Peroxy acids intramolecular

Infrared measurements 1145 indicate that peroxy acids aiy present in solution largely in the monomeric, intramolecularly hydrogen-bonded form (XXXVIII), in accordance with the fact tW they Are more volatile than the corresponding carboxylic acids. 

The products of bromination in water are called bromohydrins. They can be treated with base, which deprotonates the alcohol. A rapid intramolecular Sjyj2 reaction follows bromide is expelled as a leaving group and an epoxide is formed. This can be a useful alternative synthesis of epoxides avoiding peroxy-acids. 

The key intermediate is a peroxy-acid formed after decarboxylation. The peroxy-acid is perfectly placed for an intramolecular epoxidatjon of a double bond in the benzene ring next to the side chain. 

Treatment of the acid (67a) with carbonyldiimidazole and 90% H2O2 furnishes the epoxide (67b equation 44). This reaction is more than 100 times faster than the epoxidation of (67a) with MCPBA (see equation 26). It has been suggested that under the experimental conditions of equation (44) the acid (67a R = OH) is transformed to the peroxy acid (67a R = O2H), which reacts regio- and stereo-selec-tively through an intramolecular reaction. 

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. 

Formation of 2-Ethyl-2(5H) Furanone. The presence of artifacts with increased retention times suggests the formation of components of increased polarity and/or the formation of higher molecular weight constituents from condensation or addition reactions. The acids, aldehydes and alcohols present can undergo oxidation to form y- and 6-lactones (14, 15). The formation of the lactone, 5-ethyl-2(5H)-furanone, probably occurs by the steps outlined in Figure 4. A plausible sequence would be reaction of 2-hexenoic acid to form a peroxy radical at the y-position followed by production of the hydroperoxide. Cleavage of the 0-0 bond with the subsequent addition of H could lead to 4-hydroxy-2-hexenoic acid. Intramolecular esterification would then produce the identified lactone. 

Peroxy acids possess strong intramolecular hydrogen bonds. The concerted progress results in a stereo-specific reaction. (Z)-alkenes yield cw-oxiranes, (jE)-alkenes ra -oxiranes. 

Overall, the stereospecificity of this method is the same as that observed in peroxy acid oxidation of alkenes. Substituents that are cis to each other in the alkene remain cis in the epoxide. This is because formation of the bromohydrin involves anti addition, and the ensuing intramolecular nucleophilic substitution reaction takes place with inversion of configuration at the carbon that bears the halide leaving group. 

Peroxy acids and diacyl peroxides are mono- and di-acyl derivatives of hydrogen peroxide. Peroxy acids form esters of which the t-butyl compounds are the best known. In contrast to carboxylic acids which form intermolecular hydrogen-bonded dimers, the peroxy acids exist as intramolecular hydrogen-bonded monomers. This leads to several differences in the properties of these two types of acids. 

As a consequence of their intramolecular hydrogen-bonding the peroxy acids differ from the carboxylic acids in a number of their physical properties. For example, their acidity is reduced about one-thousand-fold, the O-H stretching... 

Despite the attractiveness of this proposal, peroxy acids such as (83) and (84) are unlikely to function as the critical oxenoid intermediates in the enzymic process. Peroxysuccinic acid has been added to both the proline-4-hydroxylase and thymidine-2 -hydroxylase systems, but it does not replace the requirement for oxygen and 0x0 glutarate 253). Furthermore, it is unlikely that such a peroxy acid would have sufficient reactivity to carry out the specified hydroxylation. Moreover, we have prepared the peroxy acid (84) and have found that it too is incapable of performing the required intramolecular oxene transfer. No products like (85), (86) or (87) are formed 287). 

The hydroxyl proton in the intermediate 3 can migrate intramolecularly only with acylperoxo-type oxidants. Hence, acylperoxo-type oxidants are more effective than allq lperoxo oxidants. Additionally, it was observed that the presence of electron-withdrawing substituents on the peroxy acid increased the reaction rate because they made the conjugate base a better leaving group. Therefore, the reactivity of oxidants follows this order CF3CO3H > monopermaleic... 

The peroxy acid attacks the carbonyl group of the ketone, giving a tetrahedral intermediate that then undergoes an intramolecular proton transfer (or two successive intermolecular proton transfers). Finally, the C=0 double bond is re-formed by migration of an R group. This rearrangement produces the ester. 

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