Acetaldehyde → Formamide

Participants

Reaction Steps

Hydrogen abstraction from the carbonyl carbon of aldehydes by a radical source was utilized to yield the acyl radical, a highly reactive acylating agent, for the synthesis of 8-acyl-cGMP derivatives. Acetaldehyde and cGMP, in the presence of t-BuOOH, FeSO4 and 0.3 N H2SO4, yielded 8-acetylguanosine 3',5'-cyclic phosphate (6); however, in initial experiments a significant amount of 8-methyl-cGMP (2) was also formed. To avoid the possibility of methylation competing with hydrogen abstraction from the aldehyde, ammonium persulfate was subsequently used as a radical source. In this manner, 6 was readily obtained in 43% yield. Using the appropriate aldehyde under these conditions, 8-n-butyryl (7), 8-isobutyryl (8), and 8-benzoylguanosine 3',5'-cyclic phosphate (9) were prepared from cGMP. Formamide and cGMP under these conditions gave 8-carbamoylguanosine 3',5'-cyclic phosphate (10).

Provenance & Evidence