Introduction

Synthesis of complicated molecules by one-pot multi-component reactions (MCRs) can be achieved in a very fast, efficient and high yield without isolation of intermediate. MCRs are convergent reactions, in which three or more starting materials react to form a product, where basically all or most of the atoms contribute to the newly formed product. In the MCRs, a product is assembled according to a cascade of elementary chemical reactions. The result is clearly dependent on the reaction conditions: solvent, temperature, catalyst, concentration, the kind of starting materials and functional groups. In general, using the catalyst is the most popular approach for the synthesis by the MCRs method for industrial applications [1,2,3].

1,3-Thiazolidin-4-ones having sulfur and nitrogen in a five-membered ring belong to thiazolidines which have efficient activities in biological, pharmaceutical and agricultural fields. They have been employed in the preparation of different important drugs such as famotidine, pramipexole and riluzole. [4, 5]. Nowadays, their antifungal, antimicrobial, anticancer, antidiabetic, antiviral and antiHIV activities have been reported [6, 7]. The popular method for the preparation of the 1,3-thizolidinone involves the condensation of an amine, an aldehyde and thioglycolic acid in one or two steps by refluxing in a toxic solvent at high temperature following by azeotropic distillation or under microwave irradiation by the drastic condition of removing the water [8,9,10]. Also, another way for approaching 1,3-thiazolidinone consisting of the condensation of amine, chloroacetylchloride and thiocyanate by refluxing in two steps has been reported [11]. According to the importance of this compound, several catalytic syntheses of thiazolidinones have been recently reported. These involve a coupling reagent like DCC [12], Bi(SCH2CO2H)3, solvent-free, 80 °C [13], silica gel [14], Schiff base MCM-41/CuSO4 [15], DIPEA reagent [16], Pd NPs, solvent-free [17], free catalyst in water [18], etc. [19,20,21]. However, most of them have limitations including long reaction times in multi-step synthesis, the use of expensive and toxic catalysts or reagents, low yields and tedious separation of the pure product from the reaction mixture. Therefore, the pursuance of more convenient and practical synthetic methods for the preparation of these compounds is still demanded as an active research area. On the other hand, it is known that, if an active core ring is linked to another nucleus, the resulting molecule may possess more powerful potential for biological activity. Also, reports show that the benzimidazole derivatives are used for their antiviral [22, 23], anti-ulcer [24], antimicrobial [25,26,27,28], antifungal [29, 30], anti-inflammatory [31], anthelmintic [32, 33], anticancer, anti-HIV-1 and antihistaminic properties [34,35,36,37].

Looking at the above facts and as a part of our ongoing studies on the catalytic synthesis of compounds containing the benzimidazole nucleus [11, 34, 38], this paper aims to report the one-pot, three-component synthesis of 2-((1H-benzo[d]imidazol-2-ylamino)(aryl) 1,3-thiazolidin-4-ones 4a–j using La(NO3)3·6H2O as an efficient catalyst with good to excellent yield in EtOH at room temperature.

Experimental

Materials and instruments

All the compounds were identified by their physical and spectroscopic data. Melting points were measured by using capillary tubes on an electrothermal digital apparatus and are uncorrected. IR spectra were recorded using a KBr disc on a galaxy series FT-IR 5000 spectrometer. 1H NMR and 13C NMR spectra were recorded on a Brucker spectrophotometer (300 MHz) in DMSO-d 6 using Me4Si as an internal standard. The mass spectra were recorded on an Agilent model: 5975C VL MSD with a Triple-Axis detector spectrometer at 70 eV. Reactions were monitored by thin layer chromatography (TLC) (Table 1).

Table 1 Optimizing the model reaction conditions of 2-aminobenzimidazole, 4-nitrobenzaldehyde and thioglycolic acid using different kinds and amounts of catalyst and solvents at room temperature
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General procedure for the preparation of 1,3-thiazolidinones 4a–j

To a mixture of aromatic aldehyde (1 mmol), 2-aminobenzimidazole (1.1 mmol) and thioglicolic acid (1.2 mmol) in 5 ml ethanol, La(NO3)3·6H2O (10 mol%) as catalyst was added. The reaction mixture was stirred magnetically at room temperature for the appropriate time as shown in Table 2 (the progress of reaction being monitored by TLC and using n-hexane/ethyl acetate (2:1 v/v) as an eluent). After completion of the reaction, 5 mL water were added and the precipitated product was filtered and washed with cold ethanol–water. The residue was recrystallized from the ethanol–water and air-dried.

Table 2 Synthesis of 2-((1H-benzo[d]imidazol-2-ylamino)(Aryl) 1,3-thiazolidin-4-ones, 4a–j in the presence of 10 mol% La(NO3)3·6H2O in ethanol at room temperature
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Spectroscopic data for new compounds

3-(1H-benzo[d]imidazol-2-yl)-2-phenylthiazolidin-4-one (4a)

IR (KBr) (ν max): 3360 (NH), 1700 (C=O), 1532 (C=N), 1381, 1269 (C=C), 1117 (C-N), 655 (C-S-C) cm−1; 1H-NMR (300 MHz, DMSO-d 6 ) δ H : 3.93 (1H, d, J = 16.53 Hz, SCH2), 4.17 (1H, d, J = 16.56 Hz, SCH2), 6.77 (1H, s, CH), 7.06–7.11 (2H, m, H-Ar), 7.24–7.39 (6H, m, H-Ar), 7.50 (1H, d, J = 7.50 Hz, H-Ar), 12.44 (1H, s, NH) ppm; 13C-NMR (75 MHz, DMSO-d 6 ) δ C: 32.0, 61.5, 111.2, 121.6, 125.3, 127.9, 128.6, 134.4, 141.4, 144.4, 171.7 ppm; MS (m/z, %): 295.1 (M+, 40), 249.1 (31), 220.1 (44), 133.1 (100), 105.1 (69), 77.1 (40).

3-(1H-benzo[d]imidazol-2-yl)-2-(2-hydroxyphenyl)thiazolidin-4-one (4b)

IR (KBr) (ν max): 3553 (OH), 3329 (NH), 1705 (C=O), 1599 (C = N), 1456, 1363, 1274 (C=C), 1231 (C-N), 669 (C-S-C) cm−1; 1H-NMR (300 MHz, DMSO-d 6 ) δ H : 3.88 (1H, d, J = 16.38 Hz, SCH2), 4.04 (1H, d, J = 16.44 Hz, SCH2), 6.68 (1H, t, J = 7.47 Hz, H-Ar), 6.76 (1H, s, CH), 6.83 (1H, d, J = 8.01 Hz, H-Ar), 6.92 (1H, d, J = 7.59 Hz, H-Ar), 7.06–7.13 (3H, m, H-Ar), 7.37 (1H, d, J = 7.32 Hz, H-Ar), 7.51 (1H, d, J = 7.23 Hz, H-Ar), 10.11 (1H, s, OH), 12.43 (1H, s, NH) ppm; 13C-NMR (75 MHz, DMSO-d 6) δ C: 32.1, 57.8, 111.8, 115.6, 117.5, 118.8, 121.5, 121.6, 124.4, 127.0, 128.8, 132.7, 139.8, 144.5, 154.1, 172.1 ppm; MS (m/z, %): 311.1 (M+, 63), 238.1 (81), 220.1 (66), 160.1 (38), 118.1 (44), 77.1 (14), 58.1 (62), 43.1 (100).

3-(1H-benzo[d]imidazol-2-yl)-2-(5-bromo-2-hydroxyphenyl)thiazolidin-4-one (4c)

IR (KBr) (ν max) 3412 (OH), 3348 (NH), 1690 (C = O), 1617, 1537 (C = N), 1467, 1369, 1274 (C = C), 1228 (C-N), 658 (C-S-C) cm−1; 1H-NMR (300 MHz, DMSO-d 6 ) δ H 3.88 (1H, d, J = 16.38 Hz, SCH2), 4.13 (1H, d, J = 16.35 Hz, SCH2), 6.70 (1H, s, CH), 6.78 (1H, d, J = 8.61 Hz, H-Ar), 7.10 (3H, d br, H-Ar), 7.23 (1H, dd, J = 2.37 Hz, H-Ar), 7.39–7.51 (2H, t br, H-Ar), 10.45 (1H, s, OH), 12.43 (1H, s, NH) ppm; 13C-NMR (75 MHz, DMSO-d 6) δ C 32.3, 57.5, 109.9 (2C), 111.9, 117.8, 121.6, 127.3, 129.7, 131.4, 144.4, 153.6, 172 ppm; MS (m/z, %) 391.1 (M+, 52), 316.1 (87), 216.9 (12), 160.1 (100), 118.1 (51), 91.1 (17).

3-(1H-benzo[d]imidazol-2-yl)-2-(3-nitrophenyl)thiazolidin-4-one (4d)

IR (KBr) (ν max): 3336 (NH), 1704 (C=O), 1620 (C=N), 1520, 1349 (NO2), 1262 (C=C), 1119 (C-N), 617 (C-S-C) cm−1;1H-NMR (300 MHz, DMSO-d 6 ) δ H : 3.94 (1H, d, J = 16.56 Hz, SCH2), 4.24 (1H, d, J = 16.53 Hz, SCH2), 6.93 (1H, s, CH), 7.03-7.13 (2H, m, H-Ar), 7.34 (1H, d, J = 7.50 Hz, H-Ar), 7.50 (1H, d, J = 7.35 Hz, H-Ar), 7.62 (1H, t, J = 7.98 Hz, H-Ar), 7.85 (1H, d, J = 7.92 Hz, H-Ar), 8.09–8.12 (1H, d br, H-Ar), 8.29 (1H, t br, H-Ar), 12.47 (1H, s, NH) ppm; 13C-NMR (75 MHz, DMSO-d 6) δ C: 32.0, 60.6, 111.9, 117.6, 120.5, 121.6, 121.8, 122.9, 130.3, 131.8, 132.7, 139.8, 143.9, 144.3, 147.9, 171.6 ppm; MS (m/z, %): 340 (M+, 100), 294.1 (86), 265.1 (39), 219.1 (37), 164.1 (27), 118 (43), 91 (28).

3-(1H-benzo[d]imidazol-2-yl)-2-(4-nitrophenyl)thiazolidin-4-one (4e)

IR (KBr) (ν max): 3477 (NH), 1708 (C=O), 1617, 1514 (C=N), 1520, 1349 (NO2), 1451, 1345, 1270 (C=C), 1114 (C-N), 626 (C-S-C) cm−1; 1H-NMR (300 MHz, DMSO-d 6 ) δ H: 3.96 (1H, d, J = 16.53 Hz, SCH2), 4.20 (1H, d, J = 16.53 Hz, SCH2), 6.90 (1H, s, CH), 7.03-7.13 (2H, m, H-Ar), 7.33 (1H, d, J = 7.68 Hz, H-Ar), 7.50 (1H, d, J = 7.53 Hz, H-Ar), 7.66 (2H, d, J = 8.70 Hz, H-Ar), 8.16 (2H, d, J = 8.67 Hz, H-Ar) 12.47 (1H, s, NH) ppm; 13C-NMR (75 MHz, DMSO-d 6) δ C: 32.0, 60.7, 111.2, 121.7, 122.4, 123.2, 124.0, 126.6, 130.3, 144.3, 146.9, 149.0, 152.9, 171.5 ppm; MS (m/z, %): 340.2 (M+, 100), 294.1 (92), 219.1 (50), 164.1 (26), 118.1 (41), 91.1 (27), 77.1 (13).

3-(1H-benzo[d]imidazol-2-yl)-2-(4-chlorophenyl)thiazolidin-4-one (4f)

IR (KBr) (ν max): 3324 (NH), 1708 (C=O), 1620, 1536 (C=N), 1488, 1450, 1366, 1310, 1270 (C=C), 1227, 1213, 1117 (C-N), 1108, 1009, 828, 739, 722, 658 (C-S-C), 500 cm−1; 1H-NMR (300 MHz, DMSO-d 6 ) δ H: 3.92 (1H, d, J = 16.53 Hz, SCH2), 4.18 (1H, d, J = 16.50 Hz, SCH2), 6.76 (1H, s, CH), 7.06–7.11 (2H, m, H-Ar), 7.35-7.44(5H, q br, H-Ar), 7.49 (1H, d, J = 7.38 Hz, H-Ar), 12.42 (1H, s, NH) ppm; 13C-NMR (75 MHz, DMSO-d 6) δ C: 32.0, 60.9, 111.2, 119.7, 121.0, 121.6, 127.4, 128.3(d), 128.6, 132.1, 132.4, 140.6, 144.3, 171.6 ppm; MS (m/z, %): 329.5 (M+, 100), 287.1 (21), 254.1 (59), 175.1 (24), 135.1 (76), 91.1 (41), 46.1 (77).

3-(1H-benzo[d]imidazol-2-yl)-2-(4-bromophenyl)thiazolidin-4-one (4g)

IR (KBr) (ν max): 3413 (NH), 1706 (C=O), 1618, 1535 (C=N), 1486, 1450, 1369, 1270 (C=C), 1227, 1117 (C-N), 1006, 738, 722, 659 (C-S-C), 497 cm−1; 1H-NMR (300 MHz, DMSO-d 6) δ H: 3.92 (1H, d, J = 16.53 Hz, SCH2), 4.18 (1H, d, J = 16.53 Hz, SCH2), 6.74 (1H, s, CH), 7.04–7.13 (2H, m, H-Ar), 7.34 (3H, d, J = 8.37 Hz, H-Ar), 7.49 (3H, d, J = 8.40 Hz, H-Ar), 12.42 (1H, s, NH) ppm; 13C-NMR (75 MHz, DMSO-d 6) δ C: 32.0, 61.0, 112.0, 119.8, 121.0, 121.6, 127.6, 128.9, 131.2, 131.5, 141.0, 144.3, 171.6 ppm; MS (m/z, %): 375.1 (M+, 25), 327.1 (23), 300.1 (100), 144.1 (10), 118.1 (35), 91.1 (28).

3-(1H-benzo[d]imidazol-2-yl)-2-(2-methoxyphenyl)thiazolidin-4-one (4 h)

IR (KBr) (ν max): 3378 (NH), 2961 (C-H), 1696 (C=O), 1622, 1545, 1493 (C=N), 1450, 1373 (C=C), 1270, 1251, (C-O), 1100 (C-N), 1118,753, 746, 644 (C-S-C) cm−1; 1H-NMR (300 MHz, DMSO-d 6) δ H : 3.88 (3H, s, OCH3), 3.88 (1H, d, J = 16.23 Hz, SCH2), 4.01 (1H, d, J = 16.47 Hz, SCH2), 6.77 (1H, s, CH), 6.80 (1H, t, J = 7.47, H-Ar), 6.97 (1H, d, J = 7.14 Hz, H-Ar), 7.03–7.13 (3H, m, H-Ar), 7.25 (1H, t, J = 7.47, H-Ar), 7.36 (1H, d, J = 7.50, H-Ar), 7.51 (1H, d, J = 7.41, H-Ar), 12.44 (1H, s, NH) ppm; 13C-NMR (75 MHz, DMSO-d 6) δ C: 32.0, 55.7, 57.6, 111.4, 111.9, 117.6, 120.3, 121.5, 121.7, 124.1, 128.5, 129.2, 132.8, 139.9, 144.5, 155.9, 172.0 ppm; MS (m/z, %): 326.2 (M+, 40), 294 (100), 220.1 (40), 91.2 (19), 46.1 (15).

3-(1H-benzo[d]imidazol-2-yl)-2-(4-methoxyphenyl)thiazolidin-4-one (4i)

IR (KBr) (ν max): 3478 (NH), 1707 (C=O), 1638, 1617, 1540, 1511 (C=N), 1452, 1373 (C=C), 1270, 1254 (C-O), 1178 (C-N), 1116, 1026, 843, 726, 665 (C-S-C), 607 cm−1; 1H-NMR (300 MHz, DMSO-d 6 ) δ H : 3.68 (3H, s, OCH3), 3.91 (1H, d, J = 16.53 Hz, SCH2), 4.17 (1H, d, J = 16.53 Hz, SCH2), 6.71 (1H, s, CH), 6.83 (2H, d, J = 8.61 Hz, H-Ar), 7.04–7.12 (2H, m, H-Ar), 7.31 (2H, d, J = 8.61 Hz, H-Ar), 7.37 (1H, d, J = 7.53 Hz, H-Ar), 7.48 (1H, d, J = 7.14 Hz, H-Ar), 12.41 (1H, s, NH) ppm; 13C-NMR (75 MHz, DMSO-d 6) δ C: 32.2, 55.0, 61.5, 112.0, 113.7, 113.9, 121.6, 126.9, 133.2, 144.4, 158.9, 171.6 ppm; MS (m/z, %): 325.2 (M+, 100), 279.1 (59), 250.1 (72), 165.1 (55), 135.1 (51), 118.1 (33), 91 (22).

2-2-10 3-(1H-benzo[d]imidazol-2-yl)-2-(3,4-dimethoxyphenyl)thiazolidin-4-one (4j)

IR (KBr) (ν max): 3400 (NH), 1704 (C=O), 1637, 1617, 1537 (C=N), 1514, 1452 (C=C), 1273, 1256, 1239 (C-O), 1141 (C-N), 648 (C-S-C), 616, 478 cm−1; 1H-NMR (300 MHz, DMSO-d 6 ) δ H : 3.67 (3H, s, OCH3), 3.72 (3H, s, OCH3), 3.90 (1H, d, J = 16.50 Hz, SCH2), 4.16 (1H, d, J = 16.53 Hz, SCH2), 6.70 (1H, s, CH), 6.81 (2H, s, H-Ar), 7.05–7.13 (3H, m, H-Ar), 7.38 (1H, d, J = 7.47 Hz, H-Ar), 7.48 (1H, d, J = 7.29 Hz, H-Ar), 12.42 (1H, s, NH) ppm; 13C-NMR (75 MHz, DMSO-d 6) δ C: 32.1, 55.4 (2C), 61.6, 109.7, 111.4, 111.8, 117.0, 117.7, 121.5, 121.7, 132.7, 133.4, 140.0, 144.4, 148.5, 148.8, 171.7 ppm; MS (m/z, %): 355.2 (M+, 100), 313.2 (61), 280.2 (50), 192.1 (17), 165.1 (81), 118.1 (30), 91.1 (18).

Results and discussion

Firstly, to obtain the optimal method conditions, the effect of the solvent and the amount and type of efficient catalyst on the yield of the reaction were examined. From the data summarized in Table 1, 10 mol% of La(NO3)3·6H2O was the best catalyst in ethanol resulting in the highest yield in a model reaction of 2-aminobenzimidazole, 4-nitrobenzaldehyde and thioglycolic acid at ambient temperature (Table 1, entry 2). Also, the reaction product was evaluated in the absence of catalyst and its yield was negligible (Table 1, entry 11).

By the generality of this method, some novel 2-((1H-benzo[d]imidazol-2-ylamino)(aryl) 1,3-thiazolidin-4-ones were prepared via one-pot multi-component reaction by employing various aromatic aldehydes under the same conditions (Scheme 1). The results are presented in Table 2.

Scheme 1
scheme 1

The synthetic pathway of compounds 4a–j

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Based on our previous knowledge, a probable reaction mechanism for the synthesis of the 2-((1H-benzo[d] imidazol-2-ylamino) (Aryl) 1,3-tiazolidin-4-ones (4a–j) is proposed in Scheme 2. Initially, La(NO3)3·6H2O activates the carbonyl group of the aromatic aldehyde to afford intermediate 2 ′ a–j, and then 2-aminobenzimidazole as a nucleophile attack it to form the intermediate 5 which can followed by catalytic oxidation to form the intermediate I. The Schiff base I is a stable colored powder with a high melting point which can be separated in a two-step reaction path. However, in the three-component reactions after the formation of the corresponding Schiff base, under catalytic activating and undergoing nucleophile attack by the third molecule, thioglicolic acid, the intermediate II, has instantly formed. Immediately, by the third catalytic activation of the intermediate II following intermolecular nucleophile attack and by the loss of the second water molecule, cyclization of 1,3-thiazolidin-4-one rings 4a–j can be accomplished.

Scheme 2
scheme 2

Proposed mechanism for the synthesis of compounds 4a–j

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All products are new and their structures were assigned using the spectroscopic data. In the IR spectra of the compounds, two sharp bonds in the region between 3300–3480 and 1617–1708 cm−1 are attributed to vibrations of the NH and C=O groups. In the 1H-NMR spectra, two diastereotopic protons that clearly appear as a doublet and doublet with J = 16.23–16.53 Hz around 3.88–4.24 ppm are attributed to the methylene group of the thiazolidin-4-one ring, and the singlet signal at 12.40 ppm is referred to the resonance of the NH proton of the benzimidazole ring. The other signals were observed in the expected region which are consistent with their structures. In the mass spectra, a molecular ion peak (25–100%) can be seen for all the compounds and, by considering the relative formula mass, the cyclization mechanism in the last step of the synthesis can be proved.

Conclusion

Some novel derivatives of 2-((1H-benzo[d]imidazol-2-ylamino)(aryl)1,3-thazolidine-4-one based on 2-aminobenzimidazole core were synthesized in a small amount of ethanol as a solvent via the one-pot multi-component reaction of 2-aminobenzimidazole, aromatic aldehydes and thioglicolic acid in the presence of a catalytic amount of La(NO3)3·6H2O at room temperature. The attractive features of this procedure are its good conversions and easy workup, making it a useful and practical method for the synthesis of 2,3-substituted-1,3-thazolidine-4-ones. Also, considering all ofdvantages of this simple and readily available procedure, this chemical design can be consistent with the goal of green chemistry.