Patent GB-584917-A (GB)
Title: Secondary aromatic amines and process for obtaining the same
IPC: C07D213/74
Filed: 1943-10-26
Abstract: Ethylhexyl alcohol is employed as a defoaming agent in the condensation of 2-chloro-4 : 6-diamino-1 : 3 : 5-triazine with p-arsanilic acid by heating in suspension in dilute hydrochloric acid.  Reference has been directed by the Comptroller to Specifications 230,082, [Class 2 (iii)], and 537,690, [Group IV].ALSO:Secondary amines containing one carbonnitrogen heterocyclic radical and one aryl radical are manufactured by reacting, in an aqueous and/or an inert water-miscible organic solvent at an initial pH between 1 and 6, a primary aromatic amine of the formula R-NH2, where R is a substituted or unsubstituted aryl radical such as phenyl, naphthyl, biphenyl, Bz-quinolyl or the radical of any other carbocyclic or heterocyclic compound containing at least one benzene ring, to a carbon atom of which the primary amino group is attached, said aromatic amine being, if desired, further substituted on a carbon atom or atoms of the benzene ring by one or more atoms or groups (other than the amino group) which are not affected by the halogen of the heterocyclic compound (e.g. halogen attached to the aromatic nucleus, alkyl, aralkyl, aryl, hydroxy, alkoxy, hydroxyalkoxy, hydroxyalkoxyalkoxy, nitro, acylamino, arsono, arseno, arsinoso, sulphono, sulphamido, heterocyclic - N - substituted sulphamido, carboxyl and esterified carboxyl groups), with a halogen-substituted carbon-nitrogen heterocyclic compound having three alternate double bonds and a total of six carbon and nitrogen atoms in the heterocyclic ring and a reactive halogen substituent of not more than one carbon atom thereof at one of the positions ortho and para to a nuclear nitrogen atom, said heterocyclic compound being, if desired, substituted on a further carbon atom or atoms by a radical such as nitro, hydroxy, aryloxy, alkoxy, amino and substituted amino (e.g. alkylamino, dialkylamino, hydroxyalkylamino, carboxyalkylamino or dialkylaminoalkylamino), or by a further halogen atom in a non-reactive position.  The reaction is preferably carried out with the addition of sufficient inorganic acid to make the initial pH between 1 and 4 and the final pH not substantially less than 1. The solvent employed is preferably water or a mixture thereof with an inert water-miscible organic solvent, e.g. alcohol, acetone or ethyleneglycol monoethyl or monomethyl ether, but the organic solvents may also be used in the substantial absence of water. In examples: (1) an aqueous suspension of 2-chloro-4 : 6-diamino-1 : 3 : 5-triazine and p-arsanilic acid is boiled with the addition of hydrochloric acid and ethylhexyl alcohol (or other defoaming agent) to produce 2 : 4-diamino-6-(41-arsonophenylamino)-1 : 3 : 5-triazine; comparative results at other pH values are tabulated, alkaline conditions causing partial replacement of one of the amino groups by hydroxyl; (2) the triazine starting material in (1) is replaced by 2 : 4-di-(b -hydroxy-n-propyl)-amino-6-chloro-1 : 3 : 5-triazine, and (3) by 2 : 4-di-(monoethanolamino)-6-chloro-1 : 3 : 5-triazine; (4) an aqueous suspension of 2-chloro-4 : 6-diamino-1 : 3 : 5-triazine and 2-hydroxy-4-aminophenylarsonic acid is refluxed with the addition of hydrochloric acid; (5) the arsonic acid in (4) is replaced by 3-amino-4-hydroxyphenylarsonic acid, or by other aminophenylarsonic acids, aminobenzoic acids, aminobenzenesulphonic acids, chloroanilines, nitroanilines, aniline or toluidines; (6) sulphanilic acid and 2-amino-4-chloropyrimidine are refluxed in water with the addition of hydrochloric acid, yielding 2-amino-4-(41-sulphophenylamino) - pyrimidine; (7) the sulphanilic acid of (6) is replaced by anthranilic acid, and (8) by 4-aminobenzoic acid diethylaminoethyl ester; (9) 2-chloro-5-nitropyridine and sulphanilic acid are similarly reacted to produce 2 - (41-sulphophenylamino) - 5 - nitro - pyridine; (10) p-arsanilic acid and 3 : 9-dichloro-7-methoxyacridine similarly yield 9-(41-arsonophenylamino) - 3 - chloro - 7 - methoxyacridine.  Other starting materials specified are, on the one hand, o-, m- and p-bromoanilines, o-, m-and p - aminobenzenesulphonamides, 2 - (41 - aminobenzenesulphonamido)-pyridine, -thiazole and -pyrimidine, aminobenzamides and their substitution products, aminobenzoic esters, o-, m- and p-aminophenol, anisidines, phenetidines, p - aminophenoxyethanol, 4 - aminodiphenyl, a -and b  - naphthylamine, 8 - aminoquinoline, 1 - aminoanthracene, 4 - aminophthalic acid, 2 - amino - p - cymene, p - aminoautophenone, p - aminoacetonilide, aminocresols, aminonaphthols, aminonitrophenols, 2-aminoresorcinol, 4-aminophenylacetic acid, 5-aminosalicylic acid, cresidine, 4-aminophenylarsine oxide, 3-amino-4 - hydroxyphenylarsine oxide, 4 - di - (carboxymethylenethio) - arsenosoaniline, 4 - amino - phenoxyacetone, 3-amino-4-b -hydroxyethoxyphenylarsonic acid and 4-b -hydroxyethoxyaniline, and, on the other hand, 2 : 4-di-(methyl-and ethyl - amino) - 6 - chloro - 1 : 3 : 5 - triazine, 4 - amino - 2 - chloro-, 4 - chloro - 2 : 6 - diamino-, 2 - chloro - 4 - amino - 5 - nitro-, 2 - chloro - 5 - nitro-, 4 - chloro - 2 - methyl- and 2 - amino - 4 - chloro - 5 - bromo - pyrimidine, 2 - chloro- and 2 - bromo - pyridine, 2-chloroquinoline and its 5-, 6-, 7- and 8-nitro derivatives, 9-chloro-, 6-cyano-9-chloro-2-methoxy- and 7-nitro-9-chloro-2-methoxy-acridine, 2 - chloro-, 2 - chloro - 6 - methoxy-, 2 - chloro - 6 - nitro- and 2 - chloro - 6 - methoxy - 8 - nitro-lepidine, 4-chloro-, 4-chloro-6-methoxy-and 4 - chloro - 6 - nitro - quinaldine, 2 - chloro - cinchoninic acid, and 4-chloro- and 4-methyl-2-chloro-5 : 6-benzoquinoline.  2 : 4-Di-(ethylamino)-6-chloro-1 : 3 : 5-triazine is obtainable by reaction of cyanuric chloride with ethylamine.  2 - Amino - 4 - chloro - 5 - bromopyrimidine is obtainable from 2 : 4-dichloro-5-bromopyrimidine by heating with alcoholic ammonia. 2-Chloro-7-nitroquinoline is obtainable by the action of phosphorus pentachloride on 7-nitro-carbostyril.  2-Chloro-6-methoxylepidine is obtainable by treating 2-hydroxy-4-methyl-6-methoxyquinoline with phosphorus oxychloride.  2 - Chloro - 6 - methoxy - 8 - nitrolepidine and 4 - chloro-6-nitroquinaldine are obtainable by treating the corresponding hydroxy compounds with a mixture of phosphorus oxychloride and pentachloride.  The Specification as open to inspection under Sect. 91 comprises also the use of heterocyclic compounds containing more than one reactive halogen atom and containing atoms other than carbon and nitrogen in the ring.  In a further example, 2-amino-4 : 6-dichloropyrimidine and p-nitraniline are refluxed in water with the addition of hydrochloric acid. Additional starting materials specified are, on the one hand, phenylenediamines, diaminodiphenyl sulphone and 3-amino-4-b -(b 1-hydroxyethoxy)-ethoxy-phenylarsonic acid, and, on the other hand, 2 : 4-dichloro-6-amino-1 : 3 : 5-triazine, 4-amino-2 : 6-dichloropyrimidine, 2-chlorothiazole and 2-chlorobenzothiazole. This subject-matter does not appear in the Specification as accepted. Reference has been directed by the Comptroller to Specifications 230,082, [Class 2 (iii)], and 537,690.