Utility of ¹³C NMR spectroscopy in monitoring the course of a complex reaction sequence: Reaction of pyrrole with formaldehyde

Abstract

The complex course of the reaction of pyrrole with formaldehyde has been completely elucidated by quantitative I3C NMR spectroscopy using the inverse-gated decoupling technique. The final product is 23-bis(hydroxymethy1)pyrrole (with a free l-position), but three main intermediates containing 1-hydroxymethyl groups were identified, and the rise and subsequent fall of their populations followed. The intermediacy of additional compounds (formals) also renders the reaction more complex. The molar fractions of four hydroxymethylpyrroles present in the reaction mixtures were calculated from the I3C NMR data and plotted against time. At 45 and 65°C pyrrole reacted completely with formaldehyde in 1 h and in less than 30 min, respectively. This work illustrates the utility of the 13C NMR investigation of an industrially important reaction.KEY WORDS Reaction of pyrrole with formaldehyde Hydroxymethylpyrroles 3C NMR

Porphinogen Formation from the Co-Oligomerization of Formaldehyde and Pyrrole: Free Energy Pathways

“…Two adjacent CH 2 OH moieties can potentially form a ring via dehydration as illustrated by 5 to 7 in Figure . This reaction however is endergonic 6.6 kcal/mol with a calculated barrier of 21.3 kcal/mol, so we think species such as 7 are unlikely to remain stable in solution, and no mention of them is made in the NMR study …”

“…Katritzky and Law conducted a low-temperature 13 C NMR study for the reaction of pyrrole with formaldehyde and found that 1 is indeed the first species formed . Small amounts of 9 are observed after 10 days.…”

“…This reaction however is endergonic 6.6 kcal/mol with a calculated barrier of 21.3 kcal/mol, so we think species such as 7 are unlikely to remain stable in solution, and no mention of them is made in the NMR study. 37 Dehydration to Fulvenes and Subsequent Addition of Pyrroles. While the addition of CH 2 O to pyrrole is straightforward, adding subsequent pyrroles is more difficult.…”