Bromo(5-cyclohexyl-1-methyl-1H-1,2,4-triazol-4-ium-3-yl)bis(triphenylphosphane)palladium Tetrafluoroborate

Abstract

Transition metal complexes bearing protic N-heterocyclic carbene (pNHC) ligands are promising precatalysts for organic reactions due to their capacity for unique hydrogen-bonding interactions. Herein, we report the synthesis and structural characterization of the first Pd(II) complex featuring a pNHC derived from 1,2,4-triazole—a heterocyclic system previously unexplored for the preparation of metal/pNHC complexes. The complex was synthesized via oxidative addition of 3-bromo-5-cyclohexyl-1-methyl-1H-1,2,4-triazole to Pd(PPh₃)₄ in the presence of NH₄BF₄. Its molecular structure was characterized by NMR spectroscopy and X-ray diffraction analysis.

1. Introduction

Protic N-heterocyclic carbenes (pNHCs) are a distinct class of ligands characterized by a H substituent on a nitrogen atom of the NHC ring, setting them apart from classical NHCs [1,2]. This Brønsted-acidic NH moiety is pivotal, as it facilitates unique reactivity—such as hydrogen bonding—and enables a wide array of post-complexation modifications [3]. Palladium complexes with this class of ligands represent promising platforms for catalysis and materials science [4]. Although protic Pd/NHC complexes with ligands derived from pyridine [5,6,7], (benz)imidazole [8,9,10], theophylline [11], adenine [11,12], and indole [13] have been reported, complexes featuring protic 1,2,4-triazol-3(5)-ylidene ligands remain unexplored. In this work, we report the first example of a palladium complex with a protic 1,2,4-triazole-derived N-heterocyclic carbene, obtained by selective palladation of 3-bromo-5-cyclohexyl-1-methyl-1H-1,2,4-triazole with Pd(PPh₃)₄, and its structural characterization by NMR spectroscopy and single-crystal X-ray analysis.

2. Results and Discussion

Synthesis

The pNHC ligand precursor, 3-bromo-1-methyl-5-cyclohexyl-1,2,4-triazole (2), was obtained by a Sandmeyer reaction of aminotriazole 1 [14,15] in 47% yield (Scheme 1).

The target complex 3 was synthesized in 64% yield by reaction of bromotriazole 2 with Pd(PPh₃)₄ in toluene at 110 °C for 72 h in the presence of NH₄BF₄ (Scheme 2). Complex 3 was isolated as a pale yellow, crystalline solid, which is stable under ambient conditions. It is almost insoluble in non-polar organic solvents (e.g., hexane or Et₂O) but soluble in polar solvents such as DMF, DMSO, MeCN, CHCl₃, and EtOH. Notably, complex 3 undergoes rapid decomposition with the formation of palladium black upon heating with strong bases such as KOH or KOtBu in DMSO or EtOH, which is typical for many classical Pd/NHC complexes [16]. The molecular structure of complex 3 was confirmed by NMR spectroscopy (See Figures S3 and S4 in the Supplementary Materials) and single-crystal X-ray analysis (Figure 1,

Table 1. Selected bond lengths (Å) and angles (°) for complex 3.

Atom	Length/Å	Atom	Angle/°
Pd(1)-Br(1)	2.4721(3)	P(1)-Pd(1)-Br(1)	91.532(16)
Pd(1)-P(1)	2.3558(6)	P(2)-Pd(1)-Br(1)	92.031(15)
Pd(1)-P(2)	2.3308(6)	P(2)-Pd(1)-P(1)	175.81(2)
Pd(1)-C(1)	1.977(2)	C(1)-Pd(1)-Br(1)	177.40(7)
		C(1)-Pd(1)-P(1)	88.20(7)
		C(1)-Pd(1)-P(2)	88.34(7)

,

Table 2. Hydrogen bonds for 3.

D-H…A	d(D-H), Å	d(H…A), Å	d(D…A), Å	<(DHA)/°
N(1)-H(1)…F(4)	0.88(3)	2.03(3)	2.872(3)	159(3)
N(1)-H(1)…F(4A)	0.88(3)	1.79(3)	2.622(11)	158(3)
N(1)-H(1)…F(1B)	0.88(3)	1.92(4)	2.72(3)	150(3)

and

Table 3. Crystal data and structure refinement for 3.

Parameter	Value
Empirical formula	C45H45BBrF4N3P2Pd
Formula weight	962.90
Temperature	100.0(1) K
Wavelength	0.71073 Å
Crystal system	Monoclinic
Space group	P21/n
Unit cell dimensions	a = 12.75750(10) Å
	b = 24.1966(3) Å
	c = 13.2159(2) Å
	β = 93.4020(10)°
Volume	4072.40(9) Å3
Z	4
Density (calculated)	1.571 g/cm3
Absorption coefficient	1.571 mm−1
F(000)	1952
Crystal size	0.74 × 0.41 × 0.14 mm3
θ range for data collection	2.156 to 27.998°
Index ranges	−16 ≤ h ≤ 16, −31 ≤ k ≤ 31, −17 ≤ l ≤ 17
Reflections collected	58,724
Independent reflections	9841 [R(int) = 0.0381]
Observed reflections	9111
Completeness to θmax/θfull	1.000/1.000
Max./min. transmission	1.00000/0.51526
Data/restraints/parameters	9841/166/551
Goodness-of-fit on F2	1.033
Final R indices [I>2σ(I)]	R1 = 0.0327, wR2 = 0.0887
R indices (all data)	R1 = 0.0353, wR2 = 0.0903
Largest diff. peak/hole	1.900/−0.603 e·Å−3
CCDC deposition number	2497031

).

The ¹H NMR spectrum of 3 displays a number of multiplets between 0.8 and 1.75 ppm corresponding to the cyclohexyl group, a singlet for the NMe group at 3.34 ppm, aromatic proton resonances for the PPh₃ ligands at 7.39–7.63 ppm, and a broadened NH resonance at 13.04 ppm. The observed broadening of the NH signal is consistent with proton exchange and tautomerism, as the acidic proton may be located on either the N4 or N1 atom of the triazole ring; therefore, a prototropic equilibrium, characteristic of 1,2,4-triazoles, is anticipated [17,18,19]. Presumably due to these prototropic equilibria, some signals in the ¹³C NMR spectrum are broadened and merge into the baseline; for example, the signal for the carbenic carbon is not distinctly observed.

A crystal suitable for X-ray crystallography was obtained by slow crystallization from a 1:1 CH₂Cl₂/Et₂O mixture. Selected bond lengths and angles for 3 are presented in Table 1 (crystallographic atom numbering is used). The crystal structure of 3 (Figure 1, Table 3) belongs to the monoclinic system, space group P2₁/n, and reveals a distorted square-planar coordination geometry around the metal center with bond angles P(1)-Pd(1)-Br(1) = 91.532(16)° and C(1)-Pd(1)-Br(1) = 177.40(7)° (Table 1). In the crystalline state, the “mobile” proton is located on the N1 atom. This tautomer could be stabilized by NH···F hydrogen bonds with the BF₄⁻ anion (Table 2). Significant orientational disorder of the BF₄⁻ anion was also observed. Despite this disorder, a hydrogen bond is formed with each of the anion’s orientational isomers (Table 2). This type of disorder is not unprecedented and has been previously reported in analogous systems, such as simple tetramethylammonium salts with the BF₄⁻ anion [20]. The bond lengths Pd(1)-C(1) = 1.977(2) Å and Pd(1)-P(1) = 2.3558(6) Å are similar to those found in analogous palladium complexes with benzimidazole-type ligands (Table 1) [9].

3. Materials and Methods

¹H and ¹³C NMR spectra were recorded on a Bruker Avance Neo 300 spectrometer (Rheinstetten, Germany) operating at 300 MHz and 75 MHz, respectively. Chemical shifts are reported relative to the residual proton signals of CDCl₃ (δ 7.26 ppm) or DMSO-d₆ (δ 2.50 ppm) for ¹H NMR, and the carbon signals of CDCl₃ (δ 77.16 ppm) or DMSO-d₆ (δ 39.52 ppm) for ¹³C NMR. Compound 2 was analyzed in CDCl₃, whereas complex 3 was analyzed in a CD₂Cl₂/DMSO-d₆ mixture. Coupling constants (J) are reported in Hertz (Hz). Copies of the ¹H and ¹³C NMR spectra for compounds 2 and 3 are provided in Figures S1–S4 (Supplementary Materials).

3.1. Synthesis of 3-Bromo-5-cyclohexyl-1-methyl-1H-1,2,4-triazole (2)

3-Amino-5-cyclohexyl-1H-1,2,4-triazole (1) (0.361 g, 2.0 mmol) was dissolved in 48% aqueous HBr (10 mL) and cooled to −15 °C. Sodium nitrite (0.152 g, 2.2 mmol) was added in small portions over 30 min with vigorous stirring. The reaction mixture was stirred for an additional 30 min at this temperature. Copper(I) bromide (0.717 g, 5.0 mmol) and potassium bromide (0.476 g, 4.0 mmol) were then added sequentially. The mixture was stirred for 1 h while allowing it to warm to room temperature. The reaction mixture was carefully neutralized to pH 7–8 by the slow addition of a saturated aqueous sodium carbonate solution. The aqueous layer was extracted with dichloromethane (5 × 7 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure to a volume of approximately 3 mL. The crude product was purified by flash column chromatography on silica gel, eluting with dichloromethane to afford the title compound as a white solid. Yield 0.229 g (47%). ¹H NMR (CDCl₃, 300 MHz) 1.18–1.42 (m, 4H), 1.57–1.78 (m, 3H), 1.80–1.92 (m, 4H), 2.67 (tt, J = 11.8, 3.3 Hz, 1H), 3.79 (s, 3H). ¹³C NMR (CDCl₃, 75 MHz): 25.6, 26.0, 31.0, 35.3, 35.4, 138.4, 161.8.

3.2. Synthesis of Bromo(5-cyclohexyl-1-methyl-1H-1,2,4-triazol-4-ium-3-yl)bis(triphenylphosphane)palladium Tetrafluoroborate (3)

A 7 mL screw-capped tube equipped with a magnetic stir bar was charged with 3-bromo-1-methyl-5-cyclohexyl-1H-1,2,4-triazole (2) (0.293 g, 1.2 mmol), Pd(PPh₃)₄ (1.156 g, 1.0 mmol), NH₄BF₄ (0.734 g, 7.0 mmol), and dry toluene (3 mL) under an argon atmosphere. The tube was sealed, and the reaction mixture was heated at 110 °C with stirring for 72 h. After cooling to room temperature, the solvent was removed under reduced pressure. The residue was dissolved in dichloromethane (7 mL) and filtered through a short pad of Celite. The filtrate was concentrated under reduced pressure to a volume of approximately 1 mL and diluted with Et₂O (5 mL). The resulting precipitate was collected by filtration and recrystallized from a dichloromethane/diethyl ether mixture. The product was obtained as a pale yellow crystalline solid after drying under vacuum at 50 °C overnight. Yield: 0.616 g (64%). ¹H NMR (DMSO-d₆/CD₂Cl₂ (1/1, v/v), 300 MHz): δ 0.77–0.97 (m, 2H), 1.03–1.32 (m, 5H), 1.74 (d, J = 13.1 Hz, 3H), 2.30 (t, J = 12.5 Hz, 1H), 3.32 (s, 3H), 7.35–7.44 (m, 12H), 7.45–7.53 (m, 6H), 7.55–7.67 (m, 12H), 13.04 (s, 1H). ¹³C NMR (DMSO-d₆/CD₂Cl₂ (1/1, v/v), 75 MHz): δ 24.4, 24.5, 29.3, 32.7, 35.3, 127.6, 127.7, 127.8, 129.2, 129.5, 129.9, 130.4, 131.3, 133.8, 133.9, 134.0, 154.5.

3.3. X-Ray Crystallography

X-ray diffraction data were collected at 100K on a four-circle Rigaku XtaLAB Synergy-S diffractometer (Rigaku Corporation, Tokyo, Japan), equipped with a HyPix-6000HE area-(Rigaku Corporation, Japan) (kappa geometry, shutterless ω-scan technique), using monochromatized Mo K_α-radiation. The intensity data were integrated and corrected for absorption and decay by the CrysAlisPro program version 1.171.44 (Rigaku Oxford Diffraction: Abingdon, UK) [21]. The structure was solved by direct methods using SHELXT [22] and refined on F² using SHELXL-2018 [23] in the OLEX2 program [24]. All non-hydrogen atoms were refined with individual anisotropic displacement parameters. A location of atom H1 at N1 was found from the electron density-difference map. All other hydrogen atoms were positioned geometrically and refined as riding atoms with relative isotropic displacement parameters.

4. Conclusions

The applicability of 1-alkyl-3-brominated-1,2,4-triazoles as precursors for previously unexplored triazole-derived pNHCs has been demonstrated. The first Pd(II) complex featuring a 1,2,4-triazole-derived pNHC ligand was prepared via palladation of 3-bromo-5-cyclohexyl-1-methyl-1H-1,2,4-triazole with Pd(PPh₃)₄ in the presence of NH₄BF₄. NMR spectroscopy and single-crystal X-ray diffraction studies revealed a significant propensity for prototropic tautomerism in complexes with 1,2,4-triazole-derived pNHCs, making them particularly interesting targets for future research in coordination chemistry, catalysis, and materials science.