2-Bromo-5-hydroxy-3.6-dimethylpyrazine

Bromo-3-hydroxy-5,6-dimethylpyrazine and 2-bromo-5-hydroxy-3,6-diphenyl-pyrazine with phosphoryl chloride afforded 2,3-dichloro-5,6-dimethylpyrazine and 2,5-dichloro-3,6-diphenylpyrazine, respectively (817) and the bromo substituent in 2-amino-3-bromo-5,6-dimethylpyrazine and its p-aminobenzenesulfonyl derivative have been replaced by chlorine on treatment with aqueous hydrochloric acid in ethanol (812). 

Refluxing phosphoms tribromide converted 2-bromo-3-hydroxy-5,6-diphenyl-pyrazine and 2-bromo-5-hydroxy-3,6-diphenylpyrazine to the dibromopyrazines 2,3-dichloro-5,6-dimethylpyrazine and 2,5-dichloro-3-phenylpyrazine to the dibromopyrazines (817) 5-chloro-2,3-diphenylpyrazine (and its 6-ethyl derivative) to 5-bromo-2,3-diphenylpyrazine (and its 6-ethyl derivative) (866) and 2-hydroxy-... 

Bromo-3-methoxycarbonylpyrazine with 2,3-dimethylaniline in refluxing toluene gave 2-(2, 3 -dimethylphenyl)amino-3-methoxycarbonylpyrazine (950) [hydrolysis of this product with sodium hydroxide in ethanol gave 2-carboxy-3-(2, 3 -dimethylphenyl)aminopyrazine, which was also obtained by treatment of l-(2, 3 -dimethylphenyl)lumazine with sodium hydroxide in refluxing ethanol (950)]. 3-Bromo-2-hydroxy-5-phenylpyrazine with ammonium hydroxide and copper at 150° gave 3-amino-2-hydroxy-5-phenylpyrazine (365a). Replacement of the iodo substituent from 2-amino-5-iodo-3,6-dimethylpyrazine has been effected with ammonium hydroxide (887). 

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... 

Crystal structures of 3,5,6-tri-t-butyl-2-hydroxypyrazine (1093) 2,5-dichloro-3-methoxypyrazine (915) and 2,3-dichloro-5-ethylamino-6-methoxypyrazine (916) have been determined. The dipole moment of 2-amino-5-bromo-3-methoxypyrazine (2.94D in benzene) is consistent with the S-cis configuration (52) (749) and the polarographic behavior of 3-hydroxy(and methoxy)-2,5-dimethylpyrazine (and their A(-oxides) at various pH values has been investigated (588). 

Preparations of hydroxypyrazine A-oxides by primary syntheses have been included in Chapter III and are summarized briefly as follows Section 1II.3, 2-hydroxypyrazine 1-oxides from a-aminohydroxamic acids and 1,2-dicarbonyl compounds or a,/l-unsaturated a-bromo aldehydes (545-548) Section III.4, 2-hydroxy-3,6-dimethylpyrazine 1-oxide from the bisulfite derivatives of pyruvo-hydroxamic acid and aminoacetone (548) and Section III.5, ring closure of the C-C-N-C-C-N-0 system (545, 546, 548-553). In addition to these preparations... 

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