3-Trifluoromethyl-3-phenyldiazirine. A new carbene generating group for photolabeling reagents

Abstract

The synthesis of 3-trifluoromethyl-3-phenyldiazirine (TPD) is reported in an overall yield of 60% based on 2,2,2-trifluoroacetophenone as starting material. TPD is rapidly photolyzed on irradiation near 350 nm to yield 35% of the diazoisomer and 65% of the corresponding carbene. No internal rearrangement of the latter compound by fluorine migration was detected. Photolysis in methanol yielded the product of a formal OH insertion in greater than 95% yield. Photolysis in cyclohexane gave at least a 50% yield of the CH insertion product at a diazirine concentration of 15 mM. The products were identified by gas chromatographic mass spectra and by 19F NMR spectra. In the dark the diazirine is stable in 1 M acid or base and at temperatures as high as 75 degrees C for at least 30 min. The diazoisomer is much less photolabile and is stable in 0.1 M acetic acid for at least 12 h. The synthesis of a derivative of TPD containing the 2-hydroxyethyl[O-tosylate] group on the para position of the phenyl ring is described. This compound permits the easy attachment of the TPD function to other molecules. It is suggested that the ease of synthesis, dark stability, rapid photolysis, and reactivity of the carbene may make this group useful in the preparation of various photochemical probes.