Phenols esterifications, diazomethane

Another method is based on the same principle,112 in which the [14C]labelled methyl ester of D-galacturonan is prepared by esterification of pectic acid with [,4C]diazomethane. In the course of the enzymic de-esterification, aliquots are removed, and the unreacted substrate is precipitated with acidified ethanol or 1-propanol. After centrifugation, the labelled methanol in the supernatant liquor is determined in a liquid scintillation counter. An advantage of this method lies in the possibility of using, as substrates, short-chain oligo-D-galactosiduronates partially esterified with [14C]methanol. These substrates, beginning with the trisaccharide, are not soluble in 1 4 80% phenol-diethyl ether, which is used for the extraction of enzymically released, labelled methanol. 

The aqueous phase from the previous step, after extracting methyl ethers of phenolics, was acidified to a pH of 1-2 with sulfuric acid, and the free acids were extracted continuously with ether by the procedure previously noted. The ether extract was brought to volume and divided into aliquots for analysis. The methyl esters of the acids were formed by distilling an excess of diazomethane into an ether aliquot containing the free acids plus 10% methanol. When esterification was completed (approximately 20 min.), the ether solution was purged with nitrogen to remove excess diazomethane and was reduced in volume. This solution was analyzed immediately by GLC. 

The asymmetric cyclization of 2[( )-3-pentenyl]phenol (1) performed with (f/3-pinene)palladium acetate (see Section 4.6.2.2.2.) in the presence of copper(II) acetate in methanol under an oxygen atmosphere, gives 3,4-dihydro-2-vinyl-27/-1 -benzopyran (2) in 64% yield and 25% ee87. The enantiomeric excess is determined by H-NMR analysis, in the presence of Eu(tfc)3, of methyl 3,4-dihydro-2//-1 -benzopyran-2-carboxylate, derived from 2 by oxidation with potassium permanganate, followed by esterification with diazomethane. 

The reactions illustrated in equations (62-64) are each catalyzed by rhodium acetate. Diazo compounds, especially diazoalkanes, can also react by a simple ionic mechanism. The esterification of a carboxylic acid with diazomethane is a familiar example. The ionic pathway is especially likely when the intermediate carbocation would be stabilized. Thus, diazine (158) couples smoothly with phenols, presumably by thermal rearrangement to the corresponding diazo sugar, followed by acid-catalyzed N2 loss... 

Esterification of acids. The widely used reaction of diazomethane with carboxylic acids was discovered by von Pechmann, who noted also the effectiveness of the reagent for the melhylation of phenols, mineral acids, hydrogen cyanide, and phthalimide. The reagent also methylates tropolones, alkylsulfonic acids, " and arylsulfonic acids. " The fact that neutral alcohols do not react with diuzomethane suggests that an acidic substance supplies a proton required for catalysis of the esteriflcatlon. 

Fischer esterification works well to prepare simple carboxylic esters. The diazomethane method would also react with the phenol, making the phenyl ether. 

In the case where liquid chromatography is not available, acidic herbicides need to be derivatized because they can dissociate in water and are not usually volatile to be analyzed by gas chromatography. The basic methods used for chlorophenoxy acid herbicides are esterification, silylation, and alkylation, as described in a recent exhaustive review.The derivatization step is performed after preconcentration and cleanup. The step consists of the formation of esters and ethers from the carboxyl and phenol groups of the acidic herbicides. A lot of reagents and chemical mechanisms can be used to perform derivatization reactions. The most employed derivatization reagents are diazomethane, methyliodide, trimethylsulfonium (or anilinium) hydroxide, bis (trimethylsilyl) trifluoroacetamide (BSTFA), pentafluorobenzyl bromide, and anhydride acetate. It should be noted that explosive and hazardous diazomethane was replaced by safer agents. Authors also underline that surface water generally contains humic substances, which can interfere with the derivatization reaction. ... 

Diazomethane is not ideal for esterification of phenolic acids because the phenolic hydroxyl groups are also methylated, albeit at a slower rate, which may lead to mixtures of partially methylated products. However, esterification can usually be achieved without O-methyl ether formation by cooling the reaction mixture to below 0°C [54,55]. 

Diazomethane is a valuable reagent for one-carbon extension of acyl halides and anhydrides, as well as for ring expansion reactions of cyclic ketones " . It is also widely used in small-scale organic synthesis for the esterification of carboxylic acids and the etherification of phenols, enols and alcohols " . In these reactions, however, CH2N2 installs the label in positions that are potentially metabolically labile and usually unsuitable for use in metabolism smdies. For in vitro studies where metabolism is not an issue, tritiated diazomethane is usually preferred because of its higher specific activity. 

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