C10H

NICOTINE  ,4N2, an alkaloid, found with small quantities of nicotimine, C19H,4N2, nicoteine, C1oH,2N2, and nicotelline, C10H$N2, in tobacco . The name is taken from Nicotiana, the tobacco plant, so called after Jean Nicot (1530-1600), French ambassador at Lisbon, who introduced tobacco into France in 156o . These four alkaloids exist in combination in tobacco chiefly as malates and citrates . The alkaloid is obtained from an aqueous extract of tobacco by distillation with slaked lime, the distillate being acidified with oxalic acid, concentrated to a syrup and decomposed by potash . The free base is extracted by ether and fractionated in a current of hydrogen . It is a colourless oil, which boils at 247° C . (745 mm.), and when pure is almost odourless . It has a sharp burning taste, and is very poisonous . It is very hygroscopic, dissolves readily in water, and rapidly undergoes oxidation on exposure to air . The free alkaloid is strongly laevo-rotatory . F . Ratz (Monats., 1905, 26, p .

1241) obtained the value [a]u=-169.54° at 20 its salts are dextro-rotatory . It behaves as a di-acid as well as a di-

tertiary base . On oxidation with chromic or nitric acids, or potassium permanganate, it yields nicotinic acid or /3-pyridine carboxylic acid, C5H,N'CO2H; alkaline potassium ferricyanide gives nicotyrine, C,oH,0N2, and hydrogen peroxide oxynicotine, C,oH,4N20 . Oxidation of its isomethylhydroxide with potassium permanganate yields trigonelline, C7H7NO2 (A . Pictet and P . Genequand, Ber., 1897, 30, p . 2117) . It gives rise to various decomposition products such as pyridine, picoline, &c., when its vapour is passed through a red-hot tube . The hydrochloride on heating with hydrochloric acid gives methyl chloride (B . Blau, Ber .. 1893, 26, p . 631) .

Hydriodic acid and

phosphorus at high temperature give a dihydro-compound, whilst sodium and alcohol give hexa- and octo-hydro derivatives . Nicotine may be recognized by the addition of a drop of 3o % formaldehyde, the mixture being allowed to stand for one hour and the solid residue then moistened by a drop of concentrated sulphruic acid, when an intense rose-red colour is produced (I . Schindelmeiser, Pharm . Zentralhalle, 1899, 40, p . 704) . The constitution of nicotine was established by A . Pinner (see papers in the Berichte, 1891 to 1895) . With bromine in acetic acid solution at ordinary temperature, nicotine yields a perbromide, C,oH1oBr2N20•HBr3, which with sulphur dioxide, followed by potash, gives dibromcotinine, CioH1oBr2N2O, from which cotinine, C,oH,2N20, is obtained by distillation over zinc dust . By heating nicotine with bromine in hydrobromic acid solution for some hours at too° C., dibromticonine hydrobromide, C,oHEN2Br2O2•HBr, results . Dibromcotinine on hydrolysis yields oxalic acid, methylamine and $-methyl pyridyl ketone: C1oH10Br2N20+3H20+0= H2C204+CH3NH2+C5H4N•000H3+2HBr; whilst dibromticonine yields methylamine, malonic acid and nicotinic acid : C1oH1Br2N2O2+ 4H2O=CH3NH2+CH2(CO2H)2+CSH4N•CO2H+2HBr, or if heated with zinc and caustic potash, methylamine and pyridyl-,By-dioxybutyric acid . Thus the groupings U-C•C- —C•C— >N•CH3 and —C•C•CN exist in the molecule, and the alkaloid is to be represented as a-pyridyl-N-met hyl-pyrollidi ne . This result has been confirmed by its synthesis by A .

Pictet and P . Cr6pieux (Comptes rendus, 1903, 137, p . 86o) and Pictet and Rotschy (

Bee., 1904, 37, p . 1225): $-aminopyridine is converted into its mucate, which by dry distillation gives N-/3-pyridylpyrrol . By passing the vapour of this compound through a red-hot tube, it yields the isomeric ai3-pyridylpyrrol; the potassium salt of which with methyl iodide gives a substance methylated both in the pyridine and pyrrol nuclei . By distillation over lime, the methyl group is removed from the pyridine ring, and the resulting a-pyridyl-N-methylpyrrol gives i-nicotine on reduction . This base is resolved into its active components by d-tartaric acid, l-nicotine-d-tartrate crystallizing out first . The natural (laevo) base is twice as toxic as the dextro . The following formulae are important: N —CH 1 C =CH CH•CH2 0—C CH ~/ NH CH l\p N CH2 N / N \// N • \/ CH CH H,C CH2 N-0-Pyridylpyrrol, a$-pyridylpyrrol, nicotine . Acetyl and benzoyl derivatives of nicotine on hydrolysis do not yield nicotine, but an isomeric, inactive oily liquid (metanicotine) . It is a secondary base, and boils at 275°-278° C . Nicotimine is a colourless liquid which boils at 25o°-255° C .

Its aqueous solution is alkaline . Nicoteine is a liquid which boils at 267° C . It is separated from the other alkaloids of the group by distilling off the nicotine and nicotimine in

steam and then fractionating the residue . It is soluble in water and is very poisonous . Nicotelline crystallizes in needles which melt at 147° C. and is readily soluble in hot water .