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

Abstract

The synthesis of stilbene esters using Wittig chemistry has been used to illustrate the generic diversity micro reactors offer in terms of chemical control and rapid method development. The micro reactor consisted of a 'T' design based on channel geometries 200 microns wide and 100 microns 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 achieved 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, premixed with sodium methoxide, was reacted with 2-nitrobenzyl-triphenylphosphonium bromide in dry degassed MeOH using flow conditions for both reagents of 0.40 microL min-1 for 20 min. A product yield of 70% (2:1 reaction stoichiometry with the aldehyde in excess) was obtained representing a 10% increase compared with the traditional batch synthesis. To demonstrate the capability of micro reactors to perform atom efficient synthesis a series of experiments based 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 further three aldehydes indicated that the technology will be suitable for the development of automated device to support the generation of combinatorial libraries and rapid high throughput synthetic methods.

Micro reactors: principles and applications in organic synthesis

“…55,56 The authors used the micro reactor to prepare the cis-and trans-nitrostilbene esters 8 and 9 using the Wittig reaction (Scheme 3). A number of features such as stoichiometry and stereochemistry were investigated.…”

Multi-layer microfluidic glass chips for microanalytical applications

“…The Wittig reaction is a two-step reaction in which a phosphonium salt reacts with sodium methoxide to form an ylide. As reported u u elsewhere [13], if (2-nitrobenzyl)triphenylphosphonium bromide is chosen as the starting compound, the ylide is a colored compound that can be used to follow the reaction. The purple compound disappears when it has reacted with the third compound, an aldehyde, to yield a stilbene ester and a phosphine oxide.…”

“…It was possible in 3 h to perform a chemical reaction not previously tested in the system, including the preparation of the solutions and assembly of the set-up. The test chemical reaction chosen for this experiment was the Wittig reaction, which has previously been studied in an electrokinetically pumped continuous flow microsystem [13]. The Wittig reaction is a two-step reaction in which a phosphonium salt reacts with sodium methoxide to form an ylide.…”

“…It was possible to set up the resulting system as a continuous flow system for a chemical synthesis application over the course of a day, demonstrating its flexibility of use. The synthesis chosen as an example is the Wittig reaction for preparation of nitrostilbene ester compounds [13] by reaction of phosphonium salts with aldehydes.…”

Droplet microfluidics: A tool for biology, chemistry and nanotechnology

“…Most synthesis reactions that have been performed within droplets are single-step synthesis reactions [61][62][63][64][65]. One major issue in complex synthesis is that multiple reaction steps are involved.…”