Using immobilized lipase, we developed an enzymatic synthesis of isosorbide-2-acetate (1), a key intermediate in the preparation of isosorbide-5-mononitrate. 1 was prepared in high yield (∼92%) with excellent regioselectivity (>99.5% d.e.) through hydrolysis (Novozym 435) or alcoholysis (lipase PS IM) of isosorbide-2,5-diacetate. The conditions for the enzymatic process were optimized. The substrate concentration could be 400−500 g/L, and the enzyme to substrate ratio was <10 wt %. The feasibility of enzyme recycling was also demonstrated. In addition, the enzymatic process was carried out on a kilogram scale and was proved to be scalable, efficient, and economical.
Different schemes were studied for the recovery of wastes generated during the industrial production of isosorbide-5-mononitrate (IS-5-MN). For the wastewater, disposal was achieved by hydrolysis of isosorbide-2-mononitrate (IS-2-MN) to the starting material isosorbide (IS) utilizing its alkaline environment, where NaOAc was also recovered effectively in the form of the trihydrate. For the solid waste, two different schemes were investigated: direct crystallization and catalytic hydrogenation. The former afforded useful isosorbide dinitrate (ISDN) efficiently, and the latter provided an efficient and scalable route to synthesize IS-5-MN from ISDN. The combinations of unit operations were evaluated on a 100 kg scale and proved to be feasible and robust. The waste recycling strategy provides an eco-friendly complement for the industrial-scale preparation of IS-5-MN, which minimizes waste emission during the process.
The effects of reaction temperature, solvents, reaction time and 7-aryl on the cyclocondensation reactions of 3-amino-1,2,4-triazole with 3-(benzylidene)-6-fluorothiochroman-4-ones were studied. The experimental results show that except tetracyclic fused dihydropyrimidines and pyrimidines were produced simultaneously in the cyclocondensation reactions, the dihydropyrimidines could be directly converted into pyrimidines without any dehydrogenizing reagent under high temperature. The structures of the new synthesized compounds were confirmed by 1 H NMR, MS spectra, elemental analysis, and X-ray single crystallography. The cyclocondensation mechanism for producing the tetracyclically fused dihydropyrimidines and pyrimidines was discussed.
Fused pyrimidine derivatives R 0515 Cyclocondensation Reactions of 3-Amino-1,2,4-triazole with 3-(Benzylidene)-6-fluoro-thiochroman-4-ones to Tetracyclically Fused Dihydropyrimidines and Pyrimidines. -The investigation of the title reaction under different conditions reveals that pyrimidines (III) can be synthesized directly besides dihydropyrimidines (IV). The process is found to be regioselective. -(MA, Z.; YAN, G.; ZHU, S.; YANG*, G.; LUO, D.; Chin.
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