Replacement of Halogeno Substituents by Hydroxy Groups

Klein et al. (978) first attempted the alkaline hydrolysis of 3-chloropyrazine 1 -oxide to 3-hydroxypyrazine 1 -oxide, and although spectroscopic evidence indicated the formation of the hydroxy compound, good quality homogeneous material could not be isolated. Later work by Berkowitz and Bardos (1034) has shown that 3-chloropyrazine 1-oxide was hydrolyzed by refluxing with two equivalents of aqueous sodium hydroxide, and treatment of the product with trimethylsilyl chloride and triethylamine gave 3-(trimethylsilyl)oxypyrazine 1-oxide. 3,6-Di-s-butyl-2-hydroxypyrazine 1-oxide has been prepared from the chloro analogue (no details given) (982). Hydrolysis of 2-amino-6-chloro-3-cyano-5-methylpyrazine 

1-oxide with aqueous 0.5 Af sodium hydroxide at room temperature gave 2-amino-3-cyano-6-hydroxy-5-methylpyrazine 1-oxide (and some 2-amino-3-carbamoyl-6-chloro-5-methylpyrazine 1-oxide), whereas 95% acetic acid at 100° for 3 hours gave 82% of the cyano compound only (533). 

5-Dichloro-3,6-dimethylpyrazine 1,4-dioxide with 0.5 sodium hydroxide at 20° for 5 hours gave 2-chloro-5-hydroxy-3,6-dimethylpyrazine 1,4-dioxide which resisted further alkaline hydrolysis (842) (possibly due to anion formation, whereas sodium ethoxide and sodium benzyloxide rapidly displaced both chloro substituents). Similarly bromoaspergillic acid (3-bromo-2-s-butyl-6-hydroxy-5-isobutylpyrazine 

1- oxide) was unchanged by treatment with 0.5 A methanolic potassium hydroxide at room temperature or by 1.25Af sodium hydroxide at 100° for several hours (87). 3-Hydroxy-2,5-diisobutylpyrazine 1,4-dioxide (843) and 5-s-butyl-3-hydroxy- 

2- isobutylpyrazine 1,4-dioxide (313) were both prepared from the corresponding chloropyrazine with alcoholic potassium hydroxide. 5-( 1 -Acetoxy-2 -methylpropyl)- 

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