Aromatic methyl ethers

Birch s procedure for tropone synthesis appears to be widely applicable to 2,3- or 2,5-dihydroanisole derivatives which are readily obtained by reduction of appropriate aromatic methyl ethers by alcoholic metal-ammonia solutions. " Additional functional groups reactive to dibromocarbene or sensitive to base such as double bonds, ketones and esters would need to be protected or introduced subsequent to the expansion steps. 

The product has the following spectral properties infrared (KBr) cm.-1 3103 and 3006 (aromatic C—H), 2955, 2925, and 2830 (aliphatic C—H stretching), 1257 and 1032 (aromatic methyl ether), 841 and 812 (C—H out-of-plane bending of isoxazole C4—H and 4-substituted phenyl) proton magnetic resonance (trifluoroaeetic acid) 5, multiplicity, number of protons, assignment 3.98 (singlet,... 

Condensation of aromatic methylesters such as methyl 4-methoxybenzoate 351 a or methyl 4-hydroxybenzoate 351b with excess sodium-HMDS 486 in a mixture of THF-l,3-dimethyl-imidazolin-2-one (DMEU) at 185 °C in a closed vessel affords 59 or 93% of 4-hydroxybenzonitrile 298 as well as 26% 352 with smooth cleavage of the aromatic methyl ether in 351a (Scheme 4.47). Methyl indole-3-carboxylate gives hkewise 3-cyanoindole in 81% yield [127] (cf. also ref [92] in section 4.3). 

In recent work a serendipitous discovery showed that strongly acidic chloroaluminate-containing ionic liquids, whether in combination with trialkylam-monium or with dialkylimidzolium cations, are active and selective for the cleavage of aromatic methyl ethers, even at temperatures <40°C. The ionic liquids are consistently better catalyst than AICI3 for this type of reaction 139). 

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... 

Fig. 2.2. Cleavage of aromatic methyl ether using Sn2 reactions. In the dipolar aprotic solvent DMF, thiolate and chloride ions are particularly good nucleophiles for want of solvation through hydrogen bonding. In pyri-dinium hydrochloride a similar effect occurs because for each chloride only one N5 —H5 group is available for hydrogen bonding. The same increase in nucleophilicityin a dipolar aprotic solvent is used to cleave /i-ketomethyl esters with lithium iodide in DMF (cf. Figure 13.29).

Demethylation. AICI,-NaI (1 1) in acetonitrile selectively demethylates aliphatic methyl ethers at room temperature in the presence of aromatic methyl ethers. Acetals are also cleaved, but esters and lactones are not affected. The methyl ether of a primary alcohol is cleaved somewhat more readily than the methyl ether of a secondary alcohol. ... 

The synthesis of the aromatic methyl ether (191) and the reduction of ring C has been studied." The backbone rearrangement of the synthetic intermediate (192) has been examined in the context of the synthesis of rearranged diterpenoids. The synthesis of the phenol (193), which is a degradation product of atisine, has been reported. 

Yet another metabolite of aflatoxin Bj(i) is derived through the demethylation of the aromatic methyl ether. The resultant compound was isolated, and christened aflatoxin Pj83> 84. The structure was determined to be that depicted in (18). 

Lithiation of aromatic methyl ethers as mentioned earliar gives a new route to condensed furans. When the aromatic substrate is a quinoline, furoquinolines result. Of particular interest is the linear furoquinoline ring system which is present in several alkaloids. 

Vuori, A. Thermal and Catalytic Reactions of the C-0 Bond in Lignin and Coal Related Aromatic Methyl Ethers. Acta Poly-technica Scandinavica, Chem. Tech, and Met. Series No. 176, 1986. 

The chemo-, regio-, and stereoselectivity of the ring contraction process has been demonstrated with a variety of dienol ethers obtained by dissolving metal reduction of aromatic methyl ethers (eqs 4 and 5). ... 

Reactions.—Some examples of new methods for ether cleavage have been dealt with in an earlier section (Protection of Alcohols). Aliphatic and aromatic methyl ethers can be cleaved efficiently by an aluminium halide-ethanethiol combination the process has been rationalized according to the hard and soft acid-base principle. Several methods for the (presumed) in situ preparation of trimethylsilyl iodide, a known reagent for the cleavage of ethers (2,131), have been disclosed recently in an effort to circumvent the expense and moisture sensitivity of MeaSil. (Some of these methods have been mentioned earlier in this Report in connection with the conversion of alcohols into alkyl iodides.) Reports include two on trimethylsilyl chloride-sodium iodide, one on phenylseleno-trimethylsilane-iodine [equation (18)], and three on hexamethyldisilane-iodine [equation (jq)] 102,142,143 method has the advantage of... 

Of several reagents for ring opening or dealkylation of ethers, the AlX3-EtSH (X = Cl or Br) system is particularly useful for the demethylation of aliphatic and aromatic methyl ethers and the demethylenation of methylenedioxy-compounds. ... 

The reaction of diazomethane with carboxylic acids to form methyl esters and with phenols to produce aromatic methyl ethers is easy to perform. In addition to providing a more volatile derivative, this method can be used diagnostically to verify the presence of these compounds as the observed mass will increase by 14 for each reactive OH group. This derivatization is frequently used in drug metabolism smdies, since polar acids and phenols are often produced by the biotransformation of pharmaceutical agents. For more details on chemical derivatization, the reader is referred to the literature (18,34,35). 

M-30] loss of H2CO from aromatic methyl ethers etc. check for nitroarenes... 

BF (N-fragment) aromatic methyl ethers, NO from nitro compounds and nitro esters... 

CH3CO. C3H7. C2H4N. CONH M+-43 Acetyl, propyl, aromatic methyl ethers (M -15 - 28), nonspecific with aliphatic and alicyclic systems... 

A simple process for acidolysis of aromatic methyl ethers involves the use of methanesulphonic acid in the presence of methionine as a methyl acceptor. In this way, methoxytoluene is converted into p-cresol. 

CH3CO) methyl ketones, acetates, aromatic methyl ethers... 

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