Patent GB-788784-A (GB)
Title: Derivatives of 2-keto-2, 3, 4, 5, 6, 7 , 8, 10-octahydronaphthyl-(7)-methane and a process for preparing the same
Filed: 1954-04-28
Abstract: The invention comprises derivatives of 2-keto - 2,3,4,5,6,7,8,10 - octahydronaphthyl - (7) - methane of the formula: <FORM:0788784/IV (b)/1> wherein R1, R2 and R3 each represents hydrogen or alkyl of not more than four carbon atoms, Y is carboxy, carbomethoxy, carboethoxy, cyano, or carbamido, and Z is hydrogen, carboxy, carbomethoxy, carboethoxy, or acyl, and a process of preparing them by reacting a compound of the formula: <FORM:0788784/IV (b)/2> where Q is halogen, with a compound of the formula: <FORM:0788784/IV (b)/3> where Y1 and Z1 correspond to Y and Z except that they do not represent hydrogen, carboxy, or carbamido, or a metal compund thereof, R2, Y1 and Z1 being such as to retain the activity of the hydrogen marked with an asterisk, and then saponifying or decarboxylating the condensation product, if desired.  The reaction may be performed in an organic solvent, e.g. alcohol, ether, benzene, toluene, pyridine) in presence of an alkaline condensing agent, a metal, or an anion-exchange resin (e.g. an alkali metal alcoholate, trimethylbenzylammonium hydroxide, an alkali or alkaline earth carbonate or hydroxide, metallic sodium, potassium, or magnesium.  Reaction temperature may be room temperature or 60-100 DEG  C.  In examples: (1) 2-keto-1,10-dimethyl - 2,3,4,5,6,10 - hexahydronaphthalene is reacted with (a) diethyl malonate, to give diethyl - 2 - keto - 1,10 - dimethyl - 2,3,4,5,6,7, 8,10 - octahydronaphthyl - (7) - malonate, (b) diethyl methylmalonate, to give diethyl 2-keto - 1,10 - dimethyl - 2,3,4,5,6,7,8,10 - octahydronaphthyl - (7) - methylmalonate, (c) methyl a -methylcyanoacetate, to give methyl a  - cyano - a  - [2 - keto - 1,10 - dimethyl - 2,3,4,5,6,7,8,10 - octahydronaphthyl - (7)]-propionate, (d) ethyl acetoacetate, to give ethyl 2 - keto - 1,10 - dimethyl - 2,3,4,5,6,7,8,10-octahydronaphthyl - (7) - acetoacetate, (e) ethyl a -methylacetoacetate, to give ethyl a -[2-keto - 1,10 - dimethyl - 2,3,4,5,6,7,8,10 - octahydronaphthyl - (7)] - a  - acetopropionate, (f) diethyl methylmalonate to give diethyl 2-keto-1,10 - dimethyl - 2,3,4,5,6,7,8,10 - octahydronaphthyl - (7) - methylmalonate, (g) methyl cyanoacetate, to give methyl-2-keto-1,10-dimethyl - 2,3,4,5,6,7,8,10 - octahydronaphthyl-(7)-cyanoacetate.  Also in examples, (2) 2-keto-10 - methyl - 2,3,4,5,6,10 - hexahydronaphthalene is reacted with ethyl methylmalonate, to give ethyl-2-keto-10-methyl-2,3,4,5,6,7,8,10-octahydronaphthyl - (7) - methylmalonate, (3) 2 - keto - 1,10 - dimethyl - 8 - bromo - 2,3,4,5,6,7,8,10 - octahydronaphthalene is reacted with diethyl methyl malonate to give diethyl 2 - keto - 1,10 - dimethyl - 2,3,4,5,6,7, 8,10 - octahydronaphthyl - (7) - methylmalonate. In further examples, (4) diethyl-2-keto-1,10-dimethyl - 2,3,4,5,6,7,8,10 - octahydronaphthyl - (7) - malonate is partially hydrolysed with hydrochloric acid in dioxane to give the monoethyl ester, which last is (5) decarboxylated by melting under reduced pressure to give ethyl 2 - keto - 1,10 - dimethyl - 2,3,4,5,6,7,8,10-octahydronaphthyl-(7)-acetate, or (6) the diethyl or monoethyl ester is completely hydrolysed to give 2-keto-1,10-dimethyl-2,3,4,5,6,7, 8,10 - octahydronaphthyl - (7) - malonic acid, which (7) is decarboxylated by heating under pressure, to give 2-keto-1,10-dimethyl-2,3,4,5, 6,7,8,10 - octahydronaphthyl - (7) - acetic acid; (8) diethyl - 2 - keto - 1,10 - dimethyl - 2,3,4,5,6, 7,8,10 - octahydronaphthyl - (7) - methyl malonate is partially hydrolysed with alcoholic potash to give the monoethyl ester, or completely hydrolysed to give the acid, or the monoethyl ester is hydrolysed to the acid, and the acid and monoethyl ester are each decarboxylated by heating in pyridine to give a -[2-keto - 1,10 - dimethyl - 2,3,4,5,6,7,8,10 - octahydronaphthyl - (7)] - propionic acid and its ethyl ester; (9) 2-keto-1,10-dimethyl-2,3,4,5,6, 7,8,10 - octahydronaphthyl - (7) - methyl malonic acid is esterified with methanol in presence of sulphuric acid to give the dimethyl ester; (10) methyl a -cyano-a -[2-keto-1,10-dimethyl - 2,3,4,5,6,7,8,10 - octahydronaphthyl-(7)]-propionate is saponified to the acid, which is decarboxylated by heating in collidine to give a  - [2 - keto - 1,10 - dimethyl - 2,3,4,5,6,7,8,10-octahydronaphthyl - (7)] - propionitrile, which is saponified by heating with sulphuric acid to give a  - [2 - keto - 1,10 - dimethyl - 2,3,4,5,6,7 8,10 - octahydronaphthyl - (7)] - propionamide, which is further saponified to the acid by heating with caustic soda solution in dioxane; (11) methyl - 2 - keto - 1,10 - dimethyl - 2,3,4,5, 6,7,8,10 - octahydronaphthyl - (7) - cyanoacetate is saponified to the acid; (12) diethyl 2-keto-10-methyl - 2,3,4,5,6,7,8,10 - octahydronaphthyl-(7)-methylmalonate is saponified to the acid.