A. Coniine
Synonyms Cicutine, Conicine.
Biological Sources It is obtained from the unripe, fully grown dried fruits of Conium maculatum L. (Umbelliferae).
It also occurs in the plant Aethusa cynapium L. (Apiaceae) (Fool’s Parsley); Cicuta maculata L. (Apiaceae) (Water Hemlock).
Chemical Structure
(S)-2-Propylpiperidine. It occurs naturally as the (S)-(+)- isomer.
Isolation Coniine may be isolated by adopting the various following steps, namely:
(i) The powdered unripe, fully grown dried fruits of hemlock are mixed with a dilute solution of KOH and then subjected to stream distillation. The distillate is collected and neutrallized carefully with dilute HCl and evaporated to dryness preferably under vacuum.
(ii) The residue obtained as stated in (i) above is extracted with alcohol, filtered and the alcohol evaporated to dryness under vacuum. The alcohol helps in extracting the alkaloidal salts that are dissolved in water; it is then rendered alkaline either with diluted KOH solution or with dilute NH4OH and finally extracted with ether successively.
(iii) The ether from the combined ethereal layer is evaporated completely, when an oily liquid consisting of the free bases remains in the residue.
(iv) Finally, the residue is subjected to fractional distillation in a current of H2-gas when the alkaloids could be broadly separated and a mixture containing coniine and γ-coniceine shall pars over as the first fraction at 171-172°C. These two alkaloids are consequently made to their corresponding hydrochloride salts, evaporated to dryness and extracted with acetone.
Thus, coniine hydrochloride would be separated as an insoluble product, while the γ –coniceine may be recovered by evaporating acetone under vacuum.
Note: Coniine enjoys the unique distinction of being the First Alkaloid produced synthetically.
Characteristic Features
(i) It is a colourless alkaline liquid.
(ii) It darkens and polymerizes on being exposed to air and light.
(iii) It has a mousy odour.
(iv) Its physical parameters are as follows: mp ~ – 2°C; bp 166-166.5°C; bp20 65-66°C. d420 0. 844-0.848; - nD23 1.4505; α D25 +8.40C (c = 4.0 in CHCl3); α D23 +14.60(heat) pKa = 3.1.
(v) It is steam volatile.
(vi) Solubility: 1 ml dissolves in 90 ml of water, less soluble in hot water. The base dissolves in about 25% water at room temperature. It is found to be soluble in alcohol, ether, acetone, benzene, amyl alcohol, and slightly soluble in chloroform.
Identification Tests
(i) It readily forms the corresponding hydrobromide (C8H17N.HBr), obtained as prisms, mp 211°C, 1 g dissolves in 2 ml water, 3 ml alcohol, and soluble freely in ether and chloroform.
(ii) Its hydrochloride (C8H17N . HCl) forms rhomboids, mp 221°C, freely soluble in water, alcohol and chloroform.
(iii) It gives a red colouration with sodium nitroprusside slowly, which on addition of acetaldehyde changes to violet or blue.
Caution It exhibits potential symptoms of over exposure as: weakness, drowsiness, parasthesias, ataxia, nausea, excessive salivation, and bradycardia followed by tachycardia.*
Uses Externally, the coniine salts are used as ointments and infrequently employed for their local analgesic action in the symptomatic relief of pruritis, hemorrhoids and fissures.
