Phenol-benzyl ethers

Mel, K2CO3, acetone, reflux, 6 h. This is a veiy common and often veiy efficient method for the preparation of phenolic methyl ethers it is also applicable to the. formation of phenolic benzyl ethers. 

Sodium A-methylanilide, xylene, HMPA, 60-120°, 70-95% yield. Methyl ethers of polyhydric phenols are cleaved to give the mono-phenol. Benzyl ethers are also cleaved. Halogenated phenols are not effectively cleaved, because of competing aromatic substitution. 

Catalytic hydrogenation in acetic anhydride-benzene removes the aromatic benzyl ether and forms a monoacetate hydrogenation in ethyl acetate removes the aliphatic benzyl ether to give, after acetylation, the diacetate. Trisubstituted aDcenes can be retained during the hydrogenolysis of a phenolic benzyl ether. ... 

In the penultimate step of a synthesis of the unstable antibiotic Streptazolin, an iron tricarbonyl group co-ordinated to a 1.3-diene unit and two benzyl ethers were severed simultaneously using tribromoborane at -90 °C [Scheme 4.148].274 Tribromoborane has also been used to deprotect a phenolic benzyl ether in the presence of two phenolic methyl ethers in a synthesis of the alkaloid Lythrancepine [Scheme 4.149].275... 

Catalytic hydrogenolysis of BOM ethers is typically accomplished with Pd/C in ethanol, ethyl acetate or THF. At the close of a synthesis of FR-900482, a phenolic benzyl ether and a benzyloxy BOM ether were hydrogenolysed without... 

The phenolic benzyl ether is much more acid labile than the benzyl ethers of serine and threonine. Therefore, O-benzyltyrosine is not adequately stable for multistep SPPS with the Boc/Bzl strategy. To prevent loss of the O-benzyl protection, halogenated benzyl deriva-tivesP have been developed (Scheme 7) the most often used derivative, H-Tyr[Bzl(2,6-Cl2)]-OH, is -5000 times more stable to 50% TFA/CH2CI2 treatment than the unsubstituted benzyl compound. 

BCls-DMS, CH2CI2, 5 min to 24 h, rt, 16-100% A trityl group is cleaved in preference to a benzyl group under these conditions. A phenolic benzyl ether is stable. ... 

Mel, K2CO3, acetone, reflux, 6 h. This is a very common and often very efficient method for the preparation of phenolic methyl ethers. The method is also applicable to the formation of phenolic benzyl ethers. Stronger bases are not required because of the increased acidity of a phenol versus a typical alcohol. In the following case the ortho OH is more acidic by about 1 pA), unit therefore more reactive. ... 

The section on the cleavage of alkyl henzyl ethers should he consulted, since many of those methods are applicable to phenolic benzyl ethers. It should he noted that phenolic benzyl ethers can be retained during the hydrogenation of olehns and the hydrogenolysis of the Cbz group hy the addition of 2,2 -dipyridyl as an additive. There is also a solvent dependence with aromatic solvents allowing... 

Pd-C, 2,2 -dipyridyl, MeOH, EtOAc, H2. A phenolic benzyl ether survives... 

The reduction of the stilbene olefin in 267 occurred selectively first while the aromatic nitro group was reduced with longer reaction time. Even prolonged reaction time did not further hydrogenolyze the phenolic benzyl ether. 

In addition, a catalytic amount of pyridine or ammonium acetate also suppresses the hydrogenolysis of aliphatic 0-benzyl protective group. " Cleavage of phenolic benzyl ethers, which are more labile than alkyl benzyl ethers, can also be prevented by the addition of 2,2 -dipyridyl (Scheme 83). ° ... 

Scheme 10. Formation of a phenol-benzyl ether and its cleavage...

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