Month 2014
Hybrid 4-Aminoquinoline-1,3,5-triazine Derivatives: Design, Synthesis,
Characterization, and Antibacterial Evaluation
4-(7-Chloro-quinolin-4-yl)-piperazine-1-carbothioic acid
(4-amino-6-o-tolylamino-[1,3,5]triazin-2-yl)-amide 9d. Dark
reaction was monitored by TLC using ethanol/acetone (1:1) as
mobile phase. The reaction mixture was filtered and
concentrated under reduced pressure. The resulting residue was
dissolved in dichloromethane,washed with brine, and dried over
anhydrious Na2SO4. The dried solution was concentrated under
violet crystals; yield: 69%; mp: 275–276°C; MW: 506.03; Rf:
0.77; FTIR (νmax; cmÀ1 KBr): 3411.79 (N–Hstretch, NH2), 2921.99
(C–Hbroad), 2833.06 (C–Hstretch), 1689.27 (C–H), 1574.93
(N–Hstretch, sec. amine), 1498.77 (C═Cstretch), 1425.71 (C–Hstretch),
1382.43 (C–Nstretch), 1163.37 (C═Sstretch), 878.72, 810.01
(C–Hstretch); 1H-NMR (400 MHz, CDCl3, TMS) δ ppm: 8.86
(d, 1H J = 6.3 Hz, quinoline), 8.35 (d, 1H J = 5.2 Hz, quinoline),
7.87 (d, 1H J = 3.4 Hz, quinoline), 7.34 (d, 1H J= 2.1 Hz,
quinoline), 6.95 (s, 2H, NH2), 6.52 (d, 1H J= 1.7 Hz, quinoline),
7.15–6.54 (m, 4H, 4×CH, Ar–H), 4.15–3.04 (m, 8H, 4×CH2,
piperazine), 3.69 (br s, 1H, NH), 3.51 (s, 1H, NH), 2.32 (s, 3H,
CH3); 13C-NMR (100 MHz, DMSO-d6) δ ppm: 184.2, 181.8,
165.5, 164.9, 159.2, 154.1, 150.8, 142.4, 135.8, 131.8, 130.7,
129.3, 128.9, 126.8, 125.9, 123.6, 122.9, 121.7, 118.5, 56.7, 53.9,
18.2; MS: 508.03 (M + H)+; elemental analysis for C24H24ClN9S:
Calcd.: C, 56.96; H, 4.78; N, 24.91. Found: C, 57.01; H, 4.77; N,
reduced pressure to obtain the titled compounds 9a–j [13].
4-(7-Chloro-quinolin-4-yl)-piperazine-1-carbothioic acid
[4-amino-6-(4-hydroxy-phenylamino)-[1,3,5]triazin-2-yl]-amide
9a. Black crystals; yield: 82%; mp: 260–262°C; MW: 508.00;
Rf: 0.87; FTIR (νmax; cmÀ1 KBr): 3414.65 (N–Hstretch, –NH2),
2922.73 (C–Cstretch), 1607.74 (C–Hstretch), 1574.66 (N–Hstretch
,
sec. amine), 1512.6 (N–Hstretch, NH2), 1425.65 (C–Hstretch),
1380.39 (C–Nstretch), 1236.16 (OHstretch), 1163.29 (C═Sstretch),
1
872.39, 825.39 (C–Hstretch); H-NMR (400 MHz, CDCl3, TMS) δ
ppm: 8.78 (d, 1H J = 5.1 Hz, quinoline), 8.08 (d, 1H J = 4.8 Hz,
quinoline), 7.94 (d, 1H J = 4.2Hz, quinoline), 7.40 (d, 1H
J = 1.9 Hz, quinoline), 7.02 (s, 2H, NH2), 6.980 (d, 1H J = 2.9 Hz,
quinoline), 7.74–6.87(m, 4H, 4×CH, Ar–H), 5.46 (s, 1H, Ar–OH),
4.08–3.02 (m, 8H, 4×CH2, piperazine), 3.70 (br s, 1H, NH), 3.52
(s, 1H, NH); 13C-NMR (100 MHz, DMSO-d6) δ ppm: 182.4,
181.8, 167.4, 159.3, 154.2, 150.8, 148.6, 135.7, 131.8, 130.3,
128.9, 126.1, 122,7, 121.8, 118.4, 116.8, 56.9, 52.7; MS: 509.8
(M+ H)+; elemental analysis for C23H22ClN9OS: Calcd.: C,
54.38; H, 4.37; N, 24.82. Found: C, 55.01; H, 4.38; N, 24.83.
4-(7-Chloro-quinolin-4-yl)-piperazine-1-carbothioicacid[4-amino-
24.90.
N-(4-Amino-6-(2-carbamothioylhydrazinyl)-1,3,5-triazin-2-yl)-
4-(7-chloroquinolin-4-yl)piperazine-1-carbothioamide 9e. Light
brown crystals; yield: 56%; mp: 320–321°C; MW: 490.01; Rf: 0.86;
FTIR (νmax; cmÀ1 KBr): 3331.64 (N–Hbroad, –NH2), 3212.08
(C–Hbroad), 2058.37 (C–Hstretch), 1574.08 (N–Hstretch, sec. amine),
1379.90 (C–Nstretch), 1014.98 (C═Sstretch), 810.51 (C–Hstretch);
1H-NMR (400MHz, CDCl3, TMS) δ ppm: 8.57 (d, 1H J = 6.2 Hz,
quinoline), 8.53 (s, 2H, NH2), 8.03 (d, 1H J = 4.6 Hz, quinoline),
7.83 (d, 1H J = 3.2 Hz, quinoline), 7.28 (d, 1H J = 2.3 Hz,
quinoline), 6.91 (s, 2H, NH2), 6.36 (d, 1H J = 1.8 Hz, quinoline),
3.70 (br s, 1H, NH), 3.52 (s, 1H, NH), 3.96–2.98 (m, 8H, 4×CH2,
piperazine), 1.95 (s, 1H, NH); 13C-NMR (100 MHz, DMSO-d6) δ
ppm: 183.5, 182.4, 181.3 179.7, 168.3, 158.2, 152.8, 150.4,
135.3, 129.9, 128.7, 125.9, 122.8, 117.3, 56.9, 53.7; MS: 491.03
(M+ H)+; elemental analysis for C18H20ClN11S2: Calcd.: C,
44.12; H, 4.11; N, 31.44. Found: C, 44.14; H, 4.10; N, 31.43.
2-(4-Amino-6-(4-(7-chloroquinolin-4-yl)piperazine-1-
carbothioamido)-1,3,5-triazin-2-yl)hydrazinecarboxamide 9f.
White crystals; yield: 59%; mp: 225–226°C; MW: 473.94; Rf:
0.89; FTIR (νmax; cmÀ1 KBr): 3466.20 (N–Hstretch, –NH2),
3149.91 (C–Hbroad), 2850 (C–Hstretch), 1727.43 (C═Ostretch),
1563 (N–Hbroad, sec. amine), 1379.90 (C–Nstretch), 1016.78
(C═Sstretch), 811.00 (C–Hstretch); 1H-NMR (400 MHz, CDCl3,
TMS) δ ppm: 8.56 (d, 1H J = 6.2 Hz, quinoline), 8.02 (d, 1H
J = 4.6 Hz, quinoline), 7.83 (d, 1H J = 3.2 Hz, quinoline), 7.28
(d, 1H J = 2.3 Hz, quinoline), 6.94 (s, 2H, NH2), 6.39 (d, 1H
J = 1.6 Hz, quinoline), 5.93 (s, 2H, NH2), 3.70 (br s, 1H, NH),
3.52 (s, 1H, NH), 3.96–3.04 (m, 8H, 4×CH2, piperazine), 2.92
(s, 1H, NH); 13C-NMR (100 MHz, DMSO-d6) δ ppm: 182.6,
181.7 178.6, 169.5, 160.3, 157.5, 154.3, 150.7, 135.7, 130.2,
128.8, 127.1, 122.5, 118.4, 57.1, 53.8; MS: 474.95 (M + H)+;
elemental analysis for C18H20ClN11OS: Calcd.: C, 45.62; H,
6-(4dimethylamino-phenylamino)-[1,3,5]triazin-2-yl]-amide
9b. Dark blue crystals; yield: 71%; mp: 325–326°C; MW: 537.07;
Rf: 0.83; FTIR (νmax; cmÀ1 KBr): 3300.83 (N–Hbroad, –NH2),
3098.17 (C═Cbroad), 1626.02 (C–Hstretch) 1574.56 (N–Hstretch, sec.
amine), 1515.29 (C–Hstretch), 1472.49 (C–Hstretch), 1384.38
(C–Nstretch), 1166.09 (C═Sstretch), 871.40, 802.57(C–Hstretch);
1H-NMR (400 MHz, CDCl3, TMS) δ ppm: 8.47 (d, 1H J = 5.8 Hz,
quinoline), 8.16 (d, 1H J = 4.2Hz, quinoline), 7.87 (d, 1H
J = 3.8 Hz, quinoline), 7.32 (d, 1H J = 1.5 Hz, quinoline), 6.98
(s, 2H, NH2), 6.56 (d, 1H J = 2.3 Hz, quinoline), 6.61–6.47
(m, 4H, 4×CH, Ar–H), 3.02 (s, 6H, 2×CH3), 4.03–2.98 (m, 8H,
4×CH2, piperazine), 3.70 (br s, 1H, NH), 3.52 (s, 1H, NH);
13C-NMR (100 MHz, DMSO-d6) δ ppm: 183.3, 181.3, 165.7,
164.9, 159.2, 153.2, 151.6, 147.6, 134.8, 130.1, 128.5, 127.9,
126.2, 122.7, 118.7, 117.3, 114.1, 56.7, 53.9, 42.7; MS: 538.04
(M+ H)+; elemental analysis for C25H27ClN10S: Calcd.: C, 56.12;
H, 5.09; N, 26.18. Found: C, 56.14; H, 5.07; N, 26.21.
4-(7-Chloro-quinolin-4-yl)-piperazine-1-carbothioicacid[4-
amino-6-(3-methoxy-phenylamino)-[1,3,5]triazin-2-yl]-amide
9c. Light violet crystals; yield: 76%; mp: 310–312°C; MW:
522.03; Rf: 0.65; FTIR (νmax; cmÀ1 KBr): 3414.65(N–Hstretch
,
NH), 3059.60(C–Hbroad), 1735.72(C═Ostretch), 1689.27
(C–HStretch), 1575.06 (N–Hstretch, NH2), 1486.51(C–Hstretch
,
CH3), 1380.43 (C–Nstretch), 1115.37 (C═Sstretch), 870.28,
826.41 (C–Hstretch); 1H-NMR (400 MHz, CDCl3, TMS) δ ppm:
8.56 (d, 1H J = 5.9 Hz, quinoline), 8.27 (d, 1H J = 4.8 Hz,
quinoline), 7.83 (d, 1H J = 3.9Hz, quinoline), 7.38 (d, 1H
J = 2.6 Hz, quinoline), 6.93 (s, 2H, NH2), 6.48 (d, 1H J = 1.8 Hz,
quinoline), 7.09–6.27 (m, 4H, 4×CH, Ar–H), 3.87 (s, 3H, OCH3),
4.02–2.96 (m, 8H, 4×CH2, piperazine), 3.88 (br s, 1H, NH), 3.52
(s, 1H, NH); 13C-NMR (100 MHz, DMSO-d6) δ ppm: 185.2,
182.7, 165.2, 164.5, 161.4, 159.4, 153.0, 150.9, 143.5, 135.7,
131.1, 130.3, 128.9, 126.0, 122.4, 118.3, 111.8, 110.1, 99.5, 56.8,
54.1, 53.4; MS: 523.07 (M+ H)+; elemental analysis for
C24H24ClN9OS: Calcd,: C, 55.22; H, 4.63; N, 24.15. Found: C,
55.24; H, 4.63; N, 24.17.
4.25; N, 32.51. Found: C, 45.64; H, 4.21; N, 32.50.
4-(7-Chloro-quinolin-4-yl)-piperazine-1-carbothioic acid [4-amino-
6-(3-amino-propylamino)-[1,3,5]triazin-2-yl]-amide 9g. Brown
crystals; yield: 70%; mp: 291–292°C; MW: 473; Rf: 0.84; FTIR
(νmax; cmÀ1 KBr): 3298.72 (N–Hbroad, NH2), 2928.12 (–C═C–broad),
2053.58 (C–Hstretch) 1715.43 (C–Hstretch, CH2), 1574.89 (N–Hstretch
,
sec. amine), 1379.15 (C–Nstretch), 1123.58 (C═Sstretch), 872.80,
810.33 (C–Hstretch); 1H-NMR (400 MHz, CDCl3, TMS) δ ppm:
8.62 (d, 1H J = 6.5 Hz, quinoline), 8.04 (d, 1H J = 5.3 Hz,
quinoline), 7.87 (d, 1H J = 3.4 Hz, quinoline), 7.32 (d, 1H
J = 2.8Hz, quinoline), 6.87 (s, 2H, NH2), 6.43 (d, 1H J = 1.9 Hz,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet