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Communications to the Editor 3261 Preliminary fractionation of the benzene-extractable alkaloids by the excellent procedure of Jacobs and Craig4 yielded the five known crystalline alkaloids and a large amorphous fraction; only the latter was active as a hypotensive agent at low dosage. Further fractionation of this material guided by assay3 in hypertensive patients yielded a highly active concentrate, which on 24-plate Craig distribution, using 2 M acetate buffer at pH 5.5 and benzene as the immiscible phases, exhibited two discrete peaks. The material having a peak at tube 15 (K = 1.67) showed activity when administered orally in doses of 0.6-0.8 mg. per patient, while the material from the second peak, at tube 6 (K = 0.35), was active at about 4 mg.These fractions crystallized readily from methanol-water and ethanol-water respectively, yielding germidine (m. p. 220-223°( cor.); [a]25D + 13°( c, 1.67 in chloroform)) and germitrine (m. p. 197-199°( cor.); [ct]25D + 11°( c, 1.54 in chloroform)).Room temperature hydrolysis of germidine with 0.1 N aqueous methanolic alkali afforded germine (C27H43O8N),6 acetic acid and a-methylbutyric acid. The former was identified by rotation, analysis and conversion into monoacetonylgermine hydrochloride.6 The acids, after conversion into the p-phenylphenacyl esters followed by chromatography on alumina, yielded p-phenylphenacyl -methylbutyrate7 (m. p. 71-72°( cor.)) and pphenylphenacyl acetate8 9(m. p. 109-110°( cor.)). Analysis of the free base and the crystalline thiocyanate (m. p.242-2440 dec. (cor.)) indicates germidine to be an ester of germine with one mole each of the above acids.Hydrolysis of germitrine yielded germine, amethylbutyric acid and methyl-ethylglycolic acid. The phenylphenacyl ester of the latter (m. p. 119-120°( cor.); [q]26d + 5°( c, 0.64 in chloroform))was identical with an authentic sample.Analysis of the free base and the thiocyanate (m. p. 228-231°dec. (cor.)) indicates that germitrine is probably a mono--methylbutyrate dimethylethylglycolate of germine.The specific rotations of the branched-chain acids (isolated from the total amorphous fraction because of an insufficient supply of the crystalline alkaloids) showed these materials to be l-a-methylbutyric and d-methylethylglycolic acids. Germidine and germitrine, injected intravenously in doses of 0.6-0.8 y per kg., markedly lowered the blood pressure of anesthetized dogs and cats.

The following thermal rearrangement has been observed to occur in enough instances to establish the reaction as fairly general when X and JT are CN or COOC2H6'The allyl-type group has been shown to undergo inversion in two such cases, as indicated in the equation.2 This fact, together with first-order reaction kinetics and the observation that no interchange of migrating groups occurs when a mixture of two such compounds is heated, indicates that the rearrangement proceeds by an intramolecular cyclic mechanism.The influence of the groups, X and Y, is presumed to be derived from electron attraction, which enables the allyl group to release the electron pair binding it to the a-carbon atom. A conjugated double bond is formed in the a,,B-position while, a t the same time, the allyl group becomes attached in the y-position. Less strongly activated systems, in which the negative groups, X and U, are phenyl and nitrile groups or in which a single nitrile or carboxyl group is attached to the a-carbon atom, also undergo the rearrangement. The work now being reported was undertaken to find the least activation which would permit occurrence of the rearrangement.The hydrocarbons 111, V and VI1 have been synthesized and their behavior on heating has been determined. They rearranged at 165-185' in the manner shown in the following equations.(R = H or CHs) CfiHCCH-CH=CHg

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