Methyl-2,5-diphenylimidazole

A solution of benzamidine hydrochloride dihydrate (48 g, 0.25 mol) in water (100 ml) is added to a solution of a-bromopropiophenone (53 g, 0.25 mol) in chloroform (250 ml) to form a two-phase mixture. While stirring vigorously at room temperature, a solution of KOH (28 g, 0.5 mol) in water (100 ml) is added dropwise, then heated to boiling and refluxed (3-4h). The chloroform phase is then separated from the hot aqueous phase and cooled. Tlie ciwstalline material which separates is washed with benzene, then with diethyl ether to give the above product (which may separate as an oil, but which solidifies gradually on addition of benzene). Ilie yield is in the range 26-32 g (45-55%), m.p. 214-215°C. Similarly prepared are 4-methyl-2,5-bis-(m-nitrophenyI)-(39%), 4-methyl-2,5-bis-(m-bromophenyl)- (40%), and 4-methyl-2,5-bis-(p-nitrophenyl)imidazolcs (64%). 

2-Dicarbonyls are also capable of taking part in these reactions with amidines, but most of the references apply to guanidines or ureas acting as the NCN synthons (see below). 

They may eliminate so readily that the intermediate imidazoline cannot be isolated, but if the enamine is disubstituted, the 5,5-disubstituted imidazolines which are formed are so stable that it is necessary to heat them with 50% aqueous sulfuric acid, or in anhydrous medium with an equimolar amount of either triethylammonium or pyridinium chlorides, to effect arom-atization. Enamines derived from ketones or hindered aldehydes do not lead to imidazoles, and there are other difficulties (some enamines are difficult to prepare, only aryleneamines give good yields). Nevertheless, the reported results demonstrate the potential of the method [22-24]. 

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It is a general rule that imidazoles and benzimidazoles are resistant to Friedel-Crafts reactions. This is not surprising since such basic compounds must be markedly deactivated in the presence of Lewis acids. Imidazolin-2-ones appear to be an exception and apparently possess sufficient activation to react. Reactions between imidazoles and Af-methylfor-manilide and phosphoryl chloride are also unproductive. With 4,5-diphenylimidazole, phenyl isocyanate at 80 °C gives products of both N- and C-substitution, but in boiling nitrobenzene only the latter (86) is formed. 2-Methyl-4-phenylimidazole gives (87) under the same conditions, and 1,3-diphenylimidazolium perchlorate is transformed by potassium t-butoxide into a ylide which reacts at C-2 with phenyl isothiocyanate. Sufficient activation is present in l-methyl-2-phenyl-4-phenylaminoimidazole for it to react by substitution at C-5 with acetic anhydride (71JOC3368). 

Imidazoles and benzimidazoles are generally quite resistant to such reduction reactions. Catalytic reduction of aryl- and furyl-substituted imidazoles affects only the aryl and furyl rings, but there has been an isolated report that 2-methyl-4,5-diphenylimidazole can be reduced over palladium to give the corresponding imidazolidine (70AHC(12)103). In the presence of palladium, platinum and rhodium catalysts in acid media, benzimidazoles were found to be reduced only in the fused benzene ring (73MI40700). 

In the presence of potassium cyanide the N-methyl-C-phenylnitrone (112) takes part in yet a further cycloaddition reaction to give l-methyl-4,5-diphenylimidazole. With lithium metal the aldimine (113) forms a delocalized carbanion which will cyclize with aryl cyanides (Scheme 61) (80AHC(27)24l). See also Section 4.08.1.1.3. 

Simple imidazoles are much less soluble in nonpolar solvents. For example, 177-imidazole, 2-methyl-177-imidazole, benzimidazole, 2-methylbenzimidazole, 2-phenylimidazole, 4,5-diphenylimidazole, and 2,4,5-triphenylimidazole have very low solubility in chloroalkanes (dichloromethane, 1-chlorobutane), toluene and 2-nitrotoluene. Among them, the solubility of phenylimidazoles is significantly lower than that of 17/-imidazole or benzimidazoles in all of the solvents <2004CED1082>. 

Similarly, both the 2-phenyl- and the 2,4-diphenylimidazolate anions give, with 3-methylthio-5-phenyl-l,2-dithiolium ion, dithiadiazafulvalenes. 4-Aryl-3-methylthio-l,2-dithiolium ions react with AT-alkylarylamines, to give methyl 2-aryl-3-(4-alkylaminophenyl)dithioacrylates (Eq. 24). ... 

Values of molar Kerr constants and dipole moments of nitrogen azoles and their complexes with phenols have been obtained. " These complexes are formed by an intermolecular hydrogen bond between the pyridine-type nitrogen of the azole and the phenolic proton. " The use of dipole moments in conformational studies has shown that A-aryl- and C-aryl- and A-furyl- and C-furyl imidazoles (and benzimidazoles) are nonplanar, but l-(a-furyl)-4,5-diphenylimidazoles do have a planar bicyclic fragment. The dipole moments and conformations of azolides (A-acylazoles) have been studied. In the 1-arylimidazoles the dipole is toward the aryl group. In 4,5-di-t-butylimidazole the molecule is essentially planar, but the C-4—C-5 bond is slightly stretched. Among other imidazole derivatives which have been studied by X-ray are histidine hydrochloride, 4-acetyl-amino - 2 - bromo - 5 - isopropyl -1 - methylimidazole, 4- acetyl - 5 - methyl - 2 -phenylimidazole, and imidazole-4-acetic acid hydrochloride. 

Reactions of Imidazoles. Thermolysis of 1-triphenylmethylimidazole results in migration of the imidazolyl group to yield compound (286). Sensitized photo-oxygenation of 4,5-diphenylimidazole in methanol affords a mixture of the imidazolinone (287) and the imidazolidinone (288). The imidazole (289 R = H) undergoes lithiation at C-5 subsequent treatment with diphenyl disulphide gives the di(phenylthio)-derivative (289 R = PhS). Copyrolysis of 2,4-dimethylimidazole and chloroform results in a complex mixture, containing imidazole and methyl-, dimethyl-, and chloromethyl-pyrimidines and -pyrazines. The confusion about the structures of N-methyl derivatives of iodo-nitro-imidazoles has been cleared up the supposed 1-methyl-2,5-di-iodoimidazole is actually the 4,5-di-iodo-compound it yields 4-iodo-l-methyl-5-nitroimidazole on nitration. The reaction of the bromo-... 

Reactions of imidazoles with nucleophiles occur slowly as with thiazoles and demand vigorous conditions. Attack of the nucleophile occurs in the 2-position. For instance, l-methyl-4,5-diphenylimidazole reacts with potassium hydroxide at 300°C to give imidazol-2(3//)-one ... 

Reactions of Imidazoles. The action of sodamide on the chloro(ethynyl)-imidazole (413 R = Cl, = H) results in the formation of the isomer (413 R = H, R = Cl) similar transhalogenations have been observed for chloro(ethynyl)-pyrazoles and -1,2,4-triazoles. The imidazolium salt (414) undergoes base-induced ring-expansion to the pyrazine derivative (415). 2,4,5-Tribromo-l-methylimidazole reacts with xenon difluoride to give the imidazolidinetrione (416). Low-temperature H n.m.r. studies of the sensitized photo-oxygenation of imidazoles (417 R, R, R = H or Me) give direct evidence for the formation of unstable enr/o-peroxides (418) 2-methyl-4,5-diphenylimidazole yields the peroxy-derivative (419) in this reaction.Irradiation of the N-oxide (420) produces the diamine (422) by way of the oxaziridine (421)."" ... 

Hydroxypheny 1 )azo]-4,5-diphenylimidazole, H-00450 2-(2-Hydroxyphenylazo)-5-[A-ethyl-A -(3-sulfopropyl)amino]phenol, see E-00088 4-[(4-Hydroxyphenyl)azo]-6-methyl-1,3-benzenediamine, H-00451 2-(2-Hydroxyphenylazo)-3-methyl-5-propylpyrrolidine, see M-00263... 

A soln. of 2,3-dihydro-5,6-diphenylpyrazine in abs. ethanol irradiated with a Pyrex-filtered high-pressure Hg-vapor lamp until no more startg. m. can be detected by spectroscopy l-methyl-4,5-diphenylimidazole. Y 75%. F. e. s. P. Beak and J. L. Miesel, Am. Soc. 89, 2375 (1967). 

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