Synthesis and Evaluation of Pyrazine Derivatives with Herbicidal Activity

Abstract

The pyrazine ring is a part of many polycyclic compounds of biological and/or industrial significance; examples are quinoxalines, phenazines, and bio-luminescent natural products pteridines, flavins and their derivatives. All these compounds are characterized by a low lying unoccupied π-molecular orbital and by the ability to act as bridging ligand. Due to these two properties 1,4-diazines, and especially their parent compound pyrazine, possess a characteristic reactivity. Pyrazine is a weak diacid base (pK1 = 0.57; pK2 = -5.51), weaker than pyridine, due to the induction effect of the second nitrogen (Bird, 1992). Its inherent bifunctionality and the low lying unoccupied molecular orbital permit pyrazine to form coordination polymers having unusual electrical and magnetic properties (Brown & Knaust, 2009). 1,4-Diazines may be employed to study interand intramolecular electron transfer in organic, inorganic and biochemical reactions. Autocondenzation of α-aminocarbonyle compounds to the dihydropyrazine derivative, which is followed by oxidation on the final substituted pyrazine, or the condenzation of α,β-dicarbonyle and α,β-diamino compounds forming during the fermentation of saccharides and peptides are the main routes of pyrazine ring building. Pyrazines are found mainly in processed food, where they are formed during dry heating processes via Maillard reactions (Maillard, 1912). They are also found naturally in many vegetables, insects, terrestrial vertebrates, and marine organisms, and they are produced by microorganisms during their primary or secondary metabolism (Adams et al., 2002; Beck et al., 2003; Wagner et al., 1999; Woolfson & Rothschild, 1990). The widespread occurrence of simple pyrazine molecules in nature, especially in the flavours of many food systems, their effectiveness at very low concentrations as well as the still increasing applications of synthetic pyrazines in the flavour and fragrance industry are responsible for the high interest in these compounds (Maga, 1992). Certain pyrazines, especially dihydropyrazines, are essential for all forms of life due their DNA strandbreakage activity and/or by their influencing of apoptosis (Yamaguchi, 2007). Synthetic pyrazine derivatives are also useful as drugs (antiviral, anticancer, antimycobacterial, etc.), fungicides, and herbicides (Doležal, 2006a). Furthermore, a simple pyrazine compound, 3amino-6-chloro-pyrazine-6-carboxylic acid, has shown anti-auxin behaviour (Camper & McDonald, 1989). The importance of the pyrazine (1,4-diazine) ring for the biological