Continuous flow synthesis of the iodination agent 1,3-diiodo-5,5-dimethyl-imidazolidine-2,4-dione telescoped with semi-continuous product isolation

Abstract

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

An environmentally benign and high-rate Appel type reaction

“…6 The 1,3-dihalo-5,5-dimethylhydantoins are commercially available at low cost, 7 except for 1,3-diiodo-5,5dimehyl-hydantoin (DIH), but DIH can be synthesised at low cost by reacting I-Cl with 5,5-dimethylhydantoin. 8 DCH, DBH, and DIH reagents held two halogens, which can both be utilised. This is of course an advantage from an environmental point of view as there are no left-over halogens in the consumed reagent.…”

A Co2B Mediated NaBH4 Reduction Protocol Applicable to a Selection of Functional Groups in Organic Synthesis

“…This multi‐headed piston is assembled of multi‐jet disks that during operation is moved in oscillating movements inside the reactor tube. The MJOD flow reactor rig has successfully been utilized with processes where solid particles were formed during the course of the reaction , …”

“…Our present challenge entailed the reducing 4′‐chloro‐2‐nitro‐1,1′‐biphenyl 1 to 4′‐chloro‐[1,1′‐biphenyl]‐2‐amine 2 (Scheme ) under continuous flow conditions, a step we intended to be included as an integral part of a complete continuous flow process leading to the agrochemical Boscalid.® Operational and hassle‐free feeding of slurries implemented on currently existing continuous flow reactor platforms is still an unsolved problem. However, we have proven that our multi‐jet oscillating disk (MJOD) continuous flow reactor system can operate with slurries that were formed inside the MJOD reactor tube . This is in great contrast to most of the other existing flow chemistry approaches based on micro channels manufactured as reactor coils or reactor chips, which will be clogged by particulate material present in the reaction mixtures.…”

Imidazole Backbone Functionalization with Olefin Cross‐Metathesis

“…Given this breadth of possibilities, we have avoided the traditional formation of backbone substituted imidazoles obtained through multi‐component reactions [8] and instead focused on the functionalization of preformed imidazoles as cheap and promising starting materials, with the hope of contributing to the research of novel late‐stage backbone functionalization of imidazole‐containing molecules [9] . We have achieved this initially through the di‐ and mono‐halogenation of the imidazole backbone, [10] which has allowed Suzuki, [11] Stille, [12] and Sonogashira [13] cross‐coupling reactions. Partially dissatisfied with the production of halogen waste, we have more recently explored a greener approach that involved the C−H functionalization of 4‐vinylimidazoles with aromatic boronic acids [14] …”