Synthesis and plant-growth regulatory activities of novel imine derivatives containing 1H-1,2,4-triazole and thiazole rings

Article abstract of DOI:10.1016/j.cclet.2009.11.007

Eleven new imine derivatives 6 containing 1H-1,2,4-triazole and thiazole rings were synthesized by the condensation of 5-((1H-1,2,4-triazol-1-yl)methyl)-4-tert-butylthiazol-2-amine with various substituted benzaldehydes. The structures of the title compounds were characterized by ¹H NMR, MS and elemental analysis. The plant-growth regulatory activities of these compounds were evaluated. The primary bioassay results indicated that these target compounds exhibited promising plant-growth regulatory activities.

Full text of DOI:10.1016/j.cclet.2009.11.007

Available online at www.sciencedirect.com
Chinese Chemical Letters 21 (2010) 283–286
www.elsevier.com/locate/cclet
Synthesis and plant-growth regulatory activities of novel imine
derivatives containing 1H-1,2,4-triazole and thiazole rings
Xue Qin, Hai Bo Yu, Hong Dai, Zhen Fang Qin, Xin Zhang, Gui Fang Bing,
*
Ting Ting Wang, Jian Xin Fang
State Key Laboratory of Elemento-organic Chemistry and Tianjin Key Laboratory of Pesticide Science, Naikai University, Tianjin 300071, China
Received 2 July 2009
Abstract
Eleven new imine derivatives 6 containing 1H-1,2,4-triazole and thiazole rings were synthesized by the condensation of 5-((1H-
1,2,4-triazol-1-yl)methyl)-4-tert-butylthiazol-2-amine with various substituted benzaldehydes. The structures of the title com-
1
pounds were characterized by H NMR, MS and elemental analysis. The plant-growth regulatory activities of these compounds
were evaluated. The primary bioassay results indicated that these target compounds exhibited promising plant-growth regulatory
activities.
# 2009 Jian Xin Fang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: 1H-1,2,4-Triazole; Thiazole; Synthesis; Imine; Plant-growth regulatory activity
Molecules containing thiazole ring systems are widely studied because of its low toxicity, excellent biological
activity as well as readily access of diverse derivatives. Thiazole moiety is the key pharmacophore and intermediate for
synthesizing pharmaceuticals and it is extensively found in the field of agrochemicals [1–6]. On the other hand, 1H-
1,2,4-triazole-containing derivatives plays a vital role in many biological activities [7]. Compounds containing the 1H-
1,2,4-triazole ring system have been found to show significant plant-growth regulatory activity such as uniconazole
and paclobutrazol [8]. We also know that imine derivatives possess potent activities including antibacterial, antifungal,
and antitumor activities [9,10]. Promoted by the above observations and in continuation of our study on the biological
activities of thiazole derivatives, we designed and synthesized some new thiazole derivatives by incorporating the 1H-
1,2,4-triazole unit into the title compounds (Scheme 1). Compounds 2–4 were synthesized according to the literature
methods [11,12].
Synthesis of 5-((1H-1,2,4-triazol-1-yl)methyl)-4-tert-butylthiazol-2-amine (5). Thiourea was added to the solution
of compound 4 (9.92 mmol) in ethanol (15 mL), the mixture was heated to 50 8C and stirred for 8 h to form the
hydrobromide salt of 5 which precipitated out. The mixture was then cooled and vacuum filtered. The solid was then
stirred for 1 h in the solution of sodium bicarbonate. The precipitated product was collected by filtration, and dried
to give compound 5 as a white crystalline solid with yield 75%, m.p. 187–189 8C. 1H NMR (300 MHz, CDCl3): d 1.30
* Corresponding author.
E-mail address: fjx@nankai.edu.cn (J.X. Fang).
1001-8417/$ – see front matter # 2009 Jian Xin Fang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2009.11.007

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X. Qin et al. / Chinese Chemical Letters 21 (2010) 283–286
Scheme 1. Synthesis of the title compounds 6. (a) (CH2O)n/Me2NHÁHCl, C2H5OH; (b) 1H-1,2,4-triazole/H2O; (c) Br2/CH3COOH, CH3COONa;
(d) thiourea/C2H5OH; (e) substituted benzaldehyde/toluene/piperidine.
(s, 9H, t-butyl), 5.49 (s, 2H, CH2), 6.82 (s, 2H, NH2), 7.97 (s, 1H, TrH), 8.49 (s, 1H, TrH). Anal. calcd. (%) for
C10H15N5S: C, 50.61; H, 6.37; N, 29.51. Found: C, 50.45; H, 6.30; N, 29.78.
General preparation of the title compounds 6a–k. To the solution of compound 5 (2 mmol) in toluene (20 mL) was
added appropriate substituted benzaldehyde (2.2 mmol) and piperidine (3 drops). The reaction mixture was stirred and
refluxed for 20 h. The solvent was evaporated under the reduced pressure the residue was purified by flash
chromatography to afford the title compounds 6a–k in high purity.
Data for 6a: yellow solid, yield 53%, m.p. 87–89 8C; 1H NMR(CDCl3, 300 MHz): d 1.46 (s, 9H, t-butyl), 5.67 (s,
2H, CH2), 7.52 (q, 3H, J = 6.6 Hz, ArH), 7.97 (d, 2H, J = 6.8 Hz, ArH), 8.00 (s, 1H, TrH), 8.09 (s, 1H, TrH), 8.86 (s,
1H, N CH). Anal. calcd. for C17H19N5S: C 62.74, H 5.88, N 21.52; found C 62.55, H 6.01, N 21.61.
Data for 6b: yellow solid, yield 51%, m.p. 94–95 8C; 1H NMR(CDCl3, 300 MHz): d 1.47 (s, 9H, t-butyl), 5.68 (s,
2H, CH2), 7.12–7.27 (m, 2H, ArH), 7.50–7.54 (m, 1H, ArH), 8.01 (s, 1H, TrH), 8.09 (s, 1H, TrH), 8.21–8.27 (m, 1H,
ArH), 9.17(s, 1H, N CH). MS (ESI), m/z 344.49 ([M+1]+, 100). Anal. calcd. for C17H18FN5S: C 59.46, H 5.28, N
20.39; found C 59.21, H 5.44, N 20.44.
Data for 6c: yellow solid, yield 14%, m.p. 83–85 8C; 1H NMR(CDCl3, 300 MHz): d 1.47 (s, 9H, t-butyl), 5.59 (s,
2H, CH2), 7.68–7.72 (m, 2H, ArH), 8.00 (s, 1H, TrH), 8.10 (d, 1H, J = 8.5 Hz, ArH), 8.11 (s, 1H, TrH), 8.37 (d, 1H,
J = 7.7 Hz, ArH), 8.40 (s, 1H, N CH). MS (ESI), m/z 370.97 ([M+1]+, 100). Anal. calcd. for C17H18N6O2S: C 55.12,
H 4.90, N 22.69; found C 55.34, H 5.13, N 22.58.
Data for 6d: yellow solid, yield 62%, m.p. 130–131 8C; 1H NMR(CDCl3, 300 MHz): d 1.48 (s, 9H, t-butyl), 3.92(s,
3H, CH3), 5.67 (s, 2H, CH2), 6.93–7.04 (m, 2H, ArH), 7.44–7.53 (m, 1H, ArH), 8.00 (s, 1H, TrH), 8.09 (s, 1H, TrH),
8.23 (q, 1H, J = 7.8 Hz, ArH), 9.23 (s, 1H, N CH). MS (ESI), m/z 356.36 ([M+1]+, 100). Anal. calcd. for
C18H21N5OS: C 60.82, H 5.95, N 19.70; found C 60.72, H 6.12, N 19.74.
Data for 6e: yellow solid, yield 42%, m.p. 87–89 8C; 1H NMR(CDCl3, 300 MHz): d 1.46 (s, 9H, t-butyl), 2.42(s,
3H, CH3), 5.67 (s, 2H, CH2), 7.28 (d, 2H, J = 8.0 Hz, ArH), 7.86 (d, 2H, J = 8.1 Hz, ArH), 8.00 (s, 1H, TrH), 8.08 (s,
1H, TrH), 8.80 (s, 1H, N CH). MS (ESI), m/z 340.40 ([M+1]+, 100). Anal. calcd. for C18H21N5S: C 63.69, H 6.24, N
20.63; found C 63.49, H 6.49, N 20.78.
Data for 6f: yellow solid, yield 55%, m.p. 136–137 8C; 1H NMR(CDCl3, 300 MHz): d 1.45 (s, 9H, t-butyl), 5.67 (s,
2H, CH2), 7.46 (d, 2H, J = 8.5 Hz, ArH), 7.90 (d, 2H, J = 8.5 Hz, ArH), 8.00 (s, 1H, TrH), 8.09 (s, 1H, TrH), 8.84 (s,
1H, N CH). MS (ESI), m/z 359.96 ([M+1]+, 100). Anal. calcd. for C17H18ClN5S: C 56.74, H 5.04, N 19.46; found C
56.40, H 5.14, N 19.45.
Data for 6g: yellow solid, yield 73%, m.p. 122–123 8C; 1H NMR(CDCl3, 300 MHz): d 1.46 (s, 9H, t-butyl), 5.66 (s,
2H, CH2), 7.17 (t, 2H, J = 8.6 Hz, ArH), 7.98 (t, 2H, J = 8.6 Hz, ArH), 8.00 (s, 1H, TrH), 8.10 (s, 1H, TrH), 8.83 (s, 1H,
N CH). MS (ESI), m/z 344.36 ([M+1]+, 100). Anal. calcd. for C17H18FN5S: C 59.46, H 5.28, N 20.39; found C 59.25,
H 5.37, N 20.54.
Data for 6h: yellow solid, yield 57%, m.p. 113–114 8C; 1H NMR(CDCl3, 300 MHz): d 1.46 (s, 9H, t-butyl), 3.88 (s,
3H, CH3), 5.65 (s, 2H, CH2), 6.98 (d, 2H, J = 8.8 Hz, ArH), 7.92 (d, 2H, J = 8.8 Hz, ArH), 8.00 (s, 1H, TrH), 8.07 (s,

X. Qin et al. / Chinese Chemical Letters 21 (2010) 283–286
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Table 1
Plant-growth regulatory activity of title compounds 6a–k (c = 10 mg/L).
Compound
R
Plant-growth regulatory activity (relative ratio, %)
Active gradea
6a
6b
H
72.2
116.6
100.0
116.6
66.6
+
2-F
++
++
++
+
6c
6d
2-NO2
2-OMe
4-Me
4-Cl
6e
6f
6g
83.3
+
4-F
100.0
23.2
++
À
+
6h
6i
4-OMe
2,4-Me2
3,4-Me2
2-F-4-Br
50.0
6j
6k
88.8
+
26.7
À
+
Triadimefon
Triadimenol
80.7
120.6
++
a
Active grade: +++ ꢀ150%, ++ ꢀ100%, + ꢀ50%, and À <50%.
1H, TrH), 8.74 (s, 1H, N CH). MS (ESI), m/z 356.46 ([M+1]+, 100). Anal. calcd. for C18H21N5OS: C 60.82, H 5.95, N
19.70; found C 60.66, H 6.14, N 19.98.
Data for 6i: yellow solid, yield 37%, m.p. 125–127 8C; 1H NMR(CDCl3, 300 MHz): d 1.46 (s, 9H, t-butyl), 2.37 (s,
3H, CH3), 2.57 (s, 3H, CH3), 5.66 (s, 2H, CH2), 7.05 (s, 1H, ArH), 7.10 (d, 1H, J = 8.1 Hz, ArH), 8.00 (s, 1H, TrH),
8.06 (s, 1H, ArH), 8.07 (d, 1H, J = 9.2 Hz, ArH), 8.09 (s, 1H, TrH), 9.10 (s, 1H, N CH). MS (ESI), m/z 354.33
([M+1]+, 100). Anal. calcd. for C19H23N5S: C 64.56, H 6.56, N 19.81; found C 64.30, H 6.59, N 19.99.
Data for 6j: yellow solid, yield 35%, m.p. 82–83 8C; 1H NMR(CDCl3, 300 MHz): d 1.48 (s, 9H, t-butyl), 2.32 (d,
6H, J = 3.7 Hz, 2CH3), 5.67 (s, 2H, CH2), 7.22–7.25 (m, 1H, ArH), 7.64–7.67 (m, 1H, ArH), 7.79 (s, 1H, ArH), 8.00 (s,
1H, TrH),8.09 (s, 1H, TrH), 8.77 (s, 1H, N CH). MS (ESI), m/z 354.47 ([M+1]+, 100). Anal. calcd. for C19H23N5S: C
64.56, H 6.56, N 19.81; found C 64.39, H 6.81, N 20.04.
Data for 6k: yellow solid, yield 24%, m.p. 107–109 8C; 1H NMR(CDCl3, 300 MHz): d 1.46 (s, 9H, t-butyl), 5.67 (s,
2H, CH2), 7.34–7.42 (m, 2H, ArH), 8.00 (s, 1H, TrH), 8.08 (s, 1H, TrH), 8.13 (d, 1H, J = 7.9 Hz, ArH), 9.11 (s, 1H,
N CH). MS (ESI), m/z 423.86 ([M+1]+, 100). Anal. calcd. for C17H17BrFN5S: C 48.35, H 4.06, N 16.58; found C
48.17, H 4.31, N 16.78.
The plant-growth regulatory activity of title compounds 6a–k was screened using cucumber cotyledon rhizogenesis
method according to procedures described previously [13]. At the concentration of 10 mg/L, the plant-growth
regulatory activity results for compounds 6a–k are shown in Table 1. In comparison with triadimefon and triadimenol
[14,15], some of the target compounds showed promising plant-growth regulatory activity. For example, 6b and d
showed obvious plant regulatory activities as the same as triadimenol. And 6f, g, j exhibited higher plant-growth
regulatory activities than triadimefon. These data show that efficacy is strongly influenced by the nature of the
substitutes and their position on the benzene ring. In general, the presence of halo group such as fluorine and chlorine
atom at position 2 or 4 of phenyl ring may increase their plant-growth regulatory activity while electronic-donating
group, such as methyl and methoxy will cause the decrease of biological activity.
Acknowledgments
We gratefully acknowledge the National Natural Science Foundation of China (No. 20772068) and the National
Key Project of Scientific and Technical Supporting Programs of China (No. 2006BAE01A01-5) for financial support.
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