2-Methylpyrazine, formation

Side chain reactivity is also enhanced and is typified by the difference in reactivity of 2-methylpyrazine and 2-methylpyrazine 1,4-dioxide towards anion formation and subsequent condensation reactions. 2-Methylpyrazine undergoes condensation with benzal-dehyde at 180 °C, with zinc chloride catalysis, to yield the styrylpyrazine (58), whereas the corresponding reaction of 2-methylpyrazine 1,4-dioxide proceeds at 25 °C under base catalysis (67KGS419). 

Scheme 21.—Formation of 2-Methylpyrazine from Saccharide Fragments.

Conversion of pyrazinones into bromopyrazines is known (82MI2), as is side-chain bromination, particularly when NBS is used under conditions conducive to radical formation. Thus, 2-ethyl-3-methylpyrazine was converted into the l -bromoethyl derivative (72JOC511). 

A further relationship between reaction rate and sty has been preposed by Labuza. A linear relationship between the logarithms of reaction rate constants and ay was found to exist for many foods within a range of ay 0.3 to 0.8. Figure 4 depicts this relationship for the rate of formation of pyrazine and 2-methylpyrazine as a function of sty. Table V lists the regressions determined for the three rate constants which fell within this range. Correlation coefficients (r2) for these regressions were quite high, at 0.99 for both pyrazine and 2-methylpyrazine. 

Figure 1. The influence of pH on the rate of formation of pyrazine and 2-methylpyrazine, 0.1M lysine-glucose at 95CC.

Figure 3. Effect of water activity on the formation of 2-methylpyrazine at 95°C in NFEM.

Figure 4 Natural logarithm of rate constant for the formation of pyrazine and 2-methylpyrazine with time vs. water activity.

Quantitatively, dimethylpyrazine production was also lower, suggesting fewer available carbonyl fragments and mechanistically less desirable conditions exist for formation of dimethyl versus unsubstituted or methyl pyrazine. A linear relationship of hi< i correlation was found to exist between pH and the rate of formation of pyrazines, with r2 values of 0.974 and 0.999 for pyrazine and 2-methylpyrazine, respectively. Effect of pH on yield was investigated under standard conditions (2 hr heat treatment at 95°C). pH was found to have a great effect on yield, with a total of 13,000 ppb pyrazines produced at pH 9.0 and only 24 ppb at pH... 

Imine formation, the Amadori rearrangement, and aminoketose decomposition, with glucose or xylose and tryptophan, led to activation volumes of 14, + 8, and +17 ml, mol pressure thus accelerating the first, but retarding the other two reactions.106 As a consequence, the formation of certain volatiles, such as norfuraneol at pH 7 and 2-methylpyrazine at pH 10 in lysine-xylose systems, is greatly decreased.107... 

Koehler and Odell236 already studied a number of factors affecting the formation of pyrazines, based on a system of glucose and asparagine (0.1 mol of each), heated for 24 h at 120 °C in diethyleneglycol/water (10 1, v/v). The dichloromethane extract of a distillate was analysed by GC. Below 100 °C, essentially no pyrazines were formed, but the yield increased steeply as the temperature was increased. At 120 °C, the yield increased rapidly with time, up to about 24 h, when it levelled off. Methylpyrazine was the major product in the first 3 h, but the ratio of dimethyl/methyl derivatives continued to increase for about 9 h, when it remained essentially constant at about 3. Altering the proportions of the reactants to 3 1 decreased the yield of methylpyrazine 10-fold and that of the dimethyl compounds 25 times, whereas a proportion of 1 3 decreased the former only by about a one-fourth and hardly affected the latter. Adding... 

Correction to allow for isomeric products (fcisomer — /ctota, x % isomer) changes /cre to 1.65 for 2-methylpyrazine, which forms the 1,3-dimethyl salt. A linear free-energy relationship was found involving rate coefficients for the formation of 3-substituted pyridinium and pyrazinium ions, with the slope of correlation (1.06) demonstrating the slightly larger substituent effects in the... 

Coffee (Arabica) /3-Damascenone, 2-furylmethanethiol, 3-sulfanyl-3-methylbutyl formate (126), homofuronol (127), furaneol, guaiacol, 4-vinylguaiacol, methional, sotolone, 2-ethyl-3,5-dimethylpyrazine, 2,3-diethyl-5-methylpyrazine, vanillin, 4-ethylguaiacol, homosotolone (128) 147... 

Various Isopentyl-substituted pyrazines, such as 2-lsopentyl-3-methylpyrazine, 2-isopentyl-5-methylpyrazine, 2-isopentyl-6— methylpyrazlne, 2-i8opentyl-5,6-disiethylpyrazlne, 2-isopentyl-3,5-dimethylpyrazlne and 2-isopentyl-3,6-dimethylpyrazlne were identified from the thermal reaction of glucose and leucine (12). The formation mechanisms for these compounds may also involve the reaction of 3,6-dihydropyrazine with isovaleraldehyde, the Strecker aldehyde of leucine. Kltamura and Shibamoto (13) described 2-lsopen-tyl-5,6-dimethylpyrazlne as having a caramel-like, coffee and sweet aroma. Although isopentyl-substituted pyrazines have not yet been reported in cocoa, they could, if present, be very Important contributors to that characteristic aroma. 

Normal nucleophilic substitution reactions of alkyl and aryl chloropyrazines have been examined as follows 2-chloro-3-methyl- and 3-chloro-2,5-dimethyl(and diethyl)pyrazine with ammonia and various amines (535, 679, 680) 2-chloro-3(and 6)-methylpyrazine with methylamine and dimethylamine (681, 844), piperidine and other amines (681, 921) 2-chloro-5(and 6)-methylpyrazine with aqueous ammonia (362) alkyl (and phenyl) chloropyrazines with ammonium hydroxide at 200° (887) 2-chloro-3-methylpyrazine with aniline and substituted anilines (929), and piperazine at 140° (759) 2-chloro-3-methyl(and ethyl)pyrazine with piperidine (aqueous potassium hydroxide at reflux) (930,931) [cf. the formation of the 2,6-isomer( ) (932)] 2-chloro-3,6-dimethylpyrazine with benzylamine at 184-250° (benzaldehyde and 2-amino-3,6-dimethylpyrazine were also produced) (921) 2-chloro-3,5,6-trimethylpyrazine with aqueous ammonia and copper powder at 140-150° (933) and with dimethylamine at 180° for 3 days (934,935) 2-chloro-6-trifluoromethylpyrazine with piperazine in acetonitrile at reflux (759) 2-chloro-3-phenylpyrazine with aqueous ammonia at 200° (535) 2-chloro-5-phenylpyrazine with liquid ammonia in an autoclave at 170° (377) 2-chloro-5-phenylpyrazine with piperazine in refluxing butanol (759) but the 6-isomer in acetonitrile (759) 5-chloro-2,3-diphenylpyrazine and piperidine at reflux (741) and 5-chloro-23-diphenylpyrazine with 2-hydroxyethylamine in a sealed tube at 125° for 40 hours (834). 

Klein et al. (978) first attempted the alkaline hydrolysis of 3-chloropyrazine 1 -oxide to 3-hydroxypyrazine 1 -oxide, and although spectroscopic evidence indicated the formation of the hydroxy compound, good quality homogeneous material could not be isolated. Later work by Berkowitz and Bardos (1034) has shown that 3-chloropyrazine 1-oxide was hydrolyzed by refluxing with two equivalents of aqueous sodium hydroxide, and treatment of the product with trimethylsilyl chloride and triethylamine gave 3-(trimethylsilyl)oxypyrazine 1-oxide. 3,6-Di-s-butyl-2-hydroxypyrazine 1-oxide has been prepared from the chloro analogue (no details given) (982). Hydrolysis of 2-amino-6-chloro-3-cyano-5-methylpyrazine... 

Certain a-chloromethylpyrazine A -oxides have been deoxygenated with phosphorus trichloride. Treatment of 2-amino-5-chloromethyl-3-cyanopyrazine 1-oxide (and 2-amino-3-cyano-5-methoxymethylpyrazine 1-oxide) with phosphorus trichloride at room temperature in tetrahydrofuran resulted in smooth deoxygenation to 2-amino-5-chloromethyl-3-cyanopyrazine (and 2-amino-3-cyano-5-methoxy-methylpyrazine) (529), whereas 2-amino-6-chloromethyl-3-cyanopyrazine 1-oxide was best deoxygenated to 3-amino-5-chloromethyl-2-cyanopyrazine by phosphorus trichloride in refluxing tetrahydrofuran (534). The more vigorous conditions necessary for the last reaction may be a reflection of increased steric hindrance at the fV-oxide grouping (529). Use of solvents like chloroform or dioxane led to slow reactions which were accompanied by the formation of numerous unidentified by-products (534). 

Sodio-2-methylpyrazine with methyl picolinate afforded a mixture containing 2-(pyridin-2 -ylcarbonylmethyl)pyrazine (42.6%) (24) and 2-pyridinylbis(pyrazinyl-methyl)carbinol (22.8%), and with ethyl formate gave only bis(pyrazinylmethyl> carbinol (642). 

The formation of pteridine-2,4-diamines by this process is exemplified by the synthesis of 7-methylpteridine-2,4-diamine (1) from 3-amino-5-methylpyrazine-2-carbonitrile.148... 

The formation of pteridines by the completion of the 1,2-bond has been rarely effective, although two examples are the cyclization of 3-(guanidinomethyl)pyrazin-2-amine (3) to give 3,4-dihydropteridin-2-amine, which is subsequently aromatized by oxidation to pteridin-2-amine (4), and the cyclization of 3-(ethoxycarbonylamino)methylpyrazin-2-amine to give 3,4-dihydropteridin-2(1 //)-one, which is also subsequently aromatized by oxidation.140-160-161... 

Wolff-Kishner reduction of l-(6-methylpyrazin-2-yl)-2-propanone (117) leads to the formation of... 

Procida et al. (1997) used dynamic headspace GC-MS to characterize the aroma volatiles of green arabica and robusta coffees (six varieties of each). They declared that robusta varieties have a higher content of methanol, acetone, pyridine, methylpyrazine and furfural, and that methyl formate, /cr/-butyl alcohol, and furfuryl alcohol are almost exclusively found in robustas. When looking at the figures, the conclusions are not as clear-cut. They identified 12 original constituents, mainly hydrocarbons and alcohols. 

---