INTRODUCTION:

The benzimidazole structural motif has been of great interest in many applications, especially in pharmaceuticals, owing to its broad range of biological functions [1-5] and thus considerable effort has been expended to develop efficient methods for the preparation of benzimidazole derivatives.[6,7] Common methods involve condensation of o-phenylenediamine with carbonyl-containing compounds, such as aldehydes, carboxylic acid, and acid halides, in the presence of various catalysts and hazardus solvent [scheme 1].[8,9] Despite their efficiency, many currently available methods have limitations, such as the use of hazardous and costly materials or the requirement for harsh reaction conditions. (high temperature/pressure or the use of a microwave).

Recently, several methods have been developed, for the synthesis of benzimidazole derivative like use of catalyst such as sulphur, ultrasonic, Lewis acids like pyridinium-p-toluenesulfonate, ionic liquids like polyaniline-sulfate and Zeolite. But, all of this reported method has several disadvantages such as, use of organic solvents, harsh reaction conditions, prolonged reaction times, use of expensive reagents. To overcome all these disadvantages here we report a practical, inexpensive and green method for the synthesis of benzimidazole derivatives under solvent free-condition.

Therefore, the development of more efficient, convenient, and eco-friendly methods is still desired. Herein, we present an efficient, green process,[10] which uses ultra violate light irradiation [11,12] for benzimidazole synthesis from o-phenylenediamine and a variety of aldehydes in the presence catalytic amount of zinc sulphate under solvent free condition[Scheme 2] synthesized moieties are conformed on the basis of physical and spectral study.

RESULT AND DISCUSSION:

Benzimidazole synthesis was examined by using o-phenylenediamine (1) and substituted aromatic benzaldehydes (2a-n). Desired benzimidazole product (3a-n) was obtained in the presence of catalytic amount of zinc sulphate under Ultra –Violate light irradiation, in solvent free condition.

Screening of the catalyst for this reaction revealed that ZnSO₄7H₂O was the best catalyst for the process in term of product yield and reaction time. The reaction was also screening over different catalyst and different solvents (Table I). Reaction gives in good yield in solvent free condition also. Based on these screening experiments, the optimal reaction conditions were identified as 1 eqiv. of diamine (1), 1 equiv. Substituted aromatic aldehydes (2a-n) and 1 eqiv. Zinc sulphate irradiated under UV lamp.

With the optimized conditions in hand, we proceeded to investigate the scope and generality of this procedure using rang of various substituted aromatic aldehyde. As shown in Table 2, the corresponding products being formed in generally good yields (Table 2). Desired compounds were conformed through analytical and spectral data.

EXPERIMENTAL:

All the chemicals were obtained from commercial suppliers and used after further purification. All the melting points were determined in open capillary tubes and were uncorrected. The IR spectra (in cm^-1) were recorded on a perkin-Elmer spectrophotometer in KBr pellets. ¹HMR spectra were recorded on Varian Gemini (200 MHz) spectrometer using DMSO-d6 as solvent and TMS as an internal standard.¹³C-NMR spectra recorded on 50 MHz in DMSO-d6 solvent, in δ ppm. All chemical shifts values are reported in δ scale downfield from TMS. Homogeneity of the compound was checked by TLC on silica gel plates.

General procedure for the synthesis of Benzimidazole Derivatives:

O- phenylenediamine (0.01 mole) where stirred with aromatic aldehydes (0.01 mole) and ZnSO₄7H₂O under UV light lamp for 30-40 minutes, reaction time was monitored by TLC using solvent system CH₂Cl₂ and MeOH (9:1). Resulting precipitate was washed with water several times and recrestilised from ethanol.

Spectral study of synthesized products 3 (a-n)

2-Phenyl-1H-benzimidazole (3a):

IR (KBr) in cm^-1: 3048, 1460, 1418, 1280,972, 745.

¹H-NMR spectrum (200MHz, DMSO-d6, in δ ppm): 12.5 (s, 1H, NH), 7.92 (m, 2H), 7.25-7.38

(m,5H), 7.10 (m, 2H);

¹³C-NMR (50 MHz,DMSO-d6,in δ ppm): 114.7, 120.4, 128.4, 126.2, 128.4, 129.6, 130.0, 134.6,

143.5, 153.0.

2-(3-Nitrophenyl)-1H-benzimidazole (3c):

IR (KBr in cm^-1): 3060, 1524, 1450, 1357, 973, 746.

¹H-NMR (in δ ppm): 12.5 (s, 1H, NH), 8.86 (s, 1H), 8.46 (d,1H, J=6 Hz), 8.14 (d, 1H, J=7 Hz),

7.67 (t, 1H, J=7.2 & 6 Hz), 7.53 (m, 2H), 7.2 (m, 2H)

¹³C-NMR (in δppm): 115.3, 124.1, 123.1, 122.4, 132, 131.6, 134.6, 138.6, 50.2, 150.5.

2-(4-Chlorophenyl)-1H-benzimidazole (3e):

IR (KBr in cm-1): 3041, 1450,1402, 1280, 965, 750;

¹H-NMR (in δ ppm): 12.8 (s, 1H, NH), 8.25 (d, 2H, J=8.5 Hz), 7.8 (d, 2H, J=8.4 Hz), 7.34

(m,2H), 7.15 (m, 2H).

¹³C-NMR (in δ ppm): 116.4, 124.1, 128.8, 128.9, 130.4, 134.3, 138.9, 152.9.

2-(4-Methoxyphenyl)-1H-benzimidazole (3g):

IR (in cm^-1): 3450, 2242, 2120, 1655, 1045.

¹H NMR (in δ ppm): 12.62 ( s, 1 H, NH), 8.22 (dd, 2 H, J = 8.0,4.0 Hz,), 7.62 (d, 1 H, J = 8.0

Hz), 7.45 (d, 1 H ,J = 8.0 Hz), 7.24–7.10 (m, 2 H), 7.13 (d, 2 H ,J = 8.0 Hz,), 3.86 (s, 3 H).

¹³C NMR (in δ ppm): 150.38, 145.86, 138.88, 125.22, 124.67, 122.19, 121.40, 120.46, 116.30,

115.16, 58.31, 14.17.

2-[4-(2-propyl)phenyl]-1H-benzimidazole (3i):

IR (in cm^–1): 3456, 2350, 2127, 1665,1073.

¹H NMR (in δ ppm):= 12.76 (br. s, 1 H, NH), 8.15 (d, 2 H, J =8 Hz), 7.71–7.65 (m, 2 H), 7.36

(d, 2 H, J = 8 Hz), 7.22–7.15 (m, 2 H), 2.95 (hept.1 H ,J = 6.2 Hz,), 1.26 (d, 6H ,J = 6.2 Hz).

¹³C NMR (in δ ppm): 150.33, 147.40, 143.85, 136.16, 126.77, 125.94, 126.43, 122.23, 120.65,

115.56, 112.20, 43.30, 24.00.

2-(4-Fluorophenyl)-1H-benzimidazole (3k):

IR (in cm^–1): 3450, 2268, 2120, 1659, 1026, 833.

¹H NMR (in δ ppm): 13.21 (s, 1H, NH), 8.26 (dd, 2H ,J = 8.5 & 5.6 Hz), 7.55–7.46 (m, 2 H), 7.35 (dd, 2 H ,J = 8.5 & 5.7 Hz), 7.26–7.15 (m, 2 H).

¹³C NMR (in δ ppm): 165.62, 155.16, 145.86, 134.68, 130.14, 125.74, 124.26, 120.17, 112,110.88.

2-[3-(Trifluoromethyl)phenyl]-1H-benzimidazole (3m):

IR (in cm^–1): 3440, 2350, 2134, 1656, 1034, 832.

¹H NMR (in δ ppm): 12.65 (s, 1H, NH), 8.45 (s, 1H), 8.50 (d, 1 H, J =7.7 Hz), 7.82 (d, 1 H ,J = 7.5 Hz), 7.80 (dd, 1 H, J =7.7& 7.5 Hz), 7.72–7.65 (m, 2 H), 7.36–7.28 (m, 2 H).

¹³CNMR (δ):= 171.87, 150.57, 137.10, 128.65, 125.94, 124.93, 122.47.

2-(4-Bromophenyl)-1H-benzimidazole (3n):

IR (in cm^–1):3325, 2167, 2119, 1650, 1035, 827.

¹H NMR (in δ ppm): 12.65 ( s, 1H, NH), 8.20 (d, 2H J = 8.5 Hz), 7.66 (d,2 H J = 8.5 Hz), 7.66–7.48 (m, 2 H), 7.23–7.12 (m, 2H).

¹³C NMR (in δ ppm): 155.14, 130.85, 127.56, 128.8, 125.22, 123.37.

Table 1. Effect of various catalyst and solvent on the reaction of o-phenylenediamine with benzaldehyde.

Entry	Catalyst	Solvent	Condition	Yield (%)
1	PPA	Pyridine	Reflux at 180 ^oC	75
2	SiO₂	Solvent free	MW irradiation	0
3	No catalyst	Methanol	UV lamp	80
4	FeCl₃ 6 H₂O	Solvent free	UV lamp	60
5	No catalyst	DMF	UV lamp	50
6	Zn(OAc)₂	Solvent free	MW irradiation or UV lamp	70
7	ZnSO₄.7H₂O	Solvent free	UV lamp	90

Table 2. Analytical Data of Synthesized Compounds 3(a-n)

Entry	Product	Yield (in %)	M.P. (in ^oC)
3a		90	290
3b		92	256
3c		88	309
3d		92	314
3e		89	293
3f		90	164
3g		86	234
3h		92	238
3i		80	243
3j		90	224
3k		92	245
3l		84	131
3m		95	265
3n		90	260

CONCLUSIONS:

An efficient and eco-friendly process for the synthesis of benzimidazoles was developed by using o-phenylenediamine and aromatic aldehyde under solvent free condition and presence of catalytic amount of ZnSO₄7H₂O. This remarkable process required only UV light lamp. The use of UV light lamp significantly improved the reactivity. We present our protocol as an efficient and more ecofriendly alternative to the current methods of benzimidazole derivatisation.

ACKNOWLEDGEMENT:

The author is grateful to the authorities of M.M. Nilanga, Rahemaniya Jr. College, Nilanga, Rajarshi Shahu College, Latur and Shivneri Mahavidhyalaya, Shirur (A) for their encouragement for this work.

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