Abstract
In this research, a new Lewis acid-based deep eutectic solvent (LA-DES) was synthesized using diphenhydramine hydrochloride and CoCl2·6H2O, (2[HDPH]:CoCl42−), and identified by FT-IR and 1HNMR techniques. The physicochemical properties of this LA-DES, such as thermal behavior, thermal stability, and solubility in common solvents were also investigated. The catalytic ability of 2[HDPH]:CoCl42− was ascertained in the efficient synthesis of a novel array of thiadiazolo[2,3-b]quinazolin-6-one scaffolds via a one-pot three-component reaction of dimedone/1,3-cyclohexanedione, aldehydes, and 5-aryl-1,3,4-thiadiazol-2-amines/3-(5-amino-1,3,4-thiadiazol-2-yl)-2H-chromen-2-one under solvent-free conditions. This catalyst was also successfully utilized for the synthesis of mono- and bis-thiadiazolo[2,3-b]quinazolin-6-ones from dialdehydes or bis-1,3,4-thiadiazol-2-amine. The simplicity of enforcement, short reaction time, avoidance of toxic organic solvents, scalability of the synthesis procedure, excellent atom economy, high reaction mass efficiency, and low E-factor are other outstanding advantages of this newly developed method. Furthermore, due to the convenient recovery and reuse of LA-DES, this protocol is economically justified and environmentally friendly.
Similar content being viewed by others
Introduction
Green chemistry and sustainability are two crucial concepts that have gained particular attention in chemical processes1. In this respect, designer solvents have been introduced and developed as excellent substitutes for conventional and toxic solvents. Deep eutectic solvents (DESs) are a new generation of designer solvents, generally prepared by mixing substances capable of forming hydrogen bonds2. The formation of hydrogen bonds will be associated with charge delocalization, which causes the melting point of the DES to be lower than any of the raw materials3,4. Compared to their previous generation, ionic liquids (ILs), DESs are more cost-efficient, relatively non-toxic, more biodegradable, and have a more straightforward preparation process5,6,7,8,9,10. Among the different types of DESs, Lewis acid-based (LA-DES) and bio-based ones have been extensively used in promoting organic transformations11,12,13,14,15,16. To prepare LA-DES, the first-row transition metals can be used as Lewis acid13,17. Cobalt is an attractive candidate for catalysis in chemical syntheses18. On the other hand, the synthesis of LA-DES from CoCl2·6H2O as one of the universally used salts of cobalt can improve its catalytic activity19. Moreover, the high efficiency, easy recovery, and reusability of this LA-DES make this non-corrosive liquefy catalyst superior to other homogeneous liquid acid catalysts19.
LA-DESs have been used as the solvent20,21,22,23,24 and/or catalyst25,26,27,28,29,30 in many multicomponent reactions for the synthesis of heterocyclic compounds which is of paramount interest due to their potential pharmaceutical and biological activities31. Particularly, fused thiadiazoloquinazolines are a valuable class of fused N- and S-containing heterocyclic compounds, showing outstanding anticancer32, antifungal33, antibacterial34, and anti-inflammatory35 activities. Up to now, due to the significance of fused thiadiazoloquinazolines, several methods have been developed for the synthesis of these heterocycles36,37,38,39,40,41,42,43 However, they suffer from certain drawbacks such as multistep reaction sequences, prolonged reaction times, low yield, use of costly starting materials, corrosive reagents, and toxic solvents, as well as non-reusable catalysts which led to serious environmental and safety problems. Thus, the development of a more environmentally friendly and efficient procedure using a green and recoverable catalyst for the preparation of these worthy heterocyclic compounds is still vitally required.
Due to the synthesis of complex and structurally diverse bioactive heterocyclic compounds, multicomponent reactions (MCRs) play a paramount role in organic and medicinal chemistry44. Moreover, high convergence, facile and simple performance, pot, atom, step, and cost economy (PASCE), bond-forming-index (BFI), and minimized waste generation are unique advantages of MCRs which make them preferable to the classical stepwise fashions45,46. Due to the observance of the principles of green chemistry, MCRs have gained a special place in organic synthesis47.
As a part of our ongoing research on the synthesis of novel annulated heterocycles using green and reusable catalytic systems via multicomponent strategy48,49,50,51, we wish to describe an efficient and feasible method for the one-pot three-component synthesis of thiadiazolo[2,3-b]quinazolin-6-ones and also their mono- and bis-derivatives via the reaction of dimedone/1,3-cyclohexanedione, aldehydes/dialdehydes, and 5-substituted-1,3,4-thiadiazol-2-amines/bis-1,3,4-thiadiazol-2-amine using 2[HDPH]:CoCl42− as a novel and new LA-DES under solvent-free and green conditions (Fig. 1).
Results and discussion
Synthesis and characterization of 2[HDPH]:CoCl4 2−
As mentioned in the experimental section, the LA-DES, (2[HDPH]:CoCl42−) was easily formed by using a mixture of diphenhydramine hydrochloride and CoCl2·6H2O in a 2:1 molar ratio and identified by FT-IR, 1HNMR, DSC, and TGA/DTG techniques.
The functional groups of the desired LA-DES were recognized by FT-IR spectroscopy (Fig. 2). In the FT-IR spectrum of CoCl2·6H2O, the broad bands at 3500 and 1598 cm−1 are related to the vibrational modes of surface water19. In the spectra of [HDPH]Cl50 and [HDPH]:CoCl42−, the specific bands were observed at 3029 cm−1 (sp2 C–H) and 1111 cm−1 (C–O–C). The characteristic bands at 1454 and 1386 cm−1 are related to CH2 and CH3 stretching vibrations, respectively. Remarkably, the bands at 2400–2700 cm−1 (–N+–H) are weakened in the LA-DES spectrum, which is good evidence for the formation of hydrogen bonding.
In the 1HNMR spectrum of 2[HDPH]:CoCl42−, the aromatic hydrogens appeared as multiplet in the range of 7.42–7.31 ppm. The peaks at 4.70, 4.54, and 4.27 ppm are related to H3, H2, and H1, respectively. Surprisingly, All the mentioned peaks are down-fielded compared to the similar peaks in the [HDPH]Cl spectrum50. Also, the characteristic peak corresponding to –N+–H in 2[HDPH]:CoCl42− shifted from 12.58 to 13.21 ppm and becomes wider (Fig. 3). These observations indicate significant hydrogen bond formation in 2[HDPH]:CoCl42−.
Differential scanning calorimetry (DSC) was effectively used to diagnose the thermal behavior of 2[HDPH]:CoCl42−. The melting point of 2[HDPH]:CoCl42− in the DSC curve was observed at around − 2 °C (Fig. 4), which is lower than those of the raw materials (the melting points of [HDPH]Cl and CoCl2⋅6H2O are 169 °C, and 56 °C, respectively). Such a depression of melting point can be related to the formation of hydrogen bonds in 2[HDPH]:CoCl42− deep eutectic mixture.
To examine the thermal stability of the 2[HDPH]:CoCl42−, TGA analysis was employed. According to Fig. 5, the new LA-DES has good thermal stability up to about 329 °C; weight losses of only 5% at 136.1 °C and 10% at 232.9 °C were observed. The residual weight at 500 ℃ is 15.90%, which matches well with the theoretical CoCl2 weight % (15.80%).
Acidity is one of the most important physical properties of DESs, making them applicable for industrial usage. To determine the acidity of DES, FT-IR spectroscopy and pyridine as a probe are commonly utilized28. For this purpose, the FT-IR spectra of pyridine, 2[HDPH]:CoCl42− and pyridine-2[HDPH]:CoCl42− were investigated52. In the FT-IR spectrum of pyridine-2[HDPH]:CoCl42− (Fig. 6a), the characteristic band at 1446 cm−1, indicates that 2[HDPH]:CoCl42− has Lewis acidic sites which interact with pyridine groups. Also, the band appeared at 1635 cm−1 in the FT-IR spectrum of pyridine-2[HDPH]:CoCl42− could be attributed to the formation of pyridinium ions ([PyH]+) upon the interaction of pyridine with Brønsted acid sites of the LA-DES3,50. Such an interaction has been displayed in Fig. 6b. To confirm the acidity, pH of the solutions of CoCl2⋅6H2O (4 × 10−3 mol L−1), [HDPH]Cl (8 × 10–3 mol L−1), and 2[HDPH]:CoCl42− (8 × 10–3 mol L−1) were measured and found to be 5.17, 5.39, and 4.77, respectively. Consequently, 2[HDPH]:CoCl42− can be applied as an efficient acidic catalyst for useful organic transformations.
Optimization of the reaction conditions
For the initial investigation, the reaction between 4-methylbenzaldehyde, 5-phenyl-1,3,4-thiadiazol-2-amine, and dimedone was selected as a model to optimize the reaction conditions. In the absence of the catalyst, the desired three-component product 4a was obtained with only 5% yield even after 4 h at 120 ℃ under solvent-free conditions (Table 1, entry 1). Then, the titled reaction was performed in the presence of 0.2 mmol of catalysts including [HDPH]Cl, CoCl2·6H2O, and different LA-DESs at 120 ℃ under solvent-free conditions (Table 1, entries 2–8). Among these, 2[HDPH]:CoCl42− provided the highest yield (90%) of the desired product 4a (Table 1, entry 8). Different molar ratios of [HDPH]Cl to CoCl2·6H2O were examined (Table 1, entries 8–10); 2:1 molar ratio was found to be more suitable for this transformation (Table 1, entry 8). It is noteworthy that increasing the loading of 2[HDPH]:CoCl42− to 0.3 mmol did not improve the product yield, but decreasing the loading of the catalyst to 0.1 mmol led to a lower yield of the product (Table 1, entries 11, 12). In addition, the reaction was also tested at various temperatures (Table 1, entries 8, 13–15), and 120 ℃ was discovered to be more suitable for this transformation. Consequently, the optimum reaction conditions for the synthesis of target product 4a were attained by using 0.2 mmol of 2[HDPH]:CoCl42− at 120 ℃ under solvent-free conditions (Table 1, entry 8).
Synthesis of thiadiazolo[2,3-b]quinazolin-6-one derivatives
The applicability and scope of this protocol to the synthesis of thiadiazolo[2,3-b]quinazolin-6-one derivatives were then checked under optimal conditions. As shown in Fig. 7, the three-component reaction between dimedone/1,3-cyclohexanedione, 5-aryl-1,3,4-thiadiazol-2-amines and aromatic aldehydes with electron-donating and electron-withdrawing groups at various positions of aromatic ring proceeded smoothly in the presence of 2[HDPH]:CoCl42− at 120 ℃ under solvent-free conditions which afforded the corresponding thiadiazolo[2,3-b]quinazolin-6-ones 4a–4s in 73–96% yields. Under the same reaction conditions, 6-chloro-4-oxo-4H-chromene-3-carbaldehyde as a heterocyclic aldehyde and 3-phenyl propanal, as an aliphatic aldehyde gave the desired products 4t, 4u, and 4v in 85%, 86%, and 75% yields, respectively.
It is also interesting to note that a scale-up synthesis of 4a was carried out under these conditions. On a 5 mmol scale, dimedone reacted with 4-methylbenzaldehyde and 5-phenyl-1,3,4-thiadiazol-2-amine in the presence of 2[HDPH]:CoCl42− at 120 ℃ under solvent-free conditions to afford the corresponding thiadiazolo[2,3-b]quinazolin-6-ones 4a in 88% yields.
To further demonstrate the efficacy of the present method, the synthesis of thiadiazolo[2,3-b]quinazolin-6-one derivatives was performed under optimal conditions using 3-(5-amino-1,3,4-thiadiazol-2-yl)-2H-chromen-2-one in place of 5-aryl-1,3,4-thiadiazol-2-amine and the corresponding products 6a–6d were obtained in 71–85% yields (Fig. 8).
To spotlight the attractive performance of this catalytic system, mono- and bis-thiadiazolo[2,3-b]quinazolin-6-one scaffolds were prepared from different dialdehydes. As it is evident from Fig. 9, when dimedone/1,3-cyclohexanedione (1 mmol) reacted with 5-aryl-1,3,4-thiadiazol-2-amines (1 mmol) and dialdehydes (1 mmol) under the optimized conditions, the desired mono-thiadiazolo[2,3-b]quinazolin-6-one scaffolds were selectively produced in 65–75% yields. Also, the corresponding bis-thiadiazolo[2,3-b]quinazolin-6-ones were achieved in 60–65% yields by using 2 mmol dimedone/1,3-cyclohexanedione, 2 mmol 5-aryl-1,3,4-thiadiazol-2-amines, and 1 mmol dialdehydes under the same conditions.
To reveal further utility of the current method, mono- and bis-thiadiazolo[2,3-b]quinazolin-6-ones were synthesized under optimal conditions using bis-1,3,4-thiadiazol-2-amine in place of dialdehyde. As observed in Fig. 10, the reaction of dimedone with aryl aldehyde and 5,5′-(butane-1,4-diylbis(sulfanediyl))bis(1,3,4-thiadiazol-2-amine) in 1:1:1 and 2:2:1 molar ratios in the presence of 2[HDPH]:CoCl42− at 120 ℃ under solvent-free conditions proceeded efficiently to generate the corresponding mono- and bis-thiadiazolo[2,3-b]quinazolin-6-ones in 60–76% and 57–70% yields, respectively. Finally, it should be stressed that all the above-mentioned findings reveal the brilliant eligibility and applicability of this catalytic system in the synthesis of these vital fused heterocyclic compounds.
The structures of all the synthesized compounds were elucidated by FT-IR, 1H NMR, and 13C NMR spectra as well as elemental analysis. Furthermore, the structure of 4s was confirmed by single crystal X-ray analysis (Fig. 11; CCDC 2297765, Tables S1 and S2).
A plausible reaction mechanism for the synthesis of 4a in the presence of 2[HDPH]:CoCl42− is illustrated in Fig. 12. Initially, Knoevenagel condensation between the enol form of dimedone 1 and aldehyde 2 activated by the catalyst gives intermediate Ӏ. Then, LA-DES catalyzed Michael addition of 5-aryl-1,3,4-thiadiazol-2-amine 3 to intermediate Ӏ resulting in the formation of intermediate II, which is transformed to intermediate IIӀ after keto-enol tautomerism. Next, intermediate ӀV is formed by the cyclization of intermediate IIӀ in the presence of 2[HDPH]:CoCl42−. Finally, the elimination of water from intermediate ӀV affords the final product 4a, regenerating LA-DES, which can be used for the next catalytic cycle.
Catalyst recycling and reuse
Due to the atom economy, easy preparation, recovery, and reuse of DESs, they are considered green and sustainable solvents and catalysts in organic reactions. In this regard, the recyclability of the 2[HDPH]:CoCl42− was checked in the model reaction. After the consumption of precursors, the mixture was cooled to room temperature, water was added, and stirred to dissolve LA-DES. The resulting precipitate was collected by simple filtration followed by washing with water. The filtrate was evaporated at 80 °C under vacuum and the recovered LA-DES was reused for the subsequent cycle. As can be seen in Fig. 13a, the catalyst is reusable for up to six cycles without noticeable loss in its activity. Comparison of the FT-IR (Fig. 13b) and 1H-NMR spectra (Fig. 14) of the fresh and recovered LA-DES shows that the catalyst is stable during the reaction which is very important from the practical point of view.
Green chemistry metric evaluation
To introduce the existing method as an eco-friendly and green synthetic path for the preparation of thiadiazolo[2,3-b]quinazolin-6-one scaffolds, a number of green metric factors50,53,54,55,56 were calculated for the synthesized compounds (Figs. 15 and 16). In this respect, effective mass yield (EMY), and reaction mass efficiency (RME) for all the synthesized compounds were calculated and found to be in the range of 52.74–89.69%. To show the eco-compatibility and the atom economy of the present protocol, the E-factor, and atom economy (AE) were also determined which were found to be in ranges of 0.11–0.90 g/g and 90.27–96.18%, respectively. Due to the elimination of only water molecules in the present method, excellent results were obtained for the E-factor and atom economy. Also, the calculated atom efficiency (AEf), optimum efficiency (OE), and carbon efficiency (CE) for this procedure were up to 89.64%, 96.06%, and 96%, respectively. The obtained data together with the recoverability of the catalyst and solvent-free conditions introduce this protocol as a green and environmentally benign pathway for the preparation of thiadiazolo[2,3-b]quinazolin-6-ones. The detailed calculations are presented in the Supporting Information.
Experimental
General information
The chemicals were purchased from Fluka and Merck chemical companies. 5-aryl-1,3,4-thiadiazol-2-amines, 3-(5-amino-1,3,4-thiadiazol-2-yl)-2H-chromen-2-one, 5,5′-(butane-1,4-diylbis(sulfanediyl))bis(1,3,4-thiadiazol-2-amine) and 2,2′-(butane-1,4-diylbis(oxy))dibenzaldehyde were prepared similar to the reported methods57,58,59,60. Melting points were determined using a Stuart Scientific SMP2 apparatus. FT-IR spectra were recorded on a Nicolet-Impact 400D spectrophotometer. 1H and 13C NMR (400 and 100 MHz) spectra were recorded on a Bruker Avance 400 MHz spectrometer using CDCl3 solvent. Elemental analysis was performed on a LECO, CHNS-932 analyzer. Thermogravimetric and derivative thermogravimetric analysis (TGA/DTG) was carried out on a Perkin-Elmer STA 6000 instrument under nitrogen flow at a uniform heating rate of 10 ℃ min−1 in the range of 30–600 ℃. Differential scanning calorimetry (DSC) was carried out with a TA Instrument Model DSC13-setaram under a nitrogen atmosphere with a scan rate of 10 ℃ min−1 in the range − 60 to 20 ℃.
General procedure for the synthesis of Lewis acid-based deep eutectic solvents (LA-DESs)
Diphenhydramine hydrochloride was mixed with the metal chloride hydrate at the specified molar ratio (Table 2) and heated up to 90 ℃ with mild stirring until it turned into a transparent liquid. The synthesized LA-DES, after cooling, was utilized without any further purification.
Synthesis of thiadiazolo[2,3-b]quinazolin-6-ones catalyzed by 2[HDPH]:CoCl4 2−
In a screw-cap glass tube with a magnetic stirrer, a mixture of dimedone/1,3-cyclohexanedione 1 (1 mmol), aldehyde 2 (1 mmol), 5-substituted-1,3,4-thiadiazol-2-amine 3 or 5 (1 mmol) and 2[HDPH]:CoCl42− (0.2 mmol) was heated at 120 ℃ under solvent-free conditions for the appropriate time mentioned in Figs. 7 and 8. Upon consumption of the precursors as depicted by TLC (eluent: n-hexane/EtOAc, 2:1), the reaction mixture was allowed to cool to room temperature. To dissolve 2[HDPH]:CoCl42−, water (5 mL) was added, and the resulting solid crude product was separated by simple filtration, washed with water (5 mL), dried, and crystallized from ethyl acetate to afford the pure product. In some cases, chromatography on silica gel (eluent: n-hexane/EtOAc, 2:1) is required to obtain the pure product.
Synthesis of mono and bis-thiadiazolo[2,3-b]quinazolin-6-ones from dialdehyde catalyzed by 2[HDPH]:CoCl4 2−
In a screw-cap glass tube with a magnetic stirrer, a mixture of dimedone/1,3-cyclohexanedione 1 (1 mmol), dialdehyde 7 (1 mmol), 5-aryl-1,3,4-thiadiazol-2-amine 3 (1 mmol) and 2[HDPH]:CoCl42− (0.2 mmol) was heated at 120 ℃ under solvent-free conditions for the specified time demonstrated in Fig. 9. After completion of the reaction (monitored by TLC; eluent: n-hexane/EtOAc, 2:1), the workup was carried out according to the procedure used for thiadiazolo[2,3-b]quinazolin-6-ones to afford the pure mono-derivatives 8a–8d in 70–75% yields. For the synthesis of bis-thiadiazolo[2,3-b]quinazolin-6-ones, dimedone/1,3-cyclohexanedione 1 (1 mmol) reacted with dialdehyde 7 (0.5 mmol) and 5-aryl-1,3,4-thiadiazol-2-amine 3 (1 mmol) in the presence of LA-DES (0.2 mmol) and the mixture was heated at 120 ℃ under solvent-free conditions. The reaction progress was checked by TLC (eluent: n-hexane/EtOAc, 2:1). The workup and purification were performed according to the above-mentioned procedure to furnish the desired products 9a-9d in 60–65% yields (Fig. 9).
Synthesis of mono and bis-thiadiazolo[2,3-b]quinazolin-6-ones from bis-1,3,4-thiadiazol-2-amine catalyzed by 2[HDPH]:CoCl4 2−
In a screw-cap glass tube with a magnetic stirrer, dimedone 1 (1 mmol), aldehyde 2 (1 mmol), and 5,5′-(butane-1,4-diylbis(sulfanediyl))bis(1,3,4-thiadiazol-2-amine) 10 (1 mmol) were added to 2[HDPH]:CoCl42− (0.2 mmol) and the mixture was heated at 120 ℃ under solvent-free conditions for the specified time indicated in Fig. 10. On completion of the reaction (monitored by TLC analysis; eluent: n-hexane/EtOAc, 2:1), the workup was carried out according to the procedure for the preparation of thiadiazolo[2,3-b]quinazolin-6-one and the desired pure product 11a–11c were obtained in 60–76% yields. All the steps for the synthesis of bis-thiadiazolo[2,3-b]quinazolin-6-ones (12a–12c, 57–70%) from bis-1,3,4-thiadiazol-2-amine and their purification were the same as those of mono-thiadiazolo[2,3-b]quinazolin-6-ones except that 0.5 mmol of 5,5′-(butane-1,4-diylbis(sulfanediyl))bis(1,3,4-thiadiazol-2-amine) reacted with 1 mmol of each dimedone 1 and aldehyde 2 (Fig. 10).
Conclusions
In summary, an efficient, convenient, green, and straightforward protocol has been developed for the preparation of a series of thiadiazolo[2,3-b]quinazolin-6-ones via a one-pot, single-step, multicomponent reaction of dimedone/1,3-cyclohexanone, aldehydes, and 5-aryl-1,3,4-thiadiazol-2-amines/3-(5-amino-1,3,4-thiadiazol-2-yl)-2H-chromen-2-one) in the presence of 2[HDPH]:CoCl42− as an LA-DES under solvent-free conditions. This effective process is also applicable to the synthesis of mono- and bis-thiadiazolo[2,3-b]quinazolin-6-ones from dialdehydes or bis-1,3,4-thiadiazol-2-amine. High to excellent yields, high reaction rates, avoiding toxic organic solvents, operational simplicity, easy separation and recyclability of the catalyst, large-scale synthetic applicability, formation of water as green waste, excellent atom economy, high reaction mass efficiency, and low E-factor are outstanding features of this protocol.
Data availability
All data generated or analyzed during this study are included in this published article and its supplementary information files.
References
Zuin, V. G., Eilks, I., Elschami, M. & Kümmerer, K. Education in green chemistry and in sustainable chemistry: Perspectives towards sustainability. Green Chem. 23, 1594–1608. https://doi.org/10.1039/d0gc03313h (2021).
Francisco, M., van den Bruinhorst, A. & Kroon, M. C. Low-transition-temperature mixtures (LTTMs): A new generation of designer solvents. Angew. Chem. Int. Ed. 52, 3074–3085. https://doi.org/10.1002/anie.201207548 (2013).
Shaibuna, M., Hiba, K., Theresa, L. V. & Sreekumar, K. A new type IV DES: A competent green catalyst and solvent for the synthesis of α, β-unsaturated diketones and dicyano compounds by Knoevenagel condensation reaction. New J. Chem. 44, 14723–14732. https://doi.org/10.1039/D0NJ02852E (2020).
Smith, E. L., Abbott, A. P. & Ryder, K. S. Deep eutectic solvents (DESs) and their applications. Chem. Rev. 114, 11060–11082. https://doi.org/10.1021/cr300162p (2014).
Zhang, Q., Vigier, K. D. O., Royer, S. & Jérôme, F. Deep eutectic solvents: Syntheses, properties and applications. Chem. Soc. Rev. 41, 7108–7146. https://doi.org/10.1039/c2cs35178a (2012).
Fekri, L. Z., Nikpassand, M., Mostaghim, S. & Marvi, O. Green catalyst-free multi-component synthesis of aminobenzochromenes in deep eutectic solvents. Org. Prep. Proced. Int. 52, 81–90. https://doi.org/10.1080/00304948.2020.1714319 (2020).
Foroughi Kaldareh, M., Mokhtary, M. & Nikpassand, M. Deep eutectic solvent mediated one-pot synthesis of hydrazinyl-4-phenyl-1, 3-thiazoles. Polycycl. Aromat. Comp. 41, 1012–1019. https://doi.org/10.1080/10406638.2019.1639062 (2021).
Hooshmand, S. E., Kumar, S., Bahadur, I., Singh, T. & Varma, R. S. Deep eutectic solvents as reusable catalysts and promoter for the greener syntheses of small molecules: Recent advances. J. Mol. Liq. 371, 121013. https://doi.org/10.1016/j.molliq.2022.121013 (2022).
Monem, A., Habibi, D. & Goudarzi, H. An acid-based DES as a novel catalyst for the synthesis of pyranopyrimidines. Sci. Rep. 13, 18009. https://doi.org/10.1038/s41598-023-45352-4 (2023).
Zarei, N., Zolfigol, M. A., Torabi, M. & Yarie, M. Synthesis of new hybrid pyridines catalyzed by Fe3O4@SiO2@urea-riched ligand/Ch-Cl. Sci. Rep. 13, 9486. https://doi.org/10.1038/s41598-023-35849-3 (2023).
Cicco, L., Dilauro, G., Perna, F. M., Vitale, P. & Capriati, V. Advances in deep eutectic solvents and water: Applications in metal-and biocatalyzed processes, in the synthesis of APIs, and other biologically active compounds. Org. Biomol. Chem. 19, 2558–2577. https://doi.org/10.1039/d0ob02491k (2021).
Hansen, B. B. et al. Deep eutectic solvents: A review of fundamentals and applications. Chem. Rev. 121, 1232–1285. https://doi.org/10.1021/acs.chemrev.0c00385 (2020).
Li, Z.-M. et al. Production of methyl p-hydroxycinnamate by selective tailoring of herbaceous lignin using metal-based deep eutectic solvents (DES) as catalyst. Ind. Eng. Chem. Res. 59, 17328–17337. https://doi.org/10.1021/acs.iecr.0c01307 (2020).
Nguyen, T. T., Le, N.-P.T. & Tran, P. H. An efficient multicomponent synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a magnetic nanoparticle supported Lewis acidic deep eutectic solvent. RSC Adv. 9, 38148–38153. https://doi.org/10.1039/c9ra08074k (2019).
Qin, H. et al. Overview of acidic deep eutectic solvents on synthesis, properties and applications. Green Energy Environ. 5, 8–21. https://doi.org/10.1016/j.gee.2019.03.002 (2020).
Tran, P. H., Nguyen, H. T., Hansen, P. E. & Le, T. N. An efficient and green method for regio-and chemo-selective Friedel-Crafts acylations using a deep eutectic solvent ([CholineCl][ZnCl2]3). RSC adv. 6, 37031–37038. https://doi.org/10.1039/c6ra03551e (2016).
Nishtala, V. B. & Basavoju, S. ZnCl2+ Urea, the deep eutectic solvent promoted synthesis of the spirooxindolopyrans and xanthenes through a pseudo-three-component approach. Synth. Commun. 49, 2342–2349. https://doi.org/10.1080/00397911.2019.1620784 (2019).
Maikhuri, V. K., Prasad, A. K., Jha, A. & Srivastava, S. Recent advances in the transition metal catalyzed synthesis of quinoxalines: A review. New J. Chem. 45, 13214–13246. https://doi.org/10.1039/d1nj01442k (2021).
Tamaddon, F. & Khorram, A. New magnetic-responsive deep eutectic catalyst based on Co2+/choline chloride for the synthesis of tetrahydro-pyrazolopyridines and pyrroles in water. J. Mol. Liq. 304, 112722. https://doi.org/10.1016/j.molliq.2020.112722 (2020).
Abtahi, B. & Tavakol, H. Choline chloride-urea deep eutectic solvent as an efficient media for the synthesis of propargylamines via organocuprate intermediate. Appl. Organomet. Chem. 34, e5895. https://doi.org/10.1002/aoc.5895 (2020).
Maleki, A., Aghaei, M., Hafizi-Atabak, H. R. & Ferdowsi, M. Ultrasonic treatment of CoFe2O4@B2O3-SiO2 as a new hybrid magnetic composite nanostructure and catalytic application in the synthesis of dihydroquinazolinones. Ultrason. Sonochem. 37, 260–266. https://doi.org/10.1016/j.ultsonch.2017.01.022 (2017).
Maleki, A., Kari, T. & Aghaei, M. Fe3O4@SiO2@TiO2-OSO3H: An efficient hierarchical nanocatalyst for the organic quinazolines syntheses. J. Porous Mater. 24, 1481–1496. https://doi.org/10.1007/s10934-017-0388-z (2017).
Peñaranda Gómez, A. L., Rodríguez Bejarano, O., Kouznetsov, V. V. & Ochoa-Puentes, C. One-pot diastereoselective synthesis of tetrahydroquinolines from star anise oil in a choline chloride/zinc chloride eutectic mixture. ACS Sustain. Chem. Eng. 7, 18630–18639. https://doi.org/10.1021/acssuschemeng.9b05073 (2019).
Shaabani, A. & Afshari, R. Magnetic Ugi-functionalized graphene oxide complexed with copper nanoparticles: Efficient catalyst toward Ullman coupling reaction in deep eutectic solvents. J. Colloid Interface Sci. 510, 384–394. https://doi.org/10.1016/j.jcis.2017.09.089 (2018).
Liu, P., Hao, J.-W., Mo, L.-P. & Zhang, Z.-H. Recent advances in the application of deep eutectic solvents as sustainable media as well as catalysts in organic reactions. RSC Adv. 5, 48675–48704. https://doi.org/10.1039/c5ra05746a (2015).
Pant, P. L. & Shankarling, G. S. Deep eutectic solvent: An efficient and recyclable catalyst for synthesis of thioethers. ChemistrySelect 2, 7645–7650. https://doi.org/10.1002/slct.201701318 (2017).
Shahabi, D. & Tavakol, H. One-pot synthesis of quinoline derivatives using choline chloride/tin (II) chloride deep eutectic solvent as a green catalyst. J. Mol. Liq. 220, 324–328. https://doi.org/10.1016/j.molliq.2016.04.094 (2016).
Shaibuna, M., Theresa, L. V. & Sreekumar, K. A new green and efficient brønsted: Lewis acidic DES for pyrrole synthesis. Catal. Lett. 148, 2359–2372. https://doi.org/10.1007/s10562-018-2414-4 (2018).
Tipale, M. R., Khillare, L. D., Deshmukh, A. R. & Bhosle, M. R. An efficient four component domino synthesis of pyrazolopyranopyrimidines using recyclable choline chloride: Urea deep eutectic solvent. J. Heterocycl. Chem. 55, 716–728. https://doi.org/10.1002/jhet.3095 (2018).
Yedage, D. B. & Patil, D. V. Environmentally benign deep eutectic solvent for synthesis of 1,3-thiazolidin-4-ones. ChemistrySelect 3, 3611–3614. https://doi.org/10.1002/slct.201800157 (2018).
Younus, H. A. et al. Multicomponent reactions (MCR) in medicinal chemistry: A patent review (2010–2020). Expert Opin. Ther. Pat. 31, 267–289. https://doi.org/10.1080/13543776.2021.1858797 (2021).
El-Gohary, N. S. & Shaaban, M. I. Synthesis, antimicrobial, antiquorum-sensing, antitumor and cytotoxic activities of new series of fused [1,3,4] thiadiazoles. Eur. J. Med. Chem. 63, 185–195. https://doi.org/10.1016/j.ejmech.2013.02.010 (2013).
Gunjan, S., Sarita, U. & Vandana, D. Synthesis of some new 2-aryloxymethyl-1,3,4-thiadiazolo [2,3-b] quinazol-4-ones as antifungal agents. Asian J. Chem. 22, 6610–6612 (2010).
Jatav, V., Kashaw, S. & Mishra, P. Synthesis, antibacterial and antifungal activity of some novel 3-[5-(4-substituted phenyl) 1,3,4-thiadiazole-2-yl]-2-styryl quinazoline-4 (3H)-ones. Med. Chem. Res. 17, 169–181. https://doi.org/10.1007/s00044-007-9047-2 (2008).
Shafiee, A. & Lalezari, I. Selenium heterocycles. XV. Reaction of 2-aminoselenazoles and 2-amino-1,3,4-selenadiazoles with acetylenic compounds. J. Heterocycl. Chem. 12, 675–681. https://doi.org/10.1002/jhet.5570120413 (1975).
Abdelhamid, A. O., Hassaneen, H. M., Abbas, I. M. & Shawali, A. S. Facile synthesis of thiadiazolo [2,3-b] quinazoline derivatives via the Japp-Klingemann Reaction. Tetrahedron 38, 1527–1530. https://doi.org/10.1016/0040-4020(82)80243-3 (1982).
Ahmadi, A., Saidi, K. & Khabazzadeh, H. An efficient synthesis of substituted 2-iminothiazolidin-4-one and thiadiazoloquinazolinone derivatives. Mol. Divers. 13, 353–356. https://doi.org/10.1007/s11030-009-9124-1 (2009).
Gakhar, H., Gupta, R. & Gill, J. 2,3-Dihydro-5H-(1,3,4) thiadiazolo (2,3-b) quinazoline-2, 5-diones. Indian J. Chem. 18, 957 (1987).
Rusu, G., Koval’, D., Gutsu, Y. E. & Barba, N. Recyclization of 5-(2-Aminophenyl)-1,3,4-oxadiazolethione-2 (I) into Quinazoline Derivatives. Geterotsikl. Soedin. 27, 1001 (1996).
Zhao, B. et al. One-pot, three component synthesis of novel 5H-[1,3,4] thiadiazolo [3,2-a] pyrimidine-6-carboxylate derivatives by microwave irradiation. Tetrahedron Lett. 55, 4521–4524. https://doi.org/10.1016/j.tetlet.2014.06.073 (2014).
Khansole, G. S. et al. Tetrabutylammonium hydrogen sulfate mediated three-component reaction for the synthesis of thiadiazolo [2,3-b] quinazolin-6-(7H)-ones and antioxidant activity. Mater. Today Proc. 9, 653–660. https://doi.org/10.1016/j.matpr.2018.10.389 (2019).
Wadhwa, P., Kaur, T., Singh, N., Singh, U. P. & Sharma, A. p-Toluenesulfonic acid-mediated three-component reaction “on-water” protocol for the synthesis of novel thiadiazolo [2,3-b] quinazolin-6 (7H)-ones. Asian J. Org. Chem. 5, 120–126. https://doi.org/10.1002/ajoc.201500397 (2016).
Wadhwa, P., Kharbanda, A., Bagchi, S. & Sharma, A. Water-mediated one-pot three-component reaction to bifunctionalized thiadiazoloquinazolinone-coumarin hybrids: A green approach. ChemistrySelect 3, 2837–2841. https://doi.org/10.1002/slct.201702908 (2018).
Ruijter, E., Scheffelaar, R. & Orru, R. V. Multicomponent reaction design in the quest for molecular complexity and diversity. Angew. Chem. Int. Ed. 50, 6234–6246. https://doi.org/10.1002/anie.201006515 (2011).
Clarke, P. A., Santos, S. & Martin, W. H. Combining pot, atom and step economy (PASE) in organic synthesis. Synthesis of tetrahydropyran-4-ones. Green Chem. 9, 438–440. https://doi.org/10.1039/B700923B (2007).
Domling, A., Wang, W. & Wang, K. Chemistry and biology of multicomponent reactions. Chem. Rev. 112, 3083–3135. https://doi.org/10.1021/cr100233r (2012).
Preeti, P. & Singh, K. N. Multicomponent reactions: A sustainable tool to 1,2-and 1,3-azoles. Org. Biomol. Chem. 16, 9084–9116. https://doi.org/10.1039/c8ob01872c (2018).
Ataee-Kachouei, T. et al. Facile and green one-pot synthesis of fluorophore chromeno [4,3-b] quinolin-6-one derivatives catalyzed by halloysite nanoclay under solvent-free conditions. ChemistrySelect 4, 2301–2306. https://doi.org/10.1002/slct.201803707 (2019).
Karimi, F. et al. 3-(Propylthio) propane-1-sulfonic acid immobilized on functionalized magnetic nanoparticles as an efficient catalyst for one-pot synthesis of dihydrotetrazolo [1,5-a] pyrimidine and tetrahydrotetrazolo [5,1-b] quinazolinone derivatives. RSC Adv. 12, 22180–22187. https://doi.org/10.1039/d2ra03813g (2022).
MoeiniKorbekandi, M. et al. Diphenhydramine hydrochloride–CuCl as a new catalyst for the synthesis of tetrahydrocinnolin-5 (1H)-ones. ACS omega 8, 15883–15895. https://doi.org/10.1021/acsomega.2c06765 (2023).
MoeiniKorbekandi, M. et al. Preparation and application of a new supported nicotine-based organocatalyst for synthesis of various 1,5-benzodiazepines. Catal. Lett. 149, 1057–1066. https://doi.org/10.1007/s10562-019-02668-z (2019).
Dai, L. et al. Catalytic activity comparison of Zr–SBA-15 immobilized by a Brønsted-Lewis acidic ionic liquid in different esterifications. RSC Adv. 7, 32427–32435. https://doi.org/10.1039/c7ra04950a (2017).
Abou-Shehada, S., Mampuys, P., Maes, B., Clark, J. & Summerton, L. An evaluation of credentials of a multicomponent reaction for the synthesis of isothioureas through the use of a holistic CHEM21 green metrics toolkit. Green Chem. 19, 249–258. https://doi.org/10.1039/C6GC01928E (2017).
Brahmachari, G. et al. Series of functionalized 5-(2-arylimidazo [1,2-a] pyridin-3-yl) pyrimidine-2,4 (1H, 3H)-diones: A water-mediated three-component catalyst-free protocol revisited. J. Org. Chem. 85, 8405–8414. https://doi.org/10.1021/acs.joc.0c00732 (2020).
Chen, Y.-X., Zhang, M., Zhang, S.-Z., Hao, Z.-Q. & Zhang, Z.-H. Copper-decorated covalent organic framework as a heterogeneous photocatalyst for phosphorylation of terminal alkynes. Green Chem. 24, 4071–4081. https://doi.org/10.1039/d2gc00754a (2022).
McElroy, C. R., Constantinou, A., Jones, L. C., Summerton, L. & Clark, J. H. Towards a holistic approach to metrics for the 21st century pharmaceutical industry. Green Chem. 17, 3111–3121. https://doi.org/10.1039/c5gc00340g (2015).
Alishahi, N. et al. Nicotine-based ionic liquid supported on magnetic nanoparticles: An efficient and recyclable catalyst for selective one-pot synthesis of mono-and bis-4H-pyrimido [2,1-b] benzothiazoles. Appl. Organomet. Chem. 34, e5681. https://doi.org/10.1002/aoc.5681 (2020).
Karcz, D. et al. Design, spectroscopy, and assessment of cholinesterase inhibition and antimicrobial activities of novel coumarin–thiadiazole hybrids. Int. J. Mol. Sci. 23, 6314. https://doi.org/10.3390/ijms23116314 (2022).
Lou, J., Wang, H., Wang, S., Han, J. & Wang, M. Synthesis, antimicrobial activity and 3D-QSAR study of novel 5-substituted-1,3,4-thiadiazole Schiff base derivatives. J. Mol. Struct. 1267, 133629. https://doi.org/10.1016/j.molstruc.2022.133629 (2022).
Tomi, I. H. R., Al-Daraji, A. H. & Aziz, S. A. Synthesis, characterization, and study the inhibitory effect of thiazole and thiadiazole derivatives toward the corrosion of copper in acidic media. Synth. React. Inorg. Met. Nano-Metal Chem. 45, 605–613. https://doi.org/10.1080/15533174.2013.841226 (2015).
Acknowledgements
The authors are grateful to the research council of the University of Isfahan for financial support of this work.
Author information
Authors and Affiliations
Contributions
M.M.K.; experimental work, writing—original draft. I.M.-B.; conceptualization, supervision, project administration, writing. M.M.; investigation, review and editing. S.T. and V.M.; data curation and review. B.N.; X-ray analysis and data refinement.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher's note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
About this article
Cite this article
Korbekandi, M.M., Mohammadpoor-Baltork, I., Moghadam, M. et al. Efficient synthesis of novel thiadiazolo[2,3-b]quinazolin-6-ones catalyzed by diphenhydramine hydrochloride-CoCl2⋅6H2O deep eutectic solvent. Sci Rep 14, 1451 (2024). https://doi.org/10.1038/s41598-024-52017-3
Received:
Accepted:
Published:
DOI: https://doi.org/10.1038/s41598-024-52017-3
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.