Benzene methylation reactions

The pyrrolidine enamines of /l -3.]cetosteroids (111), on alkylation with methyl iodide, gave mainly the N-alkylated product (5,55) in nonpolar solvents such as benzene. The reaction in more polar solvents gave the 4-methylated product (5.S). The reaction of (111) with perchloryl fluoride involves attack at the C-4 atom to give, after acid hydrolysis, either 4-fluoro-zJ -3-ketone (119) or 4,4-difluoro-zJ -3-ketone 120), depending on the reaction conditions (59). 

In preparation of di-//-mcthylcncbis(incthyl-pcntamcthylcyclopcntadicnvl)dirhod-ium complexes by aerobic oxidation of a solution of the halocomplex and methyl-lithium or trimethylaluminium in ether-benzene, the reaction mixture occasionally ignited and burned violently. Full precautions and a working scale below 1 mmol are recommended. 

However, a reinvestigation of the deuteration and methylation reaction using (tert-butyl-sulfinylmethyl)benzene gave a different result49,50. In this case, and in contrast with (methyl-sulfinylmethyl)benzene, methylation and deuteration occurred with the same stereochemistry, both with retention of configuration. 

To a dry flask containing 8 gm (0.329 atom) of magnesium turnings, 150 ml of dry ether, and a crystal of iodine is added dropwise a solution of 50 gm (0.212 mole) of 2-bromo-6-methoxynaphthalene in 150 ml of dry benzene. The reaction mixture is refluxed on a water bath and 2 ml of ethyl bromide is added every hour for 5 hr. After this time, most of the magnesium has reacted, the flask is cooled, and a solution of 37 gm (0.328 mole) of 1-methyl-2-piperidone in 100 ml of ether is added dropwise. After the addition, the reaction mixture is refluxed for 3 hr, cooled, decomposed with dilute hydrochloric acid, the solid hydrochloride of the product, after filtration, reacts with warm aqueous sodium hydroxide, is extracted with ether, dried, and distilled to afford 11.0 gm (20.6%), b.p. 175°C (2.0 mm). 

The first synthesis of a derivative of 2,8-phenanthroline was reported by Merz, Weidlich, and Fink13 in 1964. They prepared 5,6-dimethoxy-2,8-phenanthroline (34) (isolated as the dipicrate) in very low yield by conducting a double Pomeranz-Fritsch isoquinoline synthesis on 4,5-dimethoxyisophthalaldehyde. The parent compound was prepared 2 years later12 in 25-35% yield, along with 1,9-phenanthroline (4%), by the photocyclization of trans-1 (3-pyridyl)-2-(4-pyridyl)ethylene in benzene. This reaction was used by Hiinig and his colleagues15 to prepare an N,N -dimethyl diquaternary salt of 2,8-phenanthroline by methylating the crude product from the irradiation reaction. 

In a parallel experiment, ethyldiisopropylamine (9.82 g, purified as in Note 16) was mixed with a solution of 20 g of methyl 3,(3 -dibromoisobutyrate in 100 mL of dry benzene. The reaction mixture was stored at room temperature for 10 hr and gently refluxed for 1 hr under nitrogen in the dark. After work-up and distillation the yield of the product was 80%. 

In this reaction, benzene methyl ketone (BMK) is reacted with formamide, followed by reaction of the products with hydrogen peroxide and HCl in methanol, to form amphetamine. There are a number of variations on the basic route. The impurities which arise include, as examples, methylphenylpyrimidines (4-methyl-5-phenylpyrimidine) (8), benzylpyrimidines (4-benzylpyrimidine) (9), iV-formylamphetamine (10), Al,Al-di(j6-phenylisopropyl)amines (Al,Al-di(/i-phenylisopropyl)amine) (11) and dimethyldiphenylpyrimidines (2,4-dimethyl-3,5-diphenylpyridine) (12) (see structures in Figure 2.8). 

N-Methylacetanilide is obtained in 96% yield by the action of methyl iodide or dimethyl sulfate on the sodium salt of acetanilide. The last compound is prepared from acetanilide and sodium wire in hot benzene. The reaction has been extended to other aliphatic and aromatic N-sub-stituted amides. Sodium hydride serves to convert the amide to its salt, and a variety of simple halides have been successfully employed as alkylating agents, ... 

Valentine et al. applied, in principle, the method of Midha and Charette for a quantitative assay of quinidines (quinidine and hydroquinidine) in plasma, using methylene chloride instead of benzene for the extraction of a small volume of plasma after basification. To the extract was added the internal standard, cinchonine evaporation to dryness and reconstituting in a methanolic solution of trimethylanilinium hydroxide followed. An aliquot of this solution was analyzed by GLC via on-column methylation reaction. Evaluation of the method over the range 0.5 - 10 ug/ml in human plasma gave a precision and accuracy overall of 4.5 %... 

Alkyl benzenes (methyl benzene, ethyl benzene, etc) react with potassium manganate (VII) to form benzoic acid. All alkyl benzenes give the same product, because all but one alkyl carbon is lost. No acidification is needed. The reaction is refluxed and generates KOH. The benzoic acid is worked up by adding a proton source (such as HCl). 

The production of para-xylene is of interest to the petrochemical industry because of its use as monomer in polyester production. In addition to Cg aromatic isomerization, there are a number of important routes to para-xylene including the alkylation of toluene with methanol and the disproportionation of toluene. The catalytic properties of the SAPO molecular sieves for toluene methylation reactions have been described(11). While both large and medium pore SAPO s were active for the alkylation reaction, the medium pore materials were distinguished by remarkably high selectivity for methylation reactions, with disproportionation of the toluene feed representing less than 2% of the total conversion. By comparison, large pore SAPO-5 had nearly 60% disproportionation selectivity and the zeolite reference LZ-105 had nearly 80% disproportionation selectivity. The very low disproportionation activity of the medium pore SAPO s, attributed to their mild acid character, resulted in reduced losses of toluene to benzene and increased xylene yields relative to LZ-105 and SAPO-5. 

Di-/z-chloro-bis[(1 -ethyl-2-methyl-Ji-allyl) palladium], like most alkyl- and aryl-substituted 7r-allylchloropalladium dimers, is a yellow, crystalline, air-stable solid, which is soluble in organic solvents of medium polarity (acetone, dichloromethane, chloroform, benzene). The reactions of these compounds have been described in several reviews.17... 

A double alkylation was effected in the reaction of 4-chlorophenol at 100°C for 10 hours with 1H-1,2,4-triazole and dichloromethyl tert-butylketone in benzene/methyl iso-propylketone(1 1)togive1-(4-chlorophenoxy)-3,3-dimethyl-1-(1,2,4-triazin-1-yl)butan-2-one ( Tridimefon ) indicated in 97% yield (ref.36). 

Oxidative coupling of other arenes (e.g., toluene, benzene, methyl benzoate) has also been investigated. The activity of Pd catalysts is enhanced by various additives, including P-diketones [36], Zr [37], Mo02(acac)2 [38], Zr /Co /Mn [39], HPMoV-type heteropolyacids (HPA) [40], and triflic acid [41]. Acetic acid is a common solvent for these reactions. It was disclosed recently that supported nanoparticle Au catalysts can be applied as catalysts in reactions of this type [42]. 

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