Allylic Oxidation Of Ionone-like Catalyzed By Copper Salt Nanoparticles In Ionic Liquids And Calcium Or Magnesium Ion

Enones, endiones, dienones are of importance in organic chemistry because which are basic blocks of natural products and synthesis chemistry, materials and intermediates in synthesis of pharmaceutical, flavor and fragrance, agricultural chemicals, functional material, and importance precursors to many chiral organic compounds e.g chiral alcohols, ethers and esters. Among methods of producing enones, the allylic oxidation is one of main protocols.To date, the methods established for allylic oxidation mainly refer to the traditional methods based on chromium compounds, the improved systems of chromium-based molecular sieve and chromium trioxide with tert-butyl hydroperoxide, the procedures of selenium dioxide and perfluorooctylseleninic acid-iodoxybenzene and the approach of dirhodium(â…¡) caprolactamate catalyzed by with tert-butyl hydroperoxide. Transition metal (e.g. Cu, Co, Pd, etc) catalyzed processes in conjunction with a terminal oxidant offer a promising alternatives. Many of these systems are useful synthetically, but several issues remain, including un-available and expensive catalyst, long reaction time, catalyst/product separation, catalyst reuse, the environmental burden of volatile organic solvents, and safety concerns of using anhydrous tert-butyl hydroperoxide. Therefore, further investigation is high desirable. The development of simple, efficient and environmentally friendly method is a challenge for chemistry communitesIonones and their derivatives are flavor components of many natural essential oil such as osmanthus, passion fruit, tea, and tobacco. They are appreciated synthetic building blocks due to their remarkable contributions in the synthesis of many medicine, biological active and flavor and fragrance compounds.4 Especially, the introduction of an active carbonyl group in their cyclohexene allylic C-H bond can not only construct more complex molecules, but also yield valued-added products, utilized to the essence of fruit, tobacco, flower and food additives. However, the direct synthesis of dienones by the allylic oxidation of ionones and their derivatives have required either stoichiometric chromium reagent (CrO₃ or (t-BuO)₂CrO₂). Recently, it is reported that using catalytic amount chromium trioxide with tert-butyl hydroperoxide,β-dihydro-ionone was converted to 4-oxo-β-dihydro-ionone. Although the latter avoided the use of stoichiometric reagents, the hazard from chromium trioxide remains.Ionic liquids as environmentally benign and recoverable solvents have received considerable attentions. Various reactions can carry out in them, and the equal or better outcome have been obtained. The oxidation of alcohols, the epoxidation of alkenes have well run in ionic liquid. However, to the best of our knowledge, no report has been presented involving the allylic oxidation of alkenes in ionic liquid, particularly ionone-like dienes.Based on the background, the development of new, efficient, environmentally friendly protocol of allylic oxidation would be not only an important subject in organic chemistry, but also become innovative and practical findings.We originally established a simple, efficient, selective method for the allylic oxidation of ionone-like dienes in imidazolium ionic liquids. In the presence of 20 mol% CuCl₂·2H₂O, ionone and their derivates were converted to corresponding eneones and the yields 45%～71% were afforded using [bmim]BF4 or [bmim]PF₆ as reaction medium and 3-5 equiv of aqueous 70% TBHP.We further utilized more low cost ionic liquids as reaction medium, and in [bpy]BF₄ or [bpy]PF₆ the enones of ionone and their derivates were provided with 47%～72% of yield under the similar conditions. This is the best results of synthesis of the enones of ionone and their derivates. Few reports were presented on the allylic oxidation in imidazolium or pyridinium ionic liquids, and without ligand and base the method of allylic oxidation exhibited many advantages including short reaction time, the use of nontoxic catalyst, low amount of TBHP, the good yields of product, and the facile recovery and recycling of reaction media.We firstly disclosed the size and shape of Cu (â…¡) nanoparticales of formation and stabilization in imidazolium or pyridinium ionic liquids by TEM, which give us insight into the CuCl₂·2H₂O-t-BuOOH-[bmim]X or [bpy]X catalytic system.,We also established a new strategy of allylic oxidation of ionone-like based on CaCl₂ or MgCl₂ catalyst. In the presence of 20 mol～30 mol% of CaCl₂ or MgCl2·6H₂O ionone and their derivates can be oxidized corresponding dienones using acetonitrile as solvent with 3-5equiv of aqueous 70% TBHP at 80℃for 4 h, and 42%～456% yields were achieved. To date, no report involved the allylic oxidation of ionone-like dienes with the catalyst of simple calcium or magnesium salt. More important, we proposed a mechanism to account for the non-redox allylic oxidation.The advantage of the new catalytic system (CaCl₂ or MgCl₂·6H₂O-TBHP) are numerous: the utilization of Ca²⁺or Mg²⁺, pretty cheap and nontoxic as well as essential for life, and low amount and direct application of aqueous 70% solution of TBHP, mild reaction conditions, relative short reaction time, and better yield of product. It is believed that the deeply explore the catalytic function of Ca²⁺ or Mg²⁺ would open new areas catalysis by Ca²⁺or Mg²⁺.Megastigmatrienone are known as key tobacco flavoring components and can improve smoking characteristics. Moreover, they serve as the composition of natural essential oil with high value and are frequently utilized to food, perfume, cosmetic and tobacco. The previous methods of synthesizing megastigmatrienone remain many problems, such as long synthetic route, low yield, and harsh reaction conditions. We successively improved the process of the allylic oxidation with low yield, and then develop a new synthetic route of megastigmatrienone using a-ionone as starting material, which are composed of oxidation, reduction and elimination and with good overall yield(＞50%). This is the simplest and efficient method in the synthesis of megastigmatrienone. No requirement of moisture-free, air-free and very low temperature make the new approach more practical in industry scale.These innovation outcome would support the research of self-dependant synthesis of tobacco flavor component and be widely used in fine chemistry, pharmaceutical and flavor and fragrance industry.