Batchwise methylations

Batchwise methylation by DMC requires no PT>catalysts, and the base can be employed in a catalytic amount (0.05 mol equivalents with respect to the substrate). Other alkaline carbonates are also effective catalytic bases, their efficacy being clearly related to their solubility in DMC. For exanq>le, in using bases from Na2C03 to CS2CO3, the solubility in DMC increases from 0.26 to 0.6 g/L likewise, the reaction time for the methylation of phenylacetonitiile by DMC at 180°C decreases from 8.75 to 5.75 h, respectively (20). The most active base is that in which cation-anion interactions are the poorest and, therefore, a "naked anion may form (21). However, selectivity always remains high. Stronger bases such as phosphazene derivatives (22), also promote the reaction but selectivity is lower (Table II). 

The alcoholysis reaction may be carried out either batchwise or continuously by treating the triglyceride with an excess of methanol for 30—60 min in a well-agitated reactor. The reactants are then allowed to settle and the glycerol [56-81-5] is recovered in methanol solution in the lower layer. The sodium methoxide and excess methanol are removed from the methyl ester, which then maybe fed directiy to the hydrogenolysis process. Alternatively, the ester may be distilled to remove unreacted material and other impurities, or fractionated into different cuts. Practionation of either the methyl ester or of the product following hydrogenolysis provides alcohols that have narrow carbon-chain distributions. 

Batchwise operated multipurpose plants are per defmitionem the vehicle for the production of fine chemicals. There are, however, a few examples of fine chemicals produced ia dedicated, coatiauous plants. These can be advantageous if the raw materials or products are gaseous or Hquid rather than soHd, if the reaction is strongly exothermic or endothermic or otherwise hazardous, and if the requirement for the product warrants a continued capacity utilization. Some fine chemicals produced by continuous processes are methyl 4-chloroacetoacetate [32807-28-6] C H CIO [32807-28-6], and malononittile [109-77-3] C2H2N2, made by Lonza dimethyl acetonedicarboxylate [1830-54-2] made by Ube and L-2-chloropropionic acid [107-94-8] C2H C102, produced by Zeneca. 

Also, in the case of DMC, reaction conditions apparently are not green the methylating ability of DMC can be exploited at a temperature >160°C (above the boiling point of DMC itself 90°C), which implies an autogenic pressure (> 3 bar) for batchwise processes. Such conditions are not prohibitive, however, especially according to the industrial practice, where pressures up to 20-30 bar and temperatures up to 250°C are not a concern. 

As a rule, the reaction is carried out at from -10° C to +62° ( preferably at from 10° to 50° C, under atmospheric or superatmospher-pressure, continuously or batchwise. The reactioti may, e.g., be carrio out as follows. The methyl ketone is introduced into a mixture " hypohalite, catalyst and water and the batch is kept at the reaction ten perature for from 1 to 1,000 minutes. The end product is now isolated f , conventional methods, e.g. by adding aqueous sodium bisulfite solution... 

Dimethylcarbonate (DMC) is an environmentally friendly substitute for dimethylsulfate (DMS) and methyl halides in methylation reactions. It is also a very selective reagent. The reactions of DMC with methylene-active compounds produce monomethylated derivatives with a selectivity not previously observed. The batchwise monomethylation of arylacetonitriles, arylacetoesters, aroxyacetonitriles, methyl aroxyacetates, ben larylsulfones and alkylarylsulfones with DMC achieve >99% selectivity at 180-220°C in the presence of K2CO3. Mono- -methylation of primary aromatic amines at 120-150 °C in the presence of Y- and X-type zeolites, achieved selectivities up to 97%. At high temperature (200°C) and in the presence of potassium carbonate as the catalyst, DMC splits benzylic and aliphatic ketones into two methyl esters in contrast, DMC converts ketone oximes bearing a methylene group to 3-methyl-4,5-disubstituted-4-oxazolin-2-ones. Dibenzylcarbonate... 

In particular, the methylation reactions by DMC can be run in the presence of weak bases (e,g. alkaline carbonates). However, since high reaction temperatures are necessary to exploit the methylating properties of DMC, new methodologies have been developed to perform the reaction under both continuous-flow (c.-f.) and batchwise conditions. 

Two polymeric supports have classically been nsed in batchwise SPPS. The first is polystyrene polymer cross-linked with 1% of 1,3-divinyl benzene. A typical dry bead has a diameter of 50 fj,m that swells five- to sixfold in DCM or DMF (144). The second was developed on the basis of the idea that the polymeric backbone should be of similar chemical composition, a polyamide, as the peptide backbone (11). Thns, copol5nnerized dimethylacrylamide, ATjAT -bisacryloylethylenediamine, and acryloylsarcosine methyl ester, or polyamide resin, was developed (146). Polyamide snpports are commercially known as Pepsyn resin. Many other supports have been developed that are compatible with batchwise SPPS and are summarized in the more comprehensive reviews (7,10-20,109). 

The exothermic reaction is carried mostly out batchwise at elevated temperature ( 150 °C) and 5-10 bar (0.5-1 MPa) pressure with alkaline (sodium or potassium hydroxide or methylate) or acidic catalysts ... 

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