THESTRUCTURE OF ANHYDROECGONINE ETHYL ESTER
March 5, 1953
1033
[CONTRIBUTION FROM THE NATIONAL INSTITUTE OF ARTHRITIS AND METABOLIC DISEASES,NATIONAL INSTITUTES OF HEALTH, PUBLIC HEALTH SERVICE, FEDERAL SECURITY AGENCY]
The Structure of Anhydroecgonine Ethyl Ester BY STEPHEN P. FINDLAY RECEIVEDAUGUST18, 1952 Anhydroecgonine ethyl ester contains an ethylenic linkage in conjugation with its carbethoxy group as indicated by its catalytic reduction to two isomeric derivatives and by its infrared absorption spectrum.
When anhydroecgonine ethyl ester (I, R = C2H5) in alcoholic solution is hydrogenated in the presence of palladized charcoal, one molecule of hydrogen is absorbed per molecule of amino ester, and a product is obtained consisting of the ethyl esters of the two diastereoisomeric hydroecgonidines (dihydroanhydroecgonines) (I11 and IV, R = C2H5). These were isolated by treating the prod-
/VCH3 H
OH
v
actions, and this is apparently not isomerized by heating a t 100’ with concentrated aqueous potasN sium hydroxide6 although similar treatment of analI\ I\ ogous aliphatic and alicyclic compounds affords mixtures of alp- and p, y-unsaturated acids.’ The absence of an isomer of anhydroecgonine is undoubtedly owing to its bridged ring system. While I 11 I11 IV there is no way of knowing a priori whether anhyuct with the stoichiometric quantity of picric acid droecgonine ethyl ester has structure I or I1 (R = and separating the isomeric picrates by fractional CzHa), the latter appears improbable and, hydrocrystallization. One picrate, obtained in relatively genated under the conditions employed in this invery small yield, is liquid; the other is crystalline vestigation, could hardly have resulted in more and melts a t 113-114’. The crystalline picrate than one product. It is therefore concluded that has the composition of hydroecgonidine ethyl ester the starting material has the structure assigned picrate and generates this ester on appropriate (R = CzHa), and it seems reasonable to infer also .treatment. The ester furnishes a crystalline oxa- that anhydroecgonine itself and eccaine1,8contain the a,P-location of the double bond, late and a chloroaurate melting a t 177.5-181’. A comparison of the infrared absorption spectra The latter derivative was obtained, though in apparently less pure condition, as hereafter explained, of the ethyl esters of anhydroecgonine and hydroby von Braun and Muller‘ and later by Gadamer ecgonidine leads to the same conclusion (Fig. 1). and John. Pseudohydroecgonidine ethyl ester, The a$-position of the double bond in I is strongly recovered from the liquid picrate gives no crystalline indicated because (1) the intense carbonyl absorpoxalate but does yield a chloroaurate melting at tion band, which is located in the normal range for 122.5’. This ester is presumably identical with the carboethoxy group, is shifted 0.07 p in the direcWillstatter’s hydroecgonidine ethyl ester13 which tion of longer wave lengths as would be expected for was obtained by esterifying the product resulting a conjugated estere and (2) the absorption of the from the reduction of anhydroecgonine with so- ethylenic linkage is much stronger than would be exdium and amyl alcohol and which gave a liquid pic- pected for an unconjugated endocyclic ethylenic linkage. lo The p, y-position of the double bond is rate and a chloroaurate melting a t 121-122’. Anhydroecgonine (I or 11,R = H) is prepared by unlikely because (1) any shift in the carbonyl abdehydrating the P-hydroxy acid, ecgonine (V),4 sorption band would be opposite to that observed with boiling phosphorus oxychloride6 or boiling and (2) the band a t 6.10 p is too strong for an isostrong hydrochloric acid.4 Only one of several lated endocyclic ethylene linkage. l o The presence conceivable isomers is ever obtained from these re- of a cyclopropane ring structure is excluded because it cannot account for the absorption a t 6.10 p.ll~lz (1) J. v. Braun and E. Miiller, Bev., 61, 235 (1918). CH3
CHI
CH3
CH3 N
(2) J , Gadamer and C. John, Arch. Phavm., 269, 227 (1921). (3) R . Willstatter, B e y . , 30, 702 (1897). (4) This structure is speculative. However, in view of the isomerization of ecgonine to pseudoecgonine in strong alkali (A. Einhorn and A. Marquardt,
