Aromatic compounds from benzylic ethers

The Friedel-Crafts alkylation reaction of various aromatic compounds with benzyl or allyl silyl ethers has been effectively promoted under mild reaction conditions using Hf(OTf)4. A mixture of the desired phenyltolylmethanes has been obtained in 80% yield from toluene with benzyl trimethylsilyl ether at 50 °C in the presence of a catalytic amount of Hf(OTf)4. ... 

Aromatic Compounds.—A number of 2,3-dihydroxyoestra-l,3,5(10)-trienes have been prepared from the corresponding 2-amino-3-hydroxy-compounds using a novel inverse oxidation procedure followed by reduction with KI. Addition of the substrate to sodium metaperiodate in high dilution ensures no coupling with the intermediate quinonimines. 2-Bromo-oestradiol was readily converted into 2-methoxyoestradiol by treatment with NaOMe-MeOH-DMF-CuI. Novel preparations of the biologically interesting 11/3-methyl- and 11/3-ethyl-oestradiol have been reported in full. The key intermediates were the 11-oxo-oestradiol 3-benzyl ether (82) and its 9/3-epimer (83). The latter was derived from the 9,H-epoxides (81) by treatment with KOH followed by benzylation. The thermodynamically unstable 9a-epimer (82) was prepared from the 9j8-epimer (83) by... 

Bromomethylation is also possible, e.g.y the preparation of benzyl bromide in 86.5% yield from benzene, formaldehyde, and hydrogen bromide in acetic plus sulfuric acid.684,685 So is iodomethylation of aromatic compounds, by reaction of bis(chloromethyl) ether and hydrogen iodide in glacial acetic acid.686... 

Another imaginative approach (Scheme 2) started with the protoberberine system (127). Reduction of the trimethoxy-compound (127 R = Me) with lithium and liquid ammonia gave the enol ether (128), and conditions could not be found for the selective reduction of only the monomethoxylated aromatic ring. However, the reduction of the benzyl ether (127 R = CHzPh), followed by methylation of the product, gave the enol ether (129), which could be hydrolysed to the a/3-unsaturated ketone (130). This ketone was also found to be obtainable in good yield from the enol ether (128) by selective aromatization by N-chlorosuccinimide in methylene chloride, hydrolysis (presumably by water in the... 

Comparison of the NMR spectra of several crown ethers or related macrocycles containing aromatic or heteroaromatic subcyclic units shows features of these compounds that are of general interest. These macrocycles have benzylic methylene signals that are sensitive to small steric or conformational differences because they lie in close proximity to the aromatic rings. These benzylic signals usually appear 0.5-1.3 ppm down field from the polyether absorptions which appear as broad multiples (or singlets) around 6 = 3.4-3.7 ppm. 

With the exception of a relatively small number of members of low molecular weight (Group I), these compounds fall into Solubility Group V. Contrary to tlie usual assumption, relatively few members from the above series are decomposed by cold concentrated sulfuric acid. Solubility in sulfuric acid without decomposition is by no means peculiar to the ethers. Differentiation between Groups V and VI, however, is not limited to solubility without decomposition in fact, wc have already discussed the behavior of the iinsaturated hydrocarl)ons in this respect. Solubility with discoloi-ation and partial polymerization will not( d especially with aliphatic aldehydes ethers of the acetal type will readily hydrolyze and marked decomposition will be noted with benzyl alcohol and its derivatives, a decomposition which may possibly be typical of many aromatic compounds with the — CH2OH side-chain. The complete decomposition of a product of the latter type with the production of solid products insoluble in concentrated H0SO4 must be accepted as evidence that the unknown is not a hydrocarbon. 

The violence of superbasic slurries towards functionalized organic molecules means that they are at their most effective with simple hydrocarbons they also tolerate ethers and fluoro substituents. LiCKOR will deprotonate allyUc, benzylic, vinylic, aromatic and cyclopropane C—H bonds with no additional assistance. From benzene, for example, it forms a mixture of mono and dimetallated compounds 617 and 618 (Scheme 241) . ( Li/K indicates metallation with a structurally ill-defined mixture of lithium and potassium.)... 

Another powerful approach to prepare a-amino acids bearing an aromatic or unsaturated side chain in /I (but also many other compounds) is based on the reactivity of 5-fluoro-4-trifluoromethyloxazole, a starting material easily accessible from hexafluoroacetone. The fluorine atom in the 5 position is easily displaced by an allylic or benzylic alcohol. Then, the obtained ethers spontaneously undergo a Claisen rearrangement to afford, after acidic hydrolysis, an a-trifluoromethyl amino acid... 

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