Development of optimal conditions for the synthesis of 4-stearylaminoantipyrine
Abstract Generated abstract
This study examines the synthesis of 4-stearylaminoantipyrine, a compound reported by the authors as previously undescribed and considered pharmacologically promising because of anti-inflammatory and antipyretic activity with low toxicity in tests. The compound was prepared by acylating 4-aminoantipyrine with stearic acid in an inert solvent using phosphorus trichloride, and the effects of solvent, reaction time, and temperature on yield were systematically compared. The highest yield, about 96 percent of theoretical, was obtained by carrying out the reaction in boiling benzene for two hours, while longer reaction times did not improve yield and toluene gave lower yields. The product was characterized as a crystalline substance with melting point 143 to 144°C, and elemental analysis was consistent with the proposed formula.
Full Text
Optimization of Conditions for the Synthesis of 4-Stearylaminoantipyrine
E. V. Shmidt, G. M. Stepnova, S. G. Medvedeva
(Presented by the scientific-methodological seminar of the Chemical-Technological Faculty)
The 4-stearylaminoantipyrine synthesized by us, not previously described in the literature, showed high anti-inflammatory and antipyretic activity and low toxicity in pharmacological tests, which gives grounds for considering it promising for medical practice.
The aim of the present work was to find the optimal conditions for obtaining this compound.
To introduce the stearyl radical into the molecule of 4-aminoantipyrine, we used the reaction, known from the literature, of the interaction of primary amines with free carboxylic acids in an inert solvent medium in the presence of a chlorinating agent [1–7].
As the solvent in our experiments we used benzene and toluene, and as the condensing agent—phosphorus trichloride.
We investigated the influence of time and temperature on the yield of 4-stearylaminoantipyrine.
The results of the experiments are presented in Table 1. From Table 1 it is seen that it is most rational to carry out the reaction in boiling benzene for two hours. A further increase in the reaction time in boiling benzene
Table 1
| No. | Solvent | Reaction time, min | Temperature of the oil bath, °C | Yield of reaction product, % | Melting temperature of the product, °C |
|---|---|---|---|---|---|
| 1 | Benzene | 15 | 100 | 79.2 | 140–142 |
| 2 | » | 30 | 100 | 86.6 | 141–143 |
| 3 | » | 60 | » | 93.2 | 142–143 |
| 4 | » | 120 | » | 96.3 | 142–143 |
| 5 | » | 180 | » | 96.0 | 142–143 |
| 6 | » | 240 | » | 96.0 | 142–143 |
| 7 | » | 120 | 40 | 83.9 | 140–142 |
| 8 | » | 120 | 60 | 88.3 | 141–142 |
| 9 | » | 120 | 80 | 92.3 | 141–142 |
| 10 | » | 120 | 90 | 96.0 | 142–143 |
| 11 | Toluene | 120 | 70 | 87.5 | 140–142 |
| 12 | » | » | 90 | 88.7 | 140–142 |
| 13 | » | » | 100 | 89.7 | 141–142 |
| 14 | » | » | 120 | 91.0 | 142–143 |
| 15 | » | » | 130 | 92.3 | 142–143 |
does not affect the yield. Acylation proceeds more completely under conditions of vigorous boiling of the solvents; moreover, replacing the low-boiling benzene with the higher-boiling toluene has an adverse effect on the yield.
Experimental Part
4-Stearylaminoantipyrine. 0.05 gram-mole of stearic acid and 0.05 gram-mole of 4-aminoantipyrine are dissolved in 50 ml of anhydrous benzene, placed in a round-bottom flask equipped with a stirrer, dropping funnel, and reflux condenser, and heated in an oil bath fitted with a thermoregulator to a temperature of 60°C. At 60–70°C, 0.23 gram-mole of phosphorus trichloride is added dropwise from the dropping funnel over 20 min. During the addition of phosphorus trichloride, the formation of a cream-colored precipitate is observed; after 10–15 min it dissolves completely. At the same time, hydrogen chloride is vigorously evolved. The mixture is heated with stirring for a specified time at a specified temperature.
After cooling, the acylation product precipitates. It is filtered off and treated successively with a 10% sodium carbonate solution and hot water.
After hot filtration and washing of the precipitate with hot water to a neutral reaction, the product is dried and the yield determined.
Purification is carried out by recrystallization from ethanol. The average yield of pure product is 90%.
4-Stearylaminoantipyrine is a colorless crystalline substance with a melting point of 143–144°C, insoluble in water, sparingly soluble in ether, and soluble in alcohol and aromatic solvents.
Calculated, %: N 8.94; C 74.11; H 10.00. C₂₉H₄₇O₂N₃.
Found, %: N 8.86; C 74.61; H 9.95.
Conclusions
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4-Stearylaminoantipyrine, not previously described in the literature, has been synthesized.
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The optimal conditions for the synthesis of 4-stearylaminoantipyrine have been determined (dependence of yield on time and temperature).
It has been shown that, under optimal conditions, 4-stearylaminoantipyrine can be obtained in a yield of 96% of theoretical.
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- R. N. Gireva. Izv. TPI, 83, 129, 1956.
- L. P. Kulev, G. M. Stepnova. Izv. Sib. otd. AN SSSR, 5, 73, 1960.
- G. M. Stepnova, E. V. Shmidt, ZhVKhO im. D. I. Mendeleeva 10, 3, 358, 1965.