DABCO-catalyzed consecutive one pot four-component protocol for the synthesis of a novel class of (Z)-5-(3-hydroxy-2-oxoindolin-3-yl)-2-iminothiazolidin-4-ones

Abstract

A DABCO catalyzed, novel and efficient one-pot, four component protocol has been developed for the synthesis of (Z)-5-(3-hydroxy-2-oxoindolin-3-yl)-2-iminothiazolidin-4-one scaffolds under metal-free conditions. By virtue of simple and readily available starting materials, mild reaction conditions, and the high bioactivity of oxindole derivatives, this reaction promises diverse applications in medical chemistry.

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Oxindoles bearing a quaternary stereogenic center at C-3 are privileged heterocyclic motifs which exist in a vast array of natural products and biologically active molecules such as maremycins A and B,^1a convolutamydines A–E,^1b arundaphine,^1c dioxibrassinine,^1d,e donaxaridine, welwitindolinone C,^2a diazonamide A,^2b leptosin D,^2c elogentin K,^2d neuroprotectins,^2e and CPC-1.^2f In particular, 3-functionalized-3-hydroxy-2-oxindoles are known to possess a broad spectrum of biological activities such as anti-inflammatory, antiviral, anticonvulsant, anti-HIV, antidepressant, antimicrobial, in addition to being potential new targets for chemotherapy (Fig. 1).³ For example, SM-130686 has been identified as a potent growth hormone secretagogue,^4a whereas compound F in Fig. 1 showed improved anti-HIV properties than FDA-approved NNRTI drug efavirenz.^4b

Fig. 1 Selected representative examples of natural products and pharmaceuticals possessing 3-functionalized-3-hydroxy-2-oxindoles and some thiazolidinone derivatives with anticancer activity.

Additionally, five-membered heterocyclic ring containing thiazolidinone moiety plays an important role in the area of medicinal chemistry with diverse biological activities such as antimicrobial,^5a,b antidiarrheal,^5c anticonvulsant,^5d–f antibacterial,^5g antidiabetic,^5h antihistaminic,^6a,b anticancer,^6c antifungal,^6d and anti-HIV.^6e Especially, 2-iminothiazolidin-4-one scaffolds have been found to possess significant pharmacological activities⁷ as well as therapeutics,⁸ fungicides and herbicides.⁹

For example, 2-heteroarylimino-1,3-thiazolidin-4-ones were possess antifungal or antibacterial properties,¹⁰ whereas darbufelone has reported anti-inflammatory activity.¹¹ Imino-1,3-thiazolidin-4-one based derivatives compound H and I (Fig. 1) have been identified as potential anticancer agents.¹² Compound K (BMS-858) (Fig. 1) recognized as a specific inhibitor of hepatitis C virus (HCV) replication in a genotype 1b replicon and showed no significant inhibitory activity in counter screens.¹³ Additionally, functionalized 2-imino-5-arylidenethiazolidin-4-one M used as an inhibitor of bacterial type III secretion system.¹⁴

Structure–activity relationship studies have shown that the biological and pharmacological activities of these scaffolds vary with substitution on C-3 position of oxindoles and C-5 position of the thiazolidinone frameworks.¹⁵ Hence it is thought of interest to accommodate oxindoles as well as iminothiazolidinones in a single molecular framework, which may result in the formation of some worthwhile molecules from a biological interest.

Multicomponent reactions (MCRs) have received much attention due to their wide range of applications in the organic, combinatorial, and medicinal chemistry for the rapid construction of novel and diverse molecular skeletons.¹⁶ The strategy offers outstanding features such as one-pot operation, single step, higher efficiency, operation simplicity, result in both atom and step-economy.¹⁷ MCRs can dramatically reduce chemical waste, energy, labor, time, cost, by-products formation, and provides an eco-friendly protocol by avoiding costly isolation and purification of intermediates.¹⁸ Due to these advantages, the design of novel multicomponent reactions has been considered as biological interest.

Tertiary amines (non-metallic bases) are the example of a privileged catalyst class. Particularly, DABCO (1,4-diazabicyclo[2,2,2]octane) has emerged as an efficient organic-hindered base which has been successfully used for various organic transformations like deprotection of peptides,^19a benzylictrimethylsilyl ethers,^19b cyclization of o-alkynylaryl isocyanides,^19c as a catalyst for the Baylis–Hillman reaction,^19d–f cross-coupling reactions,^19g o-alkylations of phenols,^19h and synthesis of glycidic amidester.¹⁹ⁱ Additionally, DABCO is commercially available, non-toxic, and inexpensive reagent that can be used without special precautions. As for literature there is no method reported for the synthesis of new (Z)-5-(3-hydroxy-2-oxoindolin-3-yl)-2-iminothiazolidin-4-ones using these current substrates. In continuation of our research work²⁰ on the synthesis of 3-substituted-3-hydroxy-2-oxindole frameworks, we wish to report a one pot four component protocol for the synthesis of a novel class of functionalized (Z)-5-(3-hydroxy-2-oxoindolin-3-yl)-2-iminothiazolidin-4-ones by the reaction of substituted isatins, phenylisothiocyanate, ethylbromoacetate, and amines with DABCO in aqueous medium (Scheme 1).

Scheme 1 Synthesis of (Z)-5-(3-hydroxy-2-oxoindolin-3-yl)-2-iminothiazolidin-4-one derivatives.

Results and discussions

Our optimization studies began by examination of reaction parameters which included catalyst, solvent and temperature for the modal product (Z)-3-butyl-5-(3-hydroxy-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one 5a. The results are summarized in Table 1. Initially, we treated simple isatin, phenylisothiocyanate, ethylbromoacetate and butylamine in the presence of 10 mol% DBU in 5 mL of H₂O at 70 °C. We obtained the solid product in 55% yield only even after 1 h. The structure of obtained product was confirmed by means of ¹H NMR, ¹³C NMR, IR and mass spectrometry analysis.

Table 1 Optimization of reaction condition^a

Entry	Catalyst (mol%)	Solvent	Time (h)	Yield^b [%]
a Reaction conditions: isatin 1a (1 mmol), butylamine 2a (1 mmol), phenylisothiocyanate 3 (1 mmol) and ethylbromoacetate 4 (1 mmol) base in solvent (5 mL) at rt and 70 °C.b Isolated yield.c At rt conditions.
1	—	H2O	12	—
2	DBU (30)	H2O	1	55
3	DBU (60)	H2O	2	50
4	DABCO (10)	H2O	12	—^c
5	DABCO (10)	H2O	1	70
6	DABCO (30)	H2O	0.5	90
7	DABCO (50)	H2O	1	80
8	DABCO (30)	EtOH	1	65
9	DABCO (30)	MeOH	1	55
10	DABCO (30)	THF	1	30
11	DABCO (30)	CH3CN	1	35
12	Quinuclidine (30)	H2O	1	40
13	Urotropine (30)	H2O	1	35
14	DBN (30)	H2O	1	50
15	Troger's base (30)	H2O	1	30
16	Pyridine (30)	H2O	1	30
17	Piperidine (30)	H2O	1	25
18	TEA (30)	H2O	1	30
19	DIPEA (30)	H2O	1	25
20	KOH (30)	H2O	1	—
21	K2CO3 (30)	H2O	1	—
22	Cs2CO3 (30)	H2O	1	—
23	MeONa (30)	H2O	1	—

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Further increase in the amount of DBU (30 mol% to 60 mmol%) did not improve the yield of the product (Table 1, entry 3). However, the reaction did not proceed in the absence of catalyst (Table 1, entry 1), which indicated that the use of base catalyst is essential for this MCR. Later, other bases also were tested for this MCR. First, DABCO (10 mol%) was used at room temperature and under heating condition (Table 1, entries 4 and 5 respectively), and the results indicated that DABCO was superior to DBU. It was noticed that there was a maximum increase in the yield (90%), when the amount of DABCO raised from 10 mol% to 30 mol% in 30 min (Table 1, entry 6). However, further raising the amount of DABCO did not increase in the yield (Table 1, entry 7). Next, quinuclidine, urotropine, DBN, troger's base, pyridine, piperidine, TEA and DIPEA as a catalyst for this reaction also were examined, but the results were inadequate (Table 1, entries 12–19). In addition, the inorganic bases such as KOH, K₂CO₃, Cs₂CO₃ and MeONa were ineffective for this reaction (Table 1, entries 20 and 23).

Further to optimize the reaction conditions, the reaction was studied in different solvents. Screening of solvents revealed that H₂O turned out to be suitable solvent, which provided not only a shorter reaction time, but also a higher yield than other tested solvents such as EtOH, MeOH, THF and CH₃CN (Table 1, entries 8–11). Therefore, the reaction conditions of 30 mmol% of DABCO as a catalyst in H₂O at 70 °C were best conditions for the preparation of 5a.

To make the present protocol general, various isatins 1 and amines 2 were examined under optimized conditions and the results are summarized in Table 2. The reaction of butylamine 2a and ethylamine 2d with simple isatin 1a underwent smoothly in the standard reaction condition to furnish the desired product in a high yield (Table 2, entries 5a and 5r). Isatins bearing different substituents on the aromatic ring could also be coupled effectively under this condition. For example 5-halo isatins like 5-fluoro isatin 1b 5-chloro isatin 1c, 5-bromo isatin 1d, and 5-iodo isatin 1e reacted with amine (2a/2b/2c/2d) under standard condition and resulted in moderate yields of product (Table 2, entries 5b, 5c, 5i, 5j, 5k, 5p, 5q, 5s, 5t, 5u and 5v). Other 5-substituted isatins like 5-(trifluoromethoxy) isatin 1h reacted smoothly with 2a to furnish desired product in high yield (Table 2, entry 5e). The reaction was not only successful with isatins having electron withdrawing substituent but also with isatins bearing electron donating group like 5-methyl isatin 1f and 5-methoxy isatin 1g (Table 2, entries 5d, 5l, 5m, 5w and 5x). As like mono-substituted isatins, di-substituted isatin like 5,7-dimethyl isatin 1i and 4,7-dichloro isatin 1j reacted in the same way and afforded comparatively less yield of desired products under standard reaction condition (Table 2, entries 5f, 5g, and 5n). To further expand the scope of the method we were keen to explore cyclic amines in this reaction under the optimized reaction conditions. In this context we performed the reaction of cyclopropylamine 2c with different substituted isatins under standard reaction conditions and found the formation of desired products in good yield (Table 2, entries 5o–5q). Moreover, this transformation is clean, easy to work up and all the structurally varied substrates reacted smoothly under the standard reaction conditions to afford their respective products in high purities with good yields (products 5a–5x).

Table 2 Scope of isatins and amines for the synthesis of (Z)-5-(3-hydroxy-2-oxoindolin-3-yl)-2-iminothiazolidin-4-ones^a

a Reaction conditions: isatin 1(a–j) (1 mmol), amine 2(a–d) (1 mmol), phenylisothiocyanate 3 (1 mmol) and ethylbromoacetate 4 (1 mmol) DABCO (30 mol%) in H₂O (5 mL) at 70 °C and yields are given as an isolated yield. All products 5(a–x) were characterized by NMR, mass and IR spectroscopic techniques.

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A plausible mechanism for this DABCO catalyzed four-componenet reaction proposed and illustrated in Scheme 2. The formation of product may be explained by the reaction of ethylbromoaectate (4) with DABCO which forms the quaternary salt A. Later it reacts with sulfur of thiourea derivative B (which was in situ generated from amine 2 and phenylisothiocyanate 3) to furnish the intermediate C by eliminating HBr and DABCO. Next, the nucleophile of amine group promptly attacked on carbonyl group of ester by proton abstraction by DABCO leading to the five-membered cyclised intermediate E. Finally, the nucleophile of E which is formed by proton abstraction by DABCO attacked on isatin to furnish the required product (Z)-5-(3-hydroxy-2-oxoindolin-3-yl)-2-iminothiazolidin-4-one 5. However the stereo chemistry of the product 5 could not be determined because of difficulty in the formation of crystal for X-ray data.

Scheme 2 Putative mechanistic pathway for the formation of (Z)-5-(3-hydroxy-2-oxoindolin-3-yl)-2-iminothiazolidin-4-ones.

Conclusion

In summary, we have described a novel and efficient method for the synthesis of (Z)-5-(3-hydroxy-2-oxoindolin-3-yl)-2-iminothiazolidin-4-one derivatives from simple, commercially cheap and readily available starting materials. The DABCO catalyzed four-component reaction of isatins, amines, phenylisothiocyanate and ethylbromoacetate proceeds smoothly under metal-free conditions. This novel method has many important features such as, high efficiency, good yields, broad substrate scope and also it involves the formation of four new bonds (2 C–N, 1 C–S, 1 C–C) in a cascade pathway.

Experimental section

General information

Isatins, amines, phenylisothiocyanate, ethylbromoacetate, DABCO and all solvents were purchased from Sigma-Aldrich and Alpha Aesar and used as received without further purification. ¹H NMR spectra were recorded at 300 MHz and ¹³C NMR spectra at 75 MHz spectrometers in DMSO-d₆ or CDCl₃ + DMSO-d₆. Chemical shifts (d) are reported in parts per million (ppm) relative to residual CHCl₃ (¹H: δ 7.26 ppm, ¹³C: δ 77.00 ppm) as an internal reference. Coupling constants (J) are reported in Hertz (Hz) and peak multiplicity abbreviations used as follows: s—singlet, d—doublet, t—triplet, q—quartet, m—multiplet and dd—doublet of doublet. Chemical shifts (δ) are reported relative to TMS (δ 0.0) as an internal standard in ppm. Melting points were measured on a BUCHI melting point machine. IR spectra were recorded on a Thermo Nicolet FT/IR-5700 spectrometer. Mass spectra were recorded using a Waters mass spectrometer. High resolution mass spectra (HRMS) were recorded using an Applied Bio-Sciences HRMS spectrometer at the National Centre for Mass Spectroscopy-IICT.

General procedure for the synthesis of (Z)-3-butyl-5-(3-hydroxy-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one (5a). A mixture of butylamine 2a (1 mmol), phenylisothiocyanate 3 (1 mmol) and DABCO (30 mol%) in H₂O (5 mL) was stirred for 5 min at room temperature then the ethylbromoacetate 4 (1 mmol) was added and the mixture was stirred at 70 °C for 10 min. After cooling to room temperature, isatin 1 (1 mmol) was added to the reaction mixture and stirred for 10 min at room temperature. After completion of the reaction (monitored by TLC), the product 5a was extracted with ethylacetate and dried over Na₂SO₄ and the solvent was removed under reduced pressure. The crude product was purified by column chromatography using ethyl acetate/hexane and the product (Z)-3-butyl-5-(3-hydroxy-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one 5a was characterized by NMR, mass and IR spectroscopic techniques.

Spectral data for all the synthesized compounds

(Z)-3-Butyl-5-(3-hydroxy-2-oxoindolin-3-yl)-2-(phenylimino) thiazolidin-4-one (5a). Yield, 90%; isatin (1 mmol), butylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); yellow solid; mp 146–148 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.11 (s, 1H), 7.57 (d, J = 7.36 Hz, 1H), 7.51 (s, 1H), 7.37 (t, J = 7.74 Hz, 2H), 7.24 (t, J = 7.74 Hz, 1H), 7.14 (t, J = 7.36 Hz, 1H), 7.03–6.93 (m, 2H), 6.86 (d, J = 7.74 Hz, 1H), 6.51 (s, 1H), 4.82 (s, 1H), 3.68–3.46 (m, 2H), 1.37–0.84 (m, 4H), 0.75 (t, J = 6.98 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 176.8, 171.5, 152.3, 147.7, 141.4, 130.9, 129.2, 126.5, 124.6, 124.5, 123.1, 120.7, 110.9, 76.7, 53.1, 42.9, 28.8, 19.7, 13.6 ppm; IR (KBr): ν = 3316, 2959, 2928, 1725, 1634, 1593, 1408, 1180, 1120, 754 cm⁻¹; MS-ESI: m/z = 396 [M + 1]⁺; HRMS (ESI) calc. C₂₁H₂₂O₃N₃S: 396.13764, found: 396.13849.

(Z)-3-Butyl-5-(5-fluoro-3-hydroxy-2-oxoindolin-3-yl)-2(phenylimino)thiazolidin-4-one (5b). Yield, 81%; 5-fluoro isatin (1 mmol), butylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); red solid; mp 176–179 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.93 (s, 1H), 10.25 (s, 1H), 7.55 (s, 1H), 7.44–7.12 (m, 3H), 7.04–6.89 (m, 2H), 6.88–6.73 (m, 2H), 4.83 (s, 1H), 3.69–3.47 (m, 2H), 1.36–0.91 (m, 4H), 0.77 (t, J = 7.17 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 183.6, 176.3, 159.0, 152.8, 147.6, 146.5, 138.0, 128.7, 124.5, 124.3, 124.0, 120.2, 113.3, 75.2, 55.1, 41.7, 28.2, 19.0, 13.1 ppm; IR (KBr): ν = 3262, 2930, 2860, 1728, 1633, 1487, 1397, 1192, 1145, 739, 694 cm⁻¹; MS-ESI: m/z = 414 [M + 1]⁺; HRMS (ESI) calc. C₂₁H₂₁O₃N₃FS: 414.12822, found: 414.12887.

(Z)-3-Butyl-5-(5-chloro-3-hydroxy-2-oxoindolin-3-yl)-2(phenylimino)thiazolidin-4-one (5c). Yield, 83%; 5-chloro isatin (1 mmol), butylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); pale red solid; mp 184–186 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.16 (s, 1H), 7.58 (s, 1H), 7.47–7.33 (m, 2H), 7.27–7.13 (m, 2H), 6.99 (d, J = 7.55 Hz, 1H), 6.82 (d, J = 8.30 Hz, 1H), 6.62 (s, 1H), 4.80 (s, 1H), 3.70–3.49 (m, 2H), 1.38–1.20 (m, 2H), 1.15–0.92 (m, 2H), 0.79 (t, J = 6.98 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 176.3, 169.7, 153.1, 147.9, 140.7, 129.8, 128.9, 128.1, 126.8, 124.7, 124.2, 120.4, 111.2, 75.3, 55.2, 42.0, 28.4, 19.2, 13.3 ppm; IR (KBr): ν = 3275, 2956, 2872, 1736, 1638, 1594, 1397, 1181, 1129, 698 cm⁻¹; MS-ESI: m/z = 430 [M + 1]⁺; HRMS (ESI) calc. C₂₁H₂₁O₃N₃ClS: 430.09867, found: 430.09928.

(Z)-3-Butyl-5-(3-hydroxy-5-methoxy-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one (5d). Yield, 85%; 5-methoxy isatin (1 mmol), butylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); block solid; mp 138–140 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.19 (s, 1H), 7.38 (t, J = 7.97 Hz, 3H), 7.23–7.12 (m, 2H), 7.01–6.94 (m, 2H), 6.82–6.73 (m, 3H), 4.80 (s, 1H), 3.75 (s, 3H), 3.64–3.43 (m, 2H), 1.12–0.81 (m, 4H), 0.74 (t, J = 7.15 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 174.7, 167.9, 153.3, 152.1, 146.6, 134.3, 127.6, 126.4, 122.7, 119.1, 113.4, 109.6, 108.8, 73.7, 54.3, 53.8, 40.2, 27.0, 17.7, 12.0 ppm; IR (KBr): ν = 3243, 2957, 2873, 1722, 1705, 1633, 1592, 1487, 1391, 1202, 1184 cm⁻¹; MS-ESI: m/z = 426 [M + 1]⁺; HRMS (ESI) calc. C₂₂H₂₄O₄N₃S: 426.14820, found: 426.14872.

(Z)-3-Butyl-5-(3-hydroxy-2-oxo-5-(trifluoromethoxy)indolin-3-yl)-2-(phenylimino)thiazolidin-4-one (5e). Yield, 84%; 5-(trifluoromethoxy) isatin (1 mmol), butylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); yellow solid; mp 193–195 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 8.18 (s, 1H), 7.39 (s, 1H), 7.33 (t, J = 8.08 Hz, 2H), 7.18–7.12 (m, 2H), 6.91 (d, J = 8.54 Hz, 2H), 6.86 (d, J = 8.08 Hz, 1H), 4.67 (s, 1H), 3.81–3.66 (m, 2H), 1.33–1.15 (m, 4H), 0.86 (t, J = 7.47 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 176.0, 168.9, 152.4, 147.5, 142.9, 141.0, 128.5, 128.3, 127.5, 123.7, 122.7, 120.0, 117.8, 110.1, 74.7, 55.3, 41.5, 27.9, 18.7, 12.7 ppm; IR (KBr): ν = 3265, 2928, 2856, 1733, 1712, 1638, 1595, 1398, 1268, 1188, 1158, 695 cm⁻¹; MS-ESI: m/z = 480 [M + 1]⁺; HRMS (ESI) calc. C₂₂H₂₁O₄N₃F₃S: 480.11994, found: 480.12021.

(Z)-3-Butyl-5-(3-hydroxy-5,7-dimethyl-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one (5f). Yield, 72%; 5,7-dimethyl isatin (1 mmol), butylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); brown solid; mp 226–228 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.42 (s, 1H), 7.40 (t, J = 7.78 Hz, 2H), 7.21–7.14 (m, 2H), 6.95 (d, J = 7.47 Hz, 2H), 6.87 (s, 1H), 6.68 (s, 1H), 4.74 (s, 1H), 3.57–3.50 (m, 2H), 2.25 (s, 3H), 2.16 (s, 3H), 1.17–1.04 (m, 1H), 0.98–0.75 (m, 3H), 0.70 (t, J = 7.17 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 176.1, 169.0, 153.0, 147.4, 137.7, 131.1, 129.9, 128.2, 125.6, 123.3, 121.6, 119.8, 118.3, 74.7, 54.8, 41.1, 27.7, 19.9, 18.4, 15.4, 12.7 ppm; IR (KBr): ν = 3297, 2954, 1715, 1698, 1634, 1596, 1486, 1398, 1155 cm⁻¹; MS-ESI: m/z = 424 [M + 1]⁺; HRMS (ESI) calc. C₂₃H₂₆O₃N₃S: 424.16894, found: 424.16918.

(Z)-3-Butyl-5-(4,7-dichloro-3-hydroxy-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one (5g). Yield, 74%; 4,7-dichloro isatin (1 mmol), butylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); brown solid; mp 136–138 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.27 (s, 1H), 7.37–7.19 (m, 3H), 7.14–6.83 (m, 4H), 4.82 (s, 1H), 3.72–3.64 (m, 2H), 1.21–0.98 (m, 4H), 0.94 (t, J = 6.98 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 173.8, 170.3, 150.5, 146.5, 141.4, 130.6, 127.9, 124.4, 123.3, 122.8, 119.9, 119.6, 113.0, 77.7, 51.4, 44.9, 27.7, 18.6, 12.6 ppm; IR (KBr): ν = 3406, 2930, 2873, 1738, 1634, 1613, 1594, 1465, 1388, 1344, 1158, 1057, 775 cm⁻¹; MS-ESI: m/z = 464 [M + 1]⁺; HRMS (ESI) calc. C₂₁H₂₀O₃N₃Cl₂S: 464.05969, found: 464.06090.

(Z)-3-Benzyl-5-(3-hydroxy-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one (5h). Yield, 90%; isatin (1 mmol), benzylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); pale yellow solid; mp 186–188 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.08 (s, 1H), 7.55 (d, J = 7.36 Hz, 1H), 7.39–7.30 (m, 3H), 7.18–7.07 (m, 4H), 6.97–6.81 (m, 5H), 6.51 (s, 1H), 4.93 (s, 1H), 4.77 (d, J = 5.09 Hz, 2H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 174.8, 168.1, 151.5, 146.3, 141.3, 133.7, 128.7, 127.6, 127.3, 126.5, 125.2, 125.0, 123.2, 122.8, 120.0, 119.2, 108.6, 73.3, 54.5, 43.6 ppm; IR (KBr): ν = 3292, 2926, 1728, 1643, 1470, 1399, 1333, 1173, 1020, 748 cm⁻¹; MS-ESI: m/z = 430 [M + 1]⁺; HRMS (ESI) calc. C₂₄H₂₀O₃N₃S: 430.12199, found: 430.12215.

(Z)-3-Benzyl-5-(5-fluoro-3-hydroxy-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one (5i). Yield, 82%; 5-fluoro isatin (1 mmol), benzylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); white solid; mp 202–204 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.37 (s, 1H), 7.42–7.33 (m, 2H), 7.26 (dd, J = 2.64, 2.64 Hz, 2H), 7.20–7.09 (m, 3H), 6.97–6.85 (m, 6H), 4.91 (s, 1H), 4.75 (d, J = 1.70 Hz, 2H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 174.8, 167.9, 157.9, 154.7, 151.4, 146.4, 137.3, 133.8, 127.7, 126.6, 125.6, 125.5, 123.0, 119.2, 115.2, 114.9, 109.3, 73.6, 54.4, 43.8 ppm; IR (KBr): ν = 3291, 2936, 1727, 1704, 1644, 1590, 1484, 1402, 1333, 1246, 1188, 1088, 817, 695 cm⁻¹; MS-ESI: m/z = 448 [M + 1]⁺; HRMS (ESI) calc. C₂₄H₁₉O₃N₃FS: 448.11257, found: 448.11293.

(Z)-3-Benzyl-5-(5-chloro-3-hydroxy-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one (5j). Yield, 84%; 5-chloro isatin (1 mmol), benzylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); white solid; mp 209–211 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.46 (s, 1H), 7.53 (d, J = 2.07 Hz, 1H), 7.41–7.34 (m, 2H), 7.19–7.11 (m, 4H), 6.97–6.89 (m, 3H), 6.87–6.82 (m, 2H), 6.75–6.69 (m, 1H), 4.89 (s, 1H), 4.75 (d, J = 10.57 Hz, 2H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 174.0, 167.5, 151.3, 146.1, 139.7, 133.4, 128.3, 127.4, 126.9, 126.3, 125.1, 124.6, 124.0, 123.0, 122.6, 118.7, 109.5, 72.9, 54.1, 43.4 ppm; IR (KBr): ν = 3278, 2923, 1732, 1703, 1646, 1589, 1479, 1401, 1174, 1097, 1022, 816, 695 cm⁻¹; MS-ESI: m/z = 464 [M + 1]⁺; HRMS (ESI) calc. C₂₄H₁₉O₃N₃ClS: 464.08302, found: 464.08364.

(Z)-3-Benzyl-5-(3-hydroxy-5-iodo-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one (5k). Yield, 86%; 5-iodo isatin (1 mmol), benzylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); white solid; mp 215–217 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.19 (s, 1H), 7.48–7.44 (m, 1H), 7.42–7.34 (m, 2H), 7.22–7.12 (m, 4H), 7.02–6.81 (m, 4H), 6.73–6.64 (m, 1H), 6.61–6.54 (m, 1H), 4.87 (s, 1H), 4.77 (d, J = 9.63 Hz, 2H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 174.4, 168.0, 151.9, 146.8, 141.2, 137.4, 133.8, 132.2, 127.9, 127.8, 127.0, 125.7, 125.4, 123.1, 119.3, 111.1, 82.6, 73.6, 54.8, 44.2 ppm; IR (KBr): ν = 3281, 2920, 1730, 1700, 1646, 1589, 1404, 1332, 1174, 1093, 1023, 815, 694 cm⁻¹; MS-ESI: m/z = 556 [M + 1]⁺; HRMS (ESI) calc. C₂₄H₁₉O₃N₃IS: 556.01239, found: 556.01345.

(Z)-3-Benzyl-5-(3-hydroxy-5-methyl-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one (5l). Yield, 78%; 5-methyl isatin (1 mmol), benzylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); white solid; mp 195–197 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 9.74 (s, 1H), 7.41–7.29 (m, 4H), 7.23–7.09 (m, 4H), 6.97–6.89 (m, 3H), 6.71 (d, J = 7.93 Hz, 1H), 6.26 (s, 1H), 4.88 (s, 1H), 4.79 (d, J = 11.08 Hz, 2H), 2.17 (s, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 174.4, 167.8, 151.6, 146.2, 138.5, 133.5, 128.7, 128.6, 127.4, 126.2, 125.2, 125.0, 124.7, 123.6, 122.5, 118.8, 107.9, 73.1, 54.3, 43.4, 19.1 ppm; IR (KBr): ν = 3288, 2919, 1728, 1644, 1589, 1489, 1398, 1362, 1330, 1201, 1155, 1087, 813, 695 cm⁻¹; MS-ESI: m/z = 444 [M + 1]⁺; HRMS (ESI) calc. C₂₅H₂₂O₃N₃S: 444.13764, found: 444.13795.

(Z)-3-Benzyl-5-(3-hydroxy-5-methoxy-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one (5m). Yield, 88%; 5-methoxy isatin (1 mmol), benzylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); brown solid; mp 105–107 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.18 (s, 1H), 7.38–7.31 (m, 3H), 7.18–7.08 (m, 4H), 6.91 (d, J = 7.17 Hz, 2H), 6.83–6.72 (m, 4H), 4.93 (s, 1H), 4.75 (d, J = 8.49 Hz, 2H), 3.58 (s, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 174.7, 168.0, 153.2, 151.6, 146.3, 134.4, 133.8, 127.6, 127.4, 126.5, 126.3, 125.3, 122.8, 119.1, 114.2, 109.3, 109.0, 73.6, 54.5, 53.7, 43.7 ppm; IR (KBr): ν = 3309, 2928, 1725, 1633, 1590, 1488, 1386, 1204, 1158, 1028, 818, 695 cm⁻¹; MS-ESI: m/z = 460 [M + 1]⁺; HRMS (ESI) calc. C₂₅H₂₂O₄N₃S: 460.13255, found: 460.13335.

(Z)-3-Benzyl-5-(3-hydroxy-5,7-dimethyl-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one (5n). Yield, 73%; 5,7-dimethyl isatin (1 mmol), benzylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); white solid; mp 238–240 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.33 (s, 1H), 7.40–7.34 (m, 3H), 7.20–7.06 (m, 3H), 6.91 (d, J = 7.36 Hz, 2H), 6.84 (s, 1H), 6.75 (d, J = 6.98 Hz, 2H), 6.66 (s, 1H), 4.87 (s, 1H), 4.72 (s, 2H), 2.16 (s, 3H), 2.15 (s, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 175.5, 168.2, 152.0, 146.7, 137.3, 133.9, 130.8, 129.2, 127.8, 127.6, 126.5, 125.5, 125.1, 122.9, 121.3, 119.3, 117.6, 73.9, 54.7, 43.9, 19.4, 15.0 ppm; IR (KBr): ν = 3314, 2920, 1717, 1700, 1637, 1593, 1485, 1398, 1200, 1153, 1073, 695 cm⁻¹; MS-ESI: m/z = 458 [M + 1]⁺; HRMS (ESI) calc. C₂₆H₂₄O₃N₃S: 458.15329, found: 458.15378.

(Z)-3-Cyclopropyl-5-(3-hydroxy-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one (5o). Yield, 81%; isatin (1 mmol), cyclopropylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); white solid; mp 190–192 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.43 (s, 1H), 7.71 (d, J = 7.36 Hz, 1H), 7.36–7.29 (m, 4H), 7.04–6.89 (m, 3H), 6.69–6.64 (m, 1H), 5.11 (s, 1H), 2.34–2.21 (m, 1H), 1.72–0.30 (m, 4H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 175.1, 168.3, 141.6, 131.3, 129.4, 129.3, 127.9, 126.0, 125.6, 123.3, 120.7, 120.5, 109.4, 74.3, 56.0, 22.3, 4.8, 4.1 ppm; IR (KBr): ν = 3270, 2931, 1720, 1695, 1621, 1471, 1371, 1185, 1145, 758 cm⁻¹; MS-ESI: m/z = 380 [M + 1]⁺; HRMS (ESI) calc. C₂₀H₁₈O₃N₃S: 380.09912, found: 380.09983.

(Z)-3-Cyclopropyl-5-(5-fluoro-3-hydroxy-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one (5p). Yield, 84%; 5-fluoro isatin (1 mmol), cyclopropylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); white solid; mp 142–144 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.36 (s, 1H), 7.57 (s, 1H), 7.49–7.42 (m, 1H), 7.40–7.34 (m, 1H), 7.30–7.24 (m, 1H), 7.05–6.93 (m, 2H), 6.89–6.79 (m, 2H), 4.90 (s, 1H), 2.39–2.30 (m, 1H), 1.06–0.41 (m, 4H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 175.3, 169.4, 137.7, 131.4, 128.2, 126.1, 115.9, 115.7, 111.5, 111.2, 111.0, 110.4, 110.2, 74.6, 55.1, 22.7, 5.0, 4.4 ppm; IR (KBr): ν = 3277, 2927, 1722, 1696, 1486, 1380, 1192, 1144, 822 cm⁻¹; MS-ESI: m/z = 398 [M + 1]⁺; HRMS (ESI) calc. C₂₀H₁₇O₃N₃FS: 398.02354, found: 398.02358.

(Z)-5-(5-Chloro-3-hydroxy-2-oxoindolin-3-yl)-3-cyclopropyl-2-(phenylimino)thiazolidin-4-one (5q). Yield, 79%; 5-chloro isatin (1 mmol), cyclopropylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); white solid; mp 149–151 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.36 (s, 1H), 7.54–7.36 (m, 4H), 7.32–7.18 (m, 2H), 6.89–6.79 (m, 2H), 4.89 (s, 1H), 2.42–2.33 (m, 1H), 1.04–0.45 (m, 4H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 175.0, 169.3, 140.3, 131.4, 129.4, 129.3, 128.2, 127.4, 126.1, 125.6, 123.6, 123.4, 110.6, 74.3, 55.1, 22.6, 5.1, 4.4 ppm; IR (KBr): ν = 3281, 1722, 1695, 1620, 1476, 1380, 1181, 823 cm⁻¹; MS-ESI: m/z = 414 [M + 1]⁺; HRMS (ESI) calc. C₂₀H₁₇O₃N₃ClS: 414.01276, found: 414.01321.

(Z)-3-Ethyl-5-(3-hydroxy-2-oxoindolin-3-yl)-2-(phenylimino)thiaz-olidin-4-one (5r). Yield, 88%; isatin (1 mmol), ethylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); white solid; mp 147–149 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.22 (s, 1H), 7.59 (d, J = 7.36 Hz, 1H), 7.51 (s, 1H), 7.37–7.18 (m, 2H), 7.07–6.82 (m, 3H), 6.81–6.61 (m, 2H), 4.97 (s, 1H), 3.38 (q, J = 7.36 Hz, 2H), 0.67 (t, J = 7.36 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 174.4, 169.1, 167.9, 141.0, 128.8, 128.6, 127.3, 125.5, 125.1, 122.6, 120.0, 119.9, 108.4, 73.3, 55.5, 34.1, 10.2 ppm; IR (KBr): ν = 3280, 2934, 1719, 1682, 1622, 1471, 1342, 1222, 1183, 1090, 755 cm⁻¹; MS-ESI: m/z = 368 [M + 1]⁺; HRMS (ESI) calc. C₁₉H₁₈O₃N₃S: 368.14319, found: 368.14381.

(Z)-3-Ethyl-5-(5-fluoro-3-hydroxy-2-oxoindolin-3-yl)-2-(phenylim-ino)thiazolidin-4-one (5s). Yield, 74%; 5-fluoro isatin (1 mmol), ethylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); white solid; mp 164–166 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.41 (s, 1H), 7.66–7.43 (m, 1H), 7.40–7.30 (m, 2H), 7.08–6.75 (m, 5H), 4.99 (s, 1H), 3.40 (q, J = 7.15 Hz, 2H), 0.70 (t, J = 7.15 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 175.4, 169.8, 168.7, 158.8, 137.8, 128.2, 127.1, 126.1, 115.9, 115.6, 111.5, 111.2, 110.2, 74.5, 56.0, 35.2, 11.1 ppm; IR (KBr): ν = 3259, 2930, 1722, 1684, 1488, 1392, 1340, 1193, 1148, 822 cm⁻¹; MS-ESI: m/z = 386 [M + 1]⁺; HRMS (ESI) calc. C₁₉H₁₇O₃N₃FS: 386.01211, found: 386.01295.

(Z)-5-(5-Chloro-3-hydroxy-2-oxoindolin-3-yl)-3-ethyl-2-(phenylimino)thiazolidin-4-one (5t). Yield, 78%; 5-chloro isatin (1 mmol), ethylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); white solid; mp 169–171 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.57 (s, 1H), 7.70 (s, 1H), 7.54 (d, J = 2.07 Hz, 1H), 7.49–7.34 (m, 1H), 7.32–7.13 (m, 2H), 7.08–6.77 (m, 3H), 4.98 (s, 1H), 3.39 (q, J = 7.17 Hz, 2H), 0.68 (t, J = 7.17 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 174.7, 169.3, 168.3, 140.2, 129.0, 128.8, 127.8, 127.5, 127.3, 125.8, 125.2, 123.3, 110.2, 73.8, 55.7, 34.8, 10.6 ppm; IR (KBr): ν = 3280, 2934, 1717, 1685, 1480, 1337, 1180, 1104, 824 cm⁻¹; MS-ESI: m/z = 402 [M + 1]⁺; HRMS (ESI) calc. C₁₉H₁₇O₃N₃ClS: 402.13492, found: 402.13512.

(Z)-5-(5-Bromo-3-hydroxy-2-oxoindolin-3-yl)-3-ethyl-2-(phenylimino)thiazolidin-4-one (5u). Yield, 76%; 5-bromo isatin (1 mmol), ethylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); pale yellow solid; mp 190–192 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.62 (s, 1H), 7.82–7.54 (m, 2H), 7.52–7.31 (m, 2H), 7.29–7.01 (m, 2H), 6.95–6.72 (m, 2H), 4.97 (s, 1H), 3.37 (q, J = 7.17 Hz, 2H), 0.66 (t, J = 7.17 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 174.2, 169.0, 168.0, 140.4, 131.6, 131.4, 127.6, 127.5, 125.6, 112.1, 110.7, 110.5, 108.6, 73.4, 55.4, 34.4, 10.3 ppm; IR (KBr): ν = 3278, 2936, 1717, 1684, 1618, 1476, 1337, 1221, 1178, 1100, 822 cm⁻¹; MS-ESI: m/z = 446 [M]⁺, 448 [M + 2]⁺; HRMS (ESI) calc. C₁₉H₁₇O₃N₃BrS: 446.08519, found: 446.08469.

(Z)-3-Ethyl-5-(3-hydroxy-5-iodo-2-oxoindolin-3-yl)-2-(phenylimino) thiazolidin-4-one (5v). Yield, 77%; 5-iodo isatin (1 mmol), ethylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); brown solid; mp 199–201 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.67 (s, 1H), 8.04–7.61 (m, 2H), 7.58–7.33 (m, 2H), 7.27–6.97 (m, 2H), 6.83–6.56 (m, 2H), 4.96 (s, 1H), 3.35 (q, J = 7.17 Hz, 2H), 0.63 (t, J = 7.17 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 174.1, 169.1, 168.1, 141.1, 137.6, 137.4, 131.3, 127.9, 127.7, 125.8, 111.4, 111.1, 82.3, 73.4, 55.6, 34.6, 10.5 ppm; IR (KBr): ν = 3295, 2974, 1715, 1694, 1467, 1378, 1332, 1222, 1175, 1093, 828 cm⁻¹; MS-ESI: m/z = 493 [M + 1]⁺; HRMS (ESI) calc. C₁₉H₁₇O₃N₃IS: 493.21462, found: 493.21493.

(Z)-3-Ethyl-5-(3-hydroxy-5-methyl-2-oxoindolin-3-yl)-2-(phenyl-imino)thiazolidin-4-one (5w). Yield, 83%; 5-methyl isatin (1 mmol), ethylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); brown solid; mp 167–169 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.35 (s, 1H), 7.84 (s, 1H), 7.54–7.28 (m, 2H), 7.23–6.95 (m, 2H), 6.92–6.59 (m, 3H), 4.94 (s, 1H), 3.34 (q, J = 7.17 Hz, 2H), 2.24 (s, 3H), 0.60 (t, J = 7.17 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 174.5, 169.3, 168.0, 138.6, 129.1, 128.8, 127.4, 127.2, 125.6, 125.2, 123.2, 108.5, 108.3, 73.5, 55.5, 34.2, 19.2, 10.1 ppm; IR (KBr): ν = 3296, 2952, 1712, 1674, 1628, 1581, 1472, 1318, 1123 cm⁻¹; MS-ESI: m/z = 382 [M + 1]⁺; HRMS (ESI) calc. C₂₀H₂₀O₃N₃S: 382.11456, found: 382.11501.

(Z)-3-Ethyl-5-(3-hydroxy-5-methoxy-2-oxoindolin-3-yl)-2-(phenylimino)thiazolidin-4-one (5x). Yield, 80%; 5-methoxy isatin (1 mmol), ethylamine (1 mmol), phenylisothiocyanate (1 mmol), ethylbromoacetate (1 mmol) and DABCO (30 mol%) in H₂O (5 mL); white solid; mp 133–135 °C; ¹H NMR (300 MHz, CDCl₃ + DMSO-d₆): δ 10.30 (s, 1H), 7.41–7.14 (m, 3H), 7.05–6.65 (m, 5H), 4.95 (s, 1H), 3.70 (s, 3H), 3.34 (q, J = 7.17 Hz, 2H), 0.62 (t, J = 7.17 Hz, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃ + DMSO-d₆): δ 174.1, 169.1, 167.7, 167.5, 153.0, 134.1, 134.0, 127.2, 126.1, 125.4, 113.3, 109.2, 108.8, 73.4, 55.3, 53.7, 34.0, 10.0 ppm; IR (KBr): ν = 3258, 2934, 1721, 1683, 1493, 1341, 1299, 1209, 1157, 1090, 887 cm⁻¹; MS-ESI: m/z = 398 [M + 1]⁺; HRMS (ESI) calc. C₂₀H₂₀O₄N₃S: 398.11568, found: 398.11591.

Acknowledgements

B M B, G S K and A S thank CSIR-UGC for the award of a fellowship and Dr Ahmed Kamal, Outstanding scientist and Head of MCP Division for his support and encouragement. The authors thank CSIR, New Delhi for financial support as part of XII five year plan programme under title ACT (CSC-0301).

References

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ra24127h

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