Description
Although this alkaloid from the bark of Cinchona species was first isolated by
Howard in 1871, it had earlier been prepared by Pasteur by heating the acid
sulphate of quinine and Hesse subsequently prepared it in a similar manner from
quinidine. The identity of the alkaloid with quinotoxine, formed by heating
quinine in H20 or dilute AcOH was proved by von Miller and his co-workers.
The base forms a bitter, yellow varnish having [α]
D + 38.6° (CHCI 3 ) and is
normally purified through the oxalate nonahydrate which has m.p. 166-7°C;[α]
20D + 24°. The alkaloid yields crystalline salts, the hydrochloride forming
colourless leaflets, m.p. l80-2°C; [α]]
13.7D + 16 26° (H20); the oxime, m.p.
l12-6°C; dipicrolonate, m.p. 210°C; the (+)-tropate monohydrate, m.p.
l12-3°C or l16-8°C (dry). The p-bromophenylhydrazone forms yellow
crystals, m.p. 141°C. Both the N-methyl and N-ethyl derivatives are yellow oils,
the former yielding a hydrochloride monohydrate, m.p. l53-5°C; [α]
23D + 16.6°
(H20) and the latter the corresponding hydrochloride, m.p. 202-4°C; [α]
23D +
68.1 ° (H20). The N-benzoyl derivative crystallizes from C6H6 or MeOH with
m.p. l13-4°C; [α]
22D + 36° (c 2.0, EtOH).
According to de Caro, the minimum lethal dose for white rats is 0.32 gm/kilo
compared with 1.25 gm/kilo for quinine and, although it has no anti-malarial
action, the alkaloid appears to be less toxic than formerly supposed.
References
Pasteur.,Jahresb., 473 (1853)
Howard.,f. Chem. Soc., 24, 6! (! 871)
Howard., ibid, 25, 101 (1872)
Hesse., Annalen, 178, 244 (1875)
von Miller, Rohde, Fussenegger., Ber., 33,3228 (1900)
Heidelberger, Jacobs.,J. Amer. Chem. Soc., 41,832 (1919)
Heidelberger, Jacobs., ibid, 44, 1093 (1922)
Frankel, Diamant., Ber., 58,554 (1925)
Prostenik, Prelog., Helv. Chim. Acta, 26, 1965 (1943)
Toxicology :
de Caro., Arch. expo Path. Pharm., 164,314 (1932)
