PHENOLS AND PHENYL ETHERS

Concerning phenyl ethers, the i.r. spectrum of anisole (Fig. 3.25), its p.m.r. spectrum (Fig. 3.46) and 13C-n.m.r. spectrum (Fig. 3.54) are discussed on pp. 325, and 337 respectively. Further illustrative analyses are included in some of the preparative examples below which also include a discussion of relevant m.s. 

The use of a palladium membrane catalyst was not very effective for this reaction, giving only a 60% yield of cyclohexanone at about 80% conversion.  

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Nowadays, rhodium or ruthenium are often the preferred catalysts. Rhodium can be used under mild conditions, whereas ruthenium needs elevated pressures. If pressure is available, it might as well be used even with rhodium, for increased pressure makes more efficient use of the catalyst, as well as decreases whatever hydrogenolysis might occur at lower pressure. Rhodium 7,8,12 20,21,38,39,45,65,66,68,69,75) and ruthenium 18,26 8,52,68,69,72,74) are especially advantageous in reductions of sensitive phenols and phenyl ethers that undergo extensive hydrogenolysis over catalysts such as platinum oxide. 

The synthesis of 3-aryltetrahydroisoquinolines was accomplished by electrophilic aromatic substitution of polysubstituted phenols and phenyl ethers with Lewis acid-generated tosyliminium ions of 2-tosyl-3-methoxytetrahydroisoquinoline derivatives <00SL801>. In addition isoquinoline was reported to react with N-tosylated (R)- or (S)-amino acid fluorides to afford optically active dihydroimidazoisoquinolinones. The reaction proceeds via acylation followed by attack of the tosylamino group at Cl of the intermediate 2-tosylaminoacylisoquinolinium salt <00TL5479>. 

The test (b) we carried out typically as follows but we have also used many variations of this procedure [18]. We used an assembly of connected reaction tubes attached to the vacuum line. In one tube we polymerised (I) by perchloric acid in methylene dichloride. Reaction was stopped by adding sodium phenate, and any phenol formed from secondary oxonium ions was neutralised with sodium hydride. The volatile compounds were distilled into a second tube where the same experiment was repeated. This technique is based on that of Saegusa and Matsumoto [19] phenol and phenyl ethers can be estimated separately by their UV spectra. 

A. The Basic Series.—In general, aromatic aldehydes condense with aromatic amines in the presence of zinc chloride to form triphenylmethane derivatives (0. Fischer) phenols and phenyl ethers behave similarly in the presence of concentrated sulphuric acid (Baeyer). The products formed are the leuco-compounds of well-known dyes. 

Of the phenols and phenyl ethers used as fragrance and flavor substances, 4-allyl-(9, R = H) and 4-propenylphenols (10 and 11, R = H) and their methyl ethers (9-11, R = CH3) occur particularly frequently in essential oils. 

Few of the phenol derivatives that have a keto substituent in their side-chain are of interest as fragrance or flavor substances. A number of phenols and phenyl ethers acetylated in the benzene ring have been identified as volatile components of foods. 4-Methoxyacetophenone is of some interest as a fragrance material. 4-Hydroxybenzylacetone, a higher mass phenol ketone, has a characteristic raspberry aroma. 

Scheme 11. Mechanistic speculation on the different pathways taken by phenolic and phenyl ether substrates in the PIFA-mediated oxidative coupling reaction.

We shall return to reactions of phenols and phenyl ethers when we consider directing effects in electrophilic aromatic substitution in other reactions and in Friedel-Crafts reactions in particular. 

Rhodium catalysts saturate phenols and phenyl ethers with little hydrogenolysis. They are recommended for the hydrogenation of sensitive compounds. Rhodium-on-alumina promotes hydrogenation of gallic acid 6 to all-c -hexahydrogallic acid 7. ... 

Aliphatic nitriles react slowly with phenols and phenyl ethers in the presence of trifluoromethanesulphonic acid to give ketones after hydrolysis, in a variation of the Houben-Hoesch reaction. The crystalline complex of copper(i) triflate and benzene induces the acylation of aromatic substrates with selenol esters, affording a transition-metal mediated version of the Friedel-Crafts reaction. Aromatic carboxylic acids can be converted into symmetrical diaryl ketones in good yield by treatment of their 5-(2-pyridyl)thioesters with bis-(l,5-cyclo-octadiene)nickel [equation (15)]. In contrast to other methods for preparing symmetrical aromatic ketones, this method allows their preparation from a single starting material. 

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