Study of the Synthesis of N,N'-Methylbenzoylurea
Abstract Generated abstract
This study investigates the preparation of N,N′-methylbenzoylurea, a compound reported in pharmacological testing to have notable anticonvulsant activity and low toxicity. The authors developed a synthesis based on acylation of N-methylurea with benzoyl chloride and examined how reagent ratio, solvent, temperature, reaction time, and catalysts affected yield and product purity. The best conditions used a 1.5:1 molar ratio of N-methylurea to benzoyl chloride in boiling benzene for 10 hours, giving a technical product yield of about 67 percent and a purified compound with melting point and elemental analysis consistent with the target substance. Xylene impaired purity, higher temperatures shortened reaction time but complicated purification, and the tested acidic and basic catalysts were ineffective.
Full Text
STUDY OF THE SYNTHESIS OF N,N′-METHYLBENZOYLUREA
N. S. DOBYCHINA, T. V. ANTONOVA, Z. M. MURAV’EVA
(Recommended by the scientific seminar of the Chemical-Technological Faculty)
In the search for anticonvulsant drugs, we synthesized N,N′-methylbenzoylurea by a method differing from that described in the literature [1].
According to pharmacological tests carried out by A. P. Gilev (Novokuznetsk Scientific Research Institute of Chemistry and Pharmacy), N,N′-methylbenzoylurea possesses considerable anticonvulsant activity, low toxicity, and is of practical interest. In this connection, we worked out the optimal conditions for obtaining N,N′-methylbenzoylurea by the method of acylating N-methylurea with benzoyl chloride. The influence on the product yield of various ratios of the starting substances, temperature and reaction time, solvents, and catalysts was studied.
The experimental results show that the highest yield of N,N′-methylbenzoylurea (67%) is obtained when N-methylurea is acylated with benzoyl chloride in molar ratios of the indicated products of 1.5 : 1 at the boiling temperature of a benzene solution for 10 hours. Raising the temperature of the process leads to a shortening of the reaction time; however, the product obtained is dirtier and is difficult to purify. Shortening the reaction time at the optimal temperature decreases the product yield.
It should be noted that the use of xylene as the medium in the reaction has an unfavorable effect on the purity of the preparation: to achieve complete purification, N,N′-methylbenzoylurea must be recrystallized 5–6 times from alcohol. It is highly probable that under the reaction conditions partial benzoylation of xylene takes place. When benzene is used for this purpose, the product is sometimes sufficiently washed with soda solution and water or recrystallized 1–2 times.
Potash and hydrochloric acid, used as catalysts, did not give the desired results. In the first case the reaction did not proceed at all; in the second, under the same temperature and time conditions, the product yield was insignificant.
Experimental Part
Into a round-bottom flask equipped with a mechanical stirrer and a reflux condenser, 22 g of N-methylurea (m.p. ...
102°C), 100 ml of benzene and 23 ml of benzoyl chloride are added. The reaction mixture is heated to the boiling point of the solution (100° in the bath) and kept at this temperature for 10 hours. Upon completion
Table 1
\[
\mathrm{CH_3NHCONH_2 + ClOCC_6H_5 \longrightarrow CH_3NHCONHCOC_6H_5}
\]
\[
-\mathrm{HCl}
\]
| No. | Amount of methylurea, g | Amount of benzoyl chloride, ml | Molar ratio of methylurea and benzoyl chloride | Solvent | Reaction temperature, °C | Reaction duration, h | Yield of technical product, g | Yield of technical product, % | Melting point of technical product, °C |
|---|---|---|---|---|---|---|---|---|---|
| 1 | 15 | 23 | 1:1 | — | 120 140 |
3 2 |
8,3 | 23 | 155—158 |
| 2 | 15 | 23 | 1:1 | — | 140 | 3,5 | 10,8 | 30 | 160—180 |
| 3 | 15 | 35,5 | 1:1,5 | — | 140 | 3,5 | noncrystallized | noncrystallized | liquid |
| 4 | 15 | 35,5 | 1:1,5 | — | 120 140 |
3 2 |
9,5 | 25,2 | 155—170 |
| 5 | 15 | 23 | 1:1 | — | 100 | 11,5 | 19 | 52,7 | 166—168 |
| 6 | 15 | 23 | 1:1 | — | 120 140 |
3 2 |
12 | 33,1 | 160—168 |
| 7 | 15 | 23 | 1:1 | xylene | 120 140 |
8 3 |
15 | 41,5 | 155—170 |
| 8 | 15 | 23 | 1:1 | xylene | 100 | 12 | 11,7 | 32,5 | 158—160 |
| 9 | 15 | 23 | 1:1 | benzene | 100 | 12 | 22,2 | 62,1 | 167—168,5 |
| 10 | 15 | 23 | 1:1 | chloroform | 90 | 13 | 22,9 | 63,7 | 166—167 |
| 11 | 15 | 23 | 1:1 | chloroform, \(\mathrm{K_2CO_3}\) |
80 | 3 | — | — | 100—101 |
| 12 | 15 | 23 | 1:1 | benzene | 100 | 7 | 19,3 | 53,5 | 166—167 |
| 13 | 15 | 23 | 1:1 | benzene | 100 | 8 | 21,1 | 58,6 | 167—168 |
| 14 | 15 | 23 | 1:1 | benzene | 100 | 10 | 21 | 58,2 | 167—168,5 |
| 15 | 22 | 23 | 1,5:1 | benzene | 100 | 10 | 24,1 | 67 | 170—171 |
| 16 | 25,5 | 23 | 1,7:1 | benzene | 100 | 13 | 23,2 | 64,5 | 165—167 |
| 17 | 30 | 23 | 2:1 | benzene | 100 | 10 | 22,7 | 63 | 166—169 |
| 18 | 22 | 23 | 1,5:1 | benzene | 100 | 10 | 24,1 | 67 | 168—170 |
| 19 | 18 | 23 | 1,2:1 | benzene | 100 | 11 | 23 | 63,6 | 167—169 |
| 20 | 15 | 23 | 1:1 | benzene, \(\mathrm{HClO_4}\) |
100 | 10 | 10 | 29 | 150—153 |
After the reaction, the cooled mass is filtered off from the benzene, treated with a 6% soda solution (1 l), and recrystallized from ethanol (10 ml of alcohol per 1 g of product).
N,N′-methylbenzoylurea consists of white needle-shaped crystals with m.p. 169–170°C; literature value—170–171° [1]. Found, %: C—60.76, H—5.68, N—15.93; calculated, %: C—60.67, H—5.62, N—15.73.
The results of the experiments are presented in Table 1.
Conclusions
-
N,N′-methylbenzoylurea was synthesized in 60–67% yield by a method not described in the literature: benzoylation of methylurea with benzoyl chloride.
-
The influence of the reaction conditions on the yield of methylbenzoylurea was studied.
-
According to pharmacological tests, the N,N′-methylbenzoylurea obtained exhibits significant anticonvulsant activity and has low toxicity.
LITERATURE
- F. Beilstein, Handbuch der organischen Chemie, IV Auflage, 9, 216.