Esterification diazomethane method

For the esterification of difficultly accessible acids the elegant diazomethane method (p. 273) is most appropriate it usually proceeds very smoothly. 

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

Vorbeck et al. [173] compared the yields of the esterification reaction of organic acids with diazomethane and two reaction mixtures methanol—hydrochloric acid and methanol—boron trifluoride. The best results were achieved when the diazomethane method was used. 

The only other esterification method which rivals the present procedure in convenience, mildness of conditions, selectivity, and yield js the preparation of methyl esters wdth diazomethane [Methane, diazo-] 10 Esterification with trialkyloxonium salts, however, allows... 

As sulfonic acid cannot be vaporized, its determination by the direct gas chromatography (GC) method is not possible. To enable determination by GC, the reactivity of the S03H group is used the esterification of the S03H group with diazomethane via acid chloride is one way to transfer the sulfonic acid to volatile compounds. By conversion of the sulfonic acid with phosphoric acid at 200-210°C, the S03H group is cleaved and the hydrocarbons are obtained [184-186]. 

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. 

Two methods for converting carboxylic acids to esters fall into the mechanistic group under discussion the reaction of carboxylic acids with diazo compounds, especially diazomethane and alkylation of carboxylate anions by halides or sulfonates. The esterification of carboxylic acids with diazomethane is a very fast and clean reaction.41 The alkylating agent is the extremely reactive methyldiazonium ion, which is generated by proton transfer from the carboxylic acid to diazomethane. The collapse of the resulting ion pair with loss of nitrogen is extremely rapid. 

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. 

Esterification of 104 with diazomethane gives 70 in quantitative yield.80 The low yield previously obtained29,31 may have been due to impure starting-material. Compound 70 is crystalline,29,31 and may be used for the preparation of the ketopyranosyl chloride 112 by the method that Kuhn and coworkers109 reported for the synthesis of the analogous halide of NeuAc. In this procedure, compound 70 is dissolved in acetyl chloride, and the solution is cooled to —70°, saturated with hydrogen chloride gas, and allowed to warm to room temperature in a sealed container. The preparation of 112 in this way was first reported by Bhattachaijee and coworkers,101 and, shortly thereafter, by Unger and coworkers.128 The Canadian authors synthesized the... 

A similar method of hydrolysis was described for poly( vinyl alcohol) used as a template. In this case, T was -CH2-CH- and, after hydrolysis, poly(vinyl alcohol) and polyacrylic or polymethacrylic acid were obtained. The hydrolyzed product gives the color reaction with I2 in the presence of H3BO3 - specific to poly(vinyl alcohol). The second product of hydrolysis, after esterification by diazomethane, was identified as polyfmethyl methacrylate) by NMR and IR spectrometry. Hydrolysis was also applied in the case of ladder-type polymers obtained by polymerization of mutliallyl monomers. The polymerization should result in polymer consisting, at least partly, ladder-type blocks ... 

Monoesterification of dicarboxylic acids. Chemiabsorption of a dicarboxylic acid on alumina or silica can be used to effect selective esterification of one acid group with diazomethane. The method was demonstrated by conversion of terephthalic acid, C6H4-l,4-(COOH)2) into the monomethyl ester in quantitative yield. 

The 1,3 dipole diazomethane is a mild reagent to furnish methyl esters (see Chapter 13), but it has some disadvantages, too it is volatile, toxic and furthermore explosive. For this reason it has to be prepared by reaction of KOH with 7V-methyl-7V-nitroso-/ ara-toluenesulfon-amide (carcinogenic ) or in situ.11 Another simple method to protect the COOH functionality of the neuraminic acid is the esterification with methanol as solvent and reactand under H+ catalysis e. g. ion exchanger. 

The methyl a-glycoside methyl ester of this sugar was prepared by the methylation of methyl (methyl 2,5-di-0-methyl-a-D-glucosid)uronate with dimethyl sulfate and sodium hydroxide, followed by esterification with diazomethane. The constitution follows from the method of synthesis. 

Esterification with diazomethane [590—593] is another possible derivatization procedure for substituted phosphates. However, it has been used for only a limited number of substrates. Some workers [592] obtained very good quantitative yields with it in comparison with other methods. 

Analysis of Chloronhenoxv Herbicides. Many important target environmental pollutants can only be detected via conventional GC methods by first converting them to derivatives that are less polar and more volatile, e.g., the chlorophenoxy herbicides. A standard EPA method (SW-846 8150) specifies soil extraction and alkaline hydrolysis of any esters present followed by (re) esterification via diazomethane and detection and confirmation by GC/MS. The methylation step is required because the free carboxylic acids will not pass through conventional GC analytical columns. Reversed phase chromatography functions equally well to resolve free carboxylic acids or the corresponding esters and thus can eliminate the diazomethylation step. An interlaboratory check sample provided by the EPA of soil spiked with the chlorophenoxy acid herbicides Silvex and 2,4-D was obtained by our laboratory to demonstrate that LC/MS can offer a simpler and effective method for these compounds. 

Settimj et al.6 described a gas chromatographic method for the estimation of reserpine and rescinnamine involving alkaline hydrolysis of the alkaloids and subsequent esterification of the acids formed by means of diazomethane. Reserpine gave quantitatively 3,4,5-trimethoxyben-zoic acid methylester, whereas the trars-3,4,5-trimethoxycinnamic acid methylester, which should be expected for rescinnamine, was partly isomerized to the cis-trimethoxycinnamic acid methylester or formed an adduct with a molecule of methanol, yielding 3-methoxy-3-(3,4,5-tr1-methoxyphenyl) propionic acid methylester. 

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