Oxidations to epoxides

The above models imply that the proton loss of the OH group of the coordinated substrate shifts the mechanism from oxidation to epoxidation with Ru(III). Such a straightforward interpretation of the pH effect was not presented for reactions of the other substrates, i.e. the protolytic reaction, which would act as a switch between the two mechanisms, cannot be identified. 

The results of the olefin oxidation catalyzed by 19, 57, and 59-62 are summarized in Tables VI-VIII. Table VI shows that linear terminal olefins are selectively oxidized to 2-ketones, whereas cyclic olefins (cyclohexene and norbomene) are selectively oxidized to epoxides. Cyclopentene shows exceptional behavior, it is oxidized exclusively to cyclopentanone without any production of epoxypentane. This exception would be brought about by the more restrained and planar pen-tene ring, compared with other larger cyclic nonplanar olefins in Table VI, but the exact reason is not yet known. Linear inner olefin, 2-octene, is oxidized to both 2- and 3-octanones. 2-Methyl-2-butene is oxidized to 3-methyl-2-butanone, while ethyl vinyl ether is oxidized to acetaldehyde and ethyl alcohol. These products were identified by NMR, but could not be quantitatively determined because of the existence of overlapping small peaks in the GC chart. The last reaction corresponds to oxidative hydrolysis of ethyl vinyl ether. Those olefins having bulky (a-methylstyrene, j8-methylstyrene, and allylbenzene) or electon-withdrawing substituents (1-bromo-l-propene, 1-chloro-l-pro-pene, fumalonitrile, acrylonitrile, and methylacrylate) are not oxidized. 

Alkenes may be oxidized to epoxides that are reactive metabolites because of ring strain [36] and can undergo nucleophilic attack. Epoxides are not always highly reactive species. In fact, some of them are relatively unreactive for example, the arene oxides that derive from oxidation of phenyl rings. Most drugs containing a phenyl... 

Furans and thiophenes are believed to be oxidized to epoxides, following the general reaction described for alkenes. However, at least in the case of tienilic add, experimental evidence shows that the reactive intermediate is an S-oxide [39]. Another example of CYP inactivation by a thiophene derivative is the covalent binding of ticlopidine to CYP2C19 [40]. 

Alkenes are also oxidized to epoxides hy peracid or peroxyacid (RCO3H), e.g. peroxyhenzoic acid (C6H5CO3H). A peroxyacid contains an extra oxygen atom compared with carboxylic acid, and this extra oxygen is added to the double bond of an alkene to give an epoxide. For example, cyclohexene reacts with peroxyhenzoic acid to produce cyclohexane oxide. 

Describing the reaction in kinetic terms, let us apply to the fact that the intermediate perFTPhPFe3+00H/Al203 formation stage (7.7) is fast, the epoxide formation stage (7.8) is slow and, consequently, limiting. For kinetic simulation of propylene oxidation to epoxide, this gives an opportunity to apply the Michaelis-Menten equation in Linuver-Berk coordinates ... 

The results of the olefin oxidation catalyzed by 1 to 6 are summarized in Tables 1-3. Table 1 shows that linear terminal olefins are selectively oxidized to 2-ketones, whereas cyclic olefins (cyclohexene and norbornene) are selectively oxidized to epoxides. Cyclopentene shows an exceptional behavior it is oxidized exclusively to cyclopentanone without any produc-... 

In contrast, trans olefins are often poor substrates for CPO. When the double bond is far from the chain terminus (i.e., from r/.v-3-alkenes upward), allylic hydro-xylation accompanies the epoxidation. In addition, with terminal monosubstituted olefins, heme alkylation occurs, thus producing inactivation of CPO. 1-Alkenes can be profitably oxidized to epoxides by CPO only when they are not monosubstituted. A detailed description of the yields and e.e. for CPO-catalyzed epoxidation of olefins has been reported by Adams and coworkers [23]. 

The patent literature claims that olefins can be partially oxidized to epoxides (73) or hydroxy epoxides (74) and alcohols may be oxidized to ketones or aldehydes (75) using various metal ion-exchanged zeolites. In the examples given, the selectivities or conversion levels to the desired products are not particularly attractive. Metal ion-exchanged zeolites do, however, appear to be quite useful catalysts for effluent treatment. For example, Cu2+X and Cu2+Y are claimed to be good catalysts for the total oxidation (incineration) of chlorinated organic compounds (76). 

L. L. Shipman, in Polynuclear Aromatic Hydrocarbons, R. Freudenthal and P. W. Jones, Eds., Raven Press, New York, 1976. Ab Initio Quantum Mechanical Characterization of the Ground Electronic State of Benzo[ ]pyrene. Implications for the Mechanism of Polynuclear Aromatic Hydrocarbon Oxidation to Epoxides by Cytochrome P-450. 

The bulk of oxidations with tert-butyl hydroperoxide consists of epoxidations of alkenes in the presence of transition metals [147, 215, 216, 217, 218]. In this way, a,p-unsaturated aldehydes [219] and ketones [220] are selectively oxidized to epoxides without the involvement of the carbonyl function. Other applications of tert-butyl hydroperoxide such as the oxidation of lactams to imides [225], of tertiary amines to amine oxides [226, 227], of phosphites to phosphates [228], and of sulfides to sulfoxides [224] are rare. In the presence of a chiral compound, enantioselective epoxidations of alcohols are successfully accomplished with moderate to high enantiomeric excesses [221, 222, 223]. 

Conjugated dienes are oxidized to epoxides (or diols, if water is present) with the MTO/H2O2 system [11]. Urea/H202 avoids the subsequent epoxide ring opening. Electron-rich and conjugated dienes are more easily oxidized than electron-poor dienes and dienes with isolated double bonds. According to kinetic measurements complex 3 plays no important role as catalyst in this case. Compound 2 is an active species [11a]. 

Functionalization reactions Some aromatic systems that can be oxidized to epoxides, quinones, or quinonimines (Fig. 5, reaction 1)... 

Independent evidence that olefin oxidation can proceed via a nonconcerted mechanism is provided by the fact that terminal olefins are not only oxidized to epoxides but, in many cases, simultaneously alkylate the P450 prosthetic heme group by covalently binding to one of its pyrrole nitrogen atoms (Fig. 4.29) [180]. It should be noted, however, that this heme alkylation process is relatively infrequent, with ratios of epoxidation to heme alkylation usually greater than 200. Despite the structures of the heme adducts, which nominally could arise by nucleophilic attack of the pyrrole nitrogen on the epoxide, epoxides are not involved in heme alkylation. This was definitely established by the fact that the synthetic epoxides do not react with the heme [181], and... 

More general application of PTC was found in oxidation of organic compounds with H2O2 and additional catalysts, oxygen derivatives ofV, W, Mo, etc. In such systems alkenes are oxidized to epoxides, alcohols to carbonyl compounds, etc. This method assures high selectivities and yields of products, operational simplicity, etc. Being simultaneously environment firiendly, it fulfills all requirements for modern industrial processes (eqs. 174-177). 

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