Tetrahydro chinolines derivates and synthetic method

Abstract

The invention relates to a method for synthesizing 2 position functionalized tetrahydroquinoline derivatives of 4-(mono or poly) aryl-substitution-3, 1'-cyclopropyl substitution by hetero Diels-Alder reaction of imine of ethyl glyoxylate and methylene cyclopropane. For various functionalizing substitutions in the reaction, which means that the reaction can be carried out smoothly whether the imine of the ethyl glyoxylate and the methylene cyclopropane is an electron donating group or an electron withdraw group, and corresponding tetrahydroquinoline derivative can be obtained with yield from medium to excellent. In the reaction process, high-strength tetrahydroquinoline derivatives with triatomic ring substitution and 2 position ethyl ester group are generated. The compounds have excellent modification property, can connect a tetrahydroquinoline module with other 2 position functional molecules, and have potential high biological activity.

Description

technical field [0001] The invention relates to a method for synthesizing tetrahydroquinoline derivatives by using a solid acid to catalyze the hetero Diels-Alder reaction of imines of ethyl glyoxylate. Background technique [0002] The chemical and physical properties of organic heterocyclic compounds are different from ordinary carbocyclic compounds due to the electronegativity of heteroatoms and the influence of the lone pair of electrons, and most of them are N-heterocyclic compounds. N-heterocyclic compounds widely exist in the fields of medicinal chemistry, materials chemistry and organic synthesis chemistry. Tetrahydroquinoline compounds exist in many natural products, and many tetrahydroquinoline derivatives with simple or complex substituents have been shown to have certain antioxidant properties [(a) Kazuo, M.; Kazuya, O.; Hironobu, H.J.Org.Chem.1989, 54, 557. (b) Pryor, W.A.; Strickland, T.; Church, D.F.J.Am.Chem.Soc. B.; Lestage, P.; Casara, P. Bioorg. Med. Che...

AI Technical Summary

Problems solved by technology

It is reported in the literature that the synthesis of tetrahydroquinolines substituted with 2-position ethyl esters is mostly obtained from the corresponding quinolinic acid with Raney-Ni hydrogenation and then esterification. The conditions are relatively strict, and esterification needs to be carried out in the presence of sulfuric acid. The compatibility of quinolinic acid has decreased, while the synthesis of quinolinic acid uses Synthetic method, there is a risk of exothermic reaction caused by too fast addition of KOH [Li, A.-H.; Ahmed, E.; Chen, X.; Cox, M.; Crew, A.P.; Dong, H.-Q .; Jin, M.; Ma, L.; Panicker, B.; Siu, K.W.; Steinig, A.G.; M.J.Org.Biomol.Chem., 2007, 5, 61.]; quinolinic acid can also be obtained from the oxidation of 2-methylquinoline, but requires the use of peroxides [Tagawa, Y.; Yamashita, K.; Higuchi, Y.; Goto, Y.Heterocycles.2003, 60, 953.], or the more toxic selenium dioxide [C.-Galcéra, M.-O.; Sidhu, A.; Plas, P.; Roubert , P.Bioorg.Med.Chem.Lett.2005, 15, 3555.], a large amount of preparation is also difficult; using sodium cyanide, 3,4,5-trimethoxybenzoyl chloride and sulfuric acid can be directly prepared from quinoline Quinolinic acid [Schwartz, A.J.Org.Chem.1982,47,2213.], but this method toxicity is bigger, and the catalyst that reports this type of reaction required in the literature can not be reused, and the price of catalyst and synthesis also are to hinder its industrialization Obstacles to production

Images