Synthesis Of Key Intermediate Of Furanone: 3,4-Dihydroxyhexane-2,5-dione

This thesis was based on the previous work of our research group. The current work systemically studied the preparation and property of 3,4-dihydroxyhexane-2,5-dione, a key intermediate in the synthesis of natural flavor Furanone, with the aid of GC, GC-MS, X-Ray single crystal diffraction, NMR, IR, MS, HPLC. The work and achievements are mainly included:1. An internal standard quantitative analysis method of threo-3,4-dihydroxyhexane-2,5-dione was established using the gas chromatography, and it was found that the yield of threo-3,4-dihydroxyhexane-2,5-dione by coupling of methylglyoxal in the present of zinc was 57%. The liquid chromatography was also used to preliminarily analyze the reaction process.2. The separation condition was optimized, and the isolated yield was improved from 36% to 47%.3. The material and energy consumption of the reaction system had been reduced as follows: (a) the water needing evaporate was reduced to 1/3 of original, (b) the extractive solvent was reduced to 2/5 of the original, and replacing the reduced pressure-low temperature solvent recovery method by the atmospheric pressure recovery method, (c) abandoned zinc powder was activatted for recycling used, (d) carrying out the reaction in air instead of an inert gas atmosphere such as N₂.4. Checked by GC-MS, it was found that hydrodimerization of methylglyoxal with zinc in aqueous acetic acid solution furnished two 3,4-dihydroxyhexane-2,5-dione with threo and erythro form. From gas chromatographic analysis, the total yield of 3,4-dihydroxyhexane-2,5-dione was about 70%, 57% being in the threo form and 12.4% in the erythro form. This result corrected the misunderstanding that the hydrodimerization of methylglyoxal in such condition only obtain threo-3,4-dihydroxyhexane-2,5-dione reported by literatures.5. The stereochemistry of 3,4-dihydroxyhexane-2,5-dione with mp 90℃ was confirmed by X-ray single crystal diffraction. The molecule is a racemic mixture of RR and SS enantiomers, confirming the conclusion that it is in the threo form. It was also found that the threo-3,4-dihydroxyhexane-2,5-dione molecule has an intramolecular hydrogen-bond, and an intermolecular hydrogen-bond interaction links the molecules into an infinite zigzag chain that different from literatures.6. To explain the experimental observations and the result from NMR analysis of reaction mixture, the thesis proposed a possible mechanism for zinc-mediated pinacol coupling and reduction of methylglyoxal. During the reaction, there are two potential pathways competing with each other generating either the pinacol coupling product 3.4-dihydroxyhexane-2,5-dione or the reduction product hydroxyacetone.7. A green conceptual flow chart for producing 3,4-dihydroxyhexane-2,5-dione and a reasonable way to deposite the reaction waste was proposed base on the experimental results.