Hua Xue Fa Zhan Qian Yan

Scientific Journal of Frontier Chemical Development

550025

10
1H NMR13C NMRIR500 g/mL
(TMV)

Synthesis and Bioactivity of Bisamide Compounds Containing

Benzothiazole Unit
Wei Xue , Haichang Li , Huitao Fan , Zhuang Xiong , Yong He , Huixue Qi , Qiujuan Qiu
Research and Development Center for Fine Chemicals, Key Laboratory of Green Pesticide and Bioengineering, Ministry of Education, Guizhou
University, Guiyang, China, 550025
Email: wxue@gzu.edu.cn
Abstract: Ten novel bisamide compounds containing benzothiazole unit were synthesized from the reactions of substituted benzoic acid
and thionyl chloride, then coupled with substituted 2-aminobenzoic acid, cyclized in the existence of acetic anhydride, then coupled with
substituted benzo[d]thiazol-2-amine.Their structures were characterized by 1H NMR,

13

C NMR, IR and elemental analyses. Preliminary

bioassay showed that some compounds exhibited anti-TMV activity at the concentration of 500 g/mL.
Key words: Bisamide; Benzothiazole; Tobacco Mosaic Virus; Synthesis

TMV
[1]
[2-3]
[4-5]

1962 Merck
[6-12]
[13]
[14-15] TMV
4a-4j

O
OH SOCl
2
reflux

R1

R2
Cl

R1

COOH

NH2

(AcO)2O

R2
COOH

NH
reflux

CH2Cl2, Et3N

R1

O
2

R2

R3

NH2

R3

N
H

O
O
3

K2CO3

R2

R1

CH3CN

R1

N
O

N
H

: (No. 21062005) (No. 201122).

SJFCD Jun. 2012 Vol.2 No.2 PP.43-47 www.sjfcd.org 2011 American V-King Scientific Publishing, LTD | 43

Scientific Journal of Frontier Chemical Development

Hua Xue Fa Zhan Qian Yan

R1=4-Cl, R2=H, R3=4-CH3 (4a); R1=4-Cl, R2= H, R3=6-OCH3 (4b); R1=4-Cl, R2= H, R3=6-OCH2CH3 (4c); R1=4-CH3,
R2=3-CH3, R3=6-OCH2CH3 (4d); R1=3,4-2OCH3, R2=3-CH3, R3=6-OCH3 (4e); R1=4-CH3, R2=H, R3=6-CH3(4f); R1=2,4-2Cl,
R2=H, R3=6-CH3 (4g); R1=2,4-2Cl, R2=H, R3=6-F (4h); R1=2,4-2Cl, R2= 3-CH3, R3= 6-OCH2CH3 (4i); R1=2,4-2Cl, R2=3-CH3,
R3=6-Cl (4j)

1.1
JEOL-ECX 500 NMR()TMSDMSO-d6IR Prestige-21(
)KBrElementar Vario-III ()X-5()

1.2 2-()2
(3 mmol)6 mL25 mL12 h
2-100 mL(3 mmol)40 mL2 mL
15 mLTLC
40 mL(40 mLx2)
Na2SO4

1.3 2-()-4(3H)-3,1-3
(200 mm )()250 mL2 0.1
mol100 mL(1/10 s)TLC
2-(2-)-4(3H)-3,1-3

1.4
3 (5 mmol) (40 mL) (0.7 g, 5 mmol) 100 mL 5 min
15 mL (5 mmol 15 mL )
TLC
[V()V()=21] 4a ~ 4j
4a 45%>300 1H NMR (500 MHz, DMSO-d6) : 12.62 (s, 1H, NH), 9.92 (s, 1H, NH), 8.85
(d, J =8.0 Hz,1H, Ph-H), 8.74 (d, J =8.6 Hz, 2H, Ph-H), 8.26 (dd, J =1.7, 1.8 Hz, 1H, Ph-H), 7.68 (d, J =7.5 Hz, 2H, Ph-H),
7.56 (t, J =7.5 Hz, 2H, Ph-H), 7.42 (t, J =8.0 Hz, 1H, Ph-H), 7.14-7.11 (m, 2H, Ph-H), 2.61 (s, 3H, CH3); 13C NMR (125
MHz, DMSO-d 6) : 170.0, 163.7, 140.7, 137.0, 134.2, 131.2, 131.0, 126.5, 125.6, 121.2, 119.7, 119.4, 21.6; IR (KBr) :
3163, 3120, 3101, 1653, 1627, 1591, 1552, 1506, 1491, 1456, 1381, 1334, 1249, 1113, 918, 815, 756; C 22H16ClN3O2S
: C, 62.63; H, 3. 82; N, 9.96; C, 62.76; H, 3. 72; N, 9.70
1
4b:
42%
>300
H NMR (500 MHz, DMSO-d 6) : 13.12 (s, 1H, NH), 10.02 (s, 1H, NH), 8.85

(d, J =8.1 Hz,1H, Ph-H), 8.72 (d, J =6.9 Hz, 2H, Ph-H), 8.25 (d, J =8.0 Hz, 1H, Ph-H), 7.66 (d, J =7.5 Hz, 2H, Ph-H), 7.59
(d, J =8.6 Hz, 1H, Ph-H), 7.42 (t, J =7.5 Hz, 1H, Ph-H), 7.35 (t, J =8.1 Hz, 1H, Ph-H), 7.13-7.12 (m, 1H, Ph-H), 6.92 (d, J
=7.5 Hz,1H, Ph-H), 3.80 (s, 3H, OCH3); 13C NMR (125 MHz, DMSO-d6) : 172.9, 163.6, 141.4, 136.1, 134.5, 130.6, 131.6,
126.2, 125.4, 121.3, 119.4, 118.7, 58.1; IR (KBr) : 3059, 2941, 2829, 1664, 1585, 1506, 1456, 1382, 1317, 1257, 1223,
1113, 1057, 1029, 925, 840, 758; C22H16ClN 3O3S C, 60.34; H, 3. 68; N, 9.60; C, 60.09; H, 3.64; N,
9.27
44 | SJFCD Jun. 2012 Vol.2 No.2 PP.43-47 www.sjfcd.org 2011 American V-King Scientific Publishing, LTD

Hua Xue Fa Zhan Qian Yan

Scientific Journal of Frontier Chemical Development

4c 41%>3001H NMR (500 MHz, DMSO-d 6) : 12.62 (s, 1H, NH), 10.46 (s, 1H, NH), 8.85
(d, J =8.6 Hz, 1H, Ph-H), 8.73 (d, J =8.6 Hz, 2H, Ph-H), 8.26 (d, J =8.0 Hz, 1H, Ph-H), 7.67 (d, J =8.5 Hz, 2H, Ph-H), 7.59
(d, J =8.6 Hz, 1H, Ph-H), 7.42 (t, J =8.0 Hz, 1H, Ph-H), 7.33 (t, J =2.3 Hz, 1H, Ph-H), 7.13-7.12 (m, 1H, Ph-H), 6.92 (d, J
=6.3 Hz, 1H, Ph-H), 4.07 (q, J =6.9 Hz, 2H, OCH2), 1.35 (t, J =6.9 Hz, 3H, CH3); 13C NMR (125 MHz, DMSO-d6) :169.7,
166.4, 163.7, 154.3, 145.1, 140.7, 137.0, 134.6, 134.2, 131.0, 130.9, 130.8, 129.1, 125.8, 122.6, 120.2, 119.5, 114.2, 105.6,
63.9, 15.4; IR (KBr) : 3055, 2980, 1664, 1585, 1506, 1492, 1451, 1381, 1317, 1255, 1217, 1130, 1111, 1056, 921, 840,
756; C23H18ClN 3O3S C, 61.13; H, 4.01; N, 9.30; C, 60.76; H, 3.74; N, 8.97
4d 39%208-209; 1H NMR (500 MHz, DMSO-d 6) : 12.54 (s, 1H, NH), 9.89 (s, 1H, NH),
7.61 (d, J =9.2 Hz, 1H, Ph-H), 7.54 (s, 1H, Ph-H), 7.50-7.46 (m, 3H, Ph-H), 7.32-7.29 (m, 2H, Ph-H), 7.25-7.20 (m, 2H,
Ph-H), 6.99 (dd, J=2.3, 2.9 Hz, 1H, Ph-H), 4.03 (q, J =6.9 Hz, 3H, OCH3), 2.32 (s, 3H, CH3), 2.31 (s, 3H, CH3), 1.32 (t, J
=6.9 Hz, 3H, CH3); 13CNMR (125 MHz, DMSO-d 6) : 168.5, 167.1, 156.9, 155.9, 137.4, 136.2, 136.0, 134.5, 133.5, 133.4,
132.7, 130.9, 130.0, 127.7, 126.9, 126.6, 126.0, 121.2, 115.7, 105.8, 64.1, 19.7, 18.6, 15.3; IR(KBr) : 3444, 3257, 3151,
2974, 2929, 1662, 1600, 1541, 1506, 1456, 1298, 1261, 1220, 1153, 1066, 939, 817, 740; C 25H23N 3O3S
C, 67.40; H,
5.20; N, 9.43; C, 67.17; H, 5.03; N, 9.61
4e 40%208-2091HNMR (500 MHz, DMSO-d 6) : 12.46 (s, 1H, NH), 9.80 (s, 1H, NH),
7.60 (d, J = 8.6 Hz, 1H, Ph-H), 7.53 (d, J = 8.0 Hz, 2H, Ph-H), 7.49-7.41 (m, 4H, Ph-H), 7.31 (t, J = 8.0 Hz, 1H, Ph-H),
7.01 (t, J = 7.5 Hz, 1H, Ph-H), 3.84 (d, J = 4.6 Hz, 3H, OCH3), 3.76 (s, 3H, OCH3), 3.75 (s, 3H, OCH3), 2.36 (s, 3H, OCH3),
2.26 (s, 3H, CH3); 13CNMR (125 MHz, DMSO-d6) : 165.7, 156.6, 152.1, 148.8, 137.9, 136.7, 133.7, 133.4, 132.4, 128.0,
127.1, 126.7, 126.2, 122.4, 121.6, 121.4, 115.4, 112.1, 111.5, 110.7, 105.1, 56.1, 56.0, 18.6; IR(KBr) : 3452, 3442, 3302,
2939, 1668, 1602, 1570, 1467, 1307, 1263, 1222, 1170, 1141, 1107, 1060, 1018, 819, 646; C 25H23N 3O5S C, 62.88;
H, 4.85; N, 8.80; C, 62.94; H, 4.66; N, 9.07
4f 34%: 224-226 1H NMR (500 MHz, DMSO-d 6) : 12.91 (s, 1H, NH), 11.23 (s, 1H,
NH), 8.33 (s, 1H, Ph-H), 8.06 (s, 1H, Ph-H), 7.88 (d, J =6.2 Hz, 2H, Ph-H), 7.79 (s, 1H, Ph-H), 7.64 (s, 2H, Ph-H), 7.39 (d,
J =6.9 Hz, 2H, Ph-H), 7.29 (d, J =6.9 Hz, 2H, Ph-H), 2.43 (s, 3H, CH3), 2.41 (s, 3H, CH3); 13CNMR (125 MHz, DMSO-d6)
: 165.4, 142.7, 133.8, 133.4, 132.2, 129.9, 128.2, 127.8, 123.9, 122.9, 122.1, 64.2, 21.5; IR (KBr) : 3066, 2916, 1643,
1591, 1552, 1489, 1446, 1425, 1342, 1292, 1267, 1249, 1058, 916, 835, 812, 750, 663; C 23H19N 3O2S C, 68.81; H,
4. 77; N, 10.47; C, 68.54; H, 4. 39; N, 10.21
4g 40% 228-2291H NMR (500 MHz, DMSO-d6) : 12. 87 (s, 1H, NH), 10.98 (s, 1H,
NH), 7.95(s, 1H, Ph-H), 7.91(s, 1H, Ph-H), 7.76 (s, 2H, Ph-H), 7.72 (d, J = 8.6 Hz, 1H, Ph-H), 7.63-7.62 (m, 3H, Ph-H),
7.35 (t, J = 7.6 Hz, 1H, Ph-H), 7.27 (d, J = 8.0 Hz, 1H, Ph-H), 2.42 (s, 3H, CH3); 13C NMR (125 MHz, DMSO-d 6) : 165.1,
156.3, 135.2, 136.4, 132.0, 131.9, 131.3, 129.5, 128.6, 125.1, 115.7, 105.0, 19.1; IR (KBr) : 3223, 3057, 2914, 1645, 1587,
1543, 1496, 1448, 1423, 1342, 1301, 1234, 1103, 1047, 918, 754; C 22H15Cl 2N3O2S C, 57.90; H, 3.31; N, 9.21;
C, 57.49; H, 3.54; N, 9.05
4h 34% 280-2811HNMR(500 MHz, DMSO-d6) : 12.91 (s, 1H, NH), 10.66 (s, 1H, NH),
8.49 (s, 1H, Ph-H), 8.18 (s, 1H, Ph-H), 7.99 (s, 1H, Ph-H), 7.76 (d, J =8.3 Hz, 1H, Ph-H), 7.61 (t, J =7.5 Hz, 2H, Ph-H),
7.46 (d, J =6.9 Hz, 2H, Ph-H), 7.17-7.16 (m, 2H, Ph-H);

13

C NMR (125 MHz, DMSO-d6): 170.0, 163.8, 157.2, 147.2,

135.6, 135.5, 134.4, 134.3, 132.4, 131.5, 130.7, 130.3, 128.4, 125.6, 123.4, 120.3, 120.2, 112.9, 107.8, 107.6; IR (KBr) :
3442, 3419, 3086, 1654, 1620, 1587, 1506, 1471, 1450, 1382, 1274, 1249, 1209, 1124, 1047, 902, 833, 758 .
C21H12Cl 2FN 3O2S C, 54.79; H, 2.63; N, 9.13C 54.50; H, 2.74; N, 8.69

SJFCD Jun. 2012 Vol.2 No.2 PP.43-47 www.sjfcd.org 2011 American V-King Scientific Publishing, LTD | 45

Hua Xue Fa Zhan Qian Yan

Scientific Journal of Frontier Chemical Development

4i 36% 216-2181HNMR(500MHz, DMSO-d6) : 12.64 (s, 1H, NH), 10.23 (s, 1H, NH),
7.72 (d, J =4.6 Hz, 1H, Ph-H), 7.66-7.65 (m, 1H, Ph-H), 7.60-7.51 (m, 5H, Ph-H), 7.36-7.35 (m, 1H, Ph-H), 7.04-7.02 (m,
1H, Ph-H), 4.07 (q, J =6.9 Hz, 2H, OCH2), 2.35 (s, 3H, CH3), 1.30 (q, J =6.9 Hz, 3H, CH3); 13CNMR (125 MHz, DMSO-d6)
: 167.0, 164.8, 156.9, 155.9, 136.1, 135.2, 133.8, 133.6, 132.4, 131.6, 130.6, 129.8, 127.9, 127.0, 121.7, 115.8, 105.8, 64.1,
18.5, 15.3, IR (KBr) : 3246, 3223, 3192, 2974, 2926, 1676, 1651, 1602, 1521, 1456, 1296, 1247, 1224, 1197, 1151, 1060,
902, 823, 783, 744, 682. C 24H19Cl2N 3O3S C, 57.61; H, 3.83; N, 8.40; C, 57.44; H, 4.03; N, 8.51
4j 35% 232-234 1HNMR(500MHz, DMSO-d6) : 12.90 (s, 1H, NH), 10.27 (s, 1H, NH),
8.16 (s, 1H, Ph-H), 7.77 (d, J =8.5 Hz, 1H, Ph-H), 7.73 (s, 1H, Ph-H), 7.59 (s, 3H, Ph-H), 7.52 (d, J =7.5 Hz, 1H, Ph-H),
7.47 (d, J =8.6 Hz, 1H, Ph-H), 7.37 (t, J =7.5 Hz, 1H, Ph-H), 2.36 (s, 3H, CH3); 13CNMR (125 MHz, DMSO-d 6) : 167.4,
164.8, 148.0, 136.1, 135.2, 133.8, 132.1, 130.6, 129.7, 128.1, 127.9, 127.0, 126.9, 122.3, 122.0, 18.6. IR(KBr) : 3221,
3182, 3066, 2968, 1672, 1653, 1593, 1541, 1517, 1467, 1300, 1099, 856, 823, 788, 769, 736;

C22H14Cl 3N 3O2S

C, 53.84; H, 2.88; N, 8.56; C, 53.64; H, 2.58; N, 8.19

1.5 TMV
TMV

231 C10000 Lux3~4

33~433~4

Y(C-A)/C100%
YC()A()

2
2.1
4a 4a 3163 cm-13120 cm-1 N-H 1653 cm-11627
cm-1 CO 1381 cm-11334 cm-1 C-N 678 cm-1
C-S-C , 1H NMR 4a

2.2
1 TMV
Compound

Inhibition rate (%)

Compound

Inhibition rate (%)

4a

44.3

4f

38.1

4b

42.2

4g

41.9

4c

33.9

4h

34.9

4d

43.3

4i

38.3

4e

34.1

4j

41.9

51.5

46 | SJFCD Jun. 2012 Vol.2 No.2 PP.43-47 www.sjfcd.org 2011 American V-King Scientific Publishing, LTD

Hua Xue Fa Zhan Qian Yan

Scientific Journal of Frontier Chemical Development

1 4a4d 4a 44.3%

[1]

. [J]. , 1999, 2: 36-38.

[2]

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. [J]. , 2004, 3: 55-56.

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,. [J]. , 2001, 22 (1): 46-48.

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[8]

Hutchinson I., Chua M S., Browne H L. et al. Antitumor benzothiazoles. 14. Synthesis and in vitro biological properties of fluorinated
2-(4-aminophenyl) benzothiazoles [J]. J Med Chem 2001, 44 (9): 1446-1455.

[9]

Bradshaw T D., Westwell A D. et al. The Development of the Antitumour Benzothiazole Prodrug, Phortress, as a Clinical Candidate [J].
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2-minobenzo-thiazolamines and their antimicrobial activity [J]. Orient J Chem, 2000, 16 (3): 549-552.
[11] Chen C. P, Chen Y. J., Liquid-phase synthesis of 2-substituted benzimidazoles, benzoxazoles and benzothiazoles [J]. Tetrahedron Lett.
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[12] ,,,. [M]. , 1993.
[13] , , ,. -[J]. , 2005, 25 (8):
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[15] Lahm G. P., Selby T. P., Freudenber J. H. et a1. Insecticidal anthranilic diamides: a new class of potent ryanodine receptor activators [J].
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1970-
: 2005 2011
Email: wxue@gzu.edu.cn

SJFCD Jun. 2012 Vol.2 No.2 PP.43-47 www.sjfcd.org 2011 American V-King Scientific Publishing, LTD | 47