Chapter XXXII: Part VI: Alkaloids and Poisonous Vegetable Principles Separated for the (6)

Strychnine is separated by the kidneys rapidly. In a suicidal case recorded by Schauenstein,[442] death took place in an hour and a half after taking strychnine, yet from 200 c.c. of the urine, Schauenstein was able to separate nitrate of strychnine in well-formed crystals. Dr. Kratter[443] has made some special researches on the times within which strychnine is excreted by the kidneys. In two patients, who were being treated by subcutaneous injection, half an hour after the injection of 7·5 mgrms. of strychnine nitrate the alkaloid was recognised in the urine. The strychnine treatment was continued for eight to ten days, and then stopped; two days after the cessation, strychnine was found in the urine, but none on the third day, and the inference drawn is that the elimination was complete within forty-eight hours.

[442] Maschka’s _Handbuch_, Band 2, p. 620.

[443] _Ibid._

Strychnine has been detected in the blood of dogs and cats in researches specially undertaken for that purpose, but sometimes a negative result has been obtained, without apparent cause. Dragendorff[444] gave dogs the largest possible dose of strychnine daily. On the first few days no strychnine was found in the urine, but later it was detected, especially if food was withheld. M’Adam was the first who detected the absorbed poison, recognising it in the muscles and urine of a poisoned horse, and also in the urine of a hound. Dragendorff has found it in traces in the kidneys, spleen, and pancreas; Gay, in different parts of the central nervous system, and in the saliva. So far as the evidence goes, the liver is the best organ to examine for strychnine; but all parts supplied with blood, and most secretions, may contain small quantities of the alkaloid. At one time it was believed that strychnine might be destroyed by putrefaction, but the question of the decomposition of the poison in putrid bodies may be said to be settled. So far as all evidence goes, strychnine is an extremely stable substance, and no amount of putrescence will destroy it. M’Adam found it in a horse a month after death, and in a duck eight weeks after; Nunneley in 15 animals forty-three days after death, when the bodies were much decomposed; Roger in a body after five weeks’ interment; Richter in putrid tissues exposed for eleven years to decomposition in open vessels; and, lastly, W. A. Noyes[445] in an exhumed body after it had been buried 308 days.

[444] In an animal rapidly killed by a subcutaneous injection of acetate of strychnine, no strychnine was detected either in the blood or liver.--_Dragendorff._

[445] _Journ. Americ. Chem. Soc._, xvi. 2.

It would appear from Ibsen’s[446] experiments that strychnine gets dissolved in the fluids of the dead body--so that whether strychnine remains or not, greatly depends as to whether the fluids are retained or are allowed to soak away; it is, therefore, most important in exhumations to save as much of the fluid as possible.

[446] _Viertel. f. gericht. Med._, Bd. viii.

§ 398. =Identification of the Alkaloid.=--A residue containing strychnine, or strychnine mixed with brucine, is identified--

(1.) By its alkaline reaction and its bitter taste. No substance can possibly be strychnine unless it tastes remarkably bitter.

(2.) By the extremely insoluble chromate of strychnine, already described.[447] A fluid containing 1 : 1000 of strychnine gives with chromate of potash (if allowed to stand over-night) a marked precipitate, dissimilar to all others, except those of lead and baryta chromates, neither of which can possibly occur if any of the processes described are followed.

[447] 1 grm. of strychnine gave 1·280 grms. of the chromate, = 78·1 per cent. of strychnine; 3 gave 3·811 of the chromate, = 78·77 per cent. of strychnine.--_Mohr._

(3.) If the chromate just described is treated on a porcelain plate with a drop of pure strong sulphuric acid, a deep rich blue colour, passing through purple into red, rapidly makes its appearance. This colour possesses an absorption spectrum (figured at p. 55). Dr. Guy, neglecting intermediate colours, aptly compares the succession--(1) to the rich blue of the Orleans plum; (2) to the darker purple of the mulberry; and (3) to the bright clear red of the sweet orange. These characters--viz., alkalinity, bitterness, and the property of precipitation by potassic chromate in a definite crystalline form, the crystals giving the colours detailed--belong to no other substance known save strychnine, and for all purposes sufficiently identify the alkaloid. The same colour is obtained by mixing a drop of sulphuric acid with strychnine and a crystal, or speck, of any one of the following substances:--Ferridcyanide of potash, permanganate of potash, peroxide of lead, peroxide of manganese, and cerous hydroxide.

Potassic permanganate and sulphuric acid is the most delicate, and will detect 0·001 mgrm. of strychnine; cerous hydroxide is, on the other hand, most convenient, for cerous hydroxide is white; all the others have colours of their own. Cerous hydroxide is prepared strychnine; 3 gave 3·811 of the chromate, = 78·77 per cent. of strychnine.--_Mohr._ by dissolving cerium oxalate in dilute sulphuric acid and precipitating with ammonia, filtering and well washing the precipitate; and the latter may be used while moist, and responds well to 1/100 mgrm. of strychnine.

The influence of mixtures on the colour reactions of strychnine have been studied by Flückiger, who states:--

“No strychnine reaction appears with sulphuric acid containing chromic acid (made by dissolving 0·02 grm. of pot. bichromate in 10 c.c. of water, and then adding 30 grms. strong sulphuric acid) when brucine and strychnine mixed in equal parts are submitted to the test; it succeeds, however, in this proportion with sulphuric acid containing potassium permanganate (·02 grm. pot. permanganate in 10 c.c. of water, and 30 grms. of strong sulphuric acid).

“If the brucine is only one-tenth of the mixture, the blue-violet colour is obtained. A large excess of atropine does not prevent or obscure the strychnine reaction. A solution of 1 milligrm. atropine sulphate evaporated to dryness, together with 5 c.c. of a solution of strychnine (1 : 100,000) has no influence on the reaction, neither in the proportion of 1 mgrm. to 1 c.c. of the same solution; neither has cinchonine nor quinine any effect.

“Morphine obscures the reaction in the following proportions:--

“A solution of 0·01 mgrm. strychnine evaporated with a solution of 1 mgrm. of morphine sulphate on a water-bath, yields a blurred strychnine reaction when the residue is dissolved in sulphuric acid, and a crystal of potassic permanganate added. But still there is evidence whereby to _suspect_ the presence of strychnine.

“A solution of 2 mgrms. of morphine sulphate treated in like manner with 0·01 mgrm. of strychnine yields like results.

“A solution of 3 mgrms. of morphine sulphate evaporated to dryness, with a solution of 0·01 mgrm. strychnine yielded results with the potassic permanganate test the same as if no strychnine was present.

“A solution of 1 mgrm. of morphine sulphate, treated as above, with a solution of 0·1 mgrm. strychnine, offered positive proof of the presence of the latter.”[448]

[448] Flückiger’s _Reactions_, translated by Nagelvoort, Detroit, 1893.

Dragendorff was able to render evident ·025 mgrm. mixed with twenty times its weight of quin. sulphate; the same observer likewise recognised ·04 mgrm. of strychnine in thirty-three times its weight of caffeine. Veratrine is likewise not injurious.

=The physiological test= consists in administering the substance to some small animal (preferably to a frog), and inducing the ordinary tetanic symptoms. It may be at once observed that if definite chemical evidence of strychnine has been obtained, the physiological test is quite unnecessary; and, on the other hand, should the application of a liquid or substance to a frog induce tetanus, while chemical evidence of the presence of strychnine was wanting, it would be hazardous to assert that strychnine was present, seeing that caffeine, carbolic acid, picrotoxin, certain of the opium alkaloids, hypaphorine, some of the ptomaines, and many other substances induce similar symptoms. The best method (if the test is used at all) is to take two frogs,[449] and insert under the skin of the one the needle of a subcutaneous syringe, previously charged with a solution of the substance, injecting a moderate quantity. The other frog is treated similarly with a very dilute solution of strychnine, and the two are then placed under small glass shades, and the symptoms observed and compared. It is not absolutely necessary to inject the solution under the skin, for if applied to the surface the same effects are produced; but, if accustomed to manipulation, the operator will find the subcutaneous application more certain, especially in dealing with minute quantities of the alkaloid.[450]

[449] A very practical disadvantage of the physiological test is the great difficulty of obtaining frogs exactly when wanted.

[450] Methyl strychnine, as well as methyl brucine, has been shown by Brown and Fraser to have an effect exactly the opposite to that of strychnine, paralysing the muscles like curare. In the case, therefore, of the methyl compounds, a physiological test would be very valuable, since these compounds do not respond to the ordinary tests.

§ 399. =Hypaphorine.=--One substance is known which neither
physiological test nor the colour reactions suffice to distinguish
from strychnine, viz., hypaphorine,[451] the active matter of a
papilionaceous tree growing in Java--the _Hypaphorus subumbrans_; a
small quantity of the alkaloid is in the bark, a larger quantity is
in the seed.

[451] Dr. C. Plugge, _Arch. f. exp. Path. u. Ph._, Bd. xxxii. 313.

Hypaphorine forms colourless crystals which brown, without melting,
above 220°, and exhale a vapour smelling like napththylamine. The
free alkaloid is soluble in water, but has no action on litmus. The
salts are less soluble than the free alkaloid, so that acids, such
as nitric or hydrochloric, produce in a short time precipitates on
standing. Solutions of the salts are not precipitated by alkalies;
chloroform, ether, benzene, all fail to extract it from either
alkaline or acid solutions. It gives no precipitate with potassic
chromate, but most general alkaloidal reagents precipitate.

It gives a precipitate with iodine trichloride, and has therefore
probably a pyridine nucleus, it may be an acid anilide.[452] It
gives the same colours as strychnine with sulphuric acid and
potassic permanganate or potassic chromate; it causes in frogs
tetanus, but the dose has to be much larger than that of strychnine.
The duration of life in doses of 15 mgrms. may extend to five days,
and frogs may even recover after 50 mgrms.

[452] Julius Tafel (_Ber._, 1890, 412) has shown that the colour reactions with H₂SO₄ and oxidising agents are the characteristic tests of an acid anilide.

The distinction between strychnine and hypaphorine is therefore
easy; besides it will not occur in a chloroform extract, and it will
not give a precipitate with potassic chromate.

§ 400. =Quantitative Estimation of Strychnine.=--The best process of
estimating the proportion of each alkaloid in a mixture of
strychnine and brucine, is to precipitate them as picrates, and to
destroy the brucine picrate by nitric acid after obtaining the
combined weight of the mixed picrates; then to weigh the undestroyed
strychnine picrate.

To carry out the process, the solution of the mixed alkaloids must
be as neutral as possible. A saturated solution of picric acid is
added drop by drop to complete precipitation. A filter paper is
dried and weighed, and the precipitate collected on to this filter
paper; the precipitate is washed with cold water, dried at 105°, and
weighed. This weight gives the combined weight of both strychnine
and brucine picrates.

The precipitate is now detached from the filter, washed into a small
flask, and heated on the water-bath for some time with nitric acid
diluted to 1·056 gravity (about 11 per cent. HNO₃). This process
destroys the brucine picrate, but leaves the strychnine picrate
untouched. The acid liquid is now neutralised with ammonia or soda,
and a trace of acetic acid added; the precipitate of strychnine
picrate is now collected and weighed. The weight of this subtracted
from the first weight, of course, gives that of the brucine picrate.

One part of strychnine picrate is equal to 0·5932 strychnine; and
one part of brucine picrate is equal to 0·6324 brucine.

From the strychnine picrate the picric acid may be recovered and
weighed by dissolving the picrate in a mineral acid and shaking out
with ether; from the acid liquid thus deprived of picric acid the
alkaloid may be separated by alkalising with ammonia and shaking out
with chloroform.

§ 401. =Brucine= (C₂₃H₂₆N₂O₄ + 4H₂O)[453] occurs associated with strychnine in the plants already mentioned; its best source is the so-called _false angustura_ bark, which contains but little strychnine. Its action is similar to that of strychnine. If crystallised out of dilute alcohol it contains 4 atoms of water, easily expelled either in a vacuum over sulphuric acid or by heat. Crystallised thus, it forms transparent four-sided prisms, or arborescent forms, like boric acid. If thrown down by ammonia from a solution of the acetate, it presents itself in needles or in tufts.

[453] Sonnenschein has asserted that brucine may be changed into strychnine by the action of NO₃. This statement has been investigated by A. J. Cownley, but not confirmed.--_Pharm. Journ._ (3), vi. p. 841.

The recently-crystallised alkaloid has a solubility different from that which has effloresced, the former dissolving in 320 parts of cold, and 150 parts of boiling water; whilst the latter (according to Pelletier and Caventou) requires 500 of boiling, and 850 parts of cold water for solution. Brucine is easily soluble in absolute, as well as in ordinary alcohol; 1 part dissolves in 1·7 of chloroform, in 60·2 of benzene. Petroleum ether, the volatile and fatty oils and glycerine, dissolve the alkaloid slightly, amyl alcohol freely; it is insoluble in _anhydrous_ ether. The behaviour of brucine in the subliming cell is described at p. 260. Anhydrous brucine melts in a tube at 178°. The alcoholic solution of brucine turns the plane of polarisation to the left [α]_r_ = -11·27°. The taste is bitter and acrid. Soubeiran maintains that it can be recognised if 1 part is dissolved in 500,000 parts of water. If nitric trioxide be passed into an alcoholic solution of brucine, first brucine nitrate is formed; but this passes again into solution, from which, after a time, a heavy, granular, blood-red precipitate separates: it consists of dinitro-brucine (C₂₃H₂₄(NO₂)₂N₂O₄). Brucine fully neutralises acids, and forms salts, which are for the most part crystalline. The neutral sulphate (C₂₃H₂₅N₂O₄SH₂O₄ + 3½H₂O) is in long needles, easily soluble in water. The acetate is not crystalline, that of strychnine is so (p. 321).

Brucine is precipitated by ammonia, by the caustic and carbonated alkalies, and by most of the group reagents. Ammonia does not precipitate brucine, if in excess; on the other hand, strychnine comes down if excess of ammonia is added immediately. This has been proposed as a method of separation; if the two alkaloids are present in acid solution, ammonia in excess is added, and the solution is immediately filtered; the quantitative results are, however, not good, the strychnine precipitate being invariably contaminated by brucine.

Chromate and dichromate of potassium give no precipitate with neutral salts of brucine; on the other hand, strychnine chromate is at once formed if present. It might, therefore, be used to separate strychnine from brucine. The author has attempted this method, but the results were not satisfactory.

§ 402. =Physiological Action.=--The difference between the action of strychnine and that of brucine on man or animals is not great. Mays states that strychnine affects more the anterior, brucine the posterior extremities. In strychnine poisoning, convulsions occur early, and invariably take place before death; but death may occur from brucine without any convulsions, and in any case they develop late. Brucine diminishes local sensibility when applied to the skin; strychnine does not.[454] In a physiological sense, brucine may be considered a diluted strychnine. The lethality of brucine, especially as compared with strychnine, has been investigated by F. A. Falck.[455] He experimented on 11 rabbits, injecting subcutaneously brucine nitrate, in doses of varying magnitude, from 100 mgrms. down to 20 mgrms. per kilogram of body-weight. He found that brucine presented three stages of symptoms. In the first, the respiration is quickened; in 3 of the 11 cases a strange injection of the ear was noticed; during this period the pupils may be dilated. In the second stage, there are tetanic convulsions, trismus, opisthotonus, oppressed respiration, and dilated pupils. In the third stage, the animal is moribund. Falck puts the minimum lethal dose for rabbits at 23 mgrms. per kilo. Strychnine kills 3·06 times more quickly than brucine, the intensity of the action of strychnine relative to that of brucine being as 1 : 117·4. Falck has also compared the minimum lethal dose of strychnine and brucine with the tetanising opium alkaloids, as shown in the following table:--

[454] _Journ. Physiol._, viii. 391-403.

[455] _Brucin u. Strychnin; eine toxikologische Parallele_, von Dr. F. A. Falck. _Vierteljahrsschr. f. gerichtl. Med._, Band xxiii. p. 78.

TABLE SHOWING THE LETHAL DOSES OF VARIOUS TETANISING POISONS.

+-----------------------+---------------+------------+
| |Minimum Lethal | |
| |Dose for every |Proportional|
| |Kilogram Weight| Strength. |
| | of Rabbit. | |
+-----------------------+---------------+------------+
| | Mgrms. | |
| | | |
|Strychnine nitrate, | 0·6 | ... |
|Thebaine nitrate, | 14·4 | 24·0 |
|Brucine nitrate, | 23·0 | 38·33 |
|Landanine nitrate, | 29·6 | 49·33 |
|Codeine nitrate, | 51·2 | 85·33 |
|Hydrocotarnine nitrate,| 203·8 | 339·66 |
+-----------------------+---------------+------------+

If these views are correct, it follows that the least fatal dose for an adult man would be 1·64 grm. (about 24·6 grains) of brucine nitrate.

§ 403. Tests.--If to a solution of brucine in strong alcohol a little methyl iodide is added, at the end of a few minutes circular rosettes of crystal groups appear (see fig.): they are composed of methyl brucine iodide (C₂₃H₂₅(CH₃)N₂O₄HI). Crystals identical in shape are also obtained if an alcoholic solution of iodine, or hydriodic acid with iodine, is added to an alcoholic solution of brucine. A solution of strychnine gives with methyl iodide no similar reaction. Strychnine in alcoholic solution, mixed with, brucine in no way interferes with the test. The methyl iodide test may be confirmed by the action of nitric acid. With that reagent it produces a scarlet colour, passing into blood-red, into yellow-red, and finally ending in yellow. This can be made something more than a mere colour test, for it is possible to obtain a crystalline body from the action of nitric acid on brucine. If a little of the latter be put in a test-tube, and treated with nitric acid of 1·4 specific gravity (immersing the test-tube in cold water to moderate the action), the red colour is produced. On spectroscopic examination of the blood-red liquid a broad, well-marked absorption band is seen, the centre of which (_see_ page 55) is between E. & F. [W. L. about 500]. There is also a development of nitric oxide and carbon dioxide, and the formation of methyl nitrite, oxalic acid, and kakotelin (C₂₃H₂₆N₂O₄ + 5NHO₃ = C₂₀H₂₂N₄O₉ + N(CH₃)O₂ + C₂H₂O₄ + 2NO + 2H₂O). On diluting abundantly with water, the kakotelin separates in yellow flocks, and may be crystallised out of dilute hydrochloric or dilute nitric acid in the form of yellow or orange-red crystals, very insoluble in water, but dissolving readily in dilute acid. On removal by dilution of the product just named, neutralisation with ammonia, and addition of a solution of chloride of calcium, the oxalate of lime is thrown down. The nitric acid test is, therefore, a combined test, consisting of--the production by the action of nitric acid (1) of a red colour; (2) of yellow scales or crystals insoluble in water; (3) of oxalic acid. No alkaloid save brucine is known to give this reaction.

There are other methods of producing the colour test. If a few drops of nitric acid are mixed with the substance in a test-tube, and then sulphuric acid cautiously added, so as to form a layer at the bottom, at the junction of the liquids a red zone, passing into yellow, is seen.

A solution of brucine is also coloured red by chlorine gas, ammonia changing the colour into yellow.

Flückiger[456] has proposed as a test mercurous nitrate, in aqueous solution with a little free nitric acid. On adding this reagent to a solution of brucine salt, and gently warming, a fine carmine colour is developed.

[456] _Archiv f. Pharm._ (3), vi. 404.

In regard to the separation of brucine from organic fluids or tissues, the process already detailed for strychnine suffices. It is of very great importance to ascertain whether both strychnine and brucine are present or not--the presence of both pointing to nux vomica or one of its preparations. The presence of brucine may, of course, be owing to impure strychnine; but if found in the tissues, that solution of the question is improbable, the commercial strychnine of the present day being usually pure, or at the most containing so small a quantity of brucine as would hardly be separated from the tissues.

§ 404. =Igasurine= is an alkaloid as yet but little studied; it
appears that it can be obtained from the boiling-hot watery extract
of nux vomica seeds, through precipitating the strychnine and
brucine by lime, and evaporation of the filtrate. According to
Desnoix,[457] it forms white crystals containing 10 per cent. of
water of crystallisation.

[457] _Journ. Pharm._ (3), xxv. 202.

It is said to be poisonous, its action being similar to that of
strychnine and brucine, and in activity standing midway between the
two.

§ 405. _Strychnic Acid._--Pelletier and Caventou obtained by boiling
with spirit small, hard, warty crystals of an organic acid, from _S.
ignatius_, as well as from nux vomica seeds. The seeds were first
exhausted by ether, the alcohol solution was filtered and
evaporated, and the extract treated with water and magnesia,
filtered, and the residue first washed with cold water, then with
hot spirit, and boiled lastly with a considerable quantity of water.
The solution thus obtained was precipitated with acetate of lead,
the lead thrown out by SH₂, and the solution evaporated, the acid
crystallising out. It is a substance as yet imperfectly studied, and
probably identical with malic acid.

2. THE QUEBRACHO GROUP OF ALKALOIDS.

§ 406. The bark of the _Quebracho Blanco_[458] (_Aspidosperma
quebracho_) contains, according to Hesse’s researches, no fewer than
six alkaloids--Quebrachine, Aspidospermine, Aspidospermatine,
Aspidosamine, and Hypoquebrachine. The more important of these are
_Aspidospermine_ and _Quebrachine_.

[458] See Liebig’s _Annal._, 211, 249-282; _Ber. der deutsch. Chem. Gesellsch._, 11, 2189; 12, 1560.

=Aspidospermine= (C₂₂H₃₀N₂O₂) forms colourless needles which melt at
206°. They dissolve in about 6000 parts of water at 14°--48 parts of
90 per cent. alcohol, and 106 parts of pure ether. The alkaloid
gives a fine magenta colour with perchloric acid.

=Quebrachine= (C₂₁H₂₆N₂O₃) crystallises in colourless needles,
melting-point (with partial decomposition) 215°. The crystals are
soluble in chloroform, with difficulty soluble in cold alcohol, but
easily in hot. The alkaloid, treated with sulphuric acid, and
peroxide of lead, strikes a beautiful blue colour. It also gives
with sulphuric acid and potassic chromate the strychnine colours.
Quebrachine, dissolved in sulphuric acid containing iron, becomes
violet-blue, passing into brown. The alkaloid, treated with strong
sulphuric acid, becomes brown; on adding a crystal of potassic
nitrate, a blue colour is developed; on now neutralising with
caustic soda no red coloration is perceived. Dragendorff has
recently studied the best method of extracting these alkaloids for
toxicological purposes. He recommends extraction of the substances
with sulphuric acid holding water, and shaking up with solvents.
Aspidospermine is not extracted by petroleum ether or benzene from
an acid watery extract, but readily by chloroform or by amyl
alcohol. It is also separated from the same solution, alkalised by
ammonia, by either amyl alcohol or chloroform; with difficulty by
petroleum ether; some is dissolved by benzene. Quebrachine may be
extracted from an acid solution by chloroform, but not by petroleum
ether. Alkalised by ammonia, it dissolves freely in chloroform and
in amyl alcohol. Traces are taken up by petroleum, somewhat more by
benzene. Aspidospermine is gradually decomposed in the body, but
Quebrachine is more resistant, and has been found in the stomach,
intestines, blood, and urine. The toxicological action of the bark
ranks it with the tetanic class of poisons. In this country it does
not seem likely to attain any importance as a poison.

3. PEREIRINE.

§ 407. =Pereirine=--an alkaloid from pereira bark--gives a play of
colours with sulphuric acid and potassic bichromate similar to but
not identical with that of strychnine. Fröhde’s reagent strikes
with it a blue colour. On dissolving pereirine in dilute sulphuric
acid, and precipitating by gold chloride, the precipitate is a
beautiful red, which, on standing and warming, is deepened.
Pereirine may be extracted from an acid solution, after alkalising
with ammonia, by ether or benzene.

4. GELSEMINE.

§ 408. Gelsemine (C₂₂H₂₈N₂O₄) is an alkaloid[459] which has been
separated from _Gelsemium sempervirens_, the Carolina jessamine, a
plant having affinities with several natural orders, and placed by
De Candolle among the _Loganiaceæ_, by Chapman among the _Rubiaceæ_
and by Decaisne among the _Apocynaceæ_. It grows wild in Virginia
and Florida.[460] Gelsemine is a strong base; it is yellowish when
impure, but a white amorphous powder when pure. It fuses below 100°
into a transparent vitreous mass, at higher temperatures it
condenses on glass in minute drops; its taste is extremely bitter;
it is soluble in 25 parts of ether, in chloroform, bisulphide of
carbon, benzene, and in turpentine; it is not very soluble in
alcohol, and still less soluble in water, but it freely dissolves in
acidulated water. The caustic alkalies precipitate it, the
precipitate being insoluble in excess; it is first white, but
afterwards brick-red. Tannin, picric acid, iodised potassic iodide,
platinic chloride, potassio-mercuric iodide, and mercuric chloride
all give precipitates. Fröhde’s reagent gives with gelsemine a brown
changing to green.

[459] Dr. T. G. Wormley separated, in 1870, a non-nitrogenised remarkably fluorescent body, which he named gelsemic acid (_Amer. Journ. of Pharm._, 1870), but Sonnenschein and C. Robbins afterwards found gelsemic acid to be identical with æsculin (_Ber. der deutsch. Chem. Ges._, 1876, 1182). Dr. Wormley has, however, contested this, stating that there are differences. (_Amer. Journ. of Pharm._, 1882, p. 337. _Yearbook of Pharmacy_, 1882, p. 169.)

[460] The following are its botanical characters:--Calyx five-parted, corolla funnel-shaped, five-lobed, somewhat oblique, the lobes almost equal, the posterior being innermost in bud; stamens five; anthers oblong sagittate, style long and slender; stigmas two, each two-parted, the divisions being linear; fruit elliptical, flattened contrary to the narrow partition, two-celled, septicidally two-valved, the valves keeled; seeds five to six in each cell, large, flat, and winged; embryo straight in fleshy albumen; the ovate flat, cotyledons much shorter than the slender radicle; stem smooth, twining and shrubby; leaves opposite, entire, ovate, or lanceolate, shining on short petioles, nearly persistent; flowers large, showy, very fragrant, yellow, one to five in the axil of the leaves.

Sulphuric acid dissolves gelsemine with a reddish or brownish
colour; after a time it assumes a pinkish hue, and if warmed on the
water-bath, a more or less purple colour; if a small crystal of
potassic bichromate be slowly stirred in the sulphuric acid
solution, reddish purple streaks are produced along the path of the
crystal; ceric oxide exhibits this better and more promptly, so
small a quantity as ·001 grain showing the reaction. This reaction
is something like that of strychnine, but nitric acid causes
gelsemine to assume a brownish-green, quickly changing to a deep
green--a reaction which readily distinguishes gelsemine from
strychnine and other alkaloids.

§ 409. =Fatal Dose.=--10 mgrms. killed a frog within four hours, and
8 mgrms. a cat within fifteen minutes. A healthy woman took an
amount of concentrated tincture, which was equivalent to 11 mgrms.
(⅙ grain), and died in seven and a half hours.

§ 410. =Effects on Animals--Physiological Action.=--Gelsemine acts
powerfully on the respiration; for example, Drs. Sydney Ringer and
Murrell[461] found, on operating on the frog, that in two minutes
the breathing had become distinctly slower; in three and a half
minutes, it had been reduced by one-third; and in six minutes, by
one-half; at the expiration of a quarter of an hour, it was only
one-third of its original frequency; and in twenty minutes, it was
so shallow and irregular that it could no longer be counted with
accuracy. In all their experiments they found that the respiratory
function was abolished before reflex and voluntary motion had become
extinct. In several instances the animals could withdraw their legs
when their toes were pinched, days after the most careful
observations had failed to detect the existence of any respiratory
movement. The heart was seen beating through the chest wall long
after the complete abolition of respiration.

[461] _Lancet_, vol. i., 1876, p. 415.

In their experiments on warm-blooded animals (cats), they noticed
that in a few minutes the respirations were slowed down to 12 and
even to 8, and there was loss of power of the posterior extremities,
while at short intervals the upper half of the body was convulsed.
In about half an hour paralysis of the hind limbs was almost
complete, and the respiratory movements so shallow that they could
not be counted. In the case of a dog, after all respiration had
ceased tracheotomy was performed, and air pumped in: the animal
recovered.

Ringer and Murrell consider that gelsemine produces no primary
quickening of the respiration, that it has no direct action on
either the diaphragm or intercostal muscles, that it paralyses
neither the phrenic nor the intercostal nerves, and that it
diminishes the rate of respiration after both vagi have been
divided. They do not consider that gelsemine acts on the cord
through Setschenow’s inhibitory centre, but that it destroys reflex
power by its direct action on the cord, and that probably it has no
influence on the motor nerves. Dr. Burdon Sanderson has also
investigated the action of gelsemine on the respiration, more
especially in relation to the movements of the diaphragm. He
operated upon rabbits; the animal being narcotised by chloral, a
small spatula, shaped like a teaspoon, was introduced into the
peritoneal cavity through an opening in the linea alba, and passed
upwards in front of the liver until its convex surface rested
against the under side of the centrum tendineum. The stem of the
spatula was brought into connection with a lever, by means of which
its to-and-fro movements (and consequently that of the diaphragm)
were inscribed. The first effect is to augment the depth but not the
frequency of the respiratory movements; the next is to diminish the
action of the diaphragm both in extent and frequency. This happens
in accordance with the general principle applicable to most cases of
toxic action--viz., that paresis of a central organ is preceded by
over-action. The diminution of movement upon the whole is
progressive, but this progression is interrupted, because the blood
is becoming more and more venous, and, therefore, the phenomena of
asphyxia are mixed up with the toxical effects. Dr. Sanderson
concludes that the drug acts by paralysing the automatic respiratory
centre; the process of extinction, which might be otherwise expected
to be gradual and progressive, is prevented from being so by the
intervention of disturbances of which the explanation is to be found
in the imperfect arterialisation of the circulating blood. Ringer
and Murrell have also experimented upon the action of gelsemine on
the frog’s heart. In all cases it decreased the number of beats; a
small fatal dose produced a white contracted heart, a large fatal
dose, a dark dilated heart; in either case arrest of the circulation
of course followed.

§ 411. =Effects on Man.=--The preparations used in medicine are the
fluid extract and the tincture of gelsemine; the latter appears to
contain the resin of the root as well as the active principle. There
are several cases on record of gelsemine, or the plant itself,
having been taken with fatal effect.[462] Besides a marked effect on
the respiration, there is an effect upon the eye, better seen in man
than in the lower animals; the motor nerves of the eye are attacked
first, objects cannot be fixed, apparently dodging their position,
the eyelids become paralysed, droop, and cannot be raised by an
effort of the will; the pupils are largely dilated, and at the same
time a feeling of lightness has been complained of in the tongue; it
ascends gradually to the roof of the mouth, and the pronunciation is
slurred. There is some paresis of the extremities, and they refuse
to support the body; the respiration becomes laboured, and the pulse
rises in frequency to 120 or 130 beats per minute, but the mind
remains clear. The symptoms occur in about an hour and a half after
taking an overdose of the drug, and, if not excessive, soon
disappear, leaving no unpleasantness behind. If, on the other hand,
the case proceeds to a fatal end, the respiratory trouble increases,
and there may be convulsions, and a course very similar to that seen
in experimenting on animals. Large doses are especially likely to
produce tetanus, which presents some clinical differences
distinguishing it from strychnine tetanus. Gelsemine tetanus is
always preceded by a loss of voluntary reflex power, respiration
ceases before the onset of convulsions, the posterior extremities
are most affected, and irritation fails to excite another paroxysm
till the lapse of some seconds, as if the exhausted cord required
time to renew its energy; finally, the convulsions only last a short
time.

[462] See _Lancet_, 1873, vol. ii. p. 475; _Brit. Med. and Surg. Journ._, April 1869; _Phil. Med. and Surg. Reporter_, 1861.

§ 412. _Extraction from Organic Matters, or the Tissues of the
Body._--Dragendorff states that, from as little as half a grain of
the root, both gelsemine and gelsemic acid may be extracted with
acid water, and identified. On extracting with water acidified with
sulphuric acid, and shaking up the acid liquid with chloroform, the
gelsemic acid (æsculin?) is dissolved, and the gelsemine left in the
liquid. The chloroform on evaporation leaves gelsemic acid in little
micro-crystals; it may be identified by (1) its crystallising in
little tufts of crystals; (2) its strong fluorescent properties, one
part dissolved in 15,000,000 parts of water showing a marked
fluorescence, which is increased by the addition of an alkali; and
(3) by splitting up into sugar and another body on boiling with a
mineral acid. After separation of gelsemic acid, the gelsemine is
obtained by alkalising the liquid, and shaking up with fresh
chloroform; on separation of the chloroform, gelsemine may be
identified by means of the reaction with nitric acid, and also the
reaction with potassic bichromate and sulphuric acid.

5. COCAINE.

§ 413. =Cocaine= (C₁₇H₂₁NO₄).--There are two cocaines--the one
rotating a ray of polarised light to the left, the other to the
right. The left cocaine is contained in the leaves of _Erythroxylon
coca_ with other alkaloids, and is in commerce.

Cocaine has been used most extensively in medicine since the year
1884--its chief use being as a local anæsthetic. Chemically cocaine
is a derivative of ecgonin, being ecgonin-methyl-ester. It has a
pyridine nucleus, and may be written
C₅H₄N(CH₃)--H₃CHO--(COC₆H₅)--CH₂COOCH₃, or expressed graphically as
follows:--

CH₂
/\
CH / \CH₂
║ |
║Py | H
║ | /
CH \ /C--CHO(C₆H₅CO)--CH₂COOCH₃.
\/
NCH₃

=Properties.=--Cocaine is in the form of four- to six-sided prisms
of the monoclinic system. It is one of the few alkaloids which melt
under the temperature of boiling water, the melting-point being as
low as 85° in water. It readily furnishes a sublimate at 100°,
partially decomposing. On boiling with hydrochloric acid cocaine is
decomposed into methyl alcohol, ecgonin, and benzoic acid, according
to the following reaction:--

Benzoic Methyl
Cocaine. acid. Ecgonin. Alcohol.
C₁₇H₂₁NO₄ + 2H₂O = C₆H₅COOH + C₉H₁₅NO₃ + CH₃OH.

Cocaine is but little soluble in water, but easily dissolves in
ether, alcohol, benzene, chloroform, and carbon disulphide; an
aqueous solution is alkaline to methyl-orange, but not to
phenol-phthalein. It can be made synthetically by the reaction of
ecgonin-methyl-ester with benzoyl chloride.

§ 414. =Cocaine Hydrochlorate= (C₁₇H₂₁NO₄HCl).--Crystallised from alcohol, cocaine hydrochlorate appears in prismatic crystals; these crystals, according to Hesse,[463] when perfectly pure, should melt at 186°, although the melting-point is generally given as 200° or even 202°. Cocaine hydrochlorate is soluble in half its weight of water, insoluble in dry ether, but readily soluble in alcohol, amyl alcohol, or chloroform.

[463] O. Hesse, _Annalen_, 276, 342-344.

§415. =Pharmaceutical Preparations.=--Cocaine hydrochlorate is officinal. Gelatine discs, weighing 1·31 mgrms. (1/50 grain), and each containing 0·33 mgrm. (1/200 grain) of the salt are officinal, and used by ophthalmic surgeons. A solution of the hydrochlorate, containing 10 per cent. of cocaine hydrochlorate and (for the purposes of preserving the solution) 0·15 per cent. of salicylic acid is also officinal. Stronger solutions may also be met with; for instance, a 20 per cent. solution in oil of cloves for external application in cases of neuralgia.

§416. =Separation of Cocaine and Tests.=--Cocaine may be shaken out of solutions made slightly alkaline by ammonia by treatment with benzene; it also passes into petroleum ether under the same circumstances. The best method is to extract a solution, made feebly alkaline, thoroughly by ether, and then shake it out by benzene and evaporate the separated benzene at the ordinary air temperature. The property of the alkaloid to melt at or below the temperature of boiling water, and the ready decomposition into benzoic acid and other products, render cocaine easy of identification. If, for instance, a small particle of cocaine is put in a tube, a drop of strong sulphuric acid added and warmed by the water-bath, colourless crystals of benzoic acid sublime along the tube, and an aromatic odour is produced.

Flückiger has recommended the production of benzoate of iron as a useful test both for cocaine and for cocaine hydrochlorate.

One drop of a dilute solution of ferric chloride added to a solution of 20 mgrms. of cocaine hydrochlorate in 2 c.c. of water, gives a yellow fluid, which becomes red on boiling from the production of iron benzoate. This reaction is of little use unless a solution of the same strength of ferric chloride, but to which the substance to be tested has not been added, is boiled at the same time for comparison, because all solutions of ferric chloride deepen in colour on heating.

A solution of the alkaloid evaporated to dryness on the water-bath, after being acidulated with nitric acid, and then a few drops of alcoholic solution of potash or soda added, develops an odour of benzoic ethyl-ester. Cocaine hydrochlorate, when triturated with calomel, blackens by the slightest humidity or by moistening it with alcohol. Cocaine in solution is precipitated by most of the group reagents, but is not affected by mercuric chloride, picric acid, nor potassic bichromate.

Added to the tests above mentioned, there is the physiological action; cocaine dilates the pupil, tastes bitter, and, for the time, arrests sensation; hence the after-effect on the tongue is a sensation of numbness.

§ 417. =Symptoms.=--A large number of accidents occur each year from the external application of cocaine; few, however, end fatally. Cocaine has thus produced poisonous symptoms when applied to the eye, to the rectum, to the gums, to the urethra, and to various other parts. There have been a few fatal cases, both from its external and internal administration; Mannheim, for example, has collected eleven of such instances.

The action of cocaine is twofold; there is an action on the central and the peripheral nervous system. In small doses cocaine excites the spinal cord and the brain; in large it may produce convulsions and then paralysis. The peripheral action is seen in the numbing of sensation. There is always interference with the accommodation of vision, and dilatation of the pupil. The eyelids are wider apart than normal, and there may be some protrusion of the eyeball.

The usual course of an acute case of poisoning is a feeling of dryness in the nose and throat, difficulty of swallowing, faintness, and there is often vomiting; the pulse is quickened; there is first cerebral excitement, followed usually by great mental depression. Occasionally there is an eruption on the skin. Hyperæsthesia of the skin is followed by great diminution of sensation, the pupils, as before stated, are dilated, the eyes protruding, the eyelids wide open, the face is pale, and the perspiration profuse. Convulsions and paralysis may terminate the scene. Death takes place from paralysis of the breathing centre; therefore the heart beats after the cessation of respiration. As an antidote, nitrite of amyl has apparently been used with success.

There is a form of chronic poisoning produced from the taking of small doses of cocaine daily. The symptoms are very various, and are referable to disturbance of the digestive organs, and to the effect on the nervous system. The patients become extremely emaciated, and it seems to produce a special form of mania.

§ 418. =Post-mortem Appearances.=--The appearances found in acute cases of poisoning have been hyperæmia of the liver, spleen, and kidneys, as well as of the brain and spinal cord.

In the experimental poisoning of mice with cocaine Ehrlich[464] found a considerable enlargement of the liver.

[464] _Deutsche med. Wochens._, 1890, No. 32.

§ 419. =Fatal Dose.=--The fatal dose, according to Mannheim,[465] must be considered as about 1 grm. (15·4 grains); the smallest dose known to have been fatal is 0·08 grm. (1·2 grain) for an adult, and 0·05 grm. (0·7 grain) for a child.

[465] _Deutsch. Arch. f. klin. Med._, Bd. viii., 1891, 380.

6. CORYDALINE.

§ 420. =Corydaline= (C₂₂H₂₈NO₄) is an alkaloid discovered by
Wackenroder (1826) in the tubers of _Corydalis tuberosa_;
crystallised in the cold and away from light, out of a mixture of
absolute alcohol and ether, corydaline forms colourless, flat,
prismatic crystals, which quickly turn yellow on exposure to light
or heat. Pure corydaline changes colour at about 125°, softens at
about 133°, and melts finally at 134° to 135°. It dissolves in
ether, chloroform, carbon disulphide, and benzene, but not so
readily in alcohol. It is almost insoluble in cold water, and but
slightly soluble in boiling water. Water precipitates it from a
solution in alcohol. It is also soluble in dilute hydrochloric and
sulphuric acids. It gives a precipitate with potassium iodide if a
solution of the hydrochloride be used. The precipitate crystallises
out of hot water in clusters of short lemon-yellow prismatic
crystals, and has the formula of C₂₂H₂₈NO₄HI. Corydaline
platinochloride has the composition of (C₂₂H₂₈NO₄)₂H₂PtCl₆,
containing Pt 16·94 per cent., and 2·44 per cent. of N.--Dobbie &
Lauder, _Journ. Chem. Soc._, March 1892, 244.

Corydaline in large doses causes epileptiform convulsions. Death
takes place from respiratory paralysis.

V.--The Aconite Group of Alkaloids.

§ 421. The officinal aconite is the _Aconitum napellus_--monkshood or wolfsbane--a very common garden plant in this country, and one cultivated for medicinal purposes. Many varieties of aconite exist in other regions, which either are, or could be, imported. Of these the most important is the _Aconitum ferox_, a native of the Himalayan mountains, imported from India.

All the aconites, so far as known, are extremely poisonous, and it appears probable that different species contain different alkaloids. The root of _A. napellus_ is from 2 to 4 inches long, conical in shape, brown externally, and white internally. The leaves are completely divided at the base into five wedge-shaped lobes, each of the five lobes being again divided into three linear segments. The numerous seeds are three-sided, irregularly twisted, wrinkled, of a dark-brown colour, in length one-sixth of an inch, and weighing 25 to the grain (_Guy_). The whole plant is one of great beauty, from 2 to 6 feet high, and having a terminal spike of conspicuous blue flowers. The root has been fatally mistaken for horse-radish, an error not easily accounted for, since no similarity exists between them.

§ 422. =Pharmaceutical Preparations of Aconite.=--The preparations of aconite used in medicine are--

=Aconitine=, officinal in all the pharmacopœias.

=Aconite liniment= (=linimentum aconiti=), made from the root with spirit, and flavoured with camphor; officinal in the British Pharmacopœia. It may contain about 2·0 per cent. of aconitine.

=Aconite tincture=, officinal in all the pharmacopœias.

=Aconite ointment=, 8 grains of aconitine to the oz. (_i.e._, 1·66 per cent.); officinal in the British Pharmacopœia.

=Aconite extract=, the juice of the leaves evaporated; officinal in most of the pharmacopœias. The strength in alkaloid of the extract varies; in six samples examined by F. Casson, the least quantity was 0·16 per cent., the maximum 0·28 per cent.[466]

[466] _Pharm. Journ._, 1894, 901.

=Fleming’s tincture of aconite= is not officinal, but is sold largely in commerce. It is from three to four times stronger than the B.P. tincture.

§ 423. =The Alkaloids of Aconite.=--The researches of Dr. Alder Wright and Luff, and especially those of Professor Dunstan,[467] have established that in the root of the true aconite there exist four alkaloids, one only of which has been as yet crystallised.

[467] Various papers in _Journ. Chem. Soc._, 1892-1894.

Three of the alkaloids have been fairly well worked out; the fourth homo-napelline has not yet been satisfactorily investigated.

The three alkaloids are aconitine, aconine and benzoyl-aconine; besides which pyraconitine and pyraconine can be obtained by suitable treatment from aconitine and aconine.

The formulæ of the alkaloids and their derivatives are as follows:--

Aconitine (acetyl-benzoyl-aconine), m.p., 188·60°, C₃₃H₄₅NO₁₂
Benzoyl-aconine, m.p., 268·0°, C₃₁H₄₃NO₁₁
Pyraconitine (anhydro-benzoyl-aconine), m.p., 188-190°, C₃₁H₄₁NO₁₀
Aconine, m.p., 132°, C₂₄H₃₉NO₁₀
Pyraconine (anhydro-aconine), C₂₄H₃₇NO₉

§ 424. =Aconitine=, C₃₃H₄₅NO₁₂.--This base has been shown by Dunstan to be acetyl-benzoyl-aconine; one molecule of the base breaking up, on complete hydrolysis, into one molecule of aconine, one of acetic acid, and one of benzoic acid--

Acetic Benzoic
Acid. Acid. Aconine.
C₃₃H₄₅NO₁₂ + 2H₂O = C₂H₄O₂ + C₇H₆O₂ + C₂₄H₃₉NO₁₀.

That is to say that 100 parts of aconitine, according to theory, should yield:--

Acetic acid, 9·37 per cent.; benzoic acid, 18·85 per cent.; and aconine, 77·52 per cent.

Pure aconitine has a tube melting-point of 188·6°. The behaviour of a sample of Merck’s aconitine in the subliming cell, which had a melting-point of 184°, was as described at page 259.

Aconitine dissolves in water at 22° in the proportion of 1 in 4431 (_Dunstan_); it is soluble in 37 of absolute alcohol, 64 of anhydrous ether, 5·5 parts of chloroform and benzene (_A. Jurgens_); it has basic properties, and a cold watery solution has an alkaline reaction to cochineal, but not to litmus nor to phenol-phthalein. Aconitine is not precipitated by mercuric potassium iodide, but gives a voluminous precipitate with an aqueous solution of iodine in potassium iodide.

It gives a crystalline yellow gold compound with gold chloride, which has a melting-point of 135·5°, and according to its composition, C₃₃H₄₅NO₁₂HAuCl₄, should give 19·9 per cent. of gold.

Aconitine is best extracted from the plant, or from organic matters generally, by a 1 per cent. sulphuric acid; this strength is stated not to hydrolyse aconitine if acting in the cold; after purifying the acid liquid by shaking it with amyl alcohol, and then with chloroform, _always operating in the cold_, the liquid is precipitated by ammonia in very slight excess, and the liquid shaken with ether; the ether is removed, dehydrated by standing over calcium chloride, and then evaporated spontaneously; should the aconitine be mixed with the other alkaloids, advantage can be taken of the method of separating aconitine by converting it into hydrobromide, as described under “Benzoyl-aconine.”

§ 425. =Tests for Aconitine.=--The most satisfactory and the most delicate is the physiological test; the minutest trace of an aconite-holding liquid, applied to the tongue or lips, causes a peculiar numbing, tingling sensation which, once felt, can readily be remembered.

An alkaloidal substance which, heated in a tube, melts approximately near the melting-point of aconitine, and gives off an acid vapour, would render one suspicious of aconitine, for most alkaloids give off alkaline vapours. Aconitine also may, by heating with dilute acids, be made to readily yield benzoic acid, an acid easy of identification. Aconitine dissolved in nitric acid, evaporated to dryness, and then treated with alcoholic potash, gives off an unmistakable odour of benzoic ester.

Should there be sufficient aconitine recovered to convert it into the gold salt, the properties of the gold salt (that is, its melting-point, and the percentage of gold left after burning) assist materially in the identification.

A minute quantity of aconitine dissolved in water, acidified with acetic acid, and a particle of KI added and the solution allowed to evaporate, gives crystals of aconitine hydriodide, from which water will dissolve out the KI. Iodine water gives a precipitate of a reddish-brown colour in a solution of 1 : 2000.[468]

[468] A. Jurgens, _Arch. Pharm._ (3), xxiv. 127, 128.

The chemical tests are supplementary to the physiological; if the alkaloidal extract does not give the tingling, numbing sensation, aconitine cannot be present.

§ 426. =Benzoyl-aconine (“isaconitine”)=, C₃₁H₄₃NO₁₁, is obtained from aconitine by heating an aqueous solution of the sulphate or hydrochloride in a closed tube at 120°-130° for two or three hours, a molecule of acetic acid (9·27 per cent.) being split off, and benzoyl-aconine left.

It may be separated from the mixed alkaloids of the _Aconitum napellus_ by dissolving in a 5 per cent. solution of hydrobromic acid (excess of acid being avoided), precipitating with a slight excess of ammonia, and shaking out with ether. The residue left after the ether is evaporated chiefly consists of aconitine; it is dissolved in just sufficient hydrobromic acid and the exactly neutral hydrobromate solution allowed to evaporate spontaneously in a desiccator; crystals of aconitine hydrobromide separate out, the mother liquor containing some benzoyl-aconine and “homonapelline.” The aqueous solution which has been exhausted with ether is now shaken out with chloroform. This chloroform solution contains most of the benzoyl-aconine, and on separation the residue is dissolved in just sufficient hydrochloric acid to form a neutral solution; this solution is concentrated on the water-bath with constant stirring, crystals of the hydrochloride form, and are filtered off from time to time and washed with a little cold water, the washings being added to the original liquid; the different fractions are mixed together, and the process repeated until they have a melting-point of 268°. Benzoyl-aconine is obtained from the hydrochloride by precipitating the aqueous solution by the addition of dilute ammonia, and extracting the solution with ether; the solution in ether is washed with water, dried by means of calcium chloride, and then distilled off. Benzoyl-aconine is left as a transparent colourless non-crystalline varnish of a melting-point near 125°.

The solution in water is alkaline to litmus. The base is readily soluble in alcohol, in chloroform, and in ether. The alcoholic solution is dextrorotatory. The solutions are bitter, but do not give the tingling sensation characteristic of aconitine. The hydrochloride, the hydrobromide, the hydriodide, and the nitrate have been obtained in a crystalline state. The most characteristic salt is, however, the aurochlor derivative. When aqueous solutions of benzoyl-aconine chloride and auric chloride are mixed, a yellow precipitate is thrown down, which (dissolved in alcohol, after being dried over calcium chloride, and slowly evaporated in a desiccator) deposits colourless crystals entirely different from the yellow crystals of aconitine gold chloride. These crystals have the composition C₃₁H₄₂(AuCl₂)NO₁₁, and therefore, by theory, should yield 22·6 per cent. of gold, and 8·2 per cent. of chlorine.

By hydrolysis benzoyl-aconine yields benzoic acid, which can be shaken out of an acid solution by ether and identified; one molecule of benzoic acid is formed from one molecule of benzoyl-aconine. Twenty per cent. of benzoic acid should, according to the formula, be obtained; Professor Dunstan found only 18·85 per cent.[469]

[469] Professor Dunstan found, as a means of two determinations, 21·6 per cent. of gold, and 7·8 per cent. of chlorine, which comes nearer his old formula of C₃₃H₄₄(AuCl₂)NO₁₂.--_Journ. Chem. Soc._, April 1893.

Benzoic acid in the subliming cell begins to give a cloud at about 77°-80°, and at or near 100° sublimes most rapidly.

Benzoic acid, recovered from an acid solution by shaking out with ether, may be recognised as follows:--To the film left on evaporating off the ether add a drop of H₂SO₄, and a few crystals of sodic nitrate, and heat gently for a short time; pour the clear liquid into ammonia water, and add a drop of ammonium sulphide. A red-brown colour indicates benzoic acid. The _rationale_ of the test is as follows:--Dinitro-benzoic acid is first formed, and next, by the action of ammonium sulphide, this is converted into the red-brown ammonium diamidobenzoate.--E. Mohler, _Bull. Soc. Chem._ (3), iii. 414-416.

§ 427. =Pyraconitine=, C₃₁H₄₁NO₁₀, is anhydro-benzoyl-aconine; it differs from benzoyl-aconine by a molecule of water; picraconitine is obtained by keeping aconitine at its melting-point (188°-190°) for some time, when acetic acid distils over and pyraconitine is left. Pyraconitine is an amorphous varnish, sparingly soluble in water, but readily dissolving in alcohol, chloroform, and ether; it gives a pale yellow precipitate with gold chloride, and forms crystalline salts with hydriodic, hydrobromic, and hydrochloric acids. Pyraconitine readily undergoes hydrolysis by the action of dilute acids, or by potash or soda, or with water in a closed tube; the products are benzoic acid and an alkaloid, to which the name of pyraconine has been given.

§ 428. =Pyraconine=, C₂₄H₃₇NO₉.--This base is anhydro-aconine, the formula differing from aconine by one atom of water. It is amorphous, closely resembling aconine; it is soluble in water and ether; the aqueous solution has a somewhat sweet taste, and is lævorotatory; it combines with acids to form crystalline salts, which are very soluble in water.