background and overview[1][2]
the chinese alias of 4′-trifluoromethylacetophenone is p-trichloromethylacetophenone, chemical formula c9h7f3o. molecular weight 188.14600. white solid, density 0.92, melting point 30-33 °c (lit.), boiling point 79-80 °c 8 mm hg (lit.), flash point 184 °f. 4′-trifluoromethylacetophenone can be used as an intermediate for pharmaceutical and chemical synthesis. if 4′-trifluoromethylacetophenone is inhaled, move the patient to fresh air; if there is skin contact, take off contaminated clothing, wash the skin thoroughly with soap and water, and seek medical attention if you feel unwell; if in case of eye 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 [2, 4-5]
method 1: add 41.6g chlorocyclohexane (0.35mol) dropwise to a suspension of 4.65g lithium particles (0.68mol) in 350g thf at -55°c and select 2 hours of addition time. after >97% conversion of chlorocyclohexane as measured by gc (10 hours in total), 38.3 g of 4-bromotrifluorotoluene (0.170 mol) was added dropwise over 15 minutes at the same temperature. after stirring for a further 30 min at -50°c, the reaction mixture was added to 25.5 g of acetic anhydride (0.25 mol) in 50 g of thf at -30°c (30 min). after stirring for a further 30 minutes, the reaction mixture was poured into 120 g of water, the ph was adjusted to 6.3 with 37% hcl and the low boilers were distilled off under slight vacuum at 45°c. the organic phase was separated and the aqueous phase was extracted twice with 70 ml of toluene each time. the combined organic phases were fractionated under vacuum to obtain 29.5 g of 4-trifluoromethylacetophenone as a colorless liquid (0.157 mol, 92.2%), gc purity >98% a/a.
method 2: add 41.6g chlorocyclohexane (0.35mol) dropwise to a suspension of 4.65g lithium particles (0.68mol) in 350g thf at -55°c and select 2 hours of addition time. after the conversion of chlorocyclohexane was >97% as determined by gc (10 hours in total), a mixture of 38.3 g of 4-bromotrifluorotoluene (0.170 mol) and 7.0 g of acetonitrile (0.170 mol) was added dropwise at the same temperature. lasts 15 minutes. after stirring for a further 30 minutes at -50°c, the reaction mixture was slowly thawed to room temperature and subjected to aqueous work-up in the usual manner. :the yield of 4-trifluoromethylacetophenone after distillation is 81%.
main reference materials
[1]wehle, detlef; forstinger, klaus; meudt, andreas patent .us20050001333.method for producing, via organometallic compounds, organic intermediate products