L-proline-catalyzed Aldol Reaction In Supercritical Fluids

In recent year,proline and its derivatives have been successfully used as chiral organocatalysts in asymmetric synthesis and have received extraordinary attentions.Most of the L-proline-catalyzed aldol reactions have been carried out in organic media such as DMF or DMSO. Purification process of products is very complex.Large amounts of organic solvents are used in chemical reactions,most of which are volatile,toxic,and flammable.From the viewpoint of greener processes,the use of non-hazardous and renewable materials is one of the most important goals of green chemistry.Supercritical carbon dioxide(scCO₂) is the most popular solvent among SCFs.The advantages of supercritical fluids(SCF) compared with conventional liquid solvents include low surface tension,high diffusivity,low viscosity and high compressibility.The reactions can carry out by a more efficient,clean,green method in scCO₂,which can reduce or eliminate environmental pollution.A number of physical parameters of supercritical fluid such as temperature and pressure can be effective regulated and controlled.Most research findings proved that solvent plays an important role in L-proline-catalyzed asymmetric aldol reactions,and some chiral asymmetric catalysis reactions were carried out in scCO₂ system.Based on these reasons,a static method coupled with gravimetric analysis was developed for measuring the solubility of L-proline in scCO₂ or HFC-134a,and L-proline-catalyzed asymmetric aldol reactions between ketones and aromatic aldehydes were carried out in scCO₂ or HFC-134a.This dissertation has undertaken the following work:1.The P-R equation is derived.Density of scCO₂ or HFC-134a at different temperatures and pressure was determined,and the results between derived by P-R equation and measured by experiment were compared.The results show that relationship between the fluid density and temperature or pressure is non-linear.The density of scCO₂ or HFC-134a decreased with the increasing of temperature and increased with the increasing of pressure.The temperature and pressure of fluids are important factors for density.The density of fluid can be adjusted by changing temperature and pressure of fluids.The equilibrium of solid in supercritical fluid is always indispensable to the development of supercritical fluid science and technology.Therefore,some works have been carried out.A static method coupled with gravimetric analysis was developed for measuring the solubility of L-proline in scCO₂ or HFC-134a.The appealing feature of this technique is its simplicity,and it requires no specialized equipment other than a suitable pressure cell.The effects of temperature and pressure on the solubility of L-proline were studied.The solubilities of L-proline in scCO₂ or HFC-134a were measured at condition of 303～328 K,10～30 MPa.In this paper,Chrastil equation was used to calculate the solubilities of L-proline in supercritical CO₂,experimental values are in good agreement with the calculated values.2.In this dissertation,the direct asymmetric aldol reaction between 4-nitrobenzaldehyde and acetone catalyzed by L-proline was successfully carried out in supercritical CO₂.The enantioselectivity of 84%ee to the targeted product was achieved.This offers a method for reaction-separation integration,and also the method simplifies the treatment process after the reaction.This provides a good foundation for the green organic synthesis.The effects of reaction temperature,pressure,the loading of catalyst,reaction time,additives and other factors on the L-proline-catalyzed asymmetric direct aldol reaction between acetone and aromatic aldehydes in scCO₂ or HFC-134a were investigated.The best reaction conditions in scCO₂ were at 40℃, 25 MPa,15 mol%amount of catalyst,the appropriate reaction time for 24 h,1:15 for molar ratio of aldehydes and ketones.However,HFC-134a as a reaction medium,the lower enantioselectivity was obtained due to the hydrogen bonds between F atoms and carboxyl in proline.3.Based on Boc-protected proline and substituted triazole as raw materials,a new catalyst (S)-5-prolylamide-triazole was synthesized and applied as catalysts for the direct asymmetric intermolecular aldol reaction.The effects of solvents,pressure,the loading of catalyst,additives, and reaction temperature on the asymmetric direct aldol reaction between acetone and aromatic aldehydes were studied.The experimental results show that the aldol reactions catalyzed by (S)-5-prolylamide-triazole carried out without solvent.The enantioselectivity of 80%ee to the targeted product was achieved at the 15 mol%catalyst loading.The addition of additives reduce catalytic performance of(S)-5-prolylamide-triazole.The reactions were finished without solvent at room temperature,which make reactions carried out in a green manner.We believe that this catalyst will be used widely.