Ethers, from acetals phenols

Historically, simple Vz-alkyl ethers formed from a phenol and a halide or sulfate were cleaved under rather drastic conditions (e.g., refluxing HBr). New ether protective groups have been developed that are removed under much milder conditions (e.g., via nucleophilic displacement, hydrogenolysis of benzyl ethers, and mild acid hydrolysis of acetal-type ethers) that seldom affect other functional groups in a molecule. 

Solid esters are easily crystallisable materials. It is important to note that esters of alcohols must be recrystallised either from non-hydroxylic solvents (e.g. toluene) or from the alcohol from which the ester is derived. Thus methyl esters should be crystallised from methanol or methanol/toluene, but not from ethanol, n-butanol or other alcohols, in order to avoid alcohol exchange and contamination of the ester with a second ester. Useful solvents for crystallisation are the corresponding alcohols or aqueous alcohols, toluene, toluene/petroleum ether, and chloroform (ethanol-free)/toluene. Carboxylic acid esters derived from phenols are more difficult to hydrolyse and exchange, hence any alcoholic solvent can be used freely. Sulphonic acid esters of phenols are even more resistant to hydrolysis they can safely be crystallised not only from the above solvents but also from acetic acid, aqueous acetic acid or boiling n-butanol. 

Cleavage conditions for alkyl benzyl ethers prepared from acid-labile benzyl alcohols are similar to those for the corresponding benzyl esters (Table 3.30). Aryl benzyl ethers, however, are generally cleaved more easily by acidolysis than esters or alkyl ethers. Phenols etherified with hydroxymethyl polystyrene, for instance, can even be released by treatment with TFA (Entry 1, Table 3.31). It has also been shown that Wang resin derived phenyl ethers are less stable than Wang resin derived esters towards refluxing acetic acid [29]. Alternatively, boron tribromide may be used to cleave aryl ethers from hydroxymethyl polystyrene [573],... 

Cyclonite is a white crystalline solid, m.p. 202°. It is insoluble in water, alcohol, ether, ethyl acetate, petroleum ether, and carbon tetrachloride, very slightly soluble in hot benzene, and soluble 1 part in about 135 parts of boiling xylene. It is readily soluble in hot aniline, phenol, ethyl benzoate, and nitrobenzene, from all of which it crystallizes in needles. It is moderately soluble in hot acetone, about 1 part in 8, and is conveniently recrystallized from this solvent from which it is deposited in beautiful, transparent, sparkling prisms. It dissolves very slowly in cold concentrated sulfuric acid, and the solution decomposes on standing. It dissolves readily in warm nitric acid (1.42 or stronger) and separates only partially again when the liquid is cooled. The chemical reactions of cyclonite indicate that the cyclotrimethylenetri-nitramine formula which Herz suggested for it is probably correct. 

Mixed ethers result when alcohols and phenols are used with thoria at 390°—420° and esterification takes place when alcohol and acid interact at 350°-400°. Esterification10 is more complete in the presence of titanic oxide at 280°—300°. One molecule of acid is used with twelve molecules of alcohol, and in this way methyl, ethyl, propyl, butyl, and benzyl esters have been prepared from acetic, propionic and butyric acids. 

Singular examples to form aromatic ethers are a base-catalyzed, multistep, one-pot reaction of aryl methyl ketones with the appropriate fluorinated arylidenemalonitriles, the mercury acetate assisted synthesis of pentahalophenylvinyl ethers from vinyl acetate and the corresponding phenol, and the radical displacements in aryloxycyclohexadienones (e.g., 27) by halophenols. 2,3-Dichloro-5,6-dicyanohydroquinone (28) and products such as 29 are readily formed when cyclohexadienone 27 is treated with different phenols. 

Phenarsazine oxide crystallises from nitrobenzene or pyridine in colourless plates, which soon become yellow, M.pt. 350° C. It is sparingly soluble in most solvents, and when boiled with alcohols yields ethers, and with phenols, phenyl ethers. Boiling with acetic acid transforms it into 10-acetyl-S lO-dikydrophenarsazine, which occurs in greenish, shimmering plates, M.pt. 228° to 224° C. The corresponding 10-n-butoxy-compound forms pale yellow needles, M.pt. 158° to 160° C., and the lO-hemsyhtxy-denvaiive, colourless needles, M.pt. 178° to 175° C. 

The allyl vinyl ethers are usually prepared in situ, but it is also possible to isolate the primarily formed mixed acetals or allyl vinyl ethers155-1 57. With low-boiling vinyl ethers the reaction is carried out in a sealed tube with an excess of the vinyl ether. For a tandem Claisen-rearrangc-ment-ene cyclization involving the Saucy-Marbet reaction cf. ref 158. The generation of isopropenyl ethers from esters is described in ref 159. For a related Claisen rearrangement by the reaction of 2-methoxybutadiene with ends and phenols see ref 160. 

Plates from chloroform + methanol, needles from benzene, mp 282-285°. uv max (ethanol) 210, 215, 220, 223 rm (c 3900, 2400, 700, 250). Sol in benzene, chloroform, ether, ethyl acetate, acetic anhydride, acetic acid, phenol, pyridine, xylene less sot in alcohol. 

In the case where liquid chromatography is not available, acidic herbicides need to be derivatized because they can dissociate in water and are not usually volatile to be analyzed by gas chromatography. The basic methods used for chlorophenoxy acid herbicides are esterification, silylation, and alkylation, as described in a recent exhaustive review.The derivatization step is performed after preconcentration and cleanup. The step consists of the formation of esters and ethers from the carboxyl and phenol groups of the acidic herbicides. A lot of reagents and chemical mechanisms can be used to perform derivatization reactions. The most employed derivatization reagents are diazomethane, methyliodide, trimethylsulfonium (or anilinium) hydroxide, bis (trimethylsilyl) trifluoroacetamide (BSTFA), pentafluorobenzyl bromide, and anhydride acetate. It should be noted that explosive and hazardous diazomethane was replaced by safer agents. Authors also underline that surface water generally contains humic substances, which can interfere with the derivatization reaction. ... 

Copper-catalyzed C-O, C-N, and C-S Coupling. While there is an extensive variety of palladium catalysts for C(aryl)-X bond formation (X = 0, N, and S), copper corrqtlexes have recently gained renewed popularity in these coupling processes. Use of the (CuOTf)2. benzene complex allows the formation of diaryl ethers from aryl bromides or iodides and phenols in very good yields (76-93%) (eq 121). The reaction occurs in toluene in the presence of cesium carbonate as the base and a catal)4ic quantity of ethyl acetate whose role is probably to increase the solubility of the copper species. In the case of less reactive phenols, yields can be increased by the addition of a stoichiometric amount of carboxylic acid. A slight modification of these conditions has been used in the key diaryl ether formation in the synthesis of verbenachalcone. ... 

Tetrahydropyranyl (THP) ethers are frequently used as a protecting group for the hydroxyl group. Their formation and cleavage from alcohols and phenols have been successfully catalyzed by Bi(N03)3 5H20 [92] and Bi(0Tf)3 %H20 [93]. The conversion of THP ethers to acetate and formate esters has been reported to be efficiently catalyzed by Bi(0Tf)3 xH20 [94]. 

Preparation.— Two procedures for the production of ethers from alky] halides have been mentioned earlier in this Report. From a study of fluoride salts on alumina as reagents for the alkylation of phenols and alcohols, potassium or caesium fluoride on alumina, in acetonitrile or 1,2-dimethoxyethane as the solvent, has been found to be the best combination for general use. A recently reported one-pot synthesis of phenyl ethers from phenol acetates involves their treatment, in solution in acetone, first with potassium carbonate and then with an alkyl halide. Another interesting new procedure for the alkylation of phenols utilizes the gas-liquid phase-transfer catalysis technique that was discussed above. In this case a phenol (or a thiophenol) and an alkyl halide, both gaseous, are passed through a bed of solid K2CO3 (or NaHCOs) at 170°C in the presence of a PEG e,g. Carbowax 6000) as the catalyst. ... 

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