Demethylation aluminum chloride

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). ... 

Berberine (15) was demethylenated and demethylated by heating with aluminum chloride to give berberoline (70), which was methylated with dimethyl sulfate to afford palmatine (64) (Scheme 17) (57). 

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. ... 

Similar methodology also provides a convenient synthesis of 2-dibenzo-furanol. Treatment of the 2,2 -biphenyldiol 208, (Scheme 52), readily available by oxidative coupling of 2,4-di-tcrt-butylphenol, with an excess of bromine in methanol affords the l-bromo-2-methoxydibenzofuran 209. This undergoes demethylation, debromination, and debutylation on treatment with aluminum chloride in boiling toluene and furnishes 2-dibenzofuranol (210). 

Reactions involving sulfur-linked substituents have been exclusively dealkylations of S-alkyl substituents to yield a thiocarbonyl group. Debenzyl-ations under mild conditions with aluminum chloride in benzene were mentioned earlier (Section IV,A,2,a). Pyridine demethylates salts 137 selectively to give 175. ° ... 

The general reaction upon which the first of the above two methods is based is that described by Dakin in 1909 the demethylation of guaiacol to catechol has been effected by heating with aluminum chloride and with hydriodic acid. Other important methods of preparation consist in treating ortho halogen-substituted phenols with alkalies under suitable... 

The above reactions in this section have been examples of addition alone or addition followed by elimination. Ligand reactions involving nucleophilic substitution are also known and these are of the dealkylation type. Lewis acids such as aluminum chloride or tin(IV) chloride have been used for many years in the selective demethylation of aromatic methyl ethers, where chelation is involved (Scheme 27). Similar cleavage of thioethers, specially using mercury(II) salts, is commonly used to remove thioacetal functions masking ketones (equation 27).104 In some cases, reactions of metal ions with thioether ligands result in isolation of complexes of the dealkylated organic moiety (equations 28 and 29).105-107... 

Acylation of 2- or 3-methoxybenzo[6]thiophene in the presence of boron trifluoride takes place in the free thiophene position183 concomitant demethylation may occur in the presence of aluminum chloride.272,666 Attempted acetylation of 3-bromo-2-methoxybenzo-... 

The synthesis of bufotenine itself followed closely upon the proof of its structure. Hoshino and Shimodaira reduced the ethyl ester of 5-ethoxy-indole-3-acetic acid by the Bouveault-Blanc procedure to the corresponding primary alcohol, which was treated with phosphorus tribromide and then dimethylamine, to give the ethyl ether of bufotenine, which was demethylated with aluminum chloride (130). In a later synthesis, 2,5-dimethoxybenzyl cyanide (XXIII) was alkylated by Eisleb s method with dimethylaminoethyl chloride in the presence of sodamide to give l-(2,5-dimethoxyphenyl)-3-dimethylaminopropyl cyanide (XXIV), which was then hydrogenated over Haney nickel to yield 2-(2,5-di-methoxyphenyl)-4-dimethylaminobutylamine (XXV R = Me). De-methylation of this with hydrobromic acid, followed by oxidation of the product (XXV R = H) with potassium ferricyanide yielded bufotenine (XIX) via the related quinone (109). 

In a total synthesis of daunomycinone (b, the aglyconc of an antitumor antibiotic). Ho et effected selective ether cleavage of (6, daunomycinone trimethyl ether) to (7, 4-0-demethyl-7-0-methyldaunomycinone) by treatment with aluminum chloride at room temperature. 

Ether cleavage. Aluminum chloride is a classical reagent for deniethylation ArOCHo-I-AICI3— ArOAlClj + CH3CI, The procedure formulated for the demethylation of 3-bromocatechol dimethyl ether is applicable also to 2,3-dimeth-oxydiphenyl. ... 

On addition of aluminum chloride to a solution of the ether in nitrobenzene at room temperature a red or violet complex is formed. After a few hours, ice and a little hydrochloric acid are added, when the complex goes into the aqueous phase. When this layer is separated and heated with dilute hydrochloric acid at 50° for 2 hrs., the demethylated product is liberated and separates on cooling. A carbomethoxy group if present remains intact. 

The commercial dinitrophenol mixture is produced by heating phenol with dilute sulfuric acid, cooling the product, and then nitrating while keeping the temperature below 50 °C, or by nitrating with a mixed acid under careful temperature control (Sax and Lewis 1987). 2,3-, 2,5-, and 3,4-DNP are prepared by nitration of m-nitrophenol. 3,5-DNP is prepared by the replacement of one nitro group by methoxyl in 1,3,5-trinitrobenzene and demethylation of the dinitroanisole by anhydrous aluminum chloride. 2,6-DNP is prepared by sulfonation and nitration of o-nitrophenol (Harvey 1959). 2,6-DNP is also produced as a byproduct in the synthesis of 2,4-DNP by way of 2,4-dinitrochlorobenzene. 

Suzuki-Miyaura coupling of D with I smoothly afforded J, which was oxidized with ceric ammonium nitrate to give K. For the final demethylation of K, several methods were tried without success treatment of K with boron tribromide, 47% hydrobromic acid, lithium chloride in DMF, trimethylsilyl iodide, and potassium thiophenolate in diethylene glycol. Finally, clean demethylation of K was achieved with aluminum chloride in dichloromethane at room temperature to give diospyrin (58) as orange plates. The proposed structure 58 was thus confirmed by its synthesis.130... 

Demethylation of 143 with aluminum chloride was too harsh to give only (i)-nocardione A [( )-142] as dark red needles. It became apparent that optically active 142 must be prepared by using a more readily removable protective group for the phenolic hydroxy group. 

Selective ether cleavage (1, 30-31). Seshadri1 noted that the methoxyl group adjacent to the formyl group of 2,3,4-trimethoxy-6-methylbenzaldehyde (1) was selectively cleaved in quantitative yield by demethylation with anhydrous aluminum chloride in ether at room temperature in 48 hours. This reaction was... 

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,... 

Demethylation of racemic laudanosine with 48 % hydrobromic acid (30) or anhydrous aluminum chloride (82) splits all four methoxyl groups and furnishes laudanosoline, but two or three methoxyl groups may be preserved if other reagents and milder conditions are chosen. When heated with 35 % hydrochloric acid at 100° for twenty minutes, all four possible monophenolic isomers are formed and may be isolated from the reaction mixture by fractional extraction and crystallization (83). They are lau-danine (LII) (m.p. 166-167°), pseudolaudanine (LIII) (m.p. 120-121°), DL-codamine (XXII) (oily), and pseudocodamine (LIV) (m.p. 129-130°). A discussion of their structure may be found on pages 57-63. 

Deacetylation of adduct 64 and a shift of the quinone moiety to ring C was accomplished by treatment with aqueous trifluoroacetic acid, followed by demethylation with aluminum chloride to give the target aglycone, (-)-y-rhodomycinone (65), in 34% yield from 62. 

The alkylation of anisole under the vigorous conditions necessary to introduce an isopropyl group (aluminum chloride at 120-140°) leads to extenave demethylation. Alkylation of phenol under many condi-... 

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