Related Experiment Video
Updated: Aug 7, 2026

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis
Published on: February 16, 2020
Microwave-assisted synthesis of 3,6-di(pyridin-2-yl)pyridazines: unexpected ketone and aldehyde cycloadditions
Richard Hoogenboom1, Brian C Moore, Ulrich S Schubert
1Laboratory of Macromolecular Chemistry and Nanoscience, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
Abstract:
3,6-Di(pyridin-2-yl)pyridazines are an interesting class of compounds because of their metal-coordinating ability resulting in the self-assembly into [2x2] gridlike metal complexes with copper(I) or silver(I) ions. These and other substituted pyridazines can be prepared by the inverse-electron-demand Diels-Alder reactions between acetylenes and 1,2,4,5-tetrazines. In this contribution, the effect of (superheated) microwave conditions on these generally slow cycloadditions is described. The cycloaddition of acetylenes to 3,6-di(pyridin-2-yl)-1,2,4,5-tetrazine could be accelerated from several days reflux in toluene or N,N-dimethylformamide to several hours in dichloromethane at 150 degrees C. In addition, the unexpected cycloaddition of the enol tautomers of various ketones and aldehydes to 3,6-di(pyridin-2-yl)-1,2,4,5-tetrazine is described in detail providing an alternative route for the synthesis of (substituted) pyridazines.
Related Concept Videos
Cycloaddition Reactions: Overview
Cycloaddition Reactions: MO Requirements for Thermal Activation
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Cycloaddition Reactions: MO Requirements for Photochemical Activation
Aldehydes and Ketones to Alkenes: Wittig Reaction Mechanism
The reaction begins with the nucleophilic addition between a phosphorus ylide and the carbonyl compound. Due to its carbanionic character, phosphorus ylide acts as a strong nucleophile and attacks the electrophilic carbonyl group. This generates a charge-separated dipolar intermediate called betaine. The negatively charged oxygen atom and...

