SYNTHESIS OF p-IODO-N₁,N-DI-(2-HYDROXYETHYL)ANILINE

A. N. NOVIKOV, A. M. SEDOV, Z. M. MURAV'EVA, N. P. POLISHCHUK

(Presented by the scientific-methodological seminar of the CTF)

In the published literature we have not encountered a description of the synthesis of hydroxyethyliodoanilines, whereas the corresponding derivatives have been obtained for fluoro- and chloro-substituted anilines [1, 2, 3].

Aryloxyethylamines are obtained by the action on the corresponding amine of ethylene chlorohydrin or ethylene oxide [3, 4].

Hydroxyethyl derivatives of iodoanilines may be of interest as intermediates for the synthesis of antitumor (chloroethyl derivatives) substances.

Experimental Part

To obtain the dioxyethyl derivative of p-iodoaniline, synthesized by the known method [5], we used ethylene oxide (method 1) and ethylene chlorohydrin (method 2).

Method 1. Into a stainless-steel vessel were charged 2.5 g of p-iodoaniline, 3–3.5 ml of o-xylene, and 1.5 ml of ethylene oxide. The bomb was kept for 6–7 hours at a temperature of 160° (temperature of the air bath). After cooling, the contents of the vessel were poured into a porcelain dish. After some time, the precipitated reaction product was filtered off and washed with a small amount of benzene. After recrystallization from benzene, p-iodo-N₁,N-di-(2-hydroxyethyl)aniline had \(T_{\mathrm{m}} = 74\text{–}75^\circ\text{C}\). Yield 2.64 g (75%).

Method 2. Into a flask was placed a mixture consisting of 5 g of p-iodoaniline, 7.67 ml of ethylene chlorohydrin, 3.18 g of chalk, and 22.7 ml of water. The reaction mixture was heated on a glycerol bath to 110° and stirred at this temperature for 3 hours. The contents of the flask, still hot, were filtered from the chalk. The chalk was washed with hot water, and then the reaction product was extracted from the filtrate with ether. The ether was distilled off, and the residue after crystallization was dissolved in acetone and passed through a column with activated alumina mixture. The acetone solution was evaporated, and the resulting p-iodo-N₁,N-di-(2-hydroxyethyl)aniline was purified as described above. Yield 1.4 g (20%).

According to the results of analysis, the product obtained by method 1 and method 2 corresponds to p-iodo-N₁,N-di-(2-hydroxyethyl)aniline. Found, %: N 4.80; OH 10.60. Calculated, %: N 4.56; OH 11.07. p-Iodo-N₁,N-di-(2-hydroxyethyl)aniline can readily be converted into the hydrochloride.

0.47 g of p-iodo-N₁,N-di-(2-hydroxyethyl)aniline was dissolved in 7 ml of anhydrous

aqueous chloroform. The chloroform solution was saturated with dry hydrogen chloride for 5 min. The hydrochloride of p-iodo-N,N-di-(2-hydroxyethyl)aniline precipitated, with \(T_{\mathrm{m}} = 118\text{–}120^\circ\mathrm{C}\). Yield 0.47 g (90%).

Conclusions

1. The previously undescribed p-iodo-N,N-di-(2-hydroxyethyl)aniline was synthesized in 75% yield by the reaction of p-iodoaniline with ethylene oxide.
2. The hydrochloride of p-iodo-N,N-di-(2-hydroxyethyl)aniline was obtained.

Literature

1. V. M. Shimanskii, A. F. Gaevskii, M. A. Chernaya. Collection of the Scientific-Research Institute of the Printing Industry, issue 6, 99–113 (1960).
2. Morris Freifelder, G. R. Stone, I. Org. Chem., 26, No. 5, 1477 (1961).
3. W. C. S. Ross, I. Chem. Soc., 183 (1949).
4. N. N. Vorozhtsov. Fundamentals of the Synthesis of Intermediates and Dyes. Goskhimizdat, pp. 532–533, 1950.
5. Syntheses of Organic Preparations. Collection 2, 271 (1949).