Epoxidation of olefin

The reactions of olefins with peracids to form epoxides allows for the selective oxidation of carbon-carbon double bonds in the presence of other functional groups which may be subject to oxidation (for example, hydroxyl groups). The epoxides that result are easily cleaved by strong acids to diols or half-esters of diols and are therefore useful intermediates in the synthesis of polyfunctional compounds. 

Caution All reactions with organic peroxides should be conducted behind a safety shield, since peroxides occasionally explode. 

A solution of 21 g (0.15 mole) of perbenzoic acid (Chapter 17, Section II) in 250 ml of chloroform is prepared in a 500-ml round-bottom flask. Styrene (15 g, 0.145 mole) is added, and the solution is maintained at 0° for 24 hours with frequent shaking during the first hour. At the end of the reaction period, only the slight excess of perbenzoic acid remains. The benzoic acid is extracted from the reaction mixture by washing several times with 10% sodium hydroxide solution. The solution is then washed with water and dried over anhydrous sodium sulfate. Fractional distillation gives 24-26 g (69-75%) of 1,2-epoxyethylbenzene, bp 101 /40 mm. 

The indirect electrochemical generation of propylene oxide via propylene chloro- or bromohydrin using anodically generated hypochlorite or hypobromite has been studied very intensively. The reason is the lack of a technically useful process for the synthesis of propylene oxide by way of heterogeneous catalysis. The propylene halohydrins are saponified using the cathodically generated sodium hydroxide (Eqs. (42)-(47)) (Table 4. No. 12-15) 

This process has, however, not yet found industrial application. Similarly, poly-isoprenoids can be epoxidized regioselectively in co-position to functional groups (Table 4, No. 16-19) Polymer-bound mediators can also be used in this 

In 2006, our research group proposed the selective epoxidation of a-olefins by combining, at room temperature and in MeCN, stoichiometric amounts of acetaldehyde with catalytic quantities of NHPI under oxygen atmosphere [12]. 

The process was successfully apphed to the synthesis of propylene oxide in MeCN [13]. 

Due to the advantageous reactor net volume versus the heating/cooling surface ratio of the MJOD reactor tube, an exceptionally good heat transfer capacity is achieved. Moreover, extremely good mixing of the components is obtained by the oscillation of the disks, resulting in an excellent mass transfer capacity. These properties usually result in a substantially increased reaction rate. 

For all the olefins investigated under continuous-flow conditions, we obtained high conversions and yields ( 80%) of the desired epoxides. Moreover, the process was substantially accelerated, shortening the residence time from 24 to 48 h (batch process) to only 1 - 4 h, with a standard production of about 80 g/day, which makes this protocol appealing for applications in pharmaceutical industry. 

Epoxides are versatile intermediates in organic synthesis. The most general reagents for conversion of aUcenes to epoxides in homogeneous conditions are peroxycarboxyUc acids. The oxidation is believed to be a concerted process. Moreover, a process to avoid acidic conditions involves reaction with hydrogen peroxide. There is a clear demand for solid materials that catalyze epoxidations, therefore heterogeneous epoxidation remains a very active field of research [51]. 

In this chapter only titanium-catalyzed reactions with organic peroxides are compared. 

The classical Ti-Si02 catalyst was initially prepared from TiCh and pyrogenic Si02 in 1969 [52]. Almost 30 years later, Maier et al. [53] synthesized calcinated xerogels via a sol-gel process with TEOS and various Ti-cyclopentadienyl complexes (entry 1, Table 5.3). In 1995, Baiker [54] demonstrated that sol-gel prepared titania-silica mixed aerogels showed better catalytic behavior in epoxidation of different bulky olefins than Ti zeolites [55] and silica supported titania described at that time [56]. The most common oxidant was cumene peroxide. The drying method, the titanium content and the calcination temperature were the most important parameters. Aerogels dried by semicontinuous extraction with supercritical CO2 at low temperature were found to be more efficient (entry 2, Table 5.3). In 2001 Baiker described the preparation of a series of titania-silica mixed 

Entry Catalyst Titanium source Ti content Substrates Yield (%) Ref. 

1 Ti-SiOj xerogel CpjTiCh (CpTiCfijO 0.08-03 mol% Ti 1,3-cyclooctadiene cyclooctene cyclohexene 1-octene 17 2 (GLC) 53 

V and Co has been widely investigated [28]. This section will highlight some novel and unique approaches to epoxide synthesis using environmentally benign oxidants and heterogeneous metal catalysts such as solid-supported Ti, polyoxometalates and hydrotaldte. 

Furthermore, the following reactions catalyzed by fiamework metal-containing zeotype materials have been reported however, there are currently no major commercial applications  

1 Epoxidation of propylene to propylene oxide with hydrogen peroxide 

There are various recent developments in this area. Forlin et al. (i84), Goebbel et al. (i85), and Hofen and Thiele ( 86) developed continuous epoxidation processes with hydrogen peroxide. The incorporation of an additional metallic element improved the activity of TS-1, as demonstrated with doubly-substituted sdicalites containing the combinations titanium-vanadium (131) or titanium-tin (187). The hydrophobicity of the catalysts was found to be important for the epoxidation activity (188). The preparation of extruded catalysts based on TS-1 for application in propylene epoxidation (26a) was described, and titanosilicate beads with hierarchical porosity (99a) were investigated. 

The TS-1-catalyzed propylene epoxidation has attracted significant interest from groups working on theoretical modeling, and numerous papers address the mechanism of epoxidation of propylene (191).WeU.setal. (191b) 

The use of a consistent level of theory allowed, for the first time, a meaningful comparison of the energetics associated with each of these pathways. The authors rigorously identified the important reaction intermediates and transition states and carried out a detailed thermochemical analysis. A summary of transition-state parameters for all of the mechanisms proposed 

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Arsenic Peroxides. Arsenic peroxides have not been isolated however, elemental arsenic, and a great variety of arsenic compounds, have been found to be effective catalysts ia the epoxidation of olefins by aqueous hydrogen peroxide. Transient peroxoarsenic compounds are beheved to be iavolved ia these systems. Compounds that act as effective epoxidation catalysts iaclude arsenic trioxide, arsenic pentoxide, arsenious acid, arsenic acid, arsenic trichloride, arsenic oxychloride, triphenyl arsiae, phenylarsonic acid, and the arsenates of sodium, ammonium, and bismuth (56). To avoid having to dispose of the toxic residues of these reactions, the arsenic can be immobi1i2ed on a polystyrene resia (57). 

The tert-huty hydroperoxide is then mixed with a catalyst solution to react with propylene. Some TBHP decomposes to TBA during this process step. The catalyst is typically an organometaHic that is soluble in the reaction mixture. The metal can be tungsten, vanadium, or molybdenum. Molybdenum complexes with naphthenates or carboxylates provide the best combination of selectivity and reactivity. Catalyst concentrations of 200—500 ppm in a solution of 55% TBHP and 45% TBA are typically used when water content is less than 0.5 wt %. The homogeneous metal catalyst must be removed from solution for disposal or recycle (137,157). Although heterogeneous catalysts can be employed, elution of some of the metal, particularly molybdenum, from the support surface occurs (158). References 159 and 160 discuss possible mechanisms for the catalytic epoxidation of olefins by hydroperoxides. 

Specialty Epoxy Resins. In addition to bisphenol, other polyols such as aUphatic glycols and novolaks are used to produce specialty resins. Epoxy resins may also include compounds based on aUphatic, cycloaUphatic, aromatic, and heterocycHc backbones. Glycidylation of active hydrogen-containing stmctures with epichlorohydrin and epoxidation of olefins with peracetic acid remain the important commercial procedures for introducing the oxirane group into various precursors of epoxy resins. 

Molybdenum compounds Hydrodesulphurization and hydrotreating of petroleum Oxidation of methanol to formaldehdye Epoxidation of olefins Decomposition of alkali metal nitrides Irritation of eyes and respiratory tract Pneumoconiosis... 

As electrophilic substitutes for peracids, the use of borate ester induced decomposition of alkyl hydroperoxides and molybdenum VI peroxy-complexes have been reported in the recent literature. Although these reagents have led to the epoxidation of olefins in greater than 90% yield there are no reports yet of their application to steroid olefins. 

Boger et al. prepared Duocarmycin SA via asymmetric epoxidation of a cyclic olefin 54." The stereochemistry set by the epoxidation step was used for subsequent C-C bond forming reactions. Epoxidation of olefin 54 was carried at -78°C to provide... 

The epoxidation of olefins, as well as other oxidative procedures, require the use of percarboxylic acids. Two of the more easily prepared and more stable compounds are given below. 

There are several available terminal oxidants for the transition metal-catalyzed epoxidation of olefins (Table 6.1). Typical oxidants compatible with most metal-based epoxidation systems are various alkyl hydroperoxides, hypochlorite, or iodo-sylbenzene. A problem associated with these oxidants is their low active oxygen content (Table 6.1), while there are further drawbacks with these oxidants from the point of view of the nature of the waste produced. Thus, from an environmental and economical perspective, molecular oxygen should be the preferred oxidant, because of its high active oxygen content and since no waste (or only water) is formed as a byproduct. One of the major limitations of the use of molecular oxygen as terminal oxidant for the formation of epoxides, however, is the poor product selectivity obtained in these processes [6]. Aerobic oxidations are often difficult to control and can sometimes result in combustion or in substrate overoxidation. In... 

Epoxidations of Olefins Catalyzed by Early Transition Metals... 

The introduction of chlorinated porphyrins (10) allowed for hydrogen peroxide to be used as terminal oxidant [62], These catalysts, discovered by Mansuy and coworkers, were demonstrated to resist decomposition, and efficient epoxidations of olefins were achieved when they were used together with imidazole or imidazo-lium carboxylates as additives, (Table 6.6, Entries 1 and 2). 

Table 6.7 Manganese sulfate-catalyzed epoxidation of olefins using aqueous H2O2 (30%).[al...

The use of rhenium-based systems for the epoxidation of olefins has increased considerably during the last ten years [87]. In 1989, Jgrgensen stated, the catalytic... 

Table 6.9 MTO-catalyzed epoxidation of olefins with H202.

Table 6.10 MTO-catalyzed epoxidation of olefins with anhydrous H2O2 or with aqueous H2O2 in fluorous solvents.131...

Asymmetric epoxidation of olefins with ruthenium catalysts based either on chiral porphyrins or on pyridine-2,6-bisoxazoline (pybox) ligands has been reported (Scheme 6.21). Berkessel et al. reported that catalysts 27 and 28 were efficient catalysts for the enantioselective epoxidation of aryl-substituted olefins (Table 6.10) [139]. Enantioselectivities of up to 83% were obtained in the epoxidation of 1,2-dihydronaphthalene with catalyst 28 and 2,6-DCPNO. Simple olefins such as oct-l-ene reacted poorly and gave epoxides with low enantioselectivity. The use of pybox ligands in ruthenium-catalyzed asymmetric epoxidations was first reported by Nishiyama et al., who used catalyst 30 in combination with iodosyl benzene, bisacetoxyiodo benzene [PhI(OAc)2], or TBHP for the oxidation of trons-stilbene [140], In their best result, with PhI(OAc)2 as oxidant, they obtained trons-stilbene oxide in 80% yield and with 63% ee. More recently, Beller and coworkers have reexamined this catalytic system, finding that asymmetric epoxidations could be perfonned with ruthenium catalysts 29 and 30 and 30% aqueous hydrogen peroxide (Table 6.11) [141]. Development of the pybox ligand provided ruthenium complex 31, which turned out to be the most efficient catalyst for asymmetric... 

Vinylepoxides can be obtained by various strategies, all with their inherent limitations. Racemic epoxidation of olefins is a straightforward route to epoxides, as pure trans- or cis-epoxides can be obtained from ( )- or (Z)-alkenes, respectively. Various oxidants - such as mCPBA and other peracids, H2O2, or VO(acac)2/TBHP - can all be employed in this transformation [1],... 

Epoxidation of olefins with meta-chloroperbenzoic acid, (MCPBA) remains to this day among the most widely used methods for research-scale applications [16], Discovered by Nikolai Prilezahev in 1909 [17], it became popular only decades later, mostly through the works of Daniel Swern in the 1940s [18]. Despite its simplicity, and not unlike most epoxidation methods in use today, it suffers from undesired epoxide opening caused by the slight acidity of the reaction milieu. Although acid-catalyzed side reactions can sometimes be minimized by use of buffered systems... 

Table 12.2 Epoxidation of olefins with bis(trimethylsilyl) peroxide (BTSP) catalyzed by high-valent oxorhenium deri-vatives> bl...

The numerous biotransformations catalyzed by cytochrome P450 enzymes include aromatic and aliphatic hydroxylations, epoxidations of olefinic and aromatic structures, oxidations and oxidative dealkylations of heteroatoms and as well as some reductive reactions. Cytochromes P450 of higher animals may be classified into two broad categories depending on whether their substrates are primarily endogenous or xenobiotic substances. Thus, CYP enzymes of families 1-3 catalyze... 

Metal-Catalyzed Direct Hydroxy-Epoxidation of Olefins," Adam. W. Richter, M.J. Accts. Chem. Res., 1994, 27, 57... 

The catalytic activities of synthesized catalysts were measured for epoxidation of olefins... 

As an example heme-models have been reported to catalyze the epoxidation of olefins to the corresponding epoxides in good yield [16, 17]. In particular, [Fe TPP)Cl] (TPP = 5,10,15,20-meso-tetraphenylporphyrin) was reported to oxidize naturally occurring propenylbenzenes to the corresponding epoxides up to 98% selectivity (conversion 98%) using H2O2 as oxidant [16]. The major drawback... 

In addition, also nonheme iron catalysts containing BPMEN 1 and TPA 2 as ligands are known to activate hydrogen peroxide for the epoxidation of olefins (Scheme 1) [20-26]. More recently, especially Que and coworkers were able to improve the catalyst productivity to nearly quantitative conversion of the alkene by using an acetonitrile/acetic acid solution [27-29]. The carboxylic acid is required to increase the efficiency of the reaction and the epoxide/diol product ratio. The competitive dihydroxylation reaction suggested the participation of different active species in these oxidations (Scheme 2). 

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