305. The alkylation of tri- and tetra-alkylpyrroles

Abstract

The action of alkyl iodides on the Grignard derivatives of 2 : 3 : 4-and 2 : 3 : 5-trialkylpyrroles and 2 : 3 : 4 : 5-tetra-alkylpyrroles is shown to give tetra-and penta-alkyl-2H-pyrroles (pyrrolenines) containing 2 : 2-gemdialkyl groups. The reaction is inhibited by the presence of ester substituents on the pyrrole ring.ALTHOUGH the structure of the alkylation products of pyrroles caused a lengthy poleniic some forty years ago, the subject has scarcely received comment since. In spite of all the early work it is impossible, because of the conflicting claims, to predict the position of alkylation in pyrrole rings containing varying numbers of alkyl groups. Ciamician and Anderlini suggested 1 : 2-dihydropyridine structures for the base C,H,,N obtained by treating sodium pyrrole-2-carboxylate with methyl iodide in methanol and for the base Cl,Hl,N from l-methylpyrrole and methyl iodide in methanol in presence of potassium carbonate. Influenced by Plancher's work on the alkylation of indoles, Ciamician later suggested that the pyrrole alkylation products were more likely to be derivatives of 2H-pyrrole (pyrrolenine) and this was eventually substantiated by Plancher himself ,3 Me \ Me Mek-JEMFLJ;: R Me20::Me (111) Me (IV)although the dihydropyridine structures were still favoured by some authors* as late as 1914. The base C,H15N thus was recognised as a pentamethyl-2H-pyrrole or -3H-pyrrole although the precise location of the substituents was not established by Ciamician or Plancher, and Beilstein 5 gives the alternative structures, (I; R = Me) and ( 11), for the methylation product. However, in a related series, an unequivocal proof of structure was apparently obtained by Hess, Wissing, and Suchier who claimed that methylation of 3-ethyl-2 : 5-dimethylpyrrole gave the same product as was formed by ethylation of 2 : 3 : 5-trimethylpyrrole, thus suggesting that in a 2 : 3 : 5-trialkylpyrrole, further alkylation occurs a t the 3-(Le. 8-)position. It will be shown subsequently that the German experimental work was at fault and the conclusion incorrect.We have prepared the base C,H15N from methyl iodide and the Grignard derivatives

Electrophilic Substitution of the Pyrrole Ring

“…With more reactive alkylating agents, e.g. (144) Similarly, the corresponding reaction with benzyl chloride yields 2-benzyl-2,5-dimethyl-2//-pyrrole and 3-benzyl-2,5-dimethylpyrrole. (4()3) Alkylation of (H39a) with propargyl bromide and with bromoferrocene also gives C-substituted products.…”

“…* 385 When the methylation of (H39a) is allowed to proceed to only 10% completion, it is found that the initially formed 2-and 3-methylpyrroles are methylated at the same rate, but that the 2,3-dimethylpyrrole is methylated at the 5-position more rapidly than the methylation of 2,5-dimethylpyrrole at the 3-position. (144,145) Contrary to earlier reports (408) that (H39a) reacts with 4-chlorobutyronitrile to give 2-(2-pyrryl)-l-pyrroline (H43a), it has been established that normal alkylation of the pyrrole ring occurs to give 2-and 3-(3-eyanopropyl)pyrrole in a ratio of 4-4 : l. (399) However, it has also been claimed that equimolar amounts of the nitrile and 2,3,4-trimethylpyrrylmagnesium halides give (H43b), whereas when there is an excess of the nitrile the 2//-pyrrole (H44) is formed. The inductive effect of alkyl groups should make the alkylpyrroles less acidic but the anions should be more nucleophilic than pyrrole.…”

Recent Advances in the Chemistry of Pyrrole.

“…The action of alkyl iodides on the Grignard derivatives of 2,3,4-and 2,3,5-trialkylpyrroles and 2,3,4,5tetraalkylpyrroles was shown to afford tetraand pentaalky 1-2,4-pyrroles (pyrrolenines) with 2,2-gemdialkyl groups. This reaction was inhibited by the presence of ester substituents on the pyrrole ring (50).…”