Ethers, demethylation

When 2-chloro-6-phenyl-phenolmethylether is transfered into the Grignard compound and then reacted with cyclohexanone, dehydrated and finally dehydrogenated, 2,6-diphenylphenolmethylether is formed61). The synthesis is versatile since a variety of cyclohexanone-derivatives can be used. This and other phenolethers can then easily be demethylated. One of the mildest demethylations is to react the methylether with borontribromide at low temperatures °21. Hydroiodine acid, Lewis acids, such as aluminium-chloride 63 , pyridine/pyridinium chloride, or sodium in pyridine 64) are also valuable tools in ether demethylations. 

P + GSH- CH2-2H 0.0157 Aromatic ether Demethylation followed by oxidation to quinone... 

Halide ions may attack 5-substituted thiiranium ions at three sites the sulfur atom (Section 5.06.3.4.5), a ring carbon atom or an 5-alkyl carbon atom. In the highly sterically hindered salt (46) attack occurs only on sulfur (Scheme 62) or the S-methyl group (Scheme 89). The demethylation of (46) by bromide and chloride ion is the only example of attack on the carbon atom of the sulfur substituent in any thiiranium salt (78CC630). Iodide and fluoride ion (the latter in the presence of a crown ether) prefer to attack the sulfur atom of (46). cis-l-Methyl-2,3-di-t-butylthiiranium fluorosulfonate, despite being somewhat hindered, nevertheless is attacked at a ring carbon atom by chloride and bromide ions. The trans isomer could not be prepared its behavior to nucleophiles is therefore unknown (74JA3146). 

Hunnemannine, CigHiB0N(0H)(0Me)(CH202). (Item 49 list, p. 173.) M.p. 209°. Diazomethane converts the base into a-oZZocryptopine, m.p. 159-60°, so that hunnemannine appears to be O-demethyl-a-oZZocrypto-pine. The ethyl ether has m.p. 168° and on degradation by the method... 

Ether groups in the benzene ring of quinazoline behave as in ethers of homocyclic aromatic compounds, e.g., they can be demethylated with anhydrous aluminum chloride. Allyl ethers also undergo a Claisen rearrangement/ ... 

Treatment of that intermediate with aluminum chloride leads to selective demethylation of that ether para to the carbonyl group (23). Cyclization by means of tosic acid gives the dihydronaphthalene nucleus (24). Alkylation of the phenol with N-(2-chloroethyl)pyrrolidine affords nafoxidine (25). ... 

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

Hydrogen was introduced into a standard hydrogenation vessel containing 10 grams 6-deoxy-6-demethyl-6-methylene-5-oxytetracycline hydrochloride (methacycline), 150 ml methanol and 5 grams 5% rhodium on carbon. The pressure was maintained at 50 psi while agitating at room temperature for 24 hours. The catalyst was then filtered off, the cake washed with methanol and the combined filtrates were evaporated to dryness. The dry solids were slurried in ether, filtered and the cake dried. The resulting solids exhibited a bioactivity of 1,345 units per mg versus K. pneumoniae. 

In early experiments, the pentamethyl ether (18) was treated with phosphorus pentachloride in the hope of obtaining a chloropentol reducible to ( — )-proto-quercitol. (Allowing for the benzoyl migration, the expected product would have been (— )-uibo-quercitol (11).) Surprisingly, the quercitol actually obtained after demethylation and dehalogena-tion was neither of these but still another previously known isomer, meso-scyllo-quercitol (24) (27). 

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

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%. 

The exact time and temperature required for complete reaction must be determined for each individual compound. It has been observed that nucleophilic demethylation of methyl o-alkoxyaryl ethers is accelerated relative to anisole [Benzene, methoxy-],6 and this reaction is no exception. Lithium diphenylphosphide cleavage of anisole is complete in about 4 hours in refluxing tetrahydrofuran, whereas the present reaction is complete within 2 hours at 25°. 

Encouraged by the short synthesis of K vitamins, the chromium-mediated benzannulation was extended to the synthesis of vitamin E 68 [59]. The problem of imperfect regioselectivity of alkyne incorporation - which did not hamper the approach to vitamin K due to the final oxidation to the quinone - was tackled by demethylation of both regioisomeric hydroquinone monomethyl ethers 67 to give the unprotected hydroquinone. Subsequent ring closure yielded a-tocopherol (vitamin E) 68 (Scheme 39). 

Selective demethylation of (63) to the phenolic ether (64) has been achieved by the use of lithium diphenylphosphide. ... 

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