Research in the Chemistry of Carbazole Derivatives
Abstract Generated abstract
This study examines the acetylation of 9-alkylcarbazoles with acetic anhydride in the presence of anhydrous aluminum chloride as a route to 3,6-diacetyl-9-alkylcarbazoles. Using 9-methylcarbazole as the model substrate, the authors varied reagent ratios, reaction time, temperature, and solvent, finding optimal solvent-free conditions of 3 mol acetic anhydride and 5 mol aluminum chloride per mole of substrate, with the best yield at 50°C for 1.5 hours, while dichloroethane allowed reaction at 30°C with a slightly higher yield. Application of the optimized conditions to 9-ethyl-, 9-n-propyl-, and 9-n-amylcarbazoles showed that the method affords the corresponding 3,6-diacetyl derivatives in approximately 40 to 68% yield, with substrate-dependent optimal temperatures.
Full Text
RESEARCH IN THE CHEMISTRY OF CARBAZOLE DERIVATIVES
46. Acetylation of 9-Alkylcarbazoles with Acetic Anhydride
V. P. Lopatinskii, M. M. Sukhoroslova, G. V. Solov’eva
(Presented by the scientific-methodological seminar of the Chemical-Technological Faculty)
According to literature data, 3,6-diacetyl-9-alkylcarbazoles were obtained by two methods: either by alkylation of 3,6-diacetylcarbazole with dimethyl sulfate [1], and also by the action on the potassium salt of 3,6-diacetylcarbazole of ethyl iodide, allyl bromide, or benzyl chloride [2], or by acetylation of 9-alkylcarbazoles with acetyl chloride in the presence of anhydrous aluminum chloride in carbon disulfide [3] or dry benzene [4, 5]. By this method, the 3,6-diacetyl derivatives of 9-ethyl-, 9-n-butyl-, and 9-isoamylcarbazoles were obtained in low yields (10–22%) [4, 5].
In our previous communications [6, 7] it was shown that 3,6-diacetyl-9-alkylcarbazoles were obtained by the interaction of 9-alkylcarbazoles with acetyl chloride (acetyl bromide) in the presence of anhydrous aluminum chloride in benzene at a temperature of 10–15°C over two hours, with yields of 42–85.5%.
In the present work, the reaction of acetylation of 9-alkylcarbazoles with acetic anhydride in the presence of aluminum chloride was studied, with the aim of obtaining 3,6-diacetyl-9-alkylcarbazoles. The work included investigation of the acetylation reaction of 9-methylcarbazole according to the scheme:
\[ \begin{gathered} \text{9-methylcarbazole} + 2(\mathrm{CH_3CO})_2\mathrm{O} \longrightarrow \text{3,6-diacetyl-9-methylcarbazole} \\ -\,2\mathrm{CH_3COOH} \end{gathered} \]
and verification of the optimal conditions for acetylation of 9-methylcarbazole on other 9-alkylcarbazoles.
In studying the reaction of acetylation of 9-methylcarbazole with acetic anhydride, the influence of the amount of aluminum chloride, acetic anhydride, temperature, reaction duration, and also the influence of solvents was investigated. The results of several experiments on the acetylation of 9-methylcarbazole with acetic anhydride without solvent are given in Table 1.
In these experiments, the following optimal quantities of reagents were established (in moles per mole of 9-methylcarbazole): acetic anhydride—3 moles, anhydrous aluminum chloride—5 moles. Maximal-
yield of the product (62.6%) was achieved at a temperature of 50°C in 1.5 hours with stirring of the reaction mass.
In studying the effect of the solvent, the following substances were tested: benzene, carbon tetrachloride, chloroform, dichloroethane, toluene, metaxylene, chlorobenzene, and acetic anhydride. Dichloroethane proved to be the best solvent; in its presence the process temperature is lowered to 30°C and the yield of 3,6-diacetyl-9-methylcarbazole is somewhat increased.
Under the optimal conditions found for the acetylation of 9-methylcarbazole in the absence of solvent, the acetylation of 9-ethyl-, 9-n-propyl-, and 9-n-amylcarbazoles was tested. It turned out that these optimal conditions are also valid for them; only the temperature changes. Thus, for the acetylation of 9-ethylcarbazole the best yields are obtained at a temperature of 10±2°C, and for 9-n-propylcarbazole and 9-n-amylcarbazole—at 20±2°C (Table 2).
Experimental Part
Starting reagents. In all experiments the following were used: acetic anhydride; benzene and other solvents of “pure” grade; anhydrous aluminum chloride, “purified” grade. 9-Alkylcarbazoles were prepared by the procedure described by us previously [8, 9, 10].
3,6-Diacetyl-9-methylcarbazole
a) 1.81 g of 9-methylcarbazole was mixed with 6.67 g of anhydrous aluminum chloride. With heating on a water bath and vigorous stirring, 2.85 ml of acetic anhydride was added dropwise to the reaction mass at a temperature of 48–52°C. The reaction mass was stirred continuously for 1.5 hours until it thickened, after which it was decomposed with ice and a dilute aqueous solution of hydrochloric acid. The precipitate that separated was filtered off, washed with cold and hot water to a neutral reaction. The crude product (94% of theoretical) was recrystallized from benzene. The yield of 3,6-diacetyl-9-methylcarbazole with m.p. 194.5–195.5°C was 1.66 g (62.6% of theoretical).
b) 1.81 g of 9-methylcarbazole was dissolved in 4 ml of dichloroethane; to the resulting solution, with stirring, 6.67 g of anhydrous aluminum chloride was added. With heating and vigorous stirring, 2.85 ml of acetic anhydride was added dropwise to the reaction mass. Stirring was continued for 1.5 hours at 30°C. The product was isolated by the method described above. Recrystallization from benzene gave 1.8 g (68.2% of theoretical) of 3,6-diacetyl-9-methylcarbazole with m.p. 194–195°C.
3,6-Diacetyl-9-ethylcarbazole
1.95 g of 9-ethylcarbazole was mixed with 6.67 g of anhydrous aluminum chloride. With vigorous stirring at a temperature of 10±2°C, 2.85 ml of acetic anhydride was added to the mixture. Stirring was continued for 1.5 hours at 10±2°C. The product was isolated by the method described above. 1.88 g (60% of theoretical) of 3,6-diacetyl-9-ethylcarbazole with m.p. 179–180°C (from benzene) was obtained.
3,6-Diacetyl-9-n-propylcarbazole
From 2.09 g of 9-n-propylcarbazole, 6.67 g of anhydrous aluminum chloride, and 2.85 ml of acetic anhydride, by the method described above, at 20±2°C, 1.35 g (46% of theoretical) of 3,6-diacetyl-9-n-propylcarbazole with m.p. 161.5–162.5°C (from benzene) was obtained.
Table 1
Acetylation of 9-methylcarbazole with acetic anhydride in the presence of aluminum chloride (without solvent)
| Amount of 9-methylcarbazole, mol | Amount of acetic anhydride, mol | Amount of aluminum chloride, mol | Duration of reaction, h | Reaction temperature, °C | Crude product: yield, % of theoretical | Crude product: melting point, °C | Product after recrystallization: yield, % of theoretical | Product after recrystallization: melting point, °C |
|---|---|---|---|---|---|---|---|---|
| 1 | 1,5 | 5 | 0,83 (50 min.) | 10—15 | — | 100—151 | 25,2 | 193—194 |
| 1 | 2,0 | 5 | 0,83 | 10—15 | 81,1 | 131—163 | 27,5 | 193—194 |
| 1 | 2,5 | 5 | 0,83 | 10—15 | 87,5 | 130—160 | 34 | 192,5—194 |
| 1 | 3,0 | 5 | 0,83 | 10—15 | 87,5 | 130—161 | 48 | 191,5—193 |
| 1 | 3,5 | 5 | 0,83 | 10—15 | 85,0 | 140—160 | 45,5 | 192,5—193 |
| 1 | 4,0 | 5 | 0,83 | 10—15 | 86,0 | 152—164 | 45,2 | 192,5—193 |
| 1 | 3,0 | 3,0 | 0,83 | 10—15 | 80,6 | 56—100 | 8,3 | 181—184 |
| 1 | 3,0 | 3,5 | 0,83 | 10—15 | 91,6 | 56—100 | 8,5 | 180—182 |
| 1 | 3,0 | 4,0 | 0,83 | 10—15 | 79,2 | 148—153 | 37,0 | 192,5—193,5 |
| 1 | 3,0 | 4,5 | 0,83 | 10—15 | 83,0 | 130—152 | 41,1 | 191,5—193 |
| 1 | 3,0 | 5,0 | 0,83 | 10—15 | 87,5 | 130—161 | 48,0 | 191,5—193 |
| 1 | 3,0 | 5,5 | 0,83 | 10—15 | 87,0 | 120—162 | 47,0 | 192—193 |
| 1 | 3,0 | 6,0 | 0,83 | 10—15 | 86,9 | 88—156 | 44,3 | 187—190 |
| 1 | 3,0 | 6,5 | 0,83 | 10—15 | 86,0 | 90—143 | 41,6 | 192 |
| 1 | 3,0 | 7,0 | 0,83 | 10—15 | 86,0 | 120—143 | 34,1 | 190—191 |
| 1 | 3,0 | 5,0 | 0,5 | 10—15 | 84,5 | 164—175 | 37,7 | 193,5—194 |
| 1 | 3,0 | 5,0 | 1,0 | 10—15 | 84,8 | 160—170 | 49,0 | 193—194,5 |
| 1 | 3,0 | 5,0 | 1,5 | 15 | 86,8 | 166—172 | 50,5 | 193—194,5 |
| 1 | 3,0 | 5,0 | 2,5 | 10—15 | 89,1 | 164—176 | 50,9 | 193—194,5 |
| 1 | 3,0 | 5,0 | 3,0 | 10—15 | 85,8 | 156—173 | 38,4 | 193—194 |
| 1 | 3,0 | 5,0 | 1,5 | −5 | 81,1 | 155—170 | 39,5 | 193,5—194,5 |
| 1 | 3,0 | 5,0 | 1,5 | 0 | 81,5 | 156—170 | 39,5 | 193—194,5 |
| 1 | 3,0 | 5,0 | 1,5 | 10 | 83,4 | 157—170 | 42,2 | 193—194 |
| 1 | 3,0 | 5,0 | 1,5 | 15 | 82,5 | 159—171 | 50,0 | 193—194 |
| 1 | 3,0 | 5,0 | 1,5 | 20 | 83,0 | 176—183 | 52,4 | 193—194,5 |
| 1 | 3,0 | 5,0 | 1,5 | 25 | 86,8 | 176—183 | 54,4 | 193,5—194,5 |
| 1 | 3,0 | 5,0 | 1,5 | 35 | 94,3 | 178—184 | 59,8 | 193—193,5 |
| 1 | 3,0 | 5,0 | 1,5 | 40 | 94,3 | 174—184 | 60,0 | 193,5—195 |
| 1 | 3,0 | 5,0 | 1,5 | 50 | 93,8 | 183—185 | 62,6 | 194,5—195,5 |
| 1 | 3,0 | 5,0 | 1,5 | 55 | 89,5 | 182—184 | 61,1 | 194—195 |
| 1 | 3,0 | 5,0 | 1,5 | 60 | 89,3 | 183—184 | 61,1 | 193—194,5 |
| 1 | 3,0 | 5,0 | 1,5 | 70 | 95,0 | 185—188 | 58,4 | 194—195 |
Table 2
Effect of reaction temperature on the acetylation of 9-alkylcarbazoles with acetic anhydride in the presence of aluminum chloride (without solvent)
| Reaction temperature, °C | 3,6-Dimethyl-9-ethylcarbazole, crude: yield, % | 3,6-Dimethyl-9-ethylcarbazole, crude: melting point, °C | 3,6-Dimethyl-9-ethylcarbazole, after recrystallization: yield, % | 3,6-Dimethyl-9-ethylcarbazole, after recrystallization: melting point, °C | 3,6-Dimethyl-9-n-propylcarbazole, crude: yield, % | 3,6-Dimethyl-9-n-propylcarbazole, crude: melting point, °C | 3,6-Dimethyl-9-n-propylcarbazole, after recrystallization: yield, % | 3,6-Dimethyl-9-n-propylcarbazole, after recrystallization: melting point, °C | 3,6-Dimethyl-9-n-amylcarbazole, crude: yield, % | 3,6-Dimethyl-9-n-amylcarbazole, crude: melting point, °C | 3,6-Dimethyl-9-n-amylcarbazole, after recrystallization: yield, % | 3,6-Dimethyl-9-n-amylcarbazole, after recrystallization: melting point, °C |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| −10 | 87.5 | 165–170 | 55.6 | 178.5–180 | 91.8 | 146–149 | 37.5 | 152.5–157 | 88.7 | 96 | traces | 120 |
| 0 | 89.6 | 167–173 | 59.3 | 179–180 | 91.1 | 146–150 | 40.8 | 160–163 | 84.1 | 125–132 | traces | 133–135 |
| 2 | 93 | 165–171 | 60 | 179–180 | ||||||||
| 10 | 90.3 | 165–170 | 59.5 | 179–180 | 91 | 147–150 | 44.2 | 159.5–162 | 85.6 | 120–128 | 36 | 132–134 |
| 15 | ||||||||||||
| 20 | 95.2 | 147–152 | 45.9 | 160–162.5 | 93.4 | 123–130 | 39.5 | 132–134 | ||||
| 25 | 93.9 | 166–170 | 57.3 | 179–180 | ||||||||
| 30 | 88.4 | 146–151 | 38.7 | 161–163 | 84.1 | 120–123 | 34.3 | 133–135 | ||||
| 35 | 87.4 | 168–170 | 54.4 | 179–180 | ||||||||
| 45 | 93 | 163–169 | 54.4 | 179–180 | 89.1 | 139–145 | 32.3 | 159–160 | ||||
| 50 |
3,6-Diacetyl-9-n-amylcarbazole
From 2.37 g of 9-n-amylcarbazole, 6.67 g of anhydrous aluminum chloride, and 2.85 ml of acetic anhydride, by the method described above at 20 ± 2°C, 1.27 g (39.5% of theory) of 3,6-diacetyl-9-n-amylcarbazole was obtained, with m.p. 132–134°C (from benzene).
Conclusions
- The possibility has been demonstrated of acetylating 9-alkylcarbazoles with acetic anhydride in the presence of aluminum chloride.
- The influence of the principal factors on the yield of 3,6-diacetyl-9-methylcarbazole has been studied.
- It has been shown that, under optimal conditions, 3,6-diacetyl-9-alkylcarbazoles can be obtained in yields of 40–68% of theory.
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