Phenols, from aryl methyl

Periodic acid dihydrate, with iodine and durene to give iododurene, 51, 94 Phenols, from aryl methyl ethers, 53, 93 Phenylacetaldehyde, from 2-lithio-1,3,5-trithiane and benzyl bromide, 51, 43 Phenylacetic acid, bromination, 50, 31... 

We said earlier that simple methyl ethers are inappropriate as protecting groups for OH because they are too hard to take off again. That is usually true, but not if the OH is phenolic— ArOH is a better leaving group than ROH, so HBr will take off methyl groups from aryl methyl ethers too. 

In practice it is often more convenient to measure the release of a phenol from an aryl phosphomonoester. Standard serum phosphatase methods employ phenyl phosphate (188), p-nitrophenyl phosphate (189), phenolphthalein monophosphate (140), or thymolphthalein monophosphate (141) where the phenol released can be determined spectrophoto-metrically [only the Bodansky method (13) uses a Pi determination]. A number of fluorogenic substrates have been used for phosphatase studies, e.g., jS-naphthyl phosphate (30, 148), 4-methylumbelliferyl phosphate (143), and 3-O-methylfluorescein phosphate (144) The main advantage here is the much greater sensitivity of fluorescence as compared with spectrophotometric assays as little as 1 pmole of 4-methyl-umbelliferone can be detected in continuous assay. 

Singular examples to form aromatic ethers are a base-catalyzed, multistep, one-pot reaction of aryl methyl ketones with the appropriate fluorinated arylidenemalonitriles, the mercury acetate assisted synthesis of pentahalophenylvinyl ethers from vinyl acetate and the corresponding phenol, and the radical displacements in aryloxycyclohexadienones (e.g., 27) by halophenols. 2,3-Dichloro-5,6-dicyanohydroquinone (28) and products such as 29 are readily formed when cyclohexadienone 27 is treated with different phenols. 

Murugavel and Punniyamurthy developed a Cul-catalyzed one-pot synthesis of iminocoumarin aryl methyl ethers from ynal, phenol, and sulfonyl azide via a cascade [3-1-2]-cycloaddition, 1,3-pseudopericyclic ketenimine rearrangement, 1,4-conjugate addition, and aldol-type condensation at room temperature under air [195] (Scheme 8.120). 

When, furthermore, phenols (368) are coupled with 1 in the presence of a Pd° catalyst, the phenoxy-methyl-1,3-dienes 369 are produced [158]. As aryl allyl ethers, these can be made to undergo a Claisen rearrangement (205 °C, DMF) and the ensuing 2-(l,3-dienylmethyl)phenols 370 finally cydize in the presence of a trace of acid to a mixture of exo-methylene chromans 371 (major product) and dihydrobenzofur-ans 372 - a remarkable generation of functional and structural complexity from simple starting materials with 100% atom economy and underlining impressively the synthetic versatility of modern allene chemistry ... 

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