Eco-Friendly Synthesis of Perimidine Derivatives Using Recyclable Fe₃O₄@Nano-Cellulose/Ti(IV)

Abstract

A novel bio-capable method has been implemented for the synthesis of newly substituted derivatives of perimidine using Fe₃O₄@nano-cellulose/Ti(IV) as a magnetic, sustainable, and eco-friendly Lewis acid nanocatalyst. The catalyst was thoroughly characterized by XRD, FESEM, and TGA analyses, confirming its crystalline structure, uniform nanoscale morphology, and high thermal stability. The reaction proceeded smoothly in eco-friendly solvents, providing outstanding yields under mild and rapid conditions, especially with ultrasonics. The catalyst, derived from renewable materials, exhibited remarkable activity, easy magnetic recovery, and excellent reusability over several cycles without significant loss of efficiency. Spectral characterization, IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR, and HRMS analyses verified that perimidine derivatives were synthesized properly. This sustainable and efficient approach demonstrates the prospect of green Lewis acid nanocatalysts for the sustainable synthesis of valuable heterocyclic compounds.

1. Introduction

Heterocycles containing nitrogen are fundamental building blocks for applications in diverse essential natural and synthetic compounds [1,2,3]. In between, perimidines stand out due to their specific electronic and aromatic properties. The unique arrangement of π-excessive and π-deficient systems within their tricyclic framework, combined with the presence of nitrogen atoms bearing lone pairs, allows for significant electron delocalization into the naphthalene ring [4]. This specific electronic configuration enables these synthetic products to show a different biological specification, making them valuable in fields such as medicine. It exhibits potent properties against several diseases with demonstrated antitumor [5], antimicrobial [6], antifungal [7], antiulcer [8], antioxidant [9], and anti-inflammatory [10] properties, and it acts as a selective antagonist for corticotropin-releasing factor (CRF) receptors [10]. Numerous strategies have been developed for synthesizing perimidine derivatives [7,11,12]. While these methods offer certain benefits, they are often accompanied by drawbacks such as suboptimal yields, prolonged reaction times, and complex purification processes. Furthermore, the use of environmentally harmful and non-recyclable catalysts limits their practical utility [13,14]. Recently, remarkable advances have been made in the green chemistry-based synthesis of heterocyclic compounds [15,16,17]. Notably, the application of nanocatalysts in the bio-based synthesis of heterocycles has garnered substantial attention, providing sustainable and efficient alternatives to conventional methods. Some of these studies have demonstrated promising results under green protocols, achieving high efficiency within shorter reaction times. To achieve these goals, the use of metal nanocatalysts supported on bio-based materials has been successfully reported [18,19,20]. The use of titanium (IV) as a Lewis acid supported on various bases, such as silica, has been reported for the synthesis of this heterocyclic compound. Specifically, it has been employed in the synthesis of dihydropyrimidones via the Biginelli condensation reaction [21] and in the preparation of 2,4,5-tetrasubstituted imidazoles [22]. In this research, we introduce a new green method for the synthesis of various substituted perimidine derivatives using Fe₃O₄@nano-cellulose/Ti (IV) as an eco-friendly magnetically recoverable nanocatalyst.

2. Results and Discussion

The Fe₃O₄@NCs/Ti(IV)-catalyzed condensation of 1,8-diaminonaphthalene with a series of aromatic aldehydes under optimized conditions efficiently afforded the corresponding 2,3-dihydro-1H-perimidine derivatives. The reactions proceeded smoothly in ethanol under either thermal or ultrasonic conditions, providing the desired products in good to excellent yields. Notably, ultrasonic irradiation significantly enhanced the reaction rate and yield, reducing the reaction time. All synthesized derivatives were isolated by simple work-up and purified when necessary, and their structures were fully confirmed by FT-IR, ¹H NMR, ¹³C NMR, (¹⁹F NMR where applicable), and HRMS analyses.

2.1. Structural and Morphological Characterization of Fe₃O₄@NCs/Ti(IV) Nanocatalysts

The structural, morphological, magnetic, and thermal properties of the Fe₃O₄@NCs/Ti(IV) nanocatalyst were investigated through a combination of advanced techniques, including FT-IR spectroscopy, FESEM, XRD, VSM, and TGA analyses.

2.2. FT-IR Analysis

The FT-IR spectra of nano-cellulose, Fe₃O₄@NCs, and Fe₃O₄@NCs/Ti (IV) (Figure 1) confirm successful composite formation. Nano-cellulose shows characteristic O-H stretching at 3337 cm⁻¹ and C-O stretching at 1055 cm⁻¹ and 1108 cm⁻¹. Fe₃O₄@NCs exhibits additional Fe-O stretching bands at 586 cm⁻¹ and 634 cm⁻¹, indicating Fe₃O₄ nanoparticles are coated with nano-cellulose. For Fe₃O₄@NCs/Ti (IV), peaks at 794 cm⁻¹ (C-O-Ti stretching) and 406 cm⁻¹ (O-Ti-O bending) confirm Ti bonding to the cellulosic shell, which shifts Fe-O stretching vibrations to lower wavenumbers (558 cm⁻¹ and 606 cm⁻¹).

2.3. FESEM Analysis

The morphology and particle size of nano-cellulose and Fe₃O₄@NCs/Ti (IV) were investigated using field emission scanning electron microscopy (FESEM). The analysis revealed that both nano-cellulose and Fe₃O₄@NCs/Ti(IV) exhibit uniform and well-defined structures with particle sizes consistently below 50 nm. The FESEM images (Figure 2) confirm the successful incorporation of Ti(IV) into the nano-cellulose-coated Fe₃O₄ nanoparticles, maintaining their nanoscale dimensions and uniform distribution. This indicates the effectiveness of the synthesis process in producing homogeneous composite material.

2.4. XRD Analysis

High-angle XRD analysis (Figure 3) was used to study the structural and phase purity of Fe₃O₄, Fe₃O₄@NCs, and Fe₃O₄NCs/Ti(IV). The XRD pattern of Fe₃O₄ showed characteristic peaks consistent with its cubic spinel structure. Similar peaks were observed for Fe₃O₄@NCs, confirming the preservation of the ferrite core after cellulose coating, along with a new peak at 2θ = 23.04°, attributed to the cellulose layer. The XRD pattern of Fe₃O₄@NCs/Ti(IV) revealed an amorphous structure, with weak peaks corresponding to Fe₃O cores and additional peaks in the range of 2θ = 21–23°, indicating the presence of cellulose and Ti bonding to the shell.

2.5. Magnetic Properties Analysis

The magnetic behavior of the catalyst was examined by vibrating sample magnetometry (VSM) measurements carried out at 300 K (Figure 4). The absence of a hysteresis loop, remanence, and coercivity confirms the superparamagnetic behavior of all samples at room temperature. The saturation magnetization values were 49.177 emu/g for Fe₃O₄, 33.057 emu/g for Fe₃O₄@NCs, and 6.062 emu/g for Fe₃O₄@NCs/Ti(IV), indicating a reduction in magnetic properties due to the nano-cellulose and Ti(IV) coating.

2.6. Thermal Stability Analysis

The thermal stability of Fe₃O₄@NCs/Ti(IV) was examined using a thermogravimetric analysis (TGA) across the temperature range of 50–372 °C (Figure 5). The curve shows four distinct stages of mass loss. The first weight reduction of 2.14%, occurring between 50 °C and 100 °C, is associated with the desorption of physically adsorbed water molecules from the catalyst surface.

2.7. Catalyst Activity Evaluation and Scope

Following the characterization of Fe₃O₄@NCs/Ti(IV), its catalytic activity was tested in the synthesis of 2,3-dihydro -1H-perimidine derivatives. To optimize the reaction conditions, a model reaction between 1,8-diaminonaphthalene and benzaldehyde was conducted (

Table 1. Optimization of reaction conditions for the synthesis of 2,3-dihydro-2-phenyl-1H-perimidine(1a) using a nanocatalyst.

Entry	Solvent	Catalyst	Condition	Time (min)	Yield (%) a
1	H2O	Fe3O4@NCs/Ti (IV)	70 °C	130	65
2	H2O	Fe3O4@NCs/Ti (IV)	25 °C	120	70
3	H2O	Fe3O4@NCs/Ti (IV)	35 °C	150	65
4	H2O	Fe3O4@NCs/BF3	100 °C	120	72
5	H2O	Fe3O4@NCs/BF3	70 °C	120	35
6	C2H5OH	Fe3O4@NCs/Ti (IV)	70 °C	30	55
7	C2H5OH	Fe3O4@NCs/Ti (IV)	60 °C	30	60
8	C2H5OH	Fe3O4@NCs/Ti (IV)	50 °C	30	66
9	C2H5OH	Fe3O4@NCs/Ti (IV)	25 °C	360	78
10	C2H5OH	Fe3O4@NCs/Ti (IV)	35 °C	360	50
11	C2H5OH	Fe3O4@NCs/BF3	80 °C	30	48
12	C2H5OH	Fe3O4@NCs/BF3	70 °C	28	45
13	C2H5OH	Fe3O4@NCs/Ti (IV)	Ultrasonic	10	89
14	C2H5OH	Fe3O4@NCs/Ti (IV)	Ultrasonic	60	88
15	C2H5OH	Fe3O4@NCs/BF3	Ultrasonic	10	60

^a: isolated yield.

).

As shown in entry 13 (Table 1), the reaction between 1,8-diaminonaphthalene and benzaldehyde in the presence of Fe₃O₄@NCs/Ti (IV) under ultrasonic conditions resulted in a significantly improved yield. Ultrasonic irradiation promotes the reaction via acoustic cavitation, generating localized high temperatures and pressures that enhance catalyst–substrate interactions and accelerate the reaction rate. This approach reduces reaction time and improves efficiency, providing a greener and more energy-efficient pathway for synthesizing 2,3-dihydro-2-phenyl-1H-perimidine derivatives.

Table 2. Comparison of the catalytic efficiency of Fe₃O₄@NCs/Ti (IV) with other catalysts under green conditions.

Entry	Solvent	Catalyst	Condition	Time (min)	Yield (%) a
1	-	Glycerol	25 °C	30	90 [23]
2	C2H5OH:H2O (1:1)	OVL@Cu	25 °C	30	95 [24]
3	C2H5OH	Fe3O4/SO3H@zeolite-Y	25 °C	25	95 [25]
4	C2H5OH	Fe3O4@NCs/Ti (IV)	Ultrasonic	10	89 (This Work)

^a: Isolated yield.

highlights the excellent performance of Fe₃O₄@NCs/Ti (IV), which produced high yields of products under environmentally friendly conditions compared to other catalysts. The optimized reaction parameters were successfully applied to synthesize a variety of 2,3-dihydro-2-phenyl-1H-perimidine derivatives with the outcomes summarized in

Table 3. C synthesis of 2,3-dihydro-perimidine derivative using nanocatalyst Fe₃O₄@NCs/Ti (IV).

Entry	R	Product	Product Structure	Time	Yield	M.P °C	Ref.
1		1b		10	80	176–179 °C	This work
2		1c		10	75	182–185 °C	[26]
3		1d		10	73	182–184 °C	This Work
4		1e		30	55	258–261 °C	This Work
5		1f		45	52	160–163 °C	[27]
6		1g		45	40	242–245 °C	This Work
7		1h		50	28	202–205 °C	This Work
8		1i		10	90	163–166 °C	This Work
9		1j		60	35	174–177 °C	This Work
10		1k		22	70	138–141 °C	[27]
11		1l		120	20	169–172 °C	This Work

.

The recyclability of the Fe₃O₄@NCs/Ti(IV) catalyst was investigated using the model reaction. Benefiting from its inherent magnetic properties, the catalyst was easily isolated from the reaction medium by applying an external magnet, followed by simple ethanol washing and air drying. This efficient magnetic recovery underscores its suitability for environmentally friendly, sustainable, and cost-effective catalytic processes.

Under optimized conditions, aromatic aldehydes with electron-donating and electron-withdrawing groups were effectively converted into products with high yields. In the first step of the mechanism, the hydrogen from the catalyst forms a bond with the lone pair of oxygen in the aldehyde, activating the C=O bond for nucleophilic attack. In the next step, 1,8-diaminonaphthalene attacks the carbonyl group, leading to the displacement of a hydrogen atom and the loss of a water molecule. This results in the formation of the desired 2,3-dihydroperimidine (Scheme 1).

The reusability of Fe₃O₄@NCs/Ti(IV) highlights its value in sustainable catalysis, offering both environmental and economic benefits. The catalyst was recovered by dissolving the reaction mixture in a minimal amount of hot ethanol, followed by separation using filtration and an external magnetic field. After washing with ethanol (EtOH) and drying at ambient temperature, it was reused in subsequent reactions.

The catalyst maintained its efficiency in the synthesis of 1,4-dihydroperimidine derivatives over multiple cycles. As shown in Figure 6, these results confirm its good recyclability and demonstrate the robustness and sustainability of the catalytic system.

3. Materials and Methods

All chemicals and solvents utilized in this research work were procured from Merck, BLD Farm, and Thermo Fisher Scientific and were also used as received without further purification.

In order to investigate the surface morphology of the synthesized materials, the surface area of the catalyst was examined using FESEM (MIRA3 TESCAN, Kashan, Iran), while the crystalline structure was analyzed through XRD measurements performed on a PANalytical X’Pert PRO diffractometer (Yazd, Iran) with Cu-Kα radiation. Due to the importance of thermal stability, the TGA method on a Mettler Toledo TGA/DSC 1 system (Kashan, Iran) was applied.

Nuclear magnetic resonance (NMR) spectra, consisting of ¹H NMR and ¹³C NMR, were recorded on a Bruker Avance III (Linz, Austria) 300 and 700 MHz spectrometer with DMSO-d₆ as solvent and also TMS as the internal standard. High-resolution mass spectra (HRMS, Linz Austria) were obtained using a Thermo Fisher Scientific LTQ Orbitrap XL (Linz, Austria) equipped with an Ion Max API Source, with analyses conducted in both negative and positive ionization modes.

Fourier-transform infrared (FT-IR) spectra were measured. IR spectra were obtained using a Bruker Alpha II FTIR spectrometer (Yazd, Iran) with a diamond ATR module. Melting points (MP) were determined using a Büchi M-560 apparatus (Kashan, Iran) and are reported in degrees Celsius (°C). Ultrasonic irradiations were carried out using an Elmasonic S 40H ultrasonic device (Yazd, Iran).

3.1. Preparation of Catalyst

Under a fume hood, TiCl₄ (3.0 mL) was added dropwise to a suspension of Fe₃O₄@NCs (0.30 g) in chloroform (15 mL). The reaction mixture was stirred at room temperature for 2 h, then filtered and washed repeatedly with chloroform to remove unreacted species. The resulting solid was dried at room temperature to afford Fe₃O₄@NCs/Ti(IV) (0.38 g).

3.2. General Procedure for the Synthesis of 2,3-Dihydro-1H-perimidine

A reaction mixture consisting of 1,8-diaminonaphthalene (1 mmol), various aromatic aldehydes (1 mmol), Fe₃O₄@nano-cellulose/Ti (IV) (0.03 g), and ethanol (8 mL) was heated under reflux or subjected to ultrasonic irradiation at 70 °C. The progress of the reaction was monitored by thin-layer chromatography (TLC) using a solvent system of ethyl acetate and n-heptane (1:3). After the reaction was complete, the catalyst was efficiently separated using an external magnet and stored for reuse in subsequent cycles. The reaction mixture was cooled to room temperature and poured into chilled ethanol to precipitate the product. The solid was collected by filtration, washed with hot ethanol, and recrystallized from ethanol to afford the desired compound in excellent yield. Certain derivatives required additional purification by column chromatography on silica gel (mesh size 25) using ethyl acetate/n-heptane as eluents or by preparative TLC under the same solvent system to ensure high purity.

3.3. Spectroscopic Data of Products

3.3.1. 1a: 2-Phenyl-2,3-dihydro-1H-perimidine

White Solid, Melting point: 300 °C, FT-IR (ATR)/ῡ(cm⁻¹): 3343–3375, 3043, 2921, 1599, ¹H NMR (300 MHz, DMSO-d₆)/δ ppm: 5.38 (1H, s, CH), 6.47 (2H, d, J = 6.5 Hz, CH), 6.75 (2H, s, NH), 6.97 (2H, d, J = 7.0 Hz, CH), 7.14 (2H, t, J = 7.7 Hz, CH), 7.40 (3H, m, CH), 7.60 (2H, m, CH). ¹³C NMR (75 MHz, DMSO-d₆, 298 K)/δ ppm: 67, 104, 112, 115, 127.2, 128.3, 128.6, 128.8, 134, 142, 143. HRMS for C₁₇H₁₄N₂[M + H]⁺: m/z: 247.123, found: 247.1238.

3.3.2. 1b: 2-(3,4,5-Trifluorophenyl)-2,3-dihydro-1H-perimidine

Dark yellow solid, Melting point: 176–179 °C, FT-IR (ATR)/ῡ (cm⁻¹): 3440, 3073, 2864, 1572, ¹H NMR (300 MHz, DMSO-d₆)/δ ppm: 5.42 (1H, s, CH), 6.50 (2H, d, J = 7.2 Hz, CH), 6.93 (2H, s, NH), 6.98 (2H, d, J = 8.4 Hz, CH), 7.14 (2H, t, J = 7.6 Hz, CH), 7.40 (2H, m, CH). ¹³C NMR (75 MHz, DMSO-d₆, 298 K)/δ ppm: 64, 105, 112.4, 112.6, 112.7, 112.8, 116, 127, 134, 142, ¹⁹F NMR (DMSO, 298 K)/δ ppm: −161, −135.09, −135.01. HRMS for C₁₇H₁₁F₃N₂[M + H]⁺: m/z: 301.0947 found: 301.0947.

3.3.3. 1c: 2-(4-Fluorophenyl)-2,3-dihydro-1H-perimidine

Dark yellow solid, Melting point: 182–189 °C, FT-IR (ATR)/ῡ (cm⁻¹): 3440, 3076, 2849, 15,742, ¹H NMR (300 MHz, DMSO-d₆)/δ ppm: 5.38 (1H, s, CH), 6.49 (2H, d, J = 8.1 Hz, CH), 6.76 (2H, s, NH), 6.98 (2H, d, J = 8.4 Hz, CH), 7.14 (2H, t, J = 7.3Hz, CH), 7.2 (2H, t, J = 8.7 Hz, CH), 7.62 (2H, m, CH). ¹³C NMR (75 MHz, DMSO-d₆, 298 K)/δ ppm: 66, 104, 112, 115.2, 115.5, 127, 130.3, 130.4, 134, 138.5, 143, 161, 164, ¹⁹F NMR (DMSO-d₆, 298 K)/δ ppm: −113.8. HRMS for C₁₇H₁₃FN₂[M + H]⁺: m/z: 265.1136 found: 265.1139.

3.3.4. 1d: 2-(3-Methyl-5-(trifluoromethyl)phenyl)-2,3-dihydro-1H-perimidine

Pink solid, Melting point: 182–184 °C, FT-IR (ATR)/ῡ (cm⁻¹): 3444, 3073, 2865, 1582, 1168, ¹H NMR (300 MHz, DMSO-d₆)/δ ppm: 5.62 (1H, s, CH), 6.50 (2H, d, J = 7.2 Hz, CH), 6.93 (2H, s, NH), 7.02 (4H, d, J = 7.6 Hz, CH), 7.2 (2H, t, J = 7.6Hz, CH), 8.14 (1H, s, CH), 8.28 (2H, s, CH), ¹³C NMR (75 MHz, DMSO-d₆, 298 K)/δ ppm: ¹⁹F NMR (DMSO-d₆, 298 K)/δ ppm: −60.18, HRMS for C₁₉H₁₅F₆N₂[M + H]⁺: m/z: 383.0977 found: 383.0979.

3.3.5. 1e: 2-(Anthracen-9-yl)-2,3-dihydro-1H-perimidine

Yellow Solid, Melting point: 258–261 °C, FT-IR (ATR)/ῡ (cm⁻¹): 3350, 3043, 2921, 1596, 1383, ¹H NMR (300 MHz, DMSO-d₆)/δ ppm: 6.50 (2H, d, J = 7.5 Hz, CH), 6.91 (1H, s, CH), 7.03 (2H, s, NH), 7.08 (2H, d, J = 8.1 Hz, CH), 7.19 (2H, t, J = 7.7 Hz, CH), 7.51 (4H, m, CH), 8.10 (2H, m, CH), 8.70 (1H, s, CH). ¹³C NMR (75 MHz, DMSO-d₆, 298 K)/δ ppm: 63, 104, 113, 115, 125, 127, 130, 135, 144. HRMS for C₂₅H₁₈N₂[M + H]⁺: m/z: 347.1543, found: 347.1544.

3.3.6. 1f: 2-([1,1′-Biphenyl]-4-yl)-2,3-dihydro-1H-perimidine

Pink Solid, Melting point: 191–194 °C, FT-IR (ATR)/ῡ (cm⁻¹): 3378, 2845, 1593, 1396, ¹H NMR (300 MHz, DMSO-d₆)/δ ppm: 5.42 (1H, s, CH), 6.50 (2H, d, J = 7.21 Hz, CH), 6.83 (2H, s, NH), 6.98 (2H, d, J = 8.0 Hz, CH), 7.14 (2H, t, J = 7.6 Hz, CH), 7.36 (1H, m, CH), 7.46 (2H, t, J = 7.5 Hz, CH), 7.67 (6H, m, CH). ¹³C NMR (75 MHz, DMSO, 298 K)/δ ppm: 66, 104, 112, 115, 127.0, 127.2, 127.3, 128, 129, 134, 140.3, 140.9, 141, 143, HRMS for C₂₃H₁₈N₂[M + H]⁺: m/z: 323.1543, found: 323.1543.

3.3.7. 1g: 2-(Pyren-1-yl)-2,3-dihydro-1H-perimidine

Red Solid, Melting point: 242–245 °C, FT-IR (ATR)/ῡ (cm⁻¹): 3429, 2864, 1610, 1397, ¹H NMR (300 MHz, DMSO-d₆)/δ ppm: 6.34 (1H, s, CH), 6.58 (2H, d, J = 7.9 Hz, CH), 7.03 (2H, s, NH), 7.08 (2H, d, J = 7.1 Hz, CH), 7.21 (2H, t, J = 7.6 Hz, CH), 8.08. (2H, t, J = 7.7 Hz, CH), 8.21 (7H, m, CH), 8.96 (1H, d, CH). ¹³C NMR (75 MHz, DMSO-d₆, 298 K)/δ ppm: 66, 104, 113, 115, 124.4, 124.7, 125.0, 125.1, 125,7, 125.8, 126.5, 126.7, 127.3, 127.5, 127.6, 127.8, 128, 129, 130, 131.2, 131.6, 134, 135, 144. HRMS for C₂₇H₁₈N₂[M + H]⁺: m/z: 369.1386, found: 369.1386.

3.3.8. 1h: 2-(Naphthalen-2-yl)-2,3-dihydro-1H-perimidine

White Solid, Melting point: 202–205 °C, FT-IR (ATR)/ῡ (cm⁻¹): 3437, 2847, 1601, 1398, ¹H NMR (300 MHz, DMSO:d₆)/δ ppm: 5.52 (1H, s, CH), 6.50 (2H, d, J = 7.5 Hz, CH), 6.83 (2H, s, NH), 6.99 (2H, d, J = 8.0 Hz, CH), 7.14 (2H, t, J = 7.7 Hz, CH), 7.53 (2H, m, CH), 7.76 (1H, m, CH), 7.93 (3H, m, CH), 8.11 (1H, s, CH). ¹³C NMR (75 MHz, DMSO:d₆, 298 K)/δ ppm: 67, 104, 112, 112, 115, 126.2, 126.3, 127.3, 127.4, 127.3, 128.0, 128.3, 128.4, 133.0, 133.4, 134, 139, 143. HRMS for C₂₁H₁₆N₂[M + H]⁺: m/z: 297.1386, found: 297.1385.

3.3.9. 1i: 2-(Perfluorophenyl)-2,3-dihydro-1H-perimidine

Dark yellow solid, Melting point: 163–166 °C, FT-IR (ATR)/ῡ (cm⁻¹): 3431, 3083, 2673, 1608, 1582, ¹H NMR (300 MHz, DMSO-d₆)/δ ppm: 5.91 (1H, s, CH), 6.50 (2H, m, CH), 6.95 (2H, s, NH), 7.09 (2H, d, J = 7.8 Hz, CH), 7.21 (2H, t, J = 7.5 Hz, CH). ¹³C NMR (75 MHz, DMSO-d₆, 298 K)/δ ppm: 58, 104, 112.4, 112, 116, 127, 134, 142, ¹⁹F NMR (DMSO-d₆, 298 K)/δ ppm: −162 (2F), −154 (1F), −1431 (2F). HRMS for C₁₇H₉F₅N₂[M + H]⁺: m/z: 337.0759, found: 337.0759.

3.3.10. 1j: 2-(4-Methylnaphthalen-1-yl)-2,3-dihydro-1H-perimidine

Yellow dark, Melting point: 174–177 °C, FT-IR (ATR)/ῡ (cm⁻¹): 3414, 3053, 2802, 1609, 144, ¹H NMR (300 MHz, DMSO:d₆)/δ ppm: 3.07 (3H, s, CH₃), 5.98 (1H, s, CH), 6.50 (2H, m, CH), 6.81 (2H, s, NH), 7.07 (2H, m, CH), 7.20 (2H, t, J = 7.5 Hz, CH), 7.44 (1H, m, CH), 7.51 (2H, m, CH), 7.72 (1H, d, J = 7.23 Hz, CH), 8.12 (1H, m, CH), 8.76 (1H, d, J = 7.91 Hz, CH), ¹³C NMR (75 MHz, DMSO-d₆, 298 K)/δ ppm: 19, 67, 104, 112, 115, 124, 125, 126.2, 126.3, 126.3, 126.9, 127,31, 133, 134.4, 134.9. 144. HRMS for C₂₂H₁₈N₂[M + H]⁺: m/z: 309.1386, found: 309.1389.

3.3.11. 1k: 2-(4-Bromophenyl)-2,3-dihydro-1H-perimidine

Brown solid, Melting point: 141–144 °C, FT-IR (ATR)/ῡ (cm⁻¹): 3443, 3079, 2856, 15,842, ¹H NMR (300 MHz, DMSO-d₆)/δ ppm: 5.36 (1H, s, CH), 6.48 (2H, d, J = 7.27 Hz, CH), 6.74 (2H, s, NH), 6.98 (2H, d, J = 7.87 Hz, CH), 7.13 (2H, t, J = 7.67 Hz, CH), 7.53 (2H, d, J = 8.47 Hz, CH), 7.62 (2H, d, J = 8.56 Hz, CH). ¹³C NMR (75 MHz, DMSO-d₆, 298 K)/δ ppm: 65, 104, 112, 115, 121, 127, 130, 131, 134, 141, 143, HRMS for C₁₇H₁₃BrN₂[M + H]⁺: m/z: 325.0325, found: 325.0327.

3.3.12. 1l: 2-(4-Ethynylphenyl)-2,3-dihydro-1H-perimidine

Yellow solid, Melting point: 169–172 °C, FT-IR (ATR)/ῡ (cm⁻¹): 3444, 3063, 2842, 1563, ¹H NMR (300 MHz, DMSO-d₆)/δ ppm: 4.21 (1H, s, CH), 5.38 (1H, s, CH), 6.48 (2H, d, J = 7.2 Hz, CH), 6.80 (2H, s, NH), 6.97 (2H, d, J = 7.8 Hz, CH), 7.12 (2H, t, J = 7.8 Hz, CH), 7.50 (2H, d, J = 8.2 Hz, CH), 7.58 (2H, d, J = 8.2 Hz, CH), ¹³C NMR (75 MHz, DMSO-d₆, 298 K)/δ ppm: 66, 81, 83, 104, 112, 115, 122, 127, 128, 132, 134, 143.1, 143.2, HRMS for C₁₉H₁₄N₂[M + H]⁺: m/z: 271.123, found: 271.1232.

3.3.13. 1e-A: 2-(Anthracen-9-yl)-2,3-dihydro-1H-perimidine

¹H NMR (700 MHz, DMSO-d6)/δ ppm: 6.50 (2H, d, J = 7.5 Hz, CH), 6.91 (1H, s, CH), 7.03 (2H, s, NH), 7.08 (2H, d, J = 8.1 Hz, CH), 7.19 (2H, t, J = 7.7 Hz, CH), 7.51 (4H, m, CH), 8.14 (2H, m, CH), 8.56 (1H, m, CH), 8.73 (1H, s, CH), 9.48 (1H, m, CH).

3.3.14. 1e-B: 2-(Anthracen-9-yl)-2,3-dihydro-1H-perimidine

¹H NMR (700 MHz, DMSO-d₆:D₂O)/δ ppm: 6.50 (2H, d, J = 7.5 Hz, CH), 6.91 (1H, s, CH), 7.08 (2H, d, J = 8.1 Hz, CH), 7.19 (2H, t, J = 7.7 Hz, CH), 7.51 (4H, m, CH), 8.14 (2H, m, CH), 8.56 (1H, m, CH), 8.73 (1H, s, CH), 9.48 (1H, m, CH).

4. Conclusions

In this study, we describe the development of a highly efficient and environmentally benign two-component reaction for the synthesis of novel 2,3-dihydroperimidine derivatives, utilizing Fe₃O₄@NCs/Ti(IV) as a robust, magnetically separable, eco-friendly, cost-effective, and innovative bio-based heterogeneous catalyst. The methodology is characterized by several remarkable features, including environmentally benign conditions, rapid reaction times, high product yields, simplified purification processes, and exceptional product quality. Moreover, this green approach enables the creation of new 2,3-dihydroperimidine derivatives, which demonstrates its versatility and promising potential for advancing sustainable synthetic chemistry.