Active site, catalytic epoxidation

Data obtained in the catalytic epoxidation of 1-hexene over Ox-Ti-P and other samples are summarized in Table 2. Catalytic properties of Ti-P zeolites were studied by Corma et al. [4,10] and Davis et al. [11,12]. Despite some discrepancies, it is agreed that these catalysts are active in the epoxidation of olefins. Our results also indicate that all of our Ox-Ti-P and Ti-P samples are active in the epoxidation of 1-hexene. The selectivity toward epoxide was very low. The major products were ethers, obtained from solvolysis of glycol by methanol which is catalyzed by the zeolite acid sites. It was found that over Ox-Ti-P samples, the reaction takes place slowly, while the hydrogen peroxide is utilized efficiently. Over Ti-P, the reaction takes place very rapidly and is usually finished in less than 1 hour. It was also found that the parent aluminosilicate P (sample 1) was completely inactive in this reaction. Davis et al. [12] demonstrated that framework Ti is the active site in epoxidation reactions, particularly in aqueous media. It is inferred that our catalysis data provide a strong evidence that Ti(IV) species in our Ox-Ti-P samples are present as isolated framework cations. 

Hydrolysis of epoxides, esters, amides, and related structures is an important biotransformation reaction that limits the therapeutic activity of many drugs and generates therapeutically active drugs from prodmg structures. In a few cases, hydrolytic reactions can generate a toxic structure. Epoxide hydrolases and esterases are members of the a/(3 hydrolase-fold family of enzymes (Morisseau and Hammock, 2005 Satoh and Hosokawa, 2006). Although their substrate specificities are radically different (e.g., lipids, peptides, epoxides, esters, amides, haloalkanes), their catalytic mechanisms are similar. All of these enzymes have an active site catalytic triad composed of a nucleophilic serine or cysteine residue (esterases/amidases), or aspartate residue (epoxide hydrolases) to activate the substrate, and histidine residue and glutamate or aspartate residues that act cooperatively in an acid—base reaction to activate a water molecule for the hydrolytic step. 

Goodstadt, L. and Ponting, C.P. (2004). Vitamin K epoxide reductase homology, active site and catalytic mechanism. Trends in Biochemical Science 29, 289-292. 

The principle of active-site-directed inactivation of glycosidases by gly-con-related epoxides can be extended to compounds having an exocyclic oxirane ring, either directly attached to the six-membered ring (32) or at some distance (33,34). Studies with -o-glucosidase from sweet almonds and intestinal sucrase-isomaltase revealed that, in spite of the higher intrinsic reactivity of these epoxides, this shift of the position of the epoxide function causes a 10- to 30-fold decrease of kj(max)/Ki, an effect which probably reflects the limited flexibility of the catalytic groups involved in the epoxide reaction. 

Despite a higher intrinsic reactivity, epoxides of type 35 and 36 show a lower inactivation rate kj(max), as seen in Table XI, than the conduritol epoxides. This is probably caused by the greater flexibility of the epoxyalkyl chain in the active-site cleft, and by non-productive binding in positions where the oxirane is not within reach of the catalytic groups of the active site. For epoxypropyl oligosaccharides, this would hold even when the inhibitor occupies the correct subsites. 

Epoxidation of alkeneic reactants is faster on titanium-grafted silicates (such as A, B and C) than on the coprecipitated titanosilicates (such as D and E). This difference was attributed to the fact that on extra-framework titanium-grafted silicates, the catalytically active sites are virtually all exposed and accessible, whereas on the coprecipitated material some of them may be buried within the silicate walls and, thus, cannot adsorb reactant molecules. 

If the tetra- and tripodal Ti structures and the titanium oxo species derived from these structures in the presence of ROOH (R = H, alkyl) are involved as active sites and reaction intermediates, the next step beyond their identification is to seek correlations between the structure and concentrations of these titanium oxo species and catalytic activity and selectivity. Clerici and Ingallina (204) were the first to propose the Ti(02H) group as the active site of alkene epoxidation by... 

The reactions of aldehydes at 313 K [69] or 323 K [70] in CoAlPO-5 in the presence of oxygen results in formation of an oxidant capable of converting olefins to epoxides and ketones to lactones (Fig. 23). This reaction is a zeolite-catalyzed variant of metal [71-73] and non-metal-catalyzed oxidations [73,74], which utilize a sacrificial aldehyde. Jarboe and Beak [75] have suggested that these reactions proceed via the intermediacy of an acyl radical that is converted either to an acyl peroxy radical or peroxy acid which acts as the oxygen-transfer agent. Although the detailed intrazeolite mechanism has not been elucidated a similar type IIaRH reaction is likely to be operative in the interior of the redox catalysts. The catalytically active sites have been demonstrated to be framework-substituted Co° or Mn ions [70]. In addition, a sufficient pore size to allow access to these centers by the aldehyde is required for oxidation [70]. 

Results of oxidation of unsaturated alcohols are shown in Table 3. Both 2-penten-1 -ol and 3-methyl-2-buten-1 -ol exhibited higher reactivity than cyclohexene. A decrease around 20-50% in catalytic activity of organically functionalized samples has been observed. This is probably due to the inhibition of access of the rather hydrophilic substrates to the Ti-active sites surrounded by the organic groups of increased hydrophobicity. It is noteworthy that the epoxidation was favorable for the organically functionalized samples whereas the alcohol oxidation was retarded. 

The catalytic properties of Del-Ti-MWW have been compared with those of other titanosilicates in the epoxidation of cyclic alkenes (Table 4.4). The TON decreased sharply for TS-1, Ti-beta and 3D Ti-MWW with increasing molecular size of cyclic alkenes. Ti-MCM-41 with mesopores, however, showed higher TONs for cyclooctene and cyclododecene. This implies that the reaction space is extremely important for the reactions of bulky molecules. The delamination of Ti-MWW increased the TON greatly for not only cyclopentene but also bulkier cycloalkenes. Especially, the catalytic activity of Del-Ti-MWW was about 6 x higher than that of Ti-MWW for cyclooctene and cyclododecene. Del-Ti-MWW even turned out to be superior to Ti-MCM-41 in the epoxidation of bulky substrates. This should be due to the high accessibility of Ti active sites in Del-Ti-MWW. Thus the delamination was able to change Ti-MWW into an effective catalyst applicable to reactions of bulky substrates. 

However, attempts to develop similar selective catalysts failed in the case of reactions that require one oxygen atom, like the oxidation of methane, ethane and other alkanes to alcohols, aromatic compounds to phenols, alkenes to epoxides, and many others. These mechanistically simple reactions assume one difficult condition the presence of active sites that upon obtaining two atoms from gas-phase 02 can transfer only one of them to the molecule to be oxidized, reserving the second atom for the next catalytic cycle with another molecule. This problem remains a hard challenge for chemical catalysis. 

Well-defined peptides of known sequence have been used to shed light on the mechanism of catalysis in the epoxidation of enones with hydrogen peroxide [91, 93-95]. The peptide sequences of the catalysts have been systematically varied and correlated with catalytic activity and selectivity. From the many variations investigated it was concluded (i) that the N-terminal region of the peptides harbors the catalytically active site, and that (ii) a helical conformation is required for the peptide catalysts to be active. The latter conclusion is supported both by the dependence of catalytic activity on chain-length and by IR investigations [91, 94]. NMR data that might aid further elucidation of catalyst structure, interaction with the substrate enones, etc., are, unfortunately, not yet available. 

Neumann and Miller (360) reported catalytic epoxidations with analogous P-W materials in a triphasic mode. The activity in the solvent-free system is influenced by the length of the hydrocarbon spacer between the silica and the ammonium group. Cyclooctene, for example, is epoxidized with only 10% conversion when a trimethyl propyl ammonium salt is used, whereas a conversion of 45% can be obtained in the presence of an immobilized octyldimethyl benzyl ammonium salt. The enhanced conversion is probably the result of a nearly ideal hydrophilic-lipophilic balance at the active site. 

---