Sulfacytine, N1-(1-ethyl-1,2-dihydro-2-oxo-4-pyrimidinyl)-sulfanilamide
(33.1.5), is synthesized by reacting 4-acetylaminobenzenesulfonyl chloride with 1-ethyl-cytosine (33.1.3) followed by reductive deacylation of the acetanilide part of the molecule (33.1.4)
using a system of zinc ¨C sodium hydroxide, which gives the desired sulfacytine.
1-Ethylcytosine (33.1.3) is in turn synthesized from 3-ethylaminopropionitrile, which is
reacted with cyanic acid (potassium cyanate¨Chydrochloric acid) in the first stage of synthesis
to give 1-(2-cyanoethyl)-1-ethylurea (33.1.1). This easily cyclizes to 1-ethyl-5,6-dihydrocytosine in the presence of sodium methoxide, and is isolated in the form of a hydrobromide
(33.1.2) for subsequent oxidation of the ordinary C5¨CC6 bond. Bromine turns out to be the
optimal oxidant for this purpose, and using nitrobenzene as the solvent gives a heteroaromatic amine, 1-ethylcytosine (33.1.3), which was transformed to the desired sulfacytine in
the aforementioned manner?a by reacting it with 4-acetylaminobenzenesulfonyl chloride and
subsequent removal of the protecting acetyl group from the amine part of the molecule.
