2.5- Dichloro-3,6-dihydropyrazine

Other chlorinations have been effected with phosphorus pentachloride alone as follows piperazine-2,5-dione in carbon tetrachloride to 2,5-dichloro-3,6-dihydropyrazine (847, 849) [but at 250°/24hours to tetrachloropyrazine (850, 851)] 2[Pg.102]

Diamino- 1,2-diphenylethane (112) and l,2-dichloro-l,2-bis (p-tolylimino) ethane (113) gave 2,3-diphenyl-5,6-di-p-toluidino-2,3-dihydropyrazine (114) (EtjN, PhMe, 20°C, until thin-layer chromatography (TLC) shows no dichloro synthon 80%) also analogues.979... 

A number of piperazine-2,5-diones (a-amino acid anhydrides ) has been converted to pyrazines by the action of phosphorus halides. Baxter and Spring (312) first described the conversion of isoleucine anhydride (45) with phosphoryl chloride to 2,5-di-s-butyl-3,6-dichloropyrazine (46, X = Cl) and 2,5-di-s-butyl-3-chloropyrazine (46, X = H), and of DL-alanine anhydride (47) similary to 2,5-dichloro-3,6-dimethylpyrazine (48, X = Q) and 3from alanine anhydride does not involve an oxidation step, whereas the formation of 2,5-dichloro-3,6-dimethylpyrazine involves the oxidation of an intermediate dihydropyrazine derivative. Treatment of DL-alanine anhydride with phosphoryl chloride in the presence of a tertiary base (dimethylaniline) gave only the monochloro derivative the intermediate dichlorodihydropyrazine presumably loses hydrogen chloride and gives the stable aromatic 3-chloro-2,5-dimethylpyrazine. 

Chlorination of tetrafluoropyrazine has been shown to give 3,6-dichloro-2,2,5,5-tetrafluoro-2,5-dihydropyrazine (2) (50%) and 5,6-dichloro-2,2,33-tetrafluoro-23-dihydropyrazine (3) (10%) (796). 

Methoxypyrazines (31) have been prepared by diazomethane methylation of 2-hydroxy-3-isobutylpyrazine (60, 311, 367), 2-hydroxy-3-isopropylpyrazine (59, 367), 2-hydroxy-3-propyl(ethyl or hexyl)pyrazine (367), 3-hydroxy-2-isobutyl-5(and 6)methylpyrazine and 2-hydroxy-3-isobutyl-5,6-dimethylpyrazine (368), 2,3-dihydroxypyrazine (832), 2-hydroxy-5-methoxy- and 2,5-dihydroxy-3,6-diphenyl-pyrazine (832), 2-hydroxy-6-methoxy(and benzyloxy)pyrazine (832), 2,6-dihydroxy-3,5-diphenylpyrazine (873), 2,3,5-trifluoro-6-hydroxypyrazine (851), 2-chloro-6-hydroxy-3,5-diphenylpyrazine (873), 2-chloro-6-hydroxy-5-methyl-3-phenylpyrazine (873), 2-chloro-6-hydroxy-3-methyl-5-phenylpyrazine (873), 5,6-dichloro-1 -cyclohexyl-34iydroxy-2-oxo-l, 2-dihydropyrazine (853), 2-chloro-5-hydroxy-3-methoxy-6-methoxycarbonylpyrazine (881), 2-(4 -amino-3, 5 -dibromo-phenylsulfonamido)-3Tiydroxy-6-methoxypyrazine (881), 2-amino-3-hydroxy-... 

In 23-dihydroxypyrazine and derivatives Honzl (853), from measurements of infrared spectra in chloroform and ultraviolet spectra in aqueous alcohol, has proposed that 5,6-dichloro-l-cyclohexyl-3-hydroxy-2-oxo-l, 2-dihydropyrazine (pA in water 4.66, 5.66) exists in the form (48). The p.m.r. spectra of some 5- and 6-methyl- and 5- and 6-phenyl-2,3-dihydroxypyrazines have been reported (483). In the 2,5-dihydroxypyrazine series, the infrared spectrum (Nujol) of 2-benzyl-3,6-dihydroxy-5-methylpyrazine has been interpreted as indicating that the major tautomeric form present in the solid state was the dihydroxy form (49), but the ultraviolet spectrum in ethanol was considered consistent with the coexistence of the dihydroxy (49) and oxo-hydroxy form, for example, (50), Although the structure (51) has been proposed for 3-butyl-2,5-dihydroxypyrazine (1092), the evidence in favor of this structure is inconclusive. 

Hydroxypyrazine 1-oxide with trimethylsilyl chloride and bistrimethylsilyl-atnine heated at 90-95° for 1 hour and the 3-(trimethylsilyl)oxypyrazine 1-oxide in 1,2-dichloro ethane treated with l,23,5-tetra-0-acetyl-(3-D-ribofuranose and titanium tetrachloride at reflux for 4 hours followed by deacetylation produced 3-oxo4-(/J-D-ribofuranosyl)-3,4-dihydropyrazine 1-oxide (1035). Treatment of 3-(trimethylsilyl)oxypyrazine 1-oxide with 2-deoxy-3,5-di-0-(p-chlorobenzoyl)-a-D-eo rtro-pentofuranosyl chloride in benzene in the presence of 4A molecular sieves gave an anomeric mixture (a/0 = 1.2 1.0) of 4-[2 -deoxy-3, 5 -di-0-(p-chlorobenzoyl)-a(and 0)-D-e/y rhro-pentofuranosyl]-3-oxo-3,4-dihydropyrazine 1 -... 

The preparation of some 2,3-dihydropyrazines from a, -dicarbonyl compounds with a,0-diamino compounds has been recorded in Section 11.2 (330, 330a, 331, 333, 334, 338-344, 349, 356, 357), with further data given in references 6, 337, 345, and 1547-1549. In addition hexamethyl-2,3-dihydropyrazine (16) has been prepared from 2,3-diamino-2,3-dimethylbutane and butane-2,3-dione (1550). Condensation of oxalyl chloride with diiminosuccinonitrile (10) in ether has been shown to give 2,3-dichloro-2,3-dicyano-5,6-dihydroxy-2,3-dihydropyrazine (17) (383). 

Fluorination of tetrafluoropyrazine with a mixture of cobalt and calcium fluorides at 80° gave 2,2,3,3,5,6-hexafluoro-2,3-dihydropyrazine (22) (886), and chlorination of tetrafluoropyrazine gave 10% 5,6-dichloro-2,2,3,3-tetrafluoro-2,3-... 

Piperazine Derivatives. Treatment of piperazine-2,5-diones with an excess of triethyloxonium fluoroborate gives 2,5-diethoxy-3,6-dihydropyrazines (390), which can be oxidized to the parent pyrazines (391) by dichloro-cyanobenzoquinone. c/s-Diben lpiperazin ione gives a mixture of cis- and /ra j-dihydropyrazines (390). Pyrolysis of the /ro s-isomer gives 3-benzyl-2,5-diethoxypyrazine (392) in high yield with the elimination of... 

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