Polymer-Assisted Solution-Phase Synthesis Under Combined Ultrasound and Microwave Irradiation: Preparation of α,β-Unsaturated Esters and Carboxylic Acids, Key Intermediates of Novel Sigma Ligands

Abstract

The optimal conditions to prepare α,β-unsaturated methyl esters via Wittig reaction combining polymer-assisted solution-phase synthesis (PASPS) methodology and simultaneous ultrasound and microwave irradiation were established. The effects of temperature, solvent, and irradiation time were discussed. Results clearly indicated the superiority of combined ultrasound and microwave-assisted procedure over microwave-assisted methodology. Moreover, an efficient PASPS procedure to prepare α,β-unsaturated carboxylic acids via tandem Wittig olefination and hydrolysis reaction was developed under combined ultrasound and microwave irradiation. Generally, a good conversion of aldehydes to acids was observed. The optimized protocols allowed us to quickly prepare a small collection of either α,β-unsaturated esters or carboxylic acids, key intermediates for the drug-discovery process of new sigma ligands.

Keywords:

• Microwave
• PASPS
• sigma ligand intermediates
• ultrasound
• α,β-unsaturated carboxylic acids
• Wittig reaction

Notes

^a Determined on crude products by 400-MHz ¹H NMR.

^a Determined on crude products by 400-MHz ¹H NMR.

^b 110°C.

^c 150°C.

^d DMF.

^a Determined on crude products by 400-MHz ¹H NMR.

^b TMNOH.

^c Hydrolysis step performed without preliminary TPPP filtration.