Friedlander, Synthesis Of Quinoline Derivatives And Biological Activity

A new route for preparation of quinolines via vainlline by Friedlan-der condensation was brought forward in this paper. The preparation of three new quinolines was also discussed, including 8-methoxyquinolin -7-yl acetate, 7-acetoxy-8-methoxyquinoline-2-carboxylic acid and 8-methoxy-2-phenylquinolin-7-yl acetate. The acetylcholinesterase inhibition of three quinolines was studied and the antibacterial action of three quinolines and three organic intermediates was studied.(1) The synthetic craftwork of 2-Amino-4-hydroxy-3-methoxy-benzaldehyde including four reaction steps was confirmed, which was synthesized from vanillin via desertification, nitration, reduction and hydrolyzation. The optimal condition in desertification step was that adding triethylamine under 20℃, using N,N- Dimethylaniline as catalytic agent (0.15g/10.00g vanilline) at 30℃for 3h. The optimal condition in nitration step was that using fuming nitric acid as catalytic agent and the ratio of reactant 1:15 at 5℃for 1.5h. The optimal condition in reduction step was that adding HCl 15min after the addition of iron powder and keeping 30℃for 1.5h. The condition in hydrolyzation step was that using 33%NaOH at 75℃for 15min and then using HCl to regulate pH about 4-5. The production was buff crystal and the melting point was 127.3-128.2℃. The results of ~1HNMR and melting point show that the synthesized product accords with the bibliographical information.(2) The synthetic craftwork of three quinolines by Friedlander condensation was confirmed. 7-Acetoxy-8-methoxyquinoline-2-carboxylic acid was synthesized by added a solution of sodium ethoxide in a mixture of 4-acetoxy-3-methoxy-2- minobenzaldehyde and acetone in absolute ethanol and then heated at 80℃with stirring under reflux for 2h. The production was yellow acicular crystal and the melting point was 232.9-233.6℃. The results of ~1HNMR and IR spectrum show that the synthesized product accords with the target.(3) The acetylcholinesterase inhibition of three quinolines was examined, which have not been reported previous, 7-acetoxy-8-methoxy-quinoline-2-carboxylic acid had the best acetylcholinesterase inhibition while 8-methoxy-2-phenylquinolin-7-yl acetate had the worst.(4) The antimicrobial activity of six components was examined, which have not been reported previously. The experiment show that 7-acetoxy-8-methoxyquinoline-2-carboxylic acid had the best antibiotic activity, while 8-methoxyquinolin-7-yl acetate had the worst. Two organic intermediates 4-Acetoxy-3-methoxy-2-minobenzaldehyde and 2-Amino-4-hydroxy-3-methoxybenzaldehyde also show considerable antibiotic activity.