Oxidation of cyclohexene

The oxidation of simple internal alkenes is very slow. The clean selectiv oxidation of a terminal double bond in 40, even in the presence of an internt double bond, is possible under normal conditions[89,90]. The oxidation c cyclic alkenes is difficult, but can be carried out under selected condition Addition of strong mineral acids such as HCIO4, H2S04 and HBF4 accelerate the oxidation of cyclohexene and cyclopentene[48,91], A catalyst system 0 PdSO4-H3PM06W6Oii(j [92] or PdCF-CuCF m EtOH is used for the oxidatioi of cyclopentene and cyclohexene[93]. 

Cyclohexenone has been prepared by dehydrohalogenation of 2-bromocyclohexanone, by the hydrolysis and oxidation of 3-chlorocyclohexene, by the dehydration of a-hydroxycyclohexa- ione, by the oxidation of cyclohexene with chromic acid or hydrogen peroxide in the presence of a vanadium catalyst, by I lie addition of acroleiti to ethyl acetoacctate followed by cycliza-lion, hydroly.sis, and decar])oxylation, by the reduction of N,N-dimelliyliiniline with sodium and ethanol itt liquid ammonia... 

The preparation of Pans-1,2-cyclohexanediol by oxidation of cyclohexene with peroxyformic acid and subsequent hydrolysis of the diol monoformate has been described, and other methods for the preparation of both cis- and trans-l,2-cyclohexanediols were cited. Subsequently the trans diol has been prepared by oxidation of cyclohexene with various peroxy acids, with hydrogen peroxide and selenium dioxide, and with iodine and silver acetate by the Prevost reaction. Alternative methods for preparing the trans isomer are hydroboration of various enol derivatives of cyclohexanone and reduction of Pans-2-cyclohexen-l-ol epoxide with lithium aluminum hydride. cis-1,2-Cyclohexanediol has been prepared by cis hydroxylation of cyclohexene with various reagents or catalysts derived from osmium tetroxide, by solvolysis of Pans-2-halocyclohexanol esters in a manner similar to the Woodward-Prevost reaction, by reduction of cis-2-cyclohexen-l-ol epoxide with lithium aluminum hydride, and by oxymercuration of 2-cyclohexen-l-ol with mercury(II) trifluoro-acetate in the presence of ehloral and subsequent reduction. ... 

The same conclusion was drawn from the results obtained from careful studies of the stereochemistry of the glycol products formed on oxidation of cyclohexene with thallium(III) acetate 3, 83). When dry acetic acid was employed as solvent the product was mainly the tranr-diacetate (XI) in moist acetic acid, however, the mixture of glycol mono- (XII) and diacetates (XIII) which was obtained was mainly cis. These results have been interpreted in terms of initial trans oxythallation, ring inversion. 

The viabiUty of using site-isolated Ta(V) centers for cyclohexene epoxi-dation was explored by grafting ( PrO)2Ta[OSi(O Bu)3]3 onto a mesoporous silica material [83]. After calcinations, the material formed is less active and selective in the oxidation of cyclohexene than the surface-supported Ti(IV) catalysts using organic peroxides however, the site-isolated Ta(V) catalysts are more active under aqueous conditions. 

Sato, K., Aoki, M., Noyori, R. (1998) A Green Route to Adipic Acid Direct Oxidation of Cyclohexenes with 30 Percent Hydrogen Peroxide. Science, 281, 1646-1647. 

In pursuit of green chemistry, Mr. Clean aqueous H2O2 leaves only water. Thus readily available aqueous 30% H2O2 has been used for oxidation of cyclohexene to adipic acid using a PTC and a noble metal catalyst (Sato, 1998). 

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 oxidation reactions were performed in a 25 mL ronnd bottom flask. In a typical reaction the catalyst (0.5 % Fe mol) was added to 0.125 M olefin solntion in acetone then dry TBHP (3.5 M in CH2CI2 or in PhCl) was added in one step, and the reaction mixture was stirred and heated in an oil bath at 40°C for 7 h. For the allyhc oxidation of cyclohexene with isotopically labelled oxygen ( 02) the following procedure was carried out the suspension of the catalyst (0.5% Fe mol) in cyclohexene (4 mL, 0.125 M) was frozen and the air in the reactor was evacuated and replaced by an oxygen (21% mol) - argon (79% mol) mixture. Then, the suspension was allowed to warm at room temperatnre and 1.3 mmol of degasified TBHP was added to the solution and the reaction mixtnre was stirred at 40°C for 3 h. 

It has been reported that molecnlar oxygen plays an important role in the allylic oxidation of olefins with TBHP (25, 26). Rothenberg and coworkers (25) proposed the formation of an alcoxy radical via one-electron transfer to hydroperoxide, Equation 4, as the initiation step of the allylic oxidation of cyclohexene in the presence of molecnlar oxygen. Then, the alcoxy radical abstracts an allylic hydrogen from the cyclohexene molecnle. Equation 5. The allylic radical (8) formed reacts with molecular oxygen to yield 2-cyclohexenyl hydroperoxide... 

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. 

Several catalytic systems based on copper can also achieve allylic oxidation. These reactions involve induced decomposition of peroxy esters (see Part A, Section 11.1.4). When chiral copper ligands are used, enantioselectivity can be achieved. Table 12.1 shows some results for the oxidation of cyclohexene under these conditions. 

Table 12.1. Enantioselective Copper-Catalyzed Allylic Oxidation of Cyclohexene...

It has been pointed out earlier that the anti/syn ratio of ethyl bicyclo[4.1,0]heptane-7-carboxylate, which arises from cyclohexene and ethyl diazoacetate, in the presence of Cul P(OMe)3 depends on the concentration of the catalyst57). Doyle reported, however, that for most combinations of alkene and catalyst (see Tables 2 and 7) neither concentration of the catalyst (G.5-4.0 mol- %) nor the rate of addition of the diazo ester nor the molar ratio of olefin to diazo ester affected the stereoselectivity. Thus, cyclopropanation of cyclohexene in the presence of copper catalysts seems to be a particular case, and it has been stated that the most appreciable variations of the anti/syn ratio occur in the presence of air, when allylic oxidation of cyclohexene becomes a competing process S9). As the yields for cyclohexene cyclopropanation with copper catalysts [except Cu(OTf)2] are low (Table 2), such variations in stereoselectivity are not very significant in terms of absolute yields anyway. 

Oxalate 111 is formed when the reaction is carried out in the presence of air. In that case, catalytic oxidation of cyclohexene to cyclohexen-3-ol takes place. The alcohol reacts with... 

The mechanism of direct oxidation of cyclohexene to cyclohexanone by N20 mediated oxidation was analyzed by density functional theory (DFT) using B3LYP/6-31G approximation. A two-step reaction mechanism was predicted where the substituted 1,2,3-oxadiazoline ring system 5 forms as the first intermediate in the process before subsequent conversion to the cyclohexanone <1999JOC6710, 2003CC42, 2005MI177>. 

Pfaltz and co-workers (108) reported that the allylic oxidation of cyclohexene proceeds in moderate selectivity using stoichiometric amounts of semicorrin-Cu(II) complexes. In catalytic reactions, the enantioselectivity decreased drastically. Better results were realized using bis(oxazolines) as ligands. Upon... 

The application of dinuclear metal catalysts to the Kharasch-Sosnovsky reaction is mechanistically intriguing due to their illustrated role in mediating biological oxidations (119). Fahmi (120) examined a variety of dinucleating ligands with Cu(MeCN)4PF6 as catalysts in the allylic oxidation of cyclohexene, Eq. 102. In these studies, early results have been inferior to those obtained from bis(oxa-zoline)-copper catalysts. 

Present developments. One might think that an established reaction such as aerobic oxidation (or autoxidation) is not the subject of further research and improvement, but this is definitely not the case and both new homogeneous and heterogeneous catalysts are in development. In the introduction we already mentioned the drawbacks of oxidation of cyclohexene to adipic acid and several researchers address this challenge. Also a highly developed reaction such as the oxidation of paraxylene is subject to further improvements. 

In 1999, Sanjuan and co-workers [27] reported a very elegant type IIavRH oxidation of cyclohexene to give a mixture of cyclohexane-1, 2-diol, 2-cyclohexenol, and 2-cyclohexenone. The reaction is initiated by excitation of the zeolite-embedded 2,4,6-triphenylpyrylium cation to produce a hydroxy radical (steps 1 and 2... 

Kinetic studies on the oxidations of cyclohexene, benzyl alcohol, phenol, and trans-stiVoene by [Ru (0)(tpy)(bpy(P03H2)2)] (bpy(P03H2)2) = 2,2 -bipyridine-4,4 -diphosphonic acid adsorbed to thin films of Ti02 nanoparticles on glass have been reported. There is evidence for initial two-electron steps to give Ru intermediates in all four cases. 

Products from the electrochemical oxidation of cyclohexene (Scheme 2.1) illustrate the general course of reaction [28, 29]. The radical-cation either undergoes loss of an allylic proton or reacts, at the centre of liighest positive charge density, with a nucleophile. Either reaction leads to a carbon radical, which is oxidised to the carbonium ion. A Wagncr-Meerwein rearrangement then gives the most stable carbonium ion, which subsequently reacts with a nucleophile. 

Scheme 2. . Steps in the electrochemical oxidation of cyclohexene using methanol as solvent.

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