2-取代-4-氯-5-芳基-2H-1,2,3-三唑类化合物的合成及生物活性
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摘要
以芳醛、硝基甲烷及叠氮化钠为起始原料,经环化、氯化、烃化反应,以收率53%～94%合成了15个2-取代-4-氯-5-芳基-2H-1,2,3-三唑类化合物(Ⅳa～o),经核磁共振波谱、质谱和元素分析对目标化合物的结构进行确证。采用菌丝生长速率测定法,在质量浓度25mg/L下,目标化合物对小麦赤霉病菌、辣椒疫霉病菌、烟草赤星病菌、黄瓜灰霉病菌、水稻纹枯病菌及油菜菌核病菌6种作物病菌进行离体抑菌活性实验。初步的抑菌活性测试结果表明:化合物Ⅳd对小麦赤霉病菌、黄瓜灰霉病菌及油菜菌核病菌的抑制率分别为70.4%、74.1%和72.9%,化合物Ⅳk对黄瓜灰霉病菌及油菜菌核病菌的抑制率分别为87.0%及84.7%。Ⅳd对辣椒疫霉病菌的抑制率为61.4%,高于商品化品种苯醚甲环唑的42.5%。
Fifteen 2-substituted-4-chloro-5-aryl-2 H-1,2,3-triazole derivatives(Ⅳa～o) were synthesized using aryl aldehyde, nitromethane and sodium azide as starting materials by cyclization, chlorination and alkylation reactions with the yield of 53%～94%. The structures of title compounds were confirmed by 1 HNMR,13 CNMR, mass spectra and elemental analysis techniques. Their antifungal activities were evaluated in vitro against six phytopathogenic fungi(Gibberella zeae, Phytophythora capsici, Alternaria alternate, Botrytis cinerea, Rhizoctonia solani and Sclerotonia sclerotiorum) using mycelium growth rate method at 25 mg/L.The results of bioassay showed that some compounds exhibited excellent fungicidal activities. For example,the inhibition rates of compound Ⅳd against Gibberella zeae, Botrytis cinerea and Sclerotonia sclerotiorum were 70.4%, 74.1% and 72.9%, respectively. The inhibition rates of compound Ⅳk against Botrytis cinerea and Sclerotonia sclerotiorum were 87.0% and 84.7%, respectively. The inhibition rate of Ⅳd against Phytophythora capsici was 61.4%, which was higher than that of commercial difenoconazole 42.5%.
Fifteen 2-substituted-4-chloro-5-aryl-2 H-1,2,3-triazole derivatives(Ⅳa～o) were synthesized using aryl aldehyde, nitromethane and sodium azide as starting materials by cyclization, chlorination and alkylation reactions with the yield of 53%～94%. The structures of title compounds were confirmed by 1 HNMR,13 CNMR, mass spectra and elemental analysis techniques. Their antifungal activities were evaluated in vitro against six phytopathogenic fungi(Gibberella zeae, Phytophythora capsici, Alternaria alternate, Botrytis cinerea, Rhizoctonia solani and Sclerotonia sclerotiorum) using mycelium growth rate method at 25 mg/L.The results of bioassay showed that some compounds exhibited excellent fungicidal activities. For example,the inhibition rates of compound Ⅳd against Gibberella zeae, Botrytis cinerea and Sclerotonia sclerotiorum were 70.4%, 74.1% and 72.9%, respectively. The inhibition rates of compound Ⅳk against Botrytis cinerea and Sclerotonia sclerotiorum were 87.0% and 84.7%, respectively. The inhibition rate of Ⅳd against Phytophythora capsici was 61.4%, which was higher than that of commercial difenoconazole 42.5%.
引文
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[21]Santo R D,Tafi A,Costi R,et al.Antifungal agents.11.N-substituted derivatives of 1-[(aryl)(4-aryl-1H-pyrrol-3-yl)methyl]-1H-imidazole:?Synthesis,anti-candida activity and QSAR Studies[J].Journal of Medicinal Chemistry,2005,48(16):5140-5153.
[22]Mistry S N,J?rg M,Lim H,et al.4-Phenylpyridin-2-one derivatives:A novel class of positive allosteric modulator of the M1 muscarinic acetylcholine receptor[J].Journal of Medicinal Chemistry,2016,59(1):388-409.
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[24]Liu Yang(刘阳),Liu Ming(刘明),Chen Minggui(陈明桂),et al.Design,synthesis and bioactivities of novel strobilurin derivatives containing 1,3,4-oxadiazole moity[J].Chinese Journal Organic Chemistry(有机化学),2017,37(2):403-410.
[25]Neelakandeswari N,Sangami G,Emayavaramban P,et al.Mesoporous nickel hydroxyapatite nanocomposite for microwave-assisted Henry reaction[J].Tetrahedron Letters,2012,53(24):2980-2984.
[26]Zefirov N S,Chapovskaya N K,Kolesnikov V V.Synthesis of 1,2,3-triazoles by reaction of azide ion with a,b-unsaturated nitro compounds and nitriles[J].Journal of the Chemical Society D:Chemical Communications,1971,17:1001-1002.
[2]Wang Jingmei(王景梅),Li Lingjun(李凌君),Zhang Guisheng(张贵生).Progress in syntheses of 1,2,3-triazoles[J].Chinese Journal Organic Chemistry(有机化学),2009,29(1):13-19.
[3]Bai S P,Li S H,Xu J B,et al.Synthesis and structure-activity relationship studies of conformationally flexible tetrahydroisoquinolinyl triazole carboxamide and triazole substituted benzamide analogues asσ2 receptor ligands[J].Journal of Medicinal Chemistry,2014,57(10):4239-4251.
[4]Katarzyna K,Krystian P,Marcelina M K,et al.Synthesis,antibacterial,and anticancer evaluation of novel spiramycin-Like conjugates containing C(5)triazole arm[J].Journal of Medicinal Chemistry,2016,59(17):7963-7973.
[5]Ma Y M,Liu R H,Gong X Y,et al.Synthesis and herbicidal activity of N,N-diethyl-3-(arylselenonyl)-1H-1,2,4-triazole-1-carboxamide[J].Journal of Agricultural and Food Chemistry,2006,54(20):7724-7728.
[6]Cao X F,Li F,Hu M,et al.Chiralγ-aryl-1H-1,2,4-triazole derivatives as highly potential antifungal agents:Design,synthesis,structure,and in vitro fungicidal activities[J].Journal of Agricultural and Food Chemistry,2008,56(23):11367-11375.
[7]Li W To,Yan L,Zhou H X,et al.A general approach toward electron deficient triazole units to construct conjugated polymers for solar cells[J].Chemistry of Materials,2015,27(18):6470-6476.
[8]Dontsova D,Fettkenhauer C,Papaefthimiou V,et al.1,2,4-Triazolebased approach to noble-metal-free visible-light driven water splitting over carbon nitrides[J].Chemistry of Materials,2016,28(3):772-778.
[9]Rohrig U F,Majjigapu S R,Grosdidier A,et al.Rational design of4-aryl-1,2,3-triazoles for indoleamine 2,3-dioxygenase 1 inhibition[J].Journal of Medicinal Chemistry,2012,55(11):5270-5290.
[10]Lee S M,Yoon K B,Lee H J,et al.The discovery of 2,5-isomers of triazole-pyrrolopyrimidine as selective Janus kinase 2(JAK2)inhibitors versus JAK1 and JAK3[J].Bioorganic&Medicinal Chemistry,2016,24(21):5036-5046.
[11]Pokrovskaya V,Belakhov V,Hainrichson M,et al.Design,synthesis and evaluation of novel fluoroquinolone-aminoglycoside hybrid antibiotics[J].Journal of Medicinal Chemistry,2009,52(8):2243-2254.
[12]Wang B L,Shi Y X,Ma Y,et al.Synthesis and biological activity of some novel trifluoromethyl-substituted 1,2,4-triazole and bis(1,2,4-triazole)mannich bases containing piperazine rings[J].Journal of Agricultural and Food Chemistry,2010,58(9):5515-5522.
[13]Wang Z J,Gao Y,Zhao W G,et al.Design,synthesis and fungicidal evaluation of a series of novel 5-methyl-1H-1,2,3-trizole-4-carboxyl amide and ester analogues[J].European Journal of Medicinal Chemistry,2014,86:87-94.
[14]Liu N,Dong F S,Xu J,et al.Stereoselective determination of tebuconazole in water and zebrafish by supercritical fluid chromatography tandem mass spectrometry[J].Journal of Agricultural and Food Chemistry,2015,63(28):6297-6303.
[15]Gestel J V,Heeres J,Janssen M,et al.Synthesis and screening of a new group of fungicides:1-(2-phenyl-1,3-dioxolan-2-ylmethyl)-1,2,4-triazoles[J].Pesticide Science,1980,11(1):95-99.
[16]Li Zhengming(李正名),Dong Liwen(董丽雯),Li Guowei(李国炜),et al.Stereochemistry of new systemic fungicides triadimenol and triadimefonII[J].Chinese Journal Organic Chemistry(有机化学),1985,5(2):188-192.
[17]Li Yuanxiang(李元祥),Lei Sufang(雷素芳),Chen Dizhao(陈迪钊),et al.Preparation of benzene ring containing halogenated triazole compounds as fungicides:CN105859645[P].2018-03-30.
[18]Hu Q Q,Liu Y,Deng X C,et al.Aluminium(Ⅲ)chloride-catalyzed three-component condensation of aromatic aldehydes,nitroalkanes and sodium azide for the synthesis of 4-aryl-NH-1,2,3-triazoles[J].Advanced Synthesis&Catalysis,2016,358(10):1689-1693.
[19]Zefirov N S,Chapovskaya N K.New method for synthesizing 1,2,3-triazoles[J].Vestnik Moskovskogo Universiteta,Seriya 2:Khimiya,1969,24(5):113-114.
[20]Zhang W S,Kuang C X,Yang Q.Palladium-catalyzed one-pot synthesis of 4-aryl-1H-1,2,3-triazoles from anti-3-aryl-2,3-dibromopropanoic acids and sodium azide[J].Synthesis,2010,2:283-287.
[21]Santo R D,Tafi A,Costi R,et al.Antifungal agents.11.N-substituted derivatives of 1-[(aryl)(4-aryl-1H-pyrrol-3-yl)methyl]-1H-imidazole:?Synthesis,anti-candida activity and QSAR Studies[J].Journal of Medicinal Chemistry,2005,48(16):5140-5153.
[22]Mistry S N,J?rg M,Lim H,et al.4-Phenylpyridin-2-one derivatives:A novel class of positive allosteric modulator of the M1 muscarinic acetylcholine receptor[J].Journal of Medicinal Chemistry,2016,59(1):388-409.
[23]Agricultural Industry Standard of the People's Republic of China(中华人民共和国农业行业标准).NY/T 1156.6-2006.Pesticides guidelines for laboratory bioactivity tests,Part 6:Determining combined action of fungicide mixtures(混配的联合作用测定)[S].Ministry of Agriculture,2006.
[24]Liu Yang(刘阳),Liu Ming(刘明),Chen Minggui(陈明桂),et al.Design,synthesis and bioactivities of novel strobilurin derivatives containing 1,3,4-oxadiazole moity[J].Chinese Journal Organic Chemistry(有机化学),2017,37(2):403-410.
[25]Neelakandeswari N,Sangami G,Emayavaramban P,et al.Mesoporous nickel hydroxyapatite nanocomposite for microwave-assisted Henry reaction[J].Tetrahedron Letters,2012,53(24):2980-2984.
[26]Zefirov N S,Chapovskaya N K,Kolesnikov V V.Synthesis of 1,2,3-triazoles by reaction of azide ion with a,b-unsaturated nitro compounds and nitriles[J].Journal of the Chemical Society D:Chemical Communications,1971,17:1001-1002.