Research in the Chemistry of Carbazole Derivatives

30. Alkanolcarbazoles and Some of Their Derivatives

I. P. Zherebtsov, V. P. Lopatinskii

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

It was shown earlier [1–6] that certain 9-ethanolcarbazoles and their derivatives can be used for the synthesis of 9-vinyl derivatives of carbazole. It was of interest to obtain new ethanolcarbazoles and their derivatives, which was the aim of the present work. In addition, the objective of our work included refining the methods for the synthesis of certain derivatives of this series described earlier [4]. The availability of a simple and effective method for the synthesis of 9-(β-hydroxy)ethylcarbazole makes this product accessible and allows one to proceed from it to other derivatives, for example to 9-(β-chloro)ethylcarbazole, obtained for the first time by the action of chloroethyl ester of p-toluenesulfonic acid on carbazole [1] and used to obtain 9-vinylcarbazole [1] and physiologically active substances [7].

The same route can be used to obtain C-substituted carbazoles with a chloroethyl group in the 9-position, the synthesis of which by another method is for some reason inconvenient. Thus, for example, in the synthesis of 3-nitro-9-(β-chloro)ethylcarbazole one may start from 3-nitrocarbazole, usually obtained by a three-stage synthesis, or else nitrate 9-(β-chloro)ethylcarbazole, which is simpler. 9-(β-Chloro)ethylcarbazole was obtained by us by the action of thionyl chloride on 9-(β-hydroxy)ethylcarbazole in a yield of 40%, i.e., the same as in the synthesis by the method of [1]. It was nitrated with nitric acid in glacial acetic acid, and the nitro compound obtained was converted into 3-nitro-9-vinylcarbazole in a yield of 59% of theory. This method was also tested on other 9-ethanolcarbazoles, in particular on 3,6-dichloro-9-(β-hydroxy)ethylcarbazole. At the same time, the influence of the duration of boiling and of the amount of solvent on the yield of 3,6-dichloro-9-(β-chloro)ethylcarbazole during its preparation by the method previously described by us [6], by the action of phosphorus pentachloride, was studied. It was established that good yields can be achieved with a boiling time of 1 hour and an amount of solvent equal to 7.5 ml per 1 g of 3,6-dichloro-9-(β-hydroxy)ethylcarbazole.

When carrying out the reaction of ethylene oxide with 3-nitrocarbazole in alkaline acetone, it was observed that the reaction proceeds somewhat more difficultly than with carbazole [4] and its halogen-substituted derivatives [5], which is probably connected with the increased acidity of 3-nitrocarbazole (pKa = 14.10) [8].

however, here too the 9-oxyethyl derivative can be obtained in satisfactory yield.

For the identification of certain ethanolcarbazoles, their picrates were obtained; these are characterized by a deeper color than the original carbazole and halogenocarbazoles. Data on the picrates are given in Table 1.

The substances obtained were identified by melting points (for those previously known) and by the results of elemental and functional analysis.

Table 1

Picrates of carbazole and its derivatives

Experimental Part

Starting materials and reagents

9-(β-Oxy)ethylcarbazole. Prepared by the previously described method [4] and had m.p. 81—82°C.

3,6-Dichloro-9-(β-oxy)ethylcarbazole. Prepared by the previously described [5] method and had m.p. 162°C.

Phosphorus pentachloride—“chemically pure for analysis” grade.

Carbon tetrachloride—“chemically pure for analysis” grade.

Thionyl chloride—“chemically pure” grade.

Pyridine. Obtained by purification, according to the known method [9], from a preparation of “pure” grade.

Acetic acid—“chemically pure” grade.

Picric acid—“chemically pure” grade.

Nitric acid—“chemically pure for analysis” grade, with density = 1.34.

9-(β-Chloro)ethylcarbazole.

Into a flask equipped with a dropping funnel, reflux condenser, and stirrer are charged 30 g of 9-(β-oxy)ethylcarbazole and 12.6 ml of pyridine. At a temperature of 10°C, with stirring, 10.7 ml of thionyl chloride is added dropwise from the dropping funnel over 20 min. With further stirring, the contents are heated to 60°C and kept at this temperature for 1.5 h, after which the pasty mass almost completely goes into solution. To remove pyridine, the reaction mixture is washed several times with water while stirring. The residue is dissolved in acetone and poured into water. The greenish solid that separates is extracted three times with fresh portions of benzine (b.p. 70—190°C) under boiling. On standing, the benzine solution deposits crystals with m.p. 114—116°C. After recrystalliza-

from ethanol gives a substance with m.p. 125–126°C in a yield of 12.7 g (42% of theory). According to the literature, m.p. 125–126°C, 131°C [1].

3-Nitro-9-(β-chloro)ethylcarbazole. To 5 g of 9-(β-chloro)ethylcarbazole, suspended in 35 ml of acetic acid, at room temperature, with stirring, a mixture of 2 ml of nitric acid and 5 ml of acetic acid is added over 0.5 h. The resulting yellow mass is stirred for another 0.5 h, after which it is heated with stirring to 40°C; after half an hour of stirring and cooling, it is filtered off. The precipitate is washed on the filter with water to remove acids and dried. This gives 6.3 g of substance with m.p. 194–195°C (92% of theory). After two recrystallizations from toluene the m.p. rises to 197–198°C. 3-Nitro-9-(β-chloro)ethylcarbazole consists of prismatic crystals of dark-yellow color, moderately soluble in toluene, acetic acid, and ethanol. It dissolves well in acetone.

Analyses. Found, %: N 10.25; 9.98. C₁₄H₁₁O₂N₂Cl;
calculated, %: N 10.04.

3-Nitro-9-vinylcarbazole. 3 g of 3-nitro-9-(β-chloro)ethylcarbazole is boiled with a reflux condenser in 50 ml of methanol with 8 g of caustic potash for 3 h. On cooling, 1.5 g of dark-yellow needles crystallizes out (59% of theory). After two recrystallizations from methanol and toluene, m.p. 111–112°C.

Analyses. Found, %: C 70.50; H 4.05; N 11.82. C₁₄H₁₀O₂N₂;
calculated, %: C 70.58; H 4.20; N 11.76.

3-Nitrocarbazole. Obtained by the known method [10] and had m.p. 211–212°C.

3-Nitro-9-(β-hydroxy)ethylcarbazole. To a mixture of 10 g of 3-nitrocarbazole, 25 ml of acetone, and 2.7 g of powdered caustic potash, 3 ml of ethylene oxide is added at 0°C. The tightly stoppered flask is kept in a thermostat for 1 h 45 min at 50°C. After cooling, the reaction product is poured into water; a yellow precipitate immediately separates, which is filtered off, washed with water, and dried. This gives 10.85 g of yellow product with m.p. 151–154°C. It is recrystallized from methanol until the red coloration from the addition of alkali and acetone ceases to appear, which indicates the absence of 3-nitrocarbazole. This gives 4.85 g (40% of theory) of a substance crystallizing from methanol in the form of thin small yellow needles with m.p. 183.5–184°C.

Analyses. Found, %: C 65.80; H 4.60; N 11.06; OH (by Verley) 6.43; 6.85. C₁₄H₁₂O₃N₂;
calculated, %: C 65.6; H 4.69; N 10.95; OH 6.65.

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

1. Into a flask equipped with a reflux condenser and a gas outlet tube are charged 20 g (0.071 mole) of 3,6-dichloro-9-(β-hydroxy)ethylcarbazole, 150 ml of carbon tetrachloride, and 14.9 g (0.071 mole) of phosphorus pentachloride. The contents are boiled for an hour on a water bath. The evolved hydrogen chloride is absorbed by alkali in a Tishchenko bottle. After the reaction is complete, the contents are cooled, washed with water free of acids, and dried over calcium chloride. The solvent is removed by distillation; a residue is obtained with m.p. 127–130°C in a yield of 20.66 g (97%). After recrystallization from glacial acetic acid and carbon tetrachloride, the yield of substance with m.p. 132–132.5°C is 12.8 g (60.6% of theory). According to the literature, m.p. 132–133°C [6].

1. Into a flask equipped with a stirrer, dropping funnel, and reflux condenser are charged 20 g of 3,6-dichloro-9-(β-hydroxy)ethylcarbazole in 79 ml of pyridine, and, at a temperature of about 10°C and with vigorous stirring, 5.12 ml of thionyl chloride is added dropwise over half an hour. The mixture is stirred for 2 hours at room temperature and for 1 hour on a boiling water bath, after which it is poured into water; 19.17 g of substance is obtained (90% of theoretical), m.p. 106–107°C. After recrystallization from alcohol and acetic acid, 10.39 g (53.5% of theoretical) of fine needles is isolated, m.p. 132–133°C. The melting point of a mixture of the substances obtained by methods 1 and 2 shows no depression.

Obtaining picrates. The picrates were obtained by the usual method. It should be noted that some picrates cannot be obtained when alcohol is used as the solvent, and therefore a less polar solvent was chosen—carbon tetrachloride or chloroform.

Conclusions

1. Certain ethanolcarbazoles and their derivatives have been obtained and characterized.

2. By replacement of hydroxyl by chlorine with thionyl chloride in pyridine, 9-(β-chloro)ethylcarbazole and 3,6-dichloro-9-(β-chloro)ethylcarbazole were obtained from 9-(β-hydroxy)ethylcarbazole and 3,6-dichloro-9-(β-hydroxy)ethylcarbazole, respectively.

3. Using the nitration of 9-(β-chloro)ethylcarbazole as an example, the possibility has been shown of obtaining nucleus-substituted derivatives from 9-(β-chloro)ethylcarbazole. 3-Nitro-9-(β-chloro)ethylcarbazole was obtained and then converted into 3-nitro-9-vinylcarbazole.

4. The oxyethylation reaction, previously applied to carbazole and its halogen-substituted derivatives, has been extended to 3-nitrocarbazole, and 3-nitro-9-(β-hydroxy)ethylcarbazole was obtained.

LITERATURE

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2. R. Flowers, H. Miller, L. Flomers, J. Am. Ch. Soc. 70, 3019, 1948.

3. H. Otsuki, I. Okano, T. Takeda, J. Soc. Ch. Ind. Jap. 49, 169, 1946; C. A. 42, 6354, 1948.

4. V. P. Lopatinskii, E. E. Sirotkina, I. P. Zherebtsov. Izvestiya Tomskogo politekhnicheskogo instituta, 112, 42, 1963.

5. V. P. Lopatinskii, I. P. Zherebtsov, E. E. Sirotkina, S. K. Vereshchagina. Izvestiya Tomskogo politekhnicheskogo instituta, 126, 1964.

6. V. P. Lopatinskii, I. P. Zherebtsov. Izvestiya Tomskogo politekhnicheskogo instituta, 136, 1964.

7. P. Pratesi, et al., Farmaco EL. Sci. 9, No. 3, 135–143, 1954.

8. R. Stewart, J. O’Donnell, J. Am. Chem. Soc. 84, 494, 1962.

9. Yu. K. Yur’ev. Practical Work in Organic Chemistry, issue 2, Moscow State University, 1957.

10. R. K. Eikhman, V. O. Lukashevich, E. L. Silaeva. POKh, 6, 93, 1939.