Aryl methyl ethers, demethylation

Xn. Demethylation of Aryl Methyl Ethers by Boron Tribromide... 

Aryl methyl ethers. A great deal of attention has been directed to the demethylation of aryl methyl ethers on account of interest in the degradation of lignin and related compounds by both aerobic and anaerobic organisms. 

Thiolate ions are also useful for the demethylation of certain ethers, esters, amines, and quaternary ammonium salts. Aryl methyl ethers can be cleaved by heating with EtS in the dipolar aprotic solvent DMF ROAr + EtS ArO +EtSR. Carboxylic esters and lactones are cleaved (the lactones give co-alkylthio carboxylic acids) with a thiol and AICI3 or AlBrs. Esters and lactones... 

Use of this coupling for synthesis of a number of isoquinoline alkaloids also has been published.2 VOF3 is usually used in this coupling, but this reagent can lead to overoxidation and oxidative demethylation of aryl methyl ether groups. 

Conversion into ipalbidine 83 required reduction of the lactam 81 and demethylation of the aryl methyl ether 82. Though the yield in the cycloaddition was poor, this is a short synthesis. 

Demethylation of aryl methyl ethers. Koutek and Setinek1 reported that aryl methyl ethers can be demethylated by sodium thioethoxide (C2H5SNa) they used ethanol as solvent and temperatures of 190° (autoclave). However, if DMF is used as solvent, demethylation is complete at reflux temperatures in about an hour.2 Yields are high (94-88%). Ethers of dihydric phenols give selective mono-demethylation. 

Even without the advantage ol a stable earbocation. other ethers may be cleaved under forcing conditions. Simple alkyl ethers lead to mi.vtures including elimination but little substitution, and have little synthetic use. However, aryl methyl ethers may be usefully demethylated to the phenol by heating with Grignard reagents (e.g.. eq. 2.48) 53]. 

Demethylation. An unconventional application of the bulky reducing agent is ne cleavage of aryl methyl ethers (68-100% yield). 

In situ method for reduction and sulfurization. The combination of Me SiCl and Na2S successfully reduces arylamines and sulfoxides, converts nitriles to thioamides, alkyl halides to sulfides, as well as demethylates aryl methyl ethers. 

O-demethylation of aryl methyl ethers of nonphenolic aporphine alkaloids. Regioselective demethylation by this method occurs at positions 1,8, and 11 of the aporphine nucleus methylenedioxy functions survive the reaction (447). Selective cleavage of the methylenedioxy group in O-methyl-bulbocapnine with boron trichloride is discussed in Section III,C (448). The ether cleavage of methoxy- and methylenedioxy-substituted isoquinoline has been reviewed (346). 

Demethylation of ethers. Primary and secondary alkyl methyl ethers and aryl methyl ethers are cleaved to alcohols by BF3 etherate in several thiols (ethanethiol is particularly effective). The reaction occurs at room temperature, but requires 1-12 days. Retention of stereochemistry is observed. ... 

Catechols, hydroquinones, and their methyl ethers readily afford quinones on Ce oxidation.Partial demethylative oxidation is feasible, as shown in the preparation of several intramolecular quinhydrones (eq 5) and a precursor of daunomy-cinone. Sometimes the dual oxidant system of CAN-NaBrOs is useful. In a synthesis of methoxatin (eq 6) the o-quinone moiety was generated from an aryl methyl ether. 

Demethylation of acid-sensitive aryl methyl ethers, such as 2,4-dimethoxyquinolines, can be accomplished using a trimethylsilyl iodide/DMAP reagent system, where DMAP is used as a Lewis base to prevent protonation of the alkene from the HIby-product. This reaction was utilized to form the quinoline-containing alkaloid natural product, atanine, from the Rutaceae family. 

Aryl methyl ethers may be demethylated with boron tribromide as shown below ... 

Fang, Z., G.-C. Zhou, S.-L. Zheng, G.-L. He, J.-L. Li, L. He, and D. BeL 2007. Lithium chloride-catalyzed selective demethylation of aryl methyl ethers under microwave irradiation. Journal of Molecular Catalysis A Chemical 274(1—2) 16—23. 

Preparative uses of thiolates, quite apart from syntheses of other sulphur functional groups discussed elsewhere in this Volume, include the demethyl-ation of aryl methyl ethers with EtS in hot DMF, and a similar use of thiophenol for demethylating aza-heterocyclic O-methyl ethers, of type =N—C(OMe)=. 2-Methylthio-l-methylbenzimidazole does not react with thiophenol, though an alternative reaction path is available for certain hetero-aryl methyl sulphides (17). ... 

Reactions.—Cleavage of prenyl and allyl ethers has been discussed earlier in this Report. Some aliphatic ethers can be cleaved by thallium(iii) nitrate in acetic anhydride.New reagents for the demethylation of aryl methyl ethers include the stable, crystalline, and easily handled complexes of boron halides BBr3 and BCI3 with dimethyl sulphide,and the salt obtained from treatment of N-methylaniline with sodium hydride in HMPA. The latter system cleaves methyl aryl ethers more readily than benzyl aryl ethers. 

The present procedure illustrates the facile demethylation of methyl aryl ethers by lithium diphenylphosphide.3 This reaction is specific for methyl ethers and may be carried out in the presence of ethyl ethers in high yield.4 Use of excess reagent allows cleavage in the presence of enolizable ketones.5 In the present case, the cleavage may be performed without protection of the aldehyde, but two equivalents of reagent are required, and the yield is reduced to ca. 60%. 

Thiolate ions are also useful for the demethylation of certain ethers,761 esters, amines, and quaternary ammonium salts. Aryl methyl ethers762 can be cleaved by heating with EtS... 

Esters, from diazoketones and organo-boranes, 53, 82 Esters, a-deuterio-, S3, 82 Esters, 7,6-unsaturated by Claisen rearrangement, 53,122 Ethers, by oxymercuration, 53, 96 Ethers, aryl methyl-, selective mono-demethylation of, 53, 93 Ethyl diazoacetate, as source of car-bethoxycarbene, 50, 94 Ethylenediamine, complexes with chromium(II) salts, 52, 62 Ethylene, with p-methoxyphenylacetyl chloride and aluminum chloride to give 6-methoxy-/3-tetralone,... 

ArOMe - ArOH. Demethylation of a methyl ether without disturbing the chiral amino acid moiety attached to the aryl ring is accomplished with HBr-NaI-H20 in a sealed tube. 

Reactions.—A new study of the reaction of various ethers with iodotrimethylsilane has appeared. Dialkyl ethers are found to be cleaved (Scheme 41), methyl ethers showing predominant demethylation and aryl alkyl ethers leading to exclusive... 

DEMETHYLATION OF METHYL ARYL ETHERS 4-ETHOXY-3-HYDROX YBEN Z ALDEHYDE... 

---