Pyrazine-based compounds

Procedures employing less harsh reaction conditions for the functionalization of pyrazine-based compounds were reported in 2013. The Buch-wald group developed two procedures for adding functional groups to the pyrazine core. The first was a selective palladium-catalyzed monoarylation of ammonia under mild reaction conditions using bulky biarylphosphine... 

Koehler and Odell236 already studied a number of factors affecting the formation of pyrazines, based on a system of glucose and asparagine (0.1 mol of each), heated for 24 h at 120 °C in diethyleneglycol/water (10 1, v/v). The dichloromethane extract of a distillate was analysed by GC. Below 100 °C, essentially no pyrazines were formed, but the yield increased steeply as the temperature was increased. At 120 °C, the yield increased rapidly with time, up to about 24 h, when it levelled off. Methylpyrazine was the major product in the first 3 h, but the ratio of dimethyl/methyl derivatives continued to increase for about 9 h, when it remained essentially constant at about 3. Altering the proportions of the reactants to 3 1 decreased the yield of methylpyrazine 10-fold and that of the dimethyl compounds 25 times, whereas a proportion of 1 3 decreased the former only by about a one-fourth and hardly affected the latter. Adding... 

The discovery of a variety of new phenazine- and pyrazine-based natural products was reported in 2014. In addition to 1,6-phenazine-diol (92), a compound previously isolated from a number of different microorganisms, Jansen and collaborators extracted and identified its gjycosyl derivative, l-hydroxyphenazin-6-yI-a-D-arabinofuranoside (93), from Narmocystispusilla... 

Amino-pyrazines and -pyridazines have been shown to exist predominantly in the amino form by infrared spectroscopic studies (cf. Table VI). Ultraviolet spectral data have been interpreted to indicate that 4-aminocinnoline exists predominantly in the imino form 256, but this conclusion, which was based on comparison of its spectrum with those of cinnolin-4-one and 4-ethoxycinnoline, is probably incorrect. Ultraviolet spectroscopic data strongly support the predominance of amino structures for 2-aminopyrazine (257) and 2-aminoquin-oxaline how ever, the former compound was at first erroneously concluded to exist in the imino form from ultraviolet spectral evidence. Isolation of two isomers of 2-amino-8-dimethylamino-3-methylphenazine, assigned the amino and imino structures 258 and 259, respectively, has been claimed, but it is very unlikely that these assignments are correct. 

The mass spectrum of 3-citroneIlyl-2,5-dimethylpyrazine (201) exhibits a parent peak at m/z 246 and a normal base peak (484a) at m/z 122, indicative of a dimethylpyrazine having an unsaturated Cjq alkyl chain without branching at the a-methylene group. The pyrazine is identified by direct comparison with the compounds synthesized on the assumption that the alkyl chain is isoprenoid 142). 

As part of an extensive study of the 1,3-dipolar cycloadditions of cyclic nitrones, Ali et al. (392-397) found that the reaction of the 1,4-oxazine 349 with various dipolarophiles afforded the expected isoxazolidinyloxazine adducts (Scheme 1.78) (398). In line with earlier results (399,400), oxidation of styrene-derived adduct 350 with m-CPBA facilitated N—O cleavage and further oxidation as above to afford a mixture of three compounds, an inseparable mixture of ketonitrone 351 and bicyclic hydroxylamine 352, along with aldonitrone 353 with a solvent-dependent ratio (401). These workers have prepared the analogous nitrones based on the 1,3-oxazine ring by oxidative cleavage of isoxazolidines to afford the hydroxylamine followed by a second oxidation with benzoquinone or Hg(ll) oxide (402-404). These dipoles, along with a more recently reported pyrazine nitrone (405), were aU used in successful cycloaddition reactions with alkenes. Elsewhere, the synthesis and cycloaddition reactions of related pyrazine-3-one nitrone 354 (406,407) or a benzoxazine-3-one dipolarophile 355 (408) have been reported. These workers have also reported the use of isoxazoles with an exocychc alkene in the preparation of spiro[isoxazolidine-5,4 -isoxazolines] (409). 

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