Ethers or phenols

Reduction of phenols, phenolic ethers, or phenolic esters... 

Intramolecular anodic coupling of diaryl amides is a synthetically interesting reaction that may be applied to the synthesis of alkaloidal structures [210]. However, this aryl coupling is initiated by the oxidation of an aromatic ring (aryl ether or phenol) and not by oxidation of the nitrogen. Therefore, it is not discussed further in this chapter. 

The biotransformation of salicylates takes place in many tissues, but particularly in the liver. The three chief metabolic products are salicyluric acid (the glycine conjugate), the ether or phenolic glucuronide, and the ester or acyl glucuronide. 

A learning set of 1663 structurally diverse compounds was built. It contained 28 aliphatic hydrocarbons 52 aromatic hydrocarbons 74 alcohols, ethers, or phenols 27 aldehydes and ketones 42 acids and esters 66 amines and nitriles 23 amides and anilides 9 sulfur-containing hydrocarbons 18 nitro arenes 10 amino acids 54 halogenated hydrocarbons 35 nucleosides 25 nucleoside bases and 1200 multifunctional compounds. 

By interaction of hydrogen cyanide and hydrogen chloride with an anxnatic compound (hydrocarbon, phenol or phenol ether) in the presence of aluminium chloride (or zinc chloride). This is known as the Gattermann... 

By the condensation of a nitrile with a phenol or phenol ether in the presence of zinc chloride and hydrogen chloride a hydroxyaryl- or alkoxyaryl-ketone is produced. The procedure is termed the Hoesch reaction and is clearly an extension of the Gattermann aldehyde reaction (Section IV,121). The reaction gives the best results with polyhydric phenols and their ethers with simple monohydric phenols the imino ester hydrochloride is frequently the sole product for example ... 

Methylation with diazomethane may be carried out as follows (FUME CUPBOARD )-. Dissolve 2-3 g. of the compound (say, a phenol or a carboxylic acid) in a little anhydrous ether or absolute methanol, cool in ice, and add the ethereal solution of diazomethane in small portions until gas evolution ceases and the solution acquires a pale yellow colour. Test the coloured solution for the presence of excess of diazomethane by removing a few drops into a test-tube and introducing a glass rod moistened with glacial acetic acid immediate evolution of gas should... 

Aqueous alkaline solution. This will contain any acids or phenols present. Cool, acidify (litmus) with dilute HjSO, and add excess of solid NaHCO,. Extract with ether. 

Vinylation. Acetylene adds weak acids across the triple bond to give a wide variety of vinyl derivatives. Alcohols or phenols give vinyl ethers and carboxyHc acids yield vinyl esters (see Vinyl polymers). 

Substitution Reactions on Side Chains. Because the benzyl carbon is the most reactive site on the propanoid side chain, many substitution reactions occur at this position. Typically, substitution reactions occur by attack of a nucleophilic reagent on a benzyl carbon present in the form of a carbonium ion or a methine group in a quinonemethide stmeture. In a reversal of the ether cleavage reactions described, benzyl alcohols and ethers may be transformed to alkyl or aryl ethers by acid-catalyzed etherifications or transetherifications with alcohol or phenol. The conversion of a benzyl alcohol or ether to a sulfonic acid group is among the most important side chain modification reactions because it is essential to the solubilization of lignin in the sulfite pulping process (17). 

The reaction of alcohols and acid chlorides in the presence of magnesium has been described (68). With primary and secondary alcohols the reaction is very smooth, and affords high and sometimes quantitative yields. Difficulty esteritiable hydroxy compounds such as tertiary alcohols and phenols can be esteritied by this method. The reaction carried out in ether or benzene is usually very vigorous with evolution of hydrogen. 

Alkyl tertiary alkyl ethers can be prepared by the addition of an alcohol or phenol to a tertiary olefin under acid catalysis (Reycler reaction) sulfuric acid, phosphoric acid, hydrochloric acid, and boron trifluoride have all been used as catalysts ... 

Several examples of cost-effective liquid-hquid extraction processes include the recovery of acetic acid from water (Fig. 15-1), using ethyl ether or ethyl acetate as described by Brown [Chem. Eng. Prog., 59(10), 6.5 (1963)], or the recoveiy of phenolics from water as described by Lauer, Littlewood, and Butler [7/Steel Eng., 46(5), 99 (1969)] with butyl acetate, or with isopropyl ether as described by Wurm [Gliickauf, 12, 517 (1968)], or with methyl isobutyl ketone as described by Scheibel [ Liqmd-Liquid Extraction, in Periy Weiss-... 

Phenol with carbon tetrachloride, ethanol, diethyl ether or xylene. 

Ethers that are solids (e.g. phenyl ethers) can be steam distilled from an alkaline solution which will hold back any phenolic impurity. After the distillate is made alkaline with sodium carbonate, the insoluble ether is collected either by extraction (e.g. with chloroform, diethyl ether or toluene) or by filtration. It is then crystallised from alcohols, alcohol/petroleum ether, petroleum ether, toluene or mixtures of these solvents, sublimed in a vacuum and recrystallised if necessary. 

Because phenols are weak acids, they can be freed from neutral impurities by dissolution in aqueous N sodium hydroxide and extraction with a solvent such as diethyl ether, or by steam distillation to remove the non-acidic material. The phenol is recovered by acidification of the aqueous phase with 2N sulfuric acid, and either extracted with ether or steam distilled. In the second case the phenol is extracted from the steam distillate after saturating it with sodium chloride (salting out). A solvent is necessary when large quantities of liquid phenols are purified. The phenol is fractionated by distillation under reduced pressure, preferably in an atmosphere of nitrogen to minimise oxidation. Solid phenols can be crystallised from toluene, petroleum ether or a mixture of these solvents, and can be sublimed under vacuum. Purification can also be effected by fractional crystallisation or zone refining. For further purification of phenols via their acetyl or benzoyl derivatives (vide supra). 

Chemical Reactivity - Reactivity with Water No reaction Reactivity with Common Materials Contact with copper or aluminum can cause polymerization Stability During Transport Stable Neutralizing Agents for Acids and Caustics Not pertinent Polymerization Can occur if the product is exposed to sunlight, air, copper, aluminum, or heat Inhibitor of Polymerization Methyl Ether of Hydroquinone (200 ppm) and or phenol (0.6 to 0.8 %). 

Add and Phenol, if present together, may be separated b) adding sodium bicarbonate in excess and extracting with ether, or by dissolving in caustic soda solution, saturating with caibon dioxide and then extracting with ether. The ether extracts the phenol, n-hicb is insolul le in sodium carbonate, leaving the acid. 

Historically, simple n-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, or mild acid hydrolysis of acetal-type ethers) that often do not affect other functional groups in a molecule. 

Repeat this analysis for the reaction of phenyl methyl ether with HI leading to phenol and methyl iodide or methanol and phenyl iodide and involving protonated phenyl methyl ether as an intermediate. (Note In this case, the appropriate empty molecular orbital is LUMO+2 the LUMO is concentrated primarily on the CO bond.) Which reaction, with ethyl propyl ether or phenyl methyl ether, appears to be more likely to give selective ether cleavage ... 

Sjwyer and coworkers have developed an efficient alternative UUmann synthesis of diaryl ethers, diaryl thioethers, and diarylamines using the SnAt reaction. Phenol, thiophenol, or aniline reacts v/ith an appropriate aryl halide, In the presence of KF-aliunina and 18-crovm-6 In acetonitrile or DMSO to give the corresponding diaryl ether or diaryl thio ether as shovm In Eqs. 9.6 and 9.7. ... 

In Figure 13.2, the intensity of the ion at m/z 170 represents a molecular ion of an aromatic compound. The characteristic losses from the molecular ion (M - 1, M - 28, and M - 29) suggest an aromatic aldehyde, phenol, or aryl ether. The molecular formula of Ci2H 0O is suggested by the molecular ion at m/z 170, which can be either a biphenyl ether or a phenylphenol. The simplest test to confirm the structure is to prepare a TMS derivative, even though m/z 11 strongly indicates the diaryl ether. 

The mem-dichlorobenzene complex reacts with protected 0-aryltyrosines to give aryl ethers. Both chlorine atoms can be sequentially substituted to give symmetrical or disymmetrical triaryl diethers (Scheme XVI). The building up of such diaryl ethers from phenolic compounds which have amino groups in their side chains... 

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