Pyrazines from Heterobicyclic Systems

Like their selena analogues (Section 2.1.15), these thiadiazoles have been neglected as substrates for pyrazines. However, 4-p-anisidino-2-(3-ethoxycarbony-lacetonyl)-2,3-dihydro-l,2,5-thiadiazol-3-one 1-oxide (80) afforded 3-p-anisidino-5-cthoxycarbonyhnethyl-2( I // )-pyra/iiione (81) in 30% yield by standing with N,. V-diet hyI - (V- i sopropy I a m i n e at 20°C for 3 days.289 

Although thiirenes have not been used recently to make pyrazines, the ring-reduced 2-chloromethylthiirane (82) reacted with l,2-bis(methylamino)ethane in refluxing toluene to furnish 2-mercaptomethyl-l,4-dimethylpiperazine (83) as the major product.1655 

Most such heterobicyclic substrates are fused pyrazines from which the second ring must be removed completely or in part by oxidation, hydrolysis, or some other means to afford the desired monocyclic pyrazine derivatives. However, some such bicyclic substrates do not already incorporate a pyrazine ring, so that more profound processes (like rearrangement, ring expansion, or use of a cosynthon) must be employed to furnish pyrazines. 

The various syntheses are classified simply according to the bicyclic substrate systems in alphabetical order. 

Primary Syntheses from Other Heterocyclic Systems 

5-cthoxycarb()nylmethyl-2fl//)-pyrazinone (81) in 30% yield by standing with N, 7V-diethyl- /-isopropylamine at 20°C for 3 days.  

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