A phosphate buffer was found to significantly promote tetramethylpyrazine (TMP) formation in an acetoin (3-hydroxy-2-butanone)/ammonium hydroxide system. The effect of the phosphate ion on TMP formation was additive in the range of 0.05-0.2 M. The change in pH value of the system reveals that a proton-coupled redox type of reaction occurred during TMP formation, Phosphate serves both as proton donor and acceptor to facilitate proton transfer during the Schiff base formation between ammonia and 3-hydroxy-2-butanone. Protic solvents, methanol, and ethanol, were found to attract the water released from the system, The combination of a phosphate buffer and protic solvent led to the completion of TMP formation, The TMP formation mechanism in a phosphate buffer (pH 7.2) is proposed.