PART VI.—ALKALOIDS AND POISONOUS VEGETABLE PRINCIPLES SEPARATED FOR THE MOST PART BY ALCOHOLIC SOLVENTS.

DIVISION I.—VEGETABLE ALKALOIDS.

I.—General Methods of Testing and Extracting Alkaloids.

§ 301. General Tests for Alkaloids.—In order to ascertain whether an alkaloid is present or not, a method of extraction must be pursued which, while disposing of fatty matters, salts, &c., shall dissolve as little as possible of foreign substances—such a method, e.g., as the original process of Stas, or one of its modern modifications.

If to the acid aqueous solution finally obtained by this method a dilute solution of soda be added, drop by drop, until it is rendered feebly alkaline, and no precipitate appear, whatever other poisonous plant-constituents may be present, all ordinary alkaloids[324] are absent.

In addition to this negative test, there are also a number of substances which give well-marked crystalline or amorphous precipitates with alkaloids.

§ 302. These may be called “group reagents.” The chief members of the group-reagents are—Iodine dissolved in hydriodic acid, iodine dissolved in potassic iodide solution, bromine dissolved in potassic bromide solution, hydrargo-potassic iodide, bismuth-potassic iodide, cadmic potassic iodide; the chlorides of gold, of platinum, and mercury; picric acid, gallic acid, tannin, chromate of potash, bichromate of potash, phospho-molybdic acid, phospho-tungstic acid, silico-tungstic acid, and Fröhde’s reagent. It will be useful to make a few general remarks on some of these reagents.

Iodine in hydriodic acid gives either crystalline or amorphous precipitates with nearly all alkaloids; the compound with morphine, for example, is in very definite needles; with dilute solutions of atropine, the precipitate is in the form of minute dots, but the majority of the precipitates are amorphous, and all are more or less coloured.

Iodine dissolved in a solution of potassic iodide gives with alkaloids a reddish or red-brown precipitate, and this in perhaps a greater dilution than almost any reagent. When added to an aqueous solution, the precipitates are amorphous, but if added to an alcoholic solution, certain alkaloids then form crystalline precipitates; this, for example, is the case with berberine and narceine. By treating the precipitate with aqueous sulphurous acid, a sulphate of the alkaloid is formed and hydriodic acid, so that by suitable operations the alkaloid may readily be recovered from this compound. A solution of bromine in potassic bromide solution also gives similar precipitates to the above, but it forms insoluble compounds with phenol, orcin, and other substances.

Mercuric potassic iodide is prepared by decomposing mercuric chloride with potassic iodide in excess. The proportions are 13·546 grms. of mercuric chloride and 49·8 of potassic iodide, and water sufficient to measure, when dissolved, 1 litre. The precipitates from this reagent are white and flocculent; many of them become, on standing, crystalline.

Bismuthic potassic iodide in solution precipitates alkaloids, and the compounds formed are of great insolubility, but it also forms compounds with the various albuminoid bodies.

Chloride of gold forms with the alkaloids compounds, many of which are crystalline, and most admit of utilisation for quantitative determinations. Chloride of gold does not precipitate amides or ammonium compounds, and on this account its value is great. The precipitates are yellow, and after a while are partly decomposed, when the colour is of a reddish-brown.

Platinic chloride also forms precipitates with most of the alkaloids, but since it also precipitates ammonia and potassic salts, it is inferior to gold chloride in utility.

§ 303. (1.) Phosphomolybdic Acid as a Reagent for Alkaloids.—Preparation; Molybdate of ammonia is precipitated by phosphate of soda; and the well-washed yellow precipitate is suspended in water and warmed with carbonate of soda, until it is entirely dissolved. This solution is evaporated to dryness, and the ammonia fully expelled by heating. If the molybdic acid is fairly reduced by this means, it is to be moistened by nitric acid, and the heating repeated. The now dry residue is warmed with water, nitric acid added to strong acid reaction, and the mixture diluted with water, so that 10 parts of the solution contain 1 of the dry salt. The precipitates of the alkaloids are as follows:—

Aniline, Bright-yellow, flocculent.

Morphine, Bright„yellow, floc „

Narcotine, Brownish-yellow, c„

Quinine, Whitish-yellow, oc„

Cinchonine, Whitis„yellow, floc„

Codeine, Brownish-yellow, voluminous.

Strychnine, White-yellow, w, volum„

Brucine, Yelk-yellow, flocculent.

Veratrine, Bright-yellow, oc„

Jervine, Bright„ yellow, fl„

Aconitine, Bright„ yellow, fl„

Emetine, Bright„ yellow, fl„

Theine, Bright-yellow, voluminous.

Theobromine, Bright„yellow, volu„

Solanine, Citron-yellow, pulverulent.

Atropine, Bright-yellow, flocculent.

Hyoscyamine, Bright„yellow, floc„

Colchicine, Orange-yellow,loc „

Delphinine, Grey-yellow, voluminous.

Berberine, Dirty-yellow, flocculent.

Coniine, Bright-yellow, voluminous.

Nicotine, Bright„yellow, volu„

Piperine, Brownish-yellow, flocculent.

(2.) Silico-Tungstic Acid as a Reagent for Alkaloids.—Sodium tungstate is boiled with freshly precipitated gelatinous silica. To the solution is added mercurous nitrate, which precipitates the yellow mercurous silico-tungstate. This is filtered, well-washed, and decomposed by an equivalent quantity of hydrochloric acid; silico-tungstic acid then goes into solution, and mercurous chloride (calomel) remains behind. The clear filtrate is evaporated to drive off the excess of hydrochloric acid, and furnishes, on spontaneous evaporation, large, shining, colourless octahedra of silico-tungstic acid, which effloresce in the air, melt at 36°, and are easily soluble in water or alcohol.

This agent produces no insoluble precipitate with any metallic salt. Cæsium and rubidium salts, even in dilute solutions, are precipitated by it; neutral solutions of ammonium chloride give with it a white precipitate, soluble with difficulty in large quantities of water. It precipitates solutions of the salts of quinine, cinchonine, morphine, atropine, &c.; if in extremely dilute solution, an opalescence only is produced: for instance, it has been observed that cinchonine hydrochlorate in ¹⁄₂₀₀₀₀₀, quinia hydrochlorate in ¹⁄₂₀₀₀₀, morphia hydrochlorate in ¹⁄₁₅₂₈₅ dilution, all gave a distinct opalescence.—Archiv der Pharm., Nov., Dr. Richard Godeffroy.

(3.) Scheibler’s Method for Alkaloids: Phospho-Tungstic Acid.—Ordinary commercial sodium tungstate is digested with half its weight of phosphoric acid, specific gravity 1·13, and the whole allowed to stand for some days, when the acid separates in crystals. A solution of these crystals will give a distinct precipitate with the most minute quantities of alkaloids, ¹⁄₂₀₀₀₀₀ of strychnine, and ¹⁄₁₀₀₀₀₀ of quinine. The alkaloid is liberated by digestion with barium hydrate (or calcium hydrate); and if volatile, may be distilled off, if fixed, dissolved out by chloroform. In complex mixtures, colouring-matter may be removed by plumbic acetate, the lead thrown out by SH₂, and concentrated, so as to remove the excess of SH₂.

§ 304. Schulze’s reagent is phospho-antimonic acid. It is prepared by dropping a strong solution of antimony trichloride into a saturated solution of sodic phosphate. The precipitation of the alkaloids is effected by this reagent in a sulphuric acid solution.

§ 305. Dragendorff’s reagent is a solution of potass-bismuth iodide; it is prepared by dissolving bismuth iodide in a hot solution of potassium iodide, and then diluting with an equal volume of iodide of potassium solution. On the addition of an acid solution of an alkaloid, a kermes-red precipitate falls down, which is in many cases crystalline.

Marm’s reagent is a solution of potass-cadmium iodide. It is made on similar principles.

Potass-zinc iodide in solution is also made similarly. The precipitates produced in solutions of narceine and codeine are crystalline and very characteristic.

§ 306. Colour Tests.—Fröhde’s reagent is made by dissolving 1 part of sodic molybdate in 10 parts of strong sulphuric acid; it strikes distinctive colours with many alkaloids.

Mandelin’s reagent is a solution of meta-vanadate of ammonia in mono- or dihydrated sulphuric acid. The strength should be 1 part of the salt to 200 of the acid. This reagent strikes a colour with many alkaloids, and aids to their identification. It is specially useful to supplement and correct other tests. The following table gives the chief colour reactions, with the alkaloids. (See also p. 55 for the spectroscopic appearances of certain of the colour tests.)

METHODS OF SEPARATION.

§ 307. Stas’s Process.—The original method of Stas[325] (afterwards modified by Otto)[326] consisted in extraction of the organic matters by strong alcohol, with the addition of tartaric acid; the filtered solution was then carefully neutralised with soda, and shaken up with ether, the ethereal solution being separated by a pipette. Subsequent chemists proposed chloroform instead of ether,[327] the additional use of amyl-alcohol,[328] and the substitution of acetic, hydrochloric, and sulphuric for tartaric acid.

COLOUR REACTIONS[329] OF CERTAIN ALKALOIDS.

Name of Substance. Strong Sulphuric Acid. Fröhde’s Reagent. Mandelin’s Reagent.

Strychnine. ... ... Violet-blue, then lastly cinnabar-red.

Brucine. Pale red. Red, then yellow. Yellow-red to orange, afterwards blood-red.

Curarine. Fine red. ... ...

Quinine. ... Greenish. Weak orange, then blue-green, lastly green-brown.

Atropine. ... ... Red, then yellow-red, and lastly yellow.

Aconitine. ... ... ...

Veratrine. Yellow, then orange, blood-red, lastly carmine-red. Gamboge-yellow, then cherry-red. Yellow, orange, blood-red, lastly carmine-red.

Morphine. ... Violet, green, blue-green, and yellow. Reddish, then blue-violet.

Narcotine. Yellow, then raspberry colour. Green, then brown-green, yellow, lastly red. Cinnabar-red, then carmine-red.

Codeine. ... Dirty green, then blue, lastly yellow. Green-blue to blue.

Papaverine. ... Green, then blue-violet, lastly cherry-red. Blue-green to blue.

Thebaine. Blood-red, then yellow-red. Orange, then colourless. Red to orange.

Narceine. Grey-brown, then blood-red. Brown, green, red, lastly blue. Violet, then orange.

Nicotine. ... Yellowish, then red. Transitory dark colour.

Coniine. ... Yellow. ...

Colchicine. Intense yellow. Yellow to green-yellow. Blue-green, then brown.

Delphinidine. Red. Red-brown. Red-brown to brown.

Solanine. Red-yellow, then brown. Cherry-red, red-brown, yellow, yellow-green. Yellow-orange, cherry-red, and lastly violet.

§ 308. Selmi’s Process for Separating Alkaloids.—A method of separating alkaloids from an ethereal solution has been proposed by Selmi.[330] The alcoholic extract of the viscera, acidified and filtered, is evaporated at 65°; the residue taken up with water, filtered, and decolorised by basic acetate of lead. The lead is thrown out by sulphuretted hydrogen; the solution, after concentration, repeatedly extracted with ether; and the ethereal solution saturated with dry CO₂, which generally precipitates some of the alkaloids. The ethereal solution is then poured into clean vessels, and mixed with about half its volume of water, through which a current of CO₂ is passed for twenty minutes; this may cause the precipitation of other alkaloids not thrown down by dry CO₂. If the whole of the alkaloids are not obtained by these means, the solution is dehydrated by agitation with barium oxide, and a solution of tartaric acid in ether is added (care being taken to avoid excess); this throws down any alkaloid still present. The detection of any yet remaining in the viscera is effected by mixing with barium hydrate and a little water, and agitating with purified amylic alcohol; from the alcohol the alkaloids may be subsequently extracted by agitation with very dilute sulphuric acid.

Another ingenious method (also the suggestion of Selmi) is to treat the organic substance with alcohol, to which a little sulphuric acid has been added, to filter, digest with alcohol, and refilter. The filtrates are united, evaporated down to a smaller bulk, filtered, concentrated to a syrup, alkalised by barium hydrate, and, after the addition of freshly ignited barium oxide and some powdered glass, exhausted with dry ether; the ether filtered, the filtrate digested with lead hydrate; the ethereal solution filtered, evaporated to dryness, and finally again taken up with ether, which, this time, should leave on evaporation the alkaloid almost pure.

§ 309. Dragendorff’s Process.—To Dragendorff we owe an elaborate general method of separation, since it is applicable not only to alkaloids, but to glucosides, and other active principles derived from plants. His process is essentially a combination of those already known, and its distinctive features are the shaking up—(1) of the acid fluid with the solvent, thus removing colouring matters and certain non-alkaloidal principles; and (2) of the same fluid made alkaline. The following is his method in full. It may be advantageously used when the analyst has to search generally for vegetable poison, although it is, of course, far too elaborate for every case; and where, from any circumstance, there is good ground for suspecting the presence of one or two particular alkaloids or poisons, the process may be much shortened and modified.[331]

I. The substance, in as finely-divided form as possible, is digested for a few hours in water acidified with sulphuric acid, at a temperature of 40° to 50°, and this operation is repeated two or three times, with filtering and pressing of the substances; later, the extracts are united. This treatment (if the temperature mentioned is not exceeded) does not decompose the majority of alkaloids or other active substances; but there are a few (e.g., solanine and colchicine) which would be altered by it; and, if such are suspected, maceration at the common temperature is necessary, with substitution of acetic for sulphuric acid.[332]

II. The extract is next evaporated until it begins to be of a syrupy consistence; the residue mixed with three to four times its volume of alcohol, macerated for twenty-four hours at about 34°, allowed to become quite cool, and filtered from the foreign matters which have separated. The residue is washed with alcohol of 70 per cent.

III. The filtrate is freed from alcohol by distillation, the watery residue poured into a capacious flask, diluted (if necessary) with water, and filtered. Acid as it is, it is extracted at the common temperature, with frequent shaking, by freshly-rectified petroleum ether; and, after the fluids have again separated, the petroleum ether is removed, carrying with it certain impurities (colouring matter, &c.), which are in this way advantageously displaced. By this operation ethereal oils, carbolic acid, picric acid, &c., which have not been distilled, besides piperin, may also be separated. The shaking up with petroleum ether is repeated several times (as long as anything remains to be dissolved), and the products are evaporated on several watch-glasses.

RESIDUE OF PETROLEUM ETHER FROM THE ACID SOLUTION.

1. It is Crystalline. 2. It is Amorphous. 3. It is Volatile, with a powerful odour;

ethereal oil, carbolic acid, &c.

A. It is yellowish, and with difficulty volatilised. A. It is fixed.

α. The crystals are dissolved by concentrated sulphuric acid, with the production of a clear yellow colour, passing into brown and greenish-brown. α. Concentrated sulphuric acid dissolves it immediately—violet, and later greenish-blue.

Piperin. Constituents of the black hellebore.

β. The solution in sulphuric acid remains yellow; potassic cyanide and caustic potash colour it, on warming, blood-red. β. It dissolves with a yellow colour, changing into fallow-brown.

Picric acid. Constituents of aconite plant and products of the decomposition of Aconitine.

B. It Is Colourless, Liquefies easily, and Smells Strongly. B. It Is White, Sharp-Tasting, and Reddens the Skin.

Camphor and similar matters. Capsicin.

It may be expected that the substances mentioned under the heads 1, 2, and 3 will be, in general, fully obtained by degrees. This is not the case, however, as regards piperin and picric acid.

IV. The watery fluid is now similarly shaken up with benzene, and the benzene removed and evaporated. Should the evaporated residue show signs of an alkaloid (and especially of theine), the watery fluid is treated several times with a fresh mixture of benzene, till a little of the last-obtained benzene extraction leaves on evaporation no residue. The benzene extracts are now united, and washed by shaking with distilled water; again separated and filtered, the greater part of the benzene distilled from the filtrate, and the remainder of the fluid divided and evaporated on several watch-glasses.

The evaporated residue may contain theine, colchicine, cubebin, digitalin, cantharidin, colocynthin, elaterin, caryophylline, absinthin, cascarillin, populin, santonin, &c., and traces of veratrine, delphinine, physostigmine, and berberine.

A remnant of piperin and picric acid may remain from the previous treatment with petroleum ether.

THE BENZENE RESIDUE FROM THE ACID SOLUTION.

1. It is Crystalline. 2. It is Amorphous.

A. Well-formed, Colourless Crystals. A. Colourless or Pale Yellow Residue.

α. Sulphuric acid dissolves the hair-like crystals without change of colour; evaporation with chlorine water, and subsequent treatment with ammonia, gives a murexide reaction. α. Sulphuric acid dissolves it at first yellow; the solution becoming later red. Fröhde’s reagent does not colour it violet.

Theine. Elaterin.

β. Sulphuric acid leaves the rhombic crystals uncoloured. The substance, taken up by oil, and applied to the skin, produces a blister. β. Sulphuric acid dissolves red; Fröhde’s reagent violet-red;[333] tannic acid does not precipitate.

Cantharidin. Populin.

γ. Sulphuric acid leaves the scaly crystals at first uncoloured, then slowly develops a reddening. It does not blister. Warm alcoholic potash-lye colours it a transitory red. γ. Sulphuric acid dissolves it with a red colour; Fröhde’s reagent[334] a beautiful cherry-red; tannic acid precipitates a yellowish-white.

Santonin. Colocynthin.

δ. Sulphuric acid colours the crystals almost black, whilst it takes itself a beautiful red colour. δ. Sulphuric acid colours it gradually a beautiful red, whilst tannin does not precipitate.

Cubebin. Constituents of the Pimento.

B. Crystals Pale to Clear Yellow. B. Pure Yellow Residue.

α. Piperin. α. Sulphuric acid dissolves it yellow; on the addition of nitric acid, this solution is green, quickly changing to blue and violet.

Colchicine.

β. Picric Acid. β. Sulphuric acid dissolves with separation of a violet powder; caustic potash colours it red; sulphide of ammonia violet, and, by heating, indigo-blue.

Chrysammic acid.

γ. Caustic potash dissolves it purple.

Aloetin.

C. Mostly Undefined Colourless Crystals. C. A Greenish Bitter Residue, which dissolves brown in concentrated sulphuric acid; in Fröhde’s reagent, likewise, at first brown, then at the edge green, changing into blue-violet, and lastly violet.

Constituents of wormwood, with absynthin, besides quassiin, menyanthin, ericolin, daphnin, cnicin, and others.

α. Sulphuric acid dissolves it green-brown; bromine colours this solution red; dilution with water again green. The substance renders the heart-action of a frog slower.

Digitalin.

β. Sulphuric acid dissolves it orange, then brown, lastly red-violet. Nitric acid dissolves it yellow, and water separates as a jelly out of the latter solution. Sulphuric acid and bromine do not colour it red.

Gratiolin.

γ. Sulphuric acid dissolves it red-brown. Bromine produces in this solution red-violet stripes. It does not act on frogs.

Cascarillin.

D. Generally Undefined Yellow Crystallisation.—Sulphuric acid dissolves it olive-green. The alcoholic solution gives with potassic iodide a colourless and green crystalline precipitate.

Berberin.

V. As a complete exhaustion of the watery solution is not yet attained by the benzene agency, another solvent is tried.

THE WATERY SOLUTION IS NOW EXTRACTED IN THE SAME WAY BY CHLOROFORM.

In chloroform the following substances are especially taken up:—Theobromine, narceine, papaverine, cinchonine, jervine, besides picrotoxin, syringin, digitalin, helleborin, convallamarin, saponin, senegin, smilacin. Lastly, portions of the bodies named in Process IV., which benzene failed to extract entirely, enter into solution, as well as traces of brucine, narcotine, physostigmine, veratrine, delphinine. The evaporation of the chloroform is conducted at the ordinary temperature in four or five watch-glasses.

THE CHLOROFORM RESIDUE FROM THE ACID SOLUTION.[335]

1. The Residue is more or less markedly Crystalline. 2. The Residue is Amorphous.

A. It gives in the sulphuric acid solution evidence of an alkaloid by its action towards iodine and iodide of potassium. A. In acetic acid solution it renders the action of the frog’s heart slower, or produces local anæsthesia.

aa. It does not produce local anæsthesia.

α. Sulphuric acid dissolves it without the production of colour, and chlorine and ammonia give no murexide reaction. α. Sulphuric acid dissolves it red-brown, bromine produces a beautiful purple colour, water changes it into green, hydrochloric acid dissolves it greenish-brown.

Cinchonine. Digitalin.

β. Sulphuric acid dissolves it without colour, chlorine and ammonia give, as with theine, a murexide reaction. β. Sulphuric acid dissolves it yellow, then brown-red; on addition of water this solution becomes violet. Hydrochloric acid, on warming, dissolves it red.

Theobromine. Convallamarin.

bb. It produces local anæsthesia.

α. Sulphuric acid dissolves it brown. The solution becomes, by extracting with water, violet, and can even be diluted with two volumes of water without losing its colour.

Saponin.

β. Sulphuric acid dissolves it yellow. On diluting with water the same reaction occurs as in the previous case, but more feebly.

Senegin.

γ. Sulphuric acid does not colour in the cold; on warming, the solution becomes a blue violet. γ. Sulphuric acid dissolves brown, and the solution becomes red by the addition of a little water. The action is very weak.

Papaverine. Smilacin.

cc. Sulphuric acid dissolves it with the production of a dirty red, hydrochloric acid, in the cold, with that of a reddish-brown colour, and the last solution becomes brown on boiling.

Constituents of the hellebore, particularly Jervine.

δ. Sulphuric acid dissolves it in the cold with the production of a blue colour.

Unknown impurities, many commercial samples of Papaverine.

ε. Sulphuric acid dissolves it at first grey-brown; the solution becomes in about twenty-four hours blood-red. Iodine water colours it blue.

Narceine.

B. It gives no Alkaloid Reaction. B. Is inactive, and becomes blue by sulphuric acid; by Fröhde’s reagent[336] dark cherry-red. Hydrochloric acid dissolves it red. The solution becomes, by boiling, colourless.

Syringin.

α. Sulphuric acid dissolves it with a beautiful yellow colour; mixed with nitre, then moistened with sulphuric acid, and lastly treated with concentrated soda-lye, it is coloured a brick-red.

Picrotoxin.

β. Sulphuric acid dissolves it with the production of a splendid red colour. The substance renders the heart-action of a frog slower.

Helleborin.

VI. THE WATERY FLUID IS NOW AGAIN SHAKEN UP WITH PETROLEUM ETHER,

in order to take up the rest of the chloroform, and the watery fluid is saturated with ammonia. The watery solution of aconitine and emetine is liable to undergo, through free ammonia, a partial decomposition; but, on the other hand, it is quite possible to obtain, with very small mixtures of the substances, satisfactory reactions, even out of ammoniacal solutions.

VII. THE AMMONIACAL WATERY FLUID WITH PETROLEUM ETHER.

In the earlier stages Dragendorff advises the shaking up with petroleum ether at about 40°, and the removal of the ether as quickly as possible whilst warm. This is with the intention of separating by this fluid strychnine, brucine, emetine, quinine, veratrine, &c. Finding, however, that a full extraction by petroleum ether is either difficult or not practicable, he prefers, as we have seen, to conclude the operation by other agents, coming back again upon the ether for certain special cases. Such are the volatile alkaloids; and here he recommends treatment of the fluid by cold petroleum ether, taking care not to hasten the removal of the latter. Strychnine and other fixed alkaloids are then only taken up in small quantities, and the greater portion remains for the later treatment of the watery fluid by benzene.

A portion of the petroleum ether, supposed to contain in solution volatile alkaloids, is evaporated in two watch-glasses; to the one, strong hydrochloric acid is added, the other being evaporated without this agent. On the evaporation of the petroleum ether, it is seen whether the first portion is crystalline or amorphous, or whether the second leaves behind a strongly-smelling fluid mass, which denotes a volatile alkaloid. If the residue in both glasses is without odour and fixed, the absence of volatile acids and the presence of fixed alkaloids, strychnine, emetine, veratrine, &c., are indicated.

THE PETROLEUM ETHER RESIDUE FROM AMMONIACAL SOLUTION.

1. It is fixed and Crystalline. 2. It is fixed and Amorphous. 3. It is fixed and Odorous.

A. The crystals are volatilised with difficulty. A. On adding to the watch-glass a little hydrochloric acid, crystals are left behind.

aa. Sulphuric acid dissolves it without colour. aa. Its solution is not precipitated by platin chloride.

α. Potassic chromate colours this solution a transitory blue, then red. α. The purest sulphuric acid dissolves it almost without colour; sulphuric acid containing nitric acid, red quickly becoming orange. α. The crystals of the hydrochloric compound act on polarised light; and are mostly needle-shaped and columnar.

Strychnine. Brucine. Coniine and Methyl-Coniine.

β. Potassic chromate does not colour it blue; with chlorine water and ammonia it gives a green colour. β. Sulphuric acid dissolves it yellow, becoming deep red. β. The crystals are cubical or tetrahedral.

Quinine. Veratrine. Alkaloid from Capsicum.

γ. Sulphuric acid dissolves it brown-green; Fröhde’s reagent red, changing into green.

Emetine.

bb. The solution of the hydrochlorate of the alkaloid is precipitated by platin chloride.

Sarracinin.

γ. Sulphuric acid dissolves it yellow, and the solution becomes gradually a beautiful deep red. B. The residue of the hydrochlorate of the alkaloid is amorphous, or, by further additions of HCl, becomes crystalline.

Sabadilline.

δ. The crystals are easily volatilised.

Coniine.

aa. Its diluted aqueous solution is precipitated by platin chloride.

α. The hydrochlorate salt, being quickly treated with Fröhde’s reagent, gives after about two minutes a violet solution which gradually fades.

Lobeliin.

β. The hydrochlorate smells like nicotine, and becomes by Fröhde’s reagent yellow, and after twenty-four hours pale red.

Nicotine.

γ. The hydrochlorate is without odour, the free base smells faintly like aniline.

Sparteine.

bb. The substance is not precipitated from a diluted solution by platin chloride.

α. Its petroleum ether solution produces no turbidity with a solution of picric acid in petroleum ether; but it leaves behind, when mixed with the above, crystals mostly of three-sided plates.

Trimethylamine.

β. The petroleum ether solution gives, on evaporation, when treated similarly, moss-like crystals. The substance is made blue by chloride of lime, as well as by diluted sulphuric acid and bichromate of potash.

Aniline.

γ. The alkaloid does not smell like methylamine, and is not coloured by chloride of lime, sulphuric acid, or chromate of potash.

Volatile alkaloid of the Pimento.

VIII. THE AMMONIACAL SOLUTION IS SHAKEN UP WITH BENZENE.

In most cases petroleum ether, benzene, and chloroform are more easily separated from acid watery fluids than from ammoniacal, benzene and chloroform causing here a difficulty which has perhaps deterred many from using this method. Dragendorff, however, maintains that he has never examined a fluid in which he could not obtain a complete separation of the benzene and water. If the upper benzene layer is fully gelatinous and emulsive, the under layer of water is to be removed with a pipette as far as possible, and the benzene with a few drops of absolute alcohol and filtration. As a rule, the water goes through first alone, and by the time the greater part has run through, the jelly in the filter, by dint of stirring, has become separated from the benzene, and, finally, the jelly shrinks up to a minimum, and the clear benzene filters off. Dragendorff filters mostly into a burette, from which ultimately the benzene and the water are separated.

The principal alkaloids which are dissolved in benzene are—strychnine, methyl and ethyl strychnine, brucine, emetine, quinine, cinchonine, atropine, hyoscyamine, physostigmine, aconitine, nepalin, the alkaloid of the Aconitum lycoctonum, aconellin, napellin, delphinine, veratrine, sabatrin, sabadilline, codeine, thebaine, and narcotine.

THE BENZENE RESIDUE DERIVED FROM THE AMMONIACAL SOLUTION.

1. It is for the most part Crystalline. 2. It is for the most part Amorphous.

a. Sulphuric acid dissolves it without colour, the solution being coloured neither on standing nor on the addition of nitric acid. a. Pure sulphuric acid dissolves it either whitish-red or yellowish.

aa. It dilates the pupil of a cat.

α. Platin chloride does not precipitate the aqueous solution. The sulphuric acid solution gives, on warming, a peculiar smell. α. The solution becomes by nitric acid immediately red, then quickly orange.

Atropine. Brucine.

β. Platin chloride applied to the solution precipitates. β. The solution becomes by little and little brownish-red. The substance is coloured red by chloride of lime solution, and it contracts the pupil.

Hyoscyamine. Physostigmine.

bb. It does not dilate the pupil.

α. The sulphuric acid solution becomes blue by chromate of potash.

αα. The substance applied to a frog produces tetanus.

Strychnine.

ββ. It lowers the number of respirations in a frog.

Ethyl and Methyl Strychnine.

β. Sulphuric acid and bichromate of potash do not colour it blue.

αα. The sulphuric acid watery solution is fluorescent, and becomes green on the addition of chlorine water and ammonia.

Quinine and Cinchonine.

(The last is more difficult to dissolve in petroleum ether than quinine.)

ββ. The solution is not fluorescent.

Cinchonine.

b. Sulphuric acid dissolves it at first colourless; the solution takes on standing a rose or violet-blue; on addition of nitric acid, a blood-red or brown coloration. b. Pure sulphuric acid dissolves it yellow, and the solution becomes later beautiful red (with delphinine, more quickly a darker cherry-red.)

α. A solution in diluted sulphuric acid becomes, on heating, gradually deep blood-red, and, when cooled, violet, with nitric acid. The aqueous solution is precipitated by ammonia. α. The hydrochloric acid solution becomes red on heating.

Narcotine.

αα. The substance acts on a frog, causing, in large doses, tetanus.

Veratrine.

ββ. It is almost without action on frogs.

Sabatrin.

β. The solution in diluted sulphuric acid becomes, on heating, a beautiful blue. Excess of ammonia does not precipitate in a diluted watery solution. β. The hydrochloric acid solution does not, on heating, become red.

Codeine. Delphinine.

c. Sulphuric acid dissolves it with the production of a yellow colour. c. Pure sulphuric acid dissolves it yellow, and the solution becomes later red-brown, and gradually violet-red.

α. The solution remains yellow on standing. α. The substance even in small doses paralyses frogs, and dilates the pupil of a cat’s eye. Ether dissolves it with difficulty.

Acolyctin. Nepalin.

β. It becomes beautifully red. β. It is easily soluble in ether, its effects are not so marked, and it does not dilate the pupil.

Sabadilline. Aconitine.

γ. Its effects are still feeble; it does not dilate the pupil, and is with difficulty dissolved by ether.

Napellin.

d. Sulphuric acid dissolves it with an immediate deep red-brown colour. d. Sulphuric acid dissolves it with a dark green colour, and the solution becomes, even after a few seconds, a beautiful blood-red.

Thebaine. Alkaloidal substances out of the Aconitum lycoctonum.

e. Sulphuric acid dissolves it immediately blue. e. Sulphuric acid dissolves it brown-green, and Fröhde’s reagent red, becoming beautifully green.

Substances accompanying the Papaverins. Emetine.

IX. SHAKING OF THE AMMONIACAL WATERY SOLUTION WITH CHLOROFORM.

This extracts the remainder of the cinchonine and papaverine, narceine, and a small portion of morphine, as well as an alkaloid from the celandine.

The Residue from the Chloroform.

aa. The solution, on warming, is only slightly coloured.

α. But, after it is again cooled, it strikes with nitric acid a violet-blue; chloride of iron mixed with the substance gives a blue colour; Fröhde’s reagent also dissolves it violet.

Morphine.

β. It is not coloured by nitric acid; it is also indifferent to chloride of iron.

Cinchonine.

bb. The solution becomes by warming violet-blue.

Papaverine.

γ. Sulphuric acid dissolves it greenish-brown, and the solution becomes, on standing, blood-red.

Narceine.

δ. Sulphuric acid dissolves it a violet-blue.

Alkaloidal constituent of the Celandine.

X. SHAKING UP OF THE WATERY FLUID WITH AMYL ALCOHOL.

From this process, besides morphine and solanine, as well as salicin, the remnants of the convallamarin, saponin, senegin, and narceine are also to be expected.

The Amyl Alcohol Residue.

a. Sulphuric acid dissolves it without colour in the cold.

Morphine (see above).

b. Sulphuric acid dissolves it with the production of a clear yellow-red and the solution becomes brownish. Iodine water colours it a deep brown. The alcoholic solution gelatinises.

Solanine.

c. Sulphuric acid dissolves it green-brown, becoming red.

Narceine (see above).

d. Sulphuric acid dissolves it yellow, then brown-red, becoming violet on dilution with water. Hydrochloric acid dissolves it, and it becomes red on warming. It stops the heart-action in the systole.

Convallamarin.

e. Hydrochloric acid dissolves it for the most part without colour.

Saponin.

f. As the foregoing, but acting more feebly.

Senegin.

g. Sulphuric acid dissolves it immediately a pure red. On warming with sulphuric acid and bichromate of potash, a smell of salicylic acid is developed.

Salicin.

XI. DRYING THE WATERY FLUID WITH THE ADDITION OF POWDERED GLASS, AND EXTRACTION OF THE FINELY-DIVIDED RESIDUE BY CHLOROFORM.

The residue of the first chloroform extract lessens the number of respirations of a frog; the residue of the second and third chloroform extract becomes, by sulphuric acid and bichromate of potash, blue, passing into a permanent red.

Another portion of this residue becomes red on warming with diluted sulphuric acid.

Curarine.

Shorter Process for Separating some of the Alkaloids.

§ 310. A shorter process, recommended conditionally by Dragendorff, for brucine, strychnine, quinine, cinchonine, and emetine, is as follows:—

The substance, if necessary, is finely divided, and treated with sulphuric acid (dilute) until it has a marked acid reaction. To every 100 c.c. of the pulp (which has been diluted with distilled water to admit of its being filtered later), at least 5 to 10 c.c. of diluted sulphuric acid (1 : 5) are added. It is digested at 50° for a few hours, filtered, and the residue treated again with 100 c.c. of water at 50°. This extract is, after a few hours, again filtered; both the filtrates are mixed and evaporated in the water-bath to almost the consistency of a thin syrup. The fluid, however, must not be concentrated too much, or fully evaporated to dryness. The residue is now placed in a flask, and treated with three to four times its volume of alcohol of 90 to 95 per cent.; the mixture is macerated for twenty-four hours, and then filtered. The filtrate is distilled alcohol-free, or nearly so, but a small amount of alcohol remaining is not objectionable. The watery fluid is diluted to about 50 c.c., and treated with pure benzene; the mixture is shaken, and after a little time the benzene removed—an operation which is repeated. After the removal the second time of the benzene, the watery fluid is made alkaline with ammonia, warmed to 40° or 50°, and the free alkaloid extracted by twice shaking it up with two different applications of benzene. On evaporation of the latter, if the alkaloid is not left pure, it can be dissolved in acid, precipitated by ammonia, and again extracted by benzene.

§ 311. Scheibler’s Process.—A method very different from those just described is one practised by Scheibler. This is to precipitate the phosphotungstate of the alkaloid, and then to liberate the latter by digesting the precipitate with either hydrate of barium or hydrate of calcium, dissolving it out by chloroform, or, if volatile, by simple distillation. The convenience of Scheibler’s process is great, and it admits of very general application. In complex mixtures, it will usually be found best to precede the addition of phosphotungstic acid[337] by that of acetate of lead, in order to remove colouring matter, &c.; the excess of lead must in its turn be thrown out by SH₂, and the excess of SH₂ be got rid of by evaporation. Phosphotungstic acid is a very delicate test for the alkaloids, giving a distinct precipitate with the most minute quantities (¹⁄₂₀₀₀₀₀ of strychnine and ¹⁄₁₀₀₀₀₀ of quinine). A very similar method is practised by Sonnenschein and others with the aid of phospho-molybdic acid. The details of Scheibler’s process are as follows:—

The organic mixture is repeatedly extracted by water strongly acidified with sulphuric acid; the extract is evaporated at 30° to the consistence of a thin syrup; then diluted with water, and, after several hours’ standing, filtered in a cool place. To the filtered fluid phosphotungstic acid is added in excess, the precipitate filtered, washed with water to which some phosphotungstic acid solution has been added, and, whilst still moist, rinsed into a flask. Caustic baryta or carbonate of potash is added to alkaline reaction, and after the flask has been connected with bulbs containing HCl, it is heated at first slowly, then more strongly. Ammonia and any volatile alkaloids are driven over into the acid, and are there fixed, and can be examined later by suitable methods. The residue in the flask is carefully evaporated to dryness (the excess of baryta having been precipitated by CO₂), and then extracted by strong alcohol. On evaporation of the alcohol, the alkaloid is generally sufficiently pure to be examined, or, if not so, it may be obtained pure by re-solution, &c.

The author has had considerable experience of Scheibler’s process, and has used it in precipitating various animal fluids, but has generally found the precipitate bulky and difficult to manage.

§ 312. Grandval and Lajoux’s Method.[338]—The alkaloids are precipitated from a solution slightly acidified by hydrochloric or sulphuric acid by a solution of hydrarg-potassium iodide. The precipitate is collected on a filter, washed and then transferred to a flask; drop by drop, a solution of sodium sulphide is added; after each addition the suspended precipitate is shaken and allowed to stand for a few minutes, and a drop of the liquid taken out and tested with lead acetate; directly a slight brown colour appears, sufficient sodic sulphide has been added. The liquid is now left for half-an-hour, with occasional shaking. Then sulphuric acid is added until it is just acid, and the liquid is filtered and the mercury sulphide well washed. In the filtrate will be the sulphate of any alkaloid in solution; this liquid is now made alkaline with soda carbonate and shaken up, as in Dragendorff’s process, with appropriate solvents; such, for example, as ether, or chloroform, or acetone, or amylic alcohol, according to the particular alkaloid the analyst is searching for, and the solvent finally separated and allowed to evaporate, when the alkaloid is found in the residue.

§ 313. Identification of the Alkaloids.—Having obtained, in one way or other, a crystalline or amorphous substance, supposed to be an alkaloid, or, at all events, an active vegetable principle, the next step is to identify it. If the tests given in Dragendorff’s process have been applied, the observer will have already gone a good way towards the identification of the substance; but it is, of course, dangerous to trust to one reaction.

In medico-legal researches there is seldom any considerable quantity of the material to work upon. Hence the greatest care must be taken from the commencement not to waste the substance in useless tests, but to study well at the outset what—by the method of extraction used, the microscopic appearance, the reaction to litmus paper, and the solubility in different menstrua—it is likely to be. However minute the quantity may be, it is essential to divide it into different parts, in order to apply a variety of tests; but as any attempt to do this on the solid substance will probably entail loss, the best way is to dissolve it in a watch-glass in half a c.c. of alcohol, ether, or other suitable solvent. Droplets of this solution are then placed on watch-glasses or slips of microscopic glass, and to these drops, by the aid of a glass rod, different reagents can be applied, and the changes watched under the microscope as the drops slowly evaporate.

§ 314. Sublimation of the Alkaloids.—A very beautiful and elegant aid to the identification of alkaloids, and vegetable principles generally, is their behaviour towards heat.

Alkaloids, glucosides, the organic acids, &c., when carefully heated, either—(1) sublime wholly without decomposition (like theine, cytisin, and others); or (2) partially sublime with decomposition; or (3) are changed into new bodies (as, for example, gallic acid); or (4) melt and then char; or (5) simply char and burn away.

Many of these phenomena are striking and characteristic, taking place at different temperatures, subliming in characteristic forms, or leaving characteristic residues.

One of the first to employ sublimation systematically, as a means of recognition of the alkaloids, &c., was Helwig.[339] His method was to place a small quantity (from ¹⁄₂ to ¹⁄₄₀₀₀ of a mgrm.) in a depression on platinum foil, cover it with a slip of glass, and then carefully heat by a small flame. After Helwig, Dr. Guy[340] greatly improved the process by using porcelain discs, and more especially by the adoption of a convenient apparatus, which may be termed “the subliming cell.” It is essentially composed of a ring of glass from ¹⁄₈ to ²⁄₃ of an inch in thickness, such as may be obtained by sections of tubing, the cut surfaces being ground perfectly smooth. This circle is converted into a closed cell by resting it on one of the ordinary thin discs of glass used as a covering for microscopic purposes, and supporting a similar disc. The cell was placed on a brass plate, provided with a nipple, which carried a thermometer, and was heated by a small flame applied midway between the thermometer and the cell; the heat was raised very gradually, and the temperature at which any change took place was noted. In this way Dr. Guy made determinations of the subliming points of a large number of substances, and the microscopic appearances of the sublimates were described with the greatest fidelity and accuracy. On repeating with care Dr. Guy’s determinations, however, I could in no single instance agree with his subliming points, nor with the apparatus he figures and describes could two consecutive observations exactly coincide. Further, on examining the various subliming temperatures of substances, as stated by different authors, the widest discrepancies were found—differences of 2 or even 3 degrees might be referred to errors of observation, a want of exact coincidence in the thermometers employed, and the like; but to what, for example, can we ascribe the irreconcilable statements which have been made with regard to theine? According to Strauch, this substance sublimes at 177°; according to Mulder, at 184·7°. But that both of these observations deviate more than 70° from the truth may be proved by any one who cares to place a few mgrms. of theine, enclosed between two watch-glasses, over the water-bath; in a few minutes a distinct sublimate will condense on the upper glass, and, in point of fact, theine will be found to sublime several degrees below 100°.

Since this great divergency of opinion is not found either in the specific gravity, or the boiling-points, or any of the like determinations of the physical properties of a substance, it is self-evident that the processes hitherto used for the determination of subliming points are faulty. The sources of error are chiefly—

(1.) Defects in the apparatus employed—the temperature read being rather that of the metallic surface in the immediate vicinity of the thermometer than of the substance itself.

(2.) The want of agreement among observers as to what should be called a sublimate—one considering a sublimate only that which is evident to the naked eye, another taking cognisance of the earliest microscopic film.

(3.) No two persons employing the same process.

With regard to the apparatus employed, I adopt Dr. Guy’s subliming cell; but the cell, instead of resting on a metallic solid, floats on a metallic fluid. For any temperature a little above 100° this fluid is mercury, but for higher temperatures fusible metal is preferable.

Subliming Cell.

The exact procedure is as follows:—A porcelain crucible (a in fig.), about 3 inches in diameter, is nearly filled with mercury or fusible metal, as the case may be; a minute speck (or two or three crystals of the substance to be examined) is placed on a thin disc of microscopic covering glass, floated on the liquid, and the cell is completed by the glass ring and upper disc. The porcelain crucible is supported on a brass plate (b), fixed to a retort-stand in the usual way, and protected from the unequal cooling effects of currents of air by being covered by a flask (c), from which the bottom has been removed. The neck of the flask conveniently supports a thermometer, which passes through a cork, and the bulb of the thermometer is immersed in the bath of liquid metal. In the first examination of a substance the temperature is raised somewhat rapidly, taking off the upper disc with a forceps at every 10° and exchanging it for a fresh disc, until the substance is destroyed. The second examination is conducted much more slowly, and the discs exchanged at every 4° or 5°, whilst the final determination is effected by raising the temperature with great caution, and exchanging the discs at about the points of change (already partially determined) at every half degree. All the discs are examined microscopically. The most convenient definition of a sublimate is this—the most minute films, dots, or crystals, which can be observed by ¹⁄₄-inch power, and which are obtained by keeping the subliming cell at a definite temperature for 60 seconds. The commencement of many sublimates assumes the shape of dots of extraordinary minuteness, quite invisible to the unaided eye; and, on the other hand, since the practical value of sublimation is mainly as an aid to other methods for the recognition of substances, if we go beyond short intervals of time, the operation, otherwise simple and speedy, becomes cumbersome, and loses its general applicability.

There is also considerable discrepancy of statement with regard to the melting-point of alkaloidal bodies; in many instances a viscous state intervenes before the final complete resolution into fluid, and one observer will consider the viscous state, the other complete fluidity, as the melting-point.

In the melting-points given below, the same apparatus was used, but the substance was simply placed on a thin disc of glass floating on the metallic bath before described (the cell not being completed), and examined from time to time microscopically, for by this means alone can the first drops formed by the most minute and closely-adherent crystals to the glass be discovered.

Cocaine melts at 93°, and gives a faint sublimate at 98°; if put between two watch-glasses on the water-bath, in fifteen minutes there is a good cloud on the upper glass.

Aconitine turns brown, and melts at 179° C.; it gives no characteristic sublimate up to 190°.

Morphine, at 150°, clouds the upper disc with nebulæ; the nebulæ are resolved by high magnifying powers into minute dots; these dots gradually become coarser, and are generally converted into crystals at 188°; the alkaloid browns at or about 200°.

Thebaine sublimes in theine-like crystals at 135°; at higher temperatures (160° to 200°), needles, cubes, and prisms are observed. The residue on the lower disc, if examined before carbonisation, is fawn-coloured with non-characteristic spots.

Narcotine gives no sublimate; it melts at 155° into a yellow liquid, which, on raising the temperature, ever becomes browner to final blackness. On examining the residue before carbonisation, it is a rich brown amorphous substance; but if narcotine be heated two or three degrees above its melting-point, and then cooled slowly, the residue is crystalline—long, fine needles radiating from centres being common.

Narceine gives no sublimate; it melts at 134° into a colourless liquid, which undergoes at higher temperatures the usual transition of brown colours. The substance, heated a few degrees above its melting-point, and then allowed to cool slowly, shows a straw-coloured residue, divided into lobes or drops containing feathery crystals.

Papaverine gives no sublimate; it melts at 130°. The residue, heated a little above its melting-point, and then slowly cooled, is amorphous, of a light-brown colour, and in no way characteristic.

Hyoscyamine gives no crystalline sublimate; it melts at 89°, and appears to volatilise in great part without decomposition. It melts into an almost colourless fluid, which, when solid, may exhibit a network not unlike vegetable parenchyma; on moistening the network with water, interlacing crystals immediately appear. If, however, hyoscyamine be kept at 94° to 95° for a few minutes, and then slowly cooled, the edges of the spots are arborescent, and the spots themselves crystalline.

Atropine (daturine) melts at 97°; at 123° a faint mist appears on the upper disc. Crystals cannot be obtained; the residue is not characteristic.

Solanine.—The upper disc is dimmed with nebulæ at 190°, which are coarser and more distinct at higher temperatures; at 200° it begins to brown, and then melts; the residue consists of amber-brown, non-characteristic drops.

Strychnine gives a minute sublimate of fine needles, often disposed in lines, at 169°; about 221° it melts, the residue (at that temperature) is resinous.

Brucine melts at 151° into a pale yellow liquid, at higher temperatures becoming deep-brown. If the lower disc, after melting, be examined, no crystals are observed, the residue being quite transparent, with branching lines like the twigs of a leafless tree; light mists, produced rather by decomposition than by true sublimation, condense on the upper disc at 185°, and above.

Saponin neither melts nor sublimes; it begins to brown about 145°, is almost black at 185°, and quite so at 190°.

Delphinine begins to brown about 102°; it becomes amber at 119°, and melts, and bubbles appear. There is no crystalline sublimate; residue not characteristic.

Pilocarpine gives a distinct crystalline sublimate at 153°; but thin mists, consisting of fine dots, may be observed as low as 140°. Pilocarpine melts at 159°; the sublimates at 160° to 170° are in light yellow drops. If these drops are treated with water, and the water evaporated, feathery crystals are obtained; the residue is resinous.

Theine wholly sublimes; the first sublimate is minute dots, at 79°; at half a degree above that very small crystals may be obtained; and at such a temperature as 120°, the crystals are often long and silky.

Theobromine likewise wholly sublimes; nebulæ at 134°, crystals at 170°, and above.

Salicin melts at 170°; it gives no crystalline sublimate. The melted mass remains up to 180° almost perfectly colourless; above that temperature browning is evident. The residue is not characteristic.

Picrotoxin gives no crystalline sublimate. The lowest temperature at which it sublimes is 128°; the usual nebulæ then make their appearance; between 165° and 170° there is slight browning; at 170° it melts. The residue, slowly cooled, is not characteristic.

Cantharidin sublimes very scantily between 82° and 83°; at 85° the sublimate is copious.

The active principles of plants may, in regard to their behaviour to heat, be classed for practical purposes into—

1. Those which give a decided crystalline sublimate:

(a.) Below 100°, e.g., cocaine, theine, thebaine, cantharidin. (b.) Between 100° and 150°, e.g., quinetum. (c.) Between 150° and 200°, e.g., strychnine, morphine, pilocarpine.

2. Those which melt, but give no crystalline sublimate:

(a.) Below 100°, e.g., hyoscyamine, atropine. (b.) Between 100° and 150°, e.g., papaverine. (c.) Between 150° and 200°, e.g., salicin. (d.) Above 200°, e.g., solanine.

3. Those which neither melt nor give a crystalline sublimate, e.g., saponin.

§ 315. Melting-point.—The method of sublimation just given also determines the melting-point; such a determination will, however, seldom compare with the melting-points of the various alkaloids as given in text-books, because the latter melting-points are not determined in the same way. The usual method of determining melting-points is to place a very small quantity in a glass tube closed at one end; the tube should be almost capillary. The tube is fastened to a thermometer by means of platinum wire, and then the bulb of the thermometer, with its attached tube, is immersed in strong sulphuric acid or paraffin, contained in a flask. The thermometer should be suspended midway in the liquid and heat carefully applied, so as to raise the temperature gradually and equably. It will be found that rapidly raising the heat gives a different melting-point to that which is obtained by slowly raising the heat. During the process careful watching is necessary: most substances change in hue before they actually melt. A constant melting-point, however often a substance is purified by recrystallisation, is a sign of purity.

§ 316. Identification by Organic Analysis.—In a few cases (and in a few only) the analyst may have sufficient material at hand to make an organic analysis, either as a means of identification or to confirm other tests. By the vacuum process described in “Foods,” in which carbon and nitrogen are determined by measuring the gases evolved by burning the organic substance in as complete a vacuum as can be obtained, very minute quantities of a substance can be dealt with, and the carbon and nitrogen determined with fair accuracy. It is found in practice that the carbon determinations appear more reliable than those of the nitrogen, and there are obvious reasons why this should be so.

Theoretically, with the improved gas-measuring appliances, it is possible to measure a c.c. of gas; but few chemists would care to create a formula on less than 10 c.c. of CO₂. Now, since 10 c.c. of CO₂ is equal to 6·33 mgrms. of carbon, and alkaloids average at least half their weight of carbon, it follows that 12 mgrms. of alkaloid represent about the smallest quantity with which a reliable single combustion can be made.

The following table gives a considerable number of the alkaloids and alkaloidal bodies, arranged according to their content in carbon:—

TABLE SHOWING THE CONTENT OF CARBON AND NITROGEN IN VARIOUS ALKALOIDAL BODIES.

Carbon. Nitrogen.

Asparagin, 36 ·36 21 ·21

Methylamine, 38 ·71 45 ·17

Betaine, 44 ·44 10 ·37

Theobromine, 46 ·67 31 ·11

Theine, 49 ·48 28 ·86

Indican, 49 ·60 2 ·22

Muscarine, 50 ·42 11 ·77

Lauro-cerasin, 52 ·47 1 ·53

Amanitine, 57 ·69 13 ·46

Narceine, 59 ·63 3 ·02

Colchicine, 60 ·53 4 ·15

Oxyacanthine, 60 ·57 4 ·42

Solanine, 60 ·66 1 ·68

Trimethylamine, 61 ·02 23 ·73

Jervine, 61 ·03 5 ·14

Sabadilline, 61 ·29 3 ·46

Aconitine, 61 ·21 2 ·16

Nepaline, 63 ·09 2 ·12

Colchicein, 63 ·44 4 ·38

Veratroidine, 63 ·8 3 ·1

Narcotine, 63 ·92 3 ·39

Veratrine, 64 ·42 2 ·91

Delphinine, 64 ·55 3 ·42

Physostigmine, 65 ·49 15 ·27

Rhœadine, 65 ·79 3 ·65

Cocaine, 66 ·44 4 ·84

Gelsemine, 67 ·00 7 ·10

Conhydrine, 67 ·12 9 ·79

Staphisagrine, 67 ·5 3 ·6

Chelidonine, 68 ·06 12 ·34

Atropine, Hyoscyamine, 70 ·58 4 ·84

Sanguinarine, 70 ·59 4 ·33

Papaverine, 70 ·79 4 ·13

Delphinoidine, 70 ·9 3 ·9

Morphine and Piperine, 71 ·58 4 ·91

Berberine, 71 ·64 4 ·18

Codeine, 72 ·24 4 ·68

Thebaine, 73 ·31 4 ·50

Cytisine, 73 ·85 12 ·92

Nicotine, 74 ·08 17 ·28

Quinine, 75 ·02 8 ·64

Coniine, 76 ·81 11 ·20

Strychnine, 77 ·24 8 ·92

Curarine, 81 ·51 5 ·28

§ 317. Quantitative Estimation of the Alkaloids.—For medico-legal purposes the alkaloid obtained is usually weighed directly, but for technical purposes other processes are used. One of the most convenient of these is titration with normal or decinormal sulphuric acid, a method applicable to a few alkaloids of marked basic powers—e.g., quinine is readily and with accuracy estimated in this way, the alkaloid being dissolved in a known volume of the acid, and then titrated back with soda. If a large number of observations are to be made, an acid may be prepared so that each c.c. equals 1 mgrm. of quinine. A reagent of general application is found in the so-called Mayer’s reagent, which consists of 13·546 grms. of mercuric chloride, and 49·8 grms. of iodide of potassium in a litre of water. Each c.c. of such solution precipitates—

Of Strychnine, ·0167 grm.

„ Brucine, ·0233 „

„ Quinine, ·0108 „

„ Cinchonine, ·0102 „

„ Quinidine, ·0120 „

„ Atropine, ·0145 „

„ Aconitine, ·0268 „

„ Veratrine, ·0269 „

„ Morphine, ·0200 „

„ Narcotine, ·0213 „

„ Nicotine, ·00405 „

„ Coniine, ·00416 „

The final reaction is found by filtering, from time to time, a drop on to a glass plate, resting on a blackened surface, and adding the test until no precipitate appears. The results are only accurate when the strength of the solution of the alkaloid is about 1 : 200; so that it is absolutely necessary first to ascertain approximatively the amount present, and then to dilute or concentrate, as the case may be, until the proportion mentioned is obtained.

A convenient method of obtaining the sulphate of an alkaloid for quantitative purposes, and especially from organic fluids, is that recommended by Wagner. The fluid is acidulated with sulphuric acid, and the alkaloid precipitated by a solution of iodine in iodide of potassium. The precipitate is collected and dissolved in an aqueous solution of hyposulphite of soda. The filtered solution is again precipitated with the iodine reagent, and the precipitate dissolved in sulphurous acid, which, on evaporation, leaves behind the pure sulphate of the base.

It is also very useful for quantitative purposes to combine an alkaloid with gold or platinum, by treating the solution with the chlorides of either of those metals—the rule as to selection being to give that metal the preference which yields the most insoluble and the most crystallisable compound.

The following table gives the percentage of gold or platinum left on ignition of the double salt:—

Gold. Platinum.

Atropine, 31 ·57 ...

Aconitine 20 ·0 ...

Amanitine, 44 ·23 ...

Berberine, 29 ·16 18 ·11

Brucine, ... 16 ·52

Cinchonine, ... 27 ·36

Cinchonidine, ... 27 ·87

Codeine, ... 19 ·11

Coniine, ... 29 ·38

Curarine, ... 32 ·65

Delphinine, 26 ·7 ...

Delphinoidine, 29 ·0 15 ·8

Emetine, ... 29 ·7

Hyoscyamine, 34 ·6 ...

Morphine, ... 19 ·52

Muscarine, 43 ·01 ...

Narcotine, 15 ·7 15 ·9

Narceine, ... 14 ·52

Nicotine, ... 34 ·25

Papaverine, ... 17 ·82

Pilocarpine, 35 ·5 23 ·6 to 25·2.

Piperine, ... 12 ·7

Quinine, 40 ·0 26 ·26

Strychnine, 29 ·15 18 ·16

Thebaine, ... 18 ·71

Theine, 37 ·02 24 ·58

Theobromine, ... 25 ·55

Veratrine, 21 ·01 ...

II.—Liquid Volatile Alkaloids.

THE ALKALOIDS OF HEMLOCK—NICOTINE—PITURIE—SPARTEINE.

1. THE ALKALOIDS OF HEMLOCK (CONIUM).

§ 318. The Conium maculatum, or spotted hemlock, is a rather common umbelliferous plant, growing in waste places, and flowering from about the beginning of June to August. The stem is from three to five feet high, smooth, branched, and spotted with purple; the leaflets of the partial involucres are unilateral, ovate, lanceolate, with an attenuate point shorter than the umbels; the seeds are destitute of vittæ, and have five prominent crenate wavy ridges. The whole plant is fœtid and poisonous. Conium owes its active properties to a volatile liquid alkaloid, Coniine, united with a crystalline alkaloid, Conhydrine.

§ 319. Coniine (conia, conicine), (C₈H₁₇N)—specific gravity 0·862 at 0°; melting-point, -2·5°; boiling-point, 166·6°. Pure coniine has been prepared synthetically by Ladenburg, and found to be propyl-piperidine C₅H₁₀NC₃H₇, but the synthetically-prepared piperidine has no action on polarised light. By uniting it with dextro-tartaric acid, and evaporating, it is possible to separate the substance into dextro-propyl-piperidine and lævo-propyl-piperidine. The former is in every respect identical with coniine from hemlock; it is a clear, oily fluid, possessing a peculiarly unpleasant, mousey odour. One part is soluble in 150 parts of water,[341] in 6 parts of ether, and in almost all proportions of amyl alcohol, chloroform, and benzene. It readily volatilises, and, provided air is excluded, may be distilled unchanged. It ignites easily, and burns with a smoky flame. It acts as a strong base, precipitating the oxides of metals and alkaline earths from their solutions, and it coagulates albumen. Coniine forms salts with hydrochloric acid (C₈H₁₅N.HCl), phosphoric acid, iodic acid, and oxalic acid, which are in well-marked crystals. The sulphate, nitrate, acetate, and tartrate are, on the other hand, non-crystalline.

If coniine is oxidised with nitric acid, or bichromate of potash, and diluted sulphuric acid, butyric acid is formed; and since the latter has an unmistakable odour, and other characteristic properties, it has been proposed as a test for coniine. This may be conveniently performed thus:—A crystal of potassic bichromate is put at the bottom of a test-tube, and some diluted sulphuric acid with a drop of the supposed coniine added. On heating, the butyric acid reveals itself by its odour, and can be distilled into baryta water, the butyrate of baryta being subsequently separated in the usual way, and decomposed by sulphuric acid, &c.

Another test for coniine is the following:—If dropped into a solution of alloxan, the latter is coloured after a few minutes an intense purple-red, and white needle-shaped crystals are separated, which dissolve in cold potash-lye into a beautiful purple-blue, and emit an odour of the base.[342] Dry hydrochloric acid gives a purple-red, then an indigo-blue colour, with coniine; but if the acid is not dry, there is formed a bluish-green crystalline mass. This test, however, is of little value to the toxicologist, the pure substance alone responding with any definite result.

The ordinary precipitating agents, according to Dragendorff, act as follows:—

Potass bismuth iodide.

1 : 2000, a strong orange precipitate.

1 : 3000. The drop of the reagent is surrounded with a muddy border.

1 : 4000. The drop of the reagent is surrounded with a muddy border.

1 : 5000, still perceptible.

1 : 6000. The last limit of the reaction.

Phosphomolybdic acid gives a strong yellow precipitate; limit, 1 : 5000.

Potass. mercuric iodide gives a cheesy precipitate; limit, 1 : 1000 in neutral, 1 : 800 in acid, solutions.

Potass. cadmic iodide gives an amorphous precipitate, 1 : 300. The precipitate is soluble in excess of the precipitant. (Nicotine, under similar circumstances, gives a crystalline precipitate.)

Flückiger recommends the following reaction:[343]—“Add to 10 drops of ether in a shallow glass crystallising dish 2 drops of coniine, and cover with filter paper. Set upon the paper a common-sized watch-glass containing bromine water, and invert a beaker over the whole arrangement. Needle-shaped crystals of coniine hydro-bromine soon form in the dish as well as in the watch-glass.” Hydrochloric acid, used in the same way, instead of bromine water, forms with coniine microscopic needles of coniine hydrochlorate; both the hydro-bromide and the hydrochlorate doubly refract light. Nicotine does not respond to this reaction.

Coniine forms with carbon disulphide a thiosulphate and a sulphite. If carbon disulphide, therefore, be shaken with an aqueous solution of coniine, the watery solution gives a brown precipitate with copper sulphate, colours ferric chloride solution dark brown red, and gives a milky opalescence with dilute acids. If coniine itself is added to carbon disulphide, there is evolution of heat, separation of sulphur, and formation of thiosulphate. Nicotine does not respond to this reaction.

§ 320. Other Coniine Bases.—Methyl- and ethyl-coniine have been prepared synthetically, and are both similar in action to coniine, but somewhat more like curarine. By the reduction of coniine with zinc dust conyrine (C₈H₁₁N) is formed; between coniine and conyrine stands coniceine (C₈H₁₅NO). De Coninck has made synthetically by the addition of 6 atoms of hydrogen to β collidine, a new fluid alkaloid (C₈H₁₁N + 6H = C₈H₁₇N), which he has called isocicutine: it has the same formula as coniine. Paraconiine Schiff prepared synthetically from ammonia and normal butyl aldehyde; it has the formula C₈H₁₅N, and therefore differs from coniine in containing two atoms less of hydrogen. All the above have a similar physiological action to coniine. α-stillbazoline (C₁₁H₁₉N), prepared by Baurath from benzaldehyde and picoline, is analogous to coniine, and according to Falck has similar action, but is more powerful.

§ 321. Pharmaceutical Preparations.—The percentage of coniine in the plant itself, and in pharmaceutical preparations, can be approximately determined by distilling the coniine over, in a partial vacuum,[344] and titrating the distillate with Mayer’s reagent, each c.c. = about ·00416 grm. of coniine. It appears to be necessary to add powdered potassic chloride and a small quantity of diluted sulphuric acid before titrating, or the precipitate does not separate. In any case, the end of the reaction is difficult to observe.[345]

The fresh plant is said to contain from about ·04 to ·09 per cent., and the fruit about 0·7 per cent. of coniine.

The officinal preparations are—the leaves, the fruit, a tincture of the fruit, an extract of the leaves, the juice of the leaves (Succus conii), a compound hemlock pill (composed of extract of hemlock, ipecacuanha, and treacle), an inhalation of coniine (Vapor conii), and a poultice (Cataplasma conii) made with the leaves.

§ 322. Statistics of Coniine Poisoning.—F. A. Falck[346] has been able to collect 17 cases of death recorded in medical literature, up to the year 1880, from either coniine or hemlock. Two of these cases were criminal (murders), 1 suicidal, 2 cases in which coniine had been used medicinally (in one instance the extract had been applied to a cancerous breast; in the other, death was produced from the injection of an infusion of hemlock leaves). The remaining 12 were cases in which the root, leaves, or other portions of the plant had been ignorantly or accidentally eaten.

§ 323. Effects on Animals.—It destroys all forms of animal life. The author made some years ago an investigation as to its action on the common blow-fly. Droplets of coniine were applied to various parts of blow-flies, which were then placed under glass shades. The symptoms began within a minute by signs of external irritation, there were rapid motions of the wings, and quick and aimless movements of the legs. Torpor set in speedily, the buzz soon ceased, and the insects lay on their sides, motionless, but for occasional twitching of the legs. The wings, as a rule, became completely paralysed before the legs, and death occurred at a rather variable time, from ten minutes to two hours. If placed in a current of air in the sun, a fly completely under the influence of coniine may recover. Coniine causes in frogs, similar to curarine, peripheral paralysis of the motor nerves, combined with a transitory stimulation, and afterwards a paralysis of the motor centres; in frogs the paralysis is not preceded by convulsions. Dragendorff experimented on the action of coniine when given to five cats, the quantities used being ·05 to ·5 grm. The symptoms came on almost immediately, but with the smaller dose given to a large cat, no effect was witnessed until twenty-five minutes afterwards; this was the longest interval. One of the earliest phenomena was dilatation of the pupil, followed by weakness of the limbs passing into paralysis, the hinder legs being affected prior to the fore. The respiration became troubled, and the frequency of the breathing diminished; the heart in each case acted irregularly, and the sensation generally was blunted; death was preceded by convulsions. In the cases in which the larger dose of ·4 to ·5 grm. was administered, death took place within the hour, one animal dying in eight minutes, a second in eighteen minutes, a third in twenty minutes, and a fourth in fifty-eight minutes. With the smaller dose of ·051 grm. given to a large cat, death did not take place until eight hours and forty-seven minutes after administration.

§ 324. Effects on Man.—In a case recorded by Bennet,[347] and quoted in most works on forensic medicine, the symptoms were those of general muscular weakness deepening into paralysis. The patient had eaten hemlock in mistake for parsley; in about twenty minutes he experienced weakness in the lower extremities, and staggered in walking like a drunken man; within two hours there was perfect paralysis of both upper and lower extremities, and he died in three and a quarter hours. In another case, related by Taylor, the symptoms were also mainly those of paralysis, and in other instances stupor, coma, and slight convulsions have been noted.

§ 325. Physiological Action.—It is generally agreed that coniine paralyses, first the ends of the motor nerves, afterwards their trunks, and lastly, the motor centre itself. At a later period the sensory nerves participate. In the earlier stage the respiration is quickened, the pupils contracted, and the blood-pressure increased; but on the development of paralysis the breathing becomes slowed, the capillaries relaxed, and the blood-pressure sinks. Death takes place from cessation of the respiration, and not primarily from the heart, the heart beating after the breathing has stopped. Coniine is eliminated by the urine, and is also in part separated by the lungs, while a portion is, perhaps, decomposed in the body.

§ 326. Post-mortem Appearances.—There is nothing characteristic in the appearances after death.

Fatal Dose.—The fatal dose of coniine is not accurately known; it is about 150 mgrms. (2·3 grains). In the case of Louise Berger, 10 to 15 drops appear to have caused death in a few minutes. The auto-experiments of Dworzak, Heinrich, and Dillaberger would indicate that one drop may cause unpleasant symptoms. Albers, in the treatment of a woman suffering from cancer of the breast, witnessed convulsions and loss of consciousness from a third dose of 4 mgrms. (·06 grain); and Eulenberg, its full narcotic effects on a child after subcutaneous injection of 1 mgrm. (·015 grain).

§ 327. Separation of Coniine from Organic Matters or Tissues.—The substances are digested with water, acidulated with H₂SO₄, at a temperature not exceeding 40°, and then filtered. If the filtrate should be excessive, it must be concentrated; alcohol is then added, the liquid refiltered, and from the filtrate the alcohol separated by distillation.

On cooling, the acid fluid is agitated with benzene, and the latter separated in the usual way. The fluid is now alkalised with ammonia, and shaken up once or twice with its own volume of petroleum ether; the latter is separated and washed with distilled water, and the alkaloid is obtained almost pure. If the petroleum ether leaves no residue, it is certain that the alkaloid was not present in the contents of the stomach or intestine.

The affinity of coniine with ether or chloroform is such, that its solution in either of these fluids, passed through a dry filter, scarcely retains a drop of water. In this way it may be conveniently purified, the impurities dissolved by water remaining behind.

In searching for coniine, the stomach, intestines, blood, urine, liver, and lungs are the parts which should be examined. According to Dragendorff, it has been discovered in the body of a cat six weeks after death.

Great care must be exercised in identifying any volatile alkaloid as coniine, for the sources of error seem to be numerous. In one case[348] a volatile coniine-like ptomaine, was separated from a corpse, and thought to be coniine; but Otto found that in its behaviour to platinic chloride, it differed from coniine; it was very poisonous—·07 was fatal to a frog, ·44 to a pigeon, in a few minutes. In the seeds of Lupinus luteus there is a series of coniine-like substances,[349] but they do not give the characteristic crystals with hydrochloric acid.

2. TOBACCO—NICOTINE.

§ 328. The different forms of tobacco are furnished by three species of the tobacco plant, viz., Nicotianum tabacum, N. rustica, and N. persica.

Havanna, French, Dutch, and the American tobaccos are in the main derived from N. tabacum; Turkish, Syrian, and the Latakia tobaccos are the produce of N. rustica. There seems at present to be little of N. persica in commerce.

All the species of tobacco contain a liquid, volatile, poisonous alkaloid (Nicotine), probably united in the plant with citric and malic acids. There is also present in tobacco an unimportant camphor (nicotianin). The general composition of the plant may be gathered from the following table:—

TABLE SHOWING THE COMPOSITION OF FRESH LEAVES OF TOBACCO (POSSELT AND RIENMANN).

Nicotine, 0·060

Concrete volatile oil, 0·010

Bitter extractive, 2·870

Gum with malate of lime, 1·740

Chlorophyl, 0·267

Albumen and gluten, 1·308

Malic acid, 0·510

Lignine and a trace of starch, 4·969

Salts (sulphate, nitrate, and malate of potash, chloride of potassium, phosphate and malate of lime, and malate of ammonia,) - 0·734

Silica, 0·088

Water, 88·280

100·836

§ 329. Quantitative Estimation of Nicotine in Tobacco.—The best process (although not a perfectly accurate one) is the following:—25 grms. of the tobacco are mixed with milk of lime, and allowed to stand until there is no odour of ammonia; the mixture is then exhausted by petroleum ether, the ether shaken up with a slight excess of normal sulphuric acid, and titrated back by baryta water; the sulphate of baryta may be collected and weighed, so as to control the results. With regard to the percentage of nicotine in commercial tobacco, Kosutany found from 1·686 to 3·738 per cent. in dry tobacco; Letheby, in six samples, from 1·5 to 3·2 per cent.; whilst Schlössing gives for Havanna 2 per cent., Maryland 2·29 per cent., Kentucky 6·09 per cent., Virginian 6·87 per cent., and for French tobacco, quantities varying from 3·22 to 7·96 per cent. Again, Lenoble found in Paraguay tobacco from 1·8 to 6 per cent.; and Wittstein, in six sorts of tobacco in Germany, 1·54 to 2·72 per cent.

Mr. Cox[350] has recently determined the amount of nicotine in a number of tobaccos. The results are tabulated in the following table as follows:—

TABLE OF RESULTS, ARRANGED ACCORDING TO PER CENT. OF NICOTINE.

Variety examined. Nicotine per cent.

1. Syrian leaves (a), ·612

2. American chewing, ·935

3. Syrian leaves (b), 1 ·093

4. Chinese leaves, 1 ·902

5. Turkish (coarse cut), 2 ·500

6. Golden Virginia (whole strips), 2 ·501

7. Gold Flake (Virginia), 2 ·501

8. “Navy-cut” (light coloured), 2 ·530

9. Light returns (Kentucky), 2 ·733

10. “Navy-cut” (dark “all tobacco”), 3 ·640

11. Best “Birds-eye,” 3 ·931

12. Cut Cavendish (a), 4 ·212

13. “Best Shag” (a), 4 ·907

14. “Cut Cavendish” (b), 4 ·970

15. “Best Shag” (b), 5 ·000

16. French tobacco, 8 ·711

17. Algerian tobacco (a), 8 ·813

18. Algerian tobacco (b), 8 ·900

It is therefore obvious that the strength of tobacco in nicotine varies between wide limits.

Twenty-five grammes (or more or less, according to the amount of the sample at disposal) of the dried and powdered tobacco were intimately mixed with slaked lime, and distilled in a current of steam until the condensed steam was no longer alkaline; the distillate was slightly acidulated with dilute H₂SO₄, and evaporated to a conveniently small bulk. This was made alkaline with soda, and agitated repeatedly with successive portions of ether. The separated batches of ethereal solution of nicotine were then mixed and exposed to the air in a cool place. This exposure to the air carries away ammonia, if any be present, as well as ether.

Water was added to the ethereal residue, and the amount of nicotine present determined by decinormal H₂SO₄, using methyl-orange as an indicator. One c.c. of decinormal H₂SO₄ represents 0·0162 gramme of nicotine (C₁₀H₁₄N₂).

§ 330. Nicotine (C₁₀H₁₄N₂).—Hexahydro dipyridyl (C₅H₄N)₂H₆, when pure, is an oily, colourless fluid, of 1·0111, specific gravity at 15°.[351] It evaporates under 100° in white clouds, and boils at about 240°, at which temperature it partly distils over unchanged, and is partly decomposed—a brown resinous product remaining. It volatilises with aqueous and amyl alcohol vapour notably, and is not even fixed at -10°. It has a strong alkaline reaction, and rotates a ray of polarised light to the right. Its odour, especially on warming, is strong and unpleasantly like tobacco, and it has a sharp caustic taste. It absorbs water exposed to the air, and dissolves in water in all proportions, partly separating from such solution on the addition of a caustic alkali. The aqueous solution acts in many respects like ammonia, saturating acids fully, and may therefore be in certain cases estimated with accuracy by titration, 49 parts of H₂SO₄ corresponding to 162 of nicotine. It gives on oxidation nicotinic acid = m(β) pyridincarbo acid C₅H₄N(COOH), and by oxidation with elimination of water dipyridyl (C₅H₄N)₂, and through reduction dipiperydil (C₅H₁₀N)₂.

Alcohol and ether dissolve nicotine in every proportion; if such solutions are distilled, nicotine goes over first. The salts which it forms with hydrochloric, nitric, and phosphoric acids crystallise with difficulty; tartaric and oxalic acid form white crystalline salts, and the latter, oxalate of nicotine, is soluble in alcohol, a property which distinguishes it from the oxalate of ammonia. The best salts are the oxalate and the acid tartrate of nicotine, from which to regenerate nicotine in a pure state.

Hydrochloride of nicotine is more easily volatilised than the pure base. Nicotine is precipitated by alkalies, &c., also by many oxyhydrates, lead, copper, &c. By the action of light, it is soon coloured yellow and brown, and becomes thick, in which state it leaves, on evaporation, a brown resinous substance, only partly soluble in petroleum ether.

A very excellent test for nicotine, as confirmatory of others, is the beautiful, long, needle-like crystals obtained by adding to an ethereal solution of nicotine a solution of iodine in ether. The crystals require a few hours to form.

Chlorine gas colours nicotine blood-red or brown; the product is soluble in alcohol, and separates on evaporation in crystals.

Cyanogen also colours nicotine brown; the product out of alcohol is not crystalline. Platin chloride throws down a reddish crystalline precipitate, soluble on warming; and gallic acid gives a flocculent precipitate. A drop of nicotine poured on dry chromic acid blazes up, and gives out an odour of tobacco camphor; if the ignition does not occur in the cold, it is produced by a gentle heat. It is scarcely possible to confound nicotine with ammonia, by reason of its odour; and, moreover, ammonia may always be excluded by converting the base into the oxalate, and dissolving in absolute alcohol.

On the other hand, a confusion between coniine and nicotine is apt to occur when small quantities only are dealt with. It may, however, be guarded against by the following tests:—

(1.) If coniine be converted into oxalate, the oxalate dissolved in alcohol, and coniine regenerated by distillation (best in vacuo) with caustic lye, and then hydrochloric acid added, a crystalline hydrochlorate of coniine is formed, which doubly refracts light, and is in needle-shaped or columnar crystals, or dendritic, moss-like forms. The columns afterwards become torn, and little rows of cubical, octahedral, and tetrahedral crystals (often cross or dagger-shaped) grow out of yellow amorphous masses. Crystalline forms of this kind are rare, save in the case of dilute solutions of chloride of ammonium (the presence of the latter is, of course, rendered by the treatment impossible); and nicotine does not give anything similar to this reaction.

(2.) Coniine coagulates albumen; nicotine does not.

(3.) Nicotine yields a characteristic crystalline precipitate with an aqueous solution of mercuric chloride; the similar precipitate of coniine is amorphous.

(4.) Nicotine does not react with CS₂ to form thiosulphate (see p. 266).

§ 331. Effects on Animals.—Nicotine is rapidly fatal to all animal life—from the lowest to the highest forms. That tobacco-smoke is inimical to insect-life is known to everybody; very minute quantities in water kill infusoria. Fish of 30 grms. weight die in a few minutes from a milligram of nicotine; the symptoms observed are rapid movements, then shivering and speedy paralysis, with decreased motion of the gills, and death. With frogs, if doses not too large are employed, there is first great restlessness, then strong tetanic convulsions, and a very peculiar position of the limbs; the respiration after fatal doses soon ceases, but the heart beats even after death. Birds also show tetanic convulsions followed by paralysis and speedy death. The symptoms witnessed in mammals poisoned by nicotine are not essentially dissimilar. With large doses the effect is similar to that of prussic acid—viz., a cry, one or two shuddering convulsions, and death. If the dose is not too large, there is trembling of the limbs, excretion of fæces and urine, a peculiar condition of stupor, a staggering gait, and then the animal falls on its side. The respiration, at first quickened, is afterwards slowed, and becomes deeper than natural; the pulse, also, with moderate doses, is first slowed, then rises in frequency, and finally, again falls. Tetanic convulsions soon develop, during the tetanus the pupils have been noticed to be contracted, but afterwards dilated, the tongue and mouth are livid, and the vessels of the ear dilated. Very characteristic of nicotine poisoning as witnessed in the cat, the rabbit, and the dog, is its peculiarly violent action, for after the administration of from one to two drops, the whole course from the commencement of symptoms to the death may take place in five minutes. F. Vas has drawn the smoke of tobacco from an immense pipe, and condensed the products; he finds the well-washed tarry products without physiological action, but the soluble liquid affected the health of rabbits,—they lost weight, the number of the blood corpuscles was decreased, and the hæmoglobin of the blood diminished.[352]

The larger animals, such as the horse, are affected similarly to the smaller domestic animals. A veterinary surgeon, Mr. John Howard, of Woolwich,[353] has recorded a case in which a horse suffered from the most violent symptoms of nicotine-poisoning, after an application to his skin of a strong decoction of tobacco. The symptoms were trembling, particularly at the posterior part of the shoulders, as well as at the flanks, and both fore and hind extremities; the superficial muscles were generally relaxed and felt flabby; and the pupils were widely dilated. There was also violent dyspnœa, the respirations being quick and short, pulse 32 per minute, and extremely feeble, fluttering, and indistinct. When made to walk, the animal appeared to have partly lost the use of his hind limbs, the posterior quarter rolling from side to side in an unsteady manner, the legs crossing each other, knuckling over, and appearing to be seriously threatened with paralysis. The anus was very prominent, the bowels extremely irritable, and tenesmus was present. He passed much flatus, and at intervals of three or four minutes, small quantities of fæces in balls, partly in the liquid state, and coated with slimy mucus. There was a staring, giddy, intoxicated appearance about the head and eyes, the visible mucous membrane being of a dark-red colour. A great tendency to collapse was evident, but by treatment with cold douches and exposure to the open air, the horse recovered.

In a case occurring in 1863, in which six horses ate oats which had been kept in a granary with tobacco, the symptoms were mainly those of narcosis, and the animals died.[354]

§ 332. Effects on Man.—Poisoning by the pure alkaloid nicotine is so rare that, up to the present, only three cases are on record. The first of these is ever memorable in the history of toxicology, being the first instance in which a pure alkaloid had been criminally used. The detection of the poison exercised the attention of the celebrated chemist Stas. I allude, of course, to the poisoning of M. Fougnies by Count Bocarmé and his wife. For the unabridged narrative of this interesting case the reader may consult Tardieu’s Étude Médico-Légale sur L’Empoisonnement.

Bocarmé actually studied chemistry in order to prepare the alkaloid himself, and, after having succeeded in enticing his victim to the chateau of Bitremont, administered the poison forcibly. It acted immediately, and death took place in five minutes. Bocarmé now attempted to hide all traces of the nicotine by pouring strong acetic acid into the mouth and over the body of the deceased. The wickedness and cruelty of the crime were only equalled by the clumsy and unskilful manner of its perpetration. The quantity of nicotine actually used in this case must have been enormous, for Stas separated no less than ·4 grm. from the stomach of the victim.

The second known case of nicotine-poisoning was that of a man who took it for the purpose of suicide. The case is related by Taylor. It occurred in June 1863. The gentleman drank an unknown quantity from a bottle; he stared wildly, fell to the floor, heaving a deep sigh, and died quietly without convulsion. The third case happened at Cherbourg,[355] where an officer committed suicide by taking nicotine, but how much had been swallowed, and what were the symptoms, are equally unknown, for no one saw him during life.

Poisoning by nicotine, pure and simple, then is rare. Tobacco-poisoning is very common, and has probably been experienced in a mild degree by every smoker in first acquiring the habit. Nearly all the fatal cases are to be ascribed to accident; but criminal cases are not unknown. Christison relates an instance in which tobacco in the form of snuff was put into whisky for the purpose of robbery. In 1854, a man was accused of attempting to poison his wife by putting snuff into her ale, but acquitted. In another case, the father of a child, ten weeks old, killed the infant by putting tobacco into its mouth. He defended himself by saying that it was applied to make the child sleep.

In October 1855,[356] a drunken sailor swallowed (perhaps for the purpose of suicide) his quid of tobacco, containing from about half an ounce to an ounce. He had it some time in his mouth, and in half an hour suffered from frightful tetanic convulsions. There was also diarrhœa; the pupils were dilated widely; the heart’s action became irregular; and towards the end the pupils again contracted. He died in a sort of syncope, seven hours after swallowing the tobacco.

§ 333. In 1829 a curious instance of poisoning occurred in the case of two girls, eighteen years of age, who suffered from severe symptoms of tobacco-poisoning after drinking some coffee. They recovered; and it was found that tobacco had been mixed with the coffee-berries, and both ground up together.[357]

Accidents have occurred from children playing with old pipes. In 1877[358] a child, aged three, used for an hour an old tobacco-pipe, and blew soap bubbles with it. Symptoms of poisoning soon showed themselves, and the child died in three days.

Tobacco-juice, as expressed or distilled by the heat developed in the usual method of smoking, is very poisonous. Sonnenschein relates the case of a drunken student, who was given a dram to drink, into which his fellows had poured the juice from their pipes. The result was fatal. Death from smoking is not unknown.[359] Helwig saw death follow in the case of two brothers, who smoked seventeen and eighteen German pipefuls of tobacco. Marshall Hall[360] records the case of a young man, nineteen years of age, who, after learning to smoke for two days, attempted two consecutive pipes. He suffered from very serious symptoms, and did not completely recover for several days. Gordon has also recorded severe poisoning from the consecutive smoking of nine cigars. The external application of the leaf may, as already shown in the case of the horse, produce all the effects of the internal administration of nicotine. The old instance, related by Hildebrand, of the illness of a whole squadron of hussars who attempted to smuggle tobacco by concealing the leaf next to their skin, is well known, and is supported by several recent and similar cases. The common practice of the peasantry, in many parts of England, of applying tobacco to stop the bleeding of wounds, and also as a sort of poultice to local swellings, has certainly its dangers. The symptoms—whether nicotine has been taken by absorption through the broken or unbroken skin, by the bowel, by absorption through smoking, or by the expressed juice, or the consumption of the leaf itself—show no very great difference, save in the question of time. Pure nicotine acts with as great a rapidity as prussic acid; while if, so to speak, it is entangled in tobacco, it takes more time to be separated and absorbed; besides which, nicotine, taken in the concentrated condition, is a strong enough base to have slight caustic effects, and thus leaves some local evidences of its presence. In order to investigate the effects of pure nicotine, Dworzak and Heinrich made auto-experiments, beginning with 1 mgrm. This small dose produced unpleasant sensations in the mouth and throat, salivation, and a peculiar feeling spreading from the region of the stomach to the fingers and toes. With 2 mgrms. there was headache, giddiness, numbness, disturbances of vision, torpor, dulness of hearing, and quickened respirations. With 3 to 4 mgrms., in about forty minutes there was a great feeling of faintness, intense depression, weakness, with pallid face and cold extremities, sickness, and purging. One experimenter had shivering of the extremities and cramps of the muscles of the back, with difficult breathing. The second suffered from muscular weakness, fainting, fits of shivering, and creeping sensations about the arms. In two or three hours the severer effects passed away, but recovery was not complete for two or three days. It is therefore evident, from these experiments and from other cases, that excessive muscular prostration, difficult breathing, tetanic cramps, diarrhœa, and vomiting, with irregular pulse, represent both tobacco and nicotine poisoning. The rapidly-fatal result of pure nicotine has been already mentioned; but with tobacco-poisoning the case may terminate lethally in eighteen minutes. This rapid termination is unusual, with children it is commonly about an hour and a half, although in the case previously mentioned, death did not take place for two days.

§ 334. Physiological Action.—Nicotine is absorbed into the blood and excreted unchanged, in part by the kidneys and in part by the saliva (Dragendorff). According to the researches of Rosenthal and Krocker,[361] nicotine acts energetically on the brain, at first exciting it, and then lessening its activity; the spinal marrow is similarly affected. The convulsions appear to have a cerebral origin; paralysis of the peripheral nerves follows later than that of the nerve centres, whilst muscular irritability is unaffected. The convulsions are not influenced by artificial respiration, and are therefore to be considered as due to the direct influence of the alkaloid on the nervous system. Nicotine has a striking influence on the respiration, first quickening, then slowing, and lastly arresting the respiratory movements: section of the vagus is without influence on this action. The cause of death is evidently due to the rapid benumbing and paralysis of the respiratory centre. Death never follows from heart-paralysis, although nicotine powerfully influences the heart’s action, small doses exciting the terminations of the vagus in the heart, and causing a slowing of the beats. Large doses paralyse both the controlling and exciting nerve-centres of the heart; the heart then beats fast, irregularly, and weakly. The blood-vessels are first narrowed, then dilated, and, as a consequence, the blood-pressure first rises, then falls. Nicotine has a special action on the intestines. As O. Nasse[362] has shown, there is a strong contraction of the whole tract, especially of the small intestine, the lumen of which may be, through a continuous tetanus, rendered very small. This is ascribed to the peripheral excitation of the intestinal nerves and the ganglia. The uterus is also excited to strong contraction by nicotine; the secretions of the bile and saliva are increased.

§ 335. Fatal Dose.—The fatal dose for dogs is from ¹⁄₂ to 2 drops; for rabbits, a quarter of a drop; for an adult not accustomed to tobacco the lethal dose is probably 6 mgrms.

§ 336. Post-mortem Appearances.—There seem to be no appearances so distinctive as to be justly ascribed to nicotine or tobacco-poisoning and no other.

A more or less fluid condition of the blood, and, generally, the signs of death by the lungs, are those most frequently found. In tobacco-poisoning, when the leaves themselves have been swallowed, there may be some inflammatory redness of the stomach and intestine.

§ 337. Separation of Nicotine from Organic Matters, &c.—The process for the isolation of nicotine is precisely that used for coniine (see p. 269). It appears that it is unaltered by putrefaction, and may be separated and recognised by appropriate means a long time after death. Orfila detected it in an animal two or three months after death; Melsens discovered the alkaloid unmistakably in the tongues of two dogs, which had been buried in a vessel filled with earth for seven years; and it has been found, by several experiments, in animals buried for shorter periods. Nicotine should always be looked for in the tongue and mucous membrane of the mouth, as well as in the usual viscera. The case may be much complicated if the person supposed to be poisoned should have been a smoker; for the defence would naturally be that there had been either excessive smoking or chewing, or even swallowing accidentally a quid of tobacco.[363] A ptomaine has been discovered similar to nicotine. Wolckenhaar separated also an alkaloid not unlike nicotine from the corpse of a woman addicted to intemperate habits; but this base was not poisonous, nor did it give any crystals when an ethereal solution was added to an ether solution of iodine. It will be well always to support the chemical evidence by tests on animal life, since the intensely poisonous action of nicotine seems not to be shared by the nicotine-like ptomaines.

3. PITURIE.[364]

§ 338. Piturie (C₆H₈N) is a liquid, nicotine-like alkaloid, obtained from the Duboisia hopwoodii, a small shrub or tree belonging to the natural order Solanaceæ, indigenous in Australia. The natives mix piturie leaves with ashes from some other plant, and chew them. Piturie is obtained by extracting the plant with boiling water acidified with sulphuric acid, concentrating the liquid by evaporation, and then alkalising and distilling with caustic soda, and receiving the distillate in hydrochloric acid. The solution of the hydrochlorate is afterwards alkalised and shaken up with ether, which readily dissolves out the piturie. The ether solution of piturie is evaporated to dryness in a current of hydrogen, and the crude piturie purified by distillation in hydrogen, or by changing it into its salts, and again recovering, &c. It is clear and colourless when pure and fresh, but becomes yellow or brown when exposed to air and light. It boils and distils at 243° to 244°. It is soluble in all proportions in alcohol, water, and ether; its taste is acrid and pungent; it is volatile at ordinary temperatures, causing white fumes with hydrochloric acid; it is very irritating to the mucous membranes, having a smell like nicotine at first, and then, when it becomes browner, like pyridine. It forms salts with acids, but the acetate, sulphate, and hydrochlorate are varnish-like films having no trace of crystallisation; the oxalate is a crystalline salt. Piturie gives precipitates with mercuric chloride, cupric sulphate, gold chloride, mercur-potassic iodide, tannin, and an alcoholic solution of iodine. If an ethereal solution of iodine is added to an ethereal solution of piturie, a precipitate of yellowish-red needles, readily soluble in alcohol, is deposited. The iodine compound melts at 110°, while the iodine compound of nicotine melts at 100°. Piturie is distinguished from coniine by its aqueous solution not becoming turbid either on heating or on the addition of chlorine water; it differs from picoline in specific gravity, picoline being ·9613 specific gravity at 0°, and piturie sinking in water; it differs from aniline by not being coloured by chlorinated lime. From nicotine it has several distinguishing marks, one of the best being that it does not change colour on warming with hydrochloric acid and the addition to the mixture afterwards of a little nitric acid. The physiological action seems to be but little different from that of nicotine. It is, of course, poisonous, but as yet has no forensic importance.

4. SPARTEINE.

§ 339. In 1851 Stenhouse[365] separated a poisonous volatile alkaloid from Spartium scoparium, the common broom, to which he gave the name of sparteine. At the same time a crystalline non-poisonous substance, scoparin, was discovered.

Sparteine is separated from the plant by extraction with sulphuric acid holding water, and then alkalising the acid solution and distilling: it has the formula (C₁₅H₂₆N₂), and belongs to the class of tertiary diamines. It is a clear, thick, oily substance, scarcely soluble in water, to which it imparts a strong, alkaline reaction; it is soluble in alcohol, in ether, and chloroform; insoluble in benzene and in petroleum; it boils at 288°. Sparteine neutralises acids fully, but the oxalate is the only one which can be readily obtained in crystals. It forms crystalline salts with platinic chloride, with gold chloride, with mercuric chloride, and with zinc chloride. The picrate is an especially beautiful salt, crystallising in long needles, which, when dried and heated, explode. On sealing sparteine up in a tube with ethyl iodide and alcohol, and heating to 100° for an hour, ethyl sparteine iodide separates in long, needle-like crystals, which are somewhat insoluble in cold alcohol.

Effect on Animals.—A single drop kills a rabbit; the symptoms are similar to those produced by nicotine, but the pupils are dilated.[366]

5. ANILINE.

§ 340. Properties.—Aniline or amido-benzol (C₆H₅NH₂) is made by the reduction of nitro-benzol. It is an oily fluid, colourless when quite pure, but gradually assuming a yellow tinge on exposure to the air. It has a peculiar and distinctive smell. It boils at 182·5°, and can be congealed by a cold of 8°. It is slightly soluble in water, 100 parts of water at 16° retaining about 3 of aniline, and easily soluble in alcohol, ether, and chloroform. It does not blue red-litmus paper, but nevertheless acts as a weak alkali, for it precipitates iron from its salts. It forms a large number of crystalline salts. The hydrochloride crystallises in white plates, and has a melting-point of 192°. The platinum compound has the formula of (C₆H₅NH₂HCl)₂PtCl₄, and crystallises in yellow needles.