TBHP alcohols oxidation

The activity of the FePeCli6-S/tert-butyl hydroperoxide (TBHP) catalytic system was studied under mild reaction conditions for the synthesis of three a,p-unsaturated ketones 2-cyclohexen-l-one, carvone and veibenone by allylic oxidation of cyclohexene, hmonene, and a-pinene, respectively. Substrate conversions were higher than 80% and ketone yields decreased in the following order cyclohexen-1-one (47%), verbenone (22%), and carvone (12%). The large amount of oxidized sites of monoterpenes, especially limonene, may be the reason for the lower ketone yield obtained with this substrate. Additional tests snggested that molecular oxygen can act as co-oxidant and alcohol oxidation is an intermediate step in ketone formation. 

The heterogeneous catalytic system iron phthalocyanine (7) immobilized on silica and tert-butyl hydroperoxide, TBHP, has been proposed for allylic oxidation reactions (10). This catalytic system has shown good activity in the oxidation of 2,3,6-trimethylphenol for the production of 1,4-trimethylbenzoquinone (yield > 80%), a vitamin E precursor (11), and in the oxidation of alkynes and propargylic alcohols to a,p-acetylenic ketones (yields > 60%) (12). A 43% yield of 2-cyclohexen-l-one was obtained (10) over the p-oxo dimeric form of iron tetrasulfophthalocyanine (7a) immobilized on silica using TBHP as oxidant and CH3CN as solvent however, the catalyst deactivated under reaction conditions. 

A problem especially with oxidation catalysts is that the metals in their highest oxidation state tend to be less strongly associated with a support, so that the reaction conditions can lead to leaching of the metal complex from the support. To overcome this problem, microencapsulation, as an immobilization technique for metal complexes, has been introduced by Kobayashi and coworkers. In the microencapsulation method, the metal complex is not attached by covalent bonding but is physically enveloped by a thin film of a polymer, usually polystyrene. With this technique leaching of the metal can be prevented. In 2002, Lattanzi and Leadbeater reported on the use of microencapsulated VO(acac)2 for the epoxidation of allylic alcohols. In the presence of TBHP as oxidant, it was possible to oxidize a variety of substrates with medium to good yields (55-96%) and diastereomeric ratios (60/40 to >98/2) (equation 42). The catalyst is easily prepared and can be reused several times without significant loss in activity. 

Zrrconium(IV) and hafnium(IV) complexes have also been employed as catalysts for the epoxidation of olefins. The general trend is that with TBHP as oxidant, lower yields of the epoxides are obtained compared to titanium(IV) catalyst and therefore these catalysts will not be discussed iu detail. For example, zirconium(IV) alkoxide catalyzes the epoxidation of cyclohexene with TBHP yielding less than 10% of cyclohexene oxide but 60% of (fert-butylperoxo)cyclohexene °. The zirconium and hafnium alkoxides iu combiuatiou with dicyclohexyltartramide and TBHP have been reported by Yamaguchi and coworkers to catalyze the asymmetric epoxidation of homoallylic alcohols . The most active one was the zirconium catalyst (equation 43), giving the corresponding epoxides in yields of 4-38% and enantiomeric excesses of <5-77%. This catalyst showed the same sense of asymmetric induction as titanium. Also, polymer-attached zirconocene and hafnocene chlorides (polymer-Cp2MCl2, polymer-CpMCls M = Zr, Hf) have been developed and investigated for their catalytic activity in the epoxidation of cyclohexene with TBHP as oxidant, which turned out to be lower than that of the immobilized titanocene chlorides . ... 

Taylor and Flood could show that polystyrene-bound phenylselenic acid in the presence of TBHP can catalyze the oxidation of benzylic alcohols to ketones or aldehydes in a biphasic system (polymer-TBHP/alcohol in CCI4) in good yields (69-100%) (Scheme 117) °. No overoxidation of aldehydes to carboxylic acids was observed and unactivated allylic alcohols or aliphatic alcohols were unreactive under these conditions. In 1999, Berkessel and Sklorz presented a manganese-catalyzed method for the oxidation of primary and secondary alcohols to the corresponding carboxylic acids and ketones (Scheme 118). The authors employed the Mn-tmtacn complex (Mn/168a) in the presence of sodium ascorbate as very efficient cocatalyst and 30% H2O2 as oxidant to oxidize 1-butanol to butyric acid and 2-pentanol to 2-pentanone in yields of 90% and 97%, respectively. This catalytic system shows very good catalytic activity, as can be seen from the fact that for the oxidation of 2-pentanol as little as 0.03% of the catalyst is necessary to obtain the ketone in excellent yield. 

SCHEME 117. Alcohol oxidation under biphasic conditions using immobilized phenylseleninic acid/ TBHP as catalyst... 

TABLE 30. Comparison of the results of metal-catalyzed alcohol oxidation to ketones, carboxylic acids or aldehydes using H2O2 or TBHP... 

In 1980, Katsuki and Sharpless described the first really efficient asymmetric epoxidation of allylic alcohols with very high enantioselectivities (ee 90-95%), employing a combination of Ti(OPr-/)4-diethyl tartrate (DET) as chiral catalyst and TBHP as oxidant Stoichiometric conditions were originally described for this system, however the addition of molecular sieves (which trap water traces) to the reaction allows the epoxidation to proceed under catalytic conditions. The stereochemical course of the reaction may be predicted by the empirical rule shown in equations 40 and 41. With (—)-DET, the oxidant approaches the allylic alcohol from the top side of the plane, whereas the bottom side is open for the (-l-)-DET based reagent, giving rise to the opposite optically active epoxide. Various aspects of this reaction including the mechanism, theoretical investigations and synthetic applications of the epoxy alcohol products have been reviewed and details may be found in the specific literature . 

Oxidation of primary, secondary and benzylic alcohols with TBHP or CHP, mainly catalyzed by Mo and Zr derivatives, were performed by different authors. As an example, Ishii, Ogawa and coworkers reported the conversion of secondary alcohols such as 2-octanol to ketones mediated by catalyst 39 and TBHP. The oxidation of cyclic alcohols depended on steric factors. Zirconium alkoxides may act as catalysts in the conversion of different alcohol typologies with alkyl hydroperoxides . Secondary alcohols, if not severely hindered, are quantitatively converted to the corresponding ketones. The selectivity for equatorial alcohols is a general feature of the system, as confirmed by the oxidation of the sole cis isomer 103 of a mixture 103-bl04 (equation 68). Esters and acids could be the by-products in the oxidation of primary alcohols. 

A catalytic method for the allylic oxidation of alkenes was first reported by Umbreit and Sharpless in 1977428, who utilized TBHP as oxidant and Se02 as catalyst for selective allylic oxidation. Yields were moderate providing allylic alcohols or ketones with 54-86% yield. The reaction did not proceed under strictly anhydrous conditions but with one equivalent of water present the oxidation proceeds smoothly at room temperature. In... 

A borderline case is V(V) which has an intermediate oxidation potential [3] and can react via both mechanisms depending on the substrate used. It catalyzes epoxidations with TBHP via the peroxometal mechanism and alcohol oxidations via the oxometal pathway [7]. 

RuCls-catalyzed alcohol oxidation of carveol (4, Table 4) similarly showed a higher rate with TBHP than with PHP, suggesting that the rate-limiting step in ruthenium catalyzed oxidation of alcohols may involve reaction of a ruthenium alkoxide with RO2H, resulting in formation of the carbonyl compound with simultaneous reoxidation of the ruthenium (Scheme 4). 

The traditional method of using Cr(IV)-based oxidants is obviously unacceptable today. A number of new environmentally benign catalyst systems have recently been developed which can be used with H2O2 or TBHP as oxidant. These promote chemoselective oxidation of secondary alcohols and diols to ketones, an important class of reactions in organic synthesis. The metals used are molybdenum (Kurusu and Masuyama, 1986) and titanium. 

Contrary to the asymmetric epoxidation of allylic alcohols, the presence of water in this reaction is crucial for the enantioselection. Nevertheless, the main drawback of this method was the use of a stoichiometric amount of titanium and the use of tert-butyl hydroperoxide (TBHP) as oxidant. Efforts have been devoted to the development of more sustainable processes focusing on catalytic reactions and on the nature of oxidising agent. In 1987, Kagan and coworkers reported a catalytic version using as low as 10 mol% of titanium chiral complex in the presence of activated molecular sieves (MS). It is noteworthy that they also improved the process by using less-explosive and less-reactive cumene hydroperoxide as oxidant. A few years later, the group of Uemura developed a complementary catalytic system based on the... 

Polymer-supported tetrabromooxomolybdate(V) was claimed to be a heterogeneous catalyst for alcohol oxidations with TBHP . However, it seems likely that molybdenum is leached from the surface and the observed catalysis may be, at least partially, homogeneous in nature. The same applies to Cr(III) and Ce(IV) catalysts supported on a perfluorinated sulfonic acid resin (Nafion K) which catalyze the oxidation of alcohols with TBHP . Similarly, vanadium-pillared montmorillonite clay (V-PILC) ° and a zeolite-encapsulated vanadium picolinate complex were shown to catalyze... 

Catalyst tert-ButyUiydiperoxide (TBHP) as oxidant, and vanadyl sulfate (VOSO4) as catalyst Keywords Primary and secondary alcohols, tert-butylhydrperoxide (TBHP), vanadyl sulfate, acetonitrile-water (1 1), room temperature, oxidation, aldehydes/ketones... 

Aerobic and peroxidative oxidations of alcohols, in particular of benzylic alcohols, are typical model reactions due to their importance and generality inexpensive O2, H2O2 or tejt-butyl hydroperoxide (TBHP) oxidants, and simple procedures are usually involved. In this section, an overview of some interesting catalytic systems, which were lately introduced into the field of alcohol oxidation, is presented. This concerns mainly homogeneous systems, since recent advances on heterogeneous catalysts are included in Section 8. Moreover, a glance at new substrates and oxidants which could successfully be used in a near future and make a difference in terms of efficiency, selectivity, economy and/or sustainability of the processes, is also presented. 

Biomimetic Cu(II) and Fe(II) complexes with bis- and tris-pyridyl amino and imino thioether ligands and vacant (or potentially so) coordination positions (Fig. y are active as catalyst precursors for the solvent- and halogen-free MW-assisted oxidation of 1-phenylethanol by TBHP, in the presence of pyridazine or other N-based additives. Maximum TOF of 5220 h (corresponding to 87% yield) was achieved just after 5 min of reaction time under the low power MW irradiation. The same authors reported" the catalytic activity of related copper, iron, and vanadium systems with mixed-N,S pyridine thioether hgands. The Cu and Fe complexes proved to be useful catalysts in various MW-assisted alcohol oxidations with TBHP, at 80 °C. Thus, 5-containing ligands can also be used to create effective catalyst precursors. 

The accelerating effect of MW irradiation in the synthesis of ketones from secondary alcohols with TBHP as oxidant was also reported. 

The first practical method for asymmetric epoxidation of primary and secondary allylic alcohols was developed by K.B. Sharpless in 1980 (T. Katsuki, 1980 K.B. Sharpless, 1983 A, B, 1986 see also D. Hoppe, 1982). Tartaric esters, e.g., DET and DIPT" ( = diethyl and diisopropyl ( + )- or (— )-tartrates), are applied as chiral auxiliaries, titanium tetrakis(2-pro-panolate) as a catalyst and tert-butyl hydroperoxide (= TBHP, Bu OOH) as the oxidant. If the reaction mixture is kept absolutely dry, catalytic amounts of the dialkyl tartrate-titanium(IV) complex are suflicient, which largely facilitates work-up procedures (Y. Gao, 1987). Depending on the tartrate enantiomer used, either one of the 2,3-epoxy alcohols may be obtained with high enantioselectivity. The titanium probably binds to the diol grouping of one tartrate molecule and to the hydroxy groups of the bulky hydroperoxide and of the allylic alcohol... 

A number of reaction variables or parameters have been examined. Catalyst solutions should not be prepared and stored since the resting catalyst is not stable to long term storage. However, the catalyst solution must be aged prior to the addition of allylic alcohol or TBHP. Diethyl tartrate and diisopropyl tartrate are the ligands of choice for most allylic alcohols. TBHP and cumene hydroperoxide are the most commonly used terminal oxidant and are both extremely effective. Methylene chloride is the solvent of choice and Ti(i-OPr)4 is the titanium precatalyst of choice. Titanium (IV) t-butoxide is recommended for those reactions in which the product epoxide is particularly sensitive to ring opening from alkoxide nucleophiles. ... 

The Sharpless-Katsuki asymmetric epoxidation (AE) procedure for the enantiose-lective formation of epoxides from allylic alcohols is a milestone in asymmetric catalysis [9]. This classical asymmetric transformation uses TBHP as the terminal oxidant, and the reaction has been widely used in various synthetic applications. There are several excellent reviews covering the scope and utility of the AE reaction... 

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