Patent GB-612115-A (GB)
Title: Process for the manufacture of quinoline compounds
IPC: C07D215/54
Filed: 1945-10-23
Abstract: 4-Amino substituted quinoline compounds are prepared by reacting in acid solution or in the form of an acid salt a 4-haloquinoline of the formula <FORM:0612115/IV(b)/1> either with an aminomethyl substituted aminophenol of the formula <FORM:0612115/IV(b)/2> or with the corresponding aminophenol of the formula <FORM:0612115/IV(b)/3> followed by treatment of the latter reaction product with formaldehyde and the corresponding amine of the formula <FORM:0612115/IV(b)/4> where Z is hydrogen, halogen, -CH, -COOH, -COO alkyl, alkyl or alkoxy, n is 1, 2 or 3, R is hydrogen, halogen, -OH or saturated or unsaturated alkyl radical containing 1-8 carbon atoms inclusive, R2 is a saturated or unsaturated or unsaturated alkyl radical containing 1-8 carbon atoms inclusive, and R1 and R2 taken together with -N may form a saturated heterocyclic ring system which may be alkyl substituted, and X is a chlorine or a bromine atom.  The acids which may be present either as free acid, or as the salts are preferably the mineral acids or the lower fatty acids.  Those specifically mentioned being hydrochloric, sulphuric, phosphoric, acetic propionic and butyric acids.  Ring systems which are mentioned as being formed by R1 and R2 with nitrogen, include the pyrollidine, piperidine, morpholine and thiomorpholine rings.  In a modification of the invention the aminomethyl substituted aminophenol may be used in the form of its acyl derivative, the reaction being carried out in acid solution.  The various phases of the invention are illustrated by a large number of examples. The following compounds are the products obtained: (1) 4 - (31 - diethylaminomethyl - 41 - hydroxyanilino) - 7 - chloroquinoline; (2) 4 - (31 - N-piperidylmethyl - 41 - hydroxyanilino) - 7-chloroquinoline; (3) 4 - (31 - N - a  - methylpiperidylmethyl - 41 - hydroxyanilino) - 7-chloroquinoline; (4) 4 - (31 - N - morpholinyl methyl - 41 - hydroxyanilino) - 7 - chloroquinoline; (5) 4 - (31 - diethylaminomethyl-41-hydroxy - 51 - allylanilino) - 7 - chloroquinoline; (6) 4 - (31 - diethylaminomethyl - 41 - hydroxyanilino) - 7 - bromoquinoline; (7) 4 - (31 - N-thiomorpholenylmethyl - 41 - hydroxyanilino)-7 - chloroquinoline; (8) 4 - (31 - N - piperazinomethyl - 41 - hydroxyanilino) - 7 - chloroquinoline; (9) 4 - (31 - di - n - butylaminomethyl-41 - hydroxyanilino - 7 - chloroquinoline; (10) 4 - (31 - diethylaminomethyl - 41 - hydroxyanilino) - 6 : 7 - dimethylquinoline; (11) 4 - (31-N - piperidylmethyl - 41 - hydroxyanilino) - 6-methylquinoline; (12) 4 - (31 - N - morpholinylmethyl - 41 - hydroxyanilino) - 6 - methylquinoline; (13) 4 - (31 - N - piperidylmethyl - 41-hydroxyanilino) - 6 - methoxyquinoline; (14) 4 - (31 - N - morpholinylmethyl - 41 - hydroxyanilino) - methoxyquinoline; (15) 4 - (31 - diethylaminomethyl - 41 - hydroxyanilino) - 6-methoxyquinoline; (16) 4 - (31 - chloro - 51-diethylaminomethyl - 61 - hydroxyanilino) - 6-methoxyquinoline; (17) 3-carbethoxy - 4 - (31-N - piperdylmethyl - 41 - hydroxyanilino) - 6-methoxyquinoline; (18) 3 - methyl - 4 - (31 - diethylaminomethyl - 41 - hydroxyanilino) - 7-chloroquinoline; (19) 3 - methyl - 4 - (31 - N-piperidylmethyl - 41 - hydroxyanilino) - 7-chloroquinoline; (20) 3 - methyl - 4 - (31 - N-morpholinylmethyl - 41 - hydroxyanilino) - 7-chloroquinoline; (21) 4 - (31 - diethylaminomethyl - 41 - hydroxyanilino) - 5 - chloro - 8-methoxyquinoline; (22) 4 - (31 - diethylaminomethyl - 41 - hydroxyanilino) - 5 - methyl - 8-methoxyquinoline; (23) 2 - methyl - 4 - (31 - diethylaminomethyl - 41 - hydroxyanilino) - 6-methoxyquinoline; (24) 4 - (31 - diethylaminomethyl - 41 - hydroxyanilino) - 6 - hydroxyquinoline; (25) 4 - (31 - hydroxy - 41 - diethylaminomethylanilino) - 7 - cyanoquinoline; (26) 4 - (31 - ethylaminomethyl - 41 - hydroxyanilino)-7 - chloroquinoline; (27) 3 - methyl - 4 - (31 - n-butylaminomethyl - 41 - hydroxyanilino) - 7-chloroquinoline. Aminomethylaminophenols used above may be prepared by condensation of primary or secondary amines with formaldehyde and acylaminophenols having at least one unsubstituted position ortho or para to the phenolic hydroxyl group and hydrolysing the resulting N-substituted aminoethyl acylaminophenols.  They may also be prepared by the catalytic or nascent hydrogen reduction of aminomethyl nitrophenols. Specification 584,917 is referred to.