STUDIES IN THE CHEMISTRY OF CARBAZOLE DERIVATIVES. 76. SYNTHESIS OF 9-ETHYL-3-(1-AMINO-)ETHYLCARBAZOLE

E. E. Sirotkina, V. P. Lopatinskii, L. F. Kovaleva, O. G. Yakushina

(Submitted by the Scientific-Methodological Seminar of the Organic Departments and Laboratories of the Faculty of Chemical Technology)

The conversion of ketones of the carbazole series into aminoalkyls by the Leuckart reaction has not yet been described in the literature. Meanwhile, the preparation of such amines was of interest in view of their potential physiological activity. As the starting substance, 3-acetyl-9-ethylcarbazole was chosen. For the initial study of its hydroamination, the procedure of A. N. Kost and I. I. Grandberg [3] was used, employing an excess of formamide (4–6 moles), formic acid, and skeletal nickel. A method was developed for separating the reaction products in thin layers on silica gel, using as the mobile phase a solvent mixture consisting of benzene (95% by volume) and methanol (5%). Chromatographic study showed that the products of the Leuckart reaction with 3-acetyl-9-ethylcarbazole constitute a complex mixture of substances. In order to find conditions for more complete hydroamination of the ketone, a series of eight-hour experiments was carried out at various temperatures from 130 to 180°C, with interruption of the reaction every hour. Analysis of the chromatograms obtained showed that complete conversion of the ketone occurs at 160°C after 4 hours, and at 180°C after 1 hour. In experiments at high temperatures (170–180°C), after several hours 3-vinyl-9-ethylcarbazole appeared, identified by elemental analysis data and by the coincidence of its $R_f$ (0.97) and IR spectra with those of 3-vinyl-9-ethylcarbazole obtained by another method. Its thermal polymerization was apparently associated with the significant formation (up to 50%) of resinous substances in the reaction products at high temperatures and under harsh conditions. In order to avoid harsh synthesis conditions and thereby reduce the amount of by-products, formic acid and skeletal nickel were excluded from the recipe. In this way it was possible to achieve high yields of the hydroamination product (9-ethyl-3-(1-formylamino-)ethylcarbazole, $R_f$ 0.48), which after purification by recrystallization amounted to 75%. Upon alkaline hydrolysis of the aqueous-alcoholic solution of the formyl derivative, 9-ethyl-3-(1-amino-)ethylcarbazole was obtained.

Experimental Part

3-Acetyl-9-ethylcarbazole had m.p. 113–114°C [2]. Formamide was prepared by the known method [1].

1. 9-Ethyl-3-(1-formylamino-)ethylcarbazole.

Into a round-bottom flask equipped with a stirrer, gas-outlet tube, and thermometer are introduced 40 g of 3-acetyl-9-ethylcarbazole (0.168 mole) and 40 ml of formamide (0.89 mole). The flask is placed in a thermostat at 180°C and kept at this temperature until the evolution of ammonium carbonate ceases, the test for ketone with 2,4-dinitrophenylhydrazine is negative, and no starting ketone is present on the chromatogram. The reaction is completed in 2.5–3 hours. After the reaction is complete, the contents of the flask are cooled, the precipitate is washed with water, dried, and purified by distillation in vacuo followed by recrystallization. At 265–270°C (4 mm Hg) and after recrystallization from ethanol, 30 g (75% of theory) of a colorless crystalline substance with a melting point of 115–116°C is obtained, identified as 9-ethyl-3-(1-formylamino-)ethylcarbazole.

Found, %: N—10.42; C—77.1; H—7.13. Molecular weight (by Rast) 264. $C_{17}H_{18}N_2O$.

Calculated, %: N—10.5; C—76.7; H—6.76. Molecular weight 266.

1. 9-Ethyl-3-(1-amino-)ethylcarbazole.

To an alcoholic solution of 10 g of 9-ethyl-3-(1-formylamino-)ethylcarbazole in 20 ml of ethanol is added 20 ml of an aqueous-alcoholic (1:1) solution containing 2.1 g of caustic potash, and the resulting mixture is boiled under a reflux condenser for 2 hours. The alcohol is then distilled off, water is added to the oily residue in the flask, and the contents of the flask are stirred. A white crystalline precipitate separates in an amount of 8.2 g (92% of theory), m.p. 33–34°C, which is purified by distillation in vacuo. At 196–198°C (2 mm Hg) a colorless oil is obtained, which rapidly crystallizes into white crystals with m.p. 35–36°C, readily soluble in alcohols, ether, and aromatic hydrocarbons and identified as 9-ethyl-3-(1-amino-)ethylcarbazole.

Found, %: N—11.72; C—79.74; H—7.62. $C_{16}H_{19}N_2$.

Calculated, %: N—11.7; C—80.7; H—7.57.

REFERENCES

1. Reactions and Methods for the Study of Organic Compounds. Collection 3, Goskhimizdat, Moscow, 1954, p. 253.

2. Methods for the Preparation of Chemical Reagents and Preparations. Issue II, IREA, Moscow, 1964.

3. A. N. Kost, I. I. Grandberg. ZhOKh, 25, 1432, 1955.