Ethylbenzene hydroxylation

Filipovic D, Paulsen MD, Loida PJ, Sligar SG, Om-stein RL (1992) Ethylbenzene hydroxylation by cytochrome P450cam. Biochem Biophys Res Comm 189 488 95... 

Whereas benzyhc hydroxyl functions such as in benzyl alcohol are converted by TIS 17 into benzyl iodide 1734 [2, 7] and HMDSO 7 and I2, 1-phenylethanol 1735 [8] is reduced in high yields on longer reaction times with excess TIS 17 via the iodide 1736 to give ethylbenzene 1737 [7-11] (Scheme 12.2). Ether cleavage of 1738 with TIS 17 affords, via 1739a and 1739b, the bicyclic compound 1740 in... 

The active alkoxyl radicals formed by this reaction start new chains. Apparently, the hydroperoxide group penetrates in the polar layer of the micelle and reacts with the bromide anion. The formed hydroxyl ion remains in the aqueous phase, and the MePhCHO radical diffuses into the hydrocarbon phase and reacts with ethylbenzene. The inverse emulsion of CTAB accelerates the decay of hydroperoxide MePhCHOOH. The decomposition of hydroperoxide occurs with the rate constant k = 7.2 x 1011 exp(-91.0/R7) L mol-1 s-1 (T = 323-353 K, CTAB, ethylbenzene [28]). The decay of hydroperoxide occurs more rapidly in an 02 atmosphere, than in an N2 atmosphere. 

The tra x-[Ru (0)2(por)] complexes are active stoichiometric oxidants of alkenes and alkylaro-matics under ambient conditions. Unlike cationic macrocyclic dioxoruthenium I) complexes that give substantial C=C bond cleavage products, the oxidation of alkenes by [Ru (0)2(por)] affords epoxides in good yields.Stereoretentive epoxidation of trans- and cw-stilbenes by [Ru (0)2(L)1 (L = TPP and sterically bulky porphyrins) has been observed, whereas the reaction between [Ru (0)2(OEP)] and cix-stilbene gives a mixture of cis- and trani-stilbene oxides. Adamantane and methylcyclohexane are hydroxylated at the tertiary C—H positions. Using [Ru (0)2(i)4-por)], enantioselective epoxidation of alkenes can be achieved with ee up to 77%. In the oxidation of aromatic hydrocarbons such as ethylbenzenes, 2-ethylnaphthalene, indane, and tetrahydronaphthalene by [Ru (0)2(Z>4-por )], enantioselective hydroxylation of benzylic C—H bonds occurs resulting in enantioenriched alcohols with ee up to 76%. ... 

The metabolism of ethylbenzene in humans occurs along one major pathway which is oxidation at the a-carbon, yielding 1-phenylethanol (also called a-methylbenzyl alcohol) as the primary product. A metabolic scheme is presented in Figure 1. The a-carbon of ethylbenzene is a prochiral centre and hydroxylation thus yields a chiral product. The issue of stereoselectivity has been addressed in animal studies (see Section 4.1.2). 

Ethylbenzene is well absorbed from the skin, lungs and gastrointestinal tract. It is virtually completely metabolized, the primary pathways being hydroxylation of the two carbons of the side-chain, followed by further oxidation to a range of metabolites that are excreted principally in the urine. The fate of ethylbenzene is similar in animals and humans. 

Benzylic and allylic positions are hydroxylated by CPO in halide-dependent catalytic transformations. Toluene and p-xylene are oxidized to the respective aldehydes and carboxylic acids [247, 248]. Ethylbenzene and other substrates with longer alkyl chains form the respective benzylic/allylic alcohols with high enantio-selectivity. Straight-chain aliphatic and cyclic (Z)-alkenes are hydroxylated, favoring small unsubstituted substrates in which the double bond is not more than two carbon atoms from the terminus. Steric control is observed for benzylic hydroxylations. 

Complex (2) is an effective catalyst for the asymmetric hydroxylation of aromatic hydrocarbons with 2,6-dichloropyridine IV-oxide as terminal oxidant. Up to 76% ee was achieved for the catalytic hydroxylation of 4-ethyltoluene, 1,1-diethylindane, and benzylcyclopropane. Both electron-donating and -withdrawing substituents were found to accelerate the catalytic oxidation reaction. A large primary kinetic isotope effect (kH/kD = 11 at 298 K) was observed for the catalytic ethylbenzene-dio oxidation. A... 

A mixed oxide of ruthenium, copper, iron and alumnium has been developed as a catalyst for the synthesis of aldehydes and ketones from alcohols.258 Oxidation of chiral secondary 1,2-diols with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone under ultrasound wave promotion leads to the selective oxidation of benzylic or allylic hydroxyl group. The configuration of the adjacent chiral centre is retained.259 The kinetics of oxidation of ethylbenzene in the presence of acetic anhydride have been studied.260... 

Significant characteristics of the porphyrin iron monoxide are seen in the chemical reactivity. Naphthalene is converted initially to the corresponding arene oxide on treatment with P 450 (19), consistent with a molecular mechanism of oxygen transfer from an iron monoxide to the aromatic nucleus. Retention of stereochemistry in the P-450 catalyzed hydroxylation of d ethylbenzene also supports the molecular mechanism. The unusually large kinetic isotope effect observed for the P-450 oxidation of dideutero 1,3-diphenylpropane, kJkD = 11, demonstrates that C—H cleavage is involved in the rate determining step (20), probably in a very unusual environment, not incompatible with a molecular mechanism. 

Iron-containing cytochrome P-450 constitutes the most famous example of a selective C-H bond oxidizer. Although the exact nature of the mechanism remains controversial, the reaction most likely proceeds through radical intermediates [2]. The hydroxylation of activated C-H bonds has also been carried out in the presence of synthetic porphyrin complexes. In these biomimetic processes, ruthenium plays a relatively minor role when compared with iron. Zhang et al. [50], however, recently reported the enantioselective hydroxylation of benzylic C-H bonds using ruthenium complexes supported by a D4-sym-metric porphyrin bearing a crafted chiral cavity. Thus, complex 23 reacts in a stoichiometric manner with ethylbenzene to give phenethyl alcohol with a... 

The electro-Fenton method (or EFR) was initially used for synthetic purposes considering the hydroxylation of aromatics in the cathodic compartment of a divided cell. Thus, the production of phenol from benzene (Tomat and Vecchi 1971 Tzedakis et al. 1989), (methyl)benzaldehydes and (methyl)benzyl alcohols from toluene or polymethylbenzenes (Tomat and Rigo 1976,1979,1984,1985) by adding Fe3+ to generate Fe2+ via reaction (19.13), as well as benzaldehyde and cresol isomers from toluene or acetophenone and ethylphenol isomers from ethylbenzene (Matsue et al. 1981) with direct addition of Fe2+, have been described. Further studies have reported the polyhydroxylation of salicylic acid (Oturan et al. 1992)... 

The fungus MortiereUa isabellina (NRRL 1757) hydioxylates die ethylbenzenes (92) to the 1-aiyledui-nols (93 equation 32) with a degree of enantioselectivity as shown in Table 9. By-pioducts resulting from terminal carbon hydroxylation and overoxidation (aceu henones) are also obtained. ... 

Table 9 Benzylic Hydroxylation of Ethylbenzenes by Mortierella isellina...

Ti-MOR promoted the ring hydroxylation of toluene, ethylbenzene and xylenes with negligible oxidation of the ethyl side chain [59]. In the same study, however, and in contrast to earlier ones, a similar result was also reported for TS-1. No oxidation of benzylic methyls was observed. Cumene yielded mainly the decomposition products of cumyl hydroperoxide. The oxidation of t-butylbenzene was negligibly low. The reachvity order, toluene > benzene > ethylbenzene > cumene, reflects the reduced steric constraints in the large pores of mordenite. Accordingly, the rate of hydroxylation ofxylene isomers increased in the order para < ortho < meta, in contrast to the sterically controlled one, ortho < meta para, shown on TS-1. It is worth menhoning that the least hindered p-xylene exhibited the same reactivity on either catalyst. 

Zeolite-encapsulated perfluorinated ruthenium phthalocyanines catalyze the oxidation of cyclohexane with t-BuOOH [146]. A dioxoruthenium complex with a D4-chiral porphyrin ligand has been used for the enantioselective hydroxylation of ethylbenzene to give a-phenylethyl alcohol with 72% e.e. [147]. 

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