Solvents dioxirane oxidation

A triple-bonded nitrogen functionality (a ip-hybridized nitrogen atom), namely the cyano group, is resistant towards dioxirane oxidation. The fact that acetonitrile is widely used as a solvent for dioxirane oxidations " amply substantiates the lack of oxidative reactivity of cyano compounds. 

For most of these operations, isolated dioxirane solutions are more convenient, because simpler work-up procedures are involved. Furthermore, hydrolytically and acid/base-sensitive substrates may be employed, because the reaction is conducted under strictly anhydrous and neutral conditions. Solvents inert toward dioxirane oxidation may be used for dilution purposes in these oxidations, which include acetone, butanone, cyclohexanone, CH2C12, CHC13, CC14, benzene, and CH3CN. Alcohols (except t-BuOH) and ethers normally should be avoided as solvents, because they react slowly with dioxiranes, especially TFD [37]. 

In the case of the rhenium-catalyzed oxidation of methoxy- and hydroxy-substituted substrates, there is some complementary work concerning the general mechanism of the arene oxidation [10b, 11]. Since the major products in the oxidation of such arenes or phenols are the quinones, the formation of intermediary epoxides seems to be a predominant reaction step. When p-substituted phenols such as 2,6-di( -butyl)-4-methylphenol are treated with the MTO/H2O2 oxidant and acetic acid as solvent, the formation of hydroxydienones is observed. This is also reported for the oxidation using dimethyldioxirane as oxidant [20]. Since an arene oxide intermediate was postulated for the dioxirane oxidation, a similar mechanism is plausible here [11], e. g., for the oxidation of l,2,3-trimethoxy-5-methylbenzene (Scheme 3) or 2,6-di(f-butyl)-4-methyl-phenol. 

When the substrate and oxidized product tolerate hydrolytic conditions, the oxidation can be performed in situ. For this purpose we have found it advantageous to employ 2-butanone [5] instead of acetone as source of the dioxirane. Because of its partial solubility in water and excellent solvent properties no cosolvents such as CH2C12 or C6H6 are required. For convenience, in Table 2, we have summarized the reaction conditions and variables used for the dioxirane oxidations in the isolated and in situ modes. 

The ozonolysis of ethylene in the liquid phase (without a solvent) was shown to take place by the Criegee mechanism.This reaction has been used to study the structure of the intermediate 16 or 17. The compound dioxirane (21) was identified in the reaetion mixture at low temperatures and is probably in equilibrium with the biradical 17 (R = H). Dioxirane has been produced in solution but it oxidatively cleaves dialky] ethers (such as Et—O—Et) via a chain radical process, so the choice of solvent is important. 

In summary, transition structures with dioxirane and dimethyldioxirane are unsymmet-rical at the MP2/6-31G level, but are symmetrical at the QCISD/6-31G and B3LYP/6-31G levels. The transition states for oxidation of ethylene by carbonyl oxides do not suffer from the same difficulties as those for dioxirane and peroxyforaiic acid. Even at the MP2/6-31G level, they are symmetrical (Figure 17). The barriers at the MP2 and MP4 levels are similar and solvent has relatively little effect. The calculated barriers agree well with experiment . In a similar fashion, the oxidation of ethylene by peroxyformic acid has been studied at the MP2/6-31G, MP4/6-31G, QCISD/6-31G and CCSD(T)/6-31G and B3LYP levels of theory. The MP2/6-31G level of theory calculations lead to an unsymmetrical transition structure for peracid epoxidation that, as noted above, is an artifact of the method. However, QCISD/6-31G and B3LYP/6-31G calculations both result in symmetrical transition structures with essentially equal C—O bonds. 

AMI and PM3 calculations reveal that epoxidations by DMDO and TFDO involve peroxide-bond cr at a very early stage and that TFDO is the most reactive dioxirane as the CF3 group in it stabilizes this cr level. In accord with previous calculations a spiro transition state is predicted. Furthermore, allene is predicted to be less reactive than alkenes toward epoxidation by DMDO.192 DFT calculations on the oxidation of primary amines by dimethyldioxirane predict a late transition state with a barrier of 17.7 kcal mol-1 which is drastically lowered by hydrogen bonding to the O—O bond to just 1.3 kcal mol-1 in protic solvents.193... 

Many attempts have been made to use hydrogen peroxide as the final oxidizing agent in ketone-catalyzed epoxidations. Because hydrogen peroxide itself does not convert ketones to dioxiranes, in-situ activation of the oxidant is necessary. Shi et al. have achieved this goal by using acetonitrile as a component of the solvent mixture... 

Denmark has developed a practical dioxirane-mediated protocol for the catalytic epoxidation of alkenes, which uses Oxone as a terminal oxidant. The olefins studied were epoxidized in 83-96% yield. Of the many reaction parameters examined in this biphasic system, the most influential were found to be the reaction pH, the lipophilicity of the phase-transfer catalyst, and the counterion present. In general, optimal conditions feature 10 mol% of the catalyst l-dodecyl-l-methyl-4-oxopiperidinium triflate (30) and a pH 7.5-8.0 aqueous-methylene chloride biphasic solvent system [95JOC1391]. 

Acetonitrile is the solvent of choice for in-situ C-H oxidation. Although ethereal solvents, for example dimethoxymethane, 1,2-dimethoxyethane, 1,4-dioxane, and mixtures thereof, have been successfully used for dioxirane-mediated catalytic asymmetric epoxidations, their application in in-situ C-H oxidation has not been vigorously established. 

The dioxiranes can be used via either an in situ70 or an ex situ method.71 If the in situ method can be tolerated then better yields are afforded based on the primary oxidant employed, i.e. the peroxymonosulfate, whereas isolation of the dioxirane only yields about 5-10% based on the peroxymonosulfate. The in situ method is carried out in a two-phase manner, employing a solvent such as dichloromethane or toluene. The epoxidation ability of the dioxiranes is excellent, and the conditions relatively mild. The majority of epoxidations are carried out at ambient temperatures and pressures. Figure 3.18 summarizes the various epoxides which can be prepared in the presence of dimethyldioxirane (DMD). 

In ketone-directed peroxy acid epoxidations of cyclic alkenes the actual epoxidizing agent has been shown by 180-labeling not to involve a dioxirane <94TL6155>. Instead, an a-hydroxy-benzoylperoxide or a carbonyl oxide is believed to be responsible for observed stereoselectivities in the intramolecular epoxidations. The extent of syn-selectivity is greater for ketones than with esters the syn/anti ratios increase when ether is used as solvent rather than CH2C12, the reverse situation for hydroxyl-directed epoxidations. Fused-ring oxiranes can also be prepared from acyclic precursors. Four different approaches are discussed below. 

The fact that acetone and also butanone and cyclohexanone are fast solvents suggests that ketones possibly participate in the reaction. One might think of intermediate formation of dioxiranes (which are known to be strong oxidants) or of hydroxylation of ketones. In pyridine reaction (3) is blocked. 

While Oxone has been commonly used to generate dioxiranes from ketones, Shi s studies have shown that epoxidation with ketone 2 or 5c can be carried out with a nitrile and H2O2 as the primary oxidant, giving high enantioselectivity for a variety of olefins. Peroxyimidic acid 55 is likely to be the active oxidant that reacts with the ketone to form dioxirane 10. Mixed solvents, such as CH3CN-EtOH-CH2Cl2, improve the conversions for substrates with poor solubilities. This epoxidation system is mild and provides conversion and enantioselectivity similar to that using Oxone as oxidant. 

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