2-Halopyrroles. Synthesis and chemistry

Abstract

Following the confirmation that both 2-chloropyrrole (1.) and 2-bromopyrrole (2) were unstable species, a number of 1-alkyl-and C-alkyl-2-halopyrroles were synthesized to investigate the range of instability. The l-alkyl-2halopyrroles synthesized were 2-chloro-1 -methylpyrrole ( 14), 2-bromo-l-methylpyrrole (15), l-benzyl-2-chloropyrrole (47), and l-benzyl-2-bromopyrrole (46). The C-alkyl-2-halopyrroles synthesized were 5-chloro-2-methylpyrrole (26), 2-tertbutyl-5-chloropyrrole (36), 5-chloro-2,3,4-trimethylpyrrole (29), and 5-bromo-2,3,4-trimethylpyrrole (20). Also synthesized were the 1-methyl derivatives of 26 and 29. Electrophilic substitution of 2-chloroand 2-bromopyrroles (1 and 2) under the conditions for formylation and diazo coupling was examined. In the case of the latter reaction no crystalline compounds could be isolated, but diazo coupling of 2-chloro-1 -methylpyrrole ( 14) gave rise to exclusive a substitution. Formylation of 2-chloropyrrole (1) gave the «-substituted derivative but 2-bromopyrrole (2) gave a product arising from the displacement of bromine, 5-chloropyrrole-2-carboxaldehyde (28), in addition to 5-bromopyrrole-2-carboxaldehyde (41).Electrophilic substitution of simple pyrrole derivatives occurs regioselectively at the 2 position2 and at a rate considerably faster than in the furan and thiophene series.3 The simple electrophilic substitution reactions such as nitration,4 sulfonation,5 and formylation6 therefore give rise to the 2-substituted product almost2 to the exclusion of the 3-substituted derivative. In all cases these products are well-characterized compounds with clearly defined physical constants.7 However, 2-chloropyrrole (1) and 2-bromopyrrole (2), the expected products of halogenation, are poorly characterized compounds. In addition, there is evidence that these compounds are quite unstable.Mazzara and Borgo,8 using sulfuryl chloride in ether as the chlorinating agent, were the first to report the synthesis of 1. Attempted isolation indicated that both l8 and 2,5dichloropyrrole (3)9 were probably labile. This observation was supported by the work of Hess and Wissing,10 who heated the pyrrolyl Grignard (4) reagent11 with chlorine in ether and obtained a highly unstable yellow oil. More recently, a Russian group6 prepared 2-chloropyrrole (1) but no comment was made as to the stability of the product. Further evidence for the instability of 2-chloropyrrole (1) comes from the work of Hodge and Rickards.12 Decarboxylation of 5-chloropyrrole-2-carboxylic acid (5) under re-

A New Access to 2-(Alkylamino)- and 2-(Arylamino)pyrroles by Addition of Isocyanides to Protonated 1-Azabutadienes

“…[11,20,29] were derived from decoupling experiments, either by selec-on similar 4-and 5-unsubstituted 1H-pyrroles ( 3 J ϭ 2.4Ϫ3.1 Hz). [33] [34] The protons 3-H and 5-H in cycloadducts 4a and 4f couple only with 2.1Ϫ2.4 Hz, in agreement with the lower values of long-range coupling constants found for structurally related pyrroles ( 4 J ϭ 1.4Ϫ2.5 Hz).…”

A dataset of highly accurate homolytic NBr bond dissociation energies obtained by Means of W2 theory

“…It seems plausible that the particularly low NBr BDE of N ‐bromopyrrole (162.2 kJ mol −1 ) would render the production of this compound a significant challenge, especially given that the NCl bond of N ‐chloropyrrole is substantially stronger (203.7 kJ mol −1 ) . However, it should be noted that even 2‐ and 3‐bromopyrrole, species that contain stronger CBr bonds, are also known to possess very limited stability …”

2‐ and 3‐Monohalogenated BODIPY Dyes and Their Functionalized Analogues: Synthesis and Spectroscopy

“…Key starting compounds, 5-halogenated 2-acylpyrroles 1, are available from acylation of halogenated pyrrole and, in the initial procedure, pyrrole was halogenated using N-chlorosuccinimide (NCS). [14,15] Even though this procedure is effective, substantial variations in yields and reaction times were observed, mostly due to incomplete halogenation. Therefore, the halogenation procedure was optimized further and the use of neat sulfuryl chloride rather than NCS proved to be a facile and reproducible method.…”