CN113563281A - 一类含1,3,4-噻二唑硫醚结构的苯甲酮类化合物及其应用 - Google Patents
一类含1,3,4-噻二唑硫醚结构的苯甲酮类化合物及其应用 Download PDFInfo
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- CN113563281A CN113563281A CN202110761840.XA CN202110761840A CN113563281A CN 113563281 A CN113563281 A CN 113563281A CN 202110761840 A CN202110761840 A CN 202110761840A CN 113563281 A CN113563281 A CN 113563281A
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- -1 Benzophenone compound Chemical class 0.000 title claims abstract description 21
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- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 150000008366 benzophenones Chemical class 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
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- 238000006243 chemical reaction Methods 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 208000031888 Mycoses Diseases 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052736 halogen Inorganic materials 0.000 claims description 2
- 150000002367 halogens Chemical class 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 68
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- ITATYELQCJRCCK-UHFFFAOYSA-N Mandelic Acid, Methyl Ester Chemical compound COC(=O)C(O)C1=CC=CC=C1 ITATYELQCJRCCK-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/82—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with three ring hetero atoms
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
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- Environmental Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一类含1,3,4‑噻二唑硫醚结构的苯甲酮类化合物，其特征在于：其结构式如下：
Description
技术领域
本发明涉及药物化学领域，特别涉及一类含1,3,4-噻二唑硫醚的苯基甲酮类化合物的制备方法及在抗植物病原真菌方面的应用。
背景技术
扁桃酸(Mandelic acid,MA)，又名苦杏仁酸和苯乙醇酸。在有机合成和药物生产中有着广泛的用途，是尿路杀菌剂扁桃酸乌洛托品、末稍血管扩张剂“环扁桃酯”、头孢类抗生素(头孢羟唑、羟苄唑、皮膜林)和镇痉挛药物“扁桃酸苄酯”的重要中间体。
而扁桃酸类衍生物在农药上的应用则是在2001年先正达公司报道了新型卵菌纲病害杀菌剂“双炔酰菌胺”(mandipropamid)之后。“双炔酰菌胺”是第一个商品化的扁桃酸类衍生物，其具有特殊作用机理，既可有效地抑制孢子的萌发，又能抑制菌丝体的生长与孢子的形成；不仅活性高，而且具有很好的耐雨水冲刷性能；具有较长的持效期；使用剂量通常为100～150g a.i./hm2或10～15ga.i./100mL，对作物、人、野生动物和环境安全。
本课题组在CN108997253A中合成了一类含“1,3,4-噁二唑硫醚”的扁桃酸衍生物，其结构式如下：
在该结构中，R1为H、甲基、氟或氯，R2为含C1-3直链烷基、含C1-4支链烷基、丙烯基、丙炔基或单取代苄基。
在本课题组前期研究的基础上，将
扁桃酸结构上的“羟基”氧化成“酮”结构；将“1,3,4-噁二唑”替换成“1,3,4-噻二唑”。期望能够发现结构新颖的一类含1,3,4-噻二唑硫醚结构的苯甲酮类抗植物病原真菌活性的化合物。
发明内容
本发明要解决的技术问题是：提供一种具有抗植物病原真菌活性的新型含1,3,4-噻二唑硫醚结构的苯甲酮类化合物，用以防治由植物病原真菌引起的植物真菌病害。
本发明的技术方案：一类含1,3,4-噻二唑硫醚的苯基甲酮类化合物，其结构式如下：
其中R为烷基、苄基或取代苄基。
优选的，R为甲基、乙基或丙基。
所述的取代苄基的取代基为邻、间或对位单取代的甲基、甲氧基、三氟甲基、三氟甲氧基或卤素。
反应式如下：
所述的一类含1,3,4-噻二唑硫醚结构的苯甲酮类化合物在植物病原真菌引起的植物真菌病害上的应用。
本发明的有益效果：本发明在含“1,3,4-噁二唑硫醚”的扁桃酸衍生物的结构基础上；用“1,3,4-噻二唑硫醚”取代了“1,3,4-噁二唑硫醚”，将化合物结构中的“羟基”替换成了“酮”，合成了系列含1,3,4-噻二唑硫醚结构的苯甲酮类化合物，通过化合物的抗植物病原菌活性测试发现，该类化合物对多种植物病原菌表现出良好的抑菌活性。与课题组前期工作中报道的高活性化合物相比，该类化合物引入结构新颖的“酮”和“1,3,4-噻二唑”结构后，部分化合物对多种植物病原菌表现出良好的抑制活性，具有明显的广谱性，为新农药的研发和创制提供重要的科学基础。
具体实施方式
含1,3,4-噻二唑硫醚结构的苯甲酮类化合物的合成路线
以扁桃酸为起始原料，通过酯化、肼解、闭环、硫醚化合成目标化合物E。
中间体的制备
2-羟基-2-苯基乙酸甲酯(B)的制备
在100mL圆底烧瓶中加入扁桃酸(20.00g)，甲醇(500mL)，在5min内加入浓硫酸(1.29g)，加热回流，TLC检测反应结束后，蒸除溶剂，用乙酸乙酯萃取，加入饱和碳酸氢钠溶液洗涤2～3次后，用无水硫酸钠干燥，蒸除溶剂后粗产品经柱层析纯化得化合物B，白色固体，产率94％，熔点51-52℃。1H NMR(500MHz,CDCl3)δ:7.42(d,J＝10.0Hz,2H,benzene H),7.37(t,J＝10.0Hz,2H,benzene H),7.33(t,J＝10.0Hz,1H,benzene H),5.18(d,J＝5.0Hz,1H,CH(OH)),3.76(s,3H,CH3),3.51(d,J＝5.0Hz,OH)；13C NMR(126MHz,CDCl3)δ:174.28,138.32,128.76,128.65,126.72,72.99,53.21.
2-羟基-2-苯基乙酰肼(C)的制备
在100mL圆底烧瓶中依次加入化合物B(20.00g)，水合肼(200mL)，室温搅拌2h，TLC检测反应，反应结束后，抽滤，滤饼重结晶得化合物C，白色固体，产率90％，熔点151-152℃。1H NMR(500MHz,DMSO-d6)δ:9.19(s,1H,NH),7.41(d,J＝10.0Hz,2H,benzene H),7.31(t,J＝10.0Hz,2H,benzene H),7.25(t,J＝10.0Hz,1H,benzene H),5.99(d,J＝5.0Hz,1H,CH(OH)),4.93(d,J＝5.0Hz,1H,OH),4.22(d,J＝5.0Hz,2H,NH2)；13C NMR(126MHz,DMSO-d6)δ:171.12,141.36,127.95,127.42,126.54,72.84.
2-苯甲酮基-1,3,4-噻二唑-5-硫醇(D)的制备
在25mL圆底烧瓶中依次加入氢氧化钾(1.01g)，乙醇(50mL)，C(2.00g)和二硫化碳(1.37g)，搅拌后的大量固体，抽滤，滤饼用少量乙醇洗涤得淡黄色固体。将固体分批加入装有浓硫酸(50mL)的烧瓶中，常温反应5h后，将反应液倒入冰水中，产生大量黄色固体，抽滤，滤饼经柱层析纯化得化合物D，黄色固体，产率70％，熔点194-195℃。1H NMR(500MHz,CDCl3)δ:11.53(s,1H,SH),8.28(d,J＝10.0Hz,2H,benzene H),7.69(t,J＝10.0Hz,1H,benzeneH),7.54(t,J＝10.0Hz,2H,benzene H)；13C NMR(126MHz,CDCl3)δ:191.30,181.18,160.81,134.88,133.71,130.74,128.93.
目标化合物E1-E30的合成(以化合物E7的合成为例)
在25mL圆底烧瓶中依次加入化合物D(200.00mg)，乙腈(20ml)，三乙胺(136.58mg)和异溴丁烷(147.94mg)，常温反应2h后结束反应，蒸除溶剂，粗产物经柱层析纯化得目标化合物E7，淡黄色液体，产率93％。
目标化合物E1
黄色固体，产率95％，熔点59-60℃.1H NMR(400MHz,CDCl3)δ:8.50(d,J＝8.0Hz,2H,benzene H),7.67(t,J＝8.0Hz,1H,benzene H),7.53(t,J＝8.0Hz,2H,benzene H),2.87(s,3H,CH3)；13C NMR(101MHz,CDCl3)δ:182.97,173.53,169.13,134.53,134.51,131.28,128.74,16.63.
目标化合物E2
黄色固体，产率89％，熔点32-33℃.1H NMR(400MHz,CDCl3)δ:8.50(d,J＝8.0Hz,2H,benzene H),7.66(t,J＝8.0Hz,1H,benzene H),7.52(t,J＝8.0Hz,2H,benzene H),3.43(q,J＝8.0Hz,2H,CH2),1.53(t,J＝8.0Hz,3H,CH3)；13C NMR(101MHz,CDCl3)δ:182.94,172.74,169.02,134.57,134.45,131.25,128.71,28.71,14.57.
目标化合物E3
黄色液体，产率90％。1H NMR(400MHz,CDCl3)δ:8.50(d,J＝8.0Hz,2H,benzene H),7.66(t,J＝8.0Hz,1H,benzene H),7.53(t,J＝8.0Hz,2H,benzene H),3.40(t,J＝8.0Hz,2H,CH 2CH2CH3),1.95–1.85(m,2H,CH2 CH 2CH3),1.09(t,J＝8.0Hz,3H,CH2CH2 CH 3)；13C NMR(101MHz,CDCl3)δ:182.97,173.07,168.96,134.59,134.46,131.27,128.72,36.18,22.64,13.46.
目标化合物E4
橙红色固体，产率88％，熔点32-33℃。1H NMR(400MHz,CDCl3)δ:8.51(d,J＝8.0Hz,2H,benzene H),7.66(t,J＝8.0Hz,1H,benzene H),7.53(t,J＝8.0Hz,2H,benzene H),3.42(t,J＝8.0Hz,2H,CH 2CH2CH2CH3),1.88–1.81(m,2H,CH2 CH 2CH2CH3),1.56–1.46(m,2H,CH2CH2 CH 2CH3),0.97(t,J＝8.0Hz,3H,CH2CH2CH2 CH 3)；13C NMR(101MHz,CDCl3)δ:182.97,173.11,168.96,134.59,134.45,131.27,128.72,34.05,31.13,22.06,13.68；HRMS(ESI):m/z calcd for C13H14N2OS2[M+H]+279.06203,found 279.06174.
目标化合物E5
橙红色液体，产率91％。1H NMR(400MHz,CDCl3)δ:8.51(d,J＝8.0Hz,2H,benzeneH),7.67(t,J＝8.0Hz,1H,benzene H),7.53(t,J＝8.0Hz,2H,benzene H),3.42(t,J＝8.0Hz,2H,CH 2CH2CH2CH2CH3),1.90–1.83(m,2H,CH2 CH 2CH2CH2CH3),1.50–1.42(m,2H,CH2CH2 CH 2CH2CH3),1.41–1.33(m,2H,CH2CH2CH2 CH 2CH3),0.92(t,J＝8.0Hz,3H,CH2CH2CH2CH2 CH 3)；13C NMR(101MHz,CDCl3)δ:183.01,173.15,168.96,134.61,134.47,131.28,128.74,34.34,31.02,28.84,22.31,14.07；HRMS(ESI):m/z calcd for C14H16N2OS2[M+H]+293.07768,found 293.07712.
目标化合物E6
黄色固体，产率76％，熔点37-39℃.1H NMR(400MHz,CDCl3)δ:8.51(d,J＝8.0Hz,2H,benzene H),7.66(t,J＝8.0Hz,1H,benzene H),7.53(t,J＝8.0Hz,2H,benzene H),3.41(t,J＝8.0Hz,2H,SCH2),3.28–3.25(m,2H,CH2 CH 2(CH2)8CH3),1.89–1.82(m,2H,(CH2)2 CH 2(CH2)7CH3),1.81–1.74(m,2H,(CH2)3 CH 2(CH2)6CH3),1.51–1.33(m,8H,(CH2)3CH2(CH 2)4CH2CH2CH3),0.89–0.86(m,7H,(CH2)8 CH 2 CH 2 CH 3)；13C NMR(101MHz,CDCl3)δ:182.99,173.17,168.94,165.38,134.59,134.46,131.28,128.73,34.41(d,J＝32.0Hz),32.03,29.84,29.71(d,J＝12.0Hz),29.60(d,J＝4.0Hz),29.39(d,J＝56.0Hz),29.16(d,J＝32.0Hz),28.88(d,J＝20.0Hz),22.83,14.27
目标化合物E7
黄色液体，产率93％。1H NMR(400MHz,CDCl3)δ:8.50(d,J＝8.0Hz,2H,benzene H),7.65(t,J＝8.0Hz,1H,benzene H),7.52(t,J＝8.0Hz,2H.benzene H),3.33(d,J＝8.0Hz,2H,CH2),2.14(m,1H,CH),1.09(d,J＝8.0Hz,6H,CH3)；13C NMR(101MHz,CDCl3)δ:182.95,173.32,168.91,134.60,134.43,131.25,128.70,42.69,28.55,21.95.
目标化合物E8
黄色液体，产率90％。1H NMR(400MHz,CDCl3)δ:8.51(d,J＝8.0Hz,2H,benzene H),7.67(t,J＝8.0Hz,1H,benzene H),7.53(t,J＝8.0Hz,2H,benzene H),3.43(t,J＝8.0Hz,2H,SCH 2),1.82–1.70(m,3H,CH2 CH 2 CH(CH3)2),0.98(d,J＝4.0Hz,6H,CH2CH2CH(CH 3)2)；13CNMR(101MHz,CDCl3)δ:183.01,173.10,168.97,134.61,134.47,131.28,128.74,37.80,32.52,27.71,22.31.
目标化合物E9
橙黄色固体，产率88％，熔点56-58℃。1H NMR(400MHz,DMSO-d6)δ:8.32(d,J＝8.0Hz,2H,benzene H),7.77(t,J＝8.0Hz,1H,benzene H),7.63(t,J＝8.0Hz,2H,benzeneH),7.54(d,J＝8.0Hz,2H,benzene H),7.38(t,J＝8.0Hz,2H,benzene H),7.32(t,J＝8.0Hz,1H,benzene H),4.71(s,2H,CH2)；13C NMR(101MHz,DMSO-d6)δ:182.71,171.95,168.74,135.84,134.45,134.26,130.66,129.22,128.73,128.69,127.89,37.52.
目标化合物E10
橙黄色固体，产率90％，熔点45-47℃。1H NMR(400MHz,DMSO-d6)δ:8.34(d,J＝8.0Hz,2H,benzene H),7.78(t,J＝8.0Hz,1H,benzene H),7.63(t,J＝8.0Hz,2H,benzeneH),7.48(d,J＝8.0Hz,1H,benzene H),7.25(d,J＝8.0Hz,2H,benzene H),7.23–7.18(m,1H,benzene H),4.73(s,2H,CH2),2.42(s,3H,CH3)；13C NMR(101MHz,DMSO-d6)δ:182.75,171.74,168.81,137.06,134.50,134.28,133.18,130.69,130.59,130.20,128.77,128.35,126.26,36.13,18.86.
目标化合物E11
黄色固体，产率89％，熔点58-59℃。1H NMR(400MHz,CDCl3)δ:8.50(d,J＝8.0Hz,2H,benzene H),7.67(t,J＝8.0Hz,1H,benzene H),7.54(t,J＝8.0Hz,2H,benzene H),7.27–7.22(m,3H,benzene H),7.13(d,J＝8.0Hz,1H,benzene H),4.63(s,2H,CH2),2.36(s,3H,CH3)；13C NMR(101MHz,CDCl3)δ:183.03,172.14,169.26,138.82,135.12,134.59,134.52,131.28,130.03,129.12,128.91,128.77,126.43,38.28,21.51.
目标化合物E12
黄色固体，产率86％，熔点71-72℃。1H NMR(400MHz,DMSO-d6)δ:8.32(d,J＝8.0Hz,2H,benzene H),7.77(t,J＝8.0Hz,1H,benzene H),7.62(t,J＝8.0Hz,2H,benzene H),7.41(d,J＝8.0Hz,2H,benzene H),7.18(d,J＝8.0Hz,2H,benzene H),4.66(s,2H,CH2),2.29(s,3H,CH3)；13C NMR(101MHz,DMSO-d6)δ:182.70,172.08,168.67,137.23,134.46,134.27,132.64,130.67,129.25,129.16,128.74,37.40,20.74.
目标化合物E13
白色固体，产率87％，熔点85-86℃。1H NMR(400MHz,CDCl3)δ:8.50(d,J＝8.0Hz,2H,benzene H),7.66(t,J＝8.0Hz,1H,benzene H),7.55–7.47(m,3H,benzene H),7.30(t,J＝8.0Hz,1H,benzene H),6.94–6.90(m,2H,benzene H),4.69(s,2H,CH2),3.89(s,3H,CH3)；13C NMR(101MHz,CDCl3)δ:183.07,173.10,169.05,157.71,134.64,134.44,131.25,131.05,129.83,128.73,123.79,120.71,110.75,55.66,33.36.
目标化合物E14
白色固体，产率90％，熔点71-72℃。1H NMR(400MHz,CDCl3)δ:8.50(d,J＝8.0Hz,2H,benzene H),7.67(t,J＝8.0Hz,1H,benzene H),7.54(t,J＝8.0Hz,2H,benzene H),7.27(t,J＝8.0Hz,1H,benzene H),7.05(d,J＝8.0Hz,1H,benzene H),7.00(s,1H,benzeneH),6.85(d,J＝8.0Hz,1H,benzene H),4.63(s,2H,CH2),3.81(s,3H,CH3)；13C NMR(101MHz,CDCl3)δ:182.99,171.96,169.30,159.99,136.72,134.54,134.52,131.26,130.04,128.76,121.65,114.83,113.83,55.42,38.22.
目标化合物E15
白色固体，产率91％，熔点89-90℃。1H NMR(400MHz,CDCl3)δ:8.49(d,J＝8.0Hz,2H,benzene H),7.67(t,J＝8.0Hz,1H,benzene H),7.54(t,J＝8.0Hz,2H,benzene H),7.39(d,J＝8.0Hz,2H,benzene H),6.87(d,J＝8.0Hz,2H,benzene H),4.61(s,2H,CH2),3.80(s,3H,CH3)；13C NMR(101MHz,CDCl3)δ:183.01,172.15,169.19,159.56,134.57,134.50,131.26,130.65,128.75,127.12,114.35,55.43,37.91.
目标化合物E16
黄色固体，产率90％，熔点64-66℃。1H NMR(400MHz,DMSO-d6)δ:8.34(d,J＝8.0Hz,2H,benzene H),7.86(d,J＝8.0Hz,1H,benzene H),7.82–7.76(m,2H,benzene H),7.72(t,J＝8.0Hz,1H,benzene H),7.63(t,J＝8.0Hz,2H,benzene H),7.58(t,J＝8.0Hz,1H,benzene H),4.90(s,2H,CH2)；13C NMR(101MHz,DMSO-d6)δ:182.76,170.74,169.24,134.53,134.23,133.77(d,J＝4.0Hz),133.18,132.05,130.70,128.83,128.76,127.53,127.23,126.48(q,J＝20.0Hz),125.64,122.92,34.20(d,J＝8.0Hz)；19F NMR(376MHz,DMSO-d6)δ:-58.09.
目标化合物E17
黄色固体，产率90％，熔点74-76℃。1H NMR(400MHz,CDCl3)δ:8.49(d,J＝8.0Hz,2H,benzene H),7.73(s,1H,benzene H),7.71–7.65(m,2H,benzene H),7.58–7.52(m,3H,benzene H),7.48(t,J＝8.0Hz,1H,benzene H),4.72(s,2H,CH2)；13C NMR(101MHz,CDCl3)δ:182.95,170.92,169.69,136.79,134.61,131.53,134.49,132.81(d,J＝4.0Hz),131.26,131.20,129.47,128.81,126.08(q,J＝16.0Hz),125.10(q,J＝16.0Hz),37.25；19F NMR(376MHz,CDCl3)δ-62.65.
目标化合物E18
橙黄色固体，产率89％，熔点117-118℃。1H NMR(400MHz,DMSO-d6)δ:8.32(d,J＝8.0Hz,2H,benzene H),7.79–7.73(m,5H,benzene H),7.62(t,J＝8.0Hz,2H,benzene H),4.81(s,2H,CH2)；13C NMR(101MHz,DMSO-d6)δ:182.68,171.35,169.03,141.29(d,J＝4.0Hz),134.46,134.22,130.65,130.00,128.72,128.40,128.09,125.49(q,J＝16.0Hz),36.57；19F NMR(471MHz,CDCl3)δ:-62.50.
目标化合物E19
黄色固体，产率92％，熔点66-67℃。1H NMR(400MHz,CDCl3)δ:8.50(d,J＝8.0Hz,2H,benzene H),7.70–7.64(m,2H,benzene H),7.54(t,J＝8.0Hz,2H,benzene H),7.36(t,J＝8.0Hz,1H,benzene H),7.32–7.24(m,2H,benzene H),4.74(s,2H,CH2)；13C NMR(101MHz,CDCl3)δ:182.99,171.49,169.59,147.86(d,J＝4.0Hz),134.57,134.55,131.86,131.26,129.91,128.79,128.22,127.06,121.95,120.39(d,J＝2.0Hz),120.37,119.38,32.08；19F NMR(376MHz,CDCl3)δ:-56.88.
目标化合物E20
黄色固体，产率93％，熔点64-66℃。1H NMR(400MHz,CDCl3)δ:8.49(d,J＝8.0Hz,2H,benzene H),7.68(t,J＝8.0Hz,1H,benzene H),7.54(t,J＝8.0Hz,2H,benzene H),7.43(d,J＝8.0Hz,1H,benzene H),7.38(t,J＝8.0Hz,1H,benzene H),7.34(s,1H,benzeneH),7.16(d,J＝8.0Hz,1H,benzene H),4.67(s,2H,CH2)；13C NMR(101MHz,CDCl3)δ:182.95,171.02,169.63,149.53(d,J＝8.0Hz),137.97,134.60,134.48,131.26,130.34,128.80,127.78,121.90,121.80,120.68,119.24,37.19；19F NMR(376MHz,CDCl3)δ:-57.75
目标化合物E21
黄色固体，产率87％，熔点90-91℃。1H NMR(400MHz,CDCl3)δ:8.49(d,J＝8.0Hz,2H,benzene H),7.68(t,J＝8.0Hz,1H,benzene H),7.57–7.50(m,4H,benzene H),7.19(d,J＝8.0Hz,2H,benzene H),4.66(s,2H,CH2)；13C NMR(101MHz,CDCl3)δ:182.96,171.23,169.60,149.03(d,J＝8.0Hz),134.60,134.49,134.42,131.26,130.89,128.80,121.41,119.26(d,J＝12.0Hz),37.00；19F NMR(376MHz,CDCl3)δ:-57.83.
目标化合物E22
橙黄色固体，产率91％，熔点59-60℃。1H NMR(400MHz,DMSO-d6)δ:8.33(d,J＝8.0Hz,2H,benzene H),7.77(t,J＝8.0Hz,1H,benzene H),7.63(t,J＝8.0Hz,3H,benzeneH),7.43–7.37(m,1H,benzene H),7.29–7.24(m,1H,benzene H),7.21(t,J＝8.0Hz,1H,benzene H),4.75(s,2H,CH2)；13C NMR(101MHz,DMSO-d6)δ:182.74,171.20,169.08,161.79,159.34,134.51,134.25,131.62(d,J＝12.0Hz),130.70,130.36(d,J＝48.0Hz),128.76,124.72(d,J＝12.0Hz),122.94(d,J＝56.0Hz),115.64(d,J＝80.0Hz),31.16(d,J＝12.0Hz)；19F NMR(471MHz,CDCl3)δ:-116.31.
目标化合物E23
黄绿色固体，产率89％，熔点66-67℃。1H NMR(400MHz,CDCl3)δ:8.49(d,J＝8.0Hz,2H,benzene H),7.67(t,J＝8.0Hz,1H,benzene H),7.54(t,J＝8.0Hz,2H,benzene H),7.34–7.29(m,1H,benzene H),7.24(s,1H,benzene H),7.20(d,J＝8.0Hz,1H,benzene H),7.00(t,J＝8.0Hz,1H,benzene H),4.64(s,2H,CH2)；13C NMR(101MHz,CDCl3)δ:182.93,171.28,169.53,164.16,161.70,137.98(d,J＝28.0Hz),134.56,134.47,131.24,130.48(d,J＝32.0Hz),128.77,125.04(d,J＝12.0Hz),116.30(d,J＝88.0Hz),115.25(d,J＝84.0Hz),37.34(d,J＝8.0Hz)；19F NMR(376MHz,CDCl3)δ:-112.17.
目标化合物E24
黄色固体，产率90％，熔点96-97℃。1H NMR(400MHz,DMSO-d6)δ:8.31(d,J＝8.0Hz,2H,benzene H),7.76(t,J＝8.0Hz,1H,benzene H),7.64–7.55(m,4H,benzene H),7.20(t,J＝8.0Hz,2H,benzene H),4.70(s,2H,CH2)；13C NMR(101MHz,DMSO-d6)δ:182.70,171.71,168.82,162.88,160.45,134.46,134.25,132.26(d,J＝12.0Hz),131.33(d,J＝32.0Hz),130.66,128.73,115.49(d,J＝88.0Hz),36.61；19F NMR(376MHz,CDCl3)δ:-114.24.
目标化合物E25
橙黄色固体，产率87％，熔点103-104℃。1H NMR(400MHz,DMSO-d6)δ:8.32(d,J＝8.0Hz,2H,benzene H),7.77(t,J＝8.0Hz,1H,benzene H),7.71–7.68(m,1H,benzene H),7.62(t,J＝8.0Hz,2H,benzene H),7.54–7.51(m,1H,benzene H),7.40–7.34(m,2H,benzene H),4.80(s,2H,CH2)；13C NMR(101MHz,DMSO-d6)δ:182.73,171.07,169.09,134.48,134.23,133.50,133.28,131.72,130.67,130.05,129.71,128.74,127.56,35.52.
目标化合物E26
黄绿色固体，产率85％，熔点77-78℃.1H NMR(400MHz,CDCl3)δ:8.49(d,J＝8.0Hz,2H,benzene H),7.68(t,J＝8.0Hz,1H,benzene H),7.54(t,J＝8.0Hz,2H,benzene H),7.48(s,1H,benzene H),7.41–7.34(m,1H,benzene H),7.31–7.29(m,2H,benzene H),4.63(s,2H,CH2)；13C NMR(101MHz,CDCl3)δ:182.97,171.21,169.58,137.61,134.76,134.58,134.51,131.27,130.21,129.39,128.79,128.49,127.57,37.27.
目标化合物E27
橙黄色固体，产率90％，熔点106-108℃.1H NMR(400MHz,DMSO-d6)δ:8.32(d,J＝8.0Hz,2H,benzene H),7.77(t,J＝8.0Hz,1H,benzene H),7.62(t,J＝8.0Hz,2H,benzeneH),7.57(d,J＝8.0Hz,2H,benzene H),7.44(d,J＝8.0Hz,2H,benzene H),4.71(s,2H,CH2)；13C NMR(101MHz,DMSO-d6)δ:182.69,171.58,168.89,135.23,134.46,134.24,132.45,131.09,130.66,128.72,128.62,36.57.
目标化合物E28
淡黄色固体，产率88％，熔点105-106℃。1H NMR(400MHz,DMSO-d6)δ:8.33(d,J＝8.0Hz,2H,benzene H),7.78(t,J＝8.0Hz,1H,benzene H),7.72–7.69(m,2H,benzene H),7.63(t,J＝8.0Hz,2H,benzene H),7.41(t,J＝8.0Hz,1H,benzene H),7.30(t,J＝8.0Hz,1H,benzene H),4.80(s,2H,CH2)；13C NMR(101MHz,DMSO-d6)δ:182.75,171.05,169.12,134.92,134.51,134.25,133.02,131.79,130.70,130.27,128.76,128.16,124.25,38.16.
目标化合物E29
黄色固体，产率84％，熔点97-98℃。1H NMR(400MHz,CDCl3)δ:8.49(d,J＝8.0Hz,2H,benzene H),7.67(t,J＝8.0Hz,1H,benzene H),7.63(s,1H,benzene H),7.54(t,J＝8.0Hz,2H,benzene H),7.43(t,J＝8.0Hz,2H,benzene H),7.22(t,J＝8.0Hz,1H,benzeneH),4.62(s,2H,CH2)；13C NMR(101MHz,CDCl3)δ:182.95,171.17,169.58,137.88,134.57,134.50,132.27,131.40,131.26,130.47,128.79,128.04,122.89,37.19.
目标化合物E30
橙黄色固体，产率89％，熔点103-104℃。1H NMR(400MHz,DMSO-d6)δ:8.32(d,J＝8.0Hz,2H,benzene H),7.77(t,J＝8.0Hz,1H,benzene H),7.63(t,J＝8.0Hz,2H,benzeneH),7.58(d,J＝8.0Hz,2H,benzene H),7.50(d,J＝8.0Hz,2H,benzene H),4.69(s,2H,CH2)；13C NMR(101MHz,DMSO-d6)δ:183.16,172.04,169.37,136.14,134.93,134.71,132.01,131.89,131.13,129.20,121.48,37.09.
目标化合物的抗植物病原真菌生物活性测试方法
试验材料和培养基的配制
植物真菌：小麦赤霉病菌(Fusariumgraminearum)、茄子黄萎病菌(Verticilliumdahliae)、水稻纹枯病菌(Thanatephorus cucumeris)、油菜菌核病菌(Sclerotiniasclerotiorum)、番茄早疫病菌(Alternariasolani)、长柄链格孢病菌(Alternarialongipes(Ellis&Everh.)E.W.Mason)、葡萄座腔菌(Botryosphaeriadothidea)、和禾谷镰孢菌(Gibberella zeae(Schwein.)Petch)。对照药剂：粉绣宁(分析标准品，阿拉丁试剂上海有限公司)。
配制PDA培养基：称取800克去皮土豆，煮汁后过滤，加入琼脂80g、葡萄糖80g，混匀溶解后以每瓶90mL转移到200mL锥形瓶中，封口后在120℃条件下高压灭菌30min，冷却后备用。
配制药液：称取待测化合物10mg溶解到1.0mL DMSO中，在无菌超净台中转移至含9.0mL无菌吐温水的15mL离心管中，再加到已灭菌的90mLPDA培养基中混匀，使得药液最终浓度为100μg/mL，将培养基平均倒入9个培养皿中冷却备用，以等量的DMSO吐温水作为空白对照，以商品药萎锈灵和粉绣宁作为对照药。
化合物对植物病原菌的活性测试
采用菌丝生长速率法测定了目标化合物对8种植物病原真菌的抑制活性。取提前活化好的真菌边缘打孔制成直径为4.0mm的菌饼，用无菌接种针移接到含药培养基中央，置于28℃的恒温培养箱中培养2-6天。
待空白对照组菌落长到6.0cm左右时用直尺按十字交叉法测量菌丝直径。根据下列公式计算抑制率，计算公式如下，其中I为抑制率，C为空白对照菌丝测量直径，T为药物处理组测量直径。
I(％)＝[(C-T)/(C-0.4)]×100
化合物对植物病原真菌毒力回归方程和EC50值的测定
根据活性初步筛选数据，对高活性化合物和对照药进行了毒力回归方程和EC50值的测定。将待测药液分别配置成5个梯度浓度，以等量的DMSO吐温水作为空白对照，采用菌丝生长速率法测定了对相应植物真菌的抑菌活性，采用十字交叉法测量菌丝直径，抑制率计算方法同上，浓度取对数与抑制率做线性回归方程，从而得出其EC50值。
目标化合物的抗植物病原菌活性数据分析
采用菌丝生长速率法测定了目标化合物对油菜菌核病菌、小麦赤霉病菌、茄子黄萎病菌、番茄早疫病菌、葡萄座腔菌、禾谷镰孢菌、水稻纹枯病菌和长柄链格孢病菌的抑制活性，结果如表1、2和3所示。
表1化合物E1-E30在100μg/mL浓度下对四种植物病原菌活性测试结果a
“a”每组实验重复三次。
表2化合物E1-E30在100μg/mL浓度下对四种植物病原菌活性测试结果a
“a”每组实验重复三次，“--”为未测试。
由表1和表2化合物在100μg/mL浓度下对8种植物病原真菌的抑制活性结果可以发现，当R为烷基或支链烷基时，化合物对8中植物病原真菌表现出明显的抑菌活性。其中，当R为甲基和乙基时，化合物对水稻纹枯病菌的抑制活性分别的达到88.1％和95.3％，高于商品化杀菌剂三唑酮(79.6％)。而当R为苄基或取代苄基的时候，化合物活性明显下降。
表3化合物E1、E2和E3对五种植物病原真菌的EC50值a
“a”每组实验重复三次。
由表3中，化合物E1、E2和E3对五种植物病原菌的EC50值可以发现，化合物对小麦赤霉病菌、水稻纹枯病菌、茄子黄萎病菌、禾谷镰孢病菌和番茄早疫病菌均表现初良好的抑菌活性。其中，化合物E1、E2和E3对小麦赤霉病菌的EC50值分别为30.5、21.9和21.5μg/mL；对水稻纹枯病菌的EC50值分别为32.8、22.2和39.6μg/mL。
Claims (5)
1.一类含1,3,4-噻二唑硫醚结构的苯甲酮类化合物，其特征在于：其结构式如下：
其中R为烷基、苄基或取代苄基。
2.根据权利要求1所述的一类含1,3,4-噻二唑硫醚结构的苯甲酮类化合物，其特征在于：优选的，R为甲基、乙基或丙基。
3.根据权利要求1所述的一类含1,3,4-噻二唑硫醚结构的苯甲酮类化合物，其特征在于：所述的取代苄基的取代基为邻、间或对位单取代的甲基、甲氧基、三氟甲基、三氟甲氧基或卤素。
4.如权利要求1或2所述的一类含1,3,4-噻二唑硫醚结构的苯甲酮类化合物的制备方法，其特征在于：反应式如下：
5.如权利要求1-3之一所述的一类含1,3,4-噻二唑硫醚结构的苯甲酮类化合物在植物病原真菌引起的植物真菌病害上的应用。
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