Synthesis of some derivatives of n-(2,3,4,6-tetra-oacetyl-β-d-glucopyranosyl)-n’-(benzothiazole-2’-yl) thioureas

603 Journal of Chemistry, Vol. 47 (5), P. 603 - 607, 2009 SYNTHESIS OF SOME DERIVATIVES OF N-(2,3,4,6-TETRA-O- ACETYL-β-D-GLUCOPYRANOSYL)-N’-(BENZOTHIAZOLE-2’-YL) THIOUREAS Received 5 January 2009 Nguyen Dinh Thanh, Pham Hong Lan, Nguyen Thu Huyen Faculty of Chemistry, Hanoi University of Science, VNU Abstract Some compounds of N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-N-(benzothiazole-2- yl)thioureas have been synthesized from corresponding 2,3,4,6-tetra-O-acetyl--D- glucopyranosyl isothiocyanate and the substituted derivatives of 2-aminobenzothiazoles executing in home microwave oven. Their spectroscopic properties have been recorded and the relationships between their structures and spectral properties (IR, 1H- and 13C-NMR) have been discussed. I - INTRODUCTION Certain sugars perform important biological function [1]. They can control various gene expressions to adjust the upgrowth, development and reaction of organs. Glycosyl isothiocyanates have been widely used as valuable intermediates in the synthesis of glycosyl derivatives [2]. The isothiocyanates and glycosyl isothiocyanates have been the focus of synthetic attention during recent years because of their potential pharmacological properties [3]. They have also attracted considerable interest due to the anti- HIV activity shown by 1-deoxyno-jirimycin, castanospermine and some of their derivatives [4]. Many biologically important products have a sugar unit joined by an atom (O, S, N or C) or a group of atom [5]. In the present study, we reported on the synthesis of various peracetated glucosylthioureas containing thiazole ring executing in microwave oven. This method is becoming an increasingly popular method of heating which replaces the classical one because it proves to be a clean, cheap, and convenient method [6]. II - EXPERIMENT Melting points of the synthesized compounds were measured on STUART SMP3 (BIBBY STERILIN-UK). The FTIS-spectra was recorded on Magna 760 FT-IR Spectrometer (Nicolet, USA) in form of KBr and using reflex- measure method. NMR was recorded on an Advance Spectrometer (Bruker, Germany) at 500 MHz, using DMSO-d6 as solvent and TMS as an internal reference. 2,3,4,6-Tetra-O-acetyl- β-D-glucopyranosyl isothiocyanate was synthesized by known method [7, 8]. Synthesis of the derivative of N-(2,3,4,6-tetra- O-acetyl-β-D-glucopyranosyl)-N- (benzothiazole-2-yl) thioureas Mixed (0.002 mole) of the derivatives of 2- aminobenzothiazole and 0.778 g (0.002 mole) of 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl isothiocyanate. Then this mixture was irradiated about 5 minutes in home microwave oven. The mixture had become dark-yellow. Cooled it to room temperature, recrystallized from a mixture of ethanol and toluene (1:1 in volume) obtained ivory-white crystal. Obtained compounds were 604 represented in table 1. III - RESULTS AND DISCUSSION The derivatives of N-(2,3,4,6-tetra-O-acetyl- β-D-glucopyranosyl)-N’-(benzothiazole-2’- yl)thioureas (III) could be easily synthesized by the addition of corresponding amino compounds (II) on isothiocyanate derivatives (I). We performed this reaction by executing in microwave oven in several minutes [9]. The synthetic processes could be represented in reaction Schema 1. We have found that nucleophiles addition the derivatives of 2-aminobenzothiazole to 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl isothiocyanate has taken place fairly easily. Reaction yield were rather high in this method. All these obtained thioureas could be dissolved in a mixture of ethanol and toluene (1:1 in volume) solvent, and could not be dissolved in ethanol and water. Their structures have been affirmed by spectroscopic data (such as: IR-, NMR- spectra). O N=C=S OAc OAc AcO AcO + I 1 2 34 5 6 1' 2' 3' 3a' 5' II a-g III a-g O NH OAc OAc AcO AcO NH S S N R6' 4' S N NH2 R 7a' 7' II and III: a R=H; b R=Cl; c R=OEt; d R=Me, e R=COOMe; f R=COOEt; g R=COOPr-n Schema 1: Synthesis of substituted N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-N’-(benzothiazole-2’-yl)thioureas In the IR spectra of above glucopyranosyl thioureas, the stretching band of C=S bond in thioureas linkage appeared in regions of 1367 - 1373 cm-1, and N-H bonds in thioureas have absorption band in regions of 3490 - 3168 cm-1, specified for stretching vibrations of these bonds. These bands sometimes have been superimposed each other, hence in several cases, one absorption band was appeared in their IR spectra. These bands also appeared in IR-spectra of some N-(2,3,4,6-tetra-O-acetyl-β-D- glucopyranosyl)-N’-(4’,6’-diarylpyrimidine-2- yl) thioureas [7], and N-(2,3,4,6-tetra-O-acetyl- β-D-glucopyranosyl)-N’-(4’-arylthiazole-2’-yl) thioureas [8]. The characteristics of pentaacetated glucopyranose ring was confirmed by the present of absorption band in regions of 1750-1692 cm-1 that specified for stretching vibration of C=O bond in ester function. The 1H-NMR spectra of these above thioureas, for example, the compound IIIc, are represented in Fig.1. There are resonance signals which specified for protons in thioureas N-H groups at δ 11.966 and 8.889 ppm. Some resonance signals are in regions δ 2.096 and 1.902 ppm belong to some protons in methyl and acetyl groups. Protons C-H in pyranose ring of monosaccharide have chemical shifts from δ 5.878 ppm to 3.986 ppm which usually are observed in 1H-NMR spectra of monosaccharide compounds. Proton H-1 has chemical shift in region δ 5.878 ppm (triplet) with coupling constant J= 9.0 Hz. Resonance signal of proton H-2 appeared in triplet as region δ 5.094 ppm with coupling constant J= 5.0 Hz. The values of coupling constants correlated with trans-H-H 605 coupling interactions and indicated β-anomer configuration of NH-thiourea group [9]. Other protons, such as H-3 and H-4, have triplet resonance signals in regions δ 5.452 ppm (with coupling constants J3,4= 9.5 Hz) and δ 4.928 ppm (with coupling constants J4,3 = J4,5 = 9.5 Hz), respectively. Three protons in benzothiazole have two chemical shifts in regions from δ 7.617 ppm to δ 7.016 ppm. In the COSY spectra of thiourea IIIc, it was shown that proton H-1 interacted with proton H- 2 and proton in NH bond of thiourea linkage, and that these signals appeared in triplet. Protons H-2 had the interactions with proton H- 3 and proton H-1. Protons in phenyl also have some interactions each other in AX type. Table 1: Some derivatives of substituted N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-N’-(benzothiazole-2’-yl)thioureas IR spectra, cm-1 Compd. R Melting Point, °C Yield, % νN-H νC=O (ester) νC=S IIIa H 200-202 52 3490; 3175 1746 1373 IIIb Cl 210-212 55 3476; 3168 1747 1367 IIIc OEt 202-204 66 3483; 3196 1747 1371 IIId CH3 201-203 54 3469; 3175 1748 1370 IIIe COOMe 202-203 57 3490; 3182 1750; 1721 1373 IIIf COOEt 203-205 48 3469; 3175 1754; 1692 1370 IIIg COOPr-n 205-206 60 3471; 3172 1748; 1715 1370 Figure 1: 1H-NMR spectra of compound IIId In the 13C-NMR spectra, it could be noticed that the number of carbon atoms in spectra and this one in molecular formulas of each thioureas were identical each other. For example, the compound of thiourea IIIc is represented in Fig. 3, there were some resonance peaks in high-field 606 region of 30.609 - 14.605 ppm that’s indicated the present of ethoxy group and methyl groups on acetyl function. Six carbon atoms in pyranose ring have clearly resonance signal in region of 81.347 - 61.690 ppm. The carbon atoms in benzothiazole rings have chemical shifts in region of 115.195 - 106.004 ppm. The magnetic resonance signals of the thiocarbonyl and carbonyl groups have appeared in the low-field region of 206.473 and 169.992 - 169.336 ppm. Table 2: 1H-NMR Spectra of substituted N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-N’-(benzothiazole-2’-yl)thioureas Compd. Alkyl and acetyl groups Pyranose ring Thiourea Benzothiazole ring IIIa 2.009 - 1.955 5.902 - 30.996 12.219; 9.125 8.168 - 7.566 IIIb 2.011 - 1.879 5.904 - 3.997 12.194; 9.126 8.045 - 7.443 IIIc 2.087 - 1.833; 1.345 5.894 - 3.986 11.966; 8.899 7.617 - 7.016 IIId 2.510 - 1.956 5.927 - 3.981 12.234; 8.899 7.686 - 7.244 IIIe 3.995; 2.049 - 1.878 5.919 - 3.870 12.344; 9.206 8.539 - 7.680 IIIf 2.012 - 1.955; 1.341 5.920 - 4.020 12.213; 9.231 8.567 - 7.513 IIIg 2.016 - 1.959; 1.767; 1.012 5.925 - 4.002 12.256; 9.232 8.653 - 7.889 Figure 3: 13C-NMR spectra of compound IIId In NMR spectra using HMBC and HSQC experiments, the long-range and the short-range C-H interactions were shown, for example, the HSQC and HMBC spectra of IIIc in Figures 4 and 5. Carbon atom C1’ had long-range interaction with proton H2’ and proton H1; carbon atom C2’ interacted with protons H2’ and H3’, etc Acknowledgment. This publication is completed with financial support from the Grant QGTĐ.08-03, Vietnam National University, Hanoi. 607 Table 3: The result data analysis of 13C-NMR (ppm) of substituted N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl) –N’-(benzothiazole-2’-yl)thioureas Compd. Alkyl and Acetyl groups Pyranose ring Benzothiazole ring IIIa 20.443 - 20.223 169.896 - 169.250 81.239 - 61.638 129.348 - 115. 424 IIIb 20.451 - 20.230; 169.907 - 169.263 81.245 - 61.642 127.673 - 121.579 IIIc 30.609; 20.478 - 18.485; 14.605 169.992 - 169.336 81.347 - 61.690 155.537 - 106.004 IIId 20.883 - 20.239; 169.939 - 169.296 81.402 - 61.697 133.305 - 121.542 IIIe 53.028; 21.387 - 21.169; 170.854 - 170.210; 166.702 82.184 - 62.571 128.445 - 124.828 IIIg 66.099; 21.611 - 20.230; 10.289 169.900 - 169.259; 165.304 81.315 - 61.644 127.484 - 123.871 References 1. A. Varki. Glycobiology, Vol. 3, 97 - 99 (1993). 2. H. G. Garg, R. W. Jeanloz. Adv. Carbohydr. Chem. Biochem., Vol. 43, 135 - 140 (1985). 3. G. Yasuo, S. Isao. Synthetic Commun., Vol. 29, 1493 - 1497 (1999). 4. A. K. Mukerjee, R. Ashare. Chem. Rev. Vol. 91, 1 - 14 (1991). 5. A. S. Tims, D. L. Taylor, P. S. Sunkara, M. S. Kang. Pharmacochem. Libr. Vol. 14, 257 - 263 (1990). 6. Bama K Garnaik & Rajanik K Behera. Indian J. Chem., Vol. 27B, 1157 - 1158 (1988). 7. Nguyen Dinh Thanh, Pham Hong Lan, Dang Nhu Tai. Vietnam Journal of Chemistry, Vol. 46 (5A), 427 - 431 (2008). 8. Nguyen Dinh Thanh, Nguyen Thi Thanh Mai. Vietnam Journal of Chemistry, Vol. 46 (1), 102 - 107 (2008). 9. Carla, Nathalie Mora, Jean-Michel Lacombe. Carbohydr. Res., 321, 4 - 14 (1999). 10. C. K. Lee, A. Linden, A. Vaselle. Acta Cryst. Vol. C51, 1906 - 1907 (1995). Corresponding author: Nguyen Dinh Thanh Faculty of Chemistry, Hanoi University of Science, VNU Email: nguyendinhthanh@hus.edu.vn