L-Leucine supported on superparamagnetic silica-encapsulated γ-Fe₂O₃ nanoparticles: design, characterization, and application as a green catalyst for highly efficient synthesis of thiazoloquinolines

Abstract

A new superparamagnetic silica-encapsulated γ-Fe₂O₃ supported L-leucine was successfully prepared and characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectrum (EDS), vibrating sample magnetometery (VSM), thermo-gravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FT-IR). It catalyzed the synthesis of thiazoloquinolines through a four-component reaction of α-enolicdithioesters, cysteamine, aromatic aldehydes, and dimedone under thermal solvent-free conditions in good to excellent yields. This novel superparamagnetic catalyst could be easily separated from the reaction mixture with an external magnet and recovered at least five times without intense loss of catalytic activity.

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Introduction

Nanoparticles are widely used for organic synthesis.¹ Due to their nanometer size and magnetic properties, they are effective as homogeneous-like systems that integrate the advantages of high dispersion, high reactivity, and simple separation.² Magnetic nanoparticles (MNPs) have been well employed to immobilize organic ligands, organocatalysts, and biocatalysts through absorption or formation of covalent bonds.¹ Moreover, MNPs such as iron oxide have a high surface area, superior thermal and chemical stability, surface modification ability, ease of synthesis, and low toxicity and cost.³

Researchers' attention has been drawn to immobilization of amino acids on the surface of nanoparticles.^4,5 For example, an organocatalysts structure was based on L-proline synthesis and applied in an asymmetric aldol reaction;⁴ in addition, L-arginine supported on magnetic nanoparticles has been developed for chromenes synthesis.⁵ These compounds, having two functional groups, can be supported on a substrate and applied as a catalyst⁶ or medicine.⁷ L-leucine is one of 20 natural amino acids that can be supported on nanoparticles and act as a catalyst in organic chemistry.⁸ For instance, polyethylene glycol poly-L-leucine catalyzed asymmetric epoxidation of chalcone⁶ and silica-grafted poly-L-leucine catalyzed asymmetric epoxidation of benzalacetophenone with high enantioselectivity.⁸

Multi-component reactions (MCRs) are a center of attention because they are highly efficient and convergent, and need minimum time and effort to attain structural complexity in synthetic organic chemistry.⁹ They can be used for creating a range of compound series in the pharmaceutical chemistry field.¹⁰ Thus, MCRs are also considered in green chemical processes.

The thiazole ring is an important pharmacophore. It must be noted that many thiazolyl compounds and annulated thiazoles are applied in human therapeutics, veterinary remedies and leading structures for drugs.¹¹ Quinoline ring systems occur in various natural products, especially in alkaloids, and they are often applied for the design of many synthetic compounds with diverse pharmacological features.¹² The synthesis of thiazoloquinoline derivatives has rarely been reported in the literature. These compounds have been described as potential antispasmodics, precursors of symmetrical cyanines, anti inflammatories, and fluorescent probes.¹³ Thiazolo[3,2-a]quinoline derivatives are attractive in chemistry because of their biological activities.^14,15 They also are used in production of polymethine dyes and as spectral sensitizers of silver halide emulsions.¹⁶

In this study, we report MNPs-L-leucine as a new catalyst for the synthesis of thiazoloquinolines through the four-component reaction of α-enolicdithioesters (1), cysteamine (2), aromatic aldehydes (3), and dimedone (4) under thermal solvent-free conditions (Scheme 1).

Scheme 1 Synthesis of thiazoloquinolines in the presence of MNPs-L-leucine.

Result and discussion

Catalyst preparation

New MNPs-L-leucine as a catalyst was prepared based on the following procedure (Scheme 2). First, superparamagnetic Fe₃O₄ nanoparticles were facilely synthesized by a chemical co-precipitating method.¹⁷ Second, it was converted to γ-Fe₂O₃ at 300 °C for 3 h. Subsequently, γ-Fe₂O₃ was encapsulated by tetraethyl orthosilicate, Si(OEt)₄ (TEOS), as Fe₂O₃@SiO₂.¹⁸ Then, chloro-functionalized γ-Fe₂O₃@SiO₂ was synthesized.¹⁹ Finally, the reaction of L-leucine with chloro-functionalized γ-Fe₂O₃@SiO₂ formed a new superparamagnetic silica-encapsulated γ-Fe₂O₃ as the catalyst.

Scheme 2 Synthesis of MNPs-L-leucine.

The magnetic nanocatalyst was characterized using different techniques such as XRD, SEM, EDS, VSM, TGA, and FT-IR. The acidity of MNPs-L-leucine was determined by acid–base back-titration method.

The XRD pattern of γ-Fe₂O₃, γ-Fe₂O₃@SiO₂, and MNPs-L-leucine had six characteristic peaks which have a good accordance with the cubic structure of maghemite (γ-Fe₂O₃) (JCPDS file No 04-0755). The positions of all the peaks indicated retention of the crystalline structure during functionalization of the MNPs and the grafting process did not change the phase of the γ-Fe₂O₃ nanoparticles. The XRD pattern of γ-Fe₂O₃@SiO₂ and γ-Fe₂O₃@SiO₂@L-leucine showed that SiO₂ and L-leucine formed an amorphous phase in which their patterns showed only pattern of crystalline γ-Fe₂O₃ nanoparticles (Fig. 1).

Fig. 1 XRD pattern of (a) γ-Fe₂O₃, (b) γ-Fe₂O₃@SiO₂ and (c) MNPs-L-leucine.

Fig. 2 represents the SEM image of MNPs-L-leucine that shows spherical morphology and an average size 17.5 nm of nanoparticles using a histogram curve. The components of the MNPs-L-leucine were analyzed using EDS. EDS basically gives elemental information but it can't quantitatively determine accurate element percentage.²⁰ The EDS spectrum in Fig. 3 implicates the presence of atoms Fe, O, Si, C, N, and Cl in the catalyst. The Mohr titration method also confirms the presence of chlorine in the catalyst.²¹

Fig. 2 (a) SEM images of MNPs-L-leucine; (b) particle size distribution histogram of MNPs-L-leucine.

Fig. 3 EDS spectrum of MNPs-L-leucine.

The VSM diagram shows the magnetic properties of the synthesized catalyst (Fig. 4). The hysteresis loops of γ-Fe₂O₃ before and after immobilization of L-leucine were measured. Superparamagnetic behavior of both of them illustrates small particle size. As can be observed, the saturation magnetization value of MNPs-L-leucine is 52 amu g⁻¹.

Fig. 4 VSM diagrams of (a) MNPs-L-leucine and (b) γ-Fe₂O₃.

Thermal stability of the MNPs-L-leucine was investigated by TGA analysis (Fig. 5). A small weight loss which occurs below 100 °C is due to water desorption. The second weight loss can be attributed to decomposition of the immobilized organic part. The total weight loss was computed to be 6.8% and the amount of L-leucine loaded on γ-Fe₂O₃@SiO₂ was equal to 0.42 mmol g⁻¹.

Fig. 5 Thermogravimetric and differential thermogravimetric plots of MNPs-L-leucine.

The obtained results from TGA was confirmed by the back-titration method. First, 0.05 g of MNPs-L-leucine was weighed out and 5 mL NaOH 0.1 N was added. An excess amount of base was added that reacted with all of the catalyst, some of which was left. Next, two drops of phenolphthalein as an indicator were added to mixture followed by sonicating it. Back-titration of unreacted base began by adding 0.1 N HCl and ended with the disappearance of the purple color. This sequence was repeated for three times. The acidity value of the catalyst obtained was 0.4 mmol g⁻¹.

The characterization of MNPs-L-leucine was confirmed by FT-IR analysis. Typical bands for carbonyl (1629 cm⁻¹) and alkyl (3000 cm⁻¹) were observed together with the iron oxide peak (550–650 cm⁻¹). The stretching mode of Si–O–Si showed a strong broad peak at about 1099–1220 cm⁻¹ (Fig. 6).

Fig. 6 FT-IR spectra: (a) L-leucine, (b) γ-Fe₂O₃@SiO₂ and (c) MNPs-L-leucine.

Optimization of the reaction conditions

To evaluate the activity of the catalyst, MNPs-L-leucine was applied in the one-pot four-component reaction of 3-hydroxy-3-phenyl-prop-2-enedithioate, cysteamine, 4-nitrobenzaldehyde, and dimedone as a selected model (Scheme 3).

Scheme 3 Synthesis of 4-benzoyl-8,8-dimethyl-5-(4-nitrophenyl)-1,2,5,7,9-pentahydrothiazolo[3,2-a]quinolin-6-one.

The reaction was carried out in the absence of the catalyst, in the presence of MNPs-L-leucine, γ-Fe₂O₃, and γ-Fe₂O₃@SiO₂ and L-leucine, in EtOH, EtOH:H₂O, and H₂O as solvent and also under solvent-free conditions.

The results are summarized in Table 1. With regard to the results in Table 1, it was observed that the reaction conducted without the catalyst at room temperature didn't form any products but at 80 and 100 °C produced the desired product with 53 and 65% yield after 14 hours, respectively (Table 1, entries 1–3). The selected reaction in the presence of γ-Fe₂O_3, γ-Fe₂O₃@SiO₂, nano SiO₂, and L-leucine as catalyst formed the desired product with 68, 78, 40, and 78% yields (Table 1, entries 4–7). Table 1 shows that immobilization of SiO₂ on γ-Fe₂O₃ provides a highly active surface area, which makes γ-Fe₂O₃@SiO₂ more reactive than γ-Fe₂O₃, so that the desired product was produced with good yields, 68 and 78%, respectively (Table 1, entries 4 and 5). A control experiment using L-leucine showed the result of catalytic activity of L-leucine itself for this reaction, but moderate yields and no reusability of L-leucine are disadvantages of L-leucine alone as catalyst (Table 1, entry 7). We also carried out the selected reaction using MNPs-L-leucine as catalyst in H₂O as solvent; the results showed that the reaction didn't progress even after 24 h and all starting material remained intact (Table 1, entry 18). As shown from Table 1, the best efficiency was obtained at 80 °C, with 0.025 g of the catalyst under solvent-free conditions (Table 1, entry 9).

Table 1 Optimization of the reaction conditions for the synthesis of 4-benzoyl-8,8-dimethyl-5-(4-nitrophenyl)-1,2,5,7,9-pentahydrothiazolo[3,2-a]quinolin-6-one^a

Entry	Catalyst	Solvent	Temp. (°C)	Time (h)	Amount cat. (g)	Yield^b (%)
a Based on the reaction of 3-hydroxy-3-phenyl-prop-2-enedithioate (0.5 mmol), cysteamine (0.5 mmol), 4-nitrobenzaldehyde (0.5 mmol) and dimedone (0.5 mmol).b Isolated yields after purification using recrystallization and drying.
1	—	—	r.t	24	—	—
2	—	—	80	14	—	53
3	—	—	100	14	—	65
4	γ-Fe2O3	—	80	1	0.025	68
5	γ-Fe2O3@SiO2	—	80	1	0.025	78
6	Nano SiO2	—	80	2	0.025	40
7	L-Leucine	—	80	2	0.001	78
8	MNPs-L-leucine	—	80	2	0.0125	84
9	MNPs-L-leucine	—	80	1	0.025	93
10	MNPs-L-leucine	—	80	1	0.05	93
11	MNPs-L-leucine	—	80	1	0.1	93
12	MNPs-L-leucine	—	r.t	24	0.025	12
13	MNPs-L-leucine	—	50	4	0.025	52
14	MNPs-L-leucine	—	70	2	0.025	84
15	MNPs-L-leucine	—	90	1	0.025	93
16	MNPs-L-leucine	—	100	50 min	0.025	93
17	MNPs-L-leucine	EtOH	Reflux	24	0.025	60
18	MNPs-L-leucine	H2O	Reflux	24	0.025	Trace
19	MNPs-L-leucine	EtOH:H2O	100	24	0.025	63

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According to optimal considered conditions, in this methodology other various structural derivatives were synthesized and results are summarized in Table 2. As shown in Table 2, the products are synthesized in suitable time and good yields.

Table 2 Substrate scope for synthesis of thiazoloquinolines

Entry	R	R^1	Product	Time (min)	Yield^a (%)	Mp (°C)
a Isolated yields after purification using recrystallization and drying.
1	C6H5	H	5a	60	93	200–202 (ref. 22 and 23)
2	C6H5	4-NO2	5b	60	93	212–214 (ref. 22 and 23)
3	C6H5	4-Me	5c	90	85	208–210 (ref. 22 and 23)
4	C6H5	3-OH	5d	90	88	220–222 (ref. 22)
5	C6H5	4-Cl	5e	50	87	178–180
6	4-ClC6H4	4-Cl	5f	50	83	150–152
7	4-ClC6H4	4-NO2	5g	50	92	168–170
8	Furyl	H	5h	45	90	105–107 (ref. 22)
9	Furyl	4-NO2	5i	40	89	218–220
10	Furyl	4-Br	5j	60	90	148–150 (ref. 22)
11	Furyl	4-Me	5k	45	87	210–212 (ref. 22)
12	Thiophenyl	H	5l	60	87	220–222 (ref. 22)
13	Thiophenyl	4-NO2	5m	60	86	192–194 (ref. 22)
14	Thiophenyl	4-Cl	5n	60	88	178–180
15	Thiophenyl	4-Me	5o	90	85	195–197 (ref. 22)

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The proposed mechanism for the formation of the product is shown in Scheme 4. First, cyclic N,S-acetal I was formed through the reaction of α-enolicdithioester 1 with cysteamine 2. Next, knoevenagel product II was obtained from the reaction of aldehyde 3 with cyclic 1,3-diketone 4. The conjugate addition of the N,S-acetal I with ortho-quinone methide intermediate II formed an acyclic intermediate III. Intermediate IV was obtained by imine–enamine and keto–enol tautomerization of intermediate III. Finally, the desired heterocyclic product 5 was formed rapidly via intramolecular dehydrative N-cyclization from intermediate IV.

Scheme 4 Proposed mechanism for the synthesis of thiazoloquinolines in the presence of MNPs-L-leucine.

The recyclability of MNPs-L-leucine was examined in the one-pot four-component synthesis of thiazoloquinoline 5a under optimized conditions. After completion of the reaction, ethanol was added to the reaction mixture and the MNPs-L-leucine was separated with an external magnet (Fig. 7). To remove all organic components, the catalyst was washed with methanol and ethanol three times and dried. As shown in Fig. 8, even after five runs catalytic activity and product yield have no significant loss. Thus, this catalyst can endure reaction conditions and remain stable.

Fig. 7 Isolation of catalyst by external magnet.

Fig. 8 Reusability of MNPs-L-leucine.

Experimental

Material and methods

All reagents were purchased from Merck (Germany) and Sigma-Aldrich (USA) companies and used without further purification. All yields refer to separated products after purification. The NMR spectra were provided with a Bruker Avance 300 MHz instrument in CDCl3. Infrared (IR) spectra were recorded applying a JASCO FT-IR460 Plus spectrophotometer. Mass spectra were recorded on an Agilent technologies 5973 network mass selective detector (MSD) operating at an ionization potential of 70 eV. Melting points were determined in open capillaries using a BUCHI510 melting point apparatus. Thin-layer chromatography (TLC) was performed on silica-gel Poly Gram SIL G/UV 254 plates. Elemental compositions were determined with a Leo 1450 VP scanning electron microscope equipped with an SC7620 energy dispersive spectrometer (SEM-EDS) presenting a 133 eV resolution at 20 kV. Power X-ray diffraction (XRD) was performed on a Bruker D8-advance X-ray diffractometer with Cu Kα (λ = 0.154 nm) radiation.

Synthesis of MNPs-L-leucine

Synthesis of γ-Fe₂O₃. The Fe₃O₄ nanoparticles were synthesized by a chemical co-precipitation technique with minor modification.^17,18 FeCl₂·4H₂O (1.99 g) and FeCl₃·6H₂O (3.25 g) were dissolved in water (20 mL) separately, followed by the two iron salt solutions being mixed under continuously stirring (800 rpm). Then a NH₄OH solution (0.7 M, 200 mL) was added to the stirring mixture at room temperature, in order to maintain the reaction pH between 9 and 11. The Fe₃O₄ nanoparticles were collected by an external magnet; then, they were washed three times with water, ethanol, and dried at 100 °C for 12 h. The prepared nanoparticles at this stage were heated at 300 °C via furnace for 3 h to convert Fe₃O₄ to sustainable γ-Fe₂O₃ nanoparticles.

Synthesis of γ-Fe₂O₃@SiO₂ (ref. 18). γ-Fe₂O₃ nanoparticles (1 g) were dispersed in ethanol (40 mL) and the resulting mixture was stirred for 1 h at 40 °C. Subsequently, tetraethyl orthosilicate (TEOS, 5 mL) was charged to the reaction vessel, and the mixture was continuously stirred for 24 h. The silica-coated nanoparticles were collected by an external magnet, followed by washing three times with ethanol, diethyl ether and drying at 100 °C in vacuum for 12 h.

Synthesis of chloro-functionalized γ-Fe₂O₃@SiO₂ (ref. 19). A mixture of γ-Fe₂O₃@SiO₂ (2.0 g) in dry toluene (40 mL) was sonicated for 45 min. 3-Chloropropyl trimethoxysilane (0.5 mL) was added to the dispersed γ-Fe₂O₃@SiO₂ in toluene and was slowly heated to 105 °C. The reaction mixture was stirred for 24 h at this temperature. The resulting chloro-functionalized γ-Fe₂O₃@SiO₂ was separated by an external magnet, washed three times with diethyl ether and dichloromethane, and dried under vacuum.

Synthesis of MNPs-L-leucine. The chloro-functionalized γ-Fe₂O₃@SiO₂ (1 g) was dispersed in 20 mL distilled water and L-leucine (1 g) dissolved in 40–50 mL ethanol–water (1 : 1) was added to the dispersed MNPs and the reaction mixture stirred at room temperature for 24 h. The MNPs-L-leucine was then isolated by simple magnetic decantation, sequentially washed with water (2 × 10 mL) and ethanol (2 × 10 mL), and finally dried under vacuum at 60 °C for 2 h.

General procedure for synthesis of thiazoloquinolines (5). A round bottom flask was charged with the appropriate α-enolicdithioesters (0.5 mmol), cysteamine (0.5 mmol) and MNPs-L-leucine (0.025 g). Then, they were stirred at 80 °C over a pre-heated oil bath under solvent-free conditions. The reaction mixture was stirred for five minutes until the cyclic N,S-acetal was formed (monitored by TLC), which was continued by addition of aldehyde (0.5 mmol) and cyclohexane-1,3-dione (0.5 mmol). The reaction mixture was additionally stirred for a stipulated period of time. After completion of the reaction as shown by TLC, ethanol was added to the reaction mixture and the MNPs-L-leucine was separated by an external magnet, then the reaction was quenched with distilled water and the precipitated yellow solid was collected by filtration. The obtained crude product was dried and recrystallized from an ethanol/dichloromethane (1 : 1) mixture to give the pure products.

The spectra of novel thiazoloquinoline derivatives are given as follows:

4-Benzoyl-8,8-dimethyl-5-(4-chlorophenyl)-1,2,5,7,9-pentahydro-thiazolo[3,2-a]quinoline-6-one (5e). Yellow solid; mp 178–180 °C. ¹H NMR (300 MHz, CDCl₃): δ 7.41 (d, J = 7.2 Hz, 2H), 7.33–7.18 (m, 3H), 7.10 (d, J = 7.0 Hz, 2H), 6.85 (d, J = 8.3 Hz, 2H), 5.22 (s, 1H), 4.13–4.01 (m, 2H), 3.28–3.21 (m, 2H), 2.48 (AB_q, J¹ = 23.9 Hz, J² = 16.1 Hz, 2H), 2.22 (AB_q, J = 27.6 Hz, J = 17.2 Hz, 2H), 1.12 (s, 3H), 0.86 (s, 3H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ 195.2, 194.5, 189.4, 155.0, 148.2, 144.2, 139.4, 131.8, 130.2, 128.8, 128.3, 128.1, 127.0, 115.3, 107.5, 49.9, 40.8, 36.8, 32.3, 31.4, 29.7, 28.2, 26.8 ppm; MS (EI, 70 eV) m/z (%) = 449 (M⁺, 22), 392 (4), 338 (100), 105 (18), 77 (18).
4-(4-Chlorophenyl)-8,8-dimethyl-5-(4-chlorophenyl)-1,2,5,7,9-pentahydro-thiazolo[3,2-a]quinoline-6-one (5f). Yellow solid; mp 150–152 °C. ¹H NMR (300 MHz, CDCl₃): δ 7.36–7.16 (m, 2H), 7.11 (d, J = 8.3 Hz, 2H), 7.01 (d, J = 8.1 Hz, 2H), 6.88 (d, J = 8.3 Hz, 2H), 5.16 (s, 1H), 4.13–4.00 (m, 2H), 3.29–3.23 (m, 2H), 2.55–2.22 (m, 2H), 1.10 (s, 3H), 0.86 (s, 3H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ 195.1, 193.1, 190.5, 189.4, 148.1, 144.0, 137.8, 132.0, 131.6, 128.7, 128.6, 128.4, 128.3, 115.3, 107.0, 49.9, 40.8, 36.7, 32.4, 32.3, 29.3, 28.3, 26.8 ppm; MS (EI, 70 eV) m/z (%) = 484 (M⁺, 11), 483 (22), 374 (40), 372 (100), 344 (29), 139 (32), 111 (31), 75 (17), 41 (8).
4-(4-Nitrophenyl)-8,8-dimethyl-5-(4-chlorophenyl)-1,2,5,7,9-pentahydro-thiazolo[3,2-a]quinoline-6-one (5g). Yellow solid; mp 168–170 °C. ¹H NMR (300 MHz, CDCl₃): δ 8.00 (d, J = 8.6 Hz, 2H), 7.30 (d, J = 8.3 Hz, 2H), 7.17 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 8.6 Hz, 2H), 5.32 (s, 1H), 4.14–4.05 (m, 2H), 3.32–3.25 (m, 2H), 2.45 (AB_q, J¹ = 29.6 Hz, J² = 17.2 Hz, 2H), 2.24 (AB_q, J¹ = 25.5 Hz, J² = 16.3 Hz, 2H), 1.13 (s, 3H), 0.87 (s, 3H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ 196.1, 194.1, 190.5, 188.4, 152.5, 148.0, 138.2, 137.6, 128.6, 128.4, 128.3, 123.7, 123.7, 114.4, 106.4, 49.8,40.9, 37.7, 32.4, 32.3, 29.3, 28.2, 26.7 ppm; MS (EI, 70 eV) m/z (%) = 494 (M⁺, 22), 374 (45), 372 (100), 355 (19), 139 (20), 111 (14).
4-(Furan-2-carbonyl)-5-(4-nitrophenyl)-8,8-dimethyl-1,2,5,7,9-pentahydrothiazolo[3,2-a] quinoline-6-one (5i). Yellow solid; mp 218–220 °C. ¹H NMR (300 MHz, CDCl₃): δ 8.04 (d, J = 9.0 Hz, 2H), 7.47–7.41 (m, 3H), 7.05 (s, 1H), 6.42 (s, 1H), 6.08 (s, 1H), 4.17–4.11 (m, 1H), 4.02–3.93 (m, 1H), 3.28–3.21 (m, 2H), 2.47 (AB_q, J¹ = 28.1 Hz, J² = 17.2 Hz, 2H), 2.27 (AB_q, J¹ = 20.9 Hz, J² = 16.2 Hz, 2H), 1.11 (s, 3H), 0.87 (s, 3H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ 195.2, 177.6, 157.7, 153.1, 153.0, 149.1, 146.3, 145.0, 128.2, 123.6, 117.8, 114.8, 112.0, 105.9, 49.9, 49.8, 40.6, 35.6, 32.3, 29.9, 28.3, 26.7 ppm; MS (EI, 70 eV) m/z (%) = 450 (M⁺, 32), 355 (24), 329 (46), 328 (100), 300 (12), 244 (6), 188 (10), 95 (17).
8,8-Dimethyl-5-(4-chlorophenyl)-4-(thiophene-2-carbonyl)-1,2,5,7,9-pentahydro-thiazolo[3,2-a]quinoline-6-one (5n). Yellow solid; mp 178–180 °C. ¹H NMR (300 MHz, CDCl₃): δ 7.47 (s, 2H), 7.35 (s, 2H), 7.26–702 (m, 3H), 6.97 (s, 2H), 5.76 (s, 1H), 4.10–3.93 (m, 2H), 3.23 (s, 2H), 2.52–2.28 (m, 4H), 1.10 (s, 3H), 0.88 (s, 3H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ 195.4, 183.0, 157.6, 150.0, 148.9, 143.8, 143.3, 132.1, 130.7, 128.8, 128.6, 128.2, 127.8, 115.4, 106.1, 50.0, 49.9, 40.4, 35.3, 32.3, 30.2, 28.4, 26.6 ppm; MS (EI, 70 eV) m/z (%) = 456 (M⁺, 10), 455 (29), 344 (100), 316 (11), 111 (29).

The reaction was actually carried out in two steps regarding the sequence of addition in the one-pot process. If all the reactants and catalyst were added altogether and then heated, then the desired product was formed in low yields with some byproducts such as thiazolidines formation in carbonyl groups/cysteamine condensations.

Conclusion

In summary, we represent synthesis and characterization of MNPs-L-leucine as an efficient nanocatalyst. Its application in the preparation of thiazoloquinolines was investigated under thermal solvent-free conditions. MNPs-L-leucine catalyzed the reaction with good yields, in short time, and under mild conditions. It was separated for the reaction mixture by an external magnet after the end of the reaction. The catalyst was reused for five runs without significant loss of activity and so it also can be recycled.

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