Study On The Synthesis Of Cinchona Alkaloids Derivatives Catalyst And Cyclodextrin-catalyzed Three-component Reaction

Cinchona alkaloids are a class of natural alkaloids, which include quinine, quinidine, cinchonine, cinchonine be like. Cinchona alkaloid derivatives not only have medicinal value to treat malaria and quinine and quinidine can also be used as chiral resolving agent racemate. Since1987, Sharpless et al who successfully used the alkaloid catalyzed asymmetric dihydroxylation of olefins, A growing number of reports indicate that Cinchona alkaloid derivatives can effectively catalyzed condensation, addition, substitution and other reactions. To construct C-C C-N and C-O bond to a chiral center, and the synthesis of compounds having high optical activity.Tetrahydrobenzopyrans wide range of uses in the field of synthetic drugs and pesticides, etc.. Based on the conventional method for the synthesis of these compounds in the organic solvent, and the solvent is mostly not conducive environment, mostly synthetics need to step-wise, in the promotion and development of green chemistry-saving economy today, how to improve those reactions has become an urgent problem problems.In this paper, quinidine derivatives as raw materials for the synthesized two novel cinchona base derivatives,using two methods, and the conditions were optimized. In addition, n this paper, by choosing different cyclodextrin as a catalyst to find the best catalyst, was found with inexpensive and readily available β-cyclodextrin as a catalyst for the different functional groups substituted aromatic aldehyde substrate in an aqueous solvent environment-friendly conditions with the "one-pot" can be successfully tetrahydrobenzopyrans derivatives, which under mild conditions, high yield, easy to operate, less impact on the environment, is an effective way to achieve this type of reaction. We have synthesized thirty-two compounds in totally, among of which eight are Cinchona alkaloid derivatives compound, and two of them are new compounds. Most of them were verified by1H NMR spectrum,13C NMR spectrum and MS spectrum (HRMS).Our work was composed of two sections as follows: Part One The synthesis of Cinchona alkaloid derivativesRoute Ⅰ:Quinidine were used as the starting materials, Under the action of concentrated phosphoric acid and potassium bromide, through a ring formed by the reaction of a9-hydroxyl group and selective demethylation synthetic quinidine derivatives (3-ICD, in a yield of55%.Route Ⅱ:Quinidine were used as the starting materials, Iodocyclization under the action of halogen and potassium, Then lithium aluminum hydride or tributyltin hydride and azobisisobutyronitrile, reductive dehalogenation reaction of cinchona alkaloid derivatives, in the total yield of31%.Route Ⅲ:Quinidine were used as the starting materials, under the catalysis of sodium borohydride and iodine, quinidine’s double bond addition reaction of borane, and then add sodium hydroxide and hydrogen peroxide oxidation, the final Mitsunobu reaction catalyzed by triphenylphosphine and diethyl azodicarboxylate isopropyl give cinchona base derivative. The overall yield was24%.Part Two The synthesis of Tetrahydrobenzopyrans compounds1. Chlorobenzaldehyde were used as the starting materials water as a solvent, respectively, catalysis with the a-cyclodextrin β-cyclodextrin, y-cyclodextrin, obtained tetrahydrobenzopyrans compounds.2. Benzaldehyde, methyl benzaldehyde, chlorobenzaldehyde, terephthaldehyde other aromatic aldehyde in water as a solvent, in the β-cyclodextrin catalysis, occur Knoevenagel reaction and Michael addition with malononitrile and dimedone obtained seventeen tetrahydrobenzopyrans compounds.3. Isobutyraldehyde, isovaleraldehyde, cyclohexyl carbaldehyde were used as the starting materials, obtained seven dicyclohexyl diones.