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CONVERSION REACTION OF 4-(TETRA-O-ACETYL-β-D-GLUCOPYRANOSYL)THIOSEMICARBAZONES OF SUBSTITUTED

BENZALDEHYDES WITH ETHYL BROMOACETATE

Nguyen Dinh Thanh*, Le The Hoai, Le Khanh Toan

Faculty of Chemistry, VNU University of Science, 19 Le Thanh Tong, Hanoi

Received 12 September 2012

Abstract Optimum conditions for transformation reaction of some substituted benzaldehyde 4-(2,3,4,6-tetra-O-acetyl-β-D-

glucopyranosyl)thiosemicarbazones 1 with ethyl bromoacetate were investigated. The optimum conditions were the use of absolute ethanol as solvent, anhydrous sodium acetate as catalyst and 10 min irradiation in MW oven after stirring the reaction mixture in room temperature for 30 min. Products, 2-iminothiazolidin-4-ones 2/2’, were formed in 75−86% yields, as pair of isomers in ratio determined by NMR spectra. Structures of these 2-iminothiazolidin-4-ones were confirmed by IR, NMR and mass spectra.

1. INTRODUCTION Thiazolidin-4-one compounds have a prevalent

scaffold in drug discovery. Substances containing this moiety are potential antibacterial, antimycobacterial, anticonvulsant, antiparasitic, anti-inflammatory,…[1]. Interestingly, Garnaik reported that several 2-(arylimino)-4-tetra-O-acetyl-β-D-glucopyranosyl-4-thiazolidinones showed promising antimicrobial and antifungal activities [2].

Continuing our studies on synthesis of peracetylated glycopyranosyl isothiocyanate and conversion into corresponding thiosemicarbazons [3], we reported here the conversion reaction of 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thio-semicarbazones of substituted benzaldehydes with ethyl bromoacetate.

2. EXPERIMENTAL

Melting points were measured on STUART SMP3 (BIBBY STERILIN-UK). The FTIS-spectra was recorded on Impact 410 FT-IR Spectrometer (Nicolet, USA) in KBr pellets. The 1H NMR and 13C NMR spectra were recorded on an Avance Spectrometer AV500 (Bruker, Germany) in DMSO-d6. Mass spectra were recorded on mass spectrometer LC-MS LTQ Orbitrap XL (ThermoScientific, USA). Substituted benzaldehyde 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thio-semicarbazones was prepared by the reaction of per-

O-acetylated-β-D-glucopyranosyl thiosemicarbazide by our method [9].

General synthetic procedure for (Z)-2-[(E)-arylidenehydrazono]-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thiazolidin-4-ones (2) and (Z)-3-[(E)-arylideneamino]-2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl-1-imino)thiazolidin-4-ones (2’). To a solution of thiosemicarbazone 1 (2.5 mmol), sodium acetate (0.5 g) in chloroform (35 mL), ethyl bromoacetate (0.5 mL, 15 mmol) in chloroform (15 mL) was added dropwise with stirring. The obtained mixture was stirred at room temperature for 30 min more and then irradiated in microwave oven for 10 min. Some solvent was removed, and water was added. A white separated crude product was filtered and purified by recrystallization from 96% ethanol to afford the title isomeric compounds 2 and 2’. 1H and 13C NMR spectral data of these compounds are below.

4-NO2 (2a): 1H NMR: δ 8.71 (s, 1H, CH=N), 8.33 (d, 2H, J = 8.5 Hz, H3”& H5”), 8.10 (d, 2H, J = 9.0 Hz, H2”& H6”), 6.20 (t, 1H, J = 9.5 Hz, H2’), 5.92 (d, 1H, J = 9.5 Hz, H1’), 5.52 (t, 1H, J = 9.5 Hz, H3’), 5.01 (t, 1H, J = 975 Hz, H4’4.31−4.29 (m, 1H, H5’), 4.11−4.07 (m, 4H, H6’a, H6’b, H5a & H5b), 2.03−1.92 (s, 12H, 4×CH3CO); 13C NMR: δ 171.8 (N−C=O), 170.0−168.8 (4×COCH3), 163.8 (S−C=N & CH=N), 156.3 (C4”), 148.5 (C1”), 128.9 (C2” & C6”), 124.0 (C3” & C5”), 79.4 (C1’), 72.9 (C3’), 72.8 (C5’), 67.5 (C4’), 67.1 (C2’), 61.6 (C6’), 31.7 (C5), 20.5−20.1 (4×CH3CO). (2’a): 1H NMR: δ

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8.70 (s, 1H, CH=N), 8.33 (d, 2H, J = 8.5 Hz, H3”& H5”), 8.06 (d, 2H, J = 8.5 Hz, H2”& H6”), 6.03 (d, 1H, J = 9.5 Hz, H1’), 5.88 (t, 1H, J = 9.5 Hz, H2’), 5.51 (t, 1H, J = 7.5 Hz, H3’), 4.98 (t, 1H, J = 8.5 Hz, H4’), 4.31−4.29 (m, 1H, H5’), 4.11−4.07 (m, 4H, H6’a, H6’b, H5a & H5b), 2.03−1.92 (s, 12H, 4×CH3CO); 13C NMR: δ 171.8 (N−C=O), 170.0−168.8 (4×COCH3), 163.8 (S−C=N & CH=N), 156.3 (C4”), 148.5 (C1”), 128.9 (C2” & C6”), 124.0 (C3” & C5”), 79.4 (C1’), 72.9 (C3’), 72.3 (C5’), 67.4 (C4’), 67.3 (C2’), 61.6 (C6’), 31.7 (C5), 20.5−20.1 (4×CH3CO).

3-NO2 (2b): 1H NMR: δ 8.74 (s, 1H, CH=N), 8.67 (s, 1H, H2”), 8.32 (d, 1H, J = 8.0 Hz, H6”), 8.28 (d, 1H, J = 7.5 Hz, H4”), 7.79 (t, 1H, J = 8.0 Hz, H5”), 6.21 (t, 1H, J = 9.25 Hz, H2’), 5.90 (d, 1H, J = 9.5 Hz, H1’), 5.52 (t, 1H, J = 9.5 Hz, H3’), 5.01 (t, 1H, J = 10.0 Hz, H4’), 4.31−4.29 (m, 1H, H5’), 4.13−4.07 (m, 4H, H6’a, H6’b, H5a & H5b), 2.03−1.92 (s, 12H, 4×CH3CO); 13C NMR: δ 171.8 (N−C=O), 169.9−169.3 (4×COCH3), 163.2 (S−C=N & CH=N), 156.3 (C4”), 148.2 (C1”), 133.9 (C2” & C6”), 125.1 (C3” & C5”), 79.4 (C1’), 72.9 (C3’), 72.8 (C5’), 67.6 (C4’), 67.1 (C2’), 61.6 (C6’), 31.6 (C5), 20.5−20.1 (4×CH3CO). (2’b): 1H NMR: δ 8.69 (s, 1H, CH=N), 8.60 (s, 1H, H2”), 8.32 (d, 1H, J = 8.0 Hz, H6”), 8.24 (d, 1H, J = 7.5 Hz, H4”), 7.79 (t, 1H, J = 8.0 Hz, H5”), 6.02 (d, 1H, J = 9.0 Hz, H1’), 5.86 (d, 1H, J = 8.5 Hz, H2’), 5.52 (t, 1H, J = 9.5 Hz, H3’), 4.97 (t, 1H, J = 8.5 Hz, H4’), 4.31−4.29 (m, 1H, H5’), 4.13−4.07 (m, 4H, H6’a, H6’b, H5a & H5b), 2.03−1.92 (s, 12H, 4×CH3CO); 13C NMR: δ 171.5 (N−C=O), 169.9−169.3 (4×COCH3), 163.2 (S−C=N & CH=N), 156.3 (C4”), 148.2 (C1”), 133.9 (C2” & C6”), 125.1 (C3” & C5”), 79.4 (C1’), 73.0 (C3’), 72.3 (C5’), 67.4 (C4’), 67.3 (C2’), 61.6 (C6’), 31.6 (C5), 20.5−20.1 (4×CH3CO).

4-F (2c): 1H NMR: δ 8.55 (s, 1H, CH=N), 7.91 (dd, J = 6.0, 8.5 Hz, 2H, H2”& H6”), 7.33 (t, 2H, J = Hz, J = 8.5 Hz, H3”& H5”), 6.21 (t, 1H, J = 9.5 Hz, H2’), 5.89 (d, 1H, J = 9.0 Hz, H1’), 5.51 (t, 1H, J = 9.5 Hz, H3’), 5.00 (t, 1H, J = 9.75 Hz, H4’), 4.29−4.27 (m, 1H, H5’), 4.16−4.05 (m, 4H, H6’a, H5a, H5b, H6’b), 2.03−1.90 (s, 12H, 4×CH3CO); 13C NMR: δ 172.3 (N−C=O), 170.5-169.2 (4×COCH3), 165.2 (S−C=N), 163.2 (CH=N), 158.0 (C4”), 157.5 (C1”), 130.7 (C2” & C6”), 116.5 (C3” & C5”), 79.9 (C1’), 73.4 (C3’), 73.3 (C5’), 68.1 (C4’), 67.6 (C2’), 62.1 (C6’), 32.0 (C5), 21.0−20.7 (4×CH3CO); (2’c): 1H NMR: δ 8.53 (s, 1H, CH=N), 7.86 (dd, 2H, J = 6.0, 8.0 Hz, H2”& H6”), 7.33 (t, 2H, J = 8.5 Hz, H3”& H5”), 6.00 (d, 1H, J = 9.0 Hz, H1’), 5.87 (t, 1H, J = 8.5 Hz, H2’), 5.49 (t, 1H, J =

8.5 Hz, H3’), 4.97 (t, 1H, J = 8.5 Hz, H4’), 4.29−4.27 (m, 1H, H5’), 4.16−4.05 (m, 4H, H6’a, H5a, H5b, H6’b), 2.03−1.90 (s, 12H, 4×CH3CO). 13C NMR: δ 172.0 (N−C=O), 170.5−169.2 (4×COCH3), 163.2 (CH=N), 162.0 (S−C=N), 158.0 (C4”), 157.5 (C1”), 130.7 (C2” & C6”), 116.5 (C3” & C5”), 79.9 (C1’), 73.5 (C3’), 72.8 (C5’), 67.9 (C4’), 67.4 (C2’), 62.3 (C6’), 32.4 (C5), 21.0−20.7 (4×CH3CO).

4-Cl (2d): 1H NMR: δ 8.56 (s, 1H, CH=N), 7.87 (d, 2H, J = 8.25 Hz, H2”& H6”), 7.56 (d, 2H, J = 8.25 Hz, H3”& H5”), 6.20 (t, 1H, J = 9.5 Hz, H2’), 5.90 (d, 1H, J = 9.5 Hz, H1’), 5.51 (t, 1H, J = 9.5 Hz, H3’), 5.00 (t, 1H, J = 10.0 Hz, H4’), 4.30−4.28 (m, 1H, H5’), 4.13−4.06 (m, 4H, H6’a, H5a & H5b, H6’b), 2.03−1.91 (s, 12H, 4×CH3CO); 13C NMR: δ 171.8 (N−C=O), 169.9−168.6 (4×COCH3), 161.9 (S−C=N & CH=N), 157.1 (C4”), 140.0 (C1”), 132.8 (C2” & C6”), 129.5 (C3” & C5”), 79.4 (C1’), 72.9 (C3’), 72.8 (C5’), 67.6 (C4’), 67.1 (C2’), 61.6 (C6’), 31.6 (C5), 20.5−20.1 (4×CH3CO). (2’d): 1H NMR: δ 8.54 (s, 1H, CH=N), 7.82 (d, 2H, J = 8.0 Hz, H2”& H6”), 7.56 (d, 2H, J = 8.0 Hz, H3”& H5”), 6.01 (d, 1H, J = 9.5 Hz, H1’), 5.87 (t, 1H, J = 7.5 Hz, H2’), 5.49 (t, 1H, J = 9.5 Hz, H3’), 4.98 (t, 1H, J = 9.0 Hz, H4’), 4.30−4.28 (m, 1H, H5’), 4.13−4.06 (m, 4H, H6’a, H5a & H5b, H6’b), 2.03−1.91 (s, 12H, 4×CH3CO); 13C NMR: δ 171.3 (N−C=O), 169.9−168.6 (4×COCH3), 161.9 (S−C=N & CH=N), 157.2 (C4”), 140.0 (C1”), 132.7 (C2” & C6”), 129.0 (C3” & C5”), 80.3 (C1’), 73.0 (C3’), 72.3 (C5’), 67.4 (C4’), 67.3 (C2’), 61.6 (C6’), 31.9 (C5), 20.5−20.1 (4×CH3CO).

H (2e): 1H NMR: δ 8.54 (s, 1H, CH=N), 7.85−7.80 (m, 2H, H2”& H6”), 7.49−7.48 (m, 3H, H3”, H4” & H5”), 6.22 (t, 1H, J = 9.5 Hz, H2’), 5.89 (d, 1H, J = 9.0 Hz, H1’), 5.51 (t, 1H, J = 9.75 Hz, H3’), 5.01 (t, 1H, J = 9.75 Hz, H4’), 4.30−4.28 (m, 1H, H5’), 4.13−4.06 (m, 4H, H6’a, H6’b, H5a, & H5b), 2.03−1.91 (s, 12H, 4×CH3CO); 13C NMR: δ 171.8 (N−C=O), 169.9−168.6 (4×COCH3), 163.4 (S−C=N), 161.4 (CH=N), 158.2 (C4”), 131.0 (C1”), 128.9 (C2” & C6”), 127.9 (C3” & C5”), 79.4 (C1’), 72.9 (C3’), 72.8 (C5’), 67.6 (C4’), 67.1 (C2’), 61.6 (C6’), 31.5 (C5), 20.5−20.1 (4×CH3CO); (2’e): 1H NMR: δ 8.54 (s, 1H, CH=N), 7.81 (m, 2H, H2”& H6”), 7.56 (m, 2H, H3”, H4” & H5”), 6.01 (d, 1H, J = 9.0 Hz, H1’), 5.87 (t, 1H, J = 9.5 Hz, H2’), 5.49 (t, 1H, J = 9.5 Hz, H3’), 4.97 (t, 1H, J = 9.75 Hz, H4’), 4.30−4.28 (m, 1H, H5’), 4.13−4.06 (m, 4H, H6’a, H6’b, H5a, & H5b), 2.03−1.91 (s, 12H, 4×CH3CO); 13C NMR: δ 171.3 (N−C=O), 169.9−168.6 (4×COCH3), 163.4 (S−C=N), 161.4 (CH=N), 158.4

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(C4”), 133.9 (C1”), 128.9 (C2” & C6”), 127.9 (C3” & C5”), 80.3 (C1’), 73.0 (C3’), 72.3 (C5’), 67.4 (C4’), 67.3 (C2’), 61.6 (C6’), 31.9 (C5), 20.5−20.1 (4×CH3CO).

4-Me (2f): 1H NMR: δ 8.49 (s, 1H, CH=N), 7.73 (d, 2H, J = 7.75 Hz, H2”& H6”), 7.29 (d, 2H, J = 7.75 Hz, H3”& H5”), 6.21 (t, 1H, J = 9.5 Hz, H2’), 5.89 (d, 1H, J = 9.5 Hz, H1’), 5.51 (t, 1H, J = 9.5 Hz, H3’), 5.01 (t, 1H, J = 9.75 Hz, H4’), 4.29−4.28 (m, 1H, H5’), 4.17−4.02 (m, 4H, H6’a, H6’b, H5a & H5b), 2.03−1.90 (s, 12H, 4×CH3CO); 13C NMR: δ 171.8 (N−C=O), 169.9−168.6 (4×COCH3), 160.7 (S−C=N), 158.1 (CH=N), 141.0 (C4”), 131.2 (C1”), 129.5 (C2” & C6”), 127.9 (C3” & C5”), 79.4 (C1’), 72.9 (C3’), 72.8 (C5’), 67.5 (C4’), 67.1 (C2’), 61.6 (C6’), 31.5 (C5), 21.1−20.1 (4×CH3CO). (2’f): 1H NMR: δ 8.49 (s, 1H, CH=N), 7.69 (d, 2H, J = 7.75 Hz, H2”& H6”), 7.29 (d, 2H, J = 7.75 Hz, H3”& H5”), 6.01 (d, 1H, J = 9.0 Hz, H1’), 5.87 (t, 1H, J = 8.5 Hz, H2’), 5.51 (t, 1H, J = 9.0 Hz, H3’), 4.97 (t, 1H, J = 9.75 Hz, H4’), 4.29−4.28 (m, 1H, H5’), 4.17−4.02 (m, 4H, H6’a, H6’b, H5a & H5b), 2.03−1.90 (s, 12H, 4×CH3CO); 13C NMR: δ 171.3 (N−C=O), 169.9−168.6 (4×COCH3), 160.7 (S−C=N), 158.3 (CH=N), 141.1 (C4”), 131.1 (C1”), 129.5 (C2” & C6”), 127.9 (C3” & C5”), 80.3 (C1’), 73.0 (C3’), 72.3 (C5’), 67.4 (C4’), 67.3 (C2’), 61.6 (C6’), 31.8 (C5), 21.1−20.1 (4×CH3CO).

4-iPr (2g): 1H NMR: δ 8.49 (s, 1H, CH=N), 7.76 (d, 2H, J = 8.25 Hz, H2”& H6”), 7.36 (d, 2H, J = 8.25 Hz, H3”& H5”), 6.21 (t, 1H, J = 9.5 Hz, H2’), 5.89 (d, 1H, J = 9.5 Hz, H1’), 5.51 (t, 1H, J = 9.5 Hz, H3’), 5.00 (t, 1H, J = 9.75 Hz, H4’), 4.29−4.28 (m, 1H, H5’), 4.17−4.02 (m, 4H, H6’a, H6’b, H5a & H5b), 2.03−1.90 (s, 12H, 4×CH3CO); 13C NMR: δ 171.8 (N−C=O), 169.9−168.6 (4×COCH3), 160.8 (S−C=N), 158.1 (CH=N), 151.7 (C4”), 131.6 (C1”), 128.0 (C2” & C6”), 126.9 (C3” & C5”), 79.4 (C1’), 72.9 (C3’), 72.8 (C5’), 67.5 (C4’), 67.1 (C2’), 61.6 (C6’), 33.5 (CH(CH3)2), 31.5 (C5), 23.6 (CH(CH3)2), 20.5−20.2 (4×CH3CO); (2’g): 1H NMR: δ 8.49 (s, 1H, CH=N), 7.72 (d, 2H, J = 8.5 Hz, H2”& H6”), 7.36 (d, 2H, J = 8.5 Hz, H3”& H5”), 6.01 (d, 1H, J = 9.0 Hz, H1’), 5.87 (t, 1H, J = 8.5 Hz, H2’), 5.50 (t, 1H, J = 9.0 Hz, H3’), 4.97 (t, 1H, J = 9.5 Hz, H4’), 4.29−4.28 (m, 1H, H5’), 4.17−4.02 (m, 4H, H6’a, H6’b, H5a & H5b), 2.03−1.90 (s, 12H, 4×CH3CO); 13C NMR: δ 171.3 (N−C=O), 169.9−168.6 (4×COCH3), 160.8 (S−C=N), 158.3 (CH=N), 151.8 (C4”), 131.5 (C1”), 128.0 (C2” & C6”), 126.9 (C3” & C5”), 80.2 (C1’), 73.0 (C3’), 72.3 (C5’), 67.4 (C4’), 67.3 (C2’), 61.6 (C6’), 33.5 (CH(CH3)2), 31.5 (C5), 23.6 (CH(CH3)2), 20.5−20.2 (4×CH3CO).

4-OMe (2h): 1H NMR: δ 8.46 (s, 1H, CH=N), 7.79 (d, 2H, J = 8.75 Hz, H2”& H6”), 7.04 (d, 2H, J = 8.75 Hz, H3”& H5”), 6.21 (t, 1H, J = 9.25 Hz, H2’), 5.88 (d, 1H, J = 9.5 Hz, H1’), 5.50 (t, 1H, J = 9.75 Hz, H3’), 5.00 (t, 1H, J = 10.0 Hz, H4’), 4.28−4.27 (m, 1H, H5’), 4.13−4.08 (m, 4H, H6’a, H6’b, H5a & H5b), 2.03−1.90 (s, 12H, 4×CH3CO); 13C NMR: δ 171.8 (N−C=O), 169.9−168.6 (4×COCH3), 161.6 (CH=N), 160.0 (S−C=N), 157.8 (C4”), 129.7 (C2” & C6”), 126.5 (C1”), 114.4 (C3” & C5”), 79.4 (C1’), 72.9 (C3’), 72.8 (C5’), 67.5 (C4’), 67.1 (C2’), 61.6 (C6’), 55.3 (OCH3), 31.5 (C5), 20.5−20.1 (4×CH3CO). (2’h): 1H NMR: δ 8.46 (s, 1H, CH=N), 7.75 (d, 2H, J = 8.75 Hz, H2”& H6”), 7.04 (d, 2H, J = 8.75 Hz, H3”& H5”), 5.99 (d, 1H, J = 9.0 Hz, H1’), 5.86 (t, 1H, J = 6.5 Hz, H2’), 5.48 (t, 1H, J = 9.0 Hz, H3’), 4.97 (t, 1H, J = 8.0 Hz, H4’), 4.28−4.27 (m, 1H, H5’), 4.13−4.08 (m, 4H, H6’a, H6’b, H5a & H5b), 2.03−1.91 (s, 12H, 4×CH3CO); 13C NMR: δ 171.3 (N−C=O), 169.9−168.6 (4×COCH3), 162.1 (S−C=N), 161.6 (CH=N), 157.9 (C4”), 129.7 (C2” & C6”), 126.3 (C1”), 114.4 (C3” & C5”), 80.3 (C1’), 73.0 (C3’), 72.3 (C5’), 67.4 (C4’), 67.3 (C2’), 61.6 (C6’), 55.3 (OCH3), 31.8 (C5), 20.5−20.1 (4×CH3CO).

4-OH (2i): 1H NMR: δ 10.04 (s, 1H, OH), 8.39 (s, 1H, CH=N), 7.70 (d, 2H, J = 8.5 Hz, H2”& H6”), 6.85 (d, 2H, J = 8.5 Hz, H3”& H5”), 6.21 (t, 1H, J = 9.5 Hz, H2’), 5.87 (d, 1H, J = 9.0 Hz, H1’), 5.49 (t, 1H, J = 9.5 Hz, H3’), 5.00 (t, 1H, J = 9.75 Hz, H4’), 4.29−4.28 (m, 1H, H5’), 4.16−4.02 (m, 4H, H6’a, H6’b, H5a & H5b), 2.03−1.91 (s, 12H, 4×CH3CO); 13C NMR: δ 171.8 (N−C=O), 169.9−168.6 (4×COCH3), 160.2 (CH=N), 159.3 (S−C=N), 158.0 (C4”), 129.8 (C2” & C6”), 124.9 (C1”), 115.8 (C3” & C5”), 79.4 (C1’), 72.9 (C3’), 72.8 (C5’), 67.5 (C4’), 67.1 (C2’), 61.6 (C6’), 31.5 (C5), 20.5-20.2 (4×CH3CO). (2’i): 1H NMR: δ 10.04 (s, 1H, OH), 8.39 (s, 1H, CH=N), 7.63 (d, 2H, J = 8.5 Hz, H2”& H6”), 6.85 (d, 2H, J = 8.5 Hz, H3”& H5”), 5.98 (d, 1H, J = 9.0 Hz, H1’), 5.87 (t, 1H, J = 9.0 Hz, H2’), 5.49 (t, 1H, J = 9.5 Hz, H3’), 4.96 (t, 1H, J = 9.5 Hz, H4’), 4.29−4.28 (m, 1H, H5’), 4.16−4.02 (m, 4H, H6’a, H6’b, H5a & H5b), 2.03−1.91 (s, 12H, 4×CH3CO); 13C NMR: δ 171.3 (N−C=O), 169.9-168.6 (4×COCH3), 160.8 (S−C=N), 160.2 (CH=N), 158.2 (C4”), 129.8 (C2” & C6”), 124.8 (C1”), 115.8 (C3” & C5”), 80.2 (C1’), 73.0 (C3’), 72.3 (C5’), 67.4 (C4’), 67.3 (C2’), 61.6 (C6’), 31.8 (C5), 20.5−20.1 (4×CH3CO).

4-N(CH3)2 (2j): 1H NMR: δ 8.34 (s, 1H, CH=N), 7.64 (d, 2H, J = 9.0 Hz, H2”& H6”), 6.76 (d, 2H, J = 9.0 Hz, H3”& H5”), 6.22 (t, 1H, J = 9.5

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Hz, H2’), 5.87 (d, 1H, J = 9.0 Hz, H1’), 5.49 (t, 1H, J = 9.75 Hz, H3’), 4.99 (t, 1H, J = 10.0 Hz, H4’), 4.28−4.25 (m, 1H, H5’), 4.16−4.00 (m, 4H, H6’a, H6’b, H5a & H5b), 2.99 (s, 6H, (CH3)2N), 2.03−1.90 (s, 12H, 4×CH3CO); 13C NMR: δ 171.8 (N−C=O), 169.9−168.6 (4×COCH3), 158.3 (CH=N), 158.0 (S−C=N), 152.1 (C4”), 129.4 (C2” & C6”), 121.1 (C1”), 111.7 (C3” & C5”), 79.4 (C1’), 72.8 (C3’ & C5’), 67.5 (C4’), 67.1 (C2’), 61.6 (C6’), 55.3 (OCH3), 39.8 ((CH3)2N), 31.4 (C5), 20.5−20.1 (4×CH3CO). (2’j): 1H NMR: δ 8.34 (s, 1H, CH=N), 7.60 (d, 2H, J = 9.0 Hz, H2”& H6”), 6.76 (d, 2H, J = 9.0 Hz, H3”& H5”), 5.98 (d, 1H, J = 9.0 Hz, H1’), 5.88 (t, 1H, J = 9.5 Hz, H2’), 5.49 (t, 1H, J = 9.75 Hz, H3’), 4.96 (t, 1H, J = 9.75 Hz, H4’), 4.28−4.25 (m, 1H, H5’), 4.16−4.00 (m, 4H, H6’a, H6’b, H5a & H5b), 2.99 (s, 6H, (CH3)2N), 2.03−1.90 (s, 12H, 4×CH3CO); 13C NMR: δ 171.3 (N−C=O), 169.9−168.6 (4×COCH3), 160.1 (S−C=N), 158.3 (CH=N), 152.1 (C4”), 129.4 (C2” & C6”), 121.1 (C1”), 111.7 (C3” & C5”), 80.2 (C1’), 72.9 (C3’), 72.4 (C5’), 67.4 (C4’), 67.3 (C2’), 61.6 (C6’), 55.3 (OCH3), 39.8 ((CH3)2N), 31.7 (C5), 20.5−20.1 (4×CH3CO).

3. RESULTS AND DISCUSSION

Reaction time and yields of synthesis of 2-iminothiazolidin-4-one abundantly depend on solvents used and the presence of base catalysts [2,4]. In order to find the optimum reaction conditions (reaction time, solvent, catalysts), we have been performed these synthetic reactions in some conditions (Table 1). From Table 1, it shown that the reaction have been appropriately carried out for microwave-irradiated 10 min in 99% ethanol as solvent in the presence of anhydrous sodium acetate as catalyst. Reaction yields, in general, are not

affected by the nature of substituents on benzene ring, because these groups lie too far from the reaction center (the thiocarbonyl C=S), and this cyclization process includes two reaction: nucleophilic substitution on thiocarbonyl carbon of thiosemibarbazones and acyl nucleophilic substitution on carbonyl carbon of ester moiety.

The reaction of ethyl bromoacetate with corresponding thiosemicarbazones (1a-j) lead to new (Z)-2-[(E)-arylidenehydrazono]-3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thiazolidin-4-ones (2a-j) and (Z)-3-[(E)-arylideneamino]-2-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl-1-imino)-thiazolidin-4-ones (2’a-j) (Scheme 1). We used 99% ethanol as the reaction medium and molar ratios of ethyl bromoacetate and thioureas 1a-j in 6:1 ratio in order to obtain the higher transformation yields. Reaction mixtures were stirred in room temperature for 30 min, then irradiated for 10 min in microwave oven, otherwise it needed heat at reflux for 8-10 hrs [10]. The products 2 were soluble in ethanol, methanol, it facilitated for purification. Reaction yields are 75−86% (table 2) These isomers have some similar features in structure which made the separation of these isomers to become difficult. The isomeric ratios 2a-j and 2’a-j could been determined by 1H NMR spectra [1b].

IR spectra show the characteristic absorption bands at ν=1748–1743 cm–1 (νC=O ester), 1624–1606 cm–1 (νC=O lactam and νC=N imin), 1597–1529 cm–1 (νC=C), 1249–1228 and 1089–1033 cm–1 (νCOC ester). The evidences that confirm the success of reactions are the absence of NH bands in IR spectra at 3340−3320 cm–1 and chemical shifts of NH (thiourea) at δ=9–10 ppm (in 1H NMR spectra). Other evidence is the disappearance of C=S signals at δ=206-208 ppm and the appearance of C=N signals at δ=163.9–160.0 ppm (in 13C NMR spectra).

Scheme 1: Synthetic path for 2-iminothiazolidin-4-ones from substituted benzaldehyde 4-(tetra-O-acetyl-

β-D-glucopyranosyl)thiosemicarbazones

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Table 1: Reaction time and yields in synthesis of 2-iminothiazolidin-4-on 2/2’

Refluxing MW irradiation Room temp. Catalyst

CHCl3 Abs. EtOH CHCl3 Abs. EtOH Abs. EtOH

CH3COONa 8 hrs, 76% 12 hrs, 69% 30 min, 71% 10 min, 85% 24 hrs, 62%

NEt3 - - 30 min, 34% 15 min, 48% - No catalyst - - - 30 min, 57% -

Table 2: Compounds of 2-minothiazolidin-4-ones 2/2’

No Compd. Pair R mp, ºC Yield,

% νC=O

(lactam) νC=O

(este) 2/2’ Ratio,

%

MS (ESI)

[M+H]+

1 2a/2’a 4-NO2 223−224 85 1627 1746 61.5/38.5 555

2 2b/2’b 3-NO2 214−215 79 1624 1745 59/41 555

3 2c/2’c 4-F 216−217 86 1619 1743 61.5/38.5 -

4 2d/2’d 4-Cl 184−185 77 1619 1749 62/38 544/542

5 2e/2’e H 201−202 80 1622 1746 61/39 508

6 2f/2’f 4-Me 150−151 82 1618 1744 61/39 524*

7 2g/2’g 4-iPr 205−206 76 1616 1743 60.6/39.4 550*

8 2h/2’h 4-OH 166−167 75 1622 1746 56/44 524*

9 2i/2’i 4-OMe 172−173 84 1613 1748 60/40 538

10 2j/2’j 4-NMe2 172−173 78 1606 1744 61/39 552**

[M−H]+; ** [M]+. The 1H and 13C NMR spectral elucidations of

these products indicated the presence of two isomers in each obtained product. The isomers 2a-j and 2’a-j were distinguished one isomer from another by chemical shits of protons H-1’ and H-2’ on pyranose ring. In isomer 2a-j resonance signals of proton H-1’ show at δ=6.42–6.35 ppm and the one of proton H-2’ show at δ=5.97–5.92 ppm, while protons H-1’ and H-2’ in isomer 2’a-j had chemical shifts at δ=5.97–5.92 ppm and 6.51–6.44 ppm, respectively. Proton H-1’ in isomers 2’a-j were shielded more strongly by diamagnetic anisotropy of imino group, and its resonance signal was upfield, while this effect was absent in isomer 2a-j, so the resonance signals of proton H-1’ was downfield. 4. CONCLUSION

We have performed an efficient method for the

reaction of substituted benzaldehyde 4-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-thiosemicarbazones with ethyl bromoacetate under microwave-assisted

refluxing conditions. The obtained 2-iminothiazolidin-4-ones were two isomers and their ratio could be found using 1H NMR spectra.

Acknowledgment. Financial support for this work was provided by Vietnam's National Foundation for Science and Technology Development (NAFOSTED). REFERENCES 1. (a) M. Pulici, F. Quartieri. Traceless solid-phase

synthesis of 2-amino-5-alkylidene-thiazol-4-ones, Tetrahedron Lett., 46, 2387-2391 (2005); (b) C. G. Bonde, N. J. Gaikwad. Synthesis and preliminary evaluation of some pyrazine containing thiazolines and thiazolidinones as antimicrobial agents, Bioorg. Med. Chem., 12, 2151-2161 (2004); (c) S. G. Kucukguzel, E. G. Oruc, S. Rollas, F. Sahin, A. Ozbek. Synthesis, characterisation and biological activity of novel 4-thiazolidinones, 1,3,4-oxadiazoles and some related compounds, Eur. J. Med. Chem., 37, 197-206 (2002).

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2. B. K. Garnaik and R. K. Behera. Synthesis, Antimicrobial & Antifungal activities of some 2-arylimino-4-tetra-O-acetyl-β-D-gluco-pyranosyl-4-thiazolidinoes, Indian J. Chem., 27B, 1157-1158 (1988).

3. Nguyen Dinh Thanh, Le The Hoai, Le Khanh Toan.

Contribution to synthesis of some 4-(tetra-O-acetyl-β-D-glucopyranasyl)thiosemicarbazo-nes of substituted benzaldehydes, J. Sci.Tech. (VAST), 2012 (in press).

4. Nguyen Dinh Thanh. Reaction of N-(Per-O-acetyl-β-D-glucopyranosyl)-N’-(4’,6’-diaryl-pyrimidine-2’-yl)thioureas with ethyl bromoacetate, E-J. Chem., 8(3), 1355-1361 (2011).

Corresponding author: Nguyen Dinh Thanh

Faculty of Chemistry, VNU University of Science, 19 Le Thanh Tong, Hanoi, Vietnam Email: nguyendinhthanh@hus.edu.vn.

VJC, Vol. 50(5), 2012 Nguyen Dinh Thanh, et al.