Patent GB-414105-A (GB)
Title: Manufacture of quinoline derivatives
Filed: 1933-01-26
Abstract: Py-Bz-diaminoquinoline derivatives are prepared by reacting ammonia or an alkylamine with a compound of the general formula <FORM:0414105/IV/1> (wherein either R1 stands for halogen or an alkoxy residue and R2 for hydrogen or methyl, or R1 stands for hydrogen and R2 for halogen or an alkoxy residue, and one y stands for the group <FORM:0414105/IV/2> being hydrogen or acyl and Z2 being hydrogen or alkyl, and the other y stands for hydrogen), or by reduction of a compound of the foregoing general formula (wherein either R1 stands for a hydrazino residue and R2 for hydrogen or methyl, or R1 stands for hydrogen and R2 for a hydrazino residue, the symbols y being defined as above); in either case the halogen, alkoxy or hydrazino residue is exchanged for amino or alkylamino. Alternatively these quinoline derivatives are prepared by reducing the nitro group in compounds of the foregoing formula wherein either R1 stands for an amino group and R2 for hydrogen or methyl, or R1 stands for hydrogen and R2 for an amino group, and one y stands for the nitro group and the other y for hydrogen.  The diaminoquinolines obtained by these processes may readily be acylated in the Bz-amino group without affecting the Py-amino group.  Phosgene may be used for such acylation to give a symmetrical urea, or cyanuric acid (for example cyanuric halide, one halogen atom of which may be replaced by treatment with a reagent capable of introducing hydroxyl or alkoxyl). In examples: (1) 4-hydroxy-6-acetaminoquinaldine (prepared from p-aminoacetanilide and acetoacetic ester) is treated with phosphorus oxychloride to give the 4-chloro body which is saponified and condensed in phenol with ammonia to give 4.6-diaminoquinaldine; (2) 4.6 - diaminoquinaldine is acylated with (a) cinnamoyl chloride, (b) phosgene, (c) oxalylchloride, (d) malonyl chloride, (e) cyanuric chloride to give (2-methyl-4-aminoquinolyl-6)-dichlorcyanuramide, and this is further condensed with ammonia to give the corresponding melamine, (f) chlorcyanurdiamide to give the melamine of (e), (g) cyanuric chloride to give: N1-N2-di-(2-methyl-4-aminoquinolyl-6-) -chlorcyanurdiamide and this product is condensed with ammonia, diethylamine and b -diethylaminoethylamine to give a corresponding melamine and substituted melamines respectively, or this product is boiled with dilute hydrochloric acid to give symm. cyanuric acid-di-(2-methyl-4-aminoquinolyl-6-)-diamide, or this product is treated with sodium alcoholate to give di - (2 - methyl - 4 - aminoquinolyl - 6 - amino)-cyanuric acid ethyl ester, (h) aminocyanurdichloride to give N1-(2-methyl-4-aminoquinolyl - 6 -) - diaminocyanurchloride and this product is further condensed with ammonia to give the melamine of (e) or with more 4.6-diaminoquinaldine to give a melamine referred to in (g); (3) 4-chloro-6-acetaminoquinaldine (cf. (1) above) is condensed in phenol with ammonia to give the 4-amino body; 4-chloro-6-benzoylaminoquinaldine may be similarly converted; (4) 4-chloro-6-acetylaminoquinaldine is condensed with alcoholic ethylamine, methylamine or butylamine to give the 4-ethylamino-4-methylamino- or 4-butylamino bodies; (5) 6 - acetyl - ethylamino - 4 - chlorquinaldine (prepared from p-aminoethylacetanilide and acetoacetic ester--cf. (1) above) is condensed in phenol with ammonia and the acetyl group split off by saponification with dilute hydrochloric acid to give 4-amino-6-ethylaminoquinaldine, on treatment with cinnamoylchloride 4-amino-6-cinnamoyl-ethylaminoquinaldine is formed; 4-amino-6-propylaminoquinaldine and 4-amino-6-butylaminoquinaldine may be prepared in an analogous manner; (6) 4-amino-6-nitroquinoline is reduced in the form of its hydrochloride with iron powder; (7) 2-amino-6-nitroquinoline is reduced by hydrogen in ethanol and in presence of palladium; (8) 4 . 8 - diaminoquinaldine is prepared by converting 4-hydroxy-8-acetylaminoquinaldine (from o-aminoacetanilide and acetoacetic ester) to the 4-chloro body (cf. (1) above), condensing this with ammonia and saponifying; (9) 4.8- diaminoquinaldine is acylated with cinnamoyl chloride; 4-amino-8-methylaminoquinaldine may be similarly treated to give 4-amino-8-cinnamoyl-methylaminoquinaldine.  The alkoxy- and hydrazino-derivatives which may be used as starting materials are obtained from the corresponding halogen compounds by the action of sodium alcoholate or phenylhydrazine respectively. Specifications 282,143, [Class 2 (iii)], and 367,952 are referred to.  The Specification as open to inspection under Sect. 91 comprises the production of the desired compounds by exchanging in compounds of the foregoing general formula wherein R1 and R2 additionally represent carbamino and carbazido residues, the halogen, alkoxy, hydrazino, carbamino or carbazido residues for amino or alkylamino.  The carbamino and carbazido compounds thus employed as starting materials are prepared according to the p  processes illustrated by examples 8 and 9 of Specification 282,143.  An additional example describes the acylation of 4.6-diaminoquinaldine with fumaric acid chloride.  This subject-matter does not appear in the Specification as accepted.