Synthesis of cotarnine / by Arthur H. Salway.

  • Salway, Arthur H. (Arthur Henry)
Date:
[1910?]
Catalogue details

Licence: In copyright

Credit: Synthesis of cotarnine / by Arthur H. Salway. Source: Wellcome Collection.

    4/16 (page 1209)
    (V), and the latter converted by means of Hofmann’s reaction into fi-3-methoxyA: 5-methylenedioxy/phenylethylamine (VI) : CH <o/>h2-ch2.co-nh2 CH <0/\ch2-oh2.Nh2 OMe OMe (V.) (VI.) The 'phenylacetyl derivative of this base (VII) was then con¬ densed by heating with phosphoric oxide in the presence of xylene, according to a method similar to that employed by Pictet and Finkelstein (Ber., 1909, 42, 1979) in the synthesis of laudanosine. In this condensation it is evident that theoretically two isomeric dihydroisoquinoline derivatives (VIII and IX) may be formed. Both of these isomeric compounds have, in fact, been isolated in the form of their hydrochlorides, which decompose at 192° and 174° respectively: CH <'0/\cH2-CH2-NH-C0-CH2Ph 2 °\/ OMe (VII.) / CH YH*-? H2 2^°\//C(an7):N OMe (VIII.) c(c7h7):n ch2<Y>h2-ch2 \/ OMe (IX.) It has, furthermore, been possible to assign to the above- mentioned isomerides their respective formulae (VIII and IX), since the compound decomposing at 192°, when treated as indicated below, yielded cotarnine, and must therefore be represented by (VIII), whilst the substance decomposing at 174° gave an isomeride of cotarnine, and consequently possesses the formula (IX). For the preparation of cotarnine from S-methoxy-3: 7-methylene- dioxy-l-benzyl-3 : 4:-dihydroisoquinoline (VIII), the latter was first converted into its methochloride (X), and this reduced with tin and hydrochloric acid. The product, 1-benzylhydrocotarnine (XI), was then oxidised by manganese dioxide in the presence of sulphuric acid (compare Pyman, Trans., 1909, 95, 1751), when it yielded a substance which was identical in all respects with cotarnine (XII). The identity was established by means of analyses and by a com¬ parison of its derivatives with the corresponding derivatives of a specimen of cotarnine which had been obtained by the oxidation of narcotine.