Solvent free oxalic acid catalyzed synthesis of 1,5-benzodiazepines

Article abstract of DOI:10.4067/S0717-97072013000400064

In the present study 1, 5-benzodiazepines were synthesized from a range of α β-unsaturated ketones and o-phenylendiamine using oxalic acid 10 mol% as a catalyst under solvent free conditions. The yields of the present method are better than the reported method which explains effectiveness of oxalic acid catalyst. The cost effective, resourceful, undemanding and environment friendly are the advantageous aspects of this method.

Full text of DOI:10.4067/S0717-97072013000400064

J. Chil. Chem. Soc., 58, Nº 4 (2013)
SOLVENT FREE OXALIC ACID CATALYZED SYNTHESIS OF 1,5-BENZODIAZEPINES
ANIKET P. SARKATE,a JAIPRAKASH N. SANGSHETTI,b NANASAHEB B. DHARBALE,c AJINKYA P. SARKATE,d
PRAVIN S. WAKTE,a DEVANAND B. SHINDEa*
aDepartment of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004, MS, India.
bDepartment of Pharmaceutical Chemistry, Y. B. Chavan College of Pharmacy, Aurangabad 431003 (MS), India.
cDepartment of Pharmaceutical Chemistry, Shri Bhagwan College of Pharmacy, Aurangabad 431003 (MS), India.
dDepartment of Pharmaceutical Chemistry, Sinhgad Institute of Pharmacy, Pune 411041 (MS), India
(Received: January 8, 2013 - Accepted: April 12, 2013)
ABSTRACT
In the present study 1, 5-benzodiazepines were synthesized from a range of α, β-unsaturated ketones and o-phenylendiamine using oxalic acid 10 mol% as a
catalyst under solvent free conditions. The yields of the present method are better than the reported method which explains effectiveness of oxalic acid catalyst.
The cost effective, resourceful, undemanding and environment friendly are the advantageous aspects of this method.
Keywords: 1, 5-benzodiazepine, oxalic acid, solvent free conditions, α, β-unsaturated ketones, o-phenylenediamine.
In an attempt to identify the most optimal experimental conditions a
detailed study was performed on o-phenylenediamine (4) and α, β-unsaturated
ketones (3a) (chalcone) (Scheme 2). The reaction condition has been optimized
with respect to catalyst loading and use of solvents (Table1). Synthesis of target
molecule has been tried using different solvents like DMF, 1, 4-dioxane, THF,
etc. Different solvents promote the formation of target compounds with low to
moderate yields. The reaction has also been carried out in aqueous conditions
where the reaction found to be very sluggish and very trace amount of product
has been formed. From the result it is observed that use of 10 mol % catalyst
is more favourable, giving the product with 93% yield. However, only modest
yield of condensation product was detected at room temperature, probably due
to low nucleophilicity of the amino group, as described in previous reports.35
But, good results were registered for the formation of 1, 5 benzodiazepine
5a-j almost in quantitative yield ranging from 72-88% when the reaction was
carried out at about 800C temperature. The highest yield of 88% was registered
with ACN whilst, only traces of the product formed when the reaction was
carried out in water. Furthermore, the study was also carried out in nonpolar
solvents like DCM and chloroform (Table 1, entries 6 and 7), but the yields
registered were less with added reaction time at 800C and no product was
detected at room temperature.
Taking into consideration the green synthetic approach and hazards caused
by organic solvents the reaction was further tried under solvent free conditions.
Surprisingly, the product formed was registered with 91% yield with 20 mol%
of the catalyst and 93% with 10mol% (Table 1, entries 8 and 9 respectively).
Further reduction in mol% of the catalyst resulted in lower yields and added
reaction time (Table 1, entries 10 and 11).
Therefore, it was concluded that 10 mol% of oxalic acid catalyst was
sufficient to form 1, 5-benzodiazepine in almost quantitative yield of the
isolated product under solvent free conditions. Hence, the same reaction
conditions were followed for the further synthesis of 1, 5-benzodiazepine
analogs 5a-j (Table 2).
1. INTRODUCTION
Benzodiazepines are important class of heterocyclic scaffolds because
of their commercial importance and clinical success. The pharmacological
activities of benzodiazepines1 like anxiolytics, hypnotics, tranquilizers, and
anticonvulsants, have led to their recognition by medicinal community as
the structure of particular significance.2 Although the first benzodiazepine
was introduced as a drug nearly 40 years ago,3 the research in this area
is still very active in view of producing the compounds of enhanced
pharmacological activity. In the last decade, the area of biological interest of
1, 5-benzodiazepines has been extended to several diseases such as cancer,
viral infection, and cardiovascular disorders.4 Moreover 1, 5-benzodiazepines
are key intermediates for the synthesis of various fused ring systems such
as triazolo-, oxadiazolo-, oxazino- or furanobenzodiazepines.5 In addition,
benzodiazepine derivatives also have commercial importance as dyes for
acrylic fibres in photography.6
Most of the methods reported in the literature for the synthesis of
benzodiazepines either includes (i) condensation of o-phenylenediamine with
α,β-unsaturated ketones7 or (ii) the reaction of o-phenylenediamines with
various ketones using variety of reagents and catalysts. These includes, (i) BF .
Et2O,8 NaBH4,9 polyphosporic acid,10 ceric ammonium nitrate (CAN),11 an3d
TCT 12 in the presence of various solvents; (ii) MgO and POCl3,13 Yb(OTf)3,14
Hg(OTf)3,15 CeCl3.7H2O/NaI supported on silica gel,16 Sc(OTf) ,17 Er(OTf)3,
InBr3,18 sulphated zirconia,19 ZnCl220 and SiO /ZnCl221 under 3solvent free
conditions; (iii) Al2O3/P2O522 or acetic acid23 wit2h microwave irradiation; (iv)
Amberlyst-15 in ionic liquids;24 (v) 1,3-di-n-butylimidazolium bromide without
any catalyst.25 Literature survey also reveals the method of Shrinivasan and
co-workers, a multicomponent reaction for the synthesis of 3-Hbenzo[b]-1,4-
diazepines.26 Recently, Jiang and co-workers reveals [4+2+1] cycloaddition
of o-phenylenediamine and ethyl propionate to synthesize 3, 4-disubstituted
1,5-benzodiazepines in good yield.27
Inanattempttostudytheeffectofsubstitutedchalconesinthecondensation,
we have carried out the condensation of o-phenylenediamine (4) with these
substituted chalcones (3a-j) (Scheme 2). The best results for the condensation
were registered for the benzodiazepines substituted with electron releasing
groups like –OH, -OMe, -CH3 at ortho and para positions, however highest
yield was registered with benzodiazepine with the –OH group at ortho position
and –OMe group at para position (Table 2, Entry 5j and 5h respectively). In
addition to this the reaction was also tried for electron withdrawing substituents
which resulted in the the products with moderate yield (Table 2, Entry 5b, 5d
and 5f).
Therefore, we can conclude that we have demonstrated the method
to study an efficiency of oxalic acid catalyst by synthesizing an assorted
1,5-benzodiazepines (Table 2, Entry 5a-j) using 4 and 3a-j in solvent free
conditions. Further, we have also demonstrated observation regarding the
effect of different substituents on the quantitative yield of isolated product.
Moreover, easy work up, shorter reaction time, good to better yields and
environment friendly were the advantages of the anticipated method.
Oxalic acid is the compound in which two carboxylic groups are joined
together directly and hence supposed to be one of the strongest organic
acid. The use of oxalic acid as a catalyst was reported for the deprotection
of ketal to give the corresponding aldehydes or ketones.28 It was also found
to be used for isomerisation of δ5-cholasten-3-one to δ4-cholesten-3-one29 and
dealumination of zeolite.30 Furthermore, we have used oxalic acid as a catalyst
in our previous study for the synthesis of dihydropyrimidine 2-(1H)-ones,31
2-aryl-1-arylmethyl-1H-benzimidazoles and 2,4,5-triaryl-1H-imidazoles,32
quinazolin-4(3H)-ones33 and coumarins.34 In order to explore the use of oxalic
acid catalyst further, herein we report the synthesis of 1, 5-benzodiazepines
from o-phenylene diamine and various α, β-unsaturated ketones.
2. RESULT AND DISCUSSION
Although development of nonhazardous synthetic methodologies for
organic reactions is one latest challenge to the organic chemists, only few of the
benzodiazepine synthesis methods tried to answer this demand. Nevertheless,
the search for new methodology to synthesize benzodiazepine and analogs
continues.
e-mail: dbsaniket09@gmail.com
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J. Chil. Chem. Soc., 58, Nº 4 (2013)
Scheme 1 Synthesis of α, β-unsaturated ketones 3a-j from substituted
Scheme 2 Scheme for the synthesis of 1, 5-benzodiazepines (5a-j) from
aldehydes and ketones.
3a-j
Scheme 3 Proposed mechanism for the synthesis of benzodiazepine
Table 1 Optimization of reaction conditions and mol% of oxalic acid for the synthesis of 5a (Entry 1, Table 2).
Entry
Solvent
DMF
Oxalic acid (mol%)
Reaction time (min)
Yield (%)a
1
2
20
20
20
20
20
20
20
20
10
5
180
160
150
155
180
175
185
135
150
185
210
84
72
1,4-dioxane
THF
3
76
4
ACN
88
5
H2O
Trace
62
6
DCM
7
CHCl3
54
8
Solvent free
Solvent free
Solvent free
Solvent free
91
9
93
10
11
80
2.5
77
a yields are of pure isolated compound
MHz, CDCl3, δ ppm) δ: 1.9 (d, 2H, CH2), 2.2 (t, 1H, CH), 3.9 (s, 1H, NH),
6.9-7.2 (8H, Ar-H), 7.4-7.8 (4H, Ar-H), 7.8-8 (2H, Ar-H); 13C NMR (CDCl3)
δ= 38.2, 63.4, 113.6, 122.4, 125.9, 126.2, 127.3, 127.8, 128.1, 128.9, 129.7,
132.4, 139.9, 142.3, 144.8, 146.4, 163.3; IR (KBr): 1592 (C=C), 1643 (C=N)
cm-1; LC-MS (Scinpor ESI m/z): 298.38 (M+), 299.25 (M+1); MF: C21H18N2.
3.2.2 Compound (5b): 2-(4-chlorophenyl)-2,3-dihydro-4-phenyl-1H-
benzo[b][1,5]diazepine
3. EXPERIMENTAL
All reagents and chemicals were of analytical grade and used without
further purification.
Melting points of all the compounds were determined using digital melting
point apparatus (SRS) and were uncorrected. IR spectrum of all compounds
was recorded with FT-IR spectrophotometer (Brucker). 1HNMR (Varian NMR
400Hz) of the compound 5a-j was recorded in CDCl3 using TMS as an internal
standard and molecular weight was confirmed by using LC-MS (Scinpor ESI)
3.1 General procedure for the synthesis of 3a-j.
In a round bottom flask, 2.2 g of sodium hydroxide was added in water
& methanol. The flask was immersed in a bath of crushed ice & kept on
mechanical stirrer. The stirrer was started, freshly distilled acetophenone (0.43
mol) & pure benzaldehyde (0.43 mol) was added in the flask. The mixture
was stirred for 4-5 h at 15-200C. The thick mixture was removed & kept in a
refrigerator for overnight. The product was filtered & washed with cold water
until the washings were neutral to litmus. Further the product was washed with
ice cold rectified spirit, dried & recrystallized from rectified spirit to afford the
desired product.
Yield: 87%, MP: 110-1120C; 1HNMR (400 MHz, CDCl3, δ ppm): δ 1.7 (d,
2H, CH2), 2.9 (t, 1H, CH), 4.2 (s, 1H, NH), 7.18-7.16 (4H, Ar-H), 7.23-7.64
(5H, Ar-H), 6.8-7.2 (2H, Ar-H); 13C NMR (CDCl3) δ= 38.6, 62.1, 115.4, 120.7,
122.2, 125.7, 127.4, 127.9, 128.8, 129.5, 130.6, 133.1, 137.4, 142.2, 143.6,
146.3, 161.8; IR (KBr): 1570 (C=C), 1638 (C=N) cm-1; LC-MS (Scinpor
ESI m/z): 332.69 (M+), 334.09 (M+2, 33.9%), 333.71 (M+1, 22.8%); MF:
C21H17ClN2.
3.2.3 Compound (5c): Synthesis of 2-(2,3-dihydro-2-(3,4,5-
trimethoxyphenyl)-1H-benzo[b] [1,5]diazepin-4-yl)-5-methylphenol
Yield: 89%, MP: 96-980C; 1HNMR (400 MHz, CDCl3, δ ppm): δ 1.83 (d,
2H, CH2), 2.73 (t, 1H, CH), 3.85 (s, 1H, NH), 6.18 (2H, Ar-H), 6.65-7.2 (3H,
Ar-H), 6.42-7.11 (4H, Ar-H), 4.85 (s, 1H, OH), 2.15 (s, 3H, CH3), 3.35 (s, 9H,
OCH3); 13C NMR (CDCl3) δ= 20.9, 38.7, 55.3, 62.1, 64.9, 101.2, 113.5, 117.2,
118.8, 122.3, 124.4, 125.7, 126.4, 129.6, 136.6, 139.1, 140.1, 143.4, 146.6,
154.1, 159.9, 164.1; IR (KBr): 3417 (O-H, broad), 1543 (C=C), 1642 (C=N)
cm-1; LC-MS (Scinpor ESI m/z): 418.10 (M+), 419.45 (M+1, 27.34%); MF:
C25H26N O4.
3.2 General procedure for the synthesis of 5a-j
3.2.1 Synthesis of 2,3-dihydro-2,4-diphenyl-1H-benzo[b][1,5]diazepine
(5a)
A mixture of α, β-unsaturated ketones 3a (10mmol), o-phenylenediamine
4 (10 mmol) and oxalic acid (10 mol%) was heated at 800C under solvent free
conditions for the appropriate time about 150 min. After completion of reaction
(monitored by TLC), the reaction mixture was cooled at room temperature and
extracted with diethyl ether (3 × 10ml). The combined organic layers were dried
over anhydrous Na2SO . The solvent was removed and the solid residue was
purified further on silic4a gel column (2.5 x 45 cm), pre packed in chloroform.
Elution of the column with petroleum ether:ethyl acetate (18:2) gave a
homogeneous residue which was concentrated in vacuo to give compound 5a.
3.2.24 Compound (5d): Synthesis of 2-bromo-6-(2,3-dihydro-2-(3,4,5-
trimethoxyphenyl)-1H-benzo[b][1,5]diazepin-4-yl)-4-methylphenol
1
Yield: 76%, MP: 113-1140C; HNMR (400 MHz, CDCl , δ ppm): δ 1.56
(d, 2H, CH ), 3.12 (t, 1H, CH), 4.01 (s, 1H, NH), 6.22 (2H, 3Ar-H), 7.07-7.19
(2H, Ar-H)2, 6.37-7.01 (4H, Ar-H), 4.54 (s, 1H, OH), 2.35 (s, 3H, CH3), 3.42
(s, 9H, OCH3); 13C NMR (CDCl3) δ= 19.3, 40.1, 57.3, 62.1, 64.4, 101.3, 113.9,
116.6, 119.7, 123.1, 125.2, 126.9, 128.1, 134.1, 136.2, 137.1, 138.9, 142.6,
146.7, 151.2, 159.3, 163.9; IR (KBr): 3387 (O-H, broad), 1585 (C=C), 1641
Yield: 96%, MP (SRS melting point apparatus): 136-1370C; H NMR (400
1
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J. Chil. Chem. Soc., 58, Nº 4 (2013)
(C=N) cm-1; LC-MS (Scinpor ESI m/z): 497.10 (M+), 498.45 (M+1, 98.34%);
MF: C25H BrN2O4.
MF: C23H22N2.
3.2.8Compound(5h):Synthesisof2,3-dihydro-2,4-bis(4-methoxyphenyl)-
1H-benzo[b][1,5] diazepine
3.2.5 2C5 ompound (5e): Synthesis of 4-(2,3-dihydro-2-phenyl-1H-benzo[b]
[1,5]diazepin-4-yl) phenol
Yield: 95%, MP: 112-1140C; HNMR (400 MHz, CDCl , δ ppm): δ 2.06
(d, 2H, CH2), 3.11 (t, 1H, CH), 4.05 (s, 1H, NH), 6.66-7.22 (34H, Ar-H), 6.76-
7.62 (4H, Ar-H), 6.4-7.02 (4H, Ar-H), 3.67 (s, 6H, OCH ); 13C NMR (CDCl3)
δ= 40.1, 54.7, 63.7, 112.9, 113.7, 115.9, 124.1, 125.2, 3126.1, 127.1, 129.9,
131.7, 140.3, 143.1, 146.7, 157.3, 161.2, 164.5; IR (KBr): 1587 (C=C), 1639
(C=N) cm-1; LC-MS (Scinpor ESI m/e): m/e 358.43 (M+), 359.33 (M+1,
25.13%); MF: C23H22N2O .
1
1
Yield: 91%, MP: 122-1230C; HNMR (400 MHz, CDCl , δ ppm): δ 2.01
(d, 2H, CH2), 2.98 (t, 1H, CH), 4.11 (s, 1H, NH), 7.08-7.27 (35H, Ar-H), 6.45-
7.35 (4H, Ar-H), 6.3-7.11 (4H, Ar-H), 4.87 (s, 1H, OH); 13C NMR (CDCl3)
δ= 20.2, 40.1, 64.3, 113.3, 117.4, 120.2, 124.1, 125.4, 126.9, 127.6, 130.8,
135.2, 138.3, 142.9, 143.8, 146.2, 159.5, 164.3; IR (KBr): 3413 (O-H, broad),
1592 (C=C), 1636 (C=N) cm-1; LC-MS (Scinpor ESI m/z): 314.10 (M+); MF:
C21H18N O.
3.2.9 Compound (5i)2: Synthesis of 2-(2,3-dihydro-2-phenyl-1H-benzo[b]
[1,5]diazepin-4-yl) phenol
3.2.26 Compound (5f): Synthesis of 2,3-dihydro-2,4-bis(4-nitrophenyl)-
1H-benzo[b][1,5] diazepine
1
Yield: 84%, MP: 128-1290C; HNMR (400 MHz, CDCl , δ ppm): δ 1.84
Yield: 82%, MP: 131-1320C; HNMR (400 MHz, CDCl , δ ppm): δ 1.85
(d, 2H, CH2), 3.72 (t, 1H, CH), 4.15 (s, 1H, NH), 7.02-7.22 (35H, Ar-H), 6.66-
7.40 (4H, Ar-H), 6.3-7.02 (4H, Ar-H), 4.89 (s, 1H, OH); 13C NMR (CDCl3) δ=
40.6, 64.7, 113.2, 116.5, 117.6, 119.9, 123.4, 124.9, 125.5, 126.1, 127.2, 129.8,
130.7, 133.8, 139.2, 142.8, 146.7, 161.3, 164.2; IR (KBr): 3410 (O-H, broad),
1590 (C=C), 1640 (C=N) cm-1; LC-MS (Scinpor ESI m/z): 314.65 (M+); MF:
C21H18N O.
1
(d, 2H, CH2), 2.76 (t, 1H, CH), 3.96 (s, 1H, NH), 7.21-8.15 3(4H, Ar-H), 7.7-
8.35 (4H, Ar-H), 6.32-7.07 (4H, Ar-H); 13C NMR (CDCl3) δ= 37.9, 62.1,
113.2, 120.5, 122.3, 124.4, 125.1, 126.2, 127.4, 129.2, 140.3, 142.7, 144.2,
145.3, 147.9, 149.1, 163.9; IR (KBr): 1351, 1555 (NO2), 1577 (C=C), 1648
(C=N) cm-1; LC-MS (Scinpor ESI m/z): 388.74 (M+), 389.23 (M+1, 23.33%)
MF: C21H N4O4.
3.2.210 Compound (5j): Synthesis of 2-(2,3-dihydro-2-(4-methoxyphenyl)-
1H-benzo[b][1,5] diazepin-4-yl)phenol
3.2.7 1C6 ompound (5g): Synthesis of 2,3-dihydro-2,4-dip-tolyl-1H-benzo[b]
[1,5]diazepine
1
Yield: 96%, MP: 107-1080C; HNMR (400 MHz, CDCl3, δ ppm): δ 1.74
1
Yield: 92%, MP: 130-1320C; HNMR (400 MHz, CDCl , δ ppm): δ 2.11
(d, 2H, CH2), 3.83 (t, 1H, CH), 4.03 (s, 1H, NH), 6.67-7.0 (4H, Ar-H), 6.7-7.18
(4H, Ar-H), 6.38-7.0 (4H, Ar-H), 5.1 (s, 1H, OH), 3.7 (s, 3H, OCH ); 13C NMR
(CDCl ) δ= 40.7, 56.5, 64.2, 112.9, 115.7, 116.5, 117.6, 120.2, 1321.1, 124.9,
125.7, 3126.6, 130.8, 131.6, 132.1, 142.7, 144.9, 157.3, 161.5, 163.9; IR (KBr):
3415 (O-H, broad),1591 (C=C), 1639 (C=N) cm-1; LC-MS (Scinpor ESI m/z):
344.23 (M+), 345.12 (M+1, 24.1%); MF: C22H20N2O2.
(d, 2H, CH2), 2.99 (t, 1H, CH), 4.22 (s, 1H, NH), 6.98-7.15 (34H, Ar-H), 7.09-
7.54 (4H, Ar-H), 6.4-7.02 (4H, Ar-H), 2.23 (s, 6H, CH ); 13C NMR (CDCl3)
δ= 20.4, 40.3, 61.7, 113.3, 120.2, 124.4, 125.7, 126.5,3 128.1, 128.6, 130.3,
135.6, 136.8, 137.3, 139.9, 142.8, 146.3, 163.8; IR (KBr): 1586 (C=C), 1643
(C=N) cm-1; LC-MS (Scinpor ESI m/z): 326.34 (M+), 327.23 (M+1, 26.13%)
Table 2 Oxalic acid catalyzed synthesis of 5a-j.
Reaction time
(min)
Melting
Entry
R2
R1
Yield (%)a
93
Point(0C)
5a
150
160
136-137
110-112
5b
5c
87
89
l
C
H
3CO
155
160
96-98
H
3CO
H
H
H
H
O
C
3
H
OC
3
H
H
3CO
C
3
5d
76
113-114
3CO
O
r
B
OCH3
5e
5f
150
140
135
130
155
165
91
82
92
95
84
96
122-123
131-132
130-132
112-114
128-129
107-108
H
O
N
N
O2
O2
5g
5h
5i
H
H
3C
C
3
H
OC
H
3CO
3
H
O
5j
H
3CO
H
O
a Yield are of pure isolated compounds.
2202

J. Chil. Chem. Soc., 58, Nº 4 (2013)
12. C. W. Kuo, C. C. Wang, V. Kavala, C. F. Yao, Molecules. 13, 2313,
(2008).
4. ACKNOWLEDGEMENTS
13. M. S. Balakrishna, B. Kaboudin, Tet. Lett. 42, 1127, (2001).
14. M. Curini, F. Epifano, M. C. Marcotullio, O. Rosati, Tet. Lett. 42, 3193,
(2001).
The authors are thankful to the Head, Department of Chemical Technology,
Dr. Babasaheb Ambedkar Marathwada University, Aurangabad 431004 (MS),
India for providing the laboratory facility.
15. G. Maitri, U. Kayal, R. Karmakar, R. N. Bhattacharya, Tet. Lett. 53, 1460,
(2012).
16. G. Sabitha, G. S. K. K. Reddy, K. B. Reddy, N. M. Reddy, J. S. Yadav,
Adv. Synth. Cat. 346, 921, (2004).
17. S. K. De, R. A. Gibbs, Tet. Lett. 46, 1811, (2005).
18. J. S. Yadav, B. V. S. Reddy, S. P. Kumar, K. Nagaiah, Synthesis. 3, 480,
(2005).
19. B. M. Reddy, P. M. Sreekanth, P. Lakshmanan, J. Mol. Catal. A: Chem.
237, 93, (2005).
5. REFERENCES
1. (a) J. R. De Baun, F. M. Pallos, D. R. Baker, Chem. Abstr. 86, 5498d,
(1977). (b) H. Schultz Benzodiazepines, Springer Heidelberg, Germany,
1982. (c) R. K. Smiley Comprehensive Organic Chemistry, Pergamon,
UK, 1979. (d) A. R. Katritzky, C. W. Rees Comprehensive Heterocyclic
Chemistry, Pergamon, UK, 1984. (e) S. Garattini, E. Mussini, L. O.
Randall Benzodiazepines, Raven Press, New York, 1973.
20. M. A. Pasha, V. P. Jayashankara, Heterocycles. 68, 1017, (2006).
21. R.G. Jacob, C. S. Radatz, M. B. Ridrigues, D. Alves, G. Perin, E. J.
Lenardao, L. Savegnago, Hetero. Chem. 22, 180, (2011).
22. B. Kaboudin, K. Navaee, Heterocycles. 55, 1443, (2001).
23. M. Pozarentzi, J. S. Stephanatou, C. A. Tsoleridis, Tet. Lett. 43, 1755,
(2002).
2. (a) M. Nardia, A. Cozzaa, L. Maiuoloa, M. Oliveriob, A. Procopiob,
Tet. Lett. 52, 4827, (2011). (b) J. K. Chakrabarti, T. M. Hotten, I. A.
Pullar, D. J. Steggles, J. Med. Chem. 32, 2375, (1989). (c) S. Andronati,
E. Semenishyna, V. Pavlovsky, Y. Simonov, S. Makan, I. Boyko, N.
Burenkova, M. Gdaniec, P. Cardinael, J. P. Bouillon, A. Mazepa, Eur. J.
Med. Chem. 45, 1346, (2010). (d) R. Gitto, V. Orlando, S. Quartarone, G.
D. Sarro, A. D. Sarro, E. Russo, G. Ferreri, A. Chimirri, J. Med. Chem.
46, 3758, (2003).
24. J. S. Yadav, B. V. S. Reddy, B. Eshwaraiah, K. Anuradha, Green Chem.
4, 592, (2002).
25. D. V. Jarikote, S. A. Siddiqui, R. Rajagopal, T. Daniel, R. J. Lahoti, K. V.
Srinivasan, Tet. Lett. 44, 1835, (2003).
26. S. S. Palimkar, R. J. Lahoti, K. V. Srinivasan, Green Chem. 9, 146,
(2007).
27. Y. J. Jiang, J. J. Cai, J. P. Zou, W. Zhang, Tet. Lett. 51, 471, (2010).
28. a) A. B. Smith, S. J. Branca, M. A. Guaciaro, P. M. Wovkulich, A. Korn
Organic Synthesis Collective Volume, Wiley, New York, 1990. (b) A. I.
Meyers, M. E. Flanagan Organic Synthesis Collective Volume, Wiley,
New York, 1993. (c) I. R. Politzer, A. I. Meyers Organic Synthesis
Collective Volume, Wiley, New York, 1988.
3. L. H. Sternbach, Angew. Chem. Int. Ed. 10, 34, (1971).
4. (a) V. Merluzzi, K. D. Hargrave, M. Labadia, K. Grozinger, M. Skoog,
J. C. Wu, C. K. Shih, K. Eckner, S. Attox, J. Adams, A. S. Rosenthal,
R. Faanes, R. J. Eckner, R. A. Koup, J. L. Sullivan, Science. 250, 1411,
(1990). (b) M. Di Braccio, G. Grossi, G. Romoa, L. Vargiu, M. Mura, M.
E. Marongiu, Eur. J. Med. Chem. 36, 935, (2001).
5. (a) A. M. El-Sayed, A. Khodairy, H. Salah, H. Abdel-Ghany, Phos. Sul.
Sil. Relat. Elem. 182, 711, (2007). (b) G. K. Nagaraja, V. P. Vaidya, K.
S. Rai, K. M. Mahadevan, Phos. Sul. Sil. Relat. Elem. 181, 2797, (2006).
(c) K. Nabih, A. Baouid, A. Hasnaoui, A. Kenz, Syn. Comm. 34, 3565,
(2004). (d) K. V. V. Reddy, P. S. Rao, D. Ashok, Syn. Comm. 30, 1825,
(2000).
29. N. Rabjan Organic Synthesis Collective Volume, Wiley, New York,
1963.
30. M. R. Apelian, A. S. Fung, G. J. Kennedy, T. F. Degan, J. Phys. Chem.
100, 16577, (1996).
31. J. N. Sangshetti, N. D. Kokare, D. B. Shinde, J. Het. Chem. 45, 1191,
(2008).
32. J. N. Sangshetti, N. D. Kokare, D. B. Shinde, Synthesis. 18, 2829, (2007).
33. J. N. Sangshetti, N. D. Kokare, D. B. Shinde, Chin. J. Chem. 26, 1506,
(2008).
34. J. N. Sangshetti, N. D. Kokare, D. B. Shinde, Chin. Chem. Lett. 18, 1309,
(2007).
6. R. C. Haris, J. M. Straley, US 1537757, (1968).
7. J. S. Yadav, B. V. S. Reddy, G. Satheesh, G. Srinivasulu, A. C. Kunwar,
Arkivoc. iii, 221, (2005). (b) R. M. Claramunt, D. Sanz, S. Aggarwal, A.
Kumar, O. Prakash, S. P. Singh, J. Elgueroc, Arkivoc. xiv, 35, (2006).
8. J. A. L. Herbert, H. Suschitzky, J. Chem. Soc. Perk. Trans. 1, 2657,
(1974).
9. H. R. Morales, A. Bulbarela, R. Contreras, Heterocycles. 24, 135, (1986).
10. D. I. Jung, T. W. Choi, Y. Y. Kim, I. S. Kim, Y. M. Park, Y. G. Lee, D.
H. Jung, Syn. Comm. 29, 1941, (1999).
35. X. Q. Pan, J. P. Zou, Z. H. Huang, W. Zhang, Tet. Lett. 49, 5302, (2008).
11. R. Varala, E. Ramu, N. Sreelatha, S. R. Adapa, Synlett. 7, 1009, (2006).
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