2- 2 - styryl pyrazine

Both 2- and 3-methyl groups in pyrido[2,3-Z ]pyrazines are acylated by ethyl oxalate (71TH21500). They give (preferentially 3-) styryl derivatives with aromatic aldehydes and oximes with pentyl nitrite. 

The (Z)- and ( )-styrylpyrazine structures 20j and 20k were assigned on the base of the mass, NMR, and UV spectral data. The mass spectrum of Z isomer (20j) shows a base peak (the molecular ion) at m/z 210 with a peak at m/z 133 formed by the loss of a phenyl group firom 20j. The H-NMR spectrum shows the presence of five aromatic and two olefinic protons in addition to one heteroaromatic proton and two methyl groups attached to the heteroaromatic nucleus. Ozonolysis of the Z isomer (20j) yields 3-formyl-2,5-dimethylpyrazine (487) and benzaldehyde, confirming the styryl moiety in 20j. The ( )-styryl derivative (20k) is readily isomerized to the Z isomer (20j) on exposure to sunlight (Scheme 60). Extraction of the pyrazines from I. humillis in the dark indicates that E isomer 20k is the naturally occurring product 144,145). 

By Oxidation of Alkyl-, Styryl-, Hydroxyalkyl-, and Fused Pyrazine Systems... 

A ring methyl group condenses with benzaldehydes to yield styryl compounds, but the condensation needs an auxiliary reagent such as acetic anhydride <87S638> or zinc halide, and forcing reaction conditions at reflux or temperatures above 200 °C. In contrast, the condensation of methyl-pyrazine 7V-oxides with benzaldehyde proceeds smoothly by treatment with sodium methoxide in refluxing methanol (Scheme 27) <83JHC169>. 

The 2-or 3-methyl derivatives also undergo aldol condensation in the presence of acidic or basic catalysts. The products obtained are either secondary alcohols or their dehydrated derivatives, depending on the structure of the aldehyde used in the condensation. In acetic anhydride only nitrobenzaldehydes gave any products. 2,3-Dimethylpyrido[2,3-h]pyrazine and its 7-bromo derivative gave styryl derivatives assumed to be of type 91. p-Nitrobenzaldehyde gave the alcohols 92. Again substitution at the 3-position is assumed. In ethanolic sodium ethoxide solution,... 

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