# Multicomponent Green Synthesis Involving Aryl Aldehydes and Trapped Enols: Dimerization over Cyclization

## TL;DR

This paper corrects past mischaracterizations in a chemical synthesis method and presents a green, efficient way to make dimer products with potential use in Alzheimer’s therapy.

## Contribution

A green, one-pot synthesis method for bis-coumarins and bis-pyrones with high yields and accurate product characterization.

## Key findings

- Many previously reported cyclization products were actually dimers, not the intended cyclic compounds.
- A green synthesis method in water achieved high yields (24–96%) without hazardous solvents or chromatography.
- The first meta-substituted bis-pyrone (4i) was synthesized and characterized.

## Abstract

This report serves two main purposes: (1) to correct
the literature
in the area of multicomponent synthesis involving aryl aldehydes and
trapped enols 4-hydroxycoumarin 1 or 4-hydroxy-6-methyl-2-pyrone 2 and (2) to fully characterize the dimerization products
bis-coumarins 3 and bis-pyrones 4. There
have been many reports of cyclizations occurring with these species
and various catalysts; however, many products have been mis-characterized
and are, in fact, dimers. We successfully synthesized these dimers
using a green, one-pot reaction in water that avoids hazardous organic
solvents, uses a catalytic amount of acid, does not require chromatography
for purification, and has strong green chemistry metrics. Our simplified
procedure resulted in high yields of dimers ranging from 24 to 96%
including the first report of a meta-substituted bis-pyrone 4i. Herein, we report a green method for their synthesis,
along with their photophysical properties, full characterization,
and potential as AChE inhibitors for anti-Alzheimer’s therapy.