2,5 -Diisobutyl-3 - pyrazine

The coupling can also be extended to condensed systems. Indole, benzofurane or benzothiophene were all coupled with chloropyrazine derivatives with varying success. For example indole and the 3,6-diisobutyl-pyrazine derivative gave the desired product in moderate yield (7.58.), The coupling of the diethyl-pyrazine derivative with benzofuran led to 54% isolated yield, while the analogous process using benzothiophene afforded the 2-pyrazyl-benzothiophene in 81%.77... 

Dichloro-3,6dipropyl(or 3,6-diisopropyl or 3,6diisobutyl)pyrazine heated with hexamethylphosphoramide at 200° for 2-3 hours gave 81% 2-chloro-5-dimethylamino-3,6-dipropyl(or 3,6diisopropyl or 3,6-diisobutyl)pyrazine (937), but 2,6-dichloro-3,5diphenylpyrazine heated with hexamethylphosphoramide at 200° for 3 hours gave 64% 2,6-bisdimethylamino-3,5-diphenylpyrazine (937). 

Oxidation of nuclear and extranuclear hydroxypyrazines (and derivatives) to their Af-oxides has been achieved with hydrogen peroxide in acetic acid, and with m-chloroperoxybenzoic acid in 1,2-dichIoroethane. 3-Hydroxy-2,5-diisobutyl-pyrazine was oxidized with 30% hydrogen peroxide in acetic acid at 70 to 3-hydroxy-2,5-diisobutylpyrazine 1-oxide (101), 3-hydroxy-2-(Af-methyl-A -phenyl-carbamoyl)pyrazine 1-oxide (90) was also prepared from the conesponding pyrazine [its A -4-methyl derivative was prepared similarly and also by methylation of (90) (1055)], and 3-hydroxy-2-(A -methyl-AAp-tolylcarbamoyl)pyrazine 1-oxide (1055) was synthesized analogously. 

Cleavage of the Me-0 bond in 3,6-diisobutyl-l-methoxy-2-oxo-l,2-dihydro-pyrazine (93) with methylmagnesium iodide at 150° gave 2-hydroxy-3,6-diisobutyl-pyrazine 1-oxide (94) and the 1,4-dioxide was prepared similarly from 2,5-diisobutyl4-methoxy-3-oxo-3,4-dihydropyrazine 1-oxide and also from 2,5-diisobutyl-3-methoxypyrazine 1,4-dioxide (980). 

Boron tribromide in dry chloroform was used to convert 3-isobutyl-6-isopropyl-1-methoxy-2-oxo-l, 2-dihydropyrazine to 2-hydroxy-3-isobutyl-6-isopropylpyrazine 1-oxide, and 6-isobutyl-3-isopropyl-l-methoxy-2-oxo-l, 2-dihydropyrazine behaved similarly (740a). Ohta (843) reports the preparation of 2-hydroxy-3,6-diisobutyl-pyrazine 1-oxide from 3,6-diisobutyl-l-methoxy-2-oxo-l, 2-dihydropyrazine (as intermediate) and hydrogen iodide. 

The reactions of phosphoryl chloride and some hydroxypyrazine A-oxides with an unsubstituted position adjacent to the A-oxide function to give chlorohydroxy-pyrazines have been described in Section V.IG. In this way 3-hydroxy-2,5-diisobutylpyrazine 1-oxide was converted to 2-chloro-5-hydroxy-3,6-diisobutyl-pyrazine (101) and 2-hydroxy-3,5-diphenylpyrazine 1-oxide gave 2-chloro-6-hydroxy-3,5-diphenylpyrazine (873). 

The aspergillic acids are an important group of naturally occurring pyrazine derivatives. They are formed by cultures of the Aspergillus species and were the first natural products shown to be cyclic hydrox-amic acids.9 Aspergillic acid itself was isolated10 in 1943 from A.flavus and subsequently shown to have structure 3. An isomer of deoxy-aspergillic acid, also isolated from A. flavus, was shown to be 3,6-diisobutyl-2-pyrazinone (4) and named flavacol.11... 

Flutamide, 1-hydroxy-3,5-diisobutyl-3,6-dihydro-2,6-dihydro-2,6(lH)-pyrazine-dione (or tautomer), antiandogenic for prostate cancer [162666-34-3],... 

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