ACYLATION OF N-BENZYLUREA WITH CERTAIN SUBSTITUTED BENZOIC ACIDS

N. S. DOBYCHINA, A. G. PECHENKIN, S. G. VESHKURTSEVA

(Presented by the scientific seminar of the Faculty of Chemical Technology)

It was previously established by us [1] that benzylurea possesses high anticonvulsant activity and, at the same time, considerable toxicity. It was found that, upon acylation of benzylurea with carboxylic acids of the aliphatic series, its toxicity decreases; however, in a number of cases, depending on the acylating acid, the anticonvulsant activity also decreases.

It was of interest to determine how the acylation of benzylurea with acids of the aromatic series affects its anticonvulsant activity and toxicity.

For this purpose, a series of compounds of the general formula was synthesized:

\[ \mathrm{C_6H_5CH_2HNCON} \begin{matrix} \diagup R\\[-2pt] \diagdown R_1 \end{matrix} \]

where \(R — \mathrm{COC_6H_4Cl}\) (o, p); \(\mathrm{COC_6H_4Br}\) (p); \(\mathrm{COC_6H_3Cl_2}\) (2, 4; \(\mathrm{COC_6H_4J}\) (p, o); \(\mathrm{COC_6H_4NO_2}\) (m, o, p), \(R_1=R\) or H.

The acylation of benzylurea was carried out with acids in the presence of phosphorus trichloride.

Earlier [2] we developed a method for acylating benzylurea with acids of the aliphatic series in the presence of phosphorus trichloride. It was of interest to test the applicability of this method for acylating benzylurea with acids of the aromatic series.

When benzylurea is acylated with acids of the aliphatic series in the presence of phosphorus trichloride, N,N\(^1\)-benzylacylureas are obtained. As a result of the acylation of benzylurea with acids of the aromatic series, both mono- and diacyl derivatives of benzylurea are obtained. It may be assumed that both acyl groups in the benzylurea molecule attach to the same nitrogen atom. Confirmation of this assumption may be provided by the spectral-analysis data, which will be presented later.

The acylation was carried out under identical temperature conditions and with identical ratios of the reacting substances; however, the duration of the acylation reaction was different. (The end of the reaction was determined by the cessation of HCl evolution.)

It was noted that the rate of acylation of benzylurea with substituted benzoic acids, as a rule, is directly dependent on the strength of the acid.

Experimental Part

Benzylurea and the acid are charged in mo-

Table 1

\[ \mathrm{C_6H_5CH_2NHCON} \begin{matrix} R\\[-2pt] R_1 \end{matrix} \]

in a molar ratio of 1:1; then dry xylene is added. The reaction mixture is heated to 75°C (in a bath), after which phosphorus trichloride is added to it dropwise from a dropping funnel in a molar ratio to the acid of 1:3. After the addition of phosphorus trichloride, the bath temperature is raised to 120°C and maintained for 10–15 hours, depending on the acylating acid.

Upon completion of the reaction, the reaction mass is decanted from the yellow syrupy precipitate of phosphorous acid and separated from the solvent by evaporation in air or on a water bath.

The resulting precipitate is treated with a 10% solution of soda, washed with water, and recrystallized from a mixture of isopropyl alcohol and water (2:1).

All acylation products are white crystalline substances, insoluble in water and soluble in alcohol, benzene, chloroform, and dioxane.

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

Conclusions

1. The acylation reaction of N-benzylurea with substituted benzoic acids in the presence of phosphorus trichloride has been studied. It was found that, unlike the acylation of benzylurea with acids of the fatty series, acylation with substituted benzoic acids gives diacyl derivatives.

2. Nine acyl derivatives of benzylurea, not described in the literature, have been obtained.

References

1. N. S. Dobychina. Dissertation, Tomsk, 1966.

2. N. S. Dobychina, A. G. Pechenkin, L. G. Tignibidina. Author’s certificate No. 188957, filed 29.12.1965, published 17.11.1966.