Phenolic coupling

When an aqueous solution of a diazonium salt is added to an alkaline solution of a phenol, coupling occurs with formation of an azo-compound (p. 188). If ho vc cr the ntiueous solution of the diazonium salt, t. . ., />-bromohenzene diazonium chloride, is mixed with an excess of an aromatic hydrocarbon, and aqueous sodium hydroxide then added to the vigorously stirred mixture, the diazotate which is formed, e.g., BrC,H N OH, dissolves in the hydrocarbon and there undergoes decomposition with the formation of nitrogen and two free radicals. The aryl free radical then reacts with the hydrocarbon to give a... 

Reaction that can be carried out by the oxidative coupling of radicals may also be initiated by irradiation with UV light. This procedure is especially useful if the educt contains oleflnic double bonds since they are vulnerable to the oxidants used in the usual phenol coupling reactions. Photochemically excited benzene derivatives may even attack ester carbon atoms which is generally not observed with phenol radicals (I. Ninoraiya, 1973 N.C. Yang, 1966). 

The early yellow disperse dyes were based on phenolic coupling components, eg, Cl Disperse Yellow 3 (92) (diazotized 4-arninoacetanihde coupled to -cresol) which is still used today for the coloration of cellulose acetate and nylon fibers. 

In the first of these, the key step in the synthetic sequence involves an oxidative phenol coupling reaction patterned after the biosynthesis of the natural product. Preparation of the moiety that is to become the aromatic ring starts by methyla-tion of phloroglucinol (5) with methanolic hydrogen chloride to give the dimethyl ether (6). Treatment of that intermediate with sulfuryl chloride introduces the chlorine atom needed in the final product (7). 

Organic syntheses based on biosynthetic proposals are often extremely concise and elegant.6 Although the constitution and stereochemical complexity of carpanone may seem formidable, the sequential application of the Diels-Alder and oxidative phenolic coupling transforms7 to the natural product provides an exceedingly efficient solution. Chapman s striking synthesis of carpanone typi-... 

Schwartz MA, Holton RA (1970) Intramolecular oxidative phenol coupling. II. Biogenetic-type synthesis of (+-)-maritidine. J Am Chem Soc 92 1090-1092... 

Bisbenzylisoquinoline alkaloids are dimeric benzyltetrahydroisoquinoline alkaloids that are known for their pharmacological activities. A well-described example is the muscle relaxant (+)-tubocurarine, which in crude form serves as an arrow poison for South American Indian tribes. In the biosynthesis of this broad class of dimeric alkaloids, it has been postulated that the mechanism of phenol coupling proceeds by generation of phenolate radicals followed by radical pairing to form either an inter- or intramolecular C - O or C - C bond. Enzyme studies on the formation of bisbenzylisoquinoline alkaloids indicated that a cytochrome P-450-dependent oxidase catalyzes C - O bound formation in the biosynthesis of berbamunine in Berberis cell suspension culture.15 This enzyme, berbamunine synthase (CYP80A1), is one of the few cytochromes P-450 that can be purified to... 

KRAUS, P.F.X., KUTCHAN, T.M., Molecular cloning and heterologous expression of a cDNA encoding berbamunine synthase, a C - O phenol coupling cytochrome P450 from the higher plant Berberis stolonifera, Proc. Natl. Acad. Sci. USA, 1995, 92,2071-2075. 

Scheme 3. Phenolic coupling reactions caused by one-electron oxidations.

Oxidative phenolic coupling. Biosynthesis of the alkaloid narwedine (3) is known to involve oxidative phenolic coupling of norbelladine derivatives (1), but the usual oxidants for such coupling in vitro convert 1(R = H) into the oxomaritidine skeleton (4) rather than 3. A new biomimetic synthesis of 3 involves the palladacycle 2, formed by reaction of 1(R = CH3) with Li2PdCl4, which is known to form complexes with allylic amines or sulfides (8,176-177). Oxidation of 2 with thallium(III) trifluoroacetate effects the desired coupling to give 3. 

Biaryl phenol coupling.1 The natural dibenzylbutanolide lignans, prestegane A (la) and B (lb), are converted to the corresponding bisbenzocyclooctadiene lactones (2) by oxidation with Ru02 in TFA-TFAA in 80-85% yield. The usual reagent for this oxidation, thallium tris(trifluoroacetate), is less efficient (45-50% yields). 

Figure 14. Proposed mechanism and stereochemical model for Nakajima s phenolic coupling using proline-derived copper complexes. [Adapted from (129).]...

The one-electron reduction potentials, (E°) for the phenoxyl-phenolate and phenoxyl-phenol couples in water (pH 2-13.5) have been measured by kinetic [pulse radiolysis (41)] and electrochemical methods (cyclic voltammetry). Table I summarizes some important results (41-50). The effect of substituents in the para position relative to the OH group has been studied in some detail. Methyl, methoxy, and hydroxy substituents decrease the redox potentials making the phe-noxyls more easily accessible while acetyls and carboxyls increase these values (42). Merenyi and co-workers (49) found a linear Hammett plot of log K = E°l0.059 versus Op values of substituents (the inductive Hammett parameter) in the 4 position, where E° in volts is the one-electron reduction potential of 4-substituted phenoxyls. They also reported the bond dissociation energies, D(O-H) (and electron affinities), of these phenols that span the range 75.5 kcal mol 1 for 4-amino-... 

One-Electron Reduction Potentials (E°) of the Phenoxyl-Phenolate and Phenoxyl-Phenol Couples... 

In order to facilitate satisfactory dye uptake, the molecular size of a disperse dye must be kept small monoazo structures are therefore exceptionally important, particularly in the coloration of polyester and cellulose triacetate. In the yellow shade area, molecular size generally poses no problem and the various available coupling components can all be used without making the molecule too large. A very simple example of the type of structure employed using a phenolic coupling component is Cl Disperse Yellow 3 (4-72). This dye is known to cause skin sensitisation when on nylon [85] and can also provoke an allergic reaction [86]. 

Vanillin (4-hydroxy-3-methoxybenzaldehyde) in ethanolic solution - as supplied as a flavouring agent - was dimerized by sunlight or more rapidly under a mercury lamp to dehydrodivanillin (3). This is a typical ortho-phenol coupling reaction [20],... 

If the five resonance forms of the phenoxy radical (Figure 3.6) can couple to any other phenoxy radical, the theoretical number of dimeric structures possible is 25. The relative frequency of involvement of individual sites in the phenolic coupling reaction depends on their relative electron densities. Quantum mechanical calculations predict that the high electron densities at the phenolic oxygen atom and the carbon atom would give rise to a high proportion of fi-O-4 linkages, which is indeed observed to be the case (Table 3.1). 

A variety of phenol couplings have been described. Those reported before 1991 have been reviewed [66]. 2-Naphthol (27) was oxidized to l,l -binaphthol (28) in high current efficiency on a graphite felt electrode coated with a thin poly(acrylic acid) layer immobilizing 4-amino-2,2, 6,6-tetramethylpiperidinyl-l-oxy (4-amino-TEMPO) (Scheme 10) [67]. 

Keywords Peroxidase, Biocatalysis, Asymmetric synthesis. Kinetic resolution. Hydroperoxide, Epoxidation, Sulfoxidation, Halogenation, Hydroxylation, Phenol coupling. 

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