Butyl-4-isopropyl-5-trifluoromethylimidazole

A solution of the trifluoroacetylhydrazone (Immol) in toluene (20 ml) is refluxed (16h) under nitrogen. Removal of the solvent gives a residue which is purified by Kugelrohr distillation (bi.5 IIO C) to give the product (O.lOg, 81%) as a yellow oil. 

In the presence of base, 2-isocyanoalkanenilriles [70] react with alcohols, thiols or hydrogen sulfide to form imidazoles which have oxygen or sulfur groups in the 4(5) position. The reactions appear to proceed via the 4ff-imidazoles, which rearrange to the Iff-isomers [71]. There are similarities to the synthesis of 4-methoxyimidazole made, in 60% yield, by refluxing the Af-cyanomethylimino ester of formic acid with sodium methoxide in methanol [72]. 

To solution of 2-isocyanopropanenitrile (1.6g, 20nunol) in methanol (15 ml) is added potassium carbonate (0.2 g), and the mixture is stirred at room temperature (20 h). After filtering, and removing the solvent under reduced pressure, the cmde product is crystallized from cyclohexane (1.6 g, 70%), m.p. 88-89°C. Similarly prepared are 5-ethoxy-4-methyl- (62% from cyclohexane, m.p. 94°C), 5-methoxy-4-isopropyl- (75% from benzene, m.p. 96-97°C), 5-ethoxy-4-isopropyl- (51% from benzene, m.p. 122-123°C), 5-ethylthio-4-methyl- (58% from cyclohexane, m.p, 88°C), 5-benzylthio-4-methyl- (61% from benzene, m.p. 156 C), 5-ethylthio-4-isopropyl- (55% from cyclohexane, m.p. 124°C), and 5-benzyl thio-4-isopropylimidazoles (45% from benzene, m.p. 133°C). 

The thionamide (27) (R = Me, = H, = CHiOTHP) (0.15 g, 0.6 mmol) and triethylamine (0.25 g, 2.5 mmol) in dichloromethane (5 ml) are cooled to -78°C, when tiimethylsilyl trifluoromethanesulfonate (0.40 g, 1.8 mmol) is. added dropwise down the wall of the flask. The mixture is stirred at —78°C (5 min), then treated with methanol (5 ml) and sodium fluoride (0.5 g) before warming to 25°C and stirring (2h). The volatiles are removed under 

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