Studies on Nitrogen-free Hypnotics. I

Syntheses and Hypnotic Action of Unsaturated Carbinols

Abstract

Ten kinds of dialkylethynylcarbinol derivatives and two of their hydrogenated derivatives were prepared and their head-drop dose, HD₅₀, and toxicity, LD₅₀, were measured. It was thereby found that all the compounds tested possessed hypnotic action, without causing any side-effects such as convulsion. Approximate comparison of the effect of each carbinol derivative with 1/HD₅₀ of 3-methylpentyn-1-ol-3 as 1, for convenience, showed that the effect of 3-ethylpentyn-4-ol-3 and 3-methylpentanol-3 was greater than that of 3-methylpentyn-1-ol-3 while all the others were weaker. In general, the hypnotic action was comparatively strong when the sum of the carbon atoms in the two alkyl groups in the foregoing dlalkylethynylcarbinol derivatives was 3-6, and weak when such was 2 or above 7, the strongest being that in which both alkyls were ethyl. When one of such alkyl groups were fixed to methyl, ethyl, propyl, or butyl, and the other alkyl changed from methyl to butyl, the strongest hypnotic action appeared when the latter was an ethyl group. The presence of the ethynyl group was considered to be a requisite to a certain extent in the appearance of the hypnotic action.