Researches on the constitution of physostigmine. Pt. I[-II] / by Arthur H. Salway.
- Salway, Arthur Henry.
- Date:
- 1912-1913
Licence: In copyright
Credit: Researches on the constitution of physostigmine. Pt. I[-II] / by Arthur H. Salway. Source: Wellcome Collection.
Provider: This material has been provided by The Royal College of Surgeons of England. The original may be consulted at The Royal College of Surgeons of England.
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![35 G that the latter is a quaternary ammonium salt formed by the union of one molecule of 3-dimethylaminoacetyl-2-methylindole and one of 3-chloroacetyl-2-methylindole, and therefore has the constitution: (C«H 4< C(Cl!^H2')>OMeVN Me2CI. 3-Dimethylaminoacetylr-2-methylindole is sparingly soluble in ether, chloroform, or benzene, and moderately so in alcohol. It is a stable base, showing no tendency to absorb oxygen in the presence of alkalis. It does not respond to the pine-shaving test for indoles. Its hydrochloride, prepared by dissolving the base in dilute hydro- chloric acid, evaporating the solution to dryness and crystallising the residue from alcohol, was obtained in colourless, rhombohedral crystals, melting at 258°. Many attempts were made to reduce the above base in order to obtain from it by the addition of two atoms of hydrogen a substance of the same empirical formula as eseroline, but reduction could not be effected; thus, when the base was heated with tin and hydro- chloric acid, or with sodium in amyl alcohol, no change occurred, whilst treatment with hydriodic acid and red phosphorus at 120° caused disruption of the molecule with formation of 2-methylindole. II.—Synthesis of 2-a-DimethylamiJio-y-hydroxy])ropyli?7dole (IV). As already indicated, Madelung (loc. cit.) has shown that o-toluidides may be converted into substituted indole derivatives by heating with sodium ethoxide. Although this reaction has hitherto only been applied to the o-toluidides of acetic, benzoic, and oxalic acids, it appeared probable that the method might be extended to nuv the preparation of any indole derivative, C6H4<C.^jt^>CR, provided that the acid R-C02H could be obtained. For the purpose of the present synthesis the radicle R was required to consist of an oxygen- ated acyl group containing a tertiary basic nitrogen atom, and the corresponding acid, R’C02Ii, chosen as best fitted to meet these requirements, wa3 a-dimethylamino-y-hydroxybutyric acid, H0-CH2-CH2-CH(NMe2)-C02H. The steps which wrere necessary for the preparation of this compound and for its conversion into the desired indole derivative are as follows: CH„Br-CFT2Br PhO'CH2*CH2Br -■> Ph0-CH2*CH3-CH(C02H)., (VI.) (VII.) —> Ph0-CH2-0F2-CBr(C02H)2 —> Ph0-CH2-CII2-CHBi-C02II (VIII.) * “ (IX.) Ph0-CII2-CHo-CH(NMe0)-C0oH and](https://iiif.wellcomecollection.org/image/b2243933x_0024.jp2/full/800%2C/0/default.jpg)
