Study in the Field of Chemistry of Carbazole Derivatives

10. Oxidation of 9-Ethanolcarbazoles to 9-Carbazolylacetic Acids

I. P. Zherebtsov, V. P. Lopatinskii

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

9-Carbazolylacetic acids, or diphenyleneglycines, are of interest as potential biologically active substances (1, 2) and as intermediates for further syntheses [3].

The practical use of 9-carbazolylacetic acids is hindered to a considerable extent by the absence of a sufficiently effective method for their preparation, although recently we described [4, 5] a convenient method having broader applicability than the previously known one [6, 7, 8].

Also of interest is such a route to the synthesis of 9-carbazolylacetic acids as the oxidation of 9-ethanolcarbazoles, since the synthesis of the latter is carried out easily and from readily available reagents [9, 10, 11].

The aim of our work was to seek methods for the oxidation of 9-ethanolcarbazoles to 9-carbazolylacetic acids.

For this reason, the action of potassium permanganate, nitric acid, and alkaline fusion in the presence of various oxidizing agents was tested. Oxidation with permanganate leads only to low yields of acids, probably owing to their further oxidation. Thus, under the action of an excess of permanganate on 3,6-dichlorocarbazole, tetrachloro-9,9¹-dicarbazyl can be isolated.

The action of nitric acid on 9-ethanolcarbazoles leads, mainly, to their nitro derivatives, which is of independent interest as a route to nitro derivatives of 9-ethanolcarbazoles.

The best results were obtained on fusing 9-(β-oxy)ethylcarbazole with caustic potash or caustic soda in the presence of copper oxide. However, this method is not applicable to halogen-substituted 9-ethanolcarbazoles because of elimination of halogen under the conditions of alkaline fusion. The use of other oxidizing agents (copper sulfate, potassium or sodium nitrates, manganese dioxide) is little effective under the conditions of alkaline fusion.

The structure of the resulting substance as 9-carbazolylacetic acid was proved by the identity of its IR spectrum with the spectrum of known 9-carbazolylacetic acid obtained by the previously described method [4, 5].

Experimental Part

9-Carbazolylacetic acid

Method A. A mixture of 10 g of 9-(β-hydroxy)ethylcarbazole (m.p. 81–82°), 10 g of potassium permanganate, and 150 ml of acetone is heated for 2 hours at 40° and then kept for 12 hours at room temperature. The precipitated manganese dioxide is filtered off, and 6.0 g of unreacted alcohol is isolated from the acetone filtrate. The dioxide precipitate is boiled with an aqueous solution of caustic potash, and upon acidification 0.6 g of 9-carbazolylacetic acid, m.p. 201–202°, is isolated from the alkaline solution.

Found, %: \(N\) 6.42; \(C_{14}H_{11}O_2N\). Calculated, %: \(N\) 6.22. Molecular weight: found (by alkali titration) 220.1; calculated 225.2.

Method B. A mixture of 10.6 g of 9-(β-hydroxy)ethylcarbazole, 13 g of copper oxide, and 5.6 g of caustic potash is heated for 15 minutes at 240°. The cooled melt is extracted with boiling 10% aqueous caustic potash solution, and from the extract, by acidification with hydrochloric acid, 5.4 g (48%) of 9-carbazolylacetic acid, m.p. 200°C, is isolated.

Analysis (by alkali titration) shows that the sample contains 95% pure substance. After recrystallization from dichloroethane or xylene the degree of purity increases to 98–99%.

Heating the acid obtained in this way at 250–260° gives 9-methylcarbazole.

3,6-Dichloro-9-carbazolylacetic acid

Under conditions analogous to those for 9-carbazolylacetic acid, from 10 g of 3,6-dichloro-9-(β-hydroxy)ethylcarbazole and 15 g of potassium permanganate in 100 ml of acetone, 0.34 g of 3,6-dichloro-9-carbazolylacetic acid, m.p. 219–220°, is obtained.

Molecular weight, found (by alkali titration): 308. \(C_{14}H_9O_2NCl_2\). Calculated: 294.08.

When 10 g of 3,6-dichloro-9-(β-hydroxy)ethylcarbazole is treated with 22.5 g of potassium permanganate in 115 ml of acetone under reflux for 4 hours, 4.85 g of 3,6,3′,6′-tetrachloro-9,9′-dicarbazyl, m.p. 236° (from dichloroethane), is isolated. The substance obtained shows no depression in melting point with a sample prepared by the known procedure [12].

3-Nitro-9-(β-hydroxy)ethylcarbazole

A mixture of 10 g of 9-(β-hydroxy)ethylcarbazole and 4.5 ml of nitric acid (sp. gr. 1.35) in 85 ml of acetic acid is kept for 1 hour at 40–50°. The precipitate that separates when the mixture is poured into water (11.3 g) is recrystallized from alcohol, giving 7.1 g (58.5%) of 3-nitro-9-(β-hydroxy)ethylcarbazole, m.p. 184°. A mixture of the substance obtained with a sample prepared by the action of ethylene oxide on 3-nitrocarbazole melts without depression.

Found, %: C 65.80; H 4.60; OH (by Verley) 6.43; 6.85. \(C_{14}H_{12}O_3N_2\). Calculated, %: C 65.6; H 4.69; OH 6.55.

3-Chloro-6-(?)nitro-9-(β-hydroxy)ethylcarbazole

To 10 g of 3-chloro-9-(β-hydroxy)ethylcarbazole in 60 ml of acetic acid, 3.5 ml of nitric acid in 25 ml of acetic acid is added. After the mixture is kept for one hour at 35–50°, a precipitate separates (9 g, 76%). Recrystallization from acetic acid gives a substance with m.p. 199–200°C.

Found, %: Cl 11.87. \(C_{14}H_{11}O_3N_2Cl\). Calculated, %: Cl 12.2.

Conclusions

1. In studying the action of oxidizing agents on 9-ethanolcarbazoles, it was found that, under the action of potassium permanganate in acetone, 9-carbazolylacetic acids are obtained in insignificant yield, while nitric acid nitrates 9-ethanolcarbazoles.

2. A satisfactory yield of 9-carbazolylacetic acid was achieved by alkaline fusion of 9-ethanolcarbazole in the presence of copper oxide.

References

1. Swiss pat. 274615; C. A. 1192, 1954.

2. N. I. Melnikov, Yu. A. Baskakov. Chemistry of Herbicides and Plant Growth Regulators, Goskhimizdat, 1962.

3. German pat. 397814; C. II, 1407, 1924.

4. V. P. Lopatinskii, I. P. Zherebtsov. Author’s certificate 183210; BI 13, 1966.

5. V. P. Lopatinskii, I. P. Zherebtsov. Izvestiya TPI (in press).

6. German pat. 255304; Fr 11, 171, 1915.

7. R. Seca, Ber. 57, 1527, 1924.

8. S. I. Omelchenko, Z. V. Pushkareva, S. G. Bogomolov. ZhOKh, 27, 3225, 1957.

9. V. P. Lopatinskii, I. P. Zherebtsov, E. E. Sirotkina, S. K. Vereshchagina. Izvestiya TPI, 136, 11, 1965.

10. V. P. Lopatinskii, E. E. Sirotkina, I. P. Zherebtsov. Author’s certificate 159533; BI 1, 1964.

11. V. P. Lopatinskii, E. E. Sirotkina, I. P. Zherebtsov. Izvestiya TPI, 112, 42, 1963.

12. F. Muzik, Z. Allan. Chem. Zisty, 50, 1808, 1956.