286 Analyst, April, 1971, Vol. 96, $9, 286-287 Potentiometric Method for the Determination of Aromatic Monothiosemicarbazones BY M. J. M. CAMPBELL, R. GRZESKOWIAK AND I. D. M. TURNER (Deflartment of Chemistry, Thames Polytechnic, London, S.E.18) A method has been developed for the quantitative determination of aromatic monothiosemicarbazones, in which addition of silver nitrate to a solution of the organic compound leads to complex formation. The hydrogen ion liberated on complex formation is determined by potentiometric titration. THIOSEMICARBAZONES are compounds of great importance because of their pharmacological activity against tuberculosis,l viruses,2 protozoa,S smallpox4 and certain kinds of t ~ m o u r s . ~ During our investigation (unpublished work) of metal complexes of these compounds we observed that no reliable method for quantitative determination of these organic ligands was available.Koshkin’s method,6 which involves precipitation, filtration and back-titration, is time consuming and suffers from the disadvantage that it does not give a sharp end-point colour change; this change is, moreover, affected by the pH of the solution. In this paper we outline a simple and rapid method for the quantitative determination of monothiosemicarbazones by potentiometric titration of the hydrogen ion liberated on complex formation when silver ion is added to a solution of the organic compounds. EXPERIMENTAL REAGENTS- All reagents used were of analytical-reagent grade. Hydrochloric acid, 0.1 N-Prepared from standard volumetric acid. Sodium hydrogen carbonate solution, 0.1 N-About 8-4 g of sodium hydrogen carbonate were dissolved in 1 litre of distilled water.The solution was standardised with the above acid, the end-point being determined potentiometrically. APPARATUS- A Vibret Laboratory pH meter, Model 46A, was used in conjunction with a glass - calomel combined electrode, the results being plotted manually from the meter readings. Measurements were also carried out on the automatic instrument, Metrohm potentiograph (Series E436), fitted with a 10-ml automatic burette and a glass - calomel electrode. GENERAL PROCEDURE- Weigh accurately about 150 mg of benzaldehyde thiosemicarbazone and dissolve it in 35 ml of dioxan. To this solution add 80 ml of water and 5 ml of silver nitrate solution.Stir the mixture by using a magnetic stirrer and titrate with the standardised sodium hydrogen carbonate solution (Note). If the manual method is adopted, add 0-1-ml portions of the titrant near the end-point. A typical set of titration figures obtained by using the Vibret pH meter with manual plotting is given below. Titrant added/ml . . 0.0 6.4 6.6 6.7 6.8 6.9 7.0 7.1 7.2 7.3 7.4 7.6 7.8 pH of solution . . 2-01 2-57 2.68 2.78 2.90 3.03 3-18 3.40 4-16 4.46 4.60 4.72 4-80 Determine a blank under the same experimental conditions. The value found was about 0.02 ml of titrant. Silver nitrate solution, 5 per cent. 0 SAC and the authors.CAMPBELL, GRZESKOWIAK AND TURNER The percentage purity is easily calculated from the equation- 287 V x N x E w x 10 Percentage purity = where V is the volume of titrant in millilitres, corrected for the blank titre; N is the normality of titrant; E is the equivalent weight of organic compound in grams; and W is the weight taken in grams.NOTE-We found that the use of other basic reagents such as sodium hydroxide or sodium car- bonate causes precipitation of silver salts before the end-point is reached. RESULTS AND DISCUSSION Addition of silver nitrate to the thiosemicarbazone results in complex formation, in which an equivalent amount of hydrogen ion is released into the solution. ,NH2 ,N H2 /R + H+ c-s R + Ag+ - C-S-Ag ‘NH--N=C / nN-N=C \ ‘R, R1 The nature of the complexes formed is under investigation and the results will be reported at a later date. The determinations were carried out on ten different samples for each thiosemicarbazone studied and the results obtained were within the narrow range of 100 t 0.5 per cent.The method was also successful with thiosemicarbazones of the following carbonyl compounds : 9-isopropylbenzaldehyde (cutizone) ,2 salicylaldehyde, isatin and furfuraldehyde. With the thiosemicarbazones of alkyl ketones and acetophenone reduction of silver ion to silver took place, while with benzophenone no complex formation occurred. A satisfactory end-point could be obtained even for amounts as small as 20 mg; how- ever, the scatter of results increased to k 2 per cent. Erroneous results can be caused by the decomposition of complex on the electrode if the concentration of the solid in the mixture is too great. With the automatic titrator, con- centrations of 150mg of ligand in 25ml of dioxan and 25ml of water can be used, but greater dilution had to be used in the manual method.The potentiometric method has the advantage over the Koshkin procedure that it is rapid, even with the manual apparatus, and the end-point is easier to determine. However, Koshkin obtained good results even with alkyl thiosemicarbazones , such as acetone thiosemi- carbazone, that cannot be determined by the potentiometric method. The authors thank Burroughs Wellcome (Dartford) for the use of the Metrohm E436. REFERENCES 1. 2. Orlova, N. N., Aksensova, V. A., Selidovkin, I). A., Bogdanova, N. S., and Pershin, G. N., 3. 4. 5. 6. Koshkin, N. V., Zh. Analit. Khirn., 1963, 18, 1492. Domagk, G., Behenish, R., Mietzsch, F., and Schmidt, H., Naturwissenschaften, 1946, 33, 315. Farmakologiya i Toksikologiya, 1968, 31, 725; translated as Russ. Pharm. Toxic., 1968, 348. Butler, K., U.S. Patent No. 3 382 266, 1968. Bauer, D. J., St. Vincent, L., Kempe, C. H., and Dowine, A. W., Lancet, 1963, ii, 494. Petering, H. G., Buskirk, H. H., and Underwood, G. E., Cancer Res., 1964, 64, 367. Received May 13th, 1970 Accepted October lst, 1970