ranges making ro error-prone, as might be encountered in strong adsorption of bulky electroactive organics. Virtually the only experimental adjustment available is the back step time T , and this has only limited effect because of its square root function (Equation 6). In a situation where Qdl is adsorption-dependent, and an adjustment of T to the extent indicated by Figure 1 is impractical, it may be necessary to resort to the older single potential step method. In this method, one must include a correction experiment for the adsorption-induced change in Qdl a t Einit as well as the normal double layer charge blank correction, and such multiple corrections lessen the sensitivity and precision of the I'o measurement.
LITERATURE CITED (1)R. W. Murray, "Chronoamperometry, Chronocouiometry, and Chronopotentiometry," in "Techniques of Chemistry," Volume I, Part IIA, A.
Weissberger and E. Rossiter, Ed., Wiley-lnterscience, New York, NY, 1971.
(2) F. C. Anson, Anal. Chem., 38,55 (1966). (3)J. H. Christie, R . A. Osteryoung. and F. C. Anson. J. Nectroanal. Chem., 13, 236 (1967). (4)F. C. Anson, J. H. Christie, and R . A. Osteryoung, J. Nectroanal. Chem., 13, 343 (1967). (5) J. H. Christie, G. Lauer, R . A. Osteryoung, and F. C. Anson, Anal. Chem., 35, 1979 (1963). (6) F. C. Anson. Anal. Chem., 36, 932 (1964). (7)F. C. Anson and D. J. Barclay, Anal. Chem., 40, 1791 (1968). (8)C. M. Elliott and R. W. Murray, J. Am. Chem. SOC.,96,3321 (1974). (9)H. B. Herman, R. L. McNeely. P. Surana, C. M. Elliott, and R . W. Murray, Anal. Chem., 46, 1258 (1974). (10)S.N. Frank and F. C. Anson, J. Nectroanal. Chem., 54,55 (1974).
RECEIVEDfor review October 21, 1974. Accepted December 17, 1974. This research was assisted by the National Science Foundation under grant GP-38633X and by the Materials Research Center, U.N.C., under National Science Foundation grant GH-33632.
Titration of Acids in Benzene-Nitrobenzene, BenzeneNitromethane, and Benzene-Acetone Binary Solvent Systems A.
K. Amirjahed
College of Pharmacy, The University of Toledo, Toledo, OH 43606
Martin 1. Blake Department of Pharmacy, University of Illinois at the Medical Center, Chicago lL 606 12
Fritz ( I ) performed a series of potentiometric titrations on certain amines in acetonitrile. He observed that the millivolt reading a t the half neutralization point of a potentiometric titration designated as H N P or the half neutralization potential could be correlated with the base strength of the amine. Thus, the potentiometric measurement of H N P offered a method for relating the base strengths of amines in non-protolytic solvents. Hall (2) used this method to determine the base strength of a number of mono- and diamines in several nonaqueous solvents. He found that the observed order of the base strength of the alkylamines was similar to that found in water, and when the data obtained for the nonaqueous solvents were plotted vs. that for water, linear relationship resulted. Chatten and Harris ( 3 ) studied certain basic amines and phenothiazines in five organic solvents and reported a linear relationship between the pKb and the H N P of the amines. Miron and Hercules ( 4 ) also observed a linear relationship between the acidity strength expressed in millivolts and the pK, of the acid for a series of substituted benzoic acids and phenols which were titrated in a variety of nonaqueous solvents. Davis and Paabo (5) studied the comparative strengths of certain acids in benzene and obtained linear relationships. In a study of the relative acidity strengths of meta- and para-substituted benzoic acids and aliphatic monocarboxylic acids in pyridine and water, Streuli and Miron (6) obtained linear relationships. Other studies on acids and bases have been reported (7-16) in which relative strengths in nonaqueous and aqueous media have been compared. In general, there is considerable evidence that a linear relationship exists between the relative strengths of a series of acids or bases in nonaqueous media and their pK, or pKb values, respectively. In determining the HNP's to establish this relationship, the fluctuating variables inherent to potentiometric measurements in nonaqueous media in910
ANALYTICAL CHEMISTRY, VOL. 47, NO. 6, MAY 1975
troduce large variabilities in the results. Some of these variables are: the nature of the medium, the interactions between molecules of the medium and the acid, the standard potential of the reference electrode and the cell, the liquid junction potential, and the loss of protons by the glass membrane. Dielectric constant of the medium, (Dm),is one of the major factors influencing the linear relationship and is often difficult to control. I t can be closely controlled, however, by using one of the nonaqueous binary solvent systems previously described ( 1 7 ) . In that paper, experimental procedural details were given for determining the dielectric constant of a series of nonaqueous binary solvent systems and for preparing nonaqueous solvent mixtures having specific dielectric constants within a range of values provided by the system. Formulas relating the dielectric constant and the composition of the solvent mixture were developed. In a second paper (181, procedural details were presented for determining the H N P of a series of acids of varying pK, in the benzene-acetonitrile solvent system.
EXPERIMENTAL The details of the experimental procedures reported earlier (17, 18) are applied to the study of three additional nonaqueous binary
solvent systems. Each system consists of a polar and a nonpolar component. The nonpolar component in the three solvent systems is benzene. The polar components are nitrobenzene, nitromethane, and acetone in the three systems, respectively. In the benzene-nitrobenzene and benzene-nitromethane solvent systems, the solvent mixtures have dielectric constants of 5 , 10, 15, 20, 25, and 30. The mixtures of the benzene-acetone solvent system have dielectric constants of 5 , 10, 15, and 20. The same acids reported earlier (18)were used in this investigation. They were selected such that the effect of the structure of the acids was randomly distributed. The same principle of randomness was built into the weighing of the acids, their titration, construction of the titration curves, and in the determination of the millivolt readings corresponding to the HNP's. The HNP values of the acids determined in a specific solvent mixture (of the particular bi-
Table I, T h e Half-Neutralization Potential Values Determined in the Binary Solvent Systems pKa -30
3.12
4.09
5.30
5" 10 15 20 25 30
101.50 90.00 103.00 121.50 130.50 130.50
52.00 40.00 52.50 50.50 56.00 48.00
-32.00 -75.00 -65.50 -66.00 -51.50 -46.00
-109.00 -141.50 -114.50 -126.50 -120.00 -125.50
-238.50 -240.50 -263.50 -245.00 -248.50 -254.50
-315.00 -312.50 -220.00 -339.00 -328.00 -328.50
5*
91.50 109.00 100.50 114.00 111.50 120.50
53.00 50.50 46.50 51.00 59.50 69.50
-34.00 -129.50 -69.50 -106.00 -78.00 -77.50 -64.50 -81.00 -35.50 -11.00 4 1 . 5 0 -26.50
-249.00 -191.00 -129.50 -124.00 -71.50 -64.50
-145.50 -170.50 -97.00 -127.00 -110.00 -67.50
l),,,
10
15 20 25 30
7.16
8.34
10.43
5' -82.00 23.00 -58.00 -195.50 -290.00 -305.00 1 0 -41.00 26.00 -128.00 -244.50 -286.00 -318.00 1 5 - 5 6 . 0 0 51.50 -139.00 -240.50 -289.00 -287.00 20 -53.00 63.00 -172.00 -244.00 -292.00 -345.50 a = Benzene-nitrobenzene; b = benzene-nitromethane; c = benzene-acetone. The values given are the average of two replications in millivolts.
Table 11.The HNPo Values of the Acids Determined Separately i n the Binary Solvent Systems Benzene-Acetonitrile (A), Benzene-Nitrobenzene (B),Benzene-Nitromethane (C), a n d Benzene-Acetone (D) "Po
PKa
3.12 4.09 5.30 7.16 8.34 10.43
A
B
C
D
48.84 7.27 -51.71 -123.52 -293.54 -371.74
85.96 47.38 -56.00 -120.00 -240.36 -298.25
92.18 44.25 -59.10 -147.02 -259.55 -170.64
-74.56 7.41 -43.06 -198.58 -287.18 -293.06
nary solvent system under investigation) with a specific D, were plotted vs. the corresponding pK, values. The least squares procedure for the univariate normal regression analysis (19) was used to determine the formulas of the straight lines. These formulas provided the slopes (of the straight lines) which were plotted vs. the dielectric constants (D,) of the solvent mixtures. The resultant graphs indicated the half-neutralization potential-dielectric-constant profile of the particular solvent system. On the other hand, the HNP values determined for the same acid were plotted vs. the different D, values of the different solvent mixtures (of the particular binary solvent system under study) in which the acid was titrated. The same statistical method was employed for determining the formulas of the straight lines. From these formulas, the value of HNP when D, was equal to one was calculated and designated as HNP,. The HNP, values were then plotted vs. the corresponding pK,'s, and the formulas of the observed straight lines were determined using the same statistical procedure mentioned earlier.
RESULTS AND DISCUSSION The inert, nonleveling, wide-range-dielectric-constant nonaqueous binary solvent systems employed in this study acted as nonreactive dispersing and suspending media permitting a wide potential range for the titration of the acid molecules and for the determination of their HNP. Each of the solvent mixtures had a specific dielectric constant which reflected the degree of interaction among the solvent molecules. As the dielectric constant of the solvent
I
-400
1 P
4 E
G
-x-
5
I0
I5
20
25
33
3rr
Figure 1. The half neutralization potential-dielectric constant profile of benzene-nitrobenzene ( A ) , benzene-acetone (B), and benzenenitromethane (C)
mixtures in the same solvent system changed, the types of the molecules present remained constant, but their relative number changed. Thus, the degree of interaction among the solvent molecules changed quantitatively, but the nature of interaction remained constant qualitatively. Two replicates of H N P values for each acid in each D , were obtained. The HNP's (Table I) reported for a particular D , constituted a set of y (HNP) and x (pK,) values. The slope of the linear relationship between these two variables indicates the change in the half neutralization potentials of the randomly selected acids per unit change in the pK,. The slopes are a function of the dielectric constant of the particular solvent mixture and are plotted vs. the D, values for each one of the binary solvent systems (Figure 1).These graphs show the change in the acid strength of the randomly selected acids with change in the dielectric constant of the particular binary solvent system. Such a HNP-D, profile of the binary solvent system has been shown to be of practical value in nonaqueous differentiating titration of weak acid mixtures (18). The dielectric constant of a liquid medium is the ratio of the capacitance of the particular capacitor determined in the medium to its capacitance obtained in air. When the forces of interaction among the molecules in the medium are assumed to be absent, the medium is behaving ideally. In this reference state, the capacitance determined in the medium approaches the value obtained in air, and the dielectric constant of the medium approaches unity. The H N P values determined in different mixtures of a binary solvent system for the same acid can be plotted (as the y variable) vs. the D, (as the x variable) of the mixtures in which they were determined. The value of HNP when D , is unity can be obtained from the formulas of the straight lines fitted to these plots. The calculated H N P values are designated as "Po's, and are plotted (on the ordinate) vs. the corresponding pK, values for the same acid (on the abscissa). The HNP, values are reported in Table 11. Table I1 also lists the HNP, values for the benzene-acetonitrile solvent system reported earlier (28). Table I11 includes the formulas of the final straight line relationships for the four binary solvent systems. Theoretically, the HNP, is a measure of the intrinsic strength of the specific acid and is independent of the effect of the solvent and the D,. This was verified by analysis of variance of the data in Table I1 since the F ratio for variations among solvents was nonsignifiANALYTICAL CHEMISTRY, VOL. 47, NO. 6, MAY 1975
911
particular binary solvent system independent of the change in the dielectric constant of the system.
Table 111.The Formulas of the Straight-Line Relationships between the P K a of the Determined i n Acids and Their "Po the Binary Solvent Systems
LITERATURE CITED
Formula of the line
Binary solvent system
Benzeneacetonitrile Benzene-nitrobenzene Benzene-nitromethane Benzeneacetone
HNP, HNP, HNP, HNP,
= = = =
-60.08 -55.04 -43.27 -37.37
pKa pKa pKa pK,
+ + +
+
254.20 255.76 193.87 83.59
cant at the 95% level of probability. The inference drawn and the conclusion reached is that an acidity scale in millivolts exists which corresponds linearly to the pK, acidity scale. The existence of this scale is proved empirically by the linear relationships obtained when H N P values are plotted against the corresponding pK, values and result in values a straight line. However, by calculating the "Po and plotting these vs. the corresponding pK,'s, a single more refined acidity scale in millivolts is obtained for the
(1) J. S. Fritz, Anal. Chem., 25, 407 (1953). (2) H. K. Hall, J. Phys. Chem., 60, 63 (1956). (3) L. G. Chatten and L. E. Harris, Anal. Chem., 34, 1495 (1962). (4) R. R. Miron and D. M. Hercules, Anal. Chem., 33, 1770 (1961). (5) M. M. Davis and M. Paabo, J. Org. Chem., 31, 1804 (1966). (6) C. A. Streuli and R. R. Miron, Anal. Chem., 30, 1976 (1958). (7) C. A. Streuli, Anal. Chem., 31, 1652 (1959). (8) L. A. Wooten and L. P. Hammett, J. Am. Chem. SOC.,57, 2289 (1935). 55, 1840 (1933). (9) V. K. LaMer and H. C. Downes, J. Am. Chem. SOC., (10) M. Kilpatrick and M. L. Kilpatrick, Chern. Rev.. 13, 131 (1933). (11) H. B. Van Der Heijde and E. A. M. F. Dahmen, Anal. Chim. Acta, 16, 378 (1957). (12) J. P. Wolff, Anal. Chim. Acta, 1, 90 (1947). (13) M. Kilpatrick and W. H. Mears, J. Am. Chem. SOC.,62, 3051 (1940). (14) J. H. Elliott and M. Kilpatrick, J. Phys. Chem., 45, 485 (1941). (15) M. Kilpatrick and W. H. Mears, J. Am. Chem. SOC.,62, 3047 (1940). (16) J. H. Elliott, J. Phys. Chem., 46, 221 (1942). (17) A. K. Amirjahedand M. I. Blake, J. Pharm. Sci., 63, 81 (1974). (18) A. K. Amirjahed and M. i. Blake, J. Pharm. Sci., 63, 696 (1974). (19) H. C. Batson. "An Introduction to Statistics in the Medical Sciences", Chicago Medical Book Company, Chicago, IL, 1956, p 56.
RECEIVEDfor review October 25, 1974. Accepted January 16, 1975.
Note on the Structure of Methylene Blue Thiocyanate F. H. Hall and L. W. Marple Institute of Pharmaceutical Sciences, Syntex USA, Inc., Research Division, Palo Alto, CA 94304
The generally accepted structure for methylene blue chloride (I),proposed by Bernthsen in 1885 ( I ) , has recently been challenged by Tzung with regards to the thiocyanate salt ( 2 ) . On the basis of chemical reduction data, Tzung has proposed that the methylene blue cation exists as the sulfoxide (11) in dilute aqueous solution. He further reports that elemental analysis and molecular weight determinations on anhydrous methylene blue thiocyanate are consistent with the empirical formula (C17H17N,&)20 for which he postulates structure 111.
Ill
Interest in our laboratory has recently been directed toward obtaining a pure sample of a salt of methylene blue for use as a reagent. Commercially available methylene blue chloride is sufficiently contaminated with the lower homologs of methylene blue (Azure B, Azure A, Azure C) so that extensive purification is necessary before use. We therefore utilized the purification procedure of Tzung to obtain material with the same apparent crystalline proper912
ANALYTICAL CHEMISTRY, VOL. 47, NO. 6, M A Y 1975
ties as that for which he has postulated the dimeric structure 111. We then focused our attention on confirming the proposed sulfoxide structure of this thiocyanate salt. However, our data indicate that the structure of anhydrous methylene blue thiocyanate is represented by structure I as originally indicated by Bernthsen. The purification procedure and analytical data pertinent to this proof are described below. EXPERIMENTAL Dissolve 10 g methylene blue chloride (Matheson, Coleman and Bell, U.S.P.) in 900 ml pH 8.2 borate buffer and filter with suction through a coarse sintered glass funnel to remove any undissolved material. Charge a 2-1. liquid-liquid extractor (designed for extracting with liquids heavier than water) with this solution along with an appropriate amount of chloroform. Begin extraction of the aqueous phase and continue until the chloroform layer is no longer red. Drain the chloroform layer and discard. To the aqueous solution in a large beaker, add first 14.3 ml concentrated HC1, then a solution of 1.63 g NaSCN dissolved in 90 ml deionized water. Stir the mixture as metallic green crystals are formed. Filter the mixture through a coarse sintered glass funnel (using suction) and wash with several volumes of deionized water. Dry the green solid to constant weight in a vacuum oven at 40 OC (overnight). All materials should be reagent grade. A Perkin-Elmer Model 1-B Differential Scanning Calorimeter was used to obtain data on the thermal properties of the compound from 310-540 K a t 10 K/minute. Infrared analysis was done on a Perkin-Elmer Model 137 sodium chloride spectrophotometer with the sample as a KBr pellet. X-Ray diffraction data were obtained with a Nonius 1012 instrument having a camera diameter of 114.6 mm and X = 1.5418 A. T h e sample was finely ground, having a copper sheen. Elemental analysis was performed by Alfred Bernhardt, Mikroanalytisches Laboratorium, 5251 Elbach uber Engelskirchen, Fritz-Pregl-Strasse 14-16, West Germany. Oxygen was measured directly.
