Efficient pyrrolidine catalyzed cycloaddition of aziridines with isothiocyanates, isoselenocyanates and carbon disulfide “on water”

Abstract

The cycloaddition of aziridines with isothiocyanates, isoselenocyanates and carbon disulfide has been described using pyrrolidine as catalyst on water at moderate temperature. This protocol features the use of commercial amine as catalyst and water as solvent affording a potential route for the construction of five membered heterocycles in high yields.

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Introduction

Water is the most abundant, cheap, safe and environmentally benign solvent in nature. Development of effective methods for the use of water as a reaction medium for organic synthesis has thus received much attention in recent years.^1–3 The cycloaddition of aziridines with isothiocyanates affords efficient approach for the construction of functionalized five membered heterocycles that are important in biological and medicinal sciences.⁴ For examples, Pd,⁵ Ni,⁶ Fe,^3s Zn,⁷ PBu₃,⁸ NaI,⁹ HBF₄ (ref. 10) and Ph₄SbBr¹¹ based systems have been studied for the reaction of aziridines with carbodiimides, carbon disulfide, isocyanates, isothiocyantes or isoselenocycantes as catalyst or stoichiometric reagents. Herein, we wish to report an efficient pyrrolidine catalyzed cycloaddition reaction of aziridines with isothiocyanates, isoselenocyanates and carbon disulfide on water at moderate temperature under air.¹² The reaction occurs in aqueous suspension via a urea type intermediate affording a potential route for the construction of five membered heterocycles under mild reaction conditions (Scheme 1).

Scheme 1 Amine catalyzed cycloaddition of aziridine with heterocumulenes via urea type intermediate.

Results and discussion

First, the reaction conditions were optimized employing phenyl isothiocyanate (1a) and 1-isopropyl-2-phenylaziridine (2a) as model substrates in the presence of various amine catalysts on water at varied temperature (Table 1). Gratifyingly, the reaction occurred to give the desired thiazolidin-2-ylidene (3a) in 46% yield when the substrates 1a and 2a were stirred with 25 mol% pyrrolidine for 12 h on water at ambient conditions (entry 1). Increasing the reaction temperature to 50 °C led to completion of the process in 6 h with 97% yield (entry 2). In a set of screened amine catalysts, pyrrolidine, morpholine, piperidine, L-proline, N-methylaniline, diisopropylamine, N-Boc pyrrolidine, triethylamine, DBU, NaHCO₃ and K₂CO₃, the former afforded the superior results (entries 2–13). Control experiments confirmed that without the amine catalyst the reaction produced 3a after 12 h in <9% yield (entry 14 and 15).

Table 1 Optimization of the reaction conditions^a

Entry	Catalyst	T (°C)	t (h)	Yield 3a^b (%)
a Reaction conditions. 1a (0.5 mmol), 2a (0.5 mmol), catalyst (25 mol%), H2O (1.0 mL), 50 °C, air.b Determined by 400 MHz ^1H NMR.c 20 mol% of catalyst used. DBU = 1,8-diazabicyclo[5.4.0]-undec-7-ene.
1	Pyrrolidine	28	12	46
2	Pyrrolidine	50	6	97
3	Morpholine	50	6	36
4	Piperidine	50	6	38
5	L-Proline	50	6	75
6	N-Methylaniline	50	6	25
7	Diisopropylamine	50	6	20
8	N-Boc-pyrrolidine	50	6	9
9	Triethylamine	50	6	9
10	DBU	50	6	15
11	NaHCO3	50	6	12
12	K2CO3	50	6	13
13	Pyrrolidine	50	10	86^c
14	—	50	12	9
15	—	28	12	4

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With the optimal conditions in hand, the generality of the protocol was studied for the reactions of a series of substituted isothiocyanates with aziridine 2a (Table 2). The reactions were efficient to afford the target products in high yields. For examples, isothiocyanates 1b–h having 2-methoxy, 2-methyl, 3-fluoro, 4-ethyl, 4-methoxy, 4-methyl and 4-nitro substituents in the phenyl ring underwent reaction to give the heterocycles 3b–h in 69–88% yields. Likewise, the substrates 1i–k bearing 2,4-, 3,4- and 3,5-dimethyl substituents readily underwent reaction to provide the target products 3i–k in 79–85% yields. Furthermore, aliphatic isothiocyanate 1l was compatible affording the target heterocycle 3l in 70% yield. Similarly, 1-naphthyl isothiocyanate 1m underwent reaction to give the desired 3m in 82% yield.

Table 2 Pyrrolidine-catalyzed cycloaddition of substituted isothiocyanates with aziridine 2a^a

Entry	Isothio-cyanate	R	t (h)	Product^b (yield, %)
a Reaction conditions. 1b–m (0.5 mmol), 2a (0.5 mmol), H2O (1.0 mL), 50 °C, air.b Yield of isolated product.
1	1b	2-MeOC6H4	7.0	3b (73)
2	1c	2-MeC6H4	8.5	3c (71)
3	1d	3-FC6H4	5.5	3d (69)
4	1e	4-EtC6H4	9.5	3e (80)
5	1f	4-MeOC6H4	10.5	3f (88)
6	1g	4-MeC6H4	9.5	3g (82)
7	1h	4-NO2C6H4	10.0	3h (75)
8	1i	2,4-Me2C6H3	10.0	3i (79)
9	1j	3,4-Me2C6H3	10.5	3j (81)
10	1k	3,5-Me2C6H3	9.0	3k (85)
11	1l	α-Methylbenzyl	9.5	3l (70)
12	1m	1-Naphthyl	9.0	3m (82)

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Next, the reactions of substituted aziridines 2b–k with isothiocyanate 1b were examined and the results are summarized in Table 3. For examples, aryl aziridines 2b–e having allyl, benzyl, n-butyl and cyclohexyl substituents on the nitrogen atom underwent reaction to give the corresponding cycloaddition products 3n–q in 69–83% yields, whereas 1-tosyl-2-phenyl-aziridine 2f showed no reaction and the starting materials were recovered intact. Furthermore, the substrates 2g–k having electrons donating and electron withdrawing substituents such as 4-bromo, 4-fluoro, 4-methoxy, 4-methyl and 2,4-dimethyl groups readily underwent reaction to furnish the thiazolidin-2-ylidenes 3s–w in 73–89% yields.

Table 3 Pyrrolidine-catalyzed cycloaddition of isothiocyanate 1b with substituted aziridines^a

Entry	Aziridine	R	R′	t (h)	Product^b (yield, %)
a Reaction conditions. 1b (0.5 mmol), 2b–k (0.5 mmol), H2O (1.0 mL), 50 °C, air.b Yield of isolated product. n.d. = not detected.
1	2b	Allyl	Ph	9.5	3n (70)
2	2c	Bn	Ph	10.5	3o (78)
3	2d	n-Bu	Ph	6.5	3p (83)
4	2e	Cyclohexyl	Ph	8.5	3q (69)
5	2f	Ts	Ph	12.0	3r n.d.
6	2g	iPr	4-BrC6H4	9.0	3s (85)
7	2h	iPr	4-FC6H4	10.5	3t (74)
8	2i	iPr	4-MeOC6H4	5.0	3u (89)
9	2j	iPr	4-MeC6H4	6.0	3v (77)
10	2k	iPr	2,4-Me2C6H3	8.5	3w (73)

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Finally, the reactions of isocyanate 4, isoselenocyanates 5a–e and carbon disulfide 6 with aziridines, were investigated (Table 4). However, isocyanate 4 showed no reaction and the starting materials were recovered intact (entry 1). In contrast, isoselenocyanates 5a–e readily underwent reaction with aziridine 2a to afford the target products 8a–e in 80–91% yield. Likewise, carbon disulfide 6 underwent reaction with aziridines 2a, 2g, 2i and 2j to furnish the heterocycles 9a–d in 73–85% yields.

Table 4 Pyrrolidine-catalyzed cycloaddition of isoselenocyanates and carbon disulfide with substituted aziridines^a

Entry	Substrate	X	Y	R	t (h)	Product^b (yield, %)
a Reaction conditions. 4–5 (0.5 mmol) or 6 (2.5 mmol), 2 (0.5 mmol), H2O (1.0 mL), 50 °C, air.b Yield of isolated product. n.d. = not detected.
1	4	N(4-ClC6H4)	O	H	3.5	7 n.d.
2	5a	N(Ph)	Se	H	4.0	8a (91)
3	5b	N(2-MeOC6H4)	Se	H	2.5	8b (80)
4	5c	N(3-MeC6H4)	Se	H	4.5	8c (83)
5	5d	N(4-ClC6H4)	Se	H	3.5	8d (89)
6	5e	N(4-MeOC6H4)	Se	H	6.0	8e (85)
7	6	S	S	H	8.0	9a (73)
8	6	S	S	Br	9.5	9b (85)
9	6	S	S	MeO	5.5	9c (81)
10	6	S	S	Me	7.0	9d (77)

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To reveal the scale up of the process, the reaction of 1g with 2a was studied (Scheme 2). As above, the reaction occurred to afford 3g in 81% yield. This result clearly suggests that the protocol may be employed on the gram scale synthesis of the target heterocycles.

Scheme 2 Gram scale synthesis.

To gain insight into mechanism, optically active aziridines 2aa and 2ab having opposite configurations were reacted with isothiocyanate 1a under the optimized reaction conditions (eqn (1) and (2)). The reactions proceeded readily to yield the target heterocycles with inverted configurations (Scheme 3). These results suggest that the reaction involves S_N2 pathway. The absolute configuration of 3ab was confirmed by single crystal X-ray analysis (Fig. 1). Furthermore, we were able to isolate and characterize the reactive urea type intermediate A when a 1 : 1 mixture of isothiocyanate 1a and pyrrolidine were reacted (Scheme 4). The isolated intermediate A readily underwent reaction with aziridine 2a to give the target product 3a. These results suggest that the reaction of pyrrolidine with heterocumulene can yield the reactive urea type intermediate a that may proceed reaction with aziridine via intermediate b (S_N2) to afford c. The intramolecular cyclization of c may then give the target heterocycles and the catalyst to complete the catalytic cycle (Scheme 5).

Scheme 3 Reaction of chiral aziridines.

Fig. 1 ORTEP diagram of (Z)-N-(3-isopropyl-5-phenylthiazolidin-2-ylidene)aniline (3ab). Thermal ellipsoids are drawn at a 50% probability level.†

Scheme 4 Urea type intermediate.

Scheme 5 Proposed catalytic cycle.

Conclusions

In summary, we have developed an efficient and simple organocatalytic protocol for the (3 + 2)-cycloaddition reaction of isothiocyanates, isoselenocyanates and carbon disulfide with aziridines under mild conditions. The features of this process include the use of commercial pyrrolidine as the catalyst and involvement of urea type intermediate. These studies can open a new further development of the cycloaddition of isothiocyanates, isoselenocyanates and carbon disulfide with a variety of substrates.

Experimental

General information

All reactions were performed in pure water (>5 MΩ cm@25 °C, total organic content < 30 ppb) obtained from Elix water purification system. Amines and alkenes were purchased from Aldrich and used as received. Selenium (99.9%) and amino acids were purchased from SRL. Aziridines¹³ and heterocumulenes^3s were prepared according to the reported procedure. The reactions were monitored by analytical TLC on Merck silica gel G/GF 254 plates. The column chromatography was performed with Rankem silica gel (60–120 mesh). NMR (¹H and ¹³C) spectra were recorded on DRX-400 Varian and Bruker Avance III 600 spectrometers. The data have been accounted as follows: chemical shifts (δ ppm) (multiplicity, coupling constant (Hz), integration). The abbreviations for multiplicity are as follows: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, dd = doublet of doublets. Chemical shifts (δ) are reported relative to residual solvent signals (CHCl₃, 7.24 ppm for ¹H NMR and 77.23 ppm for ¹³C NMR). Melting points were determined with a Büchi B-545 apparatus and are uncorrected. Elemental analyses were recorded using Perkin Elmer CHNS analyzer. Optical rotation was determined by using Perkin Elmer-343 Polarimeter. FT-IR spectra were recorded using Perkin Elmer IR spectrometer. HPLC analysis was carried out using Waters-2489 with Daicel Chiralcel OJ, OJ-H columns using isopropanol and hexane as eluent.

General procedure for the cycloaddition of aziridines with isothiocyanates and isoselenocyanates

Isothiocyanate or isoselenocyanate (0.5 mmol), aziridine (0.5 mmol) and pyrrolidine (0.125 mmol) were stirred in H₂O (1 mL) at 50 °C under air (Tables 1–4). The progress of the reaction was monitored by TLC using ethyl acetate and hexane as eluent. The reaction mixture was then cooled to room temperature and extracted with diethyl ether (3 × 10 mL). The organic layer was washed with water (5 mL). Drying (Na₂SO₄) and evaporation of the solvent on a rotary evaporator gave a residue that was purified on a silica gel column chromatography using hexane and ethyl acetate as eluent.

General procedure for the cycloaddition of aziridines with carbon disulfide

Carbon disulfide (2.5 mmol) was added portion wise for 0.5 h to a stirred solution of aziridine (0.5 mmol) and pyrrolidine (0.125 mmol) were stirred in H₂O (1 mL) at 50 °C under air and the stirring continued for the appropriate time (Table 4). The progress of the reaction was monitored by TLC using ethyl acetate and hexane as eluent. The reaction mixture was then cooled to room temperature and extracted with diethyl ether (3 × 10 mL). The organic layer was washed with water (5 mL). Drying (Na₂SO₄) and evaporated on a rotary evaporator to give a residue that was purified on a silica gel column chromatography using hexane and ethyl acetate as eluent.

(Z)-N-(3-Isopropyl-5-phenylthiazolidin-2-ylidene)aniline 3a. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.60; colorless solid; yield 86% (127 mg); mp 108–109 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.40–7.34 (m, 2H), 7.32–7.22 (m, 5H), 7.02–6.96 (m, 3H), 4.69–4.64 (m, 2H), 3.86 (dd, J = 10.0, 6.8 Hz, 1H), 3.54 (dd, J = 10.0, 7.6 Hz, 1H), 1.27 (d, J = 6.8 Hz, 3H), 1.23 (d, J = 6.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 158.1, 152.3, 139.3, 128.8, 128.2, 127.5, 123.0, 122.2, 52.9, 46.7, 46.3, 20.0, 19.1; FT-IR (KBr) 3075, 3034, 2964, 2934, 2856, 1613, 1584, 1178, 1061, 855, 766 cm⁻¹; anal. calcd for C₁₈H₂₀N₂S: C, 72.93; H, 6.80; N, 9.45; S, 10.82. Found: C, 72.85; H, 6.82; N, 9.48; S, 10.85%. Compound 3aa: [α]²⁰_D = +61.0 (c 0.2 in CHCl₃); HPLC analysis: 76% ee [Daicel CHIRALCEL OJ column, hexane–iPrOH = 85 : 15, flow rate: 1 mL min⁻¹, λ = 215 nm, t_R = 12.72 min (minor), 18.24 min (major)]. Compound 3ab: [α]²⁰_D = −63.0 (c 0.2 in CHCl₃); HPLC analysis: 75% ee [Daicel CHIRALCEL OJ column, hexane–iPrOH = 85 : 15, flow rate: 1 mL min⁻¹, λ = 215 nm, t_R = 12.66 min (major), 17.21 min (minor)].

(Z)-N-(3-Isopropyl-5-phenylthiazolidin-2-ylidene)-2-methoxyaniline 3b. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.54; colorless solid; yield 73% (118 mg); mp 107–108 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.41 (d, J = 8.4 Hz, 2H), 7.32–7.23 (m, 3H), 7.00–6.96 (m, 1H), 6.92–6.90 (m, 1H), 6.86–6.82 (m, 2H), 4.75–4.68 (m, 1H), 4.64 (t, J = 7.2 Hz, 1H), 3.87 (dd, J = 9.6, 7.2 Hz, 1H), 3.80 (s, 3H), 3.54 (dd, J = 9.6, 7.6 Hz, 1H), 1.27 (d, J = 6.8 Hz, 3H), 1.23 (d, J = 6.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 159.1, 151.8, 141.7, 139.6, 128.7, 128.0, 127.5, 123.9, 123.0, 120.7, 111.6, 55.8, 53.2, 46.5, 46.4, 19.9, 19.1; FT-IR (KBr) 3056, 3032, 2973, 2947, 2926, 2867, 1623, 1585, 1493, 1187, 1064, 1024, 747 cm⁻¹; anal. calcd for C₁₉H₂₂N₂OS: C, 69.90; H, 6.79; N, 8.58; S, 9.82. Found: C, 69.98; H, 6.77; N, 8.55; S, 9.84%.

(Z)-N-(3-Isopropyl-5-phenylthiazolidin-2-ylidene)-2-methylaniline 3c. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.58; colorless solid; yield 71% (110 mg); mp 74–75 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.38 (d, J = 7.2 Hz, 2H), 7.32–7.25 (m, 3H), 7.13 (d, J = 7.2 Hz, 1H), 7.07 (t, J = 7.2 Hz, 1H), 6.92 (t, J = 7.6 Hz, 1H), 6.86 (d, J = 7.6 Hz, 1H), 4.68–4.62 (m, 2H), 3.86 (dd, J = 9.6, 6.8 Hz, 1H), 3.54 (dd, J = 9.6, 8.0 Hz, 1H), 2.20 (s, 3H), 1.28 (d, J = 6.8 Hz, 3H), 1.25 (d, J = 6.8 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 157.7, 151.1, 139.6, 130.6, 130.2, 128.9, 128.2, 127.5, 126.4, 123.2, 121.4, 53.3, 46.7, 46.5, 20.0, 19.1, 18.2; FT-IR (KBr) 3058, 3023, 2971, 2929, 2870, 1626, 1591, 1488, 1456, 1401, 1362, 1243, 1212, 1179, 1110, 1066, 939 cm⁻¹; anal. calcd for C₁₉H₂₂N₂S: C, 73.51; H, 7.14; N, 9.02; S, 10.33. Found: C, 73.59; H, 7.13; N, 8.99; S, 10.29%.

(Z)-3-Fluoro-N-(3-isopropyl-5-phenylthiazolidin-2-ylidene)aniline 3d. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.54; colorless solid; yield 69% (108 mg); mp 91–92 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.38–7.36 (m, 2H), 7.32–7.23 (m, 3H), 7.17–7.13 (m, 1H), 6.77–6.74 (m, 1H), 6.72–6.65 (m, 2H), 4.68–4.61 (m, 2H), 3.84 (dd, J = 10.0, 7.2 Hz, 1H), 3.53 (dd, J = 9.6, 7.6 Hz, 1H), 1.25 (d, J = 6.8 Hz, 3H), 1.21 (d, J = 6.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 164.4 (d, ¹J_CF = 243.4 Hz), 158.5, 154.1 (d, ³J_CF = 9.9 Hz), 139.0, 129.9 (d, ³J_CF = 9.9 Hz), 128.9, 128.3, 127.5, 118.0, 109.7 (d, ²J_CF = 16.8 Hz), 109.5 (d, ²J_CF = 17.5 Hz), 52.9, 46.8, 46.4, 20.0, 19.1; FT-IR (KBr) 3061, 3028, 2975, 2925, 2856, 1618, 1588, 1482, 1402, 1254, 1228, 1182, 1126, 1057, 963 cm⁻¹; anal. calcd for C₁₈H₁₉FN₂S: C, 68.76; H, 6.09; N, 8.91; S, 10.20. Found: C, 68.86; H, 6.07; N, 8.89; S, 10.23%.

(Z)-4-Ethyl-N-(3-isopropyl-5-phenylthiazolidin-2-ylidene)aniline 3e. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.56; colorless solid; yield 80% (130 mg); mp 63–64 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.40 (d, J = 7.6 Hz, 2H), 7.33–7.26 (m, 3H), 7.09 (d, J = 8.0 Hz, 2H), 6.91 (d, J = 8.0 Hz, 2H), 4.70–4.63 (m, 2H), 3.85 (dd, J = 10.0, 7.2 Hz, 1H), 3.54 (dd, J = 10.0, 7.6 Hz, 1H), 2.60 (q, J = 7.6 Hz, 2H), 1.27 (d, J = 6.8 Hz, 3H), 1.23–1.18 (m, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 157.9, 149.9, 139.3, 138.6, 128.8, 128.2, 128.1, 127.5, 121.9, 52.9, 46.6, 46.2, 28.3, 20.0, 19.0, 15.7; FT-IR (KBr) 3067, 3020, 2964, 2923, 2861, 1618, 1594, 1504, 1474, 1453, 1404, 1244, 1208, 1194, 1066, 848 cm⁻¹; anal. calcd for C₂₀H₂₄N₂S: C, 74.03; H, 7.46; N, 8.63; S, 9.88. Found: C, 73.93; H, 7.49; N, 8.67; S, 9.91%.

(Z)-N-(3-Isopropyl-5-phenylthiazolidin-2-ylidene)-4-methoxybenzenamine 3f^3s. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.53; colorless liquid; yield 88% (144 mg); ¹H NMR (400 MHz, CDCl₃) δ 7.37–7.35 (m, 2H), 7.31–7.22 (m, 3H), 6.91 (d, J = 9.2 Hz, 2H), 6.79 (d, J = 9.2 Hz, 2H), 4.68–4.60 (m, 2H), 3.83 (dd, J = 9.6, 6.8 Hz, 1H), 3.71 (s, 3H), 3.52 (dd, J = 9.6, 7.6 Hz, 1H), 1.24 (d, J = 6.8 Hz, 3H), 1.21 (d, J = 6.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 158.9, 155.7, 145.4, 139.2, 128.8, 128.1, 127.5, 123.1, 114.1, 55.4, 53.0, 46.7, 46.4, 20.0, 19.1; FT-IR (neat) 3032, 2970, 2934, 2871, 2059, 1870, 1614, 1504, 1455, 1402, 1364, 1290, 1237, 1179, 1126, 1103, 1066, 1035, 937 cm⁻¹; anal. calcd for C₁₉H₂₂N₂OS: C, 69.90; H, 6.79; N, 8.58; S, 9.82. Found: C, 69.98; H, 6.77; N, 8.55; S, 9.84%.

(Z)-N-(3-Isopropyl-5-phenylthiazolidin-2-ylidene)-4-methylbenzenamine 3g^3s. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.55; colorless solid; yield 82% (127 mg); mp 89–90 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.40 (d, J = 8.4 Hz, 2H), 7.33–7.26 (m, 3H), 7.05 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 8.0 Hz, 2H), 4.69–4.62 (m, 2H), 3.84 (dd, J = 9.6, 6.8 Hz, 1H), 3.53 (dd, J = 9.6, 8.0 Hz, 1H), 2.27 (s, 3H), 1.26 (d, J = 6.8 Hz, 3H), 1.22 (d, J = 6.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 158.0, 149.8, 139.3, 132.2, 129.4, 128.8, 128.1, 127.5, 121.9, 52.9, 46.7, 46.3, 21.0, 20.0, 19.1; FT-IR (KBr) 3025, 2971, 2928, 2870, 1624, 1602, 1505, 1470, 1454, 1402, 1363, 1270, 1242, 1212, 1191, 1126, 1106, 1066, 1030, 938 cm⁻¹ anal. calcd for C₁₉H₂₂N₂S: C, 73.51; H, 7.14; N, 9.02; S, 10.33. Found: C, 73.62; H, 7.11; N, 8.98; S, 10.29%.

(Z)-N-(3-Isopropyl-5-phenylthiazolidin-2-ylidene)-4-nitroaniline 3h. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.45; yellow solid; yield 75% (128 mg); mp 68–69 °C; ¹H NMR (400 MHz, CDCl₃) δ 8.12 (d, J = 8.8 Hz, 2H), 7.39–7.28 (m, 5H), 7.04 (d, J = 8.8 Hz, 2H), 4.72 (t, J = 7.6 Hz, 1H), 4.70–4.63 (m, 1H), 3.91 (dd, J = 10.0, 7.2 Hz, 1H), 3.60 (dd, J = 10.0, 8.0 Hz, 1H), 1.27 (d, J = 6.8 Hz, 3H), 1.23 (d, J = 6.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 158.4, 158.3, 142.6, 138.5, 128.8, 128.3, 127.2, 124.8, 122.4, 52.8, 46.8, 46.6, 19.7, 19.1; FT-IR (KBr) 3063, 3038, 2973, 2926, 2869, 2852, 1614, 1571, 1498, 1328, 1218, 1185, 1162, 1108, 1066, 850 cm⁻¹; anal. calcd for C₁₈H₁₉N₃O₂S: C, 63.32; H, 5.61; N, 12.31; S, 9.39. Found: C, 63.40; H, 5.60; N, 12.34; S, 9.36%.

(Z)-N-(3-Isopropyl-5-phenylthiazolidin-2-ylidene)-2,4-dimethylaniline 3i. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.58; colorless solid; yield 79% (128 mg); mp 69–70 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.38 (d, J = 7.2 Hz, 2H), 7.32–7.25 (m, 3H), 6.94 (s, 1H), 6.89 (d, J = 7.6 Hz, 1H), 6.76 (d, J = 7.6 Hz, 1H), 4.68–4.61 (m, 2H), 3.85 (dd, J = 9.2, 7.6 Hz, 1H), 3.52 (t, J = 8.4 Hz, 1H), 2.24 (s, 3H), 2.17 (s, 3H), 1.28 (d, J = 6.8 Hz, 3H), 1.24 (d, J = 6.8 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 157.8, 148.5, 139.7, 132.4, 131.0, 130.2, 128.8, 128.1, 127.5, 126.9, 121.2, 53.2, 46.6, 46.5, 21.0, 19.9, 19.1, 18.1; FT-IR (KBr) 3063, 2967, 2926, 2844, 1626, 1605, 1492, 1470, 1397, 1242, 1206, 1192, 1166, 1117, 1064, 929 cm⁻¹; anal. calcd for C₂₀H₂₄N₂S: C, 74.03; H, 7.46; N, 8.63; S, 9.88. Found: C, 74.13; H, 7.44; N, 8.59; S, 9.84%.

(Z)-N-(3-Isopropyl-5-phenylthiazolidin-2-ylidene)-3,4-dimethylaniline 3j. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.56; colorless solid; yield 81% (131 mg); mp 96–97 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.41 (d, J = 7.6 Hz, 2H), 7.34–7.27 (m, 3H), 7.02 (d, J = 8.0 Hz, 1H), 6.77 (s, 1H), 6.73 (d, J = 8.0 Hz, 1H), 4.71–4.63 (m, 2H), 3.84 (dd, J = 10.0, 6.8 Hz, 1H), 3.53 (dd, J = 9.6, 7.6 Hz, 1H), 2.21 (s, 3H), 2.19 (s, 3H), 1.27 (d, J = 6.8 Hz, 3H), 1.23 (d, J = 6.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 157.8, 150.0, 139.3, 136.8, 130.8, 129.9, 128.7, 128.0, 127.5, 123.4, 119.1, 52.8, 46.6, 46.2, 20.0, 19.9, 19.2, 19.0; FT-IR (KBr) 3060, 3025, 2973, 2852, 1618, 1594, 1493, 1467, 1454, 1234, 1180, 1149, 1060, 966, 827 cm⁻¹; anal. calcd for C₂₀H₂₄N₂S: C, 74.03; H, 7.46; N, 8.63; S, 9.88. Found: C, 74.11; H, 7.44; N, 8.60; S, 9.85%.

(Z)-N-(3-Isopropyl-5-phenylthiazolidin-2-ylidene)-3,5-dimethylbenzenamine 3k. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.58; colorless solid; yield 85% (138 mg); mp 74–75 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.45–7.34 (m, 1H), 7.38–7.31 (m, 5H), 6.72 (d, J = 8.4 Hz, 1H), 6.68 (s, 1H), 4.78–4.71 (m, 1H), 4.68 (t, J = 7.6 Hz, 1H), 3.87 (dd, J = 9.6, 6.8 Hz, 1H), 3.57 (dd, J = 9.6, 8.0 Hz, 1H), 2.33 (s, 6H), 1.32 (d, J = 6.8 Hz, 3H), 1.29 (d, J = 6.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 157.5, 152.0, 139.2, 138.1, 128.7, 128.0, 127.4, 124.6, 119.7, 52.7, 46.6, 46.2, 21.3, 19.9, 18.9; FT-IR (KBr) 3029, 2971, 2927, 2867, 1614, 1455, 1402, 1362, 1289, 1240, 1210, 1143, 1068, 1027, 953 cm⁻¹; anal. calcd for C₂₀H₂₄N₂S: C, 74.03; H, 7.46; N, 8.63; S, 9.88. Found: C, 73.95; H, 7.45; N, 8.67; S, 9.93%.

(Z)-N-(3-Isopropyl-5-phenylthiazolidin-2-ylidene)-1-phenylethanamine 3l. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.49; pale yellow liquid; yield 70% (113 mg); ¹H NMR (400 MHz, CDCl₃) δ 7.42–7.37 (m, 4H), 7.35–7.25 (m, 5H), 7.21–7.16 (m, 1H), 4.63–4.56 (m, 2H), 4.29 (q, J = 6.4 Hz, 1H), 3.69 (dd, J = 9.6, 6.8 Hz, 1H), 3.41 (dd, J = 9.6, 7.2 Hz, 1H), 1.46 (d, J = 6.8 Hz, 3H), 1.18 (d, J = 6.8 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 156.2, 147.2, 140.1, 128.8, 128.1, 128.0, 127.5, 126.5, 126.3, 64.1, 52.7, 46.6, 46.2, 25.9, 19.7, 18.9; FT-IR (neat) 3049, 3029, 2917, 2858, 1633, 1588, 1489, 1451, 1312, 1258, 1183, 1074, 1025, 908 cm⁻¹; anal. calcd for C₂₀H₂₄N₂S: C, 74.03; H, 7.46; N, 8.63; S, 9.88. Found: C, 74.14; H, 7.44; N, 8.59; S, 9.83%.

(Z)-N-(3-Isopropyl-5-phenylthiazolidin-2-ylidene)naphthalen-1-amine 3m. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.56; colorless solid; yield 82% (142 mg); mp 102–103 °C; ¹H NMR (600 MHz, CDCl₃) δ 8.06 (d, J = 3.6 Hz, 1H), 7.69–7.68 (m, 1H), 7.42 (d, J = 7.8 Hz, 1H), 7.35–7.33 (m, 2H), 7.28–7.25 (m, 3H), 7.19 (t, J = 7.2 Hz, 2H), 7.15–7.12 (m, 1H), 6.95 (d, J = 6.6 Hz, 2H), 4.80–4.78 (m, 1H), 4.55 (t, J = 7.2 Hz, 1H), 3.81 (dd, J = 9.6, 6.6 Hz, 1H), 3.49 (dd, J = 9.6, 7.8 Hz, 1H), 1.27 (d, J = 6.6 Hz, 3H), 1.23 (d, J = 6.6 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 158.2, 148.9, 139.4, 134.5, 128.9, 128.2, 127.9, 127.5, 126.0, 125.1, 124.1, 123.0, 116.2, 53.2, 46.8, 46.6, 20.2, 19.4; FT-IR (KBr) 3050, 3020, 2969, 2916, 2870, 2848, 1604, 1568, 1501, 1456, 1386, 1276, 1242, 1215, 1174, 1063, 1038, 926 cm⁻¹; anal. calcd for C₂₂H₂₂N₂S: C, 76.26; H, 6.40; N, 8.08; S, 9.26. Found: C, 76.20; H, 6.41; N, 8.11; S, 9.28%.

(Z)-N-(3-Allyl-5-phenylthiazolidin-2-ylidene)-2-methoxyaniline 3n. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.54; yellow liquid; yield 70% (113 mg); ¹H NMR (400 MHz, CDCl₃) δ 7.40 (d, J = 7.2 Hz, 2H), 7.32–7.26 (m, 3H), 7.00 (t, J = 7.2 Hz, 1H), 6.93 (d, J = 7.2 Hz, 1H), 6.87 (d, J = 6.4 Hz, 2H), 5.99–5.89 (m, 1H), 5.27–5.19 (m, 2H), 4.71 (t, J = 7.2 Hz, 1H), 4.21–4.18 (m, 2H), 3.86–3.84 (m, 1H), 3.81 (s, 3H), 3.57 (t, J = 8.4 Hz, 1H); ¹³C NMR (150 MHz, CDCl₃) δ 159.4, 151.8, 141.4, 139.2, 133.0, 128.7, 128.1, 127.6, 124.1, 122.9, 120.8, 118.0, 111.8, 58.2, 55.9, 49.3, 46.7; FT-IR (neat) 3064, 3025, 3006, 2952, 2924, 2832, 1627, 1586, 1493, 1466, 1453, 1399, 1247, 1173, 1110, 1046, 1027, 1005, 927 cm⁻¹; anal. calcd for C₁₉H₂₀N₂OS: C, 70.34; H, 6.21; N, 8.63; S, 9.88. Found: C, 70.42; H, 6.19; N, 8.60; S, 9.85%.

(Z)-N-(3-Benzyl-5-phenylthiazolidin-2-ylidene)-2-methoxyaniline 3o. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.58; colorless solid; yield 78% (117 mg); mp 87–88 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.46 (d, J = 7.6 Hz, 2H), 7.38–7.35 (m, 4H), 7.31–7.25 (m, 4H), 7.05–7.02 (m, 2H), 7.00–6.91 (m, 2H), 4.90 (d, J = 14.8, 1H), 4.80 (d, J = 14.8, 1H), 4.70 (t, J = 7.6, 1H), 3.88 (s, 3H), 3.78 (dd, J = 10.0, 7.6 Hz, 1H), 3.52 (dd, J = 10.0, 8.4 Hz, 1H); ¹³C NMR (100 MHz, CDCl₃) δ 159.6, 151.9, 141.5, 139.1, 137.2, 128.8, 128.7, 128.6, 128.1, 127.6, 127.5, 124.1, 122.9, 120.9, 111.8, 57.9, 56.0, 50.2, 46.8; FT-IR (KBr) 3080, 3061, 3025, 2990, 2960, 2916, 2867, 1624, 1585, 1493, 1452, 1407, 1360, 1240, 1213, 1152, 1110, 1023, 920 cm⁻¹; anal. calcd for C₂₃H₂₂N₂OS: C, 73.76; H, 5.92; N, 7.48; S, 8.56. Found: C, 73.69; H, 5.94; N, 7.51; S, 8.53%.

(Z)-N-(3-Butyl-5-phenylthiazolidin-2-ylidene)-2-methoxyaniline 3p. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.61; colorless solid; yield 83% (141 mg); mp 71–72 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.41 (d, J = 7.6 Hz, 2H), 7.33–7.26 (m, 3H), 7.02–6.98 (m, 1H), 6.94 (d, J = 7.2 Hz, 1H), 6.87 (t, J = 6.4 Hz, 2H), 4.67 (t, J = 7.6 Hz, 1H), 3.88 (dd, J = 9.2, 6.8 Hz, 1H), 3.81 (s, 3H), 3.63–3.57 (m, 3H), 1.68–1.63 (m, 2H), 1.42 (q, J = 7.6 Hz, 2H), 0.97 (t, J = 7.2 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 159.2, 151.8, 141.8, 139.5, 128.7, 128.0, 127.5, 123.9, 123.0, 120.7, 111.7, 58.6, 55.8, 46.7, 46.2, 29.3, 20.2, 14.0; FT-IR (KBr) 3064, 3001, 2956, 2924, 2857, 2829, 1628, 1582, 1495, 1457, 1403, 1293, 1248, 1225, 1176, 1101, 1046, 1027, 988 cm⁻¹; anal calcd for C₂₀H₂₄N₂OS: C, 70.55; H, 7.10; N, 8.23; S, 9.42. Found: C, 70.65; H, 7.09; N, 8.20; S, 9.38%.

(Z)-N-(3-Cyclohexyl-5-phenylthiazolidin-2-ylidene)-2-methoxyaniline 3q. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.59; yellow liquid; yield 69% (126 mg); ¹H NMR (400 MHz, CDCl₃) δ 7.41 (d, J = 7.2 Hz, 2H), 7.32–7.26 (m, 3H), 7.00 (t, J = 7.2 Hz, 1H), 6.93 (d, J = 7.2 Hz, 1H), 6.88–6.85 (m, 2H), 4.61 (t, J = 6.8 Hz, 1H), 4.36–4.31 (m, 1H), 3.91 (t, J = 8.8 Hz, 1H), 3.81 (s, 3H), 3.59 (t, J = 8.0 Hz, 1H), 2.03–1.65 (m, 5H), 1.48–1.06 (m, 5H); ¹³C NMR (100 MHz, CDCl₃) δ 159.3, 151.8, 141.8, 139.8, 128.7, 128.0, 127.4, 123.9, 123.3, 120.8, 111.8, 55.9, 54.5, 54.3, 46.6, 30.5, 29.7, 25.8, 25.7, 25.6; FT-IR (neat) 3060, 3020, 2937, 2851, 2829, 1628, 1583, 1493, 1466, 1401, 1302, 1231, 1173, 1111, 1046, 1028, 910, 891, 806 cm⁻¹; anal. calcd for C₂₂H₂₆N₂OS: C, 72.09; H, 7.15; N, 7.64; S, 8.75. Found: C, 72.00; H, 7.13; N, 7.66; S, 8.71%.

(Z)-N-(5-(4-Bromophenyl)-3-isopropylthiazolidin-2-ylidene)-2-methoxyaniline 3s. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.57; colorless solid; yield 85% (172 mg); mp 79–80 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.44 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.01–6.98 (m, 1H), 6.92–6.85 (m, 3H), 4.73–4.70 (m, 1H), 4.56 (t, J = 6.8 Hz, 1H), 3.87 (dd, J = 10.0, 7.2 Hz, 1H), 3.81 (s, 3H), 3.50 (dd, J = 9.2, 6.4 Hz, 1H), 1.28 (d, J = 6.8 Hz, 3H), 1.22 (d, J = 6.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 158.8, 151.7, 141.6, 139.1, 131.8, 129.2, 124.1, 123.0, 121.9, 120.8, 111.7, 55.9, 53.2, 46.5, 45.8, 19.7, 19.3; FT-IR (KBr) 3050, 3004, 2968, 2927, 2845, 2823, 1627, 1585, 1490, 1467, 1399, 1275, 1260, 1235, 1177, 1110, 1061, 934 cm⁻¹; anal. calcd for C₁₉H₂₁BrN₂OS: C, 56.30; H, 5.22; N, 6.91; S, 7.91. Found: C, 56.38; H, 5.20; N, 6.89; S, 7.87%.

(Z)-N-(5-(4-Fluorophenyl)-3-isopropylthiazolidin-2-ylidene)-2-methoxyaniline 3t. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.55; colorless solid; yield 74% (127 mg); mp 120–121 °C; ¹H NMR (600 MHz, CDCl₃) δ 7.40–7.38 (m, 2H), 7.02–6.99 (m, 3H), 6.92 (dd, J = 8.4, 1.2 Hz, 1H), 6.87–6.85 (m, 2H), 4.74–4.72 (m, 1H), 4.62 (t, J = 6.6 Hz, 1H), 3.87 (dd, J = 9.6, 6.6 Hz, 1H), 3.82 (s, 3H), 3.51 (dd, J = 9.6, 7.2 Hz, 1H), 1.28 (d, J = 6.6 Hz, 3H), 1.23 (d, J = 6.6 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 163.7, 161.2 (d, ¹J_CF = 215.3 Hz), 151.8, 141.6, 135.7, 135.6, 129.3 (d, ³J_CF = 8.0 Hz), 124.1, 123.1, 120.9, 115.8 (d, ²J_CF = 21.3 Hz), 111.8, 56.0, 53.5, 46.5, 45.9, 19.9, 19.3; FT-IR (KBr) 3053, 3034, 2965, 2927, 2861, 2834, 1625, 1585, 1510, 1493, 1466, 1240, 1224, 1174, 1114, 1026, 939 cm⁻¹; anal. calcd for C₁₉H₂₁FN₂OS: C, 66.25; H, 6.15; N, 8.13; S, 9.31. Found: C, 66.32; H, 6.13; N, 8.16; S, 9.35%.

(Z)-N-(3-Isopropyl-5-(4-methoxyphenyl)thiazolidin-2-ylidene)-2-methoxyaniline 3u. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.51; yellow liquid; yield 89% (159 mg); ¹H NMR (600 MHz, CDCl₃) δ 7.34 (d, J = 8.4 Hz, 2H), 7.01 (t, J = 7.2 Hz, 1H), 6.95 (d, J = 7.2 Hz, 1H), 6.87–6.83 (m, 4H), 4.76–4.72 (m, 1H), 4.64 (t, J = 7.2 Hz, 1H), 3.86 (dd, J = 10.2, 7.2 Hz, 1H), 3.81 (s, 3H), 3.79 (s, 3H), 3.54 (dd, J = 9.6, 7.8 Hz, 1H), 1.29 (d, J = 6.6 Hz, 3H), 1.25 (d, J = 6.6 Hz, 3H); ¹³C NMR (150 MHz, CDCl₃) δ 159.5, 152.1, 131.4, 128.8, 124.3, 123.4, 120.9, 120.8, 114.2, 111.9, 56.1, 55.5, 53.8, 46.7, 46.4, 20.1, 19.2; FT-IR (neat) 3061, 2969, 2932, 2834, 1623, 1585, 1512, 1493, 1463, 1355, 1254, 1177, 1029, 928 cm⁻¹; anal. calcd for C₂₀H₂₄N₂O₂S: C, 67.38; H, 6.79; N, 7.86; S, 8.99. Found: C, 67.30; H, 6.81; N, 7.83; S, 9.03%.

(Z)-N-(3-Isopropyl-5-(p-tolyl)thiazolidin-2-ylidene)-2-methoxyaniline 3v. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.56; colorless solid; yield 77% (131 mg); mp 117–118 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.29 (d, J = 8.0 Hz, 2H), 7.11 (d, J = 7.6 Hz, 2H), 6.98 (t, J = 6.8 Hz, 1H), 6.91 (d, J = 6.8 Hz, 1H), 6.85 (d, J = 6.8 Hz, 2H), 4.72–4.69 (m, 1H), 4.61 (t, J = 6.8 Hz, 1H), 3.84 (dd, J = 9.6, 7.2 Hz, 1H), 3.80 (s, 3H), 3.51 (dd, J = 9.2, 8.0 Hz, 1H), 2.30 (s, 3H), 1.26 (d, J = 6.8 Hz, 3H), 1.22 (d, J = 6.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 159.5, 151.9, 141.7, 137.9, 136.5, 129.5, 127.5, 124.0, 123.1, 120.8, 111.8, 56.0, 53.5, 46.6, 46.5, 21.2, 20.0, 19.2; FT-IR (KBr) 3040, 3009, 2973, 2923, 2848, 2834, 1629, 1586, 1492, 1469, 1450, 1402, 1260, 1236, 1220, 1180, 1158, 1111, 1062, 1045, 1025, 820 cm⁻¹; anal. calcd for C₂₀H₂₄N₂OS: C, 70.55; H, 7.10; N, 8.23; S, 9.42. Found: C, 70.65; H, 7.09; N, 8.20; S, 9.38%.

(Z)-N-(5-(2,4-Dimethylphenyl)-3-isopropylthiazolidin-2-ylidene)-2-methoxyaniline 3w. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.57; colorless solid; yield 73% (129 mg); mp 84–85 °C; ¹H NMR (600 MHz, CDCl₃) δ 7.52 (d, J = 7.8 Hz, 1H), 7.03–6.98 (m, 2H), 6.95 (s, 1H), 6.93 (d, J = 7.8 Hz, 1H), 6.87 (d, J = 7.8 Hz, 2H), 4.88 (t, J = 7.2 Hz, 1H), 4.76–4.74 (m, 1H), 3.85 (dd, J = 9.6, 7.2 Hz, 1H), 3.82 (s, 3H), 3.57 (dd, J = 9.6, 7.8 Hz, 1H), 2.29 (s, 3H), 2.28 (s, 3H), 1.30 (d, J = 6.6 Hz, 3H), 1.27 (d, J = 6.6 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 159.5, 151.9, 141.7, 137.5, 135.5, 134.4, 131.3, 127.3, 126.7, 123.9, 123.1, 120.8, 111.7, 55.9, 52.1, 46.5, 42.3, 21.1, 19.9, 19.6, 19.2; FT-IR (KBr) 3058, 2970, 2924, 2859, 2831, 1624, 1585, 1493, 1464, 1402, 1362, 1257, 1236, 1177, 1113, 1046, 1028, 934 cm⁻¹; anal. calcd for C₂₁H₂₆N₂OS: C, 71.15; H, 7.39; N, 7.90; S, 9.04. Found: C, 71.22; H, 7.37; N, 7.93; S, 9.00%.

(Z)-N-(3-Isopropyl-5-phenyl-1,3-selenazolidin-2-ylidene)benzenamine 8a^3s. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.67; yellow liquid; yield 91% (156 mg); ¹H NMR (400 MHz, CDCl₃) δ 7.41 (d, J = 7.2 Hz, 2H), 7.31–7.22 (m, 5H), 7.01 (t, J = 7.2 Hz, 1H), 6.96 (d, J = 7.2 Hz, 2H), 4.78–4.72 (m, 2H), 3.85 (dd, J = 10.4, 6.4 Hz, 1H), 3.65 (dd, J = 10.4, 8.0 Hz, 1H), 1.26 (t, J = 6.8 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 155.8, 153.1, 140.0, 128.5, 128.3, 127.4, 127.2, 122.8, 121.3, 53.4, 46.8, 41.6, 19.6, 19.0; FT-IR (neat) 3058, 3027, 2971, 2929, 2869, 1614, 1590, 1489, 1454, 1402, 1363, 1243, 1205, 1185, 1163, 1126, 1069, 1024 cm⁻¹; anal. calcd for C₁₈H₂₀N₂Se: C, 62.97; H, 5.87; N 8.16. Found: C, 63.07; H, 5.83; N, 8.19%.

((Z)-N-(3-Isopropyl-5-phenyl-1,3-selenazolidin-2-ylidene)-2-methoxybenzenamine 8b^3s. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.60; colorless solid; yield 80% (149 mg); mp 107–108 °C; ¹H NMR (400 MHz, CDCl₃) δ 7.40 (d, J = 7.6 Hz, 2H), 7.27–7.18 (m, 3H), 6.99 (t, J = 8.0 Hz, 1H), 6.93 (d, J = 7.2 Hz, 1H), 6.84 (t, J = 7.6 Hz, 2H), 4.83–4.80 (m, 1H), 4.72 (t, J = 7.2 Hz, 1H), 3.83 (dd, J = 10.4, 6.4 Hz, 1H), 3.76 (s, 3H), 3.63 (dd, J = 10.4, 7.6 Hz, 1H), 1.26 (t, J = 7.6 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 157.2, 151.6, 142.7, 140.2, 128.4, 127.5, 127.4, 123.9, 122.0, 120.6, 111.5, 55.6, 54.0, 47.1, 41.8, 19.8, 19.1; FT-IR (KBr) 3026, 2970, 2923, 2870, 1623, 1586, 1493, 1464, 1400, 1363, 1236, 1204, 1184, 1112, 1047, 1027 cm⁻¹; anal. calcd for C₁₉H₂₂N₂OSe: C, 61.12; H, 5.94; N, 7.50. Found: C, 61.19; H, 5.90; N, 7.47%.

(Z)-N-(3-Isopropyl-5-phenyl-1,3-selenazolidin-2-ylidene)-3-methylbenzenamine 8c^3s. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.62; colorless liquid; yield 83% (148 mg); ¹H NMR (400 MHz, CDCl₃) δ 7.40 (d, J = 7.2 Hz, 2H), 7.29–7.19 (m, 3H), 7.14 (t, J = 7.6 Hz, 1H), 6.85–6.80 (m, 3H), 4.81–4.77 (m, 1H), 4.72 (t, J = 6.8 Hz, 1H), 3.80 (dd, J = 10.4, 6.4 Hz, 1H), 3.62 (dd, J = 10.4, 8.0 Hz, 1H), 2.30 (s, 3H), 1.28 (d, J = 4.8 Hz, 3H), 1.26 (d, J = 4.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 156.0, 153.2, 140.1, 138.3, 128.5, 127.6, 127.5, 123.8, 122.3, 118.3, 53.6, 47.0, 41.8, 21.3, 19.9, 19.2; FT-IR (neat) 3030, 2971, 2927, 2862, 1613, 1593, 1455, 1400, 1362, 1282, 1207, 1185, 1069 cm⁻¹; anal. calcd for C₁₉H₂₂N₂Se: C, 63.86; H, 6.21; N, 7.84. Found: C, 63.87; H, 6.23; N, 7.80%.

(Z)-4-Chloro-N-(3-isopropyl-5-phenyl-1,3-selenazolidin-2-ylidene)benzenamine 8d^3s. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.58; yellow liquid; yield 89% (168 mg); ¹H NMR (400 MHz, CDCl₃) δ 7.39 (d, J = 8.0 Hz, 2H), 7.30–7.22 (m, 3H), 7.18 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 8.4 Hz, 2H), 4.78–4.68 (m, 2H), 3.84 (dd, J = 10.4, 6.8 Hz, 1H), 3.65 (dd, J = 10.4, 8.0 Hz, 1H), 1.24 (t, J = 6.4 Hz, 6H); ¹³C NMR (100 MHz, CDCl₃) δ 156.8, 151.8, 139.8, 128.7, 128.6, 128.0, 127.8, 127.4, 123.0, 53.8, 47.2, 42.2, 19.8, 19.2; FT-IR (neat) 3061, 3029, 2972, 2930, 2870, 1614, 1585, 1485, 1404, 1364, 1274, 1243, 1205, 1185, 1162, 1088, 1068, 1009 cm⁻¹; anal. calcd for C₁₈H₁₉ClN₂Se: C, 57.23; H, 5.07; N, 7.42. Found: C, 57.31; H, 5.08; N, 7.39%.

(Z)-N-(3-Isopropyl-5-phenyl-1,3-selenazolidin-2-ylidene)-4-methoxybenzenamine 8e^3s. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.57; yellow liquid; yield 85% (159 mg); ¹H NMR (400 MHz, CDCl₃) δ 7.44 (d, J = 7.2 Hz, 2H), 7.33–7.25 (m, 3H), 6.97 (d, J = 7.2 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 4.82–4.75 (m, 2H), 3.86 (dd, J = 10.4, 6.4 Hz, 1H), 3.73 (s, 3H), 3.67 (dd, J = 10.4, 7.6 Hz, 1H), 1.31 (d, J = 4.8 Hz, 3H), 1.29 (d, J = 4.4 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 156.8, 155.7, 146.8, 140.2, 128.6, 127.6, 127.5, 122.3, 113.9, 55.1, 53.7, 47.1, 41.8, 19.8, 19.2; FT-IR (neat) 3031, 2971, 2870, 2833, 1614, 1504, 1464, 1401, 1363, 1294, 1239, 1205, 1185, 1067, 1035, 981 cm⁻¹; anal. calcd for C₁₉H₂₂N₂OSe: C, 61.12; H, 5.94; N, 7.50. Found: C, 61.05; H, 5.96; N, 7.54%.

3-Isopropyl-5-phenylthiazolidine-2-thione 9a. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.56; colorless liquid; yield 73% (87 mg); ¹H NMR (400 MHz, CDCl₃) δ 7.36–7.25 (m, 5H), 5.21–5.14 (m, 1H), 4.79 (dd, J = 7.6, 6.8 Hz, 1H), 4.28 (dd, J = 11.6, 8.4 Hz, 1H), 3.94 (dd, J = 11.6, 6.8 Hz, 1H), 1.25 (d, J = 6.8 Hz, 3H), 1.19 (d, J = 6.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 194.7, 138.9, 129.1, 128.5, 127.2, 58.4, 49.6, 47.2, 19.6, 19.2; FT-IR (neat) 3056, 3031, 2972, 2930, 2873, 1668, 1601, 1472, 1430, 1367, 1300, 1275, 1239, 1201, 1184, 1076, 1029, 973 cm⁻¹; anal. calcd for C₁₂H₁₅NS₂: C, 60.72; H, 6.37; N, 5.90; S, 27.02. Found: C, 60.63; H, 6.38; N, 5.93; S, 27.06%.

5-(4-Bromophenyl)-3-isopropylthiazolidine-2-thione 9b. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.52; colorless solid; yield 85% (134 mg); mp 69–70 °C; ¹H NMR (400 MHz, CDCl₃) 7.46 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 5.18–5.11 (m, 1H), 4.71 (dd, J = 8.0, 6.4 Hz, 1H), 4.26 (dd, J = 11.6, 8.4 Hz, 1H), 3.87 (dd, J = 11.6, 6.4 Hz, 1H), 1.23 (d, J = 7.2 Hz, 3H), 1.17 (d, J = 6.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 194.1, 138.1, 132.1, 128.8, 122.3, 58.2, 49.6, 46.4, 19.4, 19.2; FT-IR (KBr) 3042, 2970, 2923, 2867, 1663, 1610, 1582, 1510, 1481, 1432, 1369, 1301, 1241, 1199, 1182, 1072, 1029, 1008, 823 cm⁻¹; anal. calcd for C₁₂H₁₄BrNS₂: C, 45.57; H, 4.46; N, 4.43; S, 20.28. Found: C, 45.65; H, 4.44; N, 4.40; S, 20.32%.

3-Isopropyl-5-(4-methoxyphenyl)thiazolidine-2-thione 9c. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.40; colorless solid; yield 81% (108 mg); mp 62–63 °C; ¹H NMR (400 MHz, CDCl₃) 7.27 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 5.23–5.13 (m, 1H), 4.74 (t, J = 8.0 Hz, 1H), 4.22 (dd, J = 11.6, 8.0 Hz, 1H), 3.88 (dd, J = 11.6, 6.8 Hz, 1H), 3.77 (s, 3H), 1.24 (d, J = 6.8 Hz, 3H), 1.18 (d, J = 6.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 194.3, 159.3, 130.5, 128.2, 114.7, 58.3, 55.1, 49.3, 46.5, 19.3, 19.0; FT-IR (KBr) 3009, 2975, 2948, 2925, 2898, 2828, 1662, 1607, 1509, 1480, 1465, 1433, 1369, 1303, 1280, 1250, 1200, 1175, 1075, 1033, 831 cm⁻¹; anal. calcd for C₁₃H₁₇NOS₂: C, 58.39; H, 6.41; N, 5.24; S, 23.98. Found: C, 58.50; H, 6.40; N, 5.21; S, 23.94%.

3-Isopropyl-5-(p-tolyl)thiazolidine-2-thione 9d. Analytical TLC on silica gel, 1 : 9 ethyl acetate–hexane R_f = 0.49; colorless liquid; yield 77% (97 mg); ¹H NMR (400 MHz, CDCl₃) 7.25 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 7.6 Hz, 2H), 5.20–5.13 (m, 1H), 4.77 (t, J = 8.0 Hz, 1H), 4.26 (dd, J = 11.6, 8.4 Hz, 1H), 3.91 (dd, J = 11.6, 6.8 Hz, 1H), 2.31 (s, 3H), 1.24 (d, J = 6.8 Hz, 3H), 1.19 (d, J = 6.8 Hz, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 194.6, 138.2, 135.7, 129.6, 127.0, 58.3, 49.5, 46.9, 21.0, 19.5, 19.1; FT-IR (neat) 3017, 2972, 2927, 2873, 1654, 1610, 1512, 1472, 1431, 1360, 1297, 1239, 1185, 1076, 1036, 816 cm⁻¹; anal. calcd for C₁₃H₁₇NS₂: C, 62.11; H, 6.82; N, 5.57; S, 25.50. Found: C, 62.21; H, 6.80; N, 5.54; S, 25.45%.

N-Phenylpyrrolidine-1-carbothioamide A¹⁴. Phenyl isothiocyanate (0.5 mmol) and pyrrolidine (0.5 mmol) were stirred in H₂O (1 mL) for 3 h at 50 °C under air. Then, the reaction mixture was then cooled to room temperature and extracted with dichloromethane (3 × 10 mL). The organic layer was washed with water (5 mL). Drying (Na₂SO₄) and evaporated on a rotary evaporator to give a colorless solid; yield 95% (98 mg); mp 121–122 °C; ¹H NMR (400 MHz, CDCl₃) 7.34–7.30 (m, 4H), 7.19–7.16 (m, 1H), 6.91 (s, 1H), 3.66 (s, 4H), 2.01 (s, 4H); ¹³C NMR (100 MHz, CDCl₃) δ 177.9, 139.4, 128.4, 125.8, 125.6, 52.2, 25.7; FT-IR (KBr) 3249, 3038, 2953, 2933, 2867, 1593, 1538, 1496, 1459, 1407, 1342, 1356, 1302, 1291, 1222, 949, 854, 725, 696 cm⁻¹; anal. calcd for C₁₈H₂₀N₂S: C, 64.04; H, 6.84; N, 13.58; S, 15.54. Found: C, 64.12; H, 6.82; N, 13.55; S, 15.51%.

Acknowledgements

We thank Science and Engineering Research Board (SR/S1/OC-55/2011) and Council of Scientific and Industrial Research (02(0088)/12/EMR-II) for financial Support. M.S. is grateful to UGC, New Delhi, for SRF fellowship. Central instruments facility (CIF) IIT Guwahati, for NMR analysis is thankfully acknowledged.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available: NMR (¹H, ¹³C) spectra of the products. CCDC 1025804. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4ra08902b

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