A facile strategy for the annulation of 2-phenylsulfonyl methylene thiazolidin-4-one via multicomponent reactions

Cevher Altuğ; Esra Caner

doi:10.1016/j.crci.2012.11.002

Résumé

An efficient synthesis of 5-amino-7-aryl-3-oxo-8-(phenylsulfonyl)-thiazolo[3,2-a]pyridine-6-carbonitriles was conducted utilizing multicomponent condensation reaction of malononitrile, aromatic aldehydes and 2-phenylsulfonylmethylenethiazolidin-4-one in one pot. Depending on the equivalence of the aldehyde, two different products were obtained from moderate to excellent yields. Thirteen novel structures were characterized by physical and spectroscopic methods (m.p., Rf, IR, NMR and mass analysis).

Supplementary Materials:
Supplementary material for this article is supplied as a separate file:

mmc1.doc

1 Introduction

The chemistry of 2-alkylidenethiazolidin-4-one compounds has been extensively studied over the years. These compounds can be used for the synthesis of diverse functionalized molecules, depending on the substituent of the alkylidene part [1], and scaffolds prepared using these compounds have shown to exhibit various biological properties [2]. However, the synthetic applications of 2-phenylsulfonylmethylenethiazolidin-4-one are rare in the literature comparing to those of 2-alkylidenethiazolidin-4-ones [3]. This has encouraged us to investigate this substituent in multicomponent reactions, since phenylsulfonyl substituent increases biological activity in some heterocyclic compounds [4].

Multicomponent reactions (MCRs) play a significant role to synthesize complex molecules [5] by reacting at least three reagents in one pot. Mild reaction conditions and easy purification steps attracted attention to these kinds of reactions, and placed them into one of the green chemistry routes [6]. Recently, we have reported the multicomponent reactions of 2-nitromethylenethiazolidine with various active methylene, containing nitriles and a broad range of aldehydes [7]. In continuation of our interest in heterocyclic enamine chemistry [8], we now report multicomponent reactions of 2-phenylsulfonylmethylenethiazolidin-4-one with various aromatic aldehydes and malonitrile. We found that two different products could be obtained depending on the equivalence of the aldehyde.

2 Results and discussion

2-Phenylsulfonylmethylenethiazolidin-4-one was prepared according to a literature procedure [3a], and identified by means of m.p., IR, ¹H and ¹³C NMR. After reviewing related alkylidenethiazolidin-4-ones and alkylidenepyrrolidine ester and nitrile geometries in previous publications [9], we have decided to draw the double bond geometry of the starting compound 1 Z isomer rather than E isomer. Multicomponent reactions of 2-phenylsulfonylmethylene thiazolidin-4-one with malonitrile and aromatic aldehydes were performed in anhydrous acetonitrile at reflux temperature, and monitored by thin layer chromatography (TLC). After 1 h, no 2-phenylsulfonylmethylene thiazolidin-4-one remained on the TLC plate, which is indicative of the completion of reaction. The reactions proceeded rapidly and afforded the corresponding thiazolopyridin-4-ones 4a–f and benzylidene thiazolopyridin-4-ones 5a–g in high yields. The results shown in Tables 1 and 2 clearly indicate the scope and generality of the reaction with respect to aldehydes and malononitrile. The reactions worked efficiently with a variety of aldehydes including both electron-releasing and hetero-aromatic groups. Additionally, aforementioned reactions were also performed in water as a solvent and without use of solvent via solid state reaction. In both cases desired products were not obtained.


Compound	R	Yield/%
4a	C₆H₅	73
4b	4-NCC₆H₄	84
4c	4-ClC₆H₄	74
4d	2,6-DiClC₆H₃	86
4e	2,4-DiClC₆H₃	68
4f	4-O₂NC₆H₄	71


Compound	R	Yield/%
5a	4-ClC₆H₄	68
5b	4-FC₆H₄	62
5c	4-NCC₆H₄	64
5d	3-BrC₆H₄	73
5e	2,4-DiMeOC₆H₃	69
5f	4-HO-3,5-DiMeOC₆H₂	81
5g	3-Thienyl	80

The reactions (Tables 1 and 2) proceed through the Knoevenagel condensation of the aldehyde with malononitrile, and then the addition of benzylidenemalononitrile 6 to enamine 1 followed by secondary amine attacks to one of nitrile on benzylidenemalononitrile 6 ends with ring cyclization. In our previous work, when 2-alkylidenethiazolin reacted with 2-phenylsulfonylacetonitrile and aldehyde, a mixture of enamine 4, and imine 8 tautomers was obtained [7]. In the present work, we obtained compound 4 as a sole product (Scheme 1).

Scheme 1
Possible reaction mechanism for the formation of compounds 4.

When two equivalents of aldehyde were used, benzylidene substituted 5-amino-7-aryl-3-oxo-8-(phenylsulfonyl)-thiazolo[3,2-a]pyridine-6-carbonitriles were observed in moderate to high yields as shown in Table 2. It was also found that there was no direct effect of the stoichiometric amount of Et₃N as a base to the MCR yield of 2-phenylsulfonylmethylene thiazolidin-4-one with malononitrile and aldehyde.

In infrared spectra of compounds 4a–f and 5a–g, sulfone groups showed two strong bands due to asymmetric stretching at ca. 1307–1329 cm⁻¹ and symmetric stretching at ca. 1144–1154 cm⁻¹. Bands at ca. 3312–3439 cm⁻¹ are ascribed to NH₂ groups. Stretching vibrations of carbonyl groups appeared at ca. 1658–1743 cm⁻¹ and distinct cyano peaks were observed at ca. 2189–2201 cm⁻¹. The ¹H and ¹³C NMR spectra of compounds 4a–f and 5a–g were recorded in d₆-DMSO and gave good results, although the peak due to adventitious water in the d₆-DMSO obscured the one of OCH₃ resonance in compound 5f in one case, the resulting proton, carbon NMR spectra as well as HRMS confirmed the expected structure 5f. The signals due to the NH₂ protons appeared at ca. δ 7.08–7.55 ppm, but in some cases (compounds 4c, 5g, 5b) NH₂ proton resonances overlapped with aromatic protons and they were not easily detectable. The chemical shifts of 4a–f CHAr protons showed remarkable differences (δ 5.02–5.92 ppm) compared with CHAr protons 5a–f (δ 4.49–4.70 ppm) due to the substitution of the benzylidene groups on the thiazoline fused to pyridine ring. Carbonyl carbons of compounds 5a–g showed more deshielded peaks than that of the compounds 4a–f due to electron-withdrawing effects of the benzylidene group next to carbonyl group in compounds 5a–g. In mass spectra of compounds 5e and 5f, loss of M-Ar peaks 25 and 15% were obtained, respectively.

3 Conclusion

In summary, we have achieved the synthesis of thirteen novel phenylsulfonyl substitute thiazolopyridin-4-ones via multicomponent reactions and identified these compounds by means of spectroscopic methods.

4 Experimental

4.1 General

Infrared spectra were recorded on a SHIMADZU FTIR-8400S instrument (KBr disc). Mass spectra were recorded on a Fisons VG Platform II spectrometer and on a Micromass Q-TOF Micro spectrometer. NMR spectra were recorded on a Bruker DPX 400 spectrometer operating at 400 MHz for ¹H and at 100 MHz for ¹³C at 25 °C. All chemical shifts are reported in ppm downfield from TMS. Coupling constants (J) are reported in Hz. Melting points were determined on a MELTEMP apparatus and uncorrected. TLC was performed using pre-coated plates with fluorescent indicator (Merck 5735). The stain solutions of permanganate and PMBA were used for visualization of the TLC spots.

4.2 2-Phenylsulfonylmethylenethiazolidin-4-one (1)

Phenylsulfonylacetonitrile (20 mmol, 3.624 g) and mercaptoacetic acid (20 mmol, 1.842 g) were mixed in pyridine (15 mL) in a round-bottomed flask and refluxed at 115 °C for overnight. After cooling, pyridine was removed by evaporation, and the residue was applied for column chromatography (EtOAc/Hexane: 1/3).

Obtained as yellow solid (3.2 g, 63%), m.p. 120–122 °C. υ_max, cm⁻¹ (KBr) 3101 (NH₂), 1735 (CO), 1589 (C = C), 1301 (SO₂), 1138 (SO₂). δ_H (400 MHz, DMSO-d₆) 10.1 (br s, 1H, NH), 7.89 (d, 2H, J = 7.1 Hz, aromatic CH), 7.64 (t, 1H, J = 7.4 Hz, aromatic CH), 7.57 (t, 2H, J = 7.4, 7.1 Hz, aromatic CH), 5.36 (s, 1H, CH = C), 3.80 (s, 2H, CH₂S). δ_C (100 MHz; DMSO-d₆) 171.6, 152.2, 142.2, 133.3, 129.4, 126.6, 96.1, 77.3, 77.0, 76.8, 31.2.

4.3 General reaction procedure for preparation of thiazolo[3,2-a]pyridin-4-ones

Aromatic aldehyde (1 mmol, 1.0 equiv for compounds 4a–f, 2 mmol, 2.0 equiv for compounds 5a–g), 2-phenylsulfonylmethylenethiazolidine (1 mmol, 1 equiv, 255 mg) and malononitrile (1 mmol, 1.0 equiv, 66 mg) were mixed in MeCN (10 mL) in a round-bottomed flask, and the reaction mixture was stirred and heated. Triethylamine (50 mg, 0.5 mmol) was added and the reaction mixture was heated under reflux for 1 h (Tables 1 and 2). After cooling, the solvent was removed under reduced pressure, and the residue recrystallised from hexane/ethyl acetate mixtures to give the pure products with data given below.

4.4 5-Amino-3-oxo-7-phenyl-8-(phenylsulfonyl)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (4a)

Obtained as yellow solid (300 mg, 73%), m.p. 229–230 °C. υ_max, cm⁻¹ (KBr) 3416 (NH₂), 2189 (CN), 1701 (CO), 1647 (C = C), 1307 (SO₂), 1153 (SO₂). HRMS: requires for C₂₀H₁₅N₃O₃S₂ [M⁺] 409.0555, found M⁺, 409.0558. δ_H (400 MHz, DMSO-d₆) 7.79–7.70 (m, 3H, aromatic CH of SO₂Ph), 7.61 (t, J = 7.7 Hz, 2H, aromatic CH of SO₂Ph), 7.38 (t, J = 7.4 Hz, 2H, aromatic CH), 7.30 (t, J = 7.3 Hz, 2H, aromatic CH), 7.20 (d, J = 7.0 Hz, 1H, aromatic CH), 7.16 (s, 2H, NH₂), 5.16 (s, 2H, SCH₂), 5.02 (s, 1H, CHPh). δ_C (100 MHz; DMSO-d₆) 160.7, 154.2, 152.2, 144.5, 138.1, 134.7, 129.7, 129.2, 128.5, 127.9, 127.4, 120.1, 112.8, 58.4, 55.9, 38.6.

4.5 5-amino-7-(4-cyanophenyl)-3-oxo-8-(phenylsulfonyl)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (4b)

Obtained as brown solid (365 mg, 84%), mp. 197–199 °C. υ_max, cm⁻¹ (KBr) 3331 (NH₂), 2228 (CN of Ar), 2199 (CN), 1743 (CO), 1649 (C = C), 1327 (SO₂), 1144 (SO₂). HRMS: Found M⁺ 435.0585 C₂₁H₁₅N₄O₃S₂ [M⁺] requires 435.0586. δ_H (400 MHz, DMSO-d₆) 7.87 (d, J = 8.2 Hz, 2H, aromatic CH), 7.78–7.70 (m, 3H, aromatic CH of PhSO₂), 7.61 (app. t, J = 7.9 Hz, 2H, aromatic CH), 7.41 (d, J = 8.2 Hz, 1H, aromatic CH), 7.30 (2H, br s, NH₂), 5.18 (2H, app. s, CH₂S), 5.17 (1H, app. s, CHAr). δ_C (100 MHz; DMSO-d₆) 160.9, 154.8, 152.4, 149.7, 138.0, 134.8, 133.2, 129.7, 128.6, 128.5, 122.2, 118.8, 111.4, 110.8, 58.9, 54.9, 38.5.

4.6 5-Amino-7-(4-chlorophenyl)-3-oxo-8-(phenylsulfonyl)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (4c)

Obtained as pale yellow solid (330 mg, 74%), mp. 244–246 °C. υ_max, cm⁻¹ (KBr) 3374 (NH₂), 2201 (CN), 1720 (CO), 1647 (C = C), 1329 (SO₂), 1146 (SO₂). HRMS: Found M⁺, 443.0163. C₂₀H₁₄N₃O₃S₂³⁵Cl [M⁺] requires 443.0165. δ_H (400 MHz, DMSO-d₆) 7.79–7.70 (3H, m, aromatic CH of SO₂Ph), 7.61 (2H, t, J = 7.8 Hz, aromatic CH of SO₂Ph), 7.45 (2H, d, J = 8.4 Hz, aromatic CH), 7.25–7.19 (4H, m, aromatic CH obscured with NH₂), 5.17 (2H, s, CH₂S), 5.06 (1H, s, CHAr). δ_C (100 MHz; DMSO-d₆) 160.3, 154.1, 151.9, 143.0, 137.8, 134.3, 132.1, 129.3, 129.0, 128.8, 128.1, 119.6, 111.9, 58.1, 55.3, 37.6.

4.7 5-Amino-7-(2,6-dichlorophenyl)-3-oxo-8-(phenylsulfonyl)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (4d)

Obtained as yellow solid (410 mg, 86%), mp. 277–278 °C. υ_max, cm⁻¹ (KBr) 3422 (NH₂), 2189 (CN), 1728 (CO), 1647 (C = C), 1307 (SO₂), 1154 (SO₂). HRMS: Found M⁺, 476.9758. C₂₀H₁₃N₃O₃S₂³⁵Cl₂[M⁺] requires 476.9775. δ_H (400 MHz, DMSO-d₆) 7.75–7.69 (3H, m, aromatic CH of SO₂Ph), 7.60 (2H, d, J = 7.7 Hz, aromatic CH of SO₂Ph), 7.57 (1H, dd, J = 8.0, 1.3 Hz, aromatic CH), 7.48 (1H, d, J = 6.9 Hz, aromatic CH), 7.40 (1H, t, J = 8.0 Hz, aromatic CH), 7.29 (2H, brs, NH₂), 5.92 (1H, s, CHAr), 5.20 (2H, q, J = 14.5 Hz, CH₂S). δ_C (100 MHz; DMSO-d₆) 161.6, 153.9, 153.6, 137.9, 135.7, 135.6, 134.7, 134.4, 131.5, 130.9, 129.6, 129.2, 128.6, 119.5, 108.7, 58.4, 52.4 and 35.3.

4.8 5-amino-7-(2,4-dichlorophenyl)-3-oxo-8-(phenylsulfonyl)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (4e)

Obtained as yellow solid (325 mg, 68%), mp. 251–252 °C. υ_max, cm⁻¹ (KBr) 3439 (NH₂), 2189 (CN), 1722 (CO), 1657 (C = C), 1319 (SO₂), 1152 (SO₂). HRMS: Found M⁺, 476.9764. C₂₀H₁₃N₃O₃S₂³⁵Cl₂ [M⁺] requires 476.9775. δ_H (400 MHz, DMSO-d₆) 7.74–7.69 (3H, m, aromatic CH of SO₂Ph), 7.68 (1H, d, J = 2.0 Hz, aromatic CH), 7.59 (2H, t, J = 7.8 Hz, aromatic CH of SO₂Ph), 7.50 (1H, dd, J = 8.3, 2.0 Hz, aromatic CH), 7.37 (1H, s, aromatic CH), 7.34 (2H, br s, NH₂), 5.40 (1H, s, CHAr), 5.18 (2H, d, J = 2.6 Hz, CH₂S). δ_C (100 MHz; DMSO-d₆) 161.5, 154.4, 152.7, 139.4, 138.1, 134.6, 133.6, 133.1, 131.8, 129.9, 129.7, 128.7, 128.5, 119.8, 110.5, 58.3, 53.5 and 36.3.

4.9 5-Amino-7-(4-nitrophenyl)-3-oxo-8-(phenylsulfonyl)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (4f)

Obtained as pale yellow solid (322 mg, 71%), mp. 255–256 °C. υ_max, cm⁻¹ (KBr) 3312 (NH₂), 2201 (CN), 1654 (CO), 1647 (C = C), 1327 (SO₂), 1144 (SO₂). HRMS: Found M⁺, 454.0406. C₂₀H₁₄N₄O₅S₂ [M⁺] requires 454.0406. δ_H (400 MHz, DMSO-d₆) 8.26 (2H, d, J = 7.9 Hz, aromatic CH), 7.77 – 7.70 (3H, m, aromatic CH of SO₂Ph), 7.62 (2H, t, J = 7.5 Hz, aromatic CH of SO₂Ph), 7.51 (2H, d, J = 7.9 Hz, aromatic CH), 7.33 (2H, br s, NH₂), 5.26 (1H, s, CHAr), 5.19 (2H, s, CH₂S). δ_C (100 MHz; DMSO-d₆) 160.9, 154.9, 152.5, 151.6, 147.3, 138.1, 134.7, 129.7, 129.0, 128.5, 124.6, 119.9, 111.3, 58.4, 54.9, 38.3.

4.10 5-Amino-2-(4-chlorobenzylidene)-7-(4-chlorophenyl)-3-oxo-8-(phenylsulfonyl)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (5a)

Obtained as yellow solid (384 mg, 68%), mp. 293–294 °C. υ_max, cm⁻¹ (KBr) 3373 (NH₂), 2199 (CN), 1721 (CO), 1653 (C = C), 1325 (SO₂), 1148 (SO₂). (Found: (M–H)⁺, 566.0176. C₂₇H₁₈N₃O₃S₂³⁵Cl₂ requires M, 566.0167). δ_H (400 MHz, DMSO-d₆) 7.79–7.75 (m, 3H, aromatic CH of SO₂Ph), 7.72 (d, J = 8.1 Hz, 2H, aromatic CH of SO₂Ph), 7.65–7.56 (m, 3H, CH = C and aromatic CH), 7.52 (br s, 2H, NH₂), 7.47–7.40 (m, 2H, aromatic CH), 7.28–7.21 (m, 2H, aromatic CH), 7.18–7.12 (m, 2H, aromatic CH), 4.54 (s, 1H, CHAr). δ_C (100 MHz; DMSO-d₆) 166.1, 148.2, 142.1, 141.5, 140.7, 135.5, 134.2, 132.6, 132.5, 132.3, 130.5, 130.3, 130.1, 129.6, 128.6, 127.3, 122.1, 119.0, 113.3, 65.9, 41.2. m/z (TOF ES⁺) 566 (M–H + , 100) and 331 (15).

4.11 5-Amino-2-(4-fluorobenzylidene)-7-(4-fluorophenyl)-3-oxo-8-(phenyl sulfonyl)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (5b)

Obtained as pale yellow solid (425 mg, 80%), mp. 278–279 °C. υ_max, cm⁻¹ (KBr) 3412 (NH₂), 2203 (CN), 1707 (CO), 1649 (C = C), 1327 (SO₂), 1144 (SO₂). (Found: (M–H)⁺, 534.0751. C₂₇H₁₈N₃O₃S₂F₂ requires M, 534.0758). δ_H (400 MHz, DMSO-d₆) 7.95–7.72 (m, 3H, aromatic CH of SO₂Ph and CH = C), 7.72–7.58 (m, 3H, aromatic CH of SO₂Ph), 7.58 – 7.51 (m, 4H, aromatic CH of ArF and NH₂), 7.49–7.42 (m, 2H, aromatic CH of ArF), 7.35–7.16 (m, 2H, aromatic CH of ArF), 7.01–6.80 (m, 2H), 4.57 (d, 1H). δ_C (100 MHz; DMSO-d₆) 166.2, 164.5, 163.0, 162.0, 160.6, 148.2, 142.1 140.9, 138.7, 134.2, 133.19, 130.6, 129.6, 127.3, 120.9, 119.1, 117.3, 115.6, 113.5, 66.2, 41.1. m/z (TOF ES⁺) 534 (M–H⁺, 100).

4.12 5-Amino-2-(4-cyanobenzylidene)-7-(4-cyanophenyl)-3-oxo-8-(phenyl sulfonyl)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (5c)

Obtained as yellow solid (339 mg, 62%), mp. 292–294 °C. υ_max, cm⁻¹ (KBr) 3421 (NH₂), 2245 (CN), 2230 (CN), 2195 (CN of pyridine), 1701 (CO), 1643 (C = C), 1327 (SO₂), 1146 (SO₂). (Found: (M–H)⁺, 548.0850. C₂₉H₁₈N₅O₃S₂ requires M, 548.0851). δ_H (400 MHz, DMSO-d₆) 8.08 (d, J = 7.7 Hz, 2H, aromatic CH), 7.91 (d, J = 7.6 Hz, 2H, aromatic CHof SO₂Ph), 7.84 (s, 1H, CH = C), 7.68–7.62 (m, 3H, aromatic CH of SO₂Ph), 7.59 (d, J = 7.7 Hz, 2H, aromatic CH), 7.55 (brs, 2H, NH₂), 7.45 (app d, J = 5.5 Hz, 4H), 4.65 (s, 1H, CHAr). δ_C (100 MHz; DMSO-d₆) 165.9, 148.4, 147.8, 142.5, 140.4, 138.1, 134.5, 133.7, 132.7, 131.1, 129.7, 129.6, 129.4, 127.4, 125.1, 119.1, 118.9, 118.8, 113.0, 112.4, 110.6, 65.2, 41.6. m/z (TOF ES⁺) 548 (M – H⁺, 100) and 405 (20).

4.13 5-Amino-2-(3-bromobenzylidene)-7-(3-bromophenyl)-3-oxo-8-(phenyl sulfonyl)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (5d)

Obtained as yellow solid (480 mg, 73%), mp. 275–276 °C. υ_max, cm⁻¹ (KBr) 3404 (NH₂), 2201 (CN), 1697 (CO), 1653 (C = C), 1329 (SO₂), 1147 (SO₂). (Found: (M–H)⁺, 653.9155. C₂₇H₁₈N₃O₃S₂⁷⁹Br₂ requires M, 653.9156). δ_H (400 MHz, DMSO-d₆) 7.97 (s, 1H, aromatic CH), 7.77 (s, 1H, CH = C), 7.73 (d, J = 7.8 Hz, 2H, aromatic CH), 7.67–7.56 (m, 4H, aromatic CH of SO₂Ph and aromatic CH of ArBr), 7.53 (brs, 2H, NH₂), 7.47–7.40 (m, 2H, aromatic CH of SO₂Ph), 7.38 (s, 1H, aromatic CH), 7.30 (d, J = 7.7 Hz, 1H, aromatic CH), 7.24 (d, 1H, J = 7.7 Hz, aromatic CH), 7.12 (t, J = 7.7 Hz, 1H, aromatic CH), 4.57 (s, 1H, CHAr). δ_C (100 MHz; DMSO-d₆) 166.0, 148.2, 144.8, 142.3, 140.6, 136.2, 134.4, 133.8, 133.4, 132.1, 131.4, 130.9, 130.8, 129.8, 129.6, 128.5, 127.9, 127.2, 123.3, 123.1, 122.4, 119.1, 113.0, 65.8, 41.5. m/z (TOF ES⁺) 655 (M – H⁺, 100) and 653 (52).

4.14 5-Amino-2-(2,4-dimethoxybenzylidene)-7-(2,4-dimethoxyphenyl)-3-oxo-8-(phenylsulfonyl)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (5e)

Obtained as yellow solid (395 mg, 64%), mp. 248–249 °C. υ_max, cm⁻¹ (KBr) 3309 (NH₂), 2187 (CN), 1707 (CO), 1643 (C = C), 1325 (SO₂), 1144 (SO₂). (Found: (M–H)⁺, 618.1362. C₃₁H₂₈N₃O₇S₂ requires M, 618.1369). δ_H (400 MHz, DMSO-d₆) 7.93 (s, 1H, CH = C), 7.57–7.53 (m, 3H, aromatic CH of SO₂Ph), 7.47 (app d, J = 7.6 Hz, 2H, aromatic CH of SO₂Ph), 7.37 (m, 1H, aromatic CH), 7.36 (br s, 2H, NH₂), 6.95 (d, J = 8.4 Hz, 1H), 6.84 (d, J = 8.4 Hz, 1H), 6.74 (d, J = 1.9 Hz, 1H), 6.32 (d, J = 7.2 Hz, 1H), 6.14 (s, 1H, aromatic CH), 4.63 (s, 1H, CHAr), 3.95 (s, 3H, OCH₃), 3.89 (s, 3H, OCH₃), 3.70 (s, 3H, OCH₃), 3.45 (s, 3H, OCH₃). δ_C (100 MHz; DMSO-d₆) 166.3, 163.8, 160.6, 160.3, 158.3, 153.8, 148.9, 141.9, 141.0, 133.8, 131.2, 131.0, 129.3, 126.9, 126.8, 121.2, 119.4, 116.7, 115.1, 112.6, 107.2, 105.5, 99.2, 98.9, 64.9, 56.5, 56.2, 55.9, 55.7. m/z (TOF ES⁺) 618 (M–H⁺, 100), 480 (M–Ar⁺, 15) and 336 (35).

4.15 5-Amino-2-(4-hydroxy-3,5-dimethoxybenzylidene)-7-(4-hydroxy-3,5-dimethoxy phenyl)-3-oxo-8-(phenylsulfonyl)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (5f)

Obtained as yellow solid (450 mg, 69%), mp. 220 decomp. υ_max, cm⁻¹ (KBr) 3412 (NH₂), 2203 (CN), 1701 (CO), 1649 (C = C), 1327 (SO₂), 1144 (SO₂). (Found: (M–H)⁺, 653.9155. C₂₇H₁₈N₃O₃S₂⁷⁹Br₂ requires M, 653.9156). δ_H (400 MHz, DMSO-d₆) 8.42 (s, 1H, OH), 8.24 (s, 1H, OH), 7.77 (app. d, J = 7.5 Hz, 2H, aromatic CH of SO₂Ph), 7.64–7.57 (m, 2H, CH = C and aromatic CH of SO₂Ph), 7.51–7.45 (m, 1H, aromatic CH of SO₂Ph), 7.37 (t, J = 7.1 Hz, 1H, aromatic CH of SO₂Ph), 7.08 (br s, 2H, NH₂), 6.48 (s, 1H, aromatic CH), 6.29 (s, 1H, aromatic CH), 5.16 (s, 1H, aromatic CH), 4.93 (s, 1H, aromatic CH), 4.49 (s, 1H, CHAr), 3.88 (s, 3H, CH₃O), 3.73 (s, 3H, CH₃O), 3.59 (s, 2H, CH₃O), 3.36 (s, 3H, obscured by water in DMSO, CH₃O). δ_C (100 MHz; DMSO-d₆) 160.8, 153.9, 151.9, 148.7, 148.6, 148.2, 141.2, 138.4, 135.8, 134.7, 133.8, 129.7, 129.2, 128.5, 127.2, 124.1, 120.3, 117.2, 113.6, 108.9, 106.8, 105.0, 66.6, 58.5, 56.6, 56.6, 56.5, 56.0, 42.1, 38.8. m/z (TOF ES⁺) 650 (M–H⁺, 100), 496 (M-Ar⁺, 25).

4.16 5-Amino-3-oxo-8-(phenylsulfonyl)-7-(thiophen-3-yl)-2-(thiophen-3-ylmethylene)-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbonitrile (5g)

Obtained as pale yellow solid (410 mg, 81%), mp. 265–266 °C. υ_max, cm⁻¹ (KBr) 3408 (NH₂), 2205 (CN), 1701 (CO), 1647 (C = C), 1325 (SO₂), 1144 (SO₂). (Found: (M–H)⁺, 510.0062. C₂₃H₁₆N₃O₃S₄ requires M, 510.0075). δ_H (400 MHz, DMSO-d₆) 8.16 (s, 1H, aromatic CH of thienyl), 7.90 – 7.76 (m, 2H, aromatic CH of thienyl), 7.68–7.56 (m, 3H, aromatic CH of SO₂Ph), 7.52 (s, 1H, CH = C), 7.50 – 7.36 (m, 4H, NH₂ and aromatic CH of SO₂Ph), 7.31 (s, 1H, aromatic CH of thienyl), 7.19 (s, 1H, aromatic CH of thienyl), 6.92–6.82 (m, 1H, aromatic CH of thienyl), 4.70 (s, 1H, CHAr). δ_C (100 MHz; DMSO-d₆) 166.2, 148.5, 143.1, 141.6, 140.8, 135.8, 134.1, 131.9, 129.5, 129.1, 128.6, 127.8, 127.4, 126.9, 125.8, 123.4, 119.7, 119.3, 113.3, 65.7, 36.8. m/z (TOF ES⁺) 510 (M–H⁺, 100), 336 (25) and 280 (45).

Acknowledgements

We are extremely grateful to the Abant Izzet Baysal University, Directorate of Research Projects Commission (BAP grant 2011.03.03.391).