Cyclohexa-2.4-dienone, phenol

In a general reaction known as the cyclohexadienone phenol rearrangement cyclohexa dienones are converted to phenols under conditions of acid catalysis An example is... 

Hughes, M. J., Waring, A. J. Kinetics of the dienone-phenol rearrangement and basicity studies of cyclohexa-2,5-dienones. J. Chem. Soc., Perkin Trans. 21974, 1043-1051. 

Various dienone-phenol rearrangements were carried out in spirocyclic and bicyclic systems 2 5. it was shown during investigations of cyclohexa-2,5-dienones bearing acyl... 

Interesting transformations occur in systems where the cyclohexa-2,5-dienone fragment is in a spiro connection with heterocycles. Thus, treatment of griseofulvin derivative 317 with magnesium iodide results in the xanthone derivative 318 via a dienone-phenol rearrangement (equation 152). 

Disubstituted phenols such as 350 undergo PhI(OAc)2-mediated oxidation in the presence of MeOH as a nucleophile resulting in the formation of two possible cyclohexa-dienones (351 and 352) (Scheme 73). The initially formed intermediate 353 is converted to the cyclohexadienones by two plausible routes. In route A, heterolytic dissociation generates a solvated phenoxonium ion 354, which further reacts with MeOH to afford 351 and/or 352. In route B, both 351 and 352 are produced by direct attack of MeOH on the intermediate (353). In the latter case, the reaction will be strongly influenced by steric factors and a homochiral environment using chiral solvents and chiral oxidants to induce some asymmetric induction, particularly in the formation of 352. 

Phenols are oxidized by NaBiO3 to polyphenylene oxides, quinones, or cyclohexa-2,4-dienone derivatives, depending on the substituents and the reaction conditions [263]. For example, 2,6-xylenol is oxidized in AcOH to afford a mixture of cyclohexa-dienone and diphenoquinone derivatives (Scheme 14.123) [264] and is oxidatively polymerized in benzene under reflux to give poly(2,6-dimethyl-l,4-phenylene) ether (Scheme 14.124) [265]. Substituted anilines and a poly(phenylene oxide) are oxidatively depolymerized by NaBiO, to afford the corresponding anils [266]. Nal iO, oxidizes olefins to vicinal hydroxy acetates or diacetates in low to moderate yield [267]. Polycyclic aromatic hydrocarbons bearing a benzylic methylene group are converted to aromatic ketones in AcOH under reflux (Scheme 14.125) [268]. 

Dearomatization of p-suhstituted phenols and derivatives. 2,5-Cyclohexa-dienones are the major products in the reaction. 4-Halo derivatives or p-quinol are formed in the presence of pyridinium poly(hydrogen fluoride), aqueous NaCI, or water alone as additive besides solvents. 

The mechanism is illustrated by the rearrangement of 4,4-disubstituted cyclohexa-dienones to 3,4-disubstituted phenols, as displayed here. 

The study of phenol alkylation has a long history. Claisen and co-workers (178) showed that metal phenoxides react with active alkyl halides (e.g., allyl and benzyl bromides) in nonpolar solvents to give o-alkylphenols. Cyclohexa-dienones may be prepared in this way starting from 2,6-disubstituted phenols... 

Recently, an ab initio 6-31 G basis set calculation reaffirmed that phenol is significantly more stable than both 2,4- and 2,5-cyclohexadienone. Total electronic energies at 0 K and thermodynamic parameters were calculated for phenol, 2,4-cyclohexa-dienone, and 2,5-cyclohexadienone. Energy calculations were performed using the restricted Hartree— Fock (RHF) and second-order Moller—Plesset formalisms on the RHF optimized geometries. The study has shown the following (i) phenol is more stable than the two ketones by around 18 kcal/mol (ii) the ketone with the C-sp para to the carbonyl is slightly less stable than the one with the C-sp ortho to the carbonyl (iii) thermodynamic data calculated for the ketones versus the enol forms for the three species confirm the already known fact that phenol is more stable in the enolic form (Scheme 16). 

The equilibrium constant calculated from the AH values for the equilibrium phenol — 2,4-cyclohexa-dienone was 2 x 10 , i.e., pAr = 12.7, in agreement with other experimental data. The calculation was for the gas phase however, the equilibrium constant for the tautomerization agreed with experimental results for aqueous solution. This example confirms... 

A second process that occurs concurrently with the dissociation-redistribution process is an intermolecular rearrangement hy which cyclohexa-dienone groups move along a poljuner chain. The reaction may he represented as two electrocyclic reactions analogous to a double Fries rearrangement. When the cyclohexadienone reaches a terminal position, the intermediate is the same as in equation 8, and enolization converts it to the phenol (eq. 9). 

Claisen rearrangement Thermal conversion of an allyl phenyl ether to an o-allyl phenol. The rearrangement proceeds via a cyclohexa-dienone intermediate. 

Generally, oxepins have a tendency to contract to a six-membered carbocycle when treated with acid. The driving force is the aromaticity of the phenol formed. However, when the less stable cyclohexa-2,5-diene-1,4-diol with an appropriate substitution pattern is treated with acid, the oxepin system is obtained. The treatment of cyclohexadienediols that are substituted with tert-butyl groups in the 2- and 6-positions and aryl at Cl and C4 with trifluoroacetic acid produces oxepins 1 with elimination of water.186 187 This reaction, however, is restricted to certain aryl substituents with at least some electron-donating effect. Generally, cyclohexa-2,4-dienone derivatives 2 are formed.187,188... 

The alkenylation of phenols also proceeds smoothly in the presence of TMG (Scheme 6). The major products are not aryl alkenyl ethers but a-alkenylated cyclohexa-2,4-dienones. That is, C-alkenylation occurs exclusively at the ortho position of phenols. When 2-naphthol reacts with two equivalents of the alkenylbismuthonium salt, a,a-dialkenyl ketone is obtained in good yield as the sole alkenylated product. 

The photoreactions of cyclohexa-2,5-dienones can give addition-a) products under certain conditions, especially phenols. Sometimes these arise by a subsequent photoreaction of the bicydohexenone (4.91), but they may also be produced by photoreduction if a hydrogen-donor solvent is employed and a good radical leaving group is present at C-4 (4.92). 

Great differences in product structures and product distributions are obtained by lead(IV) oxide or acetate oxidation of perfluorophenol in different solvents and media. The reaction with the former agent gives a quinoid ether in 22% yield (Table 10).173 The oxidation with lead(IV) acetate has been optimized to such a level as to give perfluoro cyclohexa-2,5-dienone (4) in 65 % yield.174 Treating the phenol with vanadium(V) fluoride or vanadium(III) fluoride as well as xenon difluoride gives a mixture of products,175 therefore, the reactions are only of minor preparative importance. 

Disubstituted cyclohexa-2,5-dienones from BTI oxidation of phenols... 

When this reaction is carried out on a p,p disubstituted a,p-unsaturated complex, cyclohexa-2,4-dienones are obtained, evidently because tautomerization to a phenol is... 

Trimethylphenol gives the 2-arylated cyclohexa-3,5-dienone derivative. The ortho and para phenylation of phenol with lead tetraphenyl is reported in a US patent53). Depending on the reaction conditions, 2-phenyl-, 2,6-diphenyl- and even... 

Zimmerman 103) applied the well known rearrangement of 4,4-disubstituted cyclohexa-2,5-dienones (e.g. the 4,4-diphenyl derivative tives the 3,4-disubstituted phenols l)). Using acetic anhydride and a small amount of concentrated sulfuric acid, 97.5 % of 3,4-diphenylphenolacetate is formed, which in turn is hydrolyzed to give 3,4-diphenylphenol. This is one of the easiest synthesis of this phenol. 2-Bromo-4,4-diphenylcyclohexa-2,5-dienone rearranges by a similar route to give a 49 % yield of 2-bromo-3,4-diphenylphenolacetate and 47 %2-bromo-4,5-diphenylphenolacetate U4). A [1.2]-phenyl shift of 4-methoxy-2,3,4,6-tetraphenyl-2,5-dienone in acetic anhydride and zinc chloride gives rise to 4-methoxy-2,3,5,6-tetraphenylacetate (m.p. 284 °C, 85% yield)115 . 

Enols are generally more acidic (pA a ca 11-12) than their corresponding carbonyl tautomer (pATa ca 17-25). Exceptions to this arise when the carbonyl derivative is either destabilized relative to the enol component, or when the enol is exceptionally stable, as in the case of phenol [pATa (H20) = 9.95] vs. cyclohexa-2,4-dienone [pATa (H20) = —3 1]. Enol acidity can be controlled by O-H bond strength. In certain cases, the relative proportion of enol content can be determined by the relative strengths of the C=0 and C—H bonds in the carbonyl tautomer versus the C=C and O—H bonds in the enol. ... 

Gas-phase properties of a molecule have, by definition, an intrinsic character and they could be modified by the environment. Although the formation and reactions of gaseous ionized phenol 21 (cf. Chart 5) and its cyclohexa-2,4-dienone isomer 22 have been studied in numerous ionization and mass spectrometric studies , thermochemical parameters of these isomers as well as information on other non-conventional isomers, such as the distonic ion 23, were rather scarce. Conventional cations of analogous aromatic systems (X—CeH5) + and their distonic isomers generated by simple 1,2-hydrogen shifts within the ring were demonstrated to be observable gas-phase species . In addition, the mechanism of the CO-loss upon phenol ionization has only recently been unraveled . ... 

FIGURE 38. Relative and ionization energies of meta- and para-X-substituted phenol and cyclohexa-2,4-dienone (a) X = methyl and (b) X = NH2. Values given in kJmoU were obtained from B3LYP/6-31H-+G(d,p)+ZPE computations... 

FIGURE 39. Schematic potential energy profiles showing the interconversion between phenol and cyclohexa-2,4-dienone in free and water-assisted systems (a) in the neutral state and (b) in the ionized state. Values given in kJ moU were obtained from B3LYP/6-31G(d,p)-hZPE computations... 

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