Preparation of Extranuclear Hydroxypyrazines

Many such hydroxypyrazines have been made by primary synthesis (see Chapters 1 and 2), some by C- or N-hydroxyalkylation procedures (see Sections 3.1.1.1 and 3.2.2.1), and a few by hydrolysis of extranuclear halogenopyrazines (see Section 4.4). Other preparative routes are illustrated in the following classified examples  

Note Such reduction is usually done with sodium borohydride but related agents, for example, AIIIBu 2, can sometimes be used to advantage.1107 l,4-Dimethyl-2-methylthio-3,6-dioxo-2-piperazinecarbaldehyde (112) gave 3-hy-droxymethyl-l,4-dimethyl-3-methylthio-3, 6-dihydro-2,5(l//,4//)-pyrazincdionc (113) [LiAlH(OBu%, THF, - 78 - 20°C, 4 h 92%].760 

2-Benzoylpyrazine gave 2-(a-hydroxybenzyl)pyrazine (114) (NaBH4, MeOH, 0 — 10°C, 3 h 93%) 181 analogues likewise.217 

3- Amino-5-propionyl-2-pyrazinecarbonitrile gave 3-amino-5-(l-hydroxypropyl)- 

5-Methyl-2-pyrazinecarboxylic acid 4-oxide (118, R = H) gave 2-hydroxymethyl-5-methyl pyrazine 4-oxide (119) [BH3.THF, (Me0CH2CH2)20, 0 — 20°C, N2, 4 h 86%] 676 methyl 5-methyl-2-pyrazinecarboxylate 4-oxide (118, R = Me) gave the same product (119) (NaBII4, MeOH—H20, 5 — 20°C, 2 h 77%).676 

Note Such reduction is usually done with sodium borohydride but related agents, for example, AIHBu 2, can sometimes be used to advantage. 

5-Mcthyl-2-pyrazinecarboxylic acid 4-oxide (118, R = H) gave 2-hydroxyrnethyl-5-methyl pyrazine 4-oxide (119) [BH3.THF, (MeOCH2CH2)2O, 0 20°C, N2, 

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Most alkoxy- or aryloxypyrazines have been made by primary synthesis (see Chapters 1 and 2), by addition of alcohols to alkynylpyrazines (see Section 3.2.4.9), by alcoholysis or phenolysis of halogenopyrazines (see Sections 4.2.3 and 4.4), by O-alkylation of tautomeric pyrazinones or extranuclear hydroxypyrazines (see Sections 5.1.2.2 and 5.2.2), or by epoxidation of alkenylpyrazines (see Section 3.2.4.1). Some of the few remaining routes (presently of minor preparative value) are illustrated briefly in the following recent examples ... 

PREPARATION OF HYDROXYPYRAZINE A-OXIDES AND EXTRANUCLEAR HYDROXYPYRAZINE A-OXIDES... 

Oxidation of nuclear and extranuclear hydroxypyrazines (and derivatives) to their Af-oxides has been achieved with hydrogen peroxide in acetic acid, and with m-chloroperoxybenzoic acid in 1,2-dichIoroethane. 3-Hydroxy-2,5-diisobutyl-pyrazine was oxidized with 30% hydrogen peroxide in acetic acid at 70 to 3-hydroxy-2,5-diisobutylpyrazine 1-oxide (101), 3-hydroxy-2-(Af-methyl-A -phenyl-carbamoyl)pyrazine 1-oxide (90) was also prepared from the conesponding pyrazine [its A -4-methyl derivative was prepared similarly and also by methylation of (90) (1055)], and 3-hydroxy-2-(A -methyl-AAp-tolylcarbamoyl)pyrazine 1-oxide (1055) was synthesized analogously. 

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