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Abstract

A new bis-N-heterocyclic carbene palladium complex, (C₁₃H₉N₂F₂)₂PdCl₂, is synthesized by a three-step reaction and characterized by ¹H NMR and ¹³C NMR spectroscopy as well as by X-ray crystallography. This new bis-N-heterocyclic carbene palladium complex has excellent stability and is capable of efficiently catalyzing the Mizoroki–Heck coupling reaction of aryl halides with acrylates.

Keywords

Mizoroki–Heck reaction palladium complex

Introduction

In recent years, the catalytic cross-coupling reactions of N-heterocyclic carbene (NHC) metal complexes have become a popular research topic.^1,2 Compared with traditional phosphine and nitrogen ligands,^3,4 NHC ligands have the following advantages: they are electron rich and strong electron donors, they strongly coordinate to metals, they are relatively stable in synthesized metal complexes^5–20 and easy to modify, and so on.^21,22 They are typically represented by an NHC-Pd complex which exhibits excellent reactivity in catalytic reactions, mainly due to the strong σ electron-donating properties of the NHC, which makes the central Pd atom more susceptible to oxidative addition at the inactive bond.

There are many reports on the catalytic cross-coupling reactions of NHC-Pd complexes.^23–27 In 1991, Arduengo et al.²¹ first synthesized a stable NHC complex and determined its molecular structure. Seven years later, Herrmann synthesized a bidentate NHC-Pd catalyst that exhibited higher activity for brominated aromatic hydrocarbons.²⁸ His project was then developed to give a NHC-Pd catalyst containing a bis-NHC that achieved the coupling of a chlorinated aromatic hydrocarbon at room temperature in high yield. In 2005, Singh et al. synthesized a monodentate NHC-Pd complex by a simple method. This NHC-Pd complex could effectively catalyze the Suzuki–Miyaura cross-coupling reaction of highly hindered chlorinated aromatic hydrocarbons, benzyl chloride, and allyl chlorides.²⁹ Recently, Lin et al.³⁰ synthesized a series of NHC-Pd complexes that catalyze the Mizoroki–Heck reaction, which was achieved with very high yields using 1 mol% of the catalyst. Zhong et al.³¹ synthesized a new NHC-Pd complex that catalyzed the Suzuki–Miyaura reaction in an aqueous solvent at room temperature, a good yield being obtained by using 1 mol% of their catalyst.

Among the NHC metal complexes that have been reported so far, most structures are monoligands, while bis-ligands are relatively rare.^32,33 A new NHC ligand containing a F atom, which is helpful in forming hydrogen bonds, was designed and synthesized in this work. This new bis-ligand complex, whose stability was greatly enhanced by the presence of the hydrogen bond and the bis-ligand structure, was obtained after complexing with palladium. A single crystal of the complex was left in the air at room temperature and standard atmospheric pressure for 1 month without any resulting changing in its properties. The crystal structure of the complex and its catalytic activity in Heck coupling reactions were then studied.

Results and discussion

Synthesis and crystal structure

The synthesis of the new (C₁₃H₉N₂F₂)₂PdCl₂ complex is depicted in Scheme 1. Reacting 2 with PdCl₂ and potassium carbonate in anhydrous tetrahydrofuran (THF) at 80 °C gave the desired palladium complex 3 as a yellow solid in 67% yield. Complex 3 was characterized by ¹H NMR and ¹³C NMR spectroscopy as well as by X-ray crystallography. Complex 3 is monoclinic, P-2_1/c space group. The crystal structure of complex 3 is depicted in Figure 1. X-ray single-crystal and structural refinement data are shown in Table 1. Selected bond lengths and bond angles are listed in Table 2.

Scheme 1.

Synthesis of complex 3.

Figure 1.

X-ray single-crystal structure of complex 3.

Table 1.

Crystal data and structure refinement for complex 3.

Formula	C₂₆H₁₈Cl₂F₄N₄Pd
FW	639.77
T (K)	113.15
Crystal system	Monoclinic
Space group	P-2_1/c
a (Å)	13.905(3)
b (Å)	12.426(3)
c (Å)	16.428(3)
α (°)	90
β (°)	100.61(3)
γ (°)	90
V (Å³)	2790.2(10)
Z	4
ρ_calc (g cm⁻³)	1.720
μ (mm⁻¹)	1.101
F (000)	1432.0
Crystal size (mm³)	0.2 × 0.18 × 0.12
2Θ range for data collection (°)	2.98–55.75
Index ranges	–18 ⩽ h ⩽ 18, –16 ⩽ k ⩽ 16, –21 ⩽ l ⩽ 21
Reflections collected	32,887
Independent reflections	6638 [R_int = 0.0560]
Data/restraints/parameters	6638/12/362
Goodness of fit on F²	1.083
Final R indexes (I⩾2σ(I))	R₁ = 0.0467, wR₂ = 0.1144
Final R indexes (all data)	R₁ = 0.0562, wR₂ = 0.1209
Largest diff. peak/hole (eÅ⁻³)	1.08/−1.23

Table 2.

Selected bond lengths (Å) and bond angles (°).

Pd(1)-Cl(1)	2.3621(10)	Pd(1)-Cl(2)	2.3644(10)
Pd(1)-Cl(7)	1.974(3)	Pd(1)-Cl(20)	1.984(3)
Cl(1)-Pd(1)-Cl(2)	93.16(3)	C(7)-Pd(1)-Cl(1)	176.24(9)
C(7)-Pd(1)-Cl(2)	88.82(9)	C(7)-Pd(1)-C(20)	89.42(13)
C(20)-Pd(1)-Cl(1)	88.76(9)	C(20)-Pd(1)-Cl(2)	176.53(9)

Symmetry transformations used to generate equivalent atoms: (a) −x + 2, −y, −z; (b) −x, −y + 1, −z.

The crystal structure of complex 3 indicates the Pd(II) is bound to the C atom in the NHC ligand and the Cl anion is located on an isosceles trapezoid center. The Pd(1)-Cl(1) distance of 2.3621(10) (Å) and the Pd(1)-Cl(2) distance of 2.3644(10) (Å) are almost equal. The Pd(1)-C(7) distance of 1.974(3) (Å) and the Pd(1)-C(20) distance of 1.984(3) (Å) are almost the same. The angle of C(7)-Pd(1)-Cl(1) (176.24 (9)°) is similar to that of C(20)-Pd(1)-Cl(2) (176.53 (9)°) which is approximately 180°. The angle of C(7)-Pd(1)-C(20) (89.42 (13)°) is close to C(7)-Pd(1)-Cl(2) (88.82 (3)°) which is approximately 90°. This shows that the angle of the Pd atom was at a right angle to the N-heterocyclic carbenes.

Complex 3 is further stabilized by hydrogen bonds. The F(3) atom formed hydrogen bonds with C(10) of another molecular complex with a D. . .A distance of 2.6020 (25) (Å). The dimeric structure is shown in Figure 2. The F(4) atom of the NHC ligand formed a hydrogen bond with the C(15) atom in another molecular complex. The one-dimensional (1D) chain structure is shown in Figure 3 where the D. . .A distance is 2.7421 (25) (Å). Apart from these interactions, the F(1) atom forms a hydrogen bond with C(10) in the same ligand and the F(2) atom forms a hydrogen bond with a molecule of CH₂ Cl_2.

Figure 2.

View of the hydrogen bonding of F(3) in two molecules of complex 3.

Figure 3.

View of the hydrogen bond of F(4) in the chain structure of complex 3.

Catalytic activity

The catalytic activity of the palladium complex 3 in the Mizoroki–Heck coupling reaction of aryl halides with acrylates was investigated. To optimize the reaction conditions, different bases and different solvents were investigated using 4-bromotoluene (1.3 mmol) and methyl acrylate (1.3 mmol) as the substrates with 0.1 mol% of complex 3 at 140 °C for 20 h under a N₂ atmosphere. The results are presented in Table 3. When dimethyl sulfoxide (DMSO) was used as the solvent, a low yield (10%) was obtained in the presence of Et₃N (Table 3, entry 2). Other solvents such as dimethylacetamide (DMA) and dimethylformamide (DMF) gave better yields (25% and 35%, respectively) (Table 3, entries 1 and 3). Screening of the base showed that Na₂CO₃ was the best (Table 3, entries 4–7). Overall, the highest yield (78%) was obtained using DMA as the solvent and Na₂CO₃ as the base (Table 3, entry 7).

Table 3.

Optimization of the reaction conditions for the coupling of 4-bromotoluene with phenylboronic catalyzed by complex 3.^a


Entry	Base	Solvent	Time (h)	Yield (%)^b
1	Et₃N	DMF	20	35
2	Et₃N	DMSO	20	10
3	Et₃N	DMA	20	25
4	K₃PO₄	DMF	20	40
5	K₃PO₄	DMA	10	45
6	Na₂CO₃	DMF	20	65
7	Na₂CO₃	DMA	10	78

DMSO: dimethyl sulfoxide; DMA: dimethylacetamide; DMF: dimethylformamide.

Reactions were carried out using 3 (1 mg, 0.0013 mmol), 4-bromotoluene (222 mg, 1.3 mmol, 1.0 equiv.), methyl acrylate (134 mg, 1.3 mmol, 1.0 equiv.), base (2.6 mmol, 2.0 equiv.), solvent (1 mL), N₂ atmosphere, 140 °C.

Isolated yields.

The scope of this reaction was then investigated under the optimal conditions and the results are summarized in Tables 4 and 5. Using methyl acrylate as a fixed substrate, various aryl halides were subjected to the coupling reaction. When the substituent on the aryl group was electron-withdrawing, such as in 1-bromo-4-nitrobenzene and 4-bromobenzaldehyde, high yields (93%, 92%) were obtained (Table 4, entries 1 and 2). Electron-donating substituents, such as those in 4-methylbromobenzene and 4-methoxybromobenzene (Table 4, entries 4 and 5), led to moderate yields (78%, 36%) being obtained (Table 3, entries 4 and 5). Even after lowering the loading, the catalyst was still quite effective for the reaction of the 4-methyliodobenzene (Table 4, entry 6). For 4-nitrochlorobenzene, much lower reactivity was observed (Table 4, entry 7) even with a higher loading of catalyst 3.

Table 4.

Heck reactions of aryl halides and methyl acrylate^a catalyzed by complex 3.


Entry	ArX	Time (h)	Product	Yield (%)^b
1		10	5a	93
2		10	5b	92
3		10	5c	85
4		10	5d	78
5		10	5e	36
6^c		2	5f	99
7^d		10	5g	19

DMA: dimethylacetamide.

Reactions were carried out using 3 (0.0013 mmol), aryl halide (1.3 mmol, 1.0 equiv.), methyl acrylate (1.3 mmol, 1.0 equiv.), Na₂CO₃ (2.6 mmol, 2.0 equiv.), DMA (1 mL), N₂ atmosphere, 140 °C, 10 h.

Isolated yields.

Reactions were carried out using 3 (0.00013 mmol).

Reaction was carried out using 3 (0.0026 mmol).

Table 5.

Heck reactions of aryl halides and ethyl acrylate^a catalyzed by complex 3.


Entry	ArX	Time (h)	Product	Yield (%)^b
1		10	6a	99
2		10	6b	99
3		10	6c	91
4		10	6d	83
5		10	6e	42
6^c		2	6f	99
7^d		10	6g	25

DMA: dimethylacetamide.

Reactions were carried out using 3 (0.0013 mmol), aryl halide (1.3 mmol, 1.0 equiv.), ethyl acrylate (1.3 mmol, 1.0 equiv.), Na₂CO₃ (2.6 mmol, 2.0 equiv.), DMA (1 mL), N₂ atmosphere, 140 °C, 10 h.

Isolated yields.

Reaction was carried out using 3 (0.00013 mmol).

Reaction was carried out using 3 (0.0026 mmol).

We found that ethyl acrylate was a better substrate for the reaction than methyl acrylate. Again the results showed that the reaction was sensitive to the electronic properties of the phenyl substituents. Much higher yields were obtained when electron-withdrawing groups such as nitro and formyl were present on the phenyl rings. In contrast, lower yields were obtained when electron-donating groups such as methyl and methoxyl were present on the phenyl rings (see Table 5). All the products in Tables 3 –5 had been reported.^34–36

Conclusion

A new bis-NHC palladium complex, (C₁₃H₉N₂F₂)₂PdCl, has been synthesized by a three-step reaction and characterized by ¹H NMR and ¹³C NMR spectroscopy as well as by X-ray crystallography. The bis-NHC palladium complex has excellent stability and enriches the diversity of NHC ligands and will aid further development of new NHC-Pd complexes. The catalytic activity of complex 3 was examined in Mizoroki–Heck reactions of a variety of aryl halides with acrylates. According to the catalytic study, the complex showed good catalytic activity in the Heck reaction.

Experimental

¹H NMR and ¹³C NMR spectra were collected on a Bruker Avance III 400 MHz spectrometer with CDCl₃ or DMSO as the solvent and tetramethylsilane (TMS) as the internal reference. Chemicals and reagents were obtained from commercial sources and used directly.

Synthesis of compound 1 [(E)-N-(2,6-difluorophenyl)-1-(pyridin-2-yl)methanimine]

To a 100-mL three-neck round-bottom flask, pyridine-2-carbaldehyde (2.00 g, 18.69 mmol) and methanol (6 mL) were added under an N₂ atmosphere.^37,38 Next, a mixed solution of 2,6-difluoroaniline (2.40 g, 18.60 mmol) in methanol (6 mL) was added dropwise. The mixture was stirred for 6 h at room temperature. On cooling in an ice bath, a solid was precipitated, and the solvent was removed under reduced pressure to give product 1 as a bright yellow solid, yield 90% (3.60 g, 16.51 mmol). ¹H NMR (400 MHz, CDCl₃): δ = 8.76 (s, 1H), 8.73 (d, J = 4.6 Hz, 1H), 8.28 (d, J = 8.0 Hz, 1H), 7.84 (t, J = 7.8 Hz, 1H), 7.41 (t, J = 6.2 Hz, 1H), 7.08–7.12 (m, 1H), 6.99 (t, J = 8.0 Hz, 2H). ¹³C NMR (101 MHz, CDCl₃): δ = 167.29 (t, J_CF = 3.4 Hz), 155.14 (dd, J_CF = 250.4, 5.1 Hz) 154.23, 149.74, 136.70, 128.26, 125.95 (t, J_CF = 9.8 Hz), 125.70, 121.89, 111.92 (dd, J_CF = 17.5, 6.9 Hz).

Synthesis of compound 2 (2-(2,6-difluorophenyl)imidazo[1,5-a]pyridin-2-ium chloride)

Product 1 (1.4 g, 6.42 mmol), paraformaldehyde (183.01 mg, 6.11 mmol), and ethyl acetate (100 mL) were added to a 250-mL three-neck round-bottom flask under an N₂ atmosphere. After heating to reflux, trimethylchlorosilane (1 mL) was added to the flask slowly, and the healing was continued for 6 h. After cooling to room temperature and filtering, the solid was washed with ethyl acetate several times. Product 2 was obtained as a yellow solid after drying, yield 85% (5.01 g, 18.79 mmol). ¹H NMR (400 MHz, CDCl₃): δ = 11.78 (s, 1H), 9.75 (d, J = 7.1 Hz, 1H), 7.95 (s, 1H), 7.80 (d, J = 9.4 Hz, 1H), 7.63–7.67 (m, 1H), 7.28 (dt, J = 26.8, 8.3 Hz, 3H), 7.13 (t, J = 7.0 Hz, 1H). ¹³C NMR (101 MHz, CDCl₃): δ = 158.76–153.30 (m), 134.11–132.59 (m), 130.33–130.07 (m), 129.87 (d, J_CF = 2.0 Hz), 126.25, 126.08, 118.15, 117.41, 113.51, 113.26 (dd, J_CF = 19.0, 3.8 Hz).

Synthesis of complex 3

Under a N₂ atmosphere, to a 10-mL Schlenk flask, palladium chloride (66.51 mg, 0.37 mmol), potassium carbonate (103.72 mg, 0.75 mmol), product 2 (100.00 mg, 0.37 mmol), and THF (3 mL) were added. The reaction solution was heated at 80 °C and for 24 h. After cooling to room temperature, the solid was filtered and washed with CH₂Cl₂ (3 × 3 mL). The solvent was removed under reduced pressure and the solid dissolved in a mixture of dichloromethane and petroleum ether, and recrystallized at room temperature, yield 67%. ¹H NMR (400 MHz, DMSO-d₆): δ = 8.06 (d, J = 7.5 Hz, 1H), 7.98 (s, 1H), 7.52 (d, J = 9.9 Hz, 2H), 7.48 (s, 1H), 6.96 (t, J = 8.1 Hz, 1H), 6.69 (s, 1H), 6.51 (t, J = 7.2 Hz, 1H). ¹³C NMR (101 MHz, DMSO-d₆): δ =162.59 (d, J_CF = 2.8 Hz), 130.23, 123.14, 117.68, 115.17, 113.58, 112.37–111.88 (m).

Heck reaction procedure

A Schlenk flask was filled with the aryl halide (1.3 mmol), methyl acrylate (1.3 mmol), Na₂CO₃ (2.6 mmol), complex 3 (0.0013 mmol), and DMA (1 mL) under a N₂ atmosphere. The mixture was then heated at 140 °C for 10 h. After the reaction was complete, the solution was cooled to room temperature. The reaction mixture was then washed with water, extracted with CH₂Cl₂ (3 × 5 mL), dried over Na₂SO₄, and filtered. The solvent was removed under reduced pressure. Further purification of the product was achieved by flash chromatography on a silica gel column.

X-ray crystallography

A single crystal of complex 3 (0.2 mm × 0.18 mm × 0.12 mm) that was suitable for X-ray analysis was obtained by slowly diffusing petroleum ether into a solution of the complex in dichloromethane. The data were collected on a XtaLAB mini (600 W, SHINE, CCD, 75 mm, 0.1 electrons/pixel/s) X-ray single-crystal diffractometer. The structure was solved and refined by direct methods using the SHELXS 97 program.^39,40 The non-hydrogen atoms were refined using anisotropic thermal parameters. All the hydrogen atoms were located at geometrically calculated positions.

Supplemental Material

supporting – Supplemental material for Synthesis and characterization of a new bis-NHC palladium complex and its catalytic activity in the Mizoroki–Heck reaction

Supplemental material, supporting for Synthesis and characterization of a new bis-NHC palladium complex and its catalytic activity in the Mizoroki–Heck reaction by Can Feng, Cheng-xin Liu, Yu-fang Wang, Jin Cui and Ming-jie Zhang in Journal of Chemical Research

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the Natural Science Foundation of Tianjin (17JCQNJC05500), P. R. China.

ORCID iD

Can Feng

Supplemental material

Supplemental material for this article is available online.

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