RESEARCH IN THE CHEMISTRY OF CARBAZOLE DERIVATIVES

XXII. SYNTHESIS OF CERTAIN 3,6-DIACETYL-9-ALKYLCARBAZOLES

V. P. Lopatinskii, E. E. Sirotkina, M. M. Anosova, T. V. Sonina

(Presented by the scientific seminar of the problem laboratories of the Chemical-Technological Faculty)

In our previous communications [1, 2] it was shown that, in the acetylation of 9-methyl- and 9-ethylcarbazoles with acetyl chloride with the addition of acetyl bromide in the presence of anhydrous aluminum chloride in benzene, 3,6-diacetyl-9-methyl- and 3,6-diacetyl-9-ethylcarbazoles can be obtained in yields of 68 and 70%, respectively.

In the present work, we studied the conditions under which a high yield of 3,6-diacetyl derivatives of other 9-alkylcarbazoles can be achieved.

According to the literature, 3,6-diacetyl-9-alkylcarbazoles have been obtained by two methods: either by alkylation of 3,6-diacetylcarbazole with dimethyl sulfate [3], and also by the action on the potassium salt of 3,6-diacetylcarbazole of ethyl iodide, allyl bromide, or benzyl chloride [4], or by acetylation of 9-alkylcarbazoles with acetyl chloride in the presence of anhydrous aluminum chloride in carbon disulfide [5] or dry benzene [6, 7]. By this method, 3,6-diacetyl derivatives of 9-ethyl-, 9-n-butyl-, and 9-isoamylcarbazoles were obtained in low yields [10–22%] [6, 7]. In the present study we used the latter method, since the availability of 3,6-diacetylcarbazole was unclear from the works of previous investigators [3, 4, 5]. We also had to determine the order of charging the components that would give the best results: either by adding aluminum chloride to a mixture of 9-alkylcarbazole and the acetylating agent, as recommended for experiments in a benzene medium [6, 7], or by adding acetyl chloride to a mixture of 9-alkylcarbazole and aluminum chloride, as recommended for work in carbon disulfide [5].

We tested both of these procedures, and the results of these experiments are given below. All experiments were carried out in benzene medium, since it had been established beforehand that solvents such as chlorobenzene, nitrobenzene, gasoline, and carbon tetrachloride do not make it possible to obtain diacetyl derivatives in yields greater than 10%. In all experiments, acetyl chloride with the addition of acetyl bromide was used as the acetylating agent [0.1 mole per mole of 9-alkylcarbazole].

In testing the first procedure (addition of aluminum chloride to a mixture of 9-alkylcarbazole and the acetylating agent), it was investigated

the effect of the amount of aluminum chloride, the temperature, and the amount of acetylating agent. The results of some experiments on the synthesis of 3,6-diacetyl-9-methylcarbazole are given in Table 1.

Table 1

Results of some experiments on the synthesis of 3,6-diacetyl-9-methylcarbazole

In these experiments the following optimum amounts of reagents were established (in moles per mole of 9-methylcarbazole): acetyl chloride—2.5 moles, acetyl bromide—0.1 mole, anhydrous aluminum chloride—3 moles, benzene—13–15 moles.

The maximum product yield (85.5%) was achieved at a temperature of 10°C in 2 hours, with intensive stirring of the reaction mixture and removal of hydrogen chloride.

A study of the influence of the principal factors on the synthesis reaction of other 3,6-diacetyl-9-alkylcarbazoles showed that these optimum conditions are also valid for them. The results of experiments on the synthesis of certain 3,6-diacetyl-9-alkylcarbazoles under optimum conditions are given in Table 2.

The second procedure (addition of the acetylating agent to a mixture of 9-alkylcarbazole and aluminum chloride) was tested in the syntheses of 3,6-diacetyl-9-ethyl-, 3,6-diacetyl-9-n-propyl-, 3,6-diacetyl-9-isopropyl-, 3,6-diacetyl-9-n-butyl-, 3,6-diacetyl-9-n-amyl-, and 3,6-diacetyl-9-isoamylcarbazoles. In these experiments only the order of charging the reagents was changed, while the remaining conditions were kept optimal. The experiments showed that changing the order of charging the reagents in all cases leads to the preparation of purer substances, which is reflected in their yields. Thus, 3,6-diacetyl-9-propylcarbazole was obtained in this case in 72% yield, and 3,6-diacetyl-9-n-butylcarbazole in 73% yield of theoretical. In the synthesis of 3,6-diacetyl-9-ethylcarbazole by this route, stable 70% yields of pure substance are readily achieved (m.p. 182.5°C, see [2]). Thus, it is preferable to carry out the syntheses of 3,6-diacetyl-9-alkylcarbazoles by the second procedure.

Table 2

3,6-Diacetyl-9-alkylcarbazoles

Note: a) obtained by the first method;
b) obtained by the second method.

Experimental Part

Starting Reagents

In all experiments the following were used: benzene, dry, cryoscopic; acetyl chloride and acetyl bromide, “pure” grade; anhydrous aluminum chloride, “purified” grade. 9-Alkylcarbazoles were prepared by the method described by us earlier [1, 2, 3].

The procedure for the synthesis of 3,6-diacetyl-9-methylcarbazole was the same as in our previous study [1] and therefore is not given here.

3,6-Diacetyl-9-ethylcarbazole

20 g of 9-ethylcarbazole was dissolved in 120 ml of dry benzene; the solution was cooled to 10°C and 34.2 g of anhydrous aluminum chloride was added to it. With cooling in an ice bath and vigorous stirring, a mixture of 20.1 g of acetyl chloride and 1.26 g of acetyl bromide was introduced dropwise into the reaction vessel. Stirring was continued for 2 hours at 10–1°C. After completion of the acetylation, ice was added to the reaction mass; the precipitate that formed was filtered off, washed with water to neutral reaction, and recrystallized from benzene. The yield of 3,6-diacetyl-9-ethylcarbazole, m.p. 182.5°C, was 20.03 g (70% of theory).

3,6-Diacetyl-9-n-propylcarbazole

a) 2 g of 9-n-propylcarbazole was dissolved in 15 ml of dry benzene, and a mixture of 1.88 g of acetyl chloride and 0.118 g of acetyl bromide was added to the solution. With the reaction vessel cooled in an ice bath, anhydrous aluminum chloride (3.82 g) was gradually introduced with continuous vigorous stirring. The reaction continued for 2 hours at a temperature of 10±1°C. After completion of the acetylation, ice was added to the reaction mass; the precipitate was filtered off and recrystallized from ethanol. The product yield was 1.96 g (70.0% of theory), m.p. 164–165°. 3,6-Diacetyl-9-n-propylcarbazole crystallizes as colorless needles and is fairly readily soluble in methanol, ethanol, benzene, toluene, and carbon tetrachloride. Analytical results: found, %: C 77.41; H 6.65; N 4.57; 4.59. C₁₉H₁₉O₂N. Calculated, %: C 77.79; H 6.52; N 4.78. It forms a red picrate, m.p. 125.5–126.5°C.

b) 20.9 g of 9-n-propylcarbazole was dissolved in 56 ml of dry benzene and then mixed with 33.4 g of anhydrous aluminum chloride.

With constant cooling in an ice bath and vigorous stirring, a mixture of 19.63 g of acetyl chloride and 1.23 g of acetyl bromide was introduced dropwise into the reaction vessel. Stirring was continued for 2 hours at 10±1°C. Isolation of the reaction product was carried out by the method described above. Recrystallization from ethanol yielded 19.26 g of substance. An additional 1.85 g of product was extracted from the benzene layer. The total yield of 3,6-diacetyl-9-n-propylcarbazole, m.p. 165–166°C, was 72%.

3,6-Diacetyl-9-isopropylcarbazole

a) 5 g of 9-isopropylcarbazole was dissolved in 38 ml of benzene, and a mixture of 5.64 g of acetyl chloride and 0.11 g of acetyl bromide was added to the solution. With cooling of the reaction mixture, 9.57 g of aluminum chloride was gradually introduced with continuous and vigorous stirring. The reaction mass was kept at a temperature of 10±2°C for two hours. After completion of the acetylation, ice was added to the reaction mass; the precipitate was filtered off and recrystallized from ethanol. The product yield was 2.80 g (40% of theory), m.p. 157–158°C. 3,6-Diacetyl-9-isopropylcarbazole crystallizes as colorless needles and is fairly readily soluble in ethanol and benzene. Analytical results: found, %: N 4.75; 4.69. C₁₉H₁₉O₂N. Calculated, %: N 4.78. It forms a red picrate with m.p. 154–5–155°C.

b) 10.45 g of 9-isopropylcarbazole was dissolved in 28 ml of benzene and then mixed with 16.02 g of aluminum chloride. With constant cooling and vigorous stirring, a mixture of 9.81 g of acetyl chloride and 0.61 g of acetyl bromide was introduced dropwise into the reaction mass.

The mixture was kept at 8–12°C for 2 hours with periodic stirring. The reaction product was isolated by the method described above. Recrystallization from ethanol gave 6.15 g (42.0%) of the pure substance.

3,6-Diacetyl-9-n-butylcarbazole

a) By the first procedure, the compound was obtained from 2 g of 9-n-butylcarbazole, 2.08 g of acetyl chloride, and 0.11 g of acetyl bromide in 15 ml of benzene in the presence of 3.6 g of aluminum chloride. The reaction was carried out for 2 hours at 10±1°C. A total of 1.66 g of substance with mp 127–128°C was isolated (60.5% of theory). It crystallizes from ethanol as fine colorless needles and is fairly readily soluble in methanol, ethanol, benzene, toluene, and carbon tetrachloride. Analytical results: found, %: C 78.55; H 6.80; N 4.31; 4.34. C₂₀H₂₁O₂N. Calculated, %: C 78.14; H 6.89; N 4.56. It forms a red picrate with mp 130–131°C.

b) By the second procedure, the compound was obtained from 22.33 g of 9-n-butylcarbazole, 19.63 g of acetyl chloride, 1.23 g of acetyl bromide, and 33.4 g of aluminum chloride in 56 ml of benzene. After isolation from the reaction mixture, the product was distilled in vacuo. At 294–298°C (6 mm Hg), 25 g of 3,6-diacetyl-9-n-butylcarbazole distilled over, which after recrystallization from ethanol had mp 127–128°C. Yield: 22.55 g (73.4% of theory).

3,6-Diacetyl-9-n-amylcarbazole

Prepared by the second procedure from 23.73 g of 9-n-amylcarbazole, 19.63 g of acetyl chloride, 1.23 g of acetyl bromide, and 33.4 g of anhydrous aluminum chloride in 56 ml of benzene. After recrystallization from ethanol, 16.72 g (52.1%) of 3,6-diacetyl-9-amylcarbazole was obtained. An additional 3.2 g (9.9%) was extracted from the benzene layer at 223–227°C (4 mm Hg); the total yield was 62% of theory. From ethanol the substance crystallizes as long needle-shaped crystals; it is readily soluble in methanol, ethanol, and benzene. Analyses: found, %: C 78.79; H 7.49; N 4.33. C₂₁H₂₃O₂N. Calculated: C 78.48; H 7.22; N 4.36. It forms a red picrate with mp 125–126.5°C.

3,6-Diacetyl-9-isoamylcarbazole

Prepared by the second procedure from 23.73 g of 9-isoamylcarbazole, 19.63 g of acetyl chloride, 1.23 g of acetyl bromide, and 33.4 g of anhydrous aluminum chloride in 48 ml of benzene. After recrystallization from ethanol, 16.70 g (52.0%) of 3,6-diacetyl-9-isoamylcarbazole was obtained. From ethanol the substance crystallizes as long needle-shaped crystals; it is readily soluble in ethanol, benzene, n-octane, and toluene. Analyses: found, %: N 4.48; 4.24. C₂₁H₂₃O₂N. Calculated, %: N 4.36. It forms a red picrate with mp 102.5–103.5°C.

Conclusions

1. The influence of the principal factors on the yield of 3,6-diacetyl derivatives of 9-methyl-, 9-ethyl-, 9-n-propyl-, 9-n-butyl-, 9-n-amyl-, and 9-isoamylcarbazoles and on the rate of acetylation has been studied.

2. It has been shown that, under optimal conditions, 3,6-diacetyl-9-alkylcarbazoles can be obtained in yields of 42–85% of theory.

References

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