RESEARCH IN THE CHEMISTRY OF CARBAZOLE DERIVATIVES

XXIV. SYNTHESIS OF CERTAIN 9-ALKYLCARBAZOLES

V. P. Lopatinskii, E. E. Sirotkina, M. M. Anosova,
L. G. Tikhonova, S. F. Pavlov

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

9-Alkylcarbazoles can be obtained by the action on potassium carbazole or carbazole-magnesium halides of the corresponding alkyl halides or alkyl sulfates \[1—5\].

A simpler method for the synthesis of 9-alkylcarbazoles is the Stevens and Tucker method \[6\], in which the need for the preliminary synthesis of potassium carbazole is eliminated.

Here 9-alkylcarbazoles are obtained by the action, on carbazole present in acetone or alcohol solution, of alkyl sulfates or alkyl iodides in the presence of a concentrated aqueous solution of NaOH (in the case of alkyl sulfates) or KOH (in the case of alkyl iodides), i.e., under conditions in which the intermediate formation of sodium or potassium carbazole is observed.

In this way 9-methyl-, 9-ethyl-, and 9-n-propylcarbazoles were obtained \[6\]. The latter was obtained in 85% yield of the theoretical. Subsequently this method was modified by Byu-Khoi and Rua \[7\], who used, instead of an aqueous-alkaline acetone solution, sodium amide in toluene. In this manner, on boiling carbazole with butyl bromide for 48 hours, they obtained 9-butylcarbazole in 66% yield of the theoretical. By the same method 9-isoamylcarbazole was obtained in 84.5% yield of the theoretical \[7\].

In carrying out our investigations, the possibility was established of further simplifying the Stevens and Tucker method. It proved that the duration of alkylation can be considerably reduced, and the yield of 9-alkyl derivatives increased, if, in acetone solutions of carbazole, not aqueous alkali solutions but powdered alkalis (NaOH or KOH) are used. The advantages of the alkylation method developed are:

1) the possibility of reducing the required amount of acetone by 1.5—2.5 times (methyl ethyl ketone may also be used instead of acetone; in dioxane the reaction proceeds more slowly);

2) the possibility of using in the syntheses only small excesses of alkyl halides (1.5—2 moles of iodide or

alkyl bromide per mole of carbazole, whereas in the Stevens and Tucker method from 2 to 11 moles of alkyl iodides are used per mole of carbazole);

3) the reaction time in the case of alkylation with lower alkyls can be shortened to 2–3 hours.

Only in the case of the synthesis of 9-n-hexyl-, 9-n-heptyl-, and 9-n-octylcarbazoles, in order to obtain them in high yields, is it necessary to increase the duration of the process to 12–25 hours or more. When introducing alkyls with a branched carbon chain, an increase in the reaction time to 5–9 hours is also required. It should be noted that alkyl bromides and iodides are interchangeable in these syntheses, while alkylation with alkyl chlorides is hardly successful.

Experimental Part

Starting reagents. Carbazole—reagent-grade “pure”; after recrystallization from benzene it had m.p. 242°C. The alkyl iodides and bromides were of “pure” grade.

The procedures for the synthesis of 9-methyl- and 9-ethylcarbazoles were given in our previous communications [8, 9].

9-n-Propylcarbazole. Into a three-necked flask equipped with a dropping funnel, reflux condenser, and stirrer were placed 167.2 g of carbazole, 60 g of powdered NaOH, and 334 ml of acetone. The contents of the flask were heated to 50°C, and then, with the stirrer running, 255.3 g of n-propyl iodide was gradually added to the flask over 30 min; after this the temperature was raised to boiling and maintained for 3 h. The reaction product was precipitated with water, filtered off, washed with water to neutral reaction, and dried at a temperature not above 40°C. After recrystallization from ethanol, 197.6 g of 9-n-propylcarbazole was obtained (85% of theory), with m.p. 50–52°C and b.p. 164–167°C (3–4 mm Hg). The picrate (dark cherry-red needles) melts at 103.5–104.5°C (according to the literature, 9-n-propylcarbazole has m.p. 48.2–49°C [10], 50°C [2]).

9-Isopropylcarbazole. Obtained by the above-described procedure from 10 g of carbazole and 15.27 g of isopropyl iodide with 3.5 g of NaOH in 20 ml of acetone, by boiling for 5 h. After recrystallization from ethanol, 8.75 g of 9-isopropylcarbazole was obtained (70% of theory), with m.p. 121.5–122.5°C and b.p. 165–167°C (3–5 mm Hg). The picrate (dark red needles) melts at 148.5–149.5°C (according to the literature, 9-isopropylcarbazole has m.p. 120°C [2]).

9-n-Butylcarbazole. Obtained by the above-described procedure from 334.4 g of carbazole and 411.06 g of n-butyl bromide with 180 g of KOH in 669 ml of acetone, by boiling for 3 h. After recrystallization from ethanol, 312.3 g of 9-n-butylcarbazole was obtained (70% of theory), with m.p. 58.5–59.5°C and b.p. 176–179°C (4 mm Hg). The picrate (cherry-red needles) melts at 88.5–89.5°C (according to the literature, 9-n-butylcarbazole has m.p. 56–57°C [11], 58°C [2, 7]).

9-n-Amylcarbazole. Obtained by the above-described procedure from 30 g of carbazole and 40.65 g of n-amyl bromide with 16.2 g of KOH in 60 ml of acetone, by boiling for 2 h. After recrystallization from ethanol, 29.82 g of 9-n-amylcarbazole was obtained (70% of theory), with m.p. 52–53°C and b.p. 181–184°C (4 mm Hg). 9-n-Amylcarbazole crystallizes as colorless needles. It is readily soluble in acetone, benzene, and pyridine, and less readily in diethyl ether. It forms a picrate (red-orange needles) with m.p. 65–66°C. Analyses: found, %: N 5.76, C₁₇H₁₉N. Calculated, %: N 5.90.

9-Isoamylcarbazole. Prepared by the procedure described above from 334 g of carbazole and 453.2 g of isoamyl bromide with 180 g of KOH in 669 ml of acetone under reflux for 9 hours.

After recrystallization from ethanol, 341.4 g of 9-isoamylcarbazole was isolated (72% of theory), mp 44–45°C and bp 195–197°C (5 mm Hg). The picrate (red needles) melts at 83.5–84.5°C. According to the literature, 9-isoamylcarbazole has mp 43°C [12], 44°C [7].

9-n-Hexylcarbazole. Prepared from 50 g of carbazole and 127 g of n-hexyl iodide with 25 g of KOH in 80 ml of methyl ethyl ketone under reflux for 18 hours. After cooling and removal of KI by filtration, the solvent was distilled off, the alkali was washed with water, and the product was extracted with carbon tetrachloride (40 ml). After removal of CCl₄, 9-n-hexylcarbazole was isolated by vacuum distillation of the residue. At 187–192°C (2–3 mm Hg), 72 g of a yellowish oil was obtained, which solidified on cooling. Recrystallization from ethanol gave 60.13 g of 9-n-hexylcarbazole (80% of theory), mp 56–57°C. 9-n-Hexylcarbazole crystallizes as small colorless needles. It is readily soluble in acetone, benzene, dioxane, diethyl ether, and carbon tetrachloride. It forms a picrate (red needles), mp 62–63°C. Analysis: found, %: N 5.40. C₁₈H₂₁N. Calculated, %: N 5.57. 9-n-Hexylcarbazole has not been described in the literature.

9-n-Heptylcarbazole. Prepared from 50 g of carbazole and 117 g of n-heptyl iodide with 25 g of KOH in 100 ml of dioxane under reflux for 12 hours. After removal of KI, distillation of the solvent, washing of the alkali with water, and drying over calcium chloride, the oily layer was subjected to vacuum distillation. At 235–240°C (4–5 mm Hg), a yellowish oily liquid was distilled off, which did not solidify on standing. After dissolving it in methanol and crystallization, 39.7 g of 9-n-heptylcarbazole was obtained (50% of theory), mp 28–29°C.

9-n-Heptylcarbazole crystallizes as small colorless needles. It is readily soluble in benzene, toluene, dioxane, and acetone. It forms a picrate (orange needles), mp 64–66°C. Analysis: found, %: N 5.35. C₁₉H₂₃N. Calculated, %: N 5.28. 9-n-Heptylcarbazole has not been described in the literature.

9-n-Octylcarbazole. Prepared from 75 g of carbazole and 81 g of n-octyl bromide with 40 g of KOH in 150 ml of acetone under reflux for 25 hours. After heating was complete, the reaction mass was poured into water, and the precipitated oily product was washed to neutral reaction and then distilled under vacuum. At 197–200°C (2–3 mm Hg), 64.0 g (51% of theory) of slightly yellowish oily 9-n-octylcarbazole distilled over, which did not solidify on standing. At room temperature, 9-n-octylcarbazole is a transparent liquid with \(n_D^{22}\) 1.5938. It is readily soluble in benzene, toluene, acetone, and dioxane, and very poorly soluble in methanol and ethanol. It forms a picrate (dark-red needles), mp 46–47°C. Analysis: found, %: N 5.35. C₂₀H₂₅N. Calculated, %: N 5.01. 9-n-Octylcarbazole has not been described in the literature.

Conclusions

1. A method has been developed for the synthesis of 9-alkylcarbazoles by the interaction of carbazole with alkyl bromides (or alkyl iodides) in the presence of powdered caustic alkalis.

1. 9-H-amyl-, 9-H-hexyl-, 9-H-heptyl-, and 9-H-octylcarbazoles have been obtained for the first time.

References

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