Silica-grafted DBU-supported NiCl2: a sustainable heterogeneous catalyst for A3 coupling

Silica-grafted DBU-supported NiCl2 complex, 1-(3-((3-(silica-trioxysilyl) propyl) amino) propyl) azepan-2-one nickel chloride (SiO2@DBU-NiCl2), has been designed and synthesized by multistep approach and characterized by FT-IR, XRD, EDS, FE-SEM, TGA and XPS. Catalytic activity of SiO2@DBU-NiCl2 has been explored for A3 coupling of terminal alkynes, aldehydes and secondary amines resulting in excellent yields (up to 97%). Special features of present protocol are high TONs (625–1212) and TOFs (52–404), low catalyst loading (0.08 mol %), solvent-free conditions, facile recyclability and reusability of the catalyst (up to 5 times).


Introduction
One of the major challenges in organic synthesis is the creation of molecular diversity and complexity from simple and readily available substrates [1]. This has necessitated need for the development of processes that allow the formation of several bonds in a single operation [2,3]. Multi-component reactions (MCRs) are convergent chemical processes involving the condensation of more than two reactants to form a product that contains significant portions of all reactants, ideally all atoms [4]. MCRs offer high level of atom efficiency by avoiding time-consuming isolation and purification of synthetic intermediates [5]. By reducing the number of reaction steps and starting from simple, inexpensive starting materials, the cost of constructing highly diverse and complex molecules is reduced to a minimum [6]. Owing to these fascinating features, MCRs have emerged as one of the most illuminating and 1 3 efficient tools of green chemistry for the formation of carbon-carbon bonds [7][8][9][10]. A large number of privileged scaffolds have been synthesized via MCRs [11][12][13].
Considering the aforementioned points and in continuation of our work in green chemistry [60], we report herein synthesis of silica-grafted DBU-supported NiCl 2 for A 3 coupling of terminal alkynes, aldehydes and secondary amines under solvent-free condition.

Instrumentation
All reactions were carried out under aerobic conditions in dry glassware. Infrared spectra were measured with a Perkin-Elmer Fourier transform infrared spectrophotometer (FTIR). 1 H and 13 C NMR spectra were recorded on a Brucker AV 400 (400 MHz for 1 H and 100 MHz for 13 C NMR) spectrometer using CDCl 3 as solvent and tetramethylsilane (TMS) as an internal standard. Chemical shift (δ) is expressed as parts per million (ppm), and coupling constants are expressed in hertz (Hz). The thermal gravimetric analysis (DSC-TGA) curve was obtained on the SDT Q600 V20.9 Build 20 instrument in the presence of nitrogen atmosphere at a linear heating rate of 10 °C/min from 0 °C to 800 °C. XRD pattern was taken using Ultima IV. FE-SEM and EDS analysis was carried out using Carlzeiss (Model: Gemini 300). The gas chromatography mass spectroscopy was performed on Shimadzu Japan (Model: QP2010). The X-ray photoelectron spectroscopy was studied using XPS-JEOL Japan (Model: 9030).

Preparation of 3-chloropropyl-functionalized silica (SiO 2 -Cl)
Silica (1.5 g) was suspended in hydrochloric acid for 24 h, washed several times with deionized water until the pH became 7 and dried under vacuum at 120 °C for 12 h. A mixture of 3-chloropropyltriethoxysilane (1.45 mL), activated silica, triethylamine (as a catalyst, 0.2 mL) and toluene (10 mL) was refluxed for 24 h. Afterward, the solvent was decanted and the residue was washed thoroughly with toluene, ethanol, deionized water and methanol to yield 3-chloropropyl-functionalized silica (SiO 2 -Cl) which was dried under vacuum at 60 °C for 12 h.

General procedure for A 3 coupling
A round-bottom flask (50 mL) equipped with a condenser was charged with aldehyde (1.0 mmol), amine (1.2 mmol), alkyne (1.5 mmol), SiO 2 @DBU-NiCl 2 (0.008 mmol) and vigorously stirred at 90-100 °C. After completion of reaction as monitored by TLC, the reaction mixture was dissolved in ethyl acetate (5 mL) filtered to remove insoluble catalyst and the filtrate was extracted with ethyl acetate (3 × 5 mL) and brine water. The combined organic layers were collected, dried over anhydrous Na 2 SO 4 and concentrated in a vacuum to afford the crude product. The product was purified by column chromatography (silica gel; Pet ether/ethyl acetate, 9:1 v/v).

X-ray diffraction (XRD) analysis
The XRD pattern of the SiO 2 @DBU-NiCl 2 is shown in Fig. 4. The broad peak at 2θ = 22.6° reflects amorphous nature of catalyst, and the spikes seen are apparently seemed to be peak, but they are not peaks as background-to-signal ratio is less than 2. Due to the lower amount of NiCl 2 with respect to SiO 2 and amorphous nature of catalyst, their patterns only show the hump at 22.6° [89,90].

Thermo-gravimetric (TGA-DSC) analysis
TGA-DSC curve of SiO 2 @DBU-NiCl 2 was examined, and three degradation phases were displayed (Fig. 5). Initial weight loss of 17.61% is attributed to the evaporation of water adsorbed on silica composite. The second loss of 18.91% corresponds to the decomposition of the supporting materials and the third loss of 2.90% is ascribed to the decomposition of the nickel complex. DTGmax of Ni catalyst was detected at 336.36 °C. The 60.58% residual mass observed is due to formation of silica and metal oxides (SiO 2 and NiO) (Fig. 5). TGA results revealed that SiO 2 @DBU-NiCl 2 has high thermal stability.

FE-SEM / EDS Analysis
The surface morphology of SiO 2 @DBU-NiCl 2 was investigated by field emission scanning electron microscope (FE-SEM). The FE-SEM images confirm the presence of Ni nanoparticles, as a rock-like particles with discrete spherical shape without any signs of aggregations (Fig. 6a-f) [87,91].
The EDS analysis of SiO 2 @DBU-NiCl 2 indicates the presence of oxygen, carbon, silicon, nitrogen, nickel and chlorine (Fig. 7a-f) which confirms the successive   (Fig. 9 a). As shown in Fig. 9 b, the high-resolution Ni 2P XPS spectrum of the SiO 2 @DBU-NiCl 2 catalyst shows peaks at 853.85 and 871.12 eV, respectively, confirming that nickel in the catalyst exists in the form of Ni +2 oxidation state. The C 1S, N 1S and O 1S spectrums reapplied to further analyze the carbon, nitrogen and oxygen forms in the SiO 2 @DBU-NiCl 2 catalyst. As observed in Fig. 9 e, the high-resolution C 1S XPS spectrum of SiO 2 @DBU-NiCl 2 can be fitted to four peaks located at 283.77, 284.63, 285.34 and 286.33 eV for C-Si, C-C, C-N and C = O bonding linkages. Similarly, as observed in Fig. 9 f, the high-resolution N 1S XPS spectrum of SiO 2 @DBU-NiCl 2 can be fitted to four peaks at 399.52, 398.18, 398.94 and 400.83 eV for N-C, N-H, N-Ni and N = C functionalities, respectively. By fitting the high-resolution O 1S spectrum ( Fig. 9 g), it can be found that the O 1S spectrum can be divided into four peaks located at 531. 91 2 and SiO x , respectively. The XPS study revealed that successive functional modification of fresh silica supported nickel(II) catalyst(SiO 2 @DBU-NiCl 2 ). Further, XPS analysis of reused SiO 2 @DBU-NiCl 2 catalyst was carried out after the recycling study, as shown in Fig. 10 a-g. Importantly, the oxidation states of the nickel (Ni +2 ) in the SiO 2 @DBU-NiCl 2 catalyst remained unchanged and were identical to those of fresh SiO 2 @DBU-NiCl 2 . The synthesized SiO 2 @DBU-NiCl 2 is therefore evidently a highly stable catalyst, as shown by the XPS analysis, which also explains why it displayed compelling catalytic performance up to several times in the A 3 coupling under solvent-free conditions [92][93][94][95][96][97].
After synthesis and characterization, the catalytic activity of SiO 2 @DBU-NiCl 2 was explored for A 3 coupling of aldehydes, amines and phenylacetylene for the synthesis of propargylamine derivatives (Scheme 2).

Synthesis of propargylamine derivatives via A 3 coupling
Using the optimized reaction conditions, the one-pot three-component coupling of various aldehydes, amines and phenyl acetylene were studied using SiO 2 @ DBU-NiCl 2 under solvent-free conditions. As the model reaction described in Scheme 2, 1.0 mmol aldehyde, 1.2 mmol of amine and 1.5 mmol phenyl acetylene along with 40 mg of SiO 2 @DBU-NiCl 2 catalyst (Ni(II) content = 0.08 mol %), under solvent-free condition, were stirred at 100 °C for 12 h. For these studies, two different strategies were employed to explore the efficiency of heterogeneous SiO 2 @DBU-NiCl 2 catalytic system for the synthesis of diverse propargylamines. In the first strategy, various structurally divergent amines were allowed to react with benzaldehyde and phenylacetylene for the three-component coupling reaction. The results obtained from these studies are presented in Table 2. As can be seen from Table 2, the SiO 2 @DBU-NiCl 2 -based catalytic protocol is rather general in nature as it is applicable for a variety of acyclic amines and cyclic amines substrates such as dimethyl amine, pyrrolidine, piperidine and morpholine as they readily react with benzaldehyde and phenyl acetylene to form the corresponding
The plausible mechanism for A 3 coupling is depicted in Scheme 3. Initially, active catalytic species Ni(0) is generated in situ from Ni(II) in SiO 2 @DBU-NiCl 2 . The mechanism involves three steps, viz. generation of Ni(II)-acetylide intermediate from alkyne and iminium ion from aldehyde and amine. The Ni(II)acetylide intermediate reacts with the iminium ion to give corresponding propargylamine forming water as a side product, and the SiO 2 @DBU-NiCl 2 catalyst is regenerated (with retention of oxidation state of Ni +2 ) for catalyzing next catalytically cycles in consequent reactions.

Comparison of SiO 2 @DBU-NiCl 2 with reported catalysts for A 3 coupling
The catalytic efficiency of SiO 2 @DBU-NiCl 2 was compared with various catalysts reported in the literature for the A 3 coupling of benzaldehyde, morpholine and phenylacetylene. The comparison revealed that SiO 2 @DBU-NiCl 2 is equally efficient as compared with other catalysts summarized in Table 3 in terms of yield and temperature. It is noteworthy that, as compared with most of the methods, SiO 2 @DBU-NiCl 2 required less reaction time, less mol % of catalyst and work under solvent-free conditions.

Reusability study of SiO 2 @DBU-NiCl 2 for A 3 coupling
The reusability of SiO 2 @DBU-NiCl 2 was examined by performing coupling of benzaldehyde, morpholine and phenylacetylene for synthesis of propargylamine as the model reaction. After completion of the reaction, the solid catalyst was filtered and washed with ethanol and ethyl acetate. The recovered catalyst was then used for the next reaction cycles (Table 4). It was observed that the catalyst retains its activity and could be reused for five-cycles without significant decrease in its catalytic performance. Additionally, hot filtration test was performed on the model reaction, after 50% completion of reaction catalyst was removed and reaction was continued. It was observed that there is no increase in the yield of product beyond 50% even after long reaction time. This illustrated heterogeneous nature of SiO 2 @DBU-NiCl 2 .

Conclusion
We have synthesized novel silica-supported nickel catalyst (SiO 2 @DBU-NiCl 2 ), characterized by FT-IR, XRD, EDS, FE-SEM, TGA and XPS and explored its catalytic activity for A 3 coupling of phenylacetylene with a variety of aldehydes and amines in solvent-free condition, for the synthesis of wide range of targeted products up to 97% yield. The catalyst featured with good recyclability, high thermal stability, easy filtration and recovery from the reaction media, high yields, high TONs and TOFs. The developed method illustrated a promising potential for A 3 coupling under umbrella of green chemistry.

Supplementary Information
The online version contains supplementary material available at https:// doi. org/ 10. 1007/ s11164-023-04980-1. Author's contribution All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by P. S. Pharande and S. K. Ghotekar. The first draft of the manuscript was written by G. S. Rashinkar, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Acknowledgements
Funding No funds, grants, or other support was received.
Data availability Data are available as electronic supplementary material. Declarations