Photochemical Synthesis of Pyrazolines from Tetrazoles in Flow

Abstract

Pyrazolines and their pyrazole congeners are important heterocyclic building blocks with numerous applications in the fine chemical industries. However, traditional routes towards these entities are based on multistep syntheses generating substantial amounts of chemical waste. Here we report an alternative approach using UV-light to convert tetrazoles to pyrazolines via a reagent-free photo-click strategy. This route generates nitrile imine dipoles in situ that are trapped with different dipolarophiles rendering a selection of these heterocyclic targets in high chemical yields. A continuous flow method is ultimately realized that generates multi-gram quantities of product in a safe and readily scalable manner thus demonstrating the value of this photochemical approach for future exploitations in industry.

Antimicrobial Evaluation of New Pyrazoles, Indazoles and Pyrazolines Prepared in Continuous Flow Mode

“…The heterocyclic compounds studied in this report were prepared in accordance with recently published synthetic procedures [ 41 , 42 , 43 ]. The following is the characterisation of most active compounds:…”

“…The tricyclic indazole scaffold 8 was accessed by a scalable photochemical flow route exploiting the in-situ formation of benzyne and its trapping with a proline derived sydnone [ 42 ]. Lastly, an interesting photochemical cycloaddition-based route converts aryl tetrazoles via nitrile imine dipoles into pyrazolines [ 43 ] (compounds 9 – 12 ). The latter approach also allowed for the accessing of pyrazoles 13 and 14 that resulted from subsequent aerobic oxidation of the selected pyrazolines.…”