Methylation of aromatics

Methylation of aromatic molecules can also be achieved ia the vapor phase, over a soHd catalyst. 

Notable examples of general synthetic procedures in Volume 47 include the synthesis of aromatic aldehydes (from dichloro-methyl methyl ether), aliphatic aldehydes (from alkyl halides and trimethylamine oxide and by oxidation of alcohols using dimethyl sulfoxide, dicyclohexylcarbodiimide, and pyridinum trifluoro-acetate the latter method is particularly useful since the conditions are so mild), carbethoxycycloalkanones (from sodium hydride, diethyl carbonate, and the cycloalkanone), m-dialkylbenzenes (from the />-isomer by isomerization with hydrogen fluoride and boron trifluoride), and the deamination of amines (by conversion to the nitrosoamide and thermolysis to the ester). Other general methods are represented by the synthesis of 1 J-difluoroolefins (from sodium chlorodifluoroacetate, triphenyl phosphine, and an aldehyde or ketone), the nitration of aromatic rings (with ni-tronium tetrafluoroborate), the reductive methylation of aromatic nitro compounds (with formaldehyde and hydrogen), the synthesis of dialkyl ketones (from carboxylic acids and iron powder), and the preparation of 1-substituted cyclopropanols (from the condensation of a 1,3-dichloro-2-propanol derivative and ethyl-... 

Drivers for Performing Methylation of Aromatics in Micro Reactors... 

Beneficial Micro Reactor Properties for Methylation of Aromatics... 

Methylation of Aromatics Investigated in Micro Reactors Organic synthesus 89 [OS 89] Methylation of a 1,3,4-substituted benzene... 

Another approach to optimize pharmacotherapy of leukemia with thiopurines is phenotyping and/or genotyping of TPMT. TPMT is a ubiquitously expressed cytosolic methyltransferase that catalyzes the S -methylation of aromatic and heterocyclic sulfhydryl compounds (130, 131). Neither the biological function of TPMT nor its endogenous substrates are known. In thiopurine-treated patients, the activity of TPMT determines the balance between 6-TGN and 6-MMPR. 

The cobalt carbonyl complex is also an effective catalyst for the siloxy-methylation of aromatic aldehydes.110 Arylethane-l,2-diol disilylethers are obtained in good yields, resulting from incorporation of one molecule of CO and two molecules of HSiR3. Good selectivity for the siloxymethylation product is observed at 0°C in hexane. At 15°C, faster reaction rates are observed, but the selectivity for the CO-incorporated product is lower. In contrast, aliphatic aldehydes react under these conditions (1 atm CO, 0°C) to give only a small amount of CO-incorporated product, with a major product resulting from hydrosilylation. 

Brown, H. C., Jungk, H. The catalytic halides. XII. The reaction of benzene and toluene with methyl bromide and Iodide in the presence of aluminum bromide evidence for a displacement mechanism in the methylation of aromatic compounds. J. Am. Chem. Soc. 1955, TT, 5584-5589. 

A series of stemofurans A-K (92-102) were isolated and identified from the methanolic extract of Stemona collinsae roots, many of which have the C-methylation of aromatic rings. The structural characteristics inferred that ring B on stemofurans A-K (92—102) was formed via the polyketide pathway always showing two oxygen substitutions in the meta position at C-3 and C-5 [57]. 

Accompanied by stemofurans A-K (92-102), the bibenzyls and stilbostemins A-F (132-137), were also isolated fi-om Stemona collinsae roots together with five known derivatives -the stilbenes pinosylvin and 4-methylpinosylvin and the dihydrophenanthrene stemanthrene D (359) [57]. Stilbostemin B (133) and D (135) have been previously isolated from Stemona tuberosa [75]. The consecutively designated stilbostemin G (138) was isolated from Stemona cf. pierrei [76]. It became apparent that the stilbenoids of Stemona genus can be characterized mainly by the C-methylation of aromatic rings and the formation of phenylbenzofurans. 

Methylation of aromatics. Aromatic substitutions effected by radicals are of more theoretical than preparative interest because the yields are low. Waters and co-workers" studied the methylation of monosubstituted benzenes with methyl radicals generated from di-f-butyl peroxide, separated the mixture of monomethyl... 

Reduction with NaBH4 in Me2SO of the Af-3-aminomethyl derivatives has been also proposed as a method for N-methylation of aromatic primary amines.248 Alternatively, N-1- or N-3-aminomethyl derivatives can be obtained by reaction of N-l- or Af-3-halohydantoins with diazomethane and the amine.249... 

Use of dimsylsodium in DMSO for formation of phosphonium ylides is particularly advantageous for the synthesis of volatile hydrocarbons because the high-boiling solvent facilitates isolation of lower-boiling products.118 Japanese workers1111 studied the methylation of aromatic hydrocarbons with dimsylsodium. Naphthalene was not sufficiently reactive, but phenanthrene gave 9-methylphenanthrene in 86%... 

Various molecular maturity parameters, based on the positions of methylation of aromatic compounds, have been developed from studies of coals and type III kero-... 

S-Methylation is also an important pathway in the biotransformation of many sulfur-containing drugs. At least two separate enzymes, thiol methyltrans-ferase (TMT) and thiopurine methyltransferase (TPMT) are known to catalyze S-methylation in humans [87], TMT, a membrane-bound enzyme, catalyzes the S-methylation of captopril, D-penicillamine, and other aliphatic sulfhydryl compounds such as 2-mercaptoethanol. On the other hand TPMT, a cytosolic enzyme, catalyzes the S-methylation of aromatic and heterocyclic sulfhydryl compounds including 6-mercaptopurine and other thiopurines. Recently, S-methyltransferase has been shown to play a critical role in the metabolism of the antipsychotic drug, ziprasi-done, in humans [72, 88]. Both TPMT and TMT have been shown to be genetically polymorphic in humans. 

Attempts to prepare tertiary amines by reductive alkylation have in general proved unsatisfactory the only significant reactions are the methylation of secondary and the dimethylation of primary amines by formaldehyde. Bowman and Stroud1008 described the preparation of a series of aliphatic dimethyl-amino acids by hydrogenation of mixtures of amino acids and formaldehyde in the presence of palladium-charcoal at atmospheric pressure. In most cases results are improved if the aldehyde is added gradually to the reaction mixture. In the methylation of aromatic amines special precautions are necessary to prevent condensation of the formaldehyde with the aromatic ring.1009... 

Such is the case also for jV-(halomethyl) carboxamides (R = H or alkyl, R = acyl)721 and iV-(halomethyl) diacylamides (R and R = acyl), which are specific for amidomethylation of / -diketones, a reaction that cannot be effected otherwise) for a review of these reactions see Gross and Hoft679). Amino- and amido-methylation of aromatic carbocyclic and heterocyclic compounds by -halo amines and amides have also been reported.707,722,723... 

Utilization of Methane in the Catalytic Methylation of Aromatics and Coal Liquefaction over Zeolite Catalysts... 

The present world rcscr es of natural gas that contains mainly methane are still underutilized due to high cost of transportation. Considerable interest is therefore presently shown in the conversion of methane to transportable liquids and feedstocks in addition to its previous sole use for heating purposes by combustion. One possible new route for the utilization of methane derived from natural gas or other sources for conversion to more valuable higher hydrocarbons is the methylation of aromatic hydrocarbons. This chapter provides a general overview of the work that has been done so far on the use of methane for catalytic methylation of model aromatic compounds and for direct liquefaction of coal for the production of liquid hydrocarbons. The review is especially focused on the use of both acidic and basic zeolites in acid-catalyzed and base-catalyzed methylation reactions, respectively. The base-catalyzed methylation reaction covered in this discussion is mainly the oxidative methylation of toluene to produce ethylbenzene and styrene. This reaction has been found to occur over basic sites incorporated into zeolites by chemical modification or by changing the electronegative charge of the zeolite framework. 

Direct Catalytic Methylation of Aromatics with Methane... 

This paper provides a general overview of the recent work that has been done on the use of methane for catalytic methylation of aromatic compounds and for direct liquefaction of coal for the production of liquid hydrocarbons. Such methylation reactions constitute a new route for the utilization of methane derived from natural gas or other sources for conversion to more valuable hydrocarbons. The review focuses on the use of both acidic and basic zeolites in acid-catalyzed and base-catalyzed reactions, respectively. 

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