Org. Synth. 1967, 47, 81
DOI: 10.15227/orgsyn.047.0081
1-(2-METHOXYCARBONYLPHENYL)PYRROLE
[Pyrrole, 1-(2-methoxycarbonylphenyl)-]
Submitted by A. D. Josey
1
Checked by William G. Dauben and Juraj Hostynek.
1. Procedure
A solution of 90 g. (0.59 mole) of methyl anthranilate (Note 1) in 265 ml. of glacial acetic acid is placed in a 1-l. round-bottomed flask equipped with a reflux condenser and a magnetic stirrer. The stirrer is started, and 78 g. (0.59 mole) of 2,5-dimethoxytetrahydrofuran (Note 2) is added during 10–15 minutes (Note 3). The solution is heated under reflux for 1 hour, during which time the solution turns deep red to black in color. The heating is discontinued, the condenser is replaced with a Vigreux column, and the acetic acid is removed by distillation at aspirator pressure. The dark residue is distilled under reduced pressure through a 25-cm. column packed with glass helices, and 84–96 g. (70–80%) of slightly yellow 1-(2-methoxycarbonylphenyl)pyrrole is collected, b.p. 90–95° (2 mm.), n25D 1.5729.
2. Notes
1.
Methyl anthranilate from Eastman Kodak Company was used without further purification.
2.
2,5-Dimethoxytetrahydrofuran from Eastman Kodak Company was used without further purification. This material also can be prepared by catalytic hydrogenation
2 of
2,5-dihydro-2,5-dimethoxyfuran.
33.
The submitter reports that much heat is liberated during the addition; the checkers did not find the reaction to be markedly exothermic.
3. Discussion
1-(2-Methoxycarbonylphenyl)pyrrole has not been prepared previously. An attempt to prepare the material via the
mucic acid pyrrole synthesis using
methyl anthranilate was unsuccessful.
4
4. Merits of the Preparation
The condensation of primary amines with 2,5-dialkoxytetrahydrofurans to give in one step N-substituted pyrroles is applicable to a variety of substituted aliphatic and aromatic amines.
5 The method, largely developed by Clauson-Kaas and associates, has the advantages of simplicity, mild conditions, and generally excellent yields from readily available starting materials.
The submitter has used the method to prepare the corresponding 1-pyrrolyl derivatives
6 from the following amines in the indicated yields:
ethyl β-aminobutyrate 88%,
methyl β-aminoglutarate 87%,
β-aminopropionitrile 58%, and
2,5-diamino-3,4-dicyanothiophene 22%.
On saponification 1-(2-methoxycarbonylphenyl)pyrrole yields 1-(2-carboxyphenyl)pyrrole, m.p. 106–107°, which on reaction with polyphosphoric acid at 70° is cyclized to 9-keto-9H-pyrrole-(1,2-a)indole in 28–32% yield. Through the choice of the appropriate amine and acetal components, the substituted 1-(2-methoxycarbonylphenyl)pyrroles become readily available intermediates in the preparation of a variety of derivatives of the pyrrolo(1,2-a)indole ring system.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
polyphosphoric
9-keto-9H-pyrrole-(1,2-a)indole
acetic acid (64-19-7)
Pyrrole (109-97-7)
mucic acid
β-Aminopropionitrile (151-18-8)
2,5-Diamino-3,4-dicyanothiophene (17989-89-8)
2,5-Dihydro-2,5-dimethoxyfuran (332-77-4)
2,5-dimethoxytetrahydrofuran (696-59-3)
1-(2-Methoxycarbonylphenyl)pyrrole,
Pyrrole, 1-(2-methoxycarbonylphenyl)- (10333-67-2)
methyl anthranilate (134-20-3)
ethyl β-aminobutyrate (5303-65-1)
methyl β-aminoglutarate
1-(2-carboxyphenyl)pyrrole (10333-68-3)
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