Pyrazines. I. Syntheses of 2,3-dihydroxypyrazines and their derivatives

Abstract

This report describes a new method for the preparations of 2,3-dihydroxypyrazines 3 containing (a) , H, (b) H, CHs, (c) CH3i CHa, (d) H, C6H5, (e) CH3, CeHs and (f) CeHs, C6H5 at 5,6 positions. As starting materials, five amino ketals lb-f were prepared by two steps from phthalimido ketones 4b-f. Amino ketals la, lb, and Id (Ri = H) were readily condensed with ethyl oxamate to provide oxamoyl amino ketals 2 in good yields, although condensations of amino ketals le, le, and If, which were stericaliy crowded with methyl or phenyl groups, with ethyl oxamate required drastic conditions. The subsequent cyclizations of oxamoyl amino ketals 2a, 2b, and 2c in acetic acid proceeded in excellent yields to 2,3-dihydroxypyrazines 3a, 3b, and 3c, respectively. While a steric hindrance due to the substituents was recognized, cyclizations of 2d, 2e, and 2f (R2 = C3H5) in acetic acid in the presence of p-toluenesulfonic acid provided the corresponding 2,3-dihydroxypyrazines in 50-60% yields. The structures of these 2,3-dihydroxypyrazines were established by conversion to 2,3-dichloropyrazines 9a-f and subsequently 2,3-diaminopyrazines 10b, lOd, and lOe.

Studies on pyrazines, Part 39.1 Synthesis and acidic hydrolysis of 2-hydroxy-5-methoxypyrazine

“…10 All compounds synthesised here exhibit the coupling constants of 1.3-1.5 Hz, which are typical in 2,5-disubstutued isomers. However, the substance claimed to be 2-hydroxy-5-methoxy pyrazine showed no coupling between two protons in aromatic region, and the chemical shifts in 1 H and 13 C NMR spectra are inconsistent with those of our synthetic sample of 2 (Table 1).…”

“…On the other hand, 2-hydroxy-3-methoxypyrazine (4) was claimed to be another product of the cycloaddition (see Scheme 1), and to be transformed into 2,3-dihydroxypyrazine (3). Those materials were still not identical with the compounds as proposed by comparison of their NMR spectral data with those of authentic samples which were previously synthesised in our laboratory 12,13 (Table 2). We were therefore prompted to reexamine the cycloaddition of methoxypyrazine with benzonitrile oxide according to the literature.…”

Conformational Behavior of Pyrazine‐Bridged and Mixed‐Bridged Cavitands: A General Model for Solvent Effects on Thermal “Vase–Kite” Switching

“…Resorcin [4]arenes 8 and 10 [13] and 2,3-dibromopyrazine [14] were prepared according to literature procedures. Solvents were dried over 3 and 4 molecular sieves.…”

“…The absence of significant hydrogen-bonding acidity (AEa % 0.00) presumably is also the reason why 2 (and 1) prefer the vase form in dipolar aprotic solvents such as Me 2 SO, acetone, carbon disulfide, and THF (entries [13][14][15][16]. Also, in the aromatic solvents series (entries 1-4) the relationship between preferential vase conformation and absence of hydrogen-bonding acidity is respected, even if in this case preferential solvation of the cavity in the vase form is presum-A C H T U N G T R E N N U N G ably the major player.…”

Studies on Pyrazines. Part 33.1 Synthesis of 2,3-Diaminopyrazines via [1,2,5]Thiadiazolo[3,4-b]pyrazines

“…We have previously 8 carried out the reduction with tin chloride with complete conversion of azidopyrazines to aminopyrazines, in which case some 2,3-diaminopyrazines 3 were obtained from 2-amino-3-azidopyrazines. Compared with the existing synthetic routes via 2-amino-3-halopyrazines 9,10 or 1,4-dihydropyrazine-2,3-diones, 11 the current method provides a most *To receive any correspondence (e-mail: nbsato@yokohama-cu.ac.jp). †This is a Short Paper as defined in the Instructions for Authors, Section 5.0 [see J. Chem.…”