Arylation phenols

Mercuration of aromatic compounds can be accomplished with mercuric salts, most often Hg(OAc)2 ° to give ArHgOAc. This is ordinary electrophilic aromatic substitution and takes place by the arenium ion mechanism (p. 675). ° Aromatic compounds can also be converted to arylthallium bis(trifluoroacetates), ArTl(OOCCF3)2, by treatment with thallium(III) trifluoroacetate in trifluoroace-tic acid. ° These arylthallium compounds can be converted to phenols, aryl iodides or fluorides (12-28), aryl cyanides (12-31), aryl nitro compounds, or aryl esters (12-30). The mechanism of thallation appears to be complex, with electrophilic and electron-transfer mechanisms both taking place. 

In hydrogenation, early transition-metal catalysts are mainly based on metallocene complexes, and particularly the Group IV metallocenes. Nonetheless, Group III, lanthanide and even actinide complexes as well as later metals (Groups V-VII) have also been used. The active species can be stabilized by other bulky ligands such as those derived from 2,6-disubstituted phenols (aryl-oxy) or silica (siloxy) (vide infra). Moreover, the catalytic activity of these systems is not limited to the hydrogenation of alkenes, but can be used for the hydrogenation of aromatics, alkynes and imines. These systems have also been developed very successfully into their enantioselective versions. 

Methylstilbenes, asymmetric hydrogenation, 10, 39-40 a-Methylstyrene, hydrocarbonylation, 11, 465 Methyl-substituted phenol, arylation with lead triacetates,... 

Aromatic alcohols are called phenols. The word phenol comes from phenyl alcohol. Phenol itself, formerly known as carbolic acid, finds application as a preservative. Three example phenols are illustrated in Figure 11.23. Hexachlo-rophene, a phenolic aryl halide, was once a common active ingredient in over-the-counter antibacterial soaps. 

Reaction of Diazonium Salts with Quinones and with Phenols. Aryl-diazonium salts couple with quinones in the presence of sodium acetate to... 

Deoxygenation of phenols. Aryl nonaflaics, readily available by reaction of phenols with this reagent and triethylamine, undergo hydrogenolysis (H., Pd/C) more rapidly and in higher yield (80-90%) than do aryl mcs> lates or tosylates. 

Protection of phenols. Aryl isopropyl ethers are also obtained by reaction of phenols with 2-bromopropane in DMF. The protective group is cleaved by BCl, in C HjCIj at 0°, but it is stable to SnCl, or TiCl, under these conditions. It is recommended for protection of phenolic groups during formylation with ilichloromethyl methyl ether in the presence of SnCl,. 

The aromatic cyanates are of much more importance. If phenols are treated with cyano halides in such a way as to definitely prevent an excess of the corresponding phenolate, aryl cyanates can be isolated in up to quantitative yields. To achieve this, triethylamine is slowly added to an equimolar mixture of the phenol and the cyano halide in a nonprotic solvent, preferably acetone or n-pentane/diethyl ether (equation 27).Heteioaromatic hydroxy compounds can be treated in the same way. The method fails, however, if various electron-attracting substituents are present, as for instance with 2,4-dinitrophenol or polyhalophenols. ... 

Arylation involves the reaction between amines and phenols, aryl halides and aryl amines, including aniline. In arylation, one reactant acts as solvent acidic catalysts and high temperatures are employed. Diphenylamine (A-phenylbenzeneamine, /V-phenylani-line) (8) is made by condensation of aniline in the presence of a small amount of mineral acid catalyst at around 300 °C catalytic reaction of chlorobenzene with aniline at high temperature and pressure and continuous vapor-phase catalytic condensation of aniline. It is a useful intermediate in azo dye manufacture. Crompton is the main US manufacturer of 8, producing 1.3 billion lbs. in 2000. Applications include as lube additives... 

Figure 1. Strong anion exchange LC separation of phenols, aryl glucuronides and aryl sulfates using a UV absorbance detector. Compounds eluted are 1, phenol 2, 4-nitrophenol 3, 1-naphthol 4, phenyl-be ta-D-glucuronide 5, 4-nitrophenyl-beta-D-glucuronide 6, 1- naphthyl-beta-D-glucuronide 7, phenyl sulfate 8, 4-nitrophenyl sulfate 9, 1-naphthyl sulfate. (Reproduced with permission from Ref. 19. Copyright 1989 Elsevier Science Publishers B.V.)...

FIGURE 11.15 Reaction mechanism for oxidation of a phenolic aryl-a-carbonyl structure with alkaline hydrogen peroxide. 

Friedel-Crafts reaction. Active arenes (phenols, aryl ethers, aryl sulhdes,...) are alkylated by A-tosyl aldimines (and benzylamines) such that 1,1-diarylalkanes result, with promotion by Bi2(S04)3-Me3SiCl. ... 

Bromination. Active arenes such as phenols, aryl ethers, and anilines are brominated by ZrBr4 in the presence of diisopropyl azodicarboxylate in CH2CI2. A free para position is the preferred site for bromination. 

Dioxan Br2, alone or in ether or dioxan, can be used to monobrominate phenol, polyhydric phenols, aryl ethers, and salicyclic acid.452... 

Cyclic imines. Alkynylamines cyclize under the influence of (MeCN)4CuPF(,. Diaryl ethers. The phenol-aryl halide coupling is promoted by CS2CO3 and (MeCN)4CuPF(,. 

Non-phenolic aryl-aryl coupling of electron rich aromatics is based on the formation of a radical cation effected by the... 

The heterocycle 3-methyl-1,2-benzisoxazole, whilst structurally distinct from the phenolic aryl ethers underwent cleavage at the 0-N bond by slow addition in tetrahydrofuran to 1M lithium diethylamide at -75 C followed by isolation of crude 1,6-dihydropyridazine and its oxidation with manganese dioxide over 1 hour to give 3,5-bis(2-hydroxyphenyl)pyridazine in 61% yield (ref.96). 

Protection of phenols. Aryl methyllhiomethyl ethers can be obtained in 90 95% yield by reaction of sodium phenoxides with chloromethyl methyl sulfide in HMPT (20 , 16 hours). Deprotection is accomplished (90-95% yield) with HgCta in refluxing CHJCN-H2O (10 hours). 

In an effort to eliminate heavy metals (Pd, Cu) from the preparation of diaryl ethers, a procedure using a sterically hindered proazaphosphatrane promoter has recently been reported using microwave heating (Scheme 2.23). Using TBDMS-protected phenols, aryl halides, 1-10% of the promoter and toluene as a solvent, this... 

Product.s phenols aryl halides benzonitriles aryl halides (deamination) azo dyes... 

Novalac resins can be produced from alkyl phenols, aryl phenols and polyhydroxy phenols to obtain special properties and Table 13.5 lists resins derived from o-cresolformaldehyde and ECH. 

Hydroxyl compoimds accelerate the rate of amine curing. A mechanism has been proposed (100) in which the hydrogen atom of the hydroxyl group partially protonates the oxygen atom on the epoxy group, rendering the methylene group more susceptible to attack by the nucleophilic amine. Reactivity is proportional to the hydroxyl acidity and fimctionality phenolics, aryl alcohols, and polyfunctional alcohols afford the best results. 

Any functional group that undergoes oxidation with permanganate interferes with the test (phenols, aryl amines, most aldehydes, primary and secondary alcohols, etc.). 

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