An Improved Preparation of 3,5-Bis(trifluoromethyl)acetophenone and Safety Considerations in the Preparation of 3,5-Bis(trifluoromethyl)phenyl Grignard Reagent

• Published in: Journal of organic chemistry Vol. 68; no. 9; pp. 3695 - 3698
• Main Authors: Leazer, Johnnie L., Cvetovich, Raymond, Tsay, Fuh-Rong, Dolling, Ulf, Vickery, Thomas, Bachert, Donald
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 02.05.2003; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Noncondensed benzenic compounds; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; MAGNESIUM; ASYMMETRIC-SYNTHESIS; ANTAGONIST; MECHANISM; REDUCTION; Thermal instability; Grignard reagent; Bromination; Acetophenone derivatives; Aromatic compound; Fluorine Organic compounds; Chemical synthesis
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo026903n

An improved and efficient bromination of 3,5-bis(trifluoromethyl)benzene was developed. A safe and reliable preparation of the potentially explosive 3,5-bis(trifluoromethyl)phenyl Grignard and 3-trifluoromethylphenyl Grignard reagents, from the precursor bromides, is described. Reaction System Screening Tool (RSST) and Differential Thermal Analysis (DTA) studies suggest these trifluoromethylphenyl Grignard reagents can detonate on loss of solvent contact or upon moderate heating. When prepared and handled according to the methods described herein, these Grignard reagents can be safely prepared and carried on to advanced intermediates.