# Periodic acid-promoted methylenation of imidazoheteroarenes: a green approach using ethylene glycol as a C1 source

## TL;DR

A green chemistry method uses ethylene glycol to create methylenated imidazoheteroarenes with high efficiency and low waste.

## Contribution

A metal-free, scalable, and environmentally sustainable methylenation method using ethylene glycol as a C1 source.

## Key findings

- The method achieves up to 97% yields in regioselective bis-heterocycle formation.
- The process is scalable with 70% yield at 5.5 mmol scale.
- The reaction uses water as a solvent and follows green chemistry principles.

## Abstract

Herein, we describe an environmentally sustainable methodology for the methylenation of C3(sp2) imidazoheteroarenes, employing formaldehyde (C1) generated in situ via oxidative cleavage of ethylene glycol—a renewable feedstock. The protocol utilizes water as a non-toxic solvent and stoichiometric reagents, aligning with green chemistry principles by ensuring high atomic economy and minimal waste. Optimized conditions enable regioselective bis-heterocycle formation with yields up to 97%. The reaction proceeds through a Malaprade oxidation-mediated ionic pathway mediated by 0.5 molar equiv. of periodic acid, and demonstrates broad substrate scope, including imidazo[1,2-a]pyridines and imidazo[2,1-b]thiazoles. Scalability was validated (70% yield at 5.5 mmol scale), highlighting its potential for industrial applications. This method offers a robust, metal-free alternative for C–H functionalization.

Periodic acid promotes metal-free methylenation of imidazoheteroarenes using ethylene glycol as a green C1 source. The reaction proceeds in water, delivers yields up to 97%, & is scalable, offering a sustainable approach to bis-heterocycle synthesis.