Isocyanates 1.3- diazetidine-2,4-dione

In addition to a series of previously well-known reactions of 2-amino-l,3,4-oxadiazoles such as the formation of SchifFs bases or phthalamido derivatives,48-69,81,93 it has been possible to convert 2-amino-5-phenyl-1,3,4-oxadiazole by addition of isocyanate via the corresponding urea into (5-phenyl-l,3,4-oxadiazol-2-yl)diazetidine-diones (45).128... 

In this volume, we have already examined some alternatives to the synthesis in situ and/or to the use of methyl isocyanate. We thought that 1,3-dimethyl diazetidine dione (XII) (methyl isocyanate dimer) should be a suitable methyl isocyanate precursor which can release methyl isocyanate in safe conditions. This dimer was prepared from N-chlorocarbonyl-N-methyl N -methyl urea (XI) obtained by phosgenation of N,N -dimethyl urea as previously described in scheme 156, section 3-3-4. Cyclization of (XI) in a suitable solvent and in presence of a base such as DABCO afforded the expected dimer (XII) as depicted in scheme 220. 

Cyclohexylamine is reported to react with formaldehyde giving a 60% yield of 1,3-diazetidine. One additional example reports a photochemical closure of iV-cyclohexylben-zaldehydeimine (68JA1666). An excellent review covers much of the earlier work on dimerizations of isocyanates (69ACR186). Aromatic isocyanates readily dimerize to uretidinediones (l,3-diazetidine-2,4-diones) when catalyzed by trialkyl phosphites or pyridine presumably by a dipolar intermediate AH = 2.1 to 4.2 kJ mol-1, AS = -251 to -293 JK-1 mol- (Scheme 86) (66JA3582, 76JGU799). 

The dimerization of aryl isocyanates to l,3-diarylazetidin-2,4-diones is one of the classical methods for the synthesis of 1,3-diazetidinones. In 1993 trimerization of phenyl isocyanate catalyzed by a fluoride ion was also reported, and a small amount of l,3-diazetidin-2,4-dione was obtained at room temperature <1993JOC1932>. 

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