Potentiometric Titration of Thioamides and Mercaptoacids With Iodine ...

Chem. Anal. (Warsaw), 50, 397 (2005)

Potentiometric Titration of Thioamides and Mercaptoacids With Iodine in Alkaline Medium by Witold Ciesielski1,*, Anna Krenc1 and Urszula ¯³obiñska2 1

Key words:

Department of Instrumental Analysis, University of £ód ul. Pomorska 163, 90236 £ód, Poland 2 Technical Chemistry School ul. Soko³owska 2 , 95100 Zgierz, Poland

iodimetry, potentiometry, ethionamide, thioamides, mercaptoacids, determination

The method of iodimetric determination of thioamides and mercaptoacids in an alkaline medium is described. In volumetric titration with the potentiometric end-point detection the determination range is 25500 µmol for ethionamide (1), 1001000 µmol for N-methylthiourea (2), 201000 µmol for N-phenylthiourea (3), 25125 µmol for N,N-dimethylthiourea (4), 5125 µmol for dithiobiurea (5), 15300 µmol for dithiooxamide (6), 30600 µmol for thioglycolic acid (7), 20250 µmol for 3-mercaptopropinic acid (8), 100500 µmol for mercaptosuccinic acid (9) and 50200 µmol for D-penicillamine (10). The errors and the relative standard deviations were below 1%. This method was applied to the determination of ethionamide (1) in tablets. The shape of potentiometric titration curve of N,N-dimethylthiourea (4) is unusual and depends on the concentration of sodium hydroxide. Addition of iodine resulted in a significant potential drop. This system did not exhibit Nernstian behaviour. Opracowano metodê jodometrycznego oznaczania tioamidów i merkaptokwasów w rodowisku zasadowym. Zakresy oznaczalnoci wynosz¹: 25500 µmoli dla etionamidu, 1001000 µmoli dla N-metylotiomocznika, 201000 µmoli dla N-fenylotiomocznika, 25125 µmoli dla N,N-dimetylotiomocznika, 5125 µmoli dla ditiodimocznika, 15300 µmoli dla ditiooksamidu, 30600 µmoli dla kwasu tioglikolowego, 20250 µmoli dla kwasu 3-merkaptopropionowego i 100500 µmoli dla kwasu merkaptobursztynowego. Metodê zastosowano do oznaczania etionamidu w leku. Stwierdzono nietypowy kszta³t krzywych miareczkowania potencjometrycznego N,N-dimetylotiomocznika i jego zale¿noæ od stê¿enia wodorotlenku sodu. Wprowadzenie jodu powodowa³o znaczny spadek potencja³u. Stwierdzono, ¿e uk³ad ten nie spe³nia równania Nernsta. * Corresponding author. E-mail: [email protected]

398

W. Ciesielski, A. Krenc and U. ¯³obiñska

Thioamides and mercaptoacids are known for their wide applications in industry and technology as corrosion inhibitors, electrolytes for electroplating bath, components of bleach-fixing baths for photographic films. Metal complexes of dithiobiurea (5) have antiphytoviral [1], herbicidal and growth regulating activities [2]. Thioglycolic (7) acid and mercaptosuccinic acid (9) are applied as active materials for depilatories and hair straightening. Thioglycolic acid (7) is used as an intermediate for PVC stabilizers and a collector in flotation. Ethionamide (1) is a treatment for pulmonary and extrapulmonary tuberculosis in conjunction with other antituberculous agents and leprosy, as part of multi-drug regimens. Mercaptosuccinic acid (9) is an antidote in mercury and copper poisoning. D-penicillamine (10) is a chelating agent recommended for the removal of excess copper in patients with Wilson's diesease. It is also used to reduce excess cystine excration in cystinuria, and to treat active rheumatoid arthritis. N,N-dimethylthiourea (4) is a titrant for spectrophotometric determination of silver in blood and urine [3]. N-methylthiourea (2), dithiobiurea (5), dithiooxamide (6) and mercaptosuccinic acid (9) are applied in analytical chemistry as reagents in quantitative determinations of metals. This paper presents the method for the determination of thioamides and mercaptoacids by direct titration with iodine in an alkaline medium using platinum indicator electrode. The reaction of ethionamide (1), N-methylthiourea (2), N-phenylthiourea (3), N,N-dimethylthiourea (4) with iodine is based on the equation 1, dithiobiurea (5) reacts with iodine according to the equation 2, dithiooxamide (6) reacts according to the equation 3, thioglycolic acid (7) reacts according to the equation 4, 3-mercaptopropinic acid (8), mercaptosuccinic acid (9) and D-penicillamine (10) react with iodine according to the equation 5. 56, 2+

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EXPERIMENTAL Reagents and apparatus The double-distilled water in glass apparatus and the following reagents of analytical grade purity: sodium hydroxide, potassium iodide, iodine (Polskie Odczynniki Chemiczne), ethionamide (1) (Sigma), N-methylthiourea (2) (Aldrich), N-phenylthiourea (3) (Aldrich), N,N-dimethylthiourea (4) (Aldrich), dithiobiurea (5) (Avocado), dithiooxamide (6) (Fluka), thioglycolic acid (7) (Aldrich), 3-mercaptopropionic acid (8) (Aldrich) mercaptosuccinic acid (9) (Aldrich) and D-penicillamine (10) (Lancaster) were used.

400


Trecator® tablets were obtained from Wyeth-Ayerst. Standard solutions of iodine in KI were prepared. Stock solutions were obtained by dissolving an appropriate weighed amount of the particular compound in a suitable solution of sodium hydroxide. The pH meter, type CP315 made by Elmetron (Gliwice, Poland), with a saturated calomel electrode and platinum electrode, was used. Procedure Thiol samples were dissolved in 50 mL of a suitable sodium hydroxide solution (concentrations are given in Tab. I and II) and titrated with iodine. The end-point was detected potentiometrically platinum electrode as the indicator and saturated calomel electrode as the reference. During titration the solution was continuously stirred. 5 s waiting time was applied after each addition of iodine to let the potential response stabilise. The equivalence point of the reaction was located from the first derivative curve. Near the endpoint of the titration small amounts of iodine (0.020.05 mL) were introduced. Determination of ethionamide content in tablet dosage forms. Ten tablets were weighed and powdered. A mass of the powder equivalent to the mass of one tablet was dissolved in 50 mL of 5 mol L1 sodium hydroxide. Then 5 mL of this solution was introduced into 45 mL of 5 mol L1 sodium hydroxide and titrated in the same way as the pure substance. The content of the tested substance in one tablet was calculated by using the equation:

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RESULTS AND DISCUSSION The results of the determination of thioamides and mercaptoacids have been presented in Table 1 and 2. In titration of larger or smaller amounts of the studied compounds than given in Tables, the error increased above 1%. We have found that in neutral or acid medium, the reaction of iodine with thioamides was very slow and thus iodimetric titration was impossible. At pH £ 7 mercaptoacides are oxidized to disulfides. A change in the stoichiometry of the reactions in alkaline medium compared with the course of reaction in neutral medium was observed. It is well known that iodine disproportionates quickly in alkaline medium to give iodide and oxoiodate (I) ions, so oxoiodate (I) is the virtual oxidizing agent. The titration in alkaline medium is only possible if the reaction of oxoiodate (I) ions with thiol is faster than the reaction of disproportionation of oxoiodate (I) ions (3IO ® 2I + IO3).


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Table 1. Results of potentiometric determination of thioamides in alkaline medium; n = 6 )RXQG

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It has been found that the number of electrons transferred in the reaction of 1 mol of N-methylthiourea (2), N-phenylthiourea (3) 3-mercaptopropionic acid (8) and mercaptosuccinic acid (9) with iodine does not depend on the concentrations of the sodium hydroxide. The number of electrons transferred was determined based on titrant consumption. Titrations were carried out in NaOH concentrations in which the reaction rate was the highest. However, the number of electrons transferred per 1 mol of ethionamide (1), dithiobiurea (5) and dithiooxamide (6) depends on the concentration of the sodium hydroxide solution and increases with an increase in concentration of sodium hydroxide. At lower concentrations of sodium hydroxide than given in Table 1 and 2 the reaction between compound and iodine did not proceed stoichiometrically and the number of electrons transferred was lower than 8 for 1, lower than 16 for (5) and lower than 12 for (6). In the case of N,N-dimethylthiourea (4), thioglycolic acid (7) and D-penicillamine (10), an increase in sodium hydroxide concentration was followed by a decrease of the number of electrons transferred. The shapes of potentiometric titration curves of N,N-dimethylthiourea (4) are noteworthy at higher concentrations of sodium hydroxide (Fig. 1). A small addition of iodine brings about a significant potential drop in the initial part of the curve, which does not appear at lower concentrations of sodium hydroxide. With the result that the larger concentration of sodium hydroxide, the smaller volume of iodine is sufficient to observe the potential drop (Fig. 1, curves 2, 3).


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Figure 1. Potentiometric titration curves of 125 µmol of N,N-dimethylthiourea (4) with 0.055 mol L1 iodine: in 0.1 mol L1 sodium hydroxide (1); in 2 mol L1 sodium hydroxide (2); in 5 mol L1 sodium hydroxide (3)

Typical potentiometric curves of ethionamide (1) are shown in Figure 2. The elaborated method was applied for the determination of ethionamide in the drug. The comparative determination of ethionamide in its tablet form by the proposed potentiometric procedure and the pharmacopoeia method [4,5] has been done for the Trecator® tablets with the declared content of ethionamide equal 250 mg (Manufacturers series V were 251±0.7 mg and Q 250±1.1 mg for the developed and reference methods, respectively. The results obtained from potentiometric titration and the pharmacopoeia method are statistically compared. The proposed determination leads to the significant potential increase at the end-point (above 650 mV/0.1 mL of the titrant) (Fig. 3). Owing to the accurate and reproducible results obtained, the proposed method is recommended for routine determination of ethionamide (1) in drugs without prior separation.

number LOT 3013445). The results reported as [ r W

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Figure 2. Potentiometric titration curves of ethionamide: 25 µmol (1); 50 µmol (2); 130 µmol (3); 500 µmol (4). Titration with 0.05 mol L1 (1,2,3) and with 0.1 mol L1 iodine solution in 5 mol L1 NaOH (4)

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Acknowledgements This work was supported in part by grants No 3 TO9A 117 16 from the Committee of Scientific Research (Warsaw, Poland) and No 505/661 from the University of £ód.

REFERENCES 1. Davavski K., Schuster G. and Vasilev G., J. Phytopathol., 125, 133 (1989). 2. Vasilev G., Davavski K. and Genchev M., Dokl. Bolg. Akad. Nauk., 36, 461 (1983); Chem. Abstr., 100 (1984) 2061c. 3. Kacimi G., Nguyen P. L., Fabiani P. and Truhaut R., Acad Sci., Ser. 2, 302, 421 (1986); Chem. Abstr., 104 (1986) 181218m. 4. Farmakopea Polska V (Polish Pharmacopoeia V), Wydawnictwo Polskiego Towarzystwa Farmaceutycznego, Warsaw 1993, Vol. 2, p. 279. 5. The International Pharmacopoeia, World Health Organization, Geneva 1988, 3rd ed., Vol. 3, p. 131.

Received July 2004 Accepted July 2004