CN112442018B - Triazole-1, 3-disulfonamide derivative and application thereof in agriculture - Google Patents

Triazole-1, 3-disulfonamide derivative and application thereof in agriculture Download PDF

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CN112442018B
CN112442018B CN201910798343.XA CN201910798343A CN112442018B CN 112442018 B CN112442018 B CN 112442018B CN 201910798343 A CN201910798343 A CN 201910798343A CN 112442018 B CN112442018 B CN 112442018B
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alkyl
compound
cycloalkyl
optionally substituted
phenyl
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CN112442018A (en
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李义涛
姚文强
林健
敬德旺
刘新烁
张兵兵
郭文举
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Dongguan Hec Pesticides R&d Co ltd
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Dongguan Hec Pesticides R&d Co ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles

Abstract

The invention relates to a triazole-1, 3-disulfonamide derivative and application thereof in agriculture; in particular, the invention relates to a compound shown in a formula (I) or a stereoisomer, nitrogen oxide or salt thereof, which has excellent bactericidal activity and good control effect on fungal diseases, especially cucumber downy mildew, and is used as a bactericide in agriculture or other fields, wherein each substituent in the formula (I) is defined as the invention.

Description

Triazole-1, 3-disulfonamide derivative and application thereof in agriculture
Technical Field
The invention relates to the field of agricultural bactericides, in particular to a 1,2, 4-triazole-1, 3-disulfonamide derivative and application thereof in agriculture as a plant disease control agent.
Background
Plant diseases can cause significant losses to agriculture, and the crop production worldwide is thereby reduced on average by more than about hundred tons per year. Historically, severe famines, and even starved disaster of a large population, have occurred many times due to the prevalence of certain plant diseases. The use of bactericides is an economical and effective method for controlling plant diseases. Triazole sulfonamide derivatives with biological activity are one of targets of new pesticide development research, wherein indazole sulfenamid developed by Nissan chemistry has higher activity on plant epidemic diseases and downy mildew caused by oomycetes. Oomycetes diseases are very common and serious diseases on fruit and vegetable crops, and the loss caused by the oomycetes diseases is not ignored. However, agents capable of effectively preventing oomycete diseases have not been so far found, and triazole sulfonamide derivatives have considerable expansibility and structural transformation potential (e.g., WO2017143803, CN106905251, etc.). The novel triazole sulfonamide derivatives disclosed by the invention are not reported.
Disclosure of Invention
The invention provides a novel triazole sulfonamide derivative and application thereof, in particular application in preventing and controlling cucumber downy mildew; the compound provided by the invention has excellent effect on cucumber downy mildew at a lower concentration, and has the characteristics of high efficiency and low toxicity.
Specifically, in one aspect, the present invention provides a compound which is a compound having the formula (I) or a stereoisomer, a nitrogen oxide, or a salt thereof of the compound having the formula (I):
wherein:
R 1 and R is 2 Each independently is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl or C 3-8 cycloalkyl-C 1-4 Alkyl-;
n is 0, 1 or 2;
R 3 is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl, C 3-8 cycloalkyl-C 1-4 Alkyl-, phenyl-or phenyl-C 1-3 Alkyl-;
R 4 is indolyl; wherein R is 4 Optionally substituted with 1, 2, 3, 4, 5 or 6 groups selected from halogen, hydroxy, cyano, nitro, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, phenyl-C 1-3 Alkyl-, C 3-8 Cycloalkyl radicals、C 3-8 cycloalkyl-C 1-3 Alkyl-, -S (=O) 2 R A 、-C(＝O)-C 1-6 Substituents for alkyl or-C (=o) -phenyl; the C is 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, phenyl-C 1-3 Alkyl-, C 3-8 Cycloalkyl and C 3-8 cycloalkyl-C 1-3 Alkyl-optionally substituted with 1 or more groups selected from halogen, hydroxy, cyano, nitro, C 1-4 Alkyl, C 1-4 Alkoxy, halo C 1-4 Alkyl or halo C 1-4 Substitution of the substituent of the alkoxy group;
R A is C 1-6 Alkyl, optionally substituted with 1 or 2 groups selected from halogen, hydroxy, cyano, nitro, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halo C 1-4 Phenyl or-NR substituted by substituents of alkoxy B R C ；
R B And R is C Each independently is hydrogen, C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 3-8 Cycloalkyl or C 3-8 cycloalkyl-C 1-3 Alkyl-.
In some embodiments, R 1 And R is 2 Each independently is hydrogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl or C 3-6 cycloalkyl-C 1-4 Alkyl-.
In some embodiments, R 1 And R is 2 Each independently is-CH 3 、-CH 2 CH 3 、-CH 2 CH 2 CH 3 、-CH(CH 3 ) 2 、-CH 2 CH 2 CH 2 CH 3 、-CH(CH 3 )CH 2 CH 3 、-CH 2 CH(CH 3 ) 2 or-C (CH) 3 ) 3 。
In some embodiments, R 3 Is hydrogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl, C 3-6 cycloalkyl-C 1-4 Alkyl-, phenyl-or phenyl-C 1-3 Alkyl-.
In some embodiments, R 3 Is cyclopropyl, cyclopentyl or cyclohexyl.
In some embodiments, R 4 Is indolyl; wherein R is 4 Optionally substituted with 1, 2, 3, 4, 5 or 6 groups selected from halogen, hydroxy, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, phenyl-C 1-3 Alkyl-, C 3-6 Cycloalkyl, C 3-6 cycloalkyl-C 1-3 Alkyl-, -S (=O) 2 R A 、-C(＝O)-C 1-4 Substituents for alkyl or-C (=o) -phenyl; the C is 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, phenyl-C 1-3 Alkyl-, C 3-6 Cycloalkyl and C 3-6 cycloalkyl-C 1-3 Alkyl-optionally substituted with 1 or more groups selected from halogen, hydroxy, cyano, nitro, C 1-4 Alkyl, C 1-4 Alkoxy, halo C 1-4 Alkyl or halo C 1-4 Substitution of the substituent of the alkoxy group;
R A is C 1-4 Alkyl, optionally substituted with 1 or 2 groups selected from halogen, hydroxy, cyano, nitro, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halo C 1-4 Phenyl or-NR substituted by substituents of alkoxy B R C ；
R B And R is C Each independently is hydrogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl or C 3-6 cycloalkyl-C 1-3 Alkyl-.
In some embodiments, R 4 Indol-3-yl, indol-4-yl or indol-6-yl; wherein R is 4 Optionally substituted with 1, 2, 3, 4, 5 or 6 groups selected from halogen, hydroxy, cyano, nitro, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, phenyl-C 1-3 Alkyl-, C 3-6 Cycloalkyl, C 3-6 cycloalkyl-C 1-3 Alkyl-, -S (=O) 2 R A 、-C(＝O)-C 1-4 Alkyl or-C (=o) -phenyl; the C is 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, phenyl-C 1-3 Alkyl-, C 3-6 Cycloalkyl and C 3-6 cycloalkyl-C 1-3 Alkyl-optionally substituted with 1 or more groups selected from halogen, hydroxy, cyano, nitro, C 1-4 Alkyl, C 1-4 Alkoxy, halo C 1-4 Alkyl or halo C 1-4 Substitution of the substituent of the alkoxy group;
R A is C 1-4 Alkyl, optionally substituted with 1 or 2 groups selected from halogen, hydroxy, cyano, nitro, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halo C 1-4 Phenyl or-NR substituted by substituents of alkoxy B R C ；
R B And R is C Each independently is hydrogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl or C 3-6 cycloalkyl-C 1-3 Alkyl-.
In some embodiments, R 4 Indol-3-yl, indol-4-yl or indol-6-yl; wherein R is 4 Optionally by C 1-4 Alkyl, phenyl-C optionally substituted with 1 or more substituents selected from halogen 1-3 Alkyl-, C 3-6 cycloalkyl-C 1-3 alkyl-or-S (=o) 2 R A Substitution;
R A is C 1-4 Alkyl, optionally substituted with 1 or 2 groups selected from halogen, C 1-4 Alkyl or halo C 1-4 Phenyl or-NR substituted by substituents of alkyl groups B R C ；
R B And R is C Each independently is C 1-4 An alkyl group.
Also in some embodiments, R 4 Indol-3-yl, indol-4-yl or indol-6-yl; wherein R is 4 Optionally by C 1-4 Alkyl, phenyl-C optionally substituted with 1 or more substituents selected from halogen 1-3 Alkyl-, cyclopropyl-C 1-3 alkyl-or-S (=o) 2 R A Substitution;
R A is C 1-4 Alkyl, optionally substituted with 1 or 2 groups selected from halogen, C 1-4 Alkyl or halo C 1-4 Phenyl or-NR substituted by substituents of alkyl groups B R C ；
R B And R is C Each independently is C 1-4 An alkyl group.
Still in some embodiments, R 4 Indol-3-yl, indol-4-yl or indol-6-yl; wherein R is 4 Optionally by C 1-4 Alkyl, benzyl optionally substituted by halogen, cyclopropyl-CH 2 -or-S (=o) 2 R A Substitution;
R A is C 1-4 Alkyl, optionally substituted with 1 or 2 groups selected from halogen, C 1-4 Alkyl or halo C 1-4 Phenyl or-NR substituted by substituents of alkyl groups B R C ；
R B And R is C Each independently is C 1-4 An alkyl group.
In some embodiments, R 4 Indol-3-yl, indol-4-yl or indol-6-yl; wherein R is 4 Optionally by-CH 3 、-CH 2 CH 3 、-CH 2 CH 2 CH 3 or-CH (CH) 3 ) 2 And (3) substitution.
In some embodiments, R 4 Indol-3-yl, indol-4-yl or indol-6-yl; wherein R is 4 Optionally substituted by the following sub-structural formula:
in some embodiments, R 4 The following sub-structural formula is shown as follows:
wherein R is 51 、R 52 And R is 53 Each independently is hydrogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, phenyl-C 1-3 Alkyl-, C 3-6 Cycloalkyl, C 3-6 cycloalkyl-C 1-3 Alkyl-, -S (=O) 2 R A1 、-C(＝O)-C 1-4 Alkyl or-C (=o) -phenyl; the C is 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, phenyl-C 1-3 Alkyl-, C 3-6 Cycloalkyl and C 3-6 cycloalkyl-C 1-3 Alkyl-optionally substituted with 1 or more groups selected from halogen, hydroxy, cyano, nitro, C 1-4 Alkyl, C 1-4 Alkoxy, halo C 1-4 Alkyl or halo C 1-4 Substitution of the substituent of the alkoxy group;
R A1 is C 1-4 Alkyl, optionally substituted with 1 or 2 groups selected from halogen, hydroxy, cyano, nitro, C 1-4 Alkyl, halogenated C 1-4 Alkyl, C 1-4 Alkoxy or halo C 1-4 Phenyl or-NR substituted by substituents of alkoxy B1 R C1 ；
R B1 And R is C1 Each independently is hydrogen, C 1-4 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 3-6 Cycloalkyl or C 3-6 cycloalkyl-C 1-3 Alkyl-.
In some embodiments, R 4 The following sub-structural formula is shown as follows:
wherein R is 51 、R 52 And R is 53 Each independently is hydrogen, C 1-4 Alkyl, phenyl-C optionally substituted with 1 or more substituents selected from halogen 1-3 Alkyl-, C 3-6 cycloalkyl-C 1-3 alkyl-or-S (=o) 2 R A1 ；
R A1 Is C 1-4 Alkyl, optionally substituted with 1 or 2 groups selected from halogen, C 1-4 Alkyl or halo C 1-4 Phenyl or-NR substituted by substituents of alkyl groups B1 R C1 ；
R B1 And R is C1 Each independently is C 1-4 An alkyl group.
Still further in some embodiments, R 4 The following sub-structural formula is shown as follows:
wherein R is 51 、R 52 And R is 53 Each independently is hydrogen, -CH 3 、-CH 2 CH 3 、-CH 2 CH 2 CH 3 、-CH(CH 3 ) 2 Benzyl, cyclopropyl-CH optionally substituted by fluorine, chlorine or bromine 2 -or-S (=o) 2 R A1 ；
R A1 is-CH 3 、-CH 2 CH 3 Optionally substituted with 1 or 2 groups selected from fluorine, chlorine, bromine, -CH 3 or-CF 3 Phenyl or-N (CH) 3 ) 2 。
Still further in some embodiments, R 4 The following sub-structural formula is shown as follows:
R 51 、R 52 And R is 53 Each independently is hydrogen, -CH 3 、-CH 2 CH 3 、-CH 2 CH 2 CH 3 or-CH (CH) 3 ) 2 ；
Or R is 51 、R 52 And R is 53 Each independently is of the following sub-structural formula:
in some embodiments, R 4 The following sub-structural formula is shown as follows:
wherein R is 51 Is hydrogen, C 1-4 Alkyl, phenyl-C optionally substituted with 1 or more substituents selected from halogen 1-3 Alkyl-, C 3-6 cycloalkyl-C 1-3 alkyl-or-S (=o) 2 R A1 ；
R A1 Is C 1-4 Alkyl, optionally substituted with 1 or 2 groups selected from halogen, C 1-4 Alkyl or halo C 1-4 Phenyl or-NR substituted by substituents of alkyl groups B1 R C1 ；
R B1 And R is C1 Each independently is C 1-4 An alkyl group.
In some embodiments, R 4 The following sub-structural formula is shown as follows:
wherein R is 52 Is hydrogen, C 1-4 Alkyl, phenyl-C optionally substituted with 1 or more substituents selected from halogen 1-3 Alkyl-or C 3-6 cycloalkyl-C 1-3 Alkyl-.
In some embodiments, R 4 The following sub-structural formula is shown as follows:
wherein R is 53 Is hydrogen, C 1-4 Alkyl, phenyl-C optionally substituted with 1 or more substituents selected from halogen 1-3 Alkyl-or C 3-6 cycloalkyl-C 1-3 Alkyl-.
Still further in some embodiments, R 4 The following sub-structural formula is shown as follows:
wherein R is 51 Is hydrogen, CH 3 -、CH 3 CH 2 -benzyl, cyclopropyl-CH optionally substituted by fluorine, chlorine, bromine or iodine 2 -or-S (=o) 2 R A1 ；
R A1 Is CH 3 -、CH 3 CH 2 Optionally substituted with 1 or 2 groups selected from fluorine, chlorine, bromine, iodine, CH 3 -or CF 3 -substituted phenyl or-N (CH) 3 ) 2 。
Still further in some embodiments, R 4 The following sub-structural formula is shown as follows:
wherein R is 52 Is hydrogen, CH 3 -、CH 3 CH 2 -benzyl or cyclopropyl-CH optionally substituted by fluorine, chlorine, bromine or iodine 2 -。
Still further in some embodiments, R 4 The following sub-structural formula is shown as follows:
wherein R is 53 Is hydrogen, CH 3 -、CH 3 CH 2 -benzyl or cyclopropyl-CH optionally substituted by fluorine, chlorine, bromine or iodine 2 -。
Still further in some embodiments, R 4 The following sub-structural formula is shown as follows:
wherein R is 51 Is hydrogen, CH 3 -or CH 3 CH 2 -；
Or R is 51 The following sub-structural formula is shown as follows:
still further in some embodiments, R 4 The following sub-structural formula is shown as follows:
wherein R is 52 Is hydrogen, CH 3 -or CH 3 CH 2 -；
Or R is 52 The following sub-structural formula is shown as follows:
still further in some embodiments, R 4 The following sub-structural formula is shown as follows:
R 53 is hydrogen, CH 3 -or CH 3 CH 2 -；
Or R is 53 The following sub-structural formula is shown as follows:
still in some embodiments, R 4 The following sub-structural formula is shown as follows:
in some embodiments of the present invention, in some embodiments,the structural formula is as follows:
in some embodiments, the present invention provides a compound that is a compound having the structure:
in another aspect, the invention provides a composition comprising at least one compound of the invention.
Further, the composition of the invention comprises auxiliary materials acceptable in the pharmacy.
In yet another aspect, the invention provides the use of a compound of the invention or a composition of the invention for controlling plant diseases in agriculture.
Further, the plant disease described in the present invention is cucumber downy mildew.
Detailed description of the invention
Definitions and general terms
Reference will now be made in detail to certain embodiments of the invention, examples of which are illustrated in the accompanying structural and chemical formulas. The invention is intended to cover all alternatives, modifications and equivalents, which may be included within the scope of the invention as defined by the appended claims. Those skilled in the art will recognize that many methods and materials similar or equivalent to those described herein can be used in the practice of the present invention. The present invention is in no way limited to the methods and materials described herein. In the event of one or more of the incorporated references, patents and similar materials differing from or contradictory to the present application (including but not limited to defined terms, term application, described techniques, etc.), the present application controls.
It should further be appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub-combination.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. All patents and publications referred to herein are incorporated by reference in their entirety.
The following definitions as used herein should be applied unless otherwise indicated. For the purposes of the present invention, chemical elements are in accordance with CAS version of the periodic Table of the elements, and handbook of chemistry and physics, 75 th edition, 1994. In addition, general principles of organic chemistry may be referenced to the descriptions in "Organic Chemistry", thomas Sorrell, university Science Books, sausalato:1999, and "March's Advanced Organic Chemistry" by Michael b.smith and Jerry March, john Wiley & Sons, new york:2007, the entire contents of which are incorporated herein by reference.
The articles "a," "an," and "the" are intended to include "at least one" or "one or more" unless the context clearly dictates otherwise or otherwise. Thus, as used herein, these articles refer to one or to more than one (i.e., to at least one) object. For example, "a component" refers to one or more components, i.e., more than one component is contemplated as being employed or used in embodiments of the described embodiments.
The term "comprising" is an open-ended expression, i.e., including what is indicated by the invention, but not excluding other aspects.
"stereoisomers" refer to compounds having the same chemical structure but different arrangements of atoms or groups in space. Stereoisomers include enantiomers, diastereomers, conformational isomers (rotamers), geometric isomers (cis/trans), atropisomers, and the like.
"enantiomer" refers to two isomers of a compound that do not overlap but are in mirror image relationship to each other.
"diastereoisomers" refers to stereoisomers which have two or more chiralities and whose molecules are not mirror images of each other. Diastereomers have different physical properties, such as melting point, boiling point, spectral properties, and reactivity. The diastereomeric mixture may be separated by high resolution analytical procedures such as electrophoresis and chromatography, e.g., HPLC.
The stereochemical definitions and rules used in the present invention generally follow S.P. Parker, ed., mcGraw-Hill Dictionary of Chemical Terms (1984) McGraw-Hill Book Company, new York; and Eliel, e.and Wilen, s., "Stereochemistry of Organic Compounds", john Wiley & Sons, inc., new York, 1994.
Many organic compounds exist in optically active form, i.e., they have the ability to rotate the plane of plane polarized light. In describing optically active compounds, the prefixes D and L or R and S are used to represent the absolute configuration of the molecule with respect to one or more of its chiral centers. The prefixes d and l or (+) and (-) are symbols for specifying the rotation of plane polarized light by a compound, where (-) or l indicates that the compound is left-handed. The compound prefixed with (+) or d is dextrorotatory. One particular stereoisomer is an enantiomer, and a mixture of such isomers is referred to as an enantiomeric mixture. A50:50 mixture of enantiomers is referred to as a racemic mixture or racemate, which can occur when there is no stereoselectivity or stereospecificity in a chemical reaction or process.
The compounds of the invention may be optionally substituted with one or more substituents, as described in the present invention, such as the compounds of the general formula above, or as specific examples within the examples, subclasses, and classes of compounds encompassed by the invention. It is to be understood that the term "optionally substituted" may be used interchangeably with the term "substituted or unsubstituted". In general, the term "substituted" means that one or more hydrogen atoms in a given structure are replaced with a specific substituent. An optional substituent group may be substituted at each substitutable position of the group unless otherwise indicated. When more than one position in a given formula can be substituted with one or more substituents selected from a particular group, then the substituents may be the same or different at each position. Wherein the substituents may be, but are not limited to, deuterium, fluorine, chlorine, bromine, iodine, cyano, hydroxyl, nitro, amino, carboxyl, alkyl, alkoxy, alkoxyalkyl, alkoxyalkoxy, alkoxyalkylamino, aryloxy, heteroaryloxy, heterocyclyloxy, arylalkoxy, heteroarylalkoxy, heterocyclylalkoxy, cycloalkylalkoxy, alkylamino alkyl, alkylamino, cycloalkylamino, cycloalkylalkylamino, alkylthio, haloalkyl, haloalkoxy, hydroxyl-substituted alkyl, hydroxyl-substituted alkylamino, cyano-substituted alkyl, cyano-substituted alkoxy, cyano-substituted alkylamino, amino-substituted alkyl, alkanoyl, heteroalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, heterocyclylacyl, aryl, arylalkyl, arylamino, heteroaryl, heteroarylalkyl, heteroarylamino, amido, sulfonyl, aminosulfonyl, and the like.
In addition, unless explicitly indicated otherwise, the descriptions used in this disclosure of the manner in which each … is independently "and" … is independently "and" … is independently "are to be construed broadly as meaning that particular items expressed between the same symbols in different groups do not affect each other, or that particular items expressed between the same symbols in the same groups do not affect each other.
In the various parts of the present specification, substituents of the presently disclosed compounds are disclosed in terms of the type or scope of groups. It is specifically noted that the present invention includes each individual subcombination of the individual members of these group classes and ranges. For example, the term "C 1 -C 6 Alkyl "or" C 1-6 Alkyl "means in particular methyl, ethyl, C independently disclosed 3 Alkyl, C 4 Alkyl, C 5 Alkyl and C 6 An alkyl group.
The term "alkyl" or "alkyl group" as used herein, means a saturated straight or branched monovalent hydrocarbon group containing 1 to 20 carbon atoms; wherein the alkyl group is optionally substituted with one or more substituents described herein. Unless otherwise specified, alkyl groups contain 1 to 20 carbon atoms. In one embodiment, the alkyl group contains 1 to 12 carbon atoms; in one embodiment, the alkyl group contains 1 to 10 carbon atoms; in one embodiment, the alkyl group contains 1 to 8 carbon atoms; in another embodiment, the alkyl group contains 1 to 6 carbon atoms; in yet another embodiment, the alkyl group contains 1 to 4 carbon atoms; in yet another embodiment, the alkyl group contains 1 to 3 carbon atoms.
Examples of alkyl groups include, but are not limited to, methyl (Me, -CH 3 ) Ethyl (Et, -CH) 2 CH 3 ) N-propyl (n-Pr, -CH) 2 CH 2 CH 3 ) Isopropyl (i-Pr, -CH (CH) 3 ) 2 ) N-butyl (n-Bu, -CH) 2 CH 2 CH 2 CH 3 ) Isobutyl (i-Bu, -CH) 2 CH(CH 3 ) 2 ) Sec-butyl (s-Bu, -CH (CH) 3 )CH 2 CH 3 ) Tert-butyl (t-Bu, -C (CH) 3 ) 3 ) N-pentyl (-CH) 2 CH 2 CH 2 CH 2 CH 3 ) 2-pentyl (-CH (CH) 3 )CH 2 CH 2 CH 3 ) 3-pentyl (-CH (CH) 2 CH 3 ) 2 ) 2-methyl-2-butyl (-C (CH) 3 ) 2 CH 2 CH 3 ) 3-methyl-2-butyl (-CH (CH) 3 )CH(CH 3 ) 2 ) 3-methyl-1-butyl (-CH) 2 CH 2 CH(CH 3 ) 2 ) 2-methyl-1-butyl (-CH) 2 CH(CH 3 )CH 2 CH 3 ) N-hexyl (-CH) 2 CH 2 CH 2 CH 2 CH 2 CH 3 ) 2-hexyl (-CH (CH) 3 )CH 2 CH 2 CH 2 CH 3 ) 3-hexyl (-CH (CH) 2 CH 3 )(CH 2 CH 2 CH 3 ) 2-methyl-2-pentyl (-C (CH) 3 ) 2 CH 2 CH 2 CH 3 ) 3-methyl-2-pentyl (-CH (CH) 3 )CH(CH 3 )CH 2 CH 3 ) 4-methyl-2-pentyl (-CH (CH) 3 )CH 2 CH(CH 3 ) 2 ) 3-methyl-3-pentyl (-C (CH) 3 )(CH 2 CH 3 ) 2 ) 2-methyl-3-pentyl (-CH (CH) 2 CH 3 )CH(CH 3 ) 2 ) 2, 3-dimethyl-2-butyl (-C (CH) 3 ) 2 CH(CH 3 ) 2 ) 3, 3-dimethyl-2-butyl (-CH (CH) 3 )C(CH 3 ) 3 ) N-heptyl, n-octyl, and the like.
The term "alkoxy" means that the alkyl group is attached to the remainder of the molecule through an oxygen atom, wherein the alkyl group has the meaning as described herein. Unless otherwise specified, the alkoxy groups contain 1 to 12 carbon atoms. In one embodiment, the alkoxy group contains 1 to 10 carbon atoms; in one embodiment, the alkoxy group contains 1 to 8 carbon atoms; in one embodiment, the alkoxy group contains 1 to 6 carbon atoms; in another embodiment, the alkoxy group contains 1 to 4 carbon atoms; in yet another embodiment, the alkoxy group contains 1 to 3 carbon atoms. The alkoxy group may be optionally substituted with one or more substituents described herein.
Examples of alkoxy groups include, but are not limited to, methoxy (MeO, -OCH) 3 ) Ethoxy (EtO, -OCH) 2 CH 3 ) 1-propoxy (n-PrO, n-propyl)Oxy, -OCH 2 CH 2 CH 3 ) 2-propoxy (i-PrO, i-propoxy, -OCH (CH) 3 ) 2 ) 1-butoxy (n-BuO, n-butoxy, -OCH) 2 CH 2 CH 2 CH 3 ) 2-methyl-l-propoxy (i-BuO, i-butoxy, -OCH) 2 CH(CH 3 ) 2 ) 2-butoxy (s-BuO, s-butoxy, -OCH (CH) 3 )CH 2 CH 3 ) 2-methyl-2-propoxy (t-BuO, t-butoxy, -OC (CH) 3 ) 3 ) 1-pentoxy (n-pentoxy, -OCH) 2 CH 2 CH 2 CH 2 CH 3 ) 2-pentoxy (-OCH (CH) 3 )CH 2 CH 2 CH 3 ) 3-pentoxy (-OCH (CH) 2 CH 3 ) 2 ) 2-methyl-2-butoxy (-OC (CH) 3 ) 2 CH 2 CH 3 ) 3-methyl-2-butoxy (-OCH (CH) 3 )CH(CH 3 ) 2 ) 3-methyl-l-butoxy (-OCH) 2 CH 2 CH(CH 3 ) 2 ) 2-methyl-l-butoxy (-OCH) 2 CH(CH 3 )CH 2 CH 3 ) And so on.
The term "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br) or iodine (I).
The term "haloalkyl" means an alkyl group substituted with one or more halogen atoms. Examples of haloalkyl groups include, but are not limited to, -CH 2 F，-CHF 2 ，-CH 2 Cl，-CH 2 Br，-CF 3 ，-CH 2 CF 3 ，-CH 2 CH 2 F，-CH 2 CH 2 Cl，-CH 2 CH 2 Br，-CH 2 CHF 2 ，-CH 2 CH 2 CF 3 ，-CH 2 CH 2 CH 2 F，-CH 2 CH 2 CH 2 Cl，-CH 2 CH 2 CH 2 Br，-CHFCH 2 CH 3 ，-CHClCH 2 CH 3 And so on.
The term "haloalkoxy" means that the alkoxy group is substituted with one or more halogen atoms. Examples of haloalkoxy groups include, but are not limited to, -OCH 2 F，-OCHF 2 ，-OCH 2 Cl，-OCH 2 Br，-OCF 3 ，-OCH 2 CF 3 ，-OCH 2 CH 2 F，-OCH 2 CH 2 Cl，-OCH 2 CH 2 Br，-OCH 2 CHF 2 ，-OCH 2 CH 2 CF 3 ，-OCH 2 CH 2 CH 2 F，-OCH 2 CH 2 CH 2 Cl，-OCH 2 CH 2 CH 2 Br，-OCHFCH 2 CH 3 ，-OCHClCH 2 CH 3 And so on.
The term "cycloalkyl" denotes a monovalent or polyvalent saturated monocyclic, bicyclic or tricyclic ring system containing 3 to 12 carbon atoms. In one embodiment, cycloalkyl groups contain 3 to 12 carbon atoms; in one embodiment, cycloalkyl groups contain 3 to 10 carbon atoms; in another embodiment, cycloalkyl groups contain 3 to 8 carbon atoms; in yet another embodiment, cycloalkyl groups contain 3 to 6 carbon atoms. The cycloalkyl group is optionally substituted with one or more substituents described herein. Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, adamantyl, and the like.
The term "cycloalkylalkyl" means that a hydrogen atom in an alkyl group is replaced by one or more cycloalkyl groups, where alkyl and cycloalkyl groups have the meaning as described herein. Examples of cycloalkylalkyl groups include cyclopropyl-CH 2 -, cyclobutyl-CH 2 -, cyclopentyl-CH 2 -, cyclohexyl-CH 2 -, cyclopropyl-CH 2 CH 2 -, etc.
The term "arylalkyl" means that a hydrogen atom in an alkyl group is replaced by one or more aryl groups, where alkyl and aryl groups have the meaning as described herein. Examples include, but are not limited to, benzyl, phenethyl, and the like.
The term "aryl" means a monocyclic, bicyclic and tricyclic carbocyclic ring system containing 6 to 14 ring atoms, or 6 to 12 ring atoms, or 6 to 10 ring atoms, wherein at least one ring system is aromatic, wherein each ring system contains a ring of 3 to 7 atoms, and wherein one or more attachment points are attached to the remainder of the molecule. The term "aryl" may be used interchangeably with the term "aromatic ring". Examples of aryl groups may include phenyl, indenyl, naphthyl and anthracenyl. The aryl group is optionally substituted with one or more substituents described herein.
In the various parts of the present specification, linking substituents are described. When the structure clearly requires a linking group, the markush variables recited for that group are understood to be linking groups. For example, if the structure requires a linking group and the markush group definition for that variable enumerates an "alkyl" or "aryl" group, it will be understood that the "alkyl" or "aryl" represents a linked alkylene group or arylene group, respectively.
The term "alkylene" means a saturated divalent hydrocarbon group resulting from the removal of two hydrogen atoms from a saturated hydrocarbon group. Unless otherwise specified, an alkylene group contains 1 to 12 carbon atoms, and in other embodiments an alkylene group contains 1 to 6 carbon atoms, and in other embodiments an alkylene group contains 1 to 4 carbon atoms, and in other embodiments an alkylene group contains 1 to 2 carbon atoms. Examples of this include methylene (-CH) 2 (-), ethylene (-CH) 2 CH 2 (-), isopropylidene (-CH (CH) 3 )CH 2 (-), etc.
When the compounds of the present invention contain one acid moiety, salts of the compounds of the present invention include those derived from alkali metals or alkaline earth metals, as well as those derived from ammonia and amines. Preferred cations include sodium, potassium, magnesium and have the formula N + (R 19 R 20 R 21 R 22 ) Wherein R is an ammonium cation of 19 、R 20 、R 21 And R is 22 Independently selected from hydrogen, C 1 -C 6 Alkyl and C 1 -C 6 A hydroxyalkyl group. Salts of the compounds of formula (I) may be prepared by reacting a metal hydroxide (e.g. sodium hydroxide) or an amine (e.g. ammonia, trimethylamine, diethanolamine, 2-methylthio)Aminopropylamine, diallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine or benzylamine) is prepared by treating a compound having the formula (I).
When the compounds of the present invention contain a base moiety, acceptable salts may be formed with organic and inorganic acids, such as acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, naphthalenesulfonic, benzenesulfonic, toluenesulfonic, camphorsulfonic, and similarly known acceptable acids.
Compositions and formulations of the compounds of the invention
The compounds of the present invention are generally useful as fungicide active ingredients in compositions or formulations which typically also comprise an agropharmaceutically acceptable adjuvant, wherein the adjuvant comprises a surfactant and/or a carrier.
The above surfactants may be various surfactants known in the art of pesticide formulation, such as anionic surfactants, cationic surfactants, nonionic surfactants and amphoteric surfactants, block polymers, polyelectrolytes, and mixtures thereof. The surfactant can be used as an emulsifier, a dispersant, a wetting agent, a penetration enhancer or an auxiliary agent.
Suitable anionic surfactants are alkali metal, alkaline earth metal or ammonium salts of sulfonic acid, sulfuric acid, phosphoric acid, carboxylic acids, and mixtures thereof. Examples of sulfonates are alkylaryl sulfonates, diphenyl sulfonates, alpha-olefin sulfonates, lignin sulfonates, fatty acid and oil sulfonates, ethoxylated alkylphenol sulfonates, alkoxylated aryl phenol sulfonates, condensed naphthalene sulfonates, dodecyl-and tridecyl benzene sulfonates, naphthalene and alkyl naphthalene sulfonates, sulfosuccinates or sulfosuccinamates. Examples of sulfates are sulfates of fatty acids and oils, sulfates of ethoxylated alkylphenols, sulfates of alcohols, sulfates of ethoxylated alcohols or sulfates of fatty acid esters. Examples of phosphates are phosphate esters. Examples of carboxylates are alkyl carboxylates and carboxylated alcohols or alkylphenol ethoxylates.
Suitable nonionic surfactants are alkoxylates, N-substituted fatty acid amides, amine oxides, esters, sugar-based surfactants, polymeric surfactants and mixtures thereof. Examples of alkoxylates are compounds such as alcohols, alkylphenols, amines, amides, arylphenols, fatty acids or fatty acid esters which have been alkoxylated by 1 to 50 equivalents. Ethylene oxide and/or propylene oxide may be used for alkoxylation, preferably ethylene oxide. Examples of N-substituted fatty acid amides are fatty acid glucamides or fatty acid alkanolamides. Examples of esters are fatty acid esters, glycerol esters or monoglycerides. Examples of sugar-based surfactants are sorbitan, ethoxylated sorbitan, sucrose and glucose esters or alkyl polyglucosides. Examples of polymeric surfactants are homopolymers or copolymers of vinylpyrrolidone, vinyl alcohol or vinyl acetate.
Suitable cationic surfactants are quaternary surfactants, for example quaternary ammonium compounds having 1 or 2 hydrophobic groups, or salts of long-chain primary amines. Suitable amphoteric surfactants are alkyl betaines and imidazolines. Suitable block polymers are A-B or A-B-A type block polymers comprising blocks of polyoxyethylene and polyoxypropylene, or A-B-C type block polymers comprising alkanols, polyoxyethylene and polyoxypropylene. Suitable polyelectrolytes are polyacids or polybases. Examples of polyacids are alkali metal salts of polyacrylic acids or polyacid comb polymers. Examples of polybases are polyvinylamines or polyvinylamines.
The carrier can be various carriers known in the pesticide preparation field, including various silicates, carbonates, sulfates, oxides, phosphates, plant carriers, and synthetic carriers. Specifically, for example: white carbon black, kaolin, diatomaceous earth, clay, talc, organic bentonite, pumice, titanium dioxide, dextrin, cellulose powder, light calcium carbonate, soluble starch, corn starch, sawdust powder, urea, an amine fertilizer, a mixture of urea and an amine fertilizer, glucose, maltose, sucrose, anhydrous potassium carbonate, anhydrous sodium carbonate, anhydrous potassium bicarbonate, anhydrous sodium bicarbonate, attapulgite, a mixture of anhydrous potassium carbonate and anhydrous potassium bicarbonate, and a mixture of anhydrous sodium carbonate and anhydrous sodium bicarbonate.
The fungicide composition according to the present invention may further contain various adjuvants for formulation commonly used in the field of agricultural chemical formulations, and specifically, the adjuvants for formulation may be one or more of solvents, co-solvents, thickeners, antifreezes, encapsulating materials, protectants, antifoaming agents, disintegrants, stabilizers, preservatives, binders, chelating agents.
Suitable solvents are water and organic solvents, such as medium to high boiling mineral oil fractions, for example kerosene, diesel oil; oils of vegetable or animal origin; aliphatic, cyclic and aromatic hydrocarbons such as toluene, paraffin, tetrahydronaphthalene, alkylated naphthalenes; alcohols such as ethanol, propanol, butanol, benzyl alcohol, cyclohexanol; glycols; DMSO; ketones, such as cyclohexanone; esters, such as lactate, carbonate, fatty acid ester, gamma-butyrolactone; a fatty acid; a phosphonate; amines; amides, such as N-methylpyrrolidone, fatty acid dimethylamide; and mixtures thereof.
The above solvents may also be used as a cosolvent.
Suitable thickeners are selected from polysaccharides (e.g. xanthan gum, carboxymethyl cellulose), inorganic clays (organically modified or unmodified), polycarboxylates and silicates.
Suitable antifreeze agents are selected from the group consisting of ethylene glycol, propylene glycol, glycerol, urea, glycerol, and mixtures thereof.
Suitable capsules are selected from the group consisting of polyurethane, polyurea, urea formaldehyde resins and mixtures thereof.
Suitable protective agents are selected from polyvinyl alcohols and/or polyethylene glycols.
Suitable defoamers are selected from the group consisting of polysiloxanes, silicone emulsions, long chain alcohols, fatty acids and salts thereof, and fluoroorganics and mixtures thereof.
Suitable disintegrants are selected from bentonite, urea, ammonium sulfate, aluminum chloride, citric acid, succinic acid, sodium bicarbonate, and mixtures thereof.
Suitable stabilizers are selected from the group consisting of triphenyl phosphite, epichlorohydrin, acetic anhydride, and mixtures thereof.
Suitable preservatives are selected from benzoic acid, sodium benzoate, 1, 2-benzisothiazolin-3-one (BIT for short), pinus koraiensis, potassium sorbate and mixtures thereof.
Suitable binders are selected from polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, polyacrylate, bio-or synthetic waxes and cellulose ethers.
The fungicide of the present invention may be applied in the form of its formulation or in the form of its use prepared therefrom, such as aerosols, capsule suspensions, cold mist concentrates (cold-fogging concentrate), hot mist concentrates, encapsulated granules, fine granules, flowable concentrates for seed treatment (flowable concentrate), ready-to-use solutions, dustable powders, emulsifiable concentrates, oil-in-water emulsions, water-in-oil emulsions, large granules, microparticles, oil-dispersible powders, oil-miscible flowable concentrates, oil-miscible liquids, aerosols (under pressure), gas-generating products, foams, pastes, suspension concentrates, soluble concentrates, suspensions, wettable powders, soluble powders, dusts and granules, water-soluble and water-dispersible granules or tablets, water-soluble or water-dispersible powders for seed treatment, wettable powders, natural products and synthetic substances impregnated with active substances, and microcapsules in polymers and seed coating materials, and ULV (ultra low volume) and hot mist formulations. All of the above forms of use can be prepared by conventional means in the art.
Use of the compounds and compositions of the invention
The compounds of the present invention are useful as plant disease control agents, i.e., as fungicides. Thus, the present invention may also include a method for controlling plant diseases caused by phytopathogenic fungi, said method comprising applying to the plant to be protected or to a part thereof or to the seed of the plant to be protected an effective amount of a compound of the invention or a fungicidal composition comprising said compound. The compounds and/or compositions of the present invention provide control of diseases caused by broad-spectrum plant pathogenic fungi of basidiomycetes, ascomycetes, oomycetes and deuteromycetes. They are effective in controlling a broad spectrum of plant diseases, especially foliar pathogens in ornamental, lawn, vegetable, field, cereal and fruit crops. These pathogens include: oomycetes, including Phytophthora (Phytophthora) diseases such as Phytophthora infestans (Phytophthora infestans), phytophthora sojae (Phytophthora megasperma), citrus foot rot (Phytophthora parasitica), phytophthora camphorata (Phytophthora cinnamomi) and Phytophthora cucurbitae (Phytophthora capsici), pythium (Pythium) species diseases such as Pythium triclopyr (Pythium aphanidermatum), and Peronospora species diseases such as downy mildew (Plasmopara viticola), peronospora diseases (Peronospora spp.) (including Peronospora tabacia (Peronospora tabacina) and Peronospora parasitica (Peronospora parasitica)), pseudoperonospora (Pseudoperonospora spp.) (including Peronospora cucumeria (Pseudoperonospora cubensis) and scentis discriminan (bria tucae)); ascomycetes (including Alternaria (Alternaria) pathogens such as Alternaria solani (Alternaria solani) and Brassica oleracea (Alternaria brassicae), fabry (Guignardia) pathogens such as Botrytis cinerea (Guignardia bidwell), venturia (Venturia) pathogens such as Botrytis cinerea (Venturia inaequalis), septoria (Septoria) pathogens such as Lesion mould (Septoria nodorum) and leaf blight (Septoria tritica), powdery mildew (powdery) pathogens such as Leuconostoc (Erysiphe spp) (including wheat mildew (Erysiphe graminis) and Asclepiaum (Erysiphe polygoni)), grape powdery mildew (Uncinula neccatur), cucumber powdery mildew (Sphaerotheca fuligena) and apple (Podosphaera leucotricha), wheat middlingia (Pseudocercosporella herpotrichoides), gray mold (Botrytis) pathogens such as Botrytis cinerea (Botrytis cinerea) and Sclerotinia (Monilinia fructicola), powdery mildew (such as Sclerotinia cinerea) and Sclerotinia (37), powdery mildew (37) pathogens (such as Sclerotinia Colletotrichum) and Sclerotina (35), and Sclerotinia (35) pathogens (such as Sclerotinia Colletotrichum) and Sclerotinia (35) and Sclerotina (35) and Sclerotinia (35), including rust diseases caused by rust (Puccinia spp.) (such as Puccinia recondita (Puccinia recondita), puccinia striolata (Puccinia striiformis), puccinia phyllanthus (Puccinia hordei), puccinia striolata (Puccinia graminis) and Puccinia pedunculata (Puccinia arachidis)), puccinia caffei (Hemileia vastatrix) and soybean rust (Phakopsora pachyrhizi); other pathogens include Rhizoctonia species (Rhizoctonia spp.) (e.g., rhizoctonia solani (Rhizoctonia solani)); fusarium (Fusarium) species diseases such as Fusarium roseum, fusarium graminearum (Fusarium graminearum), and Fusarium oxysporum (Fusarium oxysporum); verticillium dahliae (Verticillium dahliae); southern blight (Sclerotium rolfsii); the fungus (Rynchosporium secalis); black spot bacteria (Cercosporidium personatum), black spot bacteria (Cercospora arachidicola) and brown spot bacteria (Cercospora beticola); and other classes and species closely related to these pathogens. In addition to their fungicidal activity, the compositions or combinations also have resistant activity against bacteria such as Pyricularia pyrifolia (Erwinia amylovora), xanthomonas campestris (Xanthomonas campestris), pseudomonas syringae (Pseudomonas syringae), and other species.
The bactericide composition provided by the invention is simple in use method, is applied to crops and the sites where the crops grow before or after germination of plant diseases according to a conventional method, such as soil mixing, spraying, pouring and the like, and the application amount of the bactericide composition is generally 10-5000g per mu according to climatic conditions or crop states, and is diluted to 10-400mg/L (preferably 100-300 mg/L). The diluent is preferably water.
The bactericidal composition of the present invention has a bactericidal effect generally related to external factors such as climate, but the influence of climate can be alleviated by using a proper dosage form.
The composition of the present invention may be used in combination with other compounds having bactericidal, insecticidal or herbicidal properties, or may be used in combination with nematicides, acaricides, protectants, herbicide safeners, growth regulators, plant nutrients or soil conditioners, etc.
General synthetic procedure
In this specification, a structure is dominant if there is any difference between a chemical name and a chemical structure. In general, the compounds of the invention may be prepared by the methods described herein, wherein the substituents are as defined herein, unless otherwise indicated.
Those skilled in the art will recognize that: the chemical reactions described herein may be used to suitably prepare many other compounds of the present invention, and other methods for preparing the compounds of the present invention are considered to be within the scope of the present invention. For example, the synthesis of those non-exemplified compounds according to the invention can be successfully accomplished by modification methods by those skilled in the art, such as appropriate protection of interfering groups, by use of other known reagents (other than those described herein), or by making some conventional modifications to the reaction conditions. In addition, the reactions disclosed herein or known reaction conditions are also well-known to be applicable to the preparation of other compounds of the present invention. In addition, in some embodiments, unless otherwise specified, the reactions described herein are carried out at room temperature, where the room temperature is from 0 to 35 ℃.
The testing conditions of the nuclear magnetic resonance hydrogen spectrum of the invention are as follows: nuclear magnetic instrument of 400MHz or 600MHz of Bruker (Bruker) under room temperature condition, CDC1 3 ，d 6 -DMSO，CD 3 OD or d 6 Acetone as solvent (reported in ppm) with TMS (0 ppm) or chloroform (7.26 ppm) as reference standard. When multiple peaks occur, the following abbreviations will be used: s (single, singlet), d (doublet ), t (triplet, quartet), q (quartet), m (multiplet ), br (broadened, broad), dd (doublet of doublets, doublet), dt (doublet of triplets, doublet). Coupling constants are expressed in hertz (Hz).
The mass spectrum test conditions used in the invention are as follows: low resolution mass spectrometryThe conditions for (MS) data measurement are: agilent 6120 Quadragole HPLC-MS (column model: zorbax SB-C18, 2.1X30 mm,3.5 μm,6min, flow rate 0.6mL/min, mobile phase 5% -95% (CH containing 0.1% formic acid) 3 CN) in (H containing 0.1% formic acid) 2 Ratio in O)) was detected with UV at 210/254nm using electrospray ionization mode (ESI).
The following synthetic schemes describe the steps for preparing the disclosed compounds.
Synthetic scheme
Synthesis scheme one
Intermediate compound C can be prepared by a method of preparation of synthesis scheme one. The compound A and the compound a undergo substitution reaction under alkaline conditions (sodium hydride, sodium hydroxide, potassium carbonate and the like) to obtain a compound B; or the compound A and the compound B undergo substitution reaction under alkaline conditions (sodium hydride, sodium hydroxide, potassium carbonate and the like) to obtain a compound B; firstly, carrying out an amine aldehyde condensation reaction on the compound B and the compound C, and then reducing the compound B and the compound C by a reducing agent (lithium aluminum tetrahydroide, sodium borohydride and the like) to obtain an intermediate compound C;
wherein R is 3 Is C 3-6 Cycloalkyl; x is halogen; r is R x Is C 1-4 Alkyl, benzyl optionally substituted by halogen, cyclopropyl-CH 2 -or-S (=o) 2 R A ；
Wherein R is A Is C 1-4 Alkyl, optionally substituted with 1 or 2 groups selected from halogen, C 1-4 Alkyl or halo C 1-4 Alkyl-substituted phenyl or-N (CH) 3 ) 2 。
Synthesis scheme II
Intermediate compound D may be prepared by the preparation method of synthesis scheme two. Compound a and compound c undergo aldolizationAfter the combination reaction, reducing by a reducing agent (lithium aluminum hydride, sodium borohydride and the like) to obtain a compound D; wherein R is 3 Is C 3-6 Cycloalkyl groups.
Synthesis of a third embodiment
The target compound I-A or I-B can be prepared by a preparation method of a synthesis scheme III. The intermediate compound E and the intermediate compound C undergo substitution reaction under alkaline conditions (potassium carbonate, triethylamine, pyridine and the like) to obtain a target compound I-A; the intermediate compound E and the intermediate compound D undergo substitution reaction under alkaline conditions (potassium carbonate, triethylamine, pyridine and the like) to obtain a target compound I-B;
wherein R is 3 Is C 3-6 Cycloalkyl; r is R x Is C 1-4 Alkyl, benzyl optionally substituted by halogen, cyclopropyl-CH 2 -or-S (=o) 2 R A ；
Wherein R is A Is C 1-4 Alkyl, optionally substituted with 1 or 2 groups selected from halogen, C 1-4 Alkyl or halo C 1-4 Alkyl-substituted phenyl or-N (CH) 3 ) 2 。
Examples
Intermediate a: synthesis of 1- (N, N-dimethylaminosulfonyl) -1H-1,2, 4-triazole-3-sulfonyl chloride
The first step: synthesis of 1, 2-bis (1H-1, 2, 4-triazol-3-yl) disulfane
3-mercapto-1, 2, 4-triazole (101.0 g,1.00 mol) was dissolved in methylene chloride (500 mL), pyridine (79.0 g,1.00 mol) was added, stirred at 0℃and p-toluenesulfonyl chloride (95.33 g,0.50 mol) was slowly added dropwise, and stirred at 25℃for 18 hours after the completion of the dropwise addition. The dichloromethane was distilled off under reduced pressure using a rotary evaporator, and the residue was added with water (500 mL) under mechanical stirring, after stirring for 1h, filtered, and the residue was washed with water (800 mL) and ethyl acetate (300 mL), respectively, and air-dried to give 95.2g of yellow powder in 95.2% yield.
And a second step of: synthesis of 3- ((1- (N, N-dimethylaminosulfonyl) -1H-1,2, 4-triazol-3-yl) disulfide) -N, N-dimethyl-1H-1, 2, 4-triazole-1-sulfonamide
1, 2-bis (1H-1, 2, 4-triazol-3-yl) dithioalkane (60.0 g,0.30 mol) was dissolved in N, N-dimethylformamide (300 mL) under nitrogen protection, potassium carbonate (69.0 g,0.50 mol) was added, and after stirring and mixing at 0℃N, N-dimethylaminosulfonyl chloride (93.34 g,0.65 mol) was slowly added dropwise thereto, and the reaction was continued for 6 hours after the completion of the addition. After the reaction was completed, the reaction solution was slowly poured into water and stirred for 1h. Filtration and air drying of the solid gave 107.2g of white powder in 86.3% yield.
LC-MS:(M+1)m/z＝415.00.
And a third step of: synthesis of 1- (N, N-dimethylaminosulfonyl) -1H-1,2, 4-triazole-3-sulfonyl chloride
3- ((1- (N, N-dimethylaminosulfonyl) -1H-1,2, 4-triazol-3-yl) disulfide) -N, N-dimethyl-1H-1, 2, 4-triazole-1-sulfonamide (41.40 g,0.10 mol) was dissolved in 1, 2-dichloroethane (300 mL), water (300 mL) was added, cooled to 0 ℃, acetic acid (100 mL) was added, and the temperature was controlled at 10℃to 25℃for 2 hours with chlorine (35.50 g,0.50 mol) and the reaction was continued for half an hour. After the completion of the reaction, the solution was transferred to a separating funnel, left to stand for separation, and the organic phase was washed three times with water (30 mL), and the solvent was distilled off under reduced pressure using a rotary evaporator to give 48.11g of a white powder, yield 87.8%.
LC-MS:(M+1)m/z＝274.8.
Intermediate B: synthesis of N- ((1-benzyl-1H-indol-4-yl) methyl) cyclopropylamine
The first step: synthesis of 1-benzyl-1H-indole-4-carbaldehyde
Indole-4-carbaldehyde (0.803 g,2.50 mmol) was dissolved in N, N-dimethylformamide (15 mL), sodium hydride (0.138 g,6 mmol) was added at 0deg.C, and the mixture was stirred for 30min at 25deg.C, benzyl chloride (0.35 g,2.75 mmol) was added dropwise, and after 3h TLC was monitored for completion of the reaction. The reaction was quenched with 100mL of water, extracted with ethyl acetate (50 mL. Times.3), the organic phase was dried over anhydrous sodium sulfate, and the solvent was dried under reduced pressure using a rotary evaporator to give 0.56g of a reddish brown liquid in 95.56% yield.
LC-MS:(M+1)m/z＝236.10.
And a second step of: synthesis of N- ((1-benzyl-1H-indol-4-yl) methyl) cyclopropylamine
1-benzyl-1H-indole-4-carbaldehyde (0.56 g,2.38 mmol) was dissolved in methylene chloride (15 mL), anhydrous magnesium sulfate (0.9 g,7.5 mmol) was added and stirred, cyclopropylamine (0.43 g,7.5 mmol) was added dropwise, and the mixture was reacted at 25℃for 12H. The magnesium sulfate solid was removed by filtration, the dichloromethane was removed by rotary evaporator under reduced pressure, methanol (15 mL) was added, sodium borohydride (0.19 g,5 mmol) was added, stirring was carried out at 25℃for 3h, after the TLC monitoring reaction was completed, methanol was removed by rotary evaporator, water (100 mL) was added, extraction was carried out with ethyl acetate (50 mL. Times.3), the organic phase was dried over anhydrous sodium sulfate, and the solvent was removed by rotary evaporator under reduced pressure to give 0.65g of reddish brown liquid with a yield of 99.3%.
LC-MS:(M+1)m/z＝277.15.
The intermediate compound shown in the table 1 can be obtained by a similar preparation method of the intermediate B through a substitution reaction of indole-4-formaldehyde, indole-6-formaldehyde or indole-3-formaldehyde, benzyl halide, iodo-alkyl or sulfonyl chloride derivative serving as a starting material, and dehydration, condensation and reduction of cyclopropylamine, cyclopentylamine or cyclohexylamine.
TABLE 1
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Or through the second step of the preparation method of the intermediate B, indole-4-formaldehyde, indole-6-formaldehyde or indole-3-formaldehyde and cyclopropylamine, cyclopentylamine or cyclohexylamine are dehydrated, condensed and reduced to obtain the intermediate compound shown in the table 2.
TABLE 2
Example 1: n (N) 3 - ((1-benzyl-1H-indol-4-yl) methyl) -N 3 -cyclopropyl-N 1 ,N 1 Synthesis of-dimethyl-1H-1, 2, 4-triazole-1, 3-disulfonamide
Intermediate N- ((1-benzyl-1H-indol-4-yl) methyl) cyclopropylamine (0.55 g,2.0 mmol), pyridine (0.32 g,4.0 mmol) and tetrahydrofuran (15 mL) were added to a 100mL single-port flask, stirred well at 25 ℃, 1- (N, N-dimethylaminosulfonyl) -1H-1,2, 4-triazole-3-sulfonyl chloride (1.10 g,4.0 mmol) was slowly added to the reaction system, after reaction at 25 ℃ for 12H, 100mL water quench reaction was added, extracted with ethyl acetate (50 mL x 3), the organic phase was dried over anhydrous sodium sulfate, filtered, the filtrate was freed of solvent by rotary evaporator under reduced pressure, and column chromatography was purified [ ethyl acetate/petroleum ether (v/v) =1/3 ], yielding 0.32g of grey solid in 31.11% yield.
1 H NMR(400MHz,CDCl 3 )δ8.50(s,1H),7.56(d,J＝8.1Hz,1H),7.31(dd,J＝12.8,6.8Hz,4H),7.18–7.05(m,4H),6.54(d,J＝3.0Hz,1H),5.32(d,J＝20.2Hz,2H),4.65(s,2H),3.00(s,6H),2.46(ddd,J＝10.5,7.1,3.7Hz,1H),0.81–0.73(m,2H),0.68–0.56(m,2H).
LC-MS:(M+1)m/z＝515.10.
By a similar procedure as in example 1, the intermediate compounds of Table 1 or Table 2 were reacted with intermediate A (1- (N, N-dimethylaminosulfonyl) -1H-1,2, 4-triazole-3-sulfonyl chloride) to give the target compounds of Table 3, respectively.
TABLE 3 Table 3
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Test examples
Test treatment: the compound was dissolved in DMF to 1% ec for use. The bactericidal activity of these compounds against the test targets at different doses was evaluated using the living potting method.
Test example 1: cucumber downy mildew (pseudoperonosporacube)
Selection of1 pot cucumber seedling with consistent growth condition in true leaf period (picking out growing point), spraying, naturally airing, inoculating 24 hr after treatment, collecting fresh cucumber downy mildew disease leaf, dipping with brush pen, washing sporangium on the back of the disease leaf with distilled water, and preparing into sporangium suspension (2-3 x 10) 5 and/mL). Uniformly spraying and inoculating on cucumber seedlings by using an inoculating sprayer (with the pressure of 0.1 MPa), transferring the inoculated test material to a climatic chamber, keeping the relative humidity at about 100%, keeping the temperature at about 21 ℃ after 24 hours, keeping the relative humidity at about 21%, carrying out moisture preservation and induction, and carrying out grading investigation according to the disease condition of blank control after 5 days, wherein the control effect is calculated according to the disease index.
Test example 2: powdery mildew of cucumber (Sphaerotheca fuliginea)
Selecting a cucumber seedling with a true leaf period and consistent growth vigor, and drying in the shade for 24 hours after spray treatment. Washing fresh powdery mildew spores on cucumber leaves, filtering with double-layer gauze, preparing suspension with spore concentration of about 10 ten thousand/mL, and spraying for inoculation. The inoculated test material is moved into artificial climate, the relative humidity is kept between 60 and 70 percent, the temperature is kept between 21 and 23 ℃, and the grading investigation is carried out according to the disease condition of blank control for about 10 days, and the control effect is calculated according to the disease index.
The test results are shown in tables 4-5.
TABLE 4 control of cucumber downy mildew with the inventive compound at 200mg/L concentration
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TABLE 5 control of cucumber downy mildew at lower doses of the compounds of the invention
In addition, the compound of the invention, example 24 and example 25, has more than 80% of control effect on cucumber downy mildew at the concentration of 25 mg/L; and at a concentration of 200mg/L, the compounds of the invention, examples 24 and 25, the control effect on powdery mildew of cucumber is more than 80%.
The test results show that the compound has good control effect on plant pathogenic fungi, especially cucumber downy mildew, and has good development prospect.
The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the specific details of the above embodiments, and various simple modifications can be made to the technical solution of the present invention within the scope of the technical concept of the present invention, and all the simple modifications belong to the protection scope of the present invention.

Claims (6)

1. A compound which is a compound having the formula (I) or a salt of a compound represented by the formula (I):
wherein:
R 1 and R is 2 Each independently is-CH 3 ；
n is 2;
R 3 is C 3-6 Cycloalkyl;
R 4 the following sub-structural formula is shown as follows:
wherein R is 51 、R 52 And R is 53 Each independently is hydrogen, C 1-4 Alkyl, phenyl-C optionally substituted with 1 or more substituents selected from halogen 1-3 Alkyl-, C 3-6 cycloalkyl-C 1-3 alkyl-or-S (=o) 2 R A1 ；
R A1 Is C 1-4 Alkyl, optionally substituted with 1 or 2 groups selected from halogen、C 1-4 Alkyl or halo C 1-4 Phenyl or-NR substituted by substituents of alkyl groups B1 R C1 ；
R B1 And R is C1 Each independently is C 1-4 An alkyl group.
2. The compound according to claim 1, wherein,
R 51 、R 52 and R is 53 Each independently is hydrogen, -CH 3 、-CH 2 CH 3 、-CH 2 CH 2 CH 3 or-CH (CH) 3 ) 2 ；
Or R is 51 、R 52 And R is 53 Each independently is of the following sub-structural formula:
3. the compound according to claim 2, wherein,
R 4 the following sub-structural formula is shown as follows:
4. a compound according to any one of claims 1 to 3 which is a compound having the structure:
5. a composition comprising at least one compound of any one of claims 1-4.
6. Use of a compound according to any one of claims 1 to 4 or a composition according to claim 5 for controlling plant diseases in agriculture, wherein the plant diseases are cucumber downy mildew or cucumber powdery mildew.
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