Novel and Improved Method for the Synthesis of 2-Mercaptobenzimidazole Derivatives

Abstract

2-mercaptobenzimidazole derivatives were synthesized by reaction of o-phenylenediamines with N-aminorhodanine. This reaction represent a new synthesis of 2-mercaptobenzazole. The structure of the obtained products was established by spectroscopic data.

Introduction

Thiols are very useful building blocks for the synthesis of various organosulfur compounds: they have several applications in organic synthesis, in bioorganic, medicinal and heterocyclic chemistry [1]. Also, in addition to that, thiols can act as safety-catch linker in peptide chemistry [2]. Morever, thiols have been employed as sulfur-based ligands in transition metal complexes[3, 4]. In this respect, a number of synthetic methods for the preparation of thiol derivatives by the reaction of o-phenylendiamine with carbon disulphide [5, 9], thiourea [10, 11], O-isopropylxanthic acid potassium salt [12], 5-phenyl-1,3,4-oxadiazole-2(3H)-thione derivatives and N-phenylisothiocyanate [13], thiocyanic acid ammoniac salt [14]. In continuation of our research concerning benzimidazoles[15, 19]. The condensation of o-phenylenediamine with N-aminorhodanine was carried out.

Experimental Section

General Procedure

O-phenylenediamines (0.065 mol) was heated with N-aminorhodanine (0.065 mol) in xylem (50 ml) for 5 hours. The obtained residue was filtered and was crystallized from aqueous alcohol (charcoal). The obtained solid was recrystallized in ethanol.

2-mercaptobenzimidazole 3a

Yield = 87 %; mp>250°C.1HNMR (DMSO-d6): 7.10 (m, 2Har); 7.27 (m, 2Har); 12.42 (s,

NH).13CNMR (DMSO-d6): 119.43 (CH); 126.36 (CH); 138.82 (C); 167.12 (C=S). HRMS, m/z: 150(M), calcd for C₇H₆N₂S: 150.02517, found: 150.0251.

2-mercapto-5-nitrobenzimidazole 3b

Yield = 81 %; mp>250°C.1HNMR (DMSO-d6): 7.12 (d, JAB= 8.3Hz, 1Har); 7.29 (q, JBX=2.1Hz, JAB= 8.3Hz, 1Har); 7.46 (d, JBX= 2.1Hz, 1Har); 12.03 (s, NH).13CNMR (DMSO-d6):108.24 (CH); 113.46 (CH); 125.70 (CH); 137.45 (C); 141.94 (C); 148.01 (C); 167.54 (C=S).HRMS, m/z: 195(M), calcd for C₇H₅N₃O₂S: 195.01025, found: 195.0102.

2-mercapto-5-methylbenzimidazole 3c

Yield = 83 %; mp>250°C. ¹HNMR (DMSO-d₆): 2.21(s, CH₃); 6.43 (d, JAB= 8.3Hz, 1Har); 6.83 (q, JBX=1.7Hz, JAB= 8.3Hz, 1Har); 7.05 (d, JBX= 1.7Hz, 1Har); 12.03 (s, NH). ¹³CNMR (DMSO-d₆): 21.31 (CH₃); 109.50 (CH); 109.99 (CH); 123.49 (CH); 130.69 (C); 131.92 (C); 132.95 (C); 168.12 (C=S). HRMS, m/z: 164(M), calcd for C₉H₈N₂S: 164.04082, found: 164.0408.

5-chloro-2-mercaptobenzimidazole 3d

Yield = 79 %; mp>250°C. 1HNMR (DMSO-d6): 6.81 (d, JAB= 7.9Hz, 1Har); 7.03 (q, JBX=

1.9Hz, JAB= 7.9Hz, 1Har); 7.25 (d, JBX= 1.9Hz, 1Har); 11.83 (s, NH).13CNMR (DMSO-d6):101.34 (CH); 109.64 (CH); 123.71 (CH); 135.54 (C); 140.84 (C); 146.14 (C); 165.24 (C=S). HRMS, m/z: 183(M), calcd for C₇H₅ClN₂S: 183.9962, found: 183.996.

5,6-dichloro-2-mercaptobenzimidazole 3e

Yield = 75 %; mp>250°C. ¹HNMR (DMSO-d₆): 7.79 (s, 1Har); 11.82 (s, NH). ¹³CNMR (DMSO-d₆): 128.60 (CH); 127.25 (C); 135.49 (C); 168.30 (C=S). HRMS, m/z: 217(M), calcd for C₇H₄N₂S: 217.94722, found: 217.9472.

5,6-dimethyl-2-mercaptobenzimidazole 3f

Yield = 80 %; mp>250°C. ¹HNMR (DMSO-d₆): 2.32(s, CH₃); 7.02 (s, 1Har); 12.63 (s, NH). ¹³CNMR (DMSO-d₆): 20.43 (CH₃); 111.00 (CH); 131.25 (C); 131.59 (C); 168.00 (C=S). HRMS, m/z: 178(M), calcd for C₉H₁₀N₃S: 178.05647, found: 178.0564.

Result and Discussion

In this work, we report a novel method for synthesis of 2-mercaptobenzimidazole derivatives. 2- Mercptobenzimidazoles are interesting starting compounds because of their chemical reactivity and biological activities. A mixture of o-phenylenediamines 1(a-g) and N-aminorhodanine in xylene was heated during 8 hours. (Scheme 1). The structure of the products 2(a-g) has been determined by NMR and mass data. 1HNMR spectra showed the presence of the signal of NH and the signal of the C=S was observed in 13CNMR spectra which confirms the structure of the products 2(a-g).

Scheme 1: The reaction of 2-mercaptobenzimidazoles synthesis

A possible mechanism for the formation of the 2-mercaptobenzimidazole (2a-g) is shown in scheme 2. The key step is at the intermediate A, in which the cyclization goes to the C=S group not to C=O group in order to lead to the benzotriazepine product. In the reaction, the only 2-mercaptobenzimidazole product was obtained (Scheme 2)

Scheme 2: Proposed formation mechanism of the product

Conclusion

In this work, we developed a novel and improved method for 2-mercaptobenzimidazole derivatives by the condensation of o-phenylenediamines with N-aminorhodanine

Aknowledgements

This work has been supported by the Chouaib Doukkali University

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