[649] Analyst, Feb. 28, 1877.
[650] See Note on the effect of various substances in destroying the activity of the cobra poison. By T. Lauder Brunton and Sir J. Fayrer, Proc. Roy. Soc., vol. xxvii. p. 17.
[651] Some of my experiments on the cobra poison may be briefly detailed, illustrating the general statement in the text:—
1. A quantity equal to 1 mgrm. of the dried venom was injected subcutaneously into a chicken. The symptoms began in two minutes with loss of power over both legs. In eight minutes the legs were perfectly paralysed. There were convulsive movements of the head and wings, slowing of the respiration, and death in ten minutes. The same quantity of poison was treated with a little tannin, and the clear liquid which separated from the precipitate injected into another chicken. The respiration became affected in ten minutes; in eighteen minutes the bird had become very quiet, and lay insensible; in twenty minutes it was dead, the respiration ceasing before the heart.
2. In seven experiments with cobra poison, first rendered feebly alkaline with an alkaline solution of potassic permanganate, no effect followed. Three of the experiments were on chickens, four on rabbits.
3. A chicken was injected with 1 mgrm. of cobra poison in one leg, and in the other simultaneously with a solution of potassic permanganate. Death followed in sixteen minutes. Another chicken was treated in the same way, but with injections of potassic permanganate solution every few minutes. Death resulted in thirty-seven minutes. Four other similar experiments were made—two with feebly alkaline permanganate, two with permanganate made feebly acid with sulphuric acid—but death occurred with the usual symptoms.
4. Cobra poison was mixed with a weak solution of iodine, and a quantity equal to half a mgrm. was injected into a chicken. The symptoms began directly, were fully developed in ten minutes, and death took place in twenty-one minutes.
5. Equal volumes of cobra venom and aldehyde were mixed, and a quantity equivalent to 1 mgrm. of the cobra poison injected. The symptoms were immediate paralysis and insensibility, and the respiration rapidly fell. Death occurred in four minutes without convulsions.
6. The cobra venom was mixed with a feebly alkaline solution of pyrogallic acid, and injected subcutaneously into a chicken. In six minutes the usual symptoms commenced, followed in thirteen minutes by death.
7. One mgrm. was injected into a chicken. The respirations at the commencement were 120; in twenty-two minutes they sank to 96, in twenty-five minutes to 84, in twenty-seven minutes to 18, and then to occasional gasps, with slight movement of the wings and toes. There was death in thirty-two minutes after the injection.
8. A young rabbit was injected with ·5 mg. (equal to 1 mgrm. per kilo.) of cobra poison. In two hours it was apparently moribund, with occasional short gasps. Artificial respiration was now attempted. There was considerable improvement, but it was intermitted during the night, and the animal was found dead in the morning, having certainly lived six hours.
9. A strong healthy kitten was injected with 1 mgrm. of cobra venom (equal to 5 mgrms. per kilo.). In twenty minutes the symptoms were well developed, and in an hour the animal was gasping—about twelve short respirations per minute. Artificial respiration was kept up for two hours, and the animal recovered, but there was great muscular weakness lasting for more than twenty-four hours.
10. A brown rabbit, weighing about 2 kilos., was injected with 12 mgrms. (6 per kilo.) of the cobra poison. The symptoms developed within ten minutes; ammonia was injected, and also given by the nostril. The heart’s action, which, previous to the administration of the ammonia, had been beating feebly, became accelerated, but death followed within the hour, the heart beating two minutes after the respiration had ceased.
11. A brown rabbit, about 2 kilos. in weight, was injected with 1·5 mgrms. of cobra poison (·75 per kilo.). There were no symptoms for nearly an hour, then sudden convulsions, and death.
12. Another rabbit of the same size was treated similarly, but immediately after the injection made to breathe nitrous oxide; death took place in thirty minutes. A rabbit, a little over 2 kilos. in weight, was injected with 7 mgrms. of cobra venom per kilo., and then 10 mgrms. of monobromated camphor were administered. In fifteen minutes there was general paralysis of the limbs, from which in a few minutes the animal seemed to recover; thirty minutes after the injection there were no very evident symptoms, but within forty minutes there was a sudden accession of convulsions, and death. Experiments were also made with chloroform, morphine, and many other substances, but none seemed to exercise any true antidotal effect.
§ 645. Detection of the Cobra Venom.—In an experiment on a rabbit, the animal was killed by the subcutaneous injection of 8 mgrms. per kilo. of the cobra poison. Immediately after death, 2 c.c. of the blood were injected into a small rabbit; in fifteen minutes there was slow respiration with pains in the limbs; in thirty minutes this had, in a great measure, passed off, and in a little time the animal was well. In any case in which it is necessary to attempt to separate the cobra venom, the most likely method of succeeding would be to make a cold alcoholic extract, evaporate in a vacuum, take up the residue in a little water, and test its effect on small animals.
§ 646. Duboia Russellii.—The Duboia russellii or Russell’s viper is one of the best known and most deadly of the Indian vipers. The effects of the poison of this viper are altogether different from those of the cobra. The action commences by violent general convulsions, which are often at once fatal, or may be followed by rapid paralysis and death; or these symptoms, again, may be recovered from, and death follow at a later period. The convulsions do not depend on asphyxia, and with a small dose may be absent. The paralysis is general, and may precede for some time the extinction of the respiration, the pupils are widely dilated, there are bloody discharges, and the urine is albuminous. Should the victim survive the first effects, then blood-poisoning may follow, and a dangerous illness result, often attended with copious hæmorrhages. A striking example of this course is recorded in the Indian Med. Gaz., June 1, 1872.
A Mahommedan, aged 40, was bitten on the finger by Russell’s viper; the bitten part was soon after excised, and stimulants given. The hand and arm became much swollen, and on the same day he passed blood by the rectum, and also bloody urine. The next day he was sick, and still passing blood from all the channels; in this state he remained eight days, losing blood constantly, and died on the ninth day. Nothing definite is known of the chemical composition of the poison; it is probably qualitatively identical with “viperin.”
§ 647. The Poison of the Common Viper.—The common viper still abounds in certain parts of Great Britain, as, for example, on Dartmoor. The venom was analysed in a partial manner by Valentin. In 1843 Prince Lucien Bonaparte separated a gummy varnish, inodorous, glittering, and transparent, which he called echidnin or viperin; it was a neutral nitrogenous body without taste, it arrested the coagulation of the blood, and, injected into animals, produced all the effects of the bite of the viper. Phisalix and G. Bertrand have studied the symptoms produced in small animals after injection. A guinea-pig, weighing 500 grms., was killed by 0·3 grm. of the dried venom dissolved in 5000 parts of saline water; the symptoms were nausea, quickly passing into stupor. The temperature of the body fell. The autopsy showed the left auricle full of blood, the intestine, lungs, liver, and kidneys injected. The blood of the viper is also poisonous, and produces the same symptoms as the venom.[652] The same observers have shown (Compt. rend., cxviii., Jan. 1894) that the blood of the water-snake (Tropidonotus natrix) and of the Thuringian adder (Tropidonotus viperinus) is poisonous, producing the same symptoms as that of the viper.
[652] Compt. rend. Soc. de Biol., t. v. 997.
The Venom of Naja Haje (Cleopatra’s Asp).—It has been stated that 20,000 persons annually die in Ceylon from the bite of Cleopatra’s asp. Graziani (Rif. Med., October 7, 1893) has undertaken a physiological study of the venom, which has already received attention at the hands of Calmette, Wall and Armstrong, Weir Mitchell, Reichardt, and others. The venom, when dried, appears as transparent scales, easily soluble in water, very slightly so in alcohol, ether, or chloroform; its aqueous solution has an unpleasant odour, and is neutral to test paper. Chemically it gives all the tests described by Weir Mitchell and others as characteristic of the venom of Naja tripudians. The physiological effects of this dried venom were tried on guinea-pigs, rabbits, and frogs, to all of which it proved fatal in extremely minute doses. The guinea-pig, a few seconds after injection, becomes paralysed in its hind limbs, it foams at the mouth, and makes violent attempts at vomiting. The eyes are half closed, but occasionally for short periods there is a partial disappearance of the paralysis, and the animal makes feeble attempts to support itself. Respiratory embarrassment is soon added to the foregoing symptoms, and the animal lies perfectly prone, devoting all its attention to breathing, which is rendered still more difficult by the vomiting and frothy saliva which is secreted in abundance. Finally death ensues from asphyxia. The post-mortem examination reveals the heart still feebly beating, the lungs pallid, and the blood in the organs very dark. The liver and kidneys are hyperæmic, but the brain and cord, with their coverings, are anæmic. In the rabbit the course of the poisoning is practically identical with that described above. Histologically, the following facts are made out in addition to the foregoing. The red blood-corpuscles are in great measure broken down, and there are also effusions into the muscular tissues. The kidneys are very hyperæmic, and there is marked degeneration of the epithelium lining the glomeruli and convoluted tubules. The glomerular capsules are much distended, and numerous leucocytes are discernible throughout the organ. The liver, also, is hyperæmic, and shows numerous broken-down blood-corpuscles, and partial necrosis of many of the liver cells. Examination of the central nervous system reveals no particular changes.
§ 648. Definition of a Ptomaine.—A ptomaine may be considered as a basic chemical substance derived from the action of bacteria on nitrogenous substances. If this definition is accepted, a ptomaine is not necessarily formed in the dead animal tissue; it may be produced by the living, and, in all cases, it is the product of bacterial life. A ptomaine is not necessarily poisonous; many are known which are, in moderate doses, quite innocuous.
When Selmi’s researches were first published there was some anxiety lest the existence of ptomaines would seriously interfere with the detection of poison generally, because some were said to be like strychnine, others like colchicine, and so forth. Farther research has conclusively shown that at present no ptomaine is known which so closely resembles a vegetable poison as to be likely in skilled hands to cause confusion.
§ 649. Gautier’s[653] Process.—The liquid is acidified with oxalic acid, warmed, filtered, and distilled in a vacuum.
[653] Ptomaines et Leucomaines, E. J. A. Gautier, Paris, 1886.
In this way pyrrol, skatol, phenol, indol, and volatile fatty acids are separated and will be found in the distillate. The residue in the retort is treated with lime, filtered from the precipitate that forms, and distilled in a vacuum, the distillate being received in weak sulphuric acid. The bases accompanied with ammonia distil over. The distillate is now neutralised by sulphuric acid[654] and evaporated nearly to dryness, separating the mother liquid from sulphate of ammonia, which crystallises out. The mother liquids are treated with absolute alcohol, which dissolves the sulphates of the ptomaines. The alcohol is got rid of by evaporation, the residue treated with caustic soda, and the bases shaken out by successive treatment with ether, petroleum ether, and chloroform. The residue remaining in the retort with the excess of lime is dried, powdered, and exhausted with ether; the ethereal extract is separated, evaporated to dryness, the dry residue taken up in a little water, slightly acidulated, and the bases precipitated by an alkali.
[654] The first acid apparently is so dilute that the distillate more than neutralises it, hence more sulphuric acid is added to complete neutralisation.
§ 650. Brieger’s Process.—Brieger[655] thus describes his process:—
[655] Untersuchungen über Ptomaine, Theil iii., Berlin, 1886.
“The matters are finely divided and boiled with water feebly acidulated with hydrochloric acid.
“Care must be taken that on boiling, the weak acid reaction must be retained, and that this manipulation only lasts a few minutes.
“The insoluble portion is filtered off, and the filtrate evaporated, either in the gas-oven or on the water-bath, to syrupy consistency. If the substances are offensive, as alcoholic and watery extracts of flesh usually are, the use of Bocklisch’s simple apparatus (see diagram) is to be recommended. The filtrate to be evaporated is placed in a flask provided with a doubly perforated caoutchouc cork carrying two bent tubes; the tube b terminates near the bottom of the flask, while the tube a terminates a little above the level of the fluid to be evaporated. The tube a is connected with a water pump which sucks away the escaping steam. In order to avoid the running back of the condensed water forming in the cooler part of the tube, the end of the tube a is twisted into a circular form. Through the tube b, which has a fine capillary bore, a stream of air is allowed to enter, which keeps the fluid in constant agitation, continually destroying the scum on the surface, and avoiding sediments collecting at the bottom, which may cause fracture of the flask. According to the regulation of the air current, a greater or smaller vacuum can be produced. The fluid, evaporated to the consistency of a syrup, is treated with 96 per cent. alcohol, filtered, and the filtrate precipitated with lead acetate.
“The lead precipitate is filtered off, the filtrate evaporated to a syrup, and the syrup again treated with 96 per cent. alcohol. This is again filtered, the alcohol got rid of by evaporation, water added, the lead thrown down by SH2, and the fluid, after the addition of a little hydrochloric acid, evaporated to the consistence of a syrup; this syrup is exhausted with 96 per cent. alcohol, and precipitated with an alcoholic solution of mercury chloride. The mercury precipitate is boiled with water, and by the different solubility of the mercury salts of certain ptomaines some separation takes place. If it is suspected that some of the ptomaines may have been separated with the lead precipitate, this lead precipitate can be decomposed by SH2 and investigated. I have only (says Brieger) in the case of mussels been able to extract from the lead precipitate small quantities of ptomaines.
“The mercury filtrate is freed from mercury and evaporated, the excess of hydrochloric acid being carefully neutralised by means of soda (for it must only be slightly acid); then it is again treated with alcohol, so as to separate as much as possible the inorganic constituents. The alcoholic extract is evaporated, dissolved in a little water, neutralised with soda, acidulated with nitric acid, and precipitated with phospho-molybdic acid. The phospho-molybdic acid precipitate is decomposed with neutral lead acetate, which process may be facilitated by heating on the water-bath. After getting rid of the lead by treatment with SH2, the fluid is evaporated to a syrup and alcohol added, by which process many ptomaines may be eliminated as hydrochlorates; or they can be converted into double salts (of platinum or gold) for the purpose of separation. In the filtrate from phospho-molybdate, ptomaines may also be found by treating with lead acetate to get rid of the phospho-molybdic acid, and then adding certain reactives. Since it is but seldom that the hydrochlorates are obtained in a state of purity, it is preferable to convert the substance separated into a gold or platinum salt or a picrate, since the greater or less solubility of these compounds facilitates the purification of individual members; but which reagent is best to add, must be learned from experience. The melting-point of these salts must always be taken, so that an idea of their purity may be obtained. It is also to be noted that many gold salts decompose on warming the aqueous solution; this may be avoided by the addition of hydrochloric acid. The hydrochlorates of the ptomaines are obtained by decomposing the mercury, gold, or platinum combinations by the aid of SH2, while the picrates can be treated with hydrochloric acid and shaken up with ether, which latter solvent dissolves the picric acid.
“Considerable difficulty in the purification of the ptomaines is caused by a nitrogenous, amorphous, non-poisonous, albumin-like substance, which passes into all solutions, and can only be got rid of by careful precipitation with an alcoholic solution of lead acetate, in which it is soluble in excess. This albuminoid forms an amorphous compound with platinum, and acts as a strongly reducing agent (the platinum compound contains 29 per cent. platinum). When this albuminoid is eliminated, then the hydrochlorates or the double salts of the ptomaines crystallise.”
§ 651. The Benzoyl Chloride Method.—The fatty diamines in dilute aqueous solutions, shaken with benzoyl chloride and soda, are converted into insoluble dibenzoyl derivatives; these may be separated from benzamide and other nitrogenous products by dissolving the precipitate in alcohol, and pouring the solution into a large quantity of water.[656] Compounds which contain two amido groups combined with one and the same carbon atom, do not yield benzoyl derivatives when shaken with benzoyl chloride and soda. Hence this reaction can be utilised for certain of the ptomaines only. The solution must be dilute, because concentrated solutions of creatine, creatinine, and similar bodies also give precipitates with benzoyl chloride; no separation, however, occurs unless these bodies are in the proportion of five per thousand.
[656] L. V. Udrànsky and Baumann, Ber., xxi. 2744.
The process is specially applicable for the separation of ethylenediamine, pentamethylenediamine (cadaverine), and tetramethylenediamine (putrescine) from urine. In a case of cystinuria Udrànsky and E. Baumann[657] have found 0·24 grm. of benzoyltetramethylenediamine, 0·42 grm. of benzoylpentamethylenediamine in a day. Diamines are absent in normal fæces and urine. Stadthagen and Brieger[658] have also found, in a case of cystinuria diamines, chiefly pentamethylenediamine.
[657] L. V. Udrànsky and Baumann, Zeit. f. physiol. Chem., xiii. 562.
[658] Arch. pathol. Anatom., cxv. p. 3.
The operation is performed by making the liquid alkaline with soda, so that the alkalinity is equal to about 10 per cent., adding benzoyl chloride, shaking until the odour of benzoyl chloride disappears, and then filtering; to the filtrate more benzoyl chloride is added, the liquid shaken, and, if a precipitate appears, this is also filtered off, and the process repeated until all diamines are separated.
The precipitate thus obtained is dissolved in alcohol, and the alcoholic solution poured into a considerable volume of water and allowed to stand over night; the dibenzoyl compound is then usually found to be in a crystalline condition. The compound is crystallised once or twice from alcohol or ether, and its melting-point and properties studied. Mixtures of diamines may be separated by their different solubilities in ether and alcohol.
A solution of 0·00788 grm. of pentamethylenediamine in 100 c.c. of water gave 0·0218 grm. of the dibenzoyl-derivative when shaken with benzoyl chloride (5 c.c.) and 40 c.c. of soda (10 per cent.) and kept for twenty-four hours. In a second experiment with a similar solution only 0·0142 grm. of dibenzoyl-derivative was obtained;[659] hence the process is not a good quantitative process, and, although convenient for isolation, gives, so far as the total amount recovered is concerned, varying results.
[659] Ber., xxi. 2744.
§ 652. The Amines.—The amines are bases originating from ammonia and built on the same type. Those that are interesting as poisons are monamines, diamines, and the quaternary ammonium bases.
Considered as compound ammonias, the amines are divided into primary or amide bases, secondary or imid bases, and tertiary or nitrile bases, according as to whether one, two, or three atoms of hydrogen have been displaced from the ammonia molecule by an alkyl; for instance, methylamine NH2CH3 is a primary or amide base, because only one of the three atoms of H in NH3 has been replaced by methyl; similarly, dimethylamine is a secondary or imid base, and trimethylamine is a tertiary or nitrile base.
The quaternary bases are derived from the hypothetical ammonium hydroxide NH4OH, as, for example, tetraethyl ammonium hydroxide (C2H5)4N,OH.
The diamines are derived from two molecules of NH, and therefore contain, instead of one molecule of nitrogen, two molecules of nitrogen; in two molecules of ammonia there are six atoms of hydrogen, two, four, or six of which may be replaced by alkyls; as, for example,
| Ethylenediamine. | Diethylenediamine. | Triethylenediamine. |
The monamines are similar to ammonia in their reactions; some of them are stronger bases; for instance, ethylamine expels ammonia from its salts. The first members of the series are combustible gases of pungent odour, and easily soluble in water; the higher homologues are fluids; and the still higher members solids.
The hydrochlorides are soluble in absolute alcohol, while chloride of ammonium is insoluble; this property is taken advantage of for separating amines from ammonia. The amines form double salts with platinic chloride; this is also utilised for recognition, for the purpose of separation, and for purification; for instance, ammonium-platinum-chloride on ignition yields 43·99 per cent. of platinum, and methylamine-platinum-chloride yields 47·4 of platinum. It is comparatively easy to ascertain whether an amine is primary, secondary, or tertiary.
The primary and secondary amines react with nitrous acid, but not the tertiary; the primary amines, for instance, are converted into alcohols, and there is an evolution of nitrogen gas; thus methylamine is decomposed into methyl alcohol, nitrogen, and water.
CH3NH2 + (OH)NO = CH3(OH) + N2 + H2O.
The secondary amines, treated in the same way, evolve no nitrogen, but are converted into nitrosamines; thus dimethylamine, when treated with nitrous acid, yields nitrosodimethylamine,
(CH3)2NH + (OH)NO = (CH3)2(NO)N + H2O;
and the nitrosamines respond to the test known as Lieberman’s nitroso-reaction, which is thus performed:—The substance is dissolved in phenol and a few drops of concentrated sulphuric acid added. The yellow colour at first produced changes into blue by adding to the acid liquid a solution of potash.
The primary amines, and the primary amines alone, treated with chloroform and alcoholic potash, yield the peculiarly offensive smelling carbylamine or isonitrile (Hofmann’s test),
| V | |
| NH2(CH3) + CHCl3 + 3KOH = C≣N | -CH3 + 3KCl + 3H2O. |
Again the primary bases, when treated with corrosive sublimate and carbon disulphide, evolve sulphuretted hydrogen, and mustard oil is produced, e.g.,
| NH2(C2H5) | + | CS2 | = | CS=N-C2H5 | + | H2S. |
| Ethylamine. | Ethylmustard oil. |
|||||
Where a sufficient quantity of an amine is obtained, the primary, secondary, or tertiary character of the amine may be deduced with certainty by treating it with methyl or ethyl iodide.
A molecule of the base is digested with a molecule of methyl iodide and distilled with potash; the distillate is in the same manner again treated with methyl iodide and again distilled; and the process is repeated until an ammonium base is obtained, which will take up no more iodide. If three methyl groups were in this way introduced, the original substance was primary, if two, secondary, if one, tertiary.
The quaternary bases, such as tetraethyl ammoniumoxhydrate, decompose, on heating, into triethylamine and ethylene; the corresponding methyl compound in like manner yields trimethylamine and methyl-alcohol.
On the other hand, the primary, secondary, and tertiary bases do not decompose on heating, but volatilise without decomposition.
The chief distinctions between these various amines are conveniently put into a tabular form as follows:—
| Primary, NH2R. |
Secondary, NHR2. |
Tertiary, NR3. |
Quaternary, NR4(OH). |
|
|---|---|---|---|---|
| On treating with methyl iodide it takes up the following number of methyl groups, | 3 | 2 | 1 | ... |
| Reaction with nitrous acid, | Decomposes with evolution of nitrogen gas. | Formation of nitrosamine. | ... | ... |
| Mustard oil, &c., on treatment with CS2 and sublimate, | Mustard oil formed. | ... | ... | ... |
| Chloroform and alcoholic potash, | Formation of carbylamine. | ... | ... | ... |
| Effect of strong heat, | Sublimes. | Sublimes. | Sublimes. | Decomposes. |
| On addition of acids, | Combines to form salts. | Combines to form salts. | Combines to form salts. | ... |
§ 653. Methylamine, CH3NH2.—This is a gas at ordinary temperatures; it is inflammable, and possesses a strong ammoniacal odour. It has been found in herring brine, and is present in cultures of the comma bacillus; it has also been found in poisonous sausages, but it is not in itself toxic.
It forms crystalline salts, such as, for example, the hydrochloride, the platinochloride (Pt = 41·4 per cent.), and the aurochloride (Au = 53·3 per cent. when anhydrous). The best salt for estimation is the platinochloride, insoluble in absolute alcohol and ether.
§ 654. Dimethylamine, (CH3)2NH.—Dimethylamine is also a gas; it has been found in various putrefying substances. It forms crystalline salts, such as the hydrochloride, the platinochloride (Pt = 39·1 per cent.), and an aurochloride (Au = 51·35 per cent.). It is not poisonous.
In Brieger’s process it may occur in both the mercuric chloride precipitate and filtrate. From cadaverine it may be separated by platinum chloride; cadaverine platinochloride is with difficulty soluble in cold water and crystallises from hot water, while dimethylamine remains in the mother liquor. From choline it may be separated by recrystallising the mercuric precipitate from hot water. From methylamine it may be separated by converting into chloride and extracting with chloroform; dimethylamine chloride is soluble, methylamine chloride insoluble in chloroform.
§ 655. Trimethylamine, (CH3)3N.—Trimethylamine in the free state is an alkaline liquid with a fishy odour, boiling at 9·3°; it is not toxic save in large doses.
It occurs in a great variety of plants, and is also found in putrefying substances. It is a product of the decomposition of choline, betaine, and neuridine, when these substances are distilled with potash.
In Brieger’s process, if an aqueous solution of mercuric chloride is used as the precipitant, trimethylamine (if present) will be almost entirely in the filtrate, from which it can be obtained by getting rid of the mercury by SH2, filtering, evaporating to dryness, extracting with alcohol, and precipitating the alcoholic solution with platinic chloride. It forms crystalline salts with hydrochloric acid, platinum chloride, and gold chloride; the platinum double salt yields 37 per cent. of platinum, the gold salt 49·4 per cent. gold. The gold salt is easily soluble, and this property permits its separation from choline, which forms a compound with gold chloride soluble with difficulty.
§ 656. Ethylamine, C2H5NH2.—Ethylamine is in the free state an ammoniacal liquid boiling at 18·7°. It is a strong base, miscible with water in every proportion. It has been found in putrefying yeast, in wheat flour, and in the distillation of beet sugar residues. It is not poisonous; the hydrochloride forms deliquescent plates melting at 76°-80°; the platinochloride contains 39·1 per cent. of platinum, and the gold salt 51·35 per cent. of gold. In other words, the same percentages as the corresponding salts of dimethylamine, with which, however, it cannot be confused.
§ 657. Diethylamine, (C2H5)2NH, is an inflammable liquid boiling at 57·5°; it forms salts with hydrochloric acid, platinum and gold, &c.; the gold salt contains 47·71 per cent. of gold, and its melting-point is about 165°.
§ 658. Triethylamine, (C2H5)3N, is an oily base but slightly soluble in water, and boiling at 89°-89·5°. It gives no precipitate with mercuric chloride in aqueous solution; it forms a platinochloride containing 31·8 per cent. of platinum. It has been found in putrid fish.
§ 659. Propylamine.—There are two propylamines; one, normal propylamine, CH3CH2.CH2.NH2, boiling at 47°-48°, and iso-propylamine, (CH3)2CH.NH2, boiling at 31·5°; both are ammoniacal fish-like smelling liquids. The hydrochloride of normal propylamine melts at 155°-158°, and iso-propylamine chloride melts at 139·5°.
It has been found in cultures of human fæces on gelatin. None of the above amines are sufficiently active in properties to be poisonous in the small quantities they are likely to be produced in decomposing foods.
§ 660. Iso-amylamine, (CH3)2CH.CH2.CH2.NH2, is a colourless alkaline liquid, possessing a peculiar odour. It boils at 97°-98°. It forms a deliquescent hydrochloride. The platinochloride crystallises in golden yellow plates.
Iso-amylamine occurs in the putrefaction of yeast, and is a normal constituent of cod-liver oil. It is intensely poisonous, producing convulsions.
§ 661. Rate of Formation of Diamines.—Diamines are formed in putrefactive processes, generally where there is abundance of nitrogen. Garcia[660] has attempted to trace the rates at which they are formed by allowing meat extracts to decompose, precipitating by benzoyl chloride (see p. 487) the dibenzoyl compound, and weighing; the following were the results obtained:—
[660] Zeit. f. physiol. Chemie, xvii. 6. 571.
| Time. | Weight of benzoyl compound. |
|
|---|---|---|
| 24 hours, | 0·56 | grm. |
| 2 days, | 0·75 | „ |
| 3 days, | 0·82 | „ |
| 4 days, | 0·73 | „ |
| 5 days, | 0·57 | „ |
| 6 days, | 0·58 | „ |
§ 662. Ethylidenediamine.—Brieger found in putrid haddock, in the filtrate from the mercury chloride precipitate:—gadinine, neuridine, a base isomeric with ethylenediamine C2H8N2 (but which Brieger subsequently more or less satisfactorily identified with ethylidenediamine), muscarine, and triethylamine; these bases were separated as follows:—
The filtrate from the mercury chloride solution was freed from mercury by SH2, evaporated to a syrup, and then extracted with alcohol. From the alcoholic solution platinum chloride precipitated neuridine, this was filtered off, the filtrate freed from alcohol and platinum, and the aqueous solution concentrated to a small volume and precipitated with an aqueous solution of platinum chloride; this precipitated ethylidene platinum chloride. The mother liquor from this precipitate was concentrated on the water-bath, and, on cooling, the platinochloride of muscarine crystallised out. From the mother liquor (freed from the crystals), on standing in a desiccator, the gadinine double salt crystallised out, and from the mother liquor (freed from gadinine after removal of the platinum by SH2) distillation with KHO recovered trimethylamine.
From the platinochloride of ethylenediamine, the chloride can be obtained by treating with SH2, filtering, and evaporating; by distilling the chloride with a caustic alkali, the free base can be obtained by distillation.
Ethylidenediamine is isomeric with ethylenediamine, but differs from it in the following properties:—ethylidenediamine is poisonous, ethylenediamine is non-poisonous.
Ethylenediamine forms a platinochloride almost insoluble in hot water, while the ethylidene salt is more easily soluble. The properties of the gold salts are similar, ethylenediamine forming a difficultly soluble gold salt, ethylidene a rather soluble gold salt.
Ethylidenediamine forms a hydrochloride, C2H8N22HCl, crystallising in long glistening needles, insoluble in absolute alcohol, rather soluble in water. The hydrochloride gives precipitates in aqueous solution with phospho-molybdic acid, phospho-antimonic acid, and potassium bismuth iodide; the latter is in the form of red plates.
The platinochloride, C2H8N22HCl.PtCl (Pt = 41·5 per cent.), is in the form of yellow plates, not very soluble in cold water.
Ethylidenediamine, when subcutaneously injected into guinea-pigs, produces an abundant secretion from the mucous membranes of the nose, mouth, and eyes. The pupils dilate, and the eyeballs project. There is acute dyspnœa; death takes place after some twenty-four hours, and the heart is stopped in diastole.
Trimethylenediamine is believed to have been isolated by Brieger from cultivations in beef broth of the comma bacillus.
It occurs in small quantity in the mercuric chloride precipitate, and is isolated by decomposing the precipitate with SH2, evaporating the filtrate from the mercury sulphide to dryness, taking up the residue with absolute alcohol, and precipitating by an alcoholic solution of sodium picrate. The precipitate contains the picrate of trimethylenediamine, mixed with the picrates of cadaverine and creatinine. Cadaverine picrate is insoluble in boiling absolute alcohol, the other picrates soluble; so the mixed picrates are boiled with absolute alcohol, and the insoluble cadaverine filtered off. Next, the picrates of creatinine and trimethylenediamine are freed from alcohol, the solution in water acidified with hydrochloric acid, the picric acid shaken out by treatment with ether, and then the solution precipitated with platinum chloride; the platinochloride of trimethylenediamine is not very soluble, while creatinine easily dissolves; so that separation is by this means fairly easy.
It also gives a difficultly soluble salt with gold chloride.
The picrate consists of felted needles, melting-point 198°. Phospho-molybdic acid gives a precipitate crystallising in plates; potassium bismuth iodide gives dark coloured needles.
It produces in animals violent convulsions and muscular tremors; but the substance has hitherto been obtained in too small a quantity to be certain as to its identification and properties.
§ 663. Neuridine, C5H14N2.—Neuridine is a diamine, and is apparently the most common basic product of putrefaction; it has been obtained from the putrefaction of gelatin, of horseflesh, of fish, and from the yelk of eggs. It is usually accompanied by choline, from which it can be separated by converting the bases into hydrochlorides, choline hydrochloride being soluble in absolute alcohol, neuridine scarcely so. Brieger isolated neuridine from putrid flesh by precipitating the watery extract with mercuric chloride. He decomposed the mercury precipitate with SH2, and, after having got rid of the sulphide of mercury by filtration, he concentrated the liquid to a small bulk, when a substance separated in crystals similar in form to urea; this was purified by recrystallisation from absolute alcohol, and converted into the platinum salt.
Another method which may be used for the separation and purification of neuridine is to dissolve it in alcohol and precipitate with an alcoholic solution of picric acid; the picrate may be decomposed by treatment with dilute mineral acid, and the picric acid removed by shaking with ether.
The free base has a strong seminal odour. It is gelatinous, and has not been crystallised. It is insoluble in ether and in absolute alcohol, and not readily soluble in amyl alcohol. It gives white precipitates with mercuric chloride, neutral and basic lead acetates. It does not give Hofmann’s isonitrile reaction. When distilled with a fixed alkali, it yields di- and trimethylamine.
The hydrochloride, C5H14N22HCl, crystallises in long needles, which are insoluble in absolute alcohol, ether, benzol, chloroform, petroleum ether, and amyl alcohol; but the hydrochloride is very soluble in water and in dilute alcohol.
The hydrochloride gives no precipitate with mercuric chloride, potass-mercuric iodide, potass-cadmium iodide, iodine and iodide of potassium, tannic acid, ferricyanide of potassium, ferric chloride, and it does not give any colour with Fröhde’s reagent.
On the other hand, phosphotungstic acid, phospho-molybdic acid, picric acid, potass-bismuth iodide, platinum chloride, and gold chloride all give precipitates.
Neuridine hydrochloride is capable of sublimation, and at the same time it is decomposed, for the sublimed needles show red or blue colours.
Neuridine platinochloride, C5H14N22HCl.PtCl4, yields 38·14 per cent. of platinum; it crystallises in flat needles, soluble in water, from which it is precipitated on the addition of alcohol.
The aurochloride has the formula C5H14N22HCl2AuCl3; it is rather insoluble in cold water, and crystallises in bunches of yellow needles. On ignition, it should yield 41·19 per cent. of gold.
The picrate, C5H14N2,2C6H2(NO2)3OH, is almost insoluble in cold water, and crystallises in needles. It is not fusible, but decomposes at about 230°.
Neuridine is not poisonous.
§ 664. Cadaverine (Pentamethylenediamine, C5H14N2=NH2CH2-CH2-CH2-CH2CH2NH2) is formed in putrid animal matters, and in cultures of the genus Vibrio. It has been found in the urine and fæces in cases of cystinuria, and Roos[661] has separated it by the benzoyl-chloride method from the fæces of a patient suffering from tertian ague. It may be formed synthetically by dissolving trimethylcyanide in absolute alcohol, and then reducing by sodium (Mendius’ reaction).