O-methylation of phenolic

Cs-X has also been used to promote the selective O-methylation of phenol with dimethyl carbonate. 2 N-Monomethylaniline was obtained in 93% yield by reacting aniline with dimethyl carbonate over a K-Y catalyst at 180°C (Eqn. 22.46). 3 The reaction of alcohols with chloromethyl ether over Na-Y gave the resulting methoxymethyl ethers in 70%-90% yields (Eqn. 22.47). 4... 

Basak, A., Nayak, M. K., Chakraborti, A. K. Chemoselective O-methylation of phenols under nonaqueous condition. Tetrahedron Lett. 1998, 39,4883-4886. 

Esterification. Dimethyl sulfate has been used widely for O-methylation of phenols and alcohols, but has been used only a few times for esterification of carboxylic acids2 the method has not attracted much attention. Actually dimethyl sulfate is a useful reagent for this purpose, especially for esterification of hindered acids such as (l).3 This acid has been converted into the methyl ester in over 95% yield by either of two methods. Concentrated aqueous NaOH (1.1 moles) is added at room temperature to a well-stirred mixture of (1, 1 mole) and dimethyl sulfate in dioxane followed by a... 

Figure 1.12 summarizes the result of this comparative evaluation of DMC as green methylating agent. The assessment was based on atom economy (AE) and mass index (MI) for three model transformations O-methylation of phenol, the mono-C-methylation of phenylacetonitrile and the mono-N-methylation of aniline. 

CATALYSIS BY RARE EARTH PHOSPHATE II SELECTIVE O-METHYLATION OF PHENOLS BY METHANOL IN VAPOR PHASE... 

The study of O-methylation of phenol as well as 1,4-dihydroxybenzene in anisole and 4-methoxyphenol respectively and the condensation of catechol with ethylene glycol demonstrates that the use of LaP04, Cs2HP04 as a catalyst is a powerfull methodology to selectively access numerous alkylarylethers. Results are presented in Table 5. 

Alumina supported KF has been introduced by Ando etal.[42] and Clark etal.[43] as a basic catalyst for many types of the reactions such as o-methylation of phenol, crown ether synthesis, Michael addition of various nitroalkanes to unsaturated carbonyl compounds etc. 

Methyl ethers are usually prepared by some variant of the lliamson ether synthesis in which an alcohol reacts with either iodomethane. dimethyl sulfate, or methyl inflate (HAZARD) in the presence of a suitable base. A word of caution dimethyl sulfate and methyl triflate, like all powerful alkylating agents, are potentially carcinogenic and therefore should only be handled in a weil-ven-tilated fume hood. For the O-methylation of phenols (pKa 10) a comparatively weak base such as potassium carbonate in conjunction with dimethyl sulfate is sufficient, whereas simple aliphatic alcohols require stronger bases such as sodium hydride [Scheme 4.111] or lithium hexamethyldisilazide [Scheme 4.112]. The latter transformation is notable for the fact that O-methylation was accomplished without competing elimination. 

O-methylation of phenolic hydroxyls greafly reduces potency,... 

O-Methylation of phenolic compotmds can be efficiently carried out by tetra-methylammonium chloride in diglyme or poly ethyleneglycol (PEG) at temperatures of 150-160 °C and in the presence of either NaOH or K COj. The benzylation and methylation of phenols occiu, where the benzylation product was always predominating. With allyl-substituted phenols as substrates and using NaOH as a base, it was feasible to achieve both the alkylation and the double-bond isomerization of the allyl group to obtain (E/Z)-propenyl-substituted methyl and benzyl aryl ethers in a single preparative step (Maras et al., 2010). 

Usually prepared from the corresponding sulphonic acids by alkali fusion, methylation of phenol or from the aminotoluene by treatment with nitrous acid followed by boiling. Both o- and p-cresol are used as end components in azo dyes. 

A -Methylation of the NH of heterocycles using 1 is also known as exemplified by the methylation of indole/ The interesting mechanism is delineated below. O-methylation of weak acids such as phenols, carboxylic acids and oximes as well as 5-methylation such as A -phenylisorhodanine, certain thioketones, and dithiocarboxylic acids have also been reported." ... 

Allard A-S, M Remberger, AH Neilson (1987) Bacterial O-methylation of halogen-substituted phenols. Appl Environ Microbiol 53 839-845. 

Haggblom M, D Janke, PJM Middeldorp, M Salkinoja-Salonen (1988) O-Methylation of chlorinated phenols in the genus Rhodococcus. Arch Microbiol 152 6-9. 

This chapter compares the reaction of gas-phase methylation of phenol with methanol in basic and in acid catalysis, with the aim of investigating how the transformations occurring on methanol affect the catalytic performance and the reaction mechanism. It is proposed that with the basic catalyst, Mg/Fe/0, the tme alkylating agent is formaldehyde, obtained by dehydrogenation of methanol. Formaldehyde reacts with phenol to yield salicyl alcohol, which rapidly dehydrogenates to salicyladehyde. The latter was isolated in tests made by feeding directly a formalin/phenol aqueous solution. Salicylaldehyde then transforms to o-cresol, the main product of the basic-catalyzed methylation of phenol, likely by means of an intramolecular H-transfer with formaldehyde. With an acid catalyst, H-mordenite, the main products were anisole and cresols moreover, methanol was transformed to alkylaromatics. 

Shen and Li [149] extracted rubidium (and caesium) from brine samples with 4-ferf-butyl-2-(o -methyl-benzyl) phenol prior to atomic absorption determination of the metal. 

Phenol methylation to 2,6-xylenol has been widely studied for the past few deeades owing to the room for improvisation from the viewpoint of product selectivity. Generally during phenol methylation to 2,6-xylenol, occurs via sequential methylation of phenol to o-cresol to 2,6-xylenol, various reaction parameters mediate the selectivity between the two. For instance, when the reaetants stoichiometry of methanol to phenol molar ratio > 2, and significant residence time of o-cresol may favor 2,6-xylenol selectivity. However, excess methanol is often used, sinee some amount of methanol tend to undergo oxidation into various reformate produets [71] under vapor phase condition. Similarly, reaction temperature, catalyst acid-base property, and space velocity of the reaetant are the parameters that govern the selectivity to 2,6-xylenol. 

The oldest cresol production method used in the United States is through the recovery of fractional distillates from coal tars. Most domestic cresols are formed via catalytic and thermal cracking of naphtha fractions during petroleum distillation. Since 1965, quantities of coal tar and petroleum isolates have been insufficient to meet the rising demand. Consequently, several processes for the manufacture of the various isomers have been developed. One General Electric facility produces o-cresol at an annual capacity of 10,000 tons by the methylation of phenol in the presence of catalysts. The Sherman-Williams Company uses the toluene sulfonation process and maintains an annual capacity for p-cresol of 15,000 tons. The Hercules Powder Company produced p-cresol until 1972 by the cymene- cresol process. 

Ahlborg, U. G. Thurnberg, T. M. (1980). Chlorinated phenols occurrence, toxicity, metabolism, and environmental impact. Critical Reviews in Toxicology, 7, 1-35. Allard, A-S., Remberger, M. Neilson, A. H. (1987). Bacterial O-methylation of halogen substituted phenols. Applied and Environmental Microbiology, 53, 839—45. 

Haggblom, M. M., Janke, D., Middeldorp, P.J.M. Salkinoja-Salonen, M. S. (1989). O-methylation of chlorinated phenols in the genus Rhodococcus. Archives of Microbiology, 152, 6-9-... 

Shieh, W.C., Dell, S. andRepic, O., l,8-Diazabicyclo[ 5.4.0] undec-7-ene (DBU) and micro wave-accelerated green chemistry in methylation of phenols, indoles, and benzimidazoles with dimethyl carbonate, Org. Lett., 2001, 3, 4279. 

Partial N-methylation can also be accomplished with Mel. For example, tetrandrine (48) gave on treatment with 1 equiv Mel a 4 1 mixture of the monoquatemary salts 365 and 33. The pure minor isomer could be obtained by sequential quatemization of tetrandrine with 1 equiv benzyl bromide, then 1 equiv Mel, conversion of the bisquatemary salt to the dichloride form with anion-exchange resin, and cleavage of the benzyl group by catalytic reduction (H2/Pd-EtOH) (20). Partial O-methylation of alkaloids containing more than one OH can be accomplished with CH2N2 either by prior partial protection of the phenols as 0-acetates (148) or by use of less than a stoichiometric amount of CH2N2 (132) (see, e.g., Section II,C, 122). 

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