2.4- Dimethyl-3-phenylimidazole

AOM, azoxymethane MNNG, JV-methyl-JV -nitro-JV-mtrosoguamdine DMH, 1,2-dimethyl-hydrazine MNU, W-methyl-W-nitrosourea PhIP, 2-amino-l-methyl-6-phenylimidazole[4,5-b] pyridine sc, subcutaneous ip, intra-peritoneal ir, intra-rectal po, by mouth. 

Matters become more complex still in neutral conditions because now tautomeric effects can be superimposed upon steric and electronic effects. In an 5e2 process 2-methyl-4-phenylimidazole is methylated by dimethyl sulfate to give a mixture of the 4-phenyl and... 

Dimerization of ethyl 2-amino-2-cyanoacetate gives diethyl 5-aminoimidazole-2,4-dicar-boxylate (92) as in Scheme 53. At reflux temperatures in propanol, 1,1-dimethyl-1-phenacyl-hydrazinium bromide is converted into 2-benzyl-4-phenylimidazole (93). Again the cycliz-ation is a dimerization process (Scheme 53) (80AHC(27)24l). 

Less common as a synthetic method is the rearrangement under mild conditions of some hydrazinium salts. In contrast to the severe conditions necessary (200 C, solid KOH) to rearrange 1,1,1-trialkylhydrazinium salts [60], 1,1-dimethyl-l-phenacylhydrazinium bromide is transformed merely by refluxing in pentanol or pyridine into 2-benzoyl-4-phenylimidazole (65-73%). This is a Stevens-type rearrangement [61, 62]. 

In alkylimidazoles, ring protons adjacent to an A-methyl group can be differentiated from other ring protons by a characteristic shift in S with variation in solvent in addition, H-5 appears at higher field than H-4 in nonpolar solvents. The other is reversed for polar solvents (see Table II). The orientation of iV-methylation in 2-methyl-4(5)-phenylimidazole has been determined with lanthanide-shift reagents. For steric reasons the 1,2-dimethyl-5-phenyl isomer coordinates with the shift reagent while the 4-phenyl compound does not. ... 

The mass spectrum of I-methyl-4-nitroimidazole-5-carboxylic acid amide shows the elimination of water by an electron impact as distinct from the usual thermal process. In l,4,5-trimethylimidazole-2-carboxylic acid the principal loss is that of CO2. Subsequent loss of O, OH, and HCN was also observed (Schofield et al., p. 173). Ferguson and Schofield (pp. 172,173) have reported considerable data for imidazole JV-oxides. Thus 1-methoxy-4,5-dimethyl-2-phenylimidazole (which loses OCH3 and CH3CN from the fragment m/e 171) is readily distinguished from l,4,5-trimethyl-2-phenyl-imidazole 3-oxide (loss of O and OH). The spectra of 1-benzylimidazoles are dominated by the tropylium ion. ... 

Many workers in recent years have been interested in the tautomeric equilibria pertaining to oxygenated imidazoles such as imidazolones, " " N-hydroxyimidazoles, and imidazole iV-oxides. The earlier results have been critically summarized. In the solid state l,2-dimethyl-5-phenylimidazol-4-one exists in the OH form, but insolubility prevented studies in solution. Theoretically l-methylimidazol-5-ones can exist in the forms 93-96 shown in Eq. (22). French workers ... 

Triazene derivatives also continue to receive attention as potential antlneoplastic agents, based on the encou gi antitumor activity of 5-(3,3-dimethyl-l-triazenc imidazole-4-cart)oxamide in man. The compounds 4-carbethoxy-5 (3,3-dimethyl-l-triazlno)-2-phenylimidazole, and the corresponding 2-methylimidazole derivative pcil) showed activity against various experimental rodents tumors com-... 

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