Gutknecht pyrazine synthesis

What is Gutknecht pyrazine synthesis?

The Gutknecht pyrazine synthesis, also known as the Gutknecht condensation, is a chemical process that involves treating a ketone with nitrous acid HNO2 to form an oximino ketone. The oximino ketone is then reduced to an α-amino ketone that dimerizes to dihydropyrazine via a pinacol-like process. This intermediate is cyclized into pyrazine through dehydrogenation or oxidation using mercury (I) oxide Hg2O, copper (II) sulfate CuSO4, or atmospheric oxygen O2. The overall reaction, first reported by Gutknecht in 1879, produces pyrazine by cyclizing α-amino ketones.

Gutknecht pyrazine synthesis - general reaction scheme - Gutknecht condensation
Gutknecht pyrazine synthesis

Examples of the Gutknecht pyrazine synthesis include the conversion of α-amino acetone in ammonia solution to dimethylpyrazine through the oxidation of mercuric chloride HgCl2. Similarly, p-methyl-α-aminoacetophenone and α-aminopropiophenone are converted into 2,5-dip-toylypyrazine and 3,6-diphenyl-2,5-dimethylpyrazine, respectively.