Water mediated, environmentally friendly, step-wise, tandem & one-pot syntheses of 2-(1H-benzo[d]imidazole-2-yl)-N-arylbenzamides

Article abstract of DOI:10.1039/c3ra44423f

Water mediated and environmentally friendly, step-wise, tandem & one-pot syntheses of 2-(1H-benzo[d]imidazole-2-yl)-N-arylbenzamide derivatives have been developed by simply combining phthalic anhydride, anilines and phenylenediammonium dihydrogenphosphate. This reaction has an easy workup, provides excellent yields, and uses water as the solvent which is considered to be relatively environmentally benign.

Full text of DOI:10.1039/c3ra44423f

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Water mediated, environmentally friendly, step-
wise, tandem & one-pot syntheses of 2-(1H-benzo
[d]imidazole-2-yl)-N-arylbenzamides†
Cite this: RSC Adv., 2014, 4, 2974
Received 15th August 2013
Accepted 26th November 2013
*
Yervala Dathu Reddy, Chittireddy Venkata Ramana Reddy and Pramod Kumar Dubey
DOI: 10.1039/c3ra44423f
www.rsc.org/advances
Water mediated and environmentally friendly, step-wise, tandem & coupling of 1,2-phenylenediamines with carboxylic acids or their
one-pot syntheses of 2-(1H-benzo[d]imidazole-2-yl)-N-arylbenza- derivatives,9 and the second route is condensation of 1,2-phenyl-
mide derivatives have been developed by simply combining phthalic enediamines with aldehydes followed by oxidative cyclo-
anhydride, anilines and phenylenediammonium dihydrogenphosphate. dehydrogenation.10 But, these protocols fail to meet the
This reaction has an easy workup, provides excellent yields, and uses requirement of green chemistry due to long reaction time, low
water as the solvent which is considered to be relatively environ- yields, the use of toxic solvents & catalysts. Recently, Bahrami et al.
mentally benign.
reported11 green method for synthesis of simple 2-arylbenzimi-
dazole by reaction of 1,2-phenylenediamine with benzaldehyde in
water in the presence of sodium dodecylsulfate (SDS) as a catalyst,
ammonium persulfate [(NH4)2S2O8] as a promoter. In 1921,
Bistrzycki et al. reported12 the preparation of 2-(1H-benzo[d]-
imidazole-2-yl)-N-phenylbezamide by the condensation of 1-(CO)-
2-benzoylene benzimidazole with aniline. On the other hand,
benzimidazole derivatives bear versatile pharmacological prop-
erties13 based on their presence in both clinical medicines14 and
compounds of broad biological functions.15 In addition, the
treatment potency of benzimidazoles in diseases such as
ischemia-reperfusion injury,16 hypertension,17 obesity18 etc. have
been recently reported.
Keeping the above results in mind and in continuation of our
earlier work,19 we now wish to report our synthetic studies on
reactions of phthalic anhydride l with anilines and with o-phe-
nylenediammonium dihydrogenphosphate 4. To the best of our
knowledge, this is probably rst report to prepare 2-(1H-benzo[d]-
imidazole-2-yl)-N-arylbenzamide derivatives in water.
Introduction
The development of efficient, economical & environmentally
friendly syntheses is an important challenge in modern organic
syntheses.1 In many synthetic organic processes, solvents
represent a severe pollution problem. Thus, the replacement of
hazardous solvents with relatively green solvents or the alto-
gether elimination of use of hazardous solvents in chemical
processes has been one of the key achievements of green
chemistry.2 Based on the principles of green chemistry, a green
solvent should meet numerous criteria such as low toxicity,
non-volatility, non-mutagenicity, non-ammability and wide-
spread availability among others.3 In the past decade, water,4
glycerol,5 polyethylene glycol,6 ionic liquids7 have been used as
green solvents in organic reactions. Among all the green
solvents, water is the safest, cheapest & non-toxic media-free
from economic & environmental problems.8 As a result, serious
efforts are being made to develop water as a solvent for most of
the organic syntheses and processes wherever possible.
Results and discussion
As illustrated in Scheme 1, phthalic anhydride 1 was reacted
with aniline 2a to form 2-(arylcarbamoyl)benzoic acid 3a in the
presence of 5% aq. H3PO4 at RT for 10 min (Table 1, entry 1). 3a
was then reacted with o-phenylenediammonium dihy-
drogenphosphate 4 (ref. 20) in reuxing water for 90 min
resulting in the formation of 2-(1H-benzo[d]imidazole-2-yl)-N-
phenylbenzamide 5a (Table 2, entry 1). The structure of the
product was assigned on the basis of its spectral properties -IR,
NMR & mass spectra (for details, please see the Experimental
section). 5a could also be prepared by the tandem method
There are currently a number of synthetic methodologies
available for the synthesis of 2-substituted benzimidazole.
Generally, two protocols are commonly followed for the
synthesis of 2-substituted benzimidazole. The rst route is
Department of Chemistry, Jawaharlal Nehru Technological University Hyderabad
College of Engineering, Kukatpally, Hyderabad, 500 085, A.P, India. E-mail:
dathureddyjntuh@gmail.com
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c3ra44423f
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Table 2 Effect of solvent & temperature on reaction of 3a with 4
yielding 5a
Entry
Solvent
Temp./ꢀC
Time/min
5a (%)
1
2
3
4
5
6
7
8
H2O
100
50
100
120
RT
50
50
100
50
100
50
100
50
80
50
90
240
120
120
300
200
300
150
240
150
300
240
120
90
88
82
88
84
—
76
72
72
68
63
35
40
75
79
36
49
60
Glycerol
Glycerol
Glycerol
H2O
Scheme 1 Synthesis of 5a–5l by step-wise & tandem reaction in water.
4
involving the sequences (1 þ 2a/3a / 5a) (Scheme 1). In this
H2O
PEG-600
PEG-600
Ethyleneglycol
Ethyleneglycol
DMF
tandem reaction, 1 was treated with 2a in the presence of 5% aq.
H3PO4 at RT for 10 min until the disappearance of 1 was found
on TLC. To the same reaction mixture 4 was added and then the
reaction mixture reuxed for 90 min until the disappearance of
3a took place. The mixture was then processed to obtain 5a
identical with the same product obtained earlier in the step-
wise route (Scheme 1).
9
10
11
12
13
14
15
16
17
DMF
[bmim][Br]
[bmim][Br]
[bmim][OH]
[bmim][OH]
PPA
120
90
90
The reaction of 1 with 2a was examined by treating 1 (1 mmol)
with aniline 2a (1 mmol) in the presence of different acid cata-
lysts with different amounts in water to form 3a (Table 1).
However, reaction with 5% aq. H3PO4 as catalyst at RT for 10
min in water, unlike other acid catalysts HCl, H2SO4, boric acid
gave reasonably high yield (91%) of the product 3a (Table 1,
entry 1). The reaction of 3a (1 mmol) with 4 (1 mmol) was also
optimized by doing a series of experiments in the presence of
different solvents and ionic liquids at different temperatures
(Table 2). However, it is greatly notable that the reaction of 3a
80
100
Using the above-stated optimised conditions, in both, the
step-wise & tandem reactions, 5a–5l have been prepared by the
condensation of phthalic anhydride 1 with anilines 2a–2l in the
presence of 5% aq. H3PO4 to form 2-(arylcarbamoyl)benzoic
acids 3a–3l as intermediates at RT for 10–15 min. Thereaer,
3a–3l were condensed with 4 at reux for 90–120 min in water
with good yield and no side products were detected. Their
structures have been established on the basis of spectra such as
IR, NMR & H. R. mass spectra (Scheme 1) (Tables 322,23, 4 & 6,
included in ESI†).
ꢀ
with 4 at 100 C for 90 min in water, unlike in other solvents
such as glycerol, PEG-600, ethylene glycol, DMF, ionic liquids
[bmim][Br], [bmim][OH] and PPA gave reasonably high yield
(88%) of the product 5a (Table 2, entry 1).
Alternative synthesis of 5a–5l
Table 1 Effect of acid catalyst on reaction of 1 with 2a in water yielding
As illustrated in Scheme 2, 1 was reacted with 4 in water at RT
for 10 min to form 2-((2-aminophenyl)carbamoyl)benzoic acid
6. The product was characterized by comparison of its physical
data with that of the same product reported21 earlier. 6 was
converted into 2-(2-aminophenyl)isoindoline-1,3-dione 7 in
the presence of 5% aq. H3PO4 in reuxing water for 90 min
3a
Entry
Catalyst
% of catalyst (10 ml)
Time/min
3a (%)
1
2
3
4
5
6
7
8
H3PO4
H3PO4
H3PO4
H2SO4
H2SO4
H2SO4
HCl
HCl
HCl
Boric acid
Boric acid
Boric acid
5
10
10
10
15
15
15
15
15
15
15
15
15
91
87
81
80
86
82
77
83
79
81
79
75
10
15
5
10
15
5
10
15
5
10
15
9
10
11
12
Scheme 2 Alternative synthesis of 5a–5l by step-wise & tandem
reaction in water.
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General procedures for preparation of 3
A mixture of 1 (10 mM) and 2 (10 mM) was stirred at RT for 10–
15 min in the presence of 5% aq. H3PO4 (20 ml). At the end of
this period, reaction mixture was neutralized with 5% Na2CO3
solution. Further, a colourless solid separated out from the
reaction mass which was collected by ltration. The isolated
solid was washed with water (10 ml) and dried. The product was
recrystallized from a suitable solvent to obtain 3.
Scheme 3 Synthesis of 5a–5l by one pot synthesis in water.
(Scheme 2). The product was characterized by comparison of its
physical data with that of same product reported21 earlier. 7 was
then reacted with 2a–2l in reuxing water for 90 min resulting
General procedure for preparation of 5 from 3 & 4
A mixture of 3 (10 mM), 4 (10 mM) and water (20 ml) was
reuxed at 100 ꢀC for 90–120 min. At the end of this period,
reaction mixture was neutralized with 5% Na2CO3 solution.
Further, a colourless solid separated out from the reaction mass
which was collected by ltration. The isolated solid was washed
with water (10 ml) and dried. The crude product was recrystal-
lized from a suitable solvent to obtain 5.
in the formation of 5a–5l. 5a–5l could also be prepared by
2a
tandem method involving the sequence (1 þ 4/7 / 5a)
(Scheme 2). In the tandem reaction, 1 was treated with 4 in the
presence of 5% aq. H3PO4 at RT for 10 min. The completion of
reaction was checked by TLC until the disappearance of 1 took
place. To the resulting mixture, 2a–2l was added and the whole
thing reuxed for 90–120 min giving 5a–5l and on processing
the mixture no side products were detected. Structure of the
nal product was established by its comparison with authentic
sample prepared earlier in step-wise route shown in Scheme 1.
(Scheme 2) (Tables 5 & 6, included in ESI†).
General procedure for preparation of 5 by tandem reaction
4
(1 þ 2/3 / 5)
A mixture of 1 (10 mM), 2 (10 mM) and 5% aq. H3PO4 (20 ml)
was stirred at RT for 10–15 min when colourless solid sepa-
rated out from reaction mixture. Then, to this solution 4 (10
mM) was added and the mixture reuxed at 100 ꢀC for 90–120
min. At the end of this period, reaction mixture was neutral-
ized with 5% Na2CO3 solution. Further, a colourless solid
separated out from the reaction mass which was collected by
ltration. The isolated solid was washed with water (10 ml)
and dried. The crude product was recrystallized from a suit-
able solvent to obtain 5.
One-pot synthesis of 5a–5l
Encouraged by above results, the title compounds 5a–5l could
also be prepared in one-pot by heating a mixture of 1, 2a–2l and
4 (Scheme 3) in water at 100 ꢀC for 60–90 min in good yield
and no side products were detected. Structures of the products
have been established by comparison with authentic samples
which were prepared in step wise fashion in Scheme 1. (Scheme
3) (Table 6, included in ESI†).
Conclusion
2-(1H-Benzo[d]imidazole-2-yl)-N-phenylbenzamide (5a)
M.P. ¼ >250 ꢀC; IR (KBr): 3052–3450 cmꢁ1 (broad, medium,
–NH– group), 1700 cmꢁ1 (sharp, strong, –CO– of amide group);
1H NMR dH (400 MHz; DMSO-d6; Me4Si): 7.05–7.91 (m, 13H,
Ar–H), 10.43 (s, 1H, –CO–NH, D2O exchangeable), 12.69 (s, 1H,
–NH, D2O exchangeable); 13C NMR dC (400 MHz; DMSO-d6):
115.3, 120.2, 121.8, 123.2, 127.3, 128.5, 128.9, 129.0, 129.0,
130.5, 130.7, 133.2, 135.6, 137.6, 138.7, 150.9, 151.0, 167.6;
HRMS calcd for C20H15N3O [M + H]+: 314.04235, found:
314.04268.
In summary, practical and green synthetic methods have been
developed for the synthesis of 5a–5l in water through step wise
fashion, tandem reaction and one-pot, three-component
synthesis. Of all the methods discussed, one-pot, three-
component synthesis (Scheme 3) appears to be the better, less
time and efficient method of products obtained, compared to
the other two methods. Signicant rate acceleration of the
reaction in water observed and compared to commonly use of
green solvents & ionic liquids. Through this reaction, variety of
5a–5l synthesized in water with good yield.
2-(1H-Benzo[d]imidazole-2-yl)-N-(4-chlorophenyl)benzamide
(5b)
Experimental section
Melting points are uncorrected and were determined in open M.P. ¼ >250 ꢀC; IR (KBr): 3030–3354 cmꢁ1 (broad, medium,
capillary tubes in sulphuric acid bath. TLC was run on silica gel- –NH– group), 1690 cmꢁ1 (sharp, strong, –CO– of amide group);
G and visualization was done using iodine or UV light. IR 1H NMR dH (400 MHz; DMSO-d6; Me4Si): 7.04–7.91 (m, 12H, Ar–
spectra were recorded using Perkin-Elmer 1000 instrument in H), 10.54 (s, 1H, –CO–NH, D2O exchangeable), 12.58 (s, 1H,
1
KBr pellets. H NMR spectra were recorded in DMSO-d6 using –NH, D2O exchangeable); 13C NMR dC (400 MHz; DMSO-d6):
TMS as internal standard using 400 MHz spectrometer. Mass 114.3, 121.5, 121.8, 124.2, 127.3, 128.3, 128.5, 129.9, 129.9,
spectra were recorded on Agilent-LCMS instrument. Starting 130.7, 131.9, 134.1, 136.7, 138.5, 139.6, 151.4, 152.0, 169.8;
materials 1 & 2 were obtained from commercial sources and HRMS calcd for C20H14ClN3O [M + H]+: 348.32353, found:
used as such. 4 has been prepared by literature method.13
348.32329.
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1H NMR dH (400 MHz; DMSO-d6; Me4Si): 7.05–7.89 (m, 12H, Ar–
H), 8.13 (s, 1H, –OH, D2O exchangeable), 10.47 (s, 1H, –CO–NH,
D2O exchangeable), 12.66 (s, 1H, –NH, D2O exchangeable); 13C
NMR dC (400 MHz; DMSO-d6): 115.2, 120.2, 121.8, 123.3, 127.6,
128.5, 128.9, 129.0, 129.0, 130.6, 130.7, 133.1, 135.6, 137.5,
138.9, 150.9, 151.0, 167.5; HRMS calcd for C20H15N3O2 [M + H]+:
330.23416, found: 330.23456.
2-(1H-Benzo[d]imidazole-2-yl)-N-(4-methylphenyl)benzamide (5c)
M.P. ¼ >250 ꢀC; IR (KBr): 3038–3353 cmꢁ1 (broad, medium, –NH–
group), 1651 cmꢁ1 (sharp, strong, –CO– of amide group); 1H NMR
dH (400 MHz; DMSO-d6; Me4Si): 2.25 (s, 3H, CH3), 7.09–7.91 (m,
12H, Ar–H), 10.34 (s, 1H, –CO–NH, D2O exchangeable), 11.62 (s,
1H, –NH, D2O exchangeable); 13C NMR dC (400 MHz; DMSO-d6):
20.4, 115.0, 120.0, 121.9, 123.3, 127.2, 128.5, 128.8, 129.3, 129.5,
130.0, 130.8, 132.3, 136.8, 137.5, 138.9, 150.7, 151.1, 168.6; HRMS
calcd for C21H17N3O [M + H]+: 328.03145, found: 328.03111.
2-(1H-Benzo[d]imidazole-2-yl)-N-(4-nitrophenyl)benzamide (5i)
M.P. ¼ >250 ꢀC; IR (KBr): 3033–3373 cmꢁ1 (broad, medium, –NH–
group), 1692 cmꢁ1 (sharp, strong, –CO– of amide group); 1H NMR
dH (400 MHz; DMSO-d6; Me4Si): 7.05–7.91 (m, 12H, Ar–H), 10.43
(s, 1H, –CO–NH, D2O exchangeable), 12.69 (s, 1H, –NH, D2O
exchangeable); 13C NMR dC (400 MHz; DMSO-d6): 114.9, 120.0,
121.7, 122.3, 127.4, 128.5, 128.8, 129.5, 129.9, 130.2, 130.5, 132.5,
136.7, 137.9, 138.9, 150.6, 151.2, 168.5; HRMS calcd for
C20H14N4O3 [M + H]+: 359.85652, found: 359.85624.
2-(1H-Benzo[d]imidazole-2-yl)-N-(2-methylphenyl)benzamide (5d)
M.P. ¼ >250 ꢀC; IR (KBr): 3035–3355 cmꢁ1 (broad, medium, –NH–
group), 1694 cmꢁ1 (sharp, strong, –CO– of amide group); 1H NMR
dH (400 MHz; DMSO-d6; Me4Si): 2.44 (s, 3H, CH3), 7.21–7.95 (m,
12H, Ar–H), 10.43 (s, 1H, –CO–NH, D2O exchangeable), 11.66 (s,
1H, –NH, D2O exchangeable); 13C NMR dC (400 MHz; DMSO-d6):
21.0, 114.9, 120.0, 121.8, 122.3, 127.4, 128.7, 128.8, 129.5, 129.5,
130.2, 130.8, 132.4, 136.8, 137.9, 138.9, 150.7, 151.1, 168.6; HRMS
calcd for C21H17N3O [M + H]+: 328.32356, found: 328.32329.
2-(1H-Benzo[d]imidazole-2-yl)-N-(3-nitrophenyl)benzamide (5j)
M.P. ¼ >250 ꢀC; IR (KBr): 3039–3359 cmꢁ1 (broad, medium, –NH–
group), 1695 cmꢁ1 (sharp, strong, –CO– of amide group); 1H NMR
dH (400 MHz; DMSO-d6; Me4Si): 7.05–7.96 (m, 12H, Ar–H), 10.43
(s, 1H, –CO–NH, D2O exchangeable), 12.68 (s, 1H, –NH, D2O
exchangeable); 13C NMR dC (400 MHz; DMSO-d6): 114.9, 120.1,
121.7, 122.3, 127.4, 128.5, 128.8, 129.5, 129.8, 130.2, 130.5, 131.5,
136.7, 137.9, 138.9, 150.6, 151.3, 168.6; HRMS calcd for
C20H14N4O3 [M + H]+: 359.24516, found: 359.24567.
2-(1H-Benzo[d]imidazole-2-yl)-N-(4-bromophenyl)benzamide (5e)
M.P. ¼ >250 ꢀC; IR (KBr): 3034–3360 cmꢁ1 (broad, medium, –NH–
group), 1689 cmꢁ1 (sharp, strong, –CO– of amide group); 1H NMR
dH (400 MHz; DMSO-d6; Me4Si): 7.04–7.90 (m, 12H, Ar–H), 10.30
(s, 1H, –CO–NH, D2O exchangeable), 12.25 (s, 1H, –NH, D2O
exchangeable); 13C NMR dC (400 MHz; DMSO-d6): 114.3, 121.2,
121.8, 123.2, 127.3, 128.5, 128.9, 129.0, 129.1, 130.5, 130.7, 133.2,
135.7, 137.3, 138.6, 150.9, 151.0, 169.7; HRMS calcd for
C20H14BrN3O [M + H]+: 392.32356, found: 392.32387.
2-(1H-Benzo[d]imidazole-2-yl)-N-(2-chlorophenyl)benzamide (5k)
M.P. ¼ >250 ꢀC; IR (KBr): 3028–3350 cmꢁ1 (broad, medium, –NH–
group), 1682 cmꢁ1 (sharp, strong, –CO– of amide group); 1H NMR
dH (400 MHz; DMSO-d6; Me4Si): d 7.04–7.90 (m, 12H, Ar–H), 10.53
(s, 1H, –CO–NH, D2O exchangeable), 12.59 (s, 1H, –NH, D2O
exchangeable); 13C NMR dC (400 MHz; DMSO-d6): 114.6, 121.5,
121.9, 124.2, 127.3, 128.0, 128.3, 129.5, 129.9, 130.9, 131.9, 134.1,
136.7, 138.6, 139.0, 151.6, 152.1, 169.8; HRMS calcd for
C20H14ClN3O [M + H]+: 348.42396, found: 348.42356.
2-(1H-Benzo[d]imidazole-2-yl)-N-(4-iodophenyl)benzamide (5f)
ꢁ1
ꢀ
M.P. ¼ 240–242 C; IR (KBr): 3030–3350 cm (broad, medium,
–NH– group), 1690 cmꢁ1 (sharp, strong, –CO– of amide group);
1H NMR dH (400 MHz; DMSO-d6; Me4Si): d 7.04–7.90 (m, 12H, Ar–
H), 10.30 (s, 1H, –CO–NH, D2O exchangeable), 12.29 (s, 1H, –NH,
D2O exchangeable); 13C NMR dC (400 MHz; DMSO-d6): 114.3,
121.5, 121.8, 123.1, 127.3, 128.3, 128.5, 129.0, 129.1, 130.5, 130.9,
133.2, 135.7, 137.5, 138.7, 150.9, 151.1, 169.6; HRMS calcd for
C20H14IN3O [M + H]+: 440.32300, found: 440.32329.
2-(1H-Benzo[d]imidazole-2-yl)-N-(4-uorophenyl)benzamide (5l)
ꢁ1
ꢀ
M.P. ¼ 235–236 C; IR (KBr): 3040–3380 cm (broad, medium,
–NH– group), 1693 cmꢁ1 (sharp, strong, –CO– of amide group);
1H NMR dH (400 MHz; DMSO-d6; Me4Si): d 7.04–7.95 (m, 12H, Ar–
H), 10.31 (s, 1H, –CO–NH, D2O exchangeable), 12.29 (s, 1H, –NH,
D2O exchangeable); 13C NMR dC (400 MHz; DMSO-d6): 115.3,
120.0, 121.9, 123.3, 127.3, 128.5, 128.7, 129.3, 129.5, 130.0, 130.9,
132.3, 136.8, 137.0, 138.7, 150.6, 151.5, 168.6; HRMS calcd for
C20H14FN3O [M + H]+: 332.56771, found: 332.56721.
2-(1H-Benzo[d]imidazole-2-yl)-N-(4-methoxyphenyl)
benzamide (5g)
M.P. ¼ >250 ꢀC; IR (KBr): 3040–3383 cmꢁ1 (broad, medium, –NH–
group), 1692 cmꢁ1 (sharp, strong, –CO– of amide group); 1H NMR
dH (400 MHz; DMSO-d6; Me4Si): 3.35 (s, 3H, CH3), 7.22–7.99 (m,
12H, Ar–H), 10.48 (s, 1H, –CO–NH, D2O exchangeable), 11.48 (s,
1H, –NH, D2O exchangeable); 13C NMR dC (400 MHz; DMSO-d6):
55.9, 118.3, 120.2, 121.5, 123.6, 127.5, 128.5, 128.9, 129.0, 129.2,
130.6, 130.8, 133.1, 136.5, 137.0, 138.9, 150.9, 151.1, 167.9; HRMS
calcd for C21H17N3O2 [M + H]+: 344.32466, found: 344.32497.
General procedure for preparation of 6 from 1 & 4
A mixture of 1 (10 mM), 4 (10 mM) and H2O (20 ml) was stirred
at RT for 10–15 min. At the end of this period, reaction mixture
was neutralized with 5% Na2CO3 solution. Further, a colourless
2-(1H-Benzo[d]imidazole-2-yl)-N-(4-hydroxyphenyl)benzamide (5h)
M.P. ¼ >250 ꢀC; IR (KBr): 3039–3353 cmꢁ1 (broad, medium, solid separated out from the reaction mass which was collected
–NH– group), 1632 cmꢁ1 (sharp, strong, –CO– of amide group); by ltration. The isolated solid was washed with water (10 ml)
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and dried. The product was recrystallized from a suitable
solvent to obtain 6.
Notes and references
2-((2-Aminophenyl)carbamoyl)benzoic acid 6. M. P ¼ 165–
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I. T. Horvath, Chem. Rev., 2002, 35, 685.
167 C [lit.,21 167–168 C], yield ¼ 90%.
ꢀ
ꢀ
¨
2 U. K. Lindstrom, Chem. Rev., 2002, 102, 2751; C. J. Li, Chem.
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6 (10 mM) and 5% aq. H3PO4 (20 ml) was reuxed at 100 ꢀC for
90 min. At the end of this period, reaction mixture was
neutralized with 5% Na2CO3 solution. Further, a colourless
solid separated out from the reaction mass which was collected
by ltration. The isolated solid was washed with water (10 ml)
and dried. The crude product was recrystallized from a suitable
solvent to obtain 7.
¨
3 C. Capello, U. Fisher and K. Kungerbuhler, Green Chem.,
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5 H.
R
Safaei, M. Shekouhy, S. Rahmanpur and
2-(2-Aminophenyl)isoindoline-1,3-dione 7. M.P. ¼ 205–206 ꢀC
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6 J. Chen, S. K. Spear, J. G. Huddleston and R. D. Rogers, Green
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[lit.,21 206–207 ꢀC], yield ¼ 90%.
General procedure for preparation of 5 from 7 & 2
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A mixture of 7 (10 mM), 2 (10 mM) and 5% aq. H3PO4 (20 ml)
was reuxed at 100 ꢀC for 120–150 min. the end of this period,
reaction mixture was neutralized with 5% Na2CO3 solution.
Further, a colourless solid separated out from the reaction mass
which was collected by ltration. The isolated solid was washed
with hexane (10 ml) and dried. The product was recrystallized
from a suitable solvent to obtain 5.
General procedure for preparation of 5 by tandem reaction
2
(1 þ 4/7 / 5)
A mixture of 1 (10 mM), 4 (10 mM) and water (20 ml) was
ꢀ
reuxed at 100 C for 90 min. A colourless solid separated out
from reaction mixture. Then, to this mixture at RT 2a–2l (10
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12, 1237.
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´
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A mixture of 1 (10 mM), 3a–3l (10 mM), 4 (10 mM), and water (20
ml) was reuxed at 100 ꢀC for 60–90 min. At the end of this
period, reaction mixture was neutralized with 5% Na2CO3
solution. Further, a colourless solid separated out from the
reaction mass which was collected by ltration. The isolated
solid was washed with water (10 ml) and dried. The product was
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Acknowledgements
Authors are very thankful to the authorities of Jawaharlal Nehru
Technological University Hyderabad for providing laboratory
facilities. One of them, (Y. D. R) is grateful to the University for
nancial support in the form of a Fellowship.
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