Optimal Synthesis of Substituted and Branched Pyrazines via Reaction of Alpha Hydroxy Ketones with Selected Nitrogen Sources

Abstract

SummaryEmployment of 1-hydroxy-acetone as a carbon source and NH4OH as a source of base and nitrogen, has enabled arrays of pyrazines to be synthesized. Reaction conditions such as temperature, time, carbon/nitrogen mole ratios and pH were optimized to maximize the quantity of pyrazines, thereby providing the synthesis of at least 19–20 structurally different pyrazines. Addition of amino acids, selected aldehydes, and hydrolyzed tobacco-derived F1 protein has positively impacted the array of pyrazines from both qualitative and quantitative aspects. Results further showed that by changing the carbon source from 1-hydroxy-acetone to 1-hydroxy-2-butanone and/or 2-hydroxy-3-butanone, control of the type of pyrazines being synthesized could be realized in that the qualitative and quantitative distributions of the pyrazine array were shifted to higher molecular weight derivatives. A relatively large scale reaction (1.5 L) employing optimized parameters yielded > 2 g of a diverse array of pyrazines dominated by multiple dimethylpyrazine derivatives. While systematically varying reaction conditions and reagent mole ratios can predictably alter the distribution and yield of pyrazines, the two most overwhelmingly significant factors governing these two pyrazine product characteristics included the structure of the carbon source and the presence or absence of aldehydes and free amino acids.

Optimization of α-Hydroxyketone and Pyrazine Syntheses Employing Preliminary Reactions of Glucose and Buffer Solutions

“…The pyrazine distribution dramatically shifted toward C3 and C4 pyrazines having ethyl alkyl substituents, as the amount of 1-hydroxy-2-butanone was stepwise increased. This observation is consistent with our earlier work with α-hydroxyketones (13).…”

“…Reaction protocols that significantly reduce or eliminate their presence in a pyrazine array and result in a corresponding increase of other substituted pyrazines of higher molecular weight, thereby having desirable sensory properties, would be viewed very positively for flavor applications. Detailed investigations of the pyrazine literature strongly suggest that the structure of the carbon precursor in pyrazine ring formation reactions has a notable impact on structures of the pyrazine array (12)(13)(14). In addition, when amino acids capable of producing Strecker aldehydes are used in model pyrazine reactions, the alkyl portion of the Strecker aldehyde structures appear as carbon substituents on the aromatic ring of the resultant pyrazines (12).…”