Our Colleagues at the University of Delaware in the Department of Chemistry and Biochemistry’s Watson group employed the Supercritical Fluid Technologies Inc. MicroReactor to explore examine the copper catalyzed alkylation of nitroalkanes, a “post-Heck” cross-coupling reaction recently developed in the Watson lab using sc-CO2.
Nitroalkanes are highly useful intermediates in organic synthesis and in the synthesis of biologically active organic molecules. Nitroalkanes can participate in a wide range of carbon-carbon bond-forming reactions (including Henry reactions, conjugate additions, allylations and arylations). These molecules can also serve as starting materials for the installation of numerous functional groups (including alkylamines and ketones) and can serve as radical precursors. However, the simple alkylation of nitroalkanes to make more complex nitroalkanes has been a long-standing challenge int eh chemical field.
The is a powerful process for preparing complex nitroalkanes that are precursors for a range of biologically active compounds. The initial reactions were developed using non-polar traditional solvents, such as hexanes or toluene. The non-polar nature of these solvents makes them ideal candidates for replacement with sc-CO2.
Watson’s studies in this area have made significant progress towards developing reaction conditions to allow the copper-catalyzed process to run in sc-CO2. As shown in Scheme 1, they have found that the alkylation reaction can indeed be run in sc-CO2. Using two different classes of alkyl bromide electrophiles, modest yields of the desired alkylated nitroalkanes are observed. The current yields are somewhat lower than in traditional solvents; a future studies will be directed at continuing to re-optimize the reaction in the supercritical media.
The Micro Reactor developed by Supercritical Fluid Technologies Inc. is perfect for these types of demanding research and process development applications. Designed to allow for simple and inexpensive operation, the robust MicroReactor affords the researcher the opportunity to explore the use replacement solvent technologies for organic synthesis using sc-CO2 on a micro-scale.
Supercritical Fluid Technologies has extensive experience with larger, specialized, high-pressure reaction systems. Contact us for more information about the versatile reactors.