Hydroxymethylation, oxazole reactions

Proposed reaction mechanism of l-hydroxy-2-propanone or l-hydroxy-2-butanone with ammonium sulfide is shown in Figure 5. 2-Iminoalcohols, which were derived from the reaction of ammonia and a-hydroxyketones, were condensed with another molecule of a-hydroxyketone to form 2-(l-hydroxymethyl)-2,4-dialkyl-3-oxazolines. The substitution of -OH group with -SH group resulted in the formation of 2-(l-hydroxyemthyl)-2,4-dialkyl-3-thiazolines. No 2-(l-mercaptomethyl)-substituted isomers were found in either reaction. Upon heating, these intermediates were further converted to the corresponding oxazolines, oxazoles, thiazolines and thiazoles. 

These systems are reported as cyclopentaoxazolidines and can be obtained by conventional azeotropic dehydration of aldehydes with amino alcohols <85TL5303> for example, (S)-5-Hydroxymethyl-2-pyrrolidinone (236) was condensed with benzaldehyde to obtain the corresponding chiral 5-oxo-2-phenylperhydropyrrolo[l,2-c]oxazole (237) in excellent yield <86JOC3140>. Similar treatment of enantiomerically pure amino ketone (238) with paraformaldehyde or formalin under a variety of Mannich conditions yielded (239) <84ja5360>. These reactions are shown in Scheme 41. 

The reactions of (5)-5-hydroxymethyl-2-pyrrolidinone (236) with phosgene or phosgene dimer (trichloromethylchloroformate) in the presence of pyridine afforded (+)-(S)-3,5-dioxo-perhydropyrrolo[l,2-c]oxazole (243) in moderate yield <92H(33)619>. In a similar manner, tri-substituted oxazolidinones have been obtained <84EUP128120>. 

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