Demethylation with boron trichloride

A related sequence (b) with 3,5-dimethoxyfluorobenzene gave an approach to orsellinic acids as their dimethyl ethers (ref. 112). Demethylation with boron trichloride afforded a monomethyl product, resulting from complexation of the methoxyl group adjacent to the carboxyl group, while the use of aluminium chloride in chlorobenzene gave the orsellinic acid. 

The first involved cyclisation of 3, 5 -dimethoxy-3-bromopropion-anilide to the carbostyril (XVII), which was condensed with 2-iodobenzoic acid and the product cyclised to (XVIIIa). The methyl ester (XVIIIb) was demethylated with boron trichloride to (XVIIIc), which gave (XVIIId) on... 

This Pt-catalyzed hydroarylation was further applied to the total synthesis of deguelin 117, a rotenoid with promising chemopreventive properties (Scheme 12.51) [55]. Although PtCl proved to be superior to PtCl2 as catalyst in model systems for the 6-endo hydroarylation of alkynones and alkynoates, the cyclization of 115 with PtCl led only to poor yields of 116. However, the reaction of 115 with PtCl2 as catalyst provided 116 in excellent yield. The synthesis of racemic deguelin 117 was completed by selective demethylation with boron trichloride, followed by a base-catalyzed intramolecular oxa-Michael addition. 

Demetigriation (2, 34-35). The ilective demethylation of a methoxy group ortho to a carbonyl group has been reported. However, Barton ei a have observed selective demethylation para to a carbonyl group in certain polyoxygenated benzenes. For example, treatment of (I) with boron trichloride in dichloromelhane at —80° gives (2) as the only isolated product. 

Quinazolinones 1 bearing a methoxy substituent in the benzene ring, readily obtained by cyclization of the appropriate precursors (cf. Section 6.3.1.1.1.), are transformed into the corresponding hydroxyquinazolinones 2 on treatment with hydrobromic acid, - hydriodic acid, aluminum trichloride,or boron tribromide. Similarly, quinazoline-2,4-diamines bearing a methoxy group at position 6 or 8 are demethylated with boron tribro-mide in dichloromethane, sodium methanethiolate in dimethylacetamide or by pyridini-um hydrochloride fusion at 200... 

Column and paper-chromatographic methods for the separation, identification, and estimation of methylated monosaccharides have been developed, and are satisfactory, provided that the appropriate reference compounds are available. Recent developments in this field are the ready demethylation of methylated sugars with boron trichloride and the use of gas-liquid partition chromatography for the analysis of mixtures of methylated sugars. ... 

Addition of dichlorocarbene, produced by treatment of ethyl tri-chloroacetate with sodium methoxide, to 3,4,6-tri-O-methyl-D-glucal gave, apparently, one product (gas-chromatographic analysis) in 82% yield. By stereochemical analogy with epoxidations, the product was considered to be l,5-anhydro-2-deoxy-l,2-C-(dichloromethylene)-3,4,6-tri-O-methyl-D-g/j/cero-D-ido-hexitol (21). Demethylation was brought about with boron trichloride at—70°, to give atriol from which a crystalline tribenzoate was obtained and reaction with lithium aluminum hydride caused reductive cleavage of the carbon-chlorine bonds.36 A similar addition was applied to 3,4-unsaturated furanosyl compound (see p. 247). 

Demethylation normally effected with boron trichloride or tribromide has been realised with the trifluoride in a selective and partial manner. 

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). 

Ethers can be cleaved rapidly at room temperature by diborane and halogen 0-Demethylation with retention of O-tosyl groups can be achieved with boron trichloride Alcohols can be obtained by degradation of carboxylic acids through carboxy-inversion of acyl peroxides . Aldehydes can be efficiently decarbonylated under mild conditions in the presence of a rhodium complex . A new mild and potentially selective method for the prepn. of aliphatic... 

The methylenedioxy group in (—)-j8-hydrastine (23) can be selectively converted to an o-diphenol by treatment with boron trichloride, whereas (9-demethylation without affecting the methylenedioxy function can be accomplished with pyridine hydrochloride in hot pyridine. Boron tribromide cleaves both methylenedioxy and methoxyl groups. Isomerization at C-9 is known to... 

Preparation by adding phenylmagnesium bromide to 2-methoxy-5-(trifluoromethyl)benzonitrile,followed by hydrolysis of the intermediate imino compound formed, then demethylation of 2-methoxy-5-(trifluoromethyl)-benzophenone so obtained [568]. - Preparation by demethylation of 2-methoxy-5-(trifluoromethyl)benzophenone with boron trichloride in methylene chloride at -60° for 1 h, then at r.t. [569]. 

Also obtained by partial demethylation of 2,2 -dimethoxybenzophenone with boron trichloride in methylene chloride first at -70°, then at r.t. for 30 min. From 2,2 -dimethoxybenzophenone, one methyl group is lost rapidly and a second somewhat more slowly [292]. 

Preparation by partial demethylation of 4-hydroxy-2,6-dimethoxyacetophenone with boron trichloride in cooled methylene chloride (74%) [2748],... 

Preparation by partial demethylation of 2,4,5-trimethoxy-6-methylacetophenone with boron trichloride in methylene chloride at 0 (85%) [3274]. 

Methylating agents for phenolic groups are a) diazomethane (the reaction time varies from minutes to 24 hours), b) dimethyl sulphate (DMS) - potassium carbonate in acetone or dimethylformamide (DMF) and c) methyl iodide - potassium carbonate in acetone. For demethylation of a methyl ether group ortho to a methyl ester group boron tribromide is used, while demethylation of a methyl ether para to a methyl ester group is carried out with boron trichloride (see Scheme 8). 

Methylbenzofuran-3-carbaldehydes undergo ready condensation with Meldrum s acid (isopropylidene malonate) to afford arylmethylene derivatives 83. These on flash vacuum pyrolysis at 500-600 C give 3-dibenzofuranols 84 (Scheme 21). The arylmethylene derivative, e.g., 85, presumably undergoes conversion to a methylene ketene (86, Scheme 22) on pyrolysis, which undergoes a [1,5-H] shift and subsequent cyclization and tautomerization, yielding the dibenzofuranol 87. The derived methyl ether 88 has been converted by mild acetylation with acetyl chloride and aluminum chloride and subsequent boron trichloride-induced demethylation to the natural product ruscodibenzofuran (8). A limitation is imposed on this method because 3-acetyl-2-methyldibenzofurans fail to condense with Meldrum s acid so that l-methyl-3-dibenzofuranols are not available by this method. ... 

Methylation of carbazole phenolic oxygen has been achieved using dimethyl sulfate without reaction at nitrogen. Demethylation of carbazole methyl ethers has been achieved with hydrobromic acid-acetic acid, boron trichloride,and pyridine hydrochloride. Selective demethylation of methoxyl ortho to an aldehydo function has been achieved using boron trifluoride. ° ° Partial demethylation of 1-methoxy-3-formylcarbazole occurred during Wolff-Kischner reduction." ... 

Boron trichloride [1. 67-68, before references]. Boron trichloride effects selective demethylation of a methoxy group ortho to a carbonyl group.9 The neat reagent, cooled to —70°, is added to the second reactant in cold methylene chloride after reaction has occurred the methylene chloride is washed with water to free it from... 

A particularly useful feature of the above-described synthesis for (7i ,85)-( + )-490 is the possibility of preparing the enantiomeric (75, 8/ )-( — )-disparlure (584) from 577 by simply reversing the order of alkyl group introduction. Treatment of the tosylate of 577 with di- -octyllithium cuprate in ether followed by boron trichloride demethylation provides the lactone 582. This is converted to 583, where the isoamyl group is introduced in the Wittig olefination step. Subsequent group transformations provide (7i5,8/ )-( —)-disparlure (584) (Scheme 129). Both (7i ,8 S)-( + )-490 and (7 S, 8/ )-( —)-584, prepared in quantities up to one gram, are 98% optically pure [185] (Scheme 129). 

Also obtained by selective demethylation of 2,3 -dimelhoxybenzophenone in the presence of boron trichloride in methylene chloride at r.t. for 30 min [341,343]. Also obtained (poor yield) by reaction of 3-methoxybenzoyl chloride with ani-sole in the presence of aluminium chloride in refluxing carbon disulfide for 2 h [341]. 

Scheme 8. Demethylation of methyl ethers with boron tribromide and boron trichloride...

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