Benzimidazole liquid-phase synthesis

Utilizing the same aryl fluoride linker on conventional MeOPEG polymer, these authors also presented a microwave-accelerated liquid-phase synthesis of benzimidazoles (Scheme 7.70) [79]. This bicydic pharmacophore is an important and valuable structural element in medicinal chemistry, showing a broad spectrum of pharmacological activities, such as antihistaminic, antiparasitic, and antiviral effects. 

Su et al. [35] gave the mercury (ll)-catalyzed liquid phase synthesis of 1,2-disubstituted benzimidazoles (xxviii) by utilizing SnAt reactions, reduction and cyclization reaction. Tbe yield of the product ranged between 73-90%. 

Chen C, Chen YJ (2004) Liquid-phase synthesis of 2-substituted benzimidazoles, benzoxazoles and benzothiazoles. Tetrahedron Lett 45 113-115... 

Using polymer-immobilized liquid phase synthesis and controlled microwave irradiation, trisubstituted bisbenzimidazoles have been prepared and released with good yield and purity [77]. Furthermore, a wide range of benzimidazole derivatives have been synthesized with excellent yields and purities by simple washing and filtration using liquid phase synthesis on a soluble polymer support [78]. 

Cyclization to the desired head-to-taU-linked bis-benzimidazoles can also be performed by reaction of aryl or alkyl isothiocyanates with N,N -dicyclohexylcarbodi-imide (DCC) [83]. In a closely related and more recent study by the same group, mercury chloride was used as a catalyst to perform cyclization to the benzimidazoles [84]. Another application of the bis-hydroxylated polymer support PEG 6000, microwave-accelerated liquid-phase synthesis of thiohydantoins, has been reported [85, 86]. 

We next explored the applications of liquid-phase synthesis of benzofused heterocycles from a common building block PEG-bound nitro-activated aryl fluoride (Fig. 8). In these synthetic strategies, we created multiple accesses to the structurally diverse core molecules based on a fundamental scaffold 10. We focused on the construction of a variety of benzimidazole libraries starting from a versatile synthon 4-fluoro-3-nitrobenzoic acid via liquid-phase nucleo-... 

Bendale, P.M. and Sun, C.-M., Rapid microwave-assisted liquid-phase combinatorial synthesis of 2-(arylamino)benzimidazoles, /. Comb. Chem., 2002, 4, 359-361. 

As part of an efficient, facile and practical liquid-phase combinatorial synthesis of benzimidazoles under microwave irradiation, the reduction of a polymer bound o -nitroaniline with zinc metal in methanol was completed in a very short time (2 min)61 (Scheme 4.33). However, no detailed reaction conditions were given. 

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