Patent GB-743272-A (GB)
Title: New quinoxalinium salts and pseudo-bases thereof and processes for making them
IPC: A61K31/00
Filed: 1953-06-01
Abstract: The invention comprises (1) quinoxalinium salts of the formula <FORM:0743272/IV(a)/1> where R1 is phenyl or substituted phenyl, or a monocyclic heterocyclic radical of aromatic character, R2 is an aliphatic residue of not more than 10 carbon atoms, R3-R6 are hydrogen, alkyl, free or etherified hydroxyl, mercapto or halogen, and A is an anion; and (2) the corresponding pseudo-bases, which are probably substituted 2 - hydroxy - 1:2 - dihydroquinoxalines.  The compounds are prepared by reacting mono - N - substituted o - phenylene diamines with R1.CO.CH:X(X = O or NOH) or R1.CO.CH2X (X = Halogen) and in the latter case oxidizing the dihydroquinoxaline initially formed.  (Oxidation may occur spontaneously in the air or by disproportionation.)  Alternatively an unsubstituted o-phenylene diamine can be used and the group R2 introduced into the quinoxaline by normal alkylation methods.  The compounds can also be made by oxidation of the corresponding tetrahydroquinoxalines.  Either the salts or the pseudo-bases are obtained, depending on the working conditions, and one may be converted into the other by normal methods.  When the residue R2 contains an amino group this may be converted into its acid addition or quaternary salts.  Examples show the production of the following: 1 - methyl - 3 - phenylquinoxalinium iodide, methosulphate and p-toluenesulphonate, 1 - methyl - 3 - p - diphenylylquinoxalinium methosulphate, 1 - n - propyl - 3 - phenylquinoxalinium iodide, 1 - hydroxyethyl - 3-phenylquinoxalinium chloride, iodide and benzilate, 1 - hydroxyethyl - 3 - p - chlorophenyl - quinoxaliniu chloride, 1 - hydroxyethyl - 3 - (2 - thienyl) - quinoxalinium chloride, 1 - dihydroxypropyl - 3 - phenylquinoxalinium chloride, 1 - (b  - dimethylaminoethyl) - 3-phenylquinoxalinium chloride hydrochloride, 1 - (b  - dimethylaminoethyl) - 3 - p - chlorophenylquinoxalinium chloride hydrochloride, 1 - (b  - diethylaminoethyl) - 3 - phenylquinoxalinium chloride hydrochloride, pseudobase, hydroiodide, nitrate, sulphate, phosphate, perchlorate, methiodide, methyl methosulphate and methyl p - toluenesulphonate, 1 - (b  - diethylaminoethyl) - 3 - p - tolylquinoxalinium chloride hydrochloride, 1 - (b  - diethylaminoethyl) - 3 - p - chlorophenylquinoxalinium chloride hydrochloride, 1 - (b  - diethylaminoethyl) - 3 - (31:41 - dichlorophenyl) - quinoxalinium chloride hydrochloride, 1-(b -di-n-butylaminoethyl) - 3 - phenylquinoxalinium chloride hydrochloride, 1 - (b  - piperidinoethyl) - 3-phenylquinoxalinium chloride hydrochloride, 1 - (g  - diethylaminopropyl) - 3 - phenylquinoxalinium chloride hydrochloride, 1 - (b  - (b -diethylaminoethylthio) - ethyl) - 3 - phenylquinoxalinium iodide hydriodide, 1 - (b  - (b  - diethylaminoethylthio) - ethyl) - 3 - p - chlorophenylquinoxalinium iodide hydriodide, 1-hydroxyethyl - 3 - phenyl - 7 - methylquinoxalinium chloride, 1 - (b  - diethylaminoethyl) - 3-phenyl - 6 - methylquinoxalinium iodide hydriodide, 1 - (b  - diethylaminoethyl) - 3 - p-chlorophenyl - 6 - methyl - quinoxalinium chloride hydrochloride and pseudobase, 1-methyl - 3 - phenyl - chloroquinoxalinium methosulphate and 1 - hydroxyethyl - 3-phenyl - chloroquinoxaliniu chloride, the last two being derived from 4-chloro-o-phenylene diamine.  Salts may also be formed with other anions, e.g. of acetic, tartaric, citric, ascorbic, benzoic or methanesulphonic acid.  R1 may be phenyl, pyridyl or thienyl and may be substituted, e.g. by alkyl, alkoxy, phenyl or halogen.  R2 may be an alkyl or alkenyl group (e.g. methyl, butyl, allyl) and may be substituted, e.g. by dialkylamino, piperidino, pyrrolidino, morpholino, hydroxy, alkoxy or dialkylaminoalkoxy. Quinoxalines used as intermediates are prepared as follows: 2-p-diphenylyl-quinoxaline from p-phenyl-phenacyl chloride and o-phenylene diamine; 2-(2-thienyl)-quinoxaline from isonitroso-acetothienone and o-phenylene diamine; 2 - phenyl - Bz - chloroquinoxaline from 4 - chloro - o - phenylene diamine and isonitroso - acetophenone; and 1 - hydroxyethyl-3 - phenyl - 1:2:3:4 - tetrahydroquinoxaline (as hydrochloride) by catalytic hydrogenation of 1 - hydroxyethyl - 3 - phenylquinoxalinium chloride.  N - Monosubstituted - o - phenylene diamines are made as follows: N-(b -piperidinoethyl) by condensing piperidine with N-(b -chlorethyl)-o-nitraniline and reducing the nitro group; N-(b  - di - n - butylaminoethyl) similarly from dibutylamine, and N - (b  - (b  - diethylaminoethylthio) - ethyl) from b  - diethylamino - ethanethiol. 3:4 - Dichlorophenacyl bromide is obtained by bromination of 3:4-dichloroacetophenone.