Electrophilic hydroxylations

Figure 16.6 MECHANISM Mechanism of the electrophilic hydroxylation of p-hydroxyphenyl acetate, by reaction with FAD hydroperoxide. The hydroxyiating species is an "0H+ equivalent that arises by protonation of FAD hydroperoxide, RO-OH + H+ — ROH -+ 0H+.

The only reasonable explanation for these data is represented by gross structure 309. This could be derived from a pseudotabersonine-subtype precursor by a sequence of electrophilic hydroxylation at C-16, followed by acid-catalyzed... 

The triflic acid catalyzed electrophilic hydroxylation of aromatics with BTSP gives the corresponding phenols in high yields without apparent polyhydroxylation or secondary oxidation. Thus, treatment of CeHe with CF3SO3H followed by BTSP gave 11% PhOH. The isomer distributions are in accord with the electrophilic nature of the reaction. The observed ortho/para ratio in the case of toluene agrees with the expected trends (Scheme 4 and Table ll) . 

Electrophilic hydroxylation of ortho- andpara-y[ 2Ceil4 by peroxides including BTSP in the presence of Lewis acids gave mixtures of phenols, including those derived from ipso attack followed by rearrangement ipso attack by HO leads to dealkylation. For... 

For reviews of electrophilic hydroxylation. see Jacquesy Gesson Jouannetaud Rev. Chem. Intermed. 1988, 9, 1-26, pp. 5-10 Haines Methods for the Oxidation of Organic Compounds Academic Press New York, 1985, pp. 173-176, 347-350. 

H202 in superacids at —78°C converts simple straight-chain alkanes into primary alcohol (ethane), or secondary alcohols and ketones (propane, butane).1,62 89 9° Electrophilic hydroxylation of the secondary C—H bond by the incipient hydroxyl cation formed through the protolytic cleavage of hydroperoxo-nium ion accommodates these observations ... 

One-step electrophilic hydroxylation of aromatic compounds using various peroxide reagents in the presence of acid catalysts has been achieved. The systems studied include hydrogen peroxide in the presence of sulfuric acid,766 hydrogen fluoride,767 Lewis acids,768 769 and pyridinium poly(hydrogen fluoride).770 Lewis acid-promoted electrophilic hydroxylation with peracids,771,772 di-tcrt-butyl peroxide,773 and diisopropyl peroxydicarbonate774 775 were also described. A common feature of these reagents is the formation of monohydroxylated compounds in low yields. 

Oxenium Ions. Oxenium ions similar to nitronium ions are, in general, too reactive to be observed. The parent ion—that is, the hydroxyl cation HO+—is elusive, and it is improbable that it can be observed in its free form in the condensed state. However, the incipient hydroxyl cation is involved in acid-catalyzed electrophilic hydroxylation with protonated (or Lewis acid complexed) hydrogen peroxide (HO—OH2+) or ozone (HO—O—0+).125 Nitrous oxide is also apotential precursor for the hydroxyl cation (in its protonated form). The hydroxy diazonium ion HON2+ has not yet been observed. 

The hydrogen peroxonium ion may be considered as an incipient OH+ ion capable of electrophilic hydroxylation of single (effect reactions similar to such previously described electrophilic reactions as protolysis, alkylation, chlorination (chlorolysis), and nitration (nitrolysis). 

Because neither hydrogen peroxide nor Magic Acid-S02C1F alone led to any reaction under the conditions employed, the reaction must be considered to proceed via electrophilic hydroxylation. Protonated hydrogen peroxide inserts into the C H bond of the alkane. A typical reaction path is as depicted in Scheme 5.60 for isobutane. 

It is well-recognized that phenols are completely protonated in superacidic solutions.420 This raised the possibility that protonated phenols, once formed in these media, might resist further electrophilic attack. Electrophilic hydroxylations of aromatics with hydrogen peroxide (98%) in superacidic media has been achieved by Olah and Ohnishi617 in Magic Acid, which allows clean, high-yield preparation of monohydroxylated products. Benzene, alkylbenzenes, and halobenzenes are efficiently hydroxylated at low temperatures. The obtained yields and isomer distributions are shown in Table 5.36. Subsequently, Olah et al.618 found that benzene and... 

The only example of the quantitative study of the electrophilic hydroxylation of a heteroaromatic concerns quinoline [54JBC(208)741 ]. 

Quinoline is hydroxylated by electrophilic hydroxyl at the 3-position in 6% yield [54JBC(208)741 ]. Methylation by methanol/alumina at 450°C gives 41% of 3-methylquinoline (61BRP845562) once again under neutral conditions 3-substitution dominates. Moreover it is hard to believe that either of these results is due to adduct formation. 

Whilst direct electrophilic hydroxylation of the arylthallium species can be effected using peroxytriflu-oroacetic acid, further oxidation of the phenol to a quinone accompanies this process. This over-oxidation can be avoided by initial transmetallation to a lead species with concomitant reduction of the thallium trifluoroacetate (TTFA) by triphenylphosphine, followed by displacement of the lead by trifluo-roacetate to give the aryl trifluoroacetate. lliis hydroxylation method has yet to find use in the synthesis of molecules which are more complex than simple arenes. 

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