Patent GB-644702-A (GB)
Title: 2-(sulphanilamido)-6-methyl pyrimidine
IPC: C07D239/84
Filed: 1947-08-07
Abstract: Benzenesulphonamido - pyrimidines of the formula <FORM:0644702/IV (b)/1> where Y is a pyrimidyl radical which is linked by its 2-carbon atom and which may carry a methyl group in its 4- and/or 6-position, are prepared by condensing 2-amino-pyrimidine (which may be substituted as above) with a p-nitro- or p-acylamino-phenylsulphonyl halide, and reducing or hydrolysing the product.  The acyl group may be acetyl, propionyl, butyryl, valeryl, caproyl or octoyl.  The reaction is preferably carried out in a solvent such as pyridine or acetone, using excess of the aminopyrimidine.  Examples are given. The Specification as open to inspection under Sect. 91 refers to the production of sulphonamides of the formula M-Ar-SO2-NRY, where M is hydrogen, nitro, amino, alkylamino, acylamino or acylalkylamino, Ar is an aryl nucleus such as phenylene, tolylene or xylylene, R is hydrogen, alkyl or aralkyl and Y is a heterocyclic radical which is derived from an azine, an azole or a polynuclear compound, and which may contain one or more nuclear substituents.  The substituent M may be in the o- or p-position with respect to the sulphonamide group. The acyl group in M may be one of those specified above or isobutytyl, iso- or active-valeryl, heptoyl, capryl, lauryl, myristyl, palmityl, stearyl, behenyl, oleyl, ricinoleyl, a -chlorcaproyl, benzoyl, phenylacetyl, phenylpropionyl, toluyl, toluacetyl, cinnamyl, mandelyl, hydratropyl, tropyl, chlorbenzoyl, phenylchloracetyl, phenylaminoacetyl, aminobenzoyl, nitrobenzoyl, sulphobenzoyl, hexahydrobenzoyl, cyclopentanecarboyl, pyromucyl, furylacrylyl, nicotinyl or thiazole-4-carboyl.  R may be hydrogen, methyl, ethyl, propyl, butyl, amyl, hexyl, heptyl, octyl, decyl, dodecyl, hexadecyl, allyl or benzyl.  Besides pyrimidine, the nucleus of Y may be thiazole, thiazoline, thiazolone, oxazole, oxazoline, isoxazole, imidazole, benzimidazole, quinazoline, tetrahydro-benzthiazole, benzometathiazine, pyridazine, piperazine, quinoline, xanthine or piperidyl-pyridine. Substituents on these nuclei may be methyl, ethyl, propyl, butyl, isobutyl, amyl, hexyl, allyl, methallyl, cyclopentyl, cyclopentenyl, hexyl, phenyl, naphthyl, benzyl, hydroxy, methoxy, ethoxy, propoxy, methylthio, ethylthio, carbomethoxy, carbethoxy, chlorine or bromine; further, the substituent may be a polyalkylene radical as in tetrahydro-benzthiazole above.  The compounds in which R is hydrogen are prepared by condensing the appropriately-substituted arylsulphonyl halide with the appropriate amino-heterocyclic compound, except where M is an amino group, this being formed by reduction of the nitro group or hydrolysis of the acylamino group. These products may then be alkylated or aralkylated to introduce the desired substituent R, using for example an alkyl halide, alkyl sulphate or alkyl sulphonate.  In the examples, the following substituted phenyl sulphonyl chlorides are mentioned (together with the unsubstituted compound) as starting materials: 2- and 4-nitro-, 4-acetamino-, 4-caproylamino- and 2 ethylamino.  The products obtained are derived from the following amino-heterocyclic compounds: 2-amino-pyrimidine and its substitution products: 5-methyl-, 5-n-butyl-, 6-methyl-, 6-n-propyl-, 6-n-hexyl-, 6-phenyl-, 4-phenyl-6-methyl-, 4-ethoxy-6-methyl, 5-bromo-6-methyl-, 4-chloro-, 4-hydroxy-, and 6-carbethoxy-; 4-amino-pyrimidine and its substitution products: 6-methyl-, 2-ethoxy-6-methyl-, and 2-ethylthio-6-methyl-; 5-amino-pyrimidine, 2-amino-5 : 6 : 7 : 8-tetrahydro-quinazoline, 2-amino-4-methyl-thiazole, 2-amino-thiazoline, 2-amino-4 : 5 : 6 : 7-tetrahydro-benzthiazole, 2-amino-5-phenyl-oxazole, 2-amino-oxazoline, 2-amino-benzimidazole, 2-amino-4:5-benzo-1 : 3-thiazine, 8-amino-caffeine and 2-amino-6-(11-piperidyl)-pyridine.  Other reactions referred to are the production of 2-amino-4-ethoxy-6-methyl-pyrimidine from the corresponding 4-chloro-compound with sodium and alcohol, and the hydrolysis of 2-sulphanilamido-4-ethoxy-6-methyl-pyrimidine to the 4-hydroxy-compound with hydrochloric acid.  This subject-matter does not appear in the Specification as accepted.