Natural Hydroxyapatite: Green Catalyst for the Synthesis of Pyrroles, Inhibitors of Corrosion

Polysubstituted pyrroles have been synthesized in good yields via a four-component one-pot reaction of 1,3-dicarbonyl compounds, amines, aldehydes, and nitroalkanes using natural hydroxyapatite (HAp) as an efficient green catalyst. 'is strategy provides advantages such as simple experimental and work-up procedures, mild conditions, high selectivity, low cost, high atom economy, and environmental friendliness; it uses a green commercial catalyst and does not require a solvent. 'e electrochemical behavior of S300 steel in 1M hydrochloric acidic was studied in the presence of these heterocyclic compounds.'e results showed good inhibition efficiency for steel in acidic media.


Introduction
Pyrrole derivatives are an important class of heterocyclic compounds found in a large variety of natural products and important biological molecules [1] and exhibit interesting bioactivity proprieties [2]. erefore, many methods have been developed to synthesize pyrrole derivatives [3][4][5]. Among them, multicomponent reaction (MCR) coupling, a procedure allowing the synthesize of a target molecule from three or more starting materials, has emerged as a popular and core strategy to construct functionalized pyrrole derivatives, which have been extensively reviewed with different starting materials [6]. MCRs provide interesting advantages, including the synthesis of high functionalized molecules in one pot with good overall yields without the need for the isolation and purification of the intermediate product; it has high selectivity and operational simplicity and, hence, minimal waste, time, labor, and cost [7]. us, this straightforward approach could be an environmentally friendly and economical alternative to modern organic synthesis and combinatorial and medicinal chemistry [8].
Nowadays, one of the main goals of modern organic synthetic chemistry is the search for environmentally friendly processes and methods. is new age of synthesis requires the development of clean and safe processes, less expensive resources, and lower energy requirements. In this context, heterogeneous catalysts are gaining popularity in green chemistry protocols. Only a few recent studies have reported using heterogeneous catalysts in the synthesis of pyrrole derivatives with an MCR approach [17][18][19]. However, the catalysts were not readily available or contained expensive starting materials. To address this problem, the development of a green protocol using a commercially cheap heterogeneous catalyst for the synthesis of functionalized pyrroles is highly desired, especially if the catalyst can be recovered at the end of the reaction without trace amounts of metal contamination [20].
Corrosion is a costly problem for the industry field [21]. erefore, many studies have been done to determine how to prevent metallic aggression against air and water pollution or how to remove rust or any undesirable deposits on the surface of metals caused by chemical or/and electrochemical reactions. One of the most attractive methods is the utilization of synthetic organic compounds as corrosion inhibitors [22]. Heterocyclic compounds containing donor atoms such as N, O, S, and P, as well as unsaturated bonds (electron pairs or/and π-electron), and polar functional groups (e.g., -OCH 3 , -CH 3 , -NH 2 , and -Cl) were identified as the most effective inhibitors and are widely reviewed in the literature [23]. ey are adsorbed onto the metal surface and prevent metal dissolution in aggressive media [24]. Lately, we investigated the corrosion inhibition of S300 steel in 1 M HCl using a pyrrole derivative [25].
We have recently reported a simple, rapid, and efficient synthesis of β-ketoester using HAp (Ca 5 (PO 4 ) 3 OH) as a catalyst [26]. e catalyst used in this work is a bioceramic, which can be synthesized by various methods such as hydrothermal, sol-gel, precipitation, and emulsion [27]. Despite good thermal and chemical stability, bioactivity, adsorption capacity, macroligant behavior, and acid-base propriety [28], the potential of HAp applications in catalysis support in the synthesis of polyheterocyclic compounds has been less explored [29]. In our efforts for the development of ecocompatible procedures, we report here a convenient synthesis of polysubstituted pyrroles via a four-component condensation reaction catalyzed by natural HAp in mild conditions. e corrosion inhibition of different prepared compounds was also performed using the potentiodynamic polarization method.

Materials. NMR studies were performed on a Bruker
Avance 300 spectrometer in CDCl 3 ; chemical shifts are given in ppm relative to external TMS. e reaction mixtures were analyzed on a Trace GC Shimadzu chromatograph equipped with an FID detector. GC parameters for capillary columns TG-5MS (30 m × 0.25 mm) are as follows: injector, 230°C; detector, 200°C; oven, 40°C for 2 min, followed by 40°C min −1 until 280°C for 12 min; column pressure, 42.9 kPa; gas flow, 20 mL min −1 . e spectrum mass of the products was obtained by ionization on an ISQ LT single quadruple mass spectrometer in positive EI mode using a mass scan range of 50 to 400 da. Liquid chromatography was performed on silica gel (Merck 60, 220-440 mesh). All reagents and solvents used in the experiments were purchased from commercial sources and used without further purification (Aldrich, Acros).

General Procedure for the Synthesis of Pyrrole.
To a stirred mixture of amine (2.5 mmol), aldehyde (2.5 mmol), 1,3dicarbonyl (2.5 mmol), and nitroalkane (5 mmol), HAp (S/ C � 60) was added as a catalyst. e reaction was carried out at 60°C for 24 h. After completion of the reaction, the resultant crude product was cooled to room temperature, then diluted with water (5 mL), and extracted with ethyl acetate (3 y 5 mL). e organic residue was dried over Na 2 SO 4 , and the solvent was removed under reduced pressure. e residue was purified by column chromatography over silica gel (Merck 60, 220-440 mesh) using a mixture of hexane/ethylacetate (9.5/0.5 : v/v) as an eluent to get the pyrrole desired.

Synthesis of 4-(Benzylamino)pent-3-en-2-one.
By following our reported procedure [26], a mixture of 1.7 mmol of acetylacetone, 1.7 mmol of benzylamine, and 0.017 mmol of Ca 5 (PO 4 ) 3 OH were stirred at room temperature for 10 min. After completion of the reaction, 10 mL of distilled water was added, and the product was extracted by ethyl acetate (3 × 25 ml). e organic layer was dried with Na 2 SO 4 , and the solvent was eliminated under vacuum. e desired product was obtained by silica gel column chromatography by using a mixture of hexane/ethylacetate (96/4: v/v) as an eluent.

Electrochemical Measurements.
Electrochemical tests were performed using a potentiostat PGZ100 instrument piloted by VoltaMaster 4 software. e instrument was attached to a jacketed glass cell (20 ± 1°C) with a threeelectrode configuration. A platinum sheet (2 cm 2 ) was used as the auxiliary electrode, silver-silver chloride (Ag/AgCl) was selected as the reference electrode, and 0.76 cm 2 of S300 steel was used as the working electrode with a chemical composition of Fe (98.55%), C (0.15%), Mn (1.25%), and Si (0.05%). Prior to each experiment, the working electrode was polished with various grades of sand paper, washed, and immersed in an acidic solution. e electrochemical measurements were carried out after 30 min of immersion time to establish the open circuit potential (OCP). e polarization curves were studied in the potential range of −0.8 V to −0.2 V at a scanning rate of up to 1 mV/sec. e inhibition efficiency (η%) was calculated using the following relation: where i corr and i corr ′ are the corrosion current density without and with inhibitor.
We found that the one-pot synthesis (Method A) gave a better yield of the desired pyrrole 1a with a total conversion ( Table 1, entry 1). Similar results for the synthesis of 1a were described with other catalysts [11,19]. Method B (Table 1, entry 2) did not provide a good yield, and we noticed that nitrostyrene was less reactive in the process of the reaction. e same was observed for the three-component methods ( Table 1, entries 3 and 4). Our attention was then turned to the four-component reactions described in Method A. We chose the reaction of acetylacetone (2.5 mmol), methyl benzylamine (2.5 mmol), benzaldehyde (2.5 mmol), and nitromethane (5 mmol) as the standard reaction (Scheme 2) to find the optimal conditions to improve the yield. For this purpose, various amounts of the catalyst and different solvents and temperatures were screened ( Table 2).

Optimization of the Four-Component Reaction.
e experiment performed without the catalyst in solvent-free condition at 60°C was less effective; only 20% of the product 1b was isolated ( Table 2, entry 1). We then examined the effect of HAp loading in the solvent-free reaction. e results indicated that, for a molar ratio of 60, the reaction led to a good yield of 89% (Table 2, entry 3). e use of the catalyst is, therefore, crucial for the evolution of the reaction. However, we observed that an increase in the amount of the catalyst decreased the yield of the desired product ( Table 2, entries 4  and 5).
We studied different solvents in our standard reaction using HAp (S/C � 60) as the catalyst at 60°C. e use of polar solvents, such as water and ethanol, gave good yields of the desired product ( Table 2, entries 6 and 7), as opposed to acetonitrile, which only gave a yield of 6% ( Table 2, entry 8). It can be explained by the protic character of water and ethanol which participates in the reaction medium by hydrogen bonding. In the case of toluene, only traces of the product were found under the reaction conditions ( Table 2, entry 9). e best protocol for this reaction was solvent free ( Table 2, entry 3) because it allows a direct interaction of all starting materials. We also studied the effect of temperature on the catalytic reaction. At room temperature (RT) and 40°C, only 21 and 24% of the products were isolated, respectively ( Table 2, entries 10 and 11). However, the yield of the product decreased when the temperature of the reaction increased to 90°C and 120°C ( Table 2, entries 12 and 13). e result shows that the best thermodynamic condition to perform the reaction was at a temperature of 60°C that afforded the highest yield towards the product 1b. To define a more efficient catalytic system for the synthesis of pyrrolic products, we have performed the reaction with other types of phosphate-based catalysts such as AlPO 4 and fluoroapatite (FAP) ( Table 2). We found that both catalysts afforded the same yield ( Table 2, entries 14 and 15). However, the presence of natural HAp in the four-component reaction gave the best results due to a better interaction of hydroxyl groups from HAp catalyst with the starting materials.

Kinetic Study of the Four-Component Reaction.
e evolution of the reaction through the time was studied under the optimized conditions ( Figure 1). Every two hours, a sample is taken from the reaction medium and then extracted with ethyl acetate and analyzed by GC in order to determine the selectivity of the obtained products. ree main products were detected: two intermediate products-PI1: (4-phenylamino-pent-3-en-2-one) and PI2: nitrostyrene-and the corresponding pyrrole derivative (Scheme 3). ey were isolated and confirmed by RMN study.

Journal of Chemistry
As illustrated in Figure 1, the evolution of the reaction towards the formation of the pyrrole derivative goes through intermediates (PI1 and PI2). According to the curve below, at t � 2 h, the pyrrole 1b is formed in a very small amount (10%), while the intermediates PI1 and PI2 are found as the main formed products in the reaction medium with 41% and 30%, respectively.
After 4 h, the reaction showed an increase in the selectivity towards the product 1b (49%), which resulted in the decrease in the amount of the PI1 and PI2 in the reaction medium.
e reaction started to reach stabilization after 18 h, with a maximum isolated yield of 89%.

Multicomponent Synthesis of Pyrroles by Various
Substrates. After determining the optimal reaction conditions, we extended the experimental protocol by studying the scope and limitations of this straightforward fourcomponent reaction (Scheme 4), and the results are summarized in Table 3. We first ran the reaction with acetylacetone, benzaldehyde, and nitroethane with different aromatic and aliphatic amines. e 1-phenylethylamine resulted in an excellent yield (90%) of product 1d (Table 3, entry 2), and benzylamine generated the corresponding pyrrole 1e with a yield of 74% (Table 3, entry 3). Aniline and isopropylamine exhibited moderated yields of 48% and 44%, respectively ( Table 3, entries 1 and 4). us, better yields were obtained with aliphatic amines bearing an aromatic radical rather than aromatic amines and simple aliphatic amines. Encouraged by these results, we expanded the fourcomponent procedure by examining the effect of different aromatic aldehydes. e pyrrolic products prepared from pchlorobenzaldehyde and p-methylbenzaldehyde were isolated with good yields of 67% and 77%, respectively (Table 3, entries 6 and 10). is observation showed that the yield was affected by weak electron-donating and strong electronwithdrawing substituents of aromatic aldehydes.
Furthermore, this four-component method is suitable for both nitromethane and nitroethane, giving the corresponding pyrrolic products similar yields. ese results prove that this  Journal of Chemistry method is extendable to a variety of nitroalkane compounds. e structures of products 1e and 1h were successfully confirmed by single-crystal X-ray crystallographic analysis [25,31].
We have also investigated the effect of another 1,3dicarbonyl compound named ethylacetoacetate, on benzaldehyde, nitromethane, and diverse amines such as 1-phenylethanamine, benzylamine, aniline, and isopropylamine. e corresponding products were obtained in 43%, 41%, 30%, and 29% yields, respectively (Table 3, entries [17][18][19][20][21]. Compared to acetoacetylacetone, this four-component coupling reaction was found to be less reactive with β-ketoester compounds. RMN and mass spectra of products 1k, 1m, and 1p can be found in supplementary data. Based on the literature [9,10], we have proposed a plausible mechanism for the one-pot reaction (Scheme 5). e intermediate products β-nitrostyrene and β-enamino ketone were both separated and isolated in the reaction process. is corroborates with the research of Grob and Camenisch that pyrroles can be obtained from a Michael reaction of β-enamino ketones or esters and nitroalkenes followed by cyclization [32]. e synthesis of fully functionalized pyrrole derivatives by this four-component reaction was less explored in the literature. Table 4 summarizes the comparison of our work with other reported catalysts.    Reactions were carried out using aldehyde (2.5 mmol), amine (2.5 mmol), and 1,3-dicarbonyl compounds (2.5 mmol) to nitromethane ( 13  1-(4-(4-Chlorophenyl)-2,5-dimethyl-1-(1-phenylethyl)-1Hpyrrol-3-yl)ethanone (1i). Brown sticky liquid (387 mg, 44%); 1 3.6. Electrochemical Study. Corrosion leads to a significant loss of materials, energy, and money [33]. is results in a loss of products in industrial installations and can lead to serious accidents and contribute to environmental pollution. However, there are many ways to prevent and stem this Journal of Chemistry phenomenon. Among them, corrosion inhibitors are used to control and reduce metal corrosion in aqueous environments [34,35]. us, we have tested the synthesized polysubstituted pyrroles as corrosion inhibitors of S300 steel in 1 M hydrochloric acid, and the results are presented in Figure 2. e data in Figure 2 clearly show that the addition of different pyrrolic molecules inhibits the steel corrosion. e presence of an inhibitor clearly affects the corrosion mechanism. It could be attributed to the adsorption process of active molecules onto the steel surface leading to an increase in surface coverage [36,37]. e adsorption phenomena could be occurring due to the donor-acceptor interactions between the vacant d-orbital of the steel surface and the lone-pair electron of the heteroatom, as well as the aromatic rings of inhibitors [38].

Results of Mass Spectrometry and NMR Spectra.
It can be seen from Table 5 that the inhibition efficiency of different compounds varies from 82% to 96%. e results summarized in Table 5 clearly show that the maximum displacement of corrosion potential occurred around 69 mV compared to the blank.
is result reveals that different compounds act as mixed-type inhibitors [39].

Conclusion
In conclusion, we have successfully performed an environmentally friendly, operationally simple, economical, and efficient synthesis of pyrrole derivatives by a one-pot synthesis via a four-component domino reaction.
is green protocol, using 1,3-dicarbonyl compounds, aromatic aldehydes, aliphatic and aromatic amines, and nitroalkanes compounds in the presence of natural hydroxyapatite in solvent-free reaction, leads to the synthesis of highly functionalized tetra-or penta-substituted pyrroles with a wide variety of substrates. e advantage of this protocol is the use of hydroxyapatite as a cheap, natural, and nontoxic catalyst. Finally, different compounds were found to be good corrosion inhibitors for S300 steel in a 1 M HCl solution at 10 −3 M. e maximum inhibition efficiency was found to be around 96%, and the inhibitors revealed a mixed behavior.

Data Availability
No data were used to support this study.