4
08ꢀꢀꢀꢀꢁꢀN.H. Kumar Baba et al.: Microwave synthesis of bis(thiazol-2-amine) derivatives
1
3
(
(
d, J ꢀ=ꢀ237.1Hz, CF), 146, 130.5, 117.8 (d, J ꢀ=ꢀ7.6 Hz, Ar-C), 115.5, 115.3 pyridine-H), 6.82 (s, 1H, Ar-H), 6.77 (d, 2H, Jꢀ=ꢀ7.5 Hz, pyridine-H), 4.00
CF CF
+
3
13
d, J ꢀ=ꢀ7.6 Hz, Ar-C), 104.8, 96.1, 55.7; MS: m/z 523.2, [Mꢀ+ꢀH] (100%). (s, 6H, O-CH ), 2.47 (s, 6H, CH ); C NMR: δ 157.6, 156.8, 155.1, 151.3,
CF
3
3
Anal. Calcd for C H F N O S : C, 59.76; H, 3.86; N, 10.72. Found: C, 144.5, 138.1, 130.1, 115.7, 114.6, 107.8, 107.4, 96.1, 55.7, 23.5; MS: m/z
2
6
20
2
4
2 2
+
5
9.73; H, 3.84; N, 10.67.
517.2, [Mꢀ+ꢀH] (100%). Anal. Calcd for C H N O S : C, 60.44; H, 4.68;
2
6
24
6
2 2
N, 16.27. Found: C, 60.40; H, 4.65; N, 16.24.
4
,4′-(4,6-Dimethoxy-1,3-phenylene)-bis(N-(3-chloro-4-fluo-
rophenyl)thiazol-2-amine) (5d)ꢁReaction time 10 h, yield 79%, 4,4′-(4,6-Dimethoxy-1,3-phenylene)-bis(N-(4-methylpyridin-
method A; reaction time 12 min, yield 88%, method B; white solid; mp 2-yl)thiazol-2-amine) (5i)ꢁReaction time 12 h, yield 73%, method
1
65–168°C (dec); IR: 3441 (N-H), 1606 (Cꢀ=ꢀN), 1540 (Cꢀ=ꢀC), 1393 (C-N), A; reaction time 15 min, yield 89%, method B; brown solid; mp
−1 1
7
39 (C-S) cm ; H NMR: δ 10.36 (s, 2H, N-H), 8.95 (s, 1H, Ar-H), 8.05 (d, 272–275°C (dec); IR: 3460 (N-H), 1615 (Cꢀ=ꢀN), 1539 (Cꢀ=ꢀC), 1372 (C-N)
−1 1
2
H, Jꢀ=ꢀ6.2 Hz, Ar-H), 7.59 (d, 2H, Jꢀ=ꢀ8.8 Hz, Ar-H), 7.29 (s, 2H, thiazole- cm ; H NMR: δ 11.71 (s, 2H, N-H), 8.69 (s, 1H, Ar-H), 8.30–8.13 (m, 2H,
H), 6.94 (t, 2H, Jꢀ=ꢀ8.8 Hz, Ar-H), 6.85 (s, 1H, Ar-H), 4.02 (s, 6H, O-CH ); pyridine-H), 7.40 (s, 2H, thiazole-H), 7.03 (s, 2H, pyridine-H), 6.95–
3
1
3
1
C NMR: δ 160.7, 156.9, 151.3 (d, J ꢀ=ꢀ239.8 Hz, CF), 146.1, 138.5, 130.7, 6.81 (m, 3H, Ar-H, pyridine-H), 4.03 (s, 6H, O-CH ), 2.34 (s, 6H, CH );
CF
3
3
3
4
13
1
19.3 (d, J ꢀ=ꢀ18.1 Hz, Ar-C), 117.5, 116.6, 116.4 (d, J ꢀ=ꢀ4.9 Hz, Ar-C),
C NMR: δ 158.5, 157.2, 151, 150.2, 144.7, 143.6, 130.1, 118, 114.5, 111.3,
C
CF
+
+
115.3, 105.2, 96.2, 55.8; MS: m/z 591.1, [M] . Anal. Calcd for C H C F N
4
108.1, 96.3, 55.9, 20.9; MS: m/z 517.2, [Mꢀ+ꢀH] (100%). Anal. Calcd for
2
6
18 l2
2
O S : C, 52.80; H, 3.07; N, 9.47. Found: C, 52.76; H, 3.03; N, 9.45.
C H N O S : C, 60.44; H, 4.68; N, 16.27. Found: C, 60.39; H, 4.64; N,
2
2
26 24
6
2 2
1
6.25.
4
,4′-(4,6-Dimethoxy-1,3-phenylene)-bis(N-(3-(trifluoromethyl)
N,N′-(4,4′-(4,6-Dimethoxy-1,3-phenylene)-bis(thiazole-4,2-
diyl))-bis(6-methylbenzo[d] thiazol-2-amine) (5j)ꢁReaction time
phenyl)thiazol-2-amine) (5e)ꢁReaction time 12 h, yield 78%,
method A; reaction time 15 min, yield 90%, method B; white solid;
mp 230–233°C (dec); IR: 3401 (N-H), 1606 (Cꢀ=ꢀN), 1540 (Cꢀ=ꢀC), 1393
1
6 h, yield 74%, method A; reaction time 20 min, yield 90%, method
−1
1
B; green solid; mp 180–182°C (dec); IR: 3460 (N-H), 1598 (Cꢀ=ꢀN), 1541
(
C-N), 739 (C-S) cm ; H NMR: δ 10.50 (s, 2H, N-H), 8.86 (s, 1H, Ar-H),
.12 (s, 2H, Ar-H), 7.95 (d, 2H, Jꢀ=ꢀ6.9 Hz, Ar-H), 7.28 (s, 2H, thiazole-H),
.16 (t, 2H, Jꢀ=ꢀ6.9 Hz, Ar-H), 7.02 (d, 2H, Jꢀ=ꢀ6.9 Hz, Ar-H), 6.86 (s, 1H,
−
1
1
(
Cꢀ=ꢀC), 1381 (C-N), 750 (C-S) cm ; H NMR: δ 12.49 (s, 2H, N-H), 8.71
s, 1H, Ar-H), 7.67 (s, 2H, Ar-H), 7.54–7.47 (m, 2H, Ar-H), 7.39 (s, 2H,
thiazole-H), 7.22 (d, 2H, Jꢀ=ꢀ8.1 Hz, Ar-H), 6.88 (s, 1H, Ar-H), 4.04 (s,
8
(
7
13
Ar-H), 4.02 (s, 6H, O-CH ); C NMR: δ 160.6, 157, 146.3, 141.8, 130.7, 129.7,
3
1
3
2
1
6H, O-CH ), 2.40 (s, 6H, CH ); C NMR: δ 185.8, 162.6, 160, 157.1, 145.7,
1
29.5 (q, J ꢀ=ꢀ31.5 Hz, Ar-C), 124 (q, J ꢀ=ꢀ272.1 Hz, C-F), 119.8, 116.6
3
3
CF
CF
4
4
132.2, 131.5, 130.4, 128.2, 127, 121.1, 113.1, 108.7, 96.2, 55.8, 20.7; MS: m/z
(
q, J ꢀ=ꢀ4.4 Hz, Ar-C), 115.5, 112.5 (q, J ꢀ=ꢀ4.4 Hz, Ar-C), 105.4, 96.3,
CF
CF
+
+
629.2, [Mꢀ+ꢀH] (100%). Anal. Calcd for C H N O S : C, 57.30; H, 3.85;
5
5.8; MS: m/z 623.2, [Mꢀ+ꢀH] (100%). Anal. Calcd for C H F N O S :
30 24
6
2 4
2
8
20
6
4
2 2
N, 13.36. Found: C, 57.27; H, 3.82; N, 13.33.
C, 54.01; H, 3.24; N, 9.00. Found: C, 53.96; H, 3.22; N, 8.96.
4
,4′-(4,6-Dimethoxy-1,3-phenylene)-bis(N-(4-morpholinophe-
nyl)thiazol-2-amine) (5f)ꢁReaction time 10 h, yield 75%, method Antibacterial activity assay
A; reaction time 15 min, yield 88%, method B; white solid; mp
2
65–267°C; IR: 3461 (N-H), 1602 (Cꢀ=ꢀN), 1547 (Cꢀ=ꢀC), 1369 (C-N), 746
Gram-negative strains (P. aeruginosa and E. coli) and Gram-positive
strains (B. subtilis and S. aureus) were obtained from Microbial
Type Culture Collection MTCC. The biological activities of the com-
pounds were assayed using the standard disc diffusion method [25]
for 100 μg/mL solutions in DMSO. Inhibition zones were measured
and compared with the standard positive control (streptomycin) at
−1 1
(
C-S) cm ; H NMR: δ 9.92 (s, 2H, N-H), 8.91 (s, 1H, Ar-H), 7.64 (d, 4H,
Jꢀ=ꢀ8.3 Hz, Ar-H), 7.17 (s, 2H, thiazole-H), 6.81 (s, 1H, Ar-H), 6.69 (d,
H, Jꢀ=ꢀ8.3 Hz, Ar-H), 4.00 (s, 6H, O-CH ), 3.70–3.56 (m, 8H, morpho-
4
3
13
line-H), 2.86–2.73 (m, 8H, morpholine-H); C NMR: δ 161.5, 156.7, 146,
1
34.2, 130.6, 124.8, 117.5, 116.2, 115.5, 104.1, 96, 66, 55.7, 49; MS: m/z
+
6
57.3, [Mꢀ+ꢀH] (100%). Anal. Calcd for C H N O S : C, 62.17; H, 5.52;
3
4
36
6
4 2
1
00 μg/mL.
N, 12.80. Found: C, 62.12; H, 5.50; N, 12.78.
4
,4′-(4,6-Dimethoxy-1,3-phenylene)-bis(N-(pyridin-2-yl)thiazol-
-amine) (5g)ꢁReaction time 6 h, yield 72%, method A; reaction
time 10 min, yield 86%, method B; yellow solid; yield 72%; IR: 3465
Antimycobacterial activity assay
2
−1
1
(
N-H), 1599 (Cꢀ=ꢀN), 1542 (Cꢀ=ꢀC), 1372 (C-N), 771 (C-S) cm ; H NMR: Mycobacterium tuberculosis H37Rv (ATCC 27294) and Middlebrook
δ 11.43 (s, 2H, N-H), 8.64 (s, 1H, Ar-H), 8.34–8.31 (m, 2H, pyridine- 7H9 medium were used. The activity was assayed by the turbidom-
H), 7.71 (t, 2H, Jꢀ=ꢀ6.7 Hz, Ar-H), 7.35 (s, 2H, thiazole-H), 7.07 (d, 2H, etry method [26] using rifampicin as standard.
Jꢀ=ꢀ6.7 Hz, Ar-H), 6.92 (t, 2H, Jꢀ=ꢀ6.7 Hz, Ar-H), 6.85 (s, 1H, Ar-H), 4.05 (s,
1
3
6
H, O-CH ); C NMR: δ 162.4, 159.3, 157.5, 149.7, 145.3, 137.8, 128.9, 117.4,
3
+
Acknowledgments: The authors are grateful to the Head,
Department of Chemistry, Osmania University, Hyderabad
and IICT, Hyderabad for providing analytical and biologi-
cal facilities. The authors are thankful to Chemveda Life
Sciences Pvt. Ltd., IDA, Uppal, Hyderabad, for providing
laboratory facilities.
1
16.6, 108.7, 107.7, 95.7, 55.9; MS: m/z 489.2, [Mꢀ+ꢀH] (100%). Anal.
Calcd for C H N O S : C, 59.00; H, 4.13; N, 17.20. Found: C, 58.96; H,
2
4
20
6
2 2
4
.10; N, 17.17.
4
,4′-(4,6-Dimethoxy-1,3-phenylene)-bis(N-(6-methylpyridin-
2
-yl)thiazol-2-amine) (5h)ꢁReaction time 12 h, yield 77%, method
A; reaction time 15 min, yield 89%, method B; brown solid; mp 270–
73°C (dec); IR: 3461 (N-H), 1623 (Cꢀ=ꢀN), 1565 (Cꢀ=ꢀC), 1369 (C-N), 783
2
−
1
1
Online-only supplementary material: Optimization of
Jꢀ=ꢀ7.5 Hz, pyridine-H), 7.32 (s, 2H, thiazole-H), 6.90 (d, 2H, Jꢀ=ꢀ7.5 Hz, synthesis and biological activity (three Tables).
(
C-S) cm ; H NMR: δ 11.27 (s, 2H, N-H), 8.88 (s, 1H, Ar-H), 7.58 (d, 2H,
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