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An efficient and facile synthesis of 1,2,4-aryl triazoles and 4-thiazolidinones bearing 6-fluorochroman nucleus.

1. Introduction

The design and synthesis of hybrid molecules encompassing two pharmacophores in one molecular scaffold is a well-established approach to the synthesis of more potent drugs with dual activity. With this aspect, 6-fluorochroman-2carboxylic acid derivatives in connection with thiazolidinone and 1, 2, 4-triazoles were found as a promising target for the current research project. 1, 2, 4-Triazoles and 4-thiazolidinones are the broadly investigated molecules. They have proved to be the most useful framework for biological activities among nitrogen containing five membered heterocycles. Amongst the diverse classes of heterocyclic compounds chroman, a class of oxygen containing heterocycle forms an important part of many pharmacologically active compounds. For example, the chroman ring is a constituent of various bioactive compounds that are sodium channel blocker [1], 5H[T.sub.1A] inhibitor [2], and so forth. Commercially available antihypertensive drugs of chroman repinotan [3], robalzotan [4], and specifically 6-fluorochroman nebivolol [5] are well known. Hence, the synthesis of 6-fluorochroman derivatives is currently of significant interest in organic synthesis.

Aryl triazoles comprise various heterocyclic compounds possessing promising biological activity and are found as potential antimicrobial [6, 7] and adenosine [A.sub.2]A receptor antagonist [8]. According to the green chemistry approach there are many solvent free reactions of 1, 2, 4-aryl triazoles that have been reported [9,10].

4-Thiazolidinones have been widely explored for their applications in the field of medicine and agriculture [11]. They are also known as promising antimicrobial [12], anti-inflammatory [13, 14], antimalerial [15], anticancer [16], tuberculostatic [17], and antiviral agents [18]. Several one-pot multicomponent syntheses of4-thiazolidinone have been reported [19-21].

2. Result and Discussion

The syntheses of triazole and thiazolidinone derivatives have been previously reported by many researchers, and they normally required additional additives and long reaction time. So in this paper, we described an efficient and safe procedure for the synthesis of 4-aryl triazole containing chroman nucleus, using 6-fluorochroman-2-carboxylic acid. 6-Fluorochroman-2-carboxylic acid on esterification with methanol in the presence of concentrated [H.sub.2]S[O.sub.4] at room temperature gave compound 1 (Scheme 1) with good yield which on reaction with hydrazine hydrate (99%) gave compound 2. Compound 2 on reaction with carbon disulphide in the presence of KOH in methanol at RT afforded compound 3. This on further reaction with substituted aniline without use of any solvent in fused condition yielded compounds 4a-4j (Scheme 1). [sup.1]H and [sup.13]C NMR spectra of the products clearly indicated the formation of triazoles 4a-4j in 75-95% yields (Table 1). The formation of thiol group -SH was identified by a sharp singlet at around [delta] = 11.43 ppm. By the [sup.13]C NMR spectrum also supported the presence of -SH group from the deshielding value of carbon attached to -SH group at [delta] 168.71 ppm.

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Here we introduce the one-pot synthesis of thiazolidinone from hydrazide (Scheme 2) with thioglycolic acid, substituted aryl aldehydes in toluene using a Dean-Stark assembly to synthesized compounds 5a-5j (Scheme 2). [sup.1]H and [sup.13]C NMR spectra of the products clearly indicated the formation of 4-thiazolidinone 5a-5j in 71-95% yields (Table 2). The formation of -NH group was identified by a sharp singlet at around [delta] 10.46-10.43 ppm, which is further supported by [D.sub.2]O exchange. [sup.13]C NMR spectrum also supported the presence of amide group from the deshielding value of carbon attached to -CONH group at [delta] 169.3 ppm and carbonyl group (part of a five member ring) at [delta] 169.47 ppm.

3. Conclusion

In summary, an efficient protocol for the synthesis of new 1, 2, 4-aryl triazoles and 4-thiazolidinones has been described. Herein, we are reporting the solvent free protocol for the synthesis of N-substituted 1, 2, 4-aryl triazoles (4a-4j) from potassium salt (3). In literature, the synthesis of 4-thiazolidinones was carried out via 2 steps, but, to avoid multisteps and to make it more viable, we have developed a single-step reaction for the synthesis of 4-thiazolidinones (5a-5j) from hydrazide (2).

4. Experimental

Melting points were determined in open capillary tubes and are uncorrected. Formation of the compounds was checked by TLC on silica gel-G plates of 0.5 mm thickness. IR spectra were recorded on Shimadzu FT-IR-8400 instrument using DRS (diffusive reflectance system) method. Mass spectra were recorded on Shimadzu GC-MS system (model QP-2010) using direct inlet probe technique. [sup.1]H NMR and [sup.13]C NMR were determined in CD[Cl.sub.3] and DMSO-[d.sub.6] on a Bruker AC 400 MHz and 100 MHz spectrometer. Elemental analysis of all the synthesized compounds was carried out on Euro EA 3000 elemental analyzer and the results are in agreement with the structures assigned.

4.1. General Procedure for the Synthesis of Functionalized 1, 2, 4-Aryl Triazoles (4a-4j). To a stirred solution of 6-fluorochroman-2-carboxylic acid (0.01 mol) in methanol at room temperature, concentrated [H.sub.2]S[O.sub.4] (0.01 mol) was added and reaction mixture was allowed to stir at RT for 10 hours. After completion of the reaction, solvent was evaporated and the resulting mass was poured on to ice, neutralized with saturated sodium bicarbonate solution. Separated solid precipitate was filtered, washed with water, and dried to afford methyl 6-fluorochroman-2-carboxylate 1.

Compound 1 (0.01 mol) in absolute ethanol was taken into the RBF and cooled at (-5)[degrees]C. To the previously cooled solution hydrazine hydrate (99%, 0.08 mol) was added and reaction mixture was allowed to stir at 0-(-5)[degrees]C for 10 hours. After the completion of reaction separated solid residues were filtered, washed with cold ethanol, and dried to afford 6fluorochroman-2-carbohydrazide 2, yield: 2.0 g (98%).

To a mixture of compound 2 (0.1 mol) and potassium hydroxide (0.15 mol) in methanol carbon disulphide (0.15 mol) was added dropwise. Reaction mass was allowed to stir at RT for 22-24 hours. After completion of reaction the obtained solid was filtered, washed with diethyl ether, and dried to afford compound 3. There is no need to purify the salt for further reaction.

An equimolar mixture of potassium 2-[(6-fluorochroman-2-yl) carbonyl] hydrazine carbodithioate 3 (0.01 mol) and substituted aniline (0.01 mol) was taken in RBF and heated at 140-150[degrees]C for 12-15 hours until the evolution of [H.sub.2]S gas ceased. After completion of reaction solid residue was dissolved in DMF, treated with dilute HCl, and poured on crushed ice. The product was isolated and crystallized from ethanol to give compounds 4a-4j as analytical pure product.

4.1.1. 5-(6-Fluorochroman-2-yl)-4-(p-tolylf4H-1,2,4-triazole3-thiol (4a). Yield 89%, mp 170-172[degrees]C; IR (DRS): 3076(Ar, C-H str.), 2924(C-H str.), 2573(-SH str.), 1735(C=O str.), 1087(C-N str.), 1041(C-O-C str.) [cm.sup.-1]; :H NMR (400 MHz, CD[Cl.sub.3]): [delta] ppm 2.02-2.44(m, 5H, 2CH, 3CH), 2.65-2.96(m, 2H, 2CH), 4.83-4.90(dd, J = 12.6 Hz, 6 Hz, [sup.1]H, CH), 6.606.64(m, [sup.1]H, ArH), 6.73-6.76(m, 2H, ArH), 7.05-749(m, 4H, ArH), 11.43(s, [sup.1]H, SH). [sup.13]C NMR (100 MHz, CD[Cl.sub.3]): [delta] ppm 20.3(C[H.sub.3]), 26.27(C[H.sub.2]), 28.87(C[H.sub.2]), 85.3(Ch), 108.52(CH), 112.98(CH), 116.81(CH), 119.54(CH), 129.2(C), 131.16(C), 133.09(CH), 136.12(C), 139.69(C), 155.8(C), 158.29(c), 173.99(C). MS: m/z = 341 [[M].sup.+]; Anal. Calcd for [C.sub.18][H.sub.16]F[N.sub.3]OS: C, 63.32; H, 4.72; N, 12.31. Found: C, 63.23; H, 4.41; N, 12.28%.

4.1.2. 4-(3-Chlorophenyl)-5-(6-fluorochroman-2-yl)-4H-1, 2, 4-triazole-3-thiol (4b). Yield 86%, mp 205-207[degrees]C; IR (DRS): 3066(Ar, C-H str.), 2914(C-H str.), 2850(C-H str.), 2533(-SH str.), 1558(Ar, C=C bend.), 1375(C-H ben), 800(C-Cl str.), 1087(C-N str.), 1041(C-O-C str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, DMSO-[d.sub.6]): [delta] ppm 2.27-2.30(m, 2H, 2CH), 2.82-2.95(m, 2H, 2CH), 4.92-4.95(dd, J = 6.12 Hz, 12 Hz, 1H, CH), 6.50-6.54(m, 1H, ArH), 6.75-6.79(m, 2H, ArH), 741-743(m, 1H, ArH), 7.53-7.55(m, 3H, ArH), 14.0(s, 1H, SH). [sup.13]C NMR (100 MHz, DMSO-[d.sub.6]): [delta] ppm 25.27(C[H.sub.2]), 28.27(C[H.sub.2]), 85.3(CH), 112.98(CH), 116.81(CH), 120.08(CH), 122.3(CH), 125.68(CH), 129.2(C), 133.41(CH), 138.88(C), 139.69(C), 142.37(C), 155.8(C), 158.29(C), 173.99(C) MS: m/z = 361 [[M].sup.+]; Anal. Calcd for [C.sub.17][H.sub.13]ClF[N.sub.3]OS: C, 56.43; H, 3.62; N, 11.61. Found: C, 56.18; H, 3.49; N, 11.59%.

4.1.3. 5-(6-Fluorochroman-2-yl)-4-(4-fluorophenyl)-4H-1,2,4triazole-3-thiol (4c). Yield 78%, mp 188-190[degrees]C; IR (DRS): 3030(Ar, C-H str.), 2558(-SH str.), 1581(-C=C-, str.), 1225(C-O-C str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, CD[Cl.sub.3]): [delta] ppm 2.21-2.46(m, 2H, 2CH), 2.75-2.85(m, 2H, 2CH), 4.88-4.93(dd, J = 12.6 Hz, 6 Hz, [sup.1]H, CH), 6.51-6.55(m, [sup.1]H, ArH), 6.77-6.81(m, 2H, ArH), 7.53-7.57(m, 3H, ArH), 13.05(s, [sup.1]H, SH). [sup.13]C NMR (100 MHz, CD[Cl.sub.3]): 26.27(C[H.sub.2]), 28.87(C[H.sub.2]), 85.3(CH), 108.52(CH), 112.98(CH), 116.81(Ch), 118.6(CH), 122.97(CH), 129.2(C), 133.7(C), 139.69(C), 155.8(C), 158.29(C), 160.51(C), 173.99(C). MS: m/z = 345 [[M].sup.+]; Anal. Calcd for [C.sub.17][H.sub.13][F.sub.2][N.sub.3]OS: C, 59.12; H, 3.79; N, 12.17. Found: C, 59.02; H, 3.53; N, 12.01%.

4.1.4. 4-(2, 5-Dimethylphenyl)-5-(6-fluorochroman-2-yl)-4H I, 2, 4-triazole-3-thiol (4d). Yield 95%, mp 123-125[degrees]C; IR (DRS): 3074(Ar, C-H str.), 2984(C-H str.), 1645(-C=C-, str.), 1468(C-H bending) [cm.sup.-1]; [sup.1]H NMR (400 MHz, CD[Cl.sub.3]): [delta] ppm 1.92(s, 6H, 3CH, 3CH), 2.21-2.46(m, 2H, 2CH), 2.75-2.85(m, 2H, 2CH), 4.85-4.92(dd, J = 12.6 Hz, 6 Hz, [sup.1]H, CH), 6.72-6.95(m, 3H, ArH), 7.29-7.43(m, 3H, ArH), 13.05(s, [sup.1]H, SH). [sup.13]C NMR (100 MHz, CD[Cl.sub.3]): [delta] ppm 17.98(C[H.sub.3]), 26.87(C[H.sub.2]), 28.87(C[H.sub.2]), 30.2(C[H.sub.3]), 85.3(CH), 108.52(CH), 116.81(CH), 118.6(CH), 112.98(CH), 124.19(CH), 132.61(CH), 134.95(C), 138.13(C), 140.75(C), 146.2(C), 155.8(C), 158.29(C), 175.05(c). MS: m/z = 355 [[M].sup.+]; Anal. Calcd for [C.sub.19][H.sub.18]F[N.sub.3]OS: C, 64.21; H, 5.10; N, 11.82. Found: C, 64.16; H, 4.93; N, 11.78%.

4.1.5. 4-(3,4-Dimethylphenyl)-5-(6-fluorochroman-2-yl)-4H-1, 2, 4-triazole-3-thiol (4e). Yield 84%, mp 163-165[degrees]C; IR (DRS): 3081(Ar, C-H str.), 2975(C-H str.), 2575(-SH str.), 1641(C-H bending), 1579(-C=C-, str.), 1142(C-F str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, CD[Cl.sub.3]): [delta] ppm 2.34(s, 6H, 3CH, 3CH), 2.21-2.46(m, 2H, 2CH), 2.75-2.85(m, 2H, 2CH), 4.85-4.92(dd, J = 12.6 Hz, 6 Hz, [sup.1]H, CH), 6.72-6.95(m, 3H, ArH), 7.29-7.43(m, 3H, ArH), 13.05(s, [sup.1]H, SH). [sup.13]CNMR (100 MHz, CD[Cl.sub.3]): [delta] ppm 19.0(C[H.sub.3]), 20.01(C[H.sub.3]), 26.27(C[H.sub.2]), 28.87(C[H.sub.2]), 85.3(CH), 112.98(cH), 116.81(CH), 117.91(Ch), 124.04(CH), 129.2(C), 132.85(c), 133.52(C), 139.69(c), 141.78(C), 143.79(C), 155.8(C), 158.29(C), 173.998(C). MS: m/z = 355 [[M].sup.+]; Anal. Calcd for [C.sub.19][H.sub.18]F[N.sub.3]OS: C, 64.21; H, 5.10; N, 11.82. Found: C, 64.09; H, 5.03; N, 11.50%.

4.1.6. 5-(6-Fluorochroman-2-yl)-4-(2-fluorophenyl)-4H-1, 2,4triazole-3-thiol (4f). Yield 79%, mp 108-110[degrees]C; IR (DRS): 3080(Ar, C-H str.), 2983(C-H str.), 2561(-SH str.), 1629(C-H bending), 1572(C-H bending), 1525(-C=C-, str.) 1196(C-O-C str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, CD[Cl.sub.3]): [delta] ppm 2.34(s, 6H, 3CH, 3CH), 2.21-2.46(m, 2H, 2CH), 2.75-2.85(m, 2H, 2CH), 4.90-4.97(dd, J = 12.6 Hz, 6 Hz, [sup.1]H, CH), 6.72-6.95(m, 3H, ArH), 7.24-7.75(m, 3H, ArH), 13.05(s, [sup.1]H, SH). [sup.13]C NMR (100 MHz, CD[Cl.sub.3]): [delta] ppm 26.27(C[H.sub.2]), 28.87(C[H.sub.2]), 85.3(CH), 108.52(CH), 112.98(CH), 116.81(CH), 119.7(C), 119.58(CH), 129.2(C), 129.95(CH), 130.09(CH), 130.97(CH), 139.69(C), 155.8(C), 158.29(C), 162.56(C), 173.99(C). MS: m/z = 345 [[M].sup.+]; Anal. Calcd for [C.sub.17][H.sub.13][F.sub.2][N.sub.3]OS: C, 59.12; H, 3.79; N, 12.17. Found: C, 58.96; H, 3.67; N, 12.06%.

4.1.7. 4-(2-Chlorophenyl)-5-(6-fluorochroman-2-yl)-4H-1,2,4 triazole-3-thiol (4g). Yield 76%, mp 192-194[degrees]C; IR (DRS): 3077(Ar, C-H str.), 2978(C-H str.), 2563(-SH str.), 1563(-C=C str.), 1464(H-C-H bend), 1310(C-O str.), 870(C-Cl str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, CD[Cl.sub.3]): [delta] ppm 2.34(s, 6H, 3CH, 3CH), 2.21-2.46(m, 2H, 2CH), 2.75-2.85(m, 2H, 2CH), 4.90-4.97(dd, J = 12.6 Hz, 6 Hz, [sup.1]H, CH), 6.72-6.95(m, 3H, ArH), 7.39-7.50(m, 3H, ArH), 13.05(s, [sup.1]H, SH). [sup.13]C NMR (100 MHz, CD[Cl.sub.3]): [delta] ppm 26.27(C[H.sub.2]), 28.87(C[H.sub.2]), 85.3(CH), 108.52(CH), 112.98(CH), 116.81(CH), 127.83(CH), 126.39(C), 128.04(CH), 129.2(C), 131.85(CH), 132.57(CH), 140.8(C), 142.53(C), 155.8(C), 158.29(C), 175.1(c). MS: m/z = 361 [[M].sup.+]; Anal. Calcd [C.sub.17][H.sub.13]ClF[N.sub.3]OS: C, 56.43; H, 3.62; N, 11.61. Found: C, 55.97; H, 3.55; N, 11.59%.

4.1.8. 4-(3-Chloro-4-fluorophenyl)-5-(6-fluorochroman-2-yl)4H-1,2,4-triazole-3-thiol (4h). Yield 87%, mp 139-141[degrees]C; IR (DRS): 3075(Ar, C-H str.), 2553(-SH str.), 1581(-C=C-, str.), 1423(H-C-H bend), 1281(C-O str.), 870(C-Cl str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, DMSO-[d.sub.6]): [delta] ppm 2.34(s, 6H, 3CH, 3CH), 2.21-2.46(m, 2H, 2CH), 2.75-2.85(m, 2H, 2CH), 4.90-4.97(dd, J = 12.6 Hz, 6 Hz, [sup.1]H, CH), 6.72-6.95(m, 3H, ArH), 7.18-7.79(m, 3H, ArH), 13.05(s, [sup.1]H, SH). [sup.13]C NMR (100 MHz, DMSO-[d.sub.6]): [delta] ppm 26.27(C[H.sub.2]), 28.87(C[H.sub.2]), 85.3(CH), 108.52(CH), 112.98(CH), 116.81(CH), 120.08(CH), 121.91(CH), 124.85(C), 125.71(CH), 129.2(c), 139.69(c), 141.09(C), 155.8(C), 156.41(C), 158.29(C), 173.99(C). MS: m/z = 379 [[M].sup.+]; Anal. Calcd for [C.sub.17][H.sub.12]Cl[F.sub.2][N.sub.3]OS: C, 53.76; H, 3.18; N, 11.06. Found: C, 53.69; H, 3.07; N, 10.90%.

4.1.9. 5-(6-Fluorochroman-2-yl)-4-(2-methoxyphenyl)-4H-1, 2, 4-triazole-3-thiol (4i). Yield 90%, mp 251-253[degrees]C; IR (DRS): 3075(Ar, C-H str.), 2553(-SH str.), 1581(-C=C-, str.), 1423(H-C-H bend), 1281(C-O str.), 870(C-Cl str.), 1080(C-F str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, DMSO-[d.sub.6]): [delta] ppm 2.34(s, 6H, 3CH, 3CH), 2.21-2.46(m, 2H, 2CH), 2.75-2.85(m, 2H, 2CH), 3.83(s, 3H, OC[H.sub.3]), 4.90-4.97(dd, J = 12.6 Hz, 6 Hz, [sup.1]H, CH), 6.72-6.95(m, 3H, ArH), 6.99-7.51(m, 4H, ArH), 13.05(s, [sup.1]H, SH). [sup.13]C NMR (100 MHz, DMSO-[d.sub.6]): [delta] ppm 26.27(C[H.sub.2]), 28.87(C[H.sub.2]), 56.32(C[H.sub.3]), 85.3(Ch), 108.52(CH), 112.98(CH), 115.51(CH), 116.81(CH), 120.83(CH), 123.69(CH), 129.2(C), 131.19(CH), 134.73(C), 139.24(c), 155.8(C), 157.76(C), 158.29(C), 173.54(C). MS: m/z = 357 [[M].sup.+]; Anal. Calcd for [C.sub.18][H.sub.16]F[N.sub.3][O.sub.2]S: C, 60.49; H, 4.51; N, 11.76. Found: C, 60.39; H, 4.29; N, 11.37%.

4.1.10. 4-(2, 5-Difluorophenyl)-5-(6-fluorochroman-2-yl)-4Hl,2,4-triazole-3-thiol (4j). Yield 75%, mp 229-231[degrees]C; IR (DRS): 3061(Ar, C-H str.), 2951 (C-H str.), 2535(-SH str.), 1589(-C=C-, str.), 1462(H-C-H bend), 1520(C-O str.), 1075(C-F str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, CD[Cl.sub.3]): [delta] ppm 2.34(s, 6H, 3CH, 3CH), 2.21-2.46(m, 2H, 2CH), 2.752.85(m, 2H, 2Ch), 3.83(s, 3H, OC[H.sub.3]), 4.90-4.97(dd, J = 12.6 Hz, 6 Hz, [sup.1]H, CH), 6.72-6.95(m, 3H, ArH), 7.13-7.22(m, 3H, ArH), 13.05(s, [sup.1]H, SH). [sup.13]C NMR (100 MHz, CD[Cl.sub.3]): 26.27(C[H.sub.2]), 28.87(C[H.sub.2]), 85.3(CH), 108.29(CH), 108.69(CH) 112.98(CH), 116.81(CH), 117.32(CH), 118.79(C), 127.11(CH), 129.2(C), 139.69 (C), 155.8(C), 158.29(C), 159.93(C), 173.54(C). MS: m/z = 363 [[M].sup.+]; Anal. Calcd for [C.sub.17][H.sub.12][F.sub.3][N.sub.3][O.sub.2]S: C, 56.19; H, 3.33; N, 11.56. Found: C, 56.06; H, 3.14; N, 11.32%.

4.2. General Procedure for the Synthesis of Functionalized 4-Thiazolidinones 5a-5j. An equimolar mixture of 6-fluorochroman-2-carbohydrazide 2 (0.01 mol) and different aryl aldehydes (0.01 mol) was taken in RBF and to this, thioglycolic acid (mercaptoacetic acid) (0.29 mol) in toluene was added. Then reaction mixture was allowed to reflux in a Dean-Stark assembly with continuous stirring. After completion of the reaction (48 hrs monitoring by TLC), the content was cooled to room temperature and then neutralized with saturated sodium bicarbonate solution. The organic extracts were washed with water and dried over [Na.sub.2]S[O.sub.4]. The solvent was evaporated in vacuo and the resulting crude product was purified by column chromatography to give the analytical pure compounds 5a-5j. Column chromatography was carried out in hexane: ethyl acetate solvent system. Pure compound was eluted in 23% ethyl acetate in hexane.

4.2.1. 6-Fluoro-N-(2-(4-methoxyphenyl)-4-oxothiazolidine-3-yl) chroman-2-carboxamide (5a). Yield 85%, mp 98-100[degrees]C; IR (DRS): 3383(Amide-NH str.), 3081(Ar, C-H str.), 2958(CH str.), 1714(C=O str.), 1688(amide C=O str.), 1542(-NH bend), 1365(C-F str.), 1278(C-O-C str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, DMSO-[d.sub.6]): [delta] ppm 2.15-2.40(m, 2H, 2CH), 2.752.85(m, 2H, 2CH), 3.83(s, 3H, OC[H.sub.3]), 4.69-4.72(d, J = 16.0 Hz, [sup.1]H, CH), 3.91-3.95(d, J = 15.6 Hz, [sup.1]H, CH), 4.69-4.72(dd, J = 3.6 Hz, 3.2 Hz, [sup.1]H, CH), 5.92(s, [sup.1]H, CH), 6.72-6.95(m, 3H, ArH), 6.87-7.84(m, 4H, ArH), 8.0(s, [sup.1]H, NH), [sup.13]C NMR (100 MHz, DMSO-[d.sub.6]): [delta] ppm 25.25(C[H.sub.2]), 26.19(C[H.sub.2]), 34.2(C[H.sub.2]), 55.33(C[H.sub.3]), 70.50(CH), 85.58(CH), 108.7(CH), 112.44(CH), 114.1(CH), 116.43(CH), 126.91(CH), 129.9(C), 133.68(C), 154.35(C), 157.18 (C), 155.8(C), 158.08(C), 165.35(C), 169.36(C). MS: m/z = 402 [[M].sup.+]; Anal. Calcd for [C.sub.20][H.sub.19]F[N.sub.2][O.sub.4]S: C, 59.69; H, 4.76; N, 6.96. Found: C, 59.23; H, 4.61; N, 6.88%.

4.2.2. 6-Fluoro-N-(2-(2-nitrophenyl)-4-oxothiazolidine-3-yl) chroman-2-carboxamide (5b). Yield 95%, mp 190-192[degrees]C; IR (DRS): 3392(Amide-NH str.), 3205(Ar, C-H str.), 1712(C=O str.), 1678(amide C=O str.), 1523(-NH bend), 1590(N=O str.), 1259(C-O-C str.), 1190(C-F str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, DMSO-[d.sub.6]): [delta] ppm 1.81-2.05(m, 2H, 2CH), 2.61-2.74(m, 2H, 2CH), 3.68-3.72(d, J = 16.0 Hz, [sup.1]H, CH), 3.91-3.95(d, J = 15.6 Hz, [sup.1]H, CH), 4.66-4.69(dd, J = 3.6 Hz, 3.2 Hz, [sup.1]H, CH), 6.12(s, [sup.1]H, CH), 6.72-6.79(m, [sup.1]H, ArH), 6.84-6.91(m, 2H, ArH), 7.60-7.63(t, [sup.1]H, ArH), 7.78-7.87(m, 2H, ArH), 8.048.06(d, J = 8.0 Hz, [sup.1]H, ArH), 10.43-10.46(d, J = 11.6 Hz, [sup.1]H, NH). [sup.13]C NMR (100 MHz, DMSO-[d.sub.6]): [delta] ppm 25.25(C[H.sub.2]), 26.19(C[H.sub.2]), 34.2(C[H.sub.2]), 68.3(CH), 85.58(CH), 108.7(CH), 114.1(CH), 116.43(CH), 123.91(CH), 125.5(C), 129.87(CH), 129.9(C), 127.85(CH), 132.06(C), 149.87(C), 154.35(C), 157.18 (C), 169.36(C). MS: m/z = 417 [[M].sup.+]; Anal. Calcd for [C.sub.19][H.sub.16]F[N.sub.3][O.sub.5]S: C, 54.67; H, 3.86; N, 10.07. Found: C, 54.58; H, 3.49; N, 9.99%.

4.2.3. 6-Fluoro-N-(2-(4-fluorophenyl)-4-oxothiazolidine-3-yl) chroman-2-carboxamide (5c). Yield 89%, mp 106-110[degrees]C; IR (DRS): 3487(Amide-NH str.), 3041(Ar, C-H str.), 1710(C=O str.), 1676(amide C=O str.), 1537(-NH bend), 1201(C-O-C str.), 1190(C-F str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, CD[Cl.sub.3]): [delta] ppm 1.82-2.02(m, 2H, 2CH), 2.56-2.70(m, 2H, 2CH), 3.59-3.78(m, 2H, 2CH), 4.45-4.58(dd, J = 10.52 Hz, 11.52 Hz, [sup.1]H, CH), 5.79-5.83(d, J = 17.32 Hz, [sup.1]H, CH), 6.54-6.72(m, 3H, ArH), 6.86-6.90(t, [sup.1]H, ArH), 6.99-703(t, [sup.1]H, ArH), 7.20-7.22(t, [sup.1]H, ArH), 7.33-7.36(t, [sup.1]H, ArH), 8.05-8.13(d, J = 29.44 Hz, [sup.1]H, NH). [sup.13]C NMR (100 MHz, CD[Cl.sub.3]): [delta] ppm 25.25(C[H.sub.2]), 26.19(C[H.sub.2]), 34.2(C[H.sub.2]), 70.52(Ch), 85.58(CH), 108.7(CH), 113.27(CH), 114.1(CH), 116.43(CH), 127.64(Ch), 129.9(C), 136.68(C), 154.35(C), 157.18 (c), 160.07(C), 165.35(C), 169.36(C). MS: m/z = 390 [[M].sup.+]; Anal. Calcd for [C.sub.19][H.sub.16][F.sub.2][N.sub.2][O.sub.3]S: C, 58.45; H, 4.13; N, 7.18. Found: C, 58.02; H, 4.03; N, 7.10%.

4.2.4. N-(2-(3-Chlorophenyl)-4-oxothiazolidine-3-yl)-6-fluorochroman-2-carboxamide (5d). Yield 77%, mp 151-153[degrees]C; IR (DRS): 3401(Amide-NH str.), 3200(Ar, C-H str.), 1717(C=O str.), 1645(amide C=O str.), 1550(-NH bend), 1245(C-F str.), 1201(C-O-C str.), 820(C-Cl str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, DMSO): [delta] ppm 2.15-2.40(m, 2H, 2CH), 2.75-2.85(m, 2H, 2CH), 4.66-4.69(d, J = 16.0 Hz, [sup.1]H, CH), 3.91-3.95(d, J = 15.6 Hz, [sup.1]H, CH), 4.69-4.72(dd, J = 3.6 Hz, 3.2 Hz, [sup.1]H, CH), 5.92(s, [sup.1]H, CH), 6.72-6.95(m, 3H, ArH), 7.24-7.43(m, 4H, ArH), 8.0(s, [sup.1]H, NH). [sup.13]C NMR (100 MHz, CD[Cl.sub.3]): [delta] ppm 25.25(C[H.sub.2]), 26.19(C[H.sub.2]), 34.2(C[H.sub.2]), 71.78(CH), 85.58(CH), 108.7(CH), 114.1(CH), 116.43(CH), 124.5(CH), 124.93(CH), 126.41(CH), 128(CH), 132.25(C), 140.45(C), 145.35(C), 157.18 (C), 165.35(C), 169.36(C). MS: m/z = 406 [[M].sup.+]; Anal. Calcd for [C.sub.19][H.sub.16]ClF[N.sub.2][O.sub.3]S: C, 56.09; H, 3.96; N, 6.89. Found: C, 55.90; H, 3.83; N, 6.83%.

4.2.5. N-(2-(4-Bromophenyl)-4-oxothiazolidine-3-yl)-6-fluorochroman-2-carboxamide (5e). Yield 90%, mp 118-120[degrees]C; IR (DRS): 3452(Amide-NH str.), 3000(Ar, C-H str.), 1725(C=O str.), 1640(amide C=O str.), 1545(-NH bend), 1345(C-F str.), 1251(C-O-C str.), 520(C-Br str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, DMSO-[d.sub.6]): [delta] ppm 2.15-2.40(m, 2H, 2CH), 2.75-2.85(m, 2H, 2CH), 4.63-4.66(d, J = 16.0 Hz, [sup.1]H, CH), 3.91-3.95(d, J = 15.6 Hz, [sup.1]H, CH), 4.63-4.66(dd, J = 3.6 Hz, 3.2 Hz, [sup.1]H, CH), 5.92(s, [sup.1]H, CH), 6.72-6.95(m, 3H, ArH), 7.12-7.85(m, 4H, ArH), 8.0(s, [sup.1]H, NH). [sup.13]C NMR (100 MHz, DMSO[d.sub.6]): [delta] ppm 25.25(C[H.sub.2]), 26.19(C[H.sub.2]), 34.2(C[H.sub.2]), 70.50(CH), 85.58(CH), 108.7(CH), 114.1(CH), 116.43(CH), 120.41(C), 126.7(CH), 129.36(CH), 129.9(C), 138.93(C), 154.35(C), 157.18 (C), 165.35(C), 169.36(C). MS: m/z = 452 [M+1]+; Anal. Calcd for [C.sub.19][H.sub.16]BrF[N.sub.2][O.sub.3]S: C, 50.56; H, 3.57; N, 6.21. Found: C, 50.45; H, 3.28; N, 6.11%.

4.2.6. 6-Fluoro-N-(2-(4-hydroxyphenyl)-4-oxothiazolidine-3yl) chroman-2-carboxamide (5f). Yield 73%, mp 132-134[degrees]C; IR (DRS): 3452(Amide-NH str.), (-OH, broad), 3011(Ar, C-H str.), 1728(C=O str.), 1645(amide C=O str.), 1545(NH bend), 1352(C-F str.), 1278(C-O-C str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, DMSO-[d.sub.6]): [delta] ppm 2.15-2.40(m, 2H, 2CH), 2.75-2.85(m, 2H, 2CH), 4.63-4.66(d, J = 16.0 Hz, [sup.1]H, CH), 3.91-3.95(d, J = 15.6 Hz, [sup.1]H, CH), 4.63 4.66(dd, J = 3.6 Hz, 3.2 Hz, [sup.1]H, CH), 5.35(s, [sup.1]H, OH), 5.92(s, [sup.1]H, CH), 6.72-6.95(m, 3H, ArH), 7.14-7.86(m, 4H, ArH), 8.0(s, [sup.1]H, NH). [sup.13]C NMR (100 MHz, DMSO[d.sub.6]): [delta] ppm 25.25(C[H.sub.2]), 26.19(C[H.sub.2]), 34.2(c[H.sub.2]), 55.33(C[H.sub.3]), 70.50(CH), 85.58(CH), 108.7(CH), 114.1(CH), 116.43(CH), 116.68(C), 125.81(CH), 129.9(C), 132.68(C), 154.35(C), 157.46 (C), 157.18(C), 165.35(C), 169.36(C). MS: m/z = 388 [[M].sup.+]; Anal. Calcd for [C.sub.19][H.sub.17]F[N.sub.2][O.sub.4]S: C, 58.75; H, 4.41; N, 7.21. Found: C, 58.56; H, 4.34; N, 7.06%.

4.2.7. 6-Fluoro-N-(4-oxo-2-(p-tolyl) thiazolidin-3-yl) chroman-2-carboxamide (5g). Yield 84%, mp 89-91[degrees]C; IR (DRS): 3328(Amide-NH str.), 2998(Ar, C-H str.), 2900(C-H str.), 1741(C=O str.), 1652(amide C=O str.), 1548(-NH bend), 1371(C-F str.), 1300(C-O-C str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, DMSO-[d.sub.6]): Sppm 2.15-2.32(m, 2H, 2CH), 2.34(s, 3H, 3CH), 2.75-2.85(m, 2H, 2CH), 4.63-4.66(d, J = 16.0 Hz, [sup.1]H, CH), 3.91-3.95(d, J = 15.6 Hz, [sup.1]H, CH), 4.63-4.66(dd, J = 3.6 Hz, 3.2 Hz, [sup.1]H, CH), 5.92(s, [sup.1]H, CH), 6.72-6.95(m, 3H, ArH), 7.11(m, 4H, ArH), 8.0(s, [sup.1]H, NH). [sup.13]C NMR (100 MHz, DMSO-[d.sub.6]): [delta] ppm 21.03(C[H.sub.3]), 25.25(C[H.sub.2]), 26.19(C[H.sub.2]), 34.2(C[H.sub.2]), 70.50(CH), 85.58(CH), 108.7(CH), 114.1(CH), 116.43(CH), 126.73(CH), 127.98(CH), 129.9(C), 136.48(C), 136.52(C), 154.35(C), 157.18(C), 165.35(C), 169.36(C). MS: m/z = 386 [[M].sup.+]; Anal. Calcd [C.sub.20][H.sub.19]F[N.sub.2][O.sub.3]S: C, 62.16; H, 4.96; N, 7.25. Found: C, 62.07; H, 4.55; N, 7.09%.

4.2.8. N-(2-(2-Chlorophenyl)-4-oxothiazolidine-3-yl)-6-fluorochroman-2-carboxamide (5h). Yield 71%, mp 158-160[degrees]C; IR (DRS): 3412(Amide-NH str.), 3212(Ar, C-H str.), 1725(C=O str.), 1685(amide C=O str.), 1558(-NH bend), 1251(C-F str.), 1228(C-O-C str.), 800(C-Cl str.), 770(o-di substituted) cm :H NMR (400 MHz, DMSO): [delta] ppm 2.15-2.32(m, 2H, 2CH), 2.75-2.85(m, 2H, 2CH), 4.63-4.66(d, J = 16.0 Hz, [sup.1]H, CH), 3.91-3.95(d, J = 15.6 Hz, [sup.1]H, CH), 4.63- 4.66(dd, J = 3.6 Hz, 3.2 Hz, [sup.1]H, CH), 5.92(s, [sup.1]H, CH), 6.72-6.95(m, 3H, ArH), 7.17-7.65(m, 4H, ArH), 8.0(s, [sup.1]H, NH). [sup.13]C NMR (100 MHz, CD[Cl.sub.3]): [delta] ppm 25.25(C[H.sub.2]), 26.19(C[H.sub.2]), 34.2(C[H.sub.2]), 67.50(CH), 85.58(CH), 108.7(CH), 114.1(CH), 116.43(CH), 125.18(CH), 125.89(CH), 127.02(CH), 127.26(CH), 129.9(C), 131.68(C), 133.39(C), 154.35(C), 157.18 (C), 165.35(C), 169.36(C). MS: m/z = 406 [[M].sup.+]; Anal. Calcd for [C.sub.19][H.sub.16]ClF[N.sub.2][O.sub.3]S: C, 56.09; H, 3.96; N, 6.89. Found: C, 55.93; H, 3.77; N, 6.84%.

4.2.9. 6-Fluoro-N-(2-(4-nitrophenyl)-4-oxothiazolidine-3-yl) chroman-2-carboxamide (5i). Yield 79%, mp 207-209[degrees]C; IR (DRS): 3398(Amide-NH str.), 3212(Ar, C-H str.), 1728(C=O str.), 1688(amide C=O str.), 1543(-NH bend), 1595(N=O str.), 1272(C-O-C str.), 1290(C-F str.) 790(p-di substituted) [cm.sup.-1]; [sup.1]H NMR (400 MHz, CD[Cl.sub.3]): [delta] ppm 2.15-2.32(m, 2H, 2CH), 2.75-2.85(m, 2H, 2CH), 4.63-4.66(d, J = 16.0 Hz, [sup.1]H, CH), 3.91-3.95(d, J = 15.6 Hz, [sup.1]H, CH), 4.63-4.66(dd, J = 3.6 Hz, 3.2 Hz, [sup.1]H, CH), 5.92(s, [sup.1]H, CH), 6.72-6.95(m, 3H, ArH), 7.49-8.14(m, 4H, ArH), 8.0(s, [sup.1]H, NH). [sup.13]C NMR (100 MHz, CD[Cl.sub.3]): [delta] ppm 25.25(C[H.sub.2]), 26.19(C[H.sub.2]), 34.2(C[H.sub.2]), 70.52(CH), 85.58(CH), 108.7(CH), 114.1(CH), 116.43(CH), 122.91(CH), 126.32(CH), 129.9(C), 144.08(C), 145.35(C), 154.35 (C), 157.18(C), 165.35(C), 169.36(C). MS: m/z = 417 [[M].sup.+]; Anal. Calcd for [C.sub.17][H.sub.14]F[N.sub.3][O.sub.2]: C, 54.67; H, 3.86; N, 10.07. Found: C, 54.39; H, 3.79; N, 9.89%.

4.2.10. N-(2-(3-Bromophenyl)-4-oxothiazolidine-3-yl)-6-fluo rochroman-2-carboxamide (5j). Yield 88%, mp 166-168[degrees]C; IR (DRS): 3482(Amide-NH str.), 3110(Ar, C-H str.), 1745(C=O str.), 1590(amide C=O str.), 1485(-NH bend), 1354(C-F str.), 1281(C-O-C str.), 680(m-di substituted), 520(C-Br str.) [cm.sup.-1]; [sup.1]H NMR (400 MHz, CD[Cl.sub.3]): [delta] ppm 2.15-2.32(m, 2H, 2CH), 2.75-2.85(m, 2H, 2CH), 4.63-4.66(d, J = 16.0 Hz, [sup.1]H, CH), 3.91-3.95(d, J = 15.6 Hz, [sup.1]H, CH), 4.63- 4.66(dd, J = 3.6 Hz, 3.2 Hz, [sup.1]H, CH), 5.92(s, [sup.1]H, CH), 6.72-6.95(m, 3H, ArH), 7.22-7.41(m, 4H, ArH), 8.0(s, [sup.1]H, NH). [sup.13]C NMR (100 MHz, CD[Cl.sub.3]): dppm 25.25(C[H.sub.2]), 26.19(C[H.sub.2]), 34.2(C[H.sub.2]), 70.32(CH), 85.58(CH), 108.7(CH), 114.1(CH), 116.43(CH), 120.91(C), 127.55(CH), 127.95(ch), 128.17(CH), 128.74(Ch), 129.9(C), 140.65(C), 154.35(C), 157.18 (C), 165.35(C), 169.36(C).MS: m/z = 452 [[M+1].sup.+] ; Anal. Calcd for [C.sub.19][H.sub.16]F[N.sub.3][O.sub.5]S: C, 50.56; H, 3.57; N, 6.21. Found: C, 50.17; H, 3.14; N, 6.12%.

Conflict of Interests

The authors do not have a direct financial relation with the commercial identity mentioned in the paper that might lead to a conflict of interests for any of the authors.

http://dx.doi.org/10.1155/2014/186207

Acknowledgments

The authors are thankful to the department of chemistry for providing laboratory facilities. The authors are thankful for facilities and grants given under UGC-SAP for Department Research Support (DRS) and Department of Science and Technology (DST) New Delhi for Fund for Improvement of Science and Technology (FIST). The authors are also thankful to RSIC Chandigarh for providing [sup.1]H NMR and [sup.13]C NMR spectral analysis of the compounds.

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Piyush B. Vekariya, Jalpa R. Pandya, and Hitendra S. Joshi

Chemical Research Laboratory, Department of Chemistry, Saurashtra University, Rajkot 360005, India

Correspondence should be addressed to Hitendra S. Joshi; drhsjoshi49@gmail.com

Received 14 April 2014; Accepted 5 July 2014; Published 30 October 2014

Academic Editor: Xin Wang
Table 1: Physical data for 4a-4j.

Entry         Substitution R         Yield (%)

4a          4-C[H.sub.3] phenyl          89
4b              3-Cl phenyl              86
4c              4-F phenyl               78
4d          2,5-Dimethyl phenyl          95
4e          3,4-Dimethyl phenyl          84
4f              2-F phenyl               79
4g              2-Cl phenyl              76
4h            3-Cl-4-F phenyl            87
4i         2-OC[H.sub.3] phenyl          90
4j          2,5-Difluoro phenyl          75

Table 2: Physical data for 5a-5j.

Entry          Substitution R         Yield (%)

5a          4-OC[H.sub.3] phenyl          85
5b           2-N[O.sub.2] phenyl          95
5c               4-F phenyl               89
5d               3-Cl phenyl              77
5e               4-Br phenyl              90
5f               4-OH phenyl              73
5g           4-C[H.sub.3] phenyl          84
5h               2-Cl phenyl              71
5i           4-N[O.sub.2] phenyl          79
5j               3-Br phenyl              88
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Title Annotation:Research Article
Author:Vekariya, Piyush B.; Pandya, Jalpa R.; Joshi, Hitendra S.
Publication:International Scholarly Research Notices
Article Type:Report
Date:Jan 1, 2014
Words:7068
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