Methyl-4-tosylimidazole-5-thiol

Imidazoles (9) prepared from [3 + 2] cycladdition of p-tolylmethyl isocyanides and nitriles [8] 

To a stirred suspension of TOSMIC (5.0mmol) and the aldehyde (5.1 mmol) in dry ethanol (15 ml) is added finely powdered sodium cyanide (0.5 mmol). Within minutes a slightly exothermic reaction gives a clear solution from which the oxazoline separates ( 15min). Stirring is continued for an additional 10 min, or until TLC (dichloromethane diethyl ether, 95 5) shows that all of the TOSMIC has disappeared. The mixture is filtered, the crystals are washed with ether-hexanc (1 1, 15 ml) and dried. A second crop is obtained by concentration of the mother liquors and trituration with ether-hexane (1 5). 

If diastereoisomeric mixtures form, ciystallization may be prevented. In such cases the solution is concentrated in vacuo to give an oil of sufficient purity to allow subsequent reaction. Yields lie in the range 84-93%. 

The process can also be adapted to the synthesis of 4-ethyl-5-substituted imidazoles if a-(p-tosyl)propyl isocyanide is used with an aldehyde in the presence of potassium t-butoxide. 

Analogous to the TOSMIC reactions is the cyclocondensation of an isothiourea with the enolate of ethyl isocyanoacetate (12) to give an alkyl 5-aminoimidazole-4-carboxylate (13). This regioselective synthesis provides 

---