Aromatic ether acids

The S5Tithesis of polyesterketones based on aromatic ether acids is possible in the environment of trifluoromethanesulfonic acid [249, 287], The data ofnuclear magnetic resonance have revealed [249] that such poly-esterketone comprise only the -substituted benzene rings. When using the N-cyclohexyl-2-pyrrolidone as a solvent when synthesizing polyphen-ylenesterketones and polyphenylenethioesterketones the speed of polycondensation and the molecular mass of polymers [288] increase. 

Oxidation of side chains. The oxidation of halogenated toluenes and similar compounds and of compounds with side chains of the type —CHjCl and —CH OH proceeds comparatively smoothly with alkaline permanganate solution (for experimental details, see under AromcUic Hydrocarbons, Section IV.9,6 or under Aromatic Ethers, Section IV,106). The resulting acid may be identified by a m.p. determination and by other teats (see Section IV,175). 

Purely aromatic ethers e.g., diphenyl ether), which are commonly encountered, are very hmited in number. Most of the aromatic ethers are of the mixed aliphatic - aromatic type. They are not attacked by sodium nor by dilute acids or alkahs. When hquid, the physical proper-ties (b.p., d . and ) are useful constants to assist in their identification. Three important procedures are available for the characterisation of aromatic ethers. 

Cleavage with hydriodic acid. Aromatic ethers undergo fission when heated with constant boihng point hydriodic acid ... 

Sulphonamides of aryl ethers. Aromatic ethers react smoothly in chloroform solution with chlorosulphonic acid at 0° to give suljihonyl chlorides, for example ... 

Picrates of aromatic ethers. Most phenohc ethers react with picric acid in chloroform or alcoholic solution to yield crystalUne picrates (compare At oTnatic Hydrocarbons, Section IV,9,1). 

Dissolve 0 01 mol of the phenohc ether in 10 ml. of warm chloroform, and also (separately) 0 01 mol of picric acid plus 5 per cent, excess (0 -241 g.) in 10 ml. of chloroform. Stir the picric acid solution and pour in the solution of the phenohc ether. Set the mixture aside in a 100 mb beaker and ahow it to crystallise. Recrystahise the picrate from the minimum volume of chloroform. In most cases equahy satisfactory results may be obtained by conducting the preparation in rectified spirit (95 per cent. CjHgOH). The m.p. should be determined immediately after recrystallisation. It must be pointed out, however, that the picrates of aromatic ethers suflFer from the disadvantage of being comparatively unstable and may undergo decomposition during recrystaUisation. 

The mixed aliphatic - aromatic ethers are somewhat more reactive in addition to cleavage by strong hydriodio acid and also by constant b.p. hydrobromio acid in acetic acid solution into phenols and alkyl halides, they may be bromi-nated, nitrated and converted into sulphonamides (Section IV,106,2). 

Sulphonic acids. The aromatic sulphonic acids and their alkali metal salts are soluble in water, but insoluble in ether (Solubility Group II). They are best characterised by conversion into crystalline S-benzyl-iso-thiuronium salts (see Section IV,33,2 and 111,85,5), which possess characteristic melting points. A more time-consuming procedure is to treat the well-dried acid or... 

Residual aromatic ether concentrations are determined from the absorbance at 278 mfi of the crude reduction products in methanol solution. Steroidal ether concentrations of 1 mg/ml are employed. The content of 1,4-dihydro compound is determined, when possible, by hydrolysis to the a, -unsaturated ketone followed by ultraviolet analysis. A solution of the crude reaction product (usually 0.01 mg/ml cone) in methanol containing about 1/15 its volume of water and concentrated hydrochloric acid respectively is kept at room temperature for 2 to 4 hr. The absorbance at ca. 240 mfi is measured and, from this, the content of 1,4-dihydro compound can be calculated. Longer hydrolysis times do not increase the absorbance at 240 mp.. 

In the Schmidt reaction of fluonnated dicarboxyhc acids, the appropnate amides can be obtained in fairly good yield [48] Complications arise from possible cychzation if the fluorine atom is in the 8 position relative to the newly formed amino group [/] Fluonnated aromatic ethers, upon heating in dimethylformamide, undergo Smiles rearrangement to give diarylamines [49, 50] (equation 11)... 

A number of examples of the use of molten pyridinium chloride (mp 144 °C) in chemical synthesis are known, dating back to the 1940 s. Pyridinium chloride can act both as an acid and as a nucleophilic source of chloride. These properties are exploited in the deallcylation reactions of aromatic ethers [4]. An example involving the reaction of 2-methoxynaphthalene is given in Scheme 5.1-2 [16, 18], and a mechanistic explanation in Scheme 5.1-3 [18]. 

The ionization of (E)-diazo methyl ethers is catalyzed by the general acid mechanism, as shown by Broxton and Stray (1980, 1982) using acetic acid and six other aliphatic and aromatic carboxylic acids. The observation of general acid catalysis is evidence that proton transfer occurs in the rate-determining part of the reaction (Scheme 6-5). The Bronsted a value is 0.32, which indicates that in the transition state the proton is still closer to the carboxylic acid than to the oxygen atom of the methanol to be formed. If the benzene ring of the diazo ether (Ar in Scheme 6-5) contains a carboxy group in the 2-position, intramolecular acid catalysis is observed (Broxton and McLeish, 1983). 

The positive bromination of aromatics ethers was first studied by Bradfield et al.193 and by Branch and Jones194. The reaction of hypobromous acid in 75 % aqueous acetic acid with benzyl 4-nitrophenyl ether and 4-nitrophenetole at 20 °C was very rapid and approximately second-order193. The value of k2/[H+] remained constant in the [H+] range 0.005-0.090 M for the effect of added mineral acids on the bromination of 4-nitroanisole and 4-nitrophenetole (at 19.8 °C)194. The variation in reaction rate with the percentage of acetic acid in the medium was also studied and showed a large increase in the 0-10 % range with a levelling off at approximately 25 % acetic acid (Table 52) this was attributed... 

Bradfield et al.21g first studied the kinetics of molecular bromination using aromatic ethers in 50% aqueous acetic acid at 18 °C. They showed that the kinetics are complicated by the hydrogen bromide produced in the reaction which reacts with free bromine to give the tribromide in BrJ, a very unreactive electrophile. To avoid this complication, reactions were carried out in the presence of 5-10 molar excess of hydrogen bromide, and under these conditions second-order rate coefficients (believed to be I02k2 by comparison with later data) were obtained as follows after making allowance for the equilibrium Br2 + Br7 Bn, for which K = 50 at 18 °C 4-chloroanisole (1.12), 4-bromoanisole (1.20), 4-... 

The chemistry of indium metal is the subject of current investigation, especially since the reactions induced by it can be performed in aqueous solution.15 The selective reductions of ethyl 4-nitrobenzoate (entry 1), 2-nitrobenzyl alcohol (entry 2), l-bromo-4-nitrobenzene (entry 3), 4-nitrocinnamyl alcohol (entry 4), 4-nitrobenzonitrile (entry 5), 4-nitrobenzamide (entry 6), 4-nitroanisole (entry 7), and 2-nitrofluorenone (entry 8) with indium metal in the presence of ammonium chloride using aqueous ethanol were performed and the corresponding amines were produced in good yield. These results indicate a useful selectivity in the reduction procedure. For example, ester, nitrile, bromo, amide, benzylic ketone, benzylic alcohol, aromatic ether, and unsaturated bonds remained unaffected during this transformation. Many of the previous methods produce a mixture of compounds. Other metals like zinc, tin, and iron usually require acid-catalysts for the activation process, with resultant problems of waste disposal. 

Furthermore, the reaction of aromatic ethers with a stoichiometric amount of BTMA Br3 in dichloromethane-methanol or acetic acid-zinc chloride under mild conditions gave, selectively, mono-, di-, or tribromo-substituted aromatic ethers in quantitative yields (Fig. 10) (ref. 15). 

Combined effect of BTMA Br3 and ZnCl2 in acetic acid provides a new excellent bromination procedure for arenes. That is, while such reactive aromatic compounds as phenols, aromatic amines, aromatic ethers, and acetanilides have been easily brominated by BTMA Br3 in dichloromethane in the presence of methanol, the reaction of arenes, less reactive compounds, with BTMA Br3 in dichloromethane-methanol did not proceed at all, even under reflux for many hours. However, arenes could be smoothly brominated by use of this agent in acetic acid with the aid of the Lewis acid ZnCl2 (Fig. 13) (ref. 16). 

Ethers are unaffected by sodium and by acetyl (or benzoyl) chloride. Both the purely aliphatic ethers e.g., di-n-butyl ether (C4H, )30 and the mixed aliphatic - aromatic ethers (e.g., anisole C3HSOCH3) are encountered in Solubility Group V the purely aromatic ethers e.g., diphenyl ether (C,Hj)20 are generally insoluble in concentrated sulphuric acid and are found in Solubility Group VI. The purely aliphatic ethers are very inert and their final identification may, of necessity, depend upon their physical properties (b.p., density and/or refractive index). Ethers do, however, suffer fission when heated with excess of 67 per cent, hydriodic acid, but the reaction is generally only of value for the characterisation of symmetrical ethers (R = R ) ... 

Imidazolides of aromatic sulfonic acids react much more slowly in alcoholysis reactions than the carboxylic acid imidazolides. Although the reaction with phenols is quantitative when a melt is heated to 100 °C for several hours, with alcohols under these conditions only very slight alcoholysis is observed. In the presence of 0.05 equivalents (catalytic amount) of sodium ethoxide, imidazole sodium, of NaNH2, however, imidazolides of sulfonic acids react with alcohols almost quantitatively and exothermically at room temperature in a very short time to form sulfonic acid esters (sulfonates). (If the ratio of sulfonic acid imidazolide to alcoholate is 1 2, ethers are formed see Chapter 17). The mechanism of catalysis by base corresponds to that operative in the synthesis of carboxylic esters by the imidazolide method. Because of the more pronounced nucleophilic character of alkoxide ions, sulfonates can also be prepared in good yield by alcoholysis of their imidazolides in the presence of hydroxide ions i.e., with alcoholic sodium hydroxide. 45 Examples of syntheses of sulfonates are presented below. 

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