Ethyl ethers, to protect phenols

Ethyl ethers, to protect phenols, 147 Ethylidene acetals, to protect 1,2- and... 

An ether that would not undergo rearrangement to a 3-alkyl derivative during acid-catalyzed removal of — NH protective groups was required to protect the phenol group in tyrosine. Four compounds were investigated (9-cyclohexyl-, (9-isobomyl-, 0-[l-(5-pentamethylcyclopentadienyl)ethyl]-, and O-isopropyltyro-sine. 

A solution of 0.05 mol (4.7 g) of pure, water-free phenol in 20 ml of Et20 is added to 14.4 g (0.2 mol, excess) of ethyl vinyl ether. The mixture is cooled to — 5 °C and 100 mg of /7-toluenesulfonic acid is added. The cooling bath (C02-acetone) is removed and the temperature is allowed to rise to +10 °C, then the solution is cooled again to 0 °C and the second portion of 0.05 mol of phenol is added. After the exothermic reaction has subsided, the solution is stirred for an additional half hour at +10 °C. A second portion of 100 mgofacidisadded. If no evolution of heat is observed, a solution of 5 g of potassium carbonate in 25 ml of water is added with vigorous stirring. The upper layer is separated off, dried over potassium carbonate and concentrated in vacuo, giving the protected phenol in almost quantitative yield. The undistilled product is used for the metallation. 

Ethers and alcohol ethers Ethers such as ethyl ether are excellent solvents for some of the natural resins, oils, and fats. The usual forms of ether used in protective coatings are alcohol ethers such as ethylene glycol mono methyl ether, known commonly as cellosolve. Cellosolve is a good solvent for many oils, gums, natural resins, and synthetic resins such as alkyds, ethyl-cellulose, nitro-cellulose, polyvinyl acetate, pol)Tvinyl butyryl, and phenolics. Cellosolve is a slow solvent that is used in many lacquers to improve flow-out and gloss. 

Preparation of the donor 46 was started from 4,6-0-benzylidene protected thiomannoside 47 (Scheme 7.24). Alkylation with p-allyloxybenzyl chloride under phase transfer conditions78 was followed by 3-O-silylation and Pd(0)-mediated deallylation79 to give 48. The phenolic OH group was alkylated with ethyl 6-bromohexanoate and carboxylic acid, liberated by alkaline hydrolysis, was reacted with PEG monomethyl ether (MW -5000) under Mitsunobu conditions to afford 46. 

These ethers (and methoxymethyl) have not found extensive use in phenol chemistry as protecting groups possibly because their lability towards aqueous acid is so much greater than that of the conventional alkyl or benzyl group. One distinction which may be of advantage is that they are formed in the absence of base. Thus they are generated by addition of the phenol to an olefin, isobutylene or dihydropyran, under acid catalysis [12, 18]. The tetrahydropyranyl ether of 2-methyl-4-acetoxy-a-naphthol is thus formed at room temperature in ethyl acetate saturated with hydrogen chloride [18]. 

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