RESEARCH IN THE CHEMISTRY OF CARBAZOLE DERIVATIVES 77. ACETYLATION OF 9-ALKYLCARBAZOLES IN THE PRESENCE OF SMALL AMOUNTS OF CATALYSTS

M. M. Sukhoroslova, V. P. Lopatinskii, E. E. Sirotkina,
T. D. Pirogova

(Presented by the scientific-methodological seminar of the organic departments and laboratories of the CTF)

3-Acetyl- and 3,6-diacetyl-9-alkylcarbazoles were obtained by the Friedel–Crafts reaction in the acetylation of 9-alkylcarbazoles with acetyl halides or acetic anhydride in the presence of aluminum chloride [1–5].

The main drawback of this method is the considerable consumption of catalyst, which in acetylation with acetyl halides reaches 1.1 moles in the synthesis of 3-acetyl-9-alkylcarbazoles and 2.5 moles in the synthesis of 3,6-diacetyl-9-alkylcarbazoles; in acetylation with acetic anhydride, the consumption of aluminum chloride increases to 2.3 and 5 moles, respectively, per mole of 9-alkylcarbazole. Such a consumption of catalyst is necessary because of the formation of strong complexes of aluminum chloride with the acetyl derivatives.

The present work is devoted to a study of the acetylation of 9-alkylcarbazoles in the presence of small amounts of catalysts that do not form strong complexes with ketones. As catalysts, protonic acids were tested (hydrochloric, sulfuric, and phosphoric acids), Lewis acids (tin tetrachloride, zinc chloride, and ferric chloride), as well as magnesium perchlorate.

In order to compare the catalytic activity of the indicated catalysts, the reaction of acetylation of 9-methylcarbazole with acetic anhydride was studied in more detail. All experiments were carried out under identical conditions at \(98 \pm 0.5^\circ\mathrm{C}\) for 30 min, at molar ratios 9-methylcarbazole : acetic anhydride : catalyst equal to \(1:2:1.17 \cdot 10^{-3}\). After washing and drying, the products were chromatographed on silica gel in thin layers or on paper. In the reaction products, unreacted 9-methylcarbazole and 3-acetyl-9-methylcarbazole were detected. Noticeable amounts of 3,6-diacetyl-9-methylcarbazole were not found. Quantitative analysis for the content of the carbonyl group by the oximation method [6] made it possible to determine the yield of 3-acetyl-9-methylcarbazole.

In decreasing order of the yield of 3-acetyl-9-methylcarbazole (the yield as a percentage of the theoretical is given in parentheses), the catalysts studied are arranged in the following series: \(\mathrm{Mg(ClO_4)_2}\) (64), \(\mathrm{HClO_4}\) (59), \(\mathrm{SnCl_4}\) (43), \(\mathrm{ZnCl_2}\) (27), \(\mathrm{FeCl_3}\) (20), \(\mathrm{H_2SO_4}\) (16), \(\mathrm{H_3PO_4}\) (11), \(\mathrm{AlCl_3}\) (5), without catalyst (0).

A more detailed study of the effect of various factors on the yield of 3-acetyl-9-methylcarbazole was carried out using the acetylation of 9-methylcarbazole in the presence of tin tetrachloride as an example. The effects of the amount of acetic anhydride and catalyst, as well as of the duration and temperature of the process, were investigated. The results of the study are given in Table 1.

Table 1

Study of the acetylation of 9-methylcarbazole in the presence of small amounts of tin tetrachloride

The study showed that the optimal acetylation conditions are: molar ratio of the components 9-methylcarbazole : acetic anhydride : $\mathrm{SnCl_4}$, $1:2:1.17 \cdot 10^{-3}$; process duration 30 min; and temperature $100^\circ\mathrm{C}$. The yield of 3-acetyl-9-methylcarbazole is 74% of theoretical.

Increasing the amount of acetic anhydride (to 3 moles) or the amount of tin tetrachloride (to $3.51 \cdot 10^{-3}$ mole), as well as raising the temperature (to $148^\circ\mathrm{C}$) or increasing the duration of the process (to 1.5 h), leads to a decrease in the yield of 3-acetyl-9-methylcarbazole owing to the formation of resinous by-products. No appreciable formation of 3,6-diacetyl-9-methylcarbazole is observed.

For other catalysts ($\mathrm{H_2SO_4}$, $\mathrm{HClO_4}$, $\mathrm{Mg(ClO_4)_2}$), the effect of process duration on the yield of 3-acetyl-9-methylcarbazole at different temperatures was studied. Thus, for magnesium perchlorate the effect of duration was studied at 52, 63, 72, and $98^\circ\mathrm{C}$; for

for hydrochloric acid—at 45 and 98°C; for sulfuric acid—at 98 and 114°C; in this case the molar ratio of the components 9-methylcarbazole : acetic anhydride : catalyst was equal to \(1:2:1.17\cdot10^{-3}\). In all cases an increase in the yield of 3-acetyl-9-methylcarbazole was observed up to a certain limit. With an increase in duration, as a rule, the formation of traces of 3,6-diacetyl-9-methylcarbazole was observed. If the amount of catalyst \((\mathrm{HClO_4})\) was increased to 0.02 mole or more per mole of 9-methylcarbazole, then the yield of 3,6-diacetyl-9-methylcarbazole reached 7%. When the process temperature is lowered, a longer reaction time is required. Thus, identical yields of 3-acetyl-9-methylcarbazole (Table 2) were obtained in acetylation in the presence of

Table 2

Acetylation of 9-methylcarbazole

magnesium perchlorate for 30 min at 98°C, 50 min at 72°C, 70–80 min at 63°C, and 100 min at 52°C; in the presence of 57% hydrochloric acid for 30 min at 98°C and 90 min at 45°C; in the presence of sulfuric acid for 105 min at 114°C and 120–130 min at 98°C.

Experimental Part

In all experiments the following were used: acetic anhydride, phosphoric acid, 57% hydrochloric acid of “ch.d.a.” grade; sulfuric acid of “kh.ch.” grade; tin chloride (anhydrous); ferric chloride, zinc chloride, magnesium perchlorate of “pure” grade; aluminum chloride, anhydrous, of “pure” grade. 9-Alkylcarbazoles were obtained according to the procedure described earlier [7].

3-Acetyl-9-methylcarbazole

Into a flask equipped with a reflux condenser, stirrer, and thermometer were charged 0.042 g of magnesium perchlorate, 30.2 ml of acetic anhydride, and 28.96 g of 9-methylcarbazole. The mixture was heated at a temperature of 98°C for 30 min, then cooled and diluted with water with stirring. The precipitate that separated was thoroughly washed with a weak alkali solution and then with water to a neutral reaction and dried.

The analytical yield of 3-acetyl-9-methylcarbazole, calculated from the content of the carbonyl group by the oximation method [6], was-

was 64–65%. After vacuum distillation at 2–3 mm Hg, 10 g of unreacted 9-methylcarbazole and 19.6 g of 3-acetyl-9-methylcarbazole (55% of theory) were isolated. After crystallization from ethanol, a product with a melting point of 100–101°C was obtained (lit. 101–102°C [7]).

The acetylation of other 9-alkylcarbazoles was carried out by the same procedure (Table 3). Beginning with 9-n-propylcarbazole, the acetylation products formed did not precipitate upon dilution with water,

Table 3

Acetylation of 9-alkylcarbazoles
in the presence of small amounts of catalysts

but were present as oils, from which isolation of the 3-acetyl-9-alkylcarbazoles was carried out by distillation under reduced pressure after preliminary washing and drying. The 3-acetyl-9-alkylcarbazoles obtained had melting points corresponding to the literature values.

Conclusions

A series of catalyst activities has been obtained for the acetylation of 9-alkylcarbazoles with acetic anhydride in the presence of small amounts of catalysts.

For the preparative preparation of 3-acetyl-9-alkylcarbazoles, magnesium perchlorate, hydrochloric acid (57%), and stannic chloride can be used as catalysts.

Literature

1. V. P. Lopatinskii, E. E. Sirotkina, M. M. Anosova. Izvestiya Tomskogo politekhnicheskogo instituta, 111, 1961.
2. V. P. Lopatinskii, E. E. Sirotkina, L. I. Misailova. Izvestiya Tomskogo politekhnicheskogo instituta, 112, 39, 1963.
3. V. P. Lopatinskii, E. E. Sirotkina. Izvestiya Tomskogo politekhnicheskogo instituta, 126, 62, 1964.
4. V. P. Lopatinskii, E. E. Sirotkina, M. M. Anosova, G. V. Sonina. Izvestiya Tomskogo politekhnicheskogo instituta, 136, 18, 1965.
5. V. P. Lopatinskii, E. E. Sirotkina, M. M. Sukhoroslova, G. V. Solov’eva. Izvestiya Tomskogo politekhnicheskogo instituta, 175, 5, 1971.
6. Guben-Weyl. Methods of Organic Chemistry. Vol. II, Goskhimizdat, Moscow, 1963.
7. Methods for the Preparation of Chemical Reagents and Preparations. Issue II, IREA, Moscow, 1964.