Synthesis And Analysis Of 2,6-dimethyl- Gamma-pyrone

2,6-dimethyl-gamma-pyrone is an important raw material and pharmaceutical intermediate. Its various derivatives are intermediates of antibacterials, anti- cancer drugs and allergy drug in pharmaceutical industry. It is also used as the raw material in manufacturing aromatizer, dyestuff and herbicide. 2,6-dimethyl- gamma- pyrone should be synthetized, because its natural product didn't exist in nature.The synthesis conditions of 2,6-dimethyl-gamma-pyrone was harsh with so many by-products in U.S. patent. The synthesis, purification,qualitatively and quantitatively analysis were studied in this paper.According to relevant reaction mechanism, the amount and varieties of catalysts, the matching of reactant, the reaction temperature and time, varieties of the solvent and extraction solvent on the yield ratio of reaction product were studied with acetylacetone and methyl acetate as raw material. The results for this research as follows: sodium ethylate as alkaline catalyst, the mole ratio of acetylacetone: methyl acetate: sodium ethylate was 1:2.5:2, non-proton polarity solvent tetrahydrofuran for reaction medium, reaction temperature for 85℃, reaction time 6 h, ether as extractant.In this reaction conditions ,the maximum yield of 2,6-dimethyl-gamma-pyrone was 13.35%.The analytical method of 2,6-dimethyl-gamma-pyrone and acetylacetone in the reaction system of producing 2,6-dimethyl-gamma-pyrone. The qualitative analysis was conducted by infrared spectrometry and nuclear magnetic resonance spectra.The qualitative and quantitative analysis was conducted by high performance liquid chromatography(HPLC). The HPLC analysis conditions as follows: Eclipse XDB-C18 column(150 mmⅹ4.6 mm, 5μm) , tetrahydrofuran - water (20:80, V/V, including 0.5% Monosodium phosphate and 0.5% Disodium hydrogen phosphate,pH=5) as mobile phase,flow rate 0.6 mL/min, UV wavelength for 240 nm,column temperature 30℃, sample amount 3μL. Under this HPLC analysis conditions, the results showed that 2,6-dimethyl-gamma-pyrone and acetylacetone had a good linear relationship,the correlation coefficients were above 0.9999.The linear range was wide,and the linear range of 2,6-dimethyl-gamma-pyrone was 0.01~200.3 mg/L, acetylacetone 0.01~50.68 mg/L.The RSD of 2,6-dimethyl-gamma-pyrone and acetylacetone's chromatographic peak area was between 0.40% and 1.65%, RSD of retention time was 0.45~0.89%, the average recovery was 98.34~102.51%, the corresponding RSD was less than 1.0%. 2,6-dimethyl-gamma-pyrone and acetylacetone could be determinated in 15 min at the same time.Low yield is the main problem in 2,6-dimethyl-gamma-pyrone synthesis by this new synthetic routes,but it is feasible. The easy availability and low cost of reactants,the mild reaction conditions of this synthetic route have provided the basis for the study of low cost and high yield synthetic routes of 2,6-dimethyl- gamma-pyrone.This analysis method is of high sensitivity, accurate and reliable. By this method,the content of 2,6- dimethyl–gamma -pyrone and acetylacetone could be determinated, the content of reactants and intermedium could also be tracked and tested in the reaction of producing 2,6-dimethyl-gamma-pyrone with acetylacetone as raw material.It provides a rapid and effective analysis method for controlling of the reaction process, and it puts forward instructive suggestions for the optimization of 2,6-dimethyl-gamma-pyrone synthesis.