Benzyl phenol ketones

Higher esters of oxalic acid have been used, as, for example, the butyl [60] and the phenyl [15, 61]. Phenolic ketones other than the acetophenones lead to 3-substituted chromone-2-carboxylic acids although the yields are sometimes lower propiophenones give 3-methyl acids [7,14, 55,62,63] and benzyl aryl ketones lead to 3-phenylchromone-2-carboxylic acids [55]. 

Almost insoluble in cold water. Higher alcohols (including benzyl alcohol), higher phenols (e.g., naphthols), metaformaldehyde, paraldehyde, aromatic aldehydes, higher ketones (including acetophenone), aromatic acids, most esters, ethers, oxamide and domatic amides, sulphonamides, aromatic imides, aromatic nitriles, aromatic acid anhydrides, aromatic acid chlorides, sulphonyl chlorides, starch, aromatic amines, anilides, tyrosine, cystine, nitrocompounds, uric acid, halogeno-hydrocarbons, hydrocarbons. 

BF3-Et20, NaCNBHs, THF, reflux 4-24 h, 65-98% yield. Functional groups such aryl ketones and nitro compounds are reduced and electron-rich phenols tend to be alkylated with the released benzyl carbenium ion. The use of BF3 Et20 and triethylsilane as a cation scavenger is also effective." ... 

The chloromethylation can be generally employed in aromatic chemistry benzene, naphthaline, anthracene, phenanthrene, biphenyls and many derivatives thereof are appropriate substrates. The benzylic chlorides thus obtained can be further transformed, for example to aromatic aldehydes. Ketones like benzophe-none are not reactive enough. In contrast phenols are so reactive that polymeric products are obtained. ... 

The ketone 15 was eventually prepared by Grignard addition to Weinreb amide 21, as shown in Scheme 5.5. The Weinreb amide 21 was prepared from p-iodobenzoic acid (20). The phenol of readily available 3-hydroxybenzaldehyde (22) was first protected with a benzyl group, then the aldehyde was converted to chloride 24 via alcohol 23 under standard conditions. Preparation of the Grignard reagent 25 from chloride 24 was initially problematic. A large proportion of the homo-coupling side product 26 was observed in THF. The use of a 3 1 mixture of toluene THF as the reaction solvent suppressed this side reaction [7]. The iodoketone 15 was isolated as a crystalline solid and this sequence was scaled up to pilot plant scale to make around 50 kg of 15. 

Oxidation of the benzylic methylene group in cyclazocine to a ketone is also consistent with analgesic activity. Acetylation of benzomorphan 62 affords the diacetate 63. Selective hydrolysis of the phenolic acetate (64) followed by methylation of the thus uncovered phenol affords intermediate 65. 

Phenolic compounds were confirmed to be very stable against thermal treatment. Diphenyl methanol and benzophenone were stable against decomposition but hydrogenated to form diphenyl -methane quantitatively. Phenyl benzyl ketone was found to be partially hydrogenated or decarbonylated to form diphenyl alkanes. 

In contrast to phenolic hydroxyl, benzylic hydroxyl is replaced by hydrogen very easily. In catalytic hydrogenation of aromatic aldehydes, ketones, acids and esters it is sometimes difficult to prevent the easy hydrogenolysis of the benzylic alcohols which result from the reduction of the above functions. A catalyst suitable for preventing hydrogenolysis of benzylic hydroxyl is platinized charcoal [28], Other catalysts, especially palladium on charcoal [619], palladium hydride [619], nickel [43], Raney nickel [619] and copper chromite [620], promote hydrogenolysis. In the case of chiral alcohols such as 2-phenyl-2-butanol hydrogenolysis took place with inversion over platinum and palladium, and with retention over Raney nickel (optical purities 59-66%) [619]. 

The p-acetoxystyrene monomer, precursor of polymer III, is prepared from p-hydroxyacetophenone using the procedure of Corson et al. (14) which involves acetylation of the phenolic group followed by catalytic hydrogenation of the ketone and dehydration of the resulting benzylic alcohol as shown in Scheme 3. 

Although phenols are oxidized with DDQ,126 benzylic alcohols activated by phenol groups react so quickly with DDQ—delivering high yields of aldehydes or ketones—that this reagent is proposed as the best one for the oxidation of this kind of benzylic alcohols.127... 

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