Patent GB-599967-A (GB)
Title: Improvements in soluble sulfanilamide derivatives and process of preparing same
Filed: 1945-09-25
Abstract: Sulphanilamide derivatives of the general formula <FORM:0599967/IV/1> wherein R stands for hydrogen or alkyl, R1 is a quaternary nitrogen radical and R11 is a heterocyclic ring, are prepared by reacting with a tertiary amine a sulphanilamide derivative substituted in position N4 by an aliphatic a -halogeno-acyl radical and in position N1 by said heterocyclic ring.  The product may be isolated as the free base, the intramolecular anhydride of the base, or in the form of a salt of the base.  The a -halogeno-acyl compound is prepared by reacting a sulphanilamide derivative having a free amino group in position N4 and substituted in position H1 by said heterocyclic ring, with an anhydride or halogenide of an aliphatic a -halogenic acid. In examples: (1) the chloride of 2-N4-[N-pyridinium-acetyl]-sulphanilamido-thiazole is made by adding pyridine to a refluxing suspension of 2 - N4 - chloroacetyl - sulphanilamido - thiazole in dioxane; (2) the chloride of 2-N4-[N-pyridiniumacetyl]-sulphanilamido-pyridine is prepared by refluxing pyridine, 2-N4-chloroacetyl-sulphanilamido-pyridine and alcohol; (3) the chloride of 2 - N4 - [N - pyridinium - acetyl] - sulphanilamido - pyrimidine is prepared by adding pyridine to a refluxing solution of 2 - N4 - chloroacetyl - sulphanilamido-pyrimidine in dioxane; (4) 2-sulphanilamido - thiazole hydrochloride and a  - bromopropionyl bromide are reacted to give 2 - N4 - a  - bromopropionyl - sulphanilamido - thiazole, which is then reacted with pyridine in the presence of alcohol to yield the bromide of 2 - N4 - [N - a  - pyridinium - propionyl] - sulphanilanido-thiazole; (5) 2-N4-a -bromopropionyl-sulphanilamido-pyrimidine is made (a) by adding a solution of a -bromopropionyl bromide in benzene to sulphanilamido-pyrimidine hydrochloride in water, or (b) by adding a -bromopropionyl bromide to sulphanilamido-pyrimidine, acetone and pyridine; the 2-N4-a -bromopropionyl-sulphanilamido - pyrimidine is then dissolved in alcohol and reacted with pyridine to give the bromide of 2-N4-[N-a -pyridiniumpropionyl]-sulphanilamido-pyrimidine; (6) the chloride of 2-N4-a -chloropropionyl-sulphanilamido-pyrimidine is prepared from 2-sulphanilamido-pyrimidine hydrochloride and a -chloropropionyl chloride, which is then reacted with pyridine to give the chloride of 2-N4-[N-a -pyridinium-propionyl]-sulphanilamido-pyrimidine; (7) 2-N4-chloroacetyl-sulphanilamidothiazole is reacted with trimethylamine in water to give the chloride of 2 - N4 - [trimethyl - ammonium - acetyl] - sulphanilamido - thiazole; (8) 2-N4-chloroacetyl-sulphanilamido-pyridine is reacted with trimethylamine in water to give the chloride of 2-N4-[trimethylammoniumacetyl]-sulphanilamido-pyridine; (9) 2-N4 - chloroacetyl - sulphanilamido - pyrimidine is reacted with aqueous trimethylamine to give the chloride of 2-N4-[trimethylammoniumacetyl]-sulphanilamido-pyrimidine; and (10) 2-N4-a -bromoprionyl-sulphanilamido-pyrimidine is reacted with aqueous trimethylamine to give the bromide of 2 - N4 - [a  - trimethyl - ammonium-propionyl]-sulphanilamido-pyrimidine.