Reactions of Extranuclear Hydroxypyrazines

Extranuclear hydroxypyrazines react as alcohols or phenols according to the type of substituent that bears the hydroxy group. Already covered are their conversion into alkenylpyrazines by dehydration (Section 3.2.1.5) or into extranuclear halogenopyrazines (Section 4.3.1). 

The remaining reactions are illustrated by the following classified examples  

5-Hydroxymethyl-6-methyl-2,3-pyrazinedicarbonitrile (135) gave 5,6-dicyano-3-methyl-2-pyrazinecarbaldehyde (136) (activated Mn02, CH2C12, 20°C, 22 h 45%).1599 

2-Allyl-2-(2-hydroxyethyl)- (137, R = CH2OH) gave 2-allyl-2-formylmethyl-5-isopropyl-3,6-dimethoxy-2,5-dihydropyrazine (137, R = CHO) [Me2SO, (COCl)2, CH2C12, 60°C, A, 5 min then substrate J, - 60 — - 15°C, 

6-Dichloro-3-(l-hydroxyethyl)pyrazine (138, R = Me) gave 2-acetyl-3,5-dichloropyrazine (139, R = Me) (fresh Mn02, PhMe, reflux with H20 removal, 1 h 67%) 1455 2,6-dichloro-3-(a-hydroxybenzyl)pyrazine (138, R = Ph) gave 2-benzoyl-3,5-dichloropyrazine (139, R = Ph) (likewise 84%).1455 

Oxidations of hydroxypyrazines to their A -oxides are described in Section lOB. 

2-Benzoyloxypyrazine and 2-benzoyloxy-6-bromopyrazine were each prepared from the hydroxypyrazine with benzoyl chloride in anhydrous pyridine (865) but it has been reported that 3-hydroxy-2,5-diphenylpyrazine could not be acetylated (317), and 2-hydroxy-6-methylpyrazine could not be acetylated or benzoylated in pyridine solution (434). 

Extranuclear acetoxyalkylpyrazines have been prepared from hydroxyalkyl-pyrazines by acetylation with acetic anhydride and dry pyridine as follows 2-methyl-6-(D-flraho-tetraacetoxybutyl)pyrazine (182), 2,5-bis(D-araho-tetraacetoxybutyl)-pyrazine (182), and 2-acetoxymethyl-3-aminopyrazine (1075) and 2-methyI-5-(D- waho-tetrabenzoyloxybutyl 3-(D- 0 ATO-tribenzoyloxypropyl)pyrazine from 2 -methyl -5 - (D -arabo -tetrahydroxybutyl)-3-(D-eryrhTO-trihydroxypropyl)pyrazine with benzoyl chloride and dry pyridine (182). 

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The reduction of pyrazinecarboxylic acids to extranuclear hydroxypyrazines has been covered in Section 5.2.1. Other reactions are illustrated by the following classified examples ... 

Several reactions of pyrazinecarboxylic esters have been discussed already reduction to N-alkylpiperazines (Section 3.2.2.2), reduction to extranuclear hydroxypyrazines (Section 5.2.1), and hydrolysis to pyrazinecarboxylic acids (Section 8.1.1). Other reactions to be expected of carboxylic or carboximidic esters are typi-hed in the following class lied examples ... 

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