CN102686573B - 用于抵御无脊椎动物害虫的氟化的氧杂或硫杂杂芳基烷基硫化物衍生物 - Google Patents
用于抵御无脊椎动物害虫的氟化的氧杂或硫杂杂芳基烷基硫化物衍生物 Download PDFInfo
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- CN102686573B CN102686573B CN201080059345.4A CN201080059345A CN102686573B CN 102686573 B CN102686573 B CN 102686573B CN 201080059345 A CN201080059345 A CN 201080059345A CN 102686573 B CN102686573 B CN 102686573B
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- DQJCHOQLCLEDLL-UHFFFAOYSA-N tricyclazole Chemical compound CC1=CC=CC2=C1N1C=NN=C1S2 DQJCHOQLCLEDLL-UHFFFAOYSA-N 0.000 description 1
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- XAIPTRIXGHTTNT-UHFFFAOYSA-N triflumuron Chemical compound C1=CC(OC(F)(F)F)=CC=C1NC(=O)NC(=O)C1=CC=CC=C1Cl XAIPTRIXGHTTNT-UHFFFAOYSA-N 0.000 description 1
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- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
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- 229930195735 unsaturated hydrocarbon Natural products 0.000 description 1
- ITDRVJXDQOONPC-UHFFFAOYSA-N urea;hydrofluoride Chemical compound F.NC(N)=O ITDRVJXDQOONPC-UHFFFAOYSA-N 0.000 description 1
- DBXFMOWZRXXBRN-LWKPJOBUSA-N valifenalate Chemical compound CC(C)OC(=O)N[C@@H](C(C)C)C(=O)NC(CC(=O)OC)C1=CC=C(Cl)C=C1 DBXFMOWZRXXBRN-LWKPJOBUSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
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- 230000003612 virological effect Effects 0.000 description 1
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- 239000005943 zeta-Cypermethrin Substances 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical group [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- 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
-
- 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
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
- A01N43/08—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with oxygen as the ring hetero atom
-
- 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
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/06—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings
- A01N43/10—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom five-membered rings with sulfur as the ring hetero atom
-
- 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
- A01N43/02—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms
- A01N43/04—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom
- A01N43/22—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atoms with one hetero atom rings with more than six members
-
- 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
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
-
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Abstract
本发明涉及以下描绘的式I的烷基硫化物衍生化合物或其对映异构体或兽医学地可接受的盐,其有用于抵御或控制无脊椎动物害虫,尤其是节肢动物害虫和线虫。本发明也涉及通过使用这些化合物控制无脊椎动物害虫的方法及植物繁殖材料及包含所述化合物的农业和兽医学组合物,其中U,R1,R2,R3U,X,n和p如说明书中定义。
Description
【技术领域】
本发明涉及烷基硫化物化合物或其对映异构体或兽医学地可接受的盐,其有用于抵御或控制无脊椎动物害虫,尤其是节肢动物害虫和线虫。本发明也涉及通过使用这些化合物控制无脊椎动物害虫的方法及涉及植物繁殖材料及涉及包含所述化合物的农业和兽医学组合物。
【背景技术】
无脊椎动物害虫和尤其是节肢动物和线虫毁坏生长及收获的作物,并攻击木质房屋及商业结构,给食品供应及性质导致大经济损失。而知道大量的杀虫剂,由于靶害虫发展针对所述剂的抗性的能力,有对于用于抵御无脊椎动物害虫,特别是昆虫,蜘蛛和线虫的新剂的持续需求。
WO 2009/075080,WO 2009/028727,WO 2009/025397和WO2009/014268描述含有氟的有机硫化合物和提及它们的作为杀虫剂的用途。
【发明内容】
本发明旨在提供针对大量的不同无脊椎动物害虫,尤其针对难以控制的节肢动物害虫和/或线虫具有良好杀虫活性,尤其是杀昆虫活性,及显示广活性谱的化合物。
已发现这些目的可通过下式I的烷基硫化物衍生物,通过它们的立体异构体及通过它们的盐和N-氧化物,尤其是它们的农业地或兽医学地可接受的盐达到。
因此,在第1方面,本发明涉及式I的烷基硫化物化合物和其盐和N-氧化物
其中
X是O或S(=O)m;
m是0,1,2
n是0、1或2;
p是1或2
R3U是C1~C10-卤代烷基,C2~C6-卤代烯基,C3~C6-卤代炔基,C3~C6-卤代环烷基,C3~C6-卤代环烯基,且其中至少一个卤素是氟;
U是5-~12-元单环或双环杂芳族环-系统,其可含有1~4个选自O,S,N的杂原子,其中杂芳族环可被1~4个取代基V取代,
V独立地是卤素,C1~C6-烷基,C1~C6-卤代烷基,可被卤素原子取代的C3~C6-环烷基-C1~C3-烷基,C2~C6-烯基,C2~C6-卤代烯基,C2~C6-炔基,C2~C6-卤代炔基,C3~C6-环烷基,C3~C6-卤代环烷基,C1~C6-烷氧基,C1~C6-卤代烷氧基,C(=O)R4,C(=S)R4,S(O)oR10,CN,NO2,氨基,其可被下列基团取代或二取代:C1~C4-烷基或C1~C4-酰基;
o是0、1或2;
R1,R2彼此独立地选自:氢,卤素,C1~C6-烷基,其可被下列基团取代:卤素,C1~C4-烷氧基,C1~C4-烷硫基,C1~C4-烷基亚硫酰基,C1~C6-烷基磺酰基,CN,C(=O)R4,OC(=O)R4,N-(C1~C3-烷基)2或OH,C2~C6-烯基,C2~C6-卤代烯基,C2~C6-炔基,C2~C6-卤代炔基,C3~C6-环烷基,C3~C6-卤代环烷基,可被卤素原子取代的C3~C6-环烷基-C1~C3-烷基,CN,C(=O)R7,C(=S)R7,C(R11)=NR12,C(R11)=N-OR12或R1和R2可与和它们键合的碳原子一起形成C3~C6-环烷基,C=C(R5)R6或C=N-OR5;
R4是氢,羟基,C1~C6-烷基,C1~C6-卤代烷基,C1~C6-烷氧基,NR8R9;
R5是氢或C1~C4-烷基;
R6是C1~C6-烷氧基,NR8R9;
R7是氢,C1~C6-烷基,C1~C6-卤代烷基,OH,C1~C6-烷氧基,其可被下列基团取代:卤素,C1~C4-烷氧基,C1~C4-烷氧基-C1~C4-烷氧基,C1~C4-烷硫基,C1~C4-烷基亚硫酰基,C1~C6-烷基磺酰基,C3~C6-环烷基,四氢呋喃基,苯基,吡啶基[其中最后2个提及的自由基可被卤素取代],CN,C(=O)OR12或C(=O)NR11R12,C2~C6-烯基,C2~C6-卤代烯基,C2~C6-炔基,C2~C6-卤代炔基,可被卤素取代的C3~C6-环烷氧基,可被卤素取代的C3~C6-环烷硫基,NR8R9,C1~C6-烷硫基,N(R13)C(=O)N(R14)R15或下列基团:W1~W5:
R8和R9与和它们附接的氮原子一起形成氨基基团,或单-(C1~C6-烷基)氨基或二-(C1~C4-烷基)氨基或C2~C5-环状氨基基团。
R11,R12,R13,R14和R15独立地和彼此独立地是氢,C1~C6-烷基;
R10是C1~C6-烷基,其可被下列基团取代:卤素,C1~C4-烷氧基,C1~C4-烷氧基-C1~C4-烷氧基,S(O)o-C1~C6-烷基,苯基或四氢呋喃基,C2~C6-烯基,C2~C6-卤代烯基,C2~C6-炔基,C2~C6-卤代炔基,C3~C6-环烷基,C3~C6-卤代环烷基,可被卤素原子取代的C3~C6-环烷基-C1~C3-烷基。
本发明也提供农业组合物,其包含至少一种本文定义的式I的化合物和/或其农业地可接受的盐及至少一种液体和/或固体载体。
本发明也提供兽医学组合物,其包含至少一种本文定义的式I的化合物和/或其兽医学地可接受的盐及至少一种液体和/或固体载体。
本发明也提供控制无脊椎动物害虫的方法,该方法包括用杀虫有效量的本文定义的式I的化合物或其盐处理害虫,它们的食品供应,它们的栖息地或它们的繁殖地或害虫生长或可生长的栽培的植物,植物繁殖材料(诸如种子),土壤,分布区,物质或环境,或物质,栽培的植物,植物繁殖材料(诸如种子),土壤,表面或空间以保护免于害虫攻击或侵袭。
本发明也涉及植物繁殖材料,尤其是种子,包含至少一种本文定义的式I的化合物和/或其农业地可接受的盐。
本发明还涉及用于治疗或保护动物免于被寄生虫侵袭或感染的方法,其包括使动物接触杀寄生虫有效量的本文定义的式I的化合物或其兽医学地可接受的盐。使动物接触本发明的化合物I,其盐或兽医学组合物是指将其应用或施用给动物。
术语"立体异构体"包括旋光异构体,诸如对映异构体或非对映异构体,后者在分子中存在由于多于一个手性中心,以及几何异构体(顺式/反式异构体)。
依赖于取代模式,式I的化合物可具有一个或更多手性中心,在该情况中,它们作为对映异构体或非对映异构体的混合物存在。本发明提供本发明的纯对映异构体或非对映异构体和它们的混合物和化合物I的纯对映异构体或非对映异构体或其混合物的用途。适合的式I的化合物也包括全部可能的几何立体异构体(顺式/反式异构体)和其混合物。顺式/反式异构体可关于亚胺基存在。
本发明的化合物可为无定形或可以一或更多不同晶体状态(多态型)存在,其可具有不同宏观性质,诸如稳定性或显示不同生物学性质诸如活性。本发明包括无定形和晶体式I的化合物,不同晶体状态的相应化合物I的混合物,以及其无定形或晶体盐。
式I的化合物的盐优选是农业地和兽医学地可接受的盐。它们可在常规方法中形成,例如如果式I的化合物具有碱性官能性,通过使化合物与阴离子的酸反应,或通过使I的酸性化合物与适合的碱反应。
适合的农业地可接受的盐尤其是其阳离子和阴离子,分别,对本发明的化合物的作用不具有任何不利效果的那些阳离子的盐或那些酸的酸加成盐。适合的阳离子尤其是碱金属,优选锂,钠和钾,碱土金属,优选钙,镁和钡,及过渡金属,优选锰,铜,锌和铁的离子,且也是铵(NH4 +)及取代的铵,其中1~4个氢原子被下列基团取代:C1~C4-烷基,C1~C4-羟烷基,C1~C4-烷氧基,C1~C4-烷氧基-C1~C4-烷基,羟基-C1~C4-烷氧基-C1~C4-烷基,苯基或苄基。取代的铵离子的例包含:甲基铵,异丙基铵,二甲基铵,二异丙基铵,三甲基铵,四甲基铵,四乙基铵,四丁基铵,2-羟乙基铵,2-(2-羟乙氧基)乙基铵,双(2-羟乙基)铵,苄基三甲基铵和苄基三乙基铵,此外鏻离子,硫鎓离子,优选三(C1~C4-烷基)硫鎓和亚砜鎓离子,优选三(C1~C4-烷基)亚砜鎓。
有用的酸加成盐的阴离子主要是氯化物,溴化物,氟化物,硫酸氢盐,硫酸盐,磷酸二氢盐,磷酸氢盐,磷酸盐,硝酸盐,碳酸氢盐,碳酸盐,六氟硅酸盐,六氟磷酸盐,苯甲酸盐,及C1~C4-烷酸的阴离子,优选甲酸盐,乙酸盐,丙酸盐和丁酸盐。它们可通过使式I的化合物与对应阴离子的酸,优选盐酸,氢溴酸,硫酸,磷酸或硝酸反应来形成。
术语"兽医学地可接受的盐"是意指形成用于兽医学使用的盐的领域知道及接受的那些阳离子或阴离子盐。例如由含有碱性氮原子,例如氨基的式I的化合物形成的适合的酸加成盐,包括具有无机酸的盐,例如盐酸盐,硫酸盐,磷酸盐和硝酸盐和有机酸的盐,例如乙酸,马来酸,二马来酸,富马酸,二富马酸,甲烷次磺酸,甲烷磺酸,及琥珀酸。
本文所用的术语"无脊椎动物害虫"包括动物群,诸如可攻击植物,由此给攻击的植物导致实质性损伤的昆虫,蜘蛛和线虫,以及可侵袭动物,尤其是温血动物诸如例如哺乳动物或鸟,或其他高等动物诸如爬行动物,两栖动物或鱼,由此给侵袭的动物导致实质性损伤的外寄生物。
本文所用的术语"植物繁殖材料"包括植物的全部生殖部分,诸如种子和植物性植物材料诸如插枝及块茎(例如马铃薯),其可用于植物。此包括种子,根,果实,块茎,鳞茎,根状茎,苗,芽和其他植物部分。也可包括幼苗及年轻植物,其待萌芽之后或自土壤出现之后种植。这些植物繁殖材料可在种植或移植时或在种植或移植之前用植物保护化合物预防性地处理。
术语"植物"包含任何类型的植物,包括"非-栽培的植物"和尤其是"栽培的植物"。
术语"非-栽培的植物"指称任何野生型物种或相关的物种或相关的属的栽培的植物。
本文所用的术语"栽培的植物"包括已通过繁殖,诱变或遗传加工修饰的植物。遗传修饰的植物是在天然的环境下不可通过杂交育种,突变或天然的重组容易获得的,遗传物质已被通过使用重组DNA技术修饰的植物。一般而言,一种或更多基因已整合到遗传修饰的植物的遗传物质,以便改善植物的特定性质。该遗传修饰也包括但未限制于蛋白(寡-或多肽)聚的靶向的翻译后修饰,例如通过糖基化或聚合物添加,诸如异戊烯化的,乙酰化的或法呢基化的部分或PEG部分(例如公开于Biotechnol Prog.2001Jul-Aug;17(4):720-8.,Protein Eng DesSel.2004Jan;17(1):57-66,Nat.Protoc.2007;2(5):1225-35.,Curr.Opin.Chem.Biol.2006Oct;10(5):487-91.Epub 2006Aug 28,Biomaterials.2001Mar;22(5):405-17,Bioconjug Chem.2005Jan-Feb;16(1):113-21)。
本文所用的术语"栽培的植物"还包括已致使耐受特定类的除草剂应用的植物,诸如羟苯基丙酮酸二氧化酶(HPPD)抑制物;乙酰乳酸合酶(ALS)抑制物,诸如磺酰尿素(见例如US 6,222,100,WO01/82685,WO 00/26390,WO 97/41218,WO 98/02526,WO 98/02527,WO 04/106529,WO 05/20673,WO 03/14357,WO 03/13225,WO03/14356,WO 04/16073)或咪唑啉酮(见例如US 6,222,100,WO01/82685,WO 00/26390,WO 97/41218,WO 98/02526,WO 98/02527,WO 04/106529,WO 05/20673,WO 03/14357,WO 03/13225,WO03/14356,WO 04/16073);烯醇丙酮酰莽草酸-3-磷酸合酶(EPSPS)抑制物,诸如草甘膦(见例如WO 92/00377);谷氨酰胺合成酶(GS)抑制物,诸如草铵膦(见例如EP-A-0242236,EP-A-242246)或oxynil除草剂(见例如US 5,559,024)作为繁殖或遗传加工的常规方法的结果。几种栽培的植物已通过常规繁殖(诱变)方法致使耐受除草剂,例如耐受咪唑啉酮,例如甲氧咪草烟的夏播油菜(油菜)。遗传加工方法已用于致使栽培的植物,诸如大豆,棉花,玉米,甜菜和油菜,耐受除草剂,诸如草甘膦和草铵膦,一些是以商品名(草甘膦)和(草铵膦)商业上可利用的。
本文所用的术语"栽培的植物"还包括是通过使用能合成一种或更多的重组DNA技术制造的植物,所述杀昆虫蛋白尤其从细菌芽孢杆菌属(Bacillus),特别是从苏云金芽孢杆菌(Bacillus thuringiensis)知道的那些,诸如δ-内毒素,例如CryIA(b),CryIA(c),CryIF,CryIF(a2),CryIIA(b),CryIIIA,CryIIIB(bl)或Cry9c;植物性杀昆虫蛋白(VIP),例如VIP1,VIP2,VIP3或VIP3A;定居线虫的细菌,例如光杆状菌属(Photorhabdus spp.)物种或致病杆菌属(Xenorhabdus spp.)物种的杀昆虫蛋白;由动物产生的毒素,诸如蝎毒素,蜘蛛毒素,黄蜂毒素或其他昆虫-特定神经毒素;由真菌产生的毒素,如链霉菌纲(Streptomycetes)毒素,植物凝集素,诸如豌豆或大麦凝集素;凝集素;蛋白酶抑制物,诸如胰蛋白酶抑制物,丝氨酸蛋白酶抑制物,patatin,半胱氨酸蛋白酶抑制物或木瓜蛋白酶抑制物;核糖体-灭活蛋白(RIP),诸如蓖麻毒素,玉米-RIP,相思豆毒蛋白,软瓜蛋白,肥皂草毒蛋白或异株泻根毒蛋白;甾代谢酶,诸如3-羟类固醇氧化酶,蜕皮甾-IDP-糖基-转移酶,胆甾醇氧化酶,蜕皮素抑制物或HMG-CoA-还原酶;离子通道阻断剂,诸如钠或钙通道的阻断剂;保幼激素酯酶;利尿激素受体(螺旋激肽受体);茋合酶,联苄合酶,几丁质酶或葡聚糖酶。在本发明的情景中,这些杀昆虫蛋白或毒素也值得表达为前毒素,杂交体蛋白,截短的或另外修饰的蛋白。杂交体蛋白特征在于蛋白结构域的新组合,(见,例如WO02/015701)。该毒素或能合成该毒素的遗传修饰的植物的进一步例公开于,例如,EP-A 374753,WO 93/007278,WO 95/34656,EP-A 427529,EP-A 451878,WO 03/018810和WO 03/052073。遗传修饰的植物中含有的这些杀昆虫蛋白给产生这些蛋白的植物附加免于来自特定分类群的节肢动物昆虫的有害害虫的保护,特别是甲虫(鞘翅目(Coleoptera)),蝇(双翅目(Diptera)),及蝴蝶和蛾(鳞翅目(Lepidoptera))及植物寄生虫线虫(线虫纲(Nematoda))。
本文所用的术语"栽培的植物"还包括通过使用能合成一种或更多用于增加那些植物对细菌,病毒或真菌病原体的抗性或耐受性的蛋白的重组DNA技术制造的植物。该蛋白的例是所谓的"发病机制-相关的蛋白"(PR蛋白,见,例如EP-A 0392225),植物疾病抗性基因(例如,表达针对源于墨西哥野生马铃薯(Solanum bulbocastanum)的致病疫霉(Phytophthora infestans)的抗性基因作用的马铃薯品种)或T4-溶菌酶(例如能合成这些具有增加的针对细菌诸如解淀粉欧文氏菌(Erwinia amylovora)的抗性的蛋白的马铃薯品种)。
本文所用的术语"栽培的植物"还包括通过使用能合成用于增加那些植物的产率(例如生物质产生,谷粒产率,淀粉含量,油含量或蛋白含量),对旱,盐度或其他生长限制环境因素的耐受性或对害虫和真菌,细菌或病毒病原体的耐受性的一种或更多蛋白的重组DNA技术制造的植物。
本文所用的术语"栽培的植物"还包括通过使用重组DNA技术含有修饰的量的内容物物质或内容物新物质,特别对于改善人或动物营养的植物,例如产生健康-促进长链ω-3-脂肪酸或不饱和的ω-9脂肪酸(例如油菜)的油科作物。
本文所用的术语"栽培的植物"还包括通过使用重组DNA技术含有修饰的量内容物物质或内容物新物质,特别对于改善原材料产生的植物,例如产生增加的量的支链淀粉的马铃薯(例如马铃薯)。
以上变量的定义中提及的有机部分,如术语卤素,是个体基团成员的个体列的集合性术语。前缀Cx-Cy在各情况中表示基团中可能的碳原子数。
术语卤素在各情况中表示氟,溴,氯或碘,尤其是氟,氯或溴。
本文所用的术语"C1~C6-烷基"及烷氧基,烷硫基,烷基亚硫酰基,烷基磺酰基,等的烷基部分指称具有1~2("C1~C2-烷基"),1~4("C1~C4-烷基")或1~6("C1~C6-烷基")个碳原子的饱和的直链或分支的烃自由基。C1~C2-烷基是甲基或乙基。C1~C4-烷基还是丙基,异丙基,丁基,1-甲基丙基(仲-丁基),2-甲基丙基(异丁基)或1,1-二甲基乙基(叔-丁基)。C1~C6-烷基也还是,例如,戊基,1-甲基丁基,2-甲基丁基,3-甲基丁基,2,2-二甲基丙基,1-乙基丙基,1,1-二甲基丙基,1,2-二甲基丙基,己基,1-甲基戊基,2-甲基戊基,3-甲基戊基,4-甲基戊基,1,1-二甲基丁基,1,2-二甲基丁基,1,3-二甲基丁基,2,2-二甲基丁基,2,3-二甲基丁基,3,3-二甲基丁基,1-乙基丁基,2-乙基丁基,1,1,2-三甲基丙基,1,2,2-三甲基丙基,1-乙基-1-甲基丙基或1-乙基-2-甲基丙基。
本文所用的术语"C1~C10-卤代烷基",其也表示为"C1~C10-烷基,其可被下列基团取代:卤素",指称具有1~2("C1~C2-卤代烷基"),1~4("C1~C4-卤代烷基"),1~6("C1~C6-卤代烷基"),1~8("C1~C8-卤代烷基")或1~10("C1~C10-卤代烷基")个碳原子的直链或分支的烷基(上述),其中这些基团中的一些或全部氢原子被上述卤素原子取代:尤其是C1~C2-卤代烷基,诸如氯甲基,溴甲基,二氯甲基,三氯甲基,氟甲基,二氟甲基,三氟甲基,氯氟甲基,二氯氟甲基,氯二氟甲基,1-氯乙基,1-溴乙基,1-氟乙基,2-氟乙基,2,2-二氟乙基,2,2,2-三氟乙基,2-氯-2-氟乙基,2-氯-2,2-二氟乙基,2,2-二氯-2-氟乙基,2,2,2-三氯乙基,五氟乙基或1,1,1-三氟丙-2-基。
"卤代甲基"是1,2或3个氢原子被卤素原子取代的甲基。例是溴甲基,氯甲基,氟甲基,二氯甲基,三氯甲基,二氟甲基,三氟甲基,氯氟甲基,二氯氟甲基,氯二氟甲基等。
本文所用的术语"C2~C6-烯基"及在烯氧基等的烯基部分指称具有2~4("C2~C4-烯基")或2~6("C2~C6-烯基")个碳原子和任何位置的双键的单不饱和的直链或分支的烃自由基,例如C2~C4-烯基,诸如乙烯基,1-丙烯基,2-丙烯基,1-甲基乙烯基,1-丁烯基,2-丁烯基,3-丁烯基,1-甲基-1-丙烯基,2-甲基-1-丙烯基,1-甲基-2-丙烯基或2-甲基-2-丙烯基;C2~C6-烯基,诸如乙烯基,1-丙烯基,2-丙烯基,1-甲基乙烯基,1-丁烯基,2-丁烯基,3-丁烯基,1-甲基-1-丙烯基,2-甲基-1-丙烯基,1-甲基-2-丙烯基,2-甲基-2-丙烯基,1-戊烯基,2-戊烯基,3-戊烯基,4-戊烯基,1-甲基-1-丁烯基,2-甲基-1-丁烯基,3-甲基-1-丁烯基,1-甲基-2-丁烯基,2-甲基-2-丁烯基,3-甲基-2-丁烯基,1-甲基-3-丁烯基,2-甲基-3-丁烯基,3-甲基-3-丁烯基,1,1-二甲基-2-丙烯基,1,2-二甲基-1-丙烯基,1,2-二甲基-2-丙烯基,1-乙基-1-丙烯基,1-乙基-2-丙烯基,1-己烯基,2-己烯基,3-己烯基,4-己烯基,5-己烯基,1-甲基-1-戊烯基,2-甲基-1-戊烯基,3-甲基-1-戊烯基,4-甲基-1-戊烯基,1-甲基-2-戊烯基,2-甲基-2-戊烯基,3-甲基-2-戊烯基,4-甲基-2-戊烯基,1-甲基-3-戊烯基,2-甲基-3-戊烯基,3-甲基-3-戊烯基,4-甲基-3-戊烯基,1-甲基-4-戊烯基,2-甲基-4-戊烯基,3-甲基-4-戊烯基,4-甲基-4-戊烯基,1,1-二甲基-2-丁烯基,1,1-二甲基-3-丁烯基,1,2-二甲基-1-丁烯基,1,2-二甲基-2-丁烯基,1,2-二甲基-3-丁烯基,1,3-二甲基-1-丁烯基,1,3-二甲基-2-丁烯基,1,3-二甲基-3-丁烯基,2,2-二甲基-3-丁烯基,2,3-二甲基-1-丁烯基,2,3-二甲基-2-丁烯基,2,3-二甲基-3-丁烯基,3,3-二甲基-1-丁烯基,3,3-二甲基-2-丁烯基,1-乙基-1-丁烯基,1-乙基-2-丁烯基,1-乙基-3-丁烯基,2-乙基-1-丁烯基,2-乙基-2-丁烯基,2-乙基-3-丁烯基,1,1,2-三甲基-2-丙烯基,1-乙基-1-甲基-2-丙烯基,1-乙基-2-甲基-1-丙烯基,1-乙基-2-甲基-2-丙烯基等和其位置异构体。
本文所用的术语"C2~C6-卤代烯基",其也表示为"C2~C6-烯基,其可被卤素取代",且卤代烯基氧基,卤代烯基羰基等中的卤代烯基部分指称具有2~4("C2~C4-卤代烯基")或2~6("C2~C6-卤代烯基")个碳原子和任何位置的双键的不饱和的直链或分支的烃自由基(上述),其中这些基团中的一些或全部氢原子被上述卤素原子取代,尤其是氟,氯和溴,例如氯乙烯基,氯烯丙基等。
本文所用的术语"C2~C6-炔基"及炔基氧基,炔羰基等中的炔基部分指称具有2~4("C2~C4-炔基")或2~6("C2~C6-炔基")个碳原子和任何位置的1或2个三键的直链或分支的烃基,例如C2~C4-炔基,诸如乙炔基,1-丙炔基,2-丙炔基,1-丁炔基,2-丁炔基,3-丁炔基,1-甲基-2-丙炔基等,C2~C6-炔基,诸如乙炔基,1-丙炔基,2-丙炔基,1-丁炔基,2-丁炔基,3-丁炔基,1-甲基-2-丙炔基,1-戊炔基,2-戊炔基,3-戊炔基,4-戊炔基,1-甲基-2-丁炔基,1-甲基-3-丁炔基,2-甲基-3-丁炔基,3-甲基-1-丁炔基,1,1-二甲基-2-丙炔基,1-乙基-2-丙炔基,1-己炔基,2-己炔基,3-己炔基,4-己炔基,5-己炔基,1-甲基-2-戊炔基,1-甲基-3-戊炔基,1-甲基-4-戊炔基,2-甲基-3-戊炔基,2-甲基-4-戊炔基,3-甲基-1-戊炔基,3-甲基-4-戊炔基,4-甲基-1-戊炔基,4-甲基-2-戊炔基,1,1-二甲基-2-丁炔基,1,1-二甲基-3-丁炔基,1,2-二甲基-3-丁炔基,2,2-二甲基-3-丁炔基,3,3-二甲基-1-丁炔基,1-乙基-2-丁炔基,1-乙基-3-丁炔基,2-乙基-3-丁炔基,1-乙基-1-甲基-2-丙炔基等;
本文所用的术语"C2~C6-卤代炔基",其也表示为"C2~C6-炔基,其可被卤素取代",及卤代炔基氧基,卤代炔基羰基等中的卤代炔基部分指称具有2~4("C2~C4-卤代炔基"),3~4("C3~C4-卤代炔基"),2~6("C2~C6-卤代炔基"),3~6("C3~C6-卤代炔基")个碳原子和任何位置的1或2个三键的不饱和的直链或分支的烃自由基(上述),其中这些基团中的一些或全部氢原子被上述卤素原子取代,尤其是氟,氯和溴;
本文所用的术语"C3~C6-环烷基"指称具有3~6个碳原子的单-或双-或多环饱和的烃自由基。具有3~6个碳原子的单环自由基的例包含环丙基,环丁基,环戊基和环己基。
本文所用的术语"C3~C6-卤代环烷基",其也表示为"可被卤素取代的C3~C6-环烷基",及卤代环烷氧基,卤代环烷基羰基等中的卤代环烷基部分指称具有3~6("C3~C6-卤代环烷基")个碳环成员(上述)的单-或双-或多环饱和的烃基,其中一些或全部氢原子被上述卤素原子,尤其是氟,氯和溴取代。
术语"C3~C6-环烷基-C1~C3-烷基"指称经以上定义的C1~C3-烷基结合到分子残基的以上定义的C3~C6-环烷基。例是环丙基甲基,环丙基乙基,环丙基丙基,环丁基甲基,环丁基乙基,环丁基丙基,环戊基甲基,环戊基乙基,环戊基丙基,环己基甲基,环己基乙基,环己基丙基,等。
术语"C1~C2-烷氧基"是经氧原子附接的以上定义的C1~C2-烷基。术语"C1~C4-烷氧基"是经氧原子附接的以上定义的C1~C4-烷基。术语"C1~C6-烷氧基"是经氧原子附接的以上定义的C1~C6-烷基。C1~C2-烷氧基是甲氧基或乙氧基。C1~C4-烷氧基还是,例如,n-丙氧基,1-甲基乙氧基(异丙氧基),丁氧基,1-甲基丙氧基(仲-丁氧基),2-甲基丙氧基(异丁氧基)或1,1-二甲基乙氧基(叔-丁氧基)。C1~C6-烷氧基还是,例如,戊氧基,1-甲基丁氧基,2-甲基丁氧基,3-甲基丁氧基,1,1-二甲基丙氧基,1,2-二甲基丙氧基,2,2-二甲基丙氧基,1-乙基丙氧基,己氧基,1-甲基戊氧基,2-甲基戊氧基,3-甲基戊氧基,4-甲基戊氧基,1,1-二甲基丁氧基,1,2-二甲基丁氧基,1,3-二甲基丁氧基,2,2-二甲基丁氧基,2,3-二甲基丁氧基,3,3-二甲基丁氧基,1-乙基丁氧基,2-乙基丁氧基,1,1,2-三甲基丙氧基,1,2,2-三甲基丙氧基,1-乙基-1-甲基丙氧基或1-乙基-2-甲基丙氧基。
术语"C1~C2-卤代烷氧基"是经氧原子附接的以上定义的C1~C2-卤代烷基。术语"C1~C4-卤代烷氧基"是经氧原子附接的以上定义的C1~C4-卤代烷基。术语"C1~C6-卤代烷氧基"是经氧原子附接的以上定义的C1~C6-卤代烷基。C1~C2-卤代烷氧基是,例如,OCH2F,OCHF2,OCF3,OCH2Cl,OCHCl2,OCCl3,氯氟甲氧基,二氯氟甲氧基,氯二氟甲氧基,2-氟乙氧基,2-氯乙氧基,2-溴乙氧基,2-碘乙氧基,2,2-二氟乙氧基,2,2,2-三氟乙氧基,2-氯-2-氟乙氧基,2-氯-2,2-二氟乙氧基,2,2-二氯-2-氟乙氧基,2,2,2-三氯乙氧基或OC2F5。C1~C4-卤代烷氧基还是,例如,2-氟丙氧基,3-氟丙氧基,2,2-二氟丙氧基,2,3-二氟丙氧基,2-氯丙氧基,3-氯丙氧基,2,3-二氯丙氧基,2-溴丙氧基,3-溴丙氧基,3,3,3-三氟丙氧基,3,3,3-三氯丙氧基,OCH2-C2F5,OCF2-C2F5,1-(CH2F)-2-氟乙氧基,1-(CH2Cl)-2-氯乙氧基,1-(CH2Br)-2-溴乙氧基,4-氟丁氧基,4-氯丁氧基,4-溴丁氧基或九氟丁氧基。C1~C6-卤代烷氧基还是,例如,5-氟戊氧基,5-氯戊氧基,5-溴戊氧基,5-碘戊氧基,十一氟戊氧基,6-氟己氧基,6-氯己氧基,6-溴己氧基,6-碘己氧基或十二氟己氧基。
术语"C1~C2-烷硫基"是经硫原子附接的以上定义的C1~C2-烷基。术语"C1~C4-烷硫基"是经硫原子附接的以上定义的C1~C4-烷基。术语"C1~C6-烷硫基"是经硫原子附接的以上定义的C1~C6-烷基。C1~C2-烷硫基是甲硫基或乙硫基。C1~C4-烷硫基还是,例如,n-丙硫基,1-甲基乙硫基(异丙硫基),丁硫基,1-甲基丙硫基(仲-丁硫基),2-甲基丙硫基(异丁硫基)或1,1-二甲基乙硫基(叔-丁硫基)。C1~C6-烷硫基还是,例如,戊硫基,1-甲基丁硫基,2-甲基丁硫基,3-甲基丁硫基,1,1-二甲基丙硫基,1,2-二甲基丙硫基,2,2-二甲基丙硫基,1-乙基丙硫基,己硫基,1-甲基戊硫基,2-甲基戊硫基,3-甲基戊硫基,4-甲基戊硫基,1,1-二甲基丁硫基,1,2-二甲基丁硫基,1,3-二甲基丁硫基,2,2-二甲基丁硫基,2,3-二甲基丁硫基,3,3-二甲基丁硫基,1-乙基丁硫基,2-乙基丁硫基,1,1,2-三甲基丙硫基,1,2,2-三甲基丙硫基,1-乙基-1-甲基丙硫基或1-乙基-2-甲基丙硫基。
术语"C1~C2-卤代烷硫基"是经硫原子附接的以上定义的C1~C2-卤代烷基。术语"C1~C4-卤代烷硫基"是经硫原子附接的以上定义的C1~C4-卤代烷基。术语"C1~C6-卤代烷硫基"是经硫原子附接的以上定义的C1~C6-卤代烷基。C1~C2-卤代烷硫基是,例如,SCH2F,SCHF2,SCF3,SCH2Cl,SCHCl2,SCCl3,氯氟甲硫基,二氯氟甲硫基,氯二氟甲硫基,2-氟乙硫基,2-氯乙硫基,2-溴乙硫基,2-碘乙硫基,2,2-二氟乙硫基,2,2,2-三氟乙硫基,2-氯-2-氟乙硫基,2-氯-2,2-二氟乙硫基,2,2-二氯-2-氟乙硫基,2,2,2-三氯乙硫基或SC2F5。C1~C4-卤代烷硫基还是,例如,2-氟丙硫基,3-氟丙硫基,2,2-二氟丙硫基,2,3-二氟丙硫基,2-氯丙硫基,3-氯丙硫基,2,3-二氯丙硫基,2-溴丙硫基,3-溴丙硫基,3,3,3-三氟丙硫基,3,3,3-三氯丙硫基,SCH2-C2F5,SCF2-C2F5,1-(CH2F)-2-氟乙硫基,1-(CH2Cl)-2-氯乙硫基,1-(CH2Br)-2-溴乙硫基,4-氟丁硫基,4-氯丁硫基,4-溴丁硫基或九氟丁硫基。C1~C6-卤代烷硫基还是,例如,5-氟戊硫基,5-氯戊硫基,5-溴戊硫基,5-碘戊硫基,十一氟戊硫基,6-氟己硫基,6-氯己硫基,6-溴己硫基,6-碘己硫基或十二氟己硫基。
术语"C1~C2-烷基亚硫酰基"是经亚硫酰[S(O)]基团附接的以上定义的C1~C2-烷基。术语"C1~C4-烷基亚硫酰基"是经亚硫酰[S(O)]基团附接的以上定义的C1~C4-烷基。术语"C1~C6-烷基亚硫酰基"是经亚硫酰[S(O)]基团附接的以上定义的C1~C6-烷基。C1~C2-烷基亚硫酰基是甲基亚硫酰基或乙基亚硫酰基。C1~C4-烷基亚硫酰基还是,例如,n-丙基亚硫酰基,1-甲基乙基亚硫酰基(异丙基亚硫酰基),丁基亚硫酰基,1-甲基丙基亚硫酰基(仲-丁基亚硫酰基),2-甲基丙基亚硫酰基(异丁基亚硫酰基)或1,1-二甲基乙基亚硫酰基(叔-丁基亚硫酰基)。C1~C6-烷基亚硫酰基还是,例如,戊基亚硫酰基,1-甲基丁基亚硫酰基,2-甲基丁基亚硫酰基,3-甲基丁基亚硫酰基,1,1-二甲基丙基亚硫酰基,1,2-二甲基丙基亚硫酰基,2,2-二甲基丙基亚硫酰基,1-乙基丙基亚硫酰基,己基亚硫酰基,1-甲基戊基亚硫酰基,2-甲基戊基亚硫酰基,3-甲基戊基亚硫酰基,4-甲基戊基亚硫酰基,1,1-二甲基丁基亚硫酰基,1,2-二甲基丁基亚硫酰基,1,3-二甲基丁基亚硫酰基,2,2-二甲基丁基亚硫酰基,2,3-二甲基丁基亚硫酰基,3,3-二甲基丁基亚硫酰基,1-乙基丁基亚硫酰基,2-乙基丁基亚硫酰基,1,1,2-三甲基丙基亚硫酰基,1,2,2-三甲基丙基亚硫酰基,1-乙基-1-甲基丙基亚硫酰基或1-乙基-2-甲基丙基亚硫酰基。
术语"C1~C2-卤代烷基亚硫酰基"是经亚硫酰[S(O)]基团附接的以上定义的C1~C2-卤代烷基。术语"C1~C4-卤代烷基亚硫酰基"是经亚硫酰[S(O)]基团附接的以上定义的C1~C4-卤代烷基。术语"C1~C6-卤代烷基亚硫酰基"是经亚硫酰[S(O)]基团附接的以上定义的C1~C6-卤代烷基。C1~C2-卤代烷基亚硫酰基是,例如,S(O)CH2F,S(O)CHF2,S(O)CF3,S(O)CH2Cl,S(O)CHCl2,S(O)CCl3,氯氟甲基亚硫酰基,二氯氟甲基亚硫酰基,氯二氟甲基亚硫酰基,2-氟乙基亚硫酰基,2-氯乙基亚硫酰基,2-溴乙基亚硫酰基,2-碘乙基亚硫酰基,2,2-二氟乙基亚硫酰基,2,2,2-三氟乙基亚硫酰基,2-氯-2-氟乙基亚硫酰基,2-氯-2,2-二氟乙基亚硫酰基,2,2-二氯-2-氟乙基亚硫酰基,2,2,2-三氯乙基亚硫酰基或S(O)C2F5。C1~C4-卤代烷基亚硫酰基还是,例如,2-氟丙基亚硫酰基,3-氟丙基亚硫酰基,2,2-二氟丙基亚硫酰基,2,3-二氟丙基亚硫酰基,2-氯丙基亚硫酰基,3-氯丙基亚硫酰基,2,3-二氯丙基亚硫酰基,2-溴丙基亚硫酰基,3-溴丙基亚硫酰基,3,3,3-三氟丙基亚硫酰基,3,3,3-三氯丙基亚硫酰基,S(O)CH2-C2F5,S(O)CF2-C2F5,1-(CH2F)-2-氟乙基亚硫酰基,1-(CH2Cl)-2-氯乙基亚硫酰基,1-(CH2Br)-2-溴乙基亚硫酰基,4-氟丁基亚硫酰基,4-氯丁基亚硫酰基,4-溴丁基亚硫酰基或九氟丁基亚硫酰基。C1~C6-卤代烷基亚硫酰基还是,例如,5-氟戊基亚硫酰基,5-氯戊基亚硫酰基,5-溴戊基亚硫酰基,5-碘戊基亚硫酰基,十一氟戊基亚硫酰基,6-氟己基亚硫酰基,6-氯己基亚硫酰基,6-溴己基亚硫酰基,6-碘己基亚硫酰基或十二氟己基亚硫酰基。
术语"C1~C2-烷基磺酰基"是经磺酰[S(O)2]基团附接的以上定义的C1~C2-烷基。术语"C1~C4-烷基磺酰基"是经磺酰[S(O)2]基团附接的以上定义的C1~C4-烷基。术语"C1~C6-烷基磺酰基"是经磺酰[S(O)2]基团附接的以上定义的C1~C6-烷基。C1~C2-烷基磺酰基是甲基磺酰基或乙基磺酰基。C1~C4-烷基磺酰基还是,例如,n-丙基磺酰基,1-甲基乙基磺酰基(异丙基磺酰基),丁基磺酰基,1-甲基丙基磺酰基(仲-丁基磺酰基),2-甲基丙基磺酰基(异丁基磺酰基)或1,1-二甲基乙基磺酰基(叔-丁基磺酰基)。C1~C6-烷基磺酰基还是,例如,戊基磺酰基,1-甲基丁基磺酰基,2-甲基丁基磺酰基,3-甲基丁基磺酰基,1,1-二甲基丙基磺酰基,1,2-二甲基丙基磺酰基,2,2-二甲基丙基磺酰基,1-乙基丙基磺酰基,己基磺酰基,1-甲基戊基磺酰基,2-甲基戊基磺酰基,3-甲基戊基磺酰基,4-甲基戊基磺酰基,1,1-二甲基丁基磺酰基,1,2-二甲基丁基磺酰基,1,3-二甲基丁基磺酰基,2,2-二甲基丁基磺酰基,2,3-二甲基丁基磺酰基,3,3-二甲基丁基磺酰基,1-乙基丁基磺酰基,2-乙基丁基磺酰基,1,1,2-三甲基丙基磺酰基,1,2,2-三甲基丙基磺酰基,1-乙基-1-甲基丙基磺酰基或1-乙基-2-甲基丙基磺酰基。
术语"C1~C2-卤代烷基磺酰基"是经磺酰[S(O)2]基团附接的以上定义的C1~C2-卤代烷基。术语"C1~C4-卤代烷基磺酰基"是经磺酰[S(O)2]基团附接的以上定义的C1~C4-卤代烷基。术语"C1~C6-卤代烷基磺酰基"是经磺酰[S(O)2]基团附接的以上定义的C1~C6-卤代烷基。C1~C2-卤代烷基磺酰基是,例如,S(O)2CH2F,S(O)2CHF2,S(O)2CF3,S(O)2CH2Cl,S(O)2CHCl2,S(O)2CCl3,氯氟甲基磺酰基,二氯氟甲基磺酰基,氯二氟甲基磺酰基,2-氟乙基磺酰基,2-氯乙基磺酰基,2-溴乙基磺酰基,2-碘乙基磺酰基,2,2-二氟乙基磺酰基,2,2,2-三氟乙基磺酰基,2-氯-2-氟乙基磺酰基,2-氯-2,2-二氟乙基磺酰基,2,2-二氯-2-氟乙基磺酰基,2,2,2-三氯乙基磺酰基或S(O)2C2F5。C1~C4-卤代烷基磺酰基还是,例如,2-氟丙基磺酰基,3-氟丙基磺酰基,2,2-二氟丙基磺酰基,2,3-二氟丙基磺酰基,2-氯丙基磺酰基,3-氯丙基磺酰基,2,3-二氯丙基磺酰基,2-溴丙基磺酰基,3-溴丙基磺酰基,3,3,3-三氟丙基磺酰基,3,3,3-三氯丙基磺酰基,S(O)2CH2-C2F5,S(O)2CF2-C2F5,1-(CH2F)-2-氟乙基磺酰基,1-(CH2Cl)-2-氯乙基磺酰基,1-(CH2Br)-2-溴乙基磺酰基,4-氟丁基磺酰基,4-氯丁基磺酰基,4-溴丁基磺酰基或九氟丁基磺酰基。C1~C6-卤代烷基磺酰基还是,例如,5-氟戊基磺酰基,5-氯戊基磺酰基,5-溴戊基磺酰基,5-碘戊基磺酰基,十一氟戊基磺酰基,6-氟己基磺酰基,6-氯己基磺酰基,6-溴己基磺酰基,6-碘己基磺酰基或十二氟己基磺酰基。
本文所用的术语"作为环成员含有选自N,O,S,NO,SO和SO2的1,2或3个杂原子或杂原子基团(如果杂环的1或2或至多3个杂原子被氧化)的3-,4-,5-,6-,7-,8-,9-,10-,11-或12-元饱和的,部分不饱和的或芳族杂环"指称饱和,部分不饱和的单环自由基,单环自由基或芳族。杂环自由基可经碳环成员或经氮环成员附接于分子残基。
杂芳族环可为单杂芳族或双环杂芳族环系统。可提供的例示单环杂芳族环系统包括,但未限制于吡啶,嘧啶,吡嗪,哒嗪,1,3,5-三嗪,1,2,4-三嗪,吡咯,吡唑,咪唑,1,2,4-三唑,1,2,3-三唑,四唑,呋喃,噁唑,异噁唑,1,2,4-噁二唑,1,3,4-噁二唑,1,2,3-噁二唑,噻吩,噻唑,异噻唑,1,3,4-噻二唑,1,2,4-噻二唑,1,2,3-噻二唑。例示双环杂芳族环系统可提供的包括,但未限制于喹啉,吲哚,苯并呋喃,苯并噻吩,苯并咪唑,苯并噁唑,苯并异噁唑,苯并噻唑,苯并异噻唑。
3-,4-,5-,6-,7-,8-,9-,10-,11-或12-元饱和的杂环的例包括:氧杂环丙烷基,氮杂环丙烷基,氮杂环丁烷基,2-四氢呋喃基,3-四氢呋喃基,2-四氢噻吩基,3-四氢噻吩基,2-吡咯烷基,3-吡咯烷基,3-吡唑烷基,4-吡唑烷基,5-吡唑烷基,2-咪唑烷基,4-咪唑烷基,2-噁唑烷基,4-噁唑烷基,5-噁唑烷基,3-异噁唑烷基,4-异噁唑烷基,5-异噁唑烷基,2-噻唑烷基,4-噻唑烷基,5-噻唑烷基,3-异噻唑烷基,4-异噻唑烷基,5-异噻唑烷基,1,2,4-噁二唑烷-3-基,1,2,4-噁二唑烷-5-基,1,2,4-噻二唑烷-3-基,1,2,4-噻二唑烷-5-基,1,2,4-三唑烷-3-基,1,3,4-噁二唑烷-2-基,1,3,4-噻二唑烷-2-基,1,3,4-三唑烷-2-基,2-四氢吡喃基,4-四氢吡喃基,1,3-二噁烷-5-基,1,4-二噁烷-2-基,2-哌啶基,3-哌啶基,4-哌啶基,3-六氢哒嗪基,4-六氢哒嗪基,2-六氢嘧啶基,4-六氢嘧啶基,5-六氢嘧啶基,2-哌嗪基,1,3,5-六氢三嗪-2-基和1,2,4-六氢三嗪-3-基,2-吗啉基,3-吗啉基,2-硫代吗啉基,3-硫代吗啉基,1-氧代硫代吗啉-2-基,1-氧代硫代吗啉-3-基,1,1-二氧代硫代吗啉-2-基,1,1-二氧代硫代吗啉-3-基,六氢氮杂环庚三烯-1-,-2-,-3-或-4-基,六氢氧杂环庚三烯基,六氢-1,3-二氮杂环庚三烯基,六氢-1,4-二氮杂环庚三烯基,六氢-1,3-氧杂氮杂环庚三烯基,六氢-1,4-氧杂氮杂环庚三烯基,六氢-1,3-二氧杂环庚三烯基,六氢-1,4-二氧杂环庚三烯基等。
3-,4-,5-,6-或7-元部分不饱和的杂环的例包括:2,3-二氢呋喃-2-基,2,3-二氢呋喃-3-基,2,4-二氢呋喃-2-基,2,4-二氢呋喃-3-基,2,3-二氢噻吩-2-基,2,3-二氢噻吩-3-基,2,4-二氢噻吩-2-基,2,4-二氢噻吩-3-基,2-吡咯啉-2-基,2-吡咯啉-3-基,3-吡咯啉-2-基,3-吡咯啉-3-基,2-异噁唑啉-3-基,3-异噁唑啉-3-基,4-异噁唑啉-3-基,2-异噁唑啉-4-基,3-异噁唑啉-4-基,4-异噁唑啉-4-基,2-异噁唑啉-5-基,3-异噁唑啉-5-基,4-异噁唑啉-5-基,2-异噻唑啉-3-基,3-异噻唑啉-3-基,4-异噻唑啉-3-基,2-异噻唑啉-4-基,3-异噻唑啉-4-基,4-异噻唑啉-4-基,2-异噻唑啉-5-基,3-异噻唑啉-5-基,4-异噻唑啉-5-基,2,3-二氢吡唑-1-基,2,3-二氢吡唑-2-基,2,3-二氢吡唑-3-基,2,3-二氢吡唑-4-基,2,3-二氢吡唑-5-基,3,4-二氢吡唑-1-基,3,4-二氢吡唑-3-基,3,4-二氢吡唑-4-基,3,4-二氢吡唑-5-基,4,5-二氢吡唑-1-基,4,5-二氢吡唑-3-基,4,5-二氢吡唑-4-基,4,5-二氢吡唑-5-基,2,3-二氢噁唑-2-基,2,3-二氢噁唑-3-基,2,3-二氢噁唑-4-基,2,3-二氢噁唑-5-基,3,4-二氢噁唑-2-基,3,4-二氢噁唑-3-基,3,4-二氢噁唑-4-基,3,4-二氢噁唑-5-基,3,4-二氢噁唑-2-基,3,4-二氢噁唑-3-基,3,4-二氢噁唑-4-基,2-,3-,4-,5-或6-二-或四氢吡啶基,3-二-或四氢哒嗪基,4-二-或四氢哒嗪基,2-二-或四氢嘧啶基,4-二-或四氢嘧啶基,5-二-或四氢嘧啶基,二-或四氢吡嗪基,1,3,5-二-或四氢三嗪-2-基,1,2,4-二-或四氢三嗪-3-基,2,3,4,5-四氢[1H]氮杂环庚三烯-1-,-2-,-3-,-4-,-5-,-6-或-7-基,3,4,5,6-四氢[2H]氮杂环庚三烯-2-,-3-,-4-,-5-,-6-或-7-基,2,3,4,7-四氢[1H]氮杂环庚三烯-1-,-2-,-3-,-4-,-5-,-6-或-7-基,2,3,6,7-四氢[1H]氮杂环庚三烯-1-,-2-,-3-,-4-,-5-,-6-或-7-基,四氢氧杂环庚三烯基,诸如2,3,4,5-四氢[1H]氧杂环庚三烯-2-,-3-,-4-,-5,-6-或-7-基,2,3,4,7-四氢[1H]氧杂环庚三烯-2-,-3-,-4-,-5-,-6-或-7-基,2,3,6,7-四氢[1H]氧杂环庚三烯-2-,-3-,-4-,-5-,-6-或-7-基,四氢-1,3-二氮杂环庚三烯基,四氢-1,4-二氮杂环庚三烯基,四氢-1,3-氧杂氮杂环庚三烯基,四氢-1,4-氧杂氮杂环庚三烯基,四氢-1,3-二氧杂环庚三烯基和四氢-1,4-二氧杂环庚三烯基。
3-,4-,5-,6-或7-元芳族杂环是5-或6-元芳族杂环(hetaryl)。例是:2-呋喃基,3-呋喃基,2-噻吩基,3-噻吩基,2-吡咯基,3-吡咯基,3-吡唑基,4-吡唑基,5-吡唑基,2-噁唑基,4-噁唑基,5-噁唑基,2-噻唑基,4-噻唑基,5-噻唑基,2-咪唑基,4-咪唑基,1,3,4-三唑-2-基,2-吡啶基,3-吡啶基,4-吡啶基,3-哒嗪基,4-哒嗪基,2-嘧啶基,4-嘧啶基,5-嘧啶基和2-吡嗪基。
以下注释涉及式I的化合物的变量的优选的实施方式,尤其有关它们的取代基X,U,V,R1,R2,R3U,R4,R5,R6,R7,R8,R9,R10,R11,R12,R13,R14,R15,m,n,o和p,本发明的用途和方法及本发明的组合物的特征以它们的自身及,尤其是,以每可能的彼此组合有效。
在优选的实施方式中,X是S(=O)m,而m是0,1或2。优选m是0或1和更优选m是0。
在优选的实施方式中,n是0,1或2。优选地,n是1,2和更优选,n是2。
在优选的实施方式中,p是1或2。优选地,p是1。
优选地,U是5-~12-元单环或双环杂芳族环-系统,其可含有1~4个选自O,S,N的杂原子,其中杂芳族环可被1~4个取代基V取代,其具有在下文对V叙述的各优选。
优选地,U是5-~10-元单环或双环杂芳族环-系统,其可含有1~4个选自O,S,N的杂原子,其中杂芳族环可被1~4个取代基V取代,其具有在下文对V叙述的各优选。
更优选地,U是选自下列的5-~10-元杂芳族环-系统:吡啶,嘧啶,吡嗪,哒嗪,1,3,5-三嗪,喹啉,1H-吲哚,1H-苯并咪唑,苯并噻唑,苯并噁唑,苯并呋喃,苯并噻吩,1H-吡咯,1H-吡唑,1H-1,2,4-三唑,1H-咪唑,1H-1,2,3-三唑,1H-四唑,噻吩,噻唑,1,3,4-噻二唑,呋喃,噁唑,异噁唑,1,2,4-噁二唑,1,3,4-噁二唑,其中杂芳族环可被1~4个取代基V取代,其具有在下文对V叙述的各优选。更优选地,U是5-元杂芳族环,其选自:1H-吡咯,1H-吡唑,1H-1,2,4-三唑,1H-咪唑,1H-1,2,3-三唑,1H-四唑,噻吩,噻唑,1,3,4-噻二唑,呋喃,噁唑,异噁唑,1,2,4-噁二唑,1,3,4-噁二唑,其中杂芳族环可被1~4个取代基V取代,其具有在下文对V叙述的各优选。甚至更优选,U是5-元杂芳族环,其选自:1H-吡咯,1H-吡唑,1H-1,2,4-三唑,1H-咪唑,1H-1,2,3-三唑,1H-四唑,噻吩,噻唑,1,3,4-噻二唑,呋喃,噁唑,异噁唑,1,2,4-噁二唑,1,3,4-噁二唑,其中杂芳族环优选至少被下列基团取代:卤素,CN,C1~C6-烷基,C1~C6-卤代烷基,可被卤素原子取代的C3~C6-环烷基-C1~C3-烷基,C2~C6-烯基,C2~C6-卤代烯基,C2~C6-炔基,C2~C6-卤代炔基,C3~C6-环烷基,C3~C6-卤代环烷基,C1~C6-烷氧基,C1~C6-卤代烷氧基甚至更优选,U是5-元杂芳族环,其选自:1H-吡唑,1H-1,2,4-三唑,1H-咪唑,1H-四唑,异噁唑,噻唑,1,3,4-噻二唑,其中杂芳族环优选至少被下列基团取代:CN,叔-丁基,CF3或卤素优选是Cl。最优选地,U是5-元杂芳族环,其选自:1H-吡唑,1H-1,2,4-三唑,1,3,4-噻二唑,其中杂芳族环被选自下列的基团之一取代:Cl,CN,叔-丁基和CF3。
优选地,V独立地选自:卤素,C1~C6-烷基,C1~C6-卤代烷基,可被卤素原子取代的C3~C6-环烷基-C1~C3-烷基,C2~C6-烯基,C2~C6-卤代烯基,C2~C6-炔基,C2~C6-卤代炔基,C3~C6-环烷基,C3~C6-卤代环烷基,C1~C6-烷氧基,C1~C6-卤代烷氧基,C(=O)R4,C(=S)R4,S(O)oR10,CN,NO2,氨基,其可被C1~C4-烷基或C1~C4-酰基取代。
优选地,V独立地选自:卤素,C1~C6-烷基,C1~C6-卤代烷基,可被卤素原子取代的C3~C6-环烷基-C1~C3-烷基,C2~C6-烯基,C2~C6-卤代烯基,C2~C6-炔基,C2~C6-卤代炔基,C3~C6-环烷基,C3~C6-卤代环烷基,C1~C6-烷氧基,C1~C6-卤代烷氧基,C1~C6-烷硫基,C1~C6-卤代烷硫基,C1~C6-烷基亚硫酰基,C1~C6-卤代烷基亚硫酰基,C1~C6-烷基磺酰基,C1~C6-卤代烷基磺酰基,C(=O)R4,C(=S)R4,CN,NO2,氨基,其可被C1~C4-烷基或C1~C4-酰基取代。更优选V独立地选自:卤素,C1~C6-烷基,C1~C6-卤代烷基,可被卤素原子取代的C3~C6-环烷基-C1~C3-烷基,C2~C6-烯基,C2~C6-卤代烯基,C2~C6-炔基,C2~C6-卤代炔基,C3~C6-环烷基,C3~C6-卤代环烷基,C1~C6-烷氧基,C1~C6-卤代烷氧基,CN。
更优选地,V独立地选自:卤素,C1~C6-烷基,C1~C6-卤代烷基和CN。
甚至更优选,V独立地选自:叔-丁基,CN,CF3和卤素尤其是Cl。最优选地,V是CF3。
优选地,R1,R2彼此独立地选自:氢,卤素,C1~C6-烷基,其可被下列基团取代:卤素,C1~C4-烷氧基,C1~C4-烷硫基,C1~C4-烷基亚硫酰基,C1~C6-烷基磺酰基,CN,C(=O)R4,OC(=O)R4,N(C1~C3-烷基)2或OH,C2~C6-烯基,C2~C6-卤代烯基,C2~C6-炔基,C2~C6-卤代炔基,C3~C6-环烷基,C3~C6-卤代环烷基,可被卤素原子取代的C3~C6-环烷基-C1~C3-烷基,CN,C(=O)R7,C(=S)R7,C(R11)=NR12,C(R11)=N-OR12或R1和R2可与和它们键合的碳原子一起形成C3~C6-环烷基,C=C(R5)R6或C=N-OR5。
更优选地,R1,R2独立地选自:氢,卤素,C1~C4-烷基,CN,C(=O)-C1~C4-烷基,C(=0)-C1~C4-烷氧基,C(=O)-NR8R9,C(=S)-NR8R9。甚至更优选,R1,R2独立地选自:氢,C1~C4-烷基,Cl,CN,C(=O)-Me,C(=O)-Et,C(=O)-OMe,C(=O)-OEt,C(=O)-NH2,C(=O)-NMeH,C(=O)-NetH,C(=O)-NMe2,C(=O)-NMeEt,C(=O)-NEt2,C(=S)-NH2,C(=S)-NMeH,C(=S)-NEtH,C(=S)-NMe2,C(=S)-NMeEt,C(=S)-NEt2。
甚至更优选,R1和R2是选自下列的R1的各组合:H,CN,C(=O)-Me,C(=O)-Et,C(=O)-NH2,C(=O)-NMeH,C(=O)-NEtH,C(=O)-NMe2,C(=O)-NMeEt,C(=O)-NEt2,C(=S)-NH2,C(=S)-NMeH,C(=S)-NEtH,C(=S)-NMe2,C(=S)-NMeEt和C(=S)-NEt2,而R2选自:氢,Cl和C1~C4-烷基尤其是Me或Et。
优选R3U选自:C1~C10-卤代烷基,C2~C6-卤代烯基,C3~C6-卤代炔基,C3~C6-卤代环烷基和C3~C6-卤代环烯基,且其中至少一个卤素是氟。
优选地,R3U是C1~C4-卤代烷基,C2~C4-卤代烯基和C3~C4-卤代炔基其中卤素是氟或额外地氯。
更优选R3U是C1~C4-,例如C1~C2氟代烷基。也优选全氟化的基团R3U。例如,R3U是CF3,CF2H,CH2F,CF2CF3或CF2CF2CF3。甚至更优选,R3U是CF3或CF2H。最优选地,R3U是CF3。
当在文本使用时,取代基的下列标记定义如下:
| Me | =甲基, |
| Et | =乙基, |
| Pr | =丙基, |
| i-Pr | =异丙基, |
| Bu | =n-丁基, |
| i-Bu | =异丁基, |
| s-Bu | =仲丁基, |
| t-Bu | =叔-丁基, |
| c-Pr | =环丙基, |
| Pen | =戊基, |
| c-Pen | =环戊基, |
| c-Hex | =环己基, |
| Ac | =乙酰基, |
| Ph | =苯基, |
此外,下述的标记表示例如各以下所述含义:
5-CF3是在第5位的三氟甲基取代基;
3-Cl-5-CF3是在第3位的氯原子和在第5位的三氟甲基取代基;
2,6-(Cl)2是在第2和6位的氯原子取代基。
通过E1~E7代表的取代基表示相应下述的结构:
根据本发明的通式I的化合物的例是各种以上提及的取代基的组合。
特别是,优选的本发明的实施方式由以下表1~9中描绘的各例构成。
表1:描述具有以下式中代表的1-xxxx型化合物号的例:
化合物号1-01~1-0145:m=0
化合物号1-01~1-0145的类似物是化合物号1-1~1-145,其中变量具有相同的含义,除了m是1代替0之外。
表2:描述具有以下式中代表的2-xxxx型化合物号的例:
化合物号2-01~2-0113;m=0
| No. | 位置 | V | R1 | R2 | R3U | n |
| 2-01. | 2 | 4,6-(Cl)2 | H | H | CF3 | 0 |
| 2-02. | 2 | 4,6-(Cl)2 | H | H | CF2H | 0 |
| 2-03. | 2 | 4,6-(Cl)2 | H | H | CF3 | 1 |
| 2-04. | 2 | 4,6-(Cl)2 | H | H | CF2H | 1 |
| 2-05. | 2 | 4,6-(Cl)2 | H | H | CF3 | 2 |
| 2-06. | 2 | 4,6-(Cl)2 | H | H | CF2H | 2 |
| 2-07. | 2 | 4-CF3 | H | H | CF3 | 2 |
| 2-08. | 2 | 4-CF3 | H | H | CF2H | 2 |
| 2-09 | 2 | 4-CF3 | COOMe | H | CF3 | 2 |
| 2-010. | 2 | 4-CF3 | COOMe | H | CF2H | 2 |
| 2-011 | 2 | 4-CF3 | COOEt | H | CF3 | 2 |
| 2-012. | 2 | 4-CF3 | COOEt | H | CF2H | 2 |
| 2-013. | 2 | 4-CF3 | CN | H | CF3 | 2 |
| 2-014. | 2 | 4-CF3 | CN | H | CF2H | 2 |
| 2-015. | 4 | 2,6-(Cl)2 | H | H | CF3 | 0 |
| 2-016. | 4 | 2,6-(Cl)2 | H | H | CF2H | 0 |
| 2-017. | 4 | 2,6-(Cl)2 | H | H | CF3 | 1 |
| 2-018. | 4 | 2,6-(Cl)2 | H | H | CF2H | 1 |
| 2-019. | 4 | 2,6-(Cl)2 | H | H | CF3 | 2 |
| 2-020. | 4 | 2,6-(Cl)2 | H | H | CF2H | 2 |
| 2-021. | 4 | 2-CF3 | H | H | CF3 | 2 |
| 2-022. | 4 | 2-CF3 | H | H | CF2H | 2 |
| No. | 位置 | V | R1 | R2 | R3U | n |
| 2-023. | 4 | 2-CF3 | COOMe | H | CF3 | 2 |
| 2-024. | 4 | 2-CF3 | COOMe | H | CF2H | 2 |
| 2-025. | 4 | 2-CF3 | COOEt | H | CF3 | 2 |
| 2-026. | 4 | 2-CF3 | COOEt | H | CF2H | 2 |
| 2-027. | 4 | 2-CF3 | CN | H | CF3 | 2 |
| 2-028. | 4 | 2-CF3 | CN | H | CF2H | 2 |
| 2-029. | 4 | 6-CF3 | H | H | CF3 | 2 |
| 2-030. | 4 | 6-CF3 | H | H | CF2H | 2 |
| 2-031. | 4 | 6-CF3 | COOMe | H | CF3 | 2 |
| 2-032. | 4 | 6-CF3 | COOMe | H | CF2H | 2 |
| 2-033. | 4 | 6-CF3 | COOEt | H | CF3 | 2 |
| 2-034. | 4 | 6-CF3 | COOEt | H | CF2H | 2 |
| 2-035. | 4 | 6-CF3 | CN | H | CF3 | 2 |
| 2-036. | 4 | 6-CF3 | CN | H | CF2H | 2 |
| 2-037. | 5 | 2-CF3 | H | H | CF3 | 0 |
| 2-038. | 5 | 2-CF3 | H | H | CF2H | 0 |
| 2-039. | 5 | 2-CF3 | H | H | CF3 | 1 |
| 2-040. | 5 | 2-CF3 | H | H | CF2H | 1 |
| 2-041. | 5 | 2-CF3 | H | H | CF3 | 2 |
| 2-042. | 5 | 2-CF3 | H | H | CF2H | 2 |
| 2-043. | 5 | 2-CF3 | Me | H | CF3 | 2 |
| 2-044. | 5 | 2-CF3 | Me | H | CF2H | 2 |
| 2-045. | 5 | 2-CF3 | Me | Me | CF3 | 2 |
| 2-046. | 5 | 2-CF3 | Me | Me | CF2H | 2 |
| 2-047. | 5 | 2-CF3 | Et | H | CF3 | 2 |
| 2-048. | 5 | 2-CF3 | Et | H | CF2H | 2 |
| 2-049. | 5 | 2-CF3 | i-Pr | H | CF3 | 2 |
| 2-050. | 5 | 2-CF3 | i-Pr | H | CF2H | 2 |
| 2-051. | 5 | 2-CF3 | Pr | H | CF3 | 2 |
| 2-052. | 5 | 2-CF3 | Pr | H | CF2H | 2 |
| 2-053. | 5 | 2-CF3 | s-Bu | H | CF3 | 2 |
| 2-054. | 5 | 2-CF3 | s-Bu | H | CF2H | 2 |
| 2-055. | 5 | 2-CF3 | i-Bu | H | CF3 | 2 |
| 2-056. | 5 | 2-CF3 | i-Bu | H | CF2H | 2 |
| No. | 位置 | V | R1 | R2 | R3U | n |
| 2-057. | 5 | 2-CF3 | Bu | H | CF3 | 2 |
| 2-058. | 5 | 2-CF3 | Bu | H | CF2H | 2 |
| 2-059. | 5 | 2-CF3 | CH2-c-Pr | H | CF3 | 2 |
| 2-060. | 5 | 2-CF3 | CH2-c-Pr | H | CF2H | 2 |
| 2-061. | 5 | 2-CF3 | CH2CH=CH2 | H | CF3 | 2 |
| 2-062. | 5 | 2-CF3 | CH2CH=CH2 | H | CF2H | 2 |
| 2-063. | 5 | 2-CF3 | CH2C=CH | H | CF3 | 2 |
| 2-064. | 5 | 2-CF3 | CH2C=CH | H | CF2H | 2 |
| 2-065. | 5 | 2-CF3 | COOMe | H | CF3 | 2 |
| 2-066. | 5 | 2-CF3 | COOMe | H | CF2H | 2 |
| 2-067. | 5 | 2-CF3 | CONHEt | H | CF3 | 2 |
| 2-068. | 5 | 2-CF3 | CONHEt | H | CF2H | 2 |
| 2-069. | 5 | 2-CF3 | CSNHMe | H | CF3 | 2 |
| 2-070. | 5 | 2-CF3 | CSNHMe | H | CF2H | 2 |
| 2-071. | 5 | 2-CF3 | F | H | CF3 | 2 |
| 2-072. | 5 | 2-CF3 | F | H | CF2H | 2 |
| 2-073. | 5 | 2-CF3 | F | F | CF3 | 2 |
| 2-074. | 5 | 2-CF3 | F | F | CF2H | 2 |
| 2-075. | 5 | 2-CF3 | Cl | H | CF3 | 2 |
| 2-076. | 5 | 2-CF3 | Cl | H | CF2H | 2 |
| 2-077. | 5 | 2-CF3 | Cl | Cl | CF3 | 2 |
| 2-078. | 5 | 2-CF3 | Cl | Cl | CF2H | 2 |
| 2-079. | 5 | 2-CF3 | H | H | CF2CF3 | 0 |
| 2-080. | 5 | 2-CF3 | H | H | CF2CF3 | 1 |
| 2-081. | 5 | 2-CF3 | H | H | CF2CF3 | 2 |
| 2-082. | 5 | 2-CF3-4-Me | H | H | CF3 | 0 |
| 2-083. | 5 | 2-CF3-4-Me | H | H | CF2H | 0 |
| 2-084. | 5 | 2-CF3-4-Me | H | H | CF3 | 1 |
| 2-085. | 5 | 2-CF3-4-Me | H | H | CF2H | 1 |
| 2-086. | 5 | 2-CF3-4-Me | H | H | CF3 | 2 |
| 2-087. | 5 | 2-CF3-4-Me | H | H | CF2H | 2 |
| 2-088. | 5 | 2-CF3-4-Me | Me | H | CF3 | 2 |
| 2-089. | 5 | 2-CF3-4-Me | Me | H | CF2H | 2 |
| 2-090. | 5 | 2-SCF3-4-Me | H | H | CF3 | 0 |
| No. | 位置 | V | R1 | R2 | R3U | n |
| 2-091. | 5 | 2-SCF3-4-Me | H | H | CF2H | 0 |
| 2-092. | 5 | 2-SCF3-4-Me | H | H | CF3 | 1 |
| 2-093. | 5 | 2-SCF3-4-Me | H | H | CF2H | 1 |
| 2-094. | 5 | 2-SCF3-4-Me | H | H | CF3 | 2 |
| 2-095. | 5 | 2-SCF3-4-Me | H | H | CF2H | 2 |
| 2-096. | 5 | 2-SCF3-4-Me | Me | H | CF3 | 2 |
| 2-097. | 5 | 2-SCF3-4-Me | Me | H | CF2H | 2 |
| 2-098. | 5 | 2-c-Pr | H | H | CF3 | 0 |
| 2-099. | 5 | 2-c-Pr | H | H | CF2H | 0 |
| 2-0100. | 5 | 2-c-Pr | H | H | CF3 | 1 |
| 2-0101. | 5 | 2-c-Pr | H | H | CF2H | 1 |
| 2-0102. | 5 | 2-c-Pr | H | H | CF3 | 2 |
| 2-0103. | 5 | 2-c-Pr | H | H | CF2H | 2 |
| 2-0104. | 5 | 2-c-Pr | Me | H | CF3 | 2 |
| 2-0105. | 5 | 2-c-Pr | Me | H | CF2H | 2 |
| 2-0106. | 5 | 2-t-Bu | H | H | CF3 | 0 |
| 2-0107. | 5 | 2-t-Bu | H | H | CF2H | 0 |
| 2-0108. | 5 | 2-t-Bu | H | H | CF3 | 1 |
| 2-0109. | 5 | 2-t-Bu | H | H | CF2H | 1 |
| 2-0110. | 5 | 2-t-Bu | H | H | CF3 | 2 |
| 2-0111. | 5 | 2-t-Bu | H | H | CF2H | 2 |
| 2-0112. | 5 | 2-t-Bu | Me | H | CF3 | 2 |
| 2-0113. | 5 | 2-t-Bu | Me | H | CF2H | 2 |
化合物号2-01~2-0113的类似物是化合物号2-01~2-113,其中变量具有相同的含义,除了m是1代替0之外。
表3:描述具有以下式中代表的3-xxxx型的化合物号的例:
化合物号3-01~3-062:m=0
化合物号3-01~3-062的类似物是化合物号3-01~3-62,其中变量具有相同的含义,除了m是1代替0之外。
表4描述具有以下式中代表的4-xxxx型的化合物号的例:
化合物号4-01~4-0487:m=0
化合物号4-01~4-0487的类似物是化合物号4-01~4-487,其中变量具有相同的含义,除了m是1代替0之外。
表5描述具有以下式中代表的5-xxxx型的化合物号的例:
化合物号5-01~5-0973:m=0
在以上表的模拟物中,进一步例是化合物号5-0487~5-0973,其中R3U是CF2H和全部其余变量具有与表5各行中代表的相同的含义。
化合物号5-01~5-0973的类似物是化合物号5-01~5-973,其中变量具有相同的含义,除了m是1代替0之外。
表6描述具有以下式中代表的6-xxxx型的化合物号的例:
化合物号6-01~6-0267:m=0
在以上表的模拟物中,进一步例是化合物号6-0134~6-0267,其中R3U是CF2H和全部其余变量具有与表6各行中代表的相同的含义。
化合物号6-01~6-0267的类似物是化合物号6-1~6-267,其中变量具有相同的含义,除了m是1代替0之外。
表7:描述具有以下式中代表的7-xxxx型的化合物号的例:
化合物号7-01~7-0207
在以上表的模拟物中,进一步例是化合物号7-0104~7-0207,其中R3U是CF2H和全部其余变量具有与表7各行中代表的相同的含义。
化合物号7-01~7-0207的类似物是化合物号7-01~7-207,其中变量具有相同的含义,除了m是1代替0之外。
表8:描述具有以下式中代表的8-xxxx型的化合物号的例:
化合物号8-01~8-0245:m=0
| No. | Y1 | Y2 | Y3 | Y4 | R1 | R2 | R3U | n |
| 8-01. | C-H | C-NO2 | C-H | C-H | H | H | CF3 | 0 |
| 8-02. | C-H | C-NO2 | C-H | C-H | H | H | CF3 | 1 |
| 8-03. | C-H | C-NO2 | C-H | C-H | H | H | CF3 | 2 |
| 8-04. | C-Me | C-Ac | C-Me | C-H | H | H | CF3 | 0 |
| B-05. | C-Me | C-Ac | C-Me | C-H | H | H | CF3 | 1 |
| 8-06. | C-Me | C-Ac | C-Me | C-H | H | H | CF3 | 2 |
| 8-07. | C-H | N | C-CF3 | C-H | H | H | CF3 | 0 |
| 8-08. | C-H | N | C-CF3 | C-H | H | H | CF3 | 1 |
| 8-09. | C-H | N | C-CF3 | C-H | H | H | CF3 | 2 |
| 8-010. | C-H | N | C-CF3 | C-H | Me | H | CF3 | 0 |
| 8-011. | C-H | N | C-CF3 | C-H | Me | H | CF3 | 1 |
| 8-012. | C-H | N | C-CF3 | C-H | Me | H | CF3 | 2 |
| 8-013. | C-H | N | C-CF3 | C-H | Et | H | CF3 | 0 |
| 8-014. | C-H | N | C-CF3 | C-H | Et | H | CF3 | 1 |
| 8-015. | C-H | N | C-CF3 | C-H | Et | H | CF3 | 2 |
| 8-016. | C-H | N | C-CF3 | C H | i-Pr | H | CF3 | 0 |
| 8-017. | C-H | N | C-CF3 | C-H | i-Pr | H | CF3 | 1 |
| 8-018. | C-H | N | C-CF3 | C-H | i-Pr | H | CF3 | 2 |
| 8-019. | C-H | N | C-CF3 | C-H | c-Pr | H | CF3 | 0 |
| 8-020. | C-H | N | C-CF3 | C-H | c-Pr | H | CF3 | 1 |
| 8-021. | C-H | N | C-CF3 | C-H | c-Pr | H | CF3 | 2 |
| 8-022. | C-H | N | C-CF3 | C-H | Pr | H | CF3 | 0 |
| 8-023. | C-H | N | C-CF3 | C-H | Pr | H | CF3 | 1 |
| 8-024. | C-H | N | C-CF3 | C-H | Pr | H | CF3 | 2 |
| 8-025. | C-H | N | C-CF3 | C-H | s-Bu | H | CF3 | 0 |
| No. | Y1 | Y2 | Y3 | Y4 | R1 | R2 | R3U | n |
| 8-026. | C-H | N | C-CF3 | C-H | s-Bu | H | CF3 | 1 |
| 8-027. | C-H | N | C-CF3 | C-H | s-Bu | H | CF3 | 2 |
| 8-028. | C-H | N | C-CF3 | C-H | i-Bu | H | CF3 | 0 |
| 8-029. | C-H | N | C-CF3 | C-H | i-Bu | H | CF3 | 1 |
| 8-030. | C-H | N | C-CF3 | C-H | i-Bu | H | CF3 | 2 |
| 8-031. | C-H | N | C-CF3 | C-H | Bu | H | CF3 | 0 |
| 8-032. | C-H | N | C-CF3 | C-H | Bu | H | CF3 | 1 |
| 8-033. | C-H | N | C-CF3 | C-H | Bu | H | CF3 | 2 |
| 8-034. | C-H | N | C-CF3 | C-H | 2-Pen | H | CF3 | 0 |
| 8-035. | C-H | N | C-CF3 | C-H | 2-Pen | H | CF3 | 1 |
| 8-036. | C-H | N | C-CF3 | C-H | 2-Pen | H | CF3 | 2 |
| 8-037. | C-H | N | C-CF3 | C-H | 3-Pen | H | CF3 | 0 |
| 8-038. | C-H | N | C-CF3 | C-H | 3-Pen | H | CF3 | 1 |
| 8-039. | C-H | N | C-CF3 | C-H | 3-Pen | H | CF3 | 2 |
| 8-040. | C-H | N | C-CF3 | C-H | c-Pen | H | CF3 | 0 |
| 8-041. | C-H | N | C-CF3 | C-H | c-Pen | H | CF3 | 1 |
| 8-042. | C-H | N | C-CF3 | C-H | c-pen | H | CF3 | 2 |
| 8-043. | C-H | N | C-CF3 | C-H | c-Hex | H | CF3 | 0 |
| 8-044. | C-H | N | C-CF3 | C-H | c-Hex | H | CF3 | 1 |
| 8-045. | C-H | N | C-CF3 | C-H | c-Hex | H | CF3 | 2 |
| 8-046. | C-H | N | C-CF3 | C-H | CN | H | CF3 | 0 |
| 8-047. | C-H | N | C-CF3 | C-H | CN | H | CF3 | 1 |
| 8-048. | C-H | N | C-CF3 | C-H | CN | H | CF3 | 2 |
| 8-049. | C-H | N | C-CF3 | C-H | COOMe | H | CF3 | 0 |
| 8-050. | C-H | N | C-CF3 | C-H | COOMe | H | CF3 | 1 |
| 8-051. | C-H | N | C-CF3 | C-H | COOMe | H | CF3 | 2 |
| 8-052. | C-H | N | C-CF3 | C-H | COOEt | H | CF3 | 0 |
| 8-053. | C-H | N | C-CF3 | C-H | COOEt | H | CF3 | 1 |
| 8-054. | C-H | N | C-CF3 | C-H | COOEt | H | CF3 | 2 |
| 8-055. | N | N | C-CF3 | C-H | H | H | CF3 | 0 |
| 8-056. | N | N | C-CF3 | C-H | H | H | CF3 | 1 |
| 8-057. | N | N | C-CF3 | C-H | H | H | CF3 | 2 |
| 8-058. | N | N | C-CF3 | N | H | H | CF3 | 0 |
| 8-059. | N | N | C-CF3 | N | H | H | CF3 | 1 |
| 8-060. | N | N | C-CF3 | N | H | H | CF3 | 2 |
| No. | Y1 | Y2 | Y3 | Y4 | R1 | R2 | R3U | n |
| 8-061. | N | N | C-CF3 | N | Me | H | CF3 | 0 |
| 8-062. | N | N | C-CF3 | N | Me | H | CF3 | 1 |
| 8-063. | N | N | C-CF3 | N | Me | H | CF3 | 2 |
| 8-064. | N | N | C-CF3 | N | Et | H | CF3 | 0 |
| 8-065. | N | N | C-CF3 | N | Et | H | CF3 | 1 |
| 8-066. | N | N | C-CF3 | N | Et | H | CF3 | 2 |
| 8-067. | N | N | C-CF3 | N | i-Pr | H | CF3 | 0 |
| 8-068. | N | N | C-CF3 | N | i-Pr | H | CF3 | 1 |
| 8-069. | N | N | C-CF3 | N | i-Pr | H | CF3 | 2 |
| 8-070. | N | N | C-CF3 | N | c-Pr | H | CF3 | 0 |
| 8-071. | N | N | C-CF3 | N | c-Pr | H | CF3 | 1 |
| 8-072. | N | N | C-CF3 | N | c-Pr | H | CF3 | 2 |
| 8-073. | N | N | C-CF3 | N | Pr | H | CF3 | 0 |
| 8-074. | N | N | C-CF3 | N | Pr | H | CF3 | 1 |
| 8-075. | N | N | C-CF3 | N | Pr | H | CF3 | 2 |
| 8-076. | N | N | C-CF3 | N | s-Bu | H | CF3 | 0 |
| 8-077. | N | N | C-CF3 | N | s-Bu | H | CF3 | 1 |
| 8-078. | N | N | C-CF3 | N | s-Bu | H | CF3 | 2 |
| 8-079. | N | N | C-CF3 | N | i-Bu | H | CF3 | 0 |
| 8-080. | N | N | C-CF3 | N | i-Bu | H | CF3 | 1 |
| 8-081. | N | N | C-CF3 | N | i-Bu | H | CF3 | 2 |
| 8-082. | N | N | C-CF3 | N | Bu | H | CF3 | 0 |
| 8-083. | N | N | C-CF3 | N | Bu | H | CF3 | |
| 8-084. | N | N | C-CF3 | N | Bu | H | CF3 | 2 |
| 8-085. | N | N | C-CF3 | N | 2-Pen | H | CF3 | 0 |
| 8-086. | N | N | C-CF3 | N | 2-Pen | H | CF3 | 1 |
| 8-087. | N | N | C-CF3 | N | 2-Pen | H | CF3 | 2 |
| 8-088. | N | N | C-CF3 | N | 3-Pen | H | CF3 | 0 |
| 8-089. | N | N | C-CF3 | N | 3-Pen | H | CF3 | |
| 8-090. | N | N | C-CF3 | N | 3-Pen | H | CF3 | 2 |
| 8-091. | N | N | C-CF3 | N | c-Pen | H | CF3 | 0 |
| 8-092. | N | N | C-CF3 | N | c-Pen | H | CF3 | 1 |
| 8-093. | N | N | C-CF3 | N | c-Pen | H | CF3 | 2 |
| 8-094. | N | N | C-CF3 | N | c-Hex | H | CF3 | 0 |
| 8-095. | N | N | C-CF3 | N | c-Hex | H | CF3 | 1 |
| No. | Y1 | Y2 | Y3 | Y4 | R1 | R2 | R3U | n |
| 8-096. | N | N | C-CF3 | N | c-Hex | H | CF3 | 2 |
| 8-097. | N | N | C-CF3 | N | CN | H | CF3 | 0 |
| 8-098. | N | N | C-CF3 | N | CN | H | CF3 | 1 |
| 8-099. | N | N | C-CF3 | N | CN | H | CF3 | 2 |
| 8-0100. | N | N | C-CF3 | N | CO2Me | H | CF3 | 0 |
| 8-0101. | N | N | C-CF3 | N | CO2Me | H | CF3 | 1 |
| 8-0102. | N | N | C-CF3 | N | CO2Me | H | CF3 | 2 |
| 8-0103. | N | N | C-CF3 | N | CO2Et | H | CF3 | 0 |
| 8-0104. | N | N | C-CF3 | N | CO2Et | H | CF3 | 1 |
| 8-0105. | N | N | C-CF3 | N | CO2Et | H | CF3 | 2 |
| 8-0106. | N | N | C-CF3 | C-H | CO2-t-Bu | H | CF3 | 0 |
| 8-0107. | N | N | C-CF3 | C-H | CO2-t-Bu | H | CF3 | 1 |
| 8-0108. | N | N | C-CF3 | C-H | CO2-t-Bu | H | CF3 | 2 |
| 8-0109. | C-CF3 | N | C-Et | C-H | CO2Me | H | CF3 | 2 |
| 8-0110. | C-H | N | C-H | C-CF3 | Me | H | CF3 | 2 |
| 8-0111. | C-Me | N | C-CF3 | C-H | H | H | CF3 | 0 |
| 8-0112. | C-Me | N | C-CF3 | C-H | H | H | CF3 | 1 |
| 8-0113. | C-Me | N | C-CF3 | C-H | H | H | CF3 | 2 |
| 8-0114. | C-CF3 | N | C-t-Bu | C-H | CO2-t-Bu | H | CF3 | 0 |
| 8-0115. | C-CF3 | N | C-t-Bu | C-H | CO2-t-Bu | H | CF3 | 1 |
| 8-0116. | C-CF3 | N | C-t-Bu | C-H | CO2-t-Bu | H | CF3 | 2 |
| 8-0117. | C-H | N | C-t-Bu | C-H | CO2-t-Bu | Me | CF3 | 0 |
| 8-0118. | C-H | N | C-t-Bu | C-H | CO2-t-Bu | Me | CF3 | 1 |
| 8-0119. | C-H | N | C-t-Bu | C-H | CO2-t-Bu | Me | CF3 | 2 |
| 8-0120. | C-H | C-NO2 | C-H | C-H | CO2-t-Bu | H | CF3 | 0 |
| 8-0121. | C-H | C-NO2 | C-H | C-H | CO2-t-Bu | Me | CF3 | 0 |
| 8-0122. | C-H | C-NO2 | C-H | C-H | CO2-t-Bu | Me | CF3 | 2 |
在以上表的模拟物中,进一步例是化合物号8-0123~8-0245,其中R3U是CF2H和全部其余变量具有与表8各行中代表的相同的含义。
化合物号8-01~8-0245的类似物是化合物号8-01~8-245,其中变量具有相同的含义,除了m是1代替0之外。
表9:描述具有以下式中代表的9-xxxx型的化合物号的例:
化合物号9-01~9-0205:m=0
在以上表的模拟物中,进一步例是化合物号9-0103~9-205,其中R3U是CF2H和全部其余变量具有与表9各行中代表的相同的含义。
化合物号9-01~9-205的类似物是化合物号9-01~9-205,其中变量具有相同的含义,除了m是1代替0之外。
在以上列出的化合物号1-01~9-205的模拟物中,本发明的化合物的进一步例,当不明确地列在表中时,是化合物,其中n是0或1代替2。
式(I)的化合物可通过从WO 2009/075080,WO 2009/025397或WO 2009/028727中描述的那些适应的方法制备,这些因素通过引用整体并入本文。由通式[I]代表的本发明的化合物,可根据在下文给的制备方法生产,但本发明会不限制于这些过程。如果不明确地定义,不同合成例的不同结构中使用的变量与式(I)中相同。本领域技术人员会明白,在化合物和中间体中的特定官能团可被适合的保护基未保护或保护,如Greene et al.Protective Groups in OrganicSynthesis,John Wiley and Sons,Inc.,3rd edition 1999教导。而且,本领域技术人员明晰,化合物和中间体可通过标准水中工作条件分离和任选地纯化。例如,化合物或中间体可通过层析方法纯化或结晶化,以产生适合的纯度的期望的产物。
本发明的化合物也可由以下式(II)代表
其中且A=U
#是式(II)中的键合位点和式(II)中的其他变量和R3具有与上述相同的含义。
附接于离去基团Z1的R3型的化合物可例如如下制备及例如描述于WO 2007/071609和WO 2007/147888,用于还使用于式(I)的化合物的合成。
一般而言,化合物(IVR3U),如果不商业上可利用的,可经模拟J.March,Advanced Organic Chemistry,4th edition,Wiley中提及的方法转变为相应甲苯磺酸盐,甲磺酸盐或卤化物而从醇(IIIR3U)合成。
化合物(IIIR3U)可经化合物(VR3U)的烷基化获得,其中Z2是适合的离去基团诸如卤素原子,甲磺酸盐,三氟甲磺酸盐或甲苯磺酸盐,化合物(VI R3U)是模拟Can.J.Chem.1979,57,p.1958-1966andJ.Am.Chem.Soc.1924,46,p.1503中描述的方法而适宜地取代的氢硫基或其醇或盐。
特别是,也可通过使CF3-SH与乙烯基卤CH2CH-Z1反应来获得化合物(IVR3U),其中p=2,R3U是CF3,X是硫和Z1是卤素,如描述于J.Am Chem.Soc.1962,84,p.3148-3153。
可例如通过在辐射条件下烷基化巯基醇HO-(CH2)n-SH来制备化合物(IIIR3U)其中R3U是CF3和X是硫,如描述于WO 2001/36410;p.19。
可获得化合物(IVR3U),其中R3U是CF3和X是氧,如描述于J.Fluorine Chemistry 1982,21,p.133-143或J.Org.Chem.2001,66,p.1061-1063.。
【生产方法1】
由式[Ia]代表的化合物可根据下述的方法生产:
方案1
在式中,A,R1,R2,R3,Z1和Z2代表与上述相同的含义,及G2代表甲基或氨基。
【阶段(1-1)】
化合物[VII]可通过化合物[V]和化合物[VI]在溶剂中反应来生产。化合物[VI]的使用量可适当选自,正常1~3当量,优选1~2当量/1当量的化合物[V]。可用于此反应的溶剂的例:卤化的烃诸如二氯甲烷和氯仿;及醇诸如甲醇,乙醇和丙醇;或其混合物。以上-提及的溶剂的量正常是0.1~10l,优选0.2~3.0l/1mol的化合物[V]。反应温度是自0℃至在反应系统中回流温度的任何温度,优选在跨10°~120℃的温度。反应时间会根据,例如,反应温度,反应基质和反应的量改变,但正常是0.5~72小时。反应已完成之后,化合物[VII]可通过进行操作诸如浓缩来分离。分离的化合物[VII]可利用再结晶进一步纯化,根据需要。
【阶段(1-2)】
由式[Ia]代表的化合物可通过化合物[VII]和化合物[II]在溶剂中在碱的存在下反应来生产。本文所用的化合物[II]的使用量可适当选自,正常是0.8~5当量,优选0.8~2当量/1当量的化合物[VII]。可用于此反应的溶剂的例是:醚诸如二乙基醚,1,2-二甲氧基乙烷和四氢呋喃;酰胺诸如Ν,Ν-二甲基乙酰胺,N,N-二甲基甲酰胺,1,3-二甲基-2-咪唑烷酮和N-甲基-2-吡咯烷酮;硫化合物诸如二甲基亚砜和环丁砜;腈诸如乙腈和丙腈;醇诸如甲醇,乙醇和丙醇;脂肪族烃诸如己烷和庚烷;芳族烃诸如苯,甲苯和二甲苯;卤化的烃诸如1,2-二氯乙烷和氯苯;及水;或其混合物。以上-提及的溶剂的量正常是0.1~50l,优选0.2~10l/1mol的化合物[VII]。可用于此反应的碱的例是无机碱诸如:碱金属的氢氧化物,例如,氢氧化钠和氢氧化钾;碱土金属的氢氧化物,例如氢氧化钙和氢氧化镁;或醇的金属盐,例如,甲氧化钠,乙氧化钠和叔丁氧化钾。使用的碱的量可正常适当选自1~20当量,优选1~10当量/1当量的化合物[VII]。
所述反应可使用转相催化剂诸如四-n-丁基铵溴化物进行。使用的转相催化剂的量可适当选自0~1.0当量/1当量的化合物[VII]。反应温度是自-50℃至反应系统的回流温度的任何温度,优选温度跨-10°~100℃。
反应时间会根据,例如,反应温度,反应基质和反应的量而改变,但正常是1~48小时。反应已完成之后,化合物[Ia]可通过进行操作诸如将反应混合物添加到水和用有机溶剂萃取,然后浓缩来分离。分离的化合物[Ia]可利用柱层析和再结晶进一步纯化,根据需要。
【生产方法2】
由式[Ia]代表的化合物可根据下述的方法生产。
方案2
在式中,A,R1,R2,R3和Z2代表与上述相同的含义。由式[Ia]代表的化合物可通过化合物[V]和化合物[VIII]在溶剂中,在碱的存在下反应来生产。本文所用的化合物[VIII]的使用量可适当选自,正常是0.8~5当量,优选0.8~2当量/1当量的化合物[V]。可用于此反应的溶剂制备方法1的阶段(1~2)中的那些相同。以上-提及的溶剂的量正常是0.1~50l,优选0.2~10l/1mol的化合物[V]。可用于此反应的碱的例是:有机碱诸如三乙基胺和1,8-二氮杂二环[5.4.0]-7-十一碳烯;无机碱诸如:碱金属的氢氧化物,例如,氢氧化钠和氢氧化钾;碱土金属的氢氧化物,例如氢氧化钙和氢氧化镁;碱金属的碳酸盐,例如,碳酸钠和碳酸钾;及碱金属的碳酸氢盐,例如,碳酸氢钠和碳酸氢钾;醇的金属盐,例如,甲氧化钠,乙氧化钠和叔丁氧化钾;或碱金属的氢化物,例如氢化钠。碱的量可正常适当选自1~10当量,优选1~5当量/1当量的化合物[V]。反应温度是任何温度自-50℃至反应系统的回流温度,优选温度跨-10°~100℃。反应时间会根据,例如,反应温度,反应基质和反应的量而改变,但正常是1~24小时。反应已完成之后,化合物[Ia]可通过进行操作诸如将反应混合物添加到水和用有机溶剂萃取,然后浓缩来分离。分离的化合物[Ia]可利用柱层析和再结晶进一步纯化,根据需要。
【生产方法3】
由式[Ia]代表的化合物可根据下述的方法生产。
方案3
在式中,A,R1,R2,R3和Z1代表与上述相同的含义。
由式[Ia]代表的化合物可通过化合物[IX]和化合物[II]在溶剂中,在碱的存在下反应来生产。本文所用的化合物[II]的使用量可适当选自,正常是0.8~5当量,优选0.8~2当量/1当量的化合物[IX]。可用于此反应的溶剂与制备方法1的阶段(1~2)中的那些相同。以上-提及的溶剂的量正常是0.1~50l,优选0.2~10l/1mol的化合物[IX]。可用于此反应的碱的例与在制备方法2中的那些相同。使用的碱的量可正常适当选自1~10当量,优选1~5当量/1当量的化合物[IX]。反应温度是从-50℃至反应系统的回流温度的任何温度,优选温度跨-10°~100℃。反应时间会根据,例如,反应温度,反应基质和反应的量而改变,但正常是1~48小时。反应已完成之后,化合物[Ia]可通过进行操作诸如将反应混合物添加到水和用有机溶剂萃取,然后浓缩来分离。分离的化合物[Ia]可利用柱层析和再结晶进一步纯化,根据需要。
上述的化合物[VIII]和化合物[IX]也可根据描述于下列文献的方法生产:Journal of Organic Chemistry,第93~95页(1962)及Heterocycles第1331~1346页(1986)。
【生产方法4】
在由通式[I]代表的化合物,由式[Ib]代表的化合物中,其中n是1或2,可根据下述的方法生产:
方案4
在式中,A,R1,R2和R3代表与上述相同的含义,及n代表1或2。
由式[Ib]代表的化合物可通过由式[Ia]代表的化合物和氧化剂,在溶剂中反应来生产。可用于反应的氧化剂的例是:有机过氧化物诸如间氯过氧苯甲酸,过甲酸或过乙酸;过一硫酸氢钾(DuPont商品名,2KHSO5·KHSO4·K2SO4);含有卤素的酰亚胺诸如N-氯代琥珀酰亚胺;及无机过氧化物诸如过氧化氢,高锰酸钾或高碘酸钠。本文所用的氧化剂的使用量可适当选自,正常是0.8~10当量,优选0.8~5当量/1当量的化合物[Ia]。
可用于此反应的溶剂的例是:卤化的烃诸如二氯甲烷,氯仿,1,2-二氯乙烷和氯苯;醇诸如甲醇,乙醇和丙醇;芳族烃诸如苯,甲苯和二甲苯;酮诸如丙酮和2-丁酮;腈诸如乙腈;酯诸如乙酸乙酯;脂肪族羧酸诸如乙酸和三氟乙酸;水;或其混合物。以上-提及的溶剂的量正常是0.1~50l,优选0.2~10l/1mol的化合物[Ia]。反应温度是从-50℃至反应系统的回流温度的任何温度,优选温度跨-10°~60℃。
反应时间会根据,例如,反应温度,反应基质和反应的量而改变,但正常是1~24小时。反应已完成之后,化合物[Ib]可通过进行操作诸如将反应混合物添加到水和用有机溶剂萃取,然后浓缩来分离。分离的化合物[Ib]可利用柱层析和再结晶进一步纯化,根据需要。
硫化物(Ia)向亚砜(Ib)的选择性转变的优选的方法,为此n是1,在六氟异丙醇存在下,使用过氧化氢作为氧化剂(如描述于Tetrahedron Lett.1998,39,3141-3144),或使用间氯过苯甲酸作为氧化剂,非质子溶剂诸如氯仿或二氯甲烷中碱的存在或缺失下,在环境温度以下的温度。
硫化物化合物向亚砜及向砜产物的氧化的其他方法是本领域熟知的,及可使用本领域知道的任何适合的方法(例如,亚砜合成,见Varma et al.,Org.Lett.,1999,1,189-191;Kim et al.,Synthesis,2002,2484-2486;Qian et al.,Synlett,2006,709-712;Matteucci et al.,Org.Lett.,2003,5,235-237;Mba et al.,Org.Lett.,2007,9,21-24;Karimiet al.;Org.Lett.,2005,7,625-628;对于砜的制备,见Varma et al.,Org.Lett,1999,1,189-191;Jana et al.,Org.Lett.,2003,5,3787-3790;Karimi et al.,Org.Lett.,2005,7,625-628;Shaabania et al,Tetrahedron,2004,60,11415-11420)。
【生产方法5】
由式[Ic]代表的化合物可根据下述的方法生产:
方案5
在式[X]和[Ic]中,A,R3和n代表与上述相同的含义及:
R7A在式[X]和[Ic]中表示卤素,C1~C6-烷基,其可被下列基团取代:卤素,C1~C4-烷氧基,C1~C4-烷硫基,C1~C4-烷基亚硫酰基,C1~C6-烷基磺酰基,CN,C(=O)R9A或二(C1~C3-烷基)氨基,C2~C6-烯基,C2~C6-卤代烯基,C2~C6-炔基,C2~C6-卤代炔基,C3~C6-环烷基,C3~C6-卤代环烷基,可被卤素原子取代的C3~C6-环烷基-C1~C3-烷基,CN,C(=O)R10A;
R8A在式[X]和[Ic]中表示C1~C6-烷基,其可被下列基团取代:卤素,C1~C4-烷氧基,C1~C4-烷硫基,CN,C(=O)R9A或羟基,C2~C6-烯基,C2~C6-卤代烯基,C2~C6-炔基,C2~C6-卤代炔基,C3~C6-环烷基,C3~C6-卤代环烷基,可被卤素原子取代的C3~C6-环烷基-C1~C3-烷基,或C(=O)R11A;
R9A在式[X]和[Ic]中表示C1~C6-烷基,C1~C6-卤代烷基,C1~C6-烷氧基,氨基,单-(C1~C6-烷基)氨基,二-(C1~C4-烷基)氨基,C2~C5-环状氨基基团;
R10A在式[X]和[Ic]中表示C1~C6-烷氧基,二-(C1~C4-烷基)氨基,C2~C5-环状氨基基团
R11A在式[X]和[Ic]中表示C1~C6-烷基,C1~C6-卤代烷基,C1~C6-烷氧基,二-(C1~C4-烷基)氨基,C2~C5-环状氨基基团;
Z3代表离去基团诸如氯原子,溴原子,碘原子,甲磺酰氧基或三氟甲磺酰氧基。
由式[Ic]代表的化合物可通过化合物[X]和化合物[XI]在溶剂中,在碱的存在下反应来生产。本文所用的化合物[XI]的使用量可适当选自,正常1~10当量,优选1~5当量/1当量的化合物[X]。可用于此反应的溶剂的例是:醚诸如二乙基醚,1,2-二甲氧基乙烷和四氢呋喃;酰胺诸如Ν,Ν-二甲基乙酰胺,N,N-二甲基甲酰胺,1,3-二甲基-2-咪唑烷酮和N-甲基-2-吡咯烷酮;硫化合物诸如二甲基-亚砜和环丁砜;腈诸如乙腈和丙腈;及芳族烃诸如苯,甲苯和二甲苯;或其混合物。以上-提及的溶剂的量正常是0.1~50l,优选0.2~10l/1mol的化合物[X]。此反应中可使用的碱例是:有机碱诸如三乙基胺和1,8-二氮杂二环[5.4.0]-7-十一碳烯;无机碱诸如:碱金属的氢氧化物,例如,氢氧化钠和氢氧化钾;碱土金属的氢氧化物,例如氢氧化钙和氢氧化镁;碱金属的碳酸盐,例如,碳酸钠和碳酸钾;及碱金属的碳酸氢盐,例如,碳酸氢钠和碳酸氢钾;醇的金属盐,例如,甲氧化钠,乙氧化钠和叔丁氧化钾;碱金属的氢化物,例如氢化钠;或有机锂化合物诸如n-丁基锂和二异丙基氨基锂。使用的碱的量可正常适当选自1~10当量,优选1~5当量/1当量的化合物[X]。反应温度是从-100℃至反应系统的回流温度的任何温度,优选温度跨-78°~100℃。反应时间会根据,例如,反应温度,反应基质和反应的量而改变,但正常是1~24小时。反应已完成之后,化合物[Ic]可通过进行操作诸如将反应混合物添加到水和用有机溶剂萃取,然后浓缩来分离。分离的化合物[Ic]可利用柱层析和再结晶进一步纯化,根据需要。
【生产方法6】
由式[Ie]代表的化合物可根据下述的方法生产自化合物[X]。
方案6
在式[X]和[Ie]中,A,R3,R7A和n代表与上述相同的含义;R13A在式[Ie]中代表卤素原子。
由式[Ie]代表的化合物可通过化合物[X]和卤化剂[XIII],在溶剂中,在碱的存在下反应来生产。可用于反应的卤化剂[XIII]的例是:卤化的烃诸如四氯化碳和六氯乙烷;含有卤素的酰亚胺诸如N-氟苯磺酰亚胺,N-氯代琥珀酰亚胺和N-溴琥珀酰亚胺;卤化的硫化合物诸如硫酰氯和亚硫酰氯;卤化的磷化合物诸如五氯化磷和氯氧化磷;N-氟吡啶鎓盐诸如1-氟-2,4,6-三甲基吡啶鎓三氟甲磺酸盐;1-(氯甲基)-4-氟-1,4-重氮鎓双环[2.2.2]辛烷双(四氟硼酸盐);卤素诸如氟,氯,溴和碘;或卤化铜诸如氯化铜(II)和溴化铜(II)。本文所用的卤化剂[XIII]的使用量可适当选自,正常1~10当量,优选1~5当量/1当量的化合物[X]。可用于此反应的溶剂的例是:醚诸如二乙基醚,1,2-二甲氧基乙烷和四氢呋喃;酰胺诸如Ν,Ν-二甲基乙酰胺,N,N-二甲基甲酰胺,1,3-二甲基-2-咪唑烷酮和N-甲基-2-吡咯烷酮;硫化合物诸如二甲基亚砜和环丁砜;腈诸如乙腈和丙腈;芳族烃诸如苯,甲苯和二甲苯;卤化的烃诸如二氯甲烷,1,2-二氯乙烷和氯苯;水;或其混合物。以上-提及的溶剂的量正常是0.1~50l,优选0.2~20l/1mol的化合物[X]。此反应可使用的碱的例是与生产实施例5中的那些相同。使用的碱的量可正常适当选自1~10当量,优选1~5当量/1当量的化合物[X]。反应温度是从-100℃至反应系统的回流温度的任何温度,优选温度跨-78°~100℃。反应时间会根据,例如,反应温度,反应基质和反应的量而改变,但正常是1~24小时。反应已完成之后,化合物[Ie]可通过进行操作诸如将反应混合物添加到水和用有机溶剂萃取,然后浓缩来分离。分离的化合物[Ie]可利用柱层析和再结晶进一步纯化,根据需要。
【生产方法7】
由式[Ig]代表的化合物可根据下述的方法生产。
方案7
在式[XVII]和[Ig]中,A和R3代表与上述相同的含义;
R14A在式[XVII]和[Ig]中表示氰基或C(=O)R10A基团;
R10A代表与在式[X]和[Ic]中上述相同的含义;
Z5代表离去基团诸如氯原子,溴原子,碘原子或三氟甲磺酰氧基基团。
由式[Ig]代表的化合物可通过化合物[XVII]和化合物[XVIII],在溶剂中,在碱和过渡金属催化剂的存在下反应来生产。此反应可随添加膦配体诸如三苯基膦或三-叔-丁基膦进行,根据需要。
本文所用的化合物[XVIII]的使用量可适当选自,正常1~5当量,优选1~3当量/1当量的化合物[XVII]。可用于此反应的溶剂的例是:醚诸如四氢呋喃,1,4-二噁烷和1,2-二甲氧基乙烷;腈诸如乙腈和丙腈;酰胺诸如N,N-二甲基甲酰胺和N,N-二甲基乙酰胺;及芳族烃诸如苯,甲苯和二甲苯;或其混合物。以上-提及的溶剂量正常是0.1~50l,优选0.2~20l/1mol的化合物(XVII)。此反应中可使用的碱例是:有机碱诸如三乙基胺,二异丙基乙胺和1,8-二氮杂二环[5.4.0]-7-十一碳烯;无机碱诸如:碱金属的氢氧化物,例如,氢氧化钠和氢氧化钾;碱金属的碳酸盐,例如,碳酸钠和碳酸钾;及碱金属的碳酸氢盐,例如,碳酸氢钠和碳酸氢钾;及磷酸盐诸如磷酸钾;醇的金属盐诸如甲氧化钠,叔丁氧化钠和叔丁氧化钾;或碱金属的氢化物诸如氢化钠。使用的碱的量可正常适当选自1~10当量,优选1~5当量/1当量的化合物[XVII]。可在本发明中使用的过渡金属化合物的例是钯化合物诸如乙酸钯,二氯双(三苯基膦)钯,四(三苯基膦)钯和三(二亚苄基丙酮)二钯-氯仿。使用的过渡金属化合物的量可正常适当选自0.01~0.5当量,优选0.02~0.2当量/1当量的化合物[XVII]。使用的膦配体的量可适当选自0~1.5当量/1当量的化合物[XVII]。反应温度是从0℃至反应系统的回流温度的任何温度,优选温度跨20°~120℃。反应时间会根据,例如,反应温度,反应基质和反应的量而改变,但正常是1~48小时。反应已完成之后,化合物[Ig]可通过进行操作诸如将反应混合物添加到水和用有机溶剂萃取,然后浓缩来分离。分离的化合物[Ig]可为还纯化的利用柱层析,根据需要。化合物[XVII]也可根据制备方法3和制备方法4中描述的方法生产。
【生产方法8】
由式[I],化合物[Ij]代表的化合物可根据下述的方法生产。
方案8
在方案8中的式中,R1,R2和R3代表与上述相同的含义,
R19A代表C1~C6-烷基,C1~C6-卤代烷基,C2~C6-烯基,C2~C6-卤代烯基,C2~C6-炔基,C2~C6-卤代炔基,C3~C6-环烷基,C3~C6-卤代环烷基,C3~C6-环烷基-C1~C3-烷基;
Z7代表卤素原子诸如氯原子或溴原子。Z8代表离去基团诸如氯原子,溴原子,或OC(=O)R19A。
【阶段(8-2a)】
化合物[XXXI]可通过化合物[XXVI]和化合物[XXVII]在溶剂中,在碱的存在下反应来生产。本文所用的化合物[XXVII]的使用量可适当选自,正常1~5当量,优选1~2当量/1当量的化合物[XXVI]。可用于此反应的溶剂的例是:醚诸如二乙基醚,1,2-二甲氧基乙烷和四氢呋喃;腈诸如乙腈和丙腈;芳族烃诸如苯,甲苯和二甲苯;卤化的烃诸如二氯甲烷,1,2-二氯乙烷和氯苯;醇诸如甲醇,乙醇或丙醇;水;或其混合物。以上-提及的溶剂量正常是0.1~50l,优选0~0.2~20l/1mol的化合物[XXVI]。可用于此反应的碱的例是:有机碱诸如三乙基胺和1,8-二氮杂二环[5.4.0]-7-十一碳烯;无机碱诸如:碱金属的氢氧化物,例如,氢氧化钠和氢氧化钾;碱土金属的氢氧化物,例如氢氧化钙和氢氧化镁;碱金属的碳酸盐,例如,碳酸钠和碳酸钾;及碱金属的碳酸氢盐,例如,碳酸氢钠和碳酸氢钾。使用的碱的量可正常适当选自1~10当量,优选1~5当量/1当量的化合物[XXVI]。反应温度是从-50℃至反应系统的回流温度的任何温度,优选温度跨-20°~100℃。反应时间会根据,例如,反应温度,反应基质和反应的量而改变,但正常是1~24小时。反应已完成之后,化合物[XXXI]可通过进行操作诸如将反应混合物添加到水和用有机溶剂萃取,然后浓缩来分离。分离的化合物[XXXI]可利用柱层析和再结晶进一步纯化,根据需要。
【阶段(8-2b)】
化合物[XXXI]可通过化合物[XXIX]和化合物[XXX]在溶剂中,在碱的存在下反应来生产。本文所用的化合物[XXX]的使用量可适当选自,正常1~5当量,优选1~2当量/1当量的化合物[XXIX]。可用于此反应的溶剂和碱的例与阶段(8-2a)相同。以上-提及的溶剂量正常是0.1~50l,优选0~0.2~20l/1mol的化合物[XXIX]。使用的碱的量可正常适当选自1~10当量,优选1~5当量/1当量的化合物[XXIX]。反应温度是从-50℃至反应系统的回流温度的任何温度,优选温度跨-20°~100℃。反应时间会根据,例如,反应温度,反应基质和反应的量而改变,但正常是1~24小时。反应已完成之后,化合物[XXXI]可通过进行操作诸如将反应混合物添加到水和用有机溶剂萃取,然后浓缩来分离。分离的化合物[XXXI]可利用柱层析和再结晶进一步纯化,根据需要。
【阶段(8-3)】
化合物代表的由式[Ij]可通过化合物[XXXI]及硫化剂在溶剂中反应来生产。可用于此反应的溶剂的例是:醚诸如四氢呋喃和1,4-二噁烷;芳族烃诸如苯,甲苯和二甲苯;卤化的烃诸如氯仿,1,2-二氯乙烷和氯苯;腈诸如乙腈和丙腈;或其混合物。以上-提及的溶剂量正常是0.1~50l,优选0.2~20l/1mol的化合物[XXXI]。可用于反应的硫化剂的例是2,4-双(4-甲氧苯基)-1,3-二硫杂-2,4-二磷杂环丁烷-2,4-二硫化物试剂,或五硫化磷。本文所用的硫化剂的使用量可适当选自正常是0.5~10当量,优选1~5当量/1当量的化合物[XXXI]。反应温度正常是从0℃至反应系统的回流温度的任何温度,优选温度跨20°~180℃。反应时间会根据,例如,反应温度,反应基质和反应的量而改变,但正常是1~72小时。反应已完成之后,化合物[Ij]可分离通过过滤反应混合物,然后进行操作诸如浓度。分离的化合物[Ij]可为还纯化的利用柱层析,根据需要。
化合物[XXVII]可,例如,根据描述于Journal of OrganicChemistry第102~105页(1960)的方法生产。
如果个体化合物不可经以上-描述的途径制备,它们可通过其他化合物I的衍生化或通过描述的合成途径的常规修饰制备。
反应混合物以常规方式操作,例如通过用水混合,分离相,及,如果适当的,通过,例如在矾土或硅胶上层析纯化粗产物。一些中间体和终产物可以无色或淡棕粘油的形式获得,其从挥发性组分在减压下及在中度提升的温度除去或纯化。如果中间体和终产物以固体获得,它们可通过再结晶或消化纯化。
本发明也提供控制无脊椎动物害虫的方法,该方法包括用杀虫有效量的式I的化合物或其盐或N-氧化物或以上定义的组合物处理害虫,它们的食品供应,它们的栖息地或它们的繁殖地或害虫生长或可生长的栽培的植物,植物繁殖材料(诸如种子),土壤,分布区,物质或环境,或物质,栽培的植物,植物繁殖材料(诸如种子),土壤,表面或空间,以保护免于害虫攻击或侵袭。
优选地,本发明的方法用于用杀虫有效量的以上定义的式I的化合物或其农业地可接受的盐或N-氧化物或用杀虫有效量的以上及以下定义的农业组合物保护植物繁殖材料(诸如种子)和由其生长而来的植物免于无脊椎动物害虫攻击或侵袭及包含处理植物繁殖材料(诸如种子)。本发明的方法未限制于保护已根据本发明处理的"基质"(植物,植物繁殖材料,土壤物质等),而且具有预防效应,由此,例如,保护从处理的植物繁殖材料(诸如种子)生长的植物,未处理的植物本身。
在本发明的意义中,"无脊椎动物害虫"优选是选自节肢动物和线虫,更优选自有害昆虫,蜘蛛和线虫,及甚至更优选自昆虫,螨和线虫。在本发明的意义中,"无脊椎动物害虫"最优选是昆虫。
本发明还提供用于抵御该无脊椎动物害虫的农业组合物,其包含该一定量的至少一种通式I的化合物或具有杀虫作用的至少一种农业地有用的盐或其N-氧化物及至少一种惰性液体和/或固体农艺学可接受的载体及,如果需要,至少一种表面活性剂。
该组合物可含有单活性式I的化合物或其盐或N-氧化物或本发明的几种活性化合物I的混合物或它们的盐。本发明的组合物可包含个体异构体或异构体的混合物以及个体互变异构体或互变异构体的混合物。
式I的化合物和包含它们的杀虫组合物是对于控制节肢动物害虫和线虫的有效剂。通过式I的化合物控制的无脊椎动物害虫包括例如:
昆虫自鳞翅目昆虫(鳞翅目(Lepidoptera)),例如小地老虎(Agrotis ypsilon),黄地老虎(Agrotis segetum),棉叶虫(Alabamaargillacea),大豆夜蛾(Anticarsia gemmatalis),苹果银蛾(Argyresthiaconjugella),丫蚊夜蛾(Autographa gamma),松粉蝶尺蛾(Bupaluspiniarius),枞卷叶蛾(Cacoecia murinana),网纹烟卷蛾(Capuareticulana),果园秋尺蛾(Cheimatobia brumata),云杉色卷蛾(Choristoneura fumiferana),西部云杉色卷蛾(Choristoneuraoccidentalis),白点粘虫(Cirphis unipuncta),苹果皮小卷蛾(Cydiapomonella),欧洲松毛虫(Dendrolimus pini),黄瓜绢野螟(Diaphanianitidalis),西南玉米杆草螟(Diatraea grandiosella),埃及钻夜蛾(Earias insulana),南美玉米苗斑螟(Elasmopalpus lignosellus),女贞细卷蛾(Eupoecilia ambiguella),欧洲松梢小卷蛾(Evetriabouliana),斑点脏切夜蛾(Feltia subterranea),蜡螟(Galleriamellonella),柏木小食心虫(Grapholitha funebrana),梨小食心虫(Grapholitha molesta),棉铃虫(Heliothis armigera),烟芽夜蛾(Heliothis virescens),玉米夜蛾(Heliothis zea),菜心野螟(Hellulaundalis),暗点松尺蛾(Hybernia defoliaria),美国白蛾(Hyphantriacunea),苹果巢蛾(Hyponomeuta malinellus),番茄茎麦蛾(Keiferialycopersicella),西部铁杉尺蠖(Lambdina fiscellaria),甜菜贪夜蛾(Laphygma exigua),咖啡一点潜蛾(Leucoptera coffeella),旋纹潜蛾(Leucoptera scitella),苹细蛾(Lithocolletis blankardella),鲜食葡萄小卷蛾(Lobesia botrana),网锥额野螟(Loxostegesticticalis),舞毒蛾(Lymantria dispar),模毒蛾(Lymantriamonacha),桃潜蛾(Lyonetia clerkella),黄褐天幕毛虫(Malacosomaneustria),甘蓝夜蛾(Mamestra brassicae),黄杉合毒蛾(Orgyiapseudotsugata),欧洲玉米螟(Ostrinia nubilalis),小眼夜蛾(Panolisflammea),棉红铃虫(Pectinophora gossypiella),疆夜蛾(Peridromasaucia),栎银纹天社蛾(Phalera bucephala),马铃薯麦蛾(Phthorimaea operculella),柑橘叶潜蛾(Phyllocnistis citrella),欧洲粉蝶(Pieris brassicae),苜蓿绿夜蛾(Plathypena scabra),小菜蛾(Plutella xylostella),大豆尺夜蛾(Pseudoplusia includens),美松梢小卷蛾(Rhyacionia frustrana),番茄麦蛾(Scrobipalpulaabsoluta),麦蛾(Sitotroga cerealella),葡萄长须卷蛾(Sparganothispilleriana),草地贪夜蛾(Spodoptera frugiperda),棉贪夜蛾(Spodoptera littoralis),斜纹贪夜蛾(Spodoptera litura),欧洲松带蛾(Thaumetopoea pityocampa),栎绿卷蛾(Tortrix viridana),粉斑夜蛾(Trichoplusia ni)和云杉线小卷蛾(Zeiraphera canadensis);
甲虫(鞘翅目(Coleoptera)),例如梨窄吉丁(Agrilus sinuatus),直条叩甲(Agriotes lineatus),暗叩甲(Agriotes obscurus),马铃薯双绺鳃金龟(Amphimallus solstitialis),异形方胸材小蠹(Anisandrus dispar),棉铃象(Anthonomus grandis),梨花象(Anthonomus pomorum),甜菜隐食甲(Atomaria linearis),纵坑切梢小蠹(Blastophagus piniperda),波纹食植埋葬虫(Blitophagaundata),蚕豆象(Bruchus rufimanus),豌豆象(Bruchus pisorum),扁豆象(Bruchus lentis),榛绿卷象(Byctiscus betulae),甜菜大龟甲(Cassida nebulosa),菜豆萤叶甲(Cerotoma trifurcata),白菜籽龟象(Ceuthorhynchus assimilis),油菜茎龟象(Ceuthorhynchusnapi),蚤凹胫跳甲(Chaetocnema tibialis),烟草宽胸叩甲(Conoderusvespertinus),石刁柏负泥虫(Crioceris asparagi),长角叶甲(Diabrotica longicornis),十二星叶甲(Diabrotica 12punctata),玉米根叶甲(Diabrotica virgifera),墨西哥大豆瓢虫(Epilachnavarivestis),烟草跳甲(Epitrix hirtipennis),棉籽灰象(Eutinobothrusbrasiliensis),哈氏松大根颈象(Hylobius abietis),埃及苜蓿叶象(Hypera brunneipennis),紫苜蓿叶象(Hypera postica),云杉八齿小蠹(Ips typographus),烟草负泥虫(Lema bilineata),黑角负泥虫(Lema melanopa),马铃薯叶甲(Leptinotarsa decemlineata),甜菜叩甲(Limonius californicus),稻水象(Lissorhoptrusoryzophilus),普通梳爪叩头虫(Melanotus communis),油菜花露尾甲(Meligethes aeneus),东方五月鳃金龟(Melolonthahippocastani),西方五月鳃金龟(Melolontha melolontha),水稻负泥虫(Oulema oryzae),黑葡萄耳象(Otiorhynchus sulcatus),草莓根耳象(Otiorhynchus ovatus),辣根猿叶甲(Phaedon cochleariae),金头菜跳甲(Phyllotreta chrysocephala),食叶鳃金龟属(Phyllophagasp.),庭园丽金龟(Phyllopertha horticola),大豆淡足跳甲(Phyllotretanemorum),黄曲条菜跳甲(Phyllotreta striolata),日本弧丽金龟(Popillia japonica),直条根瘤象(Sitona lineatus)和谷象(Sitophilusgranarius);
双翅目(双翅目(Diptera)),例如埃及伊蚊(Aedes aegypti),刺扰伊蚊(Aedes vexans),墨西哥按实蝇(Anastrepha ludens),五斑按蚊(Anopheles maculipennis),地中海实蝇(Ceratitis capitata),蛆症金蝇(Chrysomyia bezziana),嗜人金蝇(Chrysomyiahominivorax),腐败金蝇(Chrysomyia macellaria),高粱瘿蚊(Contarinia sorghicola),嗜人瘤蝇(Cordylobia anthropophaga),尖音库蚊(Culex pipiens),瓜大实蝇(Dacus cucurbitae),油橄榄果实蝇(Dacus oleae),油菜荚叶瘿蚊(Dasineura brassicae),夏厕蝇(Fannia canicularis),肠胃蝇(Gasterophilus intestinalis),刺舌蝇(Glossina morsitans),西方角蝇(Haematobia irritans),鞍瘿瘿蚊(Haplodiplosis equestris),玉米种蝇(Hylemyia)platura),纹皮蝇(Hypoderma lineatum),美甜瓜斑潜蝇(Liriomyza sativae),三叶草斑潜蝇(Liriomyza trifolii),羊绿蝇(Lucilia caprina),铜绿蝇(Lucilia cuprina),丝光绿蝇(Lucilia sericata),胸狼毛尖眼蕈蚊(Lycoria pectoralis),小麦瘿蚊(Mayetiola destructor),家蝇(Musca domestica),厩腐蝇(Muscina stabulans),羊狂蝇(Oestrusovis),瑞典麦秆蝇(Oscinella釉料),藜泉蝇(Pegomya hyoscyami),古草种蝇(Phorbia antiqua),芸苔草种蝇(Phorbia brassicae),坚皮草种蝇(Phorbia coarctata),樱桃绕实蝇(Rhagoletis cerasi),苹绕实蝇(Rhagoletis pomonella),牛虻(Tabanus bovinus),马齿苋大蚊(Tipula oleracea)和欧洲大蚊(Tipula paludosa);
蓟马(缨翅目(Thysanoptera)),例如兰花蓟马(Dichromothripscorbetti),烟褐花蓟马(Frankliniella fusca),西花蓟马(Frankliniellaoccidentalis),东方花蓟马(Frankliniella tritici),桔实硬蓟马(Scirtothrips citri),稻蓟马(Thrips oryzae),棕榈蓟马(Thripspalmi)和烟蓟马(Thrips tabaci);
膜翅目昆虫(膜翅目(Hymenoptera)),例如菜叶蜂(Athaliarosae),热带切叶蚁(Atta cephalotes),切叶蚁(Atta sexdens),德州切叶蚁(Atta texana),李小叶蜂(Hoplocampa minuta),苹实叶蜂(Hoplocampa testudinea),小家蚁(Monomorium pharaonis),火蚁(Solenopsis geminata)和红外来火蚁(Solenopsis invicta);
异翅目昆虫(异翅目(Heteroptera)),例如拟缘蝽(Acrosternumhilare),美洲毛谷长蝽(Blissus leucopterus),黑斑烟盲蝽(Cyrtopeltisnotatus),棉红蝽(Dysdercus cingulatus),带棉红蝽(Dysdercusintermedius),麦扁盾蝽(Eurygaster integriceps),棉蝽(Euschistusimpictiventris),棉铃喙缘蝽(Leptoglossus phyllopus),美国牧草盲蝽(Lygus lineolaris),牧草盲蝽(Lygus pratensis),稻绿蝽(Nezaraviridula),方背皮蝽(Piesma quadrata),岛稻蝽(Solubea insularis)和新热带红肩蝽(Thyanta perditor);
同翅目昆虫(同翅目(Homoptera)),例如驴食草无网长管蚜(Acyrthosiphon onobrychis),落叶松球蚜(Adelges laricis),鼠李马铃薯蚜(Aphidula nasturtii),豆卫矛蚜(Aphis fabae),草莓根蚜(Aphis forbesi),苹果蚜(Aphis pomi),棉蚜(Aphis gossypii),醋粟蚜(Aphis grossulariae),茶藨蚜(Aphis schneideri),绣线菊蚜(Aphis spiraeccla),接骨木蚜(Aphis sambuci),豌豆蚜(Acyrthosiphon pisum),土豆沟无网蚜(Aulacorthum solani),银叶粉虱(Bemisia argentifolii),甘薯粉虱(Bemisia tabaci),飞廉短尾蚜(Brachycaudus cardui),李短尾蚜(Brachycaudushelichrysi),桃短尾蚜(Brachycaudus persicae),樱桃短尾蚜(Brachycaudus prunicola),甘蓝蚜(Brevicoryne brassicae),角钉毛蚜(Capitophorus horni),棉蚜(Cerosipha gossypii),草莓中瘤钉毛蚜(Chaetosiphon fragaefolii),茶藨隐瘤蚜(Cryptomyzusribis),冷杉迁移球蚜(Dreyfusia nordmannianae),云杉椎球蚜(Dreyfusia piceae),根瘤西圆尾蚜(Dysaphis radicola),Dysaulacorthum pseudosolani,车前西圆尾蚜(Dysaphis plantaginea),梨西圆尾蚜(Dysaphis pyri),蚕虫小绿叶蝉(Empoasca fabae),梅大尾蚜(Hyalopterus pruni),茶藨苦菜超瘤蚜(Hyperomyzuslactucae),麦长管蚜(Macrosiphum avenae),马铃薯长管蚜(Macrosiphum euphorbiae),蔷薇长管蚜(Macrosiphum rosae),巢菜修尾蚜(Megoura viciae),梨色蚜(Melanaphis pyrarius),麦无网蚜(麦无网蚜dirhodum),桃蚜(Myzodes persicae),冬葱瘤蚜(Myzus ascalonicus),樱桃瘤蚜(Myzus cerasi),桃蚜(Myzuspersicae),桃纵卷瘤蚜(Myzus varians),莴苣衲长管蚜(Nasonoviaribisnigri),褐飞虱(Nilaparvata lugens),柄瘿绵蚜(Pemphigusbursarius),蔗飞虱(Perkinsiella saccharicida),忽布疣蚜(Phorodonhumuli),苹木虱(Psylla mali),梨木虱(Psylla piri),冬葱缢瘤蚜(Rhopalomyzus ascalonicus),玉米缢管蚜(Rhopalosiphummaidis),禾谷缢管蚜(Rhopalosiphum padi),苹草缢管蚜(Rhopalosiphum insertum),梨砧草蚜(Sappaphis mala),苹红扎圆尾蚜(Sappaphis mali),麦二叉蚜(Schizaphis graminum),榆梨绵蚜(Schizoneura lanuginosa),麦长管蚜(Sitobion avenae),白背飞虱(Sogatella furcifera)温室粉虱(Trialeurodesvaporariorum),橘声蚜(Toxoptera aurantii)和葡萄根瘤蚜(Viteusvitifolii);
白蚁(等翅目(Isoptera)),例如欧洲木白蚁(Kalotermesflavicollis),欧美散白蚁(Leucotermes flavipes),欧美散白蚁(Reticulitermes flavipes),暗黑散白蚁(Reticulitermes lucifugus)和撒哈拉大白蚁(Termes natalensis);
直翅目昆虫(直翅目(Orthoptera)),例如居屋艾蟋(Achetadomestica),东方蜚蠊(Blatta orientalis),德国小蠊(Blattellagermanica),欧洲球螋(Forficula auricularia),欧洲蝼蛄(Gryllotalpagryllotalpa),飞蝗(Locusta migratoria),双带黑蝗(Melanoplusbivittatus),赤胫黑蝗(Melanoplus femurrubrum),墨西哥黑蝗(Melanoplus mexicanus),血黑蝗(Melanoplus sanguinipes),石枯黑蝗(Melanoplus spretus),红蝗(Nomadacris septemfasciata),美洲大蠊(Periplaneta americana),南美沙漠蝗(Schistocercaamericana),沙漠蝗(Schistocerca peregrina),摩洛哥戟纹蝗(Stauronotus maroccanus)和温室沙螽(Tachycines asynamorus);
蛛形纲(Arachnoidea),诸如蜘蛛(蜱螨目(Acarina)),例如软蜱科(Argasidae),硬蜱科(Ixodidae)和疥螨科(Sarcoptidae),诸如美洲花蜱(Amblyomma americanum),彩饰花蜱(Amblyommavariegatum),波斯锐缘蜱(Argas persicus),具环牛蜱(Boophilusannulatus),消色牛蜱(Boophilus decoloratus),微小牛蜱(Boophilusmicroplus),森林革蜱(Dermacentor silvarum),长喙璃眼蜱(Hyalomma truncatum),蓖子硬蜱(Ixodes蓖麻),浅红硬蜱(Ixodesrubicundus),非洲钝缘蜱(Ornithodoros moubata),耳残喙蜱(Otobius megnini),鸡皮刺螨(Dermanyssus gallinae),绵羊瘙螨(Psoroptes ovis),非洲扇头蜱(Rhipicephalus appendiculatus),外翻扇头蜱(Rhipicephalus evertsi),人疥螨(Sarcoptes scabiei)和瘿螨科(Eriophyidae)物种诸如斯氏针刺瘿螨(Aculus schlechtendali),柑橘皱叶刺瘿螨(Phyllocoptruta oleivora)和桔芽瘿螨(Eriophyessheldoni);跗线螨科(Tarsonemidae)物种诸如樱草植食螨(Phytonemus pallidus)和侧多食跗线螨(Polyphagotarsonemuslatus);细须螨科(Tenuipalpidae)物种诸如紫红短须螨(Brevipalpusphoenicis);叶螨科(Tetranychidae)物种诸如朱砂叶螨(Tetranychuscinnabarinus),神泽氏叶螨(Tetranychus kanzawai),太平洋叶螨(Tetranychus pacificus),椴两点叶螨(Tetranychus telarius)和二斑叶螨(Tetranychus urticae),苹果全爪螨(Panonychus ulmi),柑橘全爪螨(Panonychus citri)和草地小爪螨(Oligonychuspratensis);
蚤目(Siphonaptera),例如印鼠客蚤(Xenopsylla cheopis),角叶蚤属(Ceratophyllus spp.)物种
式I的组合物和化合物对于控制线虫有用,尤其植物寄生虫线虫诸如根节线虫,北方根结线虫(Meloidogyne hapla),南方根结线虫(Meloidogyne incognita),爪哇根结线虫(Meloidogyne javanica)和其他根结线虫属(Meloidogyne)物种;cystforming线虫,马铃薯金线虫(Globodera rostochiensis)和其他球异皮线虫属(Globodera)物种;燕麦异皮线虫(Heterodera avenae),大豆异皮线虫(Heteroderaglycines),甜菜异皮线虫(Heterodera schachtii),三叶草异皮线虫(Heterodera trifolii)和其他异皮线虫属(Heterodera)物种;种汁线虫,瘿线虫属(Anguina)物种;茎和叶线虫,滑刃线虫属(Aphelenchoides)物种;叮咬线虫,长尾刺线虫(Belonolaimuslongicaudatus)和其他刺线虫属(Belonolaimus)物种;松线虫,松材线虫(Bursaphelenchus xylophilus)和其他伞滑刃线虫属(Bursaphelenchus)物种;环线虫,环线虫属(Criconema)物种,小环线虫属(Criconemella)物种,轮线虫属(Criconemoides)物种,间环线虫属(Mesocriconema)物种;茎和鳞茎线虫,马铃薯茎线虫(Ditylenchus destructor),起绒草茎线虫(Ditylenchus dipsaci)和其他茎线虫属(Ditylenchus)物种;锥线虫,锥线虫属(Dolichodorus)物种;螺旋线虫,多带螺旋线虫(Helicotylenchus multicinctus)和其他螺旋线虫属(Helicotylenchus)物种;鞘及sheathoid线虫,鞘线虫属(Hemicycliophora)物种和半轮线虫属(Hemicriconemoides)物种;潜根线虫属(Hirschmanniella)物种;窄线虫,纽带线虫属(Hoplolaimus)物种;假根结线虫,真珠线虫属(Nacobbus)物种;针线虫,逸去长针线虫(Longidorus elongatus)和其他长针线虫属(Longidorus)物种;针线虫,针线虫属(Paratylenchus)物种;损伤线虫,落选短体线虫(Pratylenchus neglectus),穿刺短体线虫(Pratylenchus penetrans),弯曲短体线虫(Pratylenchus curvitatus),古氏短体线虫(Pratylenchus goodeyi)和其他短体线虫属(Pratylenchus)物种;Burrowing线虫,相似穿孔线虫(Radopholussimilis)和其他穿孔线虫属(Radopholus)物种;肾形线虫,强壮盘旋线虫(Rotylenchus robustus)和其他盘旋线虫属(Rotylenchus)物种;盾状线虫属(Scutellonema)物种;粗短根线虫,原始毛刺线虫(Trichodorus primitivus)和其他毛刺线虫属(Trichodorus)物种,类毛刺线虫属(Paratrichodorus)物种;发育迟缓线虫,克莱顿矮化线虫(Tylenchorhynchus claytoni),不定矮化线虫(Tylenchorhynchusdubius)和其他矮化线虫属(Tylenchorhynchus)物种;柑橘线虫,小垫刃线虫属(Tylenchulus)物种;剑线虫,剑线虫属(Xiphinema)物种;及其他植物寄生虫线虫物种。
在本发明的优选的实施方式中,式I的化合物用于控制昆虫或蜘蛛,尤其是鳞翅目(Lepidoptera)昆虫,
鞘翅目(Coleoptera),缨翅目(Thysanoptera)和同翅目(Homoptera)和蜱螨目(Acarina)的蜘蛛。本发明的式I的化合物对于控制缨翅目(Thysanoptera)和同翅目(Homoptera)昆虫特别有用。
通过使植物/作物接触杀虫有效量的式I的化合物,式I的化合物或包含它们的杀虫组合物可用于保护生长植物和作物免于被无脊椎动物害虫攻击或侵袭,尤其昆虫,粉螨科(Acaridae)或蜘蛛。术语"作物"指称生长及收获的作物。
式I的化合物可转变为常规制剂,例如溶液,乳剂,悬浮液,粉剂,粉,糊剂和颗粒剂。使用形式依赖于特定旨在的目的;在各情况中,其应确保本发明的化合物的精细和甚至分散。
制剂以知道的方式制备(见例如综述US 3,060,084,EP-A 707445(对于液体浓缩物),Browning,"Agglomeration",ChemicalEngineering,Dec.4,1967,147-48,Perry's Chemical Engineer'sHandbook,4th Ed.,McGraw-Hill,New York,1963,pages 8-57and etseq.WO 91/13546,US 4,172,714,US 4,144,050,US 3,920,442,US5,180,587,US 5,232,701,US 5,208,030,GB 2,095,558,US 3,299,566,Klingman,Weed Control as a Science,John Wiley and Sons,Inc.,NewYork,1961,Hance et al.,Weed Control Handbook,8th Ed.,BlackwellScientific Publications,Oxford,1989and Mollet,H.,Grubemann,A.,Formulation technology,Wiley VCH Verlag GmbH,Weinheim(Germany),2001,2.D.A.Knowles,Chemistry and Technology ofAgrochemical Formulations,Kluwer Academic Publishers,Dordrecht,1998(ISBN 0-7514-0443-8)),例如通过用适合于农药制剂的辅助剂,诸如溶剂和/或载体,如果需要,乳化剂,表面活性剂和分散剂,防腐剂,抗-发泡剂,抗-冷冻剂,如种子处理制剂也任选地着色剂和/或结合剂和/或胶凝剂来扩展活性化合物。
适合的溶剂的例是水,芳族溶剂(例如Solvesso产品,二甲苯),石蜡(例如矿物油级分),醇(例如甲醇,丁醇,戊醇,苄基醇),酮(例如环己酮,γ-丁内酯),吡咯烷酮(N-甲基吡咯烷酮[NMP],N-辛基吡咯烷酮[NOP]),乙酸酯(二乙酸二醇),二醇,脂肪酸二甲酰胺,脂肪酸和脂肪酸酯。原则上,也可使用溶剂混合物。
适合的乳化剂是非-离子和阴离子乳化剂(例如聚氧乙烯脂肪醇醚,烷基磺酸盐和芳基磺酸盐)。
分散剂的例是木质素亚硫酸盐废液和甲基纤维素。
使用的适合的表面活性剂是木质素磺酸,萘磺酸,苯酚磺酸,二丁基萘-磺酸的碱金属,碱土金属和铵盐,烷基芳基磺酸盐,烷基硫酸盐,烷基磺酸盐,脂肪醇硫酸盐,脂肪酸及硫酸化的脂肪醇二醇醚,此外,磺化的萘和萘衍生物与甲醛的浓缩物,萘或萘磺酸与苯酚和甲醛的浓缩物,聚氧乙烯辛基苯酚醚,乙氧基化的异辛基苯酚,辛基苯酚,壬基苯酚,烷基苯酚聚甘醇醚,三丁基苯基聚甘醇醚,三硬脂基苯基聚甘醇醚,烷基芳基聚醚醇,醇和脂肪醇环氧乙烷浓缩物,乙氧基化的蓖麻油,聚氧乙烯烷基醚,乙氧基化的聚氧丙烯,月桂基醇聚甘醇醚乙缩醛,山梨糖醇酯,木质素亚硫酸盐废液和甲基纤维素。
适合制备直接可喷洒的溶液,乳剂,糊剂或油分散的物质是中到高沸点的矿物油级分,诸如煤油或柴油,此外煤焦油和植物或动物来源的油,脂肪族,环状和芳族烃,例如甲苯,二甲苯,石蜡,四氢化萘,烷基化的萘或它们的衍生物,甲醇,乙醇,丙醇,丁醇,环己醇,环己酮,异佛尔酮,高度极性溶剂,例如二甲基亚砜,N-甲基吡咯烷酮或水。
也可将抗-冷冻剂诸如甘油,乙二醇,丙二醇和杀菌剂诸如加入制剂。
适合的抗发泡剂是例如基于硬酯酸硅或镁的抗发泡剂。
适合的防腐剂是例如双氯酚。
种子处理制剂可额外地包含结合剂和任选地着色剂。
可加入结合剂以改善处理之后种子上活性物质的粘接。适合的结合剂是嵌段共聚物EO/PO表面活性而且聚乙烯醇,聚乙烯吡咯烷酮,聚丙烯酸酯,聚甲基丙烯酸酯,聚丁烯,聚异丁烯,聚苯乙烯,聚乙烯胺,聚乙烯酰胺,聚乙烯亚胺聚醚,聚氨基甲酸酯,聚乙烯基乙酸酯,甲基纤维素和源于这些聚合物的共聚物。
任选地,着色剂也可包括在制剂中。用于种子处理制剂的适合的着色剂或染料是若丹明B,C.I.颜料红112,C.I.溶剂红1,颜料蓝15:4,颜料蓝15:3,颜料蓝15:2,颜料蓝15:1,颜料蓝80,颜料黄1,颜料黄13,颜料红112,颜料红48:2,颜料红48:1,颜料红57:1,颜料红53:1,颜料橙43,颜料橙34,颜料橙5,颜料绿36,颜料绿7,颜料白6,颜料棕25,碱性紫10,碱性紫49,酸性红51,酸性红52,酸性红14,酸性蓝9,酸性黄23,碱性红10,碱性红108。胶凝剂的一例是角叉菜胶
用于分散及可粉化产物的粉,物质可通过混合或随之研磨活性物质与固体载体来制备。
颗粒剂,例如包被的颗粒剂,浸渍的颗粒剂和均质颗粒剂,可通过将活性化合物结合到固体载体来制备。
固体载体的例是矿物质土诸如硅胶,硅酸盐,滑石粉,高岭土,镁质粘土,石灰石,石灰,白垩,胶块粘土,黄土,粘土,白云石,硅藻土,硫酸钙,硫酸镁,氧化镁,土壤合成物质,肥料,诸如,例如,硫酸铵,磷酸铵,硝酸铵,尿素和植物来源的产物,诸如谷物膳食,树皮膳食,木膳食和坚果壳膳食,纤维素粉和其他固体载体。
一般而言,制剂包含0.01~95重量%,优选0.1~90重量%的活性化合物。在此情况中,活性化合物以90~100重量%,优选95%~100重量%的纯度采用(根据NMR谱)。
种子处理目的,相应制剂可稀释2~10倍导致0.01~60重量%活性化合物(以重量计),优选0.1~40重量%即用制剂中的浓度。
式I的化合物可像这样使用,利用喷洒,雾化,落尘,扩展或投入,以它们的制剂形式或由其制备的使用形式,例如直接可喷洒的溶液,粉,悬浮液或分散,乳剂,油分散,糊剂,可粉化产物,扩散用物质,或颗粒剂形式。使用形式完全依赖于旨在的目的;它们旨在在各情况中确保本发明的活性化合物的尽可能精细的分布。
水性使用形式可通过添加水,从乳剂浓缩物,糊剂或可湿性粉剂(可喷洒的粉,油分散物)制备。为了制备乳剂,糊剂或油分散物,可将像这样或溶解在油或溶剂中的物质,在水中利用润湿剂,增粘剂,分散剂或乳化剂均质化。但是,也可能制备由活性物质,润湿剂,增粘剂,分散剂或乳化剂及,如果适当的,溶剂或油组成的浓缩物,及该浓缩物适合用水稀释。
即用制剂中的活性化合物浓度可在相对宽范围之内改变。一般而言,它们是0.0001~10%,优选0.01~1%每重量。
活性化合物也可成功地用于超-低-体积方法(ULV),其可能应用包含超过95重量%的活性化合物的制剂,或甚至应用无添加剂的活性化合物。
下列是制剂例:
1.用于用叶敷用水稀释的产物。为种子处理目的,可将该产物应用于稀释的或未稀释的种子。
(A)水-可溶性浓缩物(SL,LS)
将10重量份的活性化合物溶于90重量份的水或水溶性溶剂。作为替代,添加润湿剂或其他辅助剂。用水稀释后溶解活性化合物,其中获得具有10%(w/w)的活性化合物的制剂。
(B)可分散浓缩物(DC)
将20重量份的活性化合物溶于70重量份的环己酮,添加10重量份的分散剂,例如聚乙烯吡咯烷酮。用水稀释导致分散,其中获得含20%(w/w)的活性化合物的制剂。
(C)可乳化的浓缩物(EC)
将15重量份的活性化合物溶于7重量份的二甲苯,添加十二烷基苯磺酸钙和蓖麻油乙氧基化物(在各情况中5重量份)。用水稀释产生乳剂,其中获得含15%(w/w)的活性化合物的制剂。
(D)乳液(EW,EO,ES)
将25重量份的活性化合物溶于35重量份的二甲苯,添加十二烷基苯磺酸钙和蓖麻油乙氧基化物(在各情况中5重量份)。将此混合物利用乳化剂机(例如Ultraturrax)导入30重量份的水,及制造进均质乳剂。用水稀释产生乳剂,其中获得含25%(w/w)的活性化合物的制剂。
(E)悬浮液(SC,OD,FS)
在搅拌的球磨机中,将20重量份的活性化合物捣碎,添加10重量份的分散剂,润湿剂和70重量份的水或有机溶剂以得到精细活性化合物悬浮液。用水稀释产生活性化合物的稳定的悬浮液,其中获得含20%(w/w)的活性化合物的制剂。
(F)水-可分散颗粒剂和水溶性颗粒剂(WG,SG)
50重量份的活性化合物精致地研磨,添加50重量份的分散剂和润湿剂及利用技术器具(例如挤出,喷洒塔,流化床)制造为水-可分散或水溶性颗粒剂。用水稀释产生活性化合物的稳定的分散或溶液,其中获得含50%(w/w)的活性化合物的制剂。
(G)水-可分散粉和水溶性粉(WP,SP,SS,WS)
将75重量份的活性化合物在转子-定子碾磨机中研磨,添加25重量份的分散剂,润湿剂和硅胶。用水稀释产生活性化合物的稳定的分散或溶液,其中获得含75%(w/w)的活性化合物的制剂。
(H)凝胶-制剂(GF)
在搅拌的球磨机中,将20重量份的活性化合物捣碎,添加10重量份的分散剂,1重量份的胶凝剂润湿剂和70重量份的水或有机溶剂以得到精细活性化合物悬浮液。用水稀释产生活性化合物的稳定的悬浮液,其中获得含20%(w/w)的活性化合物的制剂。
2.未稀释的叶敷用待应用的产物。为种子处理目的,可将该产物应用于稀释的或未稀释的种子。
(I)粉剂(DP,DS)
将5重量份的活性化合物精致地研磨及与95重量份的精致地分的高岭土密切地混合。此得到具有5%(w/w)的活性化合物的可粉化产物。
(J)颗粒(GR,FG,GG,MG)
将0.5重量份的活性化合物精致地研磨及混合95.5重量份的载体,其中获得含0.5%(w/w)的有活性的化合物的制剂。现有方法是挤出,喷雾干燥或流化床。此得到用于叶使用的待应用的未稀释的颗粒剂。
(K)ULV溶液(UL)
将10重量份的活性化合物溶于90重量份的有机溶剂,例如二甲苯。此得到具有10%(w/w)的活性化合物的产物,其未稀释应用用于叶使用。
式I的化合物也适合处理植物繁殖材料(诸如种子)。常规种子处理制剂包括例如可流动的浓缩FS,溶液LS,粉用于干处理DS,水可分散粉用于浆处理WS,水溶性粉SS和乳剂ES和EC和凝胶制剂GF。可将这些制剂应用于稀释的或未稀释的种子。在进行播种之前应用到种子,直接到种子或在预发芽了后者之后。
在优选的实施方式中,FS制剂用于种子处理。一般而言,FS制剂可包含1~800g/l的活性成分,1~200g/l表面活性剂,0~200g/l抗冻剂,0~400g/l的结合剂,0~200g/l的色素和达1l的溶剂,优选水。
种子处理用式I的化合物的其他优选的FS制剂包含0.5~80wt的活性成分,0.05~5wt的润湿剂,0.5~15wt的分散剂,0.1~5wt的增稠剂,5~20wt的抗冷冻剂,0.1~2wt的抗-泡沫剂,1~20wt的色素和/或染料,0~15wt的粘结剂/粘接剂,0~75wt的填料/媒质,及0.01~1wt的防腐剂。
可将各种类型的油,润湿剂,佐剂,除草剂,杀真菌剂,其他杀虫剂,或杀菌剂加入活性成分,如果适当,在使用之前立即(桶混剂)。这些剂通常以1:10~10:1的重量比与本发明的剂混合。
式I的化合物通过接触(经土壤,玻璃,壁,蚊帐,地毯,植物部分或动物部分),及摄入(饵,或植物部分)而有效。
对于针对蚂蚁,白蚁,黄蜂,蝇,蚊,蟋蟀或蟑螂使用,式I的化合物优选用在饵组合物中。
饵可为液体,固体或半固体制备物(例如凝胶)。固体饵可形成为各种形状和适合相应应用的形式,例如颗粒剂,块,杆,盘。液体饵可填充到各种装置以确保适当的应用,例如开放容器,喷洒装置,滴源或蒸发源。凝胶可基于水性或油性基质和可根据粘稠度,湿度保留或老化特征配制成特定必要。
在组合物中采用的饵是产物,其对食其的刺激昆虫足够有吸引力,所述昆虫诸如蚂蚁,白蚁,黄蜂,蝇,蚊,蟋蟀等或蟑螂。吸引力可通过使用饲喂刺激物或性信息素操作。食品刺激物选择,例如但不完全自:动物和/或植物蛋白(肉,鱼-或血膳食,昆虫部分,卵黄),自动物和/或植物来源的脂肪和油,或单-,寡-或聚有机糖,尤其自蔗糖,乳糖,果糖,右旋糖,葡萄糖,淀粉,果胶或甚至糖蜜或蜂蜜。果实,作物,植物,动物,昆虫或其特定部分的新鲜或腐败部分也可用于饲喂刺激物。性信息素已知是更昆虫特异性的。特定信息素描述于文献及本领域技术人员已知。
作为气雾剂(例如在喷雾剂罐中),油喷雾剂或泵喷雾剂的式I的化合物的制剂高度适合于控制害虫诸如蝇,蚤,蜱,蚊或蟑螂的非-专业用户。气雾剂处方优选由下列组成:活性化合物,溶剂诸如低级醇(例如甲醇,乙醇,丙醇,丁醇),酮(例如丙酮,甲基乙基酮),具有约50~250℃的沸腾范围的石蜡烃(例如煤油),二甲基甲酰胺,N-甲基吡咯烷酮,二甲基亚砜,芳族烃诸如甲苯,二甲苯,水,此外辅助剂诸如乳化剂诸如山梨糖醇单油酸酯,具有3~7mol的环氧乙烷的乙氧基化油酯,脂肪醇乙氧基化物,香料油诸如醚油,中等脂肪酸与低级醇的酯,芳族羰基化合物,如果适当的稳定剂诸如苯甲酸钠,兼性表面活性剂,低级环氧化物,原甲酸三乙酯及,如果需要的,推进剂诸如丙烷,丁烷,氮,压缩的空气,二甲基醚,二氧化碳,一氧化二氮或这些气体的混合物。
油喷洒制剂不同于未使用推进剂的气雾剂处方。
式I的化合物和它们的相应组合物也可用于蚊及熏蒸线圈,发烟筒,气化器板或长期气化器和也用于蛾纸,蛾垫或其他热-独立气化器系统。
用式I的化合物和其相应组合物控制通过昆虫传播的感染性疾病(例如疟疾,登革热和黄热病,淋巴丝虫病和利什曼病)的方法也包括处理屋舍和屋室的表面,空气喷洒及浸渍帘,帐,衣物品,蚊帐,采采蝇捕器等。应用于纤维,织物,针织品,非-编织品,网织物质或箔和帆布的杀昆虫组合物优选包含包括杀昆虫剂,任选地驱避剂和至少一种结合剂的混合物。适合的驱避剂例如是N,N-二乙基-间-甲苯酰胺(DEET),N,N-二乙基苯基乙酰胺(DEPA),1-(3-环己烷-1-基-羰基)-2-甲基胡椒碱,(2-羟甲基环己基)乙酸内酯,2-乙基-1,3-己二醇,避蚊酮,甲基新癸酰胺(MNDA),不用于昆虫控制的拟除虫菊酯,诸如{(+/-)-3-烯丙基-2-甲基-4-氧代环戊-2-(+)-烯基-(+)-反式-菊酸酯(菊酯),源于或同一于植物提取物的驱避剂如苧烯,丁香酚,(+)-Eucamalol(1),(-)-1-表-eucamalol或自下列植物的粗植物提取物:如斑皮桉(Eucalyptus maculata),单叶蔓荆(Vitex rotundifolia),玫瑰草(Cymbopogon martinii),香茅(Cymbopogon citratus)(柠檬草),亚香茅(Cymbopogon nardus)(香茅)。适合的结合剂是例如选自:脂肪族酸的乙烯基酯的聚合物和共聚物(诸如诸如乙酸乙烯酯和乙烯基versatate),醇的丙烯酸和甲基丙烯酸酯,诸如丙烯酸丁酯,2-乙基己基丙烯酸酯和丙烯酸甲酯,单-及二乙烯键不饱和的烃,诸如苯乙烯,及脂肪族二烯,诸如丁二烯。
帘及蚊帐的浸渍通常通过将织物材料浸到式I的活性化合物的乳剂或分散剂或将它们喷洒到蚊帐上来进行。
可用于处理种子的方法是,原则上,全部适合的种子处理和尤其本领域知道的拌种技术,诸如种子包衣(例如种子压沉),种子落尘及种子吸涨(例如种子浸没)。在本文中,"种子处理"指称使种子和式I的化合物彼此接触的全部方法,及"拌种"指称提供种子一定量的式I的化合物的种子处理方法,即其产生包含式I的化合物的种子。原则上,可在从种子收获到种子播种的任何时间将处理应用于种子。种子可在种子种植之前立即或期间处理,例如使用"planter‘s盒"方法。但是,处理也可进行几周或几个月,例如达12个月,在种植种子之前,例如以拌种处理的形式,未基本上观察到减少的功效。
方便地,将处理应用于未播种的种子。如本文所用,术语"未播种的种子"意指包括为植物的萌芽和生长的目的在地从种子收获到种子播种的任何时期的种子。
特别是,过程之后是在适合的装置中的种子混合处理,例如用于固体或固体/液体混合偶体,与期望的量的种子处理制剂的混合装置,either像这样或用水之前稀释之后,直到组合物均匀分布到种子。如果适当,此之后是干燥步骤。
式I的化合物,或对映异构体,非对映异构体或其兽医学地可接受的盐尤其是是也适合用于抵御动物中及上的寄生虫。
本发明因此也旨在提供控制动物中及上的寄生虫的新方法。本发明的另一目的是提供更安全的动物用杀虫剂。本发明的另一目的还是提供动物用杀虫剂可以相比存在的杀虫剂更低剂量使用。且本发明的另一目的是提供动物用杀虫剂,其提供寄生虫的长残留控制。
本发明也涉及组合物,其含有杀寄生虫有效量的式I的化合物或其对映异构体或兽医学地可接受的盐及可接受的载体,用于抵御动物中及上的寄生虫。
本发明也提供处理,控制,防止及保护动物针对被寄生虫侵袭和感染的方法,其包括经口,局部或肠胃外施用或应用给动物杀寄生虫有效量的式I的化合物或其对映异构体或兽医学地可接受的盐或包含其的组合物。
本发明也提供处理,控制,防止及保护动物针对被寄生虫侵袭和感染的非-治疗性方法,其包括应用给位置杀寄生虫有效量的式I的化合物或其对映异构体或兽医学地可接受的盐或包含其的组合物。
本发明也提供制备用于处理,控制,防止或保护动物针对被寄生虫侵袭或感染的组合物的方法,其包含在包含其的组合物中包括杀寄生虫有效量的式I的化合物或其对映异构体或兽医学地可接受的盐。
本发明还涉及式I的化合物用于处理,控制,防止或保护动物针对被寄生虫侵袭或感染的用途。
本发明也涉及式I的化合物,或包含其的组合物,用于制备用于动物针对被寄生虫感染或侵袭的治疗性处理的药物的用途。
化合物针对农业害虫的活性不提示它们的控制动物中及上的内-及外寄生物的适应性,其在口腔应用的情况中需要,例如,低,非-催吐剂量,与动物的代谢兼容性,低毒性,及安全的操作。
意外地,现在已发现,式I的化合物适合用于抵御动物中及上的内-及外寄生物。式I的化合物或其对映异构体或兽医学地可接受的盐及包含它们的组合物是适合系统性和/或非-系统性控制外-和/或内寄生物。它们是针对全部或一些发育阶段有活性的。
式I的化合物或其对映异构体或兽医学地可接受的盐及包含它们的组合物优选用于控制及防止动物包括温血动物(包括人)和鱼的侵袭和感染。它们是例如适合控制及防止下列哺乳动物的侵袭和感染:诸如牛,绵羊,猪,骆驼,鹿,马,猪,家禽,兔,山羊,狗和猫,水牛,驴,欧洲鹿和驯鹿,及也带有毛皮的动物诸如貂,毛丝鼠和浣熊,鸟诸如鸡,鹅,火鸡和鸭和鱼诸如淡水和盐水鱼诸如鳟,鲤和鳗。
式I的化合物或其对映异构体或兽医学地可接受的盐及包含它们的组合物优选用于控制及防止家畜,诸如狗或猫的侵袭和感染。
温血动物和鱼的侵袭包括,但未限制于,虱,羽虱,蜱,鼻蝇,蜱蝇,螫蝇,苍蝇,蝇,蝇蛆,恙螨,蚋,蚊和蚤。
式I的化合物尤其有用于抵御外寄生物。
式I的化合物尤其有用于抵御内寄生物。
式I的化合物尤其有用于抵御下列目和物种的寄生虫,分别:
蚤(蚤目(Siphonaptera)),例如猫栉首蚤(Ctenocephalides felis),犬栉首蚤(Ctenocephalides canis),印鼠客蚤(Xenopsylla cheopis),人蚤(Pulex irritans),穿皮潜蚤(Tunga penetrans)和具带病蚤(Nosopsyllus fasciatus),
蟑螂(蜚蠊目(Blattaria)-蜚蠊目(Blattodea)),例如德国小蠊(Blattella germanica),亚洲小蠊(Blattella asahinai),美洲大蠊(Periplaneta americana),日本大蠊(Periplaneta japonica),褐斑大蠊(Periplaneta brunnea),黑胸大蠊(Periplaneta fuliginosa),澳洲大蠊(Periplaneta australasiae)和东方蜚蠊(Blatta orientalis),
蝇,蚊(双翅目(Diptera)),例如埃及伊蚊(Aedes aegypti),白条伊蚊(Aedes albopictus),刺扰伊蚊(Aedes vexans),墨西哥按实蝇(Anastrepha ludens),五斑按蚊(Anopheles maculipennis),灾难按蚊(Anopheles crucians),淡色按蚊(Anopheles albimanus),冈比亚按蚊(Anopheles gambiae),弗氏按蚊(Anopheles freeborni),白踝按蚊(Anopheles leucosphyrus),微小按蚊(Anopheles minimus),四斑按蚊(Anopheles quadrimaculatus),红头丽蝇(Calliphoravicina),蛆症金蝇(Chrysomya bezziana),嗜人金蝇(Chrysomyiahominivorax),腐败金蝇(Chrysomyia macellaria),灰中室斑虻(Chrysops discalis),静斑虻(Chrysops silacea),大西洋斑虻(Chrysops atlanticus),嗜人锥蝇(Cochliomyia hominivorax),嗜人瘤蝇(Cordylobia anthropophaga),毛库蠓(Culicoides furens),尖音库蚊(Culex pipiens),黑须库蚊(Culex nigripalpus),致倦库蚊(Culex quinquefasciatus),环喙库蚊(Culex tarsalis),无饰脉毛蚊(Culiseta inornata),黑尾脉毛蚊(Culiseta melanura),人肤蝇(Dermatobia hominis),夏厕蝇(Fannia canicularis),肠胃蝇(Gasterophilus intestinalis),刺舌蝇(Glossina morsitans),须舌蝇(Glossina palpalis),棕足舌蝇(Glossina fuscipes),拟寄舌蝇(Glossina tachinoides),西方角蝇(Haematobia irritans),鞍瘿瘿蚊(Haplodiplosis equestris),潜蝇属(Hippelates spp.)物种,纹皮蝇(Hypoderma lineatum),急流细蠓(Leptoconops torrens),羊绿蝇(Lucilia caprina),铜绿蝇(Lucilia cuprina),丝光绿蝇(Luciliasericata),胸狼毛尖眼蕈蚊(Lycoria pectoralis),曼蚊属(Mansoniaspp.)物种,家蝇(Musca domestica),厩腐蝇(Muscina stabulans),羊狂蝇(Oestrus ovis),银足白蛉(Phlebotomus argentipes),哥伦比亚鳞蚊(Psorophora columbiae),变色鳞蚊(Psorophora discolor),毛足原蚋(Prosimulium mixtum),红尾粪麻蝇(Sarcophagahaemorrhoidalis),麻蝇属(Sarcophaga sp.),带蚋(Simuliumvittatum),厩螫蝇(Stomoxys calcitrans),牛虻(Tabanus bovinus),黑虻(Tabanus atratus),具带马虻(Tabanus lineola)和相似虻(Tabanus similis),
虱(虱目(Phthiraptera)),例如头虱(Pediculus humanus capitis),体虱(Pediculus humanus corporis),阴虱(Pthirus pubis),牛血虱(Haematopinus eurysternus),猪血虱(Haematopinus suis),牛长颚虱(Linognathus vituli),牛羽虱(Bovicola bovis),鸡禽虱(Menopon gallinae),水鸡翎虱(Menacanthus stramineus)和牛管虱(Solenopotes capillatus)。
蜱和寄生虫螨(寄螨目(Parasitiformes)):蜱(硬蜱科(Ixodidae)),例如肩突硬蜱(Ixodes scapularis),全环硬蜱(Ixodes holocyclus),太平洋硬蜱(Ixodes pacificus),血红扇头蜱(Rhipicephalussanguineus),安氏革蜱(Dermacentor andersoni),变异革蜱(Dermacentor variabilis),美洲花蜱(Amblyomma americanum),有斑花蜱(Amblyomma maculatum),赫姆钝缘蜱(Ornithodoroshermsi),回归热钝缘蜱(Ornithodoros turicata)和寄生虫螨(中气门亚目(Mesostigmata)),例如柏氏禽刺螨(Ornithonyssus bacoti)和鸡皮刺螨(Dermanyssus gallinae),
辐螨目(Actinedida)(前气门亚目(Prostigmata))和粉螨目(Acaridida)(无气门亚目(Astigmata))例如蜂跗线螨属(Acarapisspp.)物种,姬螯螨属(Cheyletiella spp.)物种,禽螯厘螨属(Ornithocheyleia spp.)物种,肉螨属(Myobia spp.)物种,疮螨属(Psorergates spp.)物种,蠕形螨属(Demodex spp.)物种,恙螨属(Trombicula spp.)物种,牦螨属(Listrophorus spp.)物种,粉螨属(Acarus spp.)物种,食酪螨属(Tyrophagus spp.)物种,嗜木螨属(Caloglyphus spp.)物种,颈下螨属(Hypodectes spp.)物种,翅螨属(Pterolichus spp.)物种,瘙螨属(Psoroptes spp.)物种,痒螨属(Chorioptes spp.)物种,耳螨属(Otodectes spp.)物种,疥螨属(Sarcoptes spp.)物种,痂螨属(Notoedres spp.)物种,疙螨属(Knemidocoptes spp.)物种,胞螨属(Cytodites spp.)物种和皮膜螨属(Laminosioptes spp.)物种,
臭虫(异翅亚目(Heteropterida)):温带臭虫(Cimex lectularius),热带臭虫(Cimex hemipterus),老头猎蝽(Reduvius senilis),椎猎蝽属(Triatoma spp.)物种,红猎蝽属(Rhodnius ssp.)物种,全园蝽属(Panstrongylus ssp.)物种和齿背猎蝽(Arilus critatus),
虱目(Anoplurida),例如血虱属(Haematopinus spp.)物种,长颚虱属(Linognathus spp.)物种,人虱属(Pediculus spp.)物种,阴虱属(Pthirus spp.)物种,及盲虱属(Solenopotes spp.)物种,
食毛目(Mallophagida)(钝角亚目(Amblycerina)和细角亚目(Ischnocerina)),例如毛羽虱属(Trimenopon spp.)物种,禽虱属(Menopon spp.)物种,巨羽虱属(Trinoton spp.)物种,牛羽虱属(Bovicola spp.)物种,毛虱属(Werneckiella spp.)物种,Lepikentron属(Lepikentron spp.)物种,嚼虱属(Trichodectes spp.)物种和猫羽虱属(Felicola spp.)物种,
蛔虫线虫纲(Nematoda):
毛线虫和旋毛虫(毛管目(Trichosyringida)),例如毛线虫科(Trichinellidae)(毛形线虫属(Trichinella spp.)物种),(鞭虫科(Trichuridae))毛首鞭形线虫属(Trichuris spp.)物种,毛细线虫属(Capillaria spp.)物种,
杆线虫目(Rhabditida),例如小杆线虫属(Rhabditis spp.)物种,类圆线虫属(Strongyloides spp.)物种,Helicephalobus属(Helicephalobus spp.)物种,
圆线目(Strongylida),例如圆线虫属(Strongylus spp.)物种,钩口线虫属(Ancylostoma spp.)物种,美洲板口线虫(Necatoramericanus),仰口线虫属(Bunostomum spp.)物种(钩虫),毛圆线虫属(Trichostrongylus spp.)物种,捻转血矛线虫(Haemonchuscontortus),奥斯特线虫属(Ostertagia spp.)物种,古柏线虫属(Cooperia spp.)物种,细颈线虫属(Nematodirus spp.)物种,网尾线虫属(Dictyocaulus spp.)物种,杯口线虫属(Cyathostoma spp.)物种,结节线虫属(Oesophagostomum spp.)物种,齿状冠线虫(Stephanurus dentatus),沃鲁线虫属(Ollulanus spp.)物种,夏伯特线虫属(Chabertia spp.)物种,齿状冠线虫(Stephanurus dentatus),气管比翼线虫(Syngamus气管),钩口线虫属(Ancylostoma spp.)物种,钩虫属(Uncinaria spp.)物种,球头线虫属(Globocephalus spp.)物种,板口线虫属(Necator spp.)物种,后圆线虫属(Metastrongylusspp.)物种,毛细缪勒线虫(Muellerius capillaris),原圆线虫属(Protostrongylus spp.)物种,管圆线虫属(Angiostrongylus spp.)物种,副麂圆线虫属(Parelaphostrongylus spp.)物种,深奥猫圆线虫(Aelurostrongylus abstrusus)和肾膨结线虫(Dioctophyma renale),
肠蛔虫(蛔目(Ascaridida)),例如人蛔虫(Ascaris lumbricoides),猪蛔虫(Ascaris suum),鸡蛔虫(Ascaridia galli),马副蛔虫(Parascarisequorum),蠕形住肠蛲虫(Enterobius vermicularis)(Threadworm),犬弓蛔虫(Toxocara canis),狮弓蛔线虫(Toxascaris leonina),斯克里亚宾线虫属(Skrjabinema spp.)和马尖尾线虫(Oxyuris equi),
驼形目(Camallanida),例如麦地那龙线虫(Dracunculusmedinensis)
旋尾目(Spirurida),例如吸吮线虫属(Thelazia spp.)物种,吴策线虫属(Wuchereria spp.)物种,布鲁丝虫属(Brugia spp.)物种,盘尾丝虫属(Onchocerca spp.)物种,恶丝虫属(Dirofilaria spp.)物种,双瓣线虫属(Dipetalonema spp.)物种,鬃丝虫属(Setaria spp.)物种,血管丝虫属(Elaeophora spp.)物种,卢氏尾旋线虫(Spirocercalupi),and丽线虫属(Habronema spp.),
棘头虫(棘头虫纲(Acanthocephala)),例如棘头虫属(Acanthocephalus spp.)物种,猪巨吻棘头虫(Macracanthorhynchushirudinaceus)and钩棘头虫属(Oncicola spp.)物种,
涡虫(扁形动物门(Platyhelminthes)):
吸虫(吸虫纲(Trematoda)),例如片形吸虫属(Fasciola spp.)物种,大拟片形吸虫(Fascioloides magna),并殖吸虫属(Paragonimusspp.)物种,双腔吸虫属(Dicrocoelium spp.)物种,布氏姜片吸虫(Fasciolopsis buski),华支睾吸虫(Clonorchis sinensis),血吸虫属(Schistosoma spp.)物种,毛毕吸虫属(Trichobilharzia spp.),有翼重翼吸虫(Alaria alata),并殖吸虫属(Paragonimus spp.)物种和侏形吸虫属(Nanophyetus spp.)物种,
绦虫次亚门(Cercomeromorpha),尤其是多节绦虫亚纲(Cestoda)(Tapeworms),例如裂头绦虫属(Diphyllobothrium spp.)物种,带绦虫属(Taenia spp.)物种,棘球绦虫属(Echinococcus spp.)物种,犬复殖孔绦虫(Dipylidium caninum),多头绦虫属(Multiceps spp.)物种,膜壳绦虫属(Hymenolepis spp.)物种,中殖孔绦虫属(Mesocestoides spp.)物种,蝙蝠皮绦虫属(Vampirolepis spp.)物种,蒙尼茨绦虫属(Moniezia spp.)物种,裸头绦虫属(Anoplocephalaspp.)物种,迭宫绦虫属(Spirometra spp.)物种,裸头绦虫属(Anoplocephala spp.)物种和膜壳绦虫属(Hymenolepis spp.)物种。
【应用】
本发明涉及式I的化合物用于控制和/或抵御动物中和/或上的寄生虫的治疗性和非-治疗性用途。
式I的化合物可用于通过接触它们与杀寄生虫有效量的式I的化合物来保护动物免于被寄生虫攻击或侵袭。像这样,"接触"包括直接接触(将化合物/组合物直接应用于寄生虫,包括直接应用于动物或排除直接应用于动物,例如对于后者是在其位置)和间接接触(将化合物/组合物应用于寄生虫位置)。通过应用到其位置接触寄生虫是式I的化合物的非-治疗性用途的一例。
以上定义的"位置"是指寄生虫在动物外部生长或可生长的栖息地,食品供应,繁殖地,区,物质或环境。本发明的化合物也可预防性地应用于害虫或寄生虫预期发生的地点。
式I的化合物可为通过接触(经土壤,玻璃,壁,蚊帐,地毯,毯或动物部分)和摄入(例如饵)有效。
施用可预防,治疗或非-治疗性地进行。
活性化合物的施用直接或以适合的制备物形式,经口,局部/经皮或肠胃外进行。
一般而言,"杀寄生虫有效量"是指达到可观察的对生长的效应,包括对坏死,死亡,延迟,防止和去除,破坏,或另外靶生物的渐小的发生和活性的效应需要的活性成分量。本发明中使用的各种化合物/组合物的杀寄生虫有效量可改变。杀寄生虫有效量的组合物也会根据一般条件,诸如期望的杀寄生虫效应和持续时间,靶物种,应用模式,等而改变。
通常以0.5mg/kg~100mg/kg/天,优选1mg/kg~50mg/kg/天的总量应用式I的化合物是有利的。
【制剂】
对于给温血动物口服施用,式I化合物可制成动物饲料,动物饲料预混物,动物饲料浓缩物,丸剂,溶液,糊剂,悬浮液,顿服药,凝胶,片剂,药团和胶囊。此外,可将式I化合物以它们的饮用水施用于动物。对于口服施用,选择的剂型应提供动物0.01mg/kg~100mg/kg的动物体重/天的式I化合物,优选0.5mg/kg~100mg/kg的动物体重/天。
或者,可将式I化合物肠胃外,例如,通过瘤胃内,肌内,静脉内或皮下注射施用于动物。式I化合物可分散或溶解于生理学可接受的皮下注射用载体。或者,式I化合物可配制成皮下施用用植入物。此外,式I化合物可为透皮施用给动物。对于肠胃外施用,选择的剂型应提供动物0.01mg/kg~100mg/kg的动物体重/天的式I化合物。
式I化合物也可以浸剂,粉剂,粉,项圈,纪念章,喷雾剂,洗发水,点斑和投放制剂及以软膏或水包油或油包水乳剂的形式局部应用给动物。对于局部应用,浸剂及喷雾剂通常含有0.5ppm~5,000ppm和优选1ppm~3,000ppm的式I化合物。此外,式I化合物可制成动物,特别四足动物诸如牛和绵羊的耳标签。
适合的制备物是:
●溶液诸如口腔溶液,用于稀释之后口服施用的浓缩物,在皮肤上或在体腔中使用的溶液,投放剂,凝胶;
●用于口腔或真皮施用的乳液和悬浮液;半-固体制备物;
●活性化合物以基于软膏或基于水包油或油包水乳剂处理的制剂;
●固体制备物诸如粉,预混物或浓缩物,颗粒剂,沉淀,片剂,药团,胶囊;气雾剂和吸入剂,及含有活性化合物的形状的物品。
通过将活性成分溶解进适合的溶剂,并任选地添加其他成分诸如酸,碱,缓冲剂盐,防腐剂和增溶剂来制备适合注射的组合物。溶液无菌过滤及填充。
适合的溶剂是生理学容许的溶剂诸如水,烷醇诸如乙醇,丁醇,苄基醇,甘油,丙二醇,聚乙二醇,N-甲基-吡咯烷酮,2-吡咯烷酮和其混合物。
活性化合物可任选地溶于适合注射的生理学容许的植物或合成油。
适合的增溶剂是促进活性化合物溶解到主要溶剂或防止其沉淀的溶剂。例是聚乙烯吡咯烷酮,聚乙烯基醇,聚氧乙烯化的蓖麻油,及聚氧乙烯化的山梨糖醇酐酯。
适合的防腐剂是苄基醇,三氯丁醇,p-羟基苯甲酸酯,及n-丁醇。
口腔溶液直接施用。浓缩物是预先稀释成使用浓度之后经口施用。口腔溶液和浓缩物根据本领域的状态及如以上就注射溶液描述的制备,无菌过程不必需。
用于在皮肤上使用的溶液是滴,扩展,涂抹,洒或喷洒。
用于在皮肤上使用的溶液根据本领域的状态及根据以上就注射溶液描述的制备,无菌过程不必需。
还适合的溶剂是聚丙二醇,苯基乙醇,苯氧基乙醇,酯诸如乙基或乙酸丁酯,苯甲酸苄酯,醚诸如亚烷基二醇烷基醚,例如二亚丙基二醇单乙基醚,酮诸如丙酮,甲基乙基酮,芳族烃,植物和合成油,二甲基甲酰胺,二甲基乙酰胺,transcutol,solketal,丙烯基碳酸脂和其混合物。
制备期间添加增稠剂可为有利的。适合的增稠剂是无机增稠剂诸如膨润土,胶体硅酸,单硬脂酸铝,有机增稠剂诸如纤维素衍生物,聚乙烯基醇和它们的共聚物,丙烯酸盐和甲基丙烯酸盐。
将凝胶应用于或扩展到皮肤或引导人体腔。凝胶通过处理已如描述于含足够的增稠剂的注射溶液的情况制备的溶液来制备,产生具有软膏-样一致性结果的清亮的物质。采用的增稠剂是以上提供的增稠剂。
投放制剂投入或喷洒到皮肤的限制的区,活性化合物穿透皮肤及全身作用。
投放制剂通过溶解,悬浮或乳化活性化合物在适合的皮肤-相容的溶剂或溶剂混合物中来制备。如果适当的,添加其他辅助剂诸如着色剂,生物吸收-促进物质,抗氧化剂,轻稳定剂,粘合剂。
适合的溶剂是:水,烷醇,二醇,聚乙二醇,聚丙二醇,甘油,芳族醇诸如苄基醇,苯基乙醇,苯氧乙醇,酯诸如乙酸乙酯,乙酸丁酯,苯甲酸苄酯,醚诸如亚烷基二醇烷基醚诸如二丙二醇单甲基醚,二乙二醇单-丁基醚,酮诸如丙酮,甲基乙基酮,环状碳酸酯诸如碳酸丙烯酯,亚乙基碳酸酯,芳族和/或脂肪族烃,植物或合成油,DMF,二甲基乙酰胺,n-烷基吡咯烷酮诸如甲基吡咯烷酮,n-丁基吡咯烷酮或n-辛基吡咯烷酮,N-甲基吡咯烷酮,2-吡咯烷酮,2,2-二甲基-4-氧基-亚甲基-1,3-二氧杂环戊烷和甘油甲醛。
适合的着色剂全部是允许在动物上使用且可溶解或悬浮的着色剂。
适合的吸收-促进物质是,例如,DMSO,扩展油诸如异-丙基肉豆蔻酸酯,二丙二醇壬酸酯,硅酮油和其与聚-醚的共聚物,脂肪酸酯,甘油三酯,脂肪醇。
适合的抗氧化剂是亚硫酸盐或偏亚硫酸氢盐诸如偏亚硫酸氢钾,抗坏血酸,丁基羟基甲苯,丁基羟基茴香醚,生育酚。
适合的光稳定剂是,例如,novantisolic酸。
适合的粘合剂是,例如,纤维素衍生物,淀粉衍生物,聚丙烯酸酯,天然的聚合物诸如藻酸酯,明胶。
乳剂可经口,经皮或作为注射施用。
乳剂是油包水类型或水包油类型。
它们通过溶解活性化合物到疏水或亲水相及用其他相的溶剂均质化此,辅助适合的乳化剂及,如果适当的,其他辅助剂诸如着色剂,吸收-促进物质,防腐剂,抗氧化剂,光稳定剂,粘度-增强物质来制备。
适合的疏水相(油)是:
液体石蜡,硅酮油,天然的植物油诸如芝麻油,杏仁油,蓖麻油,合成甘油三酯诸如辛酸/癸酸双甘油酯,与链长度C8~C12的植物脂肪酸或其他尤其选择的天然的脂肪酸的甘油三酯混合物,可能也含有羟基的饱和的或不饱和的脂肪酸的部分甘油酯混合物,C8~C10脂肪酸的单-及二甘油脂,
脂肪酸酯诸如硬酯酸乙酯,二-n-丁酰己二酸酯,月桂酸己酯,壬酸二丙二醇,与链长度C16~C18的饱和的脂肪醇的中链长度的分支的脂肪酸酯,肉豆蔻酸异丙酯,棕榈酸异丙酯,链长度C12~C18的饱和的脂肪醇的辛酸/癸酸酯,硬酯酸异丙酯,油酸油酯,油酸癸酯,油酸乙酯,乳酸乙酯,蜡质脂肪酸酯诸如合成鸭尾骨腺脂肪,酞酸二丁酯,己二酸二异丙酯和与后者相关的酯混合物,脂肪醇诸如异十三基醇,2-辛基十二醇,鲸蜡基硬脂基醇,油基醇和其脂肪酸诸如油酸和混合物。
适合的亲水相是:水,醇诸如丙二醇,甘油,山梨糖醇和其混合物。
适合的乳化剂是:
非-离子表面活性剂,例如聚乙氧基化的蓖麻油,聚乙氧基化的山梨糖醇酐单油酸酯,山梨糖醇酐单硬脂酸酯,单硬脂酸甘油,聚氧乙基硬酯酸酯,烷基苯酚聚甘醇醚;两性表面活性剂诸如二钠N-月桂基-p-亚氨基二丙酸酯或卵磷脂;
阴离子表面活性剂,诸如月桂基硫酸钠,脂肪醇醚硫酸盐,单/二烷基聚甘醇醚磷酸酯单乙醇胺盐;
阳离子-活性表面活性剂,诸如鲸蜡基三甲基铵氯化物。
适合的辅助剂还是:增强粘度及稳定化乳剂的物质,诸如羧甲基纤维素,甲基纤维素和其他纤维素和淀粉衍生物,聚丙烯酸酯,藻酸酯,明胶,阿拉伯胶,聚乙烯吡咯烷酮,聚乙烯基醇,甲基乙烯基醚和马来酸酐的共聚物,聚乙二醇,蜡,胶体硅酸或提及的物质的混合物。
悬浮液可经口或局部/经皮施用。它们通过悬浮活性化合物在悬浮剂中,如果适当的,添加其他辅助剂诸如润湿剂,着色剂,生物吸收-促进物质,防腐剂,抗氧化剂,光稳定剂来制备。
液体悬浮剂全部是均质溶剂和溶剂混合物。
适合的润湿剂(分散剂)是以上提供的乳化剂。
可提及的其他辅助剂是以上提供的那些。
半-固体制备物可经口或局部/经皮施用。它们不同于上述悬浮液和乳剂仅在它们的更高粘度。
为产生固体制备物,将活性化合物与适合的赋形剂混合,如果适当的,添加辅助剂,并使成为期望的形式。
适合的赋形剂是全部生理学容许的固体惰性物质。那些使用的是无机和有机物质。无机物质是,例如,氯化钠,碳酸酯诸如碳酸钙,碳酸氢盐,氧化铝,氧化钛,硅酸,泥质土,沉淀的或胶体氧化硅,或磷酸盐。有机物质是,例如,糖,纤维素,食料和饲料诸如乳粉,动物膳食,谷粒膳食及碎片,淀粉。
适合的辅助剂是以上已提及的防腐剂,抗氧化剂和/或着色剂。
其他适合的辅助剂是润滑剂和助流剂诸如硬酯酸镁,硬脂酸,滑石粉,膨润土,解离-促进物质诸如淀粉或交联的聚乙烯吡咯烷酮,结合剂诸如淀粉,明胶或线性聚乙烯吡咯烷酮,及干结合剂诸如微晶纤维素。
可在本发明中使用的组合物可包含通常约0.001~95%的式I的化合物。
即用制剂以10ppm~80重量%,优选0.1~65重量%,更优选1~50重量%,最优选5~40重量%的浓度含有针对寄生虫,优选外寄生物作用的化合物。
使用之前稀释的制备物以0.5~90重量%,优选1~50重量%的浓度含有针对外寄生物作用的化合物。
此外,制备物以10ppm~2重量%,优选0.05~0.9重量%,非常特别优选0.005~0.25重量%的浓度包含针对内寄生物的式I的化合物。
然后包含式I的化合物的组合物可经口,肠胃外或局部,分别经皮应用。例如,任选地局部应用以含有化合物的形状的物品形式进行,诸如项圈,纪念章,耳标签,在身体部位固定的条带,及粘性条和箔。
通常应用在3周过程以10mg/kg~300mg/kg,优选20mg/kg~200mg/kg,最优选25mg/kg~160mg/kg处理的动物体重的总量释放式I的化合物的固体制剂是有利的。
对于形状的物品的制备物,使用热塑性和柔性的塑料以及弹性体和热塑性弹性体。适合的塑料和弹性体是聚乙烯基树脂,聚氨基甲酸酯,聚丙烯酸酯,环氧树脂,纤维素,纤维素衍生物,聚酰胺和聚酯,它们与式I的化合物足够相容。例如WO 03/086075中给出形状的物品的塑料和弹性体以及制备过程的详细列表。
活性化合物可单独或以与发挥针对病原性内-及外寄生物作用的增效剂或与其他活性化合物的混合物应用。
例如,式I的活性化合物可以与合成球虫病化合物,聚醚抗生素,如安普罗铵,罗贝胍,托曲珠利,莫能星,沙利霉素,马度米星,拉沙洛西,甲基盐霉素或生度米星或,与描述于下列M的其他杀虫剂的的混合物应用。
待在本发明中用于农业或兽医学目的的组合物也可含有其他活性成分,例如其他杀虫剂,杀昆虫剂,除草剂,杀真菌剂,杀菌剂,肥料诸如硝酸铵,脲,草碱和超-磷酸盐,植物毒素和植物生长调节物,安全剂和杀线虫剂。这些额外的成分可依次或与以上-描述的组合物组合使用,如果适当的,也仅在使用之前立即添加(桶混剂)。例如,植物可在用其他活性成分处理之前或之后喷洒本发明的组合物。
这些剂可与根据本发明使用的剂,以1:10~10:1的重量比混合。将式I的化合物或包含它们的组合物作为与其他杀虫剂混合的杀虫剂的使用形式常导致更广杀虫作用谱。
根据本发明的化合物可与之使用及与之可产生潜在协同效应的杀虫剂的下列M,旨在例证可能的组合,但不强加任何限制:
M.1.有机(硫代)磷酸酯化合物:乙酰甲胺磷,甲基吡噁磷,益棉磷,保棉磷,氯氧磷,氯芬磷,氯甲硫磷,毒死稗,甲基毒死蜱,库马磷,杀螟腈,内吸磷-S-甲基,二嗪磷,敌敌畏/DDVP,百治磷,乐果,甲基毒虫畏,乙拌磷,EPN,乙硫磷,灭线磷,伐灭磷,苯线磷,杀螟硫磷,倍硫磷,吡氟硫磷,噻唑磷,庚烯磷,噁唑磷,马拉硫磷,灭蚜磷,甲胺磷,杀扑磷,速灭磷,久效磷,二溴磷,氧乐果,亚砜磷,对硫磷,甲基对硫磷,稻丰散,甲拌磷,伏杀硫磷,亚胺硫磷,磷胺,肟硫磷,甲基嘧啶磷,丙溴磷,胺丙畏,丙硫磷,吡唑硫磷,哒嗪硫磷,喹硫磷,治螟磷,丁基嘧啶磷,替美磷,特丁磷,司替罗磷,甲基乙拌磷,三唑磷,敌百虫,蚜灭磷;
M.2.氨基甲酸酯化合物:涕灭威,棉铃威,噁虫威,丙硫克百威,丁酮威,丁酮砜威,卡巴立,克百威,丁硫克百威,乙硫苯威,仲丁威,伐虫脒,呋线威,异丙威,甲硫威,灭多威,速灭威,草氨酰基,抗蚜威,残杀威,硫双威,久效威,混杀威,XMC,灭杀威,唑蚜威;
M.3.拟除虫菊酯化合物:氟丙菊酯,丙烯除虫菊酯,d-顺式-反式丙烯除虫菊酯,d-反式-丙烯除虫菊酯,联苯菊酯,生物烯丙菊酯,生物烯丙菊酯S-环戊烯基,除虫菊酯,乙氰菊酯,氟氯氰菊酯,β-氟氯氰菊酯,氯氟氰菊酯,λ-氯氟氰菊酯,γ-氯氟氰菊酯,氯氰菊酯,α-氯氰菊酯,β-氯氰菊酯,θ-氯氰菊酯,ζ-氯氰菊酯,右旋苯醚氰菊酯,溴氰菊酯,右旋烯炔菊酯,杀灭阿菊酯,依芬普司,甲氰菊酯,氰戊菊酯,氟氰戊菊酯,氟氯苯菊酯,τ-氟胺氰菊酯,苄螨醚,炔咪菊酯,甲氧氟司林,扑灭司林,苯氧司林,右旋炔丙菊酯,环丙氟司林,除虫菊酯(pyrethrum),苄呋菊酯,氟硅菊酯,七氟菊酯,四甲司林,四溴菊酯,四氟苯菊酯;
M.4.保幼激素模拟:烯虫乙酯,烯虫炔酯,烯虫酯,苯氧威,吡丙醚;
M.5.烟碱受体激动剂/拮抗剂化合物:啶虫脒,杀虫磺,杀螟丹盐酸盐,噻虫胺,呋虫胺,吡虫啉,噻虫嗪,烯啶虫胺,烟碱,多杀菌素(变构激动剂),spinetoram(变构激动剂),噻虫啉,杀虫环,thiosultap-钠和AKD1022。
M.6.GABA选通的氯化物通道拮抗剂化合物:氯丹,硫丹,γ-HCH(林丹);ethiprole,氟虫腈,pyrafluprole,pyriprole。
M.7.氯化物通道活化物:阿巴克丁,苯甲酸埃玛菌素,弥拜菌素,lepimectin;
M.8.METI I化合物:喹螨醚,唑螨酯,嘧螨醚,哒螨灵,吡螨胺,唑虫酰胺,flufenerim,鱼藤酮;
M.9.METI II和III化合物:灭螨醌,fluacyprim,氟蚁腙;
M.10.氧化磷酸化的解偶联剂:溴虫腈,DNOC;
M.11.氧化磷酸化的抑制物:三唑锡,三环锡,丁醚脲,苯丁锡,炔螨特,三氯杀螨砜;
M.12.蜕皮破裂机:灭蝇胺,环虫酰肼,氯虫酰肼,甲氧虫酰肼,虫酰肼;
M.13.增效剂:增效醚,脱叶磷;
M.14.钠通道阻断剂化合物:茚虫威,metaflumizone;
M.15.熏剂:甲基溴,氯化苦硫酰氟;
M.16.选择性饲喂阻断剂:crylotie,吡蚜酮,flonicamid;
M.17.螨生长抑制物:四螨嗪,噻螨酮,乙螨唑;
M.18.壳多糖合成抑制物:噻嗪酮,bistrifluron,氟啶脲,除虫脲,氟环脲,氟虫脲,氟铃脲,虱螨脲,氟酰脲,noviflumuron,氟苯脲,杀铃脲;
M.19.脂质生物合成抑制物:螺螨酯,螺甲螨酯,螺虫乙酯;
M.20.章鱼胺能激动剂:双甲脒;
M.21.雷诺定受体调节物:氟虫酰胺,(R)-,(S)-3-氯-N1-{2-甲基-4-[1,2,2,2-四氟-1-(三氟甲基)乙基]苯基}-N2-(1-甲基-2-甲基磺酰乙基)酞酰胺(M21.1)
M.22.异噁唑啉化合物:4-[5-(3,5-二氯-苯基)-5-三氟甲基-4,5-二氢-异噁唑-3-基]-2-甲基-N-吡啶-2-基甲基-苯甲酰胺(M22.1),4-[5-(3,5-二氯-苯基)-5-三氟甲基-4,5-二氢-异噁唑-3-基]-2-甲基-N-(2,2,2-三氟-乙基)-苯甲酰胺(M22.2),4-[5-(3,5-二氯-苯基)-5-三氟甲基-4,5-二氢-异噁唑-3-基]-2-甲基-N-[(2,2,2-三氟-乙基氨甲酰)-甲基]-苯甲酰胺(M22.3),4-[5-(3,5-二氯-苯基)-5-三氟甲基-4,5-二氢-异噁唑-3-基]-萘-1-羧酸[(2,2,2-三氟-乙基氨甲酰)-甲基]-酰胺(M22.4)及4-[5-(3,5-二氯苯基)-5-三氟甲基-4,5-二氢-异噁唑-3-基]-N-[(甲氧基亚氨基)甲基]-2-甲基苯甲酰胺(M22.5),4-[5-(3-氯-5-三氟甲基-苯基)-5-三氟甲基-4,5-二氢-异噁唑-3-基]-2-甲基-N-[(2,2,2-三氟-乙基氨甲酰)-甲基]-苯甲酰胺(M22.6);4-[5-(3-氯-5-三氟甲基-苯基)-5-三氟甲基-4,5-二氢-异噁唑-3-基]-萘-1-羧酸[(2,2,2-三氟-乙基氨甲酰)-甲基]-酰胺(M22.7)和5-[5-(3,5-二氯-4-氟-苯基)-5-三氟甲基-4,5-二氢-异噁唑-3-基]-2-[1,2,4]三唑-1-基-苄腈(M22.8);
M.23.氨茴内酐酰胺化合物:chloranthraniliprole,cyantraniliprole,5-溴-2-(3-氯-吡啶-2-基)-2H-吡唑-3-羧酸[4-氰基-2-(1-环丙基-乙基氨甲酰)-6-甲基-苯基]-酰胺(M23.1),5-溴-2-(3-氯-吡啶-2-基)-2H-吡唑-3-羧酸[2-氯-4-氰基-6-(1-环丙基-乙基氨甲酰)-苯基]-酰胺(M23.2),5-溴-2-(3-氯-吡啶-2-基)-2H-吡唑-3-羧酸[2-溴-4-氰基-6-(1-环丙基-乙基氨甲酰)-苯基]-酰胺(M23.3),5-溴-2-(3-氯-吡啶-2-基)-2H-吡唑-3-羧酸[2-溴-4-氯-6-(1-环丙基-乙基氨甲酰)-苯基]-酰胺(M23.4),5-溴-2-(3-氯-吡啶-2-基)-2H-吡唑-3-羧酸[2,4-二氯-6-(1-环丙基-乙基氨甲酰)-苯基]-酰胺(M23.5),5-溴-2-(3-氯-吡啶-2-基)-2H-吡唑-3-羧酸[4-氯-2-(1-环丙基-乙基氨甲酰)-6-甲基-苯基]-酰胺(M23.6),N'-(2-{[5-溴-2-(3-氯-吡啶-2-基)-2H-吡唑-3-羰基]-氨基}-5-氯-3-甲基-苯甲酰基)-肼羧酸甲基酯(M23.7),N'-(2-{[5-溴-2-(3-氯-吡啶-2-基)-2H-吡唑-3-羰基]-氨基}-5-氯-3-甲基-苯甲酰基)-N'-甲基-肼羧酸甲基酯(M23.8),N'-(2-{[5-溴-2-(3-氯-吡啶-2-基)-2H-吡唑-3-羰基]-氨基}-5-氯-3-甲基-苯甲酰基)-N,N'-二甲基-肼羧酸甲基酯(M23.9),N'-(3,5-二溴-2-{[5-溴-2-(3-氯-吡啶-2-基)-2H-吡唑-3-羰基]-氨基}-苯甲酰基)-肼羧酸甲基酯(M23.10),N'-(3,5-二溴-2-{[5-溴-2-(3-氯-吡啶-2-基)-2H-吡唑-3-羰基]-氨基}-苯甲酰基)-N'-甲基-肼羧酸甲基酯(M23.11)和N'-(3,5-二溴-2-{[5-溴-2-(3-氯-吡啶-2-基)-2H-吡唑-3-羰基]-氨基}-苯甲酰基)-N,N'-二甲基-肼羧酸甲基酯(M23.12);
M.24.丙二腈化合物:2-(2,2,3,3,4,4,5,5-八氟戊基)-2-(3,3,3-三氟-丙基)丙二腈(CF2H-CF2-CF2-CF2-CH2-C(CN)2-CH2-CH2-CF3)(M24.1)和2-(2,2,3,3,4,4,5,5-八氟戊基)-2-(3,3,4,4,4-五氟丁基)-丙二二腈(CF2H-CF2-CF2-CF2-CH2-C(CN)2-CH2-CH2-CF2-CF3)(M24.2);
M.25.微生物破裂物:苏云金芽孢杆菌以色列亚种(Bacillusthuringiensis subsp.Israelensi),球形芽孢杆菌(Bacillus sphaericus),苏云金芽孢杆菌鲇泽亚种(Bacillus thuringiensis subsp.Aizawai),苏云金芽孢杆菌库尔斯塔克亚种(Bacillus thuringiensis subsp.Kurstaki),苏云金芽孢杆菌拟步行甲亚种(Bacillus thuringiensissubsp.Tenebrionis);
M.26.氨基呋喃酮化合物:
4-{[(6-溴吡啶-3-基)甲基](2-氟乙基)氨基}呋喃-2(5H)-酮(M26.1),
4-{[(6-氟吡啶-3-基)甲基](2,2-二氟乙基)氨基}呋喃-2(5H)-酮(M26.2),
4-{[(2-氯-1,3-噻唑并-5-基)甲基](2-氟乙基)氨基}呋喃-2(5H)-酮(M26.3),
4-{[(6-氯吡啶-3-基)甲基](2-氟乙基)氨基}呋喃-2(5H)-酮(M26.4),
4-{[(6-氯吡啶-3-基)甲基](2,2-二氟乙基)氨基}呋喃-2(5H)-酮(M26.5),
4-{[(6-氯-5-氟吡啶-3-基)甲基](甲基)氨基}呋喃-2(5H)-酮(M26.6),
4-{[(5,6-二氯吡啶-3-基)甲基](2-氟乙基)氨基}呋喃-2(5H)-酮(M26.7),
4-{[(6-氯-5-氟吡啶-3-基)甲基](环丙基)氨基}呋喃-2(5H)-酮(M26.8),
4-{[(6-氯吡啶-3-基)甲基](环丙基)氨基}呋喃-2(5H)-酮(M26.9)及
4-{[(6-氯吡啶-3-基)甲基](甲基)氨基}呋喃-2(5H)-酮(M26.10);
M.27.各种化合物:磷化铝,amidoflumet,benclothiaz,苯螨特,联苯肼酯,硼砂,溴螨酯,氰化物,cyenopyrafen,cyflumetofen,灭螨猛,三氯杀螨醇,氟代乙酸酯,膦,pyridalyl,pyrifluquinazon,硫,有机硫化合物,酒石酸催吐药,sulfoxaflor,N-R'-2,2-二卤代-1-R"环-丙烷甲酰胺-2-(2,6-二氯-α,α,α-三氟-p-甲苯基)腙或N-R'-2,2-二(R″′)丙酰胺-2-(2,6-二氯-α,α,α-三氟-p-甲苯基)-腙,其中R'是甲基或乙基,卤代是氯或溴,R"是氢或甲基和R″′是甲基或乙基,4-丁-2-炔基氧基-6-(3,5-二甲基-哌啶-1-基)-2-氟-嘧啶(M27.1),环丙烷乙酸,1,1'~[(3S,4R,4aR,6S,6aS,12R,12aS,12bS)-4-[[(2-环丙基乙酰)氧基]甲基]-1,3,4,4a,5,6,6a,12,12a,12b-十氢-12-羟基-4,6a,12b-三甲基-11-氧代-9-(3-吡啶基)-2H,11H-萘并[2,1-b]吡喃并[3,4-e]吡喃-3,6-二基]酯(M27.2)和8-(2-环丙基甲氧基-4-三氟甲基-苯氧基)-3-(6-三氟甲基-哒嗪-3-基)-3-氮杂-二环[3.2.1]辛烷(M27.3)。
基团M的商业上可利用的化合物可见于The Pesticide Manual,14th Edition,British Crop Protection Council(2006)。
对氧磷和它们的制备已描述于Farm Chemicals Handbook,Volume 88,Meister Publishing Company,2001。吡氟硫磷已描述于Pesticide Science 54,1988,p.237-243and in US 4822779。AKD 1022和其制备已描述于US 6300348。化合物(M22.6)和(M22.7)知道自WO 2009/126668和化合物(M22.8)知道自WO 2009/051956。氨茴内酐酰胺M23.1~M23.6已描述于WO 2008/72743和WO2008/72783,那些M23.7~M23.12已描述于WO 2007/043677。酞酰胺M 21.1知道自WO 2007/101540。炔基醚化合物M27.1已例如描述于JP 2006/131529。有机硫化合物已描述于WO 2007/060839。异噁唑啉化合物M 22.1~M 22.5已描述于例如WO 2005/085216,WO2007/079162和WO 2007/026965。氨基呋喃酮化合物M 26.1~M 26.10已例如描述于WO 2007/115644。pyripyropene衍生物M 27.2已描述于WO 2008/66153和WO 2008/108491。哒嗪化合物M 27.3已描述于JP 2008/115155。丙二腈化合物如那些(M24.1)和(M24.2)已描述于WO 2002/089579,WO 2002/090320,WO 2002/090321,WO2004/006677,WO 2005/068423,WO 2005/068432和WO 2005/063694。
根据本发明的化合物可与之使用的下列活性物质列表旨在例证可能的组合但不限于它们:
(F.I)呼吸抑制物
(F.I-1)在Qo位点的复合物III的抑制物(例如甲氧基丙烯酸酯)
甲氧基丙烯酸酯:嘧菌酯,coumethoxystrobin,coumoxystrobin,醚菌胺,enestroburin,氟嘧菌酯,醚菌酯,苯氧菌胺,肟醚菌胺,啶氧菌酯,唑菌胺酯,pyrametostrobin,pyraoxystrobin,pyribencarb,triclopyricarb/chlorodincarb,肟菌酯,2-[2-(2,5-二甲基-苯氧基甲基)-苯基]-3-甲氧基-丙烯酸甲基酯和2(2-(3-(2,6-二氯苯基)-1-甲基-亚烯丙基氨基氧基甲基)-苯基)-2-甲氧基亚氨基-N-甲基-乙酰胺;
噁唑烷二酮和咪唑啉酮:噁唑菌酮,咪唑菌酮;
(F.I-2)复合物II的抑制物(例如羧酰胺):
羧酰苯胺:麦锈灵,bixafen,啶酰菌胺,萎锈灵,甲呋酰胺,环酰菌胺,fluopyram,氟酰胺,呋吡菌胺,isopyrazam,isotianil,灭锈胺,氧化萎锈灵,penflufen,吡噻菌胺,sedaxane,叶枯酞,噻氟菌胺,噻酰菌胺,2-氨基-4-甲基-噻唑-5-羧酰苯胺,N-(3',4',5’三氟联苯基-2-基)-3-二氟甲基-1-甲基-1H-吡唑-4-羧酰胺,N-(4'-三氟甲硫基联苯基-2-基)-3-二氟甲基-1-甲基-1H-吡唑-4-羧酰胺和N-(2-(1,3,3-三甲基-丁基)-苯基)-1,3-二甲基-5-氟-1H-吡唑-4-羧酰胺;
(F.I-3)复合物III在Qi位点的抑制物:氰霜唑,amisulbrom;
(F.I-4)其他呼吸抑制物(复合物I,解偶联剂)
氟嘧菌胺;四氯硝基苯;嘧菌腙;ametoctradin;硅噻菌胺;
硝基苯基衍生物:乐杀螨,消螨通,二硝巴豆酸酯,氟啶胺,nitrthal-异丙基,
有机金属化合物:三苯锡盐,诸如三苯锡-乙酸盐,氯化三苯锡或氢氧化三苯锡;
(F.II)甾醇生物合成抑制物(SBI杀真菌剂)
(F.II-1)C14脱甲基酶抑制物(DMI杀真菌剂,例如三唑,咪唑)
三唑:阿扎康唑,联苯三唑醇,糠菌唑,环丙唑醇,苯醚甲环唑,烯唑醇,烯唑醇-M,氟环唑,腈苯唑,氟喹唑,氟硅唑,粉唑醇,己唑醇,亚胺唑,种菌唑,叶菌唑,腈菌唑,多效唑,戊菌唑,丙环唑,丙硫菌唑,硅氟唑,戊唑醇,四氟醚唑,三唑酮,三唑醇,灭菌唑,烯效唑;
咪唑:抑霉唑,稻瘟酯,噁咪唑,咪酰胺,氟菌唑;
嘧啶,吡啶和哌嗪:氯苯嘧啶醇,氟苯嘧啶醇,啶斑肟,嗪氨灵;
(F.II-2)δ14-还原酶抑制物(胺,例如吗啉,哌啶)
吗啉:aldimorph,十二环吗啉,乙酸十二环吗啉,丁苯吗啉,十三吗啉;
哌啶:苯锈啶,病花灵;
螺缩酮胺:螺环菌胺;
(F.II-3)3-酮基还原酶的抑制物:羟基酰苯胺:环酰菌胺;
(F.III)核酸合成抑制物
(F.III-1)RNA,DNA合成
苯酰胺或酰基氨基酸杀真菌剂:苯霜灵,苯霜灵-M,kiralaxyl,甲霜灵,甲霜灵-M(精甲霜灵),呋酰胺,噁霜灵;
异噁唑和异噻唑酮:噁霉灵,辛噻酮;
(F.III-2)DNA拓扑异构酶抑制物:喹菌酮酸酸;
(F.III-3)核苷酸代谢(例如adenosin-脱氨酶)
羟基(2-氨基)-嘧啶:磺嘧菌灵;
(F.IV)细胞分裂及/或细胞骨架抑制物
(F.IV-1)微管蛋白抑制物:苯并咪唑和硫菌灵:苯菌灵,多菌灵,麦穗宁,噻菌灵,甲基硫菌灵;
三唑并嘧啶:5-氯-7(4-甲基哌啶-1-基)-6-(2,4,6-三氟苯基)-[1,2,4]三唑并[1,5a]嘧啶
(F.IV-2)其他细胞分裂抑制物
苯甲酰胺和苯基乙酰胺:乙霉威,噻唑菌胺,戊菌隆,氟吡菌胺,苯酰菌胺;
(F.IV-3)肌动蛋白抑制物:二苯甲酮:苯菌酮;
(F.V)氨基酸和蛋白合成抑制物
(F.V-1)甲硫氨酸合成抑制物(苯胺基-嘧啶)
苯胺基-嘧啶:嘧菌环胺,嘧菌胺,三氯甲基吡啶,嘧霉胺;
(F.V-2)蛋白合成抑制物(苯胺基-嘧啶)
抗生素:灭瘟素-S,春雷霉素,盐酸春雷霉素-水合物,米多霉素,链霉素,土霉素,多氧霉素,有效霉素A;
(F.VI)信号转导抑制物
(F.VI-1)MAP/组氨酸激酶抑制物(例如苯胺基-嘧啶)
二甲酰亚胺:fluoroimid,异菌脲,腐霉利,乙烯菌核利;
苯基吡咯:拌种咯,咯菌腈;
(F.VI-2)G蛋白抑制物:喹啉:苯氧喹啉;
(F.VII)脂质和膜合成抑制物
(F.VII-1)磷脂生物合成抑制物
有机磷化合物:敌瘟磷,异稻瘟净,吡菌磷;
二硫杂环戊烷:稻瘟灵;
(F.VII-2)脂质过氧化
芳族烃:氯硝胺,五氯硝基苯,四氯硝基苯,tolclophos-甲基,联苯,氯苯甲醚,土菌灵;
(F.VII-3)羧基酰胺(CAA杀真菌剂)
肉桂酸或扁桃酸酰胺:烯酰吗啉,氟吗啉,mandiproamid,pyrimorph;
缬氨酸酰胺氨基甲酸{盐|酯}:苯噻菌胺酯,异丙菌胺,pyribencarb,valifenalate及N-(1-(1-(4-氰基-苯基)乙磺酰)-丁-2-基)氨基甲酸-(4-氟苯基)酯;
(F.VII-4)影响细胞膜通透性和脂肪酸的化合物
氨基甲酸酯:霜霉威,霜霉威-盐酸盐
(F.VIII)具有多位点作用的抑制物
(F.VIII-1)无机活性物质:波尔多液,乙酸铜,氢氧化铜,氯氧化铜,碱性硫酸铜,硫;
(F.VIII-2)硫代-及二硫代氨基甲酸盐:福美铁,代森锰锌,代森锰,安百亩,磺菌威,代森联,丙森锌,塞仑,代森锌,福美锌;
(F.VIII-3)有机氯化合物(例如酞酰亚胺,硫酰胺,氯腈):
敌菌灵,百菌清,敌菌丹,克菌丹,灭菌丹,苯氟磺胺,双氯酚,磺菌胺,六氯苯,五氯苯酚和其盐,四氯苯酞,甲苯氟磺胺,N-(4-氯-2-硝基-苯基)-N-乙基-4-甲基-苯磺酰胺;
(F.VIII-4)胍类:胍,多果定,多果定游离碱,双胍辛胺,双胍辛胺-乙酸盐,双胍辛胺,双胍辛胺-三乙酸盐,双胍辛胺-三(albesilate);
(F.VIII-5)蒽醌:二噻烷酮;
(F.IX)细胞壁合成抑制物
(F.IX-1)葡聚糖合成抑制物:有效霉素,多氧霉素B;
(F.IX-2)黑色素合成抑制物:咯喹酮,三环唑,carpropamide,dicyclomet,氰菌胺;
(F.X)植物防御诱导物
(F.X-1)水杨酸通路:活化酯-S-甲基;
(F.X-2)其他:烯丙苯噻唑,isotianil,噻酰菌胺,调环酸-钙;
膦酸盐:三乙磷,三乙磷-铝,磷酸和其盐;
(F.XI)未知的作用模式:
溴硝丙二醇,灭螨猛,环氟苄酰胺,霜脲氰,棉隆,咪菌威,哒菌酮,野燕枯,野燕枯-甲基硫酸盐,二苯基胺,氟酰菌胺,磺菌胺,flutianil,磺菌威,氧杂环己二烯-铜,丙氧喹啉,tebufloquin,叶枯酞,咪唑嗪,2-丁氧基-6-碘-3-丙基色原烯-4-酮,N-(环丙基甲氧基亚氨基-(6-二氟-甲氧基-2,3-二氟-苯基)-甲基)-2-苯基乙酰胺,N'-(4-(4-氯-3-三氟甲基-苯氧基)-2,5-二甲基-苯基)-N-乙基-N甲基甲脒,N'(4-(4-氟-3-三氟甲基-苯氧基)-2,5-二甲基-苯基)-N-乙基-N-甲基-甲脒,N'-(2-甲基-5-三氟甲基-4-(3-三甲基硅烷基-丙氧基)-苯基)-N-乙基-N-甲基甲脒,N'-(5-二氟甲基-2-甲基-4-(3-三甲基硅烷基-丙氧基)-苯基)-N-乙基-N-甲基甲脒,2-{1-[2-(5-甲基-3-三氟甲基-吡唑-1-基)-乙酰基]-哌啶-4-基}-噻唑-4-羧酸甲基-(1,2,3,4-四氢-萘-1-基)-酰胺,2-{1-[2-(5-甲基-3-三氟甲基-吡唑-1-基)-乙酰基]-哌啶-4-基}-噻唑-4-羧酸甲基-(R)-1,2,3,4-四氢-萘-1-基-酰胺,甲氧基-乙酸6-叔-丁基-8-氟-2,3-二甲基-喹啉-4-基酯和N-甲基-2-{1-[(5-甲基-3-三氟甲基-1-H-吡唑-1-基)-乙酰基]-哌啶-4-基}-N-[(1R)-1,2,3,4-四氢萘-1-基]-4-噻唑羧酰胺,3-[5-(4-氯-苯基)-2,3-二甲基-异噁唑烷-3-基]-吡啶(pyrisoxazole),3-[5-(4-甲基-苯基)-2,3-二甲基-异噁唑烷-3-基]-吡啶,5-氨基-2-异丙基-3-氧代-4-正-甲苯基-2,3-二氢-吡唑-1-硫代羧酸S-烯丙基酯,N-(6-甲氧基-吡啶-3-基)环丙烷羧酸酰胺,5-氯-1-(4,6-二甲氧基-嘧啶-2-基)-2-甲基-1H-苯并咪唑,2-(4-氯-苯基)-N-[4-(3,4-二甲氧基-苯基)-异噁唑-5-基]-2-丙-2-炔基氧基-乙酰胺;
(F.XI)生长调节物:
脱落酸,amidochlor,环丙嘧啶醇,6-苄氨基嘌呤,油菜素内酯,双丁乐灵,矮壮素(矮壮素),氯化胆碱,环丙酸酰胺,丁酰肼,调呋酸,噻节因,2,6-二甲基吡啶,乙烯利,氟节胺,呋嘧醇,嗪草酸,调吡脲,赤霉酸,抗倒胺,吲哚-3-乙酸,马来酸酰肼,氟磺酰草胺,mepiquat(甲哌鎓),萘乙酸,N 6苄基腺嘌呤,多效唑,调环酸(调环酸-钙),prohydrojasmon,噻苯隆,抑芽唑,三丁基三硫代磷酸酯,2,3,5-三-碘-苯甲酸,抗倒酯和烯效唑;
(F.XII)生物学对照剂
抗真菌剂生物控制剂:NRRL No.B-21661的枯草芽孢杆菌(Bacillus subtilis)株(例如MAX和ASO自AgraQuest,Inc.,USA.),NRRL No.B-30087的短小芽孢杆菌(Bacillus pumilus)株(例如加自AgraQuest,Inc.,USA),奥德曼细基格孢(Ulocladiumoudemansii)(例如产品BOTRY-ZEN自BotriZen Ltd.,新西兰),壳聚糖(例如ARMOUR-ZEN自BotriZen Ltd.,新西兰)。
可将无脊椎动物害虫,即节肢动物和线虫,植物,植物生长的土壤或水与式I的化合物或含有它们的组合物通过本领域知道的任何应用方法接触。像这样,"接触"包括直接接触(将化合物/组合物直接应用于无脊椎动物害虫或植物-一般,植物的叶,茎或根)和间接接触(将化合物/组合物应用于无脊椎动物害虫或植物的位置)。
而且,无脊椎动物害虫可通过使靶害虫,其食品供应,栖息地,繁殖地或其位置与杀虫有效量的式I的化合物接触来控制。像这样,应用可在位置,生长作物,或收获的作物被害虫感染之前或之后进行。
"位置"通常是指害虫或寄生虫生长或可生长的栖息地,繁殖地,栽培的植物,植物繁殖材料(诸如种子),土壤,分布区,物质或环境。
通常"杀虫有效量"是指达到对生长可观察的效应,包括靶生物的坏死,死亡,延迟,防止和去除,破坏,或另外渐小的发生和活性的效应需要的活性成分的量。杀虫有效量可就本发明中使用的各种化合物/组合物而改变。杀虫有效量的组合物也会根据一般条件诸如期望的杀虫效应和持续时间,气候,靶物种,位置,应用模式,等而改变。
式I的化合物和包含所述化合物的组合物可用于保护木质物质诸如树,围板,枕木,等和建筑物诸如屋室,外屋,工厂,而且建筑材料,家俱,皮革,纤维,塑料物品,电线和缆等免于蚂蚁和/或白蚁,及用于控制蚂蚁和白蚁免于伤害作物或人(例如当害虫侵入屋室和公共设备时)。式I的化合物不仅应用于周围土壤表面或进入地板下土壤以便保护木物质,但其也可应用于制材的物品诸如地板下混凝土表面,凉亭柱,束,胶合板,家俱,等,木物品诸如粒子板,半板,等和塑料物品诸如包被的电线,塑料片材,加热绝缘物质诸如苯乙烯泡沫,等。在针对蚂蚁伤害作物或人应用的情况中,将本发明的蚂蚁控制物应用于作物或周围土壤,或直接应用于蚂蚁巢等。
式I的化合物也可预防性地应用于预期害虫发生的地点。
式I的化合物也可通过使植物接触杀虫有效量的式I的化合物用于保护生长植物免于被害虫攻击或侵袭。像这样,"接触植物"包括直接接触(将化合物/组合物直接应用于害虫和/或植物-一般应用于植物的叶,茎或根)和间接接触(将化合物/组合物应用于害虫和/或植物位置)。
在土壤处理或应用到害虫居住地点或巢的情况中,活性成分的量范围是0.0001~500g/100m2,优选0.001~20g/100m2。
材料保护中的常规应用率是,例如,0.01g~1000g的活性化合物/m2处理的材料,期望地是0.1g~50g/m2。
材料浸渍中使用的杀昆虫组合物一般含有0.001~95重量%,优选0.1~45重量%,及更优选1~25重量%的至少一种驱避剂和/或杀昆虫剂。
对于在饵组合物中使用,活性成分的典型含量是0.001重量%~15重量%,期望地是0.001重量%~5重量%的活性化合物。
对于在喷雾剂组合物中使用,活性成分的含量是0.001~80重量%,优选0.01~50重量%和最优选0.01~15重量%。
对于在处理作物植物中使用,本发明的活性成分的应用率可在0.1g~4000g/公顷,期望地5g~600g/公顷,更期望地10g~300g/公顷的范围内。
在种子处理中,活性成分的应用率通常是0.1g~10kg/100kg的种子,优选1g~1kg/100kg的种子,尤其是1g~250g/100kg的种子,尤其是50g~150g/100kg的种子。
本发明将通过下列实施例更详细例证,其未旨在将本发明限制在这些实施例。
【实施例】
【I.制备例】
产品通过HPLC-MS(高效液相层析质量光谱法)表征。HPLC使用分析RP-18e柱(Chromolith Speed ROD自Merck KgaA,德国)于40℃操作而进行。三氟乙酸/水混合物的体积的0.1%和三氟乙酸的体积的0.1%的乙腈用作移动相;流速:1.8mL/min和注射体积:2μl。
本文中使用的下列标记定义如下:
| n-BuLi | n-丁基锂 |
| m-CPBA | m-氯过氧苯甲酸 |
| DCM | 二氯甲烷 |
| DIPEA | N,N-二异丙基乙胺 |
| DME | 1,2-二甲氧基乙烷 |
| DMP | 戴斯-马丁氧化剂 |
| DMSO | 二甲基亚砜 |
| EtOAc | 乙酸乙酯 |
| EtOH | 乙醇 |
| M | 摩尔 |
| NCS | N-氯代琥珀酰亚胺 |
| TFAA | 三氟乙酸酐 |
| THF | 四氢呋喃 |
| TLC | 薄层层析 |
| p-TsOH | p-甲苯磺酸 |
代表实施例7,8和9的制备方案:
【2-(三氟甲基)-5-{1-[2-(三氟甲硫基)乙硫基]乙基}-1,3,4-噻二唑的制备(7,对应于实施例I1-1)】
向二甲苯(20ml)中酰肼6(0.55g,1.59mmol)的搅拌的溶液于室温添加Lawesson氏试剂(0.64g,1.59mmol)。然后搅拌混合物及于120℃加热2h及回流18h。真空去除溶剂;粗产物残留物通过柱层析(硅胶,洗脱液:己烷/EtOAc,梯度9:1~8:2)纯化以提供作为黄油的标题化合物(0.28g,51%)。
【2-(三氟甲基)-5-{1-[2-(三氟甲硫基)乙基亚硫酰基]乙基}-1,3,4-噻二唑的制备(8,对应于实施例I1-3)】
向搅拌的及冷却的(0℃)无水CH2Cl2(10ml)中的噻二唑7(0.50g,1.46mmol)溶液添加m-CPBA(77%,0.39g,1.75mmol),并将混合物于0℃在氮下搅拌30min。反应混合物用NaHCO3(aq.sat.,50ml)淬灭及用EtOAc(2×100ml)萃取。组合的有机层用NaHCO3(aq.sat.,3×50ml),水(2×100ml),盐水(2×50ml)洗涤,在硫酸钠上干燥及在真空中浓缩。残留物通过柱层析(硅胶,洗脱液:己烷/EtOAc,梯度1:1~3:7)纯化以提供作为无色油的标题化合物(0.32g,61%)。
【2-(三氟甲基)-5-{1-[2-(三氟甲硫基)乙基磺酰基]-乙基}-1,3,4-噻二唑的制备(9,对应于实施例I1-2)】
向搅拌的及冷却的(0℃)无水CH2Cl2(15ml)中的噻二唑7(0.50g,1.46mmol)溶液添加m-CPBA(77%,0.98g,4.38mmol),并将混合物在氮下于室温搅拌30min。反应混合物用sat.NaHCO(100ml)淬灭及用EtOAc(2×100ml)萃取。组合的有机层用Na-HCO3(aq.sat.,2×150ml),水(2×100ml),盐水(2×50ml)洗涤,在硫酸钠上干燥及真空浓缩。残留物通过柱层析(硅胶,洗脱液:己烷/EtOAc,梯度4:1~1:1)纯化以提供作为白色固体的标题化合物(0.36g,66%)。
【2-[5-(三氟甲基)-1,3,4-噻二唑-2-基]-2-[2-(三氟甲基-硫代)乙硫基]丙烷-1-醇的制备(10,对应于实施例I1-4)】
向搅拌的及冷却的(-78℃)THF(20ml)中的噻二唑7(2.0g,5.8mmol)溶液滴加n-BuLi(1.6M『in』己烷,4.0ml,6.4mmol)。反应混合物在氮下在此温度搅拌30min。滴加THF(20ml)中的多聚甲醛(0.52g,17.523mmol),并将反应混合物缓慢加温到室温。持续搅拌额外的2h。混合物用NH4Cl(aq.sat.,150ml)淬灭及用EtOAc(2×150ml)萃取。组合的有机层用水(2×100ml),盐水(2×50ml)洗涤,在硫酸钠上干燥,并真空浓缩。残留物通过柱层析(硅胶,洗脱液:己烷/EtOAc,梯度7:3~3:2)纯化以提供作为黄色油的标题化合物(1.3g,60%)。
【2-{1-氯-1-[2-(三氟甲硫基)乙基亚硫酰基]乙基}-5-(三氟甲基)-1,3,4-噻二唑的制备(11,对应于实施例I-8)】
向搅拌的及冷却的(0℃)无水CH2Cl2(5ml)中的噻二唑8(0.50g,1.4mmol)溶液在氮下添加硫酰氯(0.11ml,1.4mmol)。反应混合物用NaHCO3(sat.aq.,30ml)淬灭及用EtOAc(2x50ml)萃取。组合的有机层用盐水(2×50ml)洗涤,在硫酸钠上干燥及浓缩。残留物通过制备性TLC(硅胶,多运行的;移动相:己烷/EtOAc 9:1)纯化以提供作为浅黄色油的标题化合物(0.130g,23%)。
【2-(5-(三氟甲基)-1,3,4-噻二唑-2-基)-2-(2-(三氟甲硫基)-乙硫基)苯腈唑的制备(12,对应于实施例I1-9)】
向搅拌的及冷却的(0℃)无水CH2Cl2(10ml)中的噻二唑10(0.79g,2.1mmol)溶液在氮下添加戴斯-马丁氧化剂(1.08g,2.5mmol)。搅拌于室温持续2h,反应混合物用水(50ml)淬灭及用CH2Cl2(3×50ml)萃取。组合的有机层用NaHCO3(sat.aq.,3×50ml),盐水(2×50ml)洗涤,在硫酸钠上干燥,并真空浓缩以提供作为黄色糖浆的对应醛(0.65g,82%)。
向搅拌的EtOH(7ml)中的粗醛(0.65g,1.8mmol)的溶液在氮下添加的羟基胺盐酸盐(0.366g,5.3mmol),之后是于室温添加乙酸钠(0.435g,5.3mmol)。12h之后搅拌及去除溶剂,将水(50ml)加入残留物,及将反应混合物用EtOAc(3×50ml)萃取。将组合的有机层用盐水(2×50ml)洗涤,在硫酸钠上干燥及浓缩而产生作为米黄色固体的对应肟(0.54g,80%)。
向搅拌的CH2Cl2(15ml)中的三苯基膦(0.633g,2.4mmol)和N-氯代琥珀酰亚胺(0.322g,2.4mmol)溶液于室温在氮下添加CH2Cl2(5ml)中的粗肟(0.71g,2.0mmol)。30min的搅拌之后,在减压下去除有机层,及将残留物通过柱层析(硅胶,洗脱液:己烷/EtOAc4:1)纯化以提供作为浅黄油的标题化合物(0.240g,35%)。
以上合成例中描述的过程用于通过开始化合物的适当的修饰制备其他化合物。将由此获得的化合物与物理化学数据一起列于下表。
【实施例和生物学】
r.t.是以分钟计的HPLC滞留时间
[M+]峰的m/z
【II.杀虫活性的评估】
【II.1针对桃蚜(桃蚜(Myzus persicae))的活性】
通过由含有液体人工摄食的96-孔-微孔板组成的系统性设施测试单元在人工膜下评价桃蚜(桃蚜(Myzus persicae))的控制。
化合物使用含有75%v/v水和25%v/v DMSO的溶液配制。将不同浓度的配制的化合物移液进蚜虫摄食,以2个重复使用自定义建造的移液器。应用之后,5~8个成年蚜虫放置到人工膜微孔板孔之内。然后允许蚜虫食用处理的蚜虫摄食及于约23+1℃和约50+5%相对湿度温育3天。然后视觉评定蚜虫死亡率和生殖力。
在此测试中,相比未处理的对照,化合物I1-7,I1-11和I1-14,分别在2500ppm显示100%死亡率。
【II.2针对豇豆蚜虫(豆蚜(Aphis craccivora))的活性】
活性化合物配制进50:50(vol:vol)丙酮:水。在使用日制备测试溶液。
在害虫群已记录之后喷洒定居各种阶段的100~150蚜虫的盆栽的豇豆植物。在24,72和120小时之后评估群减小。
在此测试中,相比未处理的对照,化合物I1-2,I1-3,I1-6,I1-10,I1-11和I1-12,分别,在500ppm显示至少75%的死亡率。
【II.3针对巢菜蚜虫(巢菜修尾蚜(Megoura viciae))的活性】
活性化合物用不同浓度的配制的化合物配制进1:3(vol:vol)DMSO:水。
将豆叶盘放入填充0.8%琼脂-琼脂和2.5ppm OPUSTM的微孔板。向叶盘喷洒2.5μl的测试溶液,并将5~8只成年蚜虫放入微孔板,然后将其闭合,及于23±1℃和50±5%相对湿度在荧光下保持6天。基于活的,再现的蚜虫评定死亡率。然后视觉评定蚜虫死亡率和生殖力。
在此测试中,相比未处理的对照,化合物I1-1,I1-2,I1-3,I1-6,I1-7,I1-11和I1-12,分别以2500mg/L的测试溶液浓度显示100%死亡率。
【II.4针对银叶粉虱(银叶粉虱(Bemisia argentifolii),成年)的活性】
活性化合物配制进环己酮,作为在1.3ml管中供给的10,0000ppm溶液。将这些管插入装备雾化喷嘴的自动化的静电喷雾器,并使它们作为浓储物溶液用于在50%丙酮:50%水(v/v)中制造更低稀释。非离子表面活性剂(动力学)以0.01%(v/v)的体积包括在溶液中。
通过装备雾化喷洒喷嘴的自动化的静电植物喷药器喷洒子叶阶段的棉花植物(一个植物每盆)。植物在喷雾器通风橱中干燥,然后自喷雾器移出。将各盆放入塑料杯,并引入10~12只成年粉虱(约3~5日龄)。使用抽吸器和连接屏障移液管端的0.6cm,非毒性管道(R-3603)收集昆虫。然后将含有收集的昆虫的端轻轻插入含有处理的植物的土壤,允许昆虫爬出端到达到饲喂的叶。将杯用可重复使用的筛选的盖(150μm啮合聚酯筛选Pe-Cap自Tetko,Inc.)覆盖。测试植物在生长室中于25℃和20~40%相对湿度维持3天,避免直接暴露于荧光(24小时光照期),以防止杯之内的热捕获。处理之后3天,相比未处理的对照植物,评定死亡率。
在此测试中,相比未处理的对照,化合物I1-2在500ppm和化合物I1-11在300ppm显示至少75%的死亡率。
【II.5针对棉铃象(棉铃象(Anthonomus grandis))的活性】
化合物配制进75:25(vol:vol)水:DMSO。
为评价棉铃象(Anthonomus grandis)控制,测试单元由含有昆虫摄食及20~30个棉铃象(A.grandis)卵的24-孔-微孔板组成。不同浓度的配制的化合物,使用自定义建造的微喷雾器,以2个重复以20μl喷洒到昆虫摄食。应用之后,将微孔板于23±1℃和50±5%相对湿度温育5天。然后视觉评定卵和幼虫死亡率。
在此测试中,相比未处理的对照,化合物I1-1,I1-2,I1-3,I1-6,I1-7,I1-8,I1-10,I1-11和I1-12,分别在2500mg/L的测试溶液浓度显示100%死亡率的死亡率。
【II.6针对万代兰/兰花蓟马属(Thrips)(兰花蓟马(Dichromothrips corbetti))的活性】
活性化合物制成50:50(vol:vol)丙酮:水溶液。以0.1%(vol/vol)的率添加表面活性剂(EL 620自Rhodia)。将万代兰兰花花瓣清洁,洗涤及在浸之前空气干燥。花瓣浸入测试溶液3s,空气干燥,放置在重封的塑料之内及用20只成年接种。将处理的花瓣于28~29℃和50~60%的相对湿度保持在把持室之内。72小时之后记录百分率死亡率。
在此测试中,相比未处理的对照,化合物I1-2和I1-3,分别在500ppm和化合物I1-11在300ppm显示至少75%的死亡率。
【II.7针对棕飞虱(褐飞虱(Nilaparvata lugens))的活性】
活性化合物制成50:50(vol:vol)丙酮:水溶液。以0.1%(vol/vol)的率添加表面活性剂(EL 620自Rhodia)。
在喷洒之前24h将稻幼苗清洁及洗涤。给盆栽的稻幼苗喷洒5ml测试溶液,空气干燥,放置进盒中及接种10只成年。处理的稻植物保持在28~29℃和50~60%的相对湿度。在72小时之后记录百分率死亡率。
在此测试中,相比未处理的对照,化合物I1-3,I1-8,I1-11和I1-12,分别在500ppm显示至少75%的死亡率。
【II.8针对地中海果蝇(地中海实蝇(Ceratitis capitata))的活性】
活性化合物配制进1:3(vol:vol)DMSO:水。
为了评价地中海果蝇的控制,测试单元由含有昆虫摄食及50~80个地中海实蝇(C.capitata)卵的微孔板组成。
不同浓度的配制的化合物以5μl,使用自定义建造的微喷雾器,以2个重复喷洒到昆虫摄食。应用之后,将微孔板于28±1℃和80±5%相对湿度温育5天。然后视觉评定卵和幼虫死亡率。
在此测试中,已用2500ppm的化合物I1-2,I1-9和I1-11处理的卵,分别显示至少50%的死亡率。
【II.9针对菱纹背蛾(小菜蛾(Plutella xylostella))的活性】活性化合物配制进50:50丙酮:水和0.1%(vol/vol)EL620表面活性剂。将卷心菜叶的6cm叶盘浸在测试溶液中3s,并允许在衬湿过滤纸的陪替板中空气干燥。叶盘用10/3龄幼虫接种,及保持在25~27℃和50~60%湿度3天。在72h的处理之后评定死亡率。
在此测试中,相比未处理的对照,化合物I1-3在500ppm的测试溶液的浓度显示至少75%的死亡率。
Claims (15)
1.式I的化合物和其盐
其中
X是O或S(=O)m;
m是0,1,2;
n是0、1或2;
p是1或2;
R3U是C1~C4-卤代烷基,C2~C4-卤代烯基,且其中卤素是氟或氯;
U是选自下列的5-元杂芳族环-系统:1H-1,2,4-三唑,1H-1,2,3-三唑,1,3,4-噻二唑,1,2,4-噁二唑,1,3,4-噁二唑,其中杂芳族环可被1~4个取代基V取代;
V独立地是卤素,C1~C6-烷基,C1~C6-卤代烷基,C2~C6-烯基或C2~C6-卤代烯基;
R1选自:氢,卤素,CN和C1~C6-烷基,其可被下列基团取代:卤素或OH;以及
R2为氢,卤素或C1~C6-烷基。
2.权利要求1的化合物,其中
R1选自:氢,卤素,CN和C1~C6-烷基,其可被OH取代;
R2为氢或C1~C6-烷基;
U是5-元杂芳族环,其选自:1,3,4-噻二唑,1,2,4-噁二唑和1,3,4-噁二唑,其中杂芳族环被1~4个取代基V取代;
V独立地是C1~C6-卤代烷基;
p是1;
n是0、1或2;
X是S(=O)m,且m是0;以及
R3U是C1~C3-氟代烷基。
3.权利要求1的化合物,其中
U是1,3,4-噻二唑,且其被C2F5或CF3取代;
R1为氢,卤素,CN或C1~C6-烷基,其可被OH取代;
R2为Me;
p是1;
X是S(=O)m,且m是0;
n是0、1或2;且
R3U是CF3。
4.权利要求1的化合物,其为式(I1-x)的化合物和其盐,
其中Y,R1,R2,n和R3如下表所示:
5.农业组合物,其包含:至少一种权利要求1~4之任一项中定义的化合物和至少一种农业上可接受的载体。
6.兽医学组合物,其包含:至少一种权利要求1~4之任一项中定义的化合物和至少一种兽医学上可接受的载体。
7.权利要求1~4之任一项中定义的化合物在制备组合物中的用途,所述组合物用于抵御无脊椎动物害虫。
8.权利要求1~4之任一项中定义的化合物在制备组合物中的用途,所述组合物用于处理或保护动物免于被无脊椎动物害虫侵袭或感染。
9.权利要求8的用途,其中所述动物为家畜。
10.权利要求8的用途,其中所述动物为狗或猫。
11.用于保护植物免于被无脊椎动物害虫攻击或侵袭的方法,该方法包括用杀虫有效量的至少一种权利要求1~4之任一项中定义的化合物处理植物。
12.用于保护植物繁殖材料和/或由其生长而来的植物免于被无脊椎动物害虫攻击或侵袭的方法,该方法包括用杀虫有效量的至少一种权利要求1~4之任一项中定义的化合物处理植物繁殖材料。
13.权利要求1~4之任一项中定义的化合物在制备组合物中的用途,所述组合物用于处理,控制,防止或保护动物免于被无脊椎动物害虫侵袭或感染,所述处理,控制,防止或保护包括使动物接触杀虫有效量的所述组合物。
14.权利要求1~4之任一项中定义的化合物用于制备用于针对寄生虫感染的治疗性应用的药物的用途。
15.权利要求1~4之任一项中定义的化合物在制备组合物中的用途,所述组合物用于处理,控制,防止或保护动物针对被寄生虫侵袭和感染,所述处理,控制,防止或保护包括应用给位置杀寄生虫有效量的所述组合物。
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| US26183009P | 2009-11-17 | 2009-11-17 | |
| US61/261,830 | 2009-11-17 | ||
| PCT/EP2010/067248 WO2011061110A1 (en) | 2009-11-17 | 2010-11-11 | Fluorinated oxa or thia heteroarylalkylsulfide derivatives for combating invertebrate pests |
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| US8164818B2 (en) | 2010-11-08 | 2012-04-24 | Soladigm, Inc. | Electrochromic window fabrication methods |
| US11048137B2 (en) | 2011-12-12 | 2021-06-29 | View, Inc. | Thin-film devices and fabrication |
| US12321075B2 (en) | 2011-12-12 | 2025-06-03 | View Operating Corporation | Electrochromic laminates |
| US10606142B2 (en) | 2011-12-12 | 2020-03-31 | View, Inc. | Thin-film devices and fabrication |
| US10739658B2 (en) | 2011-12-12 | 2020-08-11 | View, Inc. | Electrochromic laminates |
| CN106345366B (zh) * | 2016-08-29 | 2018-07-17 | 江苏四新界面剂科技有限公司 | 一种聚二甲基硅氧烷乳化剂的制备方法 |
| WO2019107348A1 (ja) * | 2017-12-01 | 2019-06-06 | 日本曹達株式会社 | ピリジニウム塩および有害生物防除剤 |
| KR20220016459A (ko) | 2019-05-29 | 2022-02-09 | 닛뽕소다 가부시키가이샤 | 피리디늄염 및 유해 생물 방제제 |
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| Publication number | Publication date |
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| CN102686573A (zh) | 2012-09-19 |
| EP2501686B1 (en) | 2015-05-20 |
| NZ600320A (en) | 2013-10-25 |
| US9023874B2 (en) | 2015-05-05 |
| AU2010321038B2 (en) | 2015-01-22 |
| CA2780955A1 (en) | 2011-05-26 |
| BR112012011808B1 (pt) | 2020-02-04 |
| WO2011061110A1 (en) | 2011-05-26 |
| JP5717750B2 (ja) | 2015-05-13 |
| ES2545698T3 (es) | 2015-09-15 |
| CA2780955C (en) | 2018-01-23 |
| AU2010321038C1 (en) | 2015-04-30 |
| EP2501686A1 (en) | 2012-09-26 |
| US20120289403A1 (en) | 2012-11-15 |
| MX2012005612A (es) | 2012-11-30 |
| JP2013510820A (ja) | 2013-03-28 |
| AU2010321038A1 (en) | 2012-06-21 |
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