Compound 1 reacted with cyanothioacetamide in ether in the presence of pyridine to yield the pyrazine derivative 3 or its tautomers (4 and 5). The formation.
Nitriles in Heterocyclic Synthesis: Novel Syntheses of Functionally Substituted Isoxazoles, Pyrazoles, Pyrazines and their Condensed Derivatives Said A hm ed Soliman Ghozlan, Fatma Abd El Maksoud Abd El A al, Mona Hassan M oham ed, and M ohamed Hilmy Elnagdi* D epartm ent of Chem istry, Faculty of Science, Cairo University, A. R. Egypt Z. N aturforsch. 41b, 489—495 (1986); received July 26, 1985 a-O xim inonitriles, 13C NM R Spectra, Aminoisoxazole Novel syntheses of functionally substituted isoxazoles, pyrazoles and pyrazines have been re ported utilizing ethyl tosyloximinoglyoxalate ( 1) and the pyridinium salt 2 as starting materials. Functionally substituted nitriles are versatile reagents and their utility in heterocyclic synthesis has received considerable recent attention [3 —7]. In previous work we have reported several new approaches for the synthesis of azoles, azines and azoloazines utilizing simple readily obtainable polyfunctional nitriles as starting m aterials [8—12]. Although 1 and 2 can be readily prepared from ethyl cyanoacetate, how ever, their utility in synthesis of heterocycles has received only very little attention [1, 2, 13—16].
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1 Compound 1 reacted with cyanothioacetam ide in ether in the presence of pyridine to yield the pyrazine derivative 3 or its tautomers (4 and 5). The formation o f 3 is assumed to proceed via 6 . Since the IR spec trum revealed the absence of a CO absorption, the reaction product was considered to exist mainly in the hydroxy form 4 or the hydroxymercapto form 5. Com pound 1 reacted with benzoylacetonitrile to yield a product of molecular formula C 14H 11N 3O 3 (M .W t. 269, M + = 269). This product was assumed to be formed through condensation of 1 with ben zoylacetonitrile via elimination of p-toluenesulphonic acid. Three tautomeric structures are possible for the reaction product (cf. structures 7 —9). IR and 13C NM R revealed clearly that the enol form 9 does not exist either in solid state or in solution. Thus, the IR spectrum of the reaction product revealed the absence of any absorption for the hydroxy group. A lso it revealed absorptions for two cyano groups, the carbonyl and azom ethine functions. It appears from the IR spectrum that form 7 predominates as
* Reprint requests to Prof. Dr. M. H. Elnagdi. Verlag der Zeitschrift für N aturforschung, D-7400 Tübingen 0340-5087/86/0400-0489/$ 01.00/0
the reaction product revealed a carbonyl band at 1680 cm -1. If the reaction product was 8 one would expect the ester carbonyl absorption at shorter wave length. 13C NM R also revealed that only one tautomer predom inates in DM SO solution and could be intelligably interpreted in terms of structure 8 . It was observed, however, that the o- and ra-carbons in the benzoyl m oiety are not m agnetically identical which may be rationalized in terms of existence of electrostatic attraction between the cyano group ncloud and the positive charges on the benzoyl o-carbons, a factor which slows down the rate of rotation o f the phenyl group. M oreover, the two o-carbons were observed at much higher field than expected for aroyl o-carbons. This again can be reationalized in terms of deshielding by CN group anisotropy. A ssignm ent of 13C N M R of the signals was made utilizing the data tabulated by Breitmaier and V oelter [17], as well as comparison with data obtained for m odel m olecules [18]. Compound 7 could be converted into the pyrazine derivative 10 or its tautomer 11 on treatment with hydrazine hydrate at 110 °C in the absence of sol vents. 'H NM R spectrum revealed two signals at b 2.7 ppm and b 2.8 ppm for one proton, indicating the presence of both tautomers.
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