Phenolic ethers dealkylation

Phenolic ethers, dealkylation of, 287 Phenols, nitrosation of, 394 Phenoxypropadiene, 11 3-Phenylamino-l-butyne, 97 Phenyl azide, 281-282 Phenylazoalkanes, 327 Phenylazodiphenylphosphine oxide, 328 Phenylazoethane, 308 Phenylazohydroperoxides, 331 2-Fhenylazo-l,3-indandione, 299 Phenylazo-l-naphthalene, 304, 311 PhenyIazo-2-naphthaIene, 304, 311 Phenylazonaphthalenes, 310... 

Under some conditions, phenolic ethers are dealkylated during coupling. However, the dealkylation follows the coupling step and is acid-catalyzed. Consequently, use of an excess of sodium acetate as a buffer or use of a nonaqueous medium obviates the dealkylation. 

A number of examples of dealkylations by chemical and catalytic methods are given in Table 4.7 (refs.89-93). A very general method for the cleavage of phenolic ethers consists in their reaction under reflux during 36 hours with an excess of 37% hydrobromic acid and a small amount of hexadecylammonium bromide. Phenyl n-pentyl ether gave phenol in 71% yield (ref.94). 

The recently developed dealkylation of phenol ethers with trimethylsilyl iodide has been shown to work well for OO -dialkyl-uracils. A number of ring transformations of uracils have been reported. The [2 + 2]cyclo-adducts (232) can be transformed into pyridones (233) by treatment with base overall yields of pyridines from the starting uracils (231) can be quite reasonable. The reaction is thought to proceed via electrocyclic ring-opening of the dianion of (232) (Scheme 92). 

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. 

Pyridinium chloride (]PyH]Cl) has also been used in a number of cyclization reactions of aryl ethers (Scheme 5.1-4) [4,18]. Presumably the reaction initially proceeds by dealkylation of the methyl ether groups to produce the corresponding phenol. 

O-dealkylation. Aromatic methyl and ethyl ethers may be metabolized to give the phenol and corresponding aldehyde (Fig. 4.16), as illustrated by the de-ethylation of phenacetin (Fig. 4.20). Ethers with longer alkyl chains are less readily O-dealkylated, the preferred route being co-l-hydroxylation. 

Anilines (23 R = 2-Pr, PhCPfc X = Cl, Br, I) have been obtained in high yields (40-95%) from the reaction of the primary amines 2-propylamine and benzylamine with the ethers (24 R = Me, CH2=CHCH2, CH2-oxirane) in EtOH at room temperature.127 With secondary amines dealkylation of the aromatic ether to the corresponding phenol took place rather than SNAr dealkoxylation. 

Aluminum and boron halides are sometimes used to dealkylate alkyl aryl ethers to phenols. Boron tribromide cleaves aliphatic ethers to alcohols and alkyl halides, but the reaction has no preparative value in the aliphatic series. Aluminum halide and the ether first form a complex from which a molecule of alkyl halide is eliminated upon heating. 

Carboxylic acids have reacted with phenols [59] and aryl ethers together with BF3 as catalyst. Dealkylation of an ether residue ortho to the introduced acyl group is frequently encountered, as in the synthesis of baeckeol (Eq. 32) [60]. 

Dealkylation of certain ethers occurs when they are treated with a titanium halide. This reaction has been applied to the removal of protective groups from alcohols and phenols [655,656]. Demethylation of the permethylated tetraphenol shown in Eq. (291) with TiBc4 could be performed stepwise. The second demethylation occurred specifically at the position indicated to give the bis-phenol with C2 symmetry and a chiral plane (Eq. 291) [657]. 

Studies aimed at the synthesis of the tetracyclic steroid skeleton from dehydro-abietic acid have centred, in their initial stages, on transformations of the C-13 isopropyl group. The full paper describing the conversion of methyl 12-acetyl-abieta-8,ll,13-trien-18-oate into methyl 13-hydroxypodocarpa-8,ll,13-trien-18-oate by nitrodeacylation and dealkylation reactions, has appeared. Birch reduction of the methyl ether of the phenol afforded the a/5-unsaturated ketone (56) which is a useful synthetic intermediate. Methods for the conversion of podocarpic acid into the a) -unsaturated ketones (57 R = CO2H and CHjOAc) have been investigated reduction of the ester (58 R = C02Me) with lithium in liquid ammonia, which was accompanied by decarboxylation, gave only a... 

Further efforts demonstrate that the reaction of triethyl phosphite occurs under quite mild conditions in a conjugate manner with a wide range of oc,p-unsaturated aldehydes provided that a proton source is present (Scheme 5.21). The use of protic solvents, such as alcohols or phenols, not only provides a source of proton for the anionic site of the zwitterionic adduct but also furnishes a nucleophile for the required dealkylation step. The simplest hypothesis consistent with all of these facts is that the protonation-valency expansion of the quasiphosphonium ion intennediate using a proton source proceeds at a rate greater than the intermolecular pathway to enol ether. ... 

The preferential dealkylation of a combined thio and 0-alkyl ether was selectively chemically achieved either at the O or the S atom by appropriate choice of reagent. Sodium iso-propylthiolate at 120°C added to 3-(methylthio)anisole in hexamethylphosphorictriamide in a nitrogen atmosphere followed after 2.5 hours by acidification gave 3-(methylthio)phenol in 88% yield, while sodium alone in hexamethylphosphorictriamide resulted in selective... 

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