The synthetic procedure of stable isotope-labeled Vanillin is as follows:
Under ice-salt bath, dissolve 1.52g Vanillin, 360mg methanol-D4 and 2.62g triphenylphosphine in 10mL tetrahydrofuran solution, slowly dropwise (preferably one drop every 2s) azodiisopropyl ester in tetrahydrofuran solution (2.02g/5mL) ), the temperature was kept at 0～5 ℃, continued stirring for 60min after the dropwise addition, TLC (thin layer chromatography) spot plate monitoring, after the reaction was completed, the tetrahydrofuran solvent was removed by spinning off, and the column chromatography was separated to obtain formazan with a yield of 98%. The base vanillin-D3 is the product, and the obtained product has a chemical purity of 99.5% and an isotopic abundance of 99.9%.
In a 1-liter autoclave, 100.0 g (0.66 mol) of ortho-vanillin, 350 ml of ethyl acetate, and 6.0 g of 10% palladium on carbon were added. Start stirring at 400 rmp, replace the air in the kettle with nitrogen, and then replace the nitrogen with hydrogen. After the reaction was completed, the palladium carbon was filtered off, the solvent was recovered, and 89.4 g of 6-methylguaiacol (content 99.8%) was obtained by distillation under reduced pressure, and the yield was 98.0%. MS(EI), m/s, 138(M+, 89), 123.1(100), 95.2(19), 77.2(22), 67(13), 65(10), 39.2(9). 1H NMR (500 MHz, CDCI3) δ, 2.66 (3H, s, CH3), 3.88 (3H, s, OCH3), 5.68 (1H, s, OH), 6.70-6.78 (3H, m, ArH).
55.2g (0.40mol) of 6-methylguaiacol was added to the reaction flask 1, then 80.0g of 20% aqueous sodium hydroxide solution was added to dissolve it, and 62.2g (50%w of glyoxylic acid) was added to the reaction flask 2 /w, 0.42mol) solution and 80.0g of 20% aqueous sodium hydroxide solution; the reaction solutions of the two reaction flasks were combined, and 41.6g of 20% aqueous sodium hydroxide solution was added until the pH of the reaction system was 12.0. The reaction was carried out at 30°C for 12h. The total amount of the reaction mixture was 319.0 g, and by liquid phase analysis, 4-hydroxy-3-methoxy-5-methylmandelate was 20.8%, and the yield was 84.6%.
Into a 1-liter autoclave, 361.4 g of the synthesized reaction solution (containing 77.34 g of 4-hydroxy-3-methoxy-5-methylmandelate) and 6.2 g of catalyst CuO were added. Start stirring at 400 rmp, replace the air in the kettle with nitrogen, and then replace nitrogen with oxygen. The oxygen pressure is maintained at 0.15 MPa, and the reaction is carried out at 80 ° C for 6 h. After the reaction, the catalyst was filtered out, and the reaction solution was acidified to pH 3-4 with 50% aqueous sulfuric acid solution, and extracted with chloroform; chloroform was recovered and distilled to obtain 57.7 g of 5-methyl vanillin (content 99.5%) in a yield of 57.7 g. 87.5%.