Study of the Hydrolytic Stability and Solubility of Stampirin
Abstract Generated abstract
This study examines the hydrolytic stability and solvent solubility of stampirin, a stearic acid antipyrilamide with reported anti-inflammatory activity, to support development of synthesis, purification, and analytical procedures. Hydrolysis was tested in water, sodium hydroxide, and hydrochloric acid media at elevated temperature, with 4-aminoantipyrine determined by diazotization or photocolorimetry, and solubility at 20°C was measured gravimetrically in selected organic solvents. Stampirin was found to be stable in aqueous and alkaline media but completely hydrolyzed under sufficiently strong hydrochloric acid conditions, especially boiling in 25 percent hydrochloric acid for 45 minutes, providing conditions suitable for quantitative determination. The compound was practically insoluble in water and showed differing solubility in ethanol, isopropyl alcohol, diethyl ether, benzene, and carbon tetrachloride.
Full Text
STUDY OF THE HYDROLYTIC STABILITY AND SOLUBILITY OF STAMPIRIN
G. M. STEPNOVA, E. V. SHMIDT, L. N. SURENKOVA
(Presented by the scientific-methodological seminar of the organic departments of the Faculty of Chemical Technology)
The stearic-acid antipyramid synthesized by us—stampirin—showed high anti-inflammatory activity and insignificant toxicity in a pharmacological experiment [1].
The aim of the present work was to study certain properties of this substance, knowledge of which is necessary for developing the most rational method for its synthesis and purification, as well as for its qualitative and quantitative determination.
The article presents the results of a study of the hydrolytic stability of stampirin in various media and under various conditions, and of its solubility in certain organic solvents.
The first series of experiments on the hydrolysis of stampirin was carried out in aqueous, alkaline, and hydrochloric-acid media. The determination procedure was as follows: an accurately weighed portion of stampirin in a definite volume of solvent was placed in a round-bottom flask equipped with a reflux condenser and kept for a specified time in a thermostat at 99°C. After this, the contents of the flask were rapidly cooled in snow to 5°C, and the 4-aminoantipyrine formed as a result of hydrolysis was determined by the diazotization method with an external indicator—starch-iodide paper [2]. The percentage of hydrolysis was calculated from the amount of 4-aminoantipyrine formed. Each experiment was repeated at least 3 times. The results of the experiments on the hydrolysis of stampirin in different media are given in Table 1.
The second series of experiments on the hydrolytic cleavage of stampirin was carried out by boiling an accurately weighed portion of stampirin in a definite volume of 25% hydrochloric acid in an air bath with a reflux condenser for a specified time. The 4-aminoantipyrine formed as a result of hydrolysis was determined quantitatively by a photocolorimetric method on an FEK-56 photocolorimeter according to a procedure based on the color reaction of 4-aminoantipyrine with phenols [3]. The results of these experiments are given in Table 2.
It is seen from Tables 1 and 2 that complete hydrolytic cleavage of stampirin, necessary for its quantitative determination, can be accomplished in a hydrochloric-acid medium with a sufficient concentration of hydrogen chloride. The most suitable conditions for complete hydrolysis of stampirin, which can be used in developing a method for its quantitative determination, are boiling in an air bath in a 25% hydrochloric acid solution (7.5 N) for 45 minutes (stampirin concentration 0.0375 mol/l).
In aqueous and alkaline media, stampirin is hydrolytically stable. This property of the preparation makes it possible to introduce into the procedure for purifying technical stampirin from an admixture of stearic acid its treatment with a sodium carbonate solution at elevated temperature.
Table 1
| No. | Stampirin concentration, mol/L | Medium | Time, h | % hydrolysis |
|---|---|---|---|---|
| 1 | 0,0075 | Water | 5,5 | 1,65 |
| 2 | 0,0075 | 1 N NaOH | 5,0 | 2,09 |
| 3 | 0,0075 | 1 N NaOH | 10,0 | 3,07 |
| 4 | 0,0075 | 0,5 N HCl | 2,0 | 27,8 |
| 5 | 0,0075 | 0,75 N HCl | 1,5 | 39,5 |
| 6 | 0,0075 | 1 N HCl | 1,5 | 56,4 |
| 7 | 0,0075 | 2 N HCl | 2,0 | 81,5 |
| 8 | 0,0030 | 5 N HCl | 1,0 | 91,1 |
| 9 | 0,0030 | 5 N HCl | 1,5 | 100,0 |
Table 2
| No. | Stampirin concentration, mol/L | Medium | Time, min | % hydrolysis |
|---|---|---|---|---|
| 1 | 0,0375 | 25% HCl | 15 | 54,5 |
| 2 | 0,0375 | 25% HCl | 30 | 79,3 |
| 3 | 0,0375 | 25% HCl | 45 | 100,0 |
The solubility of stampirin at 20°C in several organic solvents was determined gravimetrically after 4-hour shaking of an accurately weighed portion of the preparation in a specified volume of solvent. The weight of the undissolved residue and the weight of the amount of stampirin that had passed into solution after evaporation of the solvent were determined. The average solubility of stampirin was calculated in grams per 100 ml of solution (at 20°C). It was expressed in the following figures: in ethanol—1,31; in isopropyl alcohol—1,01; in diethyl ether—0,07; in benzene—3,77; in carbon tetrachloride—0,79. In water, stampirin proved to be practically insoluble.
Conclusions
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The conditions of hydrolytic cleavage of stampirin necessary for developing a procedure for its quantitative determination have been determined.
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It has been established that stampirin is hydrolytically stable in aqueous and alkaline media. The solubility of stampirin at 20°C in several organic solvents has been determined.
Literature
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A. S. Saratnikov, T. P. Prishchep, G. M. Stepnova, E. V. Shmidt et al. Pharmacological properties of stearic-acid antipyrilamide (stampirin). Farmakologiya i toksikologiya, 1972, 6, p. 723.
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A. L. Kolesnikov. Technical Analysis of Raw Materials, Semiproducts, and Finished Products of Synthetic Medicinal Preparations, 318, Medgiz, 1959.
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G. N. Savel’eva, N. M. Tueva. Photometric method for determining nikofezone. Collected Works of the Perm Medical Institute, 63, 43, 1966.