Research in the Chemistry of Carbazole Derivatives

PROCEEDINGS

OF THE TOMSK POLYTECHNIC INSTITUTE NAMED AFTER S. M. KIROV,
ORDER OF THE OCTOBER REVOLUTION AND ORDER OF THE RED BANNER OF LABOR

Volume 257                                                                                                1973

RESEARCH IN THE CHEMISTRY OF CARBAZOLE DERIVATIVES

92. Study of the Rearrangement of 9-Acetylcarbazole

Yu. G. Yur'ev, V. L. Ivasenko, V. P. Lopatinskii

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

It is known [1] that, when fused with anhydrous aluminum chloride, 9-acetylcarbazole undergoes rearrangement to 3-acetylcarbazole. Meitner [2], carrying out the reaction in nitrobenzene, in addition to 3-acetylcarbazole, obtained in 50–60% yield, also qualitatively isolated 1-acetylcarbazole and carbazole from the reaction product, which allowed the author to compare the reaction studied with the Fries rearrangement [3]. However, a subsequent verification of Meitner’s data showed [4] that the yields of pure 3-acetylcarbazole are considerably lower than 50%.

We have carried out a detailed study of this reaction with the aim of increasing the yields of 3-acetylcarbazole, which is of practical interest because of the possibility of synthesizing new carbazole derivatives on its basis. The influence of the nature and amount of the solvent and catalyst, the temperature and duration of the reaction, saturation of the system with hydrogen chloride, and addition of acetyl chloride on the yield and ratio of 1- and 3-acetylcarbazoles was investigated. The results obtained are presented in this communication.

In order to eliminate toxic nitrobenzene, which is inconvenient to work with, we tested a number of solvents usually used for the Fries rearrangement [3,5,6]. The data in Table I show that, when acidic solvents with a large dipole moment are used (see experiments 7, 8), the conversion of the starting product amounts to—

amounts to 89–90%, the yields of 3-acetylcarbazole reach 50.6–61.6%, while the content of 1-acetylcarbazole does not exceed 7%. In inert solvents (expts. 1–5) the conversion of 9-acetylcarbazole is considerably lower, as a result of which the yields of 3-acetylcarbazole do not exceed 25%; and in tetrahydrofuran, which already exhibits basic properties, despite its rather high dipole moment, rearrangement does not occur at all (expt. 6). Thus, the effectiveness of the solvent in the reaction under study is explained not so much by its polarity, as noted in studies of the Fries rearrangement [5, 6], but by its acidic character.

From these data it follows that the best solvents for the rearrangement of 9-acetylcarbazole are nitrobenzene and nitromethane; however, a number of substantial advantages of the latter over nitrobenzene make it preferable to use nitromethane in the reaction. It is evident from Table 1 (expts. 8–12) that, as the amount of nitromethane is increased, the yield of 3-acetylcarbazole decreases noticeably, whereas the content of 1-acetylcarbazole remains practically constant. This fact may, in our opinion, be a consequence of the difference in the mechanisms of formation of 1- and 3-acetylcarbazoles (cf. 7).

A. Terek [8], studying the rearrangement of phenyl acetate to ortho- and para-hydroxyacetophenones under the action of aluminum chloride, established an accelerating effect of hydrogen chloride on the yield of the para isomer. The author believes that the formation of para-acetophenone proceeds by an intermolecular route, in contrast to the ortho isomer, on the yield of which the presence of hydrogen chloride has no effect. A similar point of view is also held by a number of other authors [9].

When carrying out the rearrangement of 9-acetylcarbazole in pure nitromethane and in nitromethane saturated with hydrogen chloride, we observed that in the latter case the yields of 3-acetylcarbazole increase by 10–15%, whereas the content of 1-acetylcarbazole remains practically constant (Table 2, expts. 1–4).

The presence of carbazole in the rearrangement product made it possible to suppose that, in the case of formation of 3-acetylcarbazole by an intermolecular mechanism, introduction of acetyl chloride into the reaction should increase the yield of 3-acetylcarbazole. As can be seen from the data of Table 2 (expts. 4–8), this does indeed occur, while the yields of 1-acetylcarbazole, on the contrary, even decrease.

It should be emphasized that addition of acetyl chloride in amounts of 0.5–1 mole per 1 mole of 9-acetylcarbazole leads to the forma-

the presence of a small amount (5–7%) of 3,6-diacetylcarbazole, which, however, is absent when the rearrangement is carried out without the addition of acetyl chloride. The appearance of the diacetyl derivative is probably the result of secondary acetylation of 3-acetylcarbazole, which was also confirmed by the formation of 5–8% 3,6-diacetylcarbazole in the acetylation reaction of 3-acetylcarbazole with acetyl chloride under conditions analogous to the rearrangement.

In most cases a low temperature (20–60°) leads to the formation of para-, and a high temperature (80–180°) of ortho-isomers in the Fries rearrangement [10]. However, in the case of the rearrangement of 9-acetylcarbazole, with increasing temperature the yields of both isomers increase markedly (Table 3, expts. 1–4), and then, at a higher temperature (expts. 5–7), a decrease in them is observed owing to intensive resin formation. At the same time, throughout the temperature range investigated, the principal reaction product is 3-acetylcarbazole.

In addition to aluminum chloride, we also tested other acidic catalysts. The use of aluminum bromide leads to severe resinification of the reaction products and, because of this, to a decrease in the yields of I- and 3-acetylcarbazoles to 4–6% and 40–50%, respectively. \(SnCl_4\), \(TiCl_4\), and \(FeCl_3\) proved less active (the yields of 3-acetylcarbazole did not exceed 20%), while \(ZnCl_2\), \(HClO_4\), and polyphosphoric acid were completely inactive under these conditions.

Thus, of the catalysts tested, the best proved to be aluminum chloride promoted with hydrogen chloride. With a ratio of aluminum chloride to 9-acetylcarbazole equal to 0.25:1, the reaction already proceeds to 65%, and the yield of 3-acetylcarbazole reaches 48% (Table 3, expt. 9). However, only the use of equimolecular amounts of the starting product and catalyst gives the highest yield of 3-acetylcarbazole, which decreases sharply with increasing amount of aluminum chloride (expts. 12–14).

Experimental Section

Starting reagents: nitromethane, “pure” grade, dried over phosphorus pentoxide and distilled; 9-acetylcarbazole, synthesized according to the procedure of [11], \(T_{\text{mp}} = 74–75^\circ\); aluminum chloride, freshly sublimed; acetyl chloride, “pure” grade, freshly distilled.

Synthesis of 3-acetylcarbazole. A three-necked flask of 250–300 ml capacity, equipped with a reflux condenser, a stirrer, and a tube reaching to the bottom of the flask for introducing hydrogen chloride, was charged with

a solution of 21 g (0.1 M) of 9-acetylcarbazole in 50 ml of nitromethane was heated to 85–90° and, with the stirrer operating, a solution of 20 g (0.15 M) of aluminum chloride and 3.56 ml (0.05 M) of acetyl chloride in 50 ml of nitromethane was poured into the flask. While hydrogen chloride was being passed through, the contents of the flask were heated for 20–15 minutes at the indicated temperature, poured into cold water, and the precipitate that formed was filtered off and dried. After recrystallization from benzene (with addition of silica gel), the yield of 3-acetylcarbazole was 75–80%,

$T_{\mathrm{pl}} = 166–167^\circ$ (lit. $T_{\mathrm{pl}} = 167–168^\circ$ [2]).

Chromatographic analysis. For the quantitative separation of products of the rearrangement of 9-acetylcarbazole, a column chromatography method was developed. A dry adsorbent—KSK-grade silica gel, grain size 250–500 μ, preliminarily activated for 60 minutes at 110–120°—was packed into a chromatographic column 1.2 cm in diameter and 60 cm long. The column was washed with 100 ml of benzene, a solution of 100–300 mg of product in a minimal volume of benzene was applied, and the chromatogram was developed first with benzene (carbazole and a bright-yellow zone of I- and 9-acetylcarbazoles were thereby eluted from the column), then with chloroform the salad-green zone of 3-acetylcarbazole was eluted, and finally with ethanol or methanol—the violet zone of resinous substances. The individual zones were evaporated to constant weight, and the amount of component in each of them was determined by weighing. 9-Acetylcarbazole is determined by saponification with an alcoholic alkali solution according to the method [12].

Conclusions

1. The influence of experimental conditions on the rearrangement of 9-acetylcarbazole has been studied.

2. It has been found that, when nitromethane is used as the solvent and with an equimolecular ratio of the reagents, the yields of 3-acetylcarbazole reach 61–63%. When the system is saturated with hydrogen chloride, the yield of 3-acetylcarbazole increases to 73–74%, and when acetyl chloride is added to the reaction mass—to 85–90%.

3. The selective action of the solvent, hydrogen chloride, and acetyl chloride on the yields of I- and 3-acetylcarbazoles suggests a difference in the mechanisms of formation of these isomers.

Literature

1. G. Plant, S. Williams, J. Chem. Soc., 1934, 1142.

2. E. Meitzner. J. Am. Chem. Soc., 57, 2327 (1935).

Table I

Conditions of the experiment and amounts of solvents in the rearrangement of 9-acetylcarbazole

Table 2

Effect of hydrogen chloride and acetyl chloride on the isomerization of 9-acetylcarbazole

Table 3

Effect of temperature and amount of aluminum chloride on the rearrangement of 9-acetylcarbazole

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