2- Methoxypyrazine 4-oxide

The presence of an N-oxide function in pyrazine is not sufficient in itself to promote electrophilic halogenation, and even the presence of other weak donor groups may fail to promote reaction unless they can act in concert. Although 2-methoxypyrazine 1-oxide could not be bromi-nated, the 3-methoxy isomer [and 3-aminopyrazine 1-oxide (54)] was bro-minated in the 2- and 6-positions (ortho to oxide and ortho or para to the amino group cf. Scheme 47). Similarly, 2-aminopyrazine was brominated more readily than its Af-oxide (55 R = H) where the two groups are in opposition [83JOC1064 84H(22) 1195]. 

Chloro- (127, R = Cl) or 2-lluoropyrazine 1-oxide (127, X = F) gave 2-methoxypyrazine 1-oxide (128) [MeONa, MeOH, reflux 45 min 85% (from chloro substrate) or MeONa, MeOH, 20°C, 10 min 91% (from fluoro substrate)].276... 

The following alkoxypyrazine Af-oxides have been prepared from the corresponding chloropyrazine A-oxides and sodium alkoxide in the appropriate alcohol (unless otherwise specified) 3-methoxypyrazine 1-oxide (838) 2-methoxypyrazine 1-oxide (no details (838) 3-ethoxypyrazine 1-oxide (978) 3-ethoxy-2-methylpyrazine 1-oxide (potassium hydroxide in ethanol) (978) 3-ethoxy-2,5-dimethylpyrazine 1-oxide (sodium ethoxide or potassium hydroxide in ethanol) (872, 978) and 3-methoxy-2,5-dimethylpyrazine 1-oxide (588). 

Alkoxypyrazine A-oxides may also be prepared by oxidation of the alkoxypyrazine with peroxyacetic acid. In this way the following have been prepared 3-ethoxypyrazine 1-oxide (100°/20h) (978) 3-(trideuteromethoxy)pyrazine 1-oxide (757l9h) (975) 3-ethoxy-2-methylpyrazine 1-oxide (65-75724h) (978) 3-methoxy-2-phenylpyrazine 1-oxide (55720 h) (817) 3-ethoxy-2,5-dimethyl-pyrazine 1-oxide (56716 h) (872) 3-carbamoyl-2-methoxypyrazine 1-oxide (80720h) (881) and 2-cyano-5-ethoxy-3,6-dimethylpyrazine A-oxide (55720h) (288). 

Methoxypyrazine-2-one Af-oxides 341 were prepared from oxime derivatives 340 by one-pot cyclization in the presence of DCC/DME with subsequent interaction with Me2S04/K2C03 and NaOH (equation 148) . Similar intramolecular cyclizatiou of ester and oxime O-ethers groups iu the presence of lithium arylthiolate also leads to pyrazin-2-one ring formation . ... 

Raw potato possesses little aroma. Approximately 50 compounds have been reported to contribute to raw potato aroma. Raw potatoes have a high content of LOX, which catalyses the oxidation of unsaturated fatty acids into volatile degradation products (Scheme 7.2) [187]. These reactions occur as the cells are disrupted, e.g. during peeling or cutting. Freshly cut, raw potatoes contain ( ,Z)-2,4-decadienal, ( ,Z)-2,6-nonadienal, ( )-2-octenal and hexanal, which are all products of LOX-initiated reactions of unsaturated fatty acids [188,189]. It is reported that two compounds represent typical potato aroma in raw potato methional and ( ,Z)-2,6-nonadienal [189]. Other important volatiles in raw potatoes produced via the LOX pathway are l-penten-3-one, heptanal, 2-pen-tyl furan, 1-pentanol and ( , )-2,4-heptadienal [189]. Pyrazines such as 3-iso-propyl-2-methoxypyrazine could be responsible for the earthy aroma of potato [35]. Some of the most important character-impact compounds of raw potatoes are summarised in Table 7.8. Aroma compounds from cooked, fried and baked potatoes have previously been reviewed [35]. 

Azine oxides are versatile starting materials for heterocyclic synthesis and are frequently used for regioselective ring substitution reactions, most of which proceed with loss of the oxide substituent. Occasionally some unusual selectivities are observed. For example, treatment of 3-methoxypyrazine A-oxide with equimolar amounts of diethylcarbamoyl chloride and 4-methoxytoluene-a-thiol in refluxing acetonitrile gave 2-methoxy-6-(4-methoxybenzylthio)-pyrazine as the sole product in 60% yield. 

D.A. Peters et al., Structures of 3-methoxypyrazine 1-oxide (la) and 3-methoxy-5-methylpyr-azine 1-oxide (lb). Acta Crystallogr. C 48, 307-311 (1992)... 

Benzyloxy-3-isobutyl-6-mesyloxymethyl- (217) gave 2-benzyloxy-6-iodomethyl-3-isobutyl-5-methoxypyrazine 4-oxide (218) (Bu4NI, PhH, 20°C, dark, 90 min ... 

Reductive debenzylation. 2-Benzyloxy-3,6-diisobutyl-5-methoxypyrazine 4-oxide (21) gave 3,6-diisobutyl-5-methoxy-2(l//)-pyrazinone 4-oxide (22) (H2, Pd/C, EtOH, h 90% structure confirmed by X-ray analysis) 310 2,5-dibenzy-loxy-3,6-diphenylpyrazine likewise gave 5-hydroxy-3,6-diphenyl-2(l//)-pyrazinone (23) (43%).82... 

Benzyloxy-6-hydroxymethyl-3-isobutyl-5-methoxypyrazine 4-oxide (153) gave 2-benzyloxy-3-isobutyl-6-(mesyloxymethyl)-5-methoxypyrazine 4-oxide (154) (MsCl, EtjN, CH2C12,0°C, N2, 30 min > 95%).848 Also other examples.16,324,609,1614... 

Pyrazine A-oxides have continued to attract much attention in recent years, perhaps because the presence of an A-oxide entity can substantially modify the properties of the whole system, especially in respect of activities at other positions on the ring. For example, the aromaticity index for 2-methoxypyrazine is decreased by 23% on formation of its 4-oxide 383 and formation of an A-oxide activates adjacent positions toward direct bromination,782deuteration,1457 and other electrophilic attack.1078... 

Dibenzyl-3-methoxypyrazine 1-oxide (233) (60% H202, maleic anhydride, CHC13, 20°C, 12 h 95%) 312 3-acetoxymethyl-5-isobutyl-3-methoxypyrazine 1-oxide (234) (likewise 89%).329... 

Methoxypyrazine 4-oxide (273) gave 2-acetoxy-6-methoxypyrazine (272) (neat AccO, reflux, A, 2 h 60%) or 2-acetoxy-3-methoxypyrazine (274) (Ac20, Et3N, reflux, A, 2 h 63%).1575... 

Diisobutyl-3-methoxypyrazine 1-oxide (277) gave a separable mixture of 2-acetoxy-3,6-diisobutyl-5-methoxypyrazine (278) and 2-(l-acetoxy-2-methyl-propyl)-5-isobutyl-3-methoxypyrazine (279) (neat Ac20, reflux, 90 min 73 and 12%, respectively).310... 

Acetoxymethyl- -chloropyrazine 2-Acetoxymethyl-3,6-dichloro-5-methylpyrazine 2-Acetoxymethyl-3,6-dichloro-5-methylpyrazine 1-oxide 2-Acetoxymethyl-3-ethoxypyrazine 2-Acetoxymethyl-5-isobutyl-3-methoxypyrazine 2-Acetoxymethyl-5-isobutyl-3-methoxypyrazine 1-oxide 2-Acetoxymethyl-3-methoxy-5-methylpyrazine 2-Acetoxymethyl-5-methoxy-6-methylpyrazine 2-Acetoxymethyl-3-methoxy-5-methylpyrazine 1-oxide 2-Acetoxymethyl-3-methylpyrazine 2-Acetoxymethyl-5-methylpyrazine... 

Benzyloxy-6-chloropyrazine 2-Benzyloxy-3,6-diisobutyl-5-methoxypyrazine 2-Benzyloxy-3,6-diisobutyl-5-methoxypyrazine 1-oxide 2-Benzyloxy-3,6-diisobutyl-5-methoxypyrazine 4-oxide... 

Benzyloxy-6-hydroxymethyl-3-isobutylpyrazine 4-oxide 2-Benzyloxy-6-iodomethyl-3-isobutyl-5-methoxypyrazine 4-oxide 2-Benzyloxy-3-isobutyl-6-mesyloxy-methyl-5-methoxypyrazine-4-oxide 1 - Benzyloxy-3 - (2-methoxycarbonyl-ethyl)-5,6-dimethyl-2(l/7)-pyrazinone... 

Chloro-5-isobutylpyrazine 6-Chloro-5-isobutyl-2-pyrazinecarbothioamide 6-Chloro-5-isobutyl-2-pyrazinecarboxamide 2-Chloro-3-isobutylpyrazine 4-oxide 2-Chloro-5-isopentyl-3,6-dimethylpyrazine 2-Chloro-3-isopropenyl-6-isopropyl-5-methoxypyrazine 5-Chloro-6-isopropenyl-3-isopropyl-l-methyl-2(177)-pyrazinone... 

Guanidinopropyl)-3-isopropyl-2(l//)-pyrazinone 3,6,AA V,X-Hexamethyl-2,5-pyrazinedicarboxamide 2-Hexylamino-3,6-dimethylpyrazine 2-Hexylamino-3,6-dimethylpyrazine 4-oxide 2-Hexylaminopyrazine 2-Hexylaminopyrazine 4-oxide 2- Hexyl- 3,6-dimethylpyrazine 2- Hexyl- 5,6- dimethy lpy razi ne 2- Hexyl -3,6- dimethy lpy razi ne 1,4- dioxide 2-Hexyl-3-methoxypyrazine 2- Hexyl- 3-methylpyrazine... 

Hydroxy-2-methylpropyl)-5-isobutyl-6-methoxypyrazine 4-oxide 2-(l-Hydroxy-2-methylpropyl)-... 

V-Hydroxy-6-propylthio-2-pyrazinecarboxamide V-Hydroxy-6-propylthio-2-pyrazinecarboxamidine 2- (3-Hydroxyprop-1 -ynyl)-3,6-diisobutylpyrazine 2- (3-Hydroxyprop-1 -ynyl)-3,6-diisobutylpyrazine 4-oxide 2- (3-Hydroxyprop-1 -ynyl)-3,6-diisopropylpyrazine 2- (3-Hydroxyprop-1 -ynyl)-3,6-diisopropylpyrazine 4-oxide 2- (3-Hydroxyprop-1 -ynyl)-3,6-dimethylpy razi ne 2-(3-Hydroxyprop-1 -y nyl)-3,6-dimethylpyrazine 4-oxide 2-(3-Hydroxyprop-l-ynyl)-3,5-diphenylpyrazine 2-(3-Hydroxyprop-l-ynyl)-3,6-diphenylpyrazine 2-(3-Hydroxyprop-l-ynyl)-5,6-diphenylpyrazine 2-(3-Hydroxyprop-l-ynyl)-5,6-diphenylpyrazine 4-oxide 2-(3-Hydroxyprop-l-ynyl)-6-methoxy-5-(2-methylprop-l-enyl)pyrazine 2- (3-Hydroxyprop-1 -ynyl )-6-methoxypyrazine N-Hydroxy-2-pyrazinecarboxamide Af-Hydroxy-2-pyrazinecarboxamide 4-oxide... 

Isobutyl-3-methoxy-5-methylpyrazine 2-Isobutyl-3-methoxy-5-methylpyrazine 2-Isobutyl-6-methoxy-5-methylpyrazine 4-oxide 2-Isobutyl-3-methoxypyrazine... 

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