RESEARCH IN THE CHEMISTRY OF CARBAZOLE DERIVATIVES

58. STUDY OF THE REDUCTION OF CERTAIN ALIPHATIC-AROMATIC KETONES

E. E. SIROTKINA, V. P. LOPATINSKII, V. L. IVASENKO,
V. P. KOZLOVA, V. T. PEREMITINA, V. D. FILIMONOV

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

It had previously been established by some of us that alkyl aryl ketones of the carbazole series can be converted in one stage into vinyl derivatives of 9-alkylcarbazoles in 46–100% yield by reduction of 3-acetyl- and 3,6-diacetyl-9-alkylcarbazoles with aluminum isopropylate in an aromatic-hydrocarbon medium [1, 2].

It was of interest to extend this method of synthesis of vinyl derivatives to a number of other aromatic and heterocyclic compounds.

The aim of the present work was to study the influence of substituents in the nucleus of aliphatic-aromatic ketones on their reactivity in the reduction of ketones by the Meerwein–Ponndorf–Verley method.

I. Synthesis of aliphatic-aromatic ketones

The synthesis of ketones by acetylation of aromatic compounds with acid chlorides according to the Friedel–Crafts method is one of the principal methods for obtaining alkyl aryl ketones.

The acylation process is usually carried out as follows: a catalyst is added, with stirring, to a cooled solution of the aromatic hydrocarbon and the acylating agent. When the process is conducted in this manner, the acylation of certain aromatic hydrocarbons leads to low yields (15–20%) of the final products and to the formation of isomers in the case of monoacetyl derivatives, or to a deterioration of their quality in the case of diacetyl derivatives [3].

In choosing a method for the synthesis of aliphatic-aromatic ketones, we proceeded from the fact that all the starting aromatic compounds can be represented as benzene derivatives with electron-donating substituents that increase the electron density in the aromatic ring, which was confirmed by calculation of electron densities by the molecular-orbital method. Therefore we decided to apply the previously developed method for the synthesis of monoacetyl derivatives of 9-alkylcarbazoles [1, 10] to obtain the ketones listed above. This method

the synthesis differs from the generally accepted methods [4, 5] in that, upon interaction with aluminum chloride, it is not the acylating agent that is activated, but the benzene ring of the carbazole nucleus; moreover, aluminum chloride attaches itself in a strictly fixed position to the atom having the greatest electron density. This makes it possible to accelerate the subsequent condensation with the acylating agent and to obtain not mixtures of isomers, but individual compounds.

The results of the syntheses are given in Table 1.

Table 1

Characteristics of the synthesized ketones

The structure of the alkyl aryl ketones was established by infrared spectroscopy and by analyses for the ketone group. Thus, we have significantly increased the yield of the target products in comparison

Table 2

Characteristics of synthesized ketones of the carbazole series

with the known methods of synthesis [3], the synthesis time was reduced several-fold, individual products rather than mixtures of isomers were obtained.

9-Methyl-6-nitro-3-acetylcarbazole was obtained by nitration of 3-acetyl-9-methylcarbazole according to the procedure for the synthesis of 9-ethyl-6-nitro-3-acetylcarbazole [10]; purification was carried out by recrystallization from nitrobenzene.

3-Acetylcarbazole was obtained by a Fries rearrangement from 9-acetylcarbazole. E. Meitzner [6] obtained 3-acetylcarbazole in 50–60% yield by heating 9-acetylcarbazole with aluminum chloride in nitrobenzene. However, we were unable to reproduce the experimental results reported in [6], and the yields of 3-acetylcarbazole did not exceed 10–15%. Therefore, using E. Meitzner’s procedure, we decided to activate the aluminum chloride by continuously passing hydrogen chloride through the reaction mass. Subsequently, 3-acetylcarbazole was purified by vacuum distillation and recrystallization from benzene, and its yield reached 55–58%. The results of the syntheses of acetylcarbazoles are given in Table 2.

II. Analysis of the Synthesized Ketones

For the analysis of the ketones we chose polarography, because of its speed and simplicity in comparison with other analytical methods, the possibility of simultaneous determination of several compounds, and the ability to work with small quantities of substances, when concentration factors do not have an effect. In addition, we hoped to extract from the polarographic data some information about the electronic state of the functional group \(>\mathrm{C}= \mathrm{O}\). A method of analysis was developed for all synthesized ketones using lithium acetate buffers.

Method for Determining the Half-Wave Potentials of Polarographic Reduction of Ketones at Various pH Values

Apparatus used:

1. OH-101 polarograph
2. Dropping mercury electrode
3. Electrolyzer
4. OP-201/1 pH meter

Reagents and solutions used:

1. Glacial acetic acid, chemically pure.
2. Lithium hydroxide, chemically pure.
3. Ethyl alcohol, chemically pure, purified from aldehydes according to the procedure [8].
4. Dioxane, chemically pure, purified from peroxide compounds according to the procedure [8].
5. Standard solutions of ketones in ethanol.
6. Lithium acetate buffer solutions with pH = 5, 7, 9.

A measured amount of a standard solution of the ketone (0.2–1.0 ml) in ethanol is placed in a 25 ml volumetric flask; 10 ml of lithium acetate buffer is added, and the solution is brought to the mark with ethanol. Then 5–6 ml of the prepared solution is placed in the electrolyzer, nitrogen is passed through for 15 minutes, and the polarogram is recorded at a sensitivity of \(10^{-8}\ \mathrm{A/mm}\), starting from \(-1\) volt.

The values of \(E_{1/2}\) of the ketones at various pH values are given in Table 3.

It was found that the values of \(E_{1/2}\) increase with increasing pH; the electrochemical reduction proceeds by the usual two-electron mechanism; there is a linear dependence between the concentration of the ketones and the height of the polarographic wave.

Dependence — \(E^{1/2}\) on pH

III. Reduction of Aliphatic-Aromatic Ketones

The study of the reduction of aliphatic-aromatic ketones with aluminum isopropylate in p-xylene was carried out by a slightly modified procedure for the preparative synthesis of vinyl compounds developed earlier [2].

Into a three-necked flask fitted with a reflux condenser and a stirrer, 50 ml of a 0.2 M solution of aluminum isopropylate in p-xylene is charged. The flask is placed in a thermostat at 100°C. In another, single-necked flask fitted with a reflux condenser, 50 ml of a 0.2 M solution of the ketone is placed, and both flasks are thermostated at 100°C. When 100°C is reached in the flasks, the reaction solutions are combined. At specified time intervals samples are withdrawn. The unreacted aluminum isopropylate in the samples is decomposed with a 20% KOH solution. The xylene layer is dried with calcium chloride. The concentration of unreacted ketone in the sample is determined polarographically; according to the procedure described above, a graph is plotted in the coordinates “time—concentration of unreacted ketone.”

Earlier, in studying the reduction of 9-methyl-3-acetylcarbazole, it was observed that on a graph in the coordinates “time—concentration of unreacted ketone” two regions can be distinguished: a region where the reaction corresponds to second order, i.e., to the generally accepted mechanism [9], and a region where the reaction has a fractional order lying between second and third. We have established that, at high concentrations of the reacting substances (\(>0.02\) M), the order of the reduction reaction as a function of temperature has a value of 2.3–2.6; i.e., in this case the reduction process may proceed by two parallel mechanisms [11]. At reduced concentrations of the reacting components the process proceeds by a second-order reaction, i.e., evidently by the generally accepted mechanism [9]. To compare the reactivity of the ketones, we selected the portion of the curve corresponding to a second-order reaction, since in this case the rate constant of the process does not depend on the concentration of the reagents. In addition, preparative syntheses of vinyl compounds were carried out under optimal conditions and the yields were determined. The yield of vinyl compounds was found by determining unsaturation in a p-xylene solution by the mercuric-acetate method [7]. The results are summarized in Table 4.

It is seen from the table that, with an increase in the value of \(E_{1/2}\) of the ketone, the rate constant and the yield of vinyl compounds increase. This is explained by the fact that electron-donor substituents, increasing the electron density on the oxygen atom of the ketone group, hinder its electrochemical reduction and at the same time increase the reactivity of the ketone in the reduction reaction,

Table 4

Relationship between \(E_{1/2}\), the reactivity of ketones, and the yield of vinyl compounds

Note:

* — the remainder is polymer
** — the remainder is carbinol + polymer
*** — the remainder is ketone + carbinol
**** — the remainder is ketone + polymer

reactivity of the ketone in the reduction reaction, which also follows from the mechanism of the reduction reaction of fatty-aromatic ketones by aluminum isopropylate in aromatic solvents, proposed in [10], the dissertation of E. E. Sirotkina.

Conclusions

1. A method has been developed for the synthesis of monoacetyl derivatives of certain aromatic and heterocyclic compounds.
2. The method for the synthesis of 3-acetylcarbazole has been improved.
3. A method of polarographic analysis has been developed for a series of ketones.
4. The rate constants of the reduction reaction have been determined for eight fatty-aromatic ketones.
5. A relationship has been shown between the values of \(E_{1/2}\) and the reactivity of fatty-aromatic ketones.

Literature

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5. R. Donaldson. Chemistry and Technology of Compounds of the Naphthalene Series, Goskhimizdat, 1963.
6. E. Meithner. J. Am. Chem. Soc., 57, 2327–28, 1935.
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