Clean Synthesis of Propargylamines Using Novel Magnetically Recyclable Silver Nanocatalyst (AgMNPs)

Abstract A novel and green magnetic nanocatalyst were synthesized by anchoring silver (I) to (2-iminomethyl)pyridine moiety. The prepared nanocatalyst was identified by different techniques, such as FT-IR, XRD, SEM, EDX, VSM, and TGA analyses. The nanocatalyst exhibited significant catalytic activity and recoverability in a three-component coupling reaction of aldehyde, amine, and terminal alkyne to produce a variety of propargylmines. This impactful method furnished the desired products under mild reaction conditions, in excellent yield (91–98%) and lower reaction time (25–45 min). The nanocatalyst was easily recovered by an external magnet and reused in10 consecutive cycles without a considerable decrease in its activity and selectivity. Graphical Abstract


Result and discussions
The nano-magnetic catalyst was prepared and characterized by FT-IR, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), and vibrating sample magnetometer (VSM) measurements. According to previous research, 48 nano a-Fe 2 O 3 was produced by co-precipitation method from aqueous Fe 2þ /Fe 3þ salt mixture in ammonia solution. Then nanoparticles were encapsulated with HAp to support its magnetic feature. In the next step, a-Fe 2 O 3 @HAP after calcination in 450 C were added to the mixture of 3-aminopropyl trimethoxy silane in toluene and refluxed for 48 h. FT-IR spectrum of nanoparticles ( Figure 1), represents Fe À O absorption in hematite at 461 cm À1 , another vibration band was observed at 602 and 557 cm À1 due to O À PÀO in surface phosphate group of HAP, also the aromatic C ¼ C and C ¼ N was observed at 1426 and 1629 cm À1 were assigned to organic linker immobilized onto the surface.
The XRD patterns of catalyst 4 as shown in (Figure 2), indicate common peaks at 24.12, 33.   According to EDX the amount of loaded silver is about 12.25 W % ($1.14 mmol/g catalyst).
The EDX spectrum of the nanocatalyst 4 is presented in (Figure 3), also the EDS shows the presence of Fe, Si, Ca, P, N, and the peaks of the related Ag þ in the structure of the nanoparticles.
The morphological characteristic of magnetic nano catalyst 4 is observed with SEM. The SEM image of catalyst 4 depicted formations of spherical particles with average size 30 nm ( Figure 4).
Thermogravimetric analysis (TGA) of the catalyst was performed at the range of 25-800 C ( Figure 5), to investigate thermal stability and use within a wide temperature range. The weight loss on heating from 80 to 250 C is $2.25% and might be attributed to the release of moisture. Thermal degradation occurred after 250 C associated to the decomposition of organic coating and heating was continued up to 520 C with 6.95% weight loss approximately. TGA of the catalyst demonstrated high thermal stability.
The magnetic properties of the prepared nanocatalyst 4 have been analyzed by VSM. The magnetization saturation at relatively low external field indicates a narrow nanosize distribution. These results also indicate the successful preparation of heterogeneous nano catalyst 4. The M  (H) hysteresis loop for the sample was completely reversible with saturation magnetization values of 14.67 emu/g at room temperature ( Figure 6).
After characterization of the catalyst, its efficiency was examined for the synthesis of propargylamines using a one-pot three-component reaction (Scheme 2). In a preliminary test reaction of p-Cl-benzaldehyde (1.0 mmol), piperidine (1.2 mmol), and phenylacetylene (1.3 mmol) in the presence of catalyst 4 was examined. Then, various reaction parameters, such as effect of temperature, catalyst loading, solvent, and reaction time were studied in order to develop an optimal catalytic system. The results are collected in Table 1.
It is evident from the results, that 0.5 mol% of AgMNPs catalyzed the A 3 coupling reaction in H 2 O in lower reaction time and higher yield ( Table 1, Entry 2). However, increasing the amount of AgMNPs to 1 mol% did not improve the reaction profile.
In order to explore the efficiency of the present method for the synthesis of propargylamine derivatives, the synthesis of compound 5a was compared with some of those reported in the   (Table 2). It is evident from the results that AgMNPs afford excellent yield at lower temperature and reduced reaction time.
After investigation of optimal reaction condition, various aldehyde, alkyne and amine were used as substrate under optimal reaction condition to prepare the targeted propargylamines. The results of this study are collected in Table 3. As shown in Table 3 aryl aldehydes bearing both electron-withdrawing and electron-donating groups afforded the products in reasonable reaction time and excellent yield. In addition, aliphatic aldehydes with longer hydrocarbon chain (Entries 9 and 12) compared to lower hydrocarbon chain (Entries 8, 10, and 11) furnished the condensation products in higher reaction time and lower yields.
A proposed mechanism for the synthesis of propargylamines is presented in Scheme 3. Terminal C À H bond of alkyne was activated by Ag catalyst and a metal alkyne complex intermediate was formed. The resulted silver acetylide intermediate reacted with iminium ion generated in situ from aldehyde and secondary amine thus produced desired product and regenerated the silver nanocatalyst.
Recyclability of the nanomagnetic AgMNPs was determined in the synthesis of 5a. After each reaction, AgMNPs were separated simply with external magnet, washed with ethyl acetate then  reused in the next run. After 10 consecutive cycles, the catalytic efficiency of the catalyst was retained without any appreciable changes in its activity which implied that the recovered catalyst is durable and can be utilized in repeated uses (Figures 7 and 8).

General
All commercially available chemicals were purchased from Merck, and used without further purification. The products were characterized by 1 H NMR (500 MHz) and 13 C NMR (125 MHz) spectra recorded on a Bruker NMR instrument in DMSO-d 6 and CDCl 3 as solvent and TMS as an internal standard. Chemical shifts for 1 H and 13 C NMR were expressed in ppm downfield from tetramethylsilane. XRD was run by using a Philips X-Pert diffractometer with Co tube. Scanning electron microphotographs (SEM-EDX) were obtained on a MIRA3TESCAN-XMU microscope. TEM micrograph was performed by Philips CM200 microscope. The magnetic properties of catalyst were measured by VSM/alternating gradient force magnetometer (VSM/AGFM, MDK Co, Ltd, Kashan, Iran). TGA were measured by METTLER TOLEDO instrument. All solvents used were dried and distilled according to standard procedures.  3.1. 1. Preparation of a-Fe 2 O 3 @HAp@Ag a-Fe 2 O 3 @HAp-Si-(CH 2 ) 3 -NH 2 was prepared according to reported procedure. 41 Then, resulted nanomagnetic solid treated with equimolar amount of 2-pyridinecarboxaldehyde in absolute ethanol under Ar atmosphere to give compound 3. Finally, catalyst 4 was prepared by reacting compound 3 with AgNO 3 at room temperature in water. Catalyst 4 was magnetically separated by an external magnet, then rinsed by distilled water and dried under vacuum at room temperature (Scheme 1).

2. General procedure for AgMNPs catalyzed A 3 coupling reaction
Aldehyde (1 mmol), secondary amine (1.2 mmol), and terminal alkyne (1.3 mmol) were mixed with catalyst 4 (0.5 mol%) in water (5 mL) in a beaker at 60 C. The progress of the reaction was monitored by TLC using mixture of ethyl acetate and n-hexane (2:3). After completion of the reaction, catalyst easily separated by external magnet. Organic layer was extracted completely by ethyl acetate and dried over anhydrous MgSO 4 . Finally, the solvent was removed by rotary evaporator and further purification was not required.

Conclusion
Finally, a novel Ag (I) complex bearing chelating 2-imminomethyl pyridine was prepared by immobilization onto HAp-encapsulated-a-Fe 2 O 3 as recyclable and environmentally benign nanocatalyst. Its catalytic activity was investigated in the one-pot condensation of aldehydes, secondary amines, and alkynes in water as solvent to produce several propargylamines in excellent yields. The use of magnetically recoverable nanocatalyst, easy work up of the products without any need for chromatographic purification, using water as green medium instead of toxic organic solvents and recyclability of the catalyst which can be used at least in ten consecutive runs without appreciable leaching of silver and decrease in catalytic activity, are some notable achievements of this methodology.