RESEARCH IN THE CHEMISTRY OF CARBAZOLE DERIVATIVES

I. Acetylation of Carbazole with Acetic Anhydride in the Presence of Zinc Chloride and Other Catalysts

V. P. Lopatinskii, E. E. Sirotkina, M. M. Anosova¹

(Presented by Professor, Doctor of Chemical Sciences L. P. Kutsyi)

The interaction of equimolecular amounts of carbazole and acetic anhydride in sealed tubes without catalysts leads, at 220–240°C over 6–8 hours, to the formation of 9-acetylcarbazole [1]. The yield of the product was not indicated by the authors. Subsequently, Oddo [2] proposed another route for the synthesis of 9-acetylcarbazole, obtaining it in quantitative yield by heating carbazole-9-magnesium iodide with acetyl chloride in anhydrous ether. Bezeken [3], studying the acetylation of carbazole with acetic anhydride, was the first to use catalysts—sulfuric acid (monohydrate) and ferric chloride. In the presence of 0.5–1% (by weight) of the indicated catalysts, he succeeded at 100°C in 30 minutes in achieving a 90–95% yield of 9-acetylcarbazole. The acetylation of carbazole with acetic anhydride in the presence of sulfuric acid was used by Michael [4] as the basis of a method for isolating carbazole from crude anthracene. Sherlin and Berlin [5] obtained 9-acetylcarbazole by the action of a large excess of acetic anhydride on potassium carbazole at ordinary temperature. Berlin [6] repeated the experiments of Grebe and Glaser, obtaining a 63–68% yield of 9-acetylcarbazole. The use of catalysts in acetylation significantly accelerates the process and improves its results. The most active catalyst proved to be perchloric acid, which can be used in the form of a 30% aqueous solution. Berlin showed that in the presence of 0.4–0.8% (by weight) \( \mathrm{HClO_4} \), a 94–96% yield of 9-acetylcarbazole can be achieved at room temperature in 5 minutes. Taking into account that perchloric acid is not an readily available chemical reagent, and that working even with its aqueous solutions is unsafe, especially in the presence of organic substances, we set ourselves the task of investigating other catalysts for the acetylation of carbazole, from which anhydrous aluminum chloride, phosphoric acid, and anhydrous zinc chloride were selected. The principal results of the study are given in Tables 1 and 2.

In the acetylation of carbazole with acetic anhydride in the presence of sulfuric acid, the reaction product is always colored as a result of partial—

Table 1

Results of experiments on the acetylation of carbazole with acetic anhydride in the presence of aluminum chloride, sulfuric and phosphoric acids

Table 2

Results of experiments on the acetylation of carbazole with acetic anhydride in the presence of zinc chloride

resinification. Decolorization of the product is possible after boiling with animal charcoal and a number of recrystallizations; however, this leads to considerable losses of 9-acetylcarbazole. Low yields of the acetylation product are also obtained in the presence of anhydrous aluminum chloride. Thus, sulfuric acid and aluminum chloride as acetylation catalysts are not very effective; when they are used, it is impossible to obtain 9-acetylcarbazole in quantitative yield even when carbazole is heated with an excess of acetic anhydride at 100°C for 1–2 hours. The best results were obtained in experiments using phosphoric acid (Table 1). Acetylation for 40 minutes at 100°C gives a 95–96% yield of 9-acetylcarbazole, not colored by resinification products. Still greater catalytic activity was shown by anhydrous zinc chloride (Table 2, experiments 1–10). A study of the dependence of the rate of acetylation and the yield of 9-acetylcarbazole on the amount of catalyst and the temperature showed that the optimum is the addition of 2% (by weight) of anhydrous zinc chloride (based on the weight of carbazole), in the presence of which at 80°C it is possible, within 10 minutes, to achieve quantitative conversion of carbazole into 9-acetylcarbazole. After a single recrystallization from ethyl alcohol, a product with a melting point of 73.5–74°C is obtained in a yield of 96–97% of theoretical.

Table 2 gives the results of experiments in which an excess of acetic anhydride (2 and 3 moles per mole of carbazole) was used.

With an equimolecular ratio of reagents, the reaction time has to be increased 3–5-fold in order to achieve conversion of carbazole above 90%. The optimum acetylation temperature in the presence of zinc chloride is 80°C, since at this temperature quantitative conversion of carbazole is attained rather rapidly (10 min), whereas when the temperature is raised to 90–100°C, 9-acetylcarbazole is obtained that is more contaminated with partial-resinification products.

It was subsequently found that the catalytic action of zinc chloride is retained even if one uses not the anhydrous salt, but a saturated aqueous solution of it. The use of an aqueous ZnCl₂ solution as the catalyst has the advantage that resinification is not observed and the reaction product is not colored. The results of these experiments (Table 2, experiments 11–15) show that the optimum conditions remain the same as when anhydrous zinc chloride is used.

Experimental Part

Starting products. Carbazole was isolated from crude anthracene from the Kemerovo Coke-Chemical Plant by the formaldehyde method [7, 8] and had m.p. 244–244.5°C. When less pure carbazole is used, the rate of acetylation decreases as a result of inhibition of the reaction by impurities of polycyclic hydrocarbons. Acetic anhydride and all catalysts were of “chemically pure” grade.

9-Acetylcarbazole. Acetic anhydride, the catalyst, and then carbazole were placed in a round-bottom flask equipped with a thermometer and stirrer. With the stirrer switched on, the contents of the flask were quickly brought in a heated water bath to the required temperature. After the carbazole had dissolved, heating was continued for another 3–5 min. The reaction mass was then poured into a beaker with cold water and stirred until the precipitated product solidified. The precipitate was filtered off and washed on the filter with cold water to remove acetic acid.

and dried in a vacuum desiccator over $\mathrm{CaCl_2}$ and soda lime, after which it was weighed. Its melting point was determined, after which the precipitate was subjected to one or several recrystallizations, or was first boiled with animal charcoal if it was colored. Below is an example using an aqueous solution of $\mathrm{ZnCl_2}$ as catalyst. 18.03 g of acetic anhydride, 10 g of carbazole, and a solution of zinc chloride containing 2% $\mathrm{ZnCl_2}$ (relative to the weight of carbazole) were mixed. The mixture was heated for 10 minutes on a water bath at 80°C, then poured into water. After filtration and drying, 12.5 g of 9-acetylcarbazole with m.p. 68–69°C was obtained. A single recrystallization from alcohol led to the preparation of 12.12 g of substance with m.p. 73.5–74°C (yield 97% of theoretical). A second recrystallization raised the melting point to 74.5–75.5°C (according to literature data, 9-acetylcarbazole melts at 69° [1, 6], 69–70° [2, 5], 75° [9], 76° [3, 10, 11]. Found, %: N 6.71. $\mathrm{C_{14}H_{11}ON}$. Calculated, %: N 6.69.

Conclusions

1. The effectiveness of phosphoric acid, anhydrous aluminum chloride, and zinc chloride as catalysts for the reaction of acetylation of carbazole with acetic anhydride has been investigated.

2. It has been shown that an aqueous solution of zinc chloride possesses the greatest catalytic activity. In the presence of 2% of this catalyst at a temperature of 80°C and with an excess of acetic anhydride (3 mol per mol of carbazole), 9-acetylcarbazole is obtained in quantitative yield in 10 minutes.

LITERATURE

1. C. Graebe, C. Glaser. Ann. 163, 343, 1872.
2. B. Oddo, Gazz. chim. ital. 41, 1, 255, 1911.
3. I. Böeseken. Rec. trav. chim., 31, 350, 1912.
4. I. Michael. German patent 393693; Friedländer, 14, 546, 1926.
5. S. M. Sherlin, A. Ya. Berlin. ZhOKh, 7, 2273, 1937.
6. A. A. Berlin. ZhOKh, 14, 438, 1944.
7. L. P. Kulev, V. P. Lopatin. Collection of abstracts of reports at the VIII Mendeleev Congress, series on chemistry and chemical technology of fuels, 105, 1959.
8. L. P. Kulev, V. P. Lopatinskii. Proceedings of the Tomsk Polytechnic Institute, 102, 1960.
9. W. Perkin, S. Plant, J. Ch. Soc., 123, 676, 1923.
10. A. V. Blom, Helv. chim. acta, 4, 625, 1921.
11. B. Barclay, N. Campbell, R. Gow, J. Chem. Soc., 1946, 997.

1. V. P. Vasil’eva took part in the experimental portion of the work. ↩