Reactions of Alkylpyrazines

5- dimethylpyrazine (27, 32) 2,5-diethyl-3,6-dimethylpyrazine with 8 mol potassium permanganate in aqueous solution on a water bath gave 2,5-dicarboxy- 

6- dimethylpyrazine (19, 674) 2,5-dimethyl-3,6-diphenylpyrazine with 2% aqueous potassium permanganate gave 2,5-dicarboxy-3,6-diphenylpyrazine (209) 2-styrylpyrazine was oxidized to 2-carboxypyrazine (675) and 2,5-bis(4 -methoxy-styryOpyrazine was oxidized to 2,5-dicarboxypyrazine (411). 

Other oxidations include that of methylpyrazine with selenious acid in pyridine to give 64% of 2-carboxypyrazine (669) and 2,5-dimethylpyrazine with selenium dioxide to 2,5-dicarboxypyrazine (676) a patent (677) claims oxidation of methylpyrazine with sodium dichromate and aqueous phosphoric acid in an autoclave at 225-350° to give 74% 2-carboxypyrazine. likewise, 2,5-dimethylpyrazine gives 67% 2,5-dicarboxypyrazine, and 2,6-dimethylpyrazine gives 59% 

Some 2 -dialkylpyrazines have been oxidized in one step with sodium dichromate in acetic acid, in good yields, to the corresponding 2-acyl-3-alkylpyrazines (678). Thus 2-ethyl-3-methylpyrazine gave 2-acetyl-3-methylpyrazine, 23-diethylpyrazine gave 2-acetyl-3-ethylpyrazine, and 2-ethyl-3,5(or 3,6)-dimethylpyrazine gave 2-acetyl-3,5(or 3,6)-dimethylpyrazine (678). 

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Several minor reactions of alkylpyrazines are illustrated in the following examples ... 

Methylpyrazine reacts with sodamide in liquid ammonia to generate the anion, which may be alkylated to give higher alkylpyrazines (Scheme 10) (61JOC3379). The alkylpyrazines have found extensive use as fiavouring and aroma agents (see Section 2.14.4). Condensation reactions with esters, aldehydes and ketones are common, e.g. methyl benzoate yields phenacylpyrazine in 95% yield, and reactions of this type are summarized in Scheme 11. 

Photolysis of 3-phenyl-5(4//)-isoxazolone 152 gives 2,5-diphenylpyrazine 154 in 67% yield (Scheme 41) <1997JIC648>, probably through diradical intermediate 153. Radical chain reactions of a-azido ketones 155 with tributyltin hydride lead to symmetrical alkylpyrazines 156, albeit in low to moderate yields (Scheme 42) <2002T3485>. 

Lipid-Protein-Carbohydrate Interactions. Evidence for such complex interaction was recently reported by Huang et al (36) who observed that the addition of corn lipids to zein and corn carbohydrates enhanced the formation of alkylpyrazines, indicating that lipid-derived free radicals may accelerate the rate of Maillard reactions. Two of the alkylpyrazines, identified in such mixtures after heating for 30 minutes at 180°C, have 5-carbon alkyl substitution at the pyrazine ring and could only be explained by interaction of lipid or lipid decomposition products. These authors suggested that condensation of amino ketones, formed by protein-carbohydrate interaction, may yield 3,6-dihydropyrazine which would in turn react with pentanal, a lipid oxidation product, to form 2,5-dimethyl-3-pentylpyrazine. 

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. 

This chapter covers the preparations, physical properties, and reactions of pyrazine and its C-alkyl, C-aryl,. V-alkyl, or A/ -aryI derivatives as well as their respective di-, tetra-, and hexahydro derivatives (the last usually known as piperazines). In addition, it includes methods for introducing alkyl or aryl groups (substituted or otherwise) into pyrazines and hydropyrazines already bearing substituents and the reactions specific to the alkyl or aryl groups in such products. For simplicity, the term alkylpyrazine in this chapter is intended to include alkyl-, alkenyl-, alkynyl-, cycloalkyl-, and aralkylpyrazines likewise, the term arylpyrazine includes both aryl- and heteroarylpyrazines. 

Reactions of pyrazine ketones, that have been covered already, include reductive deoxygenation to alkylpyrazines (Section 3.2.1.5), reduction to extranuclear... 

The primary syntheses of pyrazine JV-oxides from aliphatic components only are described in this chapter. The preparations of pyrazine JV-oxides by oxidation of pyrazines are dealt with under the reactions of the appropriately substituted pyrazines for example, those of pyrazine and alkylpyrazine TV-oxides are described in Chapter IV, and of halogenopyrazine JV-oxides in Chapter V. The cleavage of JV-oxides of pteridines and related systems to aminopyrazine JV-oxides is described in Section VIII.3A(2). 

Preparations of alkylpyrazines by such reactions are discussed in Section V.5H. 

Proton magnetic resonance techniques have been used for the measurement of rates of hydrogen-deuterium exchange of pyrazine (in CHsOD-CHsONa at 164.6") (591) for a study of protonation of pyrazine (1472) for analysis of the reaction mixture from quatemization of 2-substituted pyrazines with methyl iodide (666) for elucidation or confirmation of the structures of alkylpyrazines obtained by alkylation of pyrazines with aldehydes and ketones in the presence of a solution of an alkali or alkaline earth metal in liquid ammonia, or a suspension of these metals in other solvents (614) for a study of changes in chemical shifts produced on ionization of 2-methyl and 2-amino derivatives of pyrazine in liquid ammonia (665) for characterization of methoxymethylpyrazines (686) for the determination of the position of the A -oxide function in monosubstituted pyrazine V-oxides and the analysis of V-oxidation reactions (838) for a study of the structure of the cations of fV-oxides of monosubstituted pyrazines (1136) and for the determination of the structure of the products of peroxyacetic and peroxysulfuric acid iV-oxidation of phenyl- and chlorophenylpyrazines (733b). 

Rizzi (1988) examined the formation of alkylpyrazines from acyloins and ammonium salts under mild conditions, and suggested that some pyrazines could be formed by non-enzymic reactions between products of cell metabolism and ammonia. 

Guyot et al. (1998) studied the inhibitory activity of 5-caffeoylquinic acid, the main component of the chlorogenic acids (see Section 2.1.4) on the formation of alkylpyrazines in Maillard reactions with model systems valine or leucine and saccharose. Applying their results to green robustas, they concluded that the aroma quality increased when the chlorogenic-acids content decreased and when the sucrose content increased. 

Like the other diazines and pyridine, alkylpyrazines can undergo base catalysed C-C bond-forming reactions of the CH groups adjacent to the heteroatom. 2-Methylpyrazine, after deprotonation with NaNH2 in liquid NH3 via anion 13, can be alkylated, acylated and nitrosated ... 

Amrani-Hemaimi, M. Cemy, C. Fay, B.F. Mechanisms of formation of alkylpyrazines in the Maillard Reaction. 

Most of the reactions that occur in amino acids also take place in peptides and proteins. Heterocyclic products are formed when the N-terminal amino acid is involved in the ring formation. Products such as N-3 substituted 2-alkylpyrazin-2-ones form, for example, in reactions of peptides with glyoxal (2-128, and = peptide residues). 

Alkylpyrazines have been recognized as important trace flavor components of a large number of cooked, roasted, toasted and deep-fat fried foods (3). As a rule, alkylpyrazines have a roasted nut-like odor and flavor. Formation pathways for alkylpyrazines have been proposed by numerous researchers (4, 5, 6). Model studies suggest that they are minor products of the Maillard reaction. 

Of the different types of lipids in foods, the phospholipids, being more unsaturated, are particularly important in relation to aroma formation in meat.151 The aroma of cooked meat was not affected by the prior extraction of triglycerides with hexane, but the use of a more polar solvent (chloroform-methanol), which extracts all lipids, including phospholipids, resulted, after cooking, in the replacement of the meaty aroma by a roast or biscuit-like one. This was reflected in the volatiles, the dominant aliphatic aldehydes and alcohols being replaced by alkylpyrazines. This implies that the participation of the lipids in the Maillard reactions inhibited the formation of heterocyclic compounds. 

The Strecker reactant, i.e., the a-dicarbonyl, picks up ammonia during the Strecker reaction and can then form heterocyclic volatiles, particularly pyrazines. The most powerful odorants among these are the 2-ethyl-3,5-dimethyl- (0.04) and the 2,3-diethyl-5-methyl-derivatives (0.09). It is worth noting that most other alkylpyrazines have much higher thresholds and thus make relatively little contribution to the aroma of heated foods. 

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