Synthesis and biological activities of cyclanone O-(2-(3-aryl-4- amino-4H-1,2,4-triazol-3-yl)thio)acetyl)oxime derivatives

Article abstract of DOI:10.1080/10426507.2017.1315419

Twelve cyclanone O-(2-(3-aryl-4-amino-4H-1,2,4-triazol-3-yl)thio)acetyl)oxime derivatives were synthesized and their structures were confirmed by spectroscopy (IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR) and elemental analysis. Their antifungal and antibacterial activities were evaluated against six fungi (Gibberella zeae, Fusarium oxysporum, Clematis mandshurica, Phytophthora infestans, Paralepetopsis sasakii, Sclerotinia sclerotiorum) and two bacteria (Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas citri subsp. Citri (Xcc)). The results indicated that most of the title compounds exhibited good antibacterial activities. Among them, compounds 6d, 6g, 6h, and 6j showed better antibacterial activities against Xoo and Xcc than that of the commercial agent thiodiazole-copper.

Full text of DOI:10.1080/10426507.2017.1315419

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: http://www.tandfonline.com/loi/gpss20
Synthesis and biological activities of cyclanone
O-(2-(3-aryl-4- amino-4H-1,2,4-triazol-3-
yl)thio)acetyl)oxime derivatives
Meihang Chen, Lijuan Chen, Xuesong Zhu, Xiaobin Wang, Qin Li, Juping
Zhang, Daowang Lu & Wei Xue
To cite this article: Meihang Chen, Lijuan Chen, Xuesong Zhu, Xiaobin Wang, Qin Li, Juping
Zhang, Daowang Lu & Wei Xue (2017): Synthesis and biological activities of cyclanone O-(2-(3-
aryl-4- amino-4H-1,2,4-triazol-3-yl)thio)acetyl)oxime derivatives, Phosphorus, Sulfur, and Silicon
and the Related Elements, DOI: 10.1080/10426507.2017.1315419
To link to this article: http://dx.doi.org/10.1080/10426507.2017.1315419
Accepted author version posted online: 07
Apr 2017.
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Date: 09 April 2017, At: 07:01

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Synthesis and biological activities of cyclanone O-(2-(3-aryl-4-
amino-4H-1,2,4-triazol-3-yl)thio)acetyl)oxime derivatives
Meihang Chenb,*,‡, Lijuan Chena,‡, Xuesong Zhua, Xiaobin Wanga, Qin Lia, Juping Zhanga,
Daowang Lub, Wei Xuea,**
aCenter for Research and Development of Fine Chemicals, Guizhou University, State Key
Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory
of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guiyang, 550025,
China
bMaterial and Chemistry Engineering Institution, Tongren College, Tongren 554300, China
‡The first and the second author contributed equally to this work
*Corresponding author Email: chenmeihang0123@126.com
**Corresponding author Email: wxue@gzu.edu.cn
Abstract
Twelve cyclanone O-(2-(3-aryl-4-amino-4H-1,2,4-triazol-3-yl)thio)acetyl)oxime derivatives
1
13
were synthesized and their structures were confirmed by spectroscopy (IR, H NMR, C NMR,
19F NMR) and elemental analysis. Their antifungal and antibacterial activities were evaluated
against six fungi (Gibberella zeae, Fusarium oxysporum, Clematis mandshurica, Phytophthora
infestans, Paralepetopsis sasakii, Sclerotinia sclerotiorum) and two bacteria (Xanthomonas
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oryzae pv. oryzae (Xoo), Xanthomonas citri subsp. Citri (Xcc)). The results indicated that most
of the title compounds exhibited good antibacterial activities. Among them, compounds 6d, 6g,
6h, and 6j showed better antibacterial activities against Xoo and Xcc than that of the commercial
agent thiodiazole-copper.
Keywords
Oxime ester derivative; 1,2,4-triazole; synthesis; biological activity
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Introduction
Oxime ester derivatives exhibit a wide spectrum of pharmacological effects, such as
antibacterial1,2, antifungal3, antitumoral4,5, anticonvulsant6 activities. Recently, oxime ester
derivatives have attracted considerable attention in pestcide research7. For example, novel aurone
oxime (ether) derivatives were synthesized and it was found that some of them displayed good
herbicidal activities against Brasica campestris8. In our previous research, a serial of novel
curcumin derivatives bearing the oxime esters moiety were synthesized and we found that some
of them exhibited excellent antiviral activities against the tobacco mosaic virus9. Moreover,
1,2,4-triazole derivatives show extensive biological activities including antibacterial10,
antifungal11, anticancer12, antioxidant13 and anti-HIV14 activities. Some novel 1,2,4-triazole
derivatives exhibited excellent antibacterial and antifungal activities and have been used as
commercial agents in agricultural production15-20
.
In recent years, crop diseases have become increasingly difficult to control, more and more
resistant fungi and bacteria have evolved due to the continued and widespread application of the
traditional pesticides, which leads to enormous losses in worldwide agricultural production each
year21. Hence, the development of novel antibacterial and antifungal agents remains a daunting
task in pesticide science. In this study, a 1,2,4-triazole fragment was introduced into an oxime
ether and a a series of novel cyclanone O-(2-(3-aryl-4-amino-4H-1,2,4-triazol-3-yl)thio)acetyl)
oxime derivatives were synthesized, and evaluated for their antibacterial activities against six
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fungi (Gibberella zeae, Fusarium oxysporum, Clematis mandshurica, Phytophthora infestans,
Paralepetopsis sasakii, Sclerotinia sclerotiorum) and two bacteria (Xanthomonas oryzae pv.
oryzae (Xoo), Xanthomonas citri subsp. Citri (Xcc)), respectively.
Results and Discussion
Chemistry
The synthesis of cyclanone O-(2-(3-aryl-4-amino-4H-1,2,4-triazol-3-yl)thio) acetyl)oxime
derivatives was achieved six steps. The schematic presentation is depicted in Scheme 1.
Intermediates 1a, 1b were synthesized following the published procedures22 by condensing
the cyclic ketone with hydroxylamine hydrochloride in ethanol at room temperature.
Intermediates 2a, 2b were prepared by condensing chloroacetyl chloride with intermediates 1a,
1b in acetone at room temperature. Intermediates 4a−4f were synthesized by following the
procedures described in the literature23-26. The preparation of intermediates 5a−5h were carried
out in boiling ethanol for 8 h. Finally, the intermediates 5a−5h were treated with intermediates
2a, 2b in acetonitrile at room temperature to get title compounds 6a−6l (Scheme 1).
The structures of 6a−6l were confirmed by spectroscopy (IR, 1H NMR, 13C NMR, 19F NMR)
and elemental analysis. In 1H NMR, the proton of --SCH2-- yielding a singlet peak and appeared
at δ 4.27--4.15 ppm; δ 6.36--6.20 ppm as singlet indicated the existences of −NH2. The chemical
13
shifts at δ 170.3--166.3 ppm confirmed the existences of carbon of carbonyl group in C NMR.
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The IR spectral data of the title compounds showed characteristic absorption bands at
3555−3320 cm−1, which were assigned to N−H of --NH2. The absorption bands of the −OC = O−
of the coumarin ring appeared at 1740−1690 cm−1. Elemental analysis also confirmed the
structures of the title compounds.
Antifungal Activity in Vitro
The title compounds 6a−6l were tested for in vitro antifungal activity against six fungi
(Gibberella zeae, Fusarium oxysporum, Clematis mandshurica, Phytophthora infestans,
Paralepetopsis sasakii, Sclerotinia sclerotiorum) by using the poison plate technique27.
Hymexazol was used as reference standard. The results of the antifungal activities are discussed
in the Supplemental Materials and presented in Table S 1.
Antibacterial Activity in Vitro
The title compounds 6a−6l were tested for in vitro antibacterial activity against Xoo and
Xcc by using the turbidimeter test28. Thiodiazole-copper was used as control. The results of the
antibacterial activities are discussed in the Supplemental Materials and presented in Table S 2.
EXPERIMENTS
1H NMR, 13C NMR and 19F NMR spectra were recorded with a JEOL-ECX 500 NMR
spectrometer at room temperature using tetramethylsilane as internal standard and DMSO-d6 as
solvent. The IR spectra were recorded on an IR Affinity-1s spectrometer using a KBr disk
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technique. Melting points were determined on a XT-4 melting apparatus and were uncorrected.
Elemental analyses were performed on an Elementar Vario-III CHN analyser.
Preparation of Intermediates 2a, 2b
A mixture of intermediates 1a, 1b (25.0 mmol) and anhydrous potassium carbonate (50.0
mmol) was dissolved in dry acetone (100 mL) and acetone solution of chloroacetyl chloride
(50.0 mmol in 30 mL) was added dropwise and stirred at room temperature for 2 h. After
completion of the reaction checked by TLC, cooled the reaction mass to RT and then poured into
water. The precipitate was filtered and recrystallized from ethyl alcohol to obtain intermediates
2a, 2b.
Cyclopentanone O-(2-chloroacetyl) oxime (2a)
1
White solid, yield 63%, m.p. 122--124°C; H NMR (500 MHz, DMSO-d6, ppm) δ: 4.24 (s, 2H,
13
CH2), 2.55--2.40(m, 4H, cyclopentanone-H), 1.90--1.75 (m, 4H, cyclopentanone-H); C NMR
(125 MHz, DMSO-d6, ppm) δ: 166.3, 31.7, 30.2, 29.0, 26.4.
Cyclohexanone O-(2-chloroacetyl) oxime (2b)
1
White solid, yield 71%, m.p. 125--126°C; H NMR (500 MHz, DMSO-d6, ppm) δ: 4.23 (s, 2H,
CH2), 2.51--2.36 (m, 4H, cyclohexanone-H), 1.76--1.69 (m, 2H, cyclohexanone-H), 1.68--1.61
(m, 4H, cyclohexanone-H); 13C NMR (125 MHz, DMSO-d6, ppm) δ: 166.3, 31.2, 26.5, 26.5,
25.8, 25.0.
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Preparation of Intermediates 5a−5h
To a stirred solution of compounds 4a−4f (20 mmol), 80% hydrazine hydrate (25.00 mmol)
was added in ethanol (200 mL). The mixture was refluxed for 8 h, monitored by TLC and after
completion of the reaction, the solution was poured into ice water. The precipitate was filtered
and recrystallized from ethanol.
4-Amino-5-phenyl-4H-1,2,4-triazole-3-thiol (5a)
White solid, yield 83%, m.p. 112--114°C; 1H NMR (500 MHz, DMSO-d6, ppm) δ: 13.90 (s, 1H,
SH), 8.00--7.97 (m, 2H, PhH), 7.52--7.48 (m, 3H, PhH), 5.76 (s, 2H, NH2); 13C NMR (125 MHz,
DMSO-d6, ppm) δ: 166.4, 144.9, 130.9, 129.0, 128.5, 126.3.
4-Amino-5-(4-fluorophenyl)-4H-1,2,4-triazole-3-thiol (5b)
White solid, yield 80%, m.p. 115--116°C; 1H NMR (500 MHz, DMSO-d6, ppm) δ: 13.90 (s, 1H,
SH), 8.07--8.03 (m, 2H, PhH), 7.38--7.33 (m, 2H, PhH), 5.75 (s, 2H, NH2); 13C NMR (125 MHz,
DMSO-d6, ppm) δ: 167.9, 161.0, 132.8, 129.9, 126.6, 123.0.
4-Amino-5-(4-chlorophenyl)-4H-1,2,4-triazole-3-thiol (5c)
White solid, yield 77%, m.p. 123--125°C; 1H NMR (500 MHz, DMSO-d6, ppm) δ: 13.96 (s, 1H,
SH), 8.03 (d, J = 8.5 Hz, 2H, PhH), 7.58 (d, J = 8.5 Hz, 2H, PhH), 5.77 (s, 2H, NH2); 13C NMR
(125 MHz, DMSO-d6, ppm) δ: 167.7, 149.0, 135.8, 130.2, 129.2, 125.1.
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4-Amino-5-(4-(trifluoromethyl)phenyl)-4H-1,2,4-triazole-3-thiol (5d)
White solid, yield 72%, m.p. 139--141°C; 1H NMR (500 MHz, DMSO-d6, ppm) δ: 14.01 (s, 1H,
SH), 8.24 (d, J = 8.5 Hz, 2H, PhH), 7.89 (d, J = 8.5 Hz, 2H, PhH), 5.81 (s, 2H, NH2); 13C NMR
(125 MHz, DMSO-d6, ppm) δ: 167.8, 149.4, 135.7, 130.2, 129.2, 126.1.
4-Amino-5-(4-nitrophenyl)-4H-1,2,4-triazole-3-thiol (5e)
White solid, yield 70%, m.p. 156--158°C; 1H NMR (500 MHz, DMSO-d6, ppm) δ: 14.16 (s, 1H,
SH), 8.37--8.34 (m, 2H, PhH), 8.33--8.30 (m, 2H, PhH), 5.83 (s, 2H, NH2); 13C NMR (125 MHz,
DMSO-d6, ppm) δ: 168.2, 148.7, 148.3, 132.1, 129.6, 124.3.
4-Amino-5-(4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol (5f)
White solid, yield 70%, m.p. 156--158°C; 1H NMR (500 MHz, DMSO-d6, ppm) δ: 13.87 (s, 1H,
SH), 8.05--8.01 (m, 2H, PhH), 7.36--7.31 (m, 2H, PhH), 5.73 (s, 2H, NH2), 3.73 (s, 3H, OCH3);
13C NMR (125 MHz, DMSO-d6, ppm) δ: 167.8, 154.1, 149.2, 138.4, 122.4, 106.2, 56.6.
Preparation Procedure of cyclanone O-(2-(3-aryl-4-amino-4H-1,2,4-triazol-3-yl)thio)
acetyl)oxime derivatives 6a−6l.
A solution of intermediates 5a−5f (1.0 mmol), potassium carbonate (1.1 mmol) and a
catalytic amount of potassium iodide in acetonitrile (50 mL) was stirred at room temperature.
The reaction was monitored by TLC (petroleum ether/ethyl acetate, V/V = 1:2) and was
completed about 3~4 h. The acetonitrile was removed under vacuum, and the residue was
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purified by silica gel column chromatography (petroleum ether/ethyl acetate, V/V = 4:1) to obtain
O-(2-(3-aryl-4-amino-4H-1,2,4- triazol-3-yl)thio)-acetyl)oxime derivatives (6a−6l).
Cyclopentanone O-(2-((4-amino-5-phenyl-4H-1,2,4-triazol-3-yl)thio)acetyl) oxime (6a)
1
White solid, yield 76%, m.p. 145--146°C; IR (KBr, cm1) ν: 3433, 1750, 1629; H NMR (500
MHz, DMSO-d6, ppm) δ: 8.00--7.95 (m, 2H, PhH), 7.55--7.50 (m, 3H, PhH), 6.23 (s, 2H, NH2),
4.24 (s, 2H, SCH2), 2.55--2.40(m, 4H, cyclopentanone-H), 1.90--1.75 (m, 4H,
13
cyclopentanone-H); C NMR (125 MHz, DMSO-d6, ppm) δ: 166.3, 165.4, 154.2, 152.9, 129.7,
128.5, 127.7, 126.7, 31.9, 30.2, 28.5, 26.3; Anal. Cald. for C15H17N5O2S; C: 54.36, H: 5.17, N:
21.13; Found: C: 54.32, H: 5.14, N: 21.16.
Cyclohexanone O-(2-((4-amino-5-phenyl-4H-1,2,4-triazol-3-yl)thio)acetyl) oxime (6b)
1
White solid, yield 83%, m.p. 149--150°C; IR (KBr, cm1) ν: 3410, 1740, 1630; H NMR (500
MHz, DMSO-d6, ppm) δ: 7.99--7.93 (m, 2H, PhH), 7.54--7.50 (m, 3H, PhH), 6.23(s, 2H, NH2),
4.23 (s, 2H, SCH2), 2.51 (t, J = 6.5 Hz, 2H, cyclohexanone-H), 2.30 (t, J = 6.5 Hz, 2H,
cyclohexanone-H), 1.77--1.68(m, 2H, cyclohexanone-H), 1.67--1.60 (m, 4H, cyclohexanone-H);
13C NMR (125 MHz, DMSO-d6, ppm) δ: 166.3, 165.4, 154.3, 152.9, 129.7, 128.5, 127.7, 126.7,
31.9, 31.3, 26.7, 26.5, 25.7, 24.9; Anal. Cald. for C16H19N5O2S; C: 55.63, H: 5.54, N: 20.27;
Found: C: 55.65, H: 5.57, N: 20.22.
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Cyclopentanone O-(2-((4-amino-5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl)thio) acetyl) oxime
(6C)
1
White solid, yield 78%, m.p. 162--163°C; IR (KBr, cm1) ν: 3555, 1720, 1655; H NMR (500
MHz, DMSO-d6, ppm) δ: 8.04--7.35 (m, 4H, PhH), 6.23 (s, 2H, NH2), 4.23 (s, 2H, SCH2),
2.56--2.42 (m, 4H, cyclopentanone-H), 1.91--1.77 (m, 4H, cyclopentanone-H); 19F NMR (471
MHz, DMSO-d6, ppm) δ: -111.0 (s); 13C NMR (125 MHz, DMSO-d6, ppm) δ: 166.2, 165.4,
162.9, 153.5, 152.8, 130.1, 123.3, 115.6, 32.0, 30.2, 28.5, 26.3; Anal. Cald. for C15H16FN5O2S;
C:51.57, H: 4.62, N: 20.04; Found: C: 51.55, H: 4.59, N: 20.08.
Cyclohexanone O-(2-((4-amino-5-(4-fluorophenyl)-4H-1,2,4-triazol-3-yl)thio) acetyl) oxime
(6d)
1
White solid, yield 74%, m.p. 159--160°C; IR (KBr, cm1) ν: 3540, 1735, 1659. H NMR (500
MHz, DMSO-d6, ppm) δ: 8.05--7.36 (m, 4H, PhH), 6.23 (s, 2H, NH2), 4.23 (s, 2H, SCH2), 2.53
(t, J = 6.2 Hz, 2H, cyclohexanone-H), 2.31 (t, J = 6.2 Hz, 2H, cyclohexanone-H), 1.72--1.69 (m,
2H, cyclohexanone-H), 1.66--1.60(m, 4H, cyclohexanone-H); 19F NMR (471 MHz, DMSO-d6,
13
ppm) δ: -111.0 (s); C NMR (125 MHz, DMSO-d6, ppm) δ: 166.3, 165.4, 162.8, 153.5, 152.8,
130.1, 123.3, 115.6, 32.0, 31.3, 26.7, 26.5, 25.7, 24.9; Anal. Cald. for C16H18FN5O2S; C:52.88, H:
4.99, N: 19.27; Found: C: 52.86, H: 4.98, N: 19.29.
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Cyclopentanone
oxime (6e)
O-(2-((4-amino-5-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl)thio)
acetyl)
1
White solid, yield 58%, m.p. 139--140°C; IR (KBr, cm1) ν: 3545, 1720, 1655; H NM (500
MHz, DMSO-d6, ppm) δ: 8.02--7.57 (m, 4H, PhH), 6.24 (s, 2H, NH2), 4.23 (s, 2H, SCH2),
2.53--2.39 (m, 4H, cyclopentanone-H), 1.89--1.74 (m, 4H, cyclopentanone-H); 13C NMR (125
MHz, DMSO-d6, ppm) δ: 166.2, 165.4, 153.3, 153.2, 134.5, 129.4, 128.7, 125.6, 32.0, 30.2, 28.5,
26.3; Anal. Cald. for C15H16ClN5O2S; C:49.25, H: 4.41, N: 19.14; Found: C: 49.23, H: 4.40, N:
19.16.
Cyclohexanone O-(2-((4-amino-5-(4-chlorophenyl)-4H-1,2,4-triazol-3-yl)thio) acetyl) oxime
(6f)
1
White solid, yield 65%, m.p. 139--140°C; IR (KBr, cm1) ν: 3540, 1725, 1659; H NMR (500
MHz, DMSO-d6, ppm) δ: 8.01--7.56 (m, 4H, PhH), 6.24 (s, 2H, NH2), 4.24 (s, 2H, SCH2), 2.53
(t, J = 6.5 Hz, 2H, Cyclohexanone-H), 2.33 (t, J = 6.5 Hz, 2H, cyclohexanone-H), 1.76--1.67 (m,
2H, cyclohexanone-H), 1.64--1.56 (m, 4H, cyclohexanone-H); 13C NMR (125 MHz, DMSO-d6,
ppm) δ: 166.2, 165.4, 153.3, 153.1, 134.5, 129.3, 128.7, 125.6, 32.0, 31.3, 26.7, 26.5, 25.7, 24.9;
Anal. Cald. for C16H18ClN5O2S; C:50.59, H: 4.78, N: 18.44; Found: C: 50.56, H: 4.77, N: 18.47.
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Cyclopentanone O-(2-((4-amino-5-(4-(trifluoromethyl)phenyl)-4H-1,2,4-triazol-
3-yl)thio)acetyl) oxime (6g)
White solid, yield 71%, m.p. >250°C; IR (KBr, cm1) ν: 3541, 1732, 1645; 1H NMR (500 MHz,
DMSO-d6, ppm) δ: 8.20 (d, J = 8.0 Hz, 2H, PhH), 7.88 (d, J = 8.0 Hz, 2H, PhH), 6.32 (s, 2H,
NH2), 4.25 (s, 2H, SCH2), 2.53--2.40 (m, 4H, cyclopentanone-H), 1.92--1.77 (m, 4H,
19
13
cyclopentanone-H); F NMR (471 MHz, DMSO-d6, ppm)δ: -61.1 (s, 3F, CF3); C NMR (125
MHz, DMSO-d6, ppm) δ: 166.2, 165.5, 153.7, 153.1, 130.6, 129.8, 128.3, 125.5, 123.9, 32.0,
30.2, 28.5, 26.3; Anal. Cald. for C16H16F3N5O2S; C: 48.12, H: 4.04, N: 17.54; Found: C: 48.10,
H: 4.02, N: 17.57.
Cyclohexanone
O-(2-((4-amino-5-(4-(trifluoromethyl)phenyl)-4H-1,2,4-triazol-
3-yl)thio)acetyl) oxime (6h)
White solid, yield 66%, m.p. >250°C; IR (KBr, cm1) ν: 3541, 1732, 1645; 1H NMR (500 MHz,
DMSO-d6, ppm) δ: 8.21 (d, J = 8.0 Hz, 2H, PhH), 7.89 (d, J = 8.5 Hz, 2H, PhH), 6.28 (s, 2H,
NH2), 4.25 (s, 2H, SCH2), 2.52 (t, J = 6.5 Hz, 2H, cyclohexanone-H), 2.31 (t, J = 6.0 Hz, 2H,
cyclohexanone-H), 1.75--1.68 (m, 2H, cyclohexanone-H), 1.63--1.56 (m, 4H, cyclohexanone-H);
13C NMR (125 MHz, DMSO-d6, ppm) δ: 166.2, 165.5, 153.7, 153.1, 130.6, 129.9, 128.3, 125.5,
122.9, 32.8, 31.3, 26.7, 26.5, 25.7, 24.9; Anal. Cald. for C17H18F3N5O2S; C: 49.39, H: 4.39, N:
16.94; Found: C: 49.41, H: 4.38, N: 16.95.
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Cyclopentanone O-(2-((4-amino-5-(4-nitrophenyl)-4H-1,2,4-triazol-3-yl)thio) acetyl) oxime
(6i)
White solid, yield 69%, m.p. >250°C; IR (KBr, cm1) ν: 3350, 1692, 1611; 1H NMR (500 MHz,
DMSO-d6, ppm) δ: 8.42--8.30 (m, 4H, PhH), 6.35 (s, 2H, NH2), 4.27 (s, 2H, SCH2), 2.55--2.41
(m, 4H, cyclopentanone-H), 1.89--1.75 (m, 4H, cyclopentanone-H); 13C NMR (125 MHz,
DMSO-d6, ppm) δ: 166.2, 165.5, 154.3, 152.6, 147.8, 132.7, 128.6, 123.8, 32.1, 30.2, 28.5, 26.3;
Anal. Cald. for C15H16N6O4S; C: 47.87, H: 4.28, N: 22.33; Found: C: 47.89, H: 4.27, N: 22.35.
Cyclohexanone O-(2-((4-amino-5-(4-nitrophenyl)-4H-1,2,4-triazol-3-yl)thio) acetyl) oxime
(6j)
White solid, yield 60%, m.p. >250°C; IR (KBr, cm1) ν: 3350, 1630, 1610, 1520; 1H NMR (500
MHz, DMSO-d6, ppm) δ: 8.41--8.29 (m, 4H, PhH), 6.36 (s, 2H, NH2), 4.27 (s, 2H, SCH2), 2.53
(t, J = 6.0 Hz, 2H, cyclohexanone-H), 2.29 (t, J = 6.0 Hz, 2H, cyclohexanone-H), 1.67 (m, 2H,
cyclohexanone-H), 1.62--1.48 (m, 4H, cyclohexanone-H); 13C NMR (125 MHz, DMSO-d6, ppm)
δ: 170.2, 166.8, 154.8, 153.1, 148.3, 133.2, 129.0, 124.3, 32.6, 31.7, 26.9, 26.8, 25.9, 25.2; Anal.
Cald. for C16H18N6O4S; C: 49.22, H: 4.65, N: 21.53; Found: C: 49.23, H: 4.64, N: 21.55.
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Cyclopentanone O-(2-((4-amino-5-(4-methoxyphenyl)-4H-1,2,4-triazol-3-yl)thio) acetyl)
oxime (6k)
1
White solid, yield 76%, m.p. 150--151°C; IR (KBr, cm1) ν: 3330, 1690, 1610; H NMR (500
MHz, DMSO-d6, ppm) δ: 7.90 (d, J = 8.5 Hz, 2H, PhH), 7.06 (d, J = 8.5 Hz, 2H, PhH), 6.20 (s,
2H, NH2), 4.23 (s, 2H, SCH2), 3.80 (s, 3H, OCH3), 2.54--2.39 (m, 4H, cyclopentanone-H),
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1.91--1.76 (m, 4H, cyclopentanone-H); C NMR (125 MHz, DMSO-d6, ppm) δ: 166.3, 165.4,
160.3, 154.1, 152.3, 129.2, 119.1, 114.0, 55.3, 32.0, 30.1, 28.5, 26.2; Anal. Cald. for
C16H19N5O3S; C: 53.17, H: 5.30, N: 19.38; Found: C: 53.15, H: 5.32, N: 19.39.
Cyclohexanone O-(2-((4-amino-5-(4-methoxyphenyl)-4H-1,2,4-triazol-3-yl)thio) acetyl)
oxime (6l)
1
White solid, yield 70%, m.p. 158--159°C; IR (KBr, cm1) ν: 3330, 1690, 1610; H NMR (500
MHz, DMSO-d6, ppm) δ: 7.90 (d, J = 8.5 Hz, 2H, PhH), 7.06 (d, J = 8.5 Hz, 2H, PhH), 6.20 (s,
2H, NH2), 4.23 (s, 2H, SCH2), 3.81 (s, 3H, OCH3), 2.50 (t, J = 6.5 Hz, 2H, cyclohexanone-H),
2.31 (t, J = 6.5 Hz, 2H, cyclohexanone-H), 1.68 (m, 2H, cyclohexanone-H), 1.63--1.59 (m, 4H,
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cyclohexanone-H); C NMR (125 MHz, DMSO-d6, ppm) δ: 166.4, 165.4, 160.4, 154.2, 152.4,
129.3, 119.1, 114.1, 55.3, 32.0, 31.4, 26.7, 26.6, 25.7, 25.0; Anal. Cald. for C17H21N5O3S; C:
54.38, H: 5.64, N: 18.65; Found: C: 54.36, H: 5.63, N: 18.68.
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Conclusion
A
series
of
novel
cyclanone
O-(2-((4-amino-5-(substitutedphenyl)-4H-1,2,4-
triazol-3-yl)thio)acetyl)oxime derivatives were synthesized and evaluated for their antifungal and
antibacterial activities. Results indicated that most of the title compounds exhibited good
antibacterial activities and poor antifungal activities. Notably, compounds 6d, 6g, 6h, and 6j
showed better antibacterial activities against Xoo and Xcc than that of the commercial agent
thiodiazole-copper. Further study on the antibacterial activities is currently underway.
Acknowledgement
This work was supported by the National Nature Science Foundation of China (No. 21462012),
the Special Fund for Outstanding Scientific and Technological Candidates of Guizhou Province
(No. 201535) and the Higher School Project of Guizhou Provinc (No. 2014233).
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Scheme 1 Synthetic route of the title compounds
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