Diazomethane, selective methylation

It is known that methylation with diazomethane selectively methylates FFAs in the presence of FA esters. Caution is required, as diazomethane is a dangerous substance. Under inappropriate conditions, derivatization with diazomethane leads to the formation of artifacts. Functional groups such as phenol, enol, and carbonyl, or olefinic bonds can be affected. The less-dangerous methylation agents such as trimethylsilyldiazomethane (TMS-CHN2) and lit-hiated TMS-CHN2 have been suggested to replace diazomethane. Benzyl esters can be produced by the use of phenyldiazomethane. 

Alkylation. Figure 15 illustrates that individual hydroxyl groups of a phenolic p-O-4 dimer may be selectively methylated with proper agents. Methyla-tion with diazomethane is largely limited to the phenolic hydroxyl group plus nonenolizable carbonyl units [332,358]. The benzylic hydroxyl group can be specifically methylated with methanolic hydrochloric acid [359]. All the phenolic and aliphatic hydroxyl groups can be methylated with dimethyl sulfate in alkali [332]. 

Selective methylation of a.,a a."-trihydroxyanthraquinones. Quinones of this type (e.g. 1) are mono-methylated by reaction with excess diazomethane in CH2CI2. This reaction can be used to convert carminomycinone into daunomycinone (3) in 45% yield. ... 

At this juncture, a series of investigations139) concerning the relative reactivities of the phenolic functions were undertaken in order to form the basis for the regio-selective generation of the 4-hydroxy-6-methoxy system. The information obtained provided the following facts (a) selective methylation (diazomethane) of (9J), gave the 4-methoxy ether (96) and, (b) selective deprotection of the dibenzyl ether (97)... 

Thus, the acidity oi a lactam is evidently not a reliable quantity for predicting the course of the methylation. The acidity gives information only as to the reaction velocity. In this connection the reaction course of isomethylreductone (6) is illuminating, " With diazomethane in ether containing 1 mole of water, the enolraethyl ether (7) is formed. However, if water is present only in traces, then the alcoholic hydroxyl group is selectively attacked to give 8. 

The latter approach is used in the enantioselective determination of a Phase I metabolite of the antihistaminic drug, terfenadine. Terfenadine is metabolized to several Phase I compounds (Fig. 7-13), among which the carboxylic acid MDL 16.455 is an active metabolite for which plasma concentrations must often be determined. Although terfenadine can be separated directly on Chiralpak AD - an amy-lose-based CSP - the adsorption of the metabolite MDL 16.455 is too high to permit adequate resolution. By derivatizing the plasma sample with diazomethane, the carboxylic acid is converted selectively to the methyl ester, which can be separated in the presence of all other plasma compounds on the above-mentioned CSP Chiralpak AD [24] (Fig. 7-14). Recently, MDL 16.455 has been introduced as a new antihistaminic drug, fexofenadine. 

The monoacetate 9a (R1 = Ac) and the diacetate 10a (R1 = R2 = Ac) are obtained by treatment of 8 with acetic anhydride in anhydrous pyridine at room temperature 4 the oxo group in position 5 of 8 is more reactive towards acetylation. Similarly, the S,S-dioxidc of 8 can be converted to the bisacetylated S,5-dioxide of 10a in 78 % yield.74 Methylation of 8 with diazomethane gives 9c (65 % yield), along with 14 % of the 3-methoxy compound 11. Other alkylation agents, such as dimethyl sulfate in the presence of potassium carbonate, selectively give 9c, albeit in lower (30 %) yield.90 The dimethyl enol ether 10c (R1 = R2 = Me) is obtained by a subsequent methylation of 9c (R1 = Me) with dimethyl sulfate and potassium teri-butoxide.90... 

Reaction of 1,4-diazocinediones with methylating agents leads to different products depending on the conditions. With dimethyl sulfate, the annulated derivative 6 gives JV-methylation selectively 7 however, on reaction with diazomethane, a mixture of the O- and iV-methylated products is obtained.9... 

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... 

Lord and Pawliszyn" developed a related technique called in-tube SPME in which analytes partition into a polymer coated on the inside of a fused-silica capillary. In automated SPME/HPLC the sample is injected directly into the SPME tube and the analyte is selectively eluted with either the mobile phase or a desorption solution of choice. A mixture of six phenylurea pesticides and eight carbamate pesticides was analyzed using this technique. Lee etal. utilized a novel technique of diazomethane gas-phase methylation post-SPE for the determination of acidic herbicides in water, and Nilsson et al. used SPME post-derivatization to extract benzyl ester herbicides. The successful analysis of volatile analytes indicates a potential for the analysis of fumigant pesticides such as formaldehyde, methyl bromide and phosphine. 

A series of reactions with gases have been selected for the rapid quantification of many of the major products from the oxidation of polyolefins. Infrared spectroscopy is used to measure absorptions after gas treatments. The gases used and the groups quantified include phosgene to convert alcohols and hydroperoxides to chloroformates, diazomethane to convert acids and peracids to their respective methyl esters, sulfur tetrafluoride to convert acids to acid fluorides and nitric oxide to convert alcohols and hydroperoxides to nitrites and nitrates respectively. 

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