Isopropylpyrazines

The aposematic beetle, Metriorrhynchus rhipidius, contains three pyrazines as warning odor components and two amides as bitter principles (Tables III, V, and VIII) (97). Of the three components with the beetlelike odor, the most characteristic is 2-methoxy-3-isopropylpyrazine (24b). The other two components are 2-methoxy-3-methylpyrazine (24a) and 2-methoxy-3-sec-butylpyrazine (24d). It would seem likely that these compounds will occur in the defensive systems of the aposematic beetles. The two amide components, detectable in the hemo-lymph exuded by adult beetles, are 3-phenylpropanamide (130) and l-methyl-2-quinolone (57), the latter being the major component. It seems likely that these bitter principles contribute to distastefulness to potential predators. 

The odor of green coffee is predominantly determined by 2-methoxy-3-isobutyl- and isopropylpyrazines (2 8). ... 

Cacao mass 2-/3-Methylbutanoic acid, 3-methylbutanal, ethyl 2-methylbutanoate, hexanal, 2-methoxy-3-isopropylpyrazine (132), ( )-2-octenal, 2-methyl-3-(methyldisulfanyl)furan (133) 150... 

Isopropylpyrazine (295) likewise gave 2-((3-hydroxy-a, a-dimethylphenethyl)-pyrazine (296) (IY2NI.i, PhCHO, and so on 21%,801 clearly precluded from dehydration to a styrylpyrazine.801... 

Chloro-3-isobutyl-6-isopropylpyrazine 1-oxide (109) gave l-hydroxy-3-isobutyl-6-isopropyl-2(l//)-pyrazinone (110) (KOH, H20—MeOH, reflux, 2 h 84%) 92 homologues likewise.1250... 

Acetoxy-6-isopropenyl-3-isopropylpyrazine (27) gave 6-isopropenyl-3-iso-propyl-2( I //)-pyrazinone (28) (KOH, MeOH—H20, 20°C, 4 h 94%) also analogues.1377... 

Acetoxy-6-(l -acetoxy-1 - methyl ethyl)-5-chloro-3-isopropylpyrazine... 

Chloro-5-iodo-2,6-pyrazinediamine 2-Chloro-3-isobutyl-6-isopropylpyrazine 2-Chloro-6-isobutyl-3-isopropylpyrazine 2-Chloro-3-isobutyl-6-isopropylpyrazine... 

Chloro-3-isopropyl-5,6-dimethylpyrazine 2-Chloro-3-isopropyl-5,6-diphenylpyrazine 2-Chloro-3-isopropyl-5-methylpyrazine 2-Chloro-3-isopropyl-6-methylpyrazine 2-Chloro-6-isopropyl-3-methylpyrazine 2-Chloro-3-isopropyl-6-methylpyrazine 1 -oxide 2-Chloro-6-isopropyl-3-methylpyrazine 1-oxide 2-Chloro-3-isopropylpyrazine... 

Isobutyl-6-isopropyl-2-pyrazinamine 3-Isobutyl-6-isopropyl-2-pyrazinamine 1-oxide 2-Isobutyl-5-isopropylpyrazine 2-Isobutyl-5-isopropylpyrazine 1,4-dioxide 2-Isobutyl-5-isopropylpyrazine 1-oxide 2-Isobutyl-5-isopropylpyrazine 4-oxide... 

A. oryzae A21 grown in media containing 0.05 Af valine and 0.01 Af isoleucine gave 3-s-butyl-2-hydroxy-6-isopropylpyrazine 1-oxide (104a). Tetramethylpyrazine has been obtained from a strain of Bacillus subtilis (105) and fromfi. natto (106), and emimycin, 3-hydroxypyrazine I-oxide (19), has been isolated from the broth of Streptomyces No 2020-1 (107,108). 

Radical anions of 2,3-dimethylpyrazine and 2,5-di-/-butyl-3-isopropylpyrazine have been prepared with metallic potassium in 1,2-dimethoxyethane, and their e.s.r. spectra examined (596a). Heats of hydrogenation of compounds containing isolated and conjugated C=N double bonds have been measured, and the empirical delocalization energy for pyrazine has been determined as 22.3 kcal/mol (93.3 kJ/mol) and corresponds to only 62% of the empirical delocalization energy of benzene (597). 

Diazotization of 2-aminopyrazine with nitrous acid in dilute or concentrated sulfuric acid gave 2 hydroxypyrazine (to 67% yield) (86, 477, 720, 818). Many such conversions have been described, mostly using nitrosylsulfuric acid in concentrated sulfuric acid solution. Preparations of hydroxypyrazines from the aminopyrazines are summarized as follows 2-hydroxy-3-methylpyrazine (sodium nitrite in concentrated sulfuric acid-acetic acid) (681), 2Jiydroxy-3,5-dimethylpyrazine (aqueous nitrous acid, then at 60°) (524), 3-hydroxy-2,5-dimethylpyrazine (477), 2,5-diethyl-3-hydroxypyrazine (aqueous nitrous acid) (478), 2-hydroxy-6-phenyl-pyrazine (365a), 24iydroxy-3,5-diphenylpyrazine (nitrous acid in N hydrochloric acid) (524), 3-hydroxy-2,5-diphenylpyrazine (282), 2-s-butyl-3-hydroxy-5-isobutyl-pyrazine (93), 5TS-butyl-3 hydroxy-2-isobutylpyrazine (92, 536), 2,5-di-s-butyl-3-hydroxypyrazine (89, 720), 3-hydroxy-2-isobutyl-5-isopropylpyrazine (103, 525), 2,3-dihydroxypyrazine (from 2 amino-3-hydroxypyrazine) (757, 1055) and its... 

Methoxypyrazines (31) have been prepared by diazomethane methylation of 2-hydroxy-3-isobutylpyrazine (60, 311, 367), 2-hydroxy-3-isopropylpyrazine (59, 367), 2-hydroxy-3-propyl(ethyl or hexyl)pyrazine (367), 3-hydroxy-2-isobutyl-5(and 6)methylpyrazine and 2-hydroxy-3-isobutyl-5,6-dimethylpyrazine (368), 2,3-dihydroxypyrazine (832), 2-hydroxy-5-methoxy- and 2,5-dihydroxy-3,6-diphenyl-pyrazine (832), 2-hydroxy-6-methoxy(and benzyloxy)pyrazine (832), 2,6-dihydroxy-3,5-diphenylpyrazine (873), 2,3,5-trifluoro-6-hydroxypyrazine (851), 2-chloro-6-hydroxy-3,5-diphenylpyrazine (873), 2-chloro-6-hydroxy-5-methyl-3-phenylpyrazine (873), 2-chloro-6-hydroxy-3-methyl-5-phenylpyrazine (873), 5,6-dichloro-1 -cyclohexyl-34iydroxy-2-oxo-l, 2-dihydropyrazine (853), 2-chloro-5-hydroxy-3-methoxy-6-methoxycarbonylpyrazine (881), 2-(4 -amino-3, 5 -dibromo-phenylsulfonamido)-3Tiydroxy-6-methoxypyrazine (881), 2-amino-3-hydroxy-... 

Boron tribromide in dry chloroform was used to convert 3-isobutyl-6-isopropyl-1-methoxy-2-oxo-l, 2-dihydropyrazine to 2-hydroxy-3-isobutyl-6-isopropylpyrazine 1-oxide, and 6-isobutyl-3-isopropyl-l-methoxy-2-oxo-l, 2-dihydropyrazine behaved similarly (740a). Ohta (843) reports the preparation of 2-hydroxy-3,6-diisobutyl-pyrazine 1-oxide from 3,6-diisobutyl-l-methoxy-2-oxo-l, 2-dihydropyrazine (as intermediate) and hydrogen iodide. 

Hydroxypyrazine 1 oxide was reduced with hydrogen at atmospheric pressure over Raney nickel to 2-hydroxypyrazine (108) [but failed to react with phosphorus trichloride in chloroform (108)], and 3-hydroxy-2-isobutyl-5-isopropylpyrazine 1,4-dioxide was reduced with hydrogen over nickel to 3-hydroxy-2-isobutyl-5-isopropylpyrazine (740a). 2-(A -Anilino-yV-methylcarbamoyl)-4-methyl-3oxo-3,4-dihydropyrazine 1 oxide with sodium dithionite produced 3-(A -anilino-A -methyl-carbamoyl)- -methyl-2oxo-l, 2-dihydropyrazine (1137). 

---