Pyrazolylamides of Toluic Acids
Abstract Generated abstract
This paper reports the synthesis of new pyrazolylamides of toluic acids as part of a study of how methyl substitution influences the physiological activity of acyl derivatives of 4-amino-5-pyrazolones. The authors prepared derivatives using isomeric toluic acids as acylating components, with phosphorus trichloride in refluxing xylene, and characterized the products by yield, melting point, empirical formula, and nitrogen analysis. Six previously undescribed antipyrilamide and tolipyrilamide derivatives of 2-, 3-, and 4-toluic acids were obtained in moderate yields and are presented as compounds of potential anti-inflammatory interest.
Full Text
PYRAZOLYLAMIDES OF TOLUIC ACIDS
G. M. STEPANOVA, E. V. SHMIDT, L. P. ERMOLAEVA, N. S. GRIGOREVSKAYA
(Presented at the scientific seminar of the Faculty of Chemical Technology)
Previously we synthesized and studied a large number of acyl derivatives of 4-aminoantipyrine and \(N\)-alkyl-4-aminoantipyrines [1—6].
As pharmacological tests have shown, compounds of this type possess anti-inflammatory, antipyretic, and analgesic activity. Some of them, moreover, surpass antipyrine and butadione.
In establishing the relationship between physiological activity and the chemical structure of pyrazolylamides, it was found that introduction of a methyl radical into the amide group enhances the physiological action of the compound.
In connection with this, it was of interest to trace the effect of methyl grouping of atoms on therapeutic properties when it is present in the phenyl radical located in position 1 of the pyrazolone ring and in the acid residue.
For this purpose, in the present work we synthesized acyl derivatives of 4-amino-5-pyrazolones of the general formula
\[ \begin{array}{c} \mathrm{H_3C{-}C{=}C{-}NH{-}CO{-}C_6H_4{-}CH_3} \qquad X = H;\ CH_3\\ \quad\ \ \big| \qquad \big|\\ \mathrm{H_3C{-}N} \qquad \mathrm{C{=}O}\\ \quad\ \ \backslash \qquad /\\ \mathrm{N}\\ \big|\\ \mathrm{C_6H_4}\\ \big|\\ X \end{array} \]
As acylating agents, isomers of toluic acids were selected, which themselves possess some anti-inflammatory activity.
Acylation was carried out with acids in the presence of phosphorus trichloride in xylene medium under reflux for 2 hours; the properties of the synthesized compounds are given in the table.
Table 2
Properties of the synthesized amides
| No. | Compound name | Yield, % | M.p., °C | Empirical formula | Nitrogen, % calculated | Nitrogen, % found |
|---|---|---|---|---|---|---|
| 1 | Tolipyrilamide of 2-toluic acid | 60 | 186 | \(C_{20}H_{21}O_{2}N_{3}\) | 12.53 | 12.64 |
| 2 | Tolipyrilamide of 3-toluic acid | 50 | 130 | \(C_{20}H_{21}O_{2}N_{3}\) | 12.53 | 12.84 |
| 3 | Tolipyrilamide of 4-toluic acid | 60 | 199 | \(C_{20}H_{21}O_{2}N_{3}\) | 12.53 | 12.73 |
| 4 | Antipyrilamide of 2-toluic acid | 65 | \(C_{19}H_{19}O_{2}N_{3}\) | 13.08 | 13.23 | |
| 5 | Antipyrilamide of 3-toluic acid | 70 | 171–172 | \(C_{19}H_{19}O_{2}N_{3}\) | 13.08 | 13.13 |
| 6 | Antipyrilamide of 4-toluic acid | 60 | \(C_{19}H_{19}O_{2}N_{3}\) | 13.08 | 13.23 |
Conclusion
Six pyrazolylamides of toluic acids not described in the literature, with potential anti-inflammatory activity, have been synthesized.
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