cedure. When it was necessary in the total titanium determination to determine insoluble matter by filtration, extended exposure of the solution to air required that the titanium be reduced again to the trivalent state. The aluniinuni foil method of Rahm ( I S ) was satisfactory. LITERATURE CITED
(1) Alpert, 11.B. (to National Lead Co.), U.S. Patent 2,734,003 (Feb. 7, 1956). ( 2 ) Alpert, 11. B., Opie, W. R., Schultz,
F. J., Svanstrom, K. (to Titan Co., Inc.), -4rgentine Patent 88,503 (hlarch 17, 1953).
(3)/4lpert, RI. B., Powell, R. L. (to hational Lead Co.). U.S. Patent 2,741,588 (April 10, 1956). (4) Slpert, 11.B., Schultz, F. J., Sullivan, W. F. (to Titan Co., Inc.), Swedish Patent 142,488 (Oct. 13, 1953). (5) Alpert, bl. B., Sullivan, W. F. (to Sational Lead Co.), U.S. Patent 2,712,523 (July 5, 1955). (6) Furman, N. H., ed., “Scott’s Standard Methods of Analysis,” 5th ed., i-01. 1, p. 985, Van Sostrand, New York, 1939. (7) Zbzd., Vol. 2, pp. 2197-8. (8) “Handbook of Chemistry and Physics, 37th ed., pp. 2142-3, Chemical Rubber Publishing Co., Cleveland,Ohio, 1955. (9) Ibid., pp. 2292-3. (10) Kerbecek, J., Jr., “Electrowinning
of Titanium and Zirconium,” Univ.
Microfilms. Ann ah-bor. Mich.. Publ.
S o . 8254, i954.
(11) Kingsbury, F. L. (to Titan Co., A.S.), German Patent 875,570 (;\lay . - 4, 1953). (12) Mellgren, S., Opie, W.,J . Metals 9, 266-9 (19571. (13) Rahm, J., ASAL. CHEM.24, 1832-3 (1952). (14) Schultz, F. J., Buck, T. 31. (to National Lead Co.), U.S. Patent 2,734,856 (Feb. 14, 1956). (15) Wainer, E. (to Horizons Titanium Corp.), Zbzd., 2,731,404 (Jan. 17, 1956). RECEIVED for review December 3, 1956. Accepted August 11, 1958.
Quantitative Colorimetric Determination of Benzimidazolone and Some Derivatives SIR: In the course of studying the pharmacological properties of benzimidazolone derivatives, need arose for analytical methods applicable to biological materials. Compounds with pharmacological activity indicative of therapeutic utility IVere not found in the series examined. Hoivever, the analytical methods which were developed are potentially adaptable to the determination of other derivatives of benzimidazolone. The compounds studied were easily extractable from blood plasma with a solvent such as ethyl acetate-chloroform, 2 to 1 (v./v.). Residues remaining after evaporation of solvents from the extracts were assayed by two methods. The first depended upon fluorescence of the compounds dissolved in O.lX hydrochloric acid. I n the AmincoBowman spectrophotofluorometer, with a n activating wave length of 270 to 285 mp, the compounds exhibited a major fluorescence peak a t 326 to 340 mp, and a minor one at 610 to 640 mp. The second, colorimetric, method is described below. Benzimidazolone is a stable compound, being resistant to oxidation by alkaline permanganate and b y hydrogen peroxide ( 5 ) . However, its imide has been reported oxidizable by hypohalites to yield unstable colored products (6). Oxidation of benzimidazolone and some of its derivatives with chromic acid produces intense red colors which rapidly change to blue and then fade. If the Oxidation is carried out in dilute solutions and in the presence of ethyl alcohol, a less intense but more stable red color is obtained. Presumably, the ethyl alcohol, by destroying excess chromic acid, prevents oxidative destruction of the colored products.
I 6
1
0 2-
0 2
04
06
ETHANOL,
08
I O
TNME
ml
Figure 1. Influence of ethyl alcohol on color development Benzimidozolone derivative and wave length of maximum absorption 1. 1,3-Dimethyl, 5 2 5 2. 1 -Methyl, 505 3. 5-fed-Butyl, 505 4. Parent compound, 505 5. 5-Chloro, 51 5
Some derivatives of benzimidazolone, upon oxidation in the presence of ethyl alcohol, yield a n evanescent, intense red color, which changes to light green and finally to the relatively stable pink. If the heterocyclic ring is ruptured b y chromic acid to yield o-phenylenediamine or its X-substituted derivatives, formation of azobenzene and phenazine or phenazonium compounds is probable (1-4, 8). The several phases of the reaction occur a t different rates for different compounds; therefore, it is necessary to establish the maximal alcohol concentration and reaction time for each derivative. COLOR REACTION
The compound is dissolved in dilute sodium hydroxide or in 10% ethyl alcohol depending upon its solubility.
NINJTES
Figure 2.
Stability of color MI. of ethyl alcohol. ( 1 ) 0.95, ( 2 ) 0.95, ( 3 ) 0.4, (4) 0.4, ( 5 ) 0.1
Table I.
Relationship of Absorbance to Concentration
Absorbance per llmole per Liter f S.D. 0 918 f 0 046
Compound Benzimidazolone S-llethylbenzimidazolone .Yj h”-Dime thylbenzimidazolone 5-tert-Butylbenzimidazolone 5-Chlorohenziniidazolone
0 783 f 0 082 1 730
+
0.153
0.715 d= 0 034
0.523 =k 0.022
One-half milliliter of this solution, which contains 10 to 150 y of compound, is diluted with water and ethyl alcohol t o 1.6 ml., the proportion of water t o ethyl alcohol depending upon the derivative under examination (Figure 1); then 1.2 ml. of 3 to 2 (v./v.) sulfuric acidwater is added and the solution is cooled to room temperature. Tn-o-tenths milliliter of 1% potassium dichromate is added, with immediate mixing. After a suitable time (Figure 2), the absorbVOL. 30, NO. 12, DECEMBER 1 9 5 8
* 2063
ance of the solution is determined against a reagent blank at the wave length of maximum absorption. RESULTS
T o illustrate the method, data obtained with benzimidazolone, its N methyl, N,N’-dimethyl, and 5-chloro derivatives, as well as with 5-tert-butylbenzimidazolone, which is an antimitotic compound (7), are presented. The wave length of maximum absorption was 505 mp for benzimidazolone, the monomethyl, and 5-tert-butyl compounds, 515 mp for the 5-chloro derivative, and 525 mp for the dimethyl derivative. Figure 1 shows that the alcohol requirement for maximal color development varies widely-Le., from 0.1 to 0.9 ml., depending upon the derivative under examination. The data of Figure 2 show that the color develops rapidly, then slowly fades. It is apparent that while no great error will result from minor differences in the timing of absorbance determinations, for precise results the reaction should be closely timed. This is particularly true for the dimethyl derivative, the color of which fades more rapidly. A 3-minute interval was allowed bet m e n addition of dichromate and absorbance determinations in establishing standard curves for the five compounds. Beer’s law was obeyed with concentra-
tions ranging from 0.02 to 0.3 mmole per liter. Absorbances a t the wave lengths of maximum absorption are shown in Table I. Qualitative observations with a number of other compounds are recorded in Table II.
Color Reaction with Various Compounds”
Compound o-Phenylenediamine p-Phenylenediamine Isatin 1,3-Diphenylbenzimidazolone 1-Phenyl-3-acetylbenzimidazolone Diacetyl-o-phenylenediamine 2,3-Ureylene-4methylpyridine 1,2-Ureylenenaphthalene
+ + -
Reactions and Remarks Brown-pink color Good pink color
-
Table 11. The reaction does not appear to be general for benzimidazolones, as the 1,3-diphenyl and diacetyl derivatives did not yield a color. Because ophenylenediamine, as well as the p isomer, produced color under the conditions of this method, some of their derivatives might also be expected to interfere. However, neither diacetyl ophenylenediamine nor o-phenylenemalonamide gave a colored product. Some compounds-e.g., 1,Bureylenenaphthalene-although chromogenic, will not interfere in the method as described because of the ephemeral nature of the color produced. LITERATURE CITED
Light pink
- Bright color,
fades rapidly
1-Phenylbenzimidazolone 3-Methyloxindole 5-Carboxvmethvlbenzoxazoione ” Benzoxazolone o-Phenylenemalonamide Benzimidazole a Reaction mixtures contained 100 y of compound and 0.5 ml. ethyl alcohol in 3ml. final volume.
+
(1) Fischer, O., Dischinger, .4.,Ber. 29, 1602 (1896). (2) Fischer, O., Heiler, O., Ibid., 26, 378 (1893). (3) Fischer, O., Hepp, E., Ibid., 22, 356 (1889). (4) Griess, P., J. prakt. Chem. 3, 143
118711. (5j Niemontowski, St. von, Ber. 43, 3012 (1910). (6) Pellizzari, G. B., Gazz. chim. ital. 48, 173 (1918). (7) Stoerk, H.C., .4rison, R. N., Hawkins, J. E., Jr., Nature 180, 1428 (1957). (8) Ullman, F., Mauthner, F., Ber. 35, 4302 (1902). CURTC. PORTER Merck Sharp & Dohme Research Laboratories West Point, Pa. RECEIVEDfor review April 16, 1958. Accepted October 14, 1958.
The Nomenclature of Thermochemical Titrimetry SIR: Interest in thermochemical titration methods has developed rapidly in the past few years and the number of publications on this subject has been growing steadily. Indicative of the trend has been the appearance of a chapter devoted to the subject in the current edition of a widely read textbook on instrumental analysis (10). The program of the 132nd National Meeting of the American Chemical Society (New York, September 1957) included a one-day Symposium on Thermoanalytical Titrimetry ( 1 ) . L’nfortunately, a multiplicity of terms has been used in the literature to describe a essentially the same method-viz., titration is an adiabatic system yielding a plot of temperature cs. volume of titrant. Prior to 1954, the designation “thermometric titration” appears to have been used exclusively. The relevant literature has been reviewed b y Linde, Rogers, and Hume (9). I n its 1952 report, the Committee on Nomenclature of the Division of Analytical Chemistry of the American Chemical 2064
ANALYTICAL CHEMISTRY
Society stated “the term thermometric is not recommended” (4). This statement is neither amplified nor elaborated. Since then, terms such as “thermal titration” (S), “calorimetric titration” (%’), and “enthalpy titration” (6, 7 , 10) have been introduced by various authors. I n other papers ( 1 , 6, 8, 9, 11) the term “thermometric titration” has continued to be used. I n order to avoid unnecessary proliferation of terms and with a view to minimizing confusion regarding nomenclature, a round-table discussion on terminology was held a t the 1957 Symposium on Thermoanalytical Titrimetry. Various views were presented by the panel, which included L. T. Hallett (Chairman), D . N. Hume, Joseph Jordan, and M. G. Mellon; a lively discussion ensued with much participation from the floor. While no vote was taken and no formal minutes of the discussion were kept, the consensus of opinion was that the term “thermometric titration” should be adhered to in the future. We
wish to place these conclusions on record for the guidance of interested persons. It is hoped that appropriate committees of the International Union of Pure and Applied Chemistry, and similar bodies, may consider this matter. We feel that official action is desirable to standardize the nomenclature a t an early date and prevent further multiplication of terms.
D.
N. HUME
Department of Chemistry Massachusetts Institute of Technology Cambridge 39, Mass.
JOSEPH JORDAN Department of Chemistry Pennsylvania State University University Park, Pa. LITERATURE CITED
(1) -4bstracts of Papers, 132nd Meeting, ACS, pp. 5B-l3B, New York, N. Y.,
September 1957.
