The Synthesis Of 6-hydroxy-2,3-dihydro-4-quinolone

As important agricultural and medical intermediates, 6-hydroxy-2,3-dihydro-4-quinolone can be used for preparing various kinds of quinolones, which are reported as antibacterial and antihypertension that have showed outstanding medical effect.6-hydroxy-2,3-dihydro-4-quinolone is synthesized by the basic material of 4-nitrochloro-benzene. It has investigated the routes, conditions and purifies methods in this paper, which provides bases to lucubration and industrialization. This study belongs to the field of medical intermediates. The experimental part of this thesis consists two aspects: 1. Employ the Raney Ni as the catalyst to study the main influence factors in using the method of catalyst hydrogen to synthesize the ammonia, so as to looking for the superior reaction condition that could acquire high acceptation rate of product. 2. Employ 4-anisidine and acrylic acid as raw material. Through the process of addition, cyclization and demethylation, 6-hydroxy-2,3-dihydro-4-quinolone and the better route and condition of the synthesis have been obtained during research work. Instead of acrylate, acrylic acid is used for the Michael addition with aromatic amine. Meanwhile, the products of addition and cyclization reactions are easily separated by column chromatography on silica gel.The result of experiment indicates the following: 1. The yield of 4-anisidine is up to 91.5%, under hydrogen at 0.6-0.8MPa pressure at 50℃in the presence of nickel catalyst (0.8g wet mass, about 50%) and in the ethanol solvent (10ml), and the purity of HPLC is 99%. 2. a. addition: 3-(4-methoxyanilino) propionic acid is obtained by the addition of 4-anisidine to acrylic acid and water at a reactant ratio of 1:1.5:10 at 45℃over the period of 8h, in 55% yield with a method of rapid chromatographic column, b. cyclization: cyclization occurs at 100℃in polyphosphoric acid for 4h in the mass ratio of 3-(4-methoxyanilino) propionic acid to PPA with 1:8, and 6-methoxy-2,3-dihydro-4-quinolone is formed in 50.5% yield with a method of rapid chromatographic column, c. demethylation: that 6-hydroxy-2,3-dihydro-4-quinolone (3g) is treated with concentrated hydrochloric acid (20ml) at 120℃for 6h gives 6-hydroxy-2,3-dihydro-4-quinolone in 83% yield. Under the optimistic conditions, the total yield of route is 23%.Compounds, including the intermediates, ending products and other relative compounds are characterized with different methods.