Background and overview of the preparation method of 2,4,6-trimethylpyranium tetrafluoroborate
2,4,6-Trimethylpyranium tetrafluoroborate can be used as a pharmaceutical synthesis intermediate.
Preparation method of 2,4,6-trimethylpyranium tetrafluoroborate
Method 1: Add acetic anhydride (100mL, 1.06mol, 13.0 equivalent) and tert-butanol (8.00mL, 84.2mmol, 1.00 eq.) to a round-bottomed flask equipped with a condenser and dropping funnel. Fluoboric acid (14 mL, 78 mmol, 0.95 equiv) was added dropwise. During its addition, the temperature increased to 80°C. After the exothermic reaction was completed, the mixture was cooled to 5°C and cold Et2O was added, the precipitate was collected, washed with cold Et2O and dried. 2,4,6-Trimethylpyranium tetrafluoroborate was obtained as a colorless solid (11.6 g, 55.4 mmol, 71%). 1H NMR (300MHz, CD3OD, 300K) δ = 7.87 (s, 2H, CHaropicoline m), 2.88 (s, 6H, 2×CH3), 2.72 (s, 3H, CH3). 13 C NMR (75MHz, CDCl 3, 300K) δ = 179.5 (Cq), 134.1 (Cq), 124.3 (CH), 21.1 (CH 3), 20.7 (CH 3). 19F NMR (282MHz, CD3OD, 300K) δ = -154.7. Calculated HRMS (ESI) m/z = 123.0804. MS (ESI): C8H11O [M] +, found: 123.0762. The spectral data are consistent with previously reported data.
Method 2: Place acetic anhydride (1kg, 9.79mol, 10 equivalents) in a 2L double-neck round-bottomed flask. At room temperature, 4-hydroxy-4-methyl-2-pentanone (122 mL, 0.98 mol, 1 equiv) was added over 5 minutes using a pressure-equalizing dropping funnel, and the solution was stirred for 5 minutes. Use a pressure-balanced dropping funnel to add HBF4 (127 mL, 48% aqueous solution, 0.97 mol, 1 equiv) dropwise in 1 hour of zinc borate. The temperature of the reaction mixture during the addition was approximately 90°C. The color of the solution gradually changes from colorless to light orange to dark brown. The reaction mixture was heated and stirred at 80°C for an additional hour and then cooled to room temperature. The light-colored precipitate was filtered off with suction and washed with a total of 1 L of diethyl ether to obtain 135 g (0.64 mol, 66%) of light yellow crystalline 2,4,6-trimethylpyridine tetrafluoroborate. Yield 135g (0.64mol, 66%) Melting point (uncalibrated): 219.6-220.3℃dec. 1H NMR (CD3CN, 300 MHz, 20°C): δ 7.72 (s, 2H, m-methyl), 2.80 (s, 6H, o-methyl), 2.65 (s, 3H, p-methyl) ppm.
