Ethyl oxalate, condensation with methyl

However, Claisen found in 1889 that a second molecule of ethyl acetate (with CH3 hydrogen atoms activated by COOEt) was not the only possible partner for a condensation reaction It could be replaced by a variety of other molecules, such as aldehydes and ketones (activation by CO group) and methyl cyanide and its derivatives (activation by CN group). Many condensation reactions of esters with nitriles were discovered, e.g. diethyl oxalate reacts with methyl cyanide in the presence of sodium ethoxide (Fleischhauer, 189320) ... 

The reactivity of the methylene group adjacent to the lactam group affords the possibility of a Claisen condensation. Thus, treatment of 2-pyrrolidone or 2-piperidone with ethyl oxalate leads to the J -pyrroline-carboxylic (70) and, d -piperideine-2-carboxylic acids (71), respectively. N-methyl lactams furnish N-methyl derivatives (72,73) (Scheme 3). 

A thioamide of isonicotinic acid has also shown tuberculostatic activity in the clinic. The additional substitution on the pyridine ring precludes its preparation from simple starting materials. Reaction of ethyl methyl ketone with ethyl oxalate leads to the ester-diketone, 12 (shown as its enol). Condensation of this with cyanoacetamide gives the substituted pyridone, 13, which contains both the ethyl and carboxyl groups in the desired position. The nitrile group is then excised by means of decarboxylative hydrolysis. Treatment of the pyridone (14) with phosphorus oxychloride converts that compound (after exposure to ethanol to take the acid chloride to the ester) to the chloro-pyridine, 15. The halogen is then removed by catalytic reduction (16). The ester at the 4 position is converted to the desired functionality by successive conversion to the amide (17), dehydration to the nitrile (18), and finally addition of hydrogen sulfide. There is thus obtained ethionamide (19)... 

Menthone has been prepared synthetically by Kotz and Hesse from methyl hexanone. This body was condensed with ethyl oxalate by adding... 

A) Ethyl Butyryl-Pyruvate 146 grams of ethyl oxalate are condensed with 86 grams of methyl-(n)-propyl-ketOne in the presence of sodium ethylate prepared from 25 grams of sodium. 135 grams of product, having a boiling point of 1l3°C/6 mm, are obtained. 

N-Nitroso-N-methyl-N -nitroguanidine, diazomethane from, 41, 10 Nitrosomethylurethane, warning because a carcinogen, 43, 86 o-Nitrotoluene, condensation with ethyl oxalate, 43,40... 

However, the presence of a negative group is not always necessary 3-phenyl-5-methyl oxadiazole reacts with benzaldehyde in the presence of zinc chloride to give j8(phenyl-3-oxadiazolyl)styrene. With ethyl oxalate (phenyl-3-oxadiazolyl) pyruvate is formed in a Claisen condensation. 

The tetrahydropyridopyrimidine 394 was obtained via condensation of 5-acetyl-4-arylamino-6-methyl-2-styrylpyr-imidine with benzaldehyde <1997PJC1232>. The 5,8-dihydropyrido[2,3 Pyrimidine derivatives 395 could be obtained from condensing 5-acetyW-amino-2,6-disubstituted pyrimidines with ethyl oxalate in the presence of alkoxide by-products of Friedlander self-condensation of 395 were also obtained <2002RCB1875>. 

In order to activate the 21 position to halogenation, it is hrst converted to an oxalate. Condensation of the triketone with ethyl oxalate in the presence of alkoxide proceeds preferentially at the 21 position to give (12-2) due to the well-known enhanced reactivity of methyl ketones. Reaction of the crude sodium enolate with bromine leads to the dibromide (12-3), the oxalate moiety being cleaved under the reaction conditions. The Favorskii rearrangement is then used to, in effect, oxidize the 17 position so as to provide a site for the future hydroxyl group. Thus, treatment of (12-3) with an excess of sodium methoxide hrst provides an anion at the 17 position (12-4). This then cyclizes to the transient cyclopropanone (12-5)... 

The reactivity of the a-methylene group in lactams allows Claisen condensation with esters of formic, oxalic, and arylcarboxylic acids. Treatment of ethyl formate with A-methylpiperidone, followed by acidification, yields a salt of 1 -methyl- J2-piperideine, whereas in an alkaline medium its dimer was isolated.34- 158 With oxalic acid ester as the condensing reagent, 1-methyl-J2-pyrroline-2-carboxylic acid159 and l-methyl-d2-piperideine-2-carboxylic acid160 were obtained (Scheme 4). 

Reactivity of the C-5 methyl group in (120) is exhibited in aldol-type condensations, e.g. benzaldehyde with an acid catalyst to give (121) or ethyl oxalate with a strong base to give (122). The greater reactivity of a methyl group at C-5 is also shown in the results of lithiation... 

Thus methyl benzoate condensed under forcing conditions with methyl acetate, propionate, or butyrate forms the a-alkylbenzoylacetates, CjHjCOCHRCOjCHj, in 45%, 6l%, and 41% yields, respectively. Similarly, condensation between ethyl oxalate and these esters produces a-ethoxalyl esters. ... 

Kompa s Synthesis of Camphoric Acid.— The synthesis of camphoric acid is accomplished by starting with di-ethyl oxalate and condensing it with the di-ethyl ester of di-methyl glutaric acid. 

Workers at the India Orchid company have shown that the condensation of 2-pentanone with diethyl oxalate may be catalyzed by sodium methoxide which is cheaper than sodium ethoxide. After further condensation with hydrazine hydrate, the pyrazole 18 was obtained as a mixture of methyl and ethyl esters. Methylation with dimethyl sulfate was performed neat, as in the Pfizer medicinal chemistry synthesis. The mixture of the methylated pyrazoles 19 was then nitrated and subjected to ammonolysis to give the desired pyrazole intermediate 5 (Scheme 16.8). 

Diaminopyridine has been condensed with glyoxal, benzil, - diacetyl,and the pyridils 4. ° Ethyl oxalate yields the 2,3-dioxo compound. The conditions employed for these condensations can be critical. Thus glyoxal in neutral solution yields an unidentified, insoluble, infusible solid, whereas in the presence of acetic acid the reaction readily provides the parent heterocycle.The preferred method makes use of glyoxal sodium bisulfite. Many symmetrical dicarbonyl compounds have been condensed with a variety of 2,3-diaminopyridines substituted in the pyridine ring by bromo, ° chloro, methyl, " or combinations of these substituents. ... 

The failure of cuscohygrine to condense with benzaldehyde, ethyl oxalate and amyl nitrite is hard to accommodate on formula X. Because of the formation of two isomeric hydrazones, and on the erroneous assumptions that base A was di-(a-iV -methylpyrrolidyl)-methane and that methylene di-isonitramine came from a methyl ketone group, Hess and Fink (22) altered Liebermann s formula X so as to represent cuscohygrine as an unsymmetrical di-(JV-methylpyrrolidyl)-propan-2-one (XIII). It has since been found, however, that base A is not identical with di-(a-IV-methyI-pyrrolidyl)-methane prepared by the action of phosgene on pyrrylmagne-sium bromide followed by reduction and methylation (25). Moreover,... 

The pyrido[3,2-rf]pyrimidine (135) was prepared by condensation of the pyrimidinedione (133) with an a-oxoester such as methyl pyruvate or ethyl mesoxalate, or with diethyl oxalate, in the presence of a base. Presumably the reaction involves initial condensation to give the imine (134) as shown in Scheme 29 (57CB728) (cf. Section VIII). 

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