CN1370162A - Derivatives of trifluoromethylpyri(mi)dine - Google Patents
Derivatives of trifluoromethylpyri(mi)dine Download PDFInfo
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Abstract
本发明公开了右式化合物,其中Z表示任选取代的六或七－元芳族或非芳族的杂环基;X是CH或N;Y是卤素;n是1、2或3;和m是0或1;以及适当时为其E/Z异构体,E/Z异构体混合物和/或其互变异构体,各自是游离形式或是盐的形式;这些化合物的生产方法和应用,其活性成分选自这些化合物或其农业化学上可接受的盐的农药,这些组合物的生产方法和应用,用这些组合物处理过的植物繁殖材料,以及控制害虫的方法。
The present invention discloses a compound of the right formula, wherein Z represents an optionally substituted six or seven-membered aromatic or non-aromatic heterocyclic group; X is CH or N; Y is halogen; n is 1, 2 or 3; and m is 0 or 1; and its E/Z isomers, E/Z isomer mixtures and/or tautomers thereof as appropriate, each in free or salt form; methods for the production of these compounds and applications, pesticides whose active ingredients are selected from these compounds or their agrochemically acceptable salts, production methods and applications of these compositions, plant propagation materials treated with these compositions, and methods of controlling pests.
Description
本发明的目的是下式化合物：其中Z表示任选取代的六或七-元芳族或非芳族的杂环基；The object of the present invention is the compound of the formula: wherein Z represents an optionally substituted six or seven-membered aromatic or non-aromatic heterocyclic group;
X是CH或N；X is CH or N;
Y是卤素；Y is halogen;
n是1、2或3；和n is 1, 2 or 3; and
m是0或1；以及适当时为其E/Z异构体，E/Z异构体混合物和/或其互变异构体，各自是游离形式或是盐的形式；这些化合物的制备方法和应用，其活性成分选自这些化合物或其农业化学上可接受的盐的农药，这些组合物的制备方法和应用，用这些组合物处理过的植物繁殖材料和控制害虫的方法。m is 0 or 1; and its E/Z isomer, E/Z isomer mixture and/or its tautomer when appropriate, each in free form or in the form of a salt; methods for the preparation of these compounds and applications, pesticides whose active ingredients are selected from these compounds or their agrochemically acceptable salts, preparation methods and applications of these compositions, plant propagation materials treated with these compositions and methods of controlling pests.
在文献中，某些吡啶衍生物可作为农药的活性成分。但在害虫防治领域中，这些已知化合物的生物性能是不能令人完全满意的，这就是为什么需要生产另外一些具有农药性能的化合物，特别是能够防治昆虫和蜱螨目成员的化合物；本发明对式(I)化合物进行了研究，从而解决了此问题。In literature, certain pyridine derivatives can be used as active ingredients of pesticides. However, in the field of pest control, the biological properties of these known compounds are not completely satisfactory, which is why it is necessary to produce other compounds with pesticide properties, especially compounds that can control insects and members of the order Acarina; the present invention Compounds of formula (I) were investigated to solve this problem.
式(I)化合物和它们适当的互变异构体可形成盐，例如酸加成盐。例如与强无机酸形成盐，具体的无机酸例如是硫酸、磷酸或氢卤酸；或与强有机羧酸形成盐，具体为C1-C4链烷羧酸，其适当时可被例如卤素所取代，例如乙酸，又如任选未被饱和的二羧酸，例如草酸、丙二酸、马来酸、富马酸或苯二甲酸，又如羟基羧酸，例如抗坏血酸、乳酸、苹果酸、酒石酸或柠檬酸，或者是苯甲酸；或与有机磺酸形成盐，具体为C1-C4链烷或芳基磺酸，其适当时可被例如卤素所取代，例如甲磺酸或对甲苯磺酸。在更广泛的意义上，具有至少一个酸基的式(I)化合物可与碱形成盐。合适的与碱形成的盐如金属盐，例如碱金属或碱土金属盐，如钠、钾或镁盐，或与氨或有机胺形成的盐，例如与吗啉、哌啶、吡咯烷、一-、二-或三-低级烷基胺(如乙基、二乙基、三乙基胺或二甲基丙基胺)，或一-、二-或三-羟基低级烷基胺(如一-、二-或三乙醇胺)形成盐。适当时也可形成相应的内盐。游离形式是优选的。在式(I)化合物的盐中，农业化学上有益的盐是优选的。可以理解的是适当时，在上文或下文中，游离的式(I)化合物或其盐也包括相应的盐，或者可以理解的是，所述的盐也包括游离的式(I)化合物。同样的概念也可用于式(I)化合物和其盐的互变异构体。The compounds of formula (I) and their appropriate tautomers may form salts, eg acid addition salts. For example salt formation with strong mineral acids, in particular sulfuric acid, phosphoric acid or hydrohalic acids; or with strong organic carboxylic acids, in particular C 1 -C 4 alkane carboxylic acids, which may, where appropriate, be replaced by, for example, halogen Substituted, for example acetic acid, and optionally unsaturated dicarboxylic acids, such as oxalic acid, malonic acid, maleic acid, fumaric acid or phthalic acid, and also hydroxycarboxylic acids, such as ascorbic acid, lactic acid, malic acid , tartaric acid or citric acid, or benzoic acid; or salts with organic sulfonic acids, in particular C 1 -C 4 alkane or aryl sulfonic acids, which may be substituted as appropriate, for example by halogen, such as methanesulfonic acid or p- Toluenesulfonic acid. In a broader sense, compounds of formula (I) having at least one acid group can form salts with bases. Suitable salts with bases such as metal salts, for example alkali metal or alkaline earth metal salts, such as sodium, potassium or magnesium salts, or salts with ammonia or organic amines, for example with morpholine, piperidine, pyrrolidine, mono- , two- or three-lower alkylamines (such as ethyl, diethyl, triethylamine or dimethylpropylamine), or one-, two- or three-hydroxyl lower alkylamines (such as one-, Di- or triethanolamine) form salts. Corresponding internal salts can also be formed where appropriate. The free form is preferred. Among the salts of the compounds of formula (I), agrochemically beneficial salts are preferred. It can be understood that where appropriate, above or below, the free compound of formula (I) or its salt also includes the corresponding salt, or it can be understood that said salt also includes the free compound of formula (I). The same concept also applies to tautomers of compounds of formula (I) and their salts.
除非另有定义，上文或下文所用的一般术语与下文给出的意义相同。Unless otherwise defined, general terms used above or below have the same meanings as given below.
卤素-其本身作为基团，或作为其它基团和化合物如卤代烷基、卤代环烷基、卤代链烯基、卤代链炔基和卤代烷氧基的结构元素—其为氟、氯、溴或碘，特别是氟、氯或溴，主要是氟或氯，尤其是氯。Halogen - as a group by itself, or as a structural element of other groups and compounds such as haloalkyl, halocycloalkyl, haloalkenyl, haloalkynyl and haloalkoxy - which is fluorine, chlorine, Bromine or iodine, especially fluorine, chlorine or bromine, mainly fluorine or chlorine, especially chlorine.
如无其它定义，含碳基团和化合物各自含有1-20，优选1-18，特别是1-10，尤其是1-6，更特别是1-4，尤其是1-3，特别是1或2个碳原子，具体地说，甲基是优选的。If not otherwise defined, carbon-containing groups and compounds each contain 1-20, preferably 1-18, especially 1-10, especially 1-6, more especially 1-4, especially 1-3, especially 1 or 2 carbon atoms, specifically, methyl is preferred.
烷基-其本身作为基团，和作为其它基团和化合物如卤代烷基、烷氧基、烷氧基烷基、卤代烷氧基、烷氧羰基、烷硫基、卤代烷硫基、烷基磺酰基和烷基磺酰氧基的结构元素，在各种情况下考虑到基团或化合物中碳原子的特定数目，可以是直链的，例如甲基、乙基、正丙基、正丁基、正己基、正辛基、正癸基、正十二烷基、正十六烷基或正十八烷基，或是支链的，例如异丙基、异丁基、仲丁基、叔丁基、异戊基、新戊基或异己基。Alkyl - as a group by itself, and as other groups and compounds such as haloalkyl, alkoxy, alkoxyalkyl, haloalkoxy, alkoxycarbonyl, alkylthio, haloalkylthio, alkylsulfonyl and alkylsulfonyloxy, in each case taking into account the specific number of carbon atoms in the group or compound, can be straight-chain, for example methyl, ethyl, n-propyl, n-butyl, n-hexyl, n-octyl, n-decyl, n-dodecyl, n-hexadecyl or n-octadecyl, or branched such as isopropyl, isobutyl, sec-butyl, tert-butyl radical, isopentyl, neopentyl or isohexyl.
链烯基和链炔基-其本身作为基团，和作为其它基团和化合物如卤代链烯基、卤代链炔基、链烯氧基、卤代链烯氧基、链炔氧基或卤代链炔氧基的结构元素-其是直链或支链的，且各自含有两个或优选一个未被饱和的碳-碳键。可作为实例的例如有乙烯基，丙-2-烯-1-基，2-甲基丙-2-烯-1-基，丁-2-烯-1-基，丁-3-烯-1-基，丙-2-炔-1-基，丁-2-炔-1-基和丁-3-炔-1-基。Alkenyl and alkynyl - as a group by itself, and as other groups and compounds such as haloalkenyl, haloalkynyl, alkenyloxy, haloalkenyloxy, alkynyloxy or haloalkynyloxy structural elements - which are linear or branched and each contain two or preferably one unsaturated carbon-carbon bond. Examples are vinyl, prop-2-en-1-yl, 2-methylprop-2-en-1-yl, but-2-en-1-yl, but-3-en-1 -yl, prop-2-yn-1-yl, but-2-yn-1-yl and but-3-yn-1-yl.
环烷基-其本身作为基团，和作为其它基团和化合物例如烷基的结构元素-其是环丙基，环丁基，环戊基，环己基，环庚基和环辛基。优选的是环戊基和环己基，特别是环丙基。Cycloalkyl - as a group by itself, and as a structural element of other groups and compounds such as alkyl - these are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl. Preferred are cyclopentyl and cyclohexyl, especially cyclopropyl.
卤素-取代的含碳基团和化合物，如卤代烷基和卤代烷氧基可以是部分卤化或全卤化，在多卤化的情况下，卤素取代基可以相同或不同。卤代烷基的实例-其本身作为基团，和作为其它基团和化合物如卤代烷氧基的结构元素-其是被氟、氯和/或溴一至三取代的甲基，如CHF2，CF3或CH2Cl；被氟、氯和/或溴一至五取代的乙基，如CH2CF3，CF2CF3，CF2CCl3，CF2CHCl2，CF2CHF2，CF2CFCl2，CH2CH2Cl，CF2CHBr2，CF2CHClF，CF2CHBrF或CClFCHClF；被氟、氯和/或溴一至七取代的丙基或异丙基，如CH2CHBrCH2Br，CF2CHFCF3，CH2CF2CF3，CF2CF2CF3，CH(CF3)2或CH2CH2CH2Cl；和被氟、氯和/或溴一至九取代的丁基或其异构体之一，如CF(CF3)CHFCF3，CF2(CF2)2CF3或CH2(CF2)2CF3。Halogen-substituted carbon-containing groups and compounds such as haloalkyl and haloalkoxy may be partially or perhalogenated, and in the case of polyhalogenation, the halogen substituents may be the same or different. Examples of haloalkyl - as a group itself, and as a structural element of other groups and compounds such as haloalkoxy - which is methyl one to three substituted by fluorine, chlorine and/or bromine, such as CHF 2 , CF 3 or CH 2 Cl; ethyl one to five substituted by fluorine, chlorine and/or bromine, such as CH 2 CF 3 , CF 2 CF 3 , CF 2 CCl 3 , CF 2 CHCl 2 , CF 2 CHF 2 , CF 2 CFCl 2 , CH 2 CH 2 Cl, CF 2 CHBr 2 , CF 2 CHClF, CF 2 CHBrF or CClFCHClF; propyl or isopropyl one to hepta substituted by fluorine, chlorine and/or bromine, such as CH 2 CHBrCH 2 Br, CF 2 CHFCF 3 , CH 2 CF 2 CF 3 , CF 2 CF 2 CF 3 , CH(CF 3 ) 2 or CH 2 CH 2 CH 2 Cl; and butyl or its isomers one to nine substituted by fluorine, chlorine and/or bromine One of the entities, such as CF(CF 3 )CHFCF 3 , CF 2 (CF 2 ) 2 CF 3 or CH 2 (CF 2 ) 2 CF 3 .
在二-(C1-C4-烷基)胺中，两个烷基基团是各自独立的。In di-(C 1 -C 4 -alkyl)amines, the two alkyl groups are independently of each other.
芳基特别是指苯基或萘基，优选苯基。Aryl is in particular phenyl or naphthyl, preferably phenyl.
杂环基是指6-或7-元、饱和或不饱和的环，该环与碳原子的基本结构键合，该环优选具有2-4个选自N、O或S的杂原子。优选具有氮原子作为杂原子和有另外两个杂原子的6-元环，所述的两个杂原子优选是氮原子或氧原子，特别是一个氧原子和一个氮原子。Heterocyclyl refers to a 6- or 7-membered, saturated or unsaturated ring bonded to the basic structure of carbon atoms, the ring preferably having 2-4 heteroatoms selected from N, O or S. Preference is given to 6-membered rings which have a nitrogen atom as heteroatom and two further heteroatoms, preferably nitrogen or oxygen atoms, in particular one oxygen atom and one nitrogen atom.
根据杂环基基团上取代的可能性，该杂环基基团可有1-3、优选有1个选自下述的取代基：C1-C6-烷基，C2-C6-链烯基，C3-C6-链炔基；卤素，硝基，氰基，-OH，-SH，C3-C8-环烷基，卤素-C3-C8-环烷基，C1-C6-烷氧基，卤素-C1-C6-烷氧基，C3-C6-链烯氧基，C1-C4-烷硫基和二-(C1-C4-烷基)胺。Depending on the possibility of substitution on the heterocyclyl group, the heterocyclyl group may have 1 to 3, preferably 1, substituents selected from the group consisting of: C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 3 -C 6 -alkynyl; halogen, nitro, cyano, -OH, -SH, C 3 -C 8 -cycloalkyl, halogen-C 3 -C 8 -cycloalkyl , C 1 -C 6 -alkoxy, halogen-C 1 -C 6 -alkoxy, C 3 -C 6 -alkenyloxy, C 1 -C 4 -alkylthio and di-(C 1 - C 4 -alkyl)amines.
根据本发明优选的实施方案，式(I)化合物为：According to a preferred embodiment of the present invention, the compound of formula (I) is:
a)其中Z是指下式的环： a) wherein Z refers to a ring of the formula:
在此键U-A，A-M，M-D，D-E，E-G和G-U是单键或双键，条件是不能出现相连的双键，where the bonds U-A, A-M, M-D, D-E, E-G and G-U are single or double bonds, provided that no consecutive double bonds occur,
A是-O-，-NR1-，-S-或-N＝；A is -O-, -NR 1 -, -S- or -N=;
M是-NR2-，-O-，-S-，-CR3R4-，-N＝或-CR3＝；M is -NR 2 -, -O-, -S-, -CR 3 R 4 -, -N= or -CR 3 =;
D是-CR5R6-，-NR7-，-O-，-S-，-N＝或-CR5＝；D is -CR 5 R 6 -, -NR 7 -, -O-, -S-, -N= or -CR 5 =;
E是-NR2-；-O-，-S-或-CR8R9-；-N＝或-CR8＝；和E is -NR 2 -; -O-, -S- or -CR 8 R 9 -; -N= or -CR 8 =; and
G是-O-，-NR10-，-S-，或-N＝；G is -O-, -NR 10 -, -S-, or -N=;
U是碳；U is carbon;
R1，R2，R7和R10各自相互独立地表示氢，C1-C20-烷基，C3-C8-环烷基，C2-C20-链烯基或C3-C20-链炔基；或一-或多取代的C1-C20-烷基，C2-C20-链烯基或C3-C20-链炔基；被一个或多个取代基任选取代的芳基，该取代基选自：C1-C6-烷基，卤素-C1-C6-烷基，C2-C6-链烯基，C3-C6-链炔基，卤素，C1-C6-烷氧基，卤素-C1-C6-烷氧基，硝基，氰基，C3-C8-环烷基，卤素-C3-C8-环烷基，C3-C6-链烯氧基，C1-C4-烷硫基和二-(C1-C4-烷基)胺；或-C(＝O)-R11；R 1 , R 2 , R 7 and R 10 each independently represent hydrogen, C 1 -C 20 -alkyl, C 3 -C 8 -cycloalkyl, C 2 -C 20 -alkenyl or C 3 - C 20 -alkynyl; or one- or more substituted C 1 -C 20 -alkyl, C 2 -C 20 -alkenyl or C 3 -C 20 -alkynyl; substituent(s) Optionally substituted aryl selected from the group consisting of: C 1 -C 6 -alkyl, halogen- C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 3 -C 6 -chain Alkynyl, halogen, C 1 -C 6 -alkoxy, halogen-C 1 -C 6 -alkoxy, nitro, cyano, C 3 -C 8 -cycloalkyl, halogen-C 3 -C 8 -cycloalkyl, C 3 -C 6 -alkenyloxy, C 1 -C 4 -alkylthio and di-(C 1 -C 4 -alkyl)amines; or -C(=O)-R 11 ;
R3，R4，R5，R6，R8和R9各自相互独立地表示氢，C1-C6-烷基，C3-C8-环烷基，C1-C6-烷氧基，C1-C6-烷硫基，C2-C6-链烯基，C3-C6-链烯氧基，C3-C6-链炔基，C3-C6-链炔氧基，芳基，杂环基，芳氧基，苄氧基或杂环氧基；C1-C6-烷基，C3-C8-环烷基，C1-C6-烷氧基，C1-C6-烷硫基，C3-C6-链烯基，C3-C6-链烯氧基，C3-C6-链炔基或C3-C6-链炔氧基，所述基团被一个或多个选自下述的取代基所取代：卤素，硝基，氰基，-OH，-SH，C3-C8-环烷基，卤素-C3-C8-环烷基，苯基和二-(C1-C4-烷基)胺；或被一至三个选自下述的取代基所取代的芳基：卤素，硝基，氰基，-OH，-SH，COOH，COH，C1-C6-烷基，C1-C6-烷氧基，C1-C6-烷硫基，卤素-C1-C6-烷基，卤素-C1-C6-烷氧基，卤素-C1-C6-烷硫基，C3-C8-环烷基，卤素-C3-C8-环烷基和二-(C1-C4-烷基)胺；R 3 , R 4 , R 5 , R 6 , R 8 and R 9 each independently represent hydrogen, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkane Oxygen, C 1 -C 6 -Alkylthio, C 2 -C 6 -Alkenyl, C 3 -C 6 -Alkenyloxy, C 3 -C 6 -Alkynyl, C 3 -C 6 - Alkynyloxy, aryl, heterocyclyl, aryloxy, benzyloxy or heterocyclyloxy; C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, C 1 -C 6 - Alkoxy, C 1 -C 6 -alkylthio, C 3 -C 6 -alkenyl, C 3 -C 6 -alkenyloxy, C 3 -C 6 -alkynyl or C 3 -C 6 -alkynyloxy, said group being substituted by one or more substituents selected from the group consisting of halogen, nitro, cyano, -OH, -SH, C 3 -C 8 -cycloalkyl, halogen -C 3 -C 8 -cycloalkyl, phenyl and di-(C 1 -C 4 -alkyl)amine; or aryl substituted by one to three substituents selected from: halogen, nitro , cyano, -OH, -SH, COOH, COH, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, halogen-C 1 -C 6 -alkyl, halogen-C 1 -C 6 -alkoxy, halogen-C 1 -C 6 -alkylthio, C 3 -C 8 -cycloalkyl, halogen-C 3 -C 8 -cycloalkyl and Di-(C 1 -C 4 -alkyl)amines;
或一起为＝O或＝S；Or be =O or =S together;
R11表示氢，OH，SH，C1-C6-烷基，C3-C8-环烷基，C1-C6-烷氧基，C1-C6-烷硫基，C2-C6-链烯基，C3-C6-链烯氧基，C3-C6-链炔基，C3-C6-链炔氧基，二-(C1-C4-烷基)胺，芳基，杂环基，芳氧基，苄氧基或杂环氧基；C1-C6-烷基，C3-C8-环烷基，C1-C6-烷氧基，C1-C6-烷硫基，C3-C6-链烯基，C3-C6-链烯氧基，C3-C6-链炔基或C3-C6-链炔氧基，所述基团被一个或多个选自下述的取代基所取代：卤素，硝基，氰基，-OH，-SH，C3-C8-环烷基，卤素-C3-C8-环烷基和二-(C1-C4-烷基)胺；或芳基，杂环基，芳氧基，苄氧基或杂环氧基，所述基团被一至三个选自下述的取代基所取代：卤素，硝基，氰基，-OH，-SH，COOH，COH，C1-C6-烷基，C1-C6-烷氧基，C1-C6-烷硫基，卤素-C1-C6-烷基，卤素-C1-C6-烷氧基，卤素-C1-C6-烷硫基，C3-C8-环烷基，卤素-C3-C8-环烷基和二(C1-C4-烷基)胺；R 11 represents hydrogen, OH, SH, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, C 2 -C 6 -alkenyl, C 3 -C 6 -alkenyloxy, C 3 -C 6 -alkynyl, C 3 -C 6 -alkynyloxy, di-(C 1 -C 4 -alk base) amine, aryl, heterocyclyl, aryloxy, benzyloxy or heterocyclyloxy; C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, C 1 -C 6 -alk Oxygen, C 1 -C 6 -alkylthio, C 3 -C 6 -alkenyl, C 3 -C 6 -alkenyloxy, C 3 -C 6 -alkynyl or C 3 -C 6 - Alkynyloxy, said group being substituted by one or more substituents selected from the group consisting of halogen, nitro, cyano, -OH, -SH, C3 - C8 -cycloalkyl, halogen- C 3 -C 8 -Cycloalkyl and di-(C 1 -C 4 -alkyl)amines; or aryl, heterocyclyl, aryloxy, benzyloxy or heterocyclyl, said groups being Substituted by one to three substituents selected from the group consisting of: halogen, nitro, cyano, -OH, -SH, COOH, COH, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -Alkylthio, Halogen-C 1 -C 6 -Alkyl, Halogen-C 1 -C 6 -Alkoxy, Halogen-C 1 -C 6 -Alkylthio, C 3 -C 8 - cycloalkyl, halo-C 3 -C 8 -cycloalkyl and di(C 1 -C 4 -alkyl)amines;
条件是，如果M或E之一，或M和E同时各自独立地是-NR2，-N＝，-O-或-S-时，D表示-CR5R6-或-CR5＝。Provided that, if one of M or E, or both M and E are each independently -NR 2 , -N=, -O- or -S-, D represents -CR 5 R 6 - or -CR 5 =.
b)其中A表示-O-，-NR1-或-N＝；和b) wherein A represents -O-, -NR 1 - or -N=; and
R1是氢，C1-C6-烷基，C3-C8-环烷基，C2-C6-链烯基；或C1-C6-烷基，C2-C6-链烯基或C3-C8-环烷基，所述基团被一个或多个选自下述的取代基所取代：卤素，硝基，氰基，-OH，-SH，C3-C8环烷基，卤素-C3-C8-环烷基，C1-C6-烷氧基，卤素-C1-C6-烷氧基，C3-C6-链烯氧基，C1-C4-烷硫基，二-(C1-C4-烷基)胺，-C(＝O)-R12，芳基，芳氧基，芳硫基，杂环基或杂环氧基；和R12是氢，OH，C1-C6-烷基，C1-C6-烷氧基，二-(C1-C4-烷基)胺，芳基，芳氧基或苄氧基；尤其是其中R1是氢或C1-C2-烷基；R 1 is hydrogen, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, C 2 -C 6 -alkenyl; or C 1 -C 6 -alkyl, C 2 -C 6 - Alkenyl or C 3 -C 8 -cycloalkyl, said group being substituted by one or more substituents selected from the group consisting of halogen, nitro, cyano, -OH, -SH, C 3 - C 8 cycloalkyl, halogen-C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkoxy, halogen-C 1 -C 6 -alkoxy, C 3 -C 6 -alkenyloxy , C 1 -C 4 -alkylthio, di-(C 1 -C 4 -alkyl)amine, -C(=O)-R 12 , aryl, aryloxy, arylthio, heterocyclyl or Heterocyclyloxy; and R 12 is hydrogen, OH, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, di-(C 1 -C 4 -alkyl)amine, aryl, aryl Oxygen or benzyloxy; especially wherein R 1 is hydrogen or C 1 -C 2 -alkyl;
特别地，其中A是-O-或-N＝，最优选是-O-；In particular, wherein A is -O- or -N=, most preferably -O-;
c)其中M是-NR2-，-O-，-CR3R4-，-N＝或-CR3＝；c) wherein M is -NR 2 -, -O-, -CR 3 R 4 -, -N= or -CR 3 =;
R2是氢，C1-C6-烷基，C3-C8-环烷基，C2-C6-链烯基；或C1-C6-烷基，C2-C6-链烯基或C3-C8-环烷基，所述基团被一个或多个选自下述的取代基所取代：卤素，硝基，氰基，-OH，-SH，C3-C8-环烷基，卤素-C3-C8-环烷基，C1-C6-烷氧基，卤素-C1-C6-烷氧基，二-(C1-C4-烷基)胺，-C(＝O)-R12，芳基，芳氧基，芳硫基，杂环基或杂环氧基；和R12是C1-C6-烷基或C1-C6-烷氧基；R 2 is hydrogen, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, C 2 -C 6 -alkenyl; or C 1 -C 6 -alkyl, C 2 -C 6 - Alkenyl or C 3 -C 8 -cycloalkyl, said group being substituted by one or more substituents selected from the group consisting of halogen, nitro, cyano, -OH, -SH, C 3 - C 8 -cycloalkyl, halogen-C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkoxy, halogen-C 1 -C 6 -alkoxy, di-(C 1 -C 4 - Alkyl)amine, -C(=O)-R 12 , aryl, aryloxy, arylthio, heterocyclyl or heterocyclyloxy; and R 12 is C 1 -C 6 -alkyl or C 1 -C 6 -alkoxy;
R3和R4相互独立地是氢，C1-C6-烷基，C3-C8-环烷基，C1-C6烷氧基，C3-C6-链烯基或芳基；或C1-C6-烷基或C3-C8-环烷基，所述基团被一个或多个选自下述的取代基所取代：卤素，硝基，氰基，C3-C8-环烷基，苯基和二(C1-C4-烷基)胺；或被一至三个选自下述的取代基取代的芳基：卤素，硝基，氰基，C1-C6-烷基，C1-C6-烷氧基，C1-C6-烷硫基，卤素-C1-C6-烷基，卤素-C1-C6-烷氧基和二-(C1-C4-烷基)胺；R 3 and R 4 are independently hydrogen, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, C 1 -C 6 alkoxy, C 3 -C 6 -alkenyl or aryl or C 1 -C 6 -alkyl or C 3 -C 8 -cycloalkyl, said group being substituted by one or more substituents selected from the group consisting of halogen, nitro, cyano, C 3 -C 8 -cycloalkyl, phenyl and di(C 1 -C 4 -alkyl)amine; or aryl substituted by one to three substituents selected from the group consisting of halogen, nitro, cyano, C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -alkylthio, halogen-C 1 -C 6 -alkyl, halogen-C 1 -C 6 -alkoxy and di-(C 1 -C 4 -alkyl)amines;
或一起为＝O或＝S；Or be =O or =S together;
尤其是其中M为-CR3R4-或-CR3＝；和Especially wherein M is -CR 3 R 4 - or -CR 3 =; and
R2和R4各自独立地是氢，C1-C6-烷基，C3-C8-环烷基，C1-C6-烷氧基，C3-C6-链烯基或芳基；或一起为＝O或＝S；R 2 and R 4 are each independently hydrogen, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkoxy, C 3 -C 6 -alkenyl or Aryl; or together =O or =S;
特别地，其中M是-CR3R4-或-CR3＝；且R3是氢或C1-C6-烷基，和R4是氢，尤其是R3和R4为氢，或R3和R4一起为＝O或＝S；In particular, wherein M is -CR 3 R 4 - or -CR 3 =; and R 3 is hydrogen or C 1 -C 6 -alkyl, and R 4 is hydrogen, especially R 3 and R 4 are hydrogen, or R 3 and R 4 together are =0 or =S;
特别地，其中M是C＝O；In particular, wherein M is C=O;
d)其中D是-CR5R6-，-NR7-或-O-，-N＝或-CR5＝；d) wherein D is -CR 5 R 6 -, -NR 7 - or -O-, -N= or -CR 5 =;
R5和R6各自独立地是氢，C1-C6-烷基，C3-C8-环烷基，C1-C6-烷氧基，芳基或芳氧基；或一起为＝O或＝S；R 5 and R 6 are each independently hydrogen, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkoxy, aryl or aryloxy; or together are =O or =S;
R7是氢，C1-C6-烷基，C3-C8-环烷基，C3-C12-链烯基或C3-C20-链炔基；或被卤素一或多取代的C1-C6-烷基，或为C1-C4-烷氧基或苯基；芳基；或-C(＝O)-R11；R11是氢，OH，C1-C6-烷基，C1-C6-烷氧基，二-(C1-C4-烷基)胺，芳基，芳氧基或苄氧基；R 7 is hydrogen, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, C 3 -C 12 -alkenyl or C 3 -C 20 -alkynyl; or by one or more halogens Substituted C 1 -C 6 -alkyl, or C 1 -C 4 -alkoxy or phenyl; aryl; or -C(=O)-R 11 ; R 11 is hydrogen, OH, C 1 - C 6 -alkyl, C 1 -C 6 -alkoxy, di-(C 1 -C 4 -alkyl)amine, aryl, aryloxy or benzyloxy;
尤其是其中D为-CR5R6-或-NR7-；R5和R6相互独立地是氢或C1-C2-烷基，和R7是氢，C1-C6-烷基，C3-C8-环烷基，苯基或苄基；特别地，其中D是CH2-或-NR7-；和R7是氢或C1-C6-烷基；Especially in which D is -CR 5 R 6 - or -NR 7 -; R 5 and R 6 are independently hydrogen or C 1 -C 2 -alkyl, and R 7 is hydrogen, C 1 -C 6 -alk radical, C 3 -C 8 -cycloalkyl, phenyl or benzyl; in particular, wherein D is CH 2 - or -NR 7 -; and R 7 is hydrogen or C 1 -C 6 -alkyl;
尤其是其中D为-NCH3-；Especially wherein D is -NCH 3 -;
e)E是-NR22-；-O-，-CR8R9-；-N＝或-CR8＝；e) E is -NR 22 -; -O-, -CR 8 R 9 -; -N= or -CR 8 =;
R8和R9各自独立地是氢或C1-C6-烷基，所述基团任选被一个或多个选自下述的取代基所取代：卤素，硝基，氰基，-OH，-SH，C3-C8-环烷基，卤素-C3-C8-环烷基，苯基和二-(C1-C4-烷基)胺；R 8 and R 9 are each independently hydrogen or C 1 -C 6 -alkyl, said groups being optionally substituted by one or more substituents selected from the group consisting of halogen, nitro, cyano, - OH, -SH, C 3 -C 8 -cycloalkyl, halogen-C 3 -C 8 -cycloalkyl, phenyl and di-(C 1 -C 4 -alkyl)amine;
或一起为＝O或＝S；和or together =O or =S; and
R22是氢或C1-C6-烷基，所述基团任选被一个或多个选自下述的取代基所取代：卤素，硝基，氰基，-OH，-SH，C3-C8-环烷基，卤素-C3-C8-环烷基，C1-C6-烷氧基，卤素-C1-C6-烷氧基，C3-C6-链烯氧基，C1-C4-烷硫基，二-(C1-C4-烷基)胺和芳基；R 22 is hydrogen or C 1 -C 6 -alkyl, which is optionally substituted by one or more substituents selected from the group consisting of halogen, nitro, cyano, -OH, -SH, C 3 -C 8 -cycloalkyl, halogen-C 3 -C 8 -cycloalkyl, C 1 -C 6 -alkoxy, halogen-C 1 -C 6 -alkoxy, C 3 -C 6 -chain alkenyloxy, C 1 -C 4 -alkylthio, di-(C 1 -C 4 -alkyl)amine and aryl;
尤其是其中E表示-CR8R9-，且R8和R9各自独立地表示氢或C1-C6-烷基，或一起为＝O，尤其是氢；In particular wherein E represents -CR 8 R 9 -, and R 8 and R 9 each independently represent hydrogen or C 1 -C 6 -alkyl, or together =O, especially hydrogen;
f)其中G表示-O-，-NR10-或-N＝；且f) wherein G represents -O-, -NR 10 - or -N=; and
R10是氢或C1-C20-烷基；R 10 is hydrogen or C 1 -C 20 -alkyl;
尤其是G表示-N＝；Especially G means -N=;
g)其中X是CH；g) wherein X is CH;
h)其中n是3；h) where n is 3;
i)其中Y是氟；i) wherein Y is fluorine;
j)其中m是0。j) where m is 0.
Z优选具有下述定义，在此R1，R2，R22和R7如上文定义：
按照本发明，特别优选的是列于表1中的式(I)化合物。According to the invention, the compounds of the formula (I) listed in Table 1 are particularly preferred.
对本领域技术人员而言，由类似的制备方法可知式(I)化合物的制备方法是已知的。这特别涉及制备下述化合物的方法：
a)在惰性溶剂中，使已知的或用本身是已知的方法制备的下式化合物：
b)使式(III)化合物与碳酰氯或硫代碳酰氯进行反应；b) reacting the compound of formula (III) with carbonyl chloride or thiocarbonyl chloride;
c)为了得到m为1的式(Ia)化合物，使m为0的式(I)化合物与氧化剂进行反应，所述的氧化剂例如是无机过氧化物如过硼酸钠、高锰酸钾或过氧化氢；或与mCPBA或有机过酸进行反应，所述的有机过酸例如是过苯甲酸或过乙酸；或是有机酸与过氧化氢的混合物，如乙酸/过氧化氢；c) To obtain a compound of formula (Ia) in which m is 1, react a compound of formula (I) in which m is 0 with an oxidizing agent, such as an inorganic peroxide such as sodium perborate, potassium permanganate or peroxide hydrogen oxide; or react with mCPBA or an organic peracid such as perbenzoic acid or peracetic acid; or a mixture of organic acid and hydrogen peroxide, such as acetic acid/hydrogen peroxide;
和/或如果需要，使按照此方法或其它方法获得的，以游离或盐形式存在的式(I)化合物转化成不同的式(I)化合物，对按照此方法可得到的异构体混合物进行分离，分离得到所需的异构体，和/或将按照此方法或其它方法获得的游离的式(I)化合物转化成盐，或将按照此方法或其它方法获得的式(I)化合物的盐转化成游离的式(I)化合物或不同的盐。And/or if desired, convert the compound of formula (I) obtained in free or salt form into different compounds of formula (I) obtained according to this method or other methods, and carry out the isomer mixture obtainable according to this method Separation, separation to obtain the desired isomer, and/or converting the free compound of formula (I) obtained by this method or other methods into a salt, or converting the compound of formula (I) obtained by this method or other methods Salts are converted into free compounds of formula (I) or into different salts.
进一步地，式(I)化合物也可用与已知方法类似的方法生产。例如其中Z是下式的式(I)化合物：
列于上文和下文中的式(II)和(III)的原料是已知的或是可用本身已知的方法制备的，这些原料可用来生产以游离形式或盐形式存在的式(I)化合物。式(IV)的原料是新的，因此也是本发明的目的。The starting materials of formulas (II) and (III) listed above and below are known or can be prepared by methods known per se, and these starting materials can be used to produce formula (I) in free form or in salt form compound. The starting materials of formula (IV) are novel and are therefore also objects of the present invention.
上文和下文所述的反应可用已知的方式进行，例如在下述条件下进行：在没有，或者如果适当的话，在有适当溶剂或稀释剂或其混合物存在下，在所需的室温冷却或加热的条件下，如在大约-80℃至反应介质的沸腾温度，优选大约-20℃至大约+150℃的温度下，在此适于在密闭的容器中，在压力下，在惰性气氛中，和/或在非水条件下。尤其有利的反应条件如实施例所述。The reactions described above and below can be carried out in a known manner, for example under the following conditions: in the absence, or if appropriate, in the presence of suitable solvents or diluents or mixtures thereof, at the desired room temperature with cooling or Under heated conditions, such as at a temperature from about -80°C to the boiling temperature of the reaction medium, preferably from about -20°C to about +150°C, suitably here in a closed vessel, under pressure, in an inert atmosphere , and/or under nonaqueous conditions. Particularly favorable reaction conditions are described in the examples.
过程a)的反应在酸存在下进行，酸例如是HCl、硫酸或磷酸。The reaction of process a) is carried out in the presence of an acid such as HCl, sulfuric acid or phosphoric acid.
反应通常在-30℃至+70℃，优选在-10℃至+50℃的温度下进行。该过程通常在有惰性溶剂或溶剂混合物存在下进行。为此目的，适合的溶剂的实例例如是脂肪和芳族烃，如苯、甲苯、二甲苯、石油醚、己烷；卤代烃，如氯苯、二氯甲烷、二氯乙烷、氯仿、四氯化碳、四氯乙烯；醚或醚类化合物，如二烷基醚(乙醚、二异丙基醚、叔丁基甲基醚等)、苯甲醚、二噁烷、四氢呋喃；腈，如乙腈、丙腈；酯，如乙酸乙酯(乙酸乙基酯)、乙酸丙酯或乙酸丁酯；酮，如丙酮、二乙基酮、甲基乙基酮或甲基异丁基酮；以及这些溶剂与另一种溶剂的混合物。The reaction is usually carried out at a temperature of -30°C to +70°C, preferably -10°C to +50°C. The process is generally carried out in the presence of an inert solvent or solvent mixture. Examples of suitable solvents for this purpose are, for example, aliphatic and aromatic hydrocarbons, such as benzene, toluene, xylene, petroleum ether, hexane; halogenated hydrocarbons, such as chlorobenzene, dichloromethane, dichloroethane, chloroform, Carbon tetrachloride, tetrachloroethylene; ethers or ether compounds, such as dialkyl ethers (diethyl ether, diisopropyl ether, tert-butyl methyl ether, etc.), anisole, dioxane, tetrahydrofuran; nitriles, such as acetonitrile , propionitrile; esters such as ethyl acetate (ethyl acetate), propyl acetate or butyl acetate; ketones such as acetone, diethyl ketone, methyl ethyl ketone or methyl isobutyl ketone; and these A mixture of a solvent and another solvent.
反应在大气压下进行，但也可以在提高压力或减压的条件下进行。The reaction is carried out under atmospheric pressure, but it can also be carried out under elevated or reduced pressure.
在过程b)的变形中，反应有利地是在惰性溶剂或溶剂混合物存在下，于-30℃至+70℃，优选-10℃至+50℃的温度下进行。反应优选在碱存在下进行，例如在有机胺如三烷基胺(三甲胺、三乙胺、三异丙基胺或二异丙基乙基胺)、吡啶(吡啶本身、4-甲基氨基吡啶或4-吡咯烷基吡啶)、吗啉(N-甲基吗啉)或N，N-二烷基苯胺(N，N-二甲基苯胺或N-甲基-N-乙基苯胺)存在下进行。为此目的，合适的溶剂的实例例如是脂肪和芳族烃，如苯、甲苯、二甲苯、石油醚、己烷；卤代烃，如氯苯、二氯甲烷、二氯乙烷、氯仿、四氯化碳、四氯乙烯；醚，如二烷基醚(乙醚、二异丙基醚、叔丁基甲基醚等)、苯甲醚、二噁烷、四氢呋喃；腈，如乙腈、丙腈；酯，如乙酸乙酯(乙酸乙基酯)、乙酸丙酯或乙酸丁酯；以及这些溶剂与另一种溶剂的混合物。In a variant of process b), the reaction is advantageously carried out in the presence of an inert solvent or solvent mixture at a temperature of -30°C to +70°C, preferably -10°C to +50°C. The reaction is preferably carried out in the presence of a base, for example in the presence of organic amines such as trialkylamines (trimethylamine, triethylamine, triisopropylamine or diisopropylethylamine), pyridine (pyridine itself, 4-methylamino Pyridine or 4-pyrrolidinylpyridine), morpholine (N-methylmorpholine) or N,N-dialkylaniline (N,N-dimethylaniline or N-methyl-N-ethylaniline) in presence. Examples of suitable solvents for this purpose are, for example, aliphatic and aromatic hydrocarbons, such as benzene, toluene, xylene, petroleum ether, hexane; halogenated hydrocarbons, such as chlorobenzene, dichloromethane, dichloroethane, chloroform, Carbon tetrachloride, tetrachloroethylene; ethers, such as dialkyl ethers (diethyl ether, diisopropyl ether, tert-butyl methyl ether, etc.), anisole, dioxane, tetrahydrofuran; nitriles, such as acetonitrile, propionitrile; esters, such as ethyl acetate (ethyl acetate), propyl acetate, or butyl acetate; and mixtures of these solvents with another solvent.
在过程c)的变形中，反应在惰性溶剂或溶剂混合物存在下，于-40℃至+120℃，优选在-20℃至+80℃的温度下进行更为有利。关于溶剂，与前述b)的变形中提及的那些相同。该过程任选在碱存在下进行，例如在碱金属或碱土金属氢氧化物、或如碱金属或碱土金属碳酸盐或碳酸氢盐、吡啶、4-二甲氨基吡啶、4-吡咯烷基吡啶、二甲基吡啶、可力丁、三烷基胺、N，N-二烷基苯胺或双环的非亲核碱如1，4-二氮杂双环[2.2.2]辛烷(DABCO)、1，5-二氮杂双环[4.3.0]壬-5-烯(DBN)或1，8-二氮杂双环[5.4.0]十一碳-7-烯(1，5-5)(DBU)。In the variant of process c), the reaction is advantageously carried out in the presence of an inert solvent or solvent mixture at a temperature from -40°C to +120°C, preferably from -20°C to +80°C. As for the solvent, it is the same as those mentioned in the variant of b) above. The process is optionally carried out in the presence of a base, such as an alkali metal or alkaline earth metal hydroxide, or such as an alkali metal or alkaline earth metal carbonate or bicarbonate, pyridine, 4-dimethylaminopyridine, 4-pyrrolidinyl Pyridine, lutidine, collidine, trialkylamines, N,N-dialkylanilines or bicyclic non-nucleophilic bases such as 1,4-diazabicyclo[2.2.2]octane (DABCO) , 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (1,5-5) (DBU).
可将按照本发明的方法或其它方法得到的式(I)化合物以本身已知的方法转化成其它的式(I)化合物，其是通过用本发明的其它取代基，按照常规方法取代式(I)的起始化合物的一个或多个取代基来进行的。The compound of formula (I) obtained by the method of the present invention or other methods can be converted into other compounds of formula (I) in a manner known per se, by substituting the formula ( One or more substituents of the starting compound of I).
根据对适当反应条件和原料的选择，在一个反应步骤中，可用本发明的另一取代基仅取代其中的一个取代基，或在同一反应步骤中，用本发明的其它取代基取代其中的几个取代基。According to the selection of appropriate reaction conditions and raw materials, in one reaction step, only one of the substituents can be replaced by another substituent of the present invention, or in the same reaction step, several substituents can be replaced by other substituents of the present invention. a substituent.
式(I)化合物的盐可按已知方法制备。例如用适当的碱或用适当的离子交换试剂处理游离化合物，可得到式(I)化合物与碱的盐。Salts of compounds of formula (I) can be prepared by known methods. Salts of compounds of formula (I) with bases can be obtained, for example, by treating the free compound with a suitable base or with a suitable ion exchange reagent.
式(I)化合物的盐可以常规方法转化成游离的式(I)化合物，例如用适当的酸或适当的离子交换试剂进行处理。Salts of compounds of formula (I) can be converted into free compounds of formula (I) in a conventional manner, for example by treatment with a suitable acid or a suitable ion exchange reagent.
式(I)化合物的盐可按公知方法转化成式(I)化合物的其它盐。Salts of compounds of formula (I) can be converted into other salts of compounds of formula (I) according to known methods.
以游离形式或盐形式存在的式(I)化合物可以可能的异构体之一的形式或以其混合物存在，例如根据分子中出现的不对称碳原子的数目、绝对或相对的构型，和/或根据分子中出现的非芳族双键的构型，为纯异构体如对映体(antipodes)和/或非对映异构体，或为异构体混合物如对映异构体混合物，如外消旋体、非对映异构体混合物或外消旋体混合物。本发明涉及纯的异构体和所有可能的异构体混合物，且这通过上下文是可以理解的，即使在各种情况下没有对立体化学的细节进行特别地说明。The compounds of formula (I) in free form or in salt form may exist as one of the possible isomers or as mixtures thereof, for example depending on the number of asymmetric carbon atoms present in the molecule, the absolute or relative configuration, and and/or pure isomers such as enantiomers (antipodes) and/or diastereomers, or mixtures of isomers such as enantiomers, depending on the configuration of non-aromatic double bonds present in the molecule Mixtures, such as racemates, diastereomeric or racemic mixtures. The present invention relates to the pure isomers and to all possible isomeric mixtures, and this is understood from the context, even if in each case no specific details of the stereochemistry are stated.
根据对原料和方法的选择，以游离形式或盐形式存在的式(I)化合物的非对映异构体混合物、外消旋体混合物和双键异构体的混合物可由本发明的方法或其它方法获得，可用公知的方法，根据各种组分物理-化学上的差异将其分离成纯的非对映异构体或外消旋体，例如分级结晶、蒸馏和/或色谱法。According to the selection of raw materials and methods, the mixture of diastereoisomers, racemic mixtures and double bond isomers of the compound of formula (I) existing in free form or salt form can be obtained by the method of the present invention or other Methods to obtain, various components can be separated into pure diastereoisomers or racemates according to their physical-chemical differences by known methods, such as fractional crystallization, distillation and/or chromatography.
对相应的可得到的如外消旋体的对映异构体混合物，可用已知的方法将其分离成旋光对映体，例如通过从光学活性溶剂中重结晶、用手性吸附剂进行色谱分离如用高压液相色谱在醋酸纤维素上进行分离，在整个的化合物制备过程中，辅助以适当的微生物，通过用特殊的固定酶进行解离，例如用手性冠醚，在此仅一种对映异构体被络合，或通过转化成非对映异构的盐并分离由此得到的非对映异构体混合物，例如根据它们溶解度的不同进行分级结晶，得到非对映异构体，其在适当的试剂作用下，可释放出所需的对映异构体。The corresponding enantiomeric mixtures, which are available as racemates, can be separated into optical antipodes by known methods, for example by recrystallization from optically active solvents, chromatography with chiral adsorbents Separation such as separation on cellulose acetate by high-pressure liquid chromatography, in the whole process of compound preparation, with the assistance of appropriate microorganisms, by dissociation with special immobilized enzymes, such as chiral crown ethers, here only one The enantiomers are complexed, or by conversion into diastereomeric salts and separation of the diastereomeric mixture thus obtained, e.g. by fractional crystallization according to differences in their solubility, to give diastereoisomeric The desired enantiomer can be liberated under the action of an appropriate reagent.
按照本发明，除相应异构体混合物的分离以外，非对映异构选择性合成或对映异构选择性合成的一般已知方法也可用于得到纯的非对映异构体或对映异构体，例如通过本发明的方法，用具有相应适当的立体化学的离析物来进行。In accordance with the present invention, generally known methods of diastereoselective or enantioselective synthesis can be used to obtain the pure diastereoisomers or enantiomers in addition to the separation of the corresponding isomeric mixtures. Isomerization is carried out, for example, by the method of the invention with the educt having the corresponding appropriate stereochemistry.
分离或合成生物活性更高的异构体如对映异构体或非对映异构体，或异构体混合物如对映异构体混合物或非对映异构体混合物是有利的，条件是各组分具有不同的生物功效。It is advantageous to isolate or synthesize more biologically active isomers such as enantiomers or diastereomers, or mixtures of isomers such as mixtures of enantiomers or diastereoisomers, provided that Each component has different biological effects.
游离形式或盐形式的式(I)化合物还可以它们的水合物形式获得和/或也可以包括其它溶剂，其例如必要时用于以固体形式存在的化合物的结晶。The compounds of formula (I) in free form or in salt form can also be obtained in the form of their hydrates and/or can also comprise further solvents, which are used, for example, if necessary for the crystallization of compounds present in solid form.
本发明涉及所述方法的所有形式，据此可由作为初始原料或该方法的任何阶段的中间体而得到的化合物开始，并进行所有的或某些缺少的步骤，或使用，或尤其是在反应条件下，生成衍生物或盐和/或其外消旋体或对映体形式的原料。The present invention relates to all forms of the process whereby it is possible to start from a compound obtained as starting material or as an intermediate at any stage of the process and to carry out all or some of the missing steps, or to use, or especially in the reaction Under these conditions, derivatives or salts and/or starting materials in the form of racemates or enantiomers thereof are produced.
在本发明的方法中，所用的原料和中间体，不管是游离形式的或是盐形式的，优选使用在开始时所述的可生成式(I)化合物或其盐的化合物，它们是尤其有用的。In the method of the present invention, the raw materials and intermediates used, no matter in free form or in salt form, preferably use the compound that can generate the compound of formula (I) or its salt as described at the beginning, they are especially useful of.
本发明特别涉及实施例P1中所述的制备方法。The invention relates in particular to the preparation described in Example P1.
发明式(I)化合物是用于害虫防治的有预防和/或治疗价值的活性成分，提供了很好的杀生物活性谱，其即使在低浓度下，对温血动物、鱼和植物也有很好的耐受性。本发明的活性成分对具有正常灵敏度的、以及有抗性的动物害虫，如昆虫或蜱螨目成员的所有或各个发育阶段都是有活性的。本发明活性物质的杀虫或杀螨效果可直接用其自身，即立刻或是在一定时间之后如在换羽后杀死害虫来表示，或是间接用杀死害虫如减少卵的数目和/或孵化率来表示，好的功效与至少50-60％的杀虫率(致死率)相应。The compound of the invention formula (I) is a prophylactically and/or therapeutically valuable active ingredient for pest control, providing a good spectrum of biocidal activity, which is very active against warm-blooded animals, fish and plants even at low concentrations. well tolerated. The active ingredients according to the invention are active against all or all stages of development of normally sensitive as well as resistant animal pests, such as insects or members of the order Acarina. The insecticidal or acaricidal effect of the active substance of the present invention can be directly expressed by itself, that is, immediately or after a certain period of time, such as killing pests after moulting, or indirectly by killing pests such as reducing the number of eggs and/or Expressed in terms of hatchability or hatchability, good efficacy corresponds to a kill rate (lethal rate) of at least 50-60%.
所述的动物害虫包括例如欧洲专利申请EP-A-736252，第2页，第55行至第6页第55行中所提到的。为本发明的目的引用其中所提及的害虫作为参考。按照本发明的化合物也是杀灭如Filariidae或Setariidae科的线虫纲的害虫以及下述害虫的活性成分：血矛属(Haemonchus)，毛圆属(Trichostrongylus)，山地奥斯特线虫(Ostertagia)，细颈属(Nematodirus)，古伯属(Cooperia)，蛔属(Ascaris)，仰口属(Bunostumum)，食道口属(Oesophagostonum)，夏伯特属(Chabertia)，毛尾属(Trichuris)，特别是狐毛尾线虫(Trichuris vulpis)，圆线属(Strongylus)，毛线属(Trichonema)，网尾属(Dictyocaulus)，毛细线虫属(Capillaria)，类圆属(Strongyloides)，异刺属(Heterakis)，弓首属(Toxocara)，特别是犬弓首线虫(Toxocara canis)，蛔型属(Ascaridia)，尖尾属(Oxyuris)，钩口属(Ancylostoma)，特别是犬钩口线虫(Ancylostoma caninum)，钩形属(Uncinaria)，弓蛔属(Toxascaris)和副蛔属(Parascaris)；恶丝虫属(Dirofilaria)，特别是犬恶丝虫(Dirofilaria immitis) (heartworm)；也特别是对有代表性的异皮线虫属(Heterodera spp.)，例如甜菜异皮线虫(Heteroderaschachtii)，燕麦异皮线虫(Heterodora avenae)和三叶草异皮线虫(Heterodora trifolii)；球异皮线虫属(Globodera spp.)，例如马铃薯金线虫(Globodera rostochiensis)；根结线虫属(Meloidogynespp.)，例如南方根结线虫(Meloidogyne incoginita)或爪哇根结线虫(Meloidogyne javanica)；穿孔线虫属(Radopholus spp.)，例如相似穿孔线虫(Radopholus similis)；短体线虫属(Pratylenchus spp.)，例如落选短体线虫(Pratylenchus neglectans)和穿刺短体线虫(Pratylenchus penetrans)；小垫刃线虫属(Tylenchulus)，例如半穿刺线虫(Tylenchulus semipenetrans)；长针线虫(Longidorus)，毛刺线虫(Trichodorus)，剑线虫(Xiphinema)，茎线虫(Ditylenchus)，滑刃线虫(Aphelenchoides)和Anguina。Said animal pests include, for example, those mentioned in European patent application EP-A-736252, page 2, line 55 to page 6, line 55. The pests mentioned therein are incorporated by reference for the purposes of the present invention. The compounds according to the invention are also active ingredients for killing pests of the class Nematodes such as Filariidae or Setariidae and the following pests: Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostumum, Oesophagostonum, Chabertia, Trichuris, especially Trichuris vulpis, Strongylus, Trichonema, Dictyocaulus, Capillaria, Strongyloides, Heterakis, Toxocara, especially Toxocara canis, Ascaridia, Oxyuris, Ancylostoma, especially Ancylostoma caninum, Uncinaria, Toxascaris and Parascaris; Dirofilaria, especially Dirofilaria immitis (heartworm); also especially for representative Heterodera spp., e.g. Heteroderaschachtii, Heterodora avenae and Heterodora trifolii; Globodera spp., e.g. Potato golden nematode (Globodera rostochiensis); Meloidogynes pp., for example Meloidogyne incoginita or Meloidogyne javanica; Radopholus similis); Pratylenchus spp., such as Pratylenchus neglectans and Pratylenchus penetrans; Tylenchulus, such as Tylenchulus semipenetrans ; Longidorus, Trichodorus, Xiphinema, Ditylenchus, Aphelenchoides and Anguina.
本发明的活性成分特别适用于防治刺吸口器害虫，特别是同翅目昆虫，优选用于防治蔬菜、水果、稻和棉花作物中的这些害虫。本发明化合物的一个特别的优点是它们的内吸作用。The active ingredients according to the invention are particularly suitable for controlling piercing-sucking mouthpart pests, in particular insects of the order Homoptera, preferably for controlling these pests in vegetable, fruit, rice and cotton crops. A particular advantage of the compounds of the invention is their systemic action.
使用本发明的活性成分，可以防治出现在植物上的，特别是在作物和农业中的观赏植物、园艺和森林，或是植物的各部分，如水果、花、叶、茎、块茎或根上的所述类型的害虫，即，使其被控制或根除，此保护作用可保留到某些植物部分中，直至该植物不再生长以后。Using the active ingredients according to the invention, it is possible to control the fungus occurring on plants, especially ornamental plants in crops and agriculture, horticulture and forests, or on various parts of plants, such as fruits, flowers, leaves, stems, tubers or roots. Pests of the type described, ie allowed to be controlled or eradicated, this protection can be retained in certain plant parts until after the plant no longer grows.
目标作物特别包括谷物，如小麦、大麦、黑麦、燕麦、稻谷、玉米或蜀粟；甜菜，如制糖甜菜或饲料甜菜；水果，如梨果、核果或软果，如苹果、梨、李子、桃、杏仁、樱桃或浆果，如草莓、木莓或黑刺莓；豆科植物，如扁豆、小扁豆、豌豆或大豆；油质作物，如油菜、芥菜、罂粟、橄榄树、向日葵、椰子、蓖麻油植物、可可豆或落花生；黄瓜植物，如南瓜、黄瓜或甜瓜；纤维植物，如棉花、亚麻、大麻或黄麻；柑橘类水果，如橙子、柠檬、柚子或柑橘；蔬菜，如菠菜、生菜、芦笋、甘蓝、胡萝卜、洋葱、番茄、马铃薯或红辣椒；樟科，如鳄梨、肉桂或樟树；和烟草、胡桃、咖啡、茄子、甜甘蔗、茶、胡椒、藤、蛇麻草、香蕉植物、天然橡胶植物和观赏植物。Target crops include in particular cereals such as wheat, barley, rye, oats, rice, maize or millet; sugar beets such as sugar beet or fodder beet; fruits such as pome, stone or soft fruit such as apples, pears, plums , peaches, almonds, cherries or berries such as strawberries, raspberries or blackberries; legumes such as lentils, lentils, peas or soybeans; oily crops such as canola, mustard, poppies, olive trees, sunflowers, coconuts , castor oil plants, cocoa beans, or groundnuts; cucumber plants, such as squash, cucumbers, or melons; fibrous plants, such as cotton, flax, hemp, or jute; citrus fruits, such as oranges, lemons, grapefruit, or mandarins; vegetables, such as spinach, Lettuce, asparagus, kale, carrot, onion, tomato, potato, or red pepper; Lauraceae, such as avocado, cinnamon, or camphor; and tobacco, walnut, coffee, eggplant, sweet cane, tea, pepper, vine, hops, banana plants, natural rubber plants and ornamental plants.
本发明活性成分的其它潜在应用领域是卫生区域中的储存产品和仓储物和材料的保护，特别是保护家养动物和家畜不受所述类型的害虫的危害。A further potential field of application of the active ingredients according to the invention is the protection of stored products and warehouses and materials in hygienic areas, in particular the protection of domestic animals and livestock against pests of the stated type.
因此，本发明还涉及农药，如乳油、悬浮浓缩液、现用现喷或现用现稀释的溶液、用于包复的糊剂、稀释乳液、喷粉、可溶粉剂、可分散粉剂、可湿性粉剂、粉剂、颗粒剂或用聚合物质封装的产品，它们根据预期的目的和具体环境进行选择，并且包括至少一种本发明的活性成分。Therefore, the present invention also relates to pesticides such as emulsifiable concentrates, suspension concentrates, ready-to-spray or ready-to-dilute solutions, pastes for encapsulation, dilute emulsions, dusting powders, soluble powders, dispersible powders, dispersible powders, Wet powders, powders, granules or products encapsulated with polymeric substances, which are selected according to the intended purpose and specific circumstances, and include at least one active ingredient of the present invention.
在这些组合物中使用的所述活性成分为纯净状态的固体活性成分，例如具有特定的颗粒尺寸，或优选与至少一种制剂领域常规使用的辅剂一起使用，该辅剂例如添加剂，如溶剂或固体载体、或表面活性化合物(表面活性剂)。The active ingredients used in these compositions are solid active ingredients in pure state, for example with a specific particle size, or preferably together with at least one adjuvant conventionally used in the field of formulation, such as additives, such as solvents Or solid carrier, or surface active compound (surfactant).
为了制剂，可使用的辅剂例如是固体载体、溶剂、稳定剂、“缓释”剂、染料，以及适当的表面活性剂。载体和辅剂可以是在作物保护剂中通常使用的任何物质，特别是控制蛞蝓或蜗牛的试剂。辅剂如溶剂、固体载体、表面活性剂、非离子表面活性剂、阳离子表面活性剂、阴离子表面活性剂、和本发明组合物中的其它辅剂，例如可与EP-A-736,252中所述的辅剂相同，其在本发明中引作参考。For formulation, adjuvants which may be used are, for example, solid carriers, solvents, stabilizers, "slow-release" agents, dyes, and suitable surfactants. Carriers and adjuvants may be any substances customary in crop protection agents, especially agents for controlling slugs or snails. Adjuvants such as solvents, solid carriers, surfactants, nonionic surfactants, cationic surfactants, anionic surfactants, and other adjuvants in the compositions of the present invention, such as those described in EP-A-736,252 The adjuvants are the same, which are incorporated by reference in the present invention.
规律是，组合物含有0.1-99％，特别是0.1-95％的活性成分，以及1-99.9％，特别是5-99.9％的至少一种固体或液体辅剂，作为规律可能还含有组合物的0-25％，特别是0.1-20％的表面活性剂(在各种情况下，％是指重量百分数)。而浓缩的组合物优选用作商品，规律是，终端消费者使用稀释的组合物，这些组合物具有实质上较低浓度的活性成分。特别地，优选组合物的组成(％＝重量百分数)如下：乳油：活性成分 1-95％，优选5-20％表面活性剂 1-30％，优选10-20％溶剂 5-98％，优选70-85％粉剂：活性成分 0.1-10％，优选0.1-1％固体载体 99.9-90％，优选99.9-90％悬浮浓缩液：活性成分 5-75％，优选10-50％水 94-24％，优选88-30％表面活性剂 1-40％，优选2-30％可湿性粉剂：活性成分 0.5-90％，优选1-80％表面活性剂 0.5-20％，优选1-15％固体载体 5-99％，优选15-98％颗粒剂活性成分 0.5-30％，优选3-15％固体载体 99.5-70％，优选97-85％As a rule, the composition contains 0.1-99%, especially 0.1-95%, of the active ingredient, and 1-99.9%, especially 5-99.9%, of at least one solid or liquid adjuvant, as a rule may also contain the composition 0-25%, especially 0.1-20% of surfactant (in each case, % means percentage by weight). While concentrated compositions are preferred for commercial use, the rule is that end consumers use diluted compositions, which have substantially lower concentrations of active ingredient. In particular, the composition (%=weight percent) of the preferred composition is as follows: emulsifiable concentrate: active ingredient 1-95%, preferably 5-20% surfactant 1-30%, preferably 10-20% solvent 5-98%, preferably 70-85 % powder: 0.1-10 % activity ingredients, preferably 0.1-1 % solid carrier 99.9-90 %, preferably 99.9-90 % suspended concentrated solution: active ingredients 5-75 %, preferably 10-50 % water 94-24 %, preferably 88-30% surfactant 1-40%, preferably 2-30% wettable powder: active ingredient 0.5-90%, preferably 1-80% surfactant 0.5-20%, preferably 1-15% solids Carrier 5-99%, preferably 15-98% granule active ingredient 0.5-30%, preferably 3-15% solid carrier 99.5-70%, preferably 97-85%
通过加入其它杀虫物质，可使本发明组合物的活性实质性地扩大，并适合于具体的环境。其它的活性成分例如为以下几类物质：有机磷化合物、硝基酚及其衍生物、甲脒、酰基脲、氨基甲酸酯、合成除虫菊酯、灭虫碱及其衍生物、吡咯、硫脲及其衍生物、氯代烃和苏云金芽孢杆菌(Bacillus thuringiensis)制剂。在该混合物中特别适合的组分是：唑啶磷；毒虫畏；氯氰菊酯；高顺式氯氰菊酯(cypermethrin high cis)；灭蝇胺；杀螨硫隆；二嗪农；敌敌畏；百治磷；dicyclanil；双氧威；氟啶蜱脲；呋线威；氯唑磷；碘硫磷；蒙七七七；氟丙氧脲；虫螨畏；杀扑磷；久效磷；磷胺；丙溴磷；噁茂醚；从苏云金芽孢杆菌菌株GC91或从NCTC 11821中得到的物质；拒嗪酮；溴螨酯；蒙五一五；乙拌磷；喹硫磷；氟胺氰菊酯；硫环杀；二甲硫吸磷；涕灭威；谷硫磷；丙硫克百威；氟氯菊酯；噻嗪酮；克百威；二丁基氨基硫(dibutylaminothio)；巴丹；定虫隆；毒死蜱；氟氯氰菊酯；λ-氯氟氰菊酯；α-氯氰菊酯；ζ-氯氰菊酯；溴氰菊酯；氟脲杀；硫丹；苯虫威；杀螟硫磷；丁苯威；杀灭菊酯；安果；灭梭威；庚虫磷；吡虫啉；异丙威；甲氨磷；灭多虫；速灭磷；对硫磷；甲基对硫磷；伏杀磷；抗蚜威；残杀威；伏虫隆；特丁磷；唑蚜威；齐墩螨素；丁苯威；双苯酰肼；锐劲特；β-氟氯氰菊酯；灭虫硅醚；唑螨酯；哒螨酮；喹螨醚；蚊蝇醚；嘧胺苯醚；硝胺烯啶；NI-25；吡虫清；齐墩螨素(Abamectin)；植物中的杀虫活性萃取物；包含有杀线虫活性的制剂；由枯草芽孢杆菌(Bacillus subtilis)得到的制剂；包含有杀虫活性真菌的制剂；包含有杀虫活性病毒的制剂；AC 303630；乙酰甲胺磷；氟酯菊酯；棉铃威；甲体氯氰菊酯；虫螨脒；AZ 60541；谷硫磷A；谷硫磷M；唑环锡；噁虫威；杀虫磺；β-氟氯氰菊酯；BPMC；brofenprox；溴硫磷A；合杀威；丁酮威(butocarboxin)；丁基哒螨酮；硫线磷；甲萘威；三硫磷；chloethocarb；壤虫氯磷；氯甲磷；顺式灭虫菊；clocythrin；四螨嗪；杀螟腈；乙氰菊酯；三环锡；内吸磷M；内吸磷S；甲基-内吸磷S；除线磷；dicliphos；乙硫磷；乐果；甲基毒虫畏；敌恶磷；克瘟散；emamectin；高氰戊菊酯；乙硫磷(ethion)；醚菊酯；灭克磷；氧嘧啶磷；克线磷；杀螨锡；苯硫威；甲氰菊酯；fenpyrad；倍硫磷；氟啶胺；氟螨脲；氟氰戊菊酯；氟虫脲；氟丙苄醚；地虫磷；噻唑酮磷；fubfenprox；HCH；氟铃脲；噻螨酮；异稻瘟净；丙胺磷；异噁唑磷；齐墩螨素；λ-氯氟氰菊酯；马拉松；灭呀蜱；甲亚砜磷；蜗牛敌；速灭威；米尔螨素；moxidectin；二溴磷；NC 184；氧乐果；甲氨叉威；砜吸磷(oxydemethon m)；异砜磷；氯菊酯；稻丰散；甲拌磷；亚胺硫磷；辛硫磷；虫螨磷M；虫螨磷A；猛杀威；丙虫磷；丙硫磷；发果；吡唑硫磷(pyrachlophos)；pyrada-phenthion；反灭虫菊；除虫菊；RH 5992；蔬果磷；硫线磷；治螟磷；乙丙硫磷；吡螨胺；嘧丙磷；七氟菊酯；双硫磷；叔丁威；杀虫畏；thiacloprid；thiamethoxam；thiafenox；硫双威；特氨叉威；治线磷；敌贝特；四溴菊酯；triarthen；三唑磷；triazuron；敌百虫；杀虫隆；混杀威；蚜灭多；灭杀威；YI 5301/5302；zetamethrin；DPX-MP062；RH-2485；D2341和XMC(3，5-二甲苯基甲基氨基甲酸酯)。The activity of the compositions of the present invention can be substantially broadened and tailored to specific circumstances by the addition of other pesticidal substances. Other active ingredients are, for example, the following types of substances: organophosphorus compounds, nitrophenols and their derivatives, formamidines, acylureas, carbamates, synthetic pyrethrins, pyrethrin and its derivatives, pyrrole, thiourea and its derivatives, chlorinated hydrocarbons and Bacillus thuringiensis preparations. Particular suitable components in this mixture are: pyrazimon; chlorpyramid; cypermethrin; cypermethrin high cis; cyromazine; thiouron; diazinon; dichlorvos; dicrotophos; dicyclanil ; Fenoxycarb; Chlorflufenuron; Fumicarb; Chlorazofos; ; Oxacene; Substances obtained from Bacillus thuringiensis strain GC91 or from NCTC 11821; Fazazinone; ; Dimethionate; Aldicarb; Azinphos; Prothiocarbafur; Bifenthrin; Buprofezin; Carbofuran; Chlorpyrifos; Cyfluthrin; λ-cyhalothrin; α-cypermethrin; ζ-cypermethrin; Deltamethrin; ; Anguo; Methorcarb; Heptaphos; Imidacloprid; Isoprocarb; Methamidophos; ; chlorfluron; terbufos; pyrimicarb; abamectin; bufencarb; diphenhydrazide; fipronil; β-cyfluthrin; insecticide silicon ether; Acaridin; Pyroxyfen; Pyridine; Nitrapyridine; NI-25; Preparations derived from Bacillus subtilis; preparations containing insecticidally active fungi; preparations containing insecticidally active viruses; AC 303630; Azinate; AZ 60541; Azinphos-A; Azinphos-M; Azocycline; (butocarboxin); butyl pyridaben; thimaphos; carbaryl; trithion; chloethocarb; Cyanothrin; Tricyclic tin; Demeton M; Demeton S; Methyl-demeton S; San; emamectin; esfenvalerate; ethion; etofenproxil; Phosphorus; Afenamiphos; Isoxazophos; Abamectin; λ-cyhalothrin; Marathon; 184; omethoate; methoxacarb; oxydemethon m; isosulfon-phos; permethrin; Daofengsan; phorate; Mitofos A; Methacarb; Profenfos; Prothion; Faguo; Pyrachlophos; pyrada-phenthion; Antipyrethrum; Pyrethrum; RH 5992; Phosphorus; Ethion; Tefluthrin; Primprofos; Tefluthrin; ; Difibrate; Tetramethrin; Triarthen; Triazophos; Triazuron; Trichlorfon; -2485; D2341 and XMC (3,5-xylylmethylcarbamate).
本发明的组合物还可含有另外的固体或液体辅剂，如稳定剂，如植物油，如果需要可以是环氧化的植物油(如环氧化椰子油、菜籽油或大豆油)，防泡剂如硅油，防腐剂，粘度调节剂，粘合剂和/或增稠剂，以及肥料或其它活性成分以达到特定的效果，如杀螨剂、抗菌剂、抗真菌剂、杀线虫剂、杀软体动物剂或选择性的除草剂。The compositions according to the invention may also contain further solid or liquid adjuvants, such as stabilizers, such as vegetable oils, if desired epoxidized vegetable oils (such as epoxidized coconut oil, rapeseed oil or soybean oil), antifoam agents such as silicone oils, preservatives, viscosity regulators, binders and/or thickeners, and fertilizers or other active ingredients to achieve specific effects, such as acaricides, antibacterials, antifungals, nematocides, Mollusc agent or selective herbicide.
本发明的组合物可按已知方法制备，在没有辅剂时，例如通过研磨、过筛，和/或压制固体活性成分或活性成分混合物，例如成为特定的颗粒大小；以及在有至少一种辅剂时，例如通过充分混合和/或研磨活性成分或活性成分混合物与一种或多种辅剂。这些用于制备本发明组合物的方法和化合物I用于制备这些组合物的应用也是本发明的目的。The compositions of the present invention can be prepared according to known methods, without adjuvants, for example by grinding, sieving, and/or compressing a solid active ingredient or active ingredient mixture, for example to a specific particle size; and in the presence of at least one In the case of adjuvants, for example by intimately mixing and/or grinding the active ingredient or active ingredient mixture with one or more adjuvants. These processes for the preparation of the compositions according to the invention and the use of the compound I for the preparation of these compositions are also objects of the invention.
施用该组合物的方法，即防治所述各类害虫的方法，例如根据预期的目的和具体环境，选择喷洒、喷雾、喷粉、涂敷、包衣、播撒或倾倒，所述各种防治害虫的组合物的应用是本发明的另一目的。活性成分的具体浓度在0.1-1000ppm之间，优选0.1-500ppm之间。施用比通常为1-2000g/ha活性成分，优选10-1000g/ha，且更优选20-600g/ha活性成分。The method of applying the composition, that is, the method of controlling the various pests, such as selecting spraying, misting, dusting, coating, coating, broadcasting or pouring according to the intended purpose and specific environment, and the various pests for controlling The application of the composition is another object of the present invention. The specific concentration of the active ingredient is between 0.1-1000 ppm, preferably between 0.1-500 ppm. The application rates are generally 1-2000 g/ha active ingredient, preferably 10-1000 g/ha, and more preferably 20-600 g/ha active ingredient.
对作物保护而言，优选的施用方法是将活性成分施用于植物的叶子(叶面应用)，施用的次数和施用比取决于被有问题的害虫感染的程度。但是，活性成分也可以通过用液体组合物浸渍植物所处的区域使之由根渗透入植物(内吸作用)，或将活性成分以固体形式施用于植物所处的区域，如土壤中，例如以颗粒的形式(固体施用)。在水稻培植中，颗粒剂可计量加入注水的稻田中。For crop protection, the preferred method of application is to apply the active ingredients to the foliage of the plants (foliar application), the number of applications and the rate of application depending on the degree of infestation by the pest in question. However, the active ingredient can also be applied in solid form to the locus of the plant, such as the soil, by impregnating the locus of the plant with a liquid composition which penetrates the plant from the roots (systemic action), e.g. In the form of granules (solid application). In rice cultivation, the granules can be metered into water-flooded rice fields.
本发明组合物也适用于保护植物繁殖材料，包括通过基因修饰的繁殖材料，如种子，例如果类、块茎或谷粒，或植物的秧苗不受动物害虫侵害，所述的繁殖材料在培育之前可用该组合物处理，例如种子在播种前进行包衣。也可以将本发明的活性成分施用于种子(涂敷)，其是通过或者将种子浸泡于液体组合物之中，或者用固体组合物涂敷种子。该组合物也可以在将繁殖材料引入培育地时施用，例如在把种子播种于种子犁沟时施用。植物繁殖材料的处理方法和如此处理的繁殖材料也是本发明的目的。The composition according to the invention is also suitable for the protection of plant propagation material, including genetically modified propagation material, such as seeds, for example fruits, tubers or grains, or seedlings of plants, from animal pests, said propagation material prior to cultivation The composition can be used to treat, for example, coat seeds before sowing. The active ingredients according to the invention can also be applied to the seeds (coating), either by soaking the seeds in a liquid composition or by coating the seeds with a solid composition. The composition may also be applied when the propagation material is introduced into the growing locus, for example when the seeds are sown in seed furrows. Methods for the treatment of plant propagation material and the propagation material so treated are also objects of the present invention.
用下面的实施例说明本发明。它们不会对本发明构成任何限制。温度为摄氏度，混合物中溶剂的比例是体积份数。制备实施例实施例P1：制备下式化合物：
将20ml乙腈放置于烧瓶中，通入1.06g氯化氢气体。然后冷却至-40℃，滴加0.58g的1，3，5-三甲基六氢-1，3，5-三嗪。于-40℃下继续搅拌10分钟，然后分批加入2.5g的4-三氟甲基-烟酰胺。使温度提高至室温，连续搅拌过夜。加入40ml叔丁基甲基醚，继续搅拌该混合物15分钟，并过滤。滤液的残余物用20ml叔丁基甲基醚洗涤两次。得到化合物(B)的固体。P1b)：制备化合物(A)20ml of acetonitrile was placed in the flask, and 1.06g of hydrogen chloride gas was introduced. Then it was cooled to -40°C, and 0.58 g of 1,3,5-trimethylhexahydro-1,3,5-triazine was added dropwise. Stirring was continued for 10 minutes at -40°C, and then 2.5 g of 4-trifluoromethyl-nicotinamide were added in portions. The temperature was allowed to increase to room temperature and stirring was continued overnight. 40 ml of tert-butyl methyl ether were added and the mixture was stirred for a further 15 minutes and filtered. The residue of the filtrate was washed twice with 20 ml of tert-butyl methyl ether. Compound (B) was obtained as a solid. P1b): Preparation of compound (A)
制备3.4g上式(B)化合物和40ml乙酸乙酯，将它们冷却至0-5℃，滴加30％的氢氧化钠溶液5ml。反应混合物用20ml乙酸乙酯萃取两次，合并的有机相用硫酸钠干燥，并用旋转蒸发器浓缩。残余物与20ml二甲氧基乙烷混合，并在1小时内，于0℃下，将其滴加到6.5g碳酰氯和20ml二甲氧基乙烷的混合物中。使混合物的温度提高至室温，然后滴加溶解于20ml二甲氧基乙烷中的2.61g吡啶。将反应物质在缓慢回流下搅拌过夜。Prepare 3.4g of the compound of the above formula (B) and 40ml of ethyl acetate, cool them to 0-5°C, and add dropwise 5ml of 30% sodium hydroxide solution. The reaction mixture was extracted twice with 20 ml of ethyl acetate, the combined organic phases were dried over sodium sulfate and concentrated using a rotary evaporator. The residue was mixed with 20 ml of dimethoxyethane and added dropwise to a mixture of 6.5 g of phosgene and 20 ml of dimethoxyethane at 0°C within 1 hour. The temperature of the mixture was raised to room temperature, and then 2.61 g of pyridine dissolved in 20 ml of dimethoxyethane was added dropwise. The reaction mass was stirred overnight at slow reflux.
然后混合物用旋转蒸发器浓缩，残余物溶于20ml乙酸乙酯中，用10ml水洗涤两次，有机相用硫酸钠干燥，且在硅胶上用己烷/乙酸乙酯(体积比3/7)纯化残余物。得到的化合物(A)为粘性油(化合物1.2)。实施例P2：表1的其余化合物可按照与上述类似的方法制备。The mixture was then concentrated with a rotary evaporator, the residue was dissolved in 20 ml of ethyl acetate, washed twice with 10 ml of water, the organic phase was dried over sodium sulfate, and washed on silica gel with hexane/ethyl acetate (volume ratio 3/7) The residue was purified. Compound (A) was obtained as a viscous oil (Compound 1.2). Example P2: The rest of the compounds in Table 1 can be prepared in a similar manner to the above.
表1：下式化合物：实施例编号R7 X A m 物理数据1.1 H CH O 01.2 甲基 CH O 0 油1.3 乙基 CH O 01.4 正丙基 CH O 01.5 异丙基 CH O 0 油1.6 正丁基 CH O 01.7 苯基 CH O 01.8 4-Cl-苯基 CH O 01.9 4-CF3-O-苯基 CH O 01.10 4-CF3-苯基 CH O 01.11 4-F-苯基 CH O 01.12 苄基 CH O 01.13 环丙基 CH O 01.14 环己基 CH O 01.15 甲基 CH O 11.16 乙基 CH O 11.17 正丙基 CH O 11.18 异丙基 CH O 1实施例编号 R7 X A m 物理数据1.19 正丁基 CH O 11.20 苯基 CH O 11.21 4-Cl-苯基 CH O 11.22 4-CF3-O-苯基 CH O 11.23 4-CF3-苯基 CH O 11.24 4-F-苯基 CH O 11.25 苄基 CH O 11.26 环丙基 CH O 11.27 环己基 CH O 11.28 甲基 N O 01.29 乙基 N O 01.30 正丙基 N O 01.31 异丙基 N O 01.32 正丁基 N O 01.33 苯基 N O 01.34 4-Cl-苯基 N O 01.35 4-CF3-O-苯基 N O 01.36 4-CF3-苯基 N O 01.37 4-F-苯基 N O 01.38 苄基 N O 01.39 环丙基 N O 01.40 环己基 N O 01.41 甲基 CH S 01.42 乙基 CH S 0制剂实施例(％为重量百分数)实施例F1：乳油 a) b) c)活性成分 25％ 40％ 50％十二烷基苯磺酸钙 5％ 8％ 6％蓖麻油聚乙二醇醚(36摩尔EO) 5％ - -三丁基酚聚乙二醇醚(30摩尔EO) - 12％ 4％环己酮 - 15％ 20％二甲苯混合物 65％ 25％ 20％Table 1: Compounds of the formula: Example No. R 7 X A m Physical Data 1.1 H CHO 01.2 Methyl CHO 0 Oil 1.3 Ethyl CHO 01.4 n-Propyl CHO 01.5 Isopropyl CHO 0 Oil 1.6 n-Butyl CHO 01.7 Phenyl CHO 01.8 4-Cl-Phenyl CH O 01.9 4-CF 3 -O -Phenyl CH O 01.10 4-CF 3 -Phenyl CH O 01.11 4-F-Phenyl CH O 01.12 Benzyl CH O 01.13 Cyclopropyl CH O 01.14 Cyclohexyl CHO 01.15 Methyl CHO 11.16 Ethyl CHO 11.17 n-Propyl CHO 11.18 Isopropyl CHO 1 Example No. R 7 X A m Physical Data 1.19 n-Butyl CHO 11.20 Phenyl CHO 11.21 4-Cl-Phenyl CHO 11.22 4-CF 3 -O-Phenyl CHO 11.23 4-CF 3 -Phenyl CHO 11.24 4-F-Phenyl CHO 11.25 Benzyl CHO 11.26 Cyclopropyl CHO 11.27 Cyclohexyl CH O 11.28 Methyl NO 01.29 Ethyl NO 01.30 n-Propyl NO 01.31 Isopropyl N O 01.32 n-Butyl N O 01.33 Phenyl N O 01.34 4-Cl-Phenyl N O 01.35 4-CF 3 -O-Phenyl NO 01.36 4-CF 3 -phenyl NO 01.37 4-F-phenyl NO 01.38 benzyl NO 01.39 cyclopropyl NO 01.40 cyclohexyl NO 01.41 methyl CH S 01.42 ethyl CH S 0 Formulation examples (% is percentage by weight ) Example F1: emulsifiable oil a) b) c) active ingredient 25% 40% 50% calcium dodecylbenzenesulfonate 5% 8% 6% castor oil polyglycol ether (36 moles EO) 5% - - Tributylphenol Polyethylene Glycol Ether (30 Moles EO) - 12% 4% Cyclohexanone - 15% 20% Xylene Mixture 65% 25% 20%
将磨细的活性成分粉末与辅剂混合，得到乳油，其用水稀释后得到所需浓度的乳液。实施例F2：溶液 a) b) c) d)活性成分 80％ 10％ 5％ 95％乙二醇单甲基醚 20％ - - -聚乙二醇(400) - 70％ - -N-甲基吡咯烷-2-酮 - 20％ - -环氧化椰子油 - - 1％ 5％汽油(沸点范围：160-190℃) - - 94％ -The finely ground active ingredient powder is mixed with adjuvants to give an emulsifiable concentrate which, after dilution with water, gives an emulsion of the desired concentration. Example F2: solution a) b) c) d) Activated ingredients 80 % 10 % 5 % 95 % ethylene glycol mononethyl ether 20 %--polyethylene glycol (400) -70 % -n-n-nomatology Kimaro-2-ketone-20 %--1 % 5 % 5 % 5 % gasoline (boiling point: 160-190 ° C)-94 %-
将磨细的活性成分粉末与辅剂混合，得到溶液，其适合于以微滴的形式施用。实施例F3：颗粒剂 a) b) c) d)活性成分 5％ 10％ 8％ 21％高岭土 94％ - 79％ 54％高分散的硅酸 1％ - 13％ 7％绿坡缕石 - 90％ - 18％The finely divided powder of active ingredient is mixed with adjuvants to give a solution suitable for administration in the form of droplets. Example F3: Granules A) B) C) D) Activated ingredients 5 % 10 % 8 % 21 % 21 % Kaolin 94 %-79 % 54 % High-decentralized silicic acid 1 %-13 % 7 % green slopes-90 % - 18%
将活性成分溶解于二氯甲烷中，将该溶液喷洒在载体混合物上，然后真空蒸发溶剂。生物实施例实施例B1：对Diabrotica balteata幼虫的效果The active ingredient was dissolved in dichloromethane, the solution was sprayed onto the carrier mixture, and the solvent was evaporated in vacuo. Biological Examples Example B1: Effect on Diabrotica balteata larvae
玉米秧苗用含水乳液喷雾混合物喷施，混合物中含有400ppm活性成分。在喷雾沉积物干燥之后，于玉米秧苗上移植10只Diabroticabalteata的二龄幼虫，并且放在塑料容器中。六天后进行评价。通过将处理植物上死亡的幼虫数目与那些未处理植物上的进行比较，测定群落减少的百分数(％响应值)。Corn seedlings were sprayed with an aqueous emulsion spray mixture containing 400 ppm active ingredient. After the spray deposits had dried, 10 second instar larvae of Diabroticabalteata were transplanted on corn seedlings and placed in plastic containers. Evaluations were made six days later. The percent reduction in colony (% response value) was determined by comparing the number of dead larvae on treated plants to those on untreated plants.
试验中，表1的化合物对Diabrotica balteata显示了良好的防治效果，特别是化合物1.2的效果超过了80％。实施例B2：对桃蚜(Myzus persicae)的内吸效果In the test, the compounds in Table 1 showed good control effects on Diabrotica balteata, especially the effect of compound 1.2 was more than 80%. Example B2: Systemic effect on green peach aphid (Myzus persicae)
豌豆苗用桃蚜感染，然后把根放入含有400ppm活性成分的喷雾混合物中，在20℃孵化。3和6天后进行评价。通过将处理植物上死亡的桃蚜数目与那些未处理的植物上的进行比较。Pea shoots were infested with green peach aphid, and the roots were placed in a spray mixture containing 400 ppm active ingredient and incubated at 20°C. Evaluations were made after 3 and 6 days. By comparing the number of dead green peach aphids on treated plants with those on untreated plants.
试验中，表1的化合物对桃蚜显示了良好的防治效果，特别是化合物1.2的效果超过了80％。In the test, the compounds in Table 1 showed good control effect on green peach aphid, especially the effect of compound 1.2 was more than 80%.
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