2 isobutylpyrazine

Chloro-3,6-diisobutylpyrazine 1-oxide 5-(l -Acetoxy-2 -methyl)propyl-3-chloro-2-isobutylpyrazine 113b... 

Bromination of 5-s-butyl-3-hydroxy-2-isobutylpyrazine (deoxyaspergillic acid) in aqueous solution or acetic acid gave 2-bromo-3-s-butyl-5-hydroxy-6-isobutylpyrazine (bromodeoxyaspergjllic acid) (87) bromination of 2-s-buty-3-hydroxy-5-isobutyl-pyrazine in acetic acid gave 2-bromo-6-s-butyl-5-hydroxy-3-isobutylpyrazine (93) and 3-hydroxy-2,5-diphenylpyrazine behaved similarly (282). This procedure with bromine in acetic acid was unsatisfactory when applied to simpler hydroxypyrazines (817), and bromination of 3,6(and 5,6)-disubstituted-2-hydroxypyrazines and 2-... 

Isobutylpyrazine with mixed phosphorus pentachloride-phosphoryl chloride at 95° gave 2-chloro-5-isobutylpyrazine (693). 

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... 

Demethylation of 5-(2 -hydroxy-2 -methylpropyl)-2-isobutyl-3-methoxypyrazine occurred on refluxing with 10% hydrochloric acid to give 3-hydroxy-5-(2 -hydroxy-2 -methylpropyl)-2-isobutylpyrazine but 2-isobutyl-3-methoxy-5-(2 -methylprop-l -enyl)pyrazine and 3-hydroxy-24sobutyl-5-(2 -methylprop-l -enyl)pyrazine were also produced (113b). 

Diazomethane methylation of 3-hydroxy-2,5-diisobutylpyrazine 1,4-dioxide has been shown to give the 4-methoxypyrazine 1-oxide, 2,5-diisobutyl4-methoxy-3-0X0-3,4-dihydropyrazine 1-oxide (96) (843, 980) [and some 3-methoxy-2,5-diisobutylpyrazine 1,4-dioxide (4 l)(980)] 5-s-butyl-3-hydroxy-2-isobutylpyrazine... 

Hydroxy-5-(1 -hydroxy-2 -methylpropyl)-2-isobutylpyrazine 1,4-dioxide was deoxygenated by titanium trichloride in dry tetrahydrofuran under nitrogen at room temperature to give 2-hydroxy-6-(r-hydroxy-2 -methylpropyl)-3-isobutyl-pyrazine 1 oxide (DL-neohydroxyaspergillic acid) (760a). 

Chocarom Pyrazine is a colorless transparent liquid consisting of a 1 1 isomeric mixture of 3,5-dimethyl-2-isobutylpyrazine and 3,6-dimethyl-2-isobutylpyrazine, as shown in Figure 1. Relevant CAS numbers are [38888-81-2] for dimethyl-isobutylpyrazine (positions not defined), and [70303-42-3] for 3,5-dimethyl-2-isobutyl-pyrazine. 

Chocarom Pyrazine isomers were isolated from the skin and flesh of potato Solanum tuberosum L.) cultivars after baking 4). 3,5-Dimethyl-2-isobutylpyrazine [2,5-dimethyl-3-(2-methylpropyl)-pyrazine] was isolated by Oruna-Concha, Craig, Duckham and Ames from the following potato cultivars - Cara, Nadine, Flanna and Marfona. 3,6-Dimethyl-2-isobutyl-pyrazine [3,5-dimethyl-2-(2-methylpropyl)pyrazine], was found by the same team in Cara and Marfona potato cultivars. 2,5-Dimethyl-3-isobutylpyrazine was also detected by Welty, Marshall and Grun in chocolate ice cream prepared from cocoa flavor (5). Both pyrazines were also found as key odorant compounds in dark chocolate by Counet, Callemien, Ouwerx and Collin (6). The role of amino acids in alkyl-substituted pyrazines formation in model systems containing pyruvaldehyde was examined by Mea (7). 2,5-Dimethyl-3-isobutylpyrazine was formed in the model system with valine. Both isomers were prepared synthetically by Chen (S) by reacting acetol, isobutyraldehyde and ammonium acetate, with low yield of 22.3%. Subsequent proprietary work by the author has improved the yield to 65%. 

The odor threshold of 3,5-dimethyl-2-isobutylpyrazine and 3,6-dimethyl-2-isobutyl-pyrazine was published by Wagner, Czerny, Bielohradski and Grosh, to be >2000 ng/1 air (P), which indicates a relatively low cp value (77), of only ca. 82,000. 

As seen in the table, both Chocarom Pyrazine isomers, i.e. 3,6-diniethyl-2-isobutylpyrazine and 3,5-dimethyl-2-isobutyl-pyrazine, have cp values of ca. 82,000, thus belonging to the low cp value pyrazines group. This characteristic shows more clearly the pyi azines odor impact, as shown in the following graphs of low, medium and... 

The structure and composition of Chocarome pyrazine was elucidated by a combination of GC, MS and NMR analyses (Figures 7 and 8 and tables III - VI). The substitution pattern of 3,5-dimethyl-2-isobutylpyrazine and 3,6-dimethyl-2-isobutyl-pyrazine was elucidated by a combination of NMR methods, especially in mixtures by gradient selected H, N HMBC experiments at natural abundance level (I /). Since the N-NMR spectrum of pyrazines was proven to be a powerful tool for their structural elucidation 12, IS) it is used to study these type of molecules. Tables V and VI details the N-NMR chemical shift of both nitrogen atoms of each isomer ... 

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