Pyrazine formation mechanism

Pyrazines are formed from transamination reactions, in addition to carbon dioxide and formaldehyde. A requirement is that the carbonyl compound contains a dione and the amino group is alpha to the carboxyl group (16). If the hydrogen on the ct-carbon oI the amino acid is substituted, a ketone is produced. Newell (17) initially proposed a pyrazine formation mechanism between sugar and amino acid precursors. (See Figure 3). The Schiff base cation is formed by addition of the amino acid to the anomeric portion of the aldo-hexose, with subsequent losses of vater and a hydroxyl ion. Decarboxylation forms an imine which can hydrolyze to an aldehyde and a dienamine. Enolization yields a ketoamine, vhich dissociates to amino acetone and glyceraldehyde. 2,5-Dimethylpyrazine is formed by the condensation of the tvo molecules of amino acetone. 

Several mechanisms have been reported for pyrazine formation by Maillard reactions (21,52,53). The carbon skeletons of pyrazines come from a-dicarbonyl (Strecker) compounds which can react with ammonia to produce ot-amino ketones as described by Flament, et al. (54) which condense by dehydration and oxidize to pyrazines (Figure 6), or the dicarbonyl compounds can initiate Strecker degradation of amino acids to form ot-amino ketones which are hydrolyzed to carbonyl amines, condensed and are oxidized to substituted... 

A maltol-ammonia browning reaction produced thirteen pyrazines, two pyrroles, two oxazoles, and one pyridine (12). The major products of this system were 2-ethyl-3-hydroxy-6-methylpyridine and 2-ethyl-3,6-dimethylpyrazine. It is difficult to construct possible formation mechanisms for these compounds from maltol and ammonia. All the carbon atoms must come from maltol. It is possible, then, that maltol degrades into smaller carbon units and that these fragments recombine to form larger carbon units, producing these compounds. Recently, the formation of thiophenones and thiophenes from the reaction of 2,5-dimethyl-4-hydroxy-3(2H)-furanone and cysteine or cystine was reported (13. 14). All these reaction mixtures were reported to possess a cooked meat-like flavor. 

Some pyrrole derivatives have pleasant flavor. For example, pyrrole-2-carboxaldehyde gives a sweet and corn-like odor and 2-acetylpyrrole has caramel-like flavor. However, some pyrroles have been found to contribute to off-flavor of food products (24). Pyrroles have not received as much attention as flavor components as other heterocyclic Maillard reaction products such as pyrazines and thiazoles even though the number of derivatives identified is almost the same as that of pyrazines (Figure 1). Proposed formation mechanisms of pyrroles in the Maillard reaction systems are similar to those of thiophenes (Figures 2). 

The importance of Maillard reaction products to the flavor of foods has received considerable attention. One group of Maillard products, the alkylpyrazines, are thought to contribute roasted, toasted and nutty flavor notes to a variety of foods. Several reviews have detailed the presence of pyrazines in a wide variety of foods (1-7). Considerable work has previously focused on mechanisms of formation and the effects of various parameters on pyrazine formation (8-17). Part one of this study reported on the effects of type of amino acid and type of sugar on the kinetics and distribution pattern of pyrazines formed (18). The current study investigates the effect of pH and water activity on the kinetics of alkylpyrazines formation. 

The identification of 49 pyrazines in heated beef and other meats has been extensively revieved (32, 43). Several mechanisms have been proposed for pyrazine formation by the Maillard reaction. Dlcarbonyl compounds can initiate Strecker degradation of amino acids to yield ot-amino ketones, vhich in turn can undergo condensations and oxidizations to form substituted pyrazines (13). 

H. Weenen, S. B. Tjan, P. J. de Valois, N. Bouter, A. Pos, and H. Vonk, Mechanism of pyrazine formation, in Thermally Generated Flavors Maillard, Microwave, and Extrusion Processes, T. H. Parliment, M. J. Morello, R. J. McGorrin (eds), American Chemical Society, Washington, DC, 1994, 142-157. 

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. 

Samples of the synthetic compounds were provided to Professor Pettit s group, who confirmed the identity of cephalostatins 7 and 12 based on NMR and chromatographic comparison. If this mechanism for pyrazine formation occurs in C. gilchristi, one would expect it to also produce ritterazine K. A search among the currently unidentified residual Cephalodiscus extracts revealed a substance with identical chromatographic profile to ritterazine K. However, it was present in only microgram quantities, and its identity could not be confirmed by NMR. 

Two mechanisms have been suggested for pyrazine formation dnring smoking pyrolytic decomposition of leaf con-stitnents and nonenzymatic sugar-amine reactions. Kato et al. (2048) showed that direct pyrolysis of serine yielded pyrazine, methylpyrazine, ethylpyrazine, 2-ethyl-6-methylpyrazine, 2,6-diethylpyrazine, and 2,6-diethyl-6-methylpyrazine. Pyrolysis of threonine gave 2,5-dimethylpyrazine, trimethylpyrazine. 

Although pyrolysis of selected leaf constituents generates pyrazines, the diversity and abundance of pyra-zines in smoke cannot be adequately accounted for by this mechanism alone. Maga and Sizer (2439) and Enomoto et al. (17B12) have reviewed the occurrence of pyrazines in roasted foods and proposed pathways for pyrazine formation. Their summaries present a large array of pyrazines found in the flavor fractions of a number of roasted foods. It is striking that nearly all pyrazines commonly found in tobacco smoke have been identified in at least one roasted food. For example, 2,3-dimethylpyrazine has been found in peanuts, barley, coffee, baked potatoes, mushrooms, lamb fat, and tobacco smoke (1587a). 

The transition-metal-catalyzed formation of pyridine-type six-membered rings was reported by Mukhopadhyay and Kundu in 2000 [94], Bis-tosylamides of 1,2-diaminobenzene derivatives 193 undergo an unusual pyrazine formation by 6-exo-dig cyclization to give l-(quinoxalin-2-yl)ketones 194 in moderate yields by treatment with 10 mol % Cul in the presence of K2CO3 (Scheme 19.49). A reaction mechanism was not proposed. 

The ring cleavage of 3-aryl-2-substituted-2//-azirines by molybdenum hexacarbonyl has been described earlier in regard to the synthesis of pyrroles, pyrazoles and isoxazoles. In contrast to this behavior, analogous reactions of 2-unsubstituted derivatives lead to the formation of mixtures of 2,5-diarylpyrazines (139) and isomeric 3,6- and 1,6-dihydropyrazine derivatives (140,141) (Scheme 163).47,53 It is possible that the pyrazine products are formed by an intermolecular nitrene mechanism akin to the intramolecular processes described earlier (see Scheme 22 in Section IV,A,1). 

Most helicates have linear axes, though a few helicates with circular axes are known - indeed the chiral (D4) molecular squares formed from Zn2+ and 2,5 -bis(2,2 -bipyridin- 6 -yl)pyrazine, 22, may be regarded as circular helicates (450). The formation of circular or linear forms seems to depend on balances between kinetic and thermodynamic control iron(II)-poly-2,2/-diimine systems with their substitutionally-inert metal centers provide useful systems for disentangling thermodynamic and kinetic contributions. The mechanism of formation of circular helicates of this type is believed to entail a kinetically favored triple helicate intermediate (484). Self-assembly of chiral-twisted iron(III)-porphyrin dimers into extended polynuclear species takes place through the intermediacy... 

Thus, ketone enolates easily substitute chlorine in position 2 of the electrophilic nucleus of pyrazine (1,4-diazabenzene), and even in the dark, the reaction proceeds via the Sj l mechanism (Carver et al. 1981). It is expected that the introduction of the second chlorine in the ortho position to 4-nitrogen in the electrophilic nucleus of pyrazine promotes the ion-radical pathway even more effectively. However, 2,6-dichloropyrazine in the dark or subjected to light reacts with the same nucleophiles by Sr.,2 and not S nI mechanism (Carver et al. 1983). The authors are of the opinion that two halogens in the pyrazine cycle facilitate the formation of a-complex to the extent that deha-logenation of anion-radicals in solution and a subsequent nucleophilic attack of free pyrazine radical become virtually impossible. Thus, the reaction may either involve or exclude the intermediate a-complex, and only special identification experiments can tell which is the true one. 

There are two theories as to the mechanism of the formation of imidazole and pyrazine compounds, namely, (a) the prior formation of glycosylamines and aminodeoxy sugars, and (b) the fragmentation mechanism. 

Several mechanisms have been proposed for the formation of pyrazines in food flavours [18, 23, 25], but the major route is from a-aminoketones, which are products of the condensation of a dicarbonyl with an amino compound via Strecker degradation (Scheme 12.3). Self-condensation of the aminoketones, or condensation with other aminoketones, affords a dihydropyrazine that is oxidised to the pyrazine. 

Many desirable meat flavor volatiles are synthesized by heating water-soluble precursors such as amino acids and carbohydrates. These latter constituents interact to form intermediates which are converted to meat flavor compounds by oxidation, decarboxylation, condensation and cyclization. 0-, N-, and S-heterocyclics including furans, furanones, pyrazines, thiophenes, thiazoles, thiazolines and cyclic polysulfides contribute significantly to the overall desirable aroma impression of meat. The Maillard reaction, including formation of Strecker aldehydes, hydrogen sulfide and ammonia, is important in the mechanism of formation of these compounds. 

Haffenden, L. J. W., and Yaylayan, V. A. (2005). Mechanism of formation of redox-reactive hydroxylated benzenes and pyrazine in 13C-labled glycine/D-glucose model systems. /. Agric. Food Chem. 53, 9742-9746. 

Figure 3. Mechanism for formation of pyrazines. (Reprinted from ref. 17. Copyright 1967 American Chemical Society.)...

Three pyrazines identified by their mass spectra in the extruded samples, 2-methyl-3(or 6)-pentylpyrazine, 2-methyl-3(or 6)-hexylpyrazine and 2,5-dimethyl-3-pentylpyrazine, appeared to be interaction products between proteins, carbohydrates and lipids. A mechanism for the formation of pyrazines with long-chain substitutions has been proposed by Huang et al. (4). 

An interesting photochemical approach to 4,5-disubstituted N-alkylimidazoles consists of the photolysis of 2,3-dihydro-5,6-disubstituted-pyrazines that can be easily prepared from 1,2-diketones and 1,2-diamino-alkanes. For example, the preparative-scale photolysis, in absolute EtOH with high-pressure Hg lamp (Pyrex filter), of 5,6-dimethyl- or 5,6-diphenyl-2,3-dihydropyrazines 54, yields the corresponding N-methyl-imidazoles 57 in high yields (Scheme 12.16). The reaction mechanism involves the formation of an enediimine intermediate 55, followed by cyclization and re-aromatization [41]. 

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