Knorr Synthesis Investigated in Micro Reactors

Organic synthesis 72 [OS 72] Pyrazole ring closure from 1,3-dicarbonyl compounds and hydrazines 

The reaction was also chosen for analytical reasons as the pyrazole ring is a good UV chromophore, facilitating analysis [20]. 

The 3x7 library in Table 4.11, consisting of diverse 1,3-dicarbonyl compounds 

The pyrazole library was created sequentially using 10 mM solutions of the 1,3-dicarbonyl compound and 0.8 M solutions of the hydrazines, each introduced as a 2.5 pi slug [20]. This requires control of feeding of both reactant solutions so that the slugs enter the chip at the same time and mix thereafter. The residence time was 210 s. Thereafter, the reaction slugs were diluted on-chip by a 1 1 methanol-water stream at 8 pi min and detected. Analysis of the nature of the products and the degree of conversion was done using standards of reactant and product materials. 

The chip micro reactor ([R 6]) was only one part of a complex serial-screening apparatus [20]. This automated system consists of an autosampler (CTC-HTS Pal system) which introduces the reactant solutions in the chip via capillaries. A pumping system (p-HPLC-CEC System) serves for fluid motion by hydro dynamic-driven flow. A dilution system [Jasco PU-15(5)] is used for slug dilution on-chip. The detection system was a Jasco UV-1575 and analysis was carried out by LC/MS (Agilent 1100 series capLC-Waters Micromass ZQ). All components were on-line and self-configured. 

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