Anodic electrosynthesis of MIL-53(Al)-N(CH2PO3H2)2 as a mesoporous catalyst for synthesis of novel (N-methyl-pyrrol)-pyrazolo[3,4-b]pyridines via a cooperative vinylogous anomeric based oxidation

In this paper, the MIL-53(Al)-NH2 metal–organic frameworks (MOFs) was prepared based on the anodic electrosynthesis under green conditions. The anodic electrosynthesis as an environmentally friendly procedure was performed in the aqueous solution, room temperature, atmospheric pressure, and in the short reaction time (30 min). Also, the employed procedure was accomplished without the need for the ex-situ salt and base/probase additives as cation source and ligand activating agent at the constant current mode (10.0 mA cm−2). The electrosynthesized MOFs was functionalized with phosphorus acid tags as a novel mesoporous catalyst. This mesoporous catalyst was successfully employed for synthesis of new series (N-methyl-pyrrol)-pyrazolo[3,4-b]pyridines by one-pot condensation reaction of 3-methyl-1-phenyl-1H-pyrazol-5-amine, 3-(1-methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile and various aromatic aldehydes (mono, bis and tripodal). This catalyst proceeded the organic synthetic reaction via a cooperative vinylogous anomeric based oxidation mechanism with a marginal decreasing its catalytic activity after recycling and reusability.

www.nature.com/scientificreports/ mechanisms were suggested for the synthesis of new molecules with pyridine structure in the presence and absence of oxygen 67,68 .
Since molecules with indole moieties are biological interest candidates 69 and our background on the comprehensive reviewing of bis and tris indolyl methanes 70 , we decided to synthesis pyridines with both indole and pyrazole moieties. Therefore, in continuation of our investigations on the development of electrosynthesis of metal-organic frameworks (MOFs) and its chemical post-functionalization with phosphorous acid tags [47][48][49][50][51] , herein we wish to report a green methodology for preparing of new MIL-53(Al)-N(CH 2 PO 3 H 2 ) 2 as an efficient mesoporous catalyst. For this purpose, the MIL-53-(Al)-NH 2 was successfully fabricated via anodic electrosynthesis technique in the aqueous solution, short reaction time (30 min), room temperature, and atmospheric pressure at the constant current mode (10.0 mA cm −2 ). It should be noted that the employed procedure was accomplished without the need for the related cation salt as a cation source and ex-situ base/probase additive for deprotonation of the ligand. The final mesoporous catalyst was prepared through functionalizing of MIL-53-(Al)-NH 2 with the phosphorous acid tags and utilized for the synthesis of new (N-methyl-pyrrol)-pyrazolo [3,4-b] pyridines by the condensation reaction of 3-methyl-1-phenyl-1H-pyrazol-5-amine, 3-(1-methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile and various aromatic aldehydes (mono, bis and tripodal) under green conditions (Fig. 3).

Experimental
Materials. 2 Instrumental measurements. From the model of the BRUKER Ultrashield FT-NMR spectrometer (δ in ppm) were recorded 1 H NMR (600 or 400 MHz), 13 C NMR (151 or 101 MHz). Recorded on a Büchi B-545 apparatus in open capillary tubes were melting points. The PerkinElmer PE-1600-FTIR device was recorded for infrared spectra of compounds. SEM was performed using a scanning electron microscope for field publishing made by TE-SCAN. Thermal gravimetry (TG) and differential thermal gravimetric (DTG) were analyzed by a Perkin Elmer (Model: Pyris 1). BET and BJH were analyzed by BELSORP-mini ii high precision Surface area and pore size. Xrd was analyzed by ITAL STRU CTU RE APD2000.
General procedure for the anodic electrosynthesis of MIL-53(Al)-NH 2 . In a typical anodic electrosynthesis procedure, (0.1 mmol, 0.127 g) potassium nitrate (KNO 3 ) as a supporting electrolyte was dissolved in 45.0 mL distilled water (Solution A). Also, (8.2 mmol, 1.5 g) of 2-amino terephthalic acid (NH 2 -H 2 BDC) as a ligand was dissolved in the 5.0 mL EtOH (solution B) and added to solution A (10 Vol% EtOH). The precursor was stirred at room temperature for 15 min before the electrosynthesis. In the following, the prepared precursor transferred to the homemade undivided two-electrode cell consists of a cap glass bottle and two Aluminum plates (100.0 mm × 30.0 mm × 2.0 mm) as working (cation source) and the auxiliary electrodes. Electrosynthesis of MOF was performed by applying 10.0 mA cm −2 current densities for 30 min. The MIL-53-(Al)-NH 3 powders were removed from the solution by centrifuge at 5000 rpm for 5 min and rinsed twice with distilled water and DMF. The final MIL-53-(Al)-NH 3 was aged overnight at 100 °C.
For more details, the EDX analysis was also accomplished for elemental analysis and elemental dispersity of prepared MOFs (Fig. 9). The emerged elemental peaks approved the existence of C, O, N, and Al elements in the MIL-53(Al)-NH 2 structure and P element in the MIL-53(Al)-N(CH 2 PO 3 H 2 ) 2 structure. Besides, the EDX mapping images indicates the uniform and homogeneous distribution of elements (Fig. 10).
Also, FE-SEM images of electro-synthesized MIL-53(Al)-NH 2 and its post-functionalized one were recorded for investigation of their morphologies (Fig. 11). The obtained images exhibit the uniform cauliflower-shaped nanoparticles with an average diameter size of around 33.0 nm. The increasing of the EtOH/H 2 O ratio than pure H 2 O solvent in the electrosynthesis procedure can lead to the lower crystallinity of structure and smaller particles 32-34 . www.nature.com/scientificreports/ The specific surface area and pore size distribution are considered as significant parameters of the prepared porous materials and can be affected on the catalysis performance. In this way, the N 2 adsorption/desorption technique was employed for the investigation of the MIL-53(Al)-NH 2 and MIL-53(Al)-N(CH 2 PO 3 H 2 ) 2 structure porosity (Fig. 12). As can be seen, the N 2 adsorption/desorption plots exhibit the IV-type isotherms with the hysteresis loops as a feature of the mesoporous materials. It is noteworthy, the created mesophase is consistent with the fact that increased EtOH/H 2 O ratio in the synthesis process can lead to mesoporosity structures [32][33][34] . According to the obtained BET results, the specific surface areas of MIL-53(Al)-NH 2 and MIL-53(Al)-N(CH 2 PO 3 H 2 ) 2 structure are 204.75 and 132.19 m 2 g −1 , respectively. Also, according to the obtained BJH information, the pore size of MIL-53(Al)-NH 2 and MIL-53(Al)-N(CH 2 PO 3 H 2 ) 2 structure was determined to be 4.2 nm and 3.2 nm, respectively. It should be noted that the surface area and pore size of functionalized MOF was decreased. Thus, it can be assigned to the presence of the larger phosphorus acid tags than amine groups during the post-modification process.
The thermogravimetric (TGA) analysis for MIL-53(Al)-N(CH 2 PO 3 H 2 ) 2 was performed to study at range of 50-800 °C, with a temperature increase rate of 10 °C min −1 in CO 2 atmosphere (Fig. 13). The first distinguished weight loss step in the temperature zone of 50-100 °C can be assigned to the evaporation and removal of solvents. The second distinguished weight loss step in the temperature zone of 150-450 °C can be assigned to the decomposition of the organic section of material includes the ligand and phosphorus acid which leads to the degradation and collapse of the framework.
After identification of MIL-53(Al)-N(CH 2 PO 3 H 2 ) 2 as mesoporous hybrid-catalyst, we tested its catalytic activity in the preparation of novel organic and biological interest candidates (N-methyl-pyrrol)-pyrazolo [3,4-b] pyridines derivatives. Optimization of reaction for synthesis of target molecules were done by one-pot reaction of benzaldehyde (1.0 mmol, 0.106 g), 3-methyl-1-phenyl-1H-pyrazol-5-amine (1.0 mmol, 0.174 g) and 3-(1-methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile (1.0 mmol, 0.148 g) as a model reaction. The optimized data is listed in Table 1. As shown, the most optimal one-pot reaction for the preparation of (N-methyl-pyrrol)-pyrazolo [3,4-b] pyridines is reported in the presence of 10.0 mg MIL-53(Al)-N(CH 2 PO 3 H 2 ) 2 at 110 °C under solvent-free condition (Table 1 entry 4). The obtained data for the model reaction using other amounts of catalyst and temperature shows that the yield and time were not improved (Table 1 entries 1-8 except 4). The model reaction was also studied by using several solvents such as EtOH, CH 2 Cl 2 , CHCl 3 , EtOAc, CH 3 CN, PEG, n-Hexane, H 2 O and DMF (5.0 mL) and solvent-free condition in the presence of 10.0 mg of catalyst. The results of the reaction did not improve (Table 1, entries 9-17).

Conclusion
In this study, electrosynthesis of MIL-53(Al)-NH 2 as a metal-organic framework was presented. The anodic electrosynthesis as an environmentally friendly technique procedure was performed in the aqueous solution, room temperature, and atmospheric pressure in the shortest possible time. Also, the employed electrochemical technique provided a promising procedure for the preparation of mesoporous catalyst with a shorter time and high yield. Then its functionalization with the phosphorus acid tags through the post-modification process has occurred. It is noteworthy, this procedure was accomplished without the need for the ex-situ salt and base/ pre-base additives as cation source and ligand activating agent, respectively. MIL-53(Al)-N(CH 2 PO 3 H 2 ) 2 as an efficient catalyst was used for the synthesis of the novel (N-methyl-pyrrol)-pyrazolo [3,4-b]pyridines as biological interest molecules via a cooperative vinylogous anomeric based oxidation mechanism. Short reaction time, clean profile of reaction, recycling and reusing of catalyst are the major advantages of the presented work. We think that the present work can open up a promising insight for developing of anomeric effect in the course of organic synthesis. www.nature.com/scientificreports/ www.nature.com/scientificreports/  www.nature.com/scientificreports/ Reprints and permissions information is available at www.nature.com/reprints.
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