1- Methyl-3- pyrazinone

Other reactions with their counterparts in the pyridine series are also well known. Thus, 2,3-dimethylpyrazine 1,4-dioxide reacts with acetic anhydride to yield 2,3-bis(acetoxy-methyl)pyrazine (S3) in good yield (72KGS1275). Pyrazine 1-oxide also reacts directly with acetic anhydride to yield 2(ljH)-pyrazinone by way of the intermediate acetate (Scheme 22). The corresponding reaction in the quinoxaline series is not so well defined and at least three products result (Scheme 23) (67YZ942). 

Alkylation of pyrazinones and quinoxalinones may be carried out under a variety of conditions and it is usually observed that while O-alkylation may occur under conditions of kinetic control, to yield the corresponding alkoxypyrazines or alkoxyquinoxalines, under thermodynamic control the A-alkylated products are formed. Alkylation using trialkyl-oxonium fluoroborate results in exclusive O-alkylation, and silylation under a variety of conditions (75MI21400) yields specifically the O-silylated products. Alkylation with methyl iodide or dimethyl sulfate invariably leads to A-methylation. 

The cycloadducts formed from the Diels-Alder reaction of 3-amino-5-chloro-2(17/)-pyrazinones with methyl acrylate in toluene are subject to two alternative modes of ring transformation yielding either methyl 6-cyano-l,2-dihydro-2-oxo-4-pyridinecarboxylates or the corresponding 3-amino-6-cyano-l,2,5,6-tetrahydro-2-oxo-4-pyridinecarboxylates. From the latter compounds, 3-amino-2-pyridones can be generated through subsequent loss of HCN <96 JOC(61)304>. Synthesis of 3-spirocyclopropane-4-pyridone and furo[2,3-c]pyridine derivatives can be achieved by the thermal rearrangement of nitrone and nitrile oxide cycloadducts of bicyclopropylidene <96JCX (61)1665>. 

The elucidation of the hydroxypyrazine-pyrazinone tautomerism has been made using spectral methods. An IR spectral analysis focuses on the carbonyl absorption of the amide group in the keto tautomer. A more useful method is UV spectroscopy, that is, the objective structure in solution is easily estimated by comparison with the UV spectra of bond-fixed compounds related to the two tautomers, namely O-methylated and N-methylated derivatives 9 and 10, which are prepared by methylation of the hydroxypyrazines or pyrazinones with diazomethane (Scheme 1). The above two investigations were achieved by this methodology. 

Ring nitrogens in pyrazines and the benzo derivatives react with electrophiles to form quaternary ammonium species such as iV-alkylpyrazinium salts and pyrazine iV-oxides. N-Alkylation has generally been performed by treatment with a reactive alkyl iodide. The N-1 nitrogen in 2(l//)-pyrazinone 5 is methylated using chloro(chloromethyl)dimethyl-silane followed by desilylation with cesium fluoride to yield l-methyl-2(l//)-pyrazinone <2000TL4933>. 

Although methylation of 2(l//)-pyrazinones with diazomethane gives a mixture of O- and N-methylated pyrazines as the fixed tautomers (Equation 20) <1993JOC7542>, the trimethylsilylation leads to the exclusive formation of 0-silyl compounds, which are effectively converted to bromopyrazines 42 (Scheme 33) <1999JHC783>. In the same... 

The stereoselective intramolecular Diels-Alder reaction of 3-alkenyl(oxy)-2(l//)-pyrazinones leading to tricyclic ring systems was investigated <02TL447>. A one-pot 7-alkoxylation of 6-arylpyrazino[2,3-c][l,2,6]thiadiazine 2,2-dioxides 169 was accomplished by using N-halosuccinimides <02EJ02109>, and the nitration of 2-(5-methyl-2-furyl)quinoxaline was shown... 

Methyl 2- 2-[Ar-(2-bromoethyl)-o-nitrobenzenesulfonamido]propionamido -2-phenylacetate (6) gave l-(a-methoxycarbonylbenzyl)-3-methyl-4-o-nitroben-zenesulfonyl-3.4.5.6-(c(rahydro-2( l//)-pyrazinone (7) [1,8-diazabicyclo [5,4,0]undec-7-ene, tetrahydrofuran(THF) > 95%].1622 Also other examples.863 1493 1772... 

Methyl A-(2-diallylamino-3-hydroxyhcxyl)-2-isopropylglycinatc (42) gave 6-(l-hydroxybutyl)-3-isopropyl-3,4,5,6-tetrahydro-2(l//)-pyrazinone (43) [(Ph3P)3 RhCl, MeCN—H20, distillation (see original for details), 5 h 47%].404 Also other examples 182,189,229,703,813,843,1347,1465,1495,1498,1535,1750... 

Amino-2-methyl-l-propylaminopropane (148) and acetone cyanohydrin (2-hydroxy-2-methylpropionoitrile 149) gave 3,3,5,5-tetramethyl-l-propyl-3,4,5,6-tetrahydro-2(l/7)-pyrazinone (150, X = 0), presumably via the imine (150, X = NH) (PhCH2Et3NCl, NaOH, CHC13—H20, 5°C, >5 h 70%) also analogues.187... 

Amino-3-methyl-2-butanone (270) and ethyl glycinate (271) gave 5,6, 6-trimcthyl-3,6-dihydro-2( I //(-pyrazinone (272) (Et3N, PhH, reflux, 5 days ... 

Dimethylamino-2,2-dimethyl-2//-azirine (27) and 4-isopropyl-2-trifluo-romethyl-5-oxazolinone (28) gave 5-dimethylamino-3-isopropyl-6,6-di-methyl-3,6-dihydro-2(l//)-pyrazinone (29) (MeCN, reflux, N2, 1 h 60% a rational mechanism was suggested) 944 analogues, like 3-allyl-5-dimethy-lamino-6,6-dimethyl-3-phcnyl-3,6-dihydro-2(l//)-pyrazinone (44%),958 were made similarly.944 958... 

C-Acetylformamido)-4-isopropyl-3-methyl-4,5-dihydro-5-isoxazolone (55) gave 6-isopropyl-3,5-dimethyl-2 (1 //)-pyrazinone (56) [Lindlar catalyst (Pd/CaC03/trace Pb), H2, EtOH, 20°C, 10 h 90%] also several homologues likewise and in comparable yields.227... 

I -Benzyl-3,6-dichloro-2( l//)-pyrazinonc (127, R = Cl) gave l-benzyl-5-chloro-3-methyl-2(17/)-pyrazinone (127, R = Me) [Me4Sn, Pd(PPh3)4, PhMe, reflux, <5 days residue from evaporation, KF, AcOEt, 20°C, 12 h 81%) or its 3-ethyl ho-mologues (127, R = Et) (Et4Sn, likewise 95%) 391 analogues similarly.391... 

Mcthyl-5-phenyl-2(l//)-pyrazinone (4) gave 2-chloro-3-methyl-5-phenylpyra-zine (5) (P0C13,175°C, sealed, 18 h 92% beware of pressure within the tube even when cooled ) 57 such a sealed reaction also converted 5-chloro-3-phcnyl-2( l//)-pyrazinone into 2,5-dichloro-3-phenylpyrazine (6) (185°C, 5 h 92%).1382... 

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