Synthesis of 1-benzyl-6-azauracil derivatives, chlorinated in the nucleus

Abstract

Glyoxylic acid 2-benzylsemicarbazone derivatives, chlorinated in the aromatic nucleus (Ia-Id) were prepared either by reaction of glyoxylic acid semicarbazone with the corresponding benzyl chlorides or by treatment of benzylidene semicarbazide with substituted benzyl chlorides and reaction of the formed semicarbazides IIIa-IIId with glyoxylic acid. The semicarbazones Ia-Id were cyclized by heating with sodium hydroxide in ethylene glycol to give the corresponding 1-benzyl-6-azauracils IIa-IId.

N2-Alkylation of semicarbazones. A general and efficient protocol for the synthesis of 2-alkylsemicarbazides from semicarbazide

“…Various base/solvent combinations for deprotonation of semicarbazones (e.g. MeONa/DMF, 25,26 Et4NOH/THF, [27][28][29] NaOH/EtOH-H2O, 30 t-BuOK/THF, 5,[31][32][33] NaH/DMF, 34 K2CO3/DMF, [35][36][37] Cs2CO3/MeCN, 38 tert-butylimino-tri(pyrrolidino)phosphorane/THF 39 ) followed by treatment with alkylating reagents were reported. We tested some base/solvent combinations for the alkylation of semicarbazones of aromatic aldehydes (E)-1a-c as model compounds.…”

A New Efficient Route to 2-Alkylsemicarbazides

“…Clearly, this alkylation can proceed only via formation of a conjugate base of the starting material. Various base/solvent combinations for deprotonation of semicarbazones (e.g., MeONa/DMF [25,26], Et4NOH/THF [27][28][29], NaOH/EtOH-H2O [30], t-BuOK/THF [5,[31][32][33], NaH/DMF [34], K2CO3/DMF [35][36][37], Cs2CO3/MeCN [38], tert-butylimino-tri(pyrrolidino)phosphorane/THF [39]), followed by treatment with alkylating reagents, were reported. We tested some base/solvent combinations for the alkylation of semicarbazones of aromatic aldehydes (E)-1a-c as model compounds (Scheme 2).…”