Cellulose sulfuric acid: Novel and efficient biodegradable and recyclable acid catalyst for the solid-state synthesis of thiadiazolo benzimidazoles

Article abstract of DOI:10.1080/00397911003632899

An efficient method for the synthesis of 2-substituted benzimidazoles has been developed. In this method, benzo[c][1,2,5]thiadiazole-4,5-diamine was condensed with different aldehydes in the presence of cellulose sulfuric acid under solvent-free condition

Full text of DOI:10.1080/00397911003632899

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Cellulose Sulfuric Acid: Novel and
Efficient Biodegradable and Recyclable
Acid Catalyst for the Solid-State
Synthesis of Thiadiazolo Benzimidazoles
B. Suresh Kuarm a , J. Venu Madhav a , B. Rajitha a , Y. Thirupathi
Reddy b , P. Narsimha Reddy b & Peter A. Crooks b
a Department of Chemistry , National Institute of Technology ,
Warangal, AP, India
b Department of Pharmaceutical Sciences, College of Pharmacy ,
University of Kentucky , Lexington, Kentucky, USA
Published online: 31 Jan 2011.
To cite this article: B. Suresh Kuarm , J. Venu Madhav , B. Rajitha , Y. Thirupathi Reddy , P. Narsimha
Reddy & Peter A. Crooks (2011) Cellulose Sulfuric Acid: Novel and Efficient Biodegradable and
Recyclable Acid Catalyst for the Solid-State Synthesis of Thiadiazolo Benzimidazoles, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:5, 662-669, DOI: 10.1080/00397911003632899
To link to this article: http://dx.doi.org/10.1080/00397911003632899
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Synthetic Communications1, 41: 662–669, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003632899
CELLULOSE SULFURIC ACID: NOVEL AND EFFICIENT
BIODEGRADABLE AND RECYCLABLE ACID CATALYST
FOR THE SOLID-STATE SYNTHESIS OF THIADIAZOLO
BENZIMIDAZOLES
B. Suresh Kuarm,1 J. Venu Madhav,1 B. Rajitha,1
Y. Thirupathi Reddy,2 P. Narsimha Reddy,2 and
Peter A. Crooks2
1Department of Chemistry, National Institute of Technology,
Warangal, AP, India
2Department of Pharmaceutical Sciences, College of Pharmacy,
University of Kentucky, Lexington, Kentucky, USA
Abstract An efficient method for the synthesis of 2-substituted benzimidazoles has been
developed. In this method, benzo[c][1,2,5]thiadiazole-4,5-diamine was condensed with
different aldehydes in the presence of cellulose sulfuric acid under solvent-free conditions
by simple physical grinding of reactants using a mortar and pestle at room temperature.
The methodology is mild, high-yielding, and green, and the catalyst could be easily recycled.
Keywords Benzimidazoles; benzo[c][1,2,5]thiadiazole-4,5-diamine; cellulose sulfuric acid;
different aldehydes
INTRODUCTION
The synthesis of substituted benzimidazoles has received significant attention
because of their biological activities such as antihistaminic, antiparasitic, antiulcer,
antihypertensive, antiviral, antifungal and anticancer activities.[1,2] The synthesis of
benzimidazole derivatives has gained importance in recent years because they exhibit
illustrious biological and pharmacological activities and are used as selective neuro-
peptide YY1 receptor antagonists,[3] factor Xa inhibitors,[4] potential antitumor
agents,[5] and antimicrobial agents.[6] They are used in diverse areas of chemistry
Received November 4, 2009.
Address correspondence to B. Rajitha, Department of Chemistry, National Institute of Technology,
Warangal, AP, India. E-mail: rajithabhargavi@ymail.com
662

SYNTHESIS OF THIADIAZOLO BENZIMIDAZOLES
663
and are very important intermediates in organic reactions.[7] The traditional
synthesis of benzimidazoles includes the condensation of o-phenylendiamine with
carboxylic acid[8] or their derivatives (nitriles, imidates, or orthoesters)[9] and the
condensation of o-phenylendiamine with aldehyde in refluxing nitrobenzene[10] or
in the presence of acidic catalysts.[11] Benzimidazoles have also been prepared in a
solid phase to provide a combinatorial approach.[12] Various oxidative and catalytic
reagents such as sulfamic acid,[13] I2,[14] 2,3-dichloro-5,6-dicyanobenzoquinone
[19]
[20]
[21]
(DDQ),[15] air,[16] oxone,[17] FeCl3 ꢀ 6H2O,[18] In(OTf)3
Yb(OTf)3
Sc(OTf)3
KHSO4,[22] and ionic liquid[23] have been used. Some of these methods suffer from
severe drawbacks, including use of large amounts of expensive reagents and cata-
lysts, poor yield, use of toxic solvents and catalysts, long reaction times, special
apparatus, and tedious workup procedures, which necessitate the development of
an alternative route for the synthesis of these biologically active molecules. Cellulose
is one of the most abundant natural biopolymers in the world and has been widely
studied during the past several decades because it is a biodegradable material and a
renewable resource. Its unique properties make it an attractive alternative to
conventional organic or inorganic supports in catalytic applications.
Recently, cellulose sulfuric acid has emerged as a promising biopolymeric
solid-support acid catalyst for acid-catalyzed reactions, such as the synthesis of
a-aminonitriles,[24]
imidazoazines,[25]
quinolines,[26]
aryl-14H-dibenzo[a.j]-
xanthenes,[27] and 3,4-dihydropyrimidine-2(1H)-ones[28] and the Pechmann
condensation.[29] Cellulose sulfuric acid can be easily prepared by the reaction of
inexpensive cellulose with chlorosulfonic acid.
RESULTS AND DISCUSSION
Cellulose sulfuric acid has emerged as an attractive alternative catalyst in terms
of acidic strength and environmentally benign character for various reactions. In
continuation of our work, we now report an efficient method for the synthesis of
thiadiazolo benzimidazoles[30] by simple physical grinding of benzo[c][1,2,
5]thiadiazole-4,5-diamine, different aldehydes, and cellulose sulfuric acid using a
mortar and pestle at room temperature.
To illustrate the need for cellulose sulfuric acid for these reactions, an
experiment was conducted in the absence of cellulose sulfuric acid. The yields
Table 1. Effect of catalysts on yield
Entry
Catalyst
Yielda (%)
1
2
3
4
5
Cellulose sulfuric acid
Silica sulfuric acid
95
91
84
53
15
p-Toluene sulfonic acid
Sulfuric acid in acetic acid
No catalyst
Notes. Reaction conditions: Mixture of cellulose sulfuric acid (0.1 g),
aldehyde (3.6 mmol), and benzo[c][1,2,5]thiadiazole-4,5-diamine (3.0 mmol)
was ground at room temperature.
aYields refer to the pure isolated recovered catalyst.

664
B. S. KUARM ET AL.
obtained were very poor, side products were formed, and reactants were not involved
completely in this reaction. Obviously, the cellulose sulfuric acid is an important
component of the reaction.
The efficiency of the cellulose sulfuric acid compared to various sulfur analog
acidic catalysts was also examined (Table 1). In this study, it was found that cellulose
sulfuric acid is more efficient and superior over other acidic catalysts with respect to
reaction time and yield. It was also observed that the yield was only 15% in the
absence of the cellulose sulfuric acid catalyst.
EXPERIMENTAL
The progress of the reaction was monitored by thin-layer chromatography
(TLC). 1H NMR spectra was measured on a Varian Gemini 200-MHz spectrometer
using tetramethylsilane (TMS) as internal standard. The C, H, and N analysis of the
compound was done on a Carlo Erba model EA1108 instrument. Mass spectra were
recorded on a Jeol JMS D-300 spectrometer.
Typical Procedure
A mixture of cellulose sulfuric acid (0.1 g), aldehyde (3.6 mmol), and
benzo[c][1,2,5]thiadiazole-4,5-diamine (3.0 mmol) was taken in a mortar and ground
with a pestle at room temperature for the appropriate time, as shown in Table 2.
Completion of the reaction was indicated by TLC monitoring. After completion
of the reaction, ethyl acetate (10 ml) was added, and the reaction mixture was washed
with water (6 ml). The organic layer was dried over anhydrous sodium sulfate and
concentrated to dryness, and the crude solid product was further purified by column
chromatography (hexane=ethyl acetate 8:2).
Water containing the catalyst could be evaporated under reduced pressure to
give a white solid. The recovered catalyst was washed with CH2Cl2 and dried in
an oven (50 mm Hg pressure) at 60 ꢁC for 5 h under high pressure prior to use in
another reaction. The recovered catalyst can be reused at least three additional times
in subsequent reactions without significant loss in product yield (Table 3).
Product Characterization Data
1
Compound 3a. Mp 185 ꢁC; IR (KBr, cmꢂ1): 1617, 3419; H NMR (CDCl3):
d ¼ 6.11 (s, 1H), 7.07–7.84 (m, 7H); EIMS, 70 ev, m=z: 252 (Mþ). Anal. calcd. for
C13H8N4S: C, 61.89; H, 3. 20; N, 22.21. Found: C, 61.83; H, 3.21; N, 22.24.
1
Compound 3l. Mp 270 ꢁC; IR (KBr, cmꢂ1): 1622, 3433; H NMR (CDCl3):
d ¼ 5.39 (s, 1H), 7.61–8.08 (m, 6H), 9.17 (s, 1H); EIMS, 70 ev, m=z: 320 (Mþ). Anal.
calcd. for C16H8N4O2S: C, 59.99; H, 2.52; N, 17.49. Found: C, 59.83; H, 2.64; N,
17.37.
Compound 3m. Mp 160 ꢁC; IR (KBr, cmꢂ1): 1612, 3406; 1H NMR (CDCl3):
d ¼ 5.40 (s, 1H), 7.58–8.12 (m, 7H); EIMS, 70 ev, m=z: 337 (Mþ). Anal. calcd. for
C16H8ClN5S: C, 56.89; H, 2.39; N, 20.73. Found: C, 56.09; H, 2.22; N, 20.13.

SYNTHESIS OF THIADIAZOLO BENZIMIDAZOLES
665
Yield (%)a
93
Table 2. Cellulose sulfuric acid–catalyzed synthesis of thiadiazolo benzimidazoles
Entry
1
Aidehyde
Product
Time (min)
2
2
3
2
3
95
90
4
5
6
3
3
2
90
95
90
7
8
3
3
2
2
90
86
82
9
10
80
(Continued )

666
B. S. KUARM ET AL.
Table 2. Continued
Entry
11
Aidehyde
Product
Time (min)
2.5
Yield (%)a
87
12
3
81
13
14
3
3
78
75
aYields refer to isolated pure products and were characterized by NMR, IR, and mass spectral data.
Table 3. Effect of reusability of catalyst on yield
Run
Cycle
Yielda (%)
1
2
3
4
0
1
2
3
95
94
91
85
Notes. Reaction conditions: Mixture of cellulose sulfuric acid (0.1 g), aldehyde
(3.6 mmol), and benzo[c][1,2,5]thiadiazole-4,5-diamine (3.0 mmol) was ground at
room temperature.
aYields refer to the pure isolated recovered catalyst.
1
Compound 3n. Mp 140 ꢁC; IR (KBr, cmꢂ1): 1653, 3492; H NMR (CDCl3):
d ¼ 2.12 (s, 3 H), 5.62 (s, 1H), 7.38–7.92 (m, 6H); EIMS, 70 ev, m=z: 351 (Mþ). Anal.
calcd. for C17H10ClN5S: C, 58.04; H, 2.86; N, 19.91. Found: C, 56.78; H, 2.23; N,
20.45.
Scheme 1. R ¼ aryl, chromone, quinoline.

SYNTHESIS OF THIADIAZOLO BENZIMIDAZOLES
667
CONCLUSIONS
In conclusion, this catalyst is an efficient, ecofriendly, and reusable acid
catalyst and has been prepared and utilized for the synthesis of biologically impor-
tant benzimidazoles via the condensation of benzo[c][1,2,5]thiadiazole-4,5-diamine
with different aldehydes under solid-state conditions. Prominent advantages of this
new methodology are the reusability of the catalyst, the operational simplicity, and
the excellent yields of product. We believe this methodology is superior to existing
methodologies for the synthesis of benzimidazoles.
ACKNOWLEDGMENT
Financial assistance from the Council of Scientific and Industrial Research
(Grant No. 01(2061)=06=EMR-II), New Delhi, is acknowledged.
REFERENCES
1. (a) Zarriumayeh, H.; Zimmerman, D. M.; Cantrell, B. E.; Schober, D. A.; Bruns, R. B.;
Gackenheimer, S. L.; Ornstein, P. L.; Hipskind, P. A.; Brittan, T. C.; Gchlert, D. R.
Structure–activity relationship of a series of diaminoalkyl substituted benzimidazole as
neuropeptide Y Y1 receptor antagonists. Bioorg. Med. Chem. Lett. 1999, 9, 647; (b)
Terzioglu, N.; Rijin, R. M. V.; Bakker, R. A.; Desch, I. J.; Lecurs, R. Synthesis and
structure–activity relationships of indole and benzimidazole piperazines as histamine H4
receptor antagonists. Bioorg. Med. Chem. Lett. 2004, 14, 5251.
2. (a) Erhardt, P. W. In search of the digitalis replacement. J. Med. Chem. 1987, 30, 231; (b)
Ries, U. J.; Mihm, G.; Narr, B.; Hasselbach, K. M.; Wittenben, H.; Entzeroth, M.; Meel,
J. C. A. V.; Wienen, W.; Hauel, N. H. 6-Substituted benzimidazoles as new nonpeptide
angiotensin II receptor antagonists: Synthesis, biological activity, and structure–activity
relationships. J. Med. Chem. 1993, 36, 4040; (c) Mann, J.; Baron, A.; Opoku–Boahen,
Y.; Johansson, E.; Parkinson, G.; Kelland, L. R.; Neidle, S. A new class of symmetric
bisbenzimidazole-based DNA minor groove binding agents showing antitumor activity.
J. Med. Chem. 2001, 44, 138; (d) Song, X.; Vig, B. S.; Lorenzi, P. L.; Darach, J. C.;
Townsend, L. B.; Amiadon, G. L. Amino acid ester prodrugs of the antiviral agent
2-bromo-5,6-dichloro-1-(b-d-ribofuranosyl) benzimidazole as potential substrates of
hPEPT1 transporter. J. Med. Chem. 2005, 48, 1274.
3. Zarrinmayeh, H.; Nunes, A. M.; Ornstein, P. L.; Zimmerman, A.; Gackenheimer, S. L.;
Bruns, R. F.; Hipskind, A.; Britton, T. C.; Cantrell, B. E.; Gehlert, D. R. Synthesis
and evaluation of a series of novel 2-[(4-chlorophenoxy)methyl]-benzimidazoles as selec-
tive neuropeptide Y Y1 receptor antagonists. J. Med. Chem. 1998, 41, 2709.
4. Zhao, J.; Arnaiz, D.; Griedel, B.; Sakata, B.; Dallas, J.; Whitlow, M.; Trinh, L.; Post, J.;
Liang, A.; Morrissey, M.; Shaw, K. Design, synthesis, and in vitro biological activity of
benzimidazole-based factor Xa inhibitors. Bioorg. Med. Chem. Lett. 2000, 10, 963–966.
5. Denny, W. A.; Rewcastle, G. W.; Bagley, B. C. Potential antitumor agents, 59: Structure–
activity relationships for 2-phenylbenzimidazole-4-carboxamides, a new class of minimal
DNA-intercalating agents which may not act via topoisomerase II. J. Med. Chem. 1990,
33, 814–819.
6. Forseca, T.; Gigante, B.; Gilchrist, T. L. A short synthesis of phenanthro[2,3-d]imidazoles
from dehydroabietic acid: Application of the methodology as a convenient route to
benzimidazoles. Tetrahedron 2001, 57, 1793–1799.

668
B. S. KUARM ET AL.
7. (a) Bai, Y.; Lu, J.; Shi, Z.; Yang, B. Synthesis of 2,15-hexadecanedione as a precursor of
muscone. Synlett 2001, 544–546; (b) Hasegawa, E.; Yoneoka, A.; Suzuki, K.; Kato, T.;
Kitazume, T.; Yangi, K. Reductive transformation of a,b-epoxy ketones and other com-
pounds promoted through photoinduced electron-transfer processes with 1,3-dimethyl-2-
phenylbenzimidazoline (DMPBI). Tetrahedron 1999, 55, 12957–12968.
8. Hisano, T.; Ichikawa, M.; Tsumoto, K.; Tasaki, M. Synthesis of benzoxazoles, benzothia-
zoles, and benzimidazoles and evaluation of their antifungal, insecticidal, and herbicidal
activities. Chem. Pharm. Bull. 1982, 30, 2996.
9. Tidwell, R. R.; Geratz, J. D.; Dann, O.; Volz, G.; Zeh, D.; Loewe, H. Diarylamidine
derivatives with one or both of the aryl moieties consisting of an indole or indole-like ring:
Inhibitors of arginine-specific esteroproteases. J. Med. Chem. 1978, 21, 613.
10. Sun, Q.; Yan, B. Single bead IR monitoring of a novel benzimidazole synthesis. Bioorg.
Med. Chem. Lett. 1998, 8, 361–364.
11. (a) Pertry, R. J.; Wilson, B. D. A novel palladium-catalyzed synthesis of 2-arylbenzimida-
zoles. J. Org. Chem. 1993, 58, 7016–7021; (b) Anastasiou, D.; Campi, E. M.; Chaouk, H.;
Jackson, W. R. Synthesis of benzimidazoles containing a fused alicyclic ring by
rhodium-catalysed hydroformylation of N-alkenyl-1,2-diaminobenzenes. Tetrahedron
1992, 48, 7467–7478; (c) Brain, C. T.; Brunton, S. A. An intramolecular palladium-
catalysed aryl amination reaction to produce benzimidazoles. Tetrahedron Lett. 2002,
43, 1893–1895.
12. (a) Wu, Z.; Rea, P.; Wickam, G. ‘‘One-pot’’ nitro reduction–cyclisation solid-phase route
to benzimidazoles. Tetrahedron Lett. 2000, 41, 9871–9874, and references cited therein; (b)
Mazurov, A. Traceless synthesis of benzimidazoles on solid support. Bioorg. Med. Chem.
Lett. 2000, 10, 67–70.
13. Chakrabarty, M.; Karmakar, S.; Mukherji, A.; Arima, S.; Harigaya, Y. Application of
sulfamic acid as an eco-friendly catalyst in an expedient synthesis of benzimidazoles.
Heterocycles 2006, 68, 967.
14. Gogoi, P.; Konwar, D. An efficient and one-pot synthesis of imidazolines and benzimida-
zoles via anaerobic oxidation of carbon–nitrogen bonds in water. Tetrahedron Lett. 2006,
47, 79.
15. Lee, K. J.; Janda, K. D. Traceless solid-phase synthesis of 5-benzoylbenzimidazoles. Can.
J. Chem. 2001, 79, 1556.
16. Lin, S.; Yang, L. A simple and efficient procedure for the synthesis of benzimidazoles
using air as the oxidant. Tetrahedron Lett. 2005, 46, 4315.
17. Beaulieu, P. L.; Hache, B., Von Moos, E. A practical oxone-mediated, high-throughput,
solution-phase synthesis of benzimidazoles from 1,2-phenylenediamines and aldehydes
and its application to preparative-scale synthesis. Synthesis 2003, 1683.
18. Singh, M. P.; Sasmal, S.; Lu, W.; Chatterjee, M. N. Synthetic utility of catalytic Fe(III)=
Fe(II) redox cycling towards fused heterocycles: A facile access to substituted benzimida-
zole, bisbenzimidazole, and imidazopyridine derivatives. Synthesis 2000, 1380.
19. Trivedi, R.; De, S. K.; Gibbs, R. A. A convenient one-pot synthesis of 2-substituted
benzimidazoles. J. Mol. Cat. A: Chem. 2005, 245, 8.
20. Massimo, C.; Francesco, E.; Francesca, M. Ytterbium triflate–promoted synthesis of
benzimidazole derivatives. Synlett 2004, 1832.
21. Itoh, T.; Nagata, K.; Ishikawa, H.; Ohsawa, A. Synthesis of 2-arylbenzothiazoles and
imidazoles using scandium triflate as a catalyst for both a ring closing and an oxidation
step. Heterocycles 2004, 63, 2769.
22. Ma, H. Q.; Wang, Y. L.; Wang J. Y. A simple KHSO4-promoted synthesis of 2-arylsub-
stituted benzimidazoles by oxidative condensation of aldehydes with o-phenylenediamine.
Heterocycles 2006, 68, 1669.

SYNTHESIS OF THIADIAZOLO BENZIMIDAZOLES
669
23. Ma, H. Q.; Wang, Y. L.; Li, J. P.; Wang, J. Y Selective synthesis of 2-aryl-1-arylmethyl-
1H-1,3-benzimidazoles promoted by ionic liquid. Heterocycles 2007, 71, 135.
24. Ahmad, S.; Ali, M. Cellulose sulfuric acid as a bio-supported and recyclable solid acid
catalyst for the one-pot, three-component synthesis of a-amino nitriles. Appl. Catal. A:
Gen. 2007, 331, 149.
25. Ahmad, S.; Ali, M.; Jafar, M. R.; Ebrahim, S. Cellulose sulfuric acid–catalyzed one-pot,
three-component synthesis of imidazoazines. Chem. Pharm. Bull. 2007, 55, 957.
26. Ahmad, S.; Abbas, R.; Zahra, B. Sulfonated cellulose and starch: New biodegradable
and renewable solid acid catalysts for efficient synthesis of quinolines. Catal. Commun.
2008, 9, 13.
27. Venu Madhav, J.; Thirupathi Reddy, Y.; Narsimha Reddy, P.; Nikhil Reddy, M.; Suresh,
K.; Crooks, P. A.; Rajitha, B. Cellulose sulfuric acid: An efficient biodegradable and
recyclable solid acid catalyst for the one-pot synthesis of aryl-14H-dibenzo[a.j]xanthenes
under solvent-free conditions. J. Mol. Catal. A 2009, 304, 85–87.
28. Narsimha Reddy, P.; Thirupathi Reddy, Y.; Nikhil Reddy, M.; Rajitha, B.; Crooks, P. A.
cellulose sulfuric acid: An efficient biodegradable and recyclable solid acid catalyst for the
one-pot synthesis of 3,4-dihydropyrimidine-2(1H)-ones. Synth. Commun. 2009, 39, 1257.
29. Suresh Kuarm, B.; Venu Madhav, J.; Vijaya Laxmi, S.; Rajitha, B.; Thirupathi Reddy, Y.;
Narsimha Reddy, P.; Crooks, P. A. An expeditious Pechmann condensation by using bio-
degradable cellulose sulfuric acid as a solid acid catalyst. Synth. Commun. 2010, 40, 3358.
30. Venu Madhav, J.; Suresh Kuarm, B.; Rajitha, B. Dipyridine copper chloride as a mild and
efficient catalyst for the solid state-synthesis of 2-substituted benzimidazoles. Arkivoc
2008, 13, 145–150.