Pyrazinamines

Most pyrazines are thermally stable, but pyrazinecarboxylic acids undergo decarboxylation at high temperature above 200 °C. This reaction is practically utilized for the synthesis of alkyl- or arylpyrazines, pyrazinones, and pyrazinamines from the corresponding pyrazinecarboxylic acids (Section 8.03.7.1). [Pg.278]

These nitriles are usually employed to afford aromatic pyrazinamines but they can be used to produce hydropyrazinamines, chloropyrazinamines, or even pyrazines without an amino substituent. The following cyclizations illustrate some of these uses ... [Pg.9]

Dichloro-3-nitro-2-pyrazinamine and ethyl 3-aminocrotonate gave 5-(2-amino-1 -ethoxycarbonylprop-1 -enyl)-6-chloro-3-nitro-2-pyrazinamine (107) (Et3N, Pr OH, 20°C, 16 h 62%).788... [Pg.95]

Benzoyl-5-bromo-2-pyrazinamine (116, R = Br) gave 3-benzoyl-5-phenyl-2-... [Pg.96]

Amino-5,6-dimethyl-2(l//)-pyrazinonc (7) gave 3-bromo-5,6-dimethyl-2-pyrazinamine (8) (neat POBr3, open vessel, 145°C, 20 min 40%) 1012 3-bromo-2-pyrazinamine was made similarly.1008 Also other examples.80,86 295 825,956 1033 1290 1386 1396... [Pg.138]

Pyrazinamine gave 5-chloro-2-pyrazinamine (27) [substrate, CHC13—pyridine, Cl2(1.2 mol)/CHCl3 [ slowly, 20°C, dark, 3 h 26% after purification].1280... [Pg.142]

Methyl-2-pyrazinamine 4-oxide (33, R = H) gave 3-bromo-5-methyl-2-pyraz-inamine 4-oxide (33, R = Br) (NBS, Me2SO—H20,15°C, 4 h 79%, initially as a complex).1508... [Pg.143]

The conversion of (primary) pyrazinamines into the corresponding halogenopyrazines by one-pot diazotization and treatment with halides has proven reasonably satisfactory for making some chloro-, bromo-, or fluoropyrazines to date, iodopyrazines... [Pg.146]

Dichloro-3-nitro-2-pyrazinamine (60, R = NH2) gave 2-bromo-5,6-dichloro-3-nitropyrazine (60, R = Br) (Bu CH2ONO, excess CHBr3, reflux, 8 h then more Bu CH2ONO J, reflux, 10 h —50%, crude product mechanism ).1313... [Pg.147]

Benzoyl-3-chloropyrazine (106, R = Cl) gave 3-benzoyl-2-pyrazinamine (106, R = NH2) (NH3, EtOH, 120°C, sealed 63%).1092 Also other examples.645 1091... [Pg.157]

Chloro-2-pyrazinamine (121, R = Cl) gave 3-benzyloxy-2-pyrazinamine (121, R = OCH2Ph) (PhCH2ONa, PhCH2OH, warmed , 72 h 58% sometimes accompanied by a separable byproduct, 2-benzylamino-3-benzy-loxypyrazine (122), in small amount.1567, cf-616... [Pg.161]

Dibromo-2-pyrazinamine (123, R = Br) gave 3-benzyloxy-5-bromo-2-pyrazinamine (123, R = OCH2Ph) (PHCH2ONa, PhCH2OH, reflux, 4 h 51%) 661 also analogues likewise.661 Also other examples.1012 1198... [Pg.161]

Bromo-2-pyrazinamine (156) gave 5-benzylthio-2-pyrazinamine (157) [PhCH2SNa (made in situ), Me2NCHO, 20°C, 48 h 93%] 1565 the same substrate (156) gave bis(5-aminopyrazin-2-yl) sulfide (NaHS, Me2NCHO, reflux, 24 h 40%).1565... [Pg.168]

Dibromo-2-pyrazinamine (158, R = Br) gave 5-bromo-3-methylthio-2-pyrazinamine (158, R = SMe) (MeSNa, MeOH, 20°C, 3 h 60%).1012 Also other examples.605... [Pg.168]

Bromo-5-methyl-2-pyrazinamine 4-oxide (187, R = Br) gave 3-amino-6-methyl-2-pyrazinecarbonitrile 1-oxide (187, R = CN) (CuCN, NaCN, Me2NCHO, 110°C, reflux, 4 h 59%).1508... [Pg.174]

Dibromo-2-pyrazinamine (212) and ethyl acetoacetate gave ethyl 2-bromo-6-methyl-5//-pyrrolo[2,3-/ ]pyrazinc-7-carboxylatc (213) (EtONa, Me2NCHO, 90°C, 2 h 45% net).965 Also other examples.349- 53°-1277... [Pg.177]

Benzylthio-2-pyrazinamine gave 5-bcnzyl thio-2( I //)-pyrazinonc (15) (NaN02, AcOH—H20—dioxane, 5°C, 15 min 46%).1565 Also other examples.54,64,397... [Pg.192]

Ethyl 3-amino-6-benzyloxy-5-isobutyl-2-pyrazinecarboxylate 4-oxide (120, R = C02Et) gave 5-benzyloxy-3-hydroxymethyl-6-isobutyl-2-pyrazinamine 1-oxide (120, R = CH2OH) (Bu 2A1H, CHC13—C6H14, 3°C, 45 min 65%).848... [Pg.209]

Dimethyl-3-methylsulfonyl-2-pyrazinamine (165) gave 3-methoxy-5,6-di-methyl-2-pyrazinamine (166) (MeONa, MeOH, reflux, 27 h 60%).1012... [Pg.217]

Most such pyrazinones have been made by primary synthesis (Chapters 1 and 2) or N-alkylation of tautomeric pyrazinones (Section 5.1.2.2). The minor route by rearrangement of alkoxypyrazines (H 184) appears to be unpresented in recent literature, but there are examples of the hydrolysis of nontautomeric iminopyrazines to corresponding pyrazinones. Thus 3-imino-4-methyl-3, 4-dihy-dro-2-pyrazinamine hydriodide (191, R = H) (i.e., 2,3-diamino-l-methyl-pyrazinium iodide) underwent hydrolysis in 2 M sodium hydroxide during 1 h at 100°C to afford 3-amino-1 -methyl-2(l//)-pyrazinonc (192, R = H) ( 40%) without any evidence of Dimroth rearrangement to 3-methylamino-2-pyrazinamine 1008 l-methyl-3-methylamino-2(l//)-pyrazinimine (191, R = Me) likewise gave 1-methyl-3-methylamino-2(l//)-pyrazinone (192, R = Me) ( 50%) 1008 and other examples have been reported.598... [Pg.221]

Benzyl-5-p-(trifluoromethyl)phenyl-2-pyrazinamine from its 1-oxide (256, R = CF3) [Raney Ni catalyst (20 X wt of substrate), EtOH, reflux, H2 (atm), 90 min 83% it seems doubtful if the H2 plays any role other than that of an inert atmosphere] 73 also 3-benzyl-5-p-methoxyphenyl-2-pyrazinamine from its 1-oxide (256, R = OMe) (likewise but at 20°C, 4 days >90%).397... [Pg.232]

Benzyl-5-methyl-2-pyrazinamine 1-oxide (275) gave 2-acetoxy-5-benzyl-6-di-acetylamino-3-methylpyrazine (276) (Ac20—AcOK, reflux, 10 min 67%).883... [Pg.235]

Pyrazinamine 4-oxide (292) gave 3-azido-2-pyrazinamine (293) (Me3SiN3, Et2NCOCl, MeCN, reflux, A, 18 h >95%) 46 analogues such as 2-azido-3,5-(>95%),46 2-azido-5,6- (85%),46 and 2-azido-3,6-diphenylpyrazine (294) (67%)231 were made similarly. [Pg.237]

Phenylthio-2-pyrazinecarbonitrile gave 3 -phenylsulfonyl-2-pyrazinecarboni-trile (49) (ot-C1C6H4C03, CHC13, 10 - 20°C, 3 h 91%) 1507 and 5-bromo-3-methylthio- gave 5-bromo-3-methylsulfonyl-2-pyrazinamine (50) (likewise, 4 days 70%).1012 Also other examples.1551... [Pg.253]

Amino-5,6-dichloro-2-pyrazinecarboxylic acid (1) gave 5,6-dichloro-3-nitro-2-pyrazinamine (2) (H2S04—HN03, 15 —> 20°C, 4 h 46% C02 f during the reaction).607,1313... [Pg.259]

Note Pyrazinamines may be converted into the corresponding dimethylsulfimidopyrazines (sometimes called dimethylsulfiliminopyrazines neither name is satisfactory ) as outlined in Section 13.2.5 these derivatives may be oxidized successively to unstable C-nitrosopyrazines and forthwith to nitropyrazines, as illustrated here. [Pg.260]

There is little recent information in this area. The tine structure of 3-acetoxy-l, 4-dinitro-2-piperazinol (14) has been elucidated by X-ray analysis.1212 Treatment of 5,6-dichloro-3-nitro-2-pyrazinamine (15) with refluxing ethanolic sodium cyanide for 4 days induced displacement of the nitro by a cyano group as well as ethanoly-sis of one chloro substituent to afford 3-amino-6-chloro-5-ethoxy-2-pyrazinecar-bonitrile (16) in 55% yield.1313 L-Methyl-4-(/>nitrobenzoyl)pipcrazine (17) gave I -(/ -aminobenzoyl)-4-methy I piperazine (18) (75%) on refluxing in ethanolic hydrazine hydrate with a little Raney nickel catalyst for 6 h 135, cf 1032 other reduction procedures have been reported.496,1741... [Pg.261]

This section covers primary, secondary, tertiary, and quaternary aminopyrazines (both nuclear and extranuclear) but not (functionally substituted amino)pyrazines such as hydrazino-, hydroxyamino-, or azidopyrazines. General discussions have appeared on the spectra of 2-pyrazinamine,255 257 991 the proton-sponge properties of 2,3,5,6-tetra(pyridin-2-yl)pyrazine in relation to its fine structure,925 the fluorescene properties of 3,6-diamino-2,5-pyrazinedicarboxylic acid derivatives in relation to their fine structures,1646,1659 the basic properties of aminopyrazines and other such azines in relation to their electronic structures,412,928 and the fine structures of 3-amino-2-pyrazinecarboxylic acid1340 and l,4-diacetyl-2,3-diphenylpiperazine.559... [Pg.265]

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