Abstract

Bringing Diazomethane to the Bench: A Lab-Scale Reactor for the Continuous Generation of Anhydrous Diazomethane

Doris Dallinger, Postdoctoral Research Associate, University of Graz

The most time- and atom-efficient routes frequently demand the use of highly reactive, often low-molecular weight compounds. One such compound is diazomethane (CH2N2) which is an exceptionally powerful and versatile reagent to introduce a methyl or a methylene group into organic compounds.1 However, as many strong alkylation agents, CH2N2 is a potent carcinogen and extremely poisonous. In addition, the extreme sensitivity to explosive decomposition makes the handling of CH2N2 challenging. New techniques for the safe and convenient preparation and handling of CH2N2 are continuously developed. We demonstrated the in-situ generation of anhydrous CH2N2 in continuous flow systems.2,3 Key to this strategy was the use of a semi-permeable membrane which selectively allows CH2N2 to cross and to be finally directly consumed by the substrate. Two different strategies can be accomplished by using such a membrane: the fully continuous tube-in-tube2 and the simplified, more flexible semi-batch tube-in-flask3 reactor technology. Both approaches allow the in-situ on-demand generation of anhydrous CH2N2 without dangerous and laborious purification operations or any exposure of the operator. With the tube-in-flask concept, larger scales (1.8 g CH2N2 per h) could be obtained via parallelization (numbering up) by simply wrapping several membrane tubings into the flask. Both reactor concepts will be presented, including their application to diverse chemistries.