2-Hydroxymethyl-6-methylpyrazine

C,H]7NO 63367-12-4) see Ibuprofen cx-hydroxy-a-methyl-4-(2-methylpropyl)benzeneethan-imidic acid methyl ester hydrochloride (C 4H22C1N02) see Ibuprofen 2-hydroxymethyl-5-methylpyrazine (C,H8N20 61892-95-3) see Acipimox... 

Dimethylpyrazine gave successively its 1-oxide (258) (H202), 2-acetoxymethyl-5-methylpyrazine (259, R = Ac), 2-hydroxymethyl-5-methylpyrazine (259, R = H) (HO ), and 5-methyl-2-pyrazinecarboxyhc acid (260) (KMn04 for details of all stages in this indirect route, see original paper).432... 

Chloromethyl-5-methylpyrazine (242) gave either 2-acetoxymethyl- (243) (AcOK, EtOH, reflux, 6 h 65%) or 2-hydroxymethyl-5-methylpyrazine (224) (AcOK, KHC03, EtOH, reflux, 6 h 74%) 221 the acetoxymethyl intermediate was confirmed as such by alkaline hydrolysis to the product (244) (NaOH, no details 85%).1353... 

Hydrolysis of 2-chloromethyl-3-ethoxy-5-methylpyrazine with aqueous potassium hydroxide gave 3-ethoxy-2-hydroxymethyl-5-methylpyrazine (872), but attempted acid hydrolysis of 2-chloromethyl-3-ethoxy-5-methylpyrazine (and 3-ethoxy-2-ethoxymethyl-5-methylpyrazine) was unsuccessful (872). Attempts to convert 2-chloromethylpyrazine to 2-hydroxymethylpyrazine were also unsuccessful (679). 

Dimethylamino-23-dimethylpyrazine 1-oxide in boiling acetic anhydride gave 2-acetoxymethyl-3-dimethylamino-5-methylpyrazine (793) which was not isolated but saponified directly to 3-dimethylamino-2-hydroxymethyl-5-methylpyrazine (793). 2-Amino-3-cyano-5-methylpyrazine 1,4-dioxide refluxed with (a) acetic anhydride gave 3-acetamido-2-cyano-5-hydroxy-6-methylpyrazine 1-oxide (532) and (6) sodium methoxide gave 3-amino-2-cyano-5-methoxy-6-methylpyrazine 1-oxide (532). 

Chloromethyl-5-methylpyrazine (283) gave 5-methyl-2-pyrazinecarboxylic acid (284) [K2C03, H20—Bu OH, 60°C, electrolysis (freshly made nickel hydroxide anode Ni alloy cathode) 82% possibly via the hydroxymethyl intermediate but mechanism not elucidated].221... 

Acetoxymethyl- (126) gave 2-hydroxymethyl-3-methoxy-5-methylpyrazine (127) (K2C03, MeOH—H20, 20°C, 24 h 89%).324... 

Dimethylpyrazine 1-oxide (280) gave 2-acetoxymethyl-3-methylpyrazine (281) (neat Ac20, reflux, 30 min 77%) 1272 the isomeric 2,6-dimethyl-pyrazine 1-oxide gave a separable mixture of 2-acetoxymethyl-6-methylpyrazine (282, R = Ac) and 2-hydroxymethyl-6-methylpyrazine (282, R = H), the latter arising presumably by hydrolysis during the work up (neat Ac20, reflux, 1 h 40 and 12%, respectively).1307... 

A large number of 2-alkyl-3-methoxypyrazines has been isolated from raw vegetables (59, 60, 64, 65, 69, 80, 1099), bell peppers (60,61) and gambanum oil (49). 2-Isobutyl-3-methoxypyrazine is already finding commercial use as a flavoring material (368) and 2-ethoxy-3-methylpyrazine may be used for pineapple flavor (981). The odor characteristics (367, 368, 976, 977) and structure (977) of some alkoxy alkylpyrazines have been examined. 3-Guanidino-6-hydroxymethyl-l-methyl-2-oxo-l,2-dihydropyrazine has been isolated from seeds of Stizolobium hassjoo and on mild alkaline hydrolysis gave 3-hydroxy-6-hydroxymethyl-l -methyl-2-oxo-l, 2-dihydropyrazine (1060). 

Peroxyacetic acid oxidation of 2-acetoxymethyl-5-methylpyrazine gave the 1,4-dioxide which hydrolyzed in 0.1% sulfuric acid to 2-hydroxymethyl-5-methyl-pyrazine 1,4-dioxide (625) and 2,3-di(acetoxymethyl)pyrazine 1,4-dioxide was subjected to transesterification with lower alcohols in the presence of a catalytic amount of alkali to give 2,3-di(hydroxymethyl)pyrazine 1,4-dioxide (739). 

A methanopterin analogue, l-allyl-6-(mesitylamino)methyl-7-methyl-3-phenylpteridine, has been synthesized using nucleophilic substitution of 2,3-dicyano-5-hydroxymethyl-6-methylpyrazine with allylamine <04JCR(S)648>. 

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