Epoxidation aromatic ring

Selective oxidation of either the aromatic ring or the side chain can also be accompHshed. For example, epoxidation of the double bond of cinnamic acid is effected in excellent yield by treatment with potassium hydrogen persulfate (10). 

The diastereomeric excess (d.e.) of 76a reached 72% (epoxidation) and 98% (dihydroxylation). Nitro substitution on the aromatic ring (as in 77a) significantly reduced the selectivity (increased the syn proportion), although anti preference was stiU retained in epoxidation (20% d.e.) and in dihydroxylation (68% d.e.). 

The wide range of oxidations catalyzed by cytochrome P450 is illustrated by the examples given in Figure 2.5. Aromatic rings are hydroxylated, as in the case of 2,6 -dichlorobiphenyl. The initial product is usually an epoxide, but this rearranges... 

FIGURE 2.6 The procarcinogen benzo[a]pyrene oriented in the CYPlAl active site (stereo view) via n- n stacking between aromatic rings on the substrate and those of the complementary amino acid side chains, such that 7,8-epoxidation can occur. The substrate is shown with pale lines in the upper structures. The position of metabolism is indicated by an arrow in the lower structure (after Lewis 1996). 

Sherrington et al. were the first to attempt the synthesis of chiral polymeric metal complexes by the chemical modification route,78,177,178 whereby the [Mn(salen)Cl] units are attached in a pendant fashion, by only one of the aromatic rings, to poly(styrene) or poly(methacrylate) resin beads of various morphology. Epoxidation of 1-phenylcyclohexene gave enantioselectivity values between 61% and 91%. 

An exploration of structural modifications on the activity of prolinol catalysts has been published <06T12264>. More electron-rich aromatic rings on the prolinol scaffold improve the activity in the epoxidation of a, 3-enones. The reaction of 10 with an enone and f-BuOOH provides the epoxy-ketones with moderate levels of enantioselectivity. 

As with an isolated double bond, epoxide formation in an aromatic ring, i.e., arene oxide formation, can occur mechanistically either by a concerted addition of oxene to form the arene oxide in a single step, pathway 1, or by a stepwise process, pathway 2 (Fig. 4.78). The stepwise process, pathway 2, would involve the initial addition of enzyme-bound Fe03+ to a specific carbon to form a tetrahedral intermediate, electron transfer from the aryl group to heme to form a carbonium ion adjacent to the oxygen adduct followed by... 

Epoxides, also known to chemists as oxiranes, result from the monooxygenation of a C=C bond in olefins or aromatic rings. Such reactions of monooxygenation to produce epoxides as metabolites or metabolic intermediates... 

Oxidation reactions can be divided into two kinds those in which oxygen is incorporated into the drug molecule, and those in which primary oxidation causes part of the molecule to be lost The former include hydroxylations, epoxidations, and sulfoxidations. Hydroxylations may involve alkyl substituents (e.g., pentobarbital) or aromatic ring systems (e.g propranolol). In both cases, products are formed that are conjugated to an organic acid residue, e.g., glucuronic add, in a subsequent Phase 11 reaction. 

---