Use of Mercuric Acetate in Potentiometric Titrations in a Nonaqueous Medium Giuseppe Mascellani and Claudlo Casalini Research Laboratories of Alfa Farmaceutici Spa, 40 133 Bologna, Via Ragazzi de1'99 n.5, Italy
The application of mercuric acetate in potentiometry is not new: Pifer and Wollish ( I ) used it for direct titrations of organic base hydrochlorides, involving the in situ formation of undissociated mercuric halides and acetate ions titratable with perchloric acid. In the course of an analytical characterization of intermediates, we noted that the addition of a solution of mercuric acetate in acetic acid to the neutralization medium made it possible to titrate potentiometrically, as bases, compounds that could not otherwise be titrated vs. perchloric acid. The types of intermediates that can be titrated in the presence of mercuric acetate are shown in Table I. None of the compounds in group 1 showed any potential jump when titrated vs. perchloric acid with acetic acid as the solvent. Only some of them (la and ld) could be titrated using acetic anhydride. The latter is used as a solvent in potentiometry because of its ability to enhance the activity of the perchloric acid (2-4). None of the compounds in groups 2 and 3 could be titrated directly, not even in acetic anhydride, if mercuric acetate was not present in acetic acid.
EXPERIMENTAL Compounds l a and I C were obtained, respectively, by esterification of pyridine-2,6-dicarboxylicacid ( 5 ) and by alcoholysis of 1methylpyrrole-2-carboxylicacid chloride (6). Compounds 2b (7), 2c ( B ) , 2e (bP0.5rnrnHg= 93-96 "C), 2f (IO), 2d (9), 3a (91, 3b ( I I ) , 3c (91, were synthesized and purified by Valerio Borzatta (Synthesis Laboratories Alfa Farmaceutici Spa) by conventional methods. The compounds 2b, 2d were obtained by bromination of phenylthioalkanols, compounds 2c, 2e, 2f by alkylation of thiophenol or its derivatives with suitable halogen derivatives. All of them possessed the characteristics described in the respective original papers. Compounds 3b, 3a, 3c were synthesized by condensation of phenylthioalkylbromides with 3,3-diphenylpropylamine or with a-1-aminoethy1)-p-hydroxybenzyl alcohol. The compounds in group 2 represent the intermediates of the compounds in group 3 that possess anti-inflammatory, antispasmodic, analgesic, anaesthetic, and anti-edemic activity in rats 3b ( 1 1 ) and hypotensive and antiarrhythmic activity in rabbits 3a, 3c (9, 12). The other compounds were purchased from Aldrich. The identity of all the compounds was confirmed by IR and NMR analysis, and their purity, determined by conventional means, was a t least 99%. A Mettler automatic titrator was used, fitted with glass and saturated calomel electrodes. The solution subjected to titration con-
Table I. List of Compounds Studied
I CH 5
la
lb
IC
R,
2
H H H H H 4-CHJ
R2
2a 2b 2c 2d 2e
= H = CH,Br = CH,COOH
= (CH2)?-Br = (CHJ2-CN
2f = CH,-S
R OH
I
3a = CHJHCHCH O *H
I
3
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ANALYTICAL CHEMISTRY, VOL. 47, NO. 14, DECEMBER 1975
D
C
H
,
400.
3
0
0
1
,
i male
25
5 male HCIO, 10.' 7 5
25
HCIO, x 1 ~ - 475
Figure 1. Changes in t h e potentiometric curves of the compounds under examination in the presence of mercuric acetate (0-0) la: diethyl pyridine-2,6-dicarboxyiate without mercuric acetate. (U-U) l a : diethyl pyridine-2,6-dicarboxylate with mercuric acetate. (0-0) I b pyrazinamide without mercuric acetate. (+-+) l b pyrazinamide with mercuric acetate. (A-A) IC: methyl-Mmethylpyrrole-2-carboxylate without mercuric acetate. (A-A) I C : methyl-Mmethylpyrrole-2-carboxylate with mercuric acetate. (0-0)I d 2-bromothiazole without mercuric acetate. (0-0) Id: 2-bromothiazolo with mercuric acetate
Figure 2. F o r m of the potentiometric curves for thioethers (x-x) 2a: thioanisoie. (0-e) 2 b phenylthioethyl bromide. (+-+) 2c: 3(pheny1thio)propionic acid. (A-A) 2d: 3-(phenylthio)propylbromide. (U-D) 2e: 3-(phenylthio)propionitrile. ( L A ) 21: 1,2-(ptolylthio)ethane. (A-A) Form of the potentiometric curve of 3-(phenylthio)propyl bromide in acetic acid without mercuric acetate. Compounds 2a, 2b, 2c, 2e, and 21 in acetic acid solution and in the absence of mercuric acetate show curves of exactly the same form
tained about 2.5-5 X mol of the base and between about 7.8 X low4,and 2.5 X mol of mercuric acetate in 50-80 ml of acetic acid. Perchloric acid, 0.1 M in acetic acid was used as the titrant. To improve the accuracy, the end point of the titration was determined from the first differential derivative of the potentiometric curve.
RESULTS AND DISCUSSION Figures 1-3 show the change in the potentiometric curves obtained for the specimens under examination as a result of the addition of mercuric acetate to the acetic acid solution. A mechanism of the type indicated below can be postulated: 2B
+ Hg(AcO),
HgB1(AcO), f 2HfC10,-
+
--+
HgB,(AcO)>
2AcOH
+ HgB,?+(ClO,-).
(1)
(2)
where the bonding of acetate by mercury is "loosened" by B. 2.5
Compound
Purity, Y
Precision
Accuracy
la
99.8 100.1
0.472
0.193
IC
98.7
Id 2a 2b 2c 2d
99.1 99.5 97.1 98.3 99.4 99 .o 100.3 100.9 98.9 100.3 98.6
2e
2f 3b
3c
HCIO,
10..
75
Figure 3. Forms of t h e potentiometric curves for thioamines
Table 11. Precision a n d Accuracy Data
lb
;.male
(0-0) 3a: l-(phydroxyphenyl)-2-(2'-phenylthioethylamino)-l-propanol. (A-A) 3b: 3,3diphenyC3'-phenyRhiodipropylamine hydrochloride. (.-a) 3c: 1-(phydroxyphenyl)-2-(3'-phenylthiopropilamino)-l-propanol hydrochloride. (A-A) Form of the, potentiometric curve for compound 3b without the addition of mercuric acetate. The amine is in the hydrochloride form, and this explains the absence of inflections
0.370
0.151
On this assumption, one can explain, presumably in terms of steric hindrance, the impossibility of titrating the thioether group in the compound (3a): OH
0.497 0.656 0.325 0.487
0.202 0.267 0.132 0.198
I
C,H,SCH2CH2NHCHCHC,H,0H I
I
CHJ
in which salification of the nitrogen by the perchloric acid ANALYTICAL CHEMISTRY, VOL. 47, NO. 14, DECEMBER 1975
2409
makes it impossible to titrate the second functional group, in contrast to what happens in the higher homologs 3b and 3c. In curve 3a, there is a single inflection related to the titration of the amino group, while in curves 3b and 3c there are two (Figure 3). For the same reason, the disulfur 2f seems to be an univalent compound in the titration with perchloric acid (Figure 2). It was impossible to titrate a thioether of the I-pyridylthioacetic acid type in acetic acid and mercuric acetate because of its very low basicity, while compounds such as furan and thiophene produced slight inflections in the titration curves, not sufficient for a precise quantitative determination. The results of the titrations carried out are shown in Table 11. The precision of the method is demonstrated for compounds la, 2a, 3b, 3c in terms of the standard deviation and the standard error, which were calculated from the results of at least six separate determinations (Table 11). The precision is lower in compounds with two functional groups when the purity calculation is based only on the second inflection since, for some compounds, this is less clear than the first. The accuracy of the determinations is demonstrated by comparing the purities found by the proposed method against those obtained by traditional methods for the same compounds. Experimental tests have shown that the molar ratio between mercuric acetate and the base to be titrated should not be smaller than 0.5. With all the compounds examined a large excess of mer-
curic acetate, up to a ratio of 5-10, gave a clearer potential variation a t the equivalence point. The excess of mercuric acetate does not impair the accuracy of the determination ( 11. The use of mercuric acetate, still in the experimental stage, makes it possible to titrate very weak bases in nonaqueous media. This enables one to avoid the use of acetic anhydride which, owing to its reactivity, is not always suitable for titrating amines or bases containing heterocyclic nitrogen. It also enables one to titrate many thioethers in a direct and convenient manner. Various suitably prepared mixtures containing aliphatic amines (free bases or in the form of hydrochlorides), heterocyclic bases of type 1, and various thioethers of types 2 and 3 have been titrated without any interference among them. LITERATURE CITED C. W. Pifer and E. G. Wollish, Anal. Chem., 24, 300 (1952). B. J. Boubli, Boll. Chim. Farm., 04, 186(1955). D. C. Wirner, Anal. Chem., 30, 77 (1958). A. Anastasi, U. Gallo, and L. Novacic, J. Pharm. Pharmacal. 7, 283 (1955). (5) R. A. Barnes and H. M. Fales, J. Am. Chem. SOC.,75, 3830 (1953). (6) P. Hodge and R. W. Richards, J. Chem. SOC.,2543 (1963). (7) B. Bellau, J. Med. Pharm. Chem., 1 , 327 (1959). (8) E. Larsson, Trans. Chalmers Unlv. Techno/, Gothenburg, 87, 3 (1949); Chem. Abstr., 44, 3893d (1950). (9) R. Andrisano and A. S.Angeloni, Chim. Ther., 6 , 474 (1971). (IO) Fr. Pat. 777.427; Chem. Abstr., 20, 4024' (1935). (11) Ger. Offen. 2.232.030; Chem. Abstr., 78, 97321b (1973). (12) C. Runti, "Fondamenti di Chimica farmaceutica", vol. IV, Lint, Ed.; Trieste, 1973, p 44. (1) (2) (3) (4)
RECEIVEDfor review February 18, 1975. Accepted July 25, 1975.
Voltammetric Characterization of a Graphite-Teflon Electrode Leon N. Klatt,' Don R. Connell,* and Robert E. Adams Department of Chemistry, University of Georgia, Athens,
GB. 30602
Irwin L. Honlgberg and James C. Price School of Pharmacy, University of Georgia, Athens,
Ga.30602
Carbon, in various forms, has found considerable use as an electrode material for electrochemical studies at potentials positive of that at which mercury is oxidized. Among the more successful forms is the carbon paste electrode prepared from an intimate mixture of graphite and an organic liquid (1, 2 ) . However, these electrodes have one serious disadvantage in that they disintegrate in nonaqueous solvents ( 3 ) .Addition of a surface active agent to graphiteNujol mixtures increases their stability in acetonitrile, propylene carbonate, and nitromethane (4),but the electrode must not be exposed to water. Alternate pasting materials can be used, but the behavior of the resulting electrodes is greatly influenced by the pasting material ( 5 ) , suggesting that no single paste is useable in every situation. Because of their high density and seemingly impervious nature, pyrolytic and glassy or vitreous carbon appeared to offer an electrode material whose behavior would be reproA u t h o r t o w h o m correspondence should b e addressed a t h i s present address, A n a l y t i c a l C h e m i s t r y D i v i s i o n , O a k R i d g e N a t i o n a l Laboratory, O a k Ridge, T e n n . 37830. Present address, M e d i c a l College of Georgia, Augusta, Ga.
30902. 2470
ducible and independent of the source of the material. The electrochemical properties of these electrodes in aqueous and nonaqueous solvents were carefully characterized by Panzer and Elving ( 6 ) ,and it was found that surface preparation has a significant effect upon their observed electrochemical behavior. A disadvantage of pyrolytic and glassy carbon stems from their brittleness, in that considerable problems are encountered in fabricating electrodes. Recently, the use of graphite mixed with a thermoplastic polymer was reported (7). Preliminary voltammetric evaluation indicated acceptable electrode behavior. An inherent advantage of this type of binder is the molding capability; however, the solubility of the thermoplastic polymer in nonaqueous solvents may limit its usefulness. Replacement of the thermoplastic polymer with Teflon (E. I. du Pont de Nemours & Co., Wilmington, Del.) would retain the molding capability and eliminate the dissolution problems. Such an electrode forms the basis of the universal potentiometric ion-selective electrode described by Ruzicka, Lamm, and Tjell (8). This communication describes the voltammetric characteristics of the graphite-Teflon electrode, GTE.
ANALYTICAL CHEMISTRY, VOL. 47, NO. 14, DECEMBER 1975
