Oxidative coupling of phenols

Phenols are biosynthesized essentially in two ways. One is along the polyketide pathway starting with acetyl-CoA (Chapter 3), the other along the shikimic acid pathway (Chapter 5). A phenol, or indeed any benzenoid compound, so formed may be at a terminus in biosynthesis or be involved in the formation of other metabolites. Of general importance in this regard is the coupling together of two phenolic residues, e.g. 1.35) 1.38). A firm mechanistic base was 

---

W. I. Taylor and A. R. Battersby, eds.. Oxidative Coupling of Phenols, Marcel Dekket, New York, 1967. 

Removal of tert-AW Groups, Alkyl groups on a phenol nucleus can be removed selectively to produce a desired synthetic result. The oxidative coupling of phenol offers a good example. 2,6-Di-/ f2 -butylphenol can be coupled under oxidative conditions to... 

Although permanganate ions are not generally used to effect oxidative coupling of phenols, it has been shown that, in the presence of a catalyst in an organic solvent, 2-methoxyphenols are coupled oxidatively under very mild conditions to produce the dimeric products (>50%) [48], Unsaturated substituents are not oxidized under the mild conditions. 

Poly(phenylene oxide) PPO, or poly(phenylene ether) PPE, is an engineering polymer developed by General Electric. It concerns the oxidative coupling of phenols discovered in 1956 by Allan S. Hay [21], Oxidative coupling leads to the formation of carbon-oxygen bonds between carbon atoms 2,4, and 6 and the phenolic oxygen atom. To avoid coupling with carbon atoms 2 and 6, alkyl substituents at these two positions were introduced. In addition to the polymer a 4,4 dimer is formed, named diphenoquinone (DPQ). The... 

Figure 15.15. Copper cataly sed oxidative coupling of phenols...

The earlier literature on oxidative coupling of phenols is reviewed in Ref. [168] and that on anodic coupling in Ref. [169, 170] some examples of the coupling reactions are summarized in Table 11, see also Chapter 6. 

In recent years, numerous applications of such peroxidase-catalyzed oxidative coupling of phenols and aromatic amines have been reported (Table 7). These peroxidase-catalyzed biotransformations lead to modified natural products with high biological activities [110-118]. Several examples have also been described for the oxidative coupling of phenols with peroxidases and other oxidative enzymes from a variety of fungal and plant sources as whole cell systems... 

Oxidation of phenols and aromatic amines using HRP is generally of little synthetic value, as oligomers and polymers are the main products (5, 260). Under certain conditions oxidative coupling of phenols or naphthols to give biaryls can be achieved, but with low selectivity (262). In contrast, HRP can catalyze a number of useful oxidative N-and 0-deaIkyIation reactions that are relatively difficult to carry out synthetically. This area has been described in detail by Meunier (263). A method for the preparation of optically active hydroperoxides using HRP C has been developed (264). Optically pure (S)-hydroperoxides... 

Oxidative coupling involves condensation reactions catalyzed by phenol oxidases. In oxidative coupling of phenol, for example, arloxy or phenolate radicals are formed by the removal of an electron and a proton from an hydroxyl group. The herbicide 2,4-D is degraded (Fig. 15.5) to 2,4 dichlorophenol, which can be oxidatively coupled by phenol oxidases (Bollag and Liu 1990). 

Nonphenolic oxidative coupling of phenol ether derivatives using IBTA can also produce seven-membered N-containing heterocyclic compounds as exemplified by Eq. (45) [96JCS(CC)1481],... 

Evidence for Specificity in the Oxidative Coupling of Phenolic Side-Chains in the Cell Wall... 

Taylor, W. L, Battersby, A. R. Oxidative coupling of phenols. New York Marcel Dekker 1968. 

Oxidative coupling of phenols and phenol ethers.2 This reaction can be conducted with ferric chloride supported on silica gel. 

Figure 14.18 Some simple products and postulated mechanisms for oxidative coupling of phenol. The subscripts o and p are used to denote ortho- and para-position, respectively. Note that many more products can be formed particularly from substituted phenols (see, e.g., Dec and Bollag, 1994 Yu et al., 1994).

Allan S. Hay In the oxidative coupling of phenols with copper-amine catalysts and oxygen the evidence is quite compelling that the active catalyst has the structure... 

Figure 5.20. Biaryl formation from resin-bound aryl bromides and arylzinc compounds [32,204], and by oxidative coupling of phenols [205],...

Phenols have been prepared on solid phase by aromatic nucleophilic substitution with hydroxide, by thermal rearrangement of vinylcyclobutenones, by oxidative coupling of phenols (Figure 5.20 [65]), by cyclocondensation reactions with simultaneous release of the phenols into solution (Entry 12, Table 7.6), and by Claisen rearrangement [66]. 

In the presence of trace amounts of water, the tetrameric p,2-oxo complex (182) in 1,2-dimethoxyethane is transformed into a p, -oxo tetrameric complex (183 equation 254), characterized by an X-ray structure.574 In contrast, (182) 572,575 is inactive towards the oxidation of phenols. The reaction of N,N,N, AT -tetramethyl-l,3-propanediamine (TMP) with CuCl, C02 and dioxygen results in the quantitative formation of the /z-carbonato complex (184 equation 255).s76 This compound acts as an initiator for the oxidative coupling of phenols by 02. 6 Such jz-carbonato complexes, also prepared from the reaction of Cu(BPI)CO with 02 [BPI = 1,3 bis(2-(4-methyl-pyridyl)imino)isoindoline],577 are presumably involved as reactive intermediates in the oxidative carbonylation of methanol to dimethyl carbonate (see below).578 Upon reaction with methanol, the tetrameric complex (182 L = Py X = Cl) produces the bis(/z-methoxo) complex (185 equation 256), which has been characterized by an X-ray structure,579 and is reactive for the oxidatiye cleavage of pyrocatechol to muconic acid derivatives.580,581... 

This reaction has been actively studied since it was first reported by Hay in 1959 (I), but most of the extensive literature, which includes several recent reviews (2-8), deals primarily with the complex polymerization mechanism. Few copolymers have been prepared by oxidative coupling of phenols, and only one copolymer system has been examined in any detail. Copolymers of 2,6-dimethylphenol (DMP) and 2,6-diphenylphenol (DPP) have been prepared and the effect of variations in polymerization procedure on the structure and properties of the copolymers examined (4, 9) this work has now been extended to copolymers of each of these monomers with a third phenol, 2-methyl-6-phenylphenol (MPP). This paper presents a study of the DMP-MPP and MPP-DPP copolymers and a comparison with the DMP-DPP system previously reported. 

The reactive intermediates in oxidative coupling of phenols are aryloxy radicals. Growth may occur by the successive addition of aryloxy units as shown in Reaction 5. 

Block and Random Copolymers by Oxidative Coupling of Phenols... 

Sequential Oxidation of DMP and DPP. The usual approach to formation of block copolymers is by the sequential polymerization of two or more monomers or by linking together preformed homopolymer blocks. In view of the importance of the redistribution process in the oxidative coupling of phenols there can be no assurance that successive polymerization of two phenols will yield block copolymers under any conditions. It is certain, however, that block copolymers can be formed only if the conditions are such that polymerization of the second monomer is much faster than redistribution of the added monomer with the polymer previously formed from the first. The extent of redistribution is followed conveniently by noting the effect of added monomer on solution viscosity, as indicated by the efflux time from a calibrated pipet. 

An excellent survey of the various methods of synthesis is available53 this section includes some of the illustrative methods of synthesis of the simpler analogues. These methods may be considered under the following headings (a) the oxidation of hydrocarbons (b) the oxidation of phenols and the oxidative coupling of phenols (c) the oxidation of dihydric phenols and aminophenols and (d) the cyclisation of aroylbenzoic acids. 

The use of hypervalent iodine reagents in carbon-carbon bond forming reactions is summarized with particular emphasis on applications in organic synthesis. The most important recent methods involve the radical decarboxylative alkylation of organic substrates with [bis(acyloxy)iodo]arenes, spirocyclization of para- and ortho-substituted phenols, the intramolecular oxidative coupling of phenol ethers, and the reactions of iodonium salts and ylides. A significant recent research activity is centered in the area of the transition metal-mediated coupling reactions of the alkenyl-, aryl-, and alkynyliodonium salts. 

---