1-[(2-Chloro­phen­yl)di­phenyl­meth­yl]-1H-pyrazole

The title compound C₂₂H₁₇ClN₂, also named as TRAM-34, crystallizes in the monoclinic space group P2₁/n. The dihedral angles between the pyrazole ring and the three six-membered rings are 62.28 (9), 69.48 (9) and 71.30 (9)°.

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Chemical scheme

Structure description

The title compound, C₂₂H₁₇ClN₂ (I) Fig. 1, also named as tri­aryl­methane-34 (TRAM-34), is a structural isomer of the anti-fungal drug clotrimazole or 1-[(2-chloro­phen­yl)di­phenyl­meth­yl]-1H-imidazole. TRAM-34 is a selective and potent inhibitor of the inter­mediate-conductance, calcium-activated K⁺ channels K_Ca3.1 (K_D = 20–25 nM) (Wulff et al., 2000, 2001). TRAM-34 was synthesized and investigated in two studies to analyze the in vivo effect of combined irradiation and K_Ca-targeting with TRAM-34 in a glioma mouse model (Stransky et al., 2023; Ganser et al., 2024).

Figure 1 The mol­ecular structure of I. Displacement ellipsoids are drawn at the 50% probability level.

The dihedral angles in I between the pyrazole ring and the three six-membered rings (C7–C12, C13–C18, and C19–C24) are 62.28 (9), 69.48 (9), and 71.30 (9)°, respectively. The 2-chloro­benzene ring (C19–C24) is almost perpendicular to the C13–C18 ring [dihedral angle = 81.27 (7)°]. The dihedral angles between the C7–C12 ring and the C13–C18 and C19–C24 rings are 71.44 (8) and 69.05 (8)°, respectively. For the crystal structure of clotrimazole, see Song et al. (1998). In the extended structure of (I), some weak C—H⋯π inter­actions (Table 1) link the mol­ecules Fig. 2.

Table 1
Hydrogen-bond geometry (Å, °)

Cg2 and Cg3 are the centroids of the C7–C12 and C13–C18 rings, respectively.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C6—H6⋯Cg3^i	0.94	2.93	3.5594 (16)	125
C16—H16⋯Cg2^ii	0.94	2.88	3.6868 (18)	145
C20—H20⋯Cg3	0.94	2.89	3.6164 (17)	135
Symmetry codes: (i) ; (ii) .

Figure 2 Part of the packing diagram viewed along the c-axis direction. Hydrogen atoms removed for clarity.

Synthesis and crystallization

The title compound was prepared using the synthetic strategy reported by Wulff et al. (2000). To a suspension of 2-chloro­trityl chloride (12.5 g, 40 mmol) in aceto­nitrile (500 ml) was added pyrazole (8.17 g, 120 mmol). The reaction mixture was heated to reflux temperature for 3 h (during this time the reaction mixture became clear). After cooling to room temperature, the solvent was removed, and the residue was dissolved in ethyl acetate (200 ml). The organic phase was washed with water (3 × 150 ml). During this process, the title compound precipitated as a white solid, which was collected by filtration and dried (3.44 g, 25%). The filtrate was dried over sodium sulfate and solvent was evaporated. The obtained residue was recrystallized from hot ethanol solution to yield additional 7.11 g (52%) of the title compound as colorless crystals.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C22H17ClN2
Mr	344.82
Crystal system, space group	Monoclinic, P21/n
Temperature (K)	233
a, b, c (Å)	8.8768 (3), 18.3002 (7), 10.5053 (3)
β (°)	95.942 (3)
V (Å^3)	1697.39 (10)
Z	4
Radiation type	Mo Kα
μ (mm^−1)	0.23
Crystal size (mm)	0.40 × 0.30 × 0.06
Data collection
Diffractometer	Stoe IPDS 2T
No. of measured, independent and observed [I > 2σ(I)] reflections	22452, 4092, 2854
Rint	0.070
(sin θ/λ)max (Å^−1)	0.661
Refinement
R[F^2 > 2σ(F^2)], wR(F^2), S	0.037, 0.089, 1.00
No. of reflections	4092
No. of parameters	226
H-atom treatment	H-atom parameters constrained
Δρmax, Δρmin (e Å^−3)	0.25, −0.26
Computer programs: X-AREA WinXpose, Recipe and Integrate (Stoe & Cie, 2019), SHELXT2014 (Sheldrick, 2015a), SHELXL2018/3 (Sheldrick, 2015b) and PLATON (Spek, 2020).