English

• 1. INTRODUCTION

  N-(Hetero)aryl azole derivatives, as structural and functional units, usually play an important role in natural products and biologically active compounds^{[1, 2]}. Considering the price and toxicity, copper catalyzed Ullmann coupling reaction of aryl halides is one of the most useful reactions for the synthesis of N-aryl azole derivatives^[3]. Traditionally, copper-catalyzed Ullmann coupling reaction of (hetero)aryl halides often requires high temperature (140 ℃ or more), high catalyst loading, and highly active (hetero)aryl halides ((hetero)aryl iodides or (hetero)aryl bromides) as coupling partners, which greatly limited the reaction scope^[4].

  During the past years, a series of effective ligands have been reported, which greatly promoted copper-catalyzed Ullmann coupling reactions^[5-21]. Despite these significant advances, it must be noted that in most cases, higher catalytic loading is still needed for the Ullmann coupling reaction of (hetero)aryl chlorides. So, more highly active catalytic systems need to be developed urgently.

  In this paper, a new dichlorobridged dimeric Cu(Ⅱ) complex is reported, which was obtained by coordination of a new 2,2΄-(1H-1,2,4-triazole-1,3-diyl)dipyridine ligand with CuCl₂^.2H₂O. The structure of the complex was characterized by X-ray single-crystal diffraction and its catalytic activity for Ullmann coupling reaction of (hetero)aryl chlorides with various N(H)-heterocycles was also investigated.

  2. EXPERIMENTAL

  2.1 Materials and methods

  All chemicals and reagents were obtained from commercial sources and used without further purification. X-ray diffraction was done from a SuperNova, Dual, Cu at home/near, AtlasS2 diffractometer. ¹H NMR and ¹³C NMR spectra were recorded on a Bruker AV 400. Fourier transform infrared spectra were recorded on a Nicolet IR200 FT-IR spectrometer using a KBr-pellet method.

  2.2 Synthesis of complex 3

  2-Cyanopyridine (2.5 g, 24.0 mmol) was added in a 25 mL Schlenk flask containing absolute ethanol (8.0 mL). Hydrazine monohydrate (2.8 mL) was slowly added dropwise to the reaction system at 0 ℃, and then the reaction was carried out for 8 h at room temperature. After completion of the reaction, half of the solvent was spun off and the residue was filtered under reduced pressure to afford 2.8 g yellow solid. After that, this yellow solid was put in a 25 mL Schlenk flask, and formic acid (7.4 mL) was added at 0 ℃. The mixture was allowed to warm to room temperature and continued to stir for 30 minutes. Then the mixture was heated at 100 ℃ for 6 h. After the reaction system was cooled to 0 ℃, 10% Na₂CO₃ was added dropwise. The mixture was extracted by dichloromethane and washed by water. The organic phase was collected and dried over anhydrous sodium sulfate. After solvent removal, the pure compound 1 (2.1 g, 14.3 mmol) as a white powder was obtained by recrystallization of chloroform in 70% yield. ¹H NMR (400 MHz, DMSO-d₆) δ 14.48 (s, 1H), 8.68 (d, J = 4.0 Hz, 1H), 8.29 (s, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.96~7.93 (m, 1H), 7.48~7.45 (m, 1H) ppm. ¹³C NMR (100 MHz, DMSO-d₆) δ 155.8, 149.7, 149.6, 147.5, 137.6, 124.7, 121.4 ppm.

  2-Bromopyridine (31.4 mg, 0.2 mmol), 2-(1H-[1,2,4]triazol-3-yl)-pyridine (35.0 mg, 0.24 mmol), CuCl (1.98 mg, 0.02 mmol) and DMF (0.4 mL) were placed in a small ampoule. Then, the reaction system was heated at 120 ℃ for 12 h. After completion of the reaction, the aqueous phase extracted with CH₂Cl₂ (3 × 2 mL). The combined organic layers were dried over anhydrous Na₂SO₄ and concentrated in vacuo. The product was further purified by flash chromatography on silica gel to afford compound 2 as a white powder (37.9 mg, 0.17 mmol) in an 85% yield. ¹H NMR (400 MHz, CDCl₃) δ 9.14~9.12 (m, 1H), 8.64 (s, 1H), 8.29 (s, 1H), 8.11 (s, 1H), 7.98~7.93 (m, 1H), 7.74~7.65 (m, 2H), 7.20~7.12 (m, 2H) ppm. ¹³C NMR (100 MHz, CDCl₃) δ 162.6, 149.7, 148.9, 148.0, 142.1, 138.8, 136.5, 123.9, 122.7, 121.9, 112.9 ppm. IR data (KBr, cm^–1): 3119(O–H), 3052(=C–H), 1589(C=N), 1480(C–C), 1446(C–C) 1326(C–N), 1244(C–H), 997(C-H), 772(C–H), 724(C–H).

  Compound 2 (40.1 mg, 0.18 mmol) and CuCl₂·2H₂O (33.7 mg, 0.20 mmol) were placed in a Schlenk flask. Dichloromethane (2.0 mL) was added. After stirring at room temperature overnight, the mixture was filtered and washed three times with dichloromethane to give complex 3 as a blue solid in 82% yield (52.5 mg, 0.15 mmol). IR data (KBr, cm^-1): 3060(=C–H), 1589(C=N), 1456(C–C), 1359(C–N), 1143(C–H), 912(C–H), 751(C–H), 567(C–H).

  2.3 Structure determination

  Single crystal of complex 3 for X-ray structural analysis was obtained by slow evaporation technique in chloroform at room temperature. A suitable crystal was selected and the data were collected on a SuperNova, Dual, Cu at home/near, AtlasS2 diffractometer. The crystal was kept at 150.00(10) K during data collection. Using Olex2^[22], the structure was solved with the ShelXT^[23] structure solution program using Intrinsic Phasing and refined with the ShelXL^[24] refinement package using full-matrix least-squares minimization. Anisotropic thermal parameters were applied to all nonhydrogen atoms.

  A total of 5688 reflections were recorded and 3102 were unique (R_int = 0.1020). The data sets were corrected for absorption by multi-scan technique in the range of 4.93≤2θ≤50.02º (–8≤h≤8, –11≤k≤12, –14≤l≤14). The final R = 0.1010 and wR = 0.1520. The selected bond lengths and bond angles of complex 3 are listed in Table 1.

  Table 1

  

  Table 1.  Selected Bond Lengths (Å) and Bond Angles (°)

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  Bond	Dist.		Bond	Dist.		Bond	Dist.
  Cl(1)–Cu(1) Cu(1)–N(5)	2.275(3) 2.061(9)		Cl(2)–Cu(1)	2.225(3)		Cu(1)–N(4)	1.979(9)
  Angle	(°)		Angle	(°)		Angle	(°)
  Cl(2)–Cu(1)–Cl(1) N(4)–Cu(1)–N(5)	94.35(12) 80.3(4)		N(4)–Cu(1)–Cl(2) N(5)–Cu(1)–Cl(2)	171.9(3) 93.9(3)		N(4)–Cu(1)–Cl(1) N(5)–Cu(1)–Cl(1)	90.9(3) 169.5(2)

  3. RESULTS AND DISCUSSION

  3.1 Crystal structural description of complex 3

  Crystal structural analysis revealed that complex 3 crystallizes in the triclinic space group P$ \overline 1 $. X-ray singlecrystal structure of complex 3 is shown in Fig. 1. In the structure unit of complex 3, two nitrogen donor atoms of the pyridine and azole rings coordinate to the copper center in a bidentate fashion. The remaining binding sites are occupied by the chloride ligands and two chloride ligands bridge the copper atoms and form a four-membered ring.

  Figure 1

  

  Figure 1.  X-ray single-crystal structure of complex 3. All hydrogen atoms are omitted for clarity. Symmetry code: 1–x, 1–y, 1–z

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  The distance of Cl(1)–Cu(1) is 2.275(3) Å slightly longer than that of Cl(2)–Cu(1) (2.225(3) Å) due to the bridging role of Cl(1) atoms. The value of Cu(1)–N(5) distance is about 2.061(9) Å longer than that of Cu(1)–N(4) (1.979(9) Å). The Cl(1)–Cu(1)–N ligand angles slightly differ from the ideal value of a square pyramid (90^o) as the angle values of N(4)–Cu(1)–Cl(1) and Cl(2)–Cu(1)–Cl(1) are 90.9(3)^o and 94.35(12)^o, respectively.

  No classical hydrogen bonds can be found in complex 3 by using PLATON Windows Taskbar crystal software to analyze. However, they are linked together by two unclassical intermolecular hydrogen bonds (C–H···Cl bonds), and a two-dimensional (2D) packing network was built through intermolecular hydrogen bonds (C–H···Cl), as shown in Fig. 2. The distances between the acceptors and donors for C(10)–H(10)···Cl(2) and C(2)–H(2)···Cl(1) hydrogen bonds are 2.71 and 2.76 Å, respectively (Table 2). Meanwhile, the 2D network structure layers are filled with solvent molecules (CHCl₃) through intermolecular hydrogen bonds (C(13)– H(13)···Cl(2)) and stacked with each other to form a 3D supramolecular network, as shown in Fig. 3.

  Figure 2

  

  Figure 2.  2D packing diagram of complex 3 formed by hydrogen bonds. Non-hydrogen bonding H atoms are omitted for clarity

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  Table 2

  

  Table 2.  Hydrogen Bonds for Complex 3 (Å, °)

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  D–H···A	d(D–H)	d(H···A)	d(D···A)	∠DHA
  C(10)–H(10)···Cl(2)	0.93	2.71	3.584(12)	157
  C(2)–H(2)···Cl(1)	0.93	2.76	3.526(12)	140
  C(13)–H(13)···Cl(2)	0.98	2.69	3.512(14)	141

  Figure 3

  

  Figure 3.  View of the 3D supramolecular network formed by hydrogen bonds (dashed lines)

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  3.2 Catalytic activity

  The catalytic activity of complex 3 for Ullmann coupling reactions of (hetero)aryl chlorides with various N(H)-heterocycles was next investigated in DMF in the presence of Cs₂CO₃ at 120 ℃, with the results shown in Table 3. The coupling reactions of imidazole, benzimidazole, 1,2,4-triazole, or 2-methylimidazole with p-chloronitrobenzene proceeded smoothly and lead to the corresponding products in high to excellent yields (98%, 96%, 85% and 80%, respectively) within 24 h (entries 1~4). When 2-chloroquinoline is used as the substrate, it can also be well coupled with imidazole, benzimidazole, 1,2,4-triazole, or 1,2,3-triazole and provided the expected products in excellent yields (92%, 90%, 88% and 85%, respectively) (entries 5~8). When 2-chloroquinoline was replaced by 2-chloro-6-fluoropyridine, the coupling with imidazole was also successfully completed (entry 9). In addition, we also investigated the double coupling reaction of 2,6-dichloropyridine with imidazole. When 2,6-dichloropyridine (1 equiv.) was used, the amounts of imidazole and Cs₂CO₃ were increased to 2.4 and 4 equiv., respectively, and the double coupling product can be obtained successfully (entry 10).

  Table 3

  

  Table 3.  Coupling of (Hetero)aryl Chlorides with Various N(H)-heterocycles^{a, c}

  DownLoad: CSV

  4. CONCLUSION

  In summary, we have synthesized a new dichlorobridged dimeric Cu(Ⅱ) complex bearing 2,2΄-(1H-1,2,4-triazole-1,3-diyl)dipyridine ligands, which has been characterized by X-ray structural analysis. In complex 3, two nitrogen donor atoms of this ligand and two chloride atoms simultaneously coordinate to the copper center, and two chloride ligands bridge the copper atoms to form a four-membered ring. In addition, the study of the catalytic activity indicated that complex 3 has high reactivity to the Ullmann coupling reaction of (hetero)aryl chlorides with various N(H)-heterocycles.

  
  
• 1. [1]

     Craig, P. N. In Comprehensive Medicinal Chemistry. Drayton, C. J., Ed.; Pergamon Press: New York 1991, Vol. 8.

  2. [2]

     Horton, D. A.; Bourne, G. T.; Smythe, M. L. The combinatorial synthesis of bicyclic privileged structures or privileged substructures. Chem. Rev. 2003, 103, 893–930. doi: 10.1021/cr020033s

  3. [3]

     Evano, G.; Blanchard, N.; Toumi, M. Copper-mediated coupling reactions and their applications in natural products and designed biomolecules synthesis. Chem. Rev. 2008, 108, 3054–3131. doi: 10.1021/cr8002505

  4. [4]

     Hassan, J.; Sévignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Aryl-aryl bond formation one century after the discovery of the Ullmann reaction. Chem. Rev. 2002, 102, 1359–1470. doi: 10.1021/cr000664r

  5. [5]

     Ley, S. V.; Thomas, A. W. Modern synthetic methods for copper-mediated C(aryl)-O, C(aryl)-N, and C(aryl)-S bond formation. Angew. Chem., Int. Ed. 2003, 42, 5400–5449. doi: 10.1002/anie.200300594

  6. [6]

     Sambiagio, C.; Marsden, S. P.; Blacker, A. J.; McGowan, P. C. Copper catalysed Ullmann type chemistry: from mechanistic aspects to modern development. Chem. Soc. Rev. 2014, 43, 3525–3550. doi: 10.1039/C3CS60289C

  7. [7]

     Bhunia, S.; Pawar, G. G.; Kumar, S. V.; Jiang, Y. W.; Ma, D. W. Selected copper-based reactions for C–N, C–O, C–S, and C–C bond formation. Angew. Chem., Int. Ed. 2017, 56, 16136–16179. doi: 10.1002/anie.201701690

  8. [8]

     Klapars, A.; Huang, X. H.; Buchwald, S. L. A general and efficient copper catalyst for the amidation of aryl halides. J. Am. Chem. Soc. 2002, 124, 7421–7428. doi: 10.1021/ja0260465

  9. [9]

     Pawar, G. G.; Wu, H. B.; De, S.; Ma, D. W. Copper(Ⅰ) oxide/N, N΄-bis[(2-furyl)methyl]oxalamide-catalyzed coupling of (hetero)aryl halides and nitrogen heterocycles at low catalytic loading. Adv. Synth. Catal. 2017, 359, 1631–1636. doi: 10.1002/adsc.201700026

  10. [10]

      Altman, R. A.; Koval, E. D.; Buchwald, S. L. Copper-catalyzed N-arylation of imidazoles and benzimidazoles. J. Org. Chem. 2007, 72, 6190–6199. doi: 10.1021/jo070807a

  11. [11]

      Zhao, Y. Y.; Wang, X. Y.; Kodama, K.; Hirose, T. Copper-catalyzed coupling reactions of aryl halides and phenols by 4,4'-dimethoxy-2,2'-bipyridine and 4,7-dimethoxy-1,10-phenanthroline. Chem. Select. 2018, 3, 12620–12624.

  12. [12]

      Yuan, Q. L.; Ma, D. W. A one-pot coupling/hydrolysis/condensation process to pyrrolo[1,2-a]quinoxaline. J. Org. Chem. 2008, 73, 5159–5162. doi: 10.1021/jo8008098

  13. [13]

      Tang, J. M.; Xu, B. Q.; Mao, X.; Yang, H. Y.; Wang, X. X.; Lv, X. One-pot synthesis of pyrrolo[3,2,1-kl]phenothiazines through copper-catalyzed tandem coupling/double cyclization reaction. J. Org. Chem. 2015, 80, 11108–11114. doi: 10.1021/acs.joc.5b01745

  14. [14]

      Shafir, A.; Buchwald, S. L. Highly selective room-temperature copper-catalyzed C-N coupling reactions. J. Am. Chem. Soc. 2006, 128, 8742–8743. doi: 10.1021/ja063063b

  15. [15]

      Liu, L. B.; Frohn, M.; Xi, N.; Dominguez, C.; Hungate, R.; Reider, P. J. A soluble base for the copper-catalyzed imidazole N-arylations with aryl halides. J. Org. Chem. 2005, 70, 10135–10138. doi: 10.1021/jo051640t

  16. [16]

      Ueda, S.; Buchwald, S. L. Catalyst-controlled chemoselective arylation of 2-aminobenzimidazoles. Angew. Chem., Int. Ed. 2012, 51, 10364–10367. doi: 10.1002/anie.201204710

  17. [17]

      Cristau, H. J.; Cellier, P. P.; Spindler, J. F.; Taillefer, M. Highly efficient and mild copper-catalyzed N- and C-arylations with aryl bromides and iodides. Chem. Eur. J. 2004, 10, 5607–5622. doi: 10.1002/chem.200400582

  18. [18]

      Enguehard, C.; Allouchi, H.; Gueiffier, A.; Buchwald, S. L. Easy access to novel substituted 6-aminoimidazo[1,2-a]pyridines using palladium- and copper-catalyzed aminations. J. Org. Chem. 2003, 68, 4367–4370. doi: 10.1021/jo0341463

  19. [19]

      Zhang, C.; Huang, B.; Bao, A. Q.; Li, X.; Guo, S. N.; Zhang, J. Q.; Xu, J. Z.; Zhang, R. H.; Cui, D. M. Copper-catalyzed arylation of biguanide derivatives via C–N cross-coupling reactions. Org. Biomol. Chem. 2015, 13, 11432–11437. doi: 10.1039/C5OB01258A

  20. [20]

      Suresh, P.; Pitchumani, K. Per-6-amino-β-cyclodextrin as an efficient supramolecular ligand and host for Cu(Ⅰ)-catalyzed N-arylation of imidazole with aryl bromides. J. Org. Chem. 2008, 73, 9121–9124. doi: 10.1021/jo801811w

  21. [21]

      Liu, G. Y.; Xu, Y.; Liu, C. X. Synthesis, structural characterization and catalytic activity of copper(Ⅰ) complexes with triphenylphosphine and pyridine derivatives. Chin. J. Struct. Chem. 2016, 35, 740–746.

  22. [22]

      Dolomanov, O. V.; Bourhis, L. J.; Gildea, R. J.; Howard, J. A. K.; Puschmann, H. OLEX2: a complete structure solution, refinement and analysis program. J Appl Crystallogr. 2009, 42, 339–341. doi: 10.1107/S0021889808042726

  23. [23]

      Sheldrick, G. M. SHELXT-integrated space-group and crystal-structure determination. Acta Crystallographica. Section A. Foundations and Advances 2015, 71, 3–8. doi: 10.1107/S2053273314026370

  24. [24]

      Sheldrick, G. M. Crystal structure refinement with SHELXL. Acta Crystallographica. Section C, Structural Chemistry 2015, 71, 3–8. doi: 10.1107/S2053229614024218

• 

  Figure 1  X-ray single-crystal structure of complex 3. All hydrogen atoms are omitted for clarity. Symmetry code: 1–x, 1–y, 1–z

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  Figure 2  2D packing diagram of complex 3 formed by hydrogen bonds. Non-hydrogen bonding H atoms are omitted for clarity

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  Figure 3  View of the 3D supramolecular network formed by hydrogen bonds (dashed lines)

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  Table 1.  Selected Bond Lengths (Å) and Bond Angles (°)

  Bond	Dist.		Bond	Dist.		Bond	Dist.
  Cl(1)–Cu(1) Cu(1)–N(5)	2.275(3) 2.061(9)		Cl(2)–Cu(1)	2.225(3)		Cu(1)–N(4)	1.979(9)
  Angle	(°)		Angle	(°)		Angle	(°)
  Cl(2)–Cu(1)–Cl(1) N(4)–Cu(1)–N(5)	94.35(12) 80.3(4)		N(4)–Cu(1)–Cl(2) N(5)–Cu(1)–Cl(2)	171.9(3) 93.9(3)		N(4)–Cu(1)–Cl(1) N(5)–Cu(1)–Cl(1)	90.9(3) 169.5(2)

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  Table 2.  Hydrogen Bonds for Complex 3 (Å, °)

  D–H···A	d(D–H)	d(H···A)	d(D···A)	∠DHA
  C(10)–H(10)···Cl(2)	0.93	2.71	3.584(12)	157
  C(2)–H(2)···Cl(1)	0.93	2.76	3.526(12)	140
  C(13)–H(13)···Cl(2)	0.98	2.69	3.512(14)	141

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  Table 3.  Coupling of (Hetero)aryl Chlorides with Various N(H)-heterocycles^{a, c}

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•