Thiolysis of Nuclear Halogenopyrazines

The conversion of halogenopyrazines into pyrazinethiones is usually done either with sodium hydrogen sulfide solution or by initial treatment with thiourea and subsequent hydrolysis of the intermediate isothiouronium salt (frequently unisolated). A third method, involving treatment of the halogeno substrate with thiosulfate, has proven promising in some heterocyclic series but not so far in the pyrazines 2-chloropyrazine did so give 2(1 //)-pyrazinethionc but only in 20% yield.1358 

3-Chloro-2-pyrazinecarboxamide (136) gave 3-thioxo-3,4-dihydro-2-pyrazinecarboxamide (137) (NaHS, EtOH—Me2NCHO, 100°C, 5 h 85%) 503 the isomeric 6-thioxo-l,6-dihydro-2-pyrazinecarboxamide (84%) was made in a similar way.503 

Methyl 6-chloro-2-pyrazinecarboxylate 4-oxide gave methyl 6-thioxo-l,6-dihy-dro-2-pyrazinecarboxylate 4-oxide (138) (NaHS, EtOH, 20°C, 3 h 46%).89 2-Chloropyrazine gave 2( l//)-pyrazincthione [NaHS/MeOH (made in situ), reflux, 1 h 91%].1602 

2-Chloropyrazine 1-oxide (139) gave a separable mixture of 1 -hydroxy-2( I//)-pyrazinethione (140) and bis (pyrazin-2-yl) sulfide (141) (Na2S J, gradually, dioxane, 20°C, h 21 and 33%, respectively).276 Also other examples.262 811,858,1076 1211 

5-l)ichloro-1 -methyl-2(l// )-pyrazinonc (142) gave 5-chloro-3-isothiouronio-I -mc(hyl-2( I // )-pyrazinonc hydrochloride (143) [H2NC(=S)NH2, EtOH, 20°C, 3 h 71%], and thence 5-chloro-1 -methyl-3-thioxo-3,4-dihydro-2(l//)- 

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