Phenol to a quinone

Thompson, D. C. Perera, K. London, R. Spontaneous hydrolysis of 4-trifluoromethyl-phenol to a quinone methide and subsequent protein alkylation. Chem.-Biol. Interact. 2000, 126, 1-14. 

Whilst direct electrophilic hydroxylation of the arylthallium species can be effected using peroxytriflu-oroacetic acid, further oxidation of the phenol to a quinone accompanies this process. This over-oxidation can be avoided by initial transmetallation to a lead species with concomitant reduction of the thallium trifluoroacetate (TTFA) by triphenylphosphine, followed by displacement of the lead by trifluo-roacetate to give the aryl trifluoroacetate. lliis hydroxylation method has yet to find use in the synthesis of molecules which are more complex than simple arenes. 

The mechanism of this reaction has been studied by several groups [133,174-177]. The consensus is that interaction of ester with the phenolic resole leads to a quinone methide at relatively low temperature. The quinone methide then reacts rapidly leading to cure. Scheme 11 shows the mechanism that we believe is operative. This mechanism is also supported by the work of Lemon, Murray, and Conner. It is challenged by Pizzi et al. Murray has made the most complete study available in the literature [133]. Ester accelerators include cyclic esters (such as y-butyrolactone and propylene carbonate), aliphatic esters (especially methyl formate and triacetin), aromatic esters (phthalates) and phenolic-resin esters [178]. Carbamates give analogous results but may raise toxicity concerns not usually seen with esters. 

An increased selectivity for phenol in the oxidation of benzene by H202 with TS-1 catalyst in sulfolane solvent was attributed to the formation of a bulky sulfolane-phenol adduct which cannot enter the pores of TS-1. Further oxidation of phenol to give quinones, tar, etc. is thus avoided. Removal of Ti ions from the surface regions of TS-1 crystals by treatment with NH4HF2 and H202 was also found to improve the activity and selectivity (227). The beneficial effects of removal of surface Al ions on the catalytic performance of zeolite catalysts for acid-catalyzed reactions have been known for a long time. 

Cumene oxidized relatively slowly, at about 1/13 the rate of p-xylene. This was not caused by the formation of phenol, as might be expected by an acid-catalyzed rearrangement of cumene hydroperoxide. No phenol or product clearly derived from phenol, as by radical attack or by oxidation to a quinone, was detected at any time in the reaction mixture. The two major products were a-methylstyrene and 2-phenylpropylene oxide their concentrations increased with time. The group at Shell also observed the formation of a-methylstyrene and 2-phenylpropylene oxide among the products of cumene oxidation in butyric acid at 140°C. with cobalt and manganese catalysts (30). 

The formation of the chromanochromans (286) during the reaction of the phenolic Mannich bases and 2-chloroprop-2-enonitrile probably arises through the decomposition of the base to a quinone methide and dimethylamine (80JOC3726). The initial product, a substituted 4//-chromene (285), undergoes a further [4+2]-cycloaddition to give the final product (Scheme 77). 

Figure 9-26. The various types of oxidation reaction catalysed by metalloenzymes. The conversion of a phenol to a 1,2-dihydroxybenzene and the ring opening oxidation both involve oxygen atom transfer to the substrate, whilst the oxidation of a 1,2-diol to a 1,2-quinone is of the type discussed earlier in this chapter.

Recently it has been shown, that iodine(v) reagents can also be used for such transformations. An efficient regioselective method for the oxidation of phenols to ortho-quinones 40 can be achieved using 2-iodoxybenzoic acid (IBX) 7. With a subsequent reduction this proves to be a useful procedure for the synthesis of a variety of catechols 41, Scheme 20 [94]. 

The Py-MS experiments have provided detailed information on the labile organic structures found in the maceral concentrates. The utility of being able to obtain precise mass measurements is demonstrated in Table II where a small selection of peaks from the pyrolysis of the Brazil Block seam sporinite is listed. Note that at nominal m/z = 108 and 122 there are actually three distinct peaks corresponding to a quinone, an alkyl-phenol and a hydrocarbon. Normally with nominal mass pyrolysis data these peaks would only be assigned to alkyl phenols. All three peaks... 

Taylor and coworkers have prepared o-fluoromethyl and o-difluoromethyl estrone sulfates82 and shown that these compounds are good substrates for steroid sulfatases.83 The phenol product of hydrolysis of o-fluoromethyl estrone sulfate undergoes heterolytic cleavage to form a quinone methide that inactivates the steroid sulfatase (Scheme 20C).83 The phenol product of hydrolysis of o-difluoromethyl estrone sulfate breaks down first to a quinone methide and then to the o-formyl estrone, which also inactivates the steroid sulfatase.83... 

IBX can also be used to oxidize phenols to ortho-quinones at room temperature. A variety of phenols 28 has been converted to the corresponding ortho-quinones 29 in good yields [22],... 

Reaction of pentafluorophenol with rerf-butyl hypobromite starts as an electrophilic substitution in the benzene ring. The electrophile is formed by dissociation of tert-butyl hypobromite to tert-butoxy anion and bromine cation. The bromine cation attacks the para position and forms a positively charged Wheland complex, a nonaromatic species that is converted by ejection of proton from the phenolic hydroxyl to a quinon-oid compound, 4-bromopentafluorocyclohexa-2,5-dienone [39]. 

Figure 17-H-6 A proposed catalytic cycle for the role of tyrosinase in oxidizing phenol to o-quinone. Cat = catecholate dianion.

The p-anisyloxymethyl group520 (abbreviated AOM) played an important role in the synthesis of Calicheamicinone reported by Clive and co-workers.521 Its removal from the sensitive multifunctional substrate 285 1 [Scheme 4.285] was accomplished with CAN in a mixture of pyridine, methanol and water. The excellent yield (89%) attests to the mildness of the conditions. Attempts to apply the same conditions to the deprotection of an AOM group from 286 1 [Scheme 4.286]522 failed but the deprotection was successful if it was conducted in the presence of 2,6-pyridinedicarboxylic acid N-oxide — conditions previously used to convert a phenol methyl ether to a quinone.523 AOM ethers undergo easy reductive cleavage to the corresponding methyl ethers with borane in toluene — a reaction that could have synthetic value when simple O-methylation procedures fail. 

The synthesis of quinones from arenes is an area which demands further research, despite the number of reagents presently available for this transformation. This is highlighted by the synthesis of the naphthoquinone (3). Direct oxidation of the dibromoarene (1) was unsatisfactory, and therefore Bruce and coworkers had to resort to a multistep sequence involving nitration, reduction, diazotization, displacement by hydroxide and finally oxidation of the phenol (2) with Fremy s salt (Scheme 1). Although there are examples of the oxidation of polynuclear aromatic hydrocarbons to quinones, the direct oxidation of an arene to a quinone is a process not encountered in the synthesis of more complex mt ecules. 

In some instances it has been demonstrated that oxidation is complete before coupling occurs, the second step thus being nonoxidative. Such cases (Scheme 5) involve oxidation to a quinone or a quinone methide whose further reactions may involve nucleophilic addition, e.g. by phenol, or cycloaddition. Examples are given below. 

Quinones. In the presence of tyrosinase and oxygen, phenols are oxidized to >-quinones which are captured by dienophiles such as ethyl vinyl ether. Chemical oxidation of phenols to p-quinones ° in refluxing benzene (6 examples, 36-65%) is mediated by a mixture of Co and Mn salts of 4-aminobenzoic acid. 

The reagent has found some use for the oxidation of aromatic hydrocarbons and phenols to para quinones. Arnold and Lawson " heated a mixture of 10 g. of naphthalene, 25 ml. of 30% hydrogen peroxide, and 50 ml. of acetic acid just above 80° for 45 min., distilled off about half of the solvent, added water to precipitate the product, and by crystallization isolated satisfactory 1,4-naphthoquinone in 20% yield. Durene (5 g.) was heated with HjOa-AcOH for 15 hrs. on the steam bath and duroquinone (2.1 g.) was separated by steam distillation. Crude 2-methyl-1,4-naphthoquinone and 2,3-dimethyl-l, 4-naphlhoquinone were obtained in yields of 30 and 78%. Unchanged hydrocarbon wax present at the end of each oxidation. 

To some extent, the geometry confers on the phenol ion a quinone-like distonic character as seen in 21a (Chart 5) in which the charge and radical centres are located at two different sites. This picture is supported by the charge distribution according to the Mul-liken population analysis suggesting that the para-C4 carbon of the ring bears the largest... 

The process depicted for phenol in equations 5 consists of an enzyme-catalyzed oxidation to a quinone, and a reduction process taking place at the electrode these reactions may serve for electrode calibration. The development of AMD biosensors for detection of phenols in environmental waters has been described for phenoloxidases such as tyrosinases and laccases and less specific oxidases such as peroxidases. Such biosensors may be part of a FIA system for direct determination of phenols or may serve as detectors for LC °. 

FIGURE 7.3 Formation of non-cyclic benzyl aryl ethers by addition of a phenolic unit to a quinone methide intermediate formed during lignin biosynthesis. 

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