Synthesis and characterization of FeCuAlO₄ as a reusable heterogeneous acidic nanocatalyst for preparation of 2-amino-1,3,4-thiadiazole derivatives in water

Abstract

2-amino-1,3,4-thiadiazole derivatives possess notable significance across therapeutic, agricultural, and industrial domains. The reaction of acid hydrazides and potassium thiocyanate in aqueous solution leads to the production of thiosemicarbazide derivatives. Hence the synthesis of 2-amino-1,3,4-thiadiazole derivatives from acid hydrazides and potassium thiocyanate in aqueous solvent and a one-step process requires efficient nanocatalysts. In this study, the synthesis of 2-amino-1,3,4-thiadiazole derivatives from acid hydrazides and potassium thiocyanate in the presence of FeCuAlO₄ NPs in aqueous solvent is reported. The synthesis of FeCuAlO₄ NPs was carried out via sol–gel auto-combustion. FeCuAlO₄ NPs were characterized using EDS, elemental mapping, FT-IR, XRD, FESEM, TEM, and BET. The analyses showed that FeCuAlO₄ NPs are single-phase, crystalline, and FCC type. The particle size distribution is about 47.76 nm, and the surface area of the FeCuAlO₄ NPs is 23.52 m²g^− 1. Ultimately, the FeCuAlO₄ NPs can be recycled across four consecutive runs with only a minor drop in performance, highlighting its robust stability. Overall, the catalyst demonstrates significant benefits, such as environmentally friendly conditions, minimal catalyst usage, operational simplicity, recyclability, and excellent product yields (80–90%).

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-025-29517-x.

Introduction

2-amino-1,3,4-thiadiazoles have attracted significant attention in chemical, pharmaceutical, and agricultural sciences due to their biological activities and unique chemical properties^1–5.

The 1,3,4-thiadiazole ring is highly stable and due to the presence of the amino group (NH₂) at position 2, allows for various chemical reactions^6,7. 2-amino-1,3,4-thiadiazole has high chemical activity and the ability to form strong hydrogen bonds due to the presence of nitrogen and sulfur in its structure^8,9. This compound plays a role in the synthesis of industrial chemicals¹⁰ and corrosion inhibitors^11,12. The most important chemical properties of this compound are the ability to carry out substitution^13,14, oxidation-reduction¹⁵, and complex formation reactions with metals¹⁶. These properties have made 2-amino-1,3,4-thiadiazole an important intermediate in the synthesis of more complex compounds¹⁷.

This compound is used in the production of organic dyes¹⁸, conductive polymers¹⁹, and electronic materials²⁰. Its stable structure and high reactivity have enabled the production of new compounds with optimal optical and electrical properties²¹.

One of the most important applications of 2-amino-1,3,4-thiadiazole derivatives is their use in the synthesis of antibacterial²², antiviral²³, antifungal²⁴, antimalaria²⁵ and anti-Alzheimer^26,27 drugs. Some of these derivatives have shown inhibitory activity against the enzymes carbonic anhydrase and alpha-glucosidase, which makes them important for the treatment of glaucoma and type 2 diabetes^28–30. The 2-amino-1,3,4-thiadiazole structure has emerged as a promising basis for the development of anticancer agents, as these compounds have shown antitumor properties in various in vitro and in vivo models and target diverse molecular pathways^31,32. These advances could lead to the production of a new generation of effective drugs with minimal side effects^6,33–35.

2-amino-1,3,4-thiadiazole derivatives are used in the formulation of pesticides, fungicides, and herbicides. The high biological activity of this structure makes it a suitable candidate for the development of plant protection compounds^36–38.

Given the high importance of 2-amino-1,3,4-thiadiazole derivatives in chemistry, pharmacy, and agriculture, much research is being done to develop new derivatives of this compound. The development of new methods for the synthesis of this compound and the investigation of its effects on biological systems can pave the way for the discovery of new drugs and the improvement of industrial processes. The use of green and sustainable synthetic methods for producing this compound is one of the hot topics in this field^39–43.

Studies on the synthesis of 2-amino-1,3,4-thiadiazole using potassium thiocyanate and acid hydrazide showed that the direct synthetic route from potassium thiocyanate and acid hydrazide for the synthesis of 2-amino-1,3,4-thiadiazole derivatives has not been studied. The reaction between acid hydrazide and potassium thiocyanate leads to the formation of the thiosemicarbazide intermediate. This intermediate can then be cyclized under acidic conditions to form 2-amino-1,3,4-thiadiazole derivatives. Inorganic acids such as sulfuric acid have been used as cyclization catalysts in the synthesis of 2-amino-1,3,4-thiadiazole derivatives^44,45.

In this report, we investigate a specific synthetic route in which 2-amino-1,3,4-thiadiazole derivatives are synthesized in a single step from potassium thiocyanate and acid hydrazide in an aqueous solvent.

The selection of the appropriate catalyst and reaction conditions (temperature, time, and solvent) are important factors in the synthesis of 2-amino-1,3,4-thiadiazole derivatives in high yield from potassium thiocyanate and acid hydrazide in a single-step reaction. Metal oxide nanoparticles (NPs), owing to their high specific surface area, have emerged as highly efficient catalysts for the synthesis of heterocyclic compounds and high catalytic activity can significantly increase the reaction rate and product yield, and prevent the formation of unwanted by-products by reducing the reaction temperature^46–49. Metal oxide NPs can act as stable, reusable, and environmentally friendly catalysts^49–53. In addition, the use of heterogeneous catalysts such as metal oxide nanoparticles can facilitate product separation and purification^54–56. The catalytic mechanism of metal oxide nanoparticles probably involves the activation of the starting materials through interaction with Lewis acidic sites on the surface of the nanoparticles⁵⁷. Mixed metal oxides have many advantages over pure metal oxides that make them preferred in many applications. Mixed oxides usually have better catalytic activity than pure oxides^58–60. This is because of the interaction between two or more metals, which changes the surface and electronic properties and increases the reactivity^61,62. Mixed oxides are usually more stable at harsh reaction temperatures and conditions and are less prone to decomposition or degradation^63–65. By changing the ratio of different metals in mixed oxides, the desired properties such as the reactivity level can be tuned⁶⁶. The combination of oxides improves the absorption properties of gases or ions and makes them more useful in catalysis of reactions^67,68.

In this study, FeCuAlO₄ NPs were used for the synthesis of 2-amino-1,3,4-thiadiazole derivatives. The main goals of the recent study were to use milder reaction conditions, reduce reaction time, improve product yield, and a one-step synthesis method that allows for the production of the product without the need for isolation and purification of intermediates.

Experimental

Methods

All chemicals, including urea, sodium bicarbonate, sodium sulfate, carboxylic acid derivatives, sulfuric acid, hydrochloric acid, hydrazine hydrate, potassium thiocyanate, Fe(NO₃)₃·9H₂O, Cu(NO₃)₂·3H₂O, Al(NO₃)₃·9H₂O and solvents (methanol, ethanol, 2-propanol, chloroform, ethyl acetate and n-hexane) were purchased from Merck and Scharlau and used without purification. Double-distilled water was used as the solvent.

Synthesis of FeCuAlO₄ NPs

Initially, Fe(NO₃)₃·9H₂O (0.03 mol, 12.12 g), Al(NO₃)₃·9H₂O (0.03 mol, 11.254 g), and Cu(NO₃)₂·3H₂O (0.03 mol, 7.25 g) were solubilized in 500 ml of distilled water. Then, Urea (0.2 mol, 12.012 g) was dissolved in 250 ml of distilled water and added to the previous mixture. After stirring the reaction mixture for 3 h at 25 °C, a gel was formed. Gel formation occurred by heating at 80 °C and evaporation of water for 24 h. The as-prepared gel was oven-dried at 120 °C for 12 h, ground in mortar to a fine powder, and subsequently calcined in air at 700–750 °C for 0.5 h.

Preparation of esters

In a 250 ml flask, carboxylic acid derivatives (0.08 mol) were poured, and absolute ethanol (100 ml) was added. After homogenization, sulfuric acid (0.05 mol, 5 g) was added and refluxed for 4 to 8 h. The end of the reaction was determined by TLC in EtOAc/n-Hexane (2/8) solvent. After cooling the reaction, by adding sodium bicarbonate to the reaction mixture, the unreacted carboxylic acids and sulfuric acid were neutralized. The addition of sodium bicarbonate continued until the complete release of carbon dioxide gas. Then, ethanol was removed from the reaction medium by distillation, and the remaining mixture was washed three times with 50 ml of distilled water each time. The remaining organic phase was dried with anhydrous Na₂SO₄^69,70.

Preparation of acid hydrazides

In a 50 mL round bottom flask equipped with a magnetic stirrer and a condenser, the ester derivatives (1 mmol) and ethanol (15 mL) were poured and after homogenization, hydrazine hydrate (80%) (2.5 mmol, 0.1 mL) in ethanol (10 mL) was added. The reaction mixture was refluxed for 4–6 h. The reaction progress was monitored by TLC in MeOH/CHCl₃ (2/5) solvent. After evaporation of ethanol and excess hydrazine under vacuum, the solid obtained from 2-propanol was purified. The products were obtained in 70–85% yield^69,70.

Preparation of 2-amino-1,3,4-thiadiazoles

A mixture of acid hydrazide derivatives (2.5 mmol), potassium thiocyanate (2.5 mmol, 243 mg) and FeCuAlO₄ NPs (0.625 mmol, 131.48 mg) in 20 mL of distilled water was stirred and heated at 100 °C under reflux conditions. The end of the reaction was determined using TLC (chloroform/methanol). Upon completion of the reaction, the mixture was allowed to cool to 25 °C, after which 5 mL of 1 M HCl was added, and Stirring of the reaction mixture was continued for 0.5 h to ensure complete mixing. The catalyst and 2-amino-1,3,4-thiadiazoles were separated by centrifugation. The 2-amino-1,3,4-thiadiazoles were separated from the catalyst with ethanol (3 × 25 mL). 2-amino-1,3,4-thiadiazoles were obtained in 80–90% yield by recrystallization from ethanol.

Catalytic recyclability

The reusability of FeCuAlO₄ NPs for the preparation of 2-amino-1,3,4-thiadiazoles was evaluated by evaluating the efficiency in several cycles, with respect to the first run. At the end of each cycle, the catalyst was recovered by centrifugation, washed several times with double-distilled water and absolute ethanol, dried at 120 °C for 2 h, and employed in the next cycle with fresh reactants under identical reaction conditions.

Instrument

Phase composition and crystal structure of the FeCuAlO₄ NPs were analyzed using X-ray diffraction (XRD) by using a D500 diffractometer (Siemens) equipped with a Cu Kα radiation source (λ = 0.15406 nm). The XRD pattern of FeCuAlO₄ NPs was obtained at 25 °C and a scanning speed of 2 °/min. The diffraction data were acquired over a 10–80° 2θ range at 0.5°/s scanning rate. The morphology and size information of FeCuAlO₄ NPs were analyzed using a field emission scanning electron microscope (FESEM) (FESEM, TESCAN MIRA III) with an accelerating voltage of 20 kV and transmission electron microscopy (TEM) image was obtained using a FEI CM 120 operating at 100 kV. The relative abundances of elements in the sample were determined via energy- dispersive X-ray spectroscopy (EDS) using a SAMX detector. The bond types of FeCuAlO₄ NPs were investigated by Fourier transform infrared spectroscopy (FT-IR) in the range of 400–4000 cm⁻¹ using the KBr disk method and Nexus 670 spectrometer. Specific surface area, average pore diameter, and total pore volume were determined from nitrogen adsorption–desorption isotherms measured on a BEL SORP MINI II coupled with a BEL PREP VAC II analyzer, using the multipoint Brunauer–Emmett–Teller (BET) method. The progress of the reaction was followed by thin-layer chromatography (TLC), (Silica gel PolyGram SILG/UV254). Melting points were determined using an Electrothermal 9200 apparatus with open capillary tubes. The reaction yields were calculated after product isolation. Obtained yields were determined after work-up.

Results and discussion

FeCuAlO₄ NPs synthesis

The sol–gel auto-combustion method, which is a bottom-up approach, was used to prepare FeCuAlO₄ NPs. In this method, urea was used as the fuel and the combustion process included the release of CO₂, H₂O, and N₂ gases (Fig. 1). Therefore, this method is considered environmentally friendly. In the sol–gel auto-combustion method for the synthesis of FeCuAlO₄ NPs, the advantages of both sol-gel and spontaneous combustion techniques were utilized⁷¹. In this method, better control of particle size and uniformity is possible. The sol-gel process allows the production of NPs with very small size and uniform distribution⁷². Spontaneous combustion caused the reaction to proceed faster and the overall calcination time to be greatly reduced. Rapid combustion resulted in rapid removal of the organic precursor (urea) and reduced impurities. This method can be scaled up for mass production relatively easily. Due to the rapid release of energy in the combustion reaction, the particles were stabilized before they grew too much. In the sol-gel method, the precursors were well mixed, resulting in a uniform chemical composition of the final product. This method did not require complex equipment or special conditions (such as high vacuum or high pressure) (Fig. 2).

Fig. 1.

The synthesis of FeCuAlO₄ NPs.

Fig. 2.

Schematic illustration for the synthesis of FeCuAlO₄ NPs.

FeCuAlO₄ NPs characterization

EDS analysis

The chemical composition of FeCuAlO₄ NPs was analyzed by energy dispersive X-ray spectroscopy (EDS). The EDS spectrum of FeCuAlO₄ NPs, shown in Fig. 3, confirmed the presence of Fe, Cu, Al, and O elements.

Fig. 3.

EDS spectrum of FeCuAlO₄ NPs.

Peaks for Fe were observed in the range of 0–1 keV and 6–7.5 keV, peaks for Cu in the range of 0–1 keV and 7.5–9 keV, peaks for Al in the range of 1–2 keV, and peaks for O in the range of 0–1 keV. EDS analysis indicated the weight% of each element present in FeCuAlO₄ NPs, which was represented by different peaks (Table 1).

Table 1.

Elemental analysis of FeCuAlO₄ NPs.

Element	Weight%		Atomic %
	Calc. value	EDS value	Calc. value	EDS value
O	30.42	31.73	57.14	58.31
Fe	26.55	27.76	14.29	14.61
Cu	30.21	27.21	14.29	12.59
Al	12.83	13.30	14.29	14.49
	100	100	100	100

Mapping analysis

A specific area of FeCuAlO₄ NPs was examined point by point by mapping analysis. In this analysis, the elements iron, copper, aluminium, and oxygen were displayed as colored dots, each color representing an element (Fig. 4). Elemental mapping confirmed the distribution of iron, copper, aluminium, and oxygen elements and the homogeneity of the FeCuAlO₄ NPs.

Fig. 4.

Mapping of FeCuAlO₄ NPs.

FT-IR analysis

The Fourier transform infrared (FT-IR) spectrum of FeCuAlO₄ NPs is shown in Fig. 5. In this spectrum, the broad peak appearing at 3442 cm^{− 1} is related to the stretching mode of water adsorbed by the KBr tablet. The M–O stretching and bending vibrations appear at 1637 cm^{− 1} and 588 cm^{− 1}, respectively^73–75.

Fig. 5.

FT-IR spectrum of FeCuAlO₄ NPs.

XRD analysis

The X-ray diffraction (XRD) pattern for FeCuAlO₄ NPs as a function of angle is shown in Fig. 6. Table 2 lists the diffraction angles (2θ), crystallographic planes (h k l) and relative intensities of each peak. According to the X-ray diffraction pattern, the structure of the sample is crystalline and there is only one type of crystal structure in the sample.

Fig. 6.

XRD pattern of FeCuAlO₄ NPs.

Table 2.

Peak list of FeCuAlO₄ NPs.

Pos. [°2Th.]	Height [cts]	FWHM left [°2Th.]	d-spacing [Th]	Rel. Int. [%]	Tip width	(h k l)	Matched by
19.0017	214.84	0.4920	4.67059	6.63	0.5904	(1 1 1)	00–047-0324
30.9569	1205.77	0.3444	2.88875	37.21	0.4133	(2 2 0)	00–047-0324
36.3313	3240.73	0.3936	2.47281	100.00	0.4723	(3 1 1)	00–047-0324
39.0517	178.15	0.5904	2.30659	5.50	0.7085	(2 2 2)
44.2520	718.73	0.2952	2.04685	22.18	0.3542	(4 0 0)	00–047-0324
54.7333	324.67	0.4920	1.67711	10.02	0.5904	(4 2 2)	00–047-0324
58.5750	866.68	0.4428	1.57594	26.74	0.5314	(5 1 1)	00–047-0324
64.0861	1223.09	0.3936	1.45307	37.74	0.4723	(4 4 0)	00–047-0324

The peak locations and relative peak intensities of FeCuAlO₄ NPs are consistent with the reference JCPDS 00–047-0324 (Fig. 7). As reported in the cited reference, the FeCuAlO₄ NPs exhibits a face-centered cubic (FCC) crystal structure.

Fig. 7.

Plot of Identified phases of FeCuAlO₄ NPs.

The Debye-Scherer (D = 0.9λ/β cos θ) and Williamson-Hall (β cos θ = ε 4 sin θ + 0.9λ/D, ε = β/4tan θ) equations was used to estimate the average crystallite size of FeCuAlO₄ NPs. Where, D represents the crystallite size, λ represents the X-ray wavelength, β represents the full width at half maximum (FWHM) of the diffraction peak, θ represents the Bragg angle, and ε is the lattice strain. The crystallite size of FeCuAlO₄ NPs was reported in Table 3. W-H Plot of FeCuAlO₄ NPs showed that the dominant strain in the crystals is compressive (Fig. 8).

Table 3.

Crystallite size of FeCuAlO₄ NPs.

Debye-Scherer	Williamson-Hall
D (nm)	D (nm)	ε
21.23	16.31	1.1 × 10− 3

Fig. 8.

W-H Plot of FeCuAlO₄ NPs.

FESEM analysis

The surface morphology of FeCuAlO₄ NPs was analyzed using field emission scanning electron microscopy (FESEM). In Fig. 9, FE-SEM images of FeCuAlO₄ NPs are taken at different magnification scales (200 nm and 1 μm). These images show that the average size of FeCuAlO₄ NPs is about 47.76 nm.

Fig. 9.

FESEM images of FeCuAlO₄ NPs.

TEM analysis

Figure 10 shows the TEM image of the FeCuAlO₄ NPs. Examination of the TEM image confirms the results obtained by FESEM. As shown in Fig. 10, TEM images show that the nanoparticles are homogeneous in shape and size. These images also indicate a regular morphology.

Fig. 10.

TEM image of FeCuAlO₄ NPs.

Textural analysis

N₂ adsorption and desorption isotherms were used to measure the specific surface area, total pore volume, and average pore diameter of FeCuAlO₄ NPs at 77 K (Fig. 11). The N₂ adsorption–desorption isotherms of FeCuAlO₄ NPs are classified as type IV according to IUPAC, indicating the presence of a mesoporous structure. A type H3 hysteresis loop is observed in the N₂ adsorption–desorption isotherm.

Fig. 11.

N₂ adsorption-desorption isotherms, BET plot, t-plot, and BJH plot of FeCuAlO₄ NPs.

Table 4 Describes the parameters related to the porosimetry of FeCuAlO₄ NPs. According to the Brunauer-Emmett-Teller (BET) method, the specific surface area of FeCuAlO₄ NPs was 23.52 m²g^− 1 with a pore volume of 0.1103 cm³g^− 1 and an average pore diameter of 18.75 nm in the initial part of the isotherm. The mesopore distribution was performed from the desorption branch data according to the BJH method (Barrett, Joyner, Halenda). Pore size distribution analysis using the BJH method on the desorption branch reveals that pores with a radius of 3.09 nm predominate in the catalyst structure. According to the t-plot analysis of the desorption branch data, FeCuAlO₄ NPs are devoid of micropores.

Table 4.

The computed data of BET, t, and BJH plots.

Method	Surface area, m2g− 1	Pore volume, cm3g− 1	Average pore diameter, nm
BET	23.52	0.1103	18.75
t- plot adsorption	13.56	0	-
BJH adsorption	38.46	0.1165	3.09

The catalytic performance of FeCuAlO₄ NPs is strongly influenced by their specific surface area and pore structure. The observed surface area of FeCuAlO₄ NPs indicates a high adsorption capacity of starting materials. The mesoporous structure of FeCuAlO₄ NPs plays an important role in increasing the specific surface area and catalytic activity.

FeCuAlO₄ NPs activity

Fischer esterification was used to prepare ester derivatives from carboxylic acids and ethanol in the presence of sulfuric acid as a catalyst (Fig. 12; Table 5). Then, to prepare acid hydrazide derivatives, the esters produced were reacted with hydrazine (Fig. 12).

Fig. 12.

Synthesis of acid hydrazide derivatives.

Table 5.

Fischer esterification of carboxylic acids.

Entry	Acids	Time (h)	Yields (%)
1	PhCO2H	4	81
2	2-HO-PhCO2H	6	78
3	4-HO-PhCO2H	8	68
4	2-O2N-PhCO2H	6	75
5	3-O2N-PhCO2H	4	83
6	4-O2N-PhCO2H	4	85
7	2-Cl-PhCO2H	7	80
8	4-Cl-PhCO2H	5	85
9	2-MeO-PhCO2H	8	70
10	4-MeO-PhCO2H	8	73

RCO₂H (0.08 mol), EtOH (100 ml), and H₂SO₄ (0.05 mmol, 5 g) under reflux

The reaction of hydrazine with ester is much easier than the reaction of hydrazine with carboxylic acid. Therefore, the carboxylic acid derivatives were first converted into ester derivatives and then reacted with hydrazine. It should be noted that the reaction of hydrazine with ester derivatives does not require a special catalyst. Also, due to the mild reaction conditions, we will not see any by-products.

First, the reaction of phenylcarbohydrazide with potassium thiocyanate in the presence of hydrochloric acid in aqueous solvent and reflux conditions was investigated. Reaction progress was followed using TLC analysis. After 6 h of reaction, the product 2-amino-1,3,4-thiadiazole was not produced. The use of an excess amount of hydrochloric acid yielded a similar result. The investigation of the reaction showed that only the intermediate 1-benzylthiosemicarbazide was produced (Fig. 13). Next, the reaction of phenylcarbohydrazide with potassium thiocyanate in the presence of 20 mol% of CuO NPs, Al₂O₃ NPs, and Fe₂O₃ NPs in aqueous solvent and reflux conditions was investigated to prepare 2-amino-1,3,4-thiadiazole. After a long period of time, the reaction yielded a similar result to hydrochloric acid (Fig. 13). According to the reaction mechanism, the first step involves the activation of thiocyanate and the attack of acid hydrazide, in which case the intermediate thiosemicarbazide is produced. This highlighted the need for a catalyst for the preparation of 2-amino-1,3,4-thiadiazole from acid hydrazides and potassium thiocyanate in water solvent.

Fig. 13.

Synthesis of 1-benzoyl thiosemicarbazide.

Considering the capability and efficiency of mixed metal oxide NPs, the reaction of phenyl carbohydrazide and potassium thiocyanate in the presence of 20 mol% FeCuAlO₄ NPs in aqueous solvent and reflux conditions was investigated. In this case, the conditions were completely different, and the product 2-amino-1,3,4-thiadiazole was produced (Fig. 14). All acid catalysts including Brønsted acid and Lewis acid promote the production of the thiosemicarbazide intermediate. However, not all acids in aqueous solvent and reflux conditions are able to carry out the subsequent reaction steps and produce the final product 2-amino-1,3,4-thiadiazole.

Fig. 14.

Synthesis of 2-amino-5-phenyl-1,3,4-thiadiazole.

The morphology of the catalyst determines the active sites and stability of the particles and directly affects the activity of the catalyst. The spherical morphology of FeCuAlO₄ NPs results in an increased contact surface area with the reactants, facilitating improved interaction. The surface area of FeCuAlO₄ NPs contributed to faster reaction and efficient use of minimal catalyst. Due to the hydrophobic nature of FeCuAlO₄ NPs, the adsorption of the reactant in aqueous media is well carried out and the reaction conditions are provided at 100 °C. Under different catalyst concentrations at the same temperature and equal time, the reaction efficiency was calculated (Table 6). Catalyst amounts of 25 and 30 mol% showed similar results, so 25 mol% is the most efficient (Table 6, entries 5 and 6).

Table 6.

Optimization of FeCuAlO₄ NPs.

Entry	Solvent	Temperature (oC)	Catalyst (mol %)	Time (h)	Yields (%)
1	EtOH	Reflux	20	6	68
2	EtOH	Reflux	25	6	80
3	EtOH	Reflux	30	4.5	80
4	H2O	Reflux	20	2	76
5	H2O	Reflux	25	1.5	89
6	H2O	Reflux	30	1.5	90
7	H2O/EtOH (1:1)	Reflux	20	6	79
8	H2O/EtOH (1:1)	Reflux	25	6	85
9	H2O/EtOH (1:1)	Reflux	30	6	90

PhCONHNH₂ (2.5 mmol) and KSCN (2.5 mmol, 243 mg)

the behavior of other acid Hydrazides containing electron-donating or electron-withdrawing functional groups with potassium thiocyanate was investigated to prepare 2-amino-1,3,4-thiadiazoles. Reactions were conducted in the presence of FeCuAlO₄ NPs using a catalytic amount (25 mol %) in water at 100 °C. the synthesis of 2-amino-1,3,4-thiadiazoles was achieved in 80–90% yield (Table 7). According to the information in Table 7, functional groups in the ortho position slow down the reaction due to steric hindrance and reduce the efficiency. On the other hand, electron-donating or electron-withdrawing functional groups did not have a significant effect on the progress of the reaction.

Table 7.

Synthesis of 2-amino-1,3,4-thiadiazoles.

Entry	X	Yield (%)	MP (oC)
			Found	Reported41,76–79
1	H	89	220–222	222–224
2	2-HO	83	228–230	229–231
3	4-HO	87	219–221	214–216
4	2-O2N	81	233–235	230–232
5	3-O2N	89	216–218	217–219
6	4-O2N	88	256–258	257–259
7	2-Cl	80	205–207	202–204
8	4-Cl	90	231–233	227–229
9	2-MeO	82	201–203	204–206
10	4-MeO	85	220–222	225–227

RCONHNH₂ (2.5 mmol), KSCN (2.5 mmol, 243 mg) and FeCuAlO₄ NPs (0.625 mmol, 131.48 mg) in water at 100 °C for 1.5 h.

The suggested reaction mechanism is grounded on the reactivity of acid hydrazide derivatives for the preparation of 2-amino-1,3,4-thiadiazoles (Fig. 15). In the first step, FeCuAlO₄ NPs lead to the activation of thiocyanate. Then, acid hydrazide reacts with thiocyanate, and cyclization occurs. Finally, 2-amino-1,3,4-thiadiazole is produced by the elimination of water. This nanocatalyst also assists in the intramolecular attack step, ultimately enabling an efficient reaction pathway with high product yields.

Fig. 15.

The suggested mechanism for synthesis of 2-amino-1,3,4-thiadiazoles.

FeCuAlO₄ NPs reusability

Catalyst recycling is of great importance because it helps to preserve the environment, save resources, and reduce production costs. Disposal of catalysts can lead to waste generation and environmental pollution. Therefore, recycling of catalysts prevents this and helps to conserve natural resources. Catalysts contain significant amounts of metals, which are expensive and time-consuming to extract from mines. Therefore, recycling of catalysts reduces the need for re-mining and thus conserves natural resources. Procuring raw materials for catalyst production can be very expensive. While recycling of catalysts helps to reduce production costs. The ability of a catalyst to be reused plays a critical role in assessing its sustainability and efficiency for industrial applications. In this study, the reusability of FeCuAlO₄ NPs in the synthesis of 2-amino-5-phenyl-1,3,4-thiadiazole was investigated. In each cycle, FeCuAlO₄ NPs and the product were first separated from the reaction mixture by centrifugation, and the product was separated from the catalyst with ethanol and centrifugation. The catalyst was washed three times with ethanol and water and dried at 120 °C for 2 h. The results of the FeCuAlO₄ NPs recycling are summarized in Fig. 16. As shown, this catalyst can be recycled up to 4 times without significant reduction in its catalytic activity.

Fig. 16.

Reusability of FeCuAlO₄ NPs.

The FESEM image of the FeCuAlO₄ NPs shows that after 5 recycling cycles, there was no significant change in the size of the nanoparticles and the efficiency of the recycled catalyst was maintained (Fig. 17). Also, the FT-IR spectrum of the recycled catalyst proves the purity and stability of the FeCuAlO₄ NPs structure (Fig. 18).

Fig. 17.

FESEM image of FeCuAlO₄ NPs after 5th recycling.

Fig. 18.

FT-IR spectrum of FeCuAlO₄ NPs after 5th recycling.

Conclusion

In this study, FeCuAlO₄ NPs were synthesized and characterized. EDS analysis correctly showed the ratio of elements constituting FeCuAlO₄ NPs. metal-oxygen bonds were confirmed by FT-IR analysis. FESEM and TEM images of FeCuAlO₄ NPs revealed the spherical structure of these nanoparticles. XRD analysis showed that the crystal structure of FeCuAlO₄ NPs is of the face-centered cubic (FCC) type. Nitrogen adsorption-desorption isotherms confirmed the porous structure with mesopores. Then, the ability of FeCuAlO₄ NPs to carry out organic reactions was investigated. The preparation of 2-amino-1,3,4-thiadiazole derivatives in water solvent from acid hydrazides and potassium thiocyanate was possible in a one-step reaction, which is a very difficult reaction, in the presence of 25 mol% of FeCuAlO₄ NPs. The possibility of catalyst recovery, short reaction time, high yield, and easy separation of the catalyst showed that FeCuAlO₄ NPs have high catalytic ability. This research proved the potential of mixed metal oxides and showed that mixed metal oxides can catalyze reactions that are difficult to perform.

Supplementary Information

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Author contributions

I have performed the laboratory activities, interpreted the analyses, and written the paper myself.

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All data obtained and data analysis in this research work are included in this article and its supplementary information file.

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Competing interests

The authors declare no competing interests.