Phenolic ethers cleavage

Use of the ionic liquid, [bmim] BF4 in the presence of a strong protic acid such as HBr or TsOH results in clean phenolic ether cleavage at 115"C, 80-95% yield. AUcyl ethers are also cleaved but in poor yield. 

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). 

Oxidative Reactions. The majority of pesticides, or pesticide products, are susceptible to some form of attack by oxidative enzymes. For more persistent pesticides, oxidation is frequently the primary mode of metaboHsm, although there are important exceptions, eg, DDT. For less persistent pesticides, oxidation may play a relatively minor role, or be the first reaction ia a metaboHc pathway. Oxidation generally results ia degradation of the parent molecule. However, attack by certain oxidative enzymes (phenol oxidases) can result ia the condensation or polymerization of the parent molecules this phenomenon is referred to as oxidative coupling (16). Examples of some important oxidative reactions are ether cleavage, alkyl-hydroxylation, aryl-hydroxylation, AJ-dealkylation, and sulfoxidation. 

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 ... 

Unlike the acid-catalyzed ether cleavage reaction discussed in the previous section, which is general to all ethers, the Claisen rearrangement is specific to allyl aryl ethers, Ar—O—CH2CH = CH2. Treatment of a phenoxide ion with 3-bromopropene (allyl bromide) results in a Williamson ether synthesis and formation of an allyl aryl ether. Heating the allyl aryl ether to 200 to 250 °C then effects Claisen rearrangement, leading to an o-allylphenol. The net result is alkylation of the phenol in an ortho position. 

Cleavage of phenolic ethers with sulfonic acids... 

The quinone methide can also be generated in situ, at least in aqueous NaOH, directly from the peracetate, as hydrolysis of the phenolic acetate is faster than the benzylic acetate (see an example in Section 12.5.3). This method was used to demonstrate the addition of anthrahydroquinone (AHQ) and anthranol to (actual polymeric) lignin quinone methides in studies elucidating the anthraquinone (AQ)-catalyzed 8-0-4-aryl ether cleavage mechanisms in alkaline pulping.64-66... 

The inertness of phenols and phenoxy phenols toward Na/liq. NH3 can be attributed to the fact that phenols are powerful proton-donors in this system, and resistance of the resultant anions toward reduction is believed to result from stabilization by resonance (10). While alkylation of low-rank coals before treatment with Na/liq. NH3 therefore offers means for establishing the presence of phenoxy phenol ethers in them, an alternative is afforded by the observation that some phenols can be reduced by concentrated solutions of lithium (11). If this latter reaction also reduces phenoxy phenols in coal, a second treatment should then cause ether-cleavage. 

The final coal product in the MeOH/KOH experiments was 20%-25% soluble in the methanol. When the methanol was removed, the resultant product was a room temperature liquid with the properties described in Table V. Apparently the polymethylphenol fraction is formed by the cleavage of phenolic ethers and subsequent methyla-tion by the CO that is present in the reaction mixture as a result of methanol decomposition. The methylation reaction has been observed before for similar systems (3). 

It is evident that some leeway is available in the substituents tolerable in the m-position. The bronchodilator sulfonterol (28) is descended from this observation. Chloromethylanisole (29) is reacted with methylmereaptan to give 30, and the newly introduced group is oxidized to the methyl-sulfonyl moiety of 31 with hydrogen peroxide. Ether cleavage, acetylation and Fries rearrangement of the phenolic acetate produces 32, which is next brominated with pyrrolidinone hydrobromide tribromide and then oxidized to the glyoxal (33) with dimethyl sulfoxide. 

Other procedures include zinc-dust distillation, not generally useful except for exhaustive degradation of phenols to hydrocarbons, and various sodium and liquid ammonia cleavages of phenol ethers.3-7 These latter reactions lack generality and are often unpredictable. They require conditions too harsh for... 

R" may be alkyl or aryl. For dialkyl ethers, the reaction does not end as indicated above, since R OH is rapidly converted to R OR by the sulfonic acid (reaction 0-16), which in turn is further cleaved to R 0S02R" so that the product is a mixture of the two sulfonates. For aryl alkyl ethers, cleavage always takes place to give the phenol, which is not converted to the aryl ether under these conditions. Ethers can also be cleaved in a similar manner by mixed anhydrides of sulfonic and carboxylic acids733 (prepared as in 0-33). p-Hydroxy alkyl perchlorates734 and sulfonates can be obtained from epoxides.735 Epoxides and oxetanes give dinitrates when treated with N2Os,736 e.g.,... 

Cleavage of phenolic ethers 0-46 Cleavage of phenolic ethers... 

The nitrosative decomposition of phenoxy azides leads predominantly to the formation of phenol by cleavage of the ether moiety (Table 17).84... 

If boron tribromide is used for the ether cleavage, adduct 41 (from a combination of ether 39 and the electrophilic boron reagent) is attacked by bromide ion. The resulting intermediate 42 can than react further to phenol 43. 

Alcohols, phenols, ethers. The molecular ion of alcohols is weak or undetectable. Characteristic ions result from alpha-cleavage giving rise to resonance-stabilised carbocations ions the loss of the largest alkyl group is the preferred pathway although ions resulting from losses of the other groups may also be observed. 

Time-resolved CIDEP and optical emission studies provide further definitive characterization of the triplet and excited singlet states followed by their primary photochemical reactions producing transient radicals in individual mechanistic steps in the photolysis of a-guaiacoxylacetoveratrone. Both fluorescence and phosphorescence are observed and CIDEP measurements confirm the mainly n,n character of the lowest triplet state. The results indicate a photo triplet mechanism involving the formation of the ketyl radical prior to the P-ether cleavage to form phenacyl radicals and phenols. Indirect evidence of excited singlet photo decomposition mechanism is observed in the photolysis at 77 K. 

Additional examples of ether cleavages may be found in Section 45A (Protection of Alcohols and Phenols). 

In a reversal of the ether cleavage reactions described above, benzyl alcohols and ethers may be transformed to alkyl or aryl ethers via acid-catalyzed etherification or transetherification, respectively, by reaction with the appropriate alcohol or phenol (reaction R, Fig. 1.5). 

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