2- pyrazine, with ethanolic potassium

The reaction of 2,3-dichloropyrido[2,3-0]pyrazine (9) with ethanolic potassium hydroxide is reported to give 3-ethoxypyrido[2,3-( ]pyrazin-2(1 H)-one (10), whereas by the same treatment 2,3,7-trichloropyrido[2,3-0]pyrazine is converted into 2,3-diethoxy-7-chloropyrido[2,3-fr]pyrazine.46... 

Cyano-6-methylaminopyrazine was also prepared from the chloro compound with methylamine hydrochloride and sodium hydroxide in aqueous dioxane (945) and 2-cyano-6-(2, 2 -dimethylhydrazino)pyrazine was prepared similarly (945). 2-Chloro-6-cyanopyrazine with methanol (and similarly with ethanol) and triethylamine gave 2-methoxy-6-(C-methoxyformidoyl)pyrazine (32) [see Section 5D(2)], and 2-chloro-6-carbamoylpyrazine with concentrated aqueous ammonia at 170-175° gave 2 -amino-b-carboxypyrazine (744). 2-Chloro-3-cyano-5,6-diphenylpyrazine with ammonium hydroxide and potassium iodide formed 2-amino-3-carbamoyl-5,6-diphenylpyrazine, but on fusion with ammonium acetate it gave 2-amino-3-cyano-5,6-diphenylpyrazine (848). 

Bis(azidocarbonyl)pyrazine heated with anhydrous benzyl alcohol at 180° for 30 minutes, and then at 220° for 15 minutes gave 2,5-bis(benzyloxycarbonyl-amino)pyrazine (5), which with concentrated sulfuric acid foUowed by pouring onto ice afforded 2,5-diaminopyrazine (1176) but 2,5-bis(azidocarbonyl)pyrazine refluxed with ethanol gave 2,5-bis(ethoxycarbonylamino)pyrazine, which could not be converted into the amine with (fuming) hydrochloric acid to 210°, with concentrated sulfuric acid, or with potassium hydroxide (1172). 

A complication in these reactions is the similar properties for trans dimer 6 and the cis dimer 20. The only noticeable difference in the NMR spectrum is the shift of one H resonance by 0.01 ppm, and a shift in the pyrazine l3C resonances by about 0.1 ppm, while the optical rotations are identical ([a]D = +82°). However, the compounds have very different solubilities - trituration of the mixture with ethanol yields the trans dimer upon filtration, while the crude cis dimer is obtained by evaporation of the filtrate. This separation procedure enabled purification of the mixture obtained from reaction of 2ot,3a-diaminocholestane (obtained by borane reduction of 22) and 2,3-diketocholestane (obtained by oxidation of 3-cholestanone with potassium t-butoxide and oxygen) (Figure 11). 

During the course of investigating the Beckmann rearrangement, Neber observed unexpected reactivity of some tosyloximes. When he treated oxime 6 with sodium ethoxide he obtained pyrazine 7, clearly not the result of a Beckmann rearrangement. Furthermore, he learned that by treating 6 with potassium ethoxide followed by acetic acid, the product obtained was aminoacetal 5. Similarly, treatment of 9 with ethanolic ammonia provided pyrazine 10, whereas treatment with potassium ethoxide followed by acid gave the a-aminoketone 8, which could be converted to 10 via treatment with... 

The condensation of a, dicarbonyl compounds (49) with aj3-diamino compounds (50), which proceeds through the dihydropyrazine (51), has been much used for the synthesis of alkyl- and arylpyrazines (52). These reactions are usually carried out in methanol, ethanol, or ether in the presence of sodium or potassium hydroxide. The dihydropyrazines may be isolated, or oxidized directly to the pyrazine. Dehydrogenating agents that have been employed include oxygen in aqueous alkali (329), air in the presence of potassium hydroxide (330), sodium amylate in amyl alcohol (330a), alcoholic ferric chloride (24), and copper chromite catalyst at 300° (331) (see also Section 1). Pyrazines prepared by this method and modifications described below are listed in Table II.8 (2, 6, 24, 60, 80,195, 329-382) and some additional data are provided in Sections VI. 1 A, VlII.lA(l), and IX.4A(1). 

Dehydrogenations of some 2,3-dihydropyrazines to the corresponding pyrazines have been effected as follows 2,3-dimethyI-5,6-dihydro [reflux with potassium hydroxide in ethanol (333) heat in ethylene glycol at 197° (653, 1558) reflux with potassium hydroxide and manganous oxide in ethanol (633a) vapor phase reaction in the presence of a catalyst, such as copper chromite, and clay (472) heat... 

In cases of ethyl AT-methyl-A,-(3-nitro-2-pyridyl)aminoacetates 5 with a tertiary amino nitrogen as the corresponding sarcosine ester, treatment with bases such as sodium ethoxide or potassium carbonate in ethanol produces 4-alkyl-l-hydroxypyrido[2,3-b]pyrazine-2,3(l/f,4//)-diones 6 as the principal products in low yield.8 9... 

---