Patent GB-347515-A (GB)
Title: Manufacture of quinoline- and acridine-compounds
IPC: C07D215/56
Filed: 1930-05-29
Abstract: Quinoline and acridine compounds of the general formula <FORM:0347515/IV/1> where y=hydrogen or any univalent residue, X=O, S or NH, and R=a substituted quinoline or acridine residue containing at least one substituted or unsubstituted NH2 in its nuclei are made (1) by reaction between a correspondingly substituted benzthiazolyl-, benzoxazolyl-, benzimidazolyl-, halogenquinoline or acridine compound, directly or after conversion into the corresponding ether, with ammonia or a primary or secondary amine, or (2) by converting a quinoline- or acridine-carboxylic acid which contains in the nucleus a nitro group or a primary, secondary or tertiary amino group, into the corresponding benzthiazole, benzoxazole or benzimidazole, the nitro group being reduced where necessary. Compounds containing an alkoxy group can be hydrolysed to the corresponding oxy compound and converted into other alkoxy derivatives.  In examples (1)-(5) 6-(61-methylbenzthiazolyl-21)-4-chloroquinaldine is heated with alcoholic ammonia, ethylamine, piperidine, g -diethylamino-b -oxypropylamine or p-aminophenol-b -diethylaminoethylether, (6) the chloro-compound of (1) is treated with phenol and sodium ethylate and the g -phenylether obtained condensed with glycocol, (7)-(9) 6-(61-methoxybenzthiazolyl-21)-4-chlorquinaldine is heated with alcoholic ammonia or isoamylamine and the corresponding ethoxy compound with alcoholic ammonia, (10) 7-(61-ethoxybenzthiazolyl-21)-4-chlorquinaldine is heated with alcoholic ammonia, (11)-(13) 2-(61-methylbenzthiazolyl-21)-9-chloracridine is heated with alcoholic ammonia or with phenol and g -diethylamino-b -oxypropylamine and the corresponding 61-ethoxy compound with phenol and ammonia, (14)-(15) 4-(61- ethoxybenzthiazolyl - 21) - 2 - chlorquinaldine i heated with alcoholic ammonia or with g -dimethylamino-b -oxypropylamine, (16) 3-(61-ethoxybenzthiazolyl-21)-4-chlorquinoline is heated with alcoholic ammonia, (17) 2-(g -chlorquinaldyl-61)-6-methyloxazole is heated with alcoholic ammonia, (18) a -chlorcinchoninic acid (from the oxy-acid and phosphorus oxychloride) is treated with ethylamine and thionylchloride, and the a -ethylaminocinchonic acid chloride obtained condensed with 3 : 4-diaminotoluene to form the benziminazole, and with (19) 2-amino-5-ethoxythiophenol (zinc salt) to form the benzthiazole, (20) 8-nitro-6-quinolinecarboxylic acid (from 3-nitro-4-aminobenzoic acid by Skraup's reaction) is treated with thionyl chloride and the acid chloride condensed with 2-amino-5-ethoxythiophenol to form 6-(61-ethoxybenzthiazolyl-21)-8-nitroquinoline which is reduced to the amino compound, (21) the methoxy compound obtained in (7) is saponified with hydrobromic acid and the oxy-compound etherified with chlorethyldiethylamine or with (22) allylbromide, (23) 6-(61-ethoxybenzthiazolyl-21)-4-chloroquinaldine (example 9) is heated with hydrobromic acid, the oxy-compound treated with sodium ethoxide and isoamylbromide to form the isoamylether and the chlorine replaced by the amino group, (24) the chloro compound of (1) is treated with monomethylaniline, (25) 6-(nitro-61-methylbenzthiazolyl-21-)-4-chlorquinaldine made from Bz-nitrodehydrothio-p-toluidine or by nitration of the chloro compound of (1) is treated with phenol and diethylamine; reduction gives the corresponding amino compound, (26) the nitrochlor compound of (25) is treated with phenol and ammonia; the product forms a salt with glycollic acid; the same product is obtained by nitration of the compound obtained in the first example, (27) the chloro compound in (25) is reduced and the aminochloro compound treated with ammonia in phenol solution; the same product is obtained by reducing the compound described in (26), (28) 2-(nitromethylbenzthiazolyl)-9-chloroacridine, is dissolved in phenol and treated with ammonia; it gives a salt with glycollic acid and a diamino compound on reduction.  Chloroquinaldine derivatives.-6-(61-Methylbenzthiazolyl-21) -4-chloroquinaldine is made by heating dehydrothiotoluidine with acetoacetic ester, heating the Schiff's base thus obtained in a -chloronaphthalene to form 2-(21-methyl-41-oxyquinolyl-61) -6-methylbenzthiazole and treating this with phosphorus oxychloride.  6-(61-Methoxy and 61-ethoxybenzthiazolyl-21-)-4-chloroquinaldines are similarly made from 2-p-aminophenyl-6-methoxy- and 6-ethoxybenzthiazole respectively, 7-(61-ethoxybenzthiazolyl-21-)-4-chlorquinaldine from 2-m-aminophenyl-6-ethoxybenzthiazole, and 2-(g -chlorquinaldyl-61-)-6-methyloxazole from 2-p-aminophenyl-6-methylbenzoxazole.  Chloracridine derivatives.-2 - (91 - Chloroacridyl-21 - ) - 6 - methylbenzthiazole is made by boiling o-chlorbenzoic acid with amylalcohol and potassium carbonate, adding dehydrothiotoluidine and copper powder, boiling, and treating the methylbenzthiazolyl-diphenylaminocarboxylic acid thus obtained with phosphorus oxychloride.  The corresponding 6-methoxybenzthiazole is obtained starting from 2-p-aminophenyl-6-ethoxybenzthiazole and the corresponding nitro derivative starting from nitrodehydrothiotoluidine.  The latter compound is also obtained by nitrating the methylbenzthiazolyldiphenylamine carboxylic acid and ring-closure with phosphorus oxychloride.  Chlorquinoline derivatives.-4-(61-Ethoxybenzthiazolyl-21) -2-chlorquinoline is made by treating a -oxycinchoninic acid with thionylchloride, condensing the acid chloride with 2-amino-5-ethoxythiophenol and treating the oxyquinoline thus obtained with phosphorus oxychloride. 3-(61-Ethoxybenzthiazolyl-21)-4-chloroquinoline is made by condensing anthranilic acid ester with sodium formylacetic ester and treating the b -o-carbethoxyphenylaminoacrylic acid thus obtained with sodium to form g -oxy-b -quinolinecarboxylic acid which is converted into the acid chloride, condensed with 2-amino-5-ethoxythiophenol (zinc salt) forming 3-(61-ethoxybenzthiazolyl-21)-4-oxyquinoline which is heated with phosphorus pentachloride in phosphorus oxychloride to form the chloro derivative.  Specification 276,012, [Class 2 (iii), Dyes &c.], is referred to.