Introduction

Recently, the utilization of procedure with high selectivity, low waste production, simple protocol, no usage of column chromatography to purification of products, low cost and high yield of products are advantages of an ideal protocol in organic synthesis1,2,3,4,5. Grinding condition for organic synthesis has been attracted increasing consideration6,7 in the field8 of green9,10,11 chemistry due to the non-use of solvents particularly volatile organic solvents12. Grinding methods have other principal advantages such as decrease reaction times13, high yields14, increased selectivity15 and improved safety16.

Green and sustainable chemistry is one of the key research areas which can pave a way to meet the continuously increasing demand of the population. Nano-catalysis is essential for sustainable and green chemistry17,18,19,20,21,22,23,24,25,26,27,28,29,30.

One-pot multicomponent reaction has several merits over the routine and step-by-step reaction. Therefore, multicomponent reactions are part of sustainable chemistry and constitute a novel way of ideal organic synthesis. The advantages of one-pot multicomponent reactions are the rapid achievement of complexity and variety in the synthesis of organic materials through highly practical and time-saving approaches. Moreover, this synthetic tool allows chemists to meet the criteria of green chemistry, such as waste prevention, atom and step economy, saving of solvents and reagents, uncomplicated purification procedures, avoidance of hazardous materials, and energy efficiency rather than non-green process31,32,33,34,35,36,37,38. Recently, chemists, consider green chemistry law such as choice eco-friendly synthetic methods, solvent-free condition and using nano catalyst. Green chemistry is quickly expanding, offering eco-friendly path- ways significant for sustainable science and industry39,40,41,42.

Currently scientists are trying to minimize the utilization of hazardous chemicals by substituting them with eco-friendly materials. Bentonite is one kind of natural acidic clays with wide availability, low price, large surface area, layered structure and high cation-exchange capability43.

Bentonite achieve significance in the regard of the researchers as an oncoming catalyst for many organic and inorganic syntheses because of less toxic, high selectivity, high stability, non-corrosive44,45,46, and simple work-up47. Bentonite has OH groups in its structure that are suitable groups for binding of Lewis acids. In this research, we have reacted bentonite with TiCl4 to production of Bentonite/Ti(IV) as a novel natural based heterogeneous nano-catalyst.

4H-pyrimido [2, 1-b] benzothiazole derivatives show momentous structural with interesting biological attributes in medicinal and organic chemistry48,49,50,51,52. Pyrimidobenzothiazoles show various biological activities such as anti-allergic53, inhibition of lung cancer54, anti-tumor55, anthelmintic56, antiviral57, anticonvulsant58and antituberculosis59. As a consequence, developing environmentally friendly catalytic systems for the synthesis of 4H-pyrimido [2, 1-b] benzothiazole derivatives is significant. Previously, several methods for the synthesis of pyrimido[2,1-b] benzothiazoles using different catalysts such as Nano-Co-[4-chlorophenyl-salicylaldimine-pyranopyrimidine dione]Cl255, FeF360, Fe3O4@NCs/Sb(V)61, thiamin hydrochloride (VB1)62, Camphorsulphonic acid58, and Nano-Fe3O4@SiO2–TiCl363, have been reported.

The using solvent free condition or green solvents such as H2O in organic reaction decreases the environmental pollution.

Thus, in this work, we report a simple protocol for the synthesis of 4H-pyrimido [2, 1-b] benzothiazole in the presence of Bentonite/Ti(IV) via the reaction of 2-aminobenzothiazole, aldehydes and ethyl acetoacetate under grinding and solvent-free conditions at 85 °C (Fig. 1).

Fig. 1
figure 1

Graphical representation of Bentonite/Ti(IV) synthesis.

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Experimental

Materials

Chemicals were purchased from Merck, Fluka and Aldrich Chemical Companies. Fourier transform infrared (FT-IR) spectra recorded by ATR method on a Bruker (EQUINOX 55) spectrometer. The electrical mortar-heater was prepared from Borna- Kherad Co., Iran, Yazd. The nuclear magnetic resonance (NMR) spectra were recorded in Acetone and DMSO-d6 on Bruker (DRX-400, Avance) NMR 400 MHz. Melting points were determined by a Büchi B-540 instrument. Field Emission Scanning Electron Microscopy (FESEM) (MIRA 3 TESCAN) and transmission electron microscopy (TEM, CM120) apparatus were used to record of FESEM and TEM images. The XRD graph of catalyst was obtained by X-ray diffractometer (XRD, Bruker -binary V3) using a Cu kα anode (k = 1.54 Å, radiation at 36 kV and 36 mA) in the 2θ range from 10° to 80°. The X-ray diffraction (XRD Low angle) spectra was obtained by a Philips PW1730 diffractometer equipped with a Cu Kα anode (k = 1.54 Å, radiation at 40 kV and 30 mA) in the 2θ range from 0.8° to 10°. Energy-dispersive X-ray spectrometer (EDS) and MAP of catalyst were recorded by MIRA II Detector SAMX. Thermal gravimetric analysis (TGA) was done using “BÄHR-(model: STA 504)” instrument. BELSORP MINI II nitrogen adsorption apparatus (Japan) for recording Brunauer–Emmett–Teller (BET) specific surface area of nano-catalyst at 77 K. X-ray Fluorescence (XRF) is an analytical technique that used the interaction of X-rays with a material to determine its elemental composition by Philips PW1730. X-Ray Photoelectron Spectroscopy (XPS) analysis was used to identify the structure of the catalyst by UHV analysis system. All IR, 1H NMR and 13C NMR spectra data are available in ESI (Fig. S1–S33).

Preparation of Bentonite/Ti(IV)

For the synthesis of Bentonite/Ti(IV), First, in a 25 mL flask, bentonite (0.2 g) and dichloromethane (10 mL) were charged. Then, titanium tetrachloride (2.5 mL) was added dropwise to flask and mixed vigorously for one hour at room temperature. After the completion of the reaction, the resulting suspension was filtered and dried at room temperature (Fig. 1).

General procedure for the synthesis of pyrimido[2,1-b]benzothiazole derivatives

A mixture of aldehyde (1.0 mmol), 2-aminobenzothiazole (1.0 mmol, 0.15 g), ethyl acetoacetate (1.0 mmol, 0.13 mL) and Bentonite/Ti(IV) (0.06 g) was ground by an electrical mortar-heater at 85 °C. The progress of reaction was monitored by TLC (n-Hexan:EtOAc, 8:2). Finally, 5 mL of hot ethanol was added to the mixture of reaction and the catalyst was separated by filtration. Then, by adding drop-wise water to residue and the product was appeared purely in high yields.

Results and discussion

Characterization of Bentonite/Ti(IV)

The structure properties of catalyst were characterized using various techniques, including FT-IR, FESEM, EDX-MAP, XRD, XRF, TGA, XPS and BET. Fourier transform infrared (FT-IR) spectroscopy spectra of Bentonite and Bentonite/Ti(IV) were shown in Fig. 2. In spectrum of Bentonite/Ti(IV), the characteristic absorption band at 787 cm−1 (according to previously reported FT-IR about Ti(OBu)4)55,60 was appeared indicated that TiCl4 have functionalized on Bentonite successfully. The peaks at 3291 cm⁻1 and 1615 cm⁻1 are attributed to the O–H vibrations of water molecules.

Fig. 2
figure 2

FT-IR spectra of (a) Bentonite, (b) Bentonite/Ti(IV).

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Microscopic imaging technique was used to study surface morphology (Fig. 3). These images indicate that Bentonite/Ti(IV) nanoparticles have an average size of less than 40 nm. FESEM (a) Bentonite/Ti(IV), (b) Bentonite and (c) transmission electron microscopy (TEM) of Bentonite/Ti(IV) were investigated for determination of their particle size and surface morphology. The histogram of the size distribution was detected by MIRA 3 TESCAN software in FESEM (Fig. 3d).

Fig. 3
figure 3

FESEM image of (a) Bentonite/Ti(IV), (b) Bentonite, (c) TEM image Bentonite/Ti(IV) and (d) particle size distribution histogram of Bentonite/Ti(IV).

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EDX analysis was applied for the identification of elemental composition in Bentonite/Ti(IV) (Fig. 4). The EDX data confirmed the existence of O, Na, Mg, Al, Si, Cl, Ca, Ti and Fe elements in the catalyst with mass percentages of 40.79, 1.32, 0.16, 2.00, 8.79, 16.46, 1.18, 27.36, 1.94, respectively, and scale bars of 10 µm.

Fig. 4
figure 4

EDX analysis of Bentonite/Ti(IV)/

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The elemental mapping of Bentonite/Ti(IV) was shown in (Fig. 5) which confirmed homogenous distribution of O, Na, Mg, Al, Si, Cl, Ca, Ti, Fe in catalyst.

Fig. 5
figure 5

Elemental mapping images of Bentonite/Ti(IV).

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The crystalline structure of Bentonite/Ti(IV) was studied by powder X-ray diffraction (Fig. 6). Figure 6a displays sharp peaks at 2θ = 19.72, 21.92, 23.54, 26.58, 31.67, 50, 62.1 belonging to Bentonite/Ti(IV). The structure of the catalyst was investigated by X-ray analysis (Low Angle XRD) in the range of 0.8° to 10°, which was used to confirm the mesoporous nature of bentonite (Fig. 6b). The XRD analysis revealed that the pure phase of Bentonite/Ti(IV) has the same pattern as Bentonite, which confirmed the successful catalyst synthesis. Also, we calculated the Miller indices, peak width (FWHM), and particle size of the Bentonite/Ti(IV) were calculated in the range 19.72–62.1. These results can be found in (Table 1). Hence, the particle size (nm) was calculated on the basis of the Debye–Scherrer equation [D = Kλ/(βcos θ)].

Fig. 6
figure 6

XRD patterns of (a) normal, (b) Low-Angle.

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Table 1 The XRD data of Bentonite/Ti(IV).
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In order to investigate the structure of the Ti(IV)/Bentonite catalyst in more detail, XRF analysis (X-ray fluorescence spectroscopy) was used (Table 2). To determine the thermal resistance of the catalyst, thermal gravimetric analysis (TGA-DTA) was used in the temperature range of 50–600 °C and the weight changes of the catalyst were investigated (Fig. 7). The initial weight loss (endothermic effect at 50–100 °C, 6% weight loss) is related to the removal of moisture. Subsequently, the main weight loss step in the temperature ranges 100–300 °C (60%) is attributed to the loss of coordinated water and decomposition of the clay. respectively., and it cannot be used at a temperature higher than 100 °C.

Table 2 Results of XRF analysis of catalyst.
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Fig. 7
figure 7

Thermal gravimetric analysis pattern of Bentonite/Ti(IV).

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To distinguish the chemical composition information and oxidation state of the Ti in the Bentonite/Ti(IV) catalyst, X-ray photoelectron spectroscopy (XPS) was conducted in the energy range 0 to 1200 eV (Fig. 8). Figure 8a indicates the survey spectra of the Ti, Si and O elements in Bentonite/Ti(IV). As indicated in the resultant XPS analysis shown in Fig. 8b, the Ti 2p spectrum displayed two peaks with binding energies of around 459.21 and 464.6 eV, which were ascribed to the peaks of 2p3/2 and 2p1/2, respectively. The Si 2p XPS spectra in catalyst are also indicated in Fig. 8c. The high-resolution spectra of Si 2p show two peaks at 103.46 and 100.74 eV that were related to Si 2p3/2 and Si 2p1/2, respectively. Figure 8d shows the electron binding energies related to O 1 s with three peaks at 533.35, 532.86, 532.18 and 532.1 eV, which are attributed to Si–O, Al–O, Ti–O and O–H, respectively. Furthermore, the peaks observed at 199.7 and 204.7 eV correspond to Cl 2p3/2 and Cl 2p1/2, respectively (Fig. 8e).

Fig. 8
figure 8

XPS spectra of Bentonite/Ti(IV): (a) survey scan, (b) Ti 2p, (c) Si 2p, (d) O1s and (e) Cl 2p.

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BET theory was used to measure the porosity and specific surface area of the catalyst. Using the BET diagram, the area of the catalyst was 6.11554 m2g−1 (Fig. 9). Based on the nitrogen absorption and desorption isotherm curve of the catalyst with H3 type hysteresis, the third type isotherm is confirmed to be porous based on the IUPAC and mesoporous classification. According to the results obtained in BJH, the surface area is 8.3399 m2 g−1, the average pore diameter is 1.21 nm, and the total pore volume is 0.025 cm3 g−1 (Table 3).

Fig. 9
figure 9

BET plot, Adsorption/desorption isotherm, BJH plot of Bentonite/Ti(IV).

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Table 3 Obtained parameters from porosity analysis.
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Investigating the effectivity of Bentonite/Ti(IV) catalyst in the synthesis of 4H-pyrimido[2,1-b] benzothiazole

In order to investigate the performance of Ti(IV)/Bentonite in the synthesis of 4H-pyrimido[2,1-b] benzothiazole, the reaction of 2-aminobenzothiazole (1 mmol), 4-nitrobenzaldehyde (1 mmol) and ethyl acetoacetate (1 mmol) was considered as the model reaction. In order to optimize the reaction conditions such as temperature, solvent and amount of catalyst, the model reaction was carried out in different conditions of the catalyst. The results of this survey are presented in Table 4. Based on the data in this table, the best conditions for the synthesis of ethyl-2-methyl-4-(4-nitrophenyl)-4H-pyrimido[2,1-b][1,3]benzothiazole-3-carboxylate in the presence of Ti(IV)/Bentonite (0.06 g) is solvent-free condition at 85 °C. According to the obtained conditions, the desired product is obtained with an efficiency of 96% at 45 min.

Table 4 The reaction of 4-nitrobenzaldehyde (1 mmol), ethyl acetoacetate (1 mmol) and 2-aminobenzothiazole (1 mmol) under various conditions.
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According to the obtained optimal conditions, the reaction of different aromatic aldehydes with 2-aminobenzothiazole and ethyl acetoacetate in the presence of 0.06 g of Bentonite/Ti(IV) was done at 85 °C and solvent-free condition, using an electric mortar heater. The obtained results are summarized in (Table 5). Based on the results of Table 5, aldehydes with electron-donating groups show less activity than aldehydes with electron-withdrawing groups.

$$\begin{gathered} {\text{TON}}\left( {{\text{turnover}}\;{\text{number}}} \right) = {\text{Yield}}/{\text{Amount}}\,{\text{of}}\,{\text{Catalyst}}\left( {{\text{mol}}} \right) \hfill \\ {\text{TOF}}\left( {{\text{turnover}}\;{\text{frequency}}} \right){\text{ = TON}}/{\text{Time}}\left( {{\text{hours}}} \right) \hfill \\ \end{gathered}$$
Table 5 Synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives in the presence of Bentonite/Ti(IV) under solvent- free condition at 85 °C.
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The Ti in Bentonite/Ti(IV) is the active site of the catalyst. According to ICP data, the amount of Ti in the catalyst is 25%. Here, we have used 0.06 g of catalyst for 1 mmol of substrate. Thus, 0.06 g of catalyst contains 15 × 10−3 g of Ti and is equal to 31.3 × 10−5 mol of Ti. Thus, the TON and TOF of the catalyst were calculated using the above mentioned data.

The catalytic activity of Bentonite/Ti(IV) in the synthesis of, pyrimido[2,1-b]benzothiazole was compared to other reported catalysts (Table 6). According to the data presented in Table 6 displayed excellent catalytic activity with high efficiency in mild conditions. Another advantage of this catalyst is its reusability and cheapness.

Table 6 Comparison of Bentonite/Ti(IV) with other reported catalysts in the model reaction.
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The proposed mechanism for the synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives is shown in Fig. 10. Initially, the carbonyl group in aldehyde connected to titanium in the catalyst and is activated for condensation. Activated aldehyde and β-ketoester condense through Knoevenagel reaction to form compound (I). Then, with the addition of Michael, 2-aminobenzothiazole reacts with compound (I) and iminium ion is formed. Then, by proton transfer and cyclization, the final product is formed by removing water.

Fig. 10
figure 10

Proposed mechanism for the synthesis of 4H-pyrimido[2,1-b]benzothiazole derivatives by using Bentonite/Ti(IV)

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In order to study the reusability of the catalyst, after the completion of the model reaction, hot ethanol was added to reaction mixture. The catalyst was separated by filtration, washed with dichloromethane and dried at room temperature. The obtained catalyst was reused in the model reaction under the same conditions and time (45 min) for 5 runs (Fig. 11).

Fig. 11
figure 11

Recoverability of Bentonite/Ti(IV).

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The reused catalyst was analyzed for its chemical properties using XRD and IR techniques. The results revealed no significant structural differences after reusing which indicates the catalyst’s chemical stability (Fig. 12).

Fig. 12
figure 12

Comparison of the XRD spectra and FTIR analysis of before and after the reaction of the catalyst.

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The weight percentages of Ti(IV) in reused catalyst after five runs was studied by inductively coupled plasma (ICP). According to obtained data, the weight percentage of Ti(IV) is 25%.

Conclusions

In this study, the Bentonite/Ti(IV) was fabricated as natural-based catalyst to promote the reactions of 4H-pyrimido[2,1-b]benzothiazole derivatives. This catalyst was confirmed by different techniques as FT-IR, FESEM, TEM, TGA, EDS-MAP, XRD, BET, XRF, XPS and ICP- MS. The results showed that the catalyst Bentonite/Ti(IV) have high catalytic activity, and the reaction products were obtained within 40–120 min. The Bentonite/Ti(IV) displayed excellent catalytic performance in the 4H-pyrimido[2,1-b]benzothiazole derivatives synthesis and the corresponding products were synthesized in high yields without a difficult work-up procedure. We believe that the modification of the surface of Bentonite by titanium tetrachloride and then using them for the synthesis of heterocyclic compounds such as 4H-pyrimido[2,1-b]benzothiazole is an effective and practical tool to prepare a suitable catalytic system.