Identification of pyrazines

Isolation and identification of pyrazine alkaloids (Table III) have been achieved in most cases by a combination of gas chromatography and mass spectrometry (35,36,38,69,97,142). Methyl-, 2,3,6-trimethyl-, and tetramethylpyrazines (23a, 21a, and 22a) from the melon fly are identified by utilizing a solid sampling technique in conjunction with gas chromatography-mass spectroscopy (147). Methylpyrazines show the molecule ion as a base peak. Fragmentation proceeds mainly by the loss of HCN or CH3CN from the molecular ion (141). Eth-... 

Heterocyclic compounds are primarily formed through non-enzymatic browning reactions. Recent studies of deep-fat fried food flavors led to the identification of pyrazines, pyridines, thiazole, oxazoles and cyclic polysulfides which had long-chain alkyl substitutions on the heterocyclic ring. The involvement of lipid or lipid decomposition products in the formation of these compounds could account for the long-chain alkyl substitutions. Model systems were used to study the participation of lipids in the formation of pyrazines, pyridines, thiophenes and cyclic polysulfides. 

The question of the fate of the "Strecker" aldehydes requires an answer. By converting the amino acid phenylalanine to yield aroma compounds, phenyl acetaldehyde is liberated. Because of its phenyl ring it is a good detector compound. We were able to establish some of its reaction products. For example, we have identified, among others, phenylethylpyrazine, phenylfuran, phenylethylpyrrole and phenylpyri-dine. We assume that aldol condensations are responsible for the formation of these compounds. Figure 5 illustrates our assumption.We have identified several compounds the structures of which make probable an aldol condensation (3-(2 -furyl)-2-phenyl-2-propenal, phenyl hydroxyketones) likely. This assumption is supported by the identification of pyrazines with up to 5 carbon atom side chains in other experiments. 

W. Baltes and G. Bochmann, Model reactions on roast aroma formation. IV. Mass spec-trometric identification of pyrazines from the reaction of serine and threonine with... 

Fig. 5.15 Progressive identification of pyrazines in roasted coffee volatiles...

Mussinan C.J., Wilson R.A. and Katz I. (1973) Isolation and identification of pyrazines present in pressure cooked beef. J. Agric. Food Chem. 21, 871-2. 

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. 

As described above, a series of 5-pyridylaminothiazoles had been designed and synthesised as highly potent and selective antagonists at the adenosine A3 receptor (Press et al. 2004). It was essentially an extension of the structure-activity relationship to involve 5-imidazo and 5-triazolo substituted aminothiazoles which enabled the rapid identification of several dual A2B/A3 receptor antagonists with acceptable selectivity over the A and A2a receptors. Of the lead compounds, the mesylate salt of 3-[5-(meth-ylimidazol-l-yl)-2-(pyrazin-2-ylamino)-thiazol-4-yl benzonitrile (QAF805) was considered to be the superior compound (Compound 5f - Press et al. 2005). 

Formation of novel free radical products at an early stage of the Maillard reaction was demonstrated by use of ESR spectrometry. Analyses of the hyperfine structures for various sugar-amino compound systems led to the conclusion that the radical products are N,N -disubstituted pyrazine cation radicals. These new pyrazine derivatives are assumed to be formed by bimolecular condensation of a two-carbon enaminol compound involving the amino reactant residue. The presence of such a two-carbon product in an early stage reaction mixture of sugar with amine was demonstrated by isolation and identification of glyoxal dialkylimine by use of TLC, GLC, NMR, MS and IR. 

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. 

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). 

Volatile compounds generated by model systems of zeln, corn amylopectin and corn oil extruded at barrel temepratures of 120°C and 165°C were analyzed by GC and GC/MS. The largest quantities of lipid oxidation products were detected in systems containing all three components. In each system, the quantity of 2,4-deca-dienal was low relative to the quantities of hexanal, heptanal and benzaldehyde. Identification of the Maillard reaction products, 2-methyl-3(or 6)-pentyl-pyrazine, 2-methyl-3(or 6)-hexylpyrazine and 2,5-di-methyl-3-pentylpyrazine, suggested that lipid-derived aldehydes might be involved in the formation of substituted pyrazines. 4-Methylthiazole was identified as a major decomposition product of thiamin when corn meal containing 0.5% thiamin was extruded at a final temperature of 180°C. 

The first direct evidence for the existence of anionic cr-adducts was presented by Zoltewicz and Helmick (72JA682). They identified anionic (T-adducts 18, 19, and 20 by the addition of pyrazine, pyrimidine, and pyr-idazine, respectively, to excess sodium or potassium amide in liquid ammonia. Identification was made possible by H-NMR spectroscopy. 

So, NMR spectra of 4,4 -bipyridyl, pyrazine, and ethylenediamine coordinated to undecatungstocobalto(III)silicate and -borate anions. Identification of 1 1 and dumbbell-shaped 12 complexes, Bull. Korean Chem. Soc, 14 759 (1993) (c) J.L. Samonte and M.T. Pope, Derivatization of polyoxotungstates in aqueous solution. Exploration of the kinetic stability ofcobalt(II)- and cobalt(III) derivatives of lacunary anions with pyridine and pyridine-type ligands. Can. J. Chem.. In press... 

In 1960, Mold et al. (2592) reported the isolation and identification of the tricyclic A-heterocyclic 5H, QH-dipyrrolo[l,2-fl r,2 -(i]pyrazine-5,10-dione (pyrocoll) V (Figure XVlI.E-3) from CSC and demonstrated its relationship to its precursor in tobacco, the amino acid proline. Obviously, pyrocoll is not an aza-arene but an amide. Rodgman and Cook (3279) reported the identification of indole, carbazole, and several alkylated indoles and car-bazoles in CSC and confirmed the presence of 5H, QH-dipyrrolo[l,2-fl r,2 -(i]pyrazine-5,10-dione (pyrocoll) V described previously by Mold et al. (2592). Rodgman and Cook also assessed previously reported biological studies on indole, 3-methylindole (skatole), and carbazole None was reported to be tumorigenic in laboratory animals [Hartwell (1544), Shubik and Hartwell (3664)]. 

In his 1968 review of tobacco and tobacco smoke composition, Stedman (3797) discussed the identification of tumorigenic A-heterocyclic compounds [dibenz[fl,/t]acridine, dibenz[fl, ]acridine, and 7//-dibenzo[c, carbazole] reported by Van Duuren et al. (4027), as well as the identification of the following A-heterocyclic compounds 5//,10//-dipyrrolo[l,2-fl T,2 -(i]pyrazine-5,10-dione (pyrocoll), 9//-pyrido[3,4-fc] indole (norharman), l-methyl-9/f-pyrido[3,4-fc]indole (harman), and 9//-pyrido[2,3-fc]indole. 

Mold et al. (2592) reported the isolation and identification of the tricyclic iV-heterocyclic 57/,107/-dipyrrolo[l,2-a r,2 -(f] pyrazine-5,10-dione (pyrocoll) from CSC and its relationship to its precursor in tobacco, the amino acid proline. 

Rodgman and Cook (3279) conflrmed the presence in CSC of 5//,10//-dipyrrolo[l,2-a r,2 -alkylated indoles and carbazoles. Rodgman and Cook (3279) also reviewed the previously reported biological studies on indole, 3-methylindole (skatole), and carbazole None of the three was reported to be tumorigenic. 

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