iClick reaction of a Cu(II) azido complex having a Schiff base ligand

Abstract

The [3+2] cycloaddition reactions of a square-planar Cu(II) azido complex with alkynes and coordinating nitriles were investigated.

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Click chemistry, particularly the [3+2] cycloaddition reactions involving azides and alkynes or nitriles, has emerged as a powerful tool in synthesizing nitrogen-rich heterocycles such as triazoles and tetrazoles.^1,2 These heterocycles have found extensive applications as ligands in coordination chemistry, owing to their rich electronic properties and structural versatility.^3–5 Among these, pyridine-substituted triazoles and tetrazoles have been widely employed in the synthesis of metal complexes, with potential applications in various fields, including catalysis, materials science, and medicinal chemistry.^4,6–8 An intriguing development in this domain involves the in situ formation of triazolato and tetrazolato complexes within the coordination sphere of a metal center. This transformation is achieved through a [3+2] cycloaddition between metal-bound azides and alkynes or nitriles, resulting in structurally diverse and functionally significant metal complexes. In 2011, the concept of “iClick reaction” for inorganic click reactions was coined by A. S. Veige's research group, in which they reported a [3+2] cycloaddition reaction of the (triphenylphosphine)gold(I) azide with the linear (triphenylphosphine)gold(I) alkynyl complex, affording a homobimetallic triazole complex with exclusive 1,5-regioselectivity (Scheme 1).⁹ Since then, various iClick reactions have been explored using different types of metal azido complexes and dipolarophiles.^10–15 There are reports on Cu(II) tetrazolato complexes in the literature, also. These have been synthesized using various approaches, most commonly via reactions of metal salts with tetrazoles generated in situ through [3+2] cycloaddition of sodium azide and nitriles,^16–18 while solvothermal methods have been predominantly employed for the preparation of polymeric copper tetrazolate materials.^19–21 In contrast, only a limited number of copper(II) azido complexes having Schiff base ligands and other N-donor bidentate and tridentate auxiliary ligands have been reported to undergo [3+2] cycloaddition with nitriles to afford the corresponding tetrazolato complexes; notably, in all these cases, the azide functions as a bridging ligand between two Cu(II) centers.^22–25 Recently, Cazin and co-workers reported the synthesis of a Cu(I)–NHC azido complex and investigated its reactivity toward alkynes and nitriles.²⁶ Their study led to the formation of an N1-bound triazole complex, as well as several mono- and homobimetallic tetrazole complexes. Notably, such bridging of the tetrazolate group between two metal centres has also been observed in the case of Ni(II) complexes.²⁷

Scheme 1 Representative iClick reaction between the Au(I) azido complex and Au(I) acetylide.⁹

Cu(I)-catalysed click reactions for triazole synthesis are well established.^28,29 However, structurally well-defined copper-triazole complexes remain exceedingly rare. To date, only a single example has been reported in the literature, originating from a Cu(I)–NHC azido precursor. Copper-triazole formation via [3+2] cycloaddition has yet to be demonstrated for Cu(II) azido systems.²⁶ A survey of the literature further indicates that the sole example of [3+2] cycloaddition involving a Cu(II) azido complex corresponds to a dinuclear species supported by an N^N^O donor Schiff-base ligand, [Cu(N^N^O)(N₃)]₂, which features μ-1,1-bridging azide ligands.²² This complex reacts with 2-cyanopyridine to yield a bis(pyridyltetrazolato) copper(II) complex, [Cu(PTZ)₂(H₂O)₂], via a process that proceeds with concomitant displacement of the original N^N^O chelating ligand. Notably, [3+2] cycloaddition reactions of square-planar Cu(II) azido complexes with alkynes and nitriles bearing terminal azide ligands remain unexplored to date.

To investigate the inorganic click ([3+2] cycloaddition) reaction of the Cu(II) azido complex, a tridentate N^N^O Schiff base ligand (HL) was employed to stabilize a mononuclear Cu(II) azido complex 1. Infrared spectroscopy confirmed the presence of terminal azide groups, with characteristic stretching bands observed at 2050 cm⁻¹ (please see the SI). Single-crystal X-ray diffraction studies revealed that the Cu(II) center adopts a square-planar coordination geometry, defined by a tridentate deprotonated Schiff base ligand and a terminal azide ligand. The azide moiety exhibits an asymmetric canonical N–N≡N bonding motif,^30,31 with proximal and distal N–N bond lengths of 1.170(5) and 1.121(5) Å, respectively (Fig. S15).

The [3+2] cycloaddition reaction of complex 1 with an excess of ethyl 4,4,4-trifluorobut-2-ynoate gave an N1-bound Cu(II) triazolato complex 2 (Scheme 2). After 10 minutes of the onset of the reaction, the FT-IR spectrum revealed the complete disappearance of the characteristic azide stretching vibration, which indicated the completion of the reaction (see the SI). The HRMS spectrum also shows the product formation. Complex 2 was further characterised by the single-crystal X-ray diffraction technique. The coordination environment around the Cu(II) center adopts a distorted square planar geometry (Fig. 1). Three of its four coordination sites are occupied by a tridentate deprotonated Schiff base ligand. An N1-bound triazolato ligand occupies the fourth coordination site. In this complex, the Cu1–O2 bond length, 2.644 Å, is notably longer than the sum of covalent radii and smaller than the van der Waals radii of Cu and O atoms, suggesting some interaction between the two. The Cu–N_triazolate bond length in complex 2 [1.991(4) Å] is slightly longer than the corresponding Cu–N_azido bond length observed in the parent azido complex 1 (1.954(3) Å). DFT calculations reveal that the N1-bound triazole is more stable than the N2- and N3-bound isomers by 10.76 and 15.75 kJ mol⁻¹, respectively. In comparison, the same reaction with the Ni(II) azido complex yielded the homobimetallic triazolato complex in which the nitrogen atom of the triazolate ligand and the oxygen atom of the ester group serve as bridges between the two Ni(II) centers.²⁷

Scheme 2 Synthesis of complex 1 and its reaction with the dipolarophile.

Fig. 1 The molecular structure of complex 2.

The same reaction with dimethyl acetylenedicarboxylate gave a triazolato complex 3 (Scheme 2). The conversion was also confirmed by the disappearance of the azide bands in the IR spectrum taken after 10 min of the beginning of the reaction. The complex was isolated and characterized by single-crystal X-ray diffraction, which reveals a dimeric structure featuring the N1 and N3 nitrogen atoms of the hydrolyzed triazolate ligand as bridging ligands between the two Cu centers. Each Cu(II) center exhibits a distorted square-pyramidal coordination geometry (Fig. 2) with the geometry parameter τ = 0.13 and 0.18.^32,33 A tridentate, deprotonated Schiff base ligand occupies three coordination sites of each Cu(II) center, coordinating through two nitrogen atoms and one phenolate oxygen atom. The remaining two coordination sites are occupied by the nitrogen and oxygen atoms of the hydrolyzed triazolato ligand. Both the Cu–N_triazolate bond lengths in complex 3 (2.004 and 2.006 Å) are slightly longer than the one observed in 1 (1.954(3) Å). The FT-IR spectrum indicate the formation of the triazolato product, as evidenced by the appearance of an intense ester carbonyl stretching band at 1732 cm⁻¹ (after 10 min). This observation is further corroborated by the HRMS data of the monomeric triazolato complex and the dimeric triazolato complex. Notably, the product underwent hydrolysis during the crystallization step and formed the dimeric triazolato complex. Based on these data, a plausible mechanism for the formation of complex 3 is proposed, as shown in Scheme S1. Notably, the analogous Ni(II) complex with DMAD gave a new complex and, under anhydrous conditions, yielded the triazolato complex.²²

Fig. 2 The molecular structure of complex 3.

Attempts to carry out the same reactions with less electron-deficient alkynes, such as phenyl acetylene and diphenyl acetylene, did not show the cycloaddition reaction.

The [3+2] cycloaddition reactions of complex 1 with 2-cyanopyridine resulted in the formation of a bis(pyridyltetrazolato)copper(II) complex 4, accompanied by the loss of the N^N^O donor ligand. The reaction was monitored using IR spectroscopy, which indicated the complete disappearance of the azide stretching bands upon reaction completion. The geometry around the Cu(II) center is octahedral in complex 4 (Fig. S16), where the Cu(II) metal center is coordinated with two 5-(2-pyridyl)tetrazolate (PTZ) ligands in a bidentate manner and also coordinated with two water molecules. This complex is similar to the previously reported complex [Cu(PTZ)₂(H₂O)₂], which is synthesized using the bridged Cu(II) azido complex.²²

Interestingly, the reaction of complex 1 with 2-cyanopyrimidine yielded a tetrazolato copper(II) complex 5 retaining the N^N^O donor ligand (Scheme 2). This conversion was also confirmed by the disappearance of the azide bands in the IR spectrum. The complex was further characterised by HRMS and single-crystal X-ray diffraction analysis. The coordination environment around the Cu(II) center adopts a distorted square-pyramidal geometry (Fig. 3) with the geometry parameter τ = 0.24.^32,33 A tridentate, deprotonated Schiff base ligand occupies three coordination sites. The remaining two sites are occupied by nitrogen atoms from the pyrimidinyltetrazolato ligand. The axial Cu1–N6 bond length is 2.3626 Å, which is notably longer than the equatorial bond distances (ranging from 1.9342 Å to 2.1085 Å), suggesting a Jahn–Teller distortion at the copper(II) center.³⁴ The Cu–N(tetrazolato) bond length in complex 5 is slightly longer than that of parent azido complex 1. It may be noted that square planar nickel(II) azido complexes produced homobimetallic tetrazolato complexes with the coordinating nitrile.^27,35,36

Fig. 3 The molecular structure of complex 5.

The [3+2] cycloaddition reaction of complex 1 with pyridine-2,6-dicarbonitrile afforded a tetrazolato complex 7 (Scheme 2), as evidenced by the complete disappearance of the azide stretching band in the IR spectrum. The complex was characterised by the single-crystal X-ray diffraction technique. The coordination environment around the Cu(II) center adopts a distorted square-pyramidal geometry, as shown in Fig. 5 (geometry parameter τ = 0.09 and 0.21).^32,33 The complex is polymeric in nature. Single-crystal X-ray analysis reveals that the amine part of the initially employed Schiff base ligand is dissociated. Simultaneously, one cyano group of pyridine-2,6-dicarbonitrile undergoes conversion to an amide, which reacts with the aldehyde fragment of the Schiff base to generate a new imine linkage. This unprecedented transformation leads to a modified Schiff base ligand featuring an appended tetrazolate unit.

The IR spectrum recorded before crystallization exhibited a characteristic nitrile stretching band, with no evidence of an amide group. The HRMS spectrum of the reaction mixture of complex 1 and pyridine-2,6-dicarbonitrile also showed the cyclized tetrazolato product formation through one nitrile, having the initial N^N^O donor ligand. These data suggest that the complex is hydrolyzed during crystallization in the DMF solvent. The hydrolytic conversion of one cyano group of pyridine-2,6-dicarbonitrile to an amide was also confirmed by the single-crystal X-ray analysis of the intermediate complex 6, in which the tetrazolato ligand acts as a bridge between the two Cu(II) centers (Fig. 4). The direct conversion of an amide functionality into a Schiff base is relatively uncommon. However, this conversion has been reported in recent years under catalytic conditions employing either the Pd(II) or the CuCl catalyst.^37,38

Fig. 4 The molecular structure of the amide intermediate complex 6.

Fig. 5 The molecular structure of complex 7.

Based on these facts, a plausible mechanism for the formation of complex 7 is proposed, as shown in Scheme S2.

Reactions with non-coordinating nitriles, such as acetonitrile, benzonitrile, and acrylonitrile, were unsuccessful, and these nitriles remained unreactive toward either of the copper(II) azido complexes, even under reflux conditions in acetonitrile. IR spectroscopy indicated no change in the characteristic azide stretching frequencies.

The magnetic properties of the freshly synthesized Cu(II) complexes 3 and 7 were investigated at 298 K using a vibrating sample magnetometer. The M–H plots are presented in Fig. S21–S24. The observed S-shaped magnetization curves after subtracting the diamagnetic contribution and the presence of a small hysteresis loop suggest that both complexes exhibit weak ferromagnetic Cu–Cu coupling.

This study reveals the distinct reactivity patterns of a square-planar mononuclear copper(II) azido complex featuring a terminal azide group toward the [3+2] cycloaddition reaction with alkynes and nitriles. Reactions with activated alkynes led to the formation of mono and dinuclear Cu(II) triazolato complexes, whereas cycloaddition with nitriles revealed selective ligand dissociation or retention depending on the nature of the nitriles. Notably, an unprecedented transformation involving Schiff-base imine hydrolysis followed by cyano-induced re-imine formation with pyridine-2,6-dicarbonitrile is observed, representing a rare example of ligand reorganization triggered by the azide–nitrile cycloaddition chemistry. In contrast, less electron-deficient alkynes, such as phenylacetylene and diphenylacetylene, as well as non-coordinating nitriles, including acetonitrile and benzonitrile, did not participate in the cycloaddition process, highlighting the inherent selectivity of the system. Single-crystal X-ray diffraction studies confirmed distinct coordination geometries and pronounced Jahn–Teller distortions in the resulting square-pyramidal complexes. These findings expand the scope of triazole and tetrazole-based complex formation via copper(II) azido complexes, offering insights into the design of new coordination architectures with tailored reactivity. Importantly, the hydrolysis of the triazolato ester unveils a novel and generalizable strategy for accessing heterobimetallic complexes, wherein post-cycloaddition ligand modification enables metal-bridging coordination modes that are otherwise inaccessible.

Caution! Azides and azido complexes are potentially explosive. Although no problems were encountered with the preparations mentioned here. However, heating of the solid compounds was avoided.

AS designed and characterized the complexes and solved the single crystal X-ray structures. SB planned and supervised. Both authors have approved the final version of the manuscript.

Conflicts of interest

There are no conflicts to declare.

Data availability

The data supporting this article have been included as part of the supplementary information (SI). Supplementary information is available. See DOI: https://doi.org/10.1039/d6cc00423g.

CCDC 2373943, 2373944, 2383064, 2464427, 2524617, 2524619, and 2533279 contain the supplementary crystallographic data for this paper.^39a–g

Acknowledgements

A. S. thanks UGC [JRF ref. No.: 221610061961] for providing a fellowship.

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39. (a) CCDC 2373943: Experimental Crystal Structure Determination, 2026 DOI:10.5517/ccdc.csd.cc2kp8tc; (b) CCDC 2373944: Experimental Crystal Structure Determination, 2026 DOI:10.5517/ccdc.csd.cc2kp8vd; (c) CCDC 2383064: Experimental Crystal Structure Determination, 2026 DOI:10.5517/ccdc.csd.cc2kzs1d; (d) CCDC 2464427: Experimental Crystal Structure Determination, 2026 DOI:10.5517/ccdc.csd.cc2nqfnh; (e) CCDC 2524617: Experimental Crystal Structure Determination, 2026 DOI:10.5517/ccdc.csd.cc2qr28v; (f) CCDC 2524619: Experimental Crystal Structure Determination, 2026 DOI:10.5517/ccdc.csd.cc2qr2bx; (g) CCDC 2533279: Experimental Crystal Structure Determination, 2026 DOI:10.5517/ccdc.csd.cc2r12pl.

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