The Synthesis And Aromatization Of Dihydropyridine And Pyrazoline Compounds

Dihydropyridine (DHP) and pyrazoline are two kinds of heterocyclic compounds which have very important physiological activities and pharmaceutical value. Both of them have huge value and prospect in the fields of medical.Twenty eight dihydropyridine and nine pyrazoline compounds have been synthesized and the aromatization of seven of them is also studied in this paper. The structure of the product is confirmed by IR, 1HNMR and elementary analysis. The purpose of this paper is: First, For optimizing the traditional synthetic proceed for DHP, shortening the time of reaction, raising the yield and reducing the production costs; Second, attempt to introduce new groups with physiological activity into structure of DHP, so as to select more valuable compounds; Third, due to dihydropyridine agents can be oxidized to corresponding pyridine in the body which is also the source of pyridine their aromatization are studied so as to find out aromatization reagent with mild oxidation capability and less toxic to body and environment. All the research is also suitable to pyrazolines.The content of this paper includes the following four aspects:1. 16 kinds of symmetrical dihydropyridine derivatives are synthesized through one-pot method with aldehyde, dicarbonyl compounds and ammonia as materials. The structure of the product is confirmed by IR, 1HNMR and elementary analysis. The effects of different solvents (dioxane, anhydrous alcohol and homemade imidazolium-based ionic liquids) were studied from the yield and reaction time aspects. It is found that the reaction time is shortest in ionic liquid while the slowest reaction occurred in aqueous, Moreover, ionic liquids can be reused for three times which reduce the costs of production. 9 kinds of asymmetrical dihydropyridine derivatives are synthesized by three steps. Firstly, alkyl 3-aminocrotonate is obtained from reaction of dicarbonyl compound and ammonia, Secondly, the knoevenagel condensation reaction is conducted between aromatic aldehydes and dicarbonyl compound in the presence of base catalysts. Finally, target compounds are got through the Michael addition reaction between the product of condensation and alkyl 3-aminocrotonate in the presence of catalyst, The effect of catalyst kinds, the type of solvent and mode of heating on the yield of are studied and optimized in this paper. In addition, the mechanisms of formation of compounds 24-25 have also been discussed in this paper.2. Ferrocene itself have good physiological activities and have its derivatives are lipophilic and can pass the cell membrane, then interact with intracellular enzyme, Therefore we consider the introduction of ferrocene hoop to the structure of calcium antagonist, in the hope to enhance the biological activity of these compounds. Ferrocene formaldehyde is synthesized in this paper and then take part in Hantzsch reaction instead of aromatic aldehyde in order to introduce ferrocenyl into the structure of 1,4-dihydropyridine. Three kinds of symmetrical dihydropyridine derivatives in which C4 position is replaced by ferrocenyl are synthesized. The structure of the products are confirmed by IR, 1HNMR and elementary analysis.3. Similar with dihydropyridine, pyrazoline is a heterocyclic compounds which has effective pharmacological and physiological activity. Several pyrazolines are synthesized in this paper, Through the acetylation of ferrocene, ferrocene group is introduced to structure of pyrazolines, three novelty 1, 5-diaryl-3-ferrocenyl substituted pyrazoline are synthesized. All of three compounds are confirmed by IR. HNMR and elemental analysis.4. Selecting seven of the obtained compounds as example, elaborate the research on the aromatization of two kinds of compounds. The experiment shows that FeCl3·6H2O as aromatization reagent has some advantages such as mild oxidation ability, high purity and simple post-processing and so on.