1- Phenylimidazoles, from reaction

Because of the structural requirements of the bielectrophile, fully aromatized heterocycles are usually not readily available by this procedure. The dithiocarbamate (159) reacted with oxalyl chloride to give the substituted thiazolidine-4,5-dione (160) (see Chapter 4.19), and the same reagent reacted with iV-alkylbenzamidine (161) at 100-140 °C to give the 1 -alkyl-2-phenylimidazole-4,5-dione (162) (see Chapter 4.08). Iminochlorides of oxalic acid also react with iV,iV-disubstituted thioureas in this case the 2-dialkylaminothiazolidine-2,4-dione bis-imides are obtained. Thiobenzamide generally forms linear adducts, but 2-thiazolines will form under suitable conditions (70TL3781). Phenyliminooxalic acid dichloride, prepared from oxalic acid, phosphorus pentachloride and aniline in benzene, likewise yielded thiazolidine derivatives on reaction with thioureas (71KGS471). 

Starting from l-amino-2-methylthio-4-phenylimidazole, a double aza-Wittig reaction (Scheme 111) furnishes the imidazo[l,2,4]triazine (309) (89S843). 

Poly(arylene ether)s containing phenylimidazole units were initially prepared from the reaction of 2-phenyl-4,5-di(4-hydroxyphenyl)imidazole and various activated aromatic difluoro compounds according to Eq. (4) [20]. The dihydroxyimidazole was first prepared from the reaction of 4,4 -dimethoxyben-zil, benzaldehyde and ammonium acetate in refluxing acetic acid followed by... 

Further work on poly(arylene ether phenylimidazole)s led to a series of polymers containing two phenylimidazole units per mer unit (Eq. (5)) [24]. The dihydroxy monomers, 2,2 -(l,3- and l,4-phenylene)bis[(4-phenylhydroxy)-5-phenylimidazole] were prepared from the reaction of iso or terephthaldehyde, 4-hydroxybenzil and ammonium acetate in refluxing acetic acid. High molecular weight polymers as represented in Table 6 were readily prepared in DMAc. 

Methyl /3-hydroxypropionimidates (12) (prepared from ethylene cyanohydrin, methanol, and HO) condense with aminoacetaldehyde dimethylacetal (13) to yield an amidine hydrochloride (14) which undergoes ring closure to an imidazole.87 Applications of this reaction have been used in the synthesis of 2-phenylimidazole and its 4-alkyl derivatives,88 some new 2-mercaptoimidazoles,89 and isohistamine .90 Isohistamine [2-(2 -aminoethyl)imidazole], originally reported in error by Jones,01 was prepared in 50% yield by an adaptation of the method of Ellinger and Goldberg92 and proved by NMR spectroscopy to be the authentic compound. The compound prepared... 

A 25% yield of 2-phenylimidazole has been obtained136 by the action of ammonium carbonate in ethanol on l-benzoyl-2-cyanoaziri-dine (29) [from the reaction of a-chloro-j0-benzoylaminopropionitrile (30) with liquid ammonia]. Imidazolium salts have been isolated from... 

Examples of reactions which have used 1,2-diketones and ammonia with or without added aldehyde include the isolation of good yields of lophine (2,4,5-triphenylimidazole) from benzil and ammonia, a rather elegant synthesis of 4,5-di-t-butylimidazole (135), and the preparation of a series of 2-aryl-5-trifluoromethyl-4-phenylimidazoles (136) from 3,3,3-trifluoro-l-phenylpropane-l,2-dione monohydrate (Scheme 74). Additionally, the formation of 1-hydroxyimidazole 3-oxides (137) from a-diketones, hydroxylamine and aldehydes (74CI(L)38), and the preparations of 2,2 -bis- (138) and 2,2, 2"-tris-imidazolyls (139) from benzil, ammonia and polyformyl aromatics provide further examples of this versatile reaction (Scheme 74). There is yet some doubt about the pathway or pathways involved in these... 

Ethoxy-2-substituted imidazoles, too, can be made from acylglycinamides in yields of 10-35% [13]. Modification of the reaction conditions by the use of triethyloxonium fluoroborate to induce cycUzation has led to the formation of 4-ethoxy-2-phenylimidazole in 80% yield [14]. 

The versatility of this reaction is increased when a substituted hydrazine is used instead of the primary amine, providing ready access to 1-aminoimidazoles (11) (R = NHR) from the hydrazones [36]. Hydroxylamine converts the o -(acylamino)ketones into oximes. In the presence of phosphoryl chloride or the fluoride ion, imidazole A -oxides can be generated. Thus, 2-formyl-4-methyl-l-phenylimidazole 3-oxide has been made in around 50%... 

Triphenyloxazole (5g), formamide (40g) and liquid ammonia (lOOtnl) are heated in an autoclave at 200-210°C (5h). The brownish reaction product is poured into water, and the flocculent precipitate is filtered, washed with water and recrystallized from ethanol (4.3 g, 85%), m.p. 273°C. Similarly prepared are 2,5-diethyl-4-phenyl- (25%), 2-methyl-4,5-dipropyI-(70%) [41], 4-eihyl-5-phenyl- (50%), 4-phenyl-5-propyl- (40%) and4-benzyl-5-ethyl imidazoles (5%) [40]. From 2-methyloxazole-4-carboxylic acid boiled at 150°C in a sealed tube with aqueous ammonia is obtained 2-methylimidazole (22%) boiling with aniline gives 2-methyl-l-phenylimidazole (67%) [52]. 

The oxidation reactions of 2,4,5-triphenylimidazole (lophine) have received considerable attention. With chromic acid it gives benzamide and benzanilide, but even more interest has centred on its involvement in the phenomenon of chemiluminescence. Some of this material has been discussed earlier (Sections 4.06.3.6, 4.07.1.2.1 and 4.07.1.2.3). The oxidative decomposition of lophine in the presence of air is accompanied by the emission of light, and it is the excited singlet state of the diaroylarylamidine (12 Scheme 2) which is the light emitter. The radical (46) derived from oxidation of lophine with aqueous ferricyanide and ethanolic KOH forms a hydroperoxide with hydrogen peroxide with consequent luminescence. When 2,4,5-tri- and 1,2,4,5-tetra-phenylimidazoles are oxidized in dilute methanol solution in the presence of methylene blue, the dibenzoylbenzamidine is also formed under circumstances in which hydroperoxides cannot be intermediates (B-76MI40701). 

The aromatic ring system has been prepared both from quinoxaline intermediates and from 1-phenylimidazoles. Reaction of the 2-chloroquinoxalines 1 with aminoacetaldehyde dimethylacetal followed by acid treatment of the resultant aminoacetals gave imidazo[l,2-ajquinoxaline (2) and its 4-phenyl derivative (3). Compound 3 was the... 

A novel synthesis of imidazoles was reported by Junjappa and co-workers [84JCS(CC)430], in which the reaction of enaminones 316 (R = H) with nitrosyl chloride gives the nitrosoenaminones 317, which are cyclodehy-drated to the -H imdazoles 318 in high yields. Scheme 89 (path a). The transformation can be done in one step with some of the enaminones under more forcing conditions (path b). Also, 1-phenylimidazoles 319 can be prepared by heating the enaminones 316 (R = H) with nitrosobenzene in sealed tubes (path c). The method was successfully extended to the synthesis of 2,2-disubstituted 2-H imidazoles 320 for enaminones 316 (R H) (87S547). Tetrahydrobenzimidazoles are prepared similarly from the cyclodehydration of a-nitroso enaminones derived from 1,3-cyclohexanediones (80JHC1723). 

A second synthetic route to poly(aryl ethers) containing heterocyclic units involved the reaction of an aromatic dihydroxy heterocycle with conventional activated difluoro compounds. Bisphenols containing quinoxaline, phenylimidazole, oxadizaole, pyrazole, triazole, phenolphthalein, phenolphthalimidine, and phenolphthalein anilide heterocycles were prepared and polymerized to high molecular weight (84-95), However, the most noteworthy examples are the poly(aryl ether benzimidazoles), prepared from bis(4-hydroxyphenyl) bibenzimidazole, due to their unique combination of adhesive, thermal and mechanical properties (Scheme VIII) (93-95),... 

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