Esters methyl ester formation with diazomethane

As outlined above (Sections 2 and 3), methyl ester formation with diazomethane is still often employed for analysis of these labile compounds, including thromboxanes and leukotrienes. For high sensitivity analyses by negative ion electron capture GC-MS, pentafluoro-benzyl esters have proved to be very useful [168-170], with low pg sensitivities being obtained. For 6-keto-... 

The reaction of diazomethane with a Ccirboxylic acid is an efficient way to produce a methyl ester however, the procedure is dangerous. Figure 12-25 illustrates the formation of a methyl ester from benzoic acid and diazomethane. 

Gas chromatographic methods have been successfully used for the determination of penicillin molecules bearing neutral side-chains in milk and tissues (95, 97), but cannot be used for amphoteric -lactams. Gas chromatography of penicillin residues is further complicated by the necessity for derivatization with diazomethane. This derivatization step is particularly important because it not only leads to formation of the volatile penicillin methyl esters but also improves their chromatographic properties (thermal stability and decreased polarity). Using a fused-silica capillary column in connection with a thermionic nitrogen-selective detector, excellent separation and sensitivity figures were obtained. 

Azotomycin is anticancer antibiotic produced by Streptomyces ambofaciens. Total sythesis of it from y-benzyl-N-tert-butyloxycarbonyl-L-glutamic acid (y-OBzi-N-Boc-L-Glu) has been accomplished in nine steps. The mixed carbonic anhydride method was chosen for peptide bond formation. Commerically available y-OBzi-N-Boc-L-Glu was esterified with ethereal diazomethane, deprotected with trifluoroacetic acid-methylene chloride (1 1), and converted to hydrochloride y-benzyl-L-glutamic acid a-methyl ester (y-OBzi-L-Glu-a-OMe HCI) by treatment with dry hydrogen chloride in ethyl ether, MP 129°-135°C (dec.) [a]D25= + 13.3° (CHCI3). 

This acid is a mixture of cis- and trans-isomers. By esterifying the acid to the methyl ester with diazomethane a two compound mixture is formed, whereas ester formation under acidic conditions (MeOH/HCl) gives a single compound. This single compound 115 is thought to be the trans-isomer, because isomerization of the mixture of esters obtained by reaction with diazomethane to a single compound is apparently possible by an esterification relactonization mechanism by treating the mixture with acid in methanol. These results are consistent with the formulation of the ester 115 as the trans-isomer. 

Polyitaconic add is converted completdy to the methyl ester with diazomethane (7), while Fisher esterification results in partial esterification of both itaconic acid homo- and copolymers (6). DMI homopolymers and its copolymer with butadiene can be reduced with lithium aluminum hydride to the polymeric alcohols, which on the basis of solubility, may under some conditions be partially cross-linked by intermolecular ester formation (6). Hydrazine converts polydimethyl itaccmate to the polymeric dihydrazide which is water-soluble and exhibits reducing properties. The hydrazide can be treated with aldehyde or ketones to form polymeric hydrazones (45). A cross-linked polymer of bi chloroethyl ita-conate) on treatment with trietlylamine, has been converted by partial quatemization to an anion exchange resin (46). 

By the employment of other bromides O-desmethylmycophenolic acid was obtained. Thus, the C7 bromoester methyl 6-bromo-4-methylhex-4-enoate, BrCH2CH=C(Me)CH2CH2C02Me, was prepared from tritylgeraniol which was first converted in several steps to the terminal diol, Malaprade oxidation of which furnished 4-methy-6-trityloxylhex-4-enal. Mild oxidation to, the corresponding acid with silver oxide, formation of the methyl ester with diazomethane and derivation of the required allylic bromide by treatment of the alcohol, liberated from the trityl derivative, with carbon tetrabromide containing triphenylphosphine completed the synthesis. 

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