Protonated Cyclohexadienones

When dienones 39 and 40 are photolyzed in sulfuric acid they both rearrange to the same product, 2-methyl-5-hydroxybenzaldehyde (41) (Filipescu and Pavlik, 1970). The mechanism for this photorearrangement is consistent with that of the protonated cyclohexadienones already discussed, i.e., disrotatory closure to afford the intermediate bicyclic cations 42 and 43. In this case it is conceivable that the electron-withdrawing effect of the dichloromethyl group forces the subsequent thermal cyclopropyl migration entirely in the direction of the most stable cation 44 to yield the observed product. 

BHT (2,6-di-tert-butyl-4-methylphenol), a phenolic antioxidant, on reaction with NO under neutral conditions, results in scavenging of the potentially harmful NO via radical reactions [143]. Sodium phenolate under basic conditions undergoes a Traube-type reaction at the ortho-position to produce a cupferron derivative [144]. When the ortho-positions are sterically blocked and the para-position does not bear a proton, cyclohexadienone diazeniumdiolates may be formed (Scheme 3.12) [145]. 

Vitullo, V. P. Cyclohexadienyl cations. II. Evidence for a protonated cyclohexadienone during the dienone-phenol rearrangement. J. Org. Chem. 1970, 35, 3976-3978. 

A walk rearrangement of hydroxybicyclohexenyl cation 69 is involved in the acid catalyzed isomerization of bicyclohexanone 68 to cyclohexadienone 70. The reversible nature of this walk rearrangement has been demonstrated by the equilibration 69-4-CD3s=t 69-5-CD3, which precedes the ring opening to the protonated cyclohexadienone derivative (Figure 12) (109). 

The lack of any difference in the rate of isomerization between fluoro-sulfonic acid solutions of 34 which had been thoroughly degassed, and those which were saturated with oxygen, suggests that the reaction does not proceed via a triplet mechanism. In fluorosulfonic acid no unproton-ated acid is detected, ruling out the possibility of n,w excitation. Thus, there is little doubt in this case that it is the ir,Tr singlet state which is the reactive species. Experiments carried out with a variety of methyl-substituted protonated cyclohexadienones have likewise ruled out the... 

These rotatory isomers can be regarded as n- and p-protonated cyclohexadienones 2,353) jner-ing in the extent of transfer of the positive charge from the oxygen to the ring. 

An electrocyclic ring closure then leads to a cyclohexadienone complex 7, which upon migration of a proton, yields the chromium tricarbonyl-hydroquinone complex 3. 

Reaction with the electrophilic peroxodisulfate occurs preferentially at the para position, leading to formation of a cyclohexadienone derivative 5, which loses a proton to give the aromatic compound 6. Subsequent hydrolysis of the sulfate 6 yields 1,4-dihydroxybenzene 3 ... 

A plausible pathway is that the aromatisation of the cyclohexadienone 92 by a proton shift is accelerated in the presence of Ac20 under formation of acetate 93. The simultaneously generated acetic acid then cleaves the acetate to form the free phenol 94 (Scheme 44). This effect was observed for the first time during studies towards the total synthesis of the lipid-alternating and anti-atherosclerotic furochromone khellin 99 [64].The furanyl carbene chromium complex 96 was supposed to react with alkoxyalkyne 95 in a benzannulation reaction to give the densely substituted benzofuran derivative 97 (Scheme 45). Upon warming the reaction mixture in tetrahydrofuran to 65 °C the reaction was completed in 4 h, but only a dimerisation product could be isolated. This... 

Investigation of the photochemistry of protonated durene offers conclusive evidence that the mechanism for isomerization of alkyl-benzenium ions to their bicyclic counterparts is, indeed, a symmetry-allowed disrotatory closure of the pentadienyl cation, rather than a [a2a -f 7r2a] cycloaddition reaction, which has been postulated to account for many of the photoreactions of cyclohexadienones and cyclohexenones (Woodward and Hoffmann, 1970). When the tetramethyl benzenium ion (26) is irradiated in FHSO3 at — 90°, the bicyclo[3,l,0]hexenyl cation (27) is formed exclusively (Childs and Farrington, 1970). If photoisomerization had occurred via a [(r2a-t-772 ] cycloaddition, the expected... 

The voltammetric response of curcumin and carthamin must, in principle, be dominated by the oxidation of the phenol and/or methoxyphenol groups (see Scheme 2.2). The electrochemistry of methoxyphenols has claimed considerable attention because of their applications in organic synthesis [159-163]. As studied by Quideau et al., in aprotic media, 2-methoxyphenols are oxidized in two successive steps into cyclohexadienone derivatives [163], whereas a-(2)- and a-(4-methoxyphenoxy) alkanoic acids undergo electrochemically induced spirolac-tonization to develop synthetically useful orthoquinone bis- and monoketals. In the presence of methanol, the electrochemical pathway involves an initial one-electron loss, followed by proton loss, to form a monoketal radical. This undergoes a subsequent electron and proton loss coupled with the addition of alcohol to form an orthoquinone monoketal. The formal electrode potential for the second electron transfer... 

The acidity constants of protonated ketones, pA %, are needed to determine the free energy of reaction associated with the rate constants ArG° = 2.3RT(pKe + pK ). Most ketones are very weak bases, pAT < 0, so that the acidity constant K b cannot be determined from the pi I rate profile in the range 1 < PH <13 (see Equation (11) and Fig. 3). The acidity constants of a few simple ketones were determined in highly concentrated acid solutions.19 Also, carbon protonation of the enols of carboxylates listed in Table 1 (entries cyclopentadienyl 1-carboxylate to phenylcyanoacetate) give the neutral carboxylic acids, the carbon acidities of which are known and are listed in the column headed pA . As can be seen from Fig. 10, the observed rate constants k, k for carbon protonation of these enols (8 data points marked by the symbol in Fig. 10) accurately follow the overall relationship that is defined mostly by the data points for k, and k f. We can thus reverse the process by assuming that the Marcus relationship determined above holds for the protonation of enols and use the experimental rate constants to estimate the acidity constants A e of ketones via the fitted Marcus relation, Equation (19). This procedure indicates, for example, that protonated 2,4-cyclohexadienone is less acidic than simple oxygen-protonated ketones, pA = —1.3. 

This cation cannot yield the product of electrophilic aromatic substitution by loss of a proton from the ring but can lose a proton from oxygen to give a cyclohexadienone derivative. 

The C-2 proton of benzo[/ ]furan 82 underwent regioselective metallation by treatment with -butyllithium to form 2-lithiated benzo[/ ]furan, which directly reacted with electrophiles, such as 1,4-cyclohexadienone to form 4-(ben-zo[/ ]furan-2-yl) -hydroxy-2,5-cyclohexadien-l-one in high yield, as shown in Equation (71) <2005TL7511>. 

A similar observation has also been made using another MS/MS/MS experiment, where the demethylation step was realized in the high kinetic energy regime. Demethylation of protonated anisole is evaluated to be less endothermic by about 146 kJmol if ionized phenol 21 was formed rather than ionized cyclohexadienone 22 (cf. Chart 8, where values given are estimated heats of formation). 

It is generally known that the processes of reversible oxidation of phenols, i.e. the conversions of phenolic systems into quinone structures and vice versa, are of great importance in biochemical reactions. The reaction partners mentioned above can serve as donors and acceptors of electrons and protons, i.e. as antioxidant systems. The conversions of phenols into cyclohexadienones are accompanied by the loss of aromaticity and in essence are not rearrangements, although the term phenol-dienone rearrangement is found in the literature. A review which summarizes in detail the oxidation reactions of phenols under conditions of halogenation, nitration and alkylation as well as radical reactions appeared . The various transformations of phenols upon oxidation with nickel peroxide were also reviewed . Therefore, only recent reports concerning the phenols-to-quinones conversions are described in this section. 

It is reported in the literature (5-7) that m-bromo-phenolic compounds are more stable than their o- or p-brominated counterparts. An o- or p-Brominated phenol forms an unstable cyclohexadienone structure via keto-enol tautomerization. Upon heating, this unstable cyclohexadienone structure generates free radicals which, in turn, abstract a proton from a neighboring molecule to form HBr. 

The rate-determining step always corresponds to protonation or deprotonation of a carbon atom, while equilibration of oxygen acids with their conjugate bases is established rapidly. This fact can be used to determine the acidity constants of enols, ynols and ynamines by flash photolysis, Kf, either kinetically, from downward bends in the pH rate profiles indicating a pre-equilibrium, or from the changes of the transient absorption in solutions of different pH (spectrographic titration). Such studies have provided some remarkable benchmark numbers, such as the acidity constant of phenylynol (pKf < 2.1),476 phenylynamine (pKf < 18.0)477 and its pentafluoro derivative (pKf = 10.3),478 and of the carbon acid 2,4-cyclohexadienone, pKf = —2.9 475 The enolization constant of 2,4-cyclohexadienone is pKE = 12.7. 

The formation of polychlorodihydroxybiphenyls is the result of a nucleophilic attack on the protonated form of the cyclohexadienone (Fig. 12). 

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