an efficient catalyst for synthesis of 2-aryl-benzimidazole derivatives

E- ISSN: 2249 –1929Journal of Chemical, Biological and Physical SciencesAn International Peer Review E-3 Journal of SciencesAvailable online at www.jcbsc.orgResearch ArticleSection A: Chemical sciencePhenylboronic acid: an efficient catalyst forsynthesis of 2-aryl-benzimidazole derivativesSantosh V. Goswami, Prashant B. Thorat, Vijay N. Kadam and Sudhakar R. Bhusare*Department of Chemistry, Dnyanopasak College, Parbhani-431 401, MS, IndiaReceived: 8 August 2011; Revised: 29August; Accepted: 7September 2011ABSTRACTA simple and efficient method has been described for the synthesis of 2-aryl- benzimidazolederivatives from o-phenylenediamine and aromatic aldehydes using a mild phenylboronic acid as acatalyst at ambient temperature condition.Key words: 2-Aryl-benzimidazole, aromatic aldehyde, o-phenylenediamine, phenylboronic acid.INTRODUCTIONThe heterocyclic nucleus benzimidazole containing organic molecules have found to besignificant structural element in medicinal chemistry owing to its diverse biological activities.Benzimidazoles are also being developed as DNA minor groove binding agents with antitumoractivity 1 . Benzimidazole nucleus is acts as a ligand to transition metal, which will be more importantfor modeling biological systems.Benzimidazole derivatives exhibit significant activity against several viruses such as HIV, herpes(HSV-1), RNA, influenza, and human cytomegalovirus (HCMV) 2 . The widespread interest inbenzimidazole containing structures has promoted extensive studies for their synthesis. While manystrategies are available for benzimidazole synthesis, there are two general methods for the synthesis of2-substituted benzimidazoles. One is the coupling of o-phenylenediamine and carboxylic acids ortheir derivatives (nitriles, imidates, or orthoesters), which often requires strong acidic conditions, andsometimes combines with very high temperatures or microwave irradiation. The other way involves atwo-step procedure that includes the oxidative cyclo-dehydrogenation of Schiff bases, which are oftengenerated from the condensation of phenylenediamine and aldehydes. Various oxidative and catalyticJ. Chem. Bio. Phy. Sci. 2011, Vol.1, N0.2, Sec.A, 164-168. 164

Phenylboronic acid.....Sudhakar R. Bhusare et al.reagents such as DDQ 3 , Air 4 , sulfamic acid 5 , I 6 2 , FeCl 3·6H 2 O 7 , Oxone 8 , In(OTf) 9 3 , Yb(OTf) 10 3 ,Sc(OTf) 11 3 , KHSO 4 , IL 12 have been employed. Because of the availability of a vast number ofaldehydes, the condensation of o-phenylenediamine and aldehydes has been extensively used. Whilemany published methods are effective, some of these methods suffer from one or more disadvantagessuch as high reaction temperature, prolonged reaction time, and toxic solvents etc. Therefore, thediscovery of mild and practicable routes for synthesis of 2-substituted benzimidazoles continues toattract the attention of researchers.In recent years, solvent-free synthesis of benzimidazoles under microwave irradiation using KSFclay 13 , PPA 14 , metal halide supported alumina 15 and solid support 16 have been reported. Unfortunately,many of these processes suffer some limitations, such as drastic reaction conditions, low yields,tedious work up procedures and co-occurrence of several side reactions 17 .Here in we report first time the use of phenylboronic acid as catalyst for the synthesis of 2-arylbenzimidazole(Table-1) starting from o-phenylenediamine and aromatic aldehydes at ambienttemperature conditions. Boronic acids are mild Lewis acids which are generally stable and easy tohandle, making them important to organic synthesis. Phenylboronic acid is used in numerous crosscoupling reactions. Moreover in the C-C bond forming processes commonly use phenylboronic acidas a reagent.Table 1: Effect of phenylboronic acid on synthesis of 2-aryl-benzimidazole derivativesEntry Phenylboronic acid Product Time Yield (%) a(Mol %)(min)1 0 3a 45 trace2 5 3a 40 683 10 3a 20 754 15 3a 20 755 20 3a 20 906 25 3a 20 82a Isolated yield.EXPERIMENTALMelting points were determined in open capillary tube and are uncorrected. The purity of thecompounds has been checked by TLC. The IR spectra were recorded on Varian FTIR 640spectrometer. 1 H NMR spectra were recorded on Burker 300 MHz spectrometer in CDCl 3 as a solventand TMS as an internal standard.Typical procedure for Synthesis of 2-aryl-benzimidazoles: A mixture of aromatic aldehyde (10m.mol), o-phenylenediamine (10 m.mol), ethyl alcohol (15 mL) was added catalytic amount ofphenylboronic acid (20 mol %) and reaction mixture was stirred at room temperature for appropriatetime (Table 2- 3). After the completion of reaction indicated by thin layer chromatography (pet ether:ethyl acetate; 8:2), reaction mixture was poured into crushed ice. Obtained precipitate was filtered anddried to give pure product Scheme 1. All of the compounds are identified from their spectral data andby comparing their melting points with those reported in literature.J. Chem. Bio. Phy. Sci. 2011, Vol.1, N0.2, Sec.A, 164-168. 165

Phenylboronic acid.....Sudhakar R. Bhusare et al.Table 2: Effect of solvents on synthesis of 2-aryl-benzimidazole derivativesEntry Phenylboronic acid Solvent Time Yield (%) a(Mol %)(min)1 20 DCM - -2 20 DMF 35 563 20 CH3CN 25 524 20 H20 40 685 20 EtOH 20 90a Isolated yield.Table 3: Synthesis of 2-aryl-benzimdazole:Entry R Product Time(min)Mp (°C)Yield (%) a1 4-Cl 3a 20 285-2882 902 4-NO 2 3b 25 310-3112 823 2-Cl 3c 10 228-2302 854 2-Br 3d 15 230-231 845 2-OH 3e 30 205-206 756 4-OCH 3 3f 40 220-2232 777 4-CN 3g 45 255-257 888 3,4-(OCH 3 ) 2 3h 35 230-231 829 3-NO 2 3i 25 198-2012 8610 4-H 3j 20 284-2872 8211 4-CH 3 3k 30 264-2652 8512 5-Br, 2-OH 3l 35 241-242 78a Isolated yield.Spectral data of representative compounds:(3a) 2-(4-Chlorophenyl)-(1H)-benzimidazole: IR (KBr): 3042, 1452, 1408, 1278, 968, 750 cm-1;1 H-NMR (300 MHz, CDCl 3 ): δ 7.19-7.79 (m, 6H), 8.20 (d, 2H), 12.9 (s, 1H); Mass (LC/MS): m/z229.225 (M+); Anal. Calcd for C 13 H 9 ClN 2 : C, 68.28; H, 3.97; Cl, 15.50; N, 12.25 Found: C, 68.31; H,3.98; Cl, 15.52; N, 12.23.J. Chem. Bio. Phy. Sci. 2011, Vol.1, N0.2, Sec.A, 164-168. 168

Phenylboronic acid.....Sudhakar R. Bhusare et al.(3i) 2-(3-Nitrophenyl)-(1H)-benzimidazole: IR (KBr): 3053, 1530, 1443, 1352, 983, 748 cm-1; 1 HNMR (300 MHz, CDCl 3 ): δ 7.20-7.79 (m, 4H), 8.41 (m, 4H), 13.1 (s, 1H); Mass (LC/MS): m/z238.224 (M+); Anal. Calcd for C 13 H 9 N 3 O 2 : C, 65.27; H, 3.79; N, 17.56; O, 13.38 Found: C, 65.29; H,3.81; N, 17.53; O, 13.36.RESULT AND DISCUSSIONIn order to find out most favorable condition for the synthesis of 2-aryl-benzimidazole, a modelreaction is performed using different ratios of phenylboronic acid as catalyst with o-phenylenediamineand p-chlorobenzaldehyde. We found that very little of the desired product was obtained in theabsence of phenylboronic acid and the best yields were obtained with 20% phenylboronic acid (Table(1). We have also made sure the effect of solvent on reaction rate using different solvents likedichloromethane, dimethylformamide, acetonitrile, water and ethanol. Our observations are presentedin Table 3 that the ethanol stands to be the best solvent of choice, with its shorter reaction time andhigh yield.Our results demonstrate that phenylboronic acid is very effective, environmentally friendlycatalyst for the synthesis of 2-aryl-benzimidazole derivatives in good to excellent yields. The methodoffers several advantages such as mild reaction conditions, short reaction time, high yields, and asimple experimental operation leading to a useful and attractive process for the preparation of 2-arylbenzimidazolederivatives.CONCLUSIONIn summary, we have demonstrated a novel and facile method for the synthesis ofbenzimidazoles by using phenylboronic acid as a promoter under mild reaction conditions. Theadvantages of the present method include high yields of products, simple experimental procedure andnon-toxicity of the reagent. The product were obtained were isolated in satisfactory yields byconventional work up. Both analytical and spectroscopic data of synthesized compounds are in fullagreement with the proposed structures.ACKNOWLEDGEMENTWe acknowledge Dr. P. L. More and Dr. W. N. Jadhav, Dnyanopasak College, Parbhani forproviding necessary facilities and Financial support for this work by DST-SERC, New Delhi(SR/FT/CS-023/2008) is highly appreciated.REFERENCES1. M. Kidwai, A. Jahan, D. Bhatnagar, J. Chem. Sci. 2010, 122, 607.2. H. Xiangming, M. Huiqiang, W. Yulu, Arkivoc 2007, 13, 150.3. K. J. Lee, K. D. Janda, Can. J. Chem. 2001, 79, 1556.4. S. Lin, L. Yang, Tetrahedron Letter 2005, 46, 4315.5. M. Chakrabarty, S. Karmakar, A. Mukherji, S. Arima., Y. Harigaya, Heterocycles2006, 68, 967.J. Chem. Bio. Phy. Sci. 2011, Vol.1, N0.2, Sec.A, 164-168. 167

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