PART VI.--ALKALOIDS AND POISONOUS VEGETA_Poisons, Their Effects and Detection A Manual for the Use of Analytical Chemists and Experts

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.

[324] In the case of morphine tartrate, this test will not answer. See

the article on Morphine.

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, „ „

Narcotine, Brownish-yellow, „

Quinine, Whitish-yellow, „

Cinchonine, „ „

Codeine, Brownish-yellow, voluminous.

Strychnine, White-yellow, „

Brucine, Yelk-yellow, flocculent.

Veratrine, Bright-yellow, „

Jervine, „ „

Aconitine, „ „

Emetine, „ „

Theine, Bright-yellow, voluminous.

Theobromine, „ „

Solanine, Citron-yellow, pulverulent.

Atropine, Bright-yellow, flocculent.

Hyoscyamine, „ „

Colchicine, Orange-yellow, „

Delphinine, Grey-yellow, voluminous.

Berberine, Dirty-yellow, flocculent.

Coniine, Bright-yellow, voluminous.

Nicotine, „ „

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.

[325] _Annal d. Chem. u. Pharm._, 84, 379.

[326] _Ib._, 100, 44. _Anleitung zur Ausmittel. d. Gifte._

[327] Rodgers and Girwood, _Pharm. Journ. and Trans._, xvi. 497;

Prollin’s _Chem. Centralb._, 1857, 231; Thomas, _Zeitschr. für analyt.

Chem._, i. 517, &c.

[328] Erdmann and v. Ushlar, _Ann. Chem. Pharm._, cxx. pp. 121-360.

COLOUR REACTIONS[329] OF CERTAIN ALKALOIDS.

[329] Caustic potash also gives characteristic colours with certain

alkaloids. Out of seventy-two alkaloids (using 0·5 mgrm.), the following

alone gave characteristic colours when fused with KHO:--Quinine,

grass-green, and peculiar odour; quinidine, becoming yellower and

finally brown; cinchonine, at first brownish-red to violet, with green

edges, later, bluish-green; cinchonidine, blue passing into grey;

cocaine, greenish-yellow, turning to blue, and then dirty red on strong

heating.--W. Lenz, _Zeit. f. anal. Chem._, 25, 29-32.

+-----------+-----------------+------------------+-------------------+

+-----------+-----------------+------------------+-------------------+

| | | | |

|Strychnine.| ... | ... |Violet-blue, then |

| | | |red. |

| | | | |

| | | | |

|Curarine. |Fine red. | ... | ... |

| | | | |

| | | | |

|Atropine. | ... | ... |Red, then yellow- |

| | | | |

|Aconitine. | ... | ... | ... |

| | | | |

| | | | |

| | | | |

| | | | |

| | | | |

| | | | |

| | | | |

| | | | |

| | |red. |colour. |

| | | | |

|Coniine. | ... |Yellow. | ... |

| | | | |

| | | | |

| | | | |

+-----------+-----------------+------------------+-------------------+

§ 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.

[330] F. Selmi, _Gazett. Chim. Ital._, vj. 153-166, and _Journ. Chem.

Soc._, i., 1877, 93.

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]

[331] Dragendorff’s _Gerichtlich-chemische Ermittelung von Giften_, St.

Petersburg, 1876, p. 141.

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]

[332] When blood is to be examined, it is better to dry it, and then

powder and extract with water acidified with dilute sulphuric acid.

However, if the so-called volatile alkaloids are suspected, this

modification is to be omitted.

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_, A. It is fixed.

and with difficulty

volatilised.

α. The crystals are α. Concentrated sul-

dissolved by concen- phuric acid dissolves

trated sulphuric it immediately--

acid, with the pro- violet, and later

duction of a clear greenish-blue.

yellow colour, pass- _Constituents of the

ing into brown and black hellebore._

greenish-brown.

_Piperin._

β. The solution in sulphuric acid β. It dissolves with a yellow

remains yellow; potassic cyanide colour, changing into fallow-

and caustic potash colour it, on brown.

warming, blood-red. _Constituents of aconite plant

_Picric acid._ and products of the decomposition

of Aconitine._

B. IT IS COLOURLESS, LIQUEFIES B. IT IS WHITE, SHARP-TASTING,

EASILY, AND SMELLS STRONGLY. 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 A. COLOURLESS OR PALE YELLOW

CRYSTALS. RESIDUE.

α. Sulphuric acid dissolves the α. Sulphuric acid dissolves it at

hair-like crystals without change first yellow; the solution be-

of colour; evaporation with chlo- coming later red. Fröhde’s re-

rine water, and subsequent treat- agent does not colour it violet.

ment with ammonia, gives a _Elaterin._

murexide reaction. _Theine._

β. Sulphuric acid leaves the β. Sulphuric acid dissolves red;

rhombic crystals uncoloured. The Fröhde’s reagent violet-red;[333]

substance, taken up by oil, and tannic acid does not precipitate.

applied to the skin, produces a _Populin._

blister. _Cantharidin._

γ. Sulphuric acid leaves the γ. Sulphuric acid dissolves it

scaly crystals at first un- with a red colour; Fröhde’s

coloured, then slowly develops a reagent[334] a beautiful cherry-

reddening. It does not blister. red; tannic acid precipitates a

Warm alcoholic potash-lye colours yellowish-white. _Colocynthin._

it a transitory red. _Santonin._

δ. Sulphuric acid colours the δ. Sulphuric acid colours it

crystals almost black, whilst it gradually a beautiful red, whilst

takes itself a beautiful red tannin does not precipitate.

colour. _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 C. A GREENISH BITTER RESIDUE,

CRYSTALS. which dissolves brown in concen-

trated 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 dis-

solves it olive-green. The alcoholic solution gives with potassic

iodide a colourless and green crystalline precipitate. _Berberin._

[333] Fröhde’s reagent is described at page 239.

[334] Fröhde’s reagent is described at page 239.

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]

[335] Chloroform removes small portions of acetate of aconitine from

acid solution, Dunstan and Umney, _J. C. S._, 1892, p. 338.

1. THE RESIDUE IS MORE OR LESS 2. THE RESIDUE IS AMORPHOUS.

MARKEDLY CRYSTALLINE.

A. _It gives in the sulphuric A. _In acetic acid solution it

acid solution evidence of an renders the action of the frog’s

alkaloid by its action towards heart slower, or produces local

iodine and iodide of potassium._ anæsthesia._

_aa_. It does not produce local

anæsthesia.

α. Sulphuric acid dissolves it α. Sulphuric acid dissolves it

without the production of colour, red-brown, bromine produces a

and chlorine and ammonia give no beautiful purple colour, water

murexide reaction. _Cinchonine._ changes it into green, hydro-

chloric acid dissolves it

greenish-brown. _Digitalin._

β. Sulphuric acid dissolves it β. Sulphuric acid dissolves it

without colour, chlorine and yellow, then brown-red; on ad-

ammonia give, as with theine, a dition of water this solution be-

murexide reaction. _Theobromine._ comes violet. Hydrochloric acid,

on warming, dissolves it red.

_Convallamarin._

_bb_. It produces local anæsthe-

sia.

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 γ. Sulphuric acid dissolves

in the cold; on warming, the brown, and the solution becomes

solution becomes a blue violet. red by the addition of a little

_Papaverine._ water. The action is very weak.

_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 solu-

tion 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._

[336] Described at p. 239.

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 2. IT IS FIXED AND 3. IT IS FIXED AND

CRYSTALLINE. AMORPHOUS. ODOROUS.

A. _The crystals are A. _On adding to the

volatilised with watch-glass a little

difficulty._ hydrochloric acid,

crystals are left

behind._

_aa._ Sulphuric acid _aa._ Its solution is

dissolves it without not precipitated by

colour. platin chloride.

α. Potassic chromate α. The purest sulphuric α. The crystals of the

colours this solution acid dissolves it hydrochloric compound

a transitory blue, almost without colour; act on polarised

then red. sulphuric acid con- light; and are mostly

_Strychnine._ taining nitric acid, needle-shaped and

red quickly becoming columnar. _Coniine

orange. and Methyl-Coniine._

_Brucine._

β. Potassic chromate β. Sulphuric acid dis- β. The crystals are

does not colour it solves it yellow, cubical or tetra-

blue; with chlorine becoming deep red. hedral. _Alkaloid

water and ammonia it _Veratrine._ from Capsicum._

gives a green colour.

_Quinine._

γ. Sulphuric acid dis-

solves it brown-green;

Fröhde’s reagent red,

changing into green.

_Emetine._

_bb_. The solution of

the hydrochlorate of

the alkaloid is pre-

cipitated by platin

chloride.

_Sarracinin._

γ. Sulphuric acid B. The residue of the

dissolves it yellow, hydrochlorate of the

and the solution be- alkaloid is amor-

comes gradually a phous, or, by further

beautiful deep red. additions of HCl,

_Sabadilline._ becomes crystalline.

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 solu-

tion by platin

chloride.

α. Its petroleum

ether solution pro-

duces no turbidity

with a solution of

picric acid in petro-

leum 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 chlo-

ride of lime, sul-

phuric acid, or chro-

mate 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 CRYS- 2. IT IS FOR THE MOST PART AMOR-

TALLINE. PHOUS.

_a._ Sulphuric acid dissolves it _a._ Pure sulphuric acid dis-

without colour, the solution solves it either whitish-red or

being coloured neither on stand- yellowish.

ing nor on the addition of nitric

acid.

_aa._ It dilates the pupil of a

cat.

α. Platin chloride does not pre- α. The solution becomes by nitric

cipitate the aqueous solution. acid immediately red, then quickly

The sulphuric acid solution gives, orange. _Brucine._

on warming, a peculiar smell.

_Atropine._

β. Platin chloride applied to the β. The solution becomes by little

solution precipitates. and little brownish-red. The sub-

_Hyoscyamine._ stance is coloured red by chlo-

ride of lime solution, and it

contracts the pupil.

_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 res-

pirations in a frog. _Ethyl and

Methyl Strychnine._

β. Sulphuric acid and bichromate

of potash do not colour it blue.

αα. The sulphuric acid watery so-

lution is fluorescent, and be-

comes 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 fluores-

cent. _Cinchonine._

_b._ Sulphuric acid dissolves it _b._ Pure sulphuric acid dis-

at first colourless; the solution solves it yellow, and the solu-

takes on standing a rose or tion becomes later beautiful red

violet-blue; on addition of (with delphinine, more quickly a

nitric acid, a blood-red or brown darker cherry-red.)

coloration.

α. A solution in diluted sulphuric α. The hydrochloric acid solution

acid becomes, on heating, deep gradually becomes red on heating.

blood-red, and, when cooled,

violet, with nitric acid. The

aqueous solution is precipitated

by ammonia. _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 sul- β. The hydrochloric acid solution

phuric acid becomes, on heating, does not, on heating, become red.

a beautiful blue. Excess of ammo- _Delphinine._

nia does not precipitate in a

diluted watery solution.

_Codeine._

_c._ Sulphuric acid dissolves it _c._ Pure sulphuric acid dis-

with the production of a yellow solves it yellow, and the solu-

colour. tion becomes later red-brown, and

gradually violet-red.

α. The solution remains yellow α. The substance even in small

on standing. _Acolyctin._ doses paralyses frogs, and

dilates the pupil of a cat’s eye.

Ether dissolves it with diffi-

culty. _Nepalin._

β. It becomes beautifully red. β. It is easily soluble in ether,

_Sabadilline._ its effects are not so marked,

and it does not dilate the pupil.

_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 _d._ Sulphuric acid dissolves it

with an immediate deep red-brown with a dark green colour, and the

colour. _Thebaine._ solution becomes, even after a

few seconds, a beautiful blood-

red. _Alkaloidal substances out

of the Aconitum lycoctonum._

_e._ Sulphuric acid dissolves it _e._ Sulphuric acid dissolves it

immediately blue. _Substances brown-green, and Fröhde’s reagent

accompanying the Papaverins._ red, becoming beautifully green.

_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:--

[337] The method of preparing this reagent is as follows:--Ordinary

commercial sodium tungstate is treated with half its weight of

phosphoric acid, specific gravity, 1·13, and then allowed to stand for

some days. Phosphotungstic acid separates in crystals.

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.

[338] “Dosage des alcaloides à l’aide de l’iodure double de mercure et

de potassium,” par MM. A. Grandval et Henri Lajoux, _Journ. de

Pharmacie_, 5 sér. t. xxviii. 152-156.

§ 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 ½ 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 ⅛ to ⅔ 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°.

[339] _Das Mikroskop in der Toxicologie_.

[340] _Pharm. Journ. Trans_. (2), viij. 719; ix. 10, 58. _Forensic

Medicine_, London, 1875.

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.

[Illustration: 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 ¼-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.

[341] The saturated watery solution of coniine at 15°, becomes cloudy if

gently warmed, and clears again on cooling.

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.

[342] Schwarzenbach, _Vierteljahrsschr. f. prakt. Pharm._, viij. 170.

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.

[343] _Reactions_, by F. A. Flückiger, Detroit, 1893.

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]

[344] This is easily effected by uniting a flask containing the

alkaloidal fluid, air-tight, with a Liebig’s condenser and a receiver,

the latter being connected with Bunsen’s water-pump, or one of the

numerous exhausting apparatuses now in use in every laboratory.

[345] Dragendorff, _Die Chemische Werthbestimmung einiger starkwirkender

Droguen_, St. Petersb., 1874.

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.

[346] _Prakt. Toxicologie_, p. 273.

§ 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.

[347] _Edin. Med. and Surg. Journ._, July 1845, p. 169.

§ 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.

[348] Otto, _Anleitung z. Ausmittlung d. Gifte_, 1875.

[349] Sievert, _Zeitschrift für Naturwissenschaften_.

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 } 0·734

of lime, and malate of ammonia,) }

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:--

[350] _Pharm. Journ._, Jan. 20, 1894.

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.

[351] J. Skalweit, _Ber. der. deutsch. Chem. Gesell._, 14, 1809.

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]

[352] _Archiv. f. Exper. Pathol. u. Pharm._, Bd. 33.

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.

[353] _Veter. Journal_, vol. iii.

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]

[354] _Annales Vétérinaires_, Bruxelles, 1868.

§ 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_.

Poisons, Their Effects and Detection A Manual for the Use of Analytical Chemists and Experts · 第 9 / 23 章

PART VI.--ALKALOIDS AND POISONOUS VEGETABLE PRINCIPLES SEPARATED FOR THE