Para substituted phenolic ketones

Para-substituted phenols may still couple through the para position and products may be formed in good yield, especially if stable. Thus p-cresol gives Pummerer s ketone (9 63%) on treatment with silver... 

Substituted and Heat Reactive. The third class, substituted and heat-reactive resins, are made by using para-substituted phenols where the substituent is a four-carbon or higher group such as tert-butyl, tert-octyl, and phenyl. Small amounts of ortho-substituted phenols and unsubstituted phenols are sometimes coreacted but, in general, the functionality is 2, and only linear molecules are formed. They are brittle solids that do not form films. The substituent makes the resins less polar and hence they are soluble in ketones, esters, and aromatic hydrocarbons, with limited solubility in alcohols and aliphatic hydrocarbons. The phenolic resins based on longer chain aliphatic phenols are more compatible with drying oils, alkyds, and rubbers. 

The following is relevant first, the ortho- and p ra-substituted phenolic ketones can be interconverted that is, they are in equilibrium. At low temperature, the para-isomer predominates, but, as the temperature is raised, the ortho-i oxa r becomes the major product. Second, if two different esters are used, cross products are observed. Third, the rearrangement is only into the positions ortho and para to the hydroxyl group. K there is a substituent (such as a chlorine or methyl) meta to the phenol, it remains unaffected, but the product mixture seldom contains... 

Transposition of substituents takes place from aromatic compounds based on ortho effects from hydroxyphenyl ketones via assumed nucleophilic attack on the carbonyl carbon atom of the phenoxide site to give a tight tetravalent intermediate that promptly decomposes through benzyne neutral release and formation of a carboxylate anion (Scheme 17.19a). This reaction is hindered from meta- and para-substituted phenols. Alternatively, radical alkane loss is also observed that can be rationalized by considering the formation of an ion-neutral complex (Scheme 17.19b) comprised of quinone-like and alkylide groups. The relatively low ionization energy allows the generation of odd-electron quinone-like species and the elimination of the alkane radical (Scheme 17.19b). 

Fries rearrangement—that is, the transformation of phenolic esters to isomeric hydroxyphenyl ketones—is related to Friedel-Crafts acylations.392,393 Olah et al.394 have found a convenient way to perform the Fries rearrangement of a variety of substituted phenolic esters in the presence of Nafion-H in nitrobenzene as solvent [Eq. (5.153)]. A catalytic amount of Nafion-H is satisfactory, and the catalyst can be recycled. In contrast, Nafion-silica nanocomposites, in general, exhibit low activities in the Fries rearrangement of phenyl acetate to yield isomeric hydroxyacetophe-nones.239,395 In a recent study, BF3-H20 was found to be highly efficient under mild conditions (80°C, 1 h) to transform phenolic esters of aliphatic and aromatic carboxylic acids to ketones (71-99% yields).396 In most cases the para-hydroxyphenyl isomers are formed with high (up to 94%) selectivity. 

Lunarine (26), one of the typical neolignans, is biosynthesized by the ortho-para radical coupling between two molecules of p-hydroxycinnamic acid. In this connection, oxidative coupling reactions of 4-substituted phenols have been extensively stndied using thallium trifluoroacetate (TTFA), potassium ferricyanide (K3[Fe(CN)g]) and other reagents. p-Cresol (27) was also electrolyzed at a controlled potential (+0.25 V vi. SCE) in a basic medium to afford Pummerer s ketone 28 in 74% yield. The snggested mechanism is given in Scheme 4. 

The scope of the reaction is broadened by the use of the tetrahydrophosphepine ligand. In addition to heterocycles that were reactive with PCy3 or cyclohexyl-phobane as ligands, 4,5-dimethylthiazole can be arylated. The scope with respect to the bromoarene partner is also broadened to include electron-rich bromoarenes and heteroaryl bromides such as 3-bromothiophene, 5-bromo-iV-methylindole, 5-bromobenzofuran, and 5-bromobenzothiophene. Functional groups including sulfoxides, chlorides, fluorides, ketones, esters, primary and secondary amides, phenols, anilines, and pyridines can be tolerated under these conditions. Sterically hindered and/or ortho substituted substrates are unreactive, but meta and para substituted substrates are well-tolerated. 

T. S. Croft, Phosphorus Sulfur, 1976, 2, 133 [phenols -1- CF3SCI - ortho- and para-substitution products) Yu. V. Zeifman, L. T. Lantseva, and I. L. Knunyants, Izv. Akad. Nauk SSSR, Ser. Khim., 1978,1229 and K. Hiroi, Y. Matsuda, and S. Sato, Chem. Pharm. Bull., 1979,27,2338 [sulphenylation of ketone anions and 1,3-dicarbonyl dianions, respectively see also A. De Groot and... 

Electron rich olefins such as (70) readily react with phenols to give the para-substituted aminals (71) which can be hydrolysed to the corresponding aldehydes. When the pura-position is blocked reasonable yields of salicylaldehydes are obtained. Further cycloadditions of tetra-alkoxyethenes with aj8-unsaturated carbonyl compounds and 1-cyanobutadienes have been studied. T6s The latter product gives a [2 4- 2] and not a [4 + 2] adduct. Addition of silyl enol ethers to nitroalkenes leads to intermediate nitronic acids (72) which on hydrolysis give 1,4-diketones. In the presence of a Lewis acid the intermediates are not isolated and good yields of the synthetically useful ketones are obtained (Scheme 46). This procedure would seem to compare favourably with alternative syntheses of these intermediates. ... 

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