Pyrazine formation

Dioxopiperazines are amongst the most ubiquitous of natural products (75FOR(32)57) and they are formally derived by the cyclodimerization of a-amino acids (69CCC4000) or their esters. A number of methods are available for their oxidation to the corresponding pyrazines. Treatment of 2,5-dioxopiperazines with triethyl- or trimethyl-oxonium fluorobor-ate followed by oxidation with DDQ, chloranil or iodine results in pyrazine formation, usually in high yields (Scheme 63) (72JCS(P1)2494). 

A suggested scheme for pyrazine formation in roasted coffee.3... 

The presence of a 2-substitutent in 3-phenylazirines (17, R —H in Scheme 21) modifies the mode of reaction with molybdenum carbonyl.47 In contrast to pyrazine formation for (17, R =H see Section V,C,2), the alkenyl azirine (18, Scheme 22) is transformed in excellent yield into 2-phenyl-5-carboxy-methylpyrrole. This product probably arises by intramolecular cyclization within an intermediate dienylnitrene intermediate, and related reactions have been devised to synthesize isoxazoles (see Section IV,E,2) and pyrazoles (see Section IV,D,1).47 The molybdenum carbonyl-promoted formation of 2,5-disubstituted pyrroles47 has analogy in uncatalyzed thermal, but not photochemical decomposition of 3-phenyl-2//-azirine 2-acrylate.49... 

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... 

Interest in the influence of lipids on pyrazine formation has recently been generated by the identification of long-chain alkyl-substituted heterocyclic compounds in foods and in model systems. Pyrazines in this category include 2-heptylpyrazine isolated from french fried potato flavor (7), and 2-methyl-3(or 6)-pentylpyrazine and 2,5-dimethyl-3-pentylpyrazine, isolated from extruded zein/corn amylopectin/corn oil systems (8, 9). Only the involvement of lipids or lipid-decomposition products in the formation of these compounds could account for the long-chain alkyl substitution on the pyrazine ring. 

It was suggested that a-amino carbonyls such as 3-amino-butane-2-one formed a dihydropyrazine which was subsequently oxidized to a pyrazine (30, 311. The conversion of dihydropyrazine to pyrazine occurs with or without oxygen. There are two possible ways to convert dihydropyrazine into pyrazine without oxygen. One is the disproportionation of dihydropyrazine to give pyrazine and tetrahydropyrazine or piperazine. The other is the dehydration of hydroxy dihydropyrazine (32). Recently, a dialkylpyrazine radical was reported as an intermediate of pyrazine formation (33). However, this simple step from dihydropyrazine to pyrazine is not yet thoroughly understood. 

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. 

Prior studies relating to pyrazine formation have focused on the effect of drastic extremes in ptH. For example, Koehler and... 

Although a maximum rate of formation of pyrazines occurred at approximately aw 0.75 in the NFEM sanples in this study, one cannot assume that this would be the case in all types of foods or reaction systems. Addition of glycerol and hydrophilic polymers to sugar/amino acid systems has been demonstrated to shift the aw at which visible browning will occur (29, 34). It is more likely that the rate of pyrazine formation increases up to a maximum at an intermediate aw range and then decreases again, but not necessarily at aw 0.75. 

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. 

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). 

Scheme 5.8 Pyrazine formation from 1,2-aminocarbonyl derived from the Strecker degradation...

Scheme 5.9 Pyrazine formation without the need for an oxidation step234...

T. Shibamoto and R. A. Bernhard, Investigation of pyrazine formation pathways in glucose-ammonia model systems, Agric. Biol. Chem., 1977, 41, 143-153. 

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. 

A review listing the extensive occurrence of pyrazines (mostly alkylpyrazines) in foods and a discussion of the theories of pyrazine formation has been published by Maga and Sizer (69), and a review of the natural occurrence and mass spectra of pyrazines by Brophy and Cavill (69a). 

In the synthesis of various heterocycles from a-amino ketones, pyrazine formation can be a complicating side reaction due to the tendency of the a-amino ketone to dimerize. One way of avoiding this problem would be to generate the a-amino ketone in a protected form, specifically, as an a-amino acetal. Such derivatives allow the manipulation of the amino moiety as desired. Accordingly, the azirine intermediates derived from oxime tosylates by the Neber rearrangement are subsequently treated with acidic ethanol to furnish the corresponding a-amino acetals (equation 65). ° ... 

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