Patent Watch

March 12, 2012

Make high-value chemicals safely with a microreactor. The use of microreactors for rapidly screening reactions and catalysts is now common. Microreactors are also being tested to commercially produce small and medium quantities of high-value products. The major advantages of this method are that it minimizes the inventory of hazardous reagents, maximizes heat transfer, and therefore reduces potential safety problems.

R. W. E. G. Reinters and co-inventors describe the use of continuous-flow microreactors for synthetic sequences that produce hazardous intermediates such as azides or peroxo compounds. The figure shows the preparation of amine 3 from azide 2, which is obtained by treating methanesulfonyl (Ms) ester 1 with NaN3. The reaction is carried out by pumping a 3.45 wt% aq solution of NaN3 into a T-piece, where it mixes with a 6.33 wt% solution of 1 in N-methylpyrrolidone (NMP). The mixture then passes through a 21.6-m–long, 0.35-mm–diam tubular microreactor with a residence time of 2.5 min.

A sample collected between 0.5 and 1 h contained 2.2 wt% 2 and 0.22 mol% unreacted 1, corresponding to 95% conversion of 1 with 76% selectivity to 2. This mixture is diluted with NMP to 0.93 wt% 2 and hydrogenated in a 0.5-m–long, 0.53-mm–diam tubular microreactor coated with a layer of Pd/Al2O3 catalyst. The effluent from the reactor contains 0.48 wt% 2 and 0.42 wt% 3, corresponding to 48% conversion of 2 and 100% selectivity to 3.

The inventors also describe the ozonolysis of naphthalene to give o-phthalaldehyde. The reaction is carried out in a 75-mm–long falling-film microreactor that has a holdup volume of 13.6 mL. With a flow rate of 2g/min of 2 wt% naphthalene in the solvent (5% MeOH in BuOAc), the naphthalene conversion is 52.1%, and the selectivity to o-phthalaldehyde is 95.8% (49.9% yield).

A third example is the hydrogenation of cumene hydroperoxide (4) to give alcohol 5. A 1.035 wt% solution of 4 in EtOH is passed through the hydrogenation reactor used in the first example at a rate of 0.25 mL/min. Slugs of liquid flow through the reactor in a Taylor flow regime. Analysis of the effluent showed 73% conversion of 4 with >99% selectivity to 5. Hydroperoxide 4 is an intermediate in the large-scale production of phenol and acetone; it thus is readily available for producing 5.

The inventors discuss applying this method to reactions of organic compounds such as alkenes or dienes with peroxides, hydroperoxides, or singlet oxygen to give intermediates that are hydrogenated to give aldehydes, alcohols, or ketones. (DSM IP Assets B.V. [Heerlen, The Netherlands]. US Patent 8,106,242, Jan. 31, 2012; Keith Turner)

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