Preparation and application of 5-chloro-2-thiophenemethanol_Industrial additives

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 on a 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. , after the solution is clear, add the next batch of arkema, each batch is about 1 gram, and complete the addition 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 conditions at 0°C, dropwise add thionyl chloride (482mg, 4.05 mmol), after the dropwise addition is completed, heat and stir at 50°C for 3 hours. The TLC plate detects the end of the reaction. The solvent is evaporated under reduced pressure to obtain 480 mg of yellow liquid (yield: 85.5%).

Main reference materials

[1] CN107188865 Benzoxazine compounds and their preparation methods and uses

[2] CN105732570 A kind of cyclohexenone compound containing five-membered heterocyclic ring and its application