Solvent effect alcohol oxidation

We wish to report here on a new and highly efficient catalyst composition for the aerobic oxidation of alcohols to carbonyl derivatives (Scheme 1). The catalyst system is based on 2,2,6,6-tetramethylpiperidine N-oxyl (TEMPO), Mg(N03)2 (MNT) and N-Bromosuccinimide (NBS), utilizes ecologically friendly solvents and does not require any transition metal co-catalyst. It has been shown, that the described process represents a highly effective catalytic oxidation protocol that can easily and safely be scaled up and transferred to technical scale. 

The bromination with alkali hypobromite in aqueous solution gives good results with (hetero)arylacetylenes, enynes (RCH=CHOCH) and diynes (RC=CC=CH) all acetylenes that are more acidic than those acetylenes in the aliphadc or cycloaliphatic series with an isolated triple bond. For the conjugated systems the hypobromite method is superior to the reaction of metallated acetylenes with bromine. Various acetylenic alcohols are also brominated smoothly, which can be explained in part by their better solubility in water. Since in the case of primary and secondary ethynyl alcohols, oxidation of the alcohol can occur, the use of an excess of hypobromite should be avoided. The best procedure is drop wise additon of a small shot measure of hypobromite ro a mixture of alcohol and water. If the bromoalkynes to be prepared are not too volatile, small amounts of THF or dioxane may be added to effect a better solubility of the alkyne in the aqueous phase. Addition of a co-solvent may also be desired when the starting compound is a solid (e.g. ethynylcyclohexanol). 

Interesting solvent effects have also been observed189 [Eq. (9.47)]. Product distribution at secondary sites in water is almost statistical, and ketones are the main products. In acetonitrile, the y position is oxidized with the preferential formation of alcohols. 

A comparison of the suitability of solvents for use in Srn 1 reactions was made in benzenoid systems46 and in heteroaromatic systems.47 The marked dependence of solvent effect on the nature of the aromatic substrate, the nucleophile, its counterion and the temperature at which the reaction is carried out, however, often make comparisons difficult. Bunnett and coworkers46 chose to study the reaction of iodoben-zene with potassium diethyl phosphite, sodium benzenethiolate, the potassium enolate of acetone, and lithium r-butylamide. From extensive data based on the reactions with K+ (EtO)2PO (an extremely reactive nucleophile in Srn 1 reactions and a relatively weak base) the solvents of choice (based on yields of diethyl phenylphosphonate, given in parentheses) were found to be liquid ammonia (96%), acetonitrile (94%), r-butyl alcohol (74%), DMSO (68%), DMF (63%), DME (56%) and DMA (53%). The powerful dipolar aprotic solvents HMPA (4%), sulfolane (20%) and NMP (10%) were found not to be suitable. A similar but more discriminating trend was found in reactions of iodobenzene with the other nucleophilic salts listed above.46 Nearly comparable suitability of liquid ammonia and DMSO have been found with other substrate/nucleophile combinations. For example, the reaction of p-iodotoluene with Ph2P (equation (14) gives 89% and 78% isolated yields (of the corresponding phosphine oxide) in liquid ammonia and DMSO respectively.4 ... 

A few years later,3 it was shown that o-iodoxybenzoic acid (36)—itself a precursor in the preparation of Dess-Martin periodinane—is able to oxidize very effectively alcohols in DMSO solution. o-Iodoxybenzoic acid—normally referred to as IBX—exists mainly as a cyclic form 37, which crystallizes as a polymer with very low solubility in most solvents with the exception of DMSO. Although, IBX (36) was already known in 1893,4 this ultracentenial reagent found very little use till very recently, when awareness about its solubility in DMSO was raised. 

A remarkable solvent effect on the chemoselectivity was discovered by Agarwala and Bandyopadhyay (Scheme 3.24, B) [114]. When cyclohexene la was oxidized with tBuOOH in the presence of an electronegative substituted iron(III) porphyrin complex in CH2Cl2-MeOH, epoxide 4a was the predominant product (69% yield) in addition to alcohol 2a and ketone 3a as byproducts in 20% and 11% yields,... 

DMF (and its adduct with HC1, DMF HCl) is an effective catalyst (and solvent) in the oxidation-chlorination of primary alcohols to a,a-dichloroaldehydes, which can be smoothly oxidized to the corresponding a,a-dichlorocarboxylic acids (equation 158)1054. 

The Irm complex [Cp+IrClf jl Cl) ] 2 serves as a catalyst for the oxidation of primary and secondary alcohols oxidation in acetone as the solvent [63]. The moderate effectiveness of this catalyst, however, prompted the preparation of several Ir111 analogs bearing an NHC ligand [58-60] (Scheme 7). It... 

Some interesting solvent effects observed in the TBHP-SOi-initiated polymerization of MMA have been mentioned before. It has been further observed that when polymerization of MMA and AN is carried out in the presence of alcohols, the rate of polymerization is in the order methanol > ethanol > isopropyl alcohol > tert-butyl alcohol, cyclohexanol. This suggests that the over-all polymerization mechanism (or the initiation mechanism itself) depends on the polar contribution of the alcohol. A similar observation was made by Imoto et al. with a benzoic anhydride— dimethylaniline N-oxide system as the initiator (20). 

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