2.6- Diethylpyrazine

Palladium chemistry involving heterocycles has its unique characteristics stemming from the heterocycles inherently different structural and electronic properties in comparison to the corresponding carbocyclic aryl compounds. One example illustrating the striking difference in reactivity between a heteroarene and a carbocyclic arene is the heteroaryl Heck reaction (vide infra, see Section 1.4). We define a heteroaryl Heck reaction as an intermolecular or an intramolecular Heck reaction occurring onto a heteroaryl recipient. Intermolecular Heck reactions of carbocyclic arenes as the recipients are rare [12a-d], whereas heterocycles including thiophenes, furans, thiazoles, oxazoles, imidazoles, pyrroles and indoles, etc. are excellent substrates. For instance, the heteroaryl Heck reaction of 2-chloro-3,6-diethylpyrazine (1) and benzoxazole occurred at the C(2) position of benzoxazole to elaborate pyrazinylbenzoxazole 2 [12e]. 

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]. 

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... 

Figure 5. ESR spectra of the reaction mixture of ethylamine with glucose (lower) and of synthesized N,N -diethylpyrazine cation radical (upper). (Reproduced from Ref. 3. Copyright 1977, American Chemical Society.)...

As described above, the free radical products are considered as N,N -disubstituted pyrazine cation radical products. However, formation of such pyrazine derivatives in the Maillard reaction is unknown, and little work has been done on the synthesis of N.N -diethylpyrazinium salt (8), the one—electron oxidation product of the N, N -diethylpyrazine cation radical. The... 

Chloro-3,6-diethylpyrazine (119, R = H) gave 2,5-diethyl-3-methylpyrazine (118) [Me3Al, Pd(PPh3)4, dioxane—C6H14, A, reflux, 2 h 88%] 280 2,5-dichloro-3,6-diethylpyrazine (119, R = Cl) gave 2,5-diethyl-3,6-dimethyl-pyrazine (120) (likewise but reflux, 4 h 93%) 280 and many homologues and their TV-oxides were made similarly.280,282... 

Pyrazine (367) was converted into 1,4-diethylpyrazinediium bis(tetrafluorobo-rate) (368), the 1,4-diethylpyrazine radical cation iodide (369, X = I) (electrolytic reduction Nal J,), and finally the corresponding tetraphenylborate (369, X = BPh4) (NaBPh4 18%) which was sufficiently stable for elemental and X-ray analysis.548... 

Dichloro-3,6-diethylpyrazine 1,4-dioxide (112) gave 3,6-diethyl-l,4-dihy-droxy-3,6-dihydro-2,5(l//, 4//)-pyr tzinedionc (114), presumably via the dimethoxy intermediate (113) (MeONa, dioxane, 110°C (reflux ), 4 h then 10 M HC1J, 52%).1283... 

Chloro-5,6-diethylpyrazine 1-oxide (219) (K2S2Os, H2S04, 20°C, 24 h 84%) 1250 2-chloro-3-isobutyl-6-methylpyrazine 1-oxide (220) (likewise 78%) 295 and 2-fluoropyrazine 1-oxide (likewise 40%).276... 

Chloro-3,6-diethylpyrazine 1-oxide 2-Chloro-3,6-diethylpyrazine 4-oxide... 

Cyclohexyl-3-isopropyl-5,6-dimethylpyrazine 2-Cyclohexylpyrazine 2-Cyclohexylsulfinyl-3,6-diethylpyrazine 2-Cyclohexylsulfinyl-3,6-dimethylpyrazine 2-Cyclohexylsulfinyl-3,5-diphenylpyrazine 2-Cyclohexylsulfinyl-3,6-dipropylpyrazine 2-Cyclohexylsulfinylpyrazine 2-Cyclohexylthio-3,6-diethylpyrazine 5-Cyclohexylthio-3,6-diethyl-2(17/)-pyrazinone... 

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