Extractive esterification

Capturing desired products from aqueous reaction mixtures (in a form useful for further synthesis steps) using monomeric agents is well known. We successfully applied such a technology to the extractive esterification of cephalosporin derivatives from a filtered cephalosporin fermentation broth65 and a solution of a 3-... 

We envisaged that the aforementioned sulfonated polymer-DDM may prove useful for the extractive esterification of those water-soluble acidic materials from aqueous solution that would not dissolve in methylene chloride for reaction with swollen polymer-DDM beads. Such compounds could include enzymes with some acidic character, but the risk is that desired enzyme activity may be lost by reaction with the DDM group. 

Product Extraction. The little used but very efficient method of using diphenyldia-zomethane for the extractive esterification of acidic materials from aqueous solution proved to be very effective [see footnote 93(c)]. 

In order to perform quantitation, the four steps listed above are preceeded by the addition of 3H2A9-THC to the plasma. This is achieved in order to allow accurate determination of the quantity of A9-THC initially present, by correcting the non negligible losses observed during extraction, esterification and purification as shown schematically in Figure 2. 

The extractive esterification method mentioned earlier allows the desacetyl cephalosporin C derivative to be reacylated without lactone formation since the C-4 carboxyl ester does not readily participate in the lactonization reaction. For the same reason, it is possible to form a 3-halomethyl derivative of cephalosporin C from desacetyl cephalosporin ester, with the resulting halide readily displaced by the desired C-3 substituent. These reactions are shown in Figure 16. (41)... 

Each step of an isolation procedure requires confirmatory thin layer chromatographic (TLC) analysis to determine if isolation artifacts are produced (Fig. 3). Unwanted reactions include enzymatic and chemical hydrolysis during water extraction, esterification or lactonization of acidic saponins when using alcohol solvents, hydrolysis or transesterification of labile ester functions, and cyclopropane cleavage during acidic hydrolysis [10]. 

It is important to emphasize that specific difficulties arise when extracting antioxidants and preservatives from fatty foods. Most of the permitted antioxidants and preservatives are fat soluble, so it may first be necessary to extract the fat from the food and then extract the antioxidants from the fat. As a result, the determination of these additives implies the removal of triglycerides the techniques most frequently used to remove triglycerides are saponification of the extracts, esterification of the extracts in the presence of lipase, and the separation of the analytes by preparative liquid chromatography. 

Herbicides may be determined by specific extraction, esterification, and gas chromatographic conditions. Aqueous samples are extracted with diethyl ether and then esterified with either diazomethane or pentafluorobenzyl bromide. The derivatives are determined by GC with an electron capture detector. Compound identifications should be supported by GC-MS for the qualitative confirmation. Alkaline hydrolysis and subsequent solvent wash removes many chlorinated hydrocarbons and phthalates that might otherwise interfere with the electron capture analysis. 

S. is part (25%) of the nonsaponificable portion of soybean oil and is obtained from the deodorizer distillates (->soybean), a by-product of soybean oil refining (- phytosterols), together with the tocopherols. There are several processes to separate the tocopher-ols from the sterols by extraction, esterification, adsorption, molecular distillation and crystallization. 

The mother liquors from the washings and recrystallisations are saved for the recovery of the 4-nitrophthalic acid. The combined mother liquors ore concentrated to a small bulk and the acid is extracted with ether. Upon esterification by the Fischer - Speier method, the 3-nitro acid forms only the acid ester and may be removed by shaking the product with sodium carbonate solution, whilst the neutral ester of 4-iiitrophthalic acid remains unaffected. Hydrolysis of the neutral ester gives the pure 4-nltrophthalio acid, m.p. 165°. 

The sulfuric acid hydrolysis may be performed as a batch or continuous operation. Acrylonitrile is converted to acrylamide sulfate by treatment with a small excess of 85% sulfuric acid at 80—100°C. A hold-time of about 1 h provides complete conversion of the acrylonitrile. The reaction mixture may be hydrolyzed and the aqueous acryhc acid recovered by extraction and purified as described under the propylene oxidation process prior to esterification. Alternatively, after reaction with excess alcohol, a mixture of acryhc ester and alcohol is distilled and excess alcohol is recovered by aqueous extractive distillation. The ester in both cases is purified by distillation. 

Manufacture. Cyanoacetic acid and cyanoacetates are iadustrially produced by the same route as the malonates starting from a sodium chloroacetate solution via a sodium cyanoacetate solution. Cyanoacetic acid is obtained by acidification of the sodium cyanoacetate solution followed by organic solvent extraction and evaporation. Cyanoacetates are obtained by acidification of the sodium cyanoacetate solution and subsequent esterification with the water formed being distilled off. Other processes reported ia the Hterature iavolve the oxidation of partially oxidized propionittile [107-12-0] (59). Higher esters of cyanoacetic acid are usually made through transesterification of methyl cyanoacetate ia the presence of alumiaiumisopropoxide [555-31-7] as a catalyst (60). 

The methyl a-hydroxyisobutyrate produced is dehydrated to MMA and water in two stages. First, the methyl a-hydroxyisobutyrate is vaporized and passed over a modified zeoHte catalyst at ca 240°C. A second reactor containing phosphoric acid is operated at ca 150°C to promote esterification of any methacrylic acid (MAA) formed in the first reactor (74,75). Methanol is co-fed to improve selectivity in each stage. Conversions of methyl a-hydroxyisobutyrate are greater than 99%, with selectivities to MMA near 96%. The reactor effluent is extracted with water to remove methanol and yield cmde MMA. This process has not yet been used on a commercial scale. 

In typical processes, the gaseous effluent from the second-stage oxidation is cooled and fed to an absorber to isolate the MAA as a 20—40% aqueous solution. The MAA may then be concentrated by extraction into a suitable organic solvent such as butyl acetate, toluene, or dibutyl ketone. Azeotropic dehydration and solvent recovery, followed by fractional distillation, is used to obtain the pure product. Water, solvent, and low boiling by-products are removed in a first-stage column. The column bottoms are then fed to a second column where MAA is taken overhead. Esterification to MMA or other esters is readily achieved using acid catalysis. 

Methyl salicylate is produced synthetically for commercial purposes by the esterification of salicylic acid with methanol or by extraction by steam distillation of wintergreen leaves or sweet birch bark. The source, natural or synthetic, is declared on the label. The methyl salicylate NF must assay not less than 98.0% and not more than 100.5% and be processed by Good Manufacturing Practice described in USP (20). 

Various techniques have been proposed for the recovery of pure succinic acid, including extraction (141—145), selective crystalliza tion (146—151), heating to dehydrate the acid and subsequent recovery of succinic anhydride by distillation (152), esterification foUowed by fractionation of the mixture of the esters (65—69), and separation as urea adduct (118,119). 

Completion of Esterification. Because the esterification of an alcohol and an organic acid involves a reversible equiUbrium, these reactions usually do not go to completion. Conversions approaching 100% can often be achieved by removing one of the products formed, either the ester or the water, provided the esterification reaction is equiUbrium limited and not rate limited. A variety of distillation methods can be appHed to afford ester and water product removal from the esterification reaction (see Distillation). Other methods such as reactive extraction and reverse osmosis can be used to remove the esterification products to maximize the reaction conversion (38). In general, esterifications are divided into three broad classes, depending on the volatility of the esters ... 

Use of Azeotropes to Remove Water. With the aliphatic alcohols and esters of medium volatility, a variety of azeotropes is encountered on distillation (see Distillation, azeotropic and extractive). Removal of these azeotropes from the esterification reaction mixture drives the equihbrium in favor of the ester product (39). 

The following extract is taken from an example in British Patent 770,717 to the Du Pont Company as an illustration of a typical method of esterification ... 

Despite its widespread application [31,32], the kinetic resolution has two major drawbacks (i) the maximum theoretical yield is 50% owing to the consumption of only one enantiomer, (ii) the separation of the product and the remaining starting material may be laborious. The separation is usually carried out by chromatography, which is inefficient on a large scale, and several alternative methods have been developed (Figure 6.2). For example, when a cyclic anhydride is the acyl donor in an esterification reaction, the water-soluble monoester monoacid is separable by extraction with an aqueous alkaline solution [33,34]. Also, fiuorous phase separation techniques have been combined with enzymatic kinetic resolutions [35]. To overcome the 50% yield limitation, one of the enantiomers may, in some cases, be racemized and resubmitted to the resolution procedure. 

The most conspicuous concentrations of calciiun in the cell-walls of the flax hypocotyl were in the epidermal and subepidermal layers, especially at the tricellular junctions (figure 13 D), where these were filled with pectic polymers [67], Open tricellular jimctions with intercellular spaces had smaller areas of calcium accumulation where the walls of each pair of cells diverged. These sites were occupied by relatively linear pectic polymers with a low degree of esterification, which could be visualised with gold-kbeUed endopolygalacturonase [68] and were extractable by chelation of calcium with CDTA. Similar pectic polymers are located in the corresponding sites in other plant tissue, as established by susceptibility to polygalacturonase... 

The dynamic Weiflenberg number of pectin gels is influenced by the raw material used for pectin extraction and by the degree of esterification of the applied pectin. With a decreasing degree of esterification the dynamic WeiBenberg number also decreases. 

Milieu conditions in gastrointestinal tract can influence the pectin structure and properties. Under the acid conditions of the stomach (pH 2-4) extraction of pectin from plant cell walls and hydrolysis of side chains can occur. In small intestine (pH 5-6) -elimination of main chains or de-esterification seems to be possible. In caecum and colon (pH 6-8) a strong fermentation of pectin takes place causing depolymerization to oligomers and leading to formation of short chain fatty acids and gases. The presence of OligoGalA is not yet clarified. 

In a previous publication (1) we reported that the pretreatment of fresh fhiit waste using microwave heating ensured a better extraction of pectin, resulting in an increase in the yield of pectin from 10 to 50 %. It was established that this microwave pretreatment ensured retention of the degree of esterification of the extracted pectin, better expressed in citrus peels... 

The scope of the multi-residue method is extended permanently by testing and then including further active substances that can be determined by GC. Acidic analytes (such as phenoxyacetic acids or RCOOH metabolites) are included into the homogeneous partitioning by acidifying the raw extracts to a pH below the pKs value of the carboxylic acids. To include these analytes in the GC determination scheme they have to be derivatized with diazomethane, diazoethane, trimethylsilyldiazomethane, acidic esterification or benzylation, or by silanizing the COOH moiety. 

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