Synthesis of Some Derivatives of Barbituric Acid
Abstract Generated abstract
This paper reports the synthesis of new acyl derivatives of 5,5-substituted barbituric acids intended for evaluation of how nitro and halogen substituents in the acyl residue may affect anticonvulsant activity. Barbiturates were acylated with acid chlorides of meta-nitrobenzoic, ortho-nitrobenzoic, and para-chlorobenzoic acids in pyridine at 125 to 130 °C, followed by crystallization and recrystallization, and the products were characterized by melting points, yields, formulas, and nitrogen analysis. The study obtained several previously undescribed N-nitrobenzoyl and N-para-chlorobenzoylbarbituric acids, noted differences in monoacyl and diacyl product formation depending on the acid chloride, and submitted the compounds for pharmacological testing.
Full Text
Synthesis of Some Derivatives of Barbituric Acid
A. A. Shesterova, S. D. Yaroslavtseva, A. G. Pechenkin
(Presented by the scientific-methodological seminar of the organic departments of the Chemical-Technological Faculty)
In previous studies [1, 2] it was shown that introduction of a benzoyl radical at nitrogen in the molecule of 5,5-substituted barbituric acids leads to a considerable increase in their anticonvulsant activity.
\[ \begin{array}{c} \begin{array}{ccccc} & & R_3 & & \\ & & | & & \\ R_1 & \backslash & & CO{-}N & \backslash \\ & & C^{5} & & {}^{2}CO \\ R_2 & / & & CO{-}N & / \\ & & & & \\ & & & | & \\ & & & R_4 & \end{array} \end{array} \]
It was of interest to determine the influence of various substituents in the acyl residue on the anticonvulsant activity of acylbarbiturates. For this purpose we undertook the synthesis of several acyl derivatives of barbituric acids containing a nitro group and a halogen in the acyl residue. To obtain these acyl derivatives of barbituric acids, the acid chlorides of meta-nitrobenzoic, ortho-nitrobenzoic, and para-chlorobenzoic acids were used as acylating agents.
The acylation reaction of barbiturates was carried out in the presence of pyridine at the reagent ratio barbiturate : acid chloride : pyridine = 1 : 1 : 1. The reaction temperature was 125–130° (oil bath), and the duration was 6 hours. After completion of the reaction, the mass was crystallized by thorough washing with ice-cooled water and recrystallized from alcohol to a constant melting point. All the compounds obtained were colorless powders, insoluble in water and readily soluble in benzene, alcohol, and ether. The list of compounds obtained and some of their characteristics are given in the table.
It should be noted that, in the acylation of barbiturates with the acid chlorides of ortho- and meta-nitrobenzoic acids, formation of...
Table 1
| No. | Name of compound | Structure of compounds | Gross formula | Melting temperature, °C | Yield of pure product, % | Analysis for N, %, calculated | Analysis for N, %, found |
|---|---|---|---|---|---|---|---|
| 1 | 5,5-diethyl-1(3)-meta-nitrobenzoylbarbituric acid | General barbituric-acid derivative structure with substituents \(R_1, R_2, R_3, R_4\) | \(C_{15}H_{15}N_3O_6\) | 182–184 | 40 | 12.61 | 13.00 |
| 2 | 5-ethyl-5-isoamyl-1(3)-meta-nitrobenzoylbarbituric acid | General barbituric-acid derivative structure with substituents \(R_1, R_2, R_3, R_4\) | \(C_{18}H_{21}N_3O_6\) | 102–103 | 39 | 11.17 | 11.55 |
| 3 | 5-ethyl-5-phenyl-1(3)-meta-nitrobenzoylbarbituric acid | General barbituric-acid derivative structure with substituents \(R_1, R_2, R_3, R_4\) | \(C_{19}H_{15}N_3O_6\) | 157–158 | 42 | 11.02 | 11.20 |
| 4 | 5-ethyl-5-phenyl-1(3)-ortho-nitrobenzoylbarbituric acid | General barbituric-acid derivative structure with substituents \(R_1, R_2, R_3, R_4\) | \(C_{19}H_{15}N_3O_6\) | 137–139 | 45 | 11.02 | 10.75 |
| 5 | 5-ethyl-5-phenyl-1(3)-para-chlorobenzoylbarbituric acid | General barbituric-acid derivative structure with substituents \(R_1, R_2, R_3, R_4\) | \(C_{19}H_{15}N_2O_4Cl\) | 194–196 | 34 | 7.56 | 7.33 |
| 6 | 5-ethyl-5-phenyl-1,3-diparachlorobenzoylbarbituric acid | General barbituric-acid derivative structure with substituents \(R_1, R_2, R_3, R_4\) | \(C_{26}H_{18}N_2O_5Cl\) | 158–160 | 14 | 5.50 | 5.50 |
| 7 | 5-ethyl-5-isoamyl-1,3-parachlorobenzoylbarbituric acid | General barbituric-acid derivative structure with substituents \(R_1, R_2, R_3, R_4\) | \(C_{18}H_{21}N_2O_4Cl\) | 140–142 | 50 | 7.67 | 7.83 |
| 8 | 5-ethyl-5-isoamyl-1,3-diparachlorobenzoylbarbituric acid | General barbituric-acid derivative structure with substituents \(R_1, R_2, R_3, R_4\) | \(C_{25}H_{24}N_2O_5Cl\) | 125–127 | 15 | 5.56 | 5.15 |
$N, N^1$—diacyl derivatives, whereas on acylation (under identical conditions) with the acid chloride of unsubstituted benzoic acid and with the acid chloride of p-chlorobenzoic acid, diacyl derivatives are formed.
Conclusion
A total of seven N-ortho-nitrobenzoyl-, N-meta-nitrobenzoyl-, and N-para-chlorobenzoylbarbituric acids not described in the literature have been synthesized and submitted for pharmacological testing.
REFERENCES
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- L. P. Kulev, A. A. Shesterova. ZhOKh, 31, issue 4, 1378 (1961).