P. Sangeetha et al. / Journal of Molecular Structure 1198 (2019) 126899
3
(SCHOT AVS 450) in thermostat at 25 ꢁC. The CT-DNA concentration
was kept at 50 M and flow time was measured with a digital stop
watch. The values of relative specific viscosity (ɳ/ɳꢁ)1/3 where ɳꢁ
2.9.2.3. 5-Methyl-((3t-methyl-2r,6c-bis(p-chlorophenyl)piperidin-4-
ylidene)hydrazono)thiazolidin-4-one (17). White powder, yield 93%,
m.p: 245e246 ꢁC; FT-IR (cmꢂ1) 1731 (C]O), 1624 (C2' ¼ N), 1630
m
and
h
the specific viscosity contributions of DNA in the absence (ɳꢁ)
(C4¼N), 1389 (NeH); 1H NMR (
d, ppm, DMSO‑d6): 3.54 (d, 1H, H-
and in the presence of the drug (ɳꢁ), were plotted against 1/R
(R ¼ [compound]/[DNA]).
2a), 3.84 (d, 1H, H-6a), 2.58 (t, 1H, H-3a), 2.10 (t, 1H, H-5a), 3.51 (d,
1H, H-5e), 3.94 (m, 1H, H-50), 1.65 (s, 3H, CH3 at C-50), 7.51 (d, 4H, o-
H, o'-H), 7.41 (dd, 4H, m-H, m'-H); 13C NMR (
d, ppm, DMSO‑d6): 60.5
(C-2), 59.0 (C-6), 44.7 (C-3), 33.2 (C-5), 12.2 (CH3(eq)-C-3), 19.5
(CH3eC-50) 174.5 (C]O), 167.8 (C]N), 161.3 (C-20), 141.8 (C-200),
141.2 C-600), 129.6 (o-C, o'-C0), 128.0 (m-C, m'-C), 131.7, 131.5 (p-C, p'-
C), 42.3 (C-50) ppm. Anal. Found (cal.) for C22H22Cl2N4OS (%): C,
57.27 (57.24); H, 4.81 (4.79); N, 12.14 (12.18).
2.9. Material synthesis
2.9.1. General procedure for synthesis of 50-methyl-(3/5-alkyl-2r,6c-
diarylpiperidin-4-ylidene)hydrazono)thiazolidin-4-one (15e21)
Thiosemicarbazone (1 mmol) and anhydrous sodium acetate
(0.15 mmol) were dissolved in 50 mL of ethanol. The reaction
mixture was then heated to reflux and a solution of equal amount of
ethyl 2-bromopropionate (1 mmol) slowly added to the reaction
mixture. After refluxing for about 4e5 h, the reaction mixture was
cooled, excess solvent was removed under reduced pressure. The
reaction mixture was poured into crushed ice. The separated solid
was filtered off and purified by recrystallization using ethanol. For
some cases, the target compounds could be purified by column
chromatography using a mixture of chloroform e ethylacetate (8:2)
as eluent.
2.9.2.4. 5-Methyl-((3t-methyl-2r,6c-bis(p-flurophenyl)piperidin-4-
ylidene)hydrazono)thiazolidin-4-one (18). White powder, yield 90%,
m.p: 254e255 ꢁC; FT-IR (cmꢂ1) 1731 (C]O), 1610 (C2' ¼ N), 1648
(C4¼N), 1373 (NeH); 1H NMR (
d, ppm, DMSO‑d6): 3.55 (d, 1H, H-
2a), 3.88 (d, 1H, H-6a), 2.57 (t, 1H, H-3a), 2.12 (t, 1H, H-5a), 3.15 (d,
1H, H-5e), 3.90 (m, 1H, H-50), 1.62 (s, 3H, CH3 at C-50), 7.52 (d, 4H, o-
H, o'-H), 7.16 (dd, 4H, m-H, m'-H); 13C NMR (
d, ppm, DMSO‑d6): 60.7
(C-2), 58.9 (C-6), 44.7 (C-3), 33.2 (C-5), 174.2 (C]O), 167.3 (C]N),
160.7 (C-20) 139.0 (C-2'0, C-6'0), 129.5 (o-C, o'-C), 114.5 (m-C, m'-C),
162.0, 160.0 (p-C, p'-C), ppm. Anal. Found (cal.) for C22H22F2N4OS
(%): C, 61.67 (61.61); H, 5.17 (5.23); N, 13.08 (13.02).
2.9.2. General microwave method for synthesis of compound 50-
methyl-(3/5-alkyl-2r,6c-diarylpiperidin-4-ylidene)hydrazono)
thiazolidin-4-one (15e21)
2.9.2.5. 5-Methyl-((3t-methyl-2r,6c-bis(p-methylphenyl)piperidin-4-
ylidene)hydrazono)thiazolidin-4-one (19). White powder, yield 89%,
m.p: 244e245 ꢁC; FT-IR (cmꢂ1) 1740 (C]O), 1645 (C2' ¼ N), 1628
A
mixture of 3/5-alkyl-2r,6c-diarylpiperidin-4-one, thio-
semicarbazone and ethyl 2-bromopropionate (1:1 mol) were mixed
thoroughly with a catalytic amount of Amberlite IR-120H resin in
open glass vessel and subjected to the microwave irradiation at low
power setting (25%, 250 w) for 3e6 min, then allowed to cool. The
reaction mixture was dissolved in ethanol and resin was filtered off.
Finally the filtrate was evaporated to dryness in evaporator. The
crude product was further recrystallized from ethanol. The
analytical data are given in experimental section.
(C4¼N), 1383 (NeH); 1H NMR (
d, ppm, DMSO‑d6): 3.63 (d, 1H, H-
2a), 3.85 (d, 1H, H-6a), 2.58 (t, 1H, H-3a), 2.17 (t, 1H, H-5a), 3.35 (d,
1H, H-5e), 3.93 (m, 1H, H-50), 1.63 (s, 3H, CH3 at C-50), 0.91 (s, 3H,
CH3eC-3), 7.40 (d, 4H, o-H, o'-H0), 7.14 (dd, 4H, m-H, m'-H0); 13C
NMR (d, ppm, DMSO‑d6): 69.4 (C-2), 59.8 (C-6), 43.0 (C-3), 33.9 (C-
5), 174.5 (C]O), 168.1 (C]N), 161.4 (C-20) 136.1 (C-2'0, C-6'0), 126.6
(o-C, o'-C0), 127.9 (m-C, m'-C), 128.7 (p-C, p'-C), 161.4 (C-20) 22.7 (p-
CH3) ppm. Anal. Found (cal.) for C24H28N4OS (%): C, 68.54 (68.61);
H, 6.71 (6.65); N, 13.32 (13.37).
2.9.2.1. 5-Methyl-((2r,6c-diphenylpiperidin-4-ylidene)hydrazono)
thiazolidin-4-one (15). Pale yellow powder, yield 96%, m.p:
216e217 ꢁC; FT-IR (cmꢂ1) 1729 (C]O), 1608 (C2' ¼ N), 1640 (C4¼N),
2.9.2.6. 5-Methyl-((3t-methyl-2r,6c-bis(p-methoxyphenyl)piperidin-
4-ylidene)hydrazono) thiazolidin-4-one (20). White powder, yield
87%, m.p: 240e241 ꢁC; FT-IR (cmꢂ1) 1739 (C]O), 1646 (C2' ¼ N),
1386 (NeH); 1H NMR (
d, ppm, DMSO‑d6): 3.90 (d, 1H, H-2a), 3.78 (d,
1H, H-6a), 2.49 (t, 1H, H-3a), 2.37 (d, 1H, H-3e), 2.05 (t, 1H, H-5a),
3.52 (d, 1H, H-5e), 3.30 (bs, 1H, NH), 4.12 (m, 1H, H-50), 1.46 (t, 3H,
CH3 at C-50), 7.50 (d, 4H, o-H, o'-H), 7.35 (dd, 4H, m-H, m'-H), 7.26
1632 (C4¼N), 1389 (NeH); 1H NMR (
d, ppm, DMSO‑d6): 3.56 (d, 1H,
H-2a), 3.83 (d, 1H, H-6a), 2.55 (t, 1H, H-3a), 2.18 (t, 1H, H-5a), 3.45
(d, 1H, H-5e), 3.90 (m, 1H, H-50), 1.60 (s, 3H, CH3 at C-50), 0.98 (s, 3H,
CH3eC-3), 7.36 (d, 4H, o-H, o'-H), 6.90 (dd, 4H, m-H, m'-H); 13C NMR
(m, 2H, p-H, p'-H); 13C NMR (
d, ppm, DMSO‑d6): 68.7 (C-2), 60.5 (C-
6), 44 (C-3), 37.4 (C-5), 176.8 (C]O), 167.6 (C]N), 161.5 (C-20), 144.0
(C-200),143.0 (C-600) 128.2 (o-C, o-C0),127.5 (m-C, m-C0),126.5 (p-C, p-
C0) and 18.9 (CH3eC-50) ppm. Anal. Found (cal.) for C21H22N4OS (%):
C, 66.64 (66.60); H, 5.86 (5.84); N, 14.80 (14.87).
(d, ppm, DMSO‑d6): 69.0 (C-2), 59.5 (C-6), 43.1 (C-3), 33.9 (C-5),
173.6 (C]O), 167.8 (C]N), 161.2 (C-20) 132.4 (C-20', C-60'), 129.8 (o-
C, o'-C), 113.6 (m-C, m'-C), 158.4 (p-C, p'-C), 161.2 (C-20), 54.9 (p-
OCH3) ppm. Anal. Found (cal.) for C24H28N4O3S (%): C, 63.94 (63.90);
H, 6.21 (6.25); N, 12.38 (12.34).
2.9.2.2. 5-Methyl-((3t-methyl-2r,6c-diphenylpiperidin-4-ylidene)
hydrazono)thiazolidin-4-one (16). White powder, yield 98%, m.p:
2.9.2.7. 5-Methyl-((3,5-dimethyl-2r,6c-diphenylpiperidin-4-ylidene)
230e231 ꢁC; FT-IR (cmꢂ1
)
1735 (C]O), 1637 (C2' ¼ N), 1600
hydrazono)thiazolidin-4-one (21). White powder, yield 82%, m.p:
(C4¼N), 1427 (NeH); 1H NMR (
d, ppm, DMSO‑d6): 3.58 (d, 1H, H-
238e239 ꢁC; FT-IR (cmꢂ1
)
1735 (C]O), 1637 (C2' ¼ N), 1600
(C4¼N),1427 (NeH); 1H NMR (
d
, ppm, DMSO‑d6): 4.10 (d,1H, H-2a),
2a), 3.91 (d, 1H, H-6a), 2.61 (m, 1H, H-3a), 2.23 (q, 1H, H-5a), 3.71
(dd, 1H, H-5e), 3.95 (q, 1H, H-50), 1.62 (t, 3H, CH3 at C-50), 0.91 (t. 3H,
CH3 at C-3), 7.43 (d, 4H, o-H, o-H0), 7.30 (dd, 4H, m-H, m-H0), 7.20 (m,
3.78 (d, 1H, H-6a), 2.71 (t, 1H, H-3a), 2.95 (d, 1H, H-5e), 3.90 (m, 1H,
H-50), 1.60 (s, 3H, CH3 at C-50), 7.44, 7.42 (d, 4H, o-H, o-H0), 7.31 (dd,
4H, m-H, m-H0), 7.26 (m, 2H, p-H, p-H0), 0.92 (3H, CH3 e C-2); 13C
2H, p-H, p-H0); 13C NMR (
d, ppm, DMSO‑d6): 69.3 (C-2), 61.1 (C-6),
45.5 (C-3), 37.8 (C-5), 176.4 (C]O), 169.6 (C]N), 160.7 (C-20), 143.6
(C-200), 142.6 (C-600), 128.4 (o-C, o'-C), 127.9 (m-C, m'-C), 126.7 (p-C,
p'- C0), 42.2 (C-50), 19.1 (CH3eC-50) and 11.9 (CH3eC-3) ppm. Anal.
Found (cal.) for C22H24N4OS (%): C, 67.34 (67.38); H, 6.16 (6.10); N,
14.27 (14.21).
NMR (d, ppm, DMSO‑d6): 69.6 (C-2), 60.1 (C-6), 43.5 (C-3), 33.8 (C-
5), 173.6 (C]O), 169.5 (C]N), 160.7 (C-20) 143.7, 143.5 (C-200, C-600),
129.1 (o-C, o'-C), 128.1 (m-C, m'-C), 127.4 (p-C, p'- C0), 11.8 (CH3eC-
3), 11.0 (CH3 e C-5) ppm. Anal. Found (cal.) for C23H26N4OS (%): C,
67.95 (67.90); H, 6.45 (6.50); N, 13.78 (13.72).