Aryl ethers electrophilic aromatic

Friedel-Crafts type reactions of strongly deactivated arenes have been the subject of several recent studies indicating involvement of superelectrophilic intermediates. Numerous electrophilic aromatic substitution reactions only work with activated or electron-rich arenes, such as phenols, alkylated arenes, or aryl ethers.5 Since these reactions involve weak electrophiles, aromatic compounds such as benzene, chlorobenzene, or nitrobenzene, either do not react, or give only low yields of products. For example, electrophilic alkylthioalkylation generally works well only with phenolic substrates.6 This can be understood by considering the resonance stabilization of the involved thioalkylcarbenium ion and the delocalization of the electrophilic center (eq 4). With the use of excess Fewis acid, however, the electrophilic reactivity of the alkylthiocarbenium ion can be... 

If the anodic oxidation of N-alkylanilines is performed in the presence of nucleophiles like enol ethers, nucleophilic substitution in the of-position to nitrogen by the enol ether can be observed in low yields. The electrophilic intermediate is the N-aryl iminium ion or the N-aryl imine after loss of two electrons and one or two protons. These intermediates add to the enol ether to give acetals (up to 26%) as addition products, or the first addition step is followed by an electrophilic aromatic substitution to form tetrahydroqui-nolines (13-39%) [47]. It should be noted at this point that better results for the nucleophilic a-substitution to nitrogen can be obtained with N,N-dialkylanilines (see next subsection). Optimum results, however, are obtained with N-acylated compounds via the intermediate N-acyl iminium ions (see Ref. 8). 

There are several methods for the direct introduction of an aldehyde group into an aromatic compound. In the Vilsmcicr-Haack reaction, activated aromatic systems such as aryl ethers and dialkylanilines are formylated by a mixture of dimethylformamide, HCONMe2, and phosphorus oxychloride, POCl3, (Scheme 6.4). The process involves electrophilic attack by a chloroiminium ion, Me2N=CHCl, formed by interaction of dimethylformamide and phosphorus oxychloride. Hydrolysis of the dimethyl imine completes the synthesis. 

A good and comprehensive review of catalytic electrophilic acylation was published by Pearson and Buehler.i Only the catalysts most widely used were considered, with special attention to iron trichloride, zinc chloride, iodine, and elemental iron. The substrates that can be acylated using small amounts of catalysts include alkylarenes, aryl ethers, biphenyls, naphthalenes, acenaphthenes, fluorene, furans, and thiophenes. Aromatic acyl chlorides lead to better yields than aliphatic ones, reaching a maximum of 96% and a minimum of 34%. In general, fhe reactions are performed af relatively high temperatures (from 50°C to 200°C) af which hydrogen chloride evolution is fairly rapid. 

The structure of thyroxine, a thyroid hormone that helps to regulate metabolic rate, was determined in part by comparison with a synthetic compound believed to have the same structure as natural thyroxine. The final step in the laboratory synthesis of thyroxine by Harington and Barger, shown helow, involves an electrophilic aromatic substitution. Draw a detailed mechanism for this step and explain why the iodine substitutions occur ortho to the phenolic hydroxyl and not ortho to the oxygen of the aryl ether. [One reason iodine is required in our diet (e.g., in iodized salt) is for the biosynthesis of thyroxine.]... 

Bromine Water. Since the aromatic ring is electron rich, aromatic ethers can undergo electrophilic aromatic substitution with bromine to yield the corresponding aryl ether-halide (s). Therefore, if elemental tests indicate that an aromatic group is present in an ether, treatment with the bromine water reagent may substantiate the presence of an aryl ether. 

Bromine Water. Phenols, substituted phenols, aromatic ethers, and aromatic amines, since the aromatic rings are electron rich, undergo aromatic electrophilic substitution with bromine to yield substituted aryl halides. For example. 

In another approach, poly(aryl ether sulfones) were synthesized by the electrophilic Friedel-Crafts reactions of sulfonyl halides with aromatic hydrocarbons. The critical step in these polymerizations is the formation of the carbon-sulfur bond. High polymers were obtained, though they were not always completely linear. Carbonyl aryl carbon-carbon bonds are created in Friedel Craft reactions leading to poly(aryl ketones). 

In general, PAEK copolymers have been s)mthesized by two methods (1) nucleophilic substitution step copolycondensation of at least two different monomers of bisphenol and at least one dihalobenzoid compound or at least one monomer of bisphenol and at least two different dihalobenzoid compounds (2) electrophilic Fiiedel-Crafts copolycondensation of at least two different monomer of diphenyl ether and terephthaloyl chloride or at least one monomer of diphenyl ether and terephthaloyl chloride as well as isophthaloyl chloride. Some of bisfluoro, bisphenol monomers, aromatic bisbenzoyl chloride and diphenyl ether used for the synthesis of poly (aryl ether ketone) copolymers have been included in Table 10.1. 

In addition to nucleophilic aromatic substitution, there are a number of other synthetic routes to poly(aryl ethers). Friedel-Crafts condensation of arylsulfonyl chlorides and aryl carboxylic acid derivatives with aryl ethers has been employed to prepare polysulfones (2b) and poly(ether ketones) (105,106), respectively. Direct polycondensation of various benzoic acids containing a phenyl ether structure has been carried in 1 10 phosphorous pentoxide/methanesulfonic acid (107). The success of this method is a consequence of the high selectivity of the electrophilic reagent for substitution para to the ether linkage. 

Protonic acids and some other electrophiles cause the aromatization of naphthalen-l,4-imines and of derivatives of the related 1,4-epoxy-1,4-dihydronaphthalene ring system (126) to naphthalene derivatives (see Section III,F), and simple electrophilic addition to the 2,3-double bond has not been observed. Ring-opening of the ether (126) also occurs on addition of alkyl or aryl lithium reagents as a result of exo attack by the nucleophile at the 2-position. ... 

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