Background and overview[1]
2,4,6-Trifluorobenzyl alcohol is an organic intermediate that can be prepared in two steps from 1,3,5-trifluorobenzene as raw material. There are reports in the literature that it can be used to prepare the pesticides imidacloprid, acetamiprid, and the pharmaceutical intermediate 2,4,6-trifluorobenzylamide.
Preparation[1]
Report 1: Preparation of 2,4,6-trifluorobenzaldehyde
Put 500g tetrahydrofuran and 132g 1,3,5-trifluorobenzene into a 2000ml four-neck bottle, cool to -60℃, add 2.5N500ml butyllithium dropwise at -60~-90℃, add dropwise for about 1.5h, add After incubation for 2 hours, 80g N,N-dimethylformamide and 100g tetrahydrofuran solution were added dropwise to the system. The temperature was controlled below -60°C. The addition was completed and the incubation reaction was completed for 3 hours. After incubation, the temperature was raised to -30°C and set aside. Put 650g water, 226g 30% hydrochloric acid, and 190g sodium chloride into another 3000ml four-neck bottle, stir, add the above low-temperature reaction solution dropwise at 20°C, complete the addition, keep it warm for 0.5h, layer, use 200g methyl tert-butyl for the water layer Extract with base ether, combine the organic layers, and evaporate the solvent to obtain 145g of 2,4,6-trifluorobenzaldehyde, GC: 97%, yield 90%. The final product was subjected to mass spectrometry and elemental analysis, and the results were as follows: Mass spectrum: m/z: 160.01 (100.0%), 161.02 (7.6%). Elemental analysis: C, 52.52; H, 1.89; F, 35.60; O, 9.99. It was confirmed that 2,4,6-trifluorobenzaldehyde was obtained.
Report 2: Preparation of 2,4,6-trifluorobenzyl alcohol
Put 17.2g potassium borohydride and 100g ethanol into a 2000ml four-neck bottle, raise the temperature to 30°C, add dropwise 138g 2,4,6-trifluorobenzaldehyde and 200g ethanol solution, control the temperature below 35°C, and complete the insulation reaction. , control until there is no raw material, stop the reaction, evaporate the solvent, add 600g of water to the reaction bottle and stir until completely dissolved, separate the layers, extract the water layer with 150g of methyl tert-butyl ether, combine the organic layers to remove the solvent, and distill to obtain 117g GC: 96.2%, yield 86%. The final product was subjected to mass spectrometry and elemental analysis, and the results were as follows: Mass spectrum: m/z: 162.03 (100.0%), 163.03 (7.6%). Elemental analysis: C, 51.86; H, 3.11; F, 35.16; O, 9.87. It was confirmed that 2,4,6-trifluorobenzyl alcohol was obtained.
Apply[1]
2,4,6-Trifluorobenzyl alcohol is used to prepare 2,4,6-trifluorobenzylamine. The method is as follows:
Step 1, preparation of 2,4,6-trifluorobenzyl chloride
Put 171.6g 2,4,6-trifluorobenzyl alcohol, 316g tetrahydrofuran and 106g pyridine into a 2000ml four-neck bottle, cool the temperature to 20℃, add 160g thionyl chloride dropwise, control the temperature not to be higher than 30℃, add about 1.5h, after the dropwise addition is completed, raise the temperature to 50°C for reaction, control until there is no raw material and intermediate, cool down to 20°C, add 500g of water, stir for 30min, let stand for stratification, extract the water layer with 150g of methylene chloride, and combine In the organic layer, the solvent was recovered to obtain 176g of material. GC: 94.1%, yield 91.4%. The final product was subjected to mass spectrometry and elemental analysis, and the results were as follows: Mass spectrum: m/z: 145.03 (100.0%), 146.03 (7.6%). Elemental analysis: C, 57.94; H, 2.78; F, 39.28. It was confirmed that 2,4,6-trifluorobenzyl chloride was obtained.
Step 2, preparation of 2,4,6-trifluorobenzylamine
Put 700g ethanol and 141g urotropine into a 2000ml four-neck bottle, raise the temperature to 65°C, add 134g 2,4,6-trifluorobenzyl chloride dropwise under reflux, the dropping speed is equal to the reflux, the dropping time is 1 hour, add After completion of the insulation reaction, control until there is no raw material. The insulation time is 5 hours. Cool to 20°C. Add 450g of 36% hydrochloric acid dropwise. After adding, raise the temperature to 40°C. Control until there is no intermediate in the insulation reaction. Keep the temperature for 4 hours. Cool to 15°C. Filter to remove the remaining substances in the system. salt, recover ethanol from the filtrate, steam until there is no flow, add 1500g of water to the reaction vessel, stir until fully dissolved, add 10g of activated carbon for decolorization, and obtain a clear filtrate. Add 180g of 30% liquid caustic soda to adjust the pH to 12, and let stand for layering to obtain an organic layer. The aqueous layer was extracted twice with 200g of methylene chloride, the organic layers were combined, the solvent was recovered, and 98.2g of the product was obtained by distillation, GC: 98.96%, yield 82.5%. The final product was subjected to mass spectrometry and elemental analysis, and the results were as follows: Mass spectrum: m/z: 161.05 (100.0%), 162.05 (7.6%). Elemental analysis: C, 52.18; H, 3.75; F, 35.57; N, 8.69. It was confirmed that 2,4,6-trifluorobenzylamine was obtained.
References
[1][China invention, China invention authorization] CN201410853129.7 Preparation method of 2,4,6-trifluorobenzylamine compound
