2,3-Bis(4-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenyl)oxirane

Abstract

The title compound, which has two photoreactive groups in a molecule, was synthesized by the coupling reaction of 3-(4-(bromomethyl)phenyl)-3-(trifluoromethyl)-3H-diazirine in the presence of silver oxide in DMSO.

Diazirine based photoaffinity labeling is a useful chemical biology method to elucidate interactions between low molecular weight bioactive compounds and biomolecules [1]. Photoreactive compound contained two photophores [2,3] is one of the attractive tools for comprehensive analysis of ligand-biomolecule interactions by photoaffinity labeling.

We have synthesized a new two photophores containing compound, 2,3-bis(4-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenyl)oxirane 2, from 4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl bromide 1 with silver oxide in DMSO [4] without decomposition of diazirinyl ring. ¹H- and ¹³C-NMR chemical shifts for oxirane moiety (3.83 and 62.17 ppm) strongly indicated that the purified compound is trans- isomer [5,6]. The 2,3-trans two-photophores containing oxirane ring is utilized for introduction of 2 to ligand.

Experimental

Synthesis of 2,3-bis(4-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenyl)oxirane (2)

To a solution of 4-[3-(trifluoromethyl)-3H-diazirin-3-yl]benzyl bromide (1) [7,8] (0.10 g, 0.36 mmol) in anhydrous DMSO (1 mL), silver oxide (0.09 g, 0.39 mmol) was added. The resulting mixture was stirred overnight at room temperature until TLC showed the reaction to be complete. The reaction was filtered by Celite and treated with H₂O, which was extracted with diethyl ether. The combined oil layer was dried over MgSO₄ and subjected to rotary evaporation to remove the solvent. The crude product was purified by silica gel column chromatography (CH₂Cl₂/hexane, 1:1) to afford 2 (0.06 g, 41%) as a yellow solid. [α]_D −20 (c 0.5, CHCl₃). UV(CDCl₃) λ_max (ε) 250 (2120), 356 (1170). ¹H-NMR (270 MHz, CDCl₃): δ 7.37 (4H, d, J = 8.1 Hz,), 7.22 (4H, d, J = 8.1 Hz), 3.83 (2H, s). ¹³C-NMR (68 MHz, CDCl₃): δ 138.54, 129.48, 126.91, 126.02, 122.14 (q, ¹J_CF = 274.7 Hz), 62.17, 28.24 (q, ²J_CF = 40.6 Hz). ¹⁹F-NMR (470 MHz, CDCl₃): δ −65.22. HRMS (FD): m/z calcd for C₁₈H₁₀F₆N₄O: 412.0759; found: 412.0744.