1- Chloro-3,6-diisobutylpyrazine

In contrast, thiazoles and benzothiazoles are suitable recipients for the heteroaryl Heck reaction. Treatment of 2-chloro-3,6-diisobutylpyrazine (103) with thiazole led to regioselective addition at C(5), giving rise to adduct 104 [57]. A similar reaction between 2-chloro-3,6-diethylpyrazine (105) and benzo[ >]thiazole took place at C(2) exclusively to afford pyrazinylbenzothiazole 106 [57]. 

Initially, 31 was obtained as the Sonogashira adduct of 2-chloro-3,6-diisobutylpyrazine and trimethylsilylacetylene. Interestingly, 31 underwent an additional Sonogashira coupling with 2-chloropyrazine (13) to afford unsymmetrical 1,2-bispyrazinylacetylene 32 in excellent yield [26], Here, desilylation occurred in situ, and the resulting terminal alkyne was then coupled with 13. 

Along with some disubstituted furan 59, mono-arylation product 58 was isolated when 2-chloro-3,6-diethylpyrazine (57) and furan were refluxed in the presence of Pd(Ph3P)4 and KOAc. In the case of 2-chloro-3,6-dimethylpyrazine (23) and thiophene, monothienylpyrazine 60 was the sole product. When 2-chloro-3,6-diisobutylpyrazine was used as substrate, 9% of the disubstituted thiophene was detected. Analogous to the couplings with furan and thiophene, the heteroaryl... 

An alternative approach applicable both to the synthesis of racemic aspergillic acid428 and neoaspergillic acid is illustrated by the synthesis (Scheme 50) of neoaspergillic acid (8).429 The initial reaction of dl-leucine anhydride (235) with phosphoryl chloride produces, in addition to the required monochloro compound (236), some dichloro compound (237), and flavacol (4). Reaction of the latter compound with a mixture of phosphoryl chloride and phosphorus pentachloride yields further 2-chloro-3,6-diisobutylpyrazine (236). The remaining steps of the synthesis involve reactions discussed previously in this review, with the exception that the hydroxamic function is protected by diazomethane methylation and finally regenerated by ethanolic hydriodic acid treatment.429... 

Chloro-3,6-diisobutylpyrazine (179) gave 2,5-diisobutylpyrazine (180) [Pd(PPh3)4, HC02Na, Me2NCHO, 100°C, A, 2 h 89% note lack of H2] analogues likewise.245... 

Chloro-3,6-diisobutylpyrazine (190) gave 3,6-diisobutyl-2-pyrazinecarboni-trile (191) [KCN, Pd(PPh3)4, Mc2NCIIO, reflux, A, 2.5 h 77%] homologues likewise.190... 

Chloro-3,6-difluoro-5-hydrazinopyrazine 2-Chloro-3,6-difluoro-5-methoxypyrazine 2-Chloro-3,6-diisobutyl-5-methoxypyrazine 2-Chloro-3,6-diisobutylpyrazine 2-Chloro-3,6-diisobutylpyrazine 1, 4-dioxide... 

Chloro-5-dimethylamino-3, 6-difluoropyrazine 2-Chloro-6-dimethylamino-3, 5-difluoropyrazine 2-Chloro-5-dimethylamino-3, 6-diisobutylpyrazine 2-Chloro-5-dimethylamino-3,6-diisopropylpyrazine 2-Chloro-5-dimethylamino-3,6-dimethylpyrazine 2-Chloro-6-dimethylamino-3,5-diphenylpyrazine... 

Ethyl 5-bromo-2-pyrazinecarboxylate 2-(2-Ethylbut-1 -enyl)-6-methylpyrazine Ethyl 5-carbamoyl-2-pyrazinecarboxylate Ethyl 5-chloro-2-pyrazinecarboxylate Ethyl 3-cyano-5,6-dimethyl-2-pyrazinecarboximidate Ethyl 3-cyano-5,6-dimethyl-2-pyrazinecarboxylate Ethyl 3,5-diami no-6-chloro-2-pyrazi necarboximidate Ethyl 6-diethylamino-2-pyrazinecarboxylate 2-Ethyl-3,6-diisobutyl-5-methylpyrazine 2-Ethyl-3,6-diisobutylpy razi ne 2-Ethyl-3,6-diisobutylpyrazine 1 -oxide 2-Ethyl-3,6-diisobutylpyrazine 4-oxide 2-Ethyl-3,6-diisopropylpyrazine /V-Ethyl-AyV -dimethyl-3,5-bismethylamino-2,6-pyrazinedicarboxamide Ethyl 3,6-dimethyl-5-oxo-4,5-dihydro-2-pyrazinecarboxylate... 

Chloro-2,S-dimethylpyrazine was not isolated from the reaction of DL-alanine anhydride with a mixture of phosphoryl chloride and phosphorus pentachloride, but the reaction gives a poor yield of (48, X = Q) and a small quantity of (48, X = OH). Gallagher et al. (282) found that DL-phenylglycine with phosphoryl chloride gave 2,5-dichloro-3,6-diphenylpyrazine and 3-hydroxy-2,5-diphenyl-pyrazine (presumably formed by loss of the elements of hydrogen chloride from an intermediate 2-chloro-5-hydroxy-3,6-diphenyldihydropyrazine) and Dunn et al. (95) from DL-leucine anhydride and phosphoryl chloride prepared flavacol, 3-hydroxy-2,5-diisobutylpyrazine, and a mature of chloropyrazines, whereas Ohta (101) used phosphoryl chloride and phosphorus pentachloride and obtained flavacol and a little 2[Pg.26]

Chloro-3,6-diisobutylpyrazine 1-oxide 5-(l -Acetoxy-2 -methyl)propyl-3-chloro-2-isobutylpyrazine 113b... 

Chloro-5-hydroxy-3,6-dimethylpyrazine with phosphoryl chloride gave a low yield of 2,5-dichloro-3,6-dimethylpyrazine (312) 3-chloro-5-hydroxy-2-methyl-pyrazine gave 3,5-dichloro-2-methylpyrazine (535) and 2-chloro-5-hydroxy-3,6-diisobutylpyrazine with phosphoryl chloride at 150° for 5 hours gave 2,5-dichloro-3,6-diisobutylpyrazine (101). 

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). 

Coupling reaction between 2-chloro-3,6-diisobutylpyrazine (102) and benz[Z ]oxazole took place at C(2) exclusively to afford pyrazinylbenzoxazole 103 [55],... 

Both 2-chloro-3,6-diisobutylpyrazine 1-oxide (181) and the isomeric 4-oxide (183) gave 2,5-diisobutylpyrazine 1-oxide (182) [Pd(PPh j4, HC02Na, Me2NCH0, 100°C, A, 2 h 90 and 87%, respectively note survival of the oxide entity) also analogous dechlorinations " However, if HCO2Na was replaced by MeCO Na, hydrogen appeared to be necessary for dehalo-... 

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