Some derivatives of 1-phenyl-2,3-dimethyl-5-keto-4-pyrazolylamine
Abstract Generated abstract
This paper reports the synthesis of new N-methyl analogs of acyl derivatives of 1-phenyl-2,3-dimethyl-5-keto-4-pyrazolylamine, motivated by earlier findings that related benzoyl derivatives showed anti-inflammatory and antipyretic activity and by the possible activity-enhancing effect of N-methyl substitution. The compounds were prepared by acylating N-methylaminoantipyrine in benzene with the corresponding acid chlorides in the presence of sodium carbonate, followed by recrystallization from alcohol or benzene. Five previously undescribed derivatives were obtained, including dinitrobenzoic, iodobenzoic, methoxybenzoic, and stearic acid amides, and their melting points and elemental analyses are reported.
Full Text
SOME DERIVATIVES OF 1-PHENYL-, 2,3-DIMETHYL-5-KETO-4-PYRAZOLYLAMINE
E. V. Schmidt, G. M. Stepnova
(Presented by the scientific seminar of the departments and laboratories of organic synthesis, CTF)
Previously we synthesized a series of benzoyl derivatives, substituted in the benzoyl radical, of 1-phenyl-2,3-dimethyl-5-keto-4-pyrazolylamine. Some of these compounds, in pharmacological experiments, showed high anti-inflammatory and antipyretic activity along with low toxicity [1, 2, 3, 4]. Generalizations were made concerning the relationship between action and structure [5].
It is known that introduction of a methyl group at a nitrogen atom in the molecules of physiologically active organic compounds increases the effectiveness of their action.
Table 1
| No. | Compound | M.p., °C | Empirical formula | Nitrogen, % found | Nitrogen, % calculated | Carbon, % found | Carbon, % calculated | Hydrogen, % found | Hydrogen, % calculated |
|---|---|---|---|---|---|---|---|---|---|
| N-methylantipyrinamides: | |||||||||
| 1 | of 3,5-dinitrobenzoic acid | 217—218 | C₁₉H₁₇O₆N₅ | 17.09 | 17.03 | 55.74 | 55.47 | 4.12 | 4.13 |
| 2 | of 2-iodobenzoic acid | 136—137 | C₁₉H₁₈O₂N₃J | 9.51 | 9.40 | 51.19 | 51.00 | 3.90 | 4.02 |
| 3 | of 2-methoxybenzoic acid | 162—163 | C₂₀H₂₁O₃N₃ | 12.23 | 11.97 | 68.71 | 68.37 | 6.10 | 6.00 |
| 4 | of 4-methoxybenzoic acid | 170—171 | C₂₀H₂₁O₃N₃ | 11.78 | 11.97 | 68.77 | 68.37 | 6.18 | 6.00 |
| 5 | of stearic acid | 76—77 | C₃₀H₄₉O₂N₃ | 8.29 | 8.69 | 75.15 | 74.53 | 10.39 | 10.14 |
For the purpose of increasing activity and further elucidating the dependence between structure and action in the series of derivatives of 1-phenyl-2,3-dimethyl-5-keto-4-pyrazolylamine, several N-methyl analogs of its acyl derivatives were synthesized.
The N-methyl derivatives of 1-phenyl-2,3-dimethyl-5-keto-4-pyrazolylamides were obtained by acylation of N-methylaminoantipyrine in benzene solution with acid chlorides in the presence of dry sodium carbonate or its concentrated aqueous solution. The preparations
were purified by recrystallization from alcohol or benzene. They are crystalline substances, insoluble in water and soluble in ordinary organic solvents. The characteristics of the compounds obtained are given in the table.
Experimental Part
N-Methylantipyrilamide of 2-Iodobenzoic Acid
Into a round-bottom flask equipped with a reflux condenser, stirrer, and dropping funnel are placed 0.1 g-mol of 2-iodobenzoic acid, 50 ml of benzene is added, and the mixture is heated on an oil bath. At 50°C, 7 ml of thionyl chloride is added from the dropping funnel, and heating in boiling benzene is continued until the evolution of hydrogen chloride ceases (1.5 hours).
The solution is cooled to 40°, 15 g of anhydrous sodium carbonate is added, and a benzene solution of 0.1 g-mol of N-methylaminoantipyrine is introduced. The mixture is heated for 1 hour with vigorous stirring at 80°. It is cooled, filtered from inorganic salts, and the benzene is distilled off from the filtrate. The thick, resinous residue is treated with a 10% solution of sodium carbonate. In this process, crystallization of the reaction product gradually occurs. It is separated and purified by recrystallization first from aqueous alcohol and then from benzene.
If the N-methylantipyrilamide is insoluble in benzene, it is separated by filtration, thoroughly washed with water, and purified by recrystallization (N-methylantipyrilamides of methoxybenzoic acids).
When the acid chloride is available, the acylation reaction of N-methylaminoantipyrine is carried out according to the procedure described by us earlier [4].
Conclusions
Five derivatives of 1-phenyl-2,3-dimethyl-5-keto-4-N-methylpyrazolylamine not described in the literature have been synthesized.
References
- L. M. Semikolennykh, A. B. Solov’eva, G. M. Stepnova, V. Kh. Taksidi, E. V. Shmidt. Zhurn. VKHO im. D. I. Mendeleeva, 8, No. 6, 704, 1963.
- G. M. Stepnova, E. V. Shmidt. Ibid., 10, No. 3, 358, 1965.
- G. M. Stepnova, E. V. Shmidt. Izv. vuzov SSSR, 8, 3, 520, 1965.
- G. M. Stepnova, E. V. Shmidt, N. F. Matveeva. Izv. TPI, 151, 78, 1965.
- G. M. Stepnova, E. V. Shmidt. Proceedings of the scientific conference devoted to implementing the decisions of the December Plenum of the CPSU Central Committee (Tomsk, December 1964), in press.