Phenol methyl ethers

Me2BBr, CICH2CH2CI, 0°-rt, 70-93% yield.This reagent also cleaves phenolic methyl ethers. Tertiary ethers give the bromide rather than the alcohol. 

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. 

ISiCl3, rt, 20-30 min, 74-95% yield. Esters and phenolic methyl ethers are reported to survive, whereas with the related TMSI they are cleaved. 

Studies on phytotoxicity of bibenzyl derivatives were extended to duckweed axenic cultures. Bibenzyls 19 and 20 as well as the synthetic analogs 23—28 were tested by triplicate in cultures of the small aquatic plant. Analogs 23—28 were synthesized to investigate the effect on phytotoxicity of oxygenated substituents (phenolic vs. phenolic methyl ether) and their location on the bibenzyl core structure. All synthesized analogs but... 

Phenolic methyl ethers were usually prepared by treatment of the alkaloid with dimethyl sulfate and sodium hydroxide or with diazomethane 17). In the first case a side reaction was N-methylation or even cleavage of the lactone (3). In decodine (6) the C-17 OH group was methylated on treatment with ethereal diazomethane. The hindered C-21 OH group was alkylated with methanolic CH2N2 (77). 

Trihaloboranes in various guises have been extensively employed in the deprotection of phenolic methyl ethers. Methyl ethers ortho to acyl functions generally cleave selectively with Lewis acids such as trichloroborane159 and trichloro-alane.1 0 For example, trichloroborane in dichloromethane efficiently cleaved two of the three methyl ethers in 100.1 [Scheme 4.100] without affecting a... 

Oftentimes, even weak Lewis acids can accomplish the deprotection of methyl ethers activated by proximate carbonyl groups. For example, the last step in a synthesis of the protein kinase C inhibitor Calphostin A [Scheme 4,104]177 178 entailed regioselective cleavage of two phenolic methyl ethers using magnesium iodide in THF.179 The method is compatible with benzyl esters, N-Boc groups and N. 0-acetals,180... 

Strong protic acids cleave phenolic methyl ethers. Thus hydrogen bromide accomplished the same double demethylation as that depicted in Scheme 4.104.189 The final step in a Merck synthesis of the potent dopamine agonist (A,R)-4-pro-pyl-9-hydroxy naphthoxazine (106 2), a phenolic ether deprotection was accomplished on a large scale using methanesulfonic acid in the presence of methionine as the nucleophile [Scheme 4.106]. 190 191... 

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... 

The p-anisyloxymethyl group520 (abbreviated AOM) played an important role in the synthesis of Calicheamicinone reported by Clive and co-workers.521 Its removal from the sensitive multifunctional substrate 285 1 [Scheme 4.285] was accomplished with CAN in a mixture of pyridine, methanol and water. The excellent yield (89%) attests to the mildness of the conditions. Attempts to apply the same conditions to the deprotection of an AOM group from 286 1 [Scheme 4.286]522 failed but the deprotection was successful if it was conducted in the presence of 2,6-pyridinedicarboxylic acid N-oxide — conditions previously used to convert a phenol methyl ether to a quinone.523 AOM ethers undergo easy reductive cleavage to the corresponding methyl ethers with borane in toluene — a reaction that could have synthetic value when simple O-methylation procedures fail. 

Phenol methyl ethers are usually cleaved with Lewis acids. 

Kulka " developed a synthesis of o-hydroxybenzophenones in which a t-butyl group is used to block the para position of a phenol methyl ether to permit o-benzoylation and is then removed, along with the ether group, with aluminum chloride. 

Codeine, the phenolic methyl ether of morphine, has considerably less addiction liability than morphine and is used widely as a local analgesic. Since it is present in opium in smaller amount (0.5%) than morphine (7-15%), its production by selective methylation of morphine is a matter of considerable importance. Ordinary methods attack both the phenolic group and the tertiary nitrogen, but Rodionow found that morphine can be converted smoothly into codeine by reaction with phenyltrimethylammonium ethoxide. 

Cleavage of phenol methyl ethers. Prey found the reagent useful for the cleavage of phenol methyl ethers. Anisole, for example, when heated with 3 parts of the reagent at 200-220° for 5-6 hrs. afforded phenol in 83% yield. Ethers of di- and... 

Phenol, 29, 88-89, 239, 259, 334, 345, 454, 473, 503, 513, 649, 673, 828, 964, 1292 methyl ether, 72, 206 Phenol — cydohexanoi, 724 Phenol methyl ethers, 964 Phenols, 430 hydrogenation, 979 oxidation, 550-551 protective derivatives, 394 reduction ArOH ArH, 251-252 Phenothiazine, 1215 Phenoxide radicals, 640 Phenoxthin, 1120 a-Phenoxyacetophenone, 276 d-(p-Phenoxybenzoyl>propioiiic add, 435 1-Phenoxynaphthalene, 170 -(p-Phenoxyphenyl)-butyric acid, 435 Phenoxytriphenylphosphonium bromide, 1274... 

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. ... 

TFA, thioanisole, TfOH, 2 h, 0°C, 87% yield. Triflic acid alone with micro-wave heating will cleave phenolic methyl ethers. ... 

AICI3, CH2CI2, rt, 80-96% yield. The isopropyl group is selectively cleaved in the presence of a phenolic methyl ether. ... 

Cleavage of phenol methyl ethers [1, 965, after line 2]. A disadvantage of the Prey procedure is that preparation of the reagent is a little troublesome. A group at St. Louis University5 has found that the reagent can be obtained very easily by distillation of a mixture of pyridine with a slight excess of coned, hydrochloric acid at 210°. The ether to be cleaved is stirred into the hot salt and then the reaction mixture is basified and steam distilled to remove pyridine. Yields for the most part are 80-90%. 

Phenolic methyl ethers, including those of the oestrogens, are cleaved to give the free phenols by heating with lithium iodide in collidine (with benzoic acid... 

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