ETHYL PYRROLE—2-CARBOXYLATE

Pyrrolidinocyclohexene, preparation of, 54, 40 Pyrrol-2-yl-trichloromethyl ketone, with ethanol to give ethyl pyrrole-2-carboxylate, 51, 100... 

B. Ethyl pyrrole-2-carboxylate. In a 1-1. three-necked round-bottomed flask equipped with a sealed mechanical stirrer and powder funnel are place 1.0 g. of sodium and 300 ml. of anhydrous ethanol. When the sodium is dissolved, 75 g. (0.35 mole) of pyrrol-2-yl trichloromethyl ketone from Part A is added portionwise over a 10-minute period (Note 4). After the addition is complete, the solution is stirred 30 minutes, then concentrated to dryness using a rotary evaporator. The oily residue is partitioned between 200 ml. of ether and 25 ml. of 3 N hydrochloric acid. The ether layer is separated, and the aqueous layer is washed once with 100 ml. of ether. The ether solutions are combined, washed once with 25 ml. of saturated sodium bicarbonate solution, dried with magnesium sulfate, and concentrated by distillation. The residue is fractionated at reduced pressure to give 44.0-44.5 g. (91-92%) of ethyl pyrrole-2 carboxylate as a pale yellow oil, b.p. 125-128° (25 mm.) (Note 5). The yield based on pyrrole is 70-74%. Upon standing at room temperature the product crystallizes, m.p. 40-42°. 

The higher acidity of pyrroles and indoles bearing electron-withdrawing substituents at the a- or /3-positions permits their alkylation under mildly basic conditions, but although the thallium salt of 2-formylpyrrole is Af-alkylated, the corresponding alkylation of the thallium salts of ethyl pyrrole-2-carboxylate yields a complex mixture of products resulting from iV-alkylation and transesterification (B-77MI30502). N-Alkylation of pyrrolyl and indolyl esters is most conveniently effected under phase-transfer conditions. 

The apparent abnormal formation of ethyl pyrrole-2-carboxylate from the reaction of ethyl chloroformate and alkali metal salts of pyrrole could be accounted for by a thermal rearrangement during the isolation of the products. However, whilst this may be partly correct, an analysis of the reaction products prior to their isolation has established (77CJC4103) the formation of the thermodynamically more stable 2-carboxylic ester from the 1-isomer by a reaction sequence shown in Scheme 36. 

ETHYL PYRROLE-2-CARBOXYLATE (Pyrrolc-2-carboxylic acid, ethyl ester)... 

Murakami, Y, Tani, M., Ariyasu, T., Nishiyama, C., Watanabe, T., and Yokoyama, Y, The Friedel-Crafts acylation of ethyl pyrrole-2-carboxylate. Scope, limitations, and apphcation to synthesis of 7-substituted indoles, Hetemcycles, 27, 1855, 1988. 

Tani, M., Ariyasu, T., Ohtsuka, M., Koga, T., Ogawa, Y., Yokoyama, Y., and Murakami, Y, Synthetic studies on indoles and related compounds. Part 39. New strategy for indole synthesis from ethyl pyrrole-2-carboxylate, Chem. Pharm. Bull., 44, 55, 1996. 

The reader is referred to the synthesis of trimethylacetic acid,74 2-naphthoic acid,75 3,3-dimethylacrylic acid,76 3,3-dimethylglutaric acid,77 3(3-acetoxy-5-androstene-17(3-carboxylic acid,78 ethyl pyrrole-2-carboxylate,79 and bicyclo[ 1,1.1 ]pentane-1,3-dicarboxylic acid80 published in Organic Syntheses. 

Esters of other fatty acids have been used to prepare 2-acylpyrroles. Ethyl carbonate reacts with the pyrrole Grignard reagent mainly at the nitrogen atom, but a little ethyl pyrrole-2-carboxylate also results i c, 222 ... 

Garbonyl and N-H stretching frequencies in pyrrole-carboxylic acids and their esters have been examined. The N-H stretching bands of ethyl pyrrole-2-carboxylates show clear evidence of rotational isomerism in these esters " . 

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