Esters diazomethane

However, in the case of a-substituted unsaturated esters (4), as for example methacrylic or tiglic acid esters, diazomethane addition results in the formation of stable A pyrazolines (5). The latter products require halogen acids for conversion to the isomeric nonconjugated A -pyrazolines (6). 

Total fatty acids were liberated by subjecting Salmonella minnesota Re lipopolysaccharide (or free lipid A) to acidic (4 N HC1, 5 h, 100°C) followed by alkaline (1 N NaOH, 1 h, 100°C) hydrolysis. After extraction (chloroform), the free fatty acids were converted into their methyl esters (diazomethane) and analysed by combined gas-liquid chromatography/mass spectrometry. Alternatively, the fatty acids of lipid A are transesterified by treatment of lipopolysaccharide with methanolic HC1 (2 N HC1 in water-free CHaOH, 18 h, 85°C). By these procedures the following fatty acids were identified (in approximate amounts relative to 2 moles glucosamine) dodecanoic (12 0, 1.1 mole), tetradecanoic (14 0, 0.8 mole), hexadecanoic (16 0, 0.9 mole), 2-hydroxytetradecanoic (2-OH-l4 0, 0.1 mole), and 3-hydroxytetradecanoic acid (3-OH-14 0, 4 moles). In total, therefore, approximately 7 moles of fatty acids are present per mole of lipid A backbone. The stereochemistry of the hydroxylated fatty acids was determined by gas-liquid chromatography of their diastereomeric methoxyacyl-L-phenylethylamide derivatives (24). It was found that 2-hydroxyte-tradecanoic acid possesses the-Ts), and the predominating 3-hydroxytetradecanoic acid the (R) configuration. 

Sulindac has been chromatographed as the methyl ester (diazomethane) on a 6 x 10.25" 1% SE-30 on Supelcon 80/100 column under isothermal at 262°C with nitrogen as a carrier gas at 100 ml/min. Detection was with electron capture and sample sizes ranges from v50 to 100 ng. The retention time of sulindac was approximately 7 minutes. The sulfide and sulfone analogs have retention times of 1.5 and 5 mi-tion ... 

Reaction of the acid with diazomethane (CH N ) gives methyl esters. Diazomethane is a 1,3-dipolar molecule, the structure of which can be written in a number of resonance forms (Scheme 3.57a). The reaction with a carboxylic acid is accompanied by the loss of nitrogen gas (Scheme 3.57b). 

Methyl esters are the most commonly used derivatives of the carboxylic groups. There are several methods for the preparation of methyl esters diazomethane, methanolic solution of boron trifluoride, pyrolysis of tetramethylammonium salts, methylation with 2,2-dimethoxypropane, etc. 

Bromoadamantanc-l-carboxylic acid [21816-08-0] M 259.1, m 145-146 , 146.5 , 147-150 , pK 6.28 (50% aqueous EtOH). Purify the acid by recrystallising it from cyclohexane and/or subliming at 130°/10rmn. It can be converted to the methyl ester (diazomethane) with m 32° (fiom petroleum ether at -10°). [Stetter Mayer Chem Ber 95 667 1962, Stetter WuMf Chem Ber 93 1366 1960, Bayal Lantvoev J Org Chem USSR (Engl Trans) 9 291 7975 ]... 

N-Benzyloxyamino acids have also been esterified (203) to give O-protected substrates (275-277) for the synthesis of N-hydroxypeptides (Scheme 56). To obtain methyl (275), tert-hutyl (276) and benzyl (277) esters diazomethane, tert-huiy acetate with perchloric acid and benzyl chloride with acetoacetate were used, respectively. N-Isopropoxyamino acid esters (291) have also been prepared (203). 

Fig. 7.6 Chromatogram of organic acids extracted from deproteinized whole blood using diethyl ether, and separated as their methyl esters (diazomethane) and oxo acid methoximes on a glass column packed with 3 per cent Carbowax 20M plus 5 per cent silicone fluid XF-1150 on Chromosorb W (AWTMCS, 100-120 mesh) using temperature programming from 75°C to 180°C at 4°C min" Peak identifications are 1, lactate 2, pyruvate 3, acetoacetate (peak 1) plus oxalate 4, acetoacetate (peak 2) 5, 3-hydroxybutyrate 6, ethylmalonate (internal standard). (Redrawn with modifications from Hagenfeldt, 1968)...

Some straightforward, efficient cyclopentanellation procedures were developed recently. Addition of a malonic ester anion to a cyclopropane-1,1-dicarboxylic ester followed by a Dieckmann condensation (S. Danishefsky, 1974) or addition of iJ-ketoester anions to a (l-phenylthiocyclopropyl)phosphonium cation followed by intramolecular Wittig reaction (J.P, Marino. 1975) produced cyclopentanones. Another procedure starts with a (2 + 21-cycloaddition of dichloroketene to alkenes followed by regioselective ring expansion with diazomethane. The resulting 2,2-dichlorocyclopentanones can be converted to a large variety of cyclopentane derivatives (A.E. Greene. 1979 J.-P. Deprds, 1980). 

Diazomethane alkylation of A-4-thiazoline-2-ones (36, 214) or the Williamson reaction of 2-halogenothiazoles (6. 287-300) provide good yields of 2-alkoxythiazole otherwise obtained by reaction between O-esters of monothiocarbamic acid with a-halocarbonyl compounds (see Chapter II). 

These methods were not applicable to all acids, and various alternative routes were investigated. The conversion of an acid to its methri ester by diazomethane is a method of choice when other methods are unsatisfactory (6, 30, 61, 65). With appropriate alcohols thiazoleanhydrkies give the esters or diesters in good yield (64), dimethyl 2-phoiyl-4,5-thiazoledicarboxylate (13) has been prepared in this way (Scheme 8) (17). 

Although it is seldom used, esterification of pyrimidinecarboxylic acids proceeds normally. Conditions are illustrated by the conversion of pyrimidine-4-carboxylic acid (181 R = H) into its methyl ester (181 R = Me) by methanol/sulfuric acid (47%), methanol/hydrogen chloride (80%), or by diazomethane (ca. 100%) (60MI21300). The isomeric methyl pyrimidine-2-carboxylate is formed by treatment of the silver salt of the acid with methyl iodide. Higher esters, e.g. (182 R = Bu), are usually made by warming the acid (182 R = H) with the appropriate alcohol and sulfuric acid (60JOC1950). 

Furan and thiophene undergo addition reactions with carbenes. Thus cyclopropane derivatives are obtained from these heterocycles on copper(I) bromide-catalyzed reaction with diazomethane and light-promoted reaction with diazoacetic acid ester (Scheme 41). The copper-catalyzed reaction of pyrrole with diazoacetic acid ester, however, gives a 2-substituted product (Scheme 42). 

The addition of diazomethane to unsaturated esters (1), as ethyl acrylate, methyl crotonate and ethyl cinnamate, was investigated by Auwers who showed that the primary addition product is a A -pyrazoline (2) which rearranges spontaneously to the conjugated A -pyrazoline (3). 

The methyl ester (100, R = CH3), derived from this A-nor acid by treatment with diazomethane, is different from the ester (102) obtained either by Favorskii rearrangement of 2a-bromo-5a-cholestan-3-one (101) or by the action of cyanogen azide on 3-methoxy-5a-cholest-2-ene (103) followed by hydrolysis on alumina. The ketene intermediate involved in photolysis of (99) is expected to be hydrated from the less hindered a-side of the molecule to give the 2j -carboxylic acid. The reactions which afford (102) would be expected to afford the 2a-epimer. These configurational assignments are confirmed by deuteriochloroform-benzene solvent shifts in the NMR spectra of esters (100) and (102). ... 

A regiospecific addition takes place when diazomethane reacts with an acetylenic ester [17] (equation 26)... 

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