The Green Oxidation Of Alcohols By Hypervalent Iodine Reagents And CuL/TEMPO

The oxidation of alcohols is one of the fundamental reactions in organic synthesis. Traditional methods employ stoichiometric highly toxic oxidants and bring a lot of toxic waste. This kind of situation had prompted the chemists to have developed alternative methods, among which the most promising methods are the IBX(2-Iodoxybenzoic acid) mediated oxidation of alcohols, the IBS(2- Iodoxybenzenesulfonic Acid)-catalyzed oxidation of alcohols with Oxone (2KHSO5·KHSO4·K2SO4) and the CuL/TEMPO-catalyzed aerobic oxidation of alcohols. However, the IBX mediated oxidation of alcohols and the IBS-catalyzed oxidation of alcohols employ toxic organic solvents such as DMSO, CH3CN, or nitromethane; the CuL/TEMPO-catalyzed aerobic oxidation of alcohols employ toxic pyridine ligands and is not efficient in oxidizing secondary alcohols.In this dissertation, we have used ionic liquids, micelles and tetrazole ligands to develop new alcohol oxidation methods. Firstly, we employed tetrabutylammonium bromide(TBAB) and water as solvent and developed green yet inexpensive alcohol oxidation methods with IBX. Secondly, we used CTAB micelle as solvent and developed green IBS-catalyzed oxidation of alcohol in water; furthermore, the system was extended to the a-hydroxylation of β-keto esters and P-diketones. Thirdly, we used GMPGS-1000(a nonionic surfactant based on Guerbet alcohol) micelle as solvent and developed green CuL/TEMPO-catalyzed oxidation of alcohol in water Lastly, we used heterocyclic tetrazoles as ligands and developed low toxic CuL/TEMPO-catalyzed oxidation of alcohols, and proposed new mechanisms.(1) Green and inexpensive IBX mediated oxidation of alcohol in TBAB and water. The reaction of IBX mediated oxidation of alcohol was often conducted in DMSO due to the poor solubility of IBX in common solvents. Alternatives are the use of ionic liquids as green solvents, however, those ionic liquids employed in the literature are very expensive. We have used inexpensive ionic liquid TBAB and water as co-solvent, and established green and low cost IBS mediated oxidation of alcohols. The product yield can be as high as 96%. It was found that TBAB catalyzed the reaction.(2) IBS-catalyzed oxidation of alcohols with Oxone in CTAB micelle. The toxic nitromethane or acetonitrile was employed as solvent in IBS-catalyzed oxidation of alcohols. We used CTAB micelle as solvent and established green IBS-mediated oxidation of alcohols. It was found that only 2h was needed for the full conversion of the typical alcohols. The reaction was not only powerful to benzyl and other activated alcohols, but also compatible to the complicated aliphatic alcohols. The product yields were up to 99%. The reaction mechanism was also researched.(3) IBS-catalyzed a-hydroxylation of β-keto esters and β-diketones in CTAB micelle. The a-hydroxy-β-carbonyl moiety is an intriguing structural motif commonly found in natural products and pharmaceuticals. The most convenient way to synthesize such compounds is the direct a-hydroxylation of the corresponding β-dicarbonyl compounds. Traditional methods employ organic solvents and generate lots of waste. To solve the problem, we used CTAB micelle as solvent and established green a-hydroxylation of β-dicarbonyl compounds. The product yields were up to 97%. We have also researched into the reaction mechanism.(4) CuL/TEMPO-catalyzed aerobic oxidation of alcohols in GMPGS-1000 micelle. The main problem of CuL/TEMPO-catalyzed aerobic oxidation of alcohols is simply that the reaction employs organic solvents. Although there are some examples reported in the literature that uses water as solvent, the reaction conditions are harsh and the product yields are low. We have used GMPGS micelles as solvent and established green yet efficient CuL/TEMPO-catalyzed aerobic oxidation of alcohols. Compared to the literature, the substrate scope was also broadened and the product yields were increased to up to 96%.(5) CuL/TEMPO-catalyzed aerobic oxidation of alcohols using heterocyclic tetrazoles as ligands. The CuL/TEMPO-catalyzed aerobic oxidation of alcohols was not efficient in oxidizing secondary alcohols, presumably due to higher steric hinderance. What’s more, toxic pyridines were often employed as ligands. We used heterocyclic tetrazoles as ligands, established low toxic CuL/TEMPO-catalyzed aerobic oxidation of alcohols. It was found that the commercially available (S)-5-(Pyrrolidin-2-yl)-1H-tetrazole was the best ligand. Compared to the literature, the reaction time as shortened to only 1 hour, while the product yield was increased to up to 99%, furthermore, the substrate scope was broadened from merely methylbenzyl alcohols to complicated benzyl alcohols such as 1-tetralone. It was found the tert-butyl alkoxide instead of the anion from the copper source played the essential role in the catalytic cycle.