Procédé de préparation d'esters adamantane-carboxyliques du chloramphenicol

• Main Authors: LAKSHMI NARAYANAN,VENKATACHALA, DIETER HAUGWITZ,RUDIGER
• Format: Patent
• Language: French
• Published: 30.04.1973
• Edition: 1
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; METALLURGY; ORGANIC CHEMISTRY

1382438 Chloramphenicol esters E R SQUIBB & SONS Inc 3 Jan 1972 [6 Jan 1971] 179/72 Heading C2C Novel chloramphenicol esters of the general formula wherein X is a single bond or an optionally C 1-8 alkyl-substituted C 1-6 n-alkylene or alkenylene group and is attached at the 1- or 2-position of the adamantane ring, R is a halogen atom or a C 1-8 alkyl, C 1-8 alkoxy or phenyl group and n is 0, 1 or 2, are prepared by reacting chloramphenicol with an acid halide of the general formula wherein Hal is a fluorine, chlorine, bromine or iodine atom, in the presence of a basic catalyst. Acid halides of the second general formula above are prepared by treating the corresponding acid with a thionyl or oxalyl halide. 1- Adamantaneacrylic acid is prepared by reduction of 1-adamantane-carboxylic acid with lithium aluminium hydride, oxidation of the resulting 1-adamantane methanol using Jones Reagent, treatment of the resulting 1-adamantaldehyde with triethylphosphonoacetate in the presence of sodium hydride and 1,2-dimethoxyethane and alkaline hydrolysis of the resulting 1-adamantaneacrylic acid ethyl ester. #2,α- Adamantaneacetic acid is prepared by treatment of 1-hydroxyadamantane with concentrated sulphuric acid, treatment of the resulting adamantanone with triethylphosphonoacetate in the presence of sodium hydride and 1,2- dimethoxyethane and alkaline hydrolysis of the resulting #2,α-adamantaneacetic acid ethyl ester. 2-Adamantane-acetic acid is prepared by treatment of adamantanone with diethylcyanomethylphosphate in the presence of sodium hydride and 1,2-dimethoxyethane, catalytic hydrogenation of the resulting #2,α-adamantaneacetonitrile and alkaline hydrolysis of the resulting 2-adamantaneacetonitrile. Pharmaceutical and disinfectant compositions having antimicrobial activity comprise, as active ingredient, a chloramphenicol ester of the first general formula above, together with a suitable carrier.