Chloral
CHLORAL, or Trichloracetaldehyde, CCl3·CHO, a substance discovered by J. von Liebig in 1832 (Ann., 1832, 1, p. 189) and further studied by J.B.A. Dumas and Staedeler. It is a heavy, oily and colourless liquid, of specific gravity 1.541 at 0° C., and boiling-point 97.7° 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 chlorine, and dissolves bromine, iodine, phosphorus and sulphur. Chloral deliquesces in the air, and is converted by water into a hydrate, with evolution of heat; it combines with alcohols and mercaptans. An ammoniacal solution of silver nitrate is reduced by chloral; and nascent hydrogen converts it into aldehyde. By means of phosphorus pentachloride, chlorine can be substituted for the oxygen of chloral, the body CCl3·CCl2H being produced; an analogous compound, CCl3·C(C6H5)2H, is obtained by treating chloral with benzene and sulphuric acid. With an alkali, chloral gives chloroform (q.v.) and a formate; oxidizing agents give trichloracetic acid, CCl3·CO(OH). 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 (C2Cl3OH)3, a white porcellaneous body, slowly volatile in the air, and reconverted into chloral without melting at 180° C. Chloral unites directly with hydrocyanic acid to form β-trichloracetonitrile, CCl3·CH(OH)CN, and with hydroxylamine it forms chlorglyoxime, C2H3ClN2O2.
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 is converted finally into a syrupy fluid, from which chloral is procured by treatment with sulphuric acid (see P. Fritsch, Ann., 1894, pp. 279, 288). 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 (A. Staedeler, Ann. Ch. Pharm., 1847, 61, p. 101). An isomer of chloral, parachloralide, is made by passing excess of dry chlorine into absolute methyl alcohol.
Chloral hydrate, CCl3·CH(OH)2, forms oblique, often very short, rhombic prisms. The crystals are perfectly transparent, only slightly odorous, free from powder, and dry to the touch, and do not become white by exposure. The melting-point of pure chloral hydrate is 57°, the boiling-point 96-98° C. When heated with sulphuric acid it is converted into anhydrous chloral and chloralide, C6H2Cl6O3. 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 movements. Chloral hydrate does not restore the colour to a solution of fuchsine which has been decolorized by sulphurous acid, and so one must assume that the water present is combined in the molecular condition (V. Meyer, Ber., 1880, 13, p. 2343). Chloral may be estimated by distilling the hydrate with milk of lime and measuring the volume of chloroform produced (C.H. Wood, Pharm. Journ., (3) 1, p. 703), or by hydrolysis with a known volume of standard alkali and back titration with standard acid (V. Meyer, Ber., 1873, 6, p. 600). 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 glycerin, according to J. Personne, is suitable for the preservation of anatomical preparations. When heated with concentrated glycerin to a temperature of 110° to 230° C, chloral hydrate yields chloroform, CHCl3, and allyl formate, HCO(OC3H5).
Pharmacology and Therapeutics. - The breaking up of chloral hydrate, in the presence of alkalis, with the production of chloroform and formates, led Liebreich to 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. It is now known, however, that the drug circulates in the blood unchanged, and is excreted in the form of urochloralic acid. The dose is from five to twenty grains or somewhat more, and it is often given in the form of the pharmacopoeial Syrupus Chloral, which contains ten grains of chloral hydrate to the fluid drachm. Chloral hydrate must be well diluted when given by the mouth, as otherwise it may cause considerable gastro-intestinal irritation. In large doses chloral hydrate is a depressant to the circulation and the respiration, and also lowers the temperature. In the above doses the drug is a powerful and safe hypnotic, acting directly on the brain, and producing no preliminary stage of excitement. Very soon - perhaps twenty minutes - after taking such a dose, the patient falls into a sleep which lasts several hours, and is not distinguishable from natural sleep. When he wakes, it is without disagreeable after-symptoms, but with a feeling of natural refreshment. The pupils are always contracted under its influence, except in large doses. There is also rapidly induced a depression of the anterior horns of grey matter in the spinal cord, and as the symptoms of strychnine poisoning are due to violent stimulation of these areas, chloral hydrate is a valuable antidote in such cases. It should not be hypodermically injected. Its disadvantages are that it is powerless when there is pain, resembling in this feature nearly all hypnotics except opium (morphine) and hyoscin. Its action on the gastro-intestinal canal and on the respiratory and circulatory systems renders its use inadvisable when disease of these organs is present. Its action on the spinal cord has been employed with success in cases of tetanus, whooping-cough, urinary incontinence, and strychnine poisoning. In the latter case twenty grains in "normal saline" solution may be directly injected into a subcutaneous vein, but not into the subcutaneous tissues.
Toxicology. - In cases of acute poisoning by chloral hydrate, the symptoms may be summarized as those of profound coma. The treatment is to give a stimulant emetic such as mustard; to keep up the temperature by hot bottles, etc.; to prevent or disturb the patient's morbid sleep by the injection of hot strong coffee into the rectum; and by shouting, flipping with towels, etc.; to use artificial respiration in extreme cases; and to inject strychnine. Strychnine is much less likely, however, to save life after poisoning by chloral hydrate, than chloral hydrate is to save life in poisoning by strychnine.
Chronic poisoning by chloral is a most pernicious drug-habit. The vice is easily and very rapidly acquired. The victim is usually excited and loquacious. He is easily fatigued and suffers from attacks of easily induced syncope. There are signs of gastro-intestinal irritation, and a tendency to cutaneous eruptions of an erythematous type. The patient may succumb to a dose only slightly larger than usual. The treatment is on general principles, there being no specific remedy. The patient must be persuaded to put himself under restraint, and the drug must be stopped at once and entirely.
Note - this article incorporates content from Encyclopaedia Britannica, Eleventh Edition, (1910-1911)
