Study of the Acylation Reaction of N-Methyl-4-aminoantipyrine
Abstract Generated abstract
The study examines acylation of N-methyl-4-aminoantipyrine with benzoyl chloride, p-nitrobenzoyl chloride, and p-toluyl chloride, focusing on optimal reaction conditions, substituent effects, and base catalysis. Experiments in p-xylene identified 138 °C and 0.5 h as suitable conditions for noncatalytic acylation, with reaction rates increasing as the para substituent on the acid chloride changed from electron donating to electron accepting. Comparison with 4-aminoantipyrine indicated that an electron-donating substituent in the amine also increases the reaction rate. Sodium hydroxide was shown to catalyze the reaction in aqueous medium, permitting high product yields at room temperature within 0.5 h, and rate constants were calculated for the studied systems.
Full Text
STUDY OF THE ACYLATION REACTION OF N-METHYL-4-AMINOANTIPYRINE
G. M. STEPANOVA, G. A. TERENT'EVA, L. N. FILIPPOVA
(Presented by the scientific-methodological seminar of the Faculty of Chemical Technology)
Continuing work on the acylation of heterocyclic amines of the pyrazolone series, a study was carried out of the benzoylation reaction of \(N\)-methyl-4-aminoantipyrine.
The aim of the present work is to determine the optimal reaction conditions, to clarify the possibility of catalytic action of bases on the acylation process of \(N\)-methyl-4-aminoantipyrine, and also to clarify the influence of substituents in the para position of the benzene ring on the reactivity of acid chlorides in the reaction under study.
Fig. 1. Dependence of the yield of the product of the benzoylation reaction of \(N\)-methyl-4-aminoantipyrine and 4-aminoantipyrine on the reaction temperature. Curve 1—acylation of \(N\)-methyl-4-aminoantipyrine with \(p\)-nitrobenzoyl chloride. Curve 2—acylation of \(N\)-methyl-4-aminoantipyrine with benzoyl chloride. Curve 3—acylation of \(N\)-methyl-4-aminoantipyrine with \(p\)-toluyl chloride. Curve 4—acylation of 4-aminoantipyrine with benzoyl chloride [5].
The experimental results showed that the optimal conditions for noncatalytic acylation of \(N\)-methyl-4-aminoantipyrine with benzoyl chloride and its para derivatives are: solvent—p-xylene, temperature \(138^\circ\mathrm{C}\), reaction time 0.5 h (Fig. 1). As can be seen from Fig. 1, on going from an electron-donating substituent in the benzoyl chloride molecule to an electron-accepting one, the reaction rate increases. On this basis, it may be assumed that acylation of heterocyclic amines proceeds through the formation of an intermediate
Fig. 2. Dependence of the yield of the acyl derivative on the amount of caustic soda. Curve 1—acylation of \(N\)-methyl-4-aminoantipyrine with p-nitrobenzoyl chloride. Curve 2—acylation of \(N\)-methyl-4-aminoantipyrine with benzoyl chloride. Curve 3—acylation of \(N\)-methyl-4-aminoantipyrine with p-toluyl chloride.
Table 1
| Amine | Acid chloride | Reaction \(t\), °C | Reaction time, h | Catalyst, g/mol NaOH per g/mol amine | Reaction rate constant, L/mol·s |
|---|---|---|---|---|---|
| \(N\)-methyl-4-aminoantipyrine | p-nitrobenzoyl chloride | 138 | 0.5 | — | \(1.640\cdot10^{-1}\) |
| \(N\)-methyl-4-aminoantipyrine | benzoyl chloride | 138 | 0.5 | — | \(1.225\cdot10^{-1}\) |
| \(N\)-methyl-4-aminoantipyrine | p-toluyl chloride | 138 | 0.5 | — | \(0.845\cdot10^{-1}\) |
| 4-aminoantipyrine | benzoyl chloride | 138 | 0.5 | — | \(0.144\cdot10^{-1}\) [5] |
| \(N\)-methyl-4-aminoantipyrine | p-nitrobenzoyl chloride | 20 | 0.5 | 1:1 | \(0.496\cdot10^{-1}\) |
| \(N\)-methyl-4-aminoantipyrine | benzoyl chloride | 20 | 0.5 | 1:1 | \(0.300\cdot10^{-1}\) |
| \(N\)-methyl-4-aminoantipyrine | p-toluyl chloride | 20 | 0.5 | 1:1 | \(0.08\cdot10^{-1}\) |
product of addition of the amine and the acid chloride, with subsequent elimination of a molecule of hydrogen chloride [1].
As was to be expected, introduction of an electron-donating substituent into the amine molecule leads to an increase in the rate of the acylation reaction (compare curves 2 and 4 in Fig. 1).
As the main catalyst for the acylation reaction of \(N\)-methyl-4-aminoantipyrine, sodium hydroxide was used in the form of a 10% aqueous solution. The experiments showed that sodium hydroxide catalyzes the reaction under investigation and makes it possible, at room temperature in an aqueous medium, to achieve a high yield of the product within 0.5 h (Fig. 2).
On the basis of the experimental data, the rate constants of the reaction were calculated. The values of the constants are given in Table 1.
Experimental Part
Starting materials: p-xylene [2], benzoyl chloride, p-nitrobenzoyl chloride, and p-toluyl chloride [3] were purified by known procedures. \(N\)-Methyl-4-aminoantipyrine was purified by extraction of impurities with chloroform from an aqueous solution of the amine hydrochloride [4].
Acylation in an aqueous medium and in an organic-solvent medium was carried out according to the procedure described [5].
The amount of unreacted amine was determined by titration with a 0.1 N solution of sodium nitrite.
Each experiment was repeated at least three times.
Conclusions
The acylation reaction of \(N\)-methyl-4-aminoantipyrine with benzoyl chloride, p-nitrobenzoyl chloride, and p-toluyl chloride in xylene has been investigated.
The influence of electron-donating and electron-accepting substituents in the para position of the acid chloride molecule and of an electron-donating substituent in the amine molecule on the rate of the acylation reaction has been studied.
The effect of sodium hydroxide additions on the reaction under investigation has been shown. It was found that sodium hydroxide is a catalyst for the benzoylation of \(N\)-methyl-4-aminoantipyrine.
References
- T. I. Temnikova. Course on the Theoretical Foundations of Organic Chemistry. Goskhimizdat, Moscow, 446, 1962.
- L. M. Litvinenko et al. Ukrainian Chemical Journal, 27, 336, 1961.
- L. M. Litvinenko et al. Ukrainian Chemical Journal, 25, 81, 1959.
- L. A. Shabrova. Dissertation for the degree of Candidate of Chemical Sciences. Tomsk, 966.
- N. D. Pryanishnikov. Laboratory Manual in Organic Chemistry. Moscow, Goskhimizdat, 71, 1950.