Patent GB-538822-A (GB)
Title: Manufacture of amidine derivatives
Filed: 1940-02-02
Abstract: 538,822. Sulphonamide derivatives. GEIGY AKT.-GES, J. R. Feb. 2, 1940, No. 2065. Convention date, Dec. 19, 1939. Samples furnished. [Class 2 (iii)] Sulphonamide derivatives or amidines of the general formula R,-SO  2 -N =C-N       |        R 2    #<SP>R3</SP> R4  are prepared by reacting an imido halide of the general formula R 1 -SO  2 -N =C-R 2  Hal with ammonia, a primary or secondary aliphatic or hydroaromatic amine, or a primary araliphatic, aromatic or heterocyclic amine. In the above formula R, represents a benzene nucleus containing in the para position a nitro group or an acylamino group R is a substituted or unsubstituted saturated or unsaturated residue of the aliphatic, alicyclic, araliphatic, aromatic, hydroaromatic, or heterocyclic series. R  3  and R  4  represent hydrogen or substituted or unsubstituted aliphatic, araliphatic, aromatic, hydroaromatic or heterocyclic residues which in some cases may be linked to one another. The desired compounds may also be obtained bv causing an amidine of the formula HN =C-R  2  | R 3 -N-R 4  where R 2  2, R and R 4  have the meanings given above to react with a benzene sulphonic acid halide having in the para position a nitro group or an acylamino group. The parent imido halides may be made by treating a benzene sulphonacylamide substituted in the para position by a nitro group on an acylamino group with an acid halide, particularly with a chloride of carbonic acid or sulphuric or the phosphorus acids. For the acyl residue there are mentioned the residues of aliphatic mono-, and di-carboxylic acids such as acetic, chloracetic, and alkoxyacetic acids, propionic acid, butyric acid, caproic acid, lauric acid, succinic acid or di-alkyl-oxamic acid ; also saturated or unsaturated substituted or unsubstituded araliphatic carboxylic acids such as phenylacetic acids, p-chlor-phenylacetic, and methoxyphenyl-acetic acids, dihydrocinnamic acid and phenoxyacetic acid ; also substituted or unsubstituted aromatic mono-, or di-carboxylic acids such as benzoic acid or its substitution products such as p-nitro-, and p-chlorobenzoic acids ; also alicyclic carboxylic acids such as fencholic acid or naphthenic acid ; also hydroaromatic acids such as hexahydrobenzoic and methylhexahydrobenzoic acids ; also hetrocyclic acids such as furane-2-carboxylic acid, pyridine carboxylic acid and amines mentioned as suitable for the process of the present invention include methylamine, ethylamine, propylamine, isopropylamine, alkylamine, butylamine, dimethylamine, diethylamine, dialkylamine, dipropylamine, methylpropylamine, aminoethanols, laurylamine, aniline and its substitution products such as anisidine or phenetidine, also piperidine, benzylamine, cyclohexylamine, pipecoline, and lupetidine. The reaction of the amine with the imino halide may take place either directly or in the presence of an inert solvent. In examples (1) Paranitrobenzene sulphonasetamide is treated with phosphorus pentachloride and the imido chloride so produced reacted with dry ammonia to give p-nitrophenyl sulphonamidine which on reduction by catalytic hydrogenation gives N-(p-amino-benzenesulphon)-acetamine ; (2) Acetamidine hydrochloride is treated with para-nitrobenzene sulphonic acid chloride in suspension in dry pyridine and the nitrocompound so produced is reduced to give the same amidine as in example (1) ; (3) A benzene solution of para-nitrobenzenesulphonacetamido chloride is shaken with aqueous methylamine, and the product reduced catalytically to give N-(p-aminobenzenesulphon)-N<SP>1</SP>-methyl - aceta - midine. The same compound is obtained by condensation of N-methyl-acetamidine with p-nitrobenzenesulphonic acid chloride and reduction; (4) The imido chloride of example (1) is reacted with ethylamine and then reduced to N -(p-aminobenzenesulphon)- N<SP>1</SP>-ethyl acetamidine propylamine may be used instead of ethylamine ; (5) The imido chloride of pnitrobenzenesulphonacetamide is reacted with diethylamine and reduced to N-(p-aminobenzenesulphon)-N<SP>1</SP>-diethylacetamidine; (6) Dialikylamine is substituted for diethylamine in example (5) ; (7) Ethanolamine is reacted with p-nitrobenzenesulphonacetamido chloride and reduced ; (8) monoalkylamine is substituted for monomethylamine. The product may be hydrogenated to produce a saturated compound; (9) Piperidine is reacted with p-nitrobenzenesulphon-acetimido chloride and reduced. Pipecoline, lupetidine or morpholine may be substituted for pyridine ; (10) p-nitrobenzenesulphon-propionamide is reacted with phosphorus chloride and the products treated with ammonia and reduced to N-(p-aminobenzenesulphbn)-propionamidine. The ammonia may be replaced by aliphatic amines; (11) pnitrobenzenesulphonbenzamide is reacted with phosphorus pentachloride, reacted with ammonia and reduced to N (p-aminobenzenesulphon) benzamidine; (12) p-nitrobenzene sulphonamide is reacted with N-diethyloxamic acid chloride to give p-nitrobenzenesulphondiethylamideoxamide which is converted by phosphorus pentachloride into imido chloride which is reduced to N-(p-aminobenzenesulphon)- N<SP>1</SP>-diethylamido-oxamidine; (13) p-nitrobenzenesulphon-chloracetamide is treated with phosphorus pentachloride and then with dimethylamine and reduced to N-(p-aminobenzenesulphon) -N<SP>1</SP> -dimethyl- N" - dimethyl - aminoacetamidine ; (14)p-nitrobenzenesulphonhexahydrobenzamide is treated with phosphorus pentachloride and then with ammonia and reduced to N-(p-aminobenzenesulphon)-hexahydrobenzamidine. (15) p-Nitrobenzenesulphonic acid chloride is reacted with isovalerylamidine hydrochloride to give N-(p-nitrobenzenesulphon)-isovalerylamidine, which is then reduced to the amino compound. Samples have been furnished under Sect. 2 (5) of compounds which have been prepared according to the following schedules :-(1) Furanoyl chloride is reacted with p-nitrobenzenesulphonamide in the presence of aluminium chloride, the amide so obtained reacted with phosphorus pentachloride and then with ammonia and the nitro-amidine reduced to give N-(p-aminobenzenesulphon) furanoylamidine. (2) p- Nitrobenzenesulphonamide is reacted with p-nitrobenzoyl chloride, then with phosphorus pentachloride, and then with isopropylamine. Reduction gives N-(p-aminobenzenesulphon)- N'-isopropyl-p-aminobenzamidine. (3) Isopropylamine is reacted with the imido chloride of p-nitrobenzenesulphon-furanoylamide and reduced to N-(p-aminobenzenesulphon)-N<SP>1</SP>-isopropyl-furanoylamidine. (4) Butylamine is reacted with the imido chloride of p-nitropenzenesulphonfuranoylamide and reduced to N - (p - aminobenzenesulphon) - N<SP>1</SP> - - n - butyl furanoylamidine. (5) Methylamine is reacted with the imidochloride of p-nitrobenzenesulphon-p-nitro-benzamide, and reduced to N - (p - aminobenzenesulphon) - N<SP>1</SP> - methyl - p-aminobenzamidine. (6) p-Nitrobenzenesulphon-p<SP>1</SP>-chloro-phenylacetamide is reacted with phosphorus pentachloride and then with ammonia and finally reduced to N-(p-aminobenzenesulphon) -p<SP>1</SP>- chloro - phenylacetamidine. (7) The imidochloride obtained as in schedule (6) is treated with methylamine and reduced to N - (p - aminobenzenesulphon) - N<SP>1</SP> - methyl - p - chlorophenylacetamidine. (8) The imidochloride obtained as in schedule (6) is treated with ethylamine and reduced to N-(p-aminobenzenesulphon) - N<SP>1</SP> - ethyl - p - chlorophenylacetamidine. (9) p- Nitrobenzenesulphon-cinnamylamide is reacted with phosphorus pentachloride to give an imidochloride which is treated with ammonia and reduced to N-(p-aminobenzenesulphon)-cinnamylamidine. (10) Fencholic acid chloride is reacted with p-nitrobenzenesulphonamide in the presence of aluminium chloride and the p-nitrobenzenesulphon-fencholylamide reacted with phosphorus pentachloride and then reduced to give N-(p-aminobenzenesulphon)-fencholy lamidine. The Specification as open to inspection under Sect. 91 includes also the treatments of benzenesulphon acylamides which are substituted in the p-position by any group containing nitrogen or a, derivative thereof having a p-substitute which can be converted into a group containing nitrogen. Groups specified in addition to a nitro group or an acylamino group include azo. azoxy. and azomethine group. Additional acids which are specified as suitable for the acyl residue of the benzenesulphonacylamide include α- or #-substituted acrylic acids such as crotonic acid, also camphoric acid, a pyrone carboxylic acid, dimethyloxazole carboxylic acids, paramethoxy benzoic acid, veratric acid and toluylic acid. This subject-matter does not appear in the Specification as accepted.