Hydrolysis of N-alkylantipyrylamides
Abstract Generated abstract
The study examines acid hydrolysis of several acyl derivatives of N-alkylantipyrylamides to test previously proposed relationships between structure, hydrolytic cleavage, and physiological activity. Hydrolysis was measured in 0.1 N hydrochloric acid at 99°C, with products quantified colorimetrically, and rate constants were compared across compounds differing in acyl substituent position, substituent type, and N-alkyl chain length. The results support that nucleophilic substituents in the acid residue increase hydrolysis rates, while electrophilic substituents reduce them, and that longer N-alkyl radicals lower the rate. The reported data also indicate a direct relationship between hydrolysis rate and anti-inflammatory activity within the examined N-alkylantipyrylamide series.
Full Text
HYDROLYSIS OF N-ALKYLANTIPYRYLAMIDES
G. M. Stepnova, L. A. Shabrova, L. F. Sadovskaya
(Presented by the scientific-methodological seminar of the Faculty of Chemical Technology)
Earlier [1], we studied the comparative rate of hydrolysis of a series of acyl derivatives of 4-methylaminoantipyrine and drew conclusions about the relationship between their physiological activity and their ability to undergo hydrolytic cleavage, as well as about the dependence of the hydrolysis rate on the nature of the acid residue entering into the composition of N-methylantipyrylamide.
In order to confirm the results obtained, we determined the hydrolysis rate of a series of other acyl derivatives of N-alkylantipyrylamides. Hydrolysis was carried out in a medium of 0.1 N hydrochloric acid at 99°C according to the previously described procedure [1]. The substances formed were determined quantitatively by the colorimetric method. The experimental results are presented in Table 1.
Table 1
| No. | Name of substance | Hydrolysis constant, h\(^{-1}\) |
|---|---|---|
| 1 | 4-(4′-aminobenzoyl)-ethylaminoantipyrine | 0.21 |
| 2 | 4-(4′-aminobenzoyl)-propylaminoantipyrine | 0.19 |
| 3 | 4-(3′-oxybenzoyl)-methylaminoantipyrine | 0.28 |
| 4 | 4-(2′-tolyl)-methylaminoantipyrine | 0.00 |
| 5 | 4-(3′-tolyl)-methylaminoantipyrine | 0.26 |
| 6 | 4-(4′-tolyl)-methylaminoantipyrine | 0.33 |
| 7 | 4-(3′-chlorobenzoyl)-methylaminoantipyrine | 0.15 |
| 8 | 4-(4′-chlorobenzoyl)-methylaminoantipyrine | 0.17 |
The data obtained confirm the conclusion regarding the influence of the nature and position of the substituent in the acid nucleus on the hydrolysis rate of N-alkylantipyrylamides [2]. Nucleophilic substituents increase the hydrolysis rate, while electrophilic substituents decrease it.
Experiments showed that, with lengthening of the alkyl radical of the N-alkylantipyrylamide, the hydrolysis rate decreases. A direct relationship between the hydrolysis rate and physiological activity
is valid not only in a series of different acyl derivatives of 4-methylaminoantipyrine, but also in a series of different N-alkylantipyrylamides, as can be seen from Table 2.
Table 2
| Name of substance | Hydrolysis \(K\), h\(^{-1}\) | Anti-inflammatory activity |
|---|---|---|
| 4-(4′-aminobenzoyl)-methylaminoantipyrine | 0.92 | 2.4 |
| 4-(4′-aminobenzoyl)-ethylaminoantipyrine | 0.21 | 1 |
| 4-(4′-aminobenzoyl)-propylaminoantipyrine | 0.19 | 0.77 |
REFERENCES
- L. A. Shabrova, G. M. Stepnova. Izv. TPI, 151, 82, 1965.
- L. A. Shabrova. Search for anti-inflammatory agents in a series of acyl derivatives of 4-alkylaminoantipyrines. Dissertation for the degree of Candidate of Chemical Sciences, Tomsk, 1966.