RESEARCH IN THE CHEMISTRY OF CARBAZOLE DERIVATIVES

36. The action of sulfuryl chloride on carbazole and its derivatives in an acetylating medium

V. P. LOPATINSKII, I. P. ZHEREBTSOV, L. I. KUZNETSOVA, V. S. GORSHKOVA

(Recommended by the Scientific-Methodological Seminar of the Chemical-Technological Faculty)

It is known [1] that carbazole, when treated with two moles of sulfuryl chloride in a mixture of acetic anhydride and acetic acid, can be converted either into 3,6-dichlorocarbazole, which occurs at a low temperature, or into 3,6-dichloro-9-acetylcarbazole at a somewhat elevated temperature; moreover, the author does not give the yield of the latter substance.

The aim of the present work was to study the synthesis of 3,6-dichloro-9-acetylcarbazole by this one-stage method in order to find conditions under which 3,6-dichloro-9-acetylcarbazole can be obtained in the highest possible yield, and also to study the action of sulfuryl chloride on 9-(β-oxyethyl)carbazole.

It was necessary to determine in what sequence the chlorination and acetylation of carbazole proceed in the formation of 3,6-dichloro-9-acetylcarbazole. The solution of this question could provide some information on the influence of substituents on the reactivity of carbazole in electrophilic substitution.

In studying the synthesis of 3,6-dichloro-9-acetylcarbazole, the influence on the composition and yield of the products (under the action of 2.1 moles of sulfuryl chloride per mole of carbazole) of the following factors was examined: the composition of the solvent, the temperature, and the duration of the process. The results of the experiments are presented in Table 1.

The results obtained indicate that, when the content of acetic anhydride in the mixed solvent consisting of acetic acid and acetic anhydride is increased to 50% by volume, the yield of 3,6-dichloro-9-acetylcarbazole increases, while the yield of 3,6-dichlorocarbazole decreases. It proved possible to find conditions under which 3,6-dichlorocarbazole cannot be isolated; this is achieved by stirring the reaction mixture in a solvent containing not less than 50% acetic anhydride for three hours at a temperature of 60°C. Under these conditions, the yield of 3,6-dichloro-9-acetylcarbazole reaches 55.5%. From the results of the experiments one may also conclude that chlorination of carbazole precedes acetylation of the chloro derivative. This conclusion was confirmed by special experiments in which, under conditions similar to those described, we attempted to chlorinate 9-acetyl- and 3-chloro-9-acetylcarbazoles. These attempts were unsuccessful. In both cases, the starting compounds were isolated back—

are the starting substances. The facts obtained are in agreement with the observation that 9-benzoylcarbazole is incapable of being chlorinated with sulfuryl chloride [2].

Thus, when electron-acceptor groups such as acetyl or benzoyl are introduced at the nitrogen atom, the possibility of electrophilic substitution of hydrogens in the carbazole nucleus (at least in the 3 and 6 positions) decreases. The data obtained also indicate that, under the experimental conditions, 3,6-dichlorocarbazole is acetylated more rapidly than carbazole itself, since the formation of 9-acetylcarbazole was not observed.

Table 1

9-(β-Hydroxyethyl)carbazole was chlorinated in acetic anhydride with two and four moles of sulfuryl chloride, as a result of which 3,6-dichloro- and tetrachloro-9-(β-acetoxy)ethylcarbazoles were isolated. The synthesis of the latter substance by this method is of particular interest, since the tetrachlorocarbazole described by us earlier [3] is not oxyethylated under conditions known for carbazole and its halogen-substituted derivatives [4, 5]. The results of experiments on the action of sulfuryl chloride on 9-(β-hydroxyethyl)carbazole are presented in Table 2.

Table 2

Saponification of the obtained ester of tetrachloro-9-(β-oxyethyl)carbazole in an alkaline medium leads to tetrachloro-9-(β-oxyethyl)carbazole in good yield. Under the action of thionyl chloride in pyridine, tetrachloro-9-(β-chloroethyl)carbazole is obtained, which is of interest for further syntheses, for example, of tetrachloro-9-vinylcarbazole.

Experimental Part

Starting Materials

Reagent-grade carbazole, m.p. 242°C.

Acetic anhydride, acetic acid, and thionyl chloride were of “chemically pure” grade.

Sulfuryl chloride—the fraction collected at 69°C during distillation of the technical product was used.

9-(β-Oxyethyl)carbazole—obtained by the known method [4], m.p. 81–82°C.

3,6-Dichloro-9-acetylcarbazole. Into a flask equipped with a condenser, stirrer, and dropping funnel are placed 20 g of carbazole and a mixture of 75 ml of acetic acid and 75 ml of acetic anhydride. Over the course of 5 minutes, 21.3 ml of sulfuryl chloride is added with vigorous stirring, after which the temperature rises to 60°C. At this temperature and with vigorous stirring, the mixture is kept for 3 hours, then cooled; the crystals that precipitate are filtered off, washed with water, and dried. 20.0 g of a substance with m.p. 172–175°C are obtained. After recrystallization from chloroform, 18.5 g (55.5% of theory) of 3,6-dichloro-9-acetylcarbazole with m.p. 185–186°C are isolated. According to the literature, 3,6-dichloro-9-acetylcarbazole melts at 185–186°C [2], 183° [1]. When the filtrate, after isolation of 3,6-dichloro-9-acetylcarbazole, is poured into water, a viscous liquid precipitates, which thickens on standing. After recrystallization from hexane, 6 g of a substance melting at 108–110°C are obtained (20% of theory).

Analyses. Found, %N, 4.97. C₁₄H₉ONCl₂; calculated, %N 5.03.

Tetrachloro-9-(β-acetoxy)ethylcarbazole

Into a flask equipped with a stirrer, gas outlet tube, dropping funnel, and reflux condenser are charged 10 g of 9-(β-oxyethyl)carbazole and 50.1 ml of acetic anhydride. At a water-bath temperature of 60°C, over the course of 5 minutes and with stirring, 15.4 ml of sulfuryl chloride is added, after which the mixture is kept with stirring at the indicated temperature for 1.5 hours. Upon completion of the reaction, acetyl chloride is distilled off from the mixture, and the reaction product is isolated by precipitation with water and recrystallization of the precipitated solid from acetone. The yield of the substance with m.p. 149–150°C is 7.6 g (44% of theory).

Molecular weight: (by alkaline saponification) found 383; calculated 391.2.

Tetrachloro-9-(β-oxyethyl)carbazole

A mixture of 20 g of tetrachloro-9-(β-acetoxy)ethylcarbazole, 5.72 g of potassium hydroxide, and 700 ml of methanol is boiled with a reflux condenser for 2 hours. The precipitate, weighing 17.2 g (96% of theory), with m.p. 167–169°C, which separates after cooling of the reaction mass, is recrystalliz—

is recrystallized from methanol. As a result, 15.2 g (85% of theoretical) of tetrachloro-9-(β-hydroxy)ethylcarbazole is obtained, m.p. 169–170°C.

Analyses. Found, % OH (by Verley) 4.41; C₁₄H₉OCl₄N; calculated, % OH 4.9.

Tetrachloro-9-(β-chloro)ethylcarbazole

To a mixture of 3 g of tetrachloro-9-(β-hydroxy)ethylcarbazole and 7 ml of pyridine, 0.6 ml of thionyl chloride is added at a temperature of 30°C. After heating for half an hour at a temperature of 50°C, the mixture is poured into water alkalinized with soda, and the precipitate that separates, washed free of pyridine on the filter, is dried. After washing the soluble portion with acetone, the yield is 2.25 g (72.6% of theoretical). Tetrachloro-9-(β-chloro)ethylcarbazole melts at 200–201°C.

Analyses. Found, % N 3.61; C₁₄H₈NCl₅; calculated, % N 3.80.

3,6-Dichloro-9-(β-acetoxy)ethylcarbazole.

To 8 g of 9-(β-hydroxy)ethylcarbazole and 18 ml of acetic anhydride, 6.6 ml of sulfuryl chloride is added. After heating at 60°C for 2 hours, the mixture is cooled and poured into water. The precipitate that separates is recrystallized from alcohol. 3.4 g of a substance with m.p. 122–124°C is obtained.

Analyses. Found, % N 4.30; C₁₆H₁₃ONCl₂; calculated, % N 4.36.

Conclusions

1. The influence of various factors on the synthesis of 3,6-dichloro-9-acetylcarbazole by the action of sulfuryl chloride on carbazole in a mixture of acetic anhydride and acetic acid has been investigated.

2. The optimum conditions for the synthesis of 3,6-dichloro-9-acetylcarbazole with a yield of 55.5% have been found.

3. It has been established that in this case chlorination precedes acetylation; it has also been shown that introduction at the nitrogen atom of an electron-acceptor group such as acetyl hinders electrophilic substitution in the carbazole nucleus during chlorination with sulfuryl chloride.

4. It has been shown that, under the action of 2 and 4 moles of sulfuryl chloride on 9-(β-hydroxyethyl)carbazole in acetic anhydride, 3,6-dichloro-9-(β-acetoxy)ethylcarbazole and tetrachloro-9-(β-acetoxy)ethylcarbazole, respectively, can be obtained.

5. By saponification of tetrachloro-9-(β-acetoxy)ethylcarbazole, tetrachloro-9-(β-hydroxyethyl)carbazole was synthesized, which was then converted into tetrachloro-9-(β-chloroethyl)carbazole.

Literature

1. K. Sugimoto. J. Chem. Soc. Japan, Pure Chem. Sect., 71, 524, 1950.
2. G. Mazzara, M. Lamberti-Zanardi. Garr. Chim. Ital. 11, 236, 1896.
3. V. P. Lopatinskii, I. P. Zherebtsov, S. F. Zelinskaya. Izv. TPI, (in press).
4. V. P. Lopatinskii, E. E. Sirotkina, I. P. Zherebtsov. Izv. TPI, 112, 42, 1963.
5. V. P. Lopatinskii, E. E. Sirotkina, I. P. Zherebtsov, S. K. Vereshchagina. Izv. TPI, 136, 1964.