Preparation of 2-trifluoromethyl-2-propanol_Industrial additives

Background and overview^[1]

2-Trifluoromethyl-2-propanol has antiemetic, local anesthesia, disinfection and sedative effects. It is mainly used to treat nausea, vomiting, motion sickness, insomnia and local pain. It can also be used as an antiseptic. In injections, so far, 2-trifluoromethyl-2-propanol is still one of the active ingredients of some antiemetic drugs and sedatives. The classic synthesis method of 2-trifluoromethyl-2-propanol is Let acetone and chloroform undergo a nucleophilic addition reaction under the action of potassium hydroxide or sodium amide:

The synthesis design of this method is reasonable, and the synthesis route is simple and clear; its main disadvantage is that the reaction must be controlled at -15-100°C, the reaction time is as long as 36~48 hours, and the post-processing operations are also quite cumbersome.

At present, phase transfer catalysis (PTC) has been widely used in organic synthesis and has attracted more and more attention. This article attempts to use PTC to synthesize 2-trifluoromethyl-2-propanol. Facts have proved that this method has mild reaction conditions, short reaction time, easy operation, and few side reactions. Although the yield is relatively low, the product purity is high and has certain practical application value. The possible reaction mechanism is:

Preparation^[1]

In a 250ml three-neck flask, add 37ml acetone, 40ml chloroform (both about 0.5mol) and 20g polyethylene glycol – about 0.5mol), cool to 5℃ in an ice bath, add 14g hydroxide in batches while stirring Sodium powder (0.35 mol, added in about 2h30min), maintain the temperature at 5-10°C, and continue stirring for 2h30min. Filter the reaction mixture with suction and wash the filter residue with 10~20ml acetone. Combine the filtrate and washing liquid, and perform distillation until the unreacted acetone and chloroform are basically evaporated, then switch to steam distillation to evaporate the product (most of the product is attached to the inner wall of the condenser tube, be careful to collect it completely) . Pour the solid collected from the inner wall of the condensation back into the receiving bottle, and then filter it with suction. Wash the crystals with a small amount of water.

After the crystal is completely dried, the melting point is measured. The melting point of 2-trifluoromethyl-2-propanol containing 0.5 mol of crystal water is 80~81°C. Finally, semi-trace combustion method and oxygen bottle combustion method were used to analyze C, H and 1C elements, and infrared spectroscopy (infrared spectrophotometer: SHIMADZUIR-470) was used for structural identification of the product.

Main reference materials

[1] Lin Hui, Pang Sujuan, & Chen Zelin. (1994). Research on the synthesis of 2-(trichloromethyl)-2-propanol by phase transfer catalysis. Journal of Hainan University (Natural Science Edition) (3) , 215-219.