A batch synthesis to the iodinating agent 1,3-diiodo-5,5-dimethyl-imidazolidine-2,4-dione (DIH) was devised and developed. This batch process was then up-scaled (10×) and optimized by means of statistical experimental design and multivariate regression. The optimized batch procedure was then transferred and adapted for continuous flow synthesis using a multi-jet oscillating disk (MJOD) continuous flow reactor platform to provide a flow process that allowed a throughput of 47 g h−1 with a residence time of 9 min. A semi-continuous work-up step based on vacuum filtration was established and successfully telescoped to be an integrated part of the flow process. An 8 h test run using the optimized flow synthesis in combination with the semi-continuous filtration step afforded 375 g (≈90% isolated yield) of the pure title compound that was collected from 14 filtration batches of 25–27 g eac
Flow processes for mono- and di-iodination of the imidazole backbone were devised, developed, and implemented on the multi-jet oscillating disk (MJOD) flow reactor platform.
The amide bond formation is of paramount importance in organic synthesis, both within academic research and industrial development and manufacturing of pharmaceutical chemicals and other biologically active compounds. Despite this fact, as well as the ever‐increasing treatment costs of side streams and other environmental concerns regarding handling and transportation of hazardous reagents, contemporary synthesis has elicited few new reactions and methods for the preparation of amides. Herein, we reveal a high yielding and expedite two‐step telescoped synthetic process that comprises a domino oxidative amidation and transamidation for the creation of amides. The process utilizes alcohols and amines as reaction pairs with TEMPO and Fe ions as catalytic system and 1,3‐dichloro‐5,5‐dimethyl hydantoin as a terminal oxidant. The oxidative amidation and transamidation process is conducted under benign reaction conditions and short reaction time (≈ 30 min.) in a two‐step telescoped fashion by means of a multi‐jet oscillating disk (MJOD) continuous‐flow reactor platform. The disclosed process integrates alcohol oxidation and amide formation to afford target amide in yields up to 90 %. The method operates with both primary and secondary amines together, but was hampered when bulky amines and/or alcohols were used as reagent/substrate.
A high‐yielding and high‐rate reduction method that operates with alkenes, alkynes, azides, nitriles, and nitroarenes was developed and optimized. The method makes use of sodium borohydride reduction of CoSO4 under release of hydrogen along with the formation of Co2B as a nanoparticle material. The produced Co2B activates the various functional groups for hydride reduction. The protocol was proven to operate with an assortment of functional groups to provide good to excellent yields. Furthermore, the reduction method was successfully adapted, implemented, and developed for a continuous flow approach using the multi‐jet oscillating disk (MJOD) flow reactor platform at atmospheric pressure.
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