By Hydrolysis of Halogenopyrazines

The reactions of halogenopyrazines with hydroxide ion to produce the hydroxy compounds have been described in Section V.5E. 

In addition to the above preparations, the following hydrolyses have been 

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Many such pyrazinones have been made by primary synthesis (see Chapters 1 and 2) or by hydrolysis of halogenopyrazines (Section 4.2.2). Other methods of preparation are illustrated in the following examples, classified according to the type of substrate ... 

The reactivity of 2-fluoropyrazine with aqueous sodium hydroxide to give 2-hydroxypyrazine has been investigated (882, 884). In 1.07N sodium hydroxide at 26° the reaction followed pseudo-first-order kinetics with a half-life of 43 minutes, whereas under the same conditions 2-chloropyrazine had a half-life of 18 days, and 2-iodopyrazine and 2-fluoropyridine remained unchanged (882, 884). Thus, under the above conditions, 2-fluoropyrazine was 640 times more reactive than 2-chloropyrazine (882). Hydrolysis of 2-fluoropyrazine in 61V hydrochloric acid proceeded at a much slower rate with a half-life of 4 days at room temperature (884). Some literature preparations of hydroxypyrazines by hydrolysis of halogenopyrazines (chloropyrazines with aqueous sodium or potassium hydroxide unless otherwise specified) are as follows 2-hydroxy (150°) (818) 2-hydroxy-3-methyl (reflux) (680) 2-hydroxy-3,5-dimethyl (reflux) (978) 3-hydroxy-2,5-dimethyl (reflux) (98, 312, 680, 740) [at 120° (978)] 3-hydroxy-2,5-di- -butyl (powdered potassium... 

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... 

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