Patent GB-789430-A (GB)
Title: Derivatives of amino-thiochromanones and amino-thiochromones
IPC: C07D335/06
Filed: 1956-04-30
Abstract: The invention comprises 5-substituted-8-methyl-thiochromanones and thiochromones of the general formul : <FORM:0789430/IV (b)/1> wherein X represents an aliphatic chain, Y is a tertiary amino group, and the molecule can be substituted in the 2- or 3-position, e.g. by alkyl, alkoxy, aryl, halogen-aryl and alkoxy-aryl; and processes for their preparation: (a) by reacting a 5-aminothiochromanone or thiochromone with a reactive ester of an amino alcohol or a salt thereof, preferably in the presence of a dehydrating agent; (b) by reacting a 5-halogen-thiochromanone or thiochromone with an aliphatic diamine in which at least one amino group contains a free hydrogen atom; (c) by condensing a 5-hydroxy-thiochromanone or thiochromone or an ether thereof with a diamine as in (b); (d) by reacting an amino-thiochromanone or thiochromone with an alkylene oxide or alkylene halohydrin, treating the corresponding hydroxyalkyl compound with phosphorus oxychloride and reacting the resultant halide with an amine; (e) by addition of a 5-aminothiochromanone or thiochromone to acrylonitrile and subsequent hydrogenation of the cyano group to an aminomethyl group; (f) by condensation of a b -(5-aminophenylmercapto) fatty acid ester with a reactive ester of an amino alcohol and cyclization of the resulting, basically alkylated compound with a dehydrating agent.  In examples: (1) sodium pyrosulphite is added to a solution of KI, 4-nitrotoluene - 2 - sulphochloride and HCl in aqueous dioxane, giving 2,21-dimethyl-5,51-dinitrodiphenyldisulphide (A), which is suspended in alcohol and treated with sodium sulphide in NaOH and then with chloropropionic acid to yield b  - (2 - methyl - 5 - nitrophenylmercapto)-propionic acid; ferrous sulphate reduction yields the 5-amino derivative, which after cyclization with H2SO4 to 5-amino-8-methylthiochromanone is reacted with diethylaminoethyl chloride to give 5-diethylaminoethylamino - 8 - methylthiochromanone; (2) treatment of A as in (1) using b -chlorobutyric acid gives b  - (2 - methyl - 5 - nitrophenylmercapto) butyric acid, the 5-amino derivative, 2,8-dimethyl - 5 - aminothiochromanone, and finally 2,8 - dimethyl - 5 - diethylaminoethylaminothiochromanone; (3) as in (2) using b -chlorovaleric acid gives 2-ethyl-5-diethylaminoethylamino-8 - methylthiochromanone; (4) 5 - amino - 8-methylthiochromanone is acetylated, treated with sulphuryl chloride in methylene chloride and then with dimethylaniline giving 5-amino-8-methylthiochromone which is converted to 5-diethylaminoethylamino - 8 - methylthiochromone hydrochloride; similarly (5), are prepared the 2,8 - dimethyl - and 2 - ethyl - 8 - methyl-derivatives; (6) 5 - acetamino - 8 - methylthiochromanone is treated with p-nitrosodimethylaniline in aqueous ethanolic KOH and the resulting 3-hydroxy-5-amino-8-methylthiochromone reacetylated, O-methylated with dimethyl sulphate and after hydrolysis the 3-methoxy - 5 - amino - 8 - methylthiochromone is converted to 3 - methoxy - 5 - diethylaminoethylamino - 8 - methylthiochromone; (7) b  - (2 - methyl - 5 - aminophenylmercapto) propionic acid is esterified with ethanol-H2SO4, reacted with diethylaminoethyl chloride, refluxed with dilute HCl and then cyclized with H2SO4 to 5-diethylaminoethylamino-8-methylthiochromanone; (8) 2-methyl-5-chlorothiophenol is reacted with methyl methacrylate, the resulting methyl b -2-methyl-5-chlorophenylmercapto - isobutyrate saponified, cyclized to 5-chloro - 3,8 - dimethylthiochromanone and then reacted with diethylethylenediamine and copper powder yielding 5-diethylaminoethylamino-3,8-dimethylthiochromanone; (9) 5-chloro-8-methylthiochromanone prepared by method of (8) is converted by method of (6) to 3-methoxy-5-chloro - 8 - methylthiochromone and reacted with diethylethylenediamine giving 3-methoxy-5-diethylaminoethylamino - 8 - methylthiochromone; (10) to (19) the following 5-aminothiochromones are converted to the corresponding 5 - diethylaminoethylamino - thiochromones: 3,8 - dimethyl -, 2,3,8 - trimethyl -, 2,8 - dimethyl - 3 - ethyl -, 2,8 - dimethyl - 3 - propyl-, 2,8 - dimethyl - 3 - isopropyl -, 2 - phenyl - 8-methyl -, 3 - phenyl - 8 - methyl -, 2 - (21-chlorphenyl) - 8 - methyl -, 2 - (41 - chlorphenyl)-8 - methyl -, and 2 - (41 - methoxyphenyl) - 8-methyl.