5-Amino-1-phenyl-3-trifluoro­methyl-1H-pyrazole-4-carboxylic acid

Francesco Caruso; Maria Valeria Raimondi; Giuseppe Daidone; Claudio Pettinari; Miriam Rossi

doi:10.1107/S1600536809032188

. 2009 Aug 15;65(Pt 9):o2173. doi: 10.1107/S1600536809032188

5-Amino-1-phenyl-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid

Francesco Caruso ^a,^*, Maria Valeria Raimondi ^b, Giuseppe Daidone ^b, Claudio Pettinari ^c, Miriam Rossi ^d

PMCID: PMC2970016 PMID: 21577579

Abstract

In the title compound, C₁₁H₈F₃N₃O₂, there are two molecules in the asymmetric unit wherein the phenyl rings make dihedral angles of 65.3 (2) and 85.6 (2)° with the pyrazole rings. In the crystal, pairs of molecules are held together by O—H⋯O hydrogen bonds between the carboxyl groups, forming a centrosymmetric dimer with an R ² ₂(8) motif. Intramolecular N—H⋯O interactions are also present.

Related literature

For general background, see: Caruso & Rossi (2004 ▶); Maggio et al., (2008 ▶). For hydrogen-bond motifs, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C₁₁H₈F₃N₃O₂
M _r = 271.20
Monoclinic,
a = 9.757 (3) Å
b = 10.740 (3) Å
c = 21.277 (6) Å
β = 93.716 (3)°
V = 2225 (1) Å³
Z = 8
Mo Kα radiation
μ = 0.15 mm⁻¹
T = 125 K
0.30 × 0.18 × 0.05 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 1997 ▶) T _min = 0.957, T _max = 0.993
20692 measured reflections
3772 independent reflections
2737 reflections with I > 2σ(I)
R _int = 0.072

Refinement

R[F ² > 2σ(F ²)] = 0.051
wR(F ²) = 0.140
S = 1.01
3772 reflections
368 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.43 e Å⁻³
Δρ_min = −0.32 e Å⁻³

Data collection: SMART (Bruker, 1997 ▶); cell refinement: SAINT (Bruker, 1997 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809032188/bx2218sup1.cif

e-65-o2173-sup1.cif^{(23.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809032188/bx2218Isup2.hkl

e-65-o2173-Isup2.hkl^{(185KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N53—H531⋯O52	0.85 (4)	2.20 (4)	2.808 (3)	128 (3)
O51—H51⋯O2ⁱ	0.94 (4)	1.75 (4)	2.687 (3)	177 (4)
N3—H31⋯O2	0.90 (4)	2.20 (4)	2.873 (3)	132 (3)
O1—H1⋯O52ⁱⁱ	0.91 (4)	1.67 (4)	2.580 (3)	176 (4)

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

We acknowkledge US NSF grant No. 0521237 for the X-ray diffractometer.

supplementary crystallographic information

Comment

We report here the structure of the title compound (I), isolated during attempts to synthesize Ti(C₅H₅)₂(C₁₁H₇F₃N₃O₂)₂. In the title compound C₁₁H₈F₃N₃O₂, there are two molecules in the asymmetric unit that differ in the dihedral angle formed between the phenyl and pyrazole rings, 65.3 (2) and 85.6 (2)°. The pairs of molecules are held together by O—H···O hydrogen bonds between the carboxyl groups, forming a centrosymmetric dimer with an R²₂(8) motif, Fig. 2. (Bernstein et al., 1995) . Related compounds of this ligand show antiproliferative and apoptotic effects against K562, K562-R (imatinib mesilate resistant), HL60 and multidrug resistant HL60 cell lines (Maggio et al., 2008).

Experimental

The synthesis of title compound has been described by Maggio et al., 2008. The title compound was reacted with titanocene dichloride, (C₅H₅)₂TiCl₂. Elemental analysis {C, 53.50, H, 3.37, N, 11.70%. Found: C, 53.66, H, 3.45, N, 11.54%} indicated formation of Cp₂Ti(ligand)₂,= Ti(C₅H₅)₂(C₁₁H₇F₃N₃O₂)₂, ligand = 5-amino-1-phenyl-3- (trifluoromethyl)-1H-pyrazole-4-carboxylate. Melting point 190–195°C. IR(nujol, cm-1): 3439w, 3332w (N—H), 3049w (Carom-H), 1661 s, 1611 s (COO), 1537 s, 1486 s (C=N + C=C). 1H NMR (CDCl₃): 5.59br (10H, Ti—C₅H₅), 6.40br, 6.60br (6H, –NH₂), 7.55 mbr (10H, Carom-H). Good solubility in chloroform, methanol, dimethylsulfoxide; lower solubilty in acetonitrile; insoluble in water. Upon recrystallization flat needles were obtained, they were studied to determine its crystal and molecular structure and revealed only the ligand. Ligand cleavage is a non unusual feature for Ti complexes that show a marked tendency to evolve towards titanium dioxide (Caruso & Rossi, 2004). The title compound synthesis has been described (Maggio et al.). Related compounds of this ligand show antiproliferative and apoptotic effects against K562, K562—R (imatinib mesilate resistant), HL60 and multidrug resistant HL60 cell lines (Maggio et al., 2008).