-c]-
2,3-dihydro-1H-1,5-benzodiazepine (3i). Dark brown solid, mp
¼ 137ꢀC; Rf ¼ 0.47 (pet.ether - ethyl acetate ¼ 7:3); H NMR
1
d: 2.62 (d, J ¼ 13.20 Hz, 1H, methylene), 2.68 (t, J ¼ 12.4
Hz, 1H, methine), 2.70 (d, J ¼ 13.20 Hz, 1H, methylene),
2.75 (t, J ¼ 12.4 Hz, 2H, methylene), 2.90 (t, J ¼ 13.4 Hz,
2H, methylene), 3.58 (s, 1H, NH), 6.60 (d, J ¼ 2.4 Hz, 1H,
cromanyl), 6.84 (dd, J ¼ 2.1 Hz, 2H, chromanyl), 6.87 (dd, J
¼ 1.8 Hz, 2H, cromanyl), 6.89 (d, 1.8 Hz, 1H, cromanyl), 7.07
(t, J ¼ 2.1 Hz, 1H, cromanyl), 7.10 (t, J ¼ 1.8 Hz, 1H, cro-
manyl), 7.20 (d, J ¼ 2.1 Hz, 1H, phenyl), 7.24 (s, 1H, phenyl),
7.26 (d, J ¼ 2.1 Hz, 1H, phenyl); 13C NMR d : 15.70, 20.20,
20.43, 47.20, 81.40, 113.30, 114.10, 120.90, 122.10, 123.70,
124.10, 125.10, 126.35, 126.65, 127.10, 128.90, 129.10,
129.75, 137.90, 138.90, 147.70, 157.10, 158.90, 164.10; IR
(KBr, cmꢂ1) m : 3510, 3405, 2905, 1620. Anal. Calcd for
C24H19N3O4 : C, 69.71; H, 4.63; N, 10.16. Found : C, 69.74;
H, 4.65; N, 10.13.
2,4-Di(20-furyl)-2-methyl-1-(200,300,500-tri-o-benzoyl-ꢀ-D-ribo-
furanosyl)-2,3-dihydro-1,5-benzodiazepine (4a). Solid, mp ¼
146–148ꢀC; Rf ¼ 0.35 (pet.ether - ethyl acetate - 8:2 ); yield
86%; 1H NMR d : 1.69 (s, 3H, –CH3), 2.90 (d, J ¼ 7.2 Hz,
1H, methylene), 3.05 (d, J ¼ 7.2 Hz, 1H, methylene), 4.38 (d,
J ¼ 7.4 Hz, 2H, C500sugar), 4.89–4.93 (m, 3H, C200, C300, and
7-Chloro-2-spiro(20-indoline)-indolino[2,3-c]-2,3-dihydro-1H-
1,5-benzodiazepine (3j). Dark brown solid, mp ¼ 158ꢀC; Rf ¼
1
0.48 (pet.ether - ethylacetate ¼ 7:3); H NMR d : 2.60 (s, 1H,
00
00
methine), 2.68 (d, J ¼ 13.20 Hz, 1H, methylene), 2.80 (d, J ¼
13.20; 1H, methylene), 3.50 (s, 1H, NH), 3.60 (s, 1H, NH),
3.80 (s, 1H, NH), 6.33 (d, J ¼ 2.10 Hz, 1H, indolinyl), 6.38
(dd, J ¼ 2.2 Hz, 2H, indolinyl), 6.87 (t, J ¼ 2.3 Hz, 1H, indo-
linyl), 6.89 (t, J ¼ 3.04 Hz, 1H, indolinyl), 6.96 (d, J ¼ 2.0
Hz, 1H, indolinyl), 6.98 (dd, J ¼ 1.8 Hz, 1H, indolinyl), 7.01
(d, J ¼ 1.8 Hz, 1H, indolinyl), 7.33 (d, J ¼ 2.0 Hz, 1H, phe-
nyl), 7.71 (s, 1H, phenyl), 7.74 (d, J ¼ 2.2 Hz, 1H, phenyl);
13C NMR d : 52.10, 53.40, 54.20, 70.20, 72.10, 76.10, 108.20,
109.41, 109.61, 110.19, 112.28, 112.48, 117.30, 118.20,
122.30, 125.20, 127.44, 132.70, 137.36, 143.25, 143.38,
C4 sugar), 6.60 (d, J ¼ 8.4 Hz, 1H, C1 sugar), 6.85–7.25 (m,
10H, 4H phenyl and 6H furyl), 7.35–8.15 (m, 15H, OBz); 13C
NMR d : 28.40, 39.20, 45.60, 65.75, 68.90, 69.10, 70.0, 86.40,
105.10, 110.21, 112.40, 113.55, 119.25, 122.50, 123.10,
127.60, 128.45, 129.70, 130.25, 132.85, 133.40, 138.08,
164.65, 167.00; IR (KBr, cmꢂ1) m : 3050, 1750, 1660, 1595.
GC-MS : Mþ, 736.
2,4-Di(20-thiophenyl)-2-methyl-1-(200,300,500-tri-o-benzoyl-ꢀ-
D-ribofuranosyl)-2,3-dihydro-1,5-benzodiazepine (4b). Solid,
mp ¼ 142–144ꢀC; Rf ¼ 0.38 (pet.ether - ethyl acetate ¼ 8:2);
yield 90%; 1H NMR d : 1.65 (s, 3H, CH3), 2.85 (d, J ¼ 7.2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

May 2010
The Facile Syntheses of 2,3-Dihydro-1H-1,5-benzodiazepines
and Their Ribofuranosides
609
Hz, 1H, methylene), 3.0 (d, J ¼ 7.2 1H, methylene), 4.37 (d, J
130.55, 131.72, 132.85, 133.25, 136.45, 139.44, 149.32,
163.55, 164.65, 167.00; IR (KBr, cmꢂ1) m : 3040, 1750, 1620,
1590. Anal. Calcd for C46H37O7Cl : C, 69.63; H, 4.70; N,
7.06. Found : C, 69.65; H, 4.67; N, 7. 09.
00
00
00
¼ 7.4 Hz, 2H, C5 sugar), 4.87–4.92, (m, 3H, C200, C3 & C4
sugar), 6.70 (d, J ¼ 8.4 Hz, 1H, C100), 6.75–7.28 (m, 10H, 4H
phenyl and 6H thiopenyl), 7.38–8.02 (m, 15H, OBz); 13C
NMR d : 28.20, 39.10, 45.40, 65.75, 68.95, 69.10, 70.01,
86.40, 105.08, 110.20, 112.40, 113.50, 119.25, 122.40, 123.00,
127.65, 128.45, 129.70, 130.55, 132.80, 133.45, 138.00,
164.55, 167.00; IR (KBr, cmꢂ1) m : 3040, 1760, 1665, 1590.
Anal. Calcd for C44H36N2O7S2 : C, 68.71; H, 4.72; N, 3.64.
Found : 68.74; H, 4.75; N, 3.60.
7-Nitro-2,4-di(20-pyridyl)-2-methyl-1-(200,300.500-tri-o-benzoyl-
ꢀ-D-ribofuranosyl)-2,3-dihydro-1,5-benzodiazepine (4g). Solid,
mp ¼ 149ꢀC; Rf ¼ 0.44 (pet.ether - ethyl acetate ¼ 8:2); yield
78%; 1H NMR d : 1.78 (s, 3H, –CH3), 2.98 (d, J ¼ 7.4 Hz,
1H, methylene), 3.10 (d, J ¼ 7.4 Hz, 1H, methylene), 4.45 (d,
00
00
J ¼ 8.2 Hz, 2H, C5 sugar), 4.88–4.96 (m, 3H, C200, C3 and
2,4-Di(20-pyridyl)-2-methyl-1-(200,300,500-tri-o-benzoyl-ꢀ-D-ribo-
furanosyl)-2,3-dihydro-1,5-benzodiazepine (4c). Solid, mp ¼
134ꢀC; Rf ¼ 0.36 (pet.ether - ethylacetate ¼ 8:2); yield 88%;
1H NMR d : 1.78 (s, 3H, –CH3), 2.95 (d, J ¼ 7.4 Hz, 1H,
methylene), 3.10 (d, J ¼ 7.4 Hz, 1H, methylene), 4.40 (d, J ¼
C4 sugar), 6.82 (d, J ¼ 8.4 Hz, 1H, C1 sugar), 7.10–7.30 (m,
3H, phenyl), 7.38–8.65 (m, 23H, 15H OBz and 8H pyridyl);
13C NMR d : 29.65, 40.32, 46.53, 65.75, 68.92, 69.25, 70.01,
86.45, 118.42, 120.00, 121.25, 124.64, 128.45, 128.88, 129.75,
130.50, 131.92, 132.85, 133.22, 136.45, 139.65, 149.32,
163.65, 164.60, 167.00; IR (KBr, cmꢂ1) m : 3130, 1760, 1640,
1595. Anal. Calcd for C46H37N4O9 : C, 68.72; H, 4.64; N,
8.71. Found : C, 68.75; H, 4.67; N 8.68.
00
00
00
00
00
7.4 Hz, 2H, C5 sugar), 4.90–4.95 (m, 3H, C200, C3 and C4
sugar), 6.80 (d, J ¼ 8.4 Hz, 1H, C100, sugar), 6.95–7.20 (m,
4H, phenyl), 7.35–8.59 (m, 23H, 15H OBz and 8H pyridyl);
13C NMR d : 29.50, 40.20, 46.40, 65.70, 68.90, 69.15, 70.10,
86.45, 113.85, 119.80, 120.75, 123.50, 127.95, 128.40, 128.55,
129.75, 130.50, 132.78, 133.65, 136.10, 139.45, 149.10,
163.48, 164.65, 167.00; IR (KBr, cmꢂ1) m : 3015, 1750, 1635,
1590. Anal. Calcd for C48H38N4O7 : C, 72.79; H, 5.05; N
7.38. Found : 72.81; H, 5.02; N, 7.42.
7,8-Dichloro-2,4-di(20-pyridyl)-2-methyl-1-(200,300,500-tri-o-ben-
zoyl-ꢀ-D-ribofuranosyl)-2,3-dihydro-1,5-benzodiazepine (4h). Solid,
mp. ¼ 136ꢀC; Rf ¼ 0.42 (pet.ether - ethyl acetate ¼ 8:2);
yield 75%; 1H NMR d : 1.80 (s, 3H, CH3), 2.98 (d, J ¼ 7.4
Hz, 1H, methylene), 3.12 (d, J ¼ 7.4 Hz, 1H, methylene), 4.48
00
00
,
(d, J ¼ 8.2 Hz, 2H, C5 sugar), 4.88–4.99 (m, 3H, C200, C3
2,4-Di(30-pyridyl)-2-methyl-1-(200,300,500-tri-o-benzoyl-ꢀ-D-ribo-
furanosyl)-2,3-dihydro-1,5-benzodiazepine (4d). Solid, mp ¼
138ꢀC; Rf ¼ 0.40 (pet.ether - ethyl acetate ¼ 8:2); yield; 89%;
1H NMR d : 1.75 (s, 3H, –CH3); 2.94 (d, J ¼ 7.4 Hz, 1H,
methylene), 3.08 (d, J ¼ 7.4 Hz, 1H, methylene), 4.39 (d, J ¼
and C4 sugar), 6.85 (d, J ¼ 8.2 Hz, 1H, C1 sugar), 7.35–
8.75 (m, 25H, 15H OBz, 2H phenyl and 8H pyridyl); 13C
NMR d : 29.66, 40.48, 46.65, 65.75, 68.90, 69.25, 70.01,
86.45, 124.22, 124.45, 128.80, 129.75, 130.52 131.95, 132.66,
132.84, 133.25, 136.40, 139.65, 149.35, 163.60, 164.50,
167.00; IR (KBr. cmꢂ1) m : 3090, 1763, 1765, 1625, 1590.
Anal. Calcd for C46H36N4O7Cl2 : C, 66.72; H, 4.38; N, 6.77.
Found : C, 66.75; H, 4.40, N, 6.75.
00
00
00
00
00
7.4 Hz, 2H, C5 sugar), 4.89–4.93 (m, 3H, C200, C3 & C4
00
sugar), 6.78 (d, J ¼ 8.4 Hz, 1H, C1 sugar), 6.98–7.20 (m, 4H,
phenyl), 7.30–8.64 (m, 23H, 15H OBz & 8H pyridyl); 13C
NMR d : 29.42, 40.01, 46.25, 65.50, 68.91, 69.10, 70.01,
86.45, 113.85, 119.80, 120.75, 123.44, 127.85, 128.40, 128.55,
129.60, 130.55, 132.74, 133.65, 136.00, 139.45, 149.10,
163.25, 164.55, 167.00; IR (KBr, cmꢂ1) m : 3020, 1745, 1640,
1595, GC-MS; Mþ, 758.
7-Nitro-2-spiro(20-chromane)-300,400-dihydrochromano[2,3-c]-
1-(2000, 3000,5000-tri-o-benzoyl -ꢀ-D-rifuranosyl)-2,3-dihydro-1,5-
benzodiazepine (4i). Solid, mp ¼ 152–154ꢀC; Rf ¼ 0.47
1
(pet.ether - ethyl acetate ¼ 8:2); yield 75%; H NMR d : 2.35
(t, J ¼ 12.4 Hz, 2H, methylene), 2.50 (t, J ¼ 12.4 Hz, 2H,
methylene), 2.62 (d, J ¼ 12.2 Hz, 2H, methylene), 2.68 (t, J
2,4-Di(40-pyridyl)-2-methyl-1-(200,300,500-tri-o-benzoyl-ꢀ-D-ribo-
furanosyl)-2,3-dihydro-1,5-benzodiazepine (4e). Solid, mp ¼
144ꢀC; Rf ¼ 0.39 (pet.ether - ethyl acetate ¼ 8:2); yield 90%;
1H NMR d : 1.72 (s, 3H, –CH3), 2.92 (d, J ¼ 7.2 Hz, 1H,
methylene), 3.05 (d, J ¼ 7.2 Hz, 1H, methylene), 4.37 (d, J ¼
000
¼ 13.20 Hz, 1H, methine), 4.35 (d, J ¼ 7.2 Hz, 2H, C5
sugar), 4.78–4.90 (m, 3H, C2000,C3000, and C4 sugar), 6.78 (d,
000
000
J ¼ 8.2 Hz, 1H, C1 sugar), 6.85–7.30 (m, 11H, 3H phenyl
and 8H chromanyl), 7.38–8.20 (m, 15H, OBz); 13C NMR d :
25.40, 27.95, 41.90, 45.55, 46.65, 65.72, 68.92, 69.22, 70.00,
86.42, 118.45, 120.42, 120.95, 124.65, 128.42, 128.85, 129.70,
130.55, 131.75, 132.66, 133.25, 136.42, 139.55, 149.32,
163.50, 164.66, 167.00; IR (KBr, cmꢂ1) m : 2920, 1750, 1630,
1595. Anal. Calcd for C50H39N3O11 : C, 69.99; H, 4.58; N,
4.90. Found : C, 69.72; H, 4.60 N, 4.87.
00
7.4 Hz, 2H, C5 sugar), 4.87–4.92 (m, 3H, C200, C300, and C400
0
sugar), 6.82 (d, J ¼ 8.2 Hz, 1H, C1 sugar), 6.92–7.25 (m, 4H,
phenyl), 7.35–8.60 (m, 23H, 15H OBz and 8H pyridyl); 13C
NMR d : 29.20, 40.10, 46.15, 65.45, 68.90, 69.10, 70.01,
86.45. 113.80. 119.80, 120.65, 123.32, 127.75, 128.42, 128.65,
129.55, 130.45, 132.60, 133.55, 136.25, 139.35, 149.05,
163.15, 164.20. 167.00; IR (KBr, cmꢂ1) m : 3020, 1745, 1640,
1590. Anal. Calcd for C46H38N4O7 : C, 72.79; H, 5.05; N,
7.38. Found : C, 72.81; H, 5.02; N, 7.40.
7-Chloro-2-spiro(20-indoline)-indolino[2,3-c]-1-(200,300,500-tri-
o-benzoyl-ꢀ-D-ribofuranosyl)-N,N-di(200,300,500-tri-o-benzoyl-ꢀ-
ribofuranosyl)-2,3-dihydro-1,5-benzodiazepine (4j). Solid, mp
¼ 158ꢀC; Rf ¼ 0.43 (pet.ether - ethyl acetate ¼ 8:2); yield
77%; 1H NMR d : 2.50 (s, 2H, methylene), 2.70 (s, 1H,
7-Chloro-2,4-di(20-pyridyl)-2-methyl-1-(200,300,500-tri-o-benzoyl-
ꢀ-D-ribofuranosyl)-2,3-dihydro-1,5-benzodiazepine (4f). Solid,
mp ¼ 149ꢀC; Rf ¼ 0.38 (pet.ether - ethyl acetate ¼ 8:2); yield
80%; 1H NMR d : 1.78 (s, 3H, –CH3), 2.95 (d, J ¼ 7.2 Hz,
1H, methylene), 3.08 (d, J ¼ 7.2 Hz, 1H, methylene), 4.42 (d,
00
methine), 4.37 (d, J ¼ 7.4 Hz, 6H, 3 ꢁ C5 sugar) 4.80–4.93
(m, 9H, 3 ꢁ C200, C300, and C4 sugar), 6.80 (d, J ¼ 8.2 Hz,
00
00
3H, 3 ꢁ C1 sugar), 6.90–7.25 (m, 11H, 3H phenyl and 8H
J ¼ 7.4 Hz, 2H, C5 sugar), 4.89–4.95 (m, 3H, C200, C300, and
indolinyl), 7.35–8.40 (m, 45H, 3 ꢁ OBz); 13C NMR d : 27.95,
45.60, 52.50, 65.70, 68.90, 69.21, 70.01, 86.45, 118.45,
120.22, 124.65, 128.42, 128.85, 129.70, 130.50, 131.75,
132.66, 133.20, 136.45, 139.55, 149.30, 163.45, 165.65,
167.00; IR (KBr, cmꢂ1) m : 2915, 1760, 1620, 1592. Anal.
00
00
00
C4 sugar), 6.80 (d, J ¼ 8.2 Hz, 1H C1 sugar); 7.02–7.25 (m,
3H, phenyl), 7.40–8.70 (m, 23H, 15H OBz & 8H pyridyl), 13C
NMR d : 29.50, 40.25, 46.45, 65.70, 68.92, 69.10, 70.01,
86.45, 117.22, 119.75, 120.90, 124.25, 128.42, 128.85, 129.76,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

610
R. Jain, T. Yadav, M. Kumar, and A. K. Yadav
Vol 47
[11] Jung, D. I.; Choi, T. W.; Kim, Y. Y. I. S.; Park, Y. M.;
Lee, Y. G.; Jung, D. H. Synth Commun 1999, 29, 1941.
[12] Marales, R. H.; Bulbarela, A.; Contreas, R. Heterocycles
1986, 24, 135.
Calcd for C100H77N4O21 : C, 71.87; H, 4.64; N, 3.35. Found :
C, 71.90; H, 4.62, 3.38.
2-Spiro[5-(3-methyl-10-phenylpyrazoline)]-300-methyl-100-phe-
nylpyrazolino[4,5-c]-1-(2000,3000,5000-tri-o-benzoyl-ꢀ-D-ribofurano-
syl) -2,3-dihydro-1,5-benzodiazepine (4k). Solid, mp ¼ 154–
156ꢀC; Rf ¼ 0.37 (pet.ether - ethyl acetate ¼ 8:2); yield 85%,
1H NMR d : 1.85 (s, 3H, ACH3), 1.88 (s, 3H, ACH3), 2.40 (s,
2H, methylene), 2.50 (s, 1H, methine), 4.36 (d, J ¼ 7.2 Hz,
[13] Balakrishna, M. S.; Kaboudin, B. Tetrahedron Lett 2001,
42, 1127.
[14] Yadav, J. S.; Reddy, B. V. S.; Kumar, S. P.; Nagaiah, K.
Synthesis 2005, 3, 480.
000
000
2H, C5 sugar), 4.80–4.92 (m, 3H, C2000, C3000, 0a00nd C4 sugar),
6.60–7.10 (m, 15H, 14H phenyl, and 1H C1 sugar), 7.25–
8.30 (m, 15H, OBz); 13C NMR d : 27.90, 41.45, 45.62, 51.40,
51.65, 65.72, 68.92, 69.20, 70.01, 86.45, 113.50, 119.52,
123.25, 127.62, 128.45, 129.72, 130.55, 132.84, 133.45,
138.00, 162.62, 162.68, 164.65, 170.00; IR (KBr, cmꢂ1) m :
2910, 1760, 1625. Anal. Calcd for C55H44N6O7 : C, 72.19; H,
5.13; N, 9.72. Found : C, 72.22; H, 5.15, N, 9.70.
[15] Yadav, J. S.; Reddy, B. V. S.; Satheesh, G.; Srinivasulu,
G.; Kanwar, A. C. Arkivoc 2005(III), 221.
[16] Jarikote, D. V., Siddiqui, S. A.; Rajagopal, R.; Daniel, T.;
Lahoti, R. J.; Srinivasan, K. V. Tetrahedron Lett 2003, 40, 1835.
[17] Yadav, J. S.; Reddy, B. V. S.; Eshwaraiah, B.; Anuradha,
K. Green Chem 2002, 4, 592.
[18] Varala, R.; Ramu, E.; Adapa, S. R. Arkivoc 2006(III), 171
(and the references cited therein).
[19] (a) Mac Cross, M.; Robins, M. J. In Chemistry of Antitu-
mor Agents; Wilman, D. E. V., Ed; Blackie and Son: Glasgow, UK,
1990; p 261; (b) Robins, R. K.Kini, G. D. In Chemistry of Antitumor
Agents; Wilman, D. E. V., Ed.; Blackie and Son: Glasgow, UK, 1988,
p 11; (c) Robins, R. K.; Revankar, G. In Antiviral Drug Development;
De Clercq, E., Walker, R. T., Eds.; Plenum: New York, 1998; p 11;
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num: New York, 1993; p 311.
Acknowledgments. We thank Head, Department of Chemistry,
University of Rajasthan, Jaipur for providing laboratory facilities.
We are also grateful to CDRI, Lucknow for some analytical data.
We are also thankful to Prof. R.K. Bansal for valuable sugges-
tions. Financial support to TY from UGC, New Delhi, in the form
of meritorious research scholar award is gratefully
acknowledged.
[20] Lerman, L. DNA Probes, Application in Genetic and Infec-
tious Disease and Cancer; Cold Spring Harbor Laboratory: Cold
Spring Harbor, USA, 1986.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet