Organic Syntheses, CV 5, 716
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
3. The submitter reports that much heat is liberated during the addition; the checkers did not find the reaction to be markedly exothermic.
3. Discussion
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.
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.
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