Laboratory-Scale Membrane Reactor for the Generation of Anhydrous Diazomethane

• Published in: Journal of organic chemistry Vol. 81; no. 14; pp. 5814 - 5823
• Main Authors: Dallinger, Doris, Pinho, Vagner D, Gutmann, Bernhard, Kappe, C. Oliver
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 15.07.2016
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.6b01190

A configurationally simple and robust semibatch apparatus for the in situ on-demand generation of anhydrous solutions of diazomethane (CH2N2) avoiding distillation methods is presented. Diazomethane is produced by base-mediated decomposition of commercially available Diazald within a semipermeable Teflon AF-2400 tubing and subsequently selectively separated from the tubing into a solvent- and substrate-filled flask (tube-in-flask reactor). Reactions with CH2N2 can therefore be performed directly in the flask without dangerous and labor-intensive purification operations or exposure of the operator to CH2N2. The reactor has been employed for the methylation of carboxylic acids, the synthesis of α-chloro ketones and pyrazoles, and palladium-catalyzed cyclopropanation reactions on laboratory scale. The implementation of in-line FTIR technology allowed monitoring of the CH2N2 generation and its consumption. In addition, larger scales (1.8 g diazomethane per hour) could be obtained via parallelization (numbering up) by simply wrapping several membrane tubings into the flask.