The IR spectra were collected by using FTIR-Affinity -1 spectrophotometer in the region 4000–400 cm−1 in KBr pellet. The mass spectra were scanned by the EI technique at 70 eV with an Agilent Technologies 5975C spectrometer. The experimental values of 1H and 13C NMR spectra for the studied compounds were scanned on a Bruker Avance 500 MHz spectrometer. TMS as the internal standard. DMSO-d6 was used as a solvent. Melting points were measured on an electrothermal apparatus. Elemental analysis (CHNS) was measured by using elementaryVario MICRO. UV-Visible were measured by spectrophotometer type PG-instrument T80+. Microplate Reader Instrument using STAT FAX 2100, BioTek, Winooski, USA.
Two types of heterocyclic derivatives were prepared from thiosemicarbazone. The first type is thiazolidine-4-one and its derivatives, the second type is thaiadaiazoline derivatives.
4.2.1. Procedure for synthesis 2-(diphenyl methylene)hydrazine-1-carbothioamide (1):
Thiosemocarbazide (0.914g, 10 m.mol) was added to hot ethanol and (1.822g, 10m.mol) of benzophenone with 1ml of glacial acetic acid, the reaction mixture was refluxed for 3h Then cool down to room temperature, the solid product was filtered, dried and finally recrystallization from ethanol.
White crystals, yield: 90%, M.p: 173–172°C.1H NMR (DMSO, δppm):7.34 (t,3H,J= 5Hz, Ar-H)7.38(t,3H,J=5Hz,Ar-H)7.64(d,2H,J=5Hz,Ar-H)7.67 (d,2H,J=5Hz,Ar-H)8.41- 8.37 (s, 2H, NH2)8.64(s, H,NH).13C NMR (DMSO, δppm) 128 ,130,131,136.7, 149.5, 178.3..IR (υ, cm−1):3412, 3346, 3250,3053,1496,1481, 3053, 1325, 650.MS (70 eV, m/z) : 255.34[M], 238, 222.2, 195.2, 180.1, 165.1, 77.1. Anal. calc. for:C14H13N3S:C, 68.65; H, 5.83; N, 17.46; S, 13.26, found: C, 66.96; H, 5.33; N, 16.92; S, 12.87.
4.2.2.Procedure for synthesis 2-((diphenylmethylene)hydrazineylidene)thiazolidin-4-one (2):
Compound 2 was prepared from thiosemicarbazone (1) with cyclization agent chloroacetic acid and sodium acetate. The thiosemicarbazone(1) (1.2g, 4 m.mol) was dissolved in 50ml ethanol and added chloroacetic acid (0.8g, 4m.mol ), sodium acetate (1.32g, 16m.mol), the reaction mixture was refluxed for 8hrs, after the reaction completion cools down to room temperature, then it was poured to cool water, it was kept overnight, the reaction mixture filtered and recrystallization from ethanol.
Pale yellow crystals, yield: 73%, M.p: 185–186°C.1H NMR (DMSO, δ ppm): 3.86 (S,2H), 7.23(t,3H, J=5Hz,Ar-H), 7.42(t,3H, J=5Hz, Ar-H), 7.45(d,2H,J=5Hz,Ar-H), 7.53(d,2H,J=5Hz,Ar-H), 11.90(s ,H, NH). 13C NMR (DMSO, δ ppm): 33.2, 128.3-138.1,162.1, 174.3, C=O: 226.8. IR (υ, cm−1): 3124,3062, 2962, 1705, 1616,1585, 1490, 1442, 1317,1165, 696. MS (70 eV, m/z):295.36 [M], 248.2, 218.2, 207.1, 195.2, 180.1, 165, 115, 77.2. Anal. calc. for:C16H13N3OS,C, 65.07; H, 4.44; N, 14.23; S, 10.85, found: C, 64.56; H, 4.13; N; 13. 93; S, 10.16.138.1,162.1, 174.3, C=O: 226.8. IR (υ, cm−1): 3124,3062, 2962, 1705, 1616,1585, 1490, 1442, 1317,1165, 696. MS (70 eV, m/z):295.36 [M], 248.2, 218.2, 207.1, 195.2, 180.1, 165, 115, 77.2. Anal. calc. for:C16H13N3OS,C, 65.07; H, 4.44; N, 14.23; S, 10.85, found: C, 64.56; H, 4.13; N; 13. 93; S, 10.16.
4.2.3.General Procedure for synthesis thiazolidine -4-one derivatives (3a-3e)
An equimolar amount of thiazolidine-4-one (2) and the corresponding aldehyde (0.2 m.mol)
Dissolved in glacial acetic acid (20ml), then added anhydrous sodium acetate (1.2g) the was heated at 120oC in an oil bath, the reaction mixture was monitored by TLC using (chloroform: ethanol) (8:2 v/v), after cool down to room temperature, the mixture reaction was poured to (100ml) ice water and kept it overnight, the solid product was filtered, recrystallization from an appropriate solvent.
4.2.3.1.: 5-((Z)-4-hydroxybenzylidene)-2-((diphenylmethylene) hydrazineylidene)-thiazolidin-4-one (3a):
Orange crystals, recrystallized from ethanol, yield: 62%, M.p: 162–164°C.1H NMR (DMSO, δ ppm): 6.97(s,1H ,Ar-H), 7.24-7.53(m,14H, Ar-H), 8.09(s, 1H,OH), 11.92(s, 1H, NH).13C NMR (DMSO, δ ppm): 128.3-134.7,162.1, 163.4, 165.7, 194.4; IR (υ, cm−1) : 3414, 3150, 3062, 2920, 2920,1705, 1612, 1585, 1492, 1442, 1317. MS (70 eV, m/z): 399.47 [M], 322.1, 294.1, 195.2, 180.1, 165, 77.1. Anal. calc. for: C23H17N3O2S,C, 69.16 ; H, 4.29; N, 10.52; S, 8.03, found: C, 67.34; H, 4.11; N, 10.07; S, 8.56.
4.2.3.2.: 5-((Z)-2,4-dihydroxybenzylidene)-2((diphenylmethylene) hydrazineylidene) thiazolidin-4-one (3b):
Pale yellow crystals, recrystallized from ethanol, yield: =60%, M.p: 165–166°C.1H NMR (DMSO, δ ppm): 7.11( s,1H, Ar-H), 7.12(s,H,Ar-H), 7.24(d, H, J=5Hz, Ar-H),7.42 (d, H, J=10Hz,Ar-H)7.45 (t,6H, J=5Hz,Ar-H), 7.53 (d, 2H,J= 10Hz,Ar-H), 7.57 (d, 2H, J=10Hz ,Ar-H), 10.13(s, OH),11.08 (s,OH), 11.90(s ,H, NH).13C NMR (DMSO, δ ppm): 122.3-136.2, 137.2, 154.7, 161.6, 162.7, 164, 166.5, 187.7. IR (υ, cm−1):3431, 3143, 3062, 2937,1705, 1612, 1585, 1490, 1444, 1317, 696. MS (70 eV, m/z): 415.47[M],398.1, 294.1,222.2, 180.1, 165.2 77.2. Anal. calc. for:C23H17N3O3S,C, 66.49; H, 4.12; N, 10.11; S, 7.72, found: C, 65.61; H, 3.93; N, 9.66; S, 7.14.
4.2.3.3.: 5-((Z)-3,4-dihydroxybenzylidene)-2((diphenylmethylene) hydrazineylidene) thiazolidin-4-one (3c):
Pale yellow crystals, recrystallized from methanol, yield: =69%, M.p: 157–159°C.1H NMR (DMSO, δ ppm): ): 7.09( s,1H, Ar-H ), 7.12(s,H,Ar-H), 7.24(d, H,J=5Hz, Ar-H), 7.36 (d, H, J=10Hz,Ar-H), 7.42 (t,3H, J=5Hz,Ar-H), 7.47 (t,3H,J= 10Hz,Ar-H), 7.53 (d,2H, J=10Hz,Ar-H), 7.79 (d,2H,J=10Hz,Ar-H), 10.21(s,1H,OH), 11.08(s,1H, OH), 11.90(s ,1H, NH). 13C NMR (DMSO, δ ppm): 128.3-138.1, 147.7, 156.6, 162.1, 165.9, 172, 174.3, 186. IR (υ, cm−1): 3441, 3123, 3064,2937, 1705, 1622, 1585, 1492, 1429, 696. MS (70 eV, m/z): 415.47[M], 398.1, 338, 294.1, 222.1, 195.2, 165, 77.2. Anal. calc. for: C23H17N3O3S,C, 66.49; H, 4.12; N, 10.11; S, 7.72, found: C, 65.83; H, 3.83; N, 9.96; S,7.25.
4.2.3.4:5-((Z)-4-(methylthio)benzylidene)-2-((diphenylmethylene)hydrazineylidene) thiazolidin-4-one (3d):
Pale yellow crystals, recrystallized from ethylacetate, yield: =51%, M.p: 169–170°C.1H NMR (DMSO, δ ppm): 2.54(s,3H,SCH3), 7.22(s ,s,1H,olefinic protons), 7.26 (d,2H, J=10Hz,Ar-H), 7.32 (d,2H,J=10Hz,Ar-H), 7.41(t,3 H,J=5Hz,Ar-H), 7.44(t,3 H,J = 10Hz ,Ar-H), 7.49(d,2 H,J=5Hz,Ar-H), 7.58(d ,2H,J=10Hz,Ar-H). 13C NMR (DMSO, δ ppm): 16.7, 128.3-133.8, 136.7 ,136.7, 139.8, 149.5, 161.4, 178, IR (υ, cm−1): 3431, 3078,2920, 1705, 1612, 1583, 1492, 1444, 1317, 1165, 696.MS (70 eV, m/z):429.56 [M], 294.2, 195.2, 180.1, 165, 149.2, 77, 43. Anal. calc. forC24H19N3OS2:C, 67.11; H, 4.46; N, 9.78; S, 14.93, found: C, 66.15; H, 4.19; N, 9.06; S, 14.42.
4.2.3.5: (5Z)-5-(benzo[d][1, 3]dioxol-5ylmethylene)-2 ((diphenylmethylene) hydrazineylidene ) thiazolidin-4-one (3e) :
Pale yellow crystals, recrystallized from ethylacetate, yield: =81%, M.p: 174–176°C.1H NMR (DMSO, δ ppm): 6.06(s,2H,CH2), 6.89(s, 1H, Ar-H), 6.95(s, H, ,Ar-H), 7.11 (d, J=15Hz,Ar-H), 7.24 (d, J=10Hz,Ar-H), 7.41(t,3 H,J=5Hz,Ar-H), 7.48(t,2 H,J= 10Hz,Ar-H), 7.52(d,2 H,J=5Hz,Ar-H), 11.90(s ,H, NH). 13C NMR (DMSO, δ ppm) : 102, 120.2-134.7, 136.2 ,138.1,162.1,166, 171.8, 174.3, 186.6. IR (υ, cm−1): 3442, 3078,2818, 1705, 1610, 1583, 1490, 1444, 1344, 1041, 696. MS (70 eV, m/z):427.48 [M], 294.2, 248.2, 195.1, 180.1, 165, 121.4, 77.2. Anal. calc. for: C24H17N3O3S,C, 67.43; H, 4.01; N, 9.81; S, 7.50, found: C, 66.27; H, 3.82; N, 10.26; S, 7.12.
4.2.4: Procedure for synthesis N-(4-acetyl-5,5-diphenyl-4,5-dihydro-1,3,4-thiadiazol-2-yl) acetamide (4):
Thiosemicarbazone (1) (1.82g, 7.156m.mol) was dissolved in 40 ml acetic anhydride, the reaction mixture was heated in an oil bath at 118-120oC at 20 hrs, the progress of the reaction mixture was monitored by TLC using (benzene: ethyl acetate), (6:4 v/v), the reaction mixture was cool down to room temperature and poured to 200 ml ice water, then was kept it at room temperature, then the filtered it, was recrystallization from ethanol.
White crystals, yield: 61%, M.p: 195–196°C.1H NMR (DMSO, δ ppm): 2.03(s,3H ,COCH3), 2.20(s,3H ,COCH3), 7.32 (d,4H, J=10Hz,Ar-H), 7.38(t,6H, ,J=5Hz,Ar-H), 11.73(s ,H, NH). 13C NMR (DMSO, δ ppm):22.8, 24.2, 85.6, 128.1-128.4,140.8, 148, 167, C=O: 170. IR (υ, cm−1): 3450, 3059,2935, 1707, 1676, 1597, 1492, 1442, 1328, 1180, 698.MS (70 eV, m/z):339.41 [M],297.2, 281, 238.1, 195.2, 180.1, 165.2, 77.2, 43.3. Anal. calc. for: C18H17N3O2S,C, 63.70; H, 5.05; N, 12.38; S, 9.45, found: C, 62.95; H, 4.87; N, 11.66; S, 882.
4.2.5: Procedure for synthesis5,5-diphenyl -1,3,4-thiadiazoline-2-amine(5):
Compound (4) ( 0.678g, 8 m.mol) was dissolved in 10 ml of ethanol, hydrazine mono hydrate (6.8 ml) was added to the reaction mixture drop wise with stirring, slowly raising the temperature to the reflux for 3hrs. the progress of the reaction was monitored by TLC using (ethanol; chloroform) (2:8 v/v), after completion the reaction, the reaction mixture was cool down to room temperature, then it was filtered and recrystallized from ethanol. yellow crystals, yield: 62%, M.p: 90–91°C.1H NMR (DMSO, δ ppm): 6.23(s ,2H, NH2), 7.23(t,2H,J=10Hz,Ar-H), 7.28(t,2H, J=10Hz,Ar-H), 7.33(d,2H, ,J=10Hz,Ar-H), 7.49(d,2H, ,J=5Hz,Ar-H), 7.56(t,2H, J=5Hz,Ar-H), 13C NMR (DMSO, δ ppm): 25.9, 127.6-129.8, 129.8, IR (υ, cm−1): 3421, 3271,3080,1610, 1492, 1442, 1336, 1180, 696.MS (70 eV, m/z): 255.34 [M],195.3, 180.1, 165.2, 77.2. Anal. calc. for:C14H13N3S, C, 65.86; H, 5.13; N, 15.46; S, 12.56, found: C, 64.80; H, 4.92; N, 15.16; S, 11.89.
4.2.6: General Procedure for synthesis 1,3,4-thiadiazoline derivatives (6a, 6b)
5,5-diphenyl -1,3,4-thiadiazoline-2-amine (5) (0.635g, 2.5 m.mol) was dissolved in 40 ml ethanol, corresponding aldehyde (2.5 m.mol ) and 0.5 ml glacial acetic acid was added to the reaction mixture, the mixture was refluxed 5hrs, forming of the products was confirmed TLC using (ethanol; ethyl acetate) (1:9 v/v), after completion the reaction was it cool down to room temperature, then it was filtered and recrystallization from an appropriate solvent.