Vomicinic acid

That vomicine contains a phenolic hydroxyl group is not immediately obvious, for the alkaloid is insoluble in alcoholic alkali, does not give a ferric chloride color, and is not easily methylated or acetylated on the phenolic oxygen (187). Later work led to the isolation of what may be O-methylvomicine in small yield (191) and to O-acetylvomicine by the action of acetic anhydride sodium acetate (192). The presence of a phenolic grouping is evident, however, in vomicinic acid (CCXXXVIII ... 

This occurs readily with warm alcoholic potassium hydroxide vomicine gives vomicinic acid (CCXXXVIII R = R = H) and dihydro-vomicine gives dihydro vomicinic acid (187). These acids are very readily autoxidized because of the ortho amino-phenol system they contain, and must therefore be handled in the total absence of oxygen. The ring opening is easily reversed by mineral acid (191). 

Vomicinic acid is converted by successive treatment with methyl iodide and alkali into a mixture of Va-methyl- and 0,Va-dimethyl-vomicinic acids and methyl esters (191). 

Under very much milder conditions, with controlled quantities of chromic acid, oxidation of vomicinic acid (CCXXXVIII R = R = H)... 

Oxidation of Vpmicine. On oxidation with chromic acid, vomicine yields three acids (Parts I, IX, XII and XXIII) —... 

Vomicine is easily monobrominated, probably in position 3, ortho to the phenolic group (187). Mononitration may be achieved with dilute aqueous nitric acid, but is difficult and gives varying yields dihydro-vomicine on the other hand gives a dinitro derivative in very good yield (194). Nitric-concentrated sulfuric acid mixture at —18° oxidizes the aromatic ring (see Section IV, E, 2). 

Vomicine condenses with ethyl nitrite in the presence of alkoxide to give 11-isonitrosovomicine, which with thionyl chloride undergoes Beckmann rearrangement to give the nitrile CCXLV, easily hydrolyzed to norvomicinic acid (CCXLVI) (198). 

Isovomicine (CCXLVII) is formed by the action of hydrobromic acid and red phosphorus in glacial acetic acid on vomicine the corresponding 23-bromo compound surprisingly was not isolated (199, 200), contrasting with the behavior of strychnine (see Section II, B, 2). The bromo compound CCXLVIII is, however, the main product of the action of hydrobromic acid on dihydrovomicine (199). 

The action of hydriodic acid and red phosphorus in glacial acetic acid on vomicine leads to yellow deoxyvomicine, C22H24O3N2, with loss of the ether oxygen (187, 197). The structure of this compound is not yet firmly established (162) structure CCXLIX has been proposed for it... 

A minor product in the reaction of vomicine with hydriodic acid and red phosphorus in glacial acetic acid is 12-iododihydrodeoxyvomicine (CCLII R = I) (197), which is reduced to isodihydrodeoxyvomicine (CCLII R = H) by zinc and acetic acid. 

The sodium amalgam (Emde) reduction of vomicine metho salts (CCLIV) in dilute acetic acid gives two products (195, 203) base I, which has structure CCLVII (R = CH3) (202), and base II, the structure of which is not proved (202, 203). Why allylic hydrogenolysis does not occur is not known. Base I is demethylated to a secondary alcohol CCLVII (R = H) (203), which could not be oxidized by the Oppenauer method back to vomicine (202), nor could vomicine be reduced to it. 

Yellow deoxyvomicine gives the greatest number of hydrogenation products, five in all, A-E. The primary product A is dihydrodeoxy vomicine II (CCLXX), also obtained in very poor yield by the electrolytic reduction of yellow deoxyvomicine or by the zinc and acetic acid reduction of the iodo compound obtained as a minor product in the preparation of yellow deoxyvomicine. Product B (CCLXXI) simply arises by reduction of the 21,22-double bond further reduction of B does... 

The oxidation of vomicine yields three products the acid CCLXXXIV, analogous to dioxonucine dihydrate (Wielands C17 acid, CXXV), the acid CCLXXXV, the analog of carboxyaponucine (Hanssen s Cie acid, CXXVI), and the base CCLXXXVI, which has no analog in strychnine... 

The only other oxidative degradation of any importance leading to a large fragment is that of vomicine by nitrating mixture at — 18°, which gives an acid formulated as CCXCVII (allowing for the known structure of vomicine) (194). 

The products of halogen acids on vomicine are now seen to be those anticipated firom the analogous strychnine cases, involving opening of ring VII. Thus isovomicine, from HBr, is CCXLIX (R = OH), the initial iodo product from HI is 12-iodo-12,13-dihydrodeoxyvomicine (CCXLIX, R = H + HI), and the stable, colorless deoxyvomicine is CCXLIX (R = H). 

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