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The Determination of Camphor in Solution with Phenol in a High Percentage of Light Mineral Oil*
264
JOURNAL OF THE
AMERICANPHARMACEUTICAL ASSOCIATION
&phenY1 disdfide; 3-Meehyl-2‘-nikodiphenyl 2-Methyl-2’-nikodiphenyl disulfide; and 2-Nitrodiphenyl disulfide. REFERENCES (1) McDonagh, J. E. R . , Lanccf, 211, 236, 981, 1021 (1916); 212 914(1917). (2) Stir&ng, R. F., J. Comp. Pafh. Therap., 40, 274 (1928). (3) Report t o appear in a forthcoming monograph entitled “A Survey of Antimalarial Drugs. 1941-1945.” F. Y. Wiselogle, Editor.
(4) Meiser, W.,and SchBnhbfer, F.. Mcd. Y. Chcm., 4, 130-33(1942). Chcm. Zcnfr. 1943 I 2704 (5) Wohliahrt. Th., J . .brakl.’Ciem., ‘66 ( 2 ) , 551(1902). (6) Bogert M. T. and Stull A. “Organic Syntheses,” John Wiley add Sons, New York. ’coli. Vol. I, 1941, p . 220. (7) Zincke. Th., and Lenhardt, S., Ann., 400, 7(1913). (8) Hubacher, M. H . , “Organic Syntheses,” Coll. Vol. 11. 1943, p. 455. (9) Lefevre, C., and Desgres, Ch., Compf. rend., 198. 1491(1934). (10)Shukla. P . P.. J,Indian Inst. Sci.. IOA, Pt. 3, 3 3 4 1 (1927). (11) Khmel’Nitzkaya, I., and Mikel’s, V.. J . Gen. Chem. (CJ. S. S. R.),4, 452-550934); Chcm. Abslr.. 29, 1790 (1935). (12) Leuckart R. J . prakf. Chem. 41 (2) 199(1890). (13) Hiusberg: 0.: Bcr.. 41, 626-3h(lbOS).’ (14) Fromm, E., el al., A n n . , 394,335(1912).
The Determination of Camphor in Solution with Phenol in a High Percentage of Light Mineral Oil* By ERIC D. ROBINSON and S. C. WERCH The standard hydrazone method f o r the determination of camphor cannot be employed directly o n a solution of camphor with phenol i n a high percentage of mineral oil. When a large percentage of mineral oil is present, it adheres to the hydrazone crystals and interferes with the gravimetric analysis. A method i s here presented which eliminates this difficulty. This method is based o n the extraction of camphor with alcohol. A weighed sample is centrifuged after first being emulsified by the addition of 9 5 % ethyl alcohol. T h i s procedure gives recoveries averaging 99.6%.
HEN CAMPHOR is in an alcoholic soluwtion such as Spirits of Camphor or in a small amount of mineral oil as in the National Formulary preparation of Camphorated Phenol (1), the standard hydrazone method for the determination of caniphor can be employed directly. Direct application of this method, however, does not give .accurate results for camphor when this stearoptene is associated with phenol in a large quantityaof mineral oil. This is the case in many of the “Antiseptic Oils” that are available on the market. When a large quantity of mineral oil is present, i t adheres to the hydrazone crystals and interferes with the gravimetric analysis. Because OUT laboratory has had the task of determining camphor in a number of preparations containing camphor and phenol in a high percentage of mineral oil, it *Received Feb 11, 1947, from the Medical Research Division, Plough, Inc., Memphis, Tenn.
has been found necessary to devise a method for the separation of camphor from the oily base. This has been accomplished by extracting the camphor with alcohol. A weighed sample is centrifuged after first being emulsified by the addition of 95% ethyl alcohol. This procedure gives excellent recoveries. METHOD
If a large percentage of mineral oil is present, proceed as follows: A 0.3- to 1.5-Gm. sample cow taining camphor, phenol, and mineral oil is weighed into a 15-1111. centrifuge tube. To this solution 1-3 mi. of 95% ethyl alcohol is added and the mixture shaken vigorously until an opaque emulsion is formed. The alcohol-camphor layer which forms is then separated from the mineral oil by centrifuging at about.3500 r. p. m. for a t least three minutes. This separation procedure is best repeated about four times. The alcohol-camphor layer, after each extraction, is carefully poured into a 250-ml. volumetric flask. If a tiny drop of oil when warmed fails to give an odor of camphor, one can be reasonablv
SCIENTIFIC EDITION certain that all the camphor has been extracted along with the phenol. The extract is now made t o volume and gently mixed. Any oil-droplets that may appear a t this time will settle t o the bottom.of the flask. From the center of the flask draw four 25-ml. aliquots of the alcoholcamphor solution by means of a pipette. Empty each aliquot into a 500-ml. Erlenmeyer flask, then proceed with the assay for camphor as in N. F. VIII for Camphor Spirit. The amount of camphor is calculated from the weight of camphor 2,4-dinitrophenylhydrazone. If “gunk” should appear floating about the flask prior to filtering the hydrazone after it is formed, it indicates that too much alcohol had been employed in the above extraction and that some of the mineral oil got into solution. This mineral oil also must be removed. This is done by decanting off the floating material and dissolving in boiling alcohol. The globules of mineral oil will settle to the bottom. Next pour off the supernatant liquid and cool in an ice bath. Then wash what hydrazine crystals might have formed into the crucible and proceed as before t o wash with water and t o dry t o constant weight. When only a small percentage of mineral oil is present, no emulsion will result from the addition of alcohol and separation by centrifuging will not be necessary.
265
Tables I and 11. Recoveries from Stock Solution No. 1 averaged 99.6% and were included in Table I. Table I1 presents the findings obtained from Stock Solution NO. 2. .Here the recoveries averaged 98.9%.
TABLEII.-RECOVERY OF CAMPHOR FROM STOCK SOLUTIONNo. 2 Sample
Samp1e.a Gm.
Camphor Camphor Added, Recovered, Gm. Gm.
1 2 3 4 5 6
0.1543 0.1543 0.1543 0.1543 0.1543 0.1543
0.0926 0.0926 0.0926 0.0926 0.0926 0.0926
0.0913 0.0914 0.0911 0.0916 0.0919 0.0920
Re-
covery,
%
98.6 98.7 98.4 98.9 99.3 99.4 Av. 98.9
a Samples 1-6 are amounts in 25-ml. aliquots from 1.5430 Gm. in 250 ml. of alcoholic solution at 20’.
.
DISCUSSION
The addition of alcohol t o Stock Solution No. 2, which duplicates the National Formulary preparation of Camphorated Phenol, does not produce an emulsion, thus permitting the direct application of the hydrazone method. The mineral oil present in the sample goes readily into alcoholic solution with the phenol and camphor. This is due to the presence of only a small amount of mineral oil. In any case, no significant amount of mineral oil contamTABLERECOVERY OF CAMPHORFROM STOCK inates the hydrazone crystals. SOLUTIONNo. 1 When the hydrazone method for the determinaCamphor Camphor Retion of camphor was applied directly t o solutions of Sample,’ Added, Recovered, covery, camphor and phenol in a high percentage of light Sample Gm. Gm. Gm. % 1 0.1883 0.0282 0.0283 100.4 mineral oil, as in Stock Solution No. 1, results were 98.3 0.0385 0.0058 0.0057 2 about five times greater than the actual amount of 3 0.0385 0.0058 0.0058 100.0 camphor present. In these cases, mineral oil t o a 4 0.3746 0.0562 0.0559 99.5 5 1.2060 0.1809 0.1805 99.8 ’ considerable degree is adhered to the hydrazone 6 0.9910 0.1487 0.1484 99.8 crystals. thus interfering with the gravimetric Av. 99.6 evaluation. Alcoholic emulsification and subsequent separation of the camphor and alcohol by 6 Samples 1-6 are amounts of 6 different weighed samples. centrifuging eliminated this interference.
~~
~
EXPERIMENTAL Recovery experiments were carried out on two stock solutions. One (No. l), containing a large percentage of mineral oil and duplicating the general formula of many of the “Antiseptic Oils” on the market, was made up with 5% phenol, 16% camphor, and 80yo light mineral oil. The other (No. 2) included a small percentage of light mineral oil and duplicated the National Formulary preparation of Camphorated Phenol (30% phenol, 60% camphor, and 10% light mineral oil). Extraction ‘of the camphor was carried out on Stock Solution No. 1, while direct application of the hydrazone method was applied to Stock Solution No. 2. The results of the recovery tests are shown in
CONCLUSION
A method is here presented which gives excellent recoveries of camphor when it is in solution with phenol in a high percentage of mineral oil. Under such circumstances it is necessary to extract the camphor with alcohol before i t is possible to apply the hydrazone reaction. REFERENCES (1) .“The National Formulary”, Eighth Edition. Mack Printmg Company. Easton, Pa., 1946, p. 385.
JOURNAL OF THE
AMERICANPHARMACEUTICAL ASSOCIATION
&phenY1 disdfide; 3-Meehyl-2‘-nikodiphenyl 2-Methyl-2’-nikodiphenyl disulfide; and 2-Nitrodiphenyl disulfide. REFERENCES (1) McDonagh, J. E. R . , Lanccf, 211, 236, 981, 1021 (1916); 212 914(1917). (2) Stir&ng, R. F., J. Comp. Pafh. Therap., 40, 274 (1928). (3) Report t o appear in a forthcoming monograph entitled “A Survey of Antimalarial Drugs. 1941-1945.” F. Y. Wiselogle, Editor.
(4) Meiser, W.,and SchBnhbfer, F.. Mcd. Y. Chcm., 4, 130-33(1942). Chcm. Zcnfr. 1943 I 2704 (5) Wohliahrt. Th., J . .brakl.’Ciem., ‘66 ( 2 ) , 551(1902). (6) Bogert M. T. and Stull A. “Organic Syntheses,” John Wiley add Sons, New York. ’coli. Vol. I, 1941, p . 220. (7) Zincke. Th., and Lenhardt, S., Ann., 400, 7(1913). (8) Hubacher, M. H . , “Organic Syntheses,” Coll. Vol. 11. 1943, p. 455. (9) Lefevre, C., and Desgres, Ch., Compf. rend., 198. 1491(1934). (10)Shukla. P . P.. J,Indian Inst. Sci.. IOA, Pt. 3, 3 3 4 1 (1927). (11) Khmel’Nitzkaya, I., and Mikel’s, V.. J . Gen. Chem. (CJ. S. S. R.),4, 452-550934); Chcm. Abslr.. 29, 1790 (1935). (12) Leuckart R. J . prakf. Chem. 41 (2) 199(1890). (13) Hiusberg: 0.: Bcr.. 41, 626-3h(lbOS).’ (14) Fromm, E., el al., A n n . , 394,335(1912).
The Determination of Camphor in Solution with Phenol in a High Percentage of Light Mineral Oil* By ERIC D. ROBINSON and S. C. WERCH The standard hydrazone method f o r the determination of camphor cannot be employed directly o n a solution of camphor with phenol i n a high percentage of mineral oil. When a large percentage of mineral oil is present, it adheres to the hydrazone crystals and interferes with the gravimetric analysis. A method i s here presented which eliminates this difficulty. This method is based o n the extraction of camphor with alcohol. A weighed sample is centrifuged after first being emulsified by the addition of 9 5 % ethyl alcohol. T h i s procedure gives recoveries averaging 99.6%.
HEN CAMPHOR is in an alcoholic soluwtion such as Spirits of Camphor or in a small amount of mineral oil as in the National Formulary preparation of Camphorated Phenol (1), the standard hydrazone method for the determination of caniphor can be employed directly. Direct application of this method, however, does not give .accurate results for camphor when this stearoptene is associated with phenol in a large quantityaof mineral oil. This is the case in many of the “Antiseptic Oils” that are available on the market. When a large quantity of mineral oil is present, i t adheres to the hydrazone crystals and interferes with the gravimetric analysis. Because OUT laboratory has had the task of determining camphor in a number of preparations containing camphor and phenol in a high percentage of mineral oil, it *Received Feb 11, 1947, from the Medical Research Division, Plough, Inc., Memphis, Tenn.
has been found necessary to devise a method for the separation of camphor from the oily base. This has been accomplished by extracting the camphor with alcohol. A weighed sample is centrifuged after first being emulsified by the addition of 95% ethyl alcohol. This procedure gives excellent recoveries. METHOD
If a large percentage of mineral oil is present, proceed as follows: A 0.3- to 1.5-Gm. sample cow taining camphor, phenol, and mineral oil is weighed into a 15-1111. centrifuge tube. To this solution 1-3 mi. of 95% ethyl alcohol is added and the mixture shaken vigorously until an opaque emulsion is formed. The alcohol-camphor layer which forms is then separated from the mineral oil by centrifuging at about.3500 r. p. m. for a t least three minutes. This separation procedure is best repeated about four times. The alcohol-camphor layer, after each extraction, is carefully poured into a 250-ml. volumetric flask. If a tiny drop of oil when warmed fails to give an odor of camphor, one can be reasonablv
SCIENTIFIC EDITION certain that all the camphor has been extracted along with the phenol. The extract is now made t o volume and gently mixed. Any oil-droplets that may appear a t this time will settle t o the bottom.of the flask. From the center of the flask draw four 25-ml. aliquots of the alcoholcamphor solution by means of a pipette. Empty each aliquot into a 500-ml. Erlenmeyer flask, then proceed with the assay for camphor as in N. F. VIII for Camphor Spirit. The amount of camphor is calculated from the weight of camphor 2,4-dinitrophenylhydrazone. If “gunk” should appear floating about the flask prior to filtering the hydrazone after it is formed, it indicates that too much alcohol had been employed in the above extraction and that some of the mineral oil got into solution. This mineral oil also must be removed. This is done by decanting off the floating material and dissolving in boiling alcohol. The globules of mineral oil will settle to the bottom. Next pour off the supernatant liquid and cool in an ice bath. Then wash what hydrazine crystals might have formed into the crucible and proceed as before t o wash with water and t o dry t o constant weight. When only a small percentage of mineral oil is present, no emulsion will result from the addition of alcohol and separation by centrifuging will not be necessary.
265
Tables I and 11. Recoveries from Stock Solution No. 1 averaged 99.6% and were included in Table I. Table I1 presents the findings obtained from Stock Solution NO. 2. .Here the recoveries averaged 98.9%.
TABLEII.-RECOVERY OF CAMPHOR FROM STOCK SOLUTIONNo. 2 Sample
Samp1e.a Gm.
Camphor Camphor Added, Recovered, Gm. Gm.
1 2 3 4 5 6
0.1543 0.1543 0.1543 0.1543 0.1543 0.1543
0.0926 0.0926 0.0926 0.0926 0.0926 0.0926
0.0913 0.0914 0.0911 0.0916 0.0919 0.0920
Re-
covery,
%
98.6 98.7 98.4 98.9 99.3 99.4 Av. 98.9
a Samples 1-6 are amounts in 25-ml. aliquots from 1.5430 Gm. in 250 ml. of alcoholic solution at 20’.
.
DISCUSSION
The addition of alcohol t o Stock Solution No. 2, which duplicates the National Formulary preparation of Camphorated Phenol, does not produce an emulsion, thus permitting the direct application of the hydrazone method. The mineral oil present in the sample goes readily into alcoholic solution with the phenol and camphor. This is due to the presence of only a small amount of mineral oil. In any case, no significant amount of mineral oil contamTABLERECOVERY OF CAMPHORFROM STOCK inates the hydrazone crystals. SOLUTIONNo. 1 When the hydrazone method for the determinaCamphor Camphor Retion of camphor was applied directly t o solutions of Sample,’ Added, Recovered, covery, camphor and phenol in a high percentage of light Sample Gm. Gm. Gm. % 1 0.1883 0.0282 0.0283 100.4 mineral oil, as in Stock Solution No. 1, results were 98.3 0.0385 0.0058 0.0057 2 about five times greater than the actual amount of 3 0.0385 0.0058 0.0058 100.0 camphor present. In these cases, mineral oil t o a 4 0.3746 0.0562 0.0559 99.5 5 1.2060 0.1809 0.1805 99.8 ’ considerable degree is adhered to the hydrazone 6 0.9910 0.1487 0.1484 99.8 crystals. thus interfering with the gravimetric Av. 99.6 evaluation. Alcoholic emulsification and subsequent separation of the camphor and alcohol by 6 Samples 1-6 are amounts of 6 different weighed samples. centrifuging eliminated this interference.
~~
~
EXPERIMENTAL Recovery experiments were carried out on two stock solutions. One (No. l), containing a large percentage of mineral oil and duplicating the general formula of many of the “Antiseptic Oils” on the market, was made up with 5% phenol, 16% camphor, and 80yo light mineral oil. The other (No. 2) included a small percentage of light mineral oil and duplicated the National Formulary preparation of Camphorated Phenol (30% phenol, 60% camphor, and 10% light mineral oil). Extraction ‘of the camphor was carried out on Stock Solution No. 1, while direct application of the hydrazone method was applied to Stock Solution No. 2. The results of the recovery tests are shown in
CONCLUSION
A method is here presented which gives excellent recoveries of camphor when it is in solution with phenol in a high percentage of mineral oil. Under such circumstances it is necessary to extract the camphor with alcohol before i t is possible to apply the hydrazone reaction. REFERENCES (1) .“The National Formulary”, Eighth Edition. Mack Printmg Company. Easton, Pa., 1946, p. 385.