Oxidation of 2,6 Disubstituted Phenols

Depending on the reaction conditions, the oxidative coupling leads to formation of a C-0 or C-C bond  

This results in the formation of polyphenylene oxide (PPO) or diphenoquinone (4-(3,5-dimethyl-4-oxo-2,5-cyclohexadiene-l-ilidene-2,6-dimethyl-2,5-cyclohexadiene-1-one). 

Besides disubstituted phenols, organic compounds containing mobile hydrogen atoms in terminal positions can undergo the oxidative coupling reaction [123-125]  

It appears that copper(II) binuclear-type complexes bonded with each other by OH bridges play an important role in the oxidative coupling of substrates  

The formation of the binuclear structure is confirmed by the following facts IR spectroscopy detects absorption bands of OH bridges at 3350cm and Cu-O bands at 490 cm EPR spectroscopy shows the absence of the copper ion signal the magnetic susceptibility value increases with temperature and H2O is a product of O2 reduction, whereas for mononuclear copper complexes H2O2 is usually formed [120]. 

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The selectivity of the oxidation of 2,6-disubstituted phenols depends on the type of oxidizing agent. For example, with a series of cobalt-containing catalysts of the salcomine type, oxidation of 2,6-dimethylphenol produces three products the poly(phenylene oxide), the diphenoquinone, and... 

Copper(I) salts in the presence of a tertiary amine catalyze the oxidation of 2,6-disubstituted phenols by 02 into poly(phenylene oxides) (high amine/copper ratio) or biphenyl-4,4 -quinones (low amine/copper ratio). When R is a bulky substituent (e.g. Bu ), biphenyl-4,4 -quinone is the sole product (equations 270 and 271).599... 

SCHEME 68. Mushroom tyrosinase oxidation of 2,6-disubstituted phenols... 

SCHEME 131. Oxidation of 2,6-disubstituted phenols withMn(HI) complexes... 

The oxidation of 2,6-disubstituted phenols catalyzed by Co(salen) and its derivatives has gradually achieved considerable importance due to the feasibility of studies on the relationship between the mode of oxidation and the type of dioxygen adduct [19-22, 37]. 

Polymerization Mechanism. The mechanism that accounts for the experimental observations of oxidative coupling of 2,6-disubstituted phenols involves an initial formation of aryloxy radicals from oxidation of the phenol with the oxidized form of the copper—amine complex or other catalytic agent. The aryloxy radicals couple to form cyclohexadienones, which undergo enolization and redistribution steps (32). The initial steps of the polymerization scheme for 2,6-dimethylphenol are as in equation 6. 

Various 2,6-di8ubstituted p-benzoquinones have been prepared by oxidation of the corresponding 2,6-disubstituted phenols with potassium nitrosodisulfonate or lead dioxide in formic acid. Oxidative coupling of 2,6-disubstituted phenols to poly-2,6-disubstituted phenylene ethers followed by treatment of the polymers in acetic acid with lead dioxide is reported to give low yields of the corresponding 2,6-disubstituted p-benzoquinones. 

We were interested in the behaviour of polymeric catalysts in order to confirm that typical polymer effects may occur. Oxidative coupling of 2,6-disubstituted phenols, as developped by Hay (7), was chosen as a model reaction and the catalytic activities of coordination complexes of copper with several polymeric tertiary amines were compared with the activities of their low molecular weight analogs. The overall reaction scheme is presented in scheme 1. 

Table I Kinetic results on oxidative coupling of 2,6-disubstituted phenols at 25°C in the solvent mixture 1,2-dichlorobenzene/methanol (13 2 v/v).

Electro-oxidative polymerization of 2,6-disubstituted phenols is listed in Table I, with the polymerizations catalyzed by the copper-pyridine complex and oxidized by lead dioxide. 2,6-Dimethylphenol was electro-oxidatively polymerized to yield poly(2,6-dimethylphen-yleneoxide) with a molecular weight of 10000, as was attained by other polymerization methods. The NMR and IR spectra were in complete agreement with those measured for the other polymerization... 

Table I. Electro-oxidative Polymerization of 2,6-Disubstituted Phenols...

Among other in vitro enzymatic polymerizations that have been studied are the oxidative polymerizations of 2,6-disubstituted phenols to poly(p-phenylene oxide)s (Sec. 2-14b) catalyzed by horseradish peroxidase [Higashimura et al., 2000b] and the polymerization of P-cellobiosyl fluoride to cellulose catalyzed by cellulase [Kobayashi, 1999 Kobayashi et al., 2001],... 

Block copolymers may also be made by condensation polymerization. Elastomer fibers are produced in a three-step operation. A primary block of a polyether or polyester of a molecular weight of 1000-3000 is prepared, capped with an aromatic diisocyanate, and then expanded with a diamine or dihydroxy compound to a multiblock copolymer of a molecular weight of 20,000. The oxidative coupling of 2,6-disubstituted phenols to PPO is also a condensation polymerization. G. D. Cooper and coworkers report the manufacture of a block copolymer of 2,6-dimethyl-phenol with 2,6-diphenylphenol. In the first step, a homopolymer of diphenylphenol is preformed by copper-amine catalyst oxidation. In the second step, oxidation of dimethylphenol in the presence of the first polymer yields the block copolymer. 

Oxidation of mixtures of 2,6-disubstituted phenols leads to linear poly(arylene oxides). Random copolymers are obtained by oxidizing mixtures of phenols. Block copolymers can be obtained only when redistribution of the first polymer by the second monomer is slower than polymerization of the second monomer. Oxidation of a mixture of 2,6-di-methylphenol (DM ) and 2fi-diphenylphenol (DPP) yields a random copolymer. Oxidation of DPP in the presence of preformed blocks of polymer from DMP produces either a random copolymer or a mixture of DMP homopolymer and extensively randomized copolymer. Oxidation of DMP in the presence of polymer from DPP yields the block copolymer. Polymer structure is determined by a combination of differential scanning calorimetry, selective precipitation from methylene chloride, and NMR spectroscopy. 

Organic compounds having labile hydrogens, such as phenols [41,42], phenylene-diamines [43], and acetylenes [44], can be oxidatively coupled in the presence of specific metal complexes to form polymeric compounds. The oxidative polymerization of 2,6-disubstituted phenols with a copper-amine complex produces poly(2,6-disubstituted phenylene ether) [45-51], Poly(2,6-dimethylphenylene ether) and poly(2,6-diphenylphenylene ether) are commercially produced from 2,6-dimethyl phenol and 2,6-diphenylphenol, respectively (Figure 5). These polymers exhibit excellent performance as engineering plastics. 

Also of interest is the oxidative polycondensation of 2,6-disubstituted phenols with transition metal catalysts such as palladium complexes, which produces aromatic polyethers [2]. 

The oxidative coupling of 2,6-disubstituted phenols to poly-(arylene oxides) is a polycondensation reaction, in which polymer molecules couple with other polymer molecules as well as with monomer. Unstable quinone ketals formed by coupling of a polymeric aryloxy radical at the para position of the phenolic ring of a second radical are believed to be intermediates or the reaction. The ketals may be converted to polymeric phenols either by a series of intramolecular rearrangements or by disproportionation to aryloxy radicals, leading to a mobile equilibrium between polymer molecules of varying degree of polymerization. Both processes have been shown to occur, with their relative importance determined by the reaction conditions. 

Oxidation to p-ifainones (3, 289). In the oxidation of 2,6-disubstituted-4-r-butyl-phenols to 2,6-dLsubstituted-p-benzoquinones. McKillop ei at. (3. 289, ref. 6) postulated an intermediate 2.6-disubstitutcd-4-f-butyl-4-trifluoroacetoxycyclohcxa-2,5-diene-l-one. A stable quinol trifluoroacetate of this type (2) has now been isolated from the reaction of estrone (I) with 2 eq. of TTFA. ... 

In the case of 2,6-disubstituted phenols, the nature of the bismuth reagent, the nature of the alkyl substituents and the reaction conditions determined the outcome of the reactions. 2 Thus, in the reactions of 2,6-dimethylphenol (19) with pentaphenylbismuth (4) or with tetraphenylbismuthonium derivatives under basic conditions, ortho C-phenylation resulted in the formation of 6-phenylcyclo-hexadienone (20) in good yield. On the other hand, oxidative dimerisation took place in the reaction of 2,6-dimethylphenol with triphenylbismuth carbonate to afford the diphenoquinone (21) quantitatively 25... 

Amine complexes. The effect of immobilization of the Cu(II) complexes of polymeric amines has been examined and reviewed by Challa et al. ( ). The polymeric ligands were varied by using the following species polymer-bound dimethylbenzylamlne (formed by treatment of chloromethylated polystyrene with dimethylamlne), the copolymer of styrene and 4-vinyl-pyridine and the copolymer of styrene and N-vinylimidazole. The reaction examined was the Cu(II) oxidative dimerization of 2,6-disubstituted phenols (Equation 1). 

Poly(phenylene oxides) are produced by the oxidative coupling of 2,6-disubstituted phenols. The polymers are also known as poly(oxyphenylenes) or poly(phenyl ethers), and, in the case of dimethyl compounds, also as poly(xylenols). Copper (I) salts in the form of their complexes with amines catalyze the reaction. Primary and secondary aliphatic amines must be used at low temperatures, since otherwise they are oxidized. Primary aromatic amines are oxidized to azo compounds, and secondary aromatic compounds probably to hydrazo compounds. Pyridine is very suitable. 

The oxidative coupling of 2,6-disubstituted phenols occurs in the presence of an oxidizing agents like alkaline ferrocyanide [75,76], MnO [77], PbO [78], CrO [79], strong base [80], etc., but also takes... 

Oxidative coupling of 2,6-disubstituted phenols is catalyzed by copper-amine complexes [66]. Endres et al. [70] have shown that the ratio of the nitrogen-containing ligand and copper can be used to control C-0 vs. C-C coupling. 

The catalytic activity of copper complexes in oxidative coupling of 2,6-DMP to PPO is significantly improved when polymer-bound 4-aminopyridine is used as ligand [92]. Basic copper-amine complexes also catalyze the oxidative coupling of 2,6-disubstituted phenols [82]. Depending on the size of substituents and the conditions, polymerization or diphenoquinone formation may predominate [83-86]. Small substituents like methyl favor the PPO product. 

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