Heterocyclic compounds occur widely in nature and are essential to life. Nitrogen-containing heterocyclic molecules constitute one of the largest portions of chemical entities, which are part of many natural products, fine chemicals and biologically active pharmaceuticals essential for enhancing the quality of life [1].

Pyrazole and its derivatives, a class of nitrogen-containing heterocyclic compounds, are of substantial pharmacological relevance and also represent versatile building blocks in organic and medicinal chemistry [2,3]. These are important bio-active drug targets in the pharmaceutical industry, as they are the core structure of numerous biologically active compounds [4]. They possess a broad spectrum of approved biological activities, which includes anti-inflammatory [5], antipyretic [6], gastric secretion stimulatory [7], antidepressant [8], antibacterial [9], antifilarial agents [10], anti-obesity [11], estrogen receptor agonist [12], HIV-1 reverse transcriptase inhibitors [13] and anti-hyperglycemic activities [14]. In addition, many pyrazole derivatives are also used as insecticides, herbicides and fungicides [15].

With widespread industrial applications and pharmacological importance, we herein report an efficient one-pot synthesis and crystal structure of N-phenyl-3,5-difunctionalized pyrazole.

The synthetic route for the title compound, methyl 5-(4-chlorobenzoyloxy)-1-phenyl-1H-pyrazole-3-carboxylate (4) is outlined in Figure 1. The reaction of phenylhydrazine (1) with dimethyl acetylenedicarboxylate (2) and 4-chlorobenzoyl chloride (3) in dichloromethane under reflux for 10 h afforded the title compound (4) in good yield [16].

The structure of compound (4) was deduced from the FTIR and NMR spectroscopy. In the IR spectrum of the target compound, two absorption bands at 1734 and 1716 cm⁻¹, which are related to two C=O stretching frequencies, clearly indicated the most significant functional groups of the product. ¹H-NMR spectrum of (4) showed characteristic singlets at δ 7.02 (C–H_pyrazole) and δ 3.99 (OCH₃). Resonances at δ 98.4 (CH), δ 52.3 (OCH₃) and δ 144.5–124.2 (aromatic carbons) were observed in the ¹³C-NMR spectrum. The other important region of the spectrum is related to carbonyl groups, which produced 2 C=O signals at 162.4 and 160.7 ppm.

In parallel, for a full structural elucidation, the X-ray diffraction measurements were carried out for the title compound. The crystal and instrumental parameters used in the unit cell determination, the data collection, and structure refinement parameters are presented in the experimental section. A thermal ellipsoid plot at the 20% probability level for compound (4) is presented in Figure 2. The bond distances and angles for (4) all fall within the expected ranges. With the exception of the N-phenyl substituent, which is twisted out of plane with the diazole ring (dihedral angle C16–C11–N2–N1 = 48.5(3)°) the molecule is essentially co-planar (RMS deviation of the remaining atoms from the plane defined by C1–C10, N1, N2, O1, and O2 = 0.022 Å). The methoxycarbonyl moiety (O3, O4, C17, C18) is also coplanar with the aromatic system.

The crystal packing is stabilized by an offset π-stacking between the planar benzoyl-substituted diazole moieties as shown in Figure 3. The approximate distance between chlorobenzoyl ring and diazole ring is 3.6 Å.

The packing is also characterized by attractive intermolecular contacts between O4 and Cl1 as depicted in Figure 4, with intermolecular distance Cl1…O4 3.013(2) Å, being 0.257 Å less than the sum of the van der Waals radii for O and N and C–Cl…O angle 173.5° within each π-stacked plane. This is an example of halogen bonding [17,18], more generally known as σ-hole bonding. This is a common feature in the crystal structure of compounds containing the larger halogens, and has its origins in the attraction between various Lewis Base donors and the positive electrostatic regions at the terminus of a C–Halogen bond [19,20,21,22,23,24].

A concise and efficient one-pot synthesis of methyl 5-(4-chlorobenzoyloxy)-1-phenyl-1H-pyrazole-3-carboxylate has been carried out using phenylhydrazine, dimethyl acetylenedicarboxylate and 4-chlorobenzoyl chloride in good yield. The title compound was also confirmed by single crystal X-ray diffraction data.