RESEARCH IN THE CHEMISTRY OF CARBAZOLE DERIVATIVES

34. Relative reactivity of substituted carbazoles in the oxyethylation reaction

V. P. LOPATINSKII, I. P. ZHEREBTSOV, L. I. TSYBULNIK

(Recommended by the scientific-methodological seminar of the Faculty of Chemical Technology)

It was shown earlier [1–3] that carbazole and its substituted derivatives react with ethylene oxide in an acetone or methyl ethyl ketone medium in the presence of alkalis to give 9-(β-hydroxyethyl)carbazoles. In connection with the study of the mechanism of oxyethylation, it was of interest to investigate how the introduction of various substituents into the carbazole molecule affects the reactivity of carbazole in this reaction. In this respect one may note a certain analogy in the behavior of carbazole and phenols. For example, with an increase in the acidity of phenols, the rate of their reaction with ethylene oxide, catalyzed by alkali, decreases [4]. This can be explained by a decrease in the charge of the nucleophilic agent—the phenolate anion. It could be assumed that the reactivity of substituted carbazoles would also change with a change in their acidity. The solution of this question sheds light on the reaction mechanism, namely on the nature of the reagent attacking the ethylene oxide molecule. If the reagent is an anion, then the reaction rate should decrease with increasing acidity of carbazole; if, however, the reagent is an undissociated molecule, then the reaction rate should increase with increasing acidity. It is known [5] that 3-nitrocarbazole is ionized under the action of alkali already in ethyl alcohol, whereas carbazole and its halogen-substituted derivatives are considerably less acidic.

Our investigations showed that carbazole and its halogen-substituted derivatives can be arranged in a series according to the degree of their acidity: carbazole < 3-chlorocarbazole < 3,6-dichlorocarbazole [6]. It was also shown earlier [4] that 3-nitrocarbazole reacts more slowly with ethylene oxide than carbazole and its halogen-substituted derivatives. Using the ability of carbazole to give a colored anion, it is possible to study the oxyethylation reaction photocolorimetrically, and, using instead of 3-nitrocarbazole an equimolecular mixture of it with other substituted derivatives under conditions of a competing reaction, to show their relative reactivity, which was the purpose of the present work.

A preliminary study of mixtures of 3-nitrocarbazole and 3-nitro-9-(β-hydroxyethyl)carbazole showed that the optical density of the solution, caused by absorption by the 3-nitrocarbazole anion, is not affected by the presence of 3-nitro-9-(β-hydroxyethyl)carbazole, nor by carbazole and its halogen-substituted derivatives under the conditions of analysis. Experiments carried out on the oxyethylation of mixtures of 3-nitrocarbazole with carbazole, 3-chlorocarbazole, and 3,6-dichlorocarbazole by an excess of ethylene oxide in acetone in the presence of caustic potash showed that carbazole is the most reactio-

less capable; following it, in order of decreasing reactivity, are: 3-chlorocarbazole, 3,6-dichlorocarbazole, and 3-nitrocarbazole.

The data obtained indicate that the anion of carbazole or of its substituted derivative participates in the oxyethylation reaction, and that the first stage of the reaction is the formation of such an anion under the action of alkali.

The processes occurring may be represented by the following scheme:

\[ \ce{carbazole-NH + KOH <=> carbazole-N^- + H2O + K^+} \]

\[ \ce{carbazole-N^- + CH2-CH2O -> carbazole-N-CH2-CH2-O^-} \]

Since ionization, for example of 3-nitrocarbazole, occurs instantaneously, the first stage of the process should be regarded as very fast, and the second as slow, determining the rate of the reaction as a whole. The oxyethyl anion formed can add a proton from carbazole according to the scheme

\[ \ce{carbazole-N-CH2-CH2-O^- + carbazole-NH -> carbazole-N-CH2CH2OH + carbazole-N^-} \]

again giving the carbazole anion, capable of participating in the reaction with ethylene oxide. This assumption is supported by the fact that carbazole is more acidic than 9-(β-oxyethyl)carbazole [6], and also that 3-nitrocarbazole is more acidic than its 9-(β-oxyethyl) derivative.

In this scheme the role of the solvent, emphasized in works [1–3], is not yet taken into account; this is the subject of our further work.

Experimental Part

3-Nitrocarbazole was prepared by a known procedure [7]; a sample with m.p. 213°C was used.

Carbazole was prepared by recrystallization of a commercial reagent from acetone, m.p. 244–245°C.

Chlorocarbazoles were prepared by the methods described in work [8].

3-Nitro-(β-oxyethyl)carbazole was prepared by the method described in work [3].

Acetone — “chemically pure”

Methanol — “chemically pure”

Measurements were carried out on an FEK-N-57 instrument with filter No. 4, taking the reading on the left drum. All measurements were carried out at 20°C; the average value of three readings was taken.

Study of the Ionization of 3-Nitrocarbazole in a Mixture with 3-Nitro-9-(β-oxyethyl)carbazole and Other Substituted Carbazoles

A solution of 3-nitrocarbazole in methanol was introduced into a 25 ml volumetric flask so that its concentration ranged from 0.004 mg/ml to 0.036 mg/ml; a solution of 3-nitro-9-(β-oxyethyl)carbazole in methanol was added in such an amount that its concentration was from 90 to 10% of the concentration of 3-nitrocarbazole, together with 2 ml of 0.44 N KOH solution, 10 ml of acetone, and methanol to the mark.

The results of measuring the optical density of the solution in a cuvette of 2 cm thickness are given in Table 1.

Table 1

The results of measuring the optical density of solutions of mixtures of 3-nitrocarbazole at a concentration of 0.02 mg/ml with variable additions of the substituted carbazoles indicated in Table 2 are given in Table 2.

Table 2

Oxyethylation of Mixtures of 3-Nitrocarbazole with Carbazole and Its Chloro-Substituted Derivatives

Into a flask of 100 ml capacity are placed 2.5 g (0.0115 mole) of 3-nitrocarbazole; 0.0115 mole of carbazole or its substituted derivative, 1.28 g (0.023 mole) of powdered caustic potassium, and 25 ml of acetone. To the cooled mixture, 7 ml (0.14 mole) of ethylene oxide is added. The flask is tightly closed and kept in a thermostat at 47°C for the specified time. At the same time, a parallel experiment is carried out. After the required time has elapsed, the flask is cooled in running water for 3 minutes, the mixture is poured into water, and the precipitated solid is dried to constant weight, homogenized, and 25 mg of the substance is taken from the precipitate and dissolved in 25 ml of methanol. Then 0.8 ml of the resulting solution is introduced into a 25 ml volumetric flask containing 2 ml of 0.44 N KOH solution and 10 ml of acetone. The flask is filled to the mark with methanol, and the optical density of the solution is measured after mixing. The obtained results of measuring the optical density with a cuvette thickness of 1 cm are given in Table 3.

Table 3

Note. The two optical-density values were obtained in parallel experiments.

Conclusions

1. By the method of a competing reaction, the reactivity of carbazole, 3-chlorocarbazole, 3,6-dichlorocarbazole, and 3-nitrocarbazole toward ethylene oxide in an alkaline medium was investigated; it was shown that, according to reactivity, the substances studied can be arranged in the following order of decreasing reactivity: carbazole > 3-chlorocarbazole > 3,6-dichlorocarbazole > 3-nitrocarbazole.

2. A mechanism is proposed for the oxyethylation of carbazoles in an alkaline medium.

LITERATURE

1. V. P. Lopatinskii, E. E. Sirotkina, I. P. Zherebtsov. Izv. TPI, 112, 42, 1963.
2. V. P. Lopatinskii, E. E. Sirotkina, I. P. Zherebtsov, S. K. Vereshchagina. Izv. TPI, 136, 1964.
3. V. P. Lopatinskii, I. P. Zherebtsov. Izv. TPI, (in press).
4. E. Marle, D. Boyd. J. Chem. Soc., 1914, 1909.
5. M. R. Schaal, C. Gadet. Compt., 251, 2171, 1960.
6. I. P. Zherebtsov, V. P. Lopatinskii. Izv. TPI, 163, 12, 1970. (in press).
7. R. Eikhman, V. Lukashevich, E. Silaeva. POKh, 6, 93, 1939.
8. V. P. Lopatinskii, I. P. Zherebtsov, S. F. Zelinskaya. Izv. TPI (in press).