Patent GB-737080-A (GB)
Title: Hypnotic, sedative and anticonvulsant preparations and process for preparing same
Filed: 1951-08-24
Abstract: Ethinyl cyclohexanols of general formula <FORM:0737080/IV (b)/1> wherein Y is hydrogen or one or more methyl or ethyl groups are prepared by reacting cyclohexanone, or the appropriate alkyl derivative, with acetylene in the presence of an alkaline condensing agent such as sodium, sodamide, potassamide or potassium t.-amylate. With sodium as condensing agent, the reaction is conducted in liquid ammonia.  Described is the preparation of (a) 1-ethinyl cyclohexanol-1; (b) 1 - ethinyl - 2 - methylcyclohexanol - 1; (c) 1-ethinyl-3-methylcyclohexanol; (d) 1-ethinyl-4-methylcyclohexanol; (e) 3,3,5-trimethyl-1-ethinylcyclohexanol-1; (f) 2,2-diethyl-1-ethinyl-cyclohexanol-1.  Esters of the above cyclohexanols with acetic, propionic, butyric, benzoic, salicylic, phthalic, hexahydrophthalic, maleic, malic, tartaric, citric and succinic acids are prepared by reacting the ethinyl compound with the appropriate anhydride of the acid.  Described is the preparation of (a) 3,3,5-trimethyl-1-ethinylpropionoxycyclohexane and (b) acid phthalate of 1 - ethinylcyclohexanol - 1.  The ethinyl compounds and their esters are used in pharmaceutical compositions (see Group VI).ALSO:A hypnotic composition effective on human beings without toxic side reactions comprises an inert pharmaceutical carrier having incorporated therein a compound of formula <FORM:0737080/VI/1> where X is hydrogen or an acyl radacal and Y is hydrogen or one or more methyl or ethyl groups.  The acyl covers both aliphatic and aromatic carboxylic acids which are pharmaceutically acceptable. Specified are the residues of acetic, propionic, butyric, benzoic, salicylic, phthalic, hexahydrophthalic, maleic, malic, tartaric, citric and succinic acids.  The preparations are administered orally, parenterally or in the form of suppositories.  Injections may be aqueous or oily solutions or suspensions containing dispersing agents such as polyethylene glycols.  Oral medicaments are (a) soft gelatin capsules in which the active ingredient is dissolved in oil such as peanut, sesame or corn oil; (b) hard gelatin capsules in which the carbinol is absorbed on an inert absorbent such as magnesium oxide or carbonate, with or without the further addition of an oil; (c) tablets coated with resin; (d) elixir, in which the vehicle is an aqueous solution of propylene glycol or ethyl alcohol, glycerin and sucrose; (e) emulsion of oil, e.g. peanut, emulsifier, e.g. polyethylene glycol monostearate, and thickener, e.g. acacia, gelatin, dextrin, pectin, sodium alginate or agar agar. Suppositories have a basis of (a) white wax and cocoa butter, or (b) carbowax.  Described is the preparation of (a) 1 - ethinyl cyclohexanol - 1; (b) 1 - ethinyl - 1 - acetoxycyclohexane; (c) 1 - ethinyl - 4 - methyl cyclohexanol - 1; (d) 1 - ethinyl - 3 - methyl-cyclohexanol - 1; (e) 1 - ethinyl - 2 - methyl-cyclohexanol - 1; (f) 3,3,5 - trimethyl - 1-ethinylcyclohexanol - 1; (g) 2,2 - diethyl - 1-ethinylcyclohexanol - 1; (h) 3,3,5 - trimethyl-1 - ethinylpropionoxycyclohexane; and (i) acid phthalate of 1 - ethinyl - cyclohexanol - 1 (see Group IV (b)).