METHODS OF PREPARATION OF COUPLED PHENOLICSThe diversity of phenol oxidation products offers interesting synthetic possibilities forthe preparation of simple and polymeric molecules containing phenolic and/or quinoidstructural elements; these can be formed from both like and unlike radicalspecies.13,22 The successful synthesis of various natural products from phenols hasbeen well documented from the 1950s to the present.23-28Biogenetic oxidative coupling routes were first investigated in 1957,29,30 and theprevalence of the overall coupling process in the biosynthesis of natural products wasauthenticated. Thus the oxidative coupling step has been found to be extremelyimportant in the natural formation of compounds as diverse as lignins,31 lignans,32tannins,33 plant pigments,22 and an estimated 10% of all known alkaloids.23 (Lignin isa complex biopolymer that accounts for 20-30% of the dry weight of wood. It isformed by the free radical polymerization of substituted phenylpropane units to yieldpolymers which have a number of functional groups such as aryl ethers, phenols andbenzyl alcohols.34)The major difficulty with oxidative coupling reactions of phenols is that a large varietyof potential products are possible from a single substrate when carried out in thepresence of various chemical or biological oxidants. This is because the phenolicmolecules are able to undergo both carbon-carbon (Scheme 4 shows para-paracoupling, though ortho-para coupling may also occur) and carbon-oxygen (Scheme 5)coupling reactions.Scheme 4: Carbon-carbon oxidative coupling (showing para-para coupling)Scheme 5: Carbon-oxygen oxidative couplingThe type of coupled product (whether C-C or C-O coupled) is also dependent onwhether the ortho or para positions bear substituents or not. In addition to these twopotential reaction products, the oxidative coupling of phenols also often allows for theformation of polymeric materials which, in general, are undesirable (though there area few industrial processes where these are of great importance35,36). It has beenreported that when carbon-oxygen coupling occurs, there is a tendency for furthercoupling to occur on the resultant substrate, and this leads to the formation ofpolymeric products.37To understand the effect that both the nature of the reactant and oxidant has on thetype of products that are formed, one must have an understanding of the variousreaction pathways that are possible, from a mechanistic point of view. A summary ofliterature reports dealing with the various mechanisms is now briefly discussed.General Types of Coupling Reaction MechanismsThe reaction pathway for the oxidative coupling of phenols has been extensivelyinvestigated.38,39 There are two main modes of coupling that may be highlighted.These are an external and an internal oxidation process. In the former, electrons aretransferred from the phenolic compound to an external oxidizing agent, whilst theinternal oxidation process involves an internal oxidation-reduction reaction in whichone substrate molecule is oxidized whilst another is simultaneously reduced. Sincethere is no change in the net overall oxidation state, this process may be termed anon-oxidative coupling (NOC) reaction.In our investigations, only the external oxidative coupling process was studied. Forthis reason, literature reports dealing only with this mode are summarized here.External oxidative coupling reactions may be grouped into two separate classes,those involving free radical intermediates, and those that are non-radical in nature.These may further be subdivided into several general mechanistic types.a) Mechanisms involving free radical intermediatesi) Direct coupling of two phenoxyl radicals (FR1)ii) Homolytic aromatic substitution (FR2)iii) Heterolytic coupling preceded by two successive one-electron oxidationsteps (FR3)b) Mechanisms which are non-radical in characteri) Heterolytic coupling preceded by a single two-electron transfer (NR1)ii) Concerted coupling and electron transfer (NR2)It has previously been widely accepted that, in the field of phenol oxidations, the FR1mechanism is the most viable (without discounting the FR2 mechanism). Mostreviewers have included the FR3 mechanism in their discussions but have attachedlittle importance to it. Until recently, no one has considered the NR1 and NR2mechanisms as significant enough to warrant a discussion of them in this context.The para-para (C-C) coupling of a simple 2,6-disubstituted phenol is used to illustratethe five general types of processes (FR1, FR2, FR3, NR1 and NR2) as listed above.In all cases, the oxidized phenolic species is written as the neutral phenol molecule,and only intermediates are shown as unprotonated. The following scheme (Scheme6) highlights the FR1, FR2 and FR3 mechanisms.GambarThe degree of protonation of the phenolic species in each of these mechanismsdepends on various factors, such as the acidity of the species, the nature of thesolvent and the pH of the solution.The free radical processes are initiated by means of pathway (a) shown in Scheme 6.The first one-electron transfer from the disubstituted phenol (1) to an oxidant resultsin the formation of the phenoxyl radical which is stabilized by resonance, as shown inthe following scheme (Scheme 7).Scheme 7: Resonance stabilization of the phenoxyl radicalThe formation of the phenoxyl radical is well attested, for example by ESR.40,41,42 (Ithas been shown9 that the subsequent dimerization thereof fits a diffusion-controlledmodel.)The phenoxyl radical is able to react in one of three ways, each leading to the sameproduct (Scheme 6).Firstly, it may homolytically combine with another phenoxyl radical by mechanismFR1 to afford compound (2). This dicyclohexadienone rapidly tautomerizes inprotic media to the more stable aromatic biphenol product (3).Secondly, the phenoxyl radical may react with the initial substrate (1) viamechanism FR2 to generate a dimeric radical. Upon loss of an electron and aproton from this new radical, (2) is formed once again. However, the dimericradical may also disproportionate, leading to a dihydro product (4) as well as to (2).As yet, compounds such as (4), although analogous to similar products produced in free radical aromatic substitutions,45 have not yet been observed in oxidativecoupling reactions. This may perhaps be due to the fact that the conversion of (4)to (3) is a facile one since (3) has enhanced stability due to its aromaticity.Thirdly, the phenoxyl radical may be further oxidized by removal of an electron, toyield a phenoxyl cation, according to mechanism FR3. The initial substrate (1),with concomitant hydroxyl proton loss, may then heterolytically couple with thecation to afford (2).Examples of the NR1 and NR2 non-radical processes are shown in Schemes (8) and(9), respectively. In both illustrations, the oxidant is represented as a tripositive metalion (M3+), which forms an initial metal-phenolate complex with (1).

As shown in Scheme 8, the metal complex decomposes into a phenoxyl cation withconcurrent reduction of the metal ion. Subsequently, heterolytic coupling similar tothat shown in Scheme 6 (the FR3 mechanism) affords compound (2) whichundergoes tautomerization, and so the desired product (3) is a result.Objections, based on energ etic grounds, to the formation and stabilization of cationicintermediates in this mechanism may be obviated by considering the possibility of aconcerted electron transfer, as for the simple NR2 mechanism shown in Scheme 9.Scheme 9: The NR2 mechanistic pathwayChemical and Electrochemical Methods for Oxidatively CouplingPhenolicsThere has been a tremendous amount of research carried out on the oxidativecoupling of phenols that involves the use of a wide variety of chemical oxidants and/orcatalysts. These include manganese(III) complexes,26,27 silver carbonate/celite,28molybdenum(VI) and (V),45 cupric salts,46 amongst numerous others.47-55 Theoxidative coupling of phenols through the use of electricity has been documented forboth direct56,57 and indirect58 electrochemical means, but these occur to a muchlesser extent as compared to that of chemical methods.The wide variety of possible oxidation products that may be obtained under oxidativecoupling conditions is clearly indicated by examples from work done earlier byscientists such as Barton,29 Thvagarajan59 and Pummerer.60 Subsequent researchhas mainly concentrated on the coupling of di- and tri- substituted phenols, and theliterature is virtually devoid of reactions using mono-substituted substrates.Furthermore, reports suggest that higher selectivities to the carbon-carbon coupledproducts are achieved when the substituents on the aromatic ring are large and bulky,such as the t-butyl moiety, since they prevent carbon-oxygen coupling due to thesteric hindrance that their bulk offers.In the next sections, research utilizing both the chemical and electrochemicalmethods (direct and indirect) for the oxidative coupling of phenols, is summarized.Chemical oxidative couplingFrom about as early as the 1920s, chemists have been researching the oxidativecoupling of phenols using chemical oxidizing systems. It was thought that alloxidative coupling reactions involved one electron transfers, and therefore that theseoxidations were all free radical reactions. The mechanisms by which the reactionsoccurred, and the characteristics of the various oxidizing agents and/or catalysts, were not investigated successfully because they were not well understood; it wasalways assumed that coupling occurred through the bonding of two phenoxyl radicals(FR1) to form the coupled biphenol. However, it has since become clear that thetypes of mechanisms involved are extremely dependent on the nature of the oxidantand/or catalyst used. Some of these, including vanadium (IV) and (V), a(nitrosonaphtholato)metal complex, activated manganese dioxide, and cupric salts,and the reaction pathways they are involved in, will now be discussed further.