Directivity hydroxyl

Direct hydroxylation of benzene to phenol could be achieved using zeolite catalysts containing rhodium, platinum, palladium, or irridium. The oxidizing agent is nitrous oxide, which is unavoidable a byproduct from the oxidation of KA oil (see KA oil, this chapter) to adipic acid using nitric acid as the oxidant. 

Direct hydroxylation of an aromatic ring to yield a hydroxybenzene (a phenol) is difficult and rarely done in the laboratory., but occurs much more frequently in biological pathways. An example is the hydroxylation of p-hydroxyphenyl acetate to give 3,4-dihydroxyphenyl acetate. The reaction is catalyzed by p-hydroxyphenylacctate-3-hydroxylase and requires molecular oxygen plus the coenzyme reduced flavin adenine dinucleotide, abbreviated FADH2. 

Diols can be prepared either by direct hydroxylation of an alkene with 0s04 followed by reduction with NaHSOj or by acid-catalyzed hydrolysis of an epoxide (Section 7.8). The 0s04 reaction occurs with syn stereochemistry to give a cis diol, and epoxide opening occurs with anti stereochemistry to give a trans diol. 

There have been only a few reports of direct hydroxylation by an electrophilic... 

Samaha, R.R., Joseph, S., O Brien, B., O Brien, T.W., and Noller, H.F. (1999) Site-directed hydroxyl radical probing of 30S ribosomal subunits by using Fe(II) tethered to an interruption in the 16S rRNA chain. PNAS 96, 366. 

The calculations found there was no covalent intermediate in the viral neuraminidase reaction and the intermediate was more likely to be hydroxylated directly. Because there is only a small energy difference between the two options (formation of a covalent bond or direct hydroxylation) Thomas et al. proposed it might be possible to design inhibitors covalently bound to the enzyme. 

Heilek GM, Noller HF. Site-directed hydroxyl radical probing of the rRNA neighborhood of ribosomal protein S5. Science 1996 272 1659-1662. 

In addition to the epoxidation of olefins, zeolitic materials have been studied for other fine chemical transformations. Table 12.21 indexes the zeolites used for oxidative dehydrogenation of propane, direct hydroxylation of benzene to phenol and e-caprolactam synthesis. A recent review summarizes other reactions for which there is not enough space in the table [138, 139]. 

Co(ni) alkyl peroxides have been prepared and used by Mimoun and coworkers in the hydroxylation of hydrocarbons with this metal a Haber-Weiss type of reactivity is suggested. Square-planar Pt(II) complexes, of the type [(dppe)Pt(CF3)(solv)], used by Strukul in the epoxidation of alkenes and in Baeyer-Villiger oxidations of ketones (Schemes 8 and 9), are effective catalysts also in the direct hydroxylation of aromatics with hydrogen peroxide. The reactivity increases in the presence of electron releasing substituents in the aromatic ring. Ortho and para derivatives are practically the only products observed and interesting selectivity toward the ortho products has been detected (equation 85). 

Hydroxylation of 711 at C-2 can be achieved by an intramolecular conjugate addition of the benzamide to the enone system. The reaction takes place in high yield in the presence of a Lewis acid and affords direct hydroxylation with a syn relationship to the amide group via an intermediate 1,3-oxazoline (Scheme 7.223). " ... 

Hydroxypyridine and pyridin-2-one are sufficiently reactive to undergo Elbs oxidation, and in both cases the substituent directs hydroxylation mainly para (Scheme 40) (58JA3717). Quinoline may be converted into 3-hydroxyquinoline (6% yield) by Udenfriend oxidation (ascorbic acid and oxygen in the presence of iron(II)) which is believed to involve attack by OH+ rather than radicals (54JBC(208)74i). 

Oxidation to Phenols. Direct hydroxylation of benzene to phenol can be achieved in a free-radical process with H202 or 02 as oxidants.739-744 Metal ions [Fe(II), Cu(II), Ti(HI)] may be used to catalyze oxidation with H202. Of these reactions, the so-called Fenton-type oxidation is the most widely studied process.742 Oxidation in the presence of iron(II) sulfate was reported in early studies to yield phenol. Since phenol exhibits higher reactivity than benzene, varying amounts of isomeric dihydroxybenzenes were also formed. 

The formation of 3-halophenols in the metabolism of chlorobenzene, bromobenzene, and fluorobenzene215 cannot be explained on the basis of arene oxides as intermediates. These metabolites may represent examples of a direct hydroxylation of the ring. Besides, the magnitude of the isotopic effects observed during the metabolic formation of such meta-substituted phenols... 

The direct hydroxylation of benzene and aromatics with a mixture of 02 and H2 have been performed by simultaneously mixing benzene, oxygen and hydrogen in the liquid phase using a very complicated system containing a multi-component catalyst, a solvent and some additives. Besides the possibility of an explosive gas reaction, these hydroxylations gave only very low yields, 0.0014—0.69% of phenol and aromatic alcohols. For example, Pd-containing titanium silicalite zeolites catalyzed... 

Reproducibly of results, however, was questioned, because the total oxidation reaction was underestimated [84]. Possibly, these discrepancies derive from the observation of structural changes of the Pd-based membrane during direct hydroxylation of benzene to phenol [85]. The surface state of Pd during the reaction could be divided into two major regions the oxidized region near the gas... 

Figure 8.10 Phenol synthesis by direct hydroxylation of benzene using a hydrogen-permeable membrane. (Adapted from [83]).

Ricinoleic acid (Figure 3.8) is the major fatty acid found in castor oil from seeds of the castor oil plant (Ricinus communis Euphorbiaceae), and is the 12-hydroxy derivative of oleic acid. It is formed by direct hydroxylation of oleic acid (usually esterified as part of a phospholipid) by the action of an 02- and NADPH-dependent mixed function oxidase, but this is not of the cytochrome P-450 type. Castor oil has a long history of use as a domestic purgative, but it is now mainly employed as a cream base. Undecenoic acid (A9-undecenoic acid) can be obtained from ricinoleic acid by thermal degradation, and as the zinc salt or in ester form is used in fungistatic preparations. 

In the rabbit, phenol gives rise to catechol and quinol. Hydroxyquinol is a minor metabolite of catechol but not of quinol, and neither quinol nor resorcinol is further oxidized to trihydric phenols.126 Aniline and its derivatives do not undergo meta substitution, but give rise to ortho- and para-directed hydroxylation products only.122... 

The first example of the direct hydroxylation of arenes to phenols was reported in 1900 and described oxidation of benzene with a mixture of iron(II) sulfate and hydrogen peroxide (Fenton s reagent) [1], Low yields of phenol (21% yield based on H202) are typically obtained in such cases, in addition to significant amounts of biphenyl (24% yield based on H202) [1-3]. Both selectivity to phenol and overall... 

Phenanthridine undergoes direct hydroxylation on heating with a mixture of prefused potassium hydroxide and barium oxide at 225°, giving phenanthridone in fair yield.291 This appears to be the sole application of this reaction in the series, although it has been reported that 6-anilino- and 6-ethylaminophenanthridine also provide... 

BTI is suitable for the direct hydroxylation of ketones. Aliphatic, aromatic and heterocyclic ketones in acetonitrile-water and trifluoroacetic acid afforded a-hydroxymethyl ketones (in the range of 70%), whereas a-methylene ketones, such as propiophenone, gave less satisfactory yields. 

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