ONE-POT SYNTHESIS OF 2,4,5-TRISUBSTITUTED IMIDAZOLE DERIVATIVES CATALYZED BY BTPPC UNDER SOLVENT-FREE CONDITIONS

ABSTRACT. A simple and efficient method for one-pot synthesis of lophine derivatives (2,4,5-trisubstituted imidazoles) by using the benzyltriphenylphosphonium chloride (BTPPC), as a catalyst, under solvent-free conditions is described. BTPPC is an available and inexpensive catalyst; also, it can be easily supplied. This procedure led to the corresponding 2,4,5-trisubstituted imidazoles products in high yields.

BTPPC is a crystalline quaternary phosphonium salt which finds its application in Wittig reactions [29] and in phase transfer catalysis [30]. Very recently, we have reported the one-pot synthesis of dihydropyrimidinones/thiones under solvent-free conditions using BTPPC as a catalyst [31].
In this paper, we describe an efficient and practical route for the synthesis of lophine derivatives under solvent free conditions using BTPPC as catalyst (Scheme 1).

RESULTS AND DISCUSSION
In a model reaction, in the presence of the catalyst (15 mol%), the mixture of benzaldehyde (1 mmol), benzil (1 mmol) and NH 4 OAc (2 mmol) as ammonia source, stirred at 100 o C under solvent free conditions. The 2,4,5-triphenyl imidazole are obtained in 92% yield. Various kinds of substituted benzaldehydes were also subjected in the presence of BTPPC at 100 o C under solvent free conditions (Table 1).  We found that for aldehydes bearing either electron withdrawing or electron-releasing substituents in the ortho, meta or para positions; the reaction proceeded very efficiently in all cases. This procedure provides 2-aryl-4,5-diphenyl imidazoles directly, in relatively short reaction times and high yields. Furthermore, we used benzoin instead of benzyl and in this case corresponding products were achieved in good yields. In all cases, complete conversion was observed after appropriate time and the products were readily isolated in very high yields. A reasonable reaction mechanism for the BTPPC catalyzed is shown in Scheme 2.
BTPPC In summary, a one-pot, multicomponent methodology has been developed for the synthesis of lophine derivatives catalyzed by BTPPC in high yields. Moreover, easy work-up, clean reaction profiles, low cost, availability, low toxicity, stable under normal temperatures and pressures of the catalyst, and short reaction time make this methodology a valid contribution to the existing processes in the field of 2-aryl-4,5-diphenyl imidazole derivatives synthesis.

EXPERIMENTAL
All the chemicals were obtained from Merck and Fluka Company. The melting points were obtained using an Electrothermal IA 9100 digital melting point apparatus. NMR spectra were recorded on a 400 MHz spectrometer using TMS as internal standard.
Preparation of BTPPC. To prepare BTPPC, 10 mmol (3.26 g) of PPh 3 and 10 mmol (1.26 g) of benzyl chloride were carefully dissolved in 15 mL of DMF, and the mixture was stirred at 80 o C. After 2 the resulting white precipitate was collected and washed with Et 2 O (3×20 mL) and dried in a desiccator to afford a white solid. M.p. 335 o C [37].
General procedure for preparation of 2-aryl-4,5-diphenyl derivatives. A mixture of aldehyde (1 mmol), benzyl/benzoein (1 mmol) and NH 4 OAc (2 mmol), as ammonia source, and BTPPC (15 mol %) stirred at 100 o C under solvent free conditions. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mixture was dissolved in ethanol and poured into water. The resulting precipitate was filtered and purified by recrystallization from ethanol to afford the desired compound in pure form. All products were identified by comparison of their physical and spectroscopic data with those reported for authentic samples.