The preparation of a series of nitrostilbene ester compounds using micro reactor technology

摘要

The synthesis of stilbene esters using Witting chemistry has been used to illustrate the generic diversity micro reactors offer in terms of chemical control and rapid method development. The micro reactor cosisted of a T design based on channel geometries 200 #mu#m wide and 100 #mu#m deep. etched into borosilicate glass and sealed with a borosilicate top plate using a thermal bonding technique. The movement of the reagent and products was achived using electroosmotic flow (EOF), assisted by the incorporation of micro porous silica frits within the micro-channels to allow accurate solution control. To optimise the operating conditions methyl 4-formylbenzoate, prcmixed with sodium methoxide, was reacted with 2-nitrobenzyl-triphenylphosphonium bromide in dry degassed MeOH using flow conditions for both reagents of 0.40 #mu#L min~(-1) for 20 min. A product yield of 70% (2:1 reaction stoichiometry with ther aldehyde in excess)was obtained representing a 10% incrase compared with the traditional batch synthesis. To demonstrate the capability of micro reactors to perform atom efficient synthesis a series of experiments ased on an injection methodology (optimised to 30 s)were performed in the micro reactor at 1:1 stoichiometry resulting in a yield of 59%. FINALLY, the capability of micro reactors to perform a series of analogue reactions was investigated. The yields for a furtehr three aldehydes indicated that the technology will be suitable for the development of automated device to support the generation of combinatorial libraties and rapid high throughput synthetic methods.