Benzyl methyl ether, substituted

The argtiments of Norman and his co-workers seem to give affirmative answers to the first and second of these questions, but it is doubtful if the available data further require such an answer for the third question. It can be argued that the crucial comparison made between the behaviour of benzyltrimethylammonium ion and protonated benzyl methyl ether is invalid, and that it is possible to interpret the results in terms of nitration by the nitronium ion, modified by protonation of the oxygen atom of the ether a case for the possible involvement of the nitro-nium ion in specific interaction leading to o-substitution has been made. ... 

SuIfona.tlon, Sulfonation is a common reaction with dialkyl sulfates, either by slow decomposition on heating with the release of SO or by attack at the sulfur end of the O—S bond (63). Reaction products are usually the dimethyl ether, methanol, sulfonic acid, and methyl sulfonates, corresponding to both routes. Reactive aromatics are commonly those with higher reactivity to electrophilic substitution at temperatures > 100° C. Tn phenylamine, diphenylmethylamine, anisole, and diphenyl ether exhibit ring sulfonation at 150—160°C, 140°C, 155—160°C, and 180—190°C, respectively, but diphenyl ketone and benzyl methyl ether do not react up to 190°C. Diphenyl amine methylates and then sulfonates. Catalysis of sulfonation of anthraquinone by dimethyl sulfate occurs with thaHium(III) oxide or mercury(II) oxide at 170°C. Alkyl interchange also gives sulfation. 

As mentioned above, methyl loss from ionized methoxymethyl derivatives of methyl benzoate is not restricted to the ortho-isomet 93. 2H labelling has shown that the mita and para compounds 96 also eliminate CH3 specifically from the methoxymethyl group. Interestingly, neither from the unsubstituted benzyl methyl ether 97 (X = H) nor from the X-substituted analogues 97 (X = CH2OH, NQ2) loss of CH3 is observed (21). Thus, the earbomethoxy function seems to play a decisive role in the dissociation process. 

Recently two alternative procedures have been described. In one case14 methoxyacetyl chloride (MeOCH2 COCl) in the presence of anhydrous aluminium chloride is thought to provide the source of the cation (4), which substitutes in the aromatic nucleus to give the benzyl methyl ether (5), which is subsequently converted into the chloromethylated product (6). 

Aromatic and aliphatic amino ethers have been synthesized by this method. An example of the formation of a cyano ether is the preparation of p-cyano benzyl methyl ether from the substituted benzyl bromide and sodium methoxide (84%). Also, certain aryloxyacetonitriles, AtOCHjCN, are made by the condensation of chloroacetonitrile with sodium phenoxides in a solution of methyl ethyl ketone containing a small amount of sodium iodide (70-80%). Aromatic nitro ethers, like o- and p-nitrodiphenyl ether, have been prepared by the Ullmann procedure (84%). The synthesis of alkyl p-nitrophenyl ethers has also been accomplished with good yields (55-92%). ... 

Poly(methoxymethylstyrene) and co-polymers from (2,2-disubstituted 1,.5-dioxolan-4-yl)methoxymethylstyrene crosslink readily under u.v. light (Scheme 17). Here both the 1,3-dioxolane and benzyl methyl ether structures participate in the crosslinking. o-Nitrobenzyl cholate esters have been used as effective photosensitizers in resists," as have poly-(N-vinylamine) and methacrylate co-polymers with substituted cinnamic or cinnamylidene groups. 

Quinone Methides. The reaction between aldehydes and alkylphenols can also be base-catalyzed. Under mid conditions, 2,6-DTBP reacts with formaldehyde in the presence of a base to produce the methylol derivative (22) which reacts further with base to ehmmate a molecule of water and form a reactive intermediate, the quinone methide (23). Quinone methides undergo a broad array of transformations by way of addition reactions. These molecules are conjugated homologues of vinyl ketones, but ate mote reactive because of the driving force associated with rearomatization after addition. An example of this type of addition is between the quinone methide and methanol to produce the substituted benzyl methyl ether (24). 

Boron triiodide rapidly cleaves methyl ethers of o-, m-, or / -substituted aromatic aldehydes (0°, 25° 0.5-5 min 40-86% yield)." BI3 complexed with A/,A-diethylaniline is similarly effective, but benzyl ethers are converted to the iodide... 

Sodium A-methylanilide, xylene, HMPA, 60-120°, 70-95% yield. Methyl ethers of polyhydric phenols are cleaved to give the mono-phenol. Benzyl ethers are also cleaved. Halogenated phenols are not effectively cleaved, because of competing aromatic substitution. 

Loss of catalytic activity resulting from internal displacements is not usually a serious problem below temperatures of about 100 C. However, highly active R-groups, such as benzyl, methyl and allyl, undergo internal displacement more readily, particularly in the presence of strong nucleopfiles. For instance, the presence phenolates and thiolates may lead to the formation of benzyl alcohol, ethers, or sulphides from benzyl-substituted quaternary ammonium salts. 

The application of phase-transfer catalysis to the Williamson synthesis of ethers has been exploited widely and is far superior to any classical method for the synthesis of aliphatic ethers. Probably the first example of the use of a quaternary ammonium salt to promote a nucleophilic substitution reaction is the formation of a benzyl ether using a stoichiometric amount of tetraethylammonium hydroxide [1]. Starks mentions the potential value of the quaternary ammonium catalyst for Williamson synthesis of ethers [2] and its versatility in the synthesis of methyl ethers and other alkyl ethers was soon established [3-5]. The procedure has considerable advantages over the classical Williamson synthesis both in reaction time and yields and is certainly more convenient than the use of diazomethane for the preparation of methyl ethers. Under liquidrliquid two-phase conditions, tertiary and secondary alcohols react less readily than do primary alcohols, and secondary alkyl halides tend to be ineffective. However, reactions which one might expect to be sterically inhibited are successful under phase-transfer catalytic conditions [e.g. 6]. Microwave irradiation and solidrliquid phase-transfer catalytic conditions reduce reaction times considerably [7]. 

Allyl- and benzyl-thiophenes may be cyclized by a direct Bradsher reaction, using dichloromethyl methyl ether or related dichloroalkyl methyl ethers and tin(IV) chloride catalysis to give the corresponding benzo- or dibenzo-thiophenes in 55-60% yield (73JCS(P1)1099). Thus substituted thiophenes having a benzyl group at either the 2- or 3-position, e.g. (349), when treated with a 1,1-dichloroalkyl methyl ether and tin(IV)... 

Oxidations of l-(4-methoxyphenyl)-2-(4-substituted phenyl)ethanols, (6), [identical to alcohols (4a) to (4e) except for methylation of the 4-OH group] were also studied with cerium(IV) as the catalyst (Fisher, T. H., et al., J. Org. Chem., in press). To determine if oxidation occurs by electron abstraction from the benzylic hydroxyl or the aromatic ring, a competitive oxidation procedure was examined on the diaryl ethanol 6a and its methyl ether analog, 1-methoxy-l-(4-methoxyphenyl)-2-phenylethane, (7), (Fisher, T. H., et al., J. Org. Chem., in press). 

The substrate arachidonic aeid, whieh often leads to formation of inflammatory prostaglandins, is stored in tissues as one of a number of phospholipids these compounds, as the name indicates, comprise complex phosphate-containing esters. The antiinflammatory corticosteroids inhibit the action of the enzyme, phospholipase A2, that frees arachidonic acid. The many undesired effects of those steroids has led to the search for non-steroidal inhibitors of that enzyme. A highly substituted indole derivative has shown good activity as a phospholipase A2 inhibitor. Alkylation of the anion from treatment of indole (32) with benzyl chloride affords the corresponding A-benzylated derivative (33). The methyl ether at the 4 position is then cleaved by means of boron tribromide to yield 34. Alkylation of the enolate from reaction of the phenol with sodium hydride with tert-butylbromoacetate affords the corresponding... 

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