MK-10 clay-catalyzed synthesis of 2-(2',5'-disubstituted-1'h-indol-3'-yl)- 1h-benzo[d]imidazoles under conventional and microwave irradiation

Article abstract of DOI:10.1080/00397911003707071

The synthesis of benzimidazoles has been achieved in a one-pot reaction in excellent yield using a newly developed methodology. 2,5-Disubstituted-3- cyanoacetyl indoles were directly condensed with substituted orthophenylenediamine via microwave irradiati

Full text of DOI:10.1080/00397911003707071

This article was downloaded by: [University of California, San Francisco]
On: 19 December 2014, At: 22:42
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered
office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic Organic
Chemistry
Publication details, including instructions for authors and
subscription information:
http://www.tandfonline.com/loi/lsyc20
MK-10 Clay–Catalyzed Synthesis of 2-
(2′,5′-Disubstituted-1′H-indol-3′-yl)-1H-
benzo[d]imidazoles under Conventional
and Microwave Irradiation
J. S. Biradar a & B. Sharanbasappa a
a Department of Studies in Chemistry , Gulbarga University ,
Gulbarga , Karnataka , India
Published online: 25 Feb 2011.
To cite this article: J. S. Biradar & B. Sharanbasappa (2011) MK-10 Clay–Catalyzed Synthesis of 2-
(2′,5′-Disubstituted-1′H-indol-3′-yl)-1H-benzo[d]imidazoles under Conventional and Microwave
Irradiation, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 41:6, 885-890, DOI: 10.1080/00397911003707071
To link to this article: http://dx.doi.org/10.1080/00397911003707071
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the
“Content”) contained in the publications on our platform. However, Taylor & Francis,
our agents, and our licensors make no representations or warranties whatsoever as to
the accuracy, completeness, or suitability for any purpose of the Content. Any opinions
and views expressed in this publication are the opinions and views of the authors,
and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content
should not be relied upon and should be independently verified with primary sources
of information. Taylor and Francis shall not be liable for any losses, actions, claims,
proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or
howsoever caused arising directly or indirectly in connection with, in relation to or arising
out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any
substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing,
systematic supply, or distribution in any form to anyone is expressly forbidden. Terms &

Conditions of access and use can be found at http://www.tandfonline.com/page/terms-
and-conditions

Synthetic Communications1, 41: 885–890, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003707071
MK-10 CLAY–CATALYZED SYNTHESIS OF
2-(2’,5’-DISUBSTITUTED-1’H-INDOL-3’-YL)-1H-
BENZO[d]IMIDAZOLES UNDER CONVENTIONAL
AND MICROWAVE IRRADIATION
J. S. Biradar and B. Sharanbasappa
Department of Studies in Chemistry, Gulbarga University, Gulbarga,
Karnataka, India
GRAPHICAL ABSTRACT
Abstract The synthesis of benzimidazoles has been achieved in a one-pot reaction in excel-
lent yield using a newly developed methodology. 2,5-Disubstituted-3-cyanoacetyl indoles
were directly condensed with substituted orthophenylenediamine via microwave irradiation
under neat, solid support, and conventional conditions in a short time to afford the corre-
sponding products in good yields. Structures of the products thus obtained were confirmed
by their melting points, infrared, 1H NMR, 13C NMR, and mass spectral data.
Keywords Benzimidazoles; conventional method; environmentally benign; indole;
microwave irradiation; solid support
INTRODUCTION
In continuation of our ongoing interest in the green synthesis of indoles,[1–5] we
have developed a mild and expedient novel synthesis for benzimidazole[6–10] incor-
porated with the indole nucleus using montmorillonite K10 clay as the catalyst.
The method is highly efficient and free from drawbacks. A brief account of our work
and its main findings as well as the advantages of this method over the existing syn-
thetic routes is discussed in this communication. Montmorillonite K10 clay[11] is
known to behave as both a protic and a Brønsted acid (Hammett acidity function,
Received October 3, 2009.
Address correspondence to J. S. Biradar, Professor of Organic Chemistry, Department of Studies
in Chemistry, Gulbarga University, Gulbarga 585106, Karnataka State, India. E-mail: jsbiradar1@
rediffmail.com
885

886
J. S. BIRADAR AND B. SHARANBASAPPA
Scheme 1. R1 ¼ Ph, Me, H; R2 ¼ Cl, Me, OMe, H; R3 ¼ Me, H.
H0: ꢀ5.5 to 5.9) and has a large specific surface area (500–760m2=g). We therefore used
this clay in dimethylformamide (DMF; as an energy-transfer agent and homogenizer to
increase the reaction temperature) reaction of 2,5-disubstituted-3-cyanoacetyl indole
and substituted orthophenylenediamine under microwave irradiation [neat, solid
supported (montmorillonite K-10 clay)] and conventional conditions (Scheme 1) that
afforded 2-(20,50-disubstituted-1H-indol-30-yl)-1H-benzo[d]imidazoles.
RESULTS AND DISCUSSION
In the present investigation, the reaction (Scheme 1) was carried out with
microwave irradiation by taking 2,5-disubstituted 3-cyanoacetyl indoles and substi-
tuted orthophenylenediamine in the presence of a MK-10 clay in DMF for 10 min.
The products were obtained in good yields, and the use of MK-10 clay as the mineral
support eliminates the necessity of an external base or strong acid for the synthesis of
the title product, which was formed in reasonable purity. When the reaction was car-
ried out using conventional heating, the products were obtained in moderate yields
in 1–2 h (Table 1).
The reaction has also been performed under neat conditions (without solvent
support or catalyst); however, no reaction occurred under neat conditions. It could
be made successful by adding DMF. The role of DMF is that of an energy-transfer
medium and homogenizer to increase the reaction temperature. However, products
are formed in comparatively lesser yield in this case as compared to the solid-
supported reaction.
Conventional synthesis suffers from disadvantages such as long reaction peri-
ods and poor yields (Table 2). Hence, we have developed a new, economical, safe,
Scheme 2. Possible reaction mechanism.

MICROWAVE-ASSISTED BENZIMIDAZOLE SYNTHESIS
887
Table 1. Comparative study of the synthesis of 3a–e
Isolated yield (%)
Conventional (reflux)
Microwave power (%)
Reaction time
(min)
Entry
Method
D (DMF)
MW (Neat)
MW
D
3a
Reflux
50
50
60
10
10
10
90
10
10
10
60
10
10
10
120
10
10
10
60
10
10
10
—
Nil
80
92
—
Nil
77
85
—
Nil
80
90
—
Nil
74
78
—
Nil
70
80
58
—
—
—
53
—
—
—
56
—
—
—
52
—
—
—
53
—
—
—
MW (DMF)
MW (DMF þ MK-10)
50
3b
3c
3d
3e
D (DMF)
MW (Neat)
Reflux
50
50
MW (DMF)
MW (DMF þ MK-10)
50
D (DMF)
MW (Neat)
Reflux
50
50
MW (DMF)
MW (DMF þ MK-10)
50
D (DMF)
MW (Neat)
Reflux
50
50
MW (DMF)
MW (DMF þ MK-10)
50
D (DMF)
MW (Neat)
Reflux
50
50
MW (DMF)
MW (DMF þ MK-10)
50
environmentally benign, one-pot synthesis of novel 2-(20,50-disubstituted-10H-
indol-30-yl)-1H-benzo[d]imidazoles under microwave irradiation. The method of
synthesis (10 min) has given excellent yields (75–92%).
The infrared (IR) spectrum of compound 3a has shown characteristic peaks at
=
=
3278 (NꢀH), 3188 (NꢀH), 2925 (CꢀH), 1635 (C N), 1578 (C C), and 748 (C-Cl)
cmꢀ1. The H NMR spectrum of 3a displayed a downfield signal at d 11.6 (s, 1H),
1
integrating for one proton of indole, and at d 10.4 (s, 1H), integrating for one proton
of the benzimidazole NH. A multiplet was observed at d 7.1–7.8 (m, 12H, ArH),
Table 2. Comparative data of conventional (A) and MW (B) methods for the synthesis of compounds
3a–j
Conventional method
Microwave method
Entry R1
R2
R3 Time (min) Yield (%) Time (min) Power (%) Yield (%) Mp (ꢁC)
3a
3b
3c
3d
3e
3f
Ph
Ph
Cl
Me
H
H
60
90
58
53
56
52
53
56
55
60
54
51
10
10
10
10
10
10
10
10
10
10
50
50
50
50
50
50
50
50
50
50
92
85
90
78
80
85
83
88
75
80
202–204
187–189
193–195
277–279
226–228
208–210
178–180
167–169
200–201
214–216
Ph OMe
H
60
Me
H
H
H
H
120
60
H
Ph
Ph
Cl
Me
Me
Me
60
90
3g
3h
3i
Ph OMe Me
90
Me
H
H
H
Me
Me
120
60
3j

888
J. S. BIRADAR AND B. SHARANBASAPPA
integrating for 12 aromatic protons. The 13C NMR spectrum of 3a displayed a
downfield signal at d 153, integrated for benzimidazole carbon, and at d 145, 137,
132, 129, 128, 127, 122, 120, 119, 118, 116, 114, 112, and 100, integrated for aromatic
carbons. The mass spectrum of compound 3a has displayed molecular ion peaks at
343 (Mþ.) (76%), 345 (M þ 2) (25%) and peaks at m=z 252 (100%), 254 (33%), 226
(40%), 228 (13%), 217 (15%), 125 (18%), 127 (6%), and 118 (55%). This fragmen-
tation pattern supported the formation of the title compound.
EXPERIMENTAL
Melting points were determined in open capillary tubes and are uncorrected.
IR spectra were recorded in KBr on a Perkin-Elmer Fourier transform (FTIR)–
1
spectrophotometer (cmꢀ1), and H NMR spectra were recorded on a Bruker Avene
II 400-MHz NMR spectrometer (chemical shifts in d ppm downfield from
tetramethylsilane as an internal reference). The mass spectra were recorded on a
LC-MSD-Trap-SL instrument, and microwave reactions were carried out in an
Onida 20STP21 800W (MO 20SG05101262) multimode domestic microwave oven.
Conventional Method (3a–j)
A mixture of 2,5-disubstituted 3-cyanoacetyl indole (1 mmol) and substituted
orthophenylenediamine (1 mmol) was refluxed with 5 ml of DMF in a given time
(Table 2). The reaction mixture was allowed to cool to room temperature and
poured into crushed ice. The solid thus obtained was dried and recrystallized from
DMF and ethanol to afford the title compounds 3a–j with 51–60% yield (Table 2).
Microwave-Assisted Synthesis
Neat reaction. A mixture of 2,5-disubstituted 3-cyanoacetyl indole (1 mmol)
and substituted orthophenylenediamine (1 mmol) were introduced in an open borosil
glass vessel. This was subjected to microwave irradiation for 10 min with 50% micro-
wave power (Table 1), and no products were found.
Neat with DMF. A mixture of 2,5-disubstituted 3-cyanoacetyl indole
(1 mmol), substituted orthophenylenediamine (1 mmol), and DMF (1 ml) was intro-
duced in an open borosil glass vessel. This was subjected to microwave irradiation
for 10 min with 50% microwave power (Table 1) and gave an oily product, which
solidified on standing. Washing this with ice cold water gave the crude product,
which was recrystallized from DMF or ethyl alcohol to afford the title compounds
with good yield (Table 2).
Neat with DMF þ solid support. A mixture of 2,5-disubstituted 3-
cyanoacetyl indole (1 mmol), substituted orthophenylenediamine (1 mmol), and
DMF (1 ml) on 2 g of MK-10 clay was introduced in an open borosil glass vessel.
This was subjected to microwave irradiation for 10 min with 50% microwave power
(Table 1). The product was washed with ice-cold water and recrystallized from DMF
or ethyl alcohol to give the title compound, which was in good purity (thin-layer
chromatography) and yield (Table 2).

MICROWAVE-ASSISTED BENZIMIDAZOLE SYNTHESIS
889
Selected Data
2-(5-Chloro-2-phenyl-1H-indol-3-yl)-1H-benzo[d]imidazole (3a). Mp 202–
204 ꢁC; IR (KBr): nmax=cmꢀ1 ¼ 3278, 3188, 2925, 1635, 1578, 748. 1H NMR
(DMSO-d6): d ¼ 11.6 (br. s, 1H, NH), 10.4 (br. s, 1H, NH), 7.1–7.8 (m, 12H,
ArH). 13C NMR (DMSO-d6): d ¼ 153, 145, 137, 132, 129, 128, 127, 122, 120, 119,
118, 116, 114, 112, 100. MS: m=z (%) ¼ 343 (Mþ.) (76%), 345 (M þ 2) (25%), 252
(100%), 254 (33%), 226 (40%), 228 (13%), 217 (15%), 125 (18%), 127 (6%), 118
(55%). Analysis calcd. for C21H14ClN3: C, 73.36; H, 4.10; N, 12.22. Found: C,
73.38; H, 4.15; N, 12.25.
2-(5-Methyl-2-phenyl-1H-indol-3-yl)-1H-benzo[d]imidazole (3b). Mp 187–
189 ꢁC; IR (KBr): nmax=cmꢀ1 ¼ 3295, 3193, 2930, 1640, 1580. 1H NMR (DMSO-d6):
d ¼ 11.5 (br. s, 1H, NH), 10.3 (br. s, 1H, NH), 7.2–7.8 (m, 12H, ArH), 2.3 (s, 3H,
CH3). Analysis calcd. for C22H17N3: C, 81.71; H, 5.30; N, 12.99. Found: C, 81.75;
H, 5.34; N, 12.95.
2-(1H-Indol-3-yl)-1H-benzo[d]imidazole (3e). Mp 226–228 ꢁC; IR (KBr):
1
n
1H, NH), 10.1 (br. s, 1H, NH), 7.0–7.9 (m, 9H, ArH). Analysis calcd. for
C15H11N3: C, 77.23; H, 4.75; N, 18.01. Found: C, 77.25; H, 4.79; N, 18.07.
max=cmꢀ1 ¼ 3276, 3201, 2927, 1617, 1582. H NMR (DMSO-d6): d ¼ 10.8 (br. s,
2-(5-Chloro-2-phenyl-1H-indol-3-yl)-6-methyl-1H-benzo[d]imidazole (3f).
1
Mp 208–210 ꢁC; IR (KBr): nmax=cmꢀ1 ¼ 3283, 3208, 2931, 1643, 1581, 745. H
NMR (DMSO-d6): d ¼ 11.0 (br. s, 1H, NH), 9.4 (br. s, 1H, NH), 7.0–7.8 (m, 11H,
ArH), 2.2 (s, 3H, CH3). Analysis calcd. for C22H16ClN3: C, 73.84; H, 4.51; N,
11.74. Found: C, 73.88; H, 4.55; N, 11.79.
6-Methyl-2-(5-methyl-2-phenyl-1H-indol-3-yl)-1H-benzo[d]imidazole (3g).
1
Mp 178–180 ꢁC; IR (KBr): nmax=cmꢀ1 ¼ 3286, 3210, 2930, 1636, 1583. H NMR
(DMSO-d6): d ¼ 10.8 (br. s, 1H, NH), 10.0 (br. s, 1H, NH), 7.0–7.7 (m, 11H,
ArH), 2.1 (s, 3H, CH3), 2.4 (s, 3H, CH3). Analysis calcd. for C23H19N3: C, 81.87;
H, 5.68; N, 12.45. Found: C, 81.90; H, 5.73; N, 12.49.
2-(1H-Indol-3-yl)-6-methyl-1H-benzo[d]imidazole (3j). Mp 214–216 ꢁC;
IR (KBr): nmax=cmꢀ1 ¼ 3281, 3191, 2928, 1637, 1580. 1H NMR (DMSO-d6):
d ¼ 10.7 (br. s, 1H, NH), 9.3 (br. s, 1H, NH), 7.0–7.9 (m, 8H, ArH), 2.2 (s, 3H,
CH3). Analysis calcd. for C16H13N3: C, 77.71; H, 5.30; N, 16.99. Found: C, 77.75;
H, 5.36; N, 17.02.
ACKNOWLEDGMENTS
The authors thank the chairman, Department of Chemistry, Gulbarga
University, Gulbarga, for providing laboratory facilities and Punjab University
Chandigarh, Central University Hyderabad, Indian Institute for Chemical Tech-
nology, Hyderabad, for spectral and analytical data.

890
J. S. BIRADAR AND B. SHARANBASAPPA
REFERENCES
1. Biradar, J. S.; Sharanbasappa, B. MK-10 clay–catalyzed, one-pot, three-component, and
efficient synthesis of novel4-(20,50-disubstituted-10H-indol-30-yl)-2,6-bis(200,500-disubstituted-
100H-indol-300-yl)pyridine-3,5 dicarbonitrile under conventional and microwave irradiation.
Green Chem. Lett. Rev. 2009, 2 (4), 237–241.
2. Biradar, J. S.; Sasidhar, B. S.; Praveen, S. M.; Sharanabasappa, B. A versatile one-pot
synthesis of novel substituted pyrazoles, isoxazoles, and their antimicrobial activity.
Org. Chem. 2009, 5 (3), 262–265.
3. Biradar, J. S.; Mugali, P. S.; Sasidhar, B. S.; Parveen, R. One-pot synthesis of substituted
imidazoles containing indole and their antimicrobial activities. Org. Chem. 2008, 4 (6–8),
408–411.
4. Biradar, J. S.; Mugali, P. S.; Sharanabasappa, B.; Sasidhar, B. S. Improved synthesis of
some pyrazolines under microwave. Ind. J. Het. Chem. 2008, 18 (4), 141–144.
5. Manjunath, S. Y.; Biradar, J. S.; Basavaraj, R. Synthesis and anthelmintic activity of tri-
heterocycles: [50-(500-Substituted-300-phenylindol-200-yl)-10,30,40-oxadiazol-20-yl-thiomethyl]-
benzimidazoles. Ind. J. Het. Chem. 2009, 18 (2), 321–324.
6. Zhan, Z. H.; Liang, Y.; Yong, M. W. An expeditious synthesis of benzimidazole deriva-
tives catalyzed by Lewis acids. Catal. Commun. 2007, 8 (7), 1126–1131.
7. Oren, I. Y.; Yalcin, I.; Sener, E. A.; Nejat, U. Synthesis and structure–activity relation-
ships of new antimicrobial active multisubstituted benzazole derivatives. Eur. J. Med.
Chem. 2004, 39 (3), 291–298.
8. Hasegawa, E.; Yoneoka, A.; Suzuki, K.; Kato, T.; Kitazume, T.; Yangi, K. Reductive
transformation of a,b-epoxy ketones and other compounds promoted through photoin-
duced electron transfer processes with 1,3-dimethyl-2-phenylbenzimidazoline (DMPBI).
Tetrahedron 1999, 55 (45), 12957–12968.
9. Kamila, S.; Biehl, R. E. Synthesis of thiazolines by the reaction of aryl ketonitriles with
cysteamine via microwave irradiation. J. Het. Chem. 2007, 44 (2), 407–409.
10. Rao, A.; Chimirri, A.; Ferro, S.; Monforte, A. M.; Monforte, P.; Zappala, M. Microwave-
assisted synthesis of benzimidazole and thiazolidinone derivatives as HIV-1 RT inhibitors.
Arkivoc 2004, 5, 147–155.
11. Chakrabarty, M.; Ghosh, N.; Basaka, R.; Harigaya, Y. Dry reaction of indoles with
carbonyl compounds on montmorillonite K10 clay: A mild, expedient synthesis of diindo-
lylalkanes and vibrindole A. Tetrahedron Lett. 2002, 43 (22), 4075–4078.