One-Pot Synthesis of 2，4，5-Triaryl-1HImidazoles Catalyzed by NH4H2PO4-SiO2 under Solvent-Free Conditions

Zhou Zhongqiang，Deng Xiaocui，Zhang Yuliang，Wu Lamei

(College of Chemistry and Materials Science，South-Central University for Nationalities，Wuhan 430074，China)

Imidazole derivatives have a wide range of biological activities，including antiparasitic［1］，antitubercular［2］，and antiviral［3］activity.The reported method for one-pot synthesis of 2，4，5-triaryl-1H-imidazoles involves three-component condensation of aromatic aldehydes，ammonium acetate，benzil or benzoin in the presence of catalysts such as InCl3·3H2O［4］，ammonium metavanadate［5］，cellulose sulfuric acid［6］，boric acid［7］，Yb(OTf)3［8］，potassium aluminum sulfate［9］，ZrOC12·8H2O［10］，NiCl2·6H2O［11］，L-proline［12］，AcOH［13，14］，KH2PO4［15］，PEG-400［16］，and iodine［17］.In spite of their potential utility，many of these methods suffer from some limitations such as tedious work-up procedures，requirement of special apparatus，use of environmentally unfavorable solvents and difficulty in recovery and reusability of catalysts.Thus，a simple and efficient processe for synthesis of 2，4，5-triaryl-1H-imidazoles is currently needed.Solvent-free reactions provide environmental-friendly and cost-effective methods because of their good efficiency，reduced reaction and workup times，leading to energy savings［18］.Recently，one synthetically useful organic transformation using silica-supported ammonium dihydrogen phosphate(NH4H2PO4-SiO2)as a catalyst has been reported in the literature［19］.Herein，we report a simple，efficient and environmentallybenign procedureforone-pot synthesis of 2，4，5-triaryl-1H-imidazoles by three-component condensation of aromatic aldehydes，benzil and ammonium acetate using NH4H2PO4-SiO2as a catalyst under solvent-free conditions(Fig.1).

1 Experiment

1.1 Experiment instrument

FT-IR spectra were obtained on a Nexus 470 spectrophotometer.1H NMR and13C NMR spectra were recorded on a Bruker AvanceⅢ400 with TMS as internal standard.Melting points were determined on a melting point apparatus and were uncorrected.Mass spectra were recorded on Agilent 6120 using electrospray ionization technique.

1.2 Synthesis of 2，4，5-triaryl-1H-imidazoles

NH4H2PO4-SiO2was prepared according to the literature method［19］.A mixture of aromatic aldehyde(5 mmol)，benzil(5 mmol)，ammonium acetate(10 mmol)and NH4H2PO4-SiO2(200 mg)was stirred at 130℃ at the appropriate time indicated in Tab.2.The progress of the reaction was monitored by thin-layer chromatography［V(ethyl acetate)∶ V(petroleum ether)=1∶5 as eluent］.Then the reaction mixture was cooled to room temperature and diluted with THF.The solid (catalyst)wascollected byfiltration.Evaporation of the filtrate yielded the product，which was purified by recrystallization from methanol，if necessary.Some characterization data ofselected known products are given below.

2，4，5-Triphenyl-1H-imidazole(Tab.3，Entry 1):IR(KBr，cm－1):3424，3041，2972，1601，1490，1461，1126，1072，769，733，697.1H NMR(400 MHz，CDCl3/DMSO-d6)δ:7.29～7.63(m，13H)，8.12(d，J=7.6 Hz，2H).13C NMR(100 MHz，CDCl3/DMSO-d6)δ:125.9，127.6，128.4，128.7，128.8，129.1，131.1，146.3.MS(ESI):m/z=297.2［M+H］+.

2-(4-Methoxyphenyl)-4，5-diphenyl-1H-imidazole(Tab.3，Entry 3):IR(KBr，cm－1):3418，3056，2963，1611，1496，1446，1290，1248，1177，1130，1032，969，832，768，730，697.1H NMR(400 MHz，CDCl3/DMSO-d6)δ:3.85(s，3H)，6.97(d，J=8.4 Hz，2H)，7.27～7.76(m，10H)，8.06(d，J=8.4 Hz，2H).13C NMR(100 MHz，CDCl3/DMSO-d6)δ:55.7，114.5，123.9，127.4，128.4，128.8，134.0，146.4，160.1.MS(ESI):m/z=327.2［M+H］+.

2-(2-Chlorophenyl)-4，5-diphenyl-1H-imidazole(Tab.3，Entry 4):IR(KBr，cm－1):3426，3061，2955，1601，1478，1446，1126，1034，971，763，735，695.1H NMR(400 MHz，CDCl3)δ:7.31～7.58(m，13H)，8.45(d，J=7.6 Hz，1H).13C NMR(100 MHz，CDCl3)δ:127.4，127.5，127.8，128.1，128.6，129.5，129.8，130.4，130.9，143.2.MS(ESI):m/z=331.1［M+H］+.

2-(4-Fluorophenyl)-4，5-diphenyl-1H-imidazole(Tab.3，Entry 5):IR(KBr，cm－1):3425，3061，2955，1602，1479，1446，1119，1073，972，873，765，735，700.1H NMR(400 MHz，CDCl3)δ:7.31～7.58(m，12H)，8.45(d，J=7.6 Hz，2H).13C NMR(100 MHz，CDCl3/DMSO-d6)δ:127.3，127.4，127.8，128.3，128.5，129.5，130.0，130.3，131.0，143.2.MS(ESI):m/z=315.1［M+H］+.

2-(3-Methoxyphenyl)-4，5-diphenyl-1H-imidazole(Tab.3，Entry 6):IR(KBr，cm－1):3434，3058，2963，1592，1482，1444，1240，1047，988，843，769，696.1H NMR(400 MHz，CDCl3/DMSO-d6)δ:3.89(s，3H)，6.91(s，1H)，7.34～8.03(m，13H).13C NMR(100 MHz，CDCl3/DMSO-d6)δ:55.8，111.0，114.8，118.4，127.6，128.5，128.8，130.1，132.3，146.2，160.2.MS(ESI):m/z=327.2［M+H］+.

2 Results and discussions

In order to optimize the reaction conditions，the reaction of benzaldehyde(5 mmol)，benzil(5 mmol)and ammonium acetate(10 mmol)in presence of NH4H2PO4-SiO2under solvent-free conditions was used as a model reaction，and the results are presented in Tab.1.The results showed that the increase of temperature leads to the improvement of catalytic activity.The best conditions were 130℃ with 200 mg of catalyst loading(Entry 4).Using lower amounts of catalyst resulted in lower yields(Entry 6 and 7)，while higher amounts of catalyst did not affect the reaction time and yield(Entry 8).

The reusability of NH4H2PO4-SiO2was also investigated by stirring benzaldehyde(10 mmol)，benzil(10 mmol)，ammonium acetate(10 mmol)and NH4H2PO4-SiO2(400 mg)under solvent-free conditions at 130℃，and the results are presented in Tab.2.After the reaction monitored by TLC，the reaction mixture was cooled to room temperature and diluted with THF.The catalyst was separated by simple filtration and the recovered NH4H2PO4-SiO2can be reused for at least 3 additional times with only negligible loss of catalytic activity.After each catalytic run，the catalyst recovery was approximately 90%.A minor decrease in yield was observed from the 2nd run，presumably partly due to the loss of solid catalyst during the course of recovery.

A minor decrease in yield was observed from the 2nd run，due to the loss of solid catalyst during the course of recovery.

Meanwhile，we investigated one-pot synthesis of 2，4，5-triaryl-1H-imidazoles by 3 component condensation of a variety of aromatic aldehydes(5 mmol)，benzil(5 mmol)and ammonium acetate(10 mmol)at 130℃in the presence of NH4H2PO4-SiO2(200 mg)under solvent-free conditions.As shown in Tab.3，the aromatic aldehydes bearing both electron-donating and electron-withdrawing groups are desirable substrates for this reaction.As expected，the corresponding 2，4，5-triaryl-1H-imidazoles were obtained in high to excellent yields in short time.All products obtained are known compounds and were identified by comparing of their physical and spectra data with the reported ones.

In summary，we developed a simple procedure for synthesis of 2，4，5-triaryl-1H-imidazoles by one-pot three-component condensation of aromatic aldehydes，benziland ammonium acetate undersolvent-free conditions using NH4H2PO4-SiO2as a reusable，ecofriendly，inexpensive and efficientcatalyst.This method can get high yields and cleaner reaction profiles，apply non-toxic，recyclable and environmentally benign catalyst and simple experimental and work-up procedures.

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