Study in the Chemistry of Carbazole Derivatives

79. Interaction of 9-Alkylcarbazoles with Chloroacetic Acid

M. M. Sukhoroslova, V. P. Lopatinskii, V. I. Sushkov

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

1-, 4-[1], 2- and 3-carbazolylacetic acids [2] were obtained by alkaline saponification of the corresponding carbazole acetamides, which, in turn, were synthesized by the Willgerodt reaction from acetyl derivatives. By acid saponification of 3-acetamido-, 3,6-diacetamido-9-alkylcarbazoles and 3,6-diacetamidocarbazole, also obtained by the Willgerodt reaction, 9-alkyl-3-carbazolylacetic, 9-alkyl-3,6-carbazolyldiacetic and 3,6-carbazolyldiacetic acids were synthesized [3].

The synthesis of carbazolylacetic acids substituted in the nucleus through the corresponding acetamides consists of three stages. Therefore, the preparation of carbazolylacetic acids in a one-stage process is of undoubted interest.

Halogen derivatives of acids react with aromatic hydrocarbons in the presence of Lewis acids with the formation of normally substituted compounds [4]. The alkylation of naphthalene with halogen-substituted acids has been especially well studied [5].

In the present work, the interaction of 9-methylcarbazole with chloroacetic acid was studied. As catalysts, anhydrous aluminum chloride, powdered aluminum, ferric chloride, boron trifluoride etherate, and a mixture of powdered iron and potassium bromide were tested. Positive results were obtained when using boron trifluoride etherate and a mixture of powdered iron and potassium bromide.

The condensation of 9-methylcarbazole with chloroacetic acid in the presence of a mixture of powdered iron and potassium bromide was investigated in greatest detail. The influence of duration, temperature, ratio of components, and ratio of powdered iron to potassium bromide on the yield of a mixture of 9-methyl-3-carbazolyl- and 9-methyl-3,6-carbazolyldiacetic acids was studied. The qualitative composition of the reaction products was determined chromatographically in thin layers on silica gel. Quantitative analysis was performed by titration with alkali in an aqueous-alcoholic solution.

The study showed that, irrespective of the ratio of the components, a mixture of 9-methyl-3-carbazolylacetic and 9-methyl-3,6-carbazolyldiacetic acids is formed. The process proceeds without a solvent. The most favorable temperature is 170–180°C. Raising the temperature increases resinification; lowering the temperature leads to a decrease in yield. The optimal reaction time is 5 hours. The maximum yield of the mixture of acids was obtained at a molar ratio

of iron to potassium bromide of \(8.5\cdot 10^{-4}:1.7\cdot 10^{-3}\) (the ratio 9-methylcarbazole : chloroacetic acid is \(0.03:0.06\)).

Thus, the optimal conditions for the process of interaction of 9-methylcarbazole with chloroacetic acid are the molar ratio 9-methylcarbazole : chloroacetic acid : iron : potassium bromide \(1:2:2.83\cdot 10^{-2}:5.66\cdot 10^{-2}\), at a temperature of 170–180°C and a process duration of 5 hours.

Experimental Part

The starting 9-methylcarbazole was prepared according to the method of [6] and had m.p. 87–88°C.

Chloroacetic acid, anhydrous aluminum chloride, potassium bromide, and ferric chloride were of “pure” grade.

9-Methyl-3(3,6)-carbazolylacetic acids. A flask equipped with an air condenser is charged with 5.43 g (0.03 M) of 9-methylcarbazole, 5.67 g (0.06 M) of monochloroacetic acid, 0.048 g (\(8.5\cdot 10^{-4}\) M) of powdered iron, and 0.198 g (\(1.7\cdot 10^{-3}\) M) of potassium bromide. The mixture is heated in an oil bath to 170°C and kept for 5 hours. After heating is complete, the mixture is cooled to 110°C, 200 ml of a 5% alkali solution heated to 80–85°C is added to it, and it is boiled for two hours. Then the reaction mass is cooled to room temperature, the precipitate is filtered off, and washed with 100 ml of distilled water. To the filtrate are added 200 ml of diluted (1:3) hydrochloric acid. The precipitate that separates is filtered off, washed with water to a neutral reaction, and dried at 80°C. The yield of the mixture of 9-methyl-3-carbazolyl- and 9-methyl-3,6-carbazolyldiacetic acids is 8.5 g (95.4% of theoretical, calculated as 9-methyl-3,6-carbazolyldiacetic acid). Thin-layer chromatography on silica gel indicates the predominant content of carbazolyldiacetic acid in the mixture.

LITERATURE

1. R. H. F. Manske, M. Kulika, Can. J. Research, B 28, 443–52, 1950.
2. H. Gilman, S. Avakian. J. Am. Chem. Soc., 68, 2104, 1946.
3. M. M. Sukhoroslova, V. P. Lopatinskii, E. E. Sirotkina, L. P. Levchenko, T. F. Turchina. Izvestiya TPI, vol. 198, in press.
4. I. Tomas. Anhydrous Aluminum Chloride in Organic Chemistry. Foreign Literature Publishing House, 1949.
5. N. N. Mel’nikov, Yu. A. Baskakov. Chemistry of Herbicides and Plant Growth Regulators. Moscow, Goskhimizdat, 1962.
6. V. P. Lopatinskii, E. E. Sirotkina, M. M. Sukhoroslova. Methods for the Preparation of Chemical Reagents and Preparations. Issue 11, IREA, Moscow, 1964.