Efficient Synthesis of Biomass‐Derived N‐Substituted 2‐Hydroxymethyl‐5‐Methyl‐Pyrroles in Two Steps from 5‐Hydroxymethylfurfural

Abstract

An efficient two‐step synthesis for the conversion of biomass‐derived 5‐hydroxymethyl‐furfural (HMF) to a variety of N‐substituted 2‐hydroxymethyl‐5‐methylpyrroles was developed. In the first step, 1‐hydroxyhexane‐2,5‐dione (HHD) was obtained by hydrogenation of HMF and thereafter used in a Paal–Knorr reaction with a range of amines in the absence of catalyst at room temperature. The reaction could potentially be used as a click reaction.

Bio-based building blocks from 5-hydroxymethylfurfural via 1-hydroxyhexane-2,5-dione as intermediate

“…Interestingly, the utilisation of phosphate buffer solution (PBS, pH = 2.5) as the reaction medium allowed processing at lower catalyst loading (0.075 mol%) without significant losses in selectivity towards HHD; 71% HHD was obtained in the presence of [Ir]-6 catalyst (Scheme 6, conditions B). In another publication by the same group, the authors aimed to perform a large-scale synthesis of HHD under the optimised conditions in PBS 46. The reaction was conducted under 60 bar of H2 resulting in the full conversion of HMF after 1 hour.…”

“…In another publication by de Vries and co-workers, the main focus was on the utilisation of the diketone moiety of HHD 46. 1,4-diketones are common substrates in the Paal–Knorr synthesis for the production of pyrroles in reaction with primary amines.…”

Cycloamination strategies for renewable N-heterocycles

“…Starting from biomass-derived 5-hydroxymethyl-furfural (HMF, 17), N-substituted 2-hydroxymethyl-5-methylpyrroles 4 (74-99% yields) can be synthesized using ethanol as solvent at room temperature after reaction for 10 min to 48 h via a twostep catalyst-free process, involving the hydrogenation of HMF (17) to 1-hydroxyhexane-2,5-dione (HHD, 18) over Ir-complex 19, followed by Paal-Knorr reaction with amines and anilines (2) bearing both electron-withdrawing and electron-donating groups (Scheme 6). 106 The presence of hydroxyl functionality has the possibility for further modification to afford bioactive compounds and to introduce desired ligating groups, with no detailed purification steps being required to obtain the desired products, except for simple evaporation of the solvent (ethanol) and vacuum drying.…”

5-Hydroxymethylfurfural (HMF) in Organic Synthesis: A Review of its Recent Applications Towards Fine Chemicals

“…The latter was reported to be used as 1,4-diketone partner in the Paal-Knorr pyrrole synthesis. [173] HD and HHD can be converted into cyclopentanic derivatives, respectively 3-methyl-2-cyclopent-2-en-1-one (MCO) [174] and 2hydroxy-3-methylcyclopent-2-enone (MCP) [175][176] via base-catalyzed intramolecular aldol reactions. Following an acid-catalyzed aldol reaction and subsequent hydrogenation sequence, HHD can be transformed into 3hydroxymethyl cyclopentanone (HCPN) [177][178] .…”