1902 Encyclopedia > Chloral


CHLORAL, TRICHLORALDEHYDE, or HYDRIDE OF TRI-CHLORACETYL, C2C130H or CCI3.COH, a substance dis-covered by Liebig in 1832, and further studied by Dumas and Stadeler. It is a heavy, oily, and colourless liquid, of specific gravity 1*518 at 0° O, and boiling point 94°-4 C. It has a greasy, somewhat bitter taste, and gives off a vapour at ordinary temperature which has a pungent odour and an irritating effect on the eyes. The word chloral is derived from the first syllables of chlorine and alcohol, the, names of the substances employed for its preparation. Chloral is soluble in alcohol and ether, in less than its own weight of water, and in four times its weight of chloroform; it absorbs but is not acted upon by chlorine, and dissolves bromine, iodine, phosphorus, and sulphur. Chloral deli-quesces in the air, and, like aldehyde, is converted by water into a hydrate, with evolution of heat; it combines also with ethylic alcohol and its homologues, and the derived mercaptans. An ammoniacal solution of nitrate of silver is reduced by chloral; sulphites of the alkalies form with it crystalline compounds; and nascent hydrogen, by replacing its three atoms of chlorine, converts it into aldehyde (Personne, Ann. Ch. Pharm., clvii. 113). By means of phosphorus pentachloride, chlorine can be substi-tuted for the oxygen of chloral, the body CC13.CC12H being produced ; an analogous compound, CC13.C(C6H6)2H. containing the radicle phenyl in the place of the oxygen, is obtained by treating chloral with benzene and sulphuric acid. With an alkali, chloral gives chloroform and a formate of the base according to the reaction CCl3.COH + KHO = CC13H + H.CO(OK) ; it is converted by oxidiz-ing agents into trichloracetic acid CCl3.CO(OH); and forms with cyanic acid the body C5H3ClaN03 = (CC13.C0H)2 'COHN. When kept for some days, as also when placed in contact with sulphuric acid or a very small quantity of water, chloral undergoes spontaneous change into the polymeride metachloral, C^HjClgOj = (C2C130H)3, a white porcelaneous body, slowly volatile in the air, insoluble in water, alcohol, and ether, and reconverted into chloral without melting at 180° C.

Chloral is prepared by passing dry chlorine into absolute alcohol; the latter must be cooled at first, but towards the end of the operation has to be heated nearly to boiling. The alcohol becomes converted finally into a syrupy fluid, from which chloral is procured by treatment with sulphuric acid. The action of chlorine upon alcohol is complex ;— first aldehyde, CH3.COH, is produced, which combines with alcohol to form acetal, CH3.CH(OC2H5)2; this, acted on by chlorine, yields trichloracetal, CClg.CH(OC2H5)2, which is converted by the hydrochloric acid present into chloral alcohólate, CCl3.CH.OH.OC2H6, and monochlor-ethane, C2H5C1. The latter body is also formed directly from alcohol, in the process for the manufacture of chloral, and combines with aldehyde, giving monochlorinated ethylic ether, CH3CHC1.0C2H5, which is converted by chlorine into tetrachlorinated ether, CC13.CHC1.0C2H6. By the action of sulphuric acid, chloral alcohólate and tetrachlorinated ether are resolved into alcohol and chloral, and monochlorethane and chloral, respectively. The crude chloral is distilled over lime, and is purified by further treatment with sulphuric acid, and by redistillation.

A mixture of starch, or sugar with manganese peroxide and hydrochloric acid may be employed instead of alcohol and chlorine for the manufacture of chloral (Stadeler, Ann. Oh. Pharm., lxi. 101-121). An isomer of chloral, parachloralide, is made by passing excess of dry chlorine into absolute methylic alcohol; it is a colourless liquid, insoluble in water, and boils at 182° C. (Cloez, Ann. Oh. Pharm., iii. 180).

Chloral hydrate, C2C130H.H20, or CC13.CH(0H)2, the compound formed by the union of water with chloral, occurs in the form of oblique, often very short, rhombic prisms ; an acicular form of crystals is considered by Paul to be characteristic only of the alcohólate. The purest samples of chloral hydrate present the appearance of ordinary alum broken into fragments, are perfectly transparent, only slightly odorous, free from powder, and dry to the touch, and do not become white by exposure. Jacobsen gives the melting point of pure chloral hydrate as 50° to 51°, the boiling point as 99° C. It can be distilled unchanged at 120°C.; but when heated with sulphuric acid it is converted into anhydrous chloral and chloralide, C5H2C1603. When mixed with water, chloral hydrate causes a considerable degree of cold; and, as with camphor, small fragments of it placed on the surface of water exhibit gyratory move-ments. An aqueous solution should bo neutral or nearly so, and should give but a faint milkiness when boiled with Bilver nitrate. A drop or two of ammonia added to solu-tions assists in their preservation. Chloral hydrate may be detected in the presence of other substances by adding an alkali and heating, when chloroform is evolved, which may be collected in a receiver; this process can be employed for the estimation of the commercial hydrate. When ammonium sulphide is added to a solution of pure chloral hydrate, the liquid turns red, and then becomes rapidly brown and thick ; the presence of oily impurities in a solution is shown by the brown colour it acquires when shaken up with concentrated sulphuric acid. Chloral hydrate has the property of checking the decomposition of a great number of albuminous substances, such as milk and meat; and a mixture of it with glycerine, according to Personne, is suitable for the preservation of anatomical preparations. When heated with concentrated glycerine to a temperature of 110°-230°C., chloral hydrate yields chloroform, CHC13, and formate of allyl, HCO(OC3H5) ; and by the action of nitric acid and strong sunlight, at 195° C. it is transformed into trichloracetic acid, CCl3.COOH. The effect of chloral hydrate upon fresh blood, like that of formic acid, is to render it darker.

The breaking up of chloral hydrate, in the presence of alkalies, with the production of chloroform and formates, led Liebreichto the conjecture that a similar decomposition might be produced in the blood; and hence his introduction of the drug, in 1869, as an anaesthetic and hypnotic (Compt. rend., 1869, lxix., 486). It has been supposed that its physiological action may be due to formic acid as well as to chloroform set free in the blood, the effects of the formic acid being attributed to the production from it of carbon dioxide. Personne, however, has administered sodium formate to dogs, without perceiving in them the slightest anaesthetic phenomena, or the abnormal formation of carbon dioxide (Compt. rend., 1874, lxxviii. 129). He considers that chloroform is set free in the blood, but is not eliminated as such, being converted into sodium chloride and formate (ibid. 1869, lxix., 983); the prolonged action of chloral on the animal economy he explains on the supposition that, chloroform being produced at the expense of the alkali of the albumen of the blood, the latter, which may be regarded as an amide, forms with the trichlorinated aldehyde chloral a compound which, by the gradual action of fhe blood, affords a continuous supply of chloroform.

Tanret, on the other hand, suggests that as chloral hydrate, when made alkaline with caustic potash, yields in the presence of the oxidizing agent potassium permanganate the formate, chloride, and carbonate of potassium, together with carbon monoxide, the alkalinity of the serum of the blood may determine a similar decomposition of chloral hydrate, the physiological effects of which may therefore be ascribed to poisoning or deoxidation of arterial blood by carbon monoxide (Compt. rend., lxxix. 662 ; Joum. Pharm. Chim. (4), xx. 355-357).

The first effect of a dose of chloral hydrate is to produce a state of congestion of the brain, as evidenced by the con-dition of the retinal vessels ; after 5 or 10 minutes, con-traction of the vessels is observed, the retina becomes of a pale pink colour, and drowsiness ensues ; when this wears off, the retinal and cerebral vessels resume their accustomed size (Dr W. A. Hammond). In cases of death from chloral, the cerebral vessels have been found much congested.

The effects of chloral hydrate vary with different individuals; but, as a rule, a dose of 20 grains acts in a healthy subject as a mild sedative of the sensory nervous system, and produces, about half or three quarters of an hour after it has been taken, a light, refreshing, and normal sleep, without causing headache or disturbance of the respiration and pulse.

Taken in large quantities chloral hydrate is a powerful soporific; it perceptibly lowers the temperature of the body, and diminishes the frequency and force of the heart's action, probably from paralysis of its intrinsic motor-ganglia ; whilst the rate of respiration is lessened, apparently through affection of the medulla oblongata. Ex-cessive doses produce complete insensibility, and diminish, and at last abolish reflex excitability; pallor, coldness of the extremities, lividity, and muscular relaxation ensue ; and death may result from cardiac syncope.

M Ore is the originator of a plan for performing opera-tions during anaesthesia produced by the intra-venous injection of chloral hydrate. He shows (Compt. rend., 1874, lxxviii. 515, 651) that it may be harmlessly injected, and that when thus brought into immediate contact with the blood, it effects complete anaesthesia of long duration, and is a rapid and effectual remedy for tetanus. Chloral hydrate sometimes fails to afford relief from suffering, and when it does not induce sleep, may occasion excitement and delirium. In some cases a dose has produced an eruption of urticaria. It must be administered with caution to children, and to patients having disease of the heart and of the digestive tract, certain affections of the bronchi, or hysteria. It appears that chloral cannot be decomposed and thrown off by a healthy body at a greater rate than from 5 to 7 grains an hour (Richardson, Lancet, 1871, 1, 209); and as the limit of the dose that can be safely taken is not affected by the customary use of the drug, as in the case of opium, but rather the reverse, its incautious employment in large quantities, and the practise of habitually resorting to it to gain relief from sleeplessness, from neuralgia, and from the effects of alcoholic excess, have in not a few instances led to fatal results. In consequence of this risk medical practitioners now use it less extensively. The continued use of chloral hydrate, too, is apt to cause 'a hyperaemic condition of the skin, diffuse inflammatory erythema of the face and chest, conjunctivitis, and interference with re-spiration ; and may bring on deep melancholy, weakness of will, and inability to sleep without the drug.

Chloral hydrate is of special value as a soporific where opium is inadmissible, as in the case of children, in uraemia, and in some fevers. It is used in delirium tremens, rabies, severe chorea, acute mania, and phthisis, as well as in dyspnoea, pertussis, cholera, sea-sickness, cancer, chronic rheumatism, and gastralgia, and in parturition and eclampsia.

and in cases of tetanus it is employed to produce muscular relaxation. Its antagonism to strychnia was first pointed out by Liebreich (Gompt, rend., 1870, lxx. 403). When administered to rabbits it has been found to be a remedy for poisonous doses of strychnia (Bennett, Edin. Med. J own., 1870, xvi. 262); but Ore has shown (Gaz. Medic, de Paris, 1872, p. 401) that the hypodermic injection of that drug is of no avail in the case of rabbits poisoned with fatal doses of chloral hydrate. Numerous experi-ments have led to the conclusions that " chloral hydrate is more likely to save life after a fatal dose of strychnia, than strychnia is to save life after a fatal dose of chloral hydrate ; " that after a dose of strychnine has produced tetanic convulsions, these convulsions may be reduced in force and frequency, and life may be saved, by means of the influence of chloral hydrate ; but that though the effects of a poisonous dose of the hydrate may be mitigated, the coma produced by its action on the brain is not removed by strychnia (Bennett, Report in Brit. Med. Jour., 1875, 1, 97; Ogiivie Will, Edin. Med. Jour., April 1875, 907). Chloral hydrate modifies the action of a fatal dose of extract of Calabar bean, but is of little service if given some time after the latter. The effects of chloralism are combated by provoking emesis, and by stimulating freely.

Among the very numerous contributions to the history of chloral, in addition to the above-given, may be mentioned the following :— Liebig, Ann. Ch. Pharm., i. 189; Dumas, Traité de Chimie, t. v. 599 ; Städeler, Ann. Ch. Pharm., cv. 293, evi. 253 ; Bouchut, Campt, rend., lxix. 966, Bull, de Thêr., lxxvii. 433 ; Sir J. Y. Simpson, Med. Times, Jan. 1, 1870 ; Byasson and Follet, Journ. de l'Anat. et de Physiol., 1870, 570; Hofmann, Campt, rend., 1870, lxx. 906; Personne, ibid., lxxi. 227; Paul, Pharm. Journ. and Trans. (3), i. 621 ; Hausemann, Schmidt's Jahrb., cli. 81 ; Jacobsen, quoted in Journ. Chem. Soc, ix. 257; Rokitansky, Strieker's Jahrbücher (iii. and iv. Heft), 1874. (F. H. B.)

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