Green synthesis of thiourea derivatives from nitrobenzenes using Ni nanoparticles immobilized on triazine-aminopyridine-modified MIL-101(Cr) MOF

Nanohybrid metal–organic frameworks (MOF) have recently been considered next-generation catalysts regarding their unique features like large surface-to-volume ratio, tailorable geometry, uniform pore sizes, and homogeneous distribution of active sites. In this report, we address the triazine-aminopyridine-modified 3D Cr-centred MOF MIL-101(Cr)-NH2 following a post-synthetic modification approach. The excellent chelating ability of triazine-aminopyridine was applied to immobilize Ni ions over the host matrix MOF. The as-synthesized material was physicochemically characterized using various analytical techniques like FT-IR, electron microscopy, EDS, elemental mapping, XRD, and ICP-OES. Subsequently, the material has been catalytically employed in synthesizing new thiourea derivatives by reacting to nitrobenzene derivatives and phenyl isocyanate. The catalyst was isolated by centrifugation and recycled in 6 consecutive runs without momentous loss of its reactivity.

carbon disulfide in an aqueous medium allows efficient synthesis of symmetrical and unsymmetrical substituted thiourea derivatives.The synthesis of thiocarbonyl from the combination of sulfur and chloroform in a two-step process was reported by Tan in 2017.A dichloromethane-mediated reaction of carbamoyl isothiocyanates with amines was reported by Linton (SI, Fig. 1, Eqs. 1-4) [41][42][43][44] .Most of the hitherto known methods suffer from limitations such as harsh reaction conditions, and use of expensive, toxic catalysts, the formation of side products, and poor yields of desired products.Regarding the important biological properties of synthetic thiourea compounds, an effective procedure for fabricating thiourea derivatives was developed through nitroarene reduction using functionalized MOF (SI, Fig. 1, Eq. 5).
Because nitrobenzenes are toxic, they have adverse effects on humans and other organisms and are a pollutant in the environment 45 .Therefore, developing new catalytic systems for effective and economical removal methods is of great importance.Besides, reducing nitrobenzenes to synthesize thiourea derivatives is a quietly significant synthon in organic synthesis and is present in various pesticides, pharmaceuticals, and fine chemicals [46][47][48] .Despite developing heterogeneous catalysts with metals such as Pd, Au, Pt, and Mo, selective reduction of nitro compounds is still challenging under mild conditions 47 .
Regarding the mentioned points, the present article introduces the design and characterization of a new Crbased MOF functionalized triazine-aminopyridine via post-synthetic modifications.Triazine-aminopyridine is a recognized and excellent chelating ligand, and we exploited it to anchor Ni ions at the outer shell of MIL-101(Cr)-NH 2 .Ni NPs species were then successfully decorated on prepared support (MIL-101(Cr)-NH-TA-AP) (Fig. 1).The catalytic activities of this successfully synthesized nanocatalyst were tested in synthesizing thiourea derivatives through nitrobenzene reduction.Operational simplicity, green reaction conditions, simple and inexpensive procedure, high efficiency, short reaction times, easy catalyst separation, and reusability for several consecutive cycles are the key advantages of this protocol.The other key advantage of this protocol is that the reactions were found to be complete at room temperature.This method is found to tolerate substrates having electron-donating and withdrawing functionalities.In addition to the above advantages, we also observed this transformation is equally effective in water as a green solvent.

General method for the fabrication of thiourea derivatives. A mixture of nitrobenzene analogs
(1 mmol), sodium borohydride (1.5 mmol), phenyl isocyanate (1 mmol), and MIL-101(Cr)-NH-TA-AP/Ni (50 mg, 0.1 mol%) was stirred at room temperature in H 2 O (2 mL) for the suitable time, as illustrated in Table 2.After the end of the reaction, the catalyst was filtered off.The residue was extracted with ethyl acetate to obtain pure products in 91-98% yields.www.nature.com/scientificreports/XRD analysis was used to check the crystal structure of MIL-101(Cr)-NH 2 and MIL-101(Cr)-NH-TA-AP/ Ni samples (Fig. 3).The major diffraction peaks of MIL-101(Cr)-NH 2 appeared at 2θ angles of 3.25°, 8.41°, 9.02°, 10.5°, and 16.49°, which are in agreement with pattern reported in the literature (Fig. 3a) 49,50 .In the XRD spectrum of MIL-101(Cr)-NH-TA-AP/Ni, a minor shift in position and width, few intense peaks, and several sharp peaks in the pattern are observed, confirming the successful formation of the mentioned nanocatalyst (Fig. 3b).Moreover, the presence of sharp peaks in 2θ between 10° and 50° suggests the successful functionalization of MIL-101(Cr)-NH 2 .Afterward, using Scherrer and Bragg's equations, the average monthly distance and crystal size was determined to be 40 nm.These results are in good agreement with the result obtained from SEM images.Figure 3c illustrates XRD patterns of recycled MIL-101(Cr)-NH-TA-AP/Ni nanocomposite.As clearly can be seen from the XRD image, the catalyst retains its initial crystallinity and particles size (Fig. 3c).Since post-synthetic modification of MIL-101(Cr)-NH 2 leads to the synthesis of the final catalyst with less crystallinity, and the simulated pattern is only used for single crystal materials, in this research, the simulated pattern of MIL-101(Cr)-NH 2 was added to Fig. 3.In the functionalized MOF, due to the presence of functional groups, the triazine-aminopyridine groups occupy the available surface of the MOF.As a result, some peaks are removed, which is consistent with previous studies 51 .

Results and discussion
SEM analysis was applied to examine the morphological and chemical changes of MIL-101(Cr)-NH-TA-AP/ Ni.The SEM image of the MIL-101(Cr)-NH indicates almost a spherical structure morphology.In addition, according to Fig. 4A-D, there is no significant change even after the immobilization of metal species.It is of note that functionalized MOF can retain Ni NPs species in the pores and prevent their agglomeration (Fig. 4E-H).Nitrogen adsorption-desorption isotherm measurement of MIL-101(Cr)-NH-TA-AP was undertaken to confirm the porous nature of the catalyst and estimate their surface area (Fig. 7a).The analysis of the BET revealed the formation of nanoparticles with a total pore volume of 0.15 cm 3 /g, an average pore diameter of 10.61 nm, and a surface area of 22.04 m 2 /g (Table 1).The adsorption isotherm is type IV, and the presence of mesoporous structure in the material is evident from the appearance of the hysteresis loop.From this BET analysis, it is inferred that our nano-support has a mesoporous nature surface and huge surface area, which is a primary property of excellent catalysts.Figure 7b  The changes associated with the textural properties of the 6th reused catalyst can be due to the distribution of the reactants inside the pores (Table 1).
Figure 8 shows the TGA curves showing the residual masses of MIL-101(Cr)-NH-TA-AP/Ni in the temperature range of 25 to 600 °C.The TGA curve initially displays an imperceptible weight loss of 17% in the region  Optimization conditions.The optimum conditions were selected by studying the effect of solvent on the reaction rate for the preparation of 1,3-diphenyl thiourea by condensation of nitrobenzene and phenyl isocyanate in the presence of 0.1 mol% (MIL-101(Cr)-NH-TA-AP/Ni) under different solvents (e.g., ethanol, methanol, EtOH:H 2 O, toluene, and H 2 O) at 50℃ (Table 2, entry 1-5).Overall, the best results were obtained with 0.1 mol% MIL-101(Cr)-NH-TA-AP/Ni using water solvent (Table 2, entry 5).Moreover, the study set of experiments determines the optimal amount of catalyst MIL-101(Cr)-NH-TA-AP/Ni require for the reaction.The reaction was carried out by variable amounts of catalyst (Table 2, entries 6-7), and maximum yield was found with 0.1 mol% of the catalyst.Further increasing the amount of catalyst MIL-101(Cr)-NH-TA-AP/Ni in the mentioned reaction condition did not significantly improve product yields (Table 2, entry 7).Examining the model reaction at room temperature demonstrated that temperature is essential to the reaction efficiency (Table 2, entry 8).The response of the studied model at different times showed that the highest yield and conversion were obtained at 30 min (Table 2, entry 9).Finally, the efficacy of the catalyst was evaluated by performing the sample reaction by MIL-101(Cr)-NH 2 -Ni.The results indicate the functionalized MOF provides the required product with great efficiency (Table 2, entry 10 vs. 5).The generality of the method was demonstrated using different substituted nitrobenzenes.The reaction scope was expanded, and excellent reaction conversions were obtained with nitrobenzenes having electron-donating and electron-withdrawing groups.This finding reveals that the substituents on nitrobenzene have no noticeable effect on the reaction conversion (Table 3).In this work, new thiourea derivatives were developed innovatively (entries 2, 5, 8, and 9).
The proposed synthesis mechanism for phenyl thiourea is illustrated in Fig. 9.The mesoporous nature of MIL-101(Cr)-NH-TA-AP/Ni catalyst gives it unique characteristics like high surface area, tunable pore size, and large pore volume, which favor their enhanced accessibility to active sites with improved mass transport/ diffusion.A hydride molecule is transferred to the nitro group by adsorbing sodium borohydride on the NPs' surface.The nitroso intermediate A, formed by water elimination, adsorbed on the MIL-101(Cr)-NH-TA-AP/Ni, is again reduced by the hydride transfer from sodium borohydride to the hydroxylamine B. This intermediate is   www.nature.com/scientificreports/further reduced to the aniline 60,61 .Lastly, phenylthiourea is obtained by the reaction between aniline and phenyl isocyanate.
The robustness of the MIL-101(Cr)-NH-TA-AP/Ni nanocomposite, as an imperative distinctiveness of catalyst in practical applications of organic transformation, was examined by successive six runs (i.e., 98, 96, 95, 93, 91, and 88).The MIL-101(Cr)-NH-TA-AP/Ni solid was recycled via simple filtration and washed with ethanol.The catalyst MIL-101(Cr)-NH-TA-AP/Ni reusability was checked in the synthesis of 1,3-diphenyl thiourea.Based on the obtained results, robust and excellent chemical stability of MIL-101(Cr)-NH-TA-AP/Ni is confirmed by FESEM, FTIR, and EDX-elemental mapping spectral analysis after six runs (Fig. 10).The FTIR of recycled catalyst confirmed the stability of the catalysts as the regeneration data do not exhibit any change after the initial patterns (Fig. 10a).In addition, FESEM of the catalyst after the 6th recycling (Fig. 10b) along with EDX-elemental mapping spectra (Fig. 10c,d) demonstrates the presence of Ni and functionalized MIL-101(Cr)-NH 2 on the catalyst surface.The results show that the catalyst retains its initial morphology and structure without any change.As can be seen from EDX data and elemental mapping, no change occurs in elemental composition, validating the robustness of our material.The histogram in Fig. 11 represents the recyclability of the fabricated nanocatalyst for the synthesis of 1,3-diphenyl thiourea.The minor reduction observed in the catalytic ability is likely due to the normal dissipation of the catalyst in the workup process.Here, nickel concentration determined by ICP analysis changed from 8.79 mmol/g to 8.76 mmol/g after the 6th run.Therefore, the MIL-101(Cr)-NH-TA-AP/ Ni nanocomposite is highly stable under the studied reaction conditions.

Conclusion
We introduced a triazine-aminopyridine-modified MIL-101(Cr)-NH 2 metal-organic framework (MOF) with Ni NPs decorated over its surface.Ni NPs were immobilized following a post-functionalization of triazineaminopyridine over the core MIL-101(Cr)-NH 2 MOF than the typical surface deposition.The excellent chelating potential of triazine-aminopyridine was exploited to deposit Ni NPs over it.The material's structural morphology and physicochemical features were explored over different instrumental methods.In addition, atomic mapping analysis displays the uniform dispersion of active sites throughout the surface matrix.The nanocatalyst was used to synthesize thiourea derivatives through nitrobenzene reduction under mild and green conditions affording outstanding yields.The material's robustness was validated by recycling it for 6 consecutive cycles without considerable loss of its reactivity.Moreover, Ni species had negligible leaching in the reaction medium, justifying its true heterogeneity.
shows the N 2 adsorption and desorption isotherms of the MIL-101(Cr)-NH-TA-AP/Ni.These isotherms exhibit type V isotherms (typical of mesopores) and type H3 hysteresis loops (indicating slit-shaped pores).According to the Langmuir adsorption isotherm, the specific surface area of the MIL-101(Cr)-NH-TA-AP/Ni is 17.16 m 2 g −1 .Figure 7c presents the N 2 adsorption and desorption isotherms of the recovered MIL-101(Cr)-NH-TA-AP/Ni.They indicate type V isotherms (typical of mesopores) and type H3 hysteresis loops (indicating slit-shaped pores).According to the Langmuir adsorption isotherm, the specific surface area of the recovered MIL-101(Cr)-NH-TA-AP/Ni is 7.36 m 2 g −1 .

Figure 9 .
Figure 9.The mechanistic pathway proposed for the synthesis of thiourea from nitrobenzene derivatives.