Glyoxal-sodium bisulfite

With Glyoxal-Sodium Bisulfite Adduct as Synthon... 

Commercial 40% aqueous glyoxal or the glyoxal-sodium bisulfite adduct may be used satisfactorily with o-phenylenediamines to afford 2,3-unsubstituted quinoxalines the use of an irregular synthon or substrate is also illustrated in the following examples. 

Glyoxal-sodium bisulfite, 30, 86 Glyoxylic acid, w-butyl ester, 35, 18 ethyl ester, diethyl acetal, 35, 59 Grignard reaction, addition to ethyl sec-butylidenecyanoacetate, 35, 7 allylmagnesium bromide with of,(3-di-bromoethyl ethyl ether, 36, 61 allylmagnesium chloride with a,/3-di-bromoethyl ethyl ether, 36, 63 ethylmagnesium bromide with tin tetrachloride, 36, 86... 

A. Quinoxaline. One hundred thirty-five grams (1.25 moles) of o-phenylenediamine is dissolved in 2 1. of water, and the solution is heated to 70°. With stirring, a solution of 344 g. (1.29 moles) of glyoxal-sodium bisulfite (Note 1) in 1.5 1. of hot water (about 80°) is added to the o-phenylenediamine solution. The mixture is allowed to stand for 15 minutes and then is cooled to about room temperature and 500 g. of sodium carbonate monohydrate (Note 2) is added. The quinoxaline separates as an oil or as a crystalline solid if the mixture is sufficiently cool. The... 

Glyoxal-sodium bisulfite, 30, 86 Grignard reaction, N-methyl-1,2-di-phenylethylamine, 34, 64... 

An equimolar glyoxal-glycine mixture heated under reflux for 4 hours has been shown to give pyrazine and various methylpyrazines (310), but L-leucine and glyoxal sodium bisulfite gave 2-hydroxy-3-isobutylpyrazine (311). 

Glyoxal sodium bisulfite may be used for similar condensations.18... 

The reaction of 6-hydrazinopyrimidin-4-ol with glyoxal (sodium bisulfite addition compound) followed by treating the intermediate with trifluoroacetic acid gives pyrimido[4,5-c]-pyridazin-5-ol in 16% yield.40... 

Amino-4-carboxamidopyridazine can be obtained in high yield by aqueous base hydrolysis of 4(3//)-pyrimido[4,5-c]pyridazinone (Equation (43)). The pyrimido[4,5-c]pyridazinone, which is readily prepared from 6-hydrazino-4(3/ -pyrimidinone by condensation with glyoxal sodium bisulfite followed by treatment with trifluoroacetic acid, is even hydrolyzed in boiling water. This lability is shared by some derivatives <85JOC346>. 

Early lots of varenicline were routinely generated through reduction of 8 to the corresponding diaminobenzazepine 9 and condensation of 9 with glyoxal (sodium bisulfite addition adduct) to afford crystalline quinoxaline trifluoroacetamide 10 (Scheme 3.8). Deprotection, salt formation, and crystallization completed the synthesis of 1 tartrate in 44% overall yield from 6 in early... 

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. ... 

Dienes. 2 moles thenyltriphenylphosphonium chloride allowed to react 1-2 hrs. at 60° under N2 with glyoxal sodium bisulfite and 4.4 moles K-tert-butoxide in anhydrous dimethylformamide -> crude product. Y 85%. Also by single coupling (crude Y 81%) and f. e. s. G. Koszmehl and G. B. Bohn, Ang. Ch. 85, 230 (1973). 

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