Benzoyl Derivatives of Ethylalkylbarbituric Acids
Abstract Generated abstract
This study reports the synthesis of N-monobenzoyl and N,N′-dibenzoyl derivatives of 5,5-ethylalkylbarbituric acids as part of a search for anticonvulsant agents among barbituric acid derivatives. Ethylalkylmalonic esters were prepared by alkylation of malonic ester, converted to the corresponding barbituric acids by condensation with urea, and then benzoylated with benzoyl chloride in pyridine. The resulting compounds were characterized as crystalline substances, with melting points and elemental analyses reported for the series. Eleven benzoyl derivatives were obtained, ten of which were stated to be previously undescribed in the literature.
Full Text
BENZOYL DERIVATIVES OF ETHYLALKYLBARBITURIC ACIDS
A. A. Shesterova, S. D. Yaroslavtseva
(Presented by the scientific seminar of the departments and laboratories of organic synthesis, CTF)
A wide variety of derivatives of barbituric acid have been obtained and studied. Many of them have found broad application in medical practice. The dependence of the hypnotic and soporific action of barbiturates on their structure has been studied sufficiently. Continuing the investigations begun earlier \[1, 2\] in the search for anticonvulsant drugs among derivatives of barbituric acid, in the present work we undertook the synthesis of N-mono- and N,N′-dibenzoyl derivatives of 5,5-ethylalkylbarbituric acids. As alkyl radicals we selected: $\mathrm{C_2H_5}$, n-$\mathrm{C_3H_7}$, iso-$\mathrm{C_3H_7}$, n-$\mathrm{C_4H_9}$, iso-$\mathrm{C_4H_9}$, n-$\mathrm{C_5H_{11}}$, iso-$\mathrm{C_5H_{11}}$.
The ethylalkylmalonic esters necessary for the synthesis of barbituric acids were obtained by alkylation of malonic ester with alkyl bromides in absolute ethyl alcohol in the presence of sodium ethylate. Ethylalkylbarbituric acids were obtained by condensation of the corresponding malonic esters with urea \[3\].
Benzoylation was carried out by the action of benzoyl chloride on ethylalkylbarbituric acids in the presence of pyridine. The benzoyl derivatives of ethylalkylbarbituric acids are white crystalline substances, insoluble in water and soluble in alcohol, ether, benzene, acetone, and chloroform. In this series of benzoyl derivatives of ethylalkylbarbituric acids—5,5-diethyl-N-benzoyl, 5,5-ethylisoamyl-N-benzoyl, and 5,5-ethylisoamyl-N,N′-dibenzoylbarbituric acids—were described by us earlier \[2\]. 5,5-Diethyl-N,N′-dibenzoylbarbituric acid was obtained by Rosenberg by another method \[4\].
Experimental Part
Into a three-necked flask equipped with a reflux condenser, a stirrer, and a dropping funnel are placed 0.02 mole of ethylalkylbarbituric acid, 0.02 mole of pyridine, and 0.02 mole of benzoyl chloride. The reaction mixture is heated with stirring on an oil bath for 4 hours (bath temperature 125–130°C). After this, 50 ml of benzene is added to the reaction mass, and it is stirred with heating for 10 minutes. The precipitate of pyridine hydrochloride, which separates after cooling of the benzene solution, is filtered off and washed with benzene. On the following day a syrup-like product separates from the benzene filtrate; it is thoroughly washed with ice water until solidification-
Table 1
\[ \begin{array}{c} \mathrm{R'}\\[-2mm] \vert\\ \mathrm{R{-}C\!\!\begin{array}{c} \diagup\!\mathrm{CO{-}NH{-}CO}\\[-1mm] \diagdown\!\mathrm{C_2H_5}\quad\mathrm{CO{-}N{-}COC_6H_5} \end{array}} \end{array} \]
| No. | \(R\) | \(R'\) | Molecular formula | \(T_{\mathrm{m.p.}},\,^\circ\mathrm{C}\) | C found | C calculated | H found | H calculated | N found | N calculated |
|---|---|---|---|---|---|---|---|---|---|---|
| 1*) | \(\mathrm{C_2H_5}\) | \(\mathrm{COC_6H_5}\) | \(\mathrm{C_{20}H_{20}O_5N_2}\) | 236–237 | 67,64 | 67,34 | 5,28 | 5,10 | 7,38 | 7,14 |
| 2 | \(n\)-\(\mathrm{C_3H_7}\) | H | \(\mathrm{C_{16}H_{18}O_3N_2}\) | 140–142 | 63,88 | 63,57 | 6,00 | 5,96 | 9,44 | 9,27 |
| 3 | \(n\)-\(\mathrm{C_3H_7}\) | \(\mathrm{COC_6H_5}\) | \(\mathrm{C_{22}H_{24}O_5N_2}\) | 194–198 | 68,48 | 67,97 | 5,95 | 5,41 | 7,01 | 6,89 |
| 4 | \(n\)-\(\mathrm{C_4H_9}\) | H | \(\mathrm{C_{17}H_{20}O_3N_2}\) | 90–94 | 65,25 | 64,55 | 6,43 | 6,67 | 9,05 | 8,86 |
| 5 | \(n\)-\(\mathrm{C_4H_9}\) | \(\mathrm{COC_6H_5}\) | \(\mathrm{C_{23}H_{26}O_5N_2}\) | 154–156 | 69,00 | 68,5 | 5,87 | 5,71 | 6,72 | 6,62 |
| 6 | iso-\(\mathrm{C_3H_7}\) | H | \(\mathrm{C_{18}H_{22}O_3N_2}\) | 130–132 | 63,41 | 63,57 | 6,05 | 5,96 | 9,39 | 9,27 |
| 7 | iso-\(\mathrm{C_3H_7}\) | \(\mathrm{COC_6H_5}\) | \(\mathrm{C_{23}H_{26}O_5N_2}\) | 212–214 | 67,87 | 67,97 | 5,72 | 5,41 | 6,92 | 6,89 |
| 8 | iso-\(\mathrm{C_4H_9}\) | H | \(\mathrm{C_{17}H_{20}O_3N_2}\) | 113–115 | 64,97 | 64,55 | 6,61 | 6,67 | 8,89 | 8,86 |
| 9 | iso-\(\mathrm{C_4H_9}\) | \(\mathrm{COC_6H_5}\) | \(\mathrm{C_{24}H_{28}O_5N_2}\) | 153–154 | 68,54 | 68,5 | 5,97 | 5,71 | 6,56 | 6,62 |
| 10 | \(n\)-\(\mathrm{C_5H_{11}}\) | H | \(\mathrm{C_{18}H_{20}O_3N_2}\) | 92–94 | 65,61 | 65,4 | 6,64 | 6,6 | 8,8 | 8,48 |
| 11 | \(n\)-\(\mathrm{C_5H_{11}}\) | \(\mathrm{COC_6H_5}\) | \(\mathrm{C_{25}H_{30}O_5N_2}\) | 124–126 | 69,03 | 69,1 | 6,01 | 5,9 | 6,72 | 6,45 |
*) The compound was obtained by Rosenberg [4], m.p. 235–237°.
[[unclear: beginning of sentence]] The product dissolves upon heating in a minimal amount of alcohol. On cooling, the precipitated dibenzoyl derivative is filtered off. From the alcoholic filtrate, the monobenzoyl derivative is precipitated with water. The products were purified by repeated recrystallization from alcohol.
The elemental-analysis data for the synthesized compounds are given in the table.
Conclusions
Eleven benzoyl derivatives of barbituric acids were synthesized; of these, 10 have not been described in the literature.
LITERATURE
- L. P. Kulev, G. M. Stepnova, V. G. Stolyarchuk, O. N. Nechaeva. ZhOKh, 30, 1385, 1960.
- L. P. Kulev, A. A. Shesterova. ZhOKh, 31, 1378, 1961.
- Ihonle Moncent. J. Am. Chem. Soc., 45, 246, 1923.
- H. Rosenberg. German patent 631097; C. A., 30, 6136, 1936.