January 15, 1934
INDUSTRIAL AND ENGINEERING CHEMISTRY
compounds, as they prevent the formation of basic mercuric sulfate. The titration is also unsuccessful in the presence of ions that cause precipitates with mercuric nitrate, or with barium chloride, such as tartrates, phosphates, etc. Potassium iodide is an exception (Table IV) . The insoluble mercuric iodide could be made t o dissolve in excess mercuric nitrate solution by stirring the color test mixture with a glass rod, and the end point could then be determined as usual. Colored substances may also make the end point difficult or impossible to detect.
21
can then be produced with a smaller amount of titration mixture.
DISCUSSION The method is recommended for routine analysis, rather than for single determinations. All the solutions involved are of stable inorganic compounds, and can be made up in large quantities and kept for long periods of time. The biggest advantage of the method is that it is timesaving. The authors are able to finish an ordinary titration, working individually and not knowing the sulfate content, in TABLEV. EFFECT O F SOLID BARIUM SULFATE UPON ENDPOINT about 10 minutes. This is possible, in spite of the outside indicator, because the method is a direct one, and because a 0.0207 M BttClz SOLUTION NEEDEDPER MILLIMOL Bas01 .TITRATION MIXTURE 100 cc. NEUTRAL KzSO4 SOLUTION preliminary end point is reached (using one drop of titration PER DROP About 0.12 g. About 0.24 g. About 0.36 g. Hg(N0a)z Bas04 formed Bas04 formed Bas04 formed mixture) several cubic centimeters in advance of the final end Drops CC . CO. cc. point (using several drops of titration mixture). Thus the 2 42.2 44.0 44.3 barium chloride solution can be added 2 or 3 cc. a t a time 3 44.7 45.2 45.3 4 45.5 45.8 45.7 until the final end point is nearly reached. The apparatus 6 46.0 46.2 45.9 necessary is also simple and inexpensive. No attempt will be made here to give further procedure EFFECT OF BARIUMSULFATECONCENTRATION ON END for the method other than that connected with the titration POINT. The effect of concentration of barium sulfate, and itself, because of the great variety of substances and solutions of the number of drops of titration mixture per drop of mer- in which sulfate may be determined. curic nitrate on the position of the end point was deterAside from any analytical considerations, the method mined in neutral solution, using 0.02 M barium chloride employed in obtaining Table I1 seems to be useful in measursolution. The results, given in Table V, indicate that the ing the rate of formation of barium sulfate under various error due to difference in concentration of barium sulfate conditions. may be minimized by taking a sufficient number of drops of LITERATURE CITED titration mixture near the end point. This is also recommended because the end point is then more sensitive and (1) Pond, Chemist-Andust, 22 (2), 4 (1933). closer to the stoichiometric point. A small-sized drop of (2) Ray, Trans. Chem. Soc., 71, 1098 (1897). mercuric nitrate is also advantageous, since the same effect RECEIVEDAugust 12, 1933.
Chemical Examination of Trichloroethylene for Anesthesia HERMANL. TSCHENTKE, American Medical Association, Chemical Laboratory, Chicago, Ill.
A
MONG the various chemical compounds recently used for local anesthesia is trichloroethylene, CHCl=CClg. This compound has been described in the literature since 1864; it is not, therefore, a new substance. During the World War, Plessner (8) found symptoms of poisoning in men using trichloroethylene for removing grease from metal parts of machinery, and noted that the poison had special affinity for the sensory fibers of the trigeminal nerve. Oppenheim (1) recognized the possibility of lessening sensitiveness of the diseased trigeminal nerve in cases of facial neuralgia by giving the patient small doses of this compound to inhale. Trichloroethylene has also been developed commercially as a low-boiling, noninflammable solvent for extracting oils, fats, and waxes, for degreasing metals, and for purposes of dry cleaning. For these uses, a rather impure “factory” grade ordinarily has been sufficient. For therapeutic purposes, only a much more refined product is suitable. Several firms have been supplying medicinal trichloroethylene under various brand names, such as Westrosol, Gemalgene, Chlorylen, and Trethylene. Trichloroethylene was presented to the Council on Pharmacy and Chemistry of the American Medical Association for inclusion in “Kew and Nonofficial Remedies” and the Chemical Laboratory was asked to make an examination of the product. Accordingly, examination was made of two brands of trichloroethylene preparations presented; a specimen of Eastman grade and
of a practical grade purchased from Eastman Kodak Co.; and another brand used medicinally, obtained on the open market. The results of this investigation are given in Table I, which includes qualitative and quantitative determinations. The boiling point range of Chlorylen and of Trichloroaethylen zu Chlorylen was determined after extraction of the preparation with an equal volume of water to remove any interfering substances such as alcohol, and subsequent drying of the trichloroethylene layer with anhydrous sodium sulfate. After being notified of the results of the investigation of Chlorylen, the firm indicated a desire to investigate further, and to submit the product again in the future. Based in part on the information in the literature and on the results of the work reported herein, somewhat rigorous standards for identity and purity were elaborated. These were sent for comment to the firm which submitted the product; then in due time the following standards were adopted by the Council on Pharmacy and Chemistry for inclusion in “New and Nonofficial Remedies.” STANDARDS
TRICHLOROETHYLENE.~ Trichloroethylenum, trichlorethylene, CHC1:CC12, 1-chloro-2-dichloroethylene. 1 Solutions referred to in the descriptions of qualitative and quantitative teats are, unless otherwise stated. of the strength described in the current U. S. Pharmacopeia.
22
ANALYTICAL EDITION
Vol. 6 , No. 1
TABLEI. EXAMINATION OF TRICHLOROETHYLENE AND TRICHLOROETHYLENE PREPARATIONS BEILSTEIN I, 4TH ED.
N. N. R. STANDARDS
CALCO BULK SAMPLE
CALCO AMPULE8 T R E T H Y L ~ N EA8TMAlr E~
TRICHLOROAETHYLENb CHLORYLENb (MARKET SPECIMEN)
EASTMAN zu (PRACTICAL) CHLORYLEN
Bolling (u, s. p i g t
range method, 760 mm.) Specific gravity, 25' C./25' C. Refractive index, 20° C. a. Original
87.15
86-88
86.1-88.0
85.4-87.4
83.8-88.0
85.4-87.9
85.6-88.2
85.7-88.2
85.7-89.6
1.4598 (25.5/25.5)
1.458-1.460
1.460
1.460
1.452
1.460
1.460
1.450
1.447
1.4777
1.4770-1.4780
1,4777
1.4775
1.4770-1.4780 Not more than 0.1cc.O.lN
1.4770 0.05 cc.
1,4776 1.06 cc.
(ny.s)
..... ..... .....
b. Distillate Titration of aqueous extract 0.01 N " 2 1 or NadH consumed Residue on evaporation, 1000 c.
Davies, Rose & Co
White turbidity None
White turbidity None Slight
.....
None
None
..... .....
None Turbid
None, Turbid
e . . . .
Chlorides (turbidity in 5 min.) Readily oxidizing substances (chlorine, etc., blue color) Turbidity test (alcohol) a
Less than 0.0001 gram
..,..
Bromine test (lower layer) Silver ammonium nitrate (turbidity in 10 min.)
b
.....
Not weighable (25 cc.)
1.4770
0.y0 bc.
1.4774 Negligible
.....
Slight
White turbidity Darkened aqueou8 layer
Practically none
Practically none
Practically none
None
None
None Turbid
.....
1.4774
1.4767
1.4774 Negligible
1.4774 Lass than 0 . 1 cc. 0.1 N
Less than 0.0001 gram 0.0002 gram 0.0001 gram
QUALITATIVE TE8TS
.....
.....
.....
. .. . .
...... .. . .
White turbidit BlackeneB Turbid aqueous layer (much less for distillape) Practlcally None none None Turbid
None
.....
1.4756 1.4774 Less than 0 . 1 cc. 0.1 N 0.0004 gram
White turbidity Immediate turbidity None None Turbid
Schering Corp.
Actions and Uses, The actions of trichloroethvlene have not been investigated comprehensively, and it was introduced into therapeutics following some observations on man. Trichloroethylene appears t o have a selective action on the sensory endings of the trigeminal nerve, whereby it affords relief in trigeminal neuralgia, but it is not clear that the action even of therapeutic doses is limited to these endings, and different individuals seem to show rather wide differences in susceptibility t o this action; hence the dose necessary to afford relief varies correspondingly. Therapeutic doses sometimes cause transitory giddiness, with lassitude, distress, palpitation, and nausea. Large doses cause narcosis, and excessive doses cause death. There was no perceptible injury to the lungs, heart, or liver after narcosis repeated several times in the dog, but there was slight hyperemia of the gastric mucous membrane and marked reddening of the duodenum. The liquid is irritant; hence it should not be allowed to come in contact with the nose when the vapor is inhaled. Dosage. Fifteen minims by inhalation, t o be repeated after a few minutes if necessary; but it appears probable that not more than 60 minims should be inhaled within 24 hours when it is used for any considerable period of time. Trichloroethylene occurs as a clear, colorless, mobile, and volatile liquid, possessing an odor similar to that of chloroform. It is miscible with ether and verv soluble in alcohol: it is mactically insoluble in water. The" specific gravity is'from 1.458 to 1.460 at 25" C. The refractive index is from 1.4770 to 1 R~t , 2-n ~ c,. -.. - .4 - -7-. -. Transfer 25 cc. of trichloroethylene to a distilling flask. Determine the distillation range according to Method I of U. s. Pharmacopeia X. Ninety-five per cent distills over a t from 86' to 88' C. (corrected) at 760 mm. The refractive index of the distillate is the same as that of the material before distillation. Transfer 5 cc. of trichloroethylene to a glass-stoppered cylinder, add 5 cc. of bromine water and shake the mixture vigorously a t intervals of 15 minutes: a t the end of an hour a white turbid solution forms in the lower layer. Agitate gently 5 cc. of trichloroethylene with 2 cc. of silver ammonium nitrate solution in a narrow glass-stop ered cylinder of from 10 to 15 cc. capacity: No turbidity or dargening is observed in either layer at the end of 10 minutes (acetylene, etc.). Agitate 20 cc. of trichloroethylene with a 50-cc. portion of water and repeat, using a 25-cc. portion of water; transfer the combined aqueous layer to a flask and add to the aqueous solution 2 drops of methyl red indicator solution. If the color of the solution is yellow, not more than 0.1 cc. of 0.1 N hydrochloric acid is required to assume a pink color; if the color of the solu-
tion is pink, not more than 0.1 cc. of 0.1 N sodium hydroxide is required to assume a yellow color. Agitate 10 cc. of trichloroethylene with 25 cc. of water and allow the liquid to separate completely. Separate 10-cc. portions of the aqueous layer are affected as follows: No turbidity is noted 5 minutes after the addition of 0.1 cc. of nitric acid and 0.1 cc. of silver nitrate solution (chlorides); no blue color is observed after the addition of 0.1 cc. of potassium iodide test solution and 0.1 cc. of starch test solution (readily oxidizing substances such as free chlorine). Add 0.1 cc. of alcohol to 5 cc. of trichloroethylene: A turbid solution is formed (distinction from chloroform). Evaporate 25 cc. of trichloroethylene in a platinum or porcelain dish on a steam bath and dry to constant weight a t 100" C. No weighable residue is obtained. SUMMARY Comparative chemical examinations were made of several brands of medicinal trichloroethylene and of a specimen of a purified and of a technical grade. Two products were found to be markedly outside of the boiling point range and specific gravity range. The acidity of all samples but one examined was well within the range set. Four samples showed considerable turbidity in both layers when the silver ammonium nitrate test was applied. The presence of this turbidity gives rise to considerable doubt as t o whether compounds such as acetylene are absent. All samples indicated a lack of chlorides and of readily oxidizing substances. Standards for trichloroethylene for medicinal uses have been prepared, based upon the literature and upon the work herein reported.
LITERATURE CITED (1) Oppenheim, Neurol. Zentr., 34, 918 (1915); Oljeniok, J. Am. Med. Assoc., 91,1086 (1928). (2) Plessner, Berl. Gesellsch. f. Psychiut. u. Neurol., Nov. 8 , 1915; of. Neurol. Zentr.. 34, 916 (1915);' Monatschr. f. Psychiut. u . Neurol., 39, 129 (1916); Bed. Gesellsch. f. Psychiut. u. Neurol., Feb. 14,1916; Monatschr. f.Psychiat. u. Neurol., 44,374(1918): J . Am. Med. Assoc., 91, 1086 (1928). RECEIYED July 26, 1933.
CORRECTION. In the article on "Estimation of Total and Bound (D) Gossypol in Cottonseed Meal" by Smith and Halverson [IND. ENQ.CHEM.,Anal. Ed., 5,319 (1933)], 13th line from the bottom of the second column on the page, the sentence should read "Pipet (by suction) 4 cc. of aniline onto the meal."
