Continuous microchannel synthesis and crystallization engineering of tetramethylpyrazine: Process performance and product quality

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Tetramethylpyrazine (TTMP) is an aroma-active food ingredient whose manufacture requires efficient synthesis and downstream purification. This study compared continuous microchannel synthesis with magnetic stirring, high-pressure, and static heating systems and further evaluated crystallization, recrystallization, and product performance. The microchannel reactor achieved comparable TTMP concentrations within a shorter processing time and the highest space-time yield among the investigated systems. TTMP dissolution reached 77.32% at 80 °C, with little further increase at 90 °C. The apparent nucleation temperature was 65–66 °C, and cooling at 5 °C h −1 gave the highest crystal recovery of 84.70%. Solvent selection affected crystal habit and inclusion characteristics, while Raman analysis supported the presence of acetonitrile-containing mother liquor in selected inclusions. Repeated recrystallization increased the relative TTMP peak-area contribution from 98.23% to 99.23%, increased whiteness from 91.04 to 95.43, and reduced chroma from 5.25 to 0.40. XRD showed no detectable shifts in the characteristic diffraction peaks, while DSC revealed broadly similar melting behavior but differences in cooling crystallization behavior among the samples. Volatile fingerprinting differentiated TTMP products obtained through different processing routes. The magnetic-stirring sample exhibited the highest solid-state volatility and the fastest apparent release in water, whereas the microchannel-derived sample showed lower headspace responses in water and 5% ethanol. These findings link reactor performance, crystallization conditions, solid-state and thermal characteristics, recovery, and release behavior, providing an engineering basis for continuous TTMP manufacture and purification.