Epoxidation hydroperoxides

Acid-catalyzed intramolecular attack of nucleophilic hydroperoxide function on an oxirane ring results in formation of 3-(l-hydroxyalkyl)endoperoxides. For example, epoxidation of unsaturated hydroperoxide 320 affords oxirane-hydroperoxide 321 (66%), which through acid-catalyzed regioselective cyclization gives 1,2-dioxolane 322 (70%) (Scheme 79) . This type of reaction is applicable also to a more complex epoxide-hydroperoxide such as 323, which cyclizes to polyfunctionalized 5-membered cyclic... 

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... 

An oxirane process utilizes ethylbenzene to make the hydroperoxide, which then is used to make propylene oxide [75-56-9]. The hydroperoxide-producing reaction is similar to the first step of cumene LPO except that it is slower (2,224,316—318). In the epoxidation step, a-phenylethyl alcohol [98-85-1] is the coproduct. It is dehydrated to styrene [100-42-5]. The reported 1992 capacity for styrene by this route was 0.59 X 10 t/yr (319). The corresponding propylene oxide capacity is ca 0.33 x 10 t/yr. The total propylene oxide capacity based on hydroperoxide oxidation of propylene [115-07-1] (coproducts are /-butyl alcohol and styrene) is 1.05 x 10 t/yr (225). 

The addition of an oxygen atom to an olefin to generate an epoxide is often catalyzed by soluble molybdenum complexes. The use of alkyl hydroperoxides such as tert-huty hydroperoxide leads to the efficient production of propylene oxide (qv) from propylene in the so-called Oxirane (Halcon or ARCO) process (79). 

Reaction conditions depend on the reactants and usually involve acid or base catalysis. Examples of X include sulfate, acid sulfate, alkane- or arenesulfonate, chloride, bromide, hydroxyl, alkoxide, perchlorate, etc. RX can also be an alkyl orthoformate or alkyl carboxylate. The reaction of cycHc alkylating agents, eg, epoxides and a2iridines, with sodium or potassium salts of alkyl hydroperoxides also promotes formation of dialkyl peroxides (44,66). Olefinic alkylating agents include acycHc and cycHc olefinic hydrocarbons, vinyl and isopropenyl ethers, enamines, A[-vinylamides, vinyl sulfonates, divinyl sulfone, and a, P-unsaturated compounds, eg, methyl acrylate, mesityl oxide, acrylamide, and acrylonitrile (44,66). 

Hydroperoxide Process. The hydroperoxide process to propylene oxide involves the basic steps of oxidation of an organic to its hydroperoxide, epoxidation of propylene with the hydroperoxide, purification of the propylene oxide, and conversion of the coproduct alcohol to a useful product for sale. Incorporated into the process are various purification, concentration, and recycle methods to maximize product yields and minimize operating expenses. Commercially, two processes are used. The coproducts are / fZ-butanol, which is converted to methyl tert-huty ether [1634-04-4] (MTBE), and 1-phenyl ethanol, converted to styrene [100-42-5]. The coproducts are produced in a weight ratio of 3—4 1 / fZ-butanol/propylene oxide and 2.4 1 styrene/propylene oxide, respectively. These processes use isobutane (see Hydrocarbons) and ethylbenzene (qv), respectively, to produce the hydroperoxide. Other processes have been proposed based on cyclohexane where aniline is the final coproduct, or on cumene (qv) where a-methyl styrene is the final coproduct. 

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. 

Table 4. Solvents for Purification of Propylene Oxide From Epoxidation Using fe/t-Butyl Hydroperoxide...

The coproduct 1-phenylethanol from the epoxidation reactor, along with acetophenone from the hydroperoxide reactor, is dehydrated to styrene in a vapor-phase reaction over a catalyst of siUca gel (184) or titanium dioxide (170,185) at 250—280°C and atmospheric pressure. This product is then distilled to recover purified styrene and to separate water and high boiling organics for disposal. Unreacted 1-phenylethanol is recycled to the dehydrator. 

PO—SM Coproduction. The copioduction of propylene oxide and styrene (40—49) includes three reaction steps (/) oxidation of ethylbenzene to ethylbenzene hydroperoxide, (2) epoxidation of ethylbenzene hydroperoxide with propylene to form a-phenylethanol and propylene oxide, and (3) dehydration of a-phenylethanol to styrene. 

The oxidation step is similar to the oxidation of cumene to cumene hydroperoxide that was developed earlier and is widely used in the production of phenol and acetone. It is carried out with air bubbling through the Hquid reaction mixture in a series of reactors with decreasing temperatures from 150 to 130°C, approximately. The epoxidation of ethylbenzene hydroperoxide to a-phenylethanol and propylene oxide is the key development in the process. 

Peroxide Titanate Complexes. Titanates may influence reactions of organic peroxides (see Peroxides, organic). For example, /-butyl hydroperoxide epoxidizes olefins ... 

The most important chemical reaction of chi orohydrin s is dehydrochloriaation to produce epoxides. In the case of propylene oxide. The Dow Chemical Company is the only manufacturer ia the United States that still uses the chlorohydrin technology. In 1990 the U.S. propylene oxide production capacity was hsted as 1.43 x 10 t/yr, shared almost equally by Dow and Arco Chemical Co., which uses a process based on hydroperoxide iatermediates (69,70). More recentiy, Dow Europe SA, aimounced a decision to expand its propylene oxide capacity by 160,000 metric tons per year at the Stade, Germany site. This represents about a 40% iacrease over the current capacity (71). 

Physical and Chemical Properties. The (F)- and (Z)-isomers of cinnamaldehyde are both known. (F)-Cinnamaldehyde [14371-10-9] is generally produced commercially and its properties are given in Table 2. Cinnamaldehyde undergoes reactions that are typical of an a,P-unsaturated aromatic aldehyde. Slow oxidation to cinnamic acid is observed upon exposure to air. This process can be accelerated in the presence of transition-metal catalysts such as cobalt acetate (28). Under more vigorous conditions with either nitric or chromic acid, cleavage at the double bond occurs to afford benzoic acid. Epoxidation of cinnamaldehyde via a conjugate addition mechanism is observed upon treatment with a salt of /-butyl hydroperoxide (29). 

When heated in the presence of a carboxyHc acid, cinnamyl alcohol is converted to the corresponding ester. Oxidation to cinnamaldehyde is readily accompHshed under Oppenauer conditions with furfural as a hydrogen acceptor in the presence of aluminum isopropoxide (44). Cinnamic acid is produced directly with strong oxidants such as chromic acid and nickel peroxide. The use of t-butyl hydroperoxide with vanadium pentoxide catalysis offers a selective method for epoxidation of the olefinic double bond of cinnamyl alcohol (45). 

Because the epoxidation with Tl(III) is stoichiometric to produce Tl(I), reoxidation is needed. Halcon has patented processes based on such epoxidation to yield ethylene oxide (200—203). The primary benefits of such a process are claimed to be high yields of ethylene oxide, fiexibihty to produce either propylene oxide or ethylene oxide, and the potential of a useful by-product (acetaldehyde). Advances usiag organic hydroperoxides ia place of oxygen for reoxidation offer considerable promise, siace reaction rates are rapid and low pressures can be used. 

Liquid-Phase Epoxidation with Hydroperoxides. Molybdenum, vanadium, and tungsten have been proposed as Hquid-phase catalysts for the oxidation of the ethylene by hydroperoxides to ethylene oxide (205). tert- uty hydroperoxide is the preferred oxidant. The process is similar to the arsenic-catalyzed route, and iacludes the use of organometaUic complexes. 

Transition metal-catalyzed epoxidations, by peracids or peroxides, are complex and diverse in their reaction mechanisms (Section 5.05.4.2.2) (77MI50300). However, most advantageous conversions are possible using metal complexes. The use of t-butyl hydroperoxide with titanium tetraisopropoxide in the presence of tartrates gave asymmetric epoxides of 90-95% optical purity (80JA5974). 

Recently (79MI50500) Sharpless and coworkers have shown that r-butyl hydroperoxide (TBHP) epoxidations, catalyzed by molybdenum or vanadium compounds, offer advantages over peroxy acids with regard to safety, cost and, sometimes, selectivity, e.g. Scheme 73, although this is not always the case (Scheme 74). The oxidation of propene by 1-phenylethyl hydroperoxide is an important industrial route to methyloxirane (propylene oxide) (79MI5501). 

Electron deficient carbon-carbon double bonds are resistant to attack by the electrophilic reagents of Section 5.05.4.2.2(t), and are usually converted to oxiranes by nucleophilic oxidants. The most widely used of these is the hydroperoxide ion (Scheme 79). Since epoxidation by hydroperoxide ion proceeds through an intermediate ct-carbonyl anion, the reaction of acyclic alkenes is not necessarily stereospecific (Scheme 80) (unlike the case of epoxidation with electrophilic agents (Section 5.05.4.2.2(f)) the stereochemical aspects of this and other epoxidations are reviewed at length in (B-73MI50500)). 

The manufacture and uses of oxiranes are reviewed in (B-80MI50500, B-80MI50501). The industrially most important oxiranes are oxirane itself (ethylene oxide), which is made by catalyzed air-oxidation of ethylene (cf. Section 5.05.4.2.2(f)), and methyloxirane (propylene oxide), which is made by /3-elimination of hydrogen chloride from propene-derived 1-chloro-2-propanol (cf. Section 5.05.4.2.1) and by epoxidation of propene with 1-phenylethyl hydroperoxide cf. Section 5.05.4.2.2(f)) (79MI50501). 

The molybdenum-catalyzed oxidation of alkynes by /-butyl hydroperoxide has been investigated 73JCS(P1)2851) (the epoxidation of alkenes by this system has become an important reaction Section 5.05.4.2.2(i)) but the formation of oxirenes was excluded. 

SHARPLESS Asymmetne Epoxidation EnanlioselectK/e epoxidation of altyl alcohois by means of Irtanlum a5(oxide, (+) or () diethyl tartarate (OET) and t butyl hydroperoxide (TBHP)... 

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. 

Double bonds in a,/3-unsaturated keto steroids can be selectively oxidized with alkaline hydrogen peroxide to yield epoxy ketones. In contrast to the electrophilic addition mechanism of peracids, the mechanism of alkaline epoxidation involves nucleophilic attack of hydroperoxide ion on the con-... 

Henbest and Jackson have rationalized these remote directive effects on the basis of the well-supported mechanism of alkaline epoxidations. The initial step in the reaction is the reversible addition of the hydroperoxide ion... 

The Sharpless-Katsuki asymmetric epoxidation reaction (most commonly referred by the discovering scientists as the AE reaction) is an efficient and highly selective method for the preparation of a wide variety of chiral epoxy alcohols. The AE reaction is comprised of four key components the substrate allylic alcohol, the titanium isopropoxide precatalyst, the chiral ligand diethyl tartrate, and the terminal oxidant tert-butyl hydroperoxide. The reaction protocol is straightforward and does not require any special handling techniques. The only requirement is that the reacting olefin contains an 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 asymmetric epoxidation of an allylic alcohol 1 to yield a 2,3-epoxy alcohol 2 with high enantiomeric excess, has been developed by Sharpless and Katsuki. This enantioselective reaction is carried out in the presence of tetraisopropoxyti-tanium and an enantiomerically pure dialkyl tartrate—e.g. (-1-)- or (-)-diethyl tartrate (DET)—using tcrt-butyl hydroperoxide as the oxidizing agent. 

In order to obtain good yields, it is important to use dry solvent and reagents. The commercially available t-butyl hydroperoxide contains about 30% water for stabilization. For the use in a Sharpless epoxidation reaction the water has to be removed first. The effect of water present in the reaction mixture has for example been investigated by Sharpless et al. for the epoxidation of (E)-a-phenylcinnamyl alcohol, the addition of one equivalent of water led to a decrease in enantioselectivity from 99% e.e. to 48% e.e. 

The second important process for propylene oxide is epoxidation with peroxides. Many hydroperoxides have been used as oxygen carriers for this reaction. Examples are t-butylhydroperoxide, ethylbenzene hydroperoxide, and peracetic acid. An important advantage of the process is that the coproducts from epoxidation have appreciable economic values. 

Epoxidation of propylene with ethylbenzene hydroperoxide is carried out at approximately 130°C and 35 atmospheres in presence of molybdenum catalyst. A conversion of 98% on the hydroperoxide has been reported ... 

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