Background and overview[1]
5-Chloro-2-thiophenemethanol can be used as a pharmaceutical synthesis intermediate. If 5-chloro-2-thiophenemethanol is inhaled, move the patient to fresh air; if there is skin contact, take off contaminated clothing, rinse the skin thoroughly with soap and water, and seek medical attention if you feel uncomfortable; if the eyes are clear In case of contact, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.
Structure
Preparation[1-2]
The preparation of 5-chloro-2-thiophenemethanol is as follows:
Method 1: Add potassium borohydride (739 mg, 13.6 mmol) to a solution of compound 6-1 (2 g, 13.6 mmol) in ethanol (20 mL) at 0°C, slowly raise the temperature to room temperature, and stir at room temperature for 2 hours. , monitor the reaction with a TLC plate. After the reaction, add aqueous ammonium chloride solution (20mL) to the system, extract with ethyl acetate (100mL), wash the organic phase with saturated brine (50mL), dry over anhydrous sodium sulfate, and evaporate under reduced pressure. The solvent was removed, and the crude product was purified by silica gel column (mobile phase, petroleum ether: ethyl acetate = 4:1) to obtain 1.52g of yellow liquid 5-chloro-2-thiophenemethanol.
Method 2: Thiophene-2-methanol (33.60 g, 294 mmol) is dispersed in 200 ml of methylene chloride, and N-chlorosuccinimide (39.30 g, 294 mmol) is added in batches under ice bath. , add the next batch after the solution is clear, each batch is about 1 gram, and finish adding in 1 hour. After 4 hours, wash with saturated sodium carbonate solution, separate the layers, dry and dehydrate, and filter to obtain 5-chloro-2-thiophenemethanol for later use.
Apply[1]
5-Chloro-2-thiophenemethanol can be used as a pharmaceutical synthesis intermediate. If the following reaction occurs:
The specific steps are: under nitrogen protection at 0°C, add thionyl chloride (482mg, 4.05mmol) dropwise to a solution of 5-chloro-2-thiophenemethanol (500mg, 3.37mmol) in tetrahydrofuran (10mL). After the addition was completed, the mixture was heated and stirred at 50° C. for 3 hours. The TLC plate detected the end of the reaction. The solvent was evaporated under reduced pressure to obtain 480 mg of yellow liquid (yield: 85.5%).
