N-formyl-stabilizing quasi-catalytic species afford rapid and selective solvent-free amination of biomass-derived feedstocks

Hu Li,Haixin Guo,Yuya Hiraga,Yaqiong Su,Richard Lee Smith,Masaru Watanabe,Emiel J M Hensen,Zhen Fang

doi:10.1038/s41467-019-08577-4

Abstract

Nitrogen-containing compounds, especially primary amines, are vital building blocks in nature and industry. Herein, a protocol is developed that shows in situ formed N-formyl quasi-catalytic species afford highly selective synthesis of formamides or amines with controllable levels from a variety of aldehyde- and ketone-derived platform chemical substrates under solvent-free conditions. Up to 99% yields of mono-substituted formamides are obtained in 3 min. The C-N bond formation and N-formyl species are prevalent in the cascade reaction sequence. Kinetic and isotope labeling experiments explicitly demonstrate that the C-N bond is activated for subsequent hydrogenation, in which formic acid acts as acid catalyst, hydrogen donor and as N-formyl species source that stabilize amine intermediates elucidated with density functional theory. The protocol provides access to imides from aldehydes, ketones, carboxylic acids, and mixed-substrates, requires no special catalysts, solvents or techniques and provides new avenues for amination chemistry.

Highlights

Nitrogen-containing compounds, especially primary amines, are vital building blocks in nature and industry
Ketones and carboxylic acids in diverse structures are available from lignocellulosic biomass via thermal or catalytic processes, while those carbonyl compounds, especially furanic aldehydes are seldom studied for amination due to the easy furanring opening reaction and the active –CHO randomly vulnerable to amino species[23]
The mass balance for all tested reaction systems was no less than 94% and the co-products were mainly FDFAM and tertiary amide 2 besides product 1 (Table 1, entries 1–4; Supplementary Fig. 3), and tertiary amine 4 with some unknown products being generated at 200 °C after long reaction times (Supplementary Fig. 4)

Summary

Introduction

Nitrogen-containing compounds, especially primary amines, are vital building blocks in nature and industry. A protocol is developed that shows in situ formed N-formyl quasicatalytic species afford highly selective synthesis of formamides or amines with controllable levels from a variety of aldehyde- and ketone-derived platform chemical substrates under solvent-free conditions. A number of bio-based amines (e.g., aryl-amines, furyl-amines, alkyl-amines, and alkanolamines) have been reported to be efficiently synthesized from small platform molecules via a range of reaction routes like reductive amination of carbonyl compounds[12,13,14,15,16], reductive aminolysis of simple sugars[17,18,19,20], and hydrogenation-decarbonylation of amino acids[21] Among these approaches, catalytic reductive amination of carboxides using molecular hydrogen is extensively performed over either transition (Raney Ni) or noble metals (e.g., Ru, Pd) 12,22. We report an efficient solvent-free protocol for selectively controlling different levels of amination of pentose-derivable furfural (FUR) using formamide (AM) and formic acid (FA) or ammonium formate (AMF) reactants under rapid heating conditions offered by microwave irradiation (Fig. 1). We elucidate reaction pathways of in situ generated N-formyl species with kinetic and control experiments, deuterium isotope labeling reactions, and density functional theory (DFT) calculations

Methods

Results

Conclusion