Research in the Chemistry of Carbazole Derivatives
Abstract Generated abstract
This study examines the preparation of 3-monoacetic and 3,6-diacetic acids of carbazole and several 9-alkyl-substituted carbazoles from the corresponding amides and diamides. Because alcoholic alkaline saponification gave poor results owing to low solubility, prolonged heating, and resin formation, the authors investigated acid saponification in acetic acid and dilute hydrochloric acid, varying reaction time, acid quantities, and precipitation conditions. Optimized procedures allowed use of crude Willgerodt reaction amides and gave 9-alkyl-3-carbazolylacetic acids in preparative yields of about 38 to 66 percent and 9-alkyl-3,6-carbazolyldiacetic acids in yields up to about 85 percent. The work reports conditions, yields, and melting points for a series of carbazole acetic acid derivatives not previously described in the literature.
Full Text
Bulletin of the Tomsk Polytechnic Institute Named after S. M. Kirov
Vol. 198
1974
RESEARCH IN THE CHEMISTRY OF CARBAZOLE DERIVATIVES
55. Synthesis of 3-Mono- and 3,6-Diacetic Acids of Carbazole and Its 9-Alkyl-Substituted Derivatives
M. M. Sukhoroslova, V. P. Lopatinskii, E. E. Sirotkina,
L. P. Levchenko, T. F. Turchina
(Presented by the Scientific-Methodological Seminar of the Faculty of Chemical Technology)
The literature describes 2- and 3-carbazolylacetic acids obtained by saponification of the corresponding amides with an alcoholic solution of caustic potash [1]. However, the amides and diamides of 9-alkylcarbazolylacetic acids obtained by us [3] are almost insoluble in alcohols, and their saponification to the acids requires prolonged heating (12–14 hours), which leads to tar formation and to the loss of considerable amounts of products in the resins. Since in such cases a mixture of acetic and concentrated hydrochloric acids is often used for saponification [2], we studied the possibility of acid saponification of amides and the influence of various factors on the yield of 9-alkylcarbazolylacetic acids, using as examples the synthesis of 9-methyl-3-carbazolylacetic and 9-methyl-3,6-carbazolyldiacetic acids.
The investigation showed that it is better to carry out saponification of the amides using a mixture of acetic acid and dilute hydrochloric acid; moreover, in the saponification it is possible to use the crude amides obtained in the Willgerodt reaction without purifying them by crystallization. The optimal conditions for the synthesis of 9-methyl-3-carbazolylacetic acid are as follows: duration of saponification at boiling of the reaction mass, 30 min; amounts of acetic acid and hydrogen chloride (per 1 g of acetamide), 30 ml and 5.64 g, respectively. The hydrochloric acid (specific gravity 1.36) was diluted with water in a ratio of 1:3. The yield of 9-methyl-3-carbazolylacetic acid, determined in the reaction mass by titration with alkali of an alcoholic solution of the acid, is 58–60% under the optimal conditions. However, during isolation part of the acid remains in the resinous by-products, and therefore its preparative yield does not rise above 54–55% (Table 1). Under the indicated optimal conditions, other 9-alkyl-3-carbazolylacetic acids were obtained in yields of 38–65%; information on them is given in Table 2.
In studying the influence of factors on the yield of 9-methyl-3,6-carbazolyldiacetic acid, it was established that the following conditions are optimal: duration of saponification at boiling, 10 min; amounts of acetic acid and hydrogen chloride (per 1 g of diacetamide), 100 ml and 30 g, respectively (Table 3). Since in these cases tar formation was hardly observed, the preparative and
analytical yields of the acid are close to one another and, under optimal conditions, reach 85% of theory.
Table 1
Results of some experiments on the synthesis of 9-methyl-3-carbazolylacetic acid
| Reaction duration, min | Amount of HCl (gaseous), g per 0.5 g starting amide: saponification | Amount of HCl (gaseous), g per 0.5 g starting amide: precipitation | Acetic acid, ml per 0.5 g starting amide | Acid yield, % of theory: analytical | Acid yield, % of theory: preparative |
|---|---|---|---|---|---|
| 10 | 3,38 | 3,38 | 15 | 49,1 | 44,2 |
| 20 | 3,38 | 3,38 | 15 | 51,4 | 44,3 |
| 30 | 3,38 | 3,38 | 15 | 54,3 | 48,5 |
| 40 | 3,38 | 3,38 | 15 | 49,0 | 42,1 |
| 30 | 3,38 | 3,38 | 15 | 54,3 | 48,5 |
| 30 | 2,82 | 2,82 | 15 | 58,2 | 51,5 |
| 30 | 2,26 | 2,26 | 15 | 55,9 | 50,0 |
| 30 | 2,82 | 2,82 | 10 | 43,1 | 23,4 |
| 30 | 2,82 | 2,82 | 15 | 58,2 | 51,5 |
| 30 | 2,82 | 2,82 | 20 | 53,9 | 49,6 |
| 30 | 2,26 | 3,38 | 15 | 50,0 | 41,0 |
| 30 | 2,82 | 2,82 | 15 | 58,2 | 51,5 |
| 30 | 3,31⁸ | 2,26 | 15 | 55,5 | 46,2 |
| 30 | 3,38¹ | 3,38¹ | 15 | 58,5 | 33,7 |
| 30 | 3,38² | 3,38² | 15 | 45,7 | 40,7 |
| 30 | 3,38³ | 3,38³ | 15 | 54,3 | 48,5 |
| 30 | 3,38⁴ | 3,38¹ | 15 | 45,7 | 40,7 |
- Dilution of HCl 1 : 1
- ” ” 1 : 2
- ” ” 1 : 3
- ” ” 1 : 4
Under the indicated conditions, other 9-alkyl-3,6-carbazolyldiacetic acids, as well as 3,6-carbazolyldiacetic acid, were obtained (Table 2).
It should be noted that, as the alkyl radical in 3,6-diacetamido-9-alkylcarbazoles increases, their solubility in acetic acid improves; as a result, less of it is required and, correspondingly, the amount of hydrochloric acid for saponification and precipitation of the acetic acids is somewhat reduced.
Experimental Part
The starting amides and diamides of 9-alkylcarbazole-3-acetic and 3,6-diacetic acids were obtained by the methods given in the preceding communication [3], without additional purification by crystallization.
9-Methyl-3-carbazolylacetic acid
Into a flask equipped with a reflux condenser were charged 0.5 g of 3-acetamido-9-methylcarbazole and 15 ml of acetic acid. The mixture was hea-
Table 2
9-Alkyl-3-carbazolylacetic and 3,6-carbazolediacetic acids
| No. | 9-Alkyl- | 3-Carbazolylacetic acid: yield of 100% acid, % of theoretical, analytical | 3-Carbazolylacetic acid: yield of 100% acid, % of theoretical, preparative | 3-Carbazolylacetic acid: melting point, °C | 3,6-Carbazolediacetic acid: yield of 100% acid, % of theoretical | 3,6-Carbazolediacetic acid: melting point, °C |
|---|---|---|---|---|---|---|
| 1 | 9-methyl- | 59.0 | 54.0 | 156–157 | 84.6 | 255–256.5 |
| 2 | 9-ethyl- | 67.6 | 66.1 | 143–144 | 68.2 | 210–211 |
| 3 | 9-n-propyl- | 65.3 | 43.2 | 123–124 | 68.6 | 220–221 |
| 4 | 9-isopropyl- | 68.4 | 50.2 | 153–154 | 56.6 | 205–206 |
| 5 | 9-n-butyl- | 76.9 | 43.2 | 107–108 | 53.2 | 201–202 |
| 6 | 9-n-amyl- | — | — | — | 66.1 | 175–176 |
| 7 | 9-isoamyl- | 69.8 | 38.0 | 118.5–119.5 | 53.0 | 201–202 |
| 8 | 3,6-carbazolediacetic acid | — | — | — | 68.5 | 243–244 |
Table 3
Results of some experiments on the synthesis of 9-methyl-3,6-carbazolediacetic acid
| Amount of HCl (gaseous), g/g amide: for saponification | Amount of HCl (gaseous), g/g amide: for precipitation | Acetic acid, ml/g amide | Reaction duration, min | Acid yield, % of theoretical: analytical | Acid yield, % of theoretical: preparative |
|---|---|---|---|---|---|
| 18.30 | 91.5 | 100 | 10 | 72.5 | 67.0 |
| 24.40 | ″ | ″ | ″ | 75.0 | 71.5 |
| 30.5 | ″ | ″ | ″ | 87.5 | 84.5 |
| 36.60 | ″ | ″ | ″ | 82.5 | 78.4 |
| 45.75 | ″ | ″ | ″ | 70.0 | 65.5 |
| 30.5 | 54.5 | 250 | 20 | 65.0 | 57.5 |
| ″ | 73.0 | ″ | ″ | 70.0 | 65.1 |
| ″ | 91.5 | ″ | ″ | 74.2 | 71.5 |
| ″ | 109.5 | ″ | ″ | 69.5 | 65.0 |
| ″ | 122.0 | ″ | ″ | 68.5 | 64.0 |
| 30.5 | 91.5 | 50 | 20 | 18.0 | 16.5 |
| ″ | ″ | 100 | ″ | 78.5 | 78.0 |
| ″ | ″ | 150 | ″ | 76.5 | 76.5 |
| ″ | ″ | 200 | ″ | 78.0 | 74.0 |
| 30.5 | 91.5 | 100 | 5 | 70.0 | 66.6 |
| ″ | ″ | ″ | 10 | 87.5 | 84.6 |
| ″ | ″ | ″ | 20 | 65.0 | 61.8 |
| ″ | ″ | ″ | 25 | 65.0 | 61.8 |
was heated on a sand bath until the amide dissolved; the solution was then filtered. To the filtrate, for saponification, were added 25 ml (2.82 g HCl) of hydrochloric acid diluted 1:3; the mixture was brought to boiling and boiled for 30 minutes. After this the mixture was again filtered from the resin that had formed. The filtrate was poured into a beaker into which a further 25 ml of diluted hydrochloric acid (1:3) had been poured for precipitation of 9-methyl-3-carbazolylacetic acid. The product separates in the form of fine colorless needles, which after cooling are filtered off, washed with water, and dried at 60–80°C.
The yield of acid was 0.26 g (calculated as 100%), which amounts to 51.5% of the theoretical yield. The melting point of 9-methyl-3-carbazolylacetic acid recrystallized from ethanol was 156–157°C.
Analysis of the acid obtained was carried out by titration of an alcoholic solution of the acid with 0.1 N KOH solution. The acid content in the crude product was from 92.5 to 98%, and in the recrystallized product 98–100%.
9-Methyl-3,6-carbazolyldiacetic acid
Into a flask equipped with a reflux condenser were introduced 0.2 g of 3,6-diacetamido-9-methylcarbazole and 20 ml of acetic acid. The mixture was boiled on a sand bath until the amide dissolved; then 50 ml (6.1 g HCl) of diluted (1:3) hydrochloric acid was poured into the flask. The mixture was boiled for 10 minutes and filtered. To the filtrate were added 150 ml (18.3 g HCl) of diluted hydrochloric acid, 1:3. On cooling the solution, 0.18 g of 9-methyl-3,6-carbazolyldiacetic acid separates in the form of light white flakes.
The acid content in the crude product was 96.7%. The yield of 100% acid was 0.17 g (84.6% of the theoretical yield). The melting point of the acid after recrystallization from ethanol was 255–256.5°C; the acid content in it was 99.85%.
3,6-Carbazolyldiacetic acid
Obtained by the procedure described for 9-methyl-3,6-carbazolyldiacetic acid, from 1.12 g of 3,6-diacetamide, 40 ml of acetic acid, and 50 ml of diluted hydrochloric acid (1:3). For precipitation, 120 ml of hydrochloric acid (1:3) was added. 0.8 g of 3,6-carbazolyldiacetic acid separates; the acid content in it was 97.7%. The yield of 100% acid, based on the starting amide, was 68.5% of the theoretical yield; melting point 243–244°C.
Conclusions
-
The influence of the main factors on the synthesis of 3-mono- and 3,6-diacetic acids of carbazole and its 9-alkyl-substituted derivatives has been investigated.
-
Under optimal conditions, the synthesis of 14 9-alkylcarbazolylacetic acids not described in the literature was carried out.
Literature
- H. Gilman, S. Avakian. J. Am. Chem. Soc., 68, 2104, 1946.
- Organic Reactions, collection 3, IL, 1951.
- M. M. Sukhoroslova, V. P. Lopatinskii, E. E. Sirotkina, L. P. Levchenko, T. F. Turchina. Izvestiya TPI (in press).