Cyclohexene oxidation products

The role of oxygen on the allyhc oxidation of cyclohexene over the FePcCli6-S/TBHP catalytic system was determined by using 2 labelled oxygen. Since more than 70% of the main cyclohexene oxidation products, 4,11, and 12, had labelled oxygen, we can assure that molecular oxygen acts as co-oxidant. However, under the reaction conditions the over-oxidation of 4 seems to be unavoidable. Labelled 2, 3- epoxy-l-cyclohexanone (13), 2-cyclohexen-l, 4-dione (14), and 4-hydroxy-2-cyclohexen-l-one (15) were detected as reaction products. 

The cycloahphatic products are generally Hquids of lower viscosity than the standard glycidyl ether resins. The peroxidized resins contain no chlorine and low ash content and their ring-contained oxirane group (cyclohexene oxide type) reacts more readily with acidic curing agents than the bisphenol A-derived epoxy resins. 

Oxirane on thermolysis or photolysis suffers C—O homolysis to give a plethora of products (Scheme 2). Substituted oxiranes behave similarly on thermolysis although some C—C cleavage is observed (Scheme 3). Cyclopentene and cyclohexene oxides undergo only C—O cleavage (Scheme 4). 

Hydroxymethylmethyldiazirine (209 unprotonated) formed propionaldehyde as the sole product by thermal nitrogen extrusion 4-hydroxy-l,2-diazaspiro[2.5]oct-l-ene (218) formed a mixture of cyclohexanone (73%), cyclohexenol (21%) and cyclohexene oxide (5%). Thermal decomposition of difluorodiazirine (219) was investigated intensively. In this case there is no intramolecular stabilization possible. On heating for three hours to 165-180 °C hexafluorocyclopropane and tetrafluoroethylene were formed together with perfluorofor-maldazine 64JHC59). 

By studying the NMR spectra of the products, Jensen and co-workers were able to establish that the alkylation of (the presumed) [Co (DMG)2py] in methanol by cyclohexene oxide and by various substituted cyclohexyl bromides and tosylates occurred primarily with inversion of configuration at carbon i.e., by an 8 2 mechanism. A small amount of a second isomer, which must have been formed by another minor pathway, was observed in one case (95). Both the alkylation of [Co (DMG)2py] by asymmetric epoxides 129, 142) and the reduction of epoxides to alcohols by cobalt cyanide complexes 105, 103) show preferential formation of one isomer. In addition, the ratio of ketone to alcohol obtained in the reaction of epoxides with [Co(CN)5H] increases with pH and this has been ascribed to differing reactions with the hydride (reduction to alcohol) and Co(I) (isomerization to ketone) 103) (see also Section VII,C). 

The Pacman catalyst selectively oxidized a broad range of organic substrates including sulfides to the corresponding sulfoxides and olefins to epoxides and ketones. However, cyclohexene gave a typical autoxidation product distribution yielding the allylic oxidation products 2-cyclohexene-l-ol (12%) and 2-cyclohexene-1-one (73%) and the epoxide with 15% yield [115]. 

Epoxide-derived radicals are generated under very mild reaction conditions and are therefore valuable for intermolecular C-C bond-forming reactions [27,29]. The resulting products, 5-hydroxyketones, 5-hydroxyesters or 5-lactones constitute important synthetic intermediates. The first examples were reported by Nugent and RajanBabu who used a variety of epoxides, such as cyclohexene oxide and a Sharpless epoxide (Scheme 7). 

Reactions of 1 with epoxides involve some cycloaddition products, and thus will be treated here. Such reactions are quite complicated and have been studied in some depth.84,92 With cyclohexene oxide, 1 yields the disilaoxirane 48, cyclohexene, and the silyl enol ether 56 (Eq. 29). With ( )- and (Z)-stilbene oxides (Eq. 30) the products include 48, ( > and (Z)-stilbenes, the E- and Z-isomers of silyl enol ether 57, and only one (trans) stereoisomer of the five-membered ring compound 58. The products have been rationalized in terms of the mechanism detailed in Scheme 14, involving a ring-opened zwitterionic intermediate, allowing for carbon-carbon bond rotation and the observed stereochemistry. 

The resulting material is active for the gas phase epoxidation of simple olefins. Addition of cyclohexene resulted in the formation of cyclohexene oxide as the sole volatile product, detected by GC/MS. 

A chiral ethylzinc aminoalkoxide 147, synthesized by the addition of ZnEt2 to (cyclohexene oxide with C02 in almost quantitative yield and with an ee of 49%. This value is somewhat lower than that obtained by the same authors from the in situ generated monomeric form of the catalyst, which furnished product with an ee of 70%.213... 

The same structure was proposed later by Hock and Schrader [40]. It became clear only in 1939 when Criegee et al. [41] proved that peroxide formed by cyclohexene oxidation has the structure of hydroperoxide. Later studies, performed by Farmer and Sutton [42], greatly extended the number of hydroperoxides as products of olefin oxidation. Beginning from the later part of the 20th century, the chain theory of organic compound oxidation became the theoretical ground for the experimental study in this field. The main events of the development of oxidation chemistry before the chain theory of oxidation are presented in Table 1.1. 

Both McsGeLi and Me3SnLi react with cyclohexene oxide to give the trans product (equation 22)44. These reactions most likely proceed by S/v2 mechanisms. 

Titanium enolates.1 This Fischer carbene converts epoxides into titanium enolates. In the case of cyclohexene oxide, the product is a titanium enolate of cyclohexanone. But the enolates formed by reaction with 1,2-epoxybutane (equation I) or 2,3-epoxy butane differ from those formed from 2-butanone (Equation II). Apparently the reaction with epoxides does not involve rearrangement to the ketone but complexation of the epoxide oxygen to the metal and transfer of hydrogen from the substrate to the methylene group. 

It not tertiary, the product yield is lowered by transfer of the carbinol hydride ion to the aldehyde to produce a new alkoxide and an enolate ion. Thus, propylene oxide, after reductive cleavage with LDBB and trapping with isobutyraldehyde or p-anisaldehyde, provided 5-methyl-2,4-hexanediol in 40-50% yield or 1-p-anisyl-1,3-butanediol in 44% yield, respectively (in both cases about equal mixtures of diastereoisomers were obtained). The cyclohexene oxide-derived dianion, when trapped with isobutyraldehyde, gave 2-(1-hydroxy-2-methylpropyl)cyclohexanol in 71% yield as a mixture of only partially separable isomers in the ratio 15 11 39 35. 

Interestingly, the dimeric Cr(salen) catalyst 64 supported on silica showed enhanced activity for ARO of 1,2-epoxyhexane and cyclohexene oxide in the presence of ionic liquids particularly with [BMIM][PF6] (64-IL) [86] (Table 6). A significant increase in the product selectivity was also observed with silica supported ionic liquid (64-SILP) for ARO of 1,2-epoxyhexane and cyclohexene oxide (ee, of 87% and 75% respectively) as eompared to silica supported catalyst minus the ionie liquid (Table 6, entries 5,6). However, after repeated recycling, the silica support material deteriorates due to the abrasive forees in the stirred reactor. As a result, silica material was non-recoverable, but the expensive dimeric Cr(salen) catalyst 64 and the ionic liquid was recovered quantitatively by Soxhlet extraction with acetone. SILP-catalyst system was also used in a eontinuous-flow reactor. 

A number of workers have made progress on this front. Asami and coworkers have anchored the stoichiometric base on the solid phase to realize a catalytic desymmetrization using lithiated diamine 135. Andersson has shown that slow addition of LDA results in an improvement in enantioselectivity when using his bicyclic base 136, while Ahlberg has illustrated that a stoichiometric base such as lithiated 1,2-dimethylimidazole results in an efficient catalytic system using diamine 137. Alexakis has published a smdy involving a number of chiral ethane-and propane-diamines in the catalytic deprotonation of cyclohexene oxide. Enan-tioselectivities observed are moderate, with diamine 138 providing the desired product in 59% ee and 80% yield. ... 

As shown in this scheme, the presence of HMPA during the reaction of LDA with cyclohexene oxide yields exclusively the -deprotonation product. This rearrangement is... 

Hi. Role of additive. There are some reports in the literature of the beneficial effect of powerful donor solvents such as DBU on the reactivity and enantioselectivity of HCLA-mediated oxirane rearrangements for both stoichiometric and catalytic processes. However, this effect is not general (see above) and the role of such additives is still unclear. In one study, the influence of the concentration of DBU on the relationship between the ee s of catalyst and the product for the enantioselective isomerization of cyclohexene oxide mediated by substoichiometric amount of HCLA 56a (20 mol%) in the presence of LDA (2 equiv) has been investigated. At high DBU concentration (6 equiv), the enantiomeric... 

The RLi homochiral ligand complexes are seldom used for the base-promoted isomerization of oxiranes into allylic alcohols because their poor chemoselectivity lead to complex mixtures of products. As examples, the treatment of cyclohexene oxide by a 1 1 i-BuLi/(—)-sparteine mixture in ether at low temperature provides a mixture of three different products arising respectively from -deprotonation (75), a-deprotonation (76) and nucleophilic addition (77) (Scheme 32) . When exposed to similar conditions, the disubstituted cyclooctene oxide 78 affords a nearly 1 1 mixture of a- and -deprotonation products (79 and 80) with moderate ee (Scheme 32, entry 1). Further studies have demonstrated that the a//3 ratio depends strongly on the type of ligand used (Scheme 32, entry 1 vs. entry 2) . ... 

A similar catalytic system was found to copolymerize cyclohexene oxide and CS2 to afford copolymers with molecular weight ranges of 14,000-34,000 Da with narrow molecular weight distributions [70]. Of interest, the exchange of sulfur and oxygen atoms in both the copolymer and cyclic products was observed during the process, with the cyclic product enriched in sulfur atoms and the copolymer enriched in oxygen atoms (10). 

The synthesis of the Y zeolite-encapsulated manganese complex of the salen ligand has been reported recently [51]. It was found to have catalytic activity in the oxidation of cyclohexene, styrene, and stilbene with PhlO. Typically, 1 Mn(salen) is present per 15 supercages, resulting in catalytic turn-overs in the order of 60. The reactions investigated with the respective product yields are given in Scheme 5. Typical oxidation products are epoxides, alcohols and aldehydes. In comparison to the homogeneous case encapsulation seems to lower the reaction rate. From cyclohexene the expected oxidation product cyclohexene oxide is present in excess and is formed on the Mn(salen) site. 2-cyclohexene-l-ol is probably formed on residual Mn cations via a radical mechanism. 

For cyclohexene oxidation traces of 3-t-butyl-peroxy-cyclohexene, 2-cyclohexene-l-ol and 2-cyclohexene-l-one were detected as side products. 

Mo containing Y zeolites were also tested for cyclohexene oxidation with oxygen as oxidant and t-butyl hydroperoxide as initiator [86]. In this case the selectivity for cyclohexene oxide was maximum 50%, 2-cyclohexene-l-ol and 2-cyclohexene-l-one being the main side products. The proposed reaction scheme involves a free radical chain mechanism with intermediate formation of cyclohexenyl hydroperoxide. Coordination of the hydroperoxide to Mo + in the zeolite and oxygen transfer from the resulting complex to cyclohexene is believed to be the major step for formation of cyclohexene oxide under these conditions. 

In 1989, Isobe and coworkers reported on an organometallic polyoxometalate cluster [(Rhcp )4V60i9] (cp = /j -CsMcs) that catalyzes the oxidation of cyclohexene with TBHP as oxidant to give mainly ally lie oxidation products (l-ferf-butylperoxycyclohex-2-ene 42% and cyclohex-2-en-l-one 21%) and only little epoxide (15%) (equation 62). The yield of 1 -ferf-butylperoxy cyclohex-2-ene increased with decreasing molar ratio of cyclohexene to TBHP, while the yield of cyclohex-2-en-l-one has a maximum at the ratio of 0.2. 

Other examples of this type of reaction include those conducted by Andrus and co-workers using the copper(I) complex of ligand 224 in the allylic oxidation of cyclohexene.As shown in Figure 9.65, this reaction afforded the oxidation product, (15)-2-cyclohexen-l-yl 4-nitrobenzoate 225 in 76% yield and 73% ee. Clark and co-workers also experimented with the allylic oxidation of cyclohexene using inda-box ent-9h to afford the oxidation product, (15)-2-cyclohexen-l-yl benzoate, 223b in 76% yield (71% ee). ... 

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