%0 Journal Article
%T A Convenient, TiCl4/SnCl4-Mediated Synthesis of N-Phenyl or N-Aryl Benzamidines and N-Phenylpicolinamidines
%A Umesh D. Patil
%A Pramod P. Mahulikar
%J ISRN Organic Chemistry
%D 2012
%R 10.5402/2012/963195
%X A new, TiCl4-or SnCl4-mediated, solvent-free method was developed for the synthesis of N-Aryl benzamidines and N-phenylpicolinamidines, in moderate-to-good yield, using suitable amines and nitriles as starting materials. 1. Introduction The amidine nucleus is found in a wide variety of biologically active molecules [1]. N-Aryl amidine exhibits activity against Mycobacterium tuberculosis, and N-alkylfuramidine shows antiprotozoan and antimicrobial activities [2]. Similarly various amidines derived from 4-amidino-2-(2-pyridyl)quinazoline [3] and 1-amino-3-(2-pyridyl)isoquinoline [3], guanidine [4], diguanidino [5], reversed diamidino 2,5-diarylfuran [5], benzimidazole [6], pyridine [7], exhibit antimycoplasmal, antimalarial, antimicrobial, antibacterial, anti-inflammatory activities. An extensive number of monoamidines have been evaluated for their utility in blocking various stages of the thrombin cascade, and numerous highly potent molecules have been reported [8]. Amidines were used as important synthon in organic synthesis in the preparation of various heterocyclic compounds, such as pyridine [7, 9], pyrimidines [9, 10], imidazoles [11], pyrazolopyrimidine [12], iminopyrimidine [13], imidazopyridine and pyrimidinopyridine [14], purine [15], benzimidazole [16], pyrimidines [17], triazaphenalene [18], triazine [19], tetraazole [19], thiadiazine [20], oxazolotriazole [21], diazirine [22], triazolopyridine [23], azetidinone [24], and pyrrole, and also used as complexing agent [25]. Several synthetic strategies have been developed for the synthesis of amidines, in which the nucleophilic addition of amine to nitrile is the most popular. Generally, nitriles were activated to the intermediate salt in the presence of EtOH/HCl [26] or NH4Cl/MeOH [27] under anhydrous condition and then reacted with amine to get amidine. While for unreactive nitriles, Lewis acid or other condensing agents were used such as anhydrous AlCl3, ZnCl2 [28], CuCl [29], Ln (III) salts [30], CaCl2 [31], Al(CH3)3 [32], SmI2 [33], Ytterbium amide [34], MeSO3H [20], and anhyd. SnCl4 [21]. Amides can be converted to imidoyl chloride using PCl5 [35, 36], which can then react with primary or secondary amine to yield amidine. In addition, amide can be O-alkylated with triethyloxonium fluoroborate at ambient temperature to yield the corresponding imidic ester fluoroborate, which then reacts with amine to yield the targeted amidine [3]. Iron pentacarbonyl was employed to the conversion of amidoximes into amidines via reductive cleavage of the N=O bond [37]. Sometimes, strong bases like LiHMDS,
%U http://www.hindawi.com/journals/isrn.organic.chemistry/2012/963195/