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Article

Nanostructured Na2CaP2O7: A New and Efficient Catalyst for One-Pot Synthesis of 2-Amino-3-Cyanopyridine Derivatives and Evaluation of Their Antibacterial Activity

1
Laboratory of Organic Synthesis, Extraction, and Valorization, FSAC, Hassan II University of Casablanca, B.P. 2693 Maarif, Casablanca 20000, Morocco
2
Laboratory of Molecular Bacteriology, Pasteur Institute of Morocco, Casablanca 20250, Morocco
3
Laboratory for Materials, Catalysis and Valorization of Natural Resources, Faculty of Sciences and Technology, Hassan II University of Casablanca, Mohammedia 28806, Morocco
4
Laboratory of Applied Chemistry & Environment, Université Mohammed Premier, Oujda 60000, Morocco
5
Interfaces, Traitements, Organisation et Dynamique des Systèmes (ITODYS), CNRS-UMR 7086, Université Paris Cité, F-75013 Paris, France
*
Authors to whom correspondence should be addressed.
Appl. Sci. 2022, 12(11), 5487; https://doi.org/10.3390/app12115487
Received: 14 April 2022 / Revised: 24 May 2022 / Accepted: 25 May 2022 / Published: 28 May 2022

Abstract

:
A facile and novel synthesis of thirteen 2-amino-3-cyanopyridine derivatives 5(am) by a one-pot multicomponent reactions (MCRs) is described for the first time, starting from aromatic aldehydes, malononitrile, methyl ketones, or cyclohexanone and ammonium acetate in the presence of the nanostructured diphosphate Na2CaP2O7 (DIPH) at 80 °C under solvent-free conditions. These compounds were brought into existence in a short period with good to outstanding yields (84–94%). The diphosphate Na2CaP2O7 was synthesized and characterized by different techniques (FT-IR, XRD, SEM, and TEM) and used as an efficient, environmentally friendly, easy-to-handle, harmless, secure, and reusable catalyst. Our study was strengthened by combining five new pyrido[2,3-d]pyrimidine derivatives 6(b, c, g, h, j) by intermolecular cyclization of 2-amino-3-cyanopyridines 5(b, c, g, h, j) with formamide. The synthesized products were characterized by FT-IR, 1H NMR, and 13C NMR and by comparing measured melting points with known values reported in the literature. Gas chromatography/mass spectrometry was used to characterize the newly synthesized products and evaluate their purity. The operating conditions were optimized using a model reaction in which the catalyst amount, temperature, time, and solvent effect were evaluated. Antibacterial activity was tested against approved Gram-positive and Gram-negative strains for previously mentioned compounds.

Graphical Abstract

1. Introduction

Pyridine and its derivatives are known to be the essential chemical compounds in medicinal chemistry [1,2,3]. They are key scaffolds in biologically active and naturally occurring substances. Many pharmacological properties of pyridine and its derivatives have been reported, including antimicrobial [4], anticancer [5], anti-inflammatory [6], antiviral [7], antidiabetic [8], and antimalarial activities [2]. In addition, heterocyclic systems involving the β-enaminonitrile moiety represent a class of intermediates considered to be extremely reactive and used as precursors for synthesis of brand-new heterocyclic compounds [9,10,11]. The literature mentions that several different pyridine derivatives, particularly 2-amino-2-cyanopyridines, have been prepared as target structures using sustainable catalyst materials [12] coupled with environmentally benign protocols. Moreover, it is interesting to note that multicomponent reactions (MCRs) have drawn the attention of many researchers in the last decade due to their productivity and simplicity. MCRs are used for the development of biologically active compounds from accessible commercial reagents with a single step [13]. Furthermore, in our case, the combination of this process with a solvent-free medium for the preparation of these heterocyclic derivatives makes the use of MCRs compliant with the principles of green chemistry.
Several studies have reported the usefulness and importance of these processes, in which they were exploited for the synthesis of 2-amino-3-cyanopyridine in the presence of various catalysts, such as ytterbium perfluorooctanoate [Yb(PFO)3] [14], Bu4N+Br [15], [email protected] [16], cellulose-SO3H [17], MgO [18], HBF4 [19], Fe3O4@SiO2@(CH2)Im}C(CN)3 [20], FePO4 [21], and poly(ethylene glycol) (PEG-400) [22]. However, these procedures present several inconveniences, such as long reaction time, undesirable reaction conditions, the need for loads of reagents, the use of organic solvents and toxic reagents, and the non-recoverability of the catalyst. Thus, a new, efficient, and environmentally friendly protocol for the synthesis of 2-amino-3-cyanopyridines is required. The aim of this work is to investigate and examine Na2CaP2O7 as an alternative catalyst, as it has received increased attention recently, mainly in the environmental field [23,24,25].
This work is a continuation of our investigation and according to our results obtained in a previous study based on adopting Na2CaP2O7 as a catalyst in organic synthesis [26,27,28], particularly in the synthesis of heterocyclic compounds via multicomponent reactions in an ecofriendly medium [29,30]. Herein, we report here an efficient and rapid one-pot synthesis of thirteen 2-amino-3-cyanopyridine derivatives by condensation of aromatic aldehydes, malononitrile, methyl ketone, or cyclohexanone and ammonium acetate using a nanostructured diphosphate Na2CaP2O7 as a heterogeneous catalyst under solvent-free reaction conditions at 80 °C (Scheme 1). Five prepared 2-amino-3-cyanopyridine were converted to pyrido[2,3-d]pyrimidines, and we examined the antibacterial activity of all prepared compounds.

2. Results and Discussion

2.1. Synthesis and Characterization of Na2CaP2O7 Nanoparticles

Na2CaP2O7 nanoparticles were synthesized according to procedures described in the literature [31]. Nanostructured pyrophosphate was synthesized using the dry method. Stoichiometric amounts of sodium carbonate (Na2CO3), calcium carbonate (CaCO3), and ammonium dihydrogen phosphate (NH4H2PO4) with a molar ratio of 1:1:2 were blended in an agate mortar. The mixture was transferred to a porcelain crucible and heated progressively from 100 to 600 °C (Figure 1). Then, the obtained powder was characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, and transmission electron microscopy.

2.2. Characterization of Diphosphate Na2CaP2O7

The X-ray diffraction pattern of diphosphate Na2CaP2O7 is shown in Figure 2. All diffraction peaks are consistent with the standard data of the ICSD collection code: 89,468. Crystals of diphosphate Na2CaP2O7 have a triclinic structure, space group P1bar and crystal parameters a = 5.361 Å, b = 7.029 Å and c = 8.743 Å, V = 308.31 Å3, and Z = 2.
The FT-IR spectrum of Na2CaP2O7 is displayed in Figure 3. The bands at 720 cm−1 and 888 cm−1 are defined as the symmetrical (sym) and antisymmetric (anti) vibration of P-O-P, respectively. These bands confirm the presence of pyrophosphate P2O7 groups. Two fields share the associated vibrations of the PO4 groups: a symmetrical vibration field (997 cm−1, 1031 cm−1) and the other from 1112 cm−1 to 1278 cm−1. The described bands confirm that Na2CaP2O7 was prepared.
The morphology of the Na2CaP2O7 surface was elucidated by scanning electron microscopy (SEM, Figure 4). Na2CaP2O7 has a homogeneous microstructure that contains layers of various sizes and forms.
Transmission electron microscopy (TEM) was further used to study the morphology and microstructure of Na2CaP2O7. Figure 5 shows rod-like nanoparticles that agglomerate to form superstructures with different grain crystal aspect ratios. The powder forms show irregular grains with a lateral size of 90–150 nm. The specific surface of the Na2CaP2O7 areas were determined by the Brunauer–Emmett–Teller (BET) method from the adsorption–desorption isotherm of N2 at 77 K and was identified to be 4 m2·g−1.

2.3. Optimization of Reaction Conditions

In order to establish the optimal synthesis condition for substituted 2-amino-3-cyanopyridines, a reaction of benzaldehyde 1a (1 mmol), malononitrile 2 (1.1 mmol), acetophenone 3a (1 mmol), and ammonium acetate 4 (1.5 mmol) was chosen as a model and carried out under various conditions; Na2CaP2O7 was used as a catalyst (Scheme 2).

2.4. Influence of the Amount of the Catalyst

To optimize the catalyst amount, the model reaction was performed with different quantities of the catalyst and according to obtained results (Table 1, entries 2–8). An amount of 0.05 g (20%) of the nanostructured diphosphate Na2CaP2O7 was chosen as the optimal catalyst amount; with this amount, the reaction can be performed in 30 min, providing a 94% yield of 5a (Figure 6). With an increased amount of Na2CaP2O7, there was no improvement in the product yields (Table 1, entries 7 and 8). This may be due to the attainment of the maximum conversion efficiency of the catalyst. No target product was observed without the catalyst. This result suggests that our catalyst plays an important role in this transformation (Table 1, entry 1).

2.5. Influence of Reaction Time

Temperature and time also play a significant role in reaction kinetics. In order to study the effect of these two parameters, a varied range of temperature (40–100 °C) was used to carry out the model reaction for different time periods (15–120 min) and by using 0.05 g of Na2CaP2O7 (Table 1, entries 9–14). The first period, time ranges from 15 to 30 min, was characterized by significant changes in the yield of the product. During this period, the product yield increased by 12% after 5 min (from 15 to 20 min) and by 29% during the following 10 min (from 20 to 30 min). The highest yield (94%) was achieved at 80 °C after 30 min. The yield of 5a remained unchanged even after extending the reaction time and increasing the temperature (Table 1, entries 11, 13, and 14).

2.6. Influence of the Solvent

The effect of the solvent on the reaction rate was also investigated by carrying out the model reaction in the presence of 0.05 g of Na2CaP2O7 for 30 min with various solvents (1 mL), such as water, ethanol, dichloromethane (DCM), ethyl acetate (EtOAc), n-hexane, and acetonitrile (MeCN). Figure 2 summarizes the effects of various solvents on the percentage yield of 2-amino-3-cyanopyridine 5a. We observed that when solvents were used, the yield decreased, indicating that the use of a solvent has a strong inhibitory effect on the reaction yield. This effect can be explained by the dilution of the reaction medium, which leads to a decrease in the interaction between the reactant and the catalyst (Na2CaP2O7).
However, the highest yield of the desired product was achieved when the reaction was carried out under solvent-free conditions (Figure 7).
After determining the optimal conditions for the synthesis of 2-amino-3-cyanopyridine 5a, the reactions of different aromatic aldehydes containing substituents in the aromatic ring, such as Me, OMe, Cl, and NO2, with malononitrile 2, acetophenone derivatives, or cyclohexanone 3 and ammonium acetate 4 were carried out under identical reaction conditions. The thirteen desired 2-amino-3-cyanopyridine derivatives 5(a–m) were obtained with good to excellent yields (84–94%), as shown in Table 2. The nature of aromatic ring substituents had no noticeable effect on the yields of synthesized 2-amino-3-cyanopyridines 5. All reactions with aromatic aldehydes proceed without the formation of byproducts.
In order to explain the formation of 2-amino-3-cyanopyridine 5, we propose a credible mechanism, which is shown in Scheme 3.
Na2CaP2O7 catalyzes the synthesis of 2-amino-3-cyanopyridine derivatives 5 by activating the carbonyl group of aromatic aldehyde 1, making it more susceptible to nucleophilic attack by malononitrile to form arylidenemalononitrile derivative 3′, which reacted with imino derivative 2′, which was formed by the reaction between ammonium acetate and ketone 2 via Michael addition to form adduct 4′. Intermediate 4′ cyclized to dihydropyridine 4″, followed by tautomerization aromatization to afford 2-amino-3-cyanopyridine derivative 5. The proposed mechanism presented in Scheme 3 was confirmed by another mechanism reported in the literature [16,20].

2.7. Recyclability of Na2CaP2O7 Catalyst

To investigate the recyclability and regeneration of the catalyst, Na2CaP2O7 was regenerated by two procedures. In the first method, the catalyst was rinsed with acetone and dried for 1h at 100 °C after each experiment. The second method employed for regeneration involved calcination at 500 °C for 1 h after washing with acetone and drying at 100 °C. Figure 3 summarizes the reusability and regeneration research of Na2CaP2O7. This result shows that calcination of the recovered catalyst at 500 °C has a positive effect on the catalytic activity of the diphosphate Na2CaP2O7. The increase in catalytic activity upon calcination can be explained by the rearrangement of the active sites of the catalyst [32,33]. The recycled Na2CaP2O7 revealed almost the same catalytic performance compared with the first run (Figure 8).
The importance of the prepared 2-amino-3-cyanopyridines is apparent through their reactions with formamide to form the corresponding pyrido[2,3-d]pyrimidines, which have received considerable attention in recent years due to their diverse biological and pharmacological activities, such as antibacterial [34], antiallergic [35], anti-inflammatory [36], anti-HIV [37], antihypertensive [38], and antitumor activity [39]. Pyrido[2,3-d] pyrimidine 6 was synthesized by reaction of 2-amino-3-cyanopyridines 5 with formamide (Scheme 4). Our study was focused on the synthesis of the pyrido[2,3-d]pyrimidine derivatives 6(b, c, g, h, j) by the condensation of the 2-amino-3-cyanopyridines 5(b, c, g, h, j) with formamide.
As mentioned below, the five pyrido[2,3-d]pyrimidine derivatives 6(b, c, g, h, j) were obtained in moderate yields (71–81%), as shown in Table 3.

2.8. Antimicrobial Activity

Three derivatives, namely cyanopyridine (5a and 5b) and pyrimidine (6b), revealed their effectiveness against Gram-positive and Gram-negative bacteria tested with minimum inhibitory concentrations (MIC) and minimum bactericidal concentration (MBC) values ranging from 64.5 to 250 µg/mL. Table 4 reports the inhibition zone diameter (IZD), MICs, and MBC values. In general, pyrimidine (6b) was the most active in comparison with the other components. It showed a strong effect against S. aureus and B. subtillis, with IZD values of 21–20.5 mm. Cyanopyridine (5a and 5b) were less active against S. aureus and slightly less active against B. subtillis, with an IZD of 18.5 and 17 mm, respectively. Moreover, the MBC to MIC ratios calculated for the derivatives indicate that they are bactericidal rather than bacteriostatic molecules. Hence, the derivatives possessing a methyl group exhibited good antibacterial activity, as the methyl group is considered an electron-donating group, which increases the electron density, makes the compounds effective against micro-organisms, and enhances their antibacterial activity [40].

3. Discussion

In this study, we synthesized thirteen cyanopyridines and five pyrimidines and screened for antibacterial activity in eight strains. We found that cyanopyridine derivatives (5a and 5b) have an antibacterial effect against E. coli and B. subtilis. However, other synthesized molecules of the same family did not exhibit any antimicrobial effects against either bacteria or fungi at the tested concentrations [41,42].
A single pyrimidine derivative (6b) showed antibacterial activity, probably due to the nature of the heterocycle. Our results are in agreement with other scientific findings [43] from studies on the antibacterial and antifungal effect of new pyrimidine derivatives based on benzothiazole by testing on bacterial strains (S. aureus, E. coli, K. pneumonia, and P. aeruginosa) and on the fungal agent C. albicans. These studies revealed that the derivatives exert an antibacterial and antifungal effect, which varies from one molecule to another, and some of the derivatives were found to have antibacterial effects on all the strains tested, as well as an antifungal effect against C. albicans. This effect can be influenced by aromatic substituents, in particular, those with electron-donating properties.
Several targets have been described for antibacterial agents, such as disruption of cell walls, membrane permeabilization, targeting of drug efflux pumps, targeting of R plasmids, and targeting quorum sensing, which plays an important role in regulating biofilms. Several studies showed that antibacterial agents tend to act more strongly on Gram-positive than on Gram-negative bacteria. This is probably due to the differences in cell wall composition and structure, as Gram-negative bacteria possess an outer membrane [44].

4. Conclusions

Based on the results obtained in the present study, we can conclude that Na2CaP2O7 is a green and recoverable catalyst for the synthesis a series of 2-amino-3-cyanopyridine derivatives. In this paper, we reported the synthesis of five new pyrido[2,3-d]pyrimidine derivatives by intermolecular cyclization reaction of 2-amino-3-cyanopyridines with formamide. These synthesized products have a significant antibacterial effect. The absence of a solvent, simplicity of preparation, and the use of a green catalyst are some of the significant advantages of this ecofriendly procedure. Therefore, we suggest that Na2CaP2O7 should receive increased attention in the future as an alternative catalyst for the one-pot synthesis of molecules known for their various biological and pharmacological activities.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/app12115487/s1, The supporting information includes the experimental procedures, the materials used in this research work, and full characterization data for organic products. References [45,46,47,48,49,50,51,52] are cited in the supplementary materials.

Author Contributions

Conceptualization: R.A., A.E. (Abdelhakim Elmakssoudi) and J.J.; synthesis: R.A. and A.T.; antimicrobial activity: A.E. (Abdelaziz Elamrani) and Y.Z.; methodology: M.D., M.Z., A.E. (Abdelhakim Elmakssoudi), J.J. and M.M.C.; validation: all authors; writing—original draft: R.A. and A.E. (Abdelhakim Elmakssoudi); writing—review and editing: R.A., A.E. (Abdelhakim Elmakssoudi), Z.A.-T. and M.M.C.; supervision: A.E. (Abdelhakim Elmakssoudi) and J.J.; funding acquisition: J.J. All authors have read and agreed to the published version of the manuscript.

Funding

Financial support from the National Center for Scientific and Technical Research (CNRST) is gratefully acknowledged. This work was also supported by University Hassan II of Casablanca and the Molecular Bacteriology Laboratory, Pasteur Institute, Casablanca.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

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Scheme 1. Synthesis of 2-amino-3-cyanopyridine derivatives catalyzed by Na2CaP2O7.
Scheme 1. Synthesis of 2-amino-3-cyanopyridine derivatives catalyzed by Na2CaP2O7.
Applsci 12 05487 sch001
Figure 1. Schematic describing the preparation of Na2CaP2O7 nanoparticles.
Figure 1. Schematic describing the preparation of Na2CaP2O7 nanoparticles.
Applsci 12 05487 g001
Figure 2. X-ray powder diffraction pattern of Na2CaP2O7.
Figure 2. X-ray powder diffraction pattern of Na2CaP2O7.
Applsci 12 05487 g002
Figure 3. FT-IR spectrum of Na2CaP2O7.
Figure 3. FT-IR spectrum of Na2CaP2O7.
Applsci 12 05487 g003
Figure 4. SEM images of Na2CaP2O7 at different magnifications.
Figure 4. SEM images of Na2CaP2O7 at different magnifications.
Applsci 12 05487 g004
Figure 5. TEM micrographs of Na2CaP2O7 nanopowder.
Figure 5. TEM micrographs of Na2CaP2O7 nanopowder.
Applsci 12 05487 g005
Scheme 2. Synthesis of 2-amino-3-cyanopyridine (5a).
Scheme 2. Synthesis of 2-amino-3-cyanopyridine (5a).
Applsci 12 05487 sch002
Figure 6. Influence of the amount of the Na2CaP2O7 catalyst and reaction time on the synthesis of 2-amino-3-cyanopyridine 5a.
Figure 6. Influence of the amount of the Na2CaP2O7 catalyst and reaction time on the synthesis of 2-amino-3-cyanopyridine 5a.
Applsci 12 05487 g006
Figure 7. Influence of the solvent in the catalytic synthesis of 2-amino-3-cyanopyridine 5a.
Figure 7. Influence of the solvent in the catalytic synthesis of 2-amino-3-cyanopyridine 5a.
Applsci 12 05487 g007
Scheme 3. Proposed mechanism for Na2CaP2O7-catalyzed synthesis of 2-amino-3-cyanopyridine derivatives.
Scheme 3. Proposed mechanism for Na2CaP2O7-catalyzed synthesis of 2-amino-3-cyanopyridine derivatives.
Applsci 12 05487 sch003
Figure 8. Recyclability and regeneration study of Na2CaP2O7 in the synthesis of 5a.
Figure 8. Recyclability and regeneration study of Na2CaP2O7 in the synthesis of 5a.
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Scheme 4. Synthesis of pyrido[2,3-d]pyrimidine derivative 6.
Scheme 4. Synthesis of pyrido[2,3-d]pyrimidine derivative 6.
Applsci 12 05487 sch004
Table 1. Optimization of reaction conditions for the synthesis of 2-amino-3-cyanopyridine 5a.
Table 1. Optimization of reaction conditions for the synthesis of 2-amino-3-cyanopyridine 5a.
EntryAmount of Catalyst (g)Temperature
(°C)
Time (Min.)Yield (%) [a],[b]
Absence of a catalyst1080120-
Influence of the amount of the catalyst20.01803020
30.02803040
40.03803060
50.04803084
60.05803094
70.06803094
80.07803094
Influence of temperature and reaction time90.05802065
100.05801553
110.05804095
120.05403075
130.05603085
140.051003094
[a] Isolated yields; [b] reaction conditions: benzaldehyde (1 mmol), malononitrile (1.1 mmol), acetophenone (1 mmol), and ammonium acetate (1.5 mmol).
Table 2. Synthesis of 2-amino-3-cyanopyridine derivatives 5.
Table 2. Synthesis of 2-amino-3-cyanopyridine derivatives 5.
Applsci 12 05487 i001
EntryR1R2R3Product [a]Yield [b] (%)
1HPhH5a Applsci 12 05487 i00294
2CH3PhH5b Applsci 12 05487 i00385
3CH3OPhH5c Applsci 12 05487 i00484
4ClPhH5d Applsci 12 05487 i00595
5NO2PhH5e Applsci 12 05487 i00686
6NO2PhH5f Applsci 12 05487 i00793
7H4-CH3C6H4H5g Applsci 12 05487 i00892
8Cl4-CH3C6H4H5h Applsci 12 05487 i00990
9H4-CH3OC6H4H5i Applsci 12 05487 i01091
10Cl4-CH3OC6H4H5j Applsci 12 05487 i01189
11H-(CH2)4-5k Applsci 12 05487 i01294
12CH3-(CH2)4-5l Applsci 12 05487 i01388
13Cl-(CH2)4-5m Applsci 12 05487 i01494
[a] All products were characterized by 1H, 13C NMR, and IR spectral data (see Supplementary Data); [b] isolated yields.
Table 3. Synthesis of pyrido[2,3-d]pyrimidine derivative 6.
Table 3. Synthesis of pyrido[2,3-d]pyrimidine derivative 6.
Entry2-Amino-3-CyanopyridinePyrido[2,3-d]pyrimidine [a]Yield [b] (%)
1 Applsci 12 05487 i0156b Applsci 12 05487 i01674
2 Applsci 12 05487 i0176c Applsci 12 05487 i01871
3 Applsci 12 05487 i0196g Applsci 12 05487 i02081
4 Applsci 12 05487 i0216h Applsci 12 05487 i02279
5 Applsci 12 05487 i0236j Applsci 12 05487 i02471
[a] All products were characterized by 1H, 13C NMR, MS, and IR spectral data(see Supplementary Data); [b] isolated yields.
Table 4. Determination of the inhibition zone diameter of the synthesis of cyanopyridine derivatives (5a, 5b) and pyrimidine (6b).
Table 4. Determination of the inhibition zone diameter of the synthesis of cyanopyridine derivatives (5a, 5b) and pyrimidine (6b).
Cyanopyridine 5aCyanopyridine 5bPyrimidine 6b
IZD (mm)MIC (µL/mL)MBC (µL/mL)IZD (mm)MIC (µL/mL)MBC (µL/mL)IZD (mm)MIC (µL/mL)MBC (µL/mL)
P. aeruginosa (−)NS--NS--NS--
S. aureus (+)NS--NS--21125125
S. epidermidis (+)NS--NS--NS--
K. pneumonaie (−)NS--NS--NS--
B. subtillis (+)18.564.564.51764.512520.564.564.5
E. coli (−)131251251212525012125125
E. feacalis (+)NS--NS--NS--
C. albicansNS--NS--NS--
NS: not susceptible; IZD: inhibition zone diameter; MIC: minimum inhibitory concentration; MBC: minimum bactericidal concentration.
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Achagar, R.; Elmakssoudi, A.; Thoume, A.; Dakir, M.; Elamrani, A.; Zouheir, Y.; Zahouily, M.; Ait-Touchente, Z.; Jamaleddine, J.; Chehimi, M.M. Nanostructured Na2CaP2O7: A New and Efficient Catalyst for One-Pot Synthesis of 2-Amino-3-Cyanopyridine Derivatives and Evaluation of Their Antibacterial Activity. Appl. Sci. 2022, 12, 5487. https://doi.org/10.3390/app12115487

AMA Style

Achagar R, Elmakssoudi A, Thoume A, Dakir M, Elamrani A, Zouheir Y, Zahouily M, Ait-Touchente Z, Jamaleddine J, Chehimi MM. Nanostructured Na2CaP2O7: A New and Efficient Catalyst for One-Pot Synthesis of 2-Amino-3-Cyanopyridine Derivatives and Evaluation of Their Antibacterial Activity. Applied Sciences. 2022; 12(11):5487. https://doi.org/10.3390/app12115487

Chicago/Turabian Style

Achagar, Redouane, Abdelhakim Elmakssoudi, Abderrahmane Thoume, Mohamed Dakir, Abdelaziz Elamrani, Yassine Zouheir, Mohamed Zahouily, Zouhair Ait-Touchente, Jamal Jamaleddine, and Mohamed M. Chehimi. 2022. "Nanostructured Na2CaP2O7: A New and Efficient Catalyst for One-Pot Synthesis of 2-Amino-3-Cyanopyridine Derivatives and Evaluation of Their Antibacterial Activity" Applied Sciences 12, no. 11: 5487. https://doi.org/10.3390/app12115487

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