Acylation of N-(β-Hydroxyethyl)urea with Some Carboxylic Acids

N. S. Dobychina, A. G. Pechenkin, G. F. Krasnyatova

(Presented by the Scientific-Methodological Seminar of the Department of Chemical Technology)

Continuing the work [1] on the search for compounds with anticonvulsant activity, we synthesized a series of N-(β-hydroxyethyl)acyl derivatives of urea.

N-(β-Hydroxyethyl)urea was obtained by the known procedure [2] through condensation of urea with β-ethanolamine.

Acylation of N-(β-hydroxyethyl)urea was carried out with carboxylic acids of the fatty series in the presence of phosphorus trichloride, and with the acid chlorides of these same acids, according to a method previously proposed by us [3]. As a result of acylation, either N-(β-chloroethyl)-N′-acylureas or diacyl derivatives of hydroxyethylurea were obtained; acylation occurred at either the oxy or the amido group. Chlorination proceeds independently of which acylating agent—an acid in the presence of phosphorus trichloride or an acid chloride—was used in the acylation reaction. The formation of monoacyl derivatives of hydroxyethylurea is affected by the ratio of the reacting substances. Thus, when the initial hydroxyethylurea and the acylating agent were taken in equimolecular amounts, the acylation produced diacyl derivatives of hydroxyethylurea. When the ratio of the reacting substances was changed toward an increase in the amount of the acylating acid or its acid chloride, the reaction generally gave monoacyl derivatives, and the oxy group was replaced by chlorine. However, in some cases—for example, in acylation with isobutyric and isovaleric acids—diacyl derivatives could not be obtained, despite variation of the molar ratios over wide limits. Within the interval studied, the reaction temperature and the duration of the acylation reaction had no effect on the formation of mono- or diacyl derivatives.

The compounds obtained were identified by elemental analysis and IR spectra.

Experimental Part

N-(β-Hydroxyethyl)urea in xylene medium is placed in a three-necked round-bottom flask equipped with a mechanical stirrer, reflux condenser, and dropping funnel. The flask is placed in an oil bath, the temperature of which is raised to 75°, after which phosphorus trichloride is added portionwise to the flask from the dropping funnel.

Table 1

General formula: \(R_1C_2H_4NHCONHCOR_2\)

After the entire amount of phosphorus trichloride has been added, the temperature in the bath is raised to 125° and maintained for 12 hours until the reaction is complete (test for hydrogen chloride); then the reaction mixture is decanted from the syrupy precipitate of phosphorous acid that has formed, the xylene is evaporated on a water bath or in air, and the resulting white precipitate is treated with soda solution, washed with water, and recrystallized from a 1:2 aqueous-alcoholic mixture.

Data on the synthesis and analysis of the compounds obtained are given in Table 1.

Conclusions

Six N-(β-chloroethyl)-N′-acylureas not described in the literature and three diacyl derivatives of N-(β-hydroxyethyl)urea have been synthesized.

References

1. N. S. Dobychina. Dissertation. Tomsk, 1966.
2. N. A. Goldberg, V. G. Golov, L. G. Nikolaeva, E. A. Demina. USSR Author’s Certificate No. 170578, filed 5.03.65, published 30.12.65. RZhKhim, 1967, 1N 681.
3. N. S. Dobychina, A. G. Pechenkin, L. G. Tignibidina. Author’s Certificate No. 188957, filed 29.12.65, published 17.11.66. Journal “Izobreteniya, promyshlennye obraztsy, tovarnye znaki,” 1967.