CHLOROFORM.
History and Composition. Chloroform was first made in 1831 by two chemists who operated independently of each other. The liquid, which is formed by the union of equal volumes of chlorine and olefiant gas, and which is usually called Dutch liquid, was named chloric ether by Dr. Thos. Thomson (System of Chemistry, 6th ed., 1820). In consequence of a statement in Silliman’s Elements of Chemistry, that the alcoholic solution of this chloric ether was useful in medicine as a diffusible stimulant, Mr. Guthrie, an American chemist, attempted an easy method of obtaining it.[[37]] He distilled together chloride of lime and alcohol, and he considered that the product he had obtained was an alcoholic solution of the chloric ether of Dr. Thomson,[[38]] and it is still used in medicine under that name. About the same time, M. Soubeiran distilled together the above ingredients in France, and analysed the chloroform which he obtained. His analysis, which was incorrect, led him to name the liquid bichloric ether.[[39]] In 1832, Liebig examined the liquid which has been since named chloroform, but as he failed to detect the hydrogen which it contains, he called the liquid chloride of carbon,[[40]] a name which its alcoholic solution occasionally bore afterwards when used as a medicine. In 1831, Dumas examined this liquid. He proved that Soubeiran and Liebig had not obtained it pure, or had been incorrect in their analysis.[[41]] He showed that it consists of two atoms carbon, one atom hydrogen, and three atoms chlorine.
Dumas gave the name of chloroform to the liquid, on account of the relation it bears in composition to formic acid, which consists of two atoms carbon, one hydrogen, and three oxygen.[[42]] Liebig, who, in common with other chemists, admits the accuracy of Dumas’ analysis, has proposed the name of perchloride of formyle.[[43]] He supposes that the carbon and hydrogen which enter, in the same definite proportion, into numerous compounds, form a base which he calls formyle; and although this base has never been obtained in a separate form, its existence is well supported by analogy, and the term formyle is useful in assisting the memory to retain the composition of a number of substances. For all practical purposes, however, the medicine we are considering is likely to go by the name of chloroform. In the last edition of the London Pharmacopœia, the article has received a name intermediate between the other two. It is called chloroformyl, a name which departs from the brevity of the word chloroform, without having the merit of expressing the chemical constitution of the substance. I believe that no one uses the word chloroformyl; not even the Fellows of the College of Physicians in their individual capacity.
Mode of Preparation. Chloroform can be obtained in various ways, but the most convenient process, and the one which yields it in greatest purity, is that alluded to above, by which it was first procured. The following are the directions in the London Pharmacopœia for making it.
“Take of chlorinated lime, lb. iv; rectified spirit, Oss; water, Ox; chloride of calcium, broken in pieces, ʒj. Put the lime first mixed with the water into a retort, and add the spirit to them, so that the mixture may fill only the third part of the retort. Then heat them in a sand-bath, and as soon as ebullition begins, withdraw the heat as quickly as possible, lest the retort should be broken by the sudden increase of heat. Let the liquid distil into the receiver so long that there may be nothing which subsides, the heat being reapplied if necessary. To the distilled liquid add a quarter of the water, and shake them all well together. Carefully separate the heavier portion which subsides, and add the chloride to it, and frequently shake them for an hour. Lastly, let the liquid distil again from a glass retort into a glass receiver.”[[44]]
Some manufacturers of chloroform prefer to rectify it from dry carbonate of potassa, since they consider that it is liable to get an acid reaction from decomposition of the chloride of calcium, when it is distilled from that substance. The truth is, however, that there is very little occasion to use either of these substances; for the small quantity of water which chloroform can hold in solution is of no consequence.
Chemical and Physical Properties. Chloroform is a clear colourless liquid, having a hot and intensely sweet taste. It is not inflammable, but when paper moistened with it is introduced into the flame of a candle, it is destroyed with the evolution of smoke and chlorine gas. It is just half as heavy again as distilled water. Its specific gravity was formerly stated to be 1·483, but the liquid used for inhalation of late years has been heavier than this. I find that pure chloroform, when saturated with water, has a specific gravity of 1·500 at 60° Fah.; and after agitating it with sulphuric acid, to deprive it of the water, the specific gravity is 1·503. The amount of water that chloroform can hold in solution is only one part in from 200 to 300; and when this is separated by oil of vitriol, the chloroform is liable to undergo spontaneous decomposition.[[45]]
Chloroform is soluble in alcohol and ether in all proportions, but it is very sparingly soluble in water. It has been said to require 2000 parts of water for its solution, but this is an error. As the solubility of this and similar medicines in watery fluids has a very important connexion with their physiological action, I took great pains to ascertain the solubility of chloroform correctly. By admitting small quantities of water into graduated jars containing chloroform vapour, I was able to ascertain that chloroform is soluble in about 288 times its volume of water. Chloroform is itself an active solvent of many bodies; dissolving camphor, caoutchouc, gutta percha, wax, resin, iodine, and some other substances very readily. It is a very mobile liquid, and when dropped from the lip of a small phial, the drops are very small. There are three drops to a grain of the liquid, and as a minim of it weighs a grain and a half, there are nine drops in two minims. Consequently persons should not speak indiscriminately of drops and minims, as they sometimes do, when talking of chloroform.
Adulterations. The odour of chloroform is by no means disagreeable. The only liquids that resemble it in smell are Dutch liquid and the chlorinated products of hydrochloric ether, but as they are much more difficult to prepare than chloroform, they are not likely to be substituted for it, or used for its adulteration. The smell of chloroform is therefore a good criterion of its purity and identity. When dropped on the hand, it should quickly evaporate, leaving not the least moisture or smell behind. If a disagreeable odour remains on the hand after the evaporation of the chloroform, it has probably been made from impure spirit, or even from wood spirit or acetone, and is unfit for medicinal use.[[46]] When chloroform becomes decomposed from any cause, it acquires a greenish-yellow colour, and gives off chlorine and hydrochloric acid, so that the alteration is at once apparent. When chloroform is pure it has no reaction on test-paper, but is quite neutral. The best way to detect a small quantity of hydrochloric acid in it, is to moisten a slip of blue litmus paper with distilled water, and hold it just within the neck of the bottle exposed to the vapour. If sulphuric acid should be present, it may be discovered by agitating the chloroform with distilled water, and adding nitrate of baryta.
The only article that can be mixed with chloroform without altering its appearance and smell is alcohol. This can be detected by the reduction it occasions in the specific gravity of the chloroform; or, if it be present in any considerable quantity, it may be discovered by adding water to a little of the chloroform in a graduated tube or measure, when a diminution of its volume takes place, owing to the water abstracting the alcohol. The chloroform also acquires a milky opacity under these circumstances. M. Miahle[[47]] speaks of the milky opacity of the chloroform on the addition of water as a very delicate test of the presence of alcohol; but I find that it requires upwards of two per cent. of alcohol to cause this appearance on the addition of water.
It has been asserted, and often repeated, that the presence of alcohol in chloroform causes it to have caustic properties, and makes its vapour unusually irritating. I have never seen any evidence of this, although I have had hundreds of opportunities of witnessing the action of chloroform mixed with spirit. Under certain circumstances, it is advisable to dilute chloroform with alcohol previous to its administration, as will be explained hereafter.
The chloroform I have met with in London has always been sufficiently pure for inhalation, except in a few cases where a small quantity had become decomposed, probably from having been left a long time exposed to strong daylight. In these instances, its altered appearance generally prevented its being used. I am not aware of serious consequences having arisen anywhere from the impurity or adulteration of chloroform. A case occurred in the London Hospital, where cough and a feeling of suffocation were caused by hydrochloric acid with which the chloroform was contaminated, but the inhalation was discontinued, and no ill consequences resulted.[[48]]
Chloroform should be kept in well-stoppered bottles, and protected from the light. It boils at 140 Fah. under the ordinary pressure of the atmosphere. It is consequently one of the most volatile liquids employed in medicine, with the exception of sulphuric ether and amylene.
The Vapour of Chloroform is more than four times as heavy as atmospheric air. It has a specific gravity of 4·2 at 60° Fah. Under ordinary circumstances, the vapour of chloroform has of course no separate existence, but is always mixed with air. It can exist in a pure state only when the temperature is raised to 140° or upwards; or when the pressure of the atmosphere is in a great measure removed by the air-pump. The quantity of vapour of chloroform that the air will hold in solution at different temperatures, under the ordinary pressure of the atmosphere, depends on the elastic force of the vapour at these temperatures. It is governed by a law precisely analogous to that which determines the amount of watery vapour which air will hold in solution.
The following table shows the result of experiments I made to determine the quantity of vapour of chloroform that 100 cubic inches of air will take up, and retain in solution, at various temperatures.
| Temp. Fah. | Cubic inches. |
|---|---|
| 40° | 7 |
| 45 | 8 |
| 50 | 9 |
| 55 | 11 |
| 60 | 14 |
| 65 | 19 |
| 70 | 24 |
| 75 | 29 |
| 80 | 36 |
| 85 | 44 |
| 90 | 55 |
In the above table, the air is a constant quantity of 100 cubic inches which becomes expanded to 107, and so on; but it may be convenient to be able to view at a glance the quantity of vapour in 100 cubic inches of the saturated mixture of vapour and air, at different temperatures, and in the table which follows the figures are so arranged as to show this.
| Temp. Fah. | Air. | Vapour. |
|---|---|---|
| 40° | 94 | 6 |
| 45 | 93 | 7 |
| 50 | 92 | 8 |
| 55 | 90 | 10 |
| 60 | 88 | 12 |
| 65 | 85 | 15 |
| 70 | 81 | 19 |
| 75 | 78 | 22 |
| 80 | 74 | 26 |
| 85 | 70 | 30 |
| 90 | 65 | 35 |
As the effects of chloroform when inhaled depend entirely on the quantity of vapour present in the air which the patient breathes, the effect of temperature on its volatility is of great practical importance. The air, it is true, does not become fully saturated with vapour during the process of inhalation, but the effects of temperature are relatively as great. If, for instance, a person inhales chloroform from a handkerchief or an inhaler, in such a way that the air he breathes shall be half saturated with the vapour, then supposing the temperature of the apartment, the handkerchief, etc., to be 50°, the air he breathes will contain 4 per cent.; but if the temperature be 70°, the air will contain 9·5 per cent. of the vapour.
A considerable amount of caloric becomes latent during the evaporation of chloroform, and the temperature of the vapour and air which the patient breathes are generally reduced a good deal, but not to the same extent as during the inhalation of ether. In giving chloroform from a small sponge which had been squeezed out of water, I have sometimes observed, after laying it down, that it became covered with a kind of hoar frost; the minute particles of frozen water having a slight taste of chloroform. The cold produced by the evaporation of a liquid like chloroform is often the means of checking the evaporation to a certain extent, and limiting the amount of vapour which is taken up by the air.