Patent Application
20190037848
The invention relates to the technical field of the herbicides and/or plant growth regulators. Specifically, the invention primarily relates to novel isothiazolamides, and compositions comprising said novel isothiazolamides. Further, the present invention relates to processes for the preparation said novel isothiazolamides and their use as herbicides and/or plant growth regulators.
In their application, crop protection agents known to date for the selective control of harmful plants in crops of useful plants or active compounds for controlling unwanted vegetation sometimes have disadvantages, be it (a) that they have no or else insufficient herbicidal activity against particular harmful plants, (b) that the spectrum of harmful plants which can be controlled with an active compound is not wide enough, (c) that their selectivity in crops of useful plants is too low and/or (d) that they have a toxicologically unfavourable profile.
Furthermore, some active compounds which can be used as plant growth regulators for a number of useful plants cause unwanted reduced harvest yields in other useful plants or are not compatible with the crop plant, or only within a narrow application rate range. Some of the known active compounds cannot be produced economically on an industrial scale owing to precursors and reagents which are difficult to obtain, or they have only insufficient chemical stabilities.
The prior art discloses several isothiazoles and isothiazolamides.
Arch. Pharm. (Weinheim) 1987, 320, 43-50 reports on the condensation of 2-morpholino- or 2-piperidino-dithiooxalic O-esters with malondinitrile or cyanoacetate, and inter alia discloses 3-amino-5-(4-morpholinylthioxomethyl)-4-isothiazolecarbonitrile (IUPAC-name: 3-amino-5-(morpholin-4-ylcarbonothioyl)-1,2-thiazole-4-carbonitrile).
JP 2007-302617 discloses various heterocyclic compounds and their use as insecticides, inter alia several amino isothiazoles.
US 2011/0201687 A1 discloses various amide derivatives as pest control agents.
U.S. Pat. No. 3,563,985 relates to a process for preparing certain acylaminoisothiazoles and mentions the use of said isothiazole derivatives as herbicides.
U.S. Pat. No. 4,075,001 mentions the herbicidal activity of certain 1-alkyl- and 1,1-dialkyl-3-(4-substituted-3-amino-5-isothiazolyl)ureas and N-(4-substituted-3-amino-5-isothiazolyl)-alkanamides.
WO 2007/128410 relates to heteroaromatic compounds and their use as insecticides.
WO 2007/014290 discloses various fungicidal carboxamides.
EP 0761654 discloses certain isoxazole- and isothiazole-5-carboxamide derivatives and their use as herbicides.
In their application, herbicides known to date for controlling harmful plants or unwanted vegetation may have some disadvantages, be it (a) that they have no or else insufficient herbicidal activity against specific harmful plants, (b) that the spectrum of harmful plants which can be controlled with the herbicides is not broad enough, and/or (c) that the selectivity of herbicides in and the compatibility with crop plants is too low, thereby causing unwanted damage and/or unwanted reduced harvest yields of the crops.
Thus, there is still a need for alternative herbicides, in particular highly active herbicides, in particular useful at low application rates and/or having good compatibility with crop plants, for the selective application in plant crops or use on non-crop land. It is also desirable to provide alternative chemical active compounds which may be used in an advantageous manner as herbicides or plant growth regulators.
It is therefore an objective of the present invention to provide compounds having herbicidal activity which are highly effective against economically important harmful plants even at relatively low application rates and that can be used selectively in crop plants.
It has now been found that the compounds of the following formula (G) and/or the salts thereof meet said objective(s).
The present invention primarily relates to the use of one or more compounds of the formula (G) and/or salts thereof
in which
n is independently selected from 0, 1 or 2,
m is independently selected from 0 or 1,
p is independently selected from 0, 1, 2 or 3,
q is independently selected from 0, 1 or 2,
y is 0 or 1,
as herbicides and/or plant growth regulators, preferably in crops of useful plants and/or ornamental plants.
The compounds of the formula (G) used according to the invention include all stereoisomers which can occur on the basis of the centres of asymmetry or double bonds in the molecule whose configuration is not designated specifically in the formula or which are not specified explicitly, and mixtures thereof, including the racemic compounds and the mixtures enriched partly with particular stereoisomers. The invention also includes all tautomers, such as keto and enol tautomers, and their mixtures and salts, if appropriate functional groups are present.
In the case of suitable acidic sub stituents, the compounds of the formula (G) are able to form salts by reaction with bases where the acidic hydrogen is replaced by an agriculturally suitable cation.
By addition of a suitable inorganic or organic acid onto a basic group, such as, for example, amino or alkylamino, the compounds of the formula (G) are able to form salts. Suitable acidic groups present, such as, for example, carboxylic acid groups, are able to form inner salts with groups which for their part can be protonated, such as amino groups.
The compounds of the formula (G) may preferably be present in the form of agriculturally usable salts, where the type of salt is otherwise immaterial. In general, suitable salts are the salts of those cations or the acid additions salts of those acids whose cations and anions, respectively, have no adverse effect on the herbicidal activity of the compounds of formula (G).
Suitable cations are in particular the ions of the alkali metals, preferably lithium, sodium or potassium, of the alkaline earth metals, preferably calcium or magnesium, and of the transition metals, preferably manganese, copper, zinc or iron. The cation used may also be ammonium or substituted ammonium, where one to four hydrogen atoms may be replaced by (C1-C4)-alkyl, hydroxy-(C1-C4)-alkyl, (C1-C4)-alkoxy-(C1-C4)-alkyl, hydroxy-(C1-C4)-alkoxy-(C1-C4)-alkyl, phenyl or benzyl, preferably ammonium, dimethylammonium, diisopropylammonium, tetramethylammonium, tetrabutylammonium, 2-(2-hydroxyeth-1-oxy)eth-1-ylammonium, di(2-hydroxyeth-1-yl)ammonium, trimethylbenzylammonium.
Also suitable are phosphonium ions, sulphonium ions, preferably tri(C1-C4)methylsulphonium, or sulphoxonium ions, preferably tri(C1-C4)methylsulphoxonium.
Anions of useful acid addition salts are primarily chloride, bromide, fluoride, hydrogensulphate, sulphate, dihydrogenphosphate, hydrogenphosphate, nitrate, bicarbonate, carbonate, hexafluorosilicate, hexafluorophosphate, benzoate and also the anions of (C1-C4)-alkanoic acids, preferably formate, acetate, propionate, butyrate or trifluoroacetate.
The indexes n, m, p and q are used in the definitions of different structural elements which may be present in residues R1, R2, R3, R4, R5 and A, and are independently selected from the indexes n, m, p and q, respectively, which are optionally present in the respective other residues R1, R2, R3, R4, R5 and A. For example, q may be 1 in residue R1, q may be 0 in residue R2, and q may be 2 in residue R3.
In formula (G) and in all subsequent formulae, chemical radicals or substituents are referred to by names which are collective terms for the enumeration of individual group members or specifically refer to individual chemical radicals or substituents. In general, terms are used which are familiar to the person skilled in the art and/or in particular have the meanings illustrated below.
A hydrocarbon radical is an aliphatic, cycloaliphatic or aromatic monocyclic or, in the case of an optionally substituted hydrocarbon radical, also a bicyclic or polycyclic organic radical based on the elements carbon and hydrogen, including, for example, the radicals alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, phenyl, naphthyl, indanyl, indenyl, etc.; this applies correspondingly to hydrocarbon radicals in composite meanings, such as hydrocarbonoxy radicals or other hydrocarbon radicals attached via heteroatom groups.
Unless defined in more detail, the hydrocarbon radicals preferably have 1 to 20 carbon atoms, more preferably 1 to 16 carbon atoms, in particular 1 to 12 carbon atoms. The hydrocarbon radicals, also in the special radicals alkyl, alkoxy, haloalkyl, haloalkoxy, alkylamino and alkylthio, and also the corresponding unsaturated and/or substituted radicals may in each case be straight-chain or branched in the carbon skeleton.
The expression “(C1-C4)-alkyl” is a brief notation for alkyl having from 1 to 4 carbon atoms, i.e. encompasses the methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 2-methylpropyl or tert-butyl radicals. General alkyl radicals with a larger specified range of carbon atoms, e.g. “(C1-C6)-alkyl”, correspondingly also encompass straight-chain or branched alkyl radicals with a greater number of carbon atoms, i.e. according to the example also the alkyl radicals having 5 and 6 carbon atoms.
Unless stated specifically, preference is given to the lower carbon skeletons, for example having from 1 to 6 carbon atoms, or having from 2 to 6 carbon atoms in the case of unsaturated groups, in the case of the hydrocarbyl radicals such as alkyl, alkenyl and alkynyl radicals, including in composite radicals. Alkyl radicals, including in the combined definitions such as alkoxy, haloalkyl, etc., are, for example, methyl, ethyl, n- or i-propyl, n-, i-, t- or 2-butyl, pentyls, hexyls such as n-hexyl, i-hexyl and 1,3-dimethylbutyl, heptyls such as n-heptyl, 1-methylhexyl and 1,4-dimethylpentyl; alkenyl and alkynyl radicals are defined as the possible unsaturated radicals corresponding to the alkyl radicals; alkenyl is, for example, vinyl, allyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 2-butenyl, pentenyl, 2-methylpentenyl or hexenyl group, preferably allyl, 1-methylprop-2-en-1-yl, 2-methylprop-2-en-1-yl, but-2-en-1-yl, but-3-en-1-yl, 1-methylbut-3-en-1-yl or 1-methylbut-2-en-1-yl.
Alkenyl also includes in particular straight-chain or branched hydrocarbon radicals having more than one double bond, such as 1,3-butadienyl and 1,4-pentadienyl, but also allenyl or cumulenyl radicals having one or more cumulated double bonds, for example allenyl (1,2-propadienyl), 1,2-butadienyl and 1,2,3-pentatrienyl.
Alkynyl is, for example, propargyl, but-2-yn-1-yl, but-3-yn-1-yl, 1-methylbut-3-yn-1-yl.
Alkynyl also includes, in particular, straight-chain or branched hydrocarbon radicals having more than one triple bond or else having one or more triple bonds and one or more double bonds, for example 1,3-butatrienyl or 3-penten-1-yn-1-yl.
A 3- to 9-membered carbocyclic ring is (C3-C9)-cycloalkyl or (C5-C9)-cycloalkenyl.
(C3-C9)-Cycloalkyl is a carbocyclic saturated ring system having preferably 3-9 carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or cyclononyl. In the case of substituted cycloalkyl, cyclic systems with substituents are included, where the substituents may also be bonded by a double bond on the cycloalkyl radical, for example an alkylidene group such as methylidene.
(C5-C9)-Cycloalkenyl is a carbocyclic, nonaromatic, partially unsaturated ring system having 5-9 carbon atoms, for example 1-cyclobutenyl, 2-cyclobutenyl, 1-cyclopentenyl, 2-cyclopentenyl, 3-cyclopentenyl, or 1-cyclohexenyl, 2-cyclohexenyl, 3-cyclohexenyl, 1,3-cyclohexadienyl or 1,4-cyclohexadienyl. In the case of substituted cycloalkenyl, the explanations for substituted cycloalkyl apply correspondingly.
Alkylidene, for example also in the form of (C1-C10)-alkylidene, is the radical of a straight-chain or branched alkane which is bonded via a double bond, the position of the binding site not being fixed. In the case of a branched alkane, the only positions possible are, of course, those in which two hydrogen atoms can be replaced by the double bond; radicals are, for example, ═CH2, ═CH—CH3, ═C(CH3)—CH3, ═C(CH3)—C2H5 or ═C(C2H5)—C2H5.
Halogen is, for example, fluorine, chlorine, bromine or iodine. Haloalkyl, -alkenyl and -alkynyl are alkyl, alkenyl and alkynyl, respectively, which are partially or fully substituted by identical or different halogen atoms, preferably from the group consisting of fluorine, chlorine, bromine and iodine, in particular from the group consisting of fluorine, chlorine and bromine, very particularly from the group consisting of fluorine and chlorine, for example monohaloalkyl, perhaloalkyl, CF3, CHF2, CH2F, CF3CF2, CH2FCHCl, CCl3, CHCl2, CH2CH2C1; haloalkoxy is, for example, OCF3, OCHF2, OCH2F, CF3CF2O, OCH2CF3 and OCH2CH2Cl; this applies correspondingly to haloalkenyl and other halogen-substituted radicals such as, for example, halocycloalkyl.
Aryl is a mono-, bi- or polycyclic aromatic system, for example phenyl, naphthyl, tetrahydronaphthyl, indenyl, indanyl, pentalenyl, fluorenyl and the like, preferably phenyl.
Optionally substituted aryl also includes polycyclic systems, such as tetrahydronaphthyl, indenyl, indanyl, fluorenyl, biphenylyl, where the point of attachment is at the aromatic system.
A heterocyclic radical (heterocyclyl) comprises at least one heterocyclic ring (=carbocyclic ring in which at least one carbon atom is replaced by a heteroatom, preferably by a heteroatom from the group consisting of N, O, S, P, B, Si, Se), which is saturated, unsaturated or heteroaromatic and may be unsubstituted or substituted, where the point of attachment is located at a ring atom.
Unless defined otherwise it preferably contains one or more, in particular 1, 2 or 3, heteroatoms in the heterocyclic ring, preferably from the group consisting of N, O, and S; it is preferably an aliphatic heterocyclyl radical having 3 to 7 ring atoms or a heteroaromatic radical having 5 or 6 ring atoms. The heterocyclic radical may, for example, be a heteroaromatic radical or ring (heteroaryl), such as, for example, a monocyclic, bicyclic or polycyclic aromatic system in which at least 1 ring contains one or more heteroatoms.
If the heterocyclyl radical or the heterocyclic ring is optionally substituted, it can be fused to other carbocyclic or heterocyclic rings. Preference is given to benzo-fused heterocyclic or heteroaromatic rings.
Optionally substituted heterocyclyl also includes polycyclic systems, such as, for example, 8-aza-bicyclo[3.2.1]octanyl or 1-aza-bicyclo[2.2.1]heptyl.
Optionally substituted heterocyclyl also includes spirocyclic systems, such as, for example, 1-oxa-5-aza-spiro[2.3]hexyl.
It is preferably a radical of a heteroaromatic ring having a heteroatom from the group consisting of N, O and S, for example the radical of a five- or six-membered ring, such as pyridyl, pyrrolyl, thienyl or furyl; it is furthermore preferably a radical of a corresponding heteroaromatic ring having 2, 3 or 4 heteroatoms, for example pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, tetrazinyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl or triazolyl or tetrazolyl.
Here, preference is given to a radical of a heteroaromatic five- or six-membered ring having 1 to 4 heteroatoms, such as, for example, 1,2,3-triazolyl, 1,2,4-triazolyl, tetrazolyl, isothiazolyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, tetrazolyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1,2,3,4-tetrazinyl, 1,2,3,5-tetrazinyl, 1,2,4,5-tetrazinyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl.
More preference is given here to heteroaromatic radicals of five-membered heterocycles having 3 nitrogen atoms, such as 1,2,3-triazol-1-yl, 1,2,3-triazol-4-yl, 1,2,3-triazol-5-yl, 1,2,5-triazol-1-yl, 1,2,5-triazol-3-yl, 1,3,4-triazol-1-yl, 1,3,4-triazol-2-yl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl;
more preference is also given here to heteroaromatic radicals of six-membered heterocycles having 3 nitrogen atoms, such as 1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl, 1,2,4-triazin-6-yl, 1,2,3-triazin-4-yl, 1,2,3-triazin-5-yl;
more preference is also given here to heteroaromatic radicals of five-membered heterocycles having two nitrogen atoms and one oxygen atom, such as 1,2,4-oxadiazol-3-yl; 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,2,3-oxadiazol-4-yl, 1,2,3-oxadiazol-5-yl, 1,2,5-oxadiazol-3-yl,
more preference is also given here to heteroaromatic radicals of five-membered heterocycles having two nitrogen atoms and one sulphur atom, such as 1,2,4-thiadiazol-3-yl, 1,2,4-thiadiazol-5-yl, 1,3,4-thiadiazol-2-yl, 1,2,3-thiadiazol-4-yl, 1,2,3-thiadiazol-5-yl, 1,2,5-thiadiazol-3-yl;
more preference is also given here to heteroaromatic radicals of five-membered heterocycles having four nitrogen atoms, such as 1,2,3,4-tetrazol-1-yl, 1,2,3,4-tetrazol-5-yl, 1,2,3,5-tetrazol-1-yl, 1,2,3,5-tetrazol-4-yl, 2H-1,2,3,4-tetrazol-5-yl, 1H-1,2,3,4-tetrazol-5-yl,
more preference is also given here to heteroaromatic radicals of six-membered heterocycles such as 1,2,4,5-tetrazin-3-yl;
more preference is also given here to heteroaromatic radicals of five-membered heterocycles having three nitrogen atoms and one oxygen or sulphur atom, such as 1,2,3,4-oxatriazol-5-yl; 1,2,3,5-oxatriazol-4-yl; 1,2,3,4-thiatriazol-5-yl; 1,2,3,5-thiatriazol-4-yl;
more preference is also given here to heteroaromatic radicals of six-membered heterocycles such as, for example, 1,2,4,6-thiatriazin-1-yl; 1,2,4,6-thiatriazin-3-yl; 1,2,4,6-thiatriazin-5-yl.
Furthermore preferably, the heterocyclic radical or ring is a partially or fully hydrogenated heterocyclic radical having one heteroatom from the group consisting of N, O and S, for example oxiranyl, oxetanyl, oxolanyl (=tetrahydrofuryl), oxanyl, pyrrolinyl, pyrrolidyl or piperidyl.
It is also preferably a partially or fully hydrogenated heterocyclic radical having 2 heteroatoms from the group consisting of N, O and S, for example piperazinyl, dioxolanyl, oxazolinyl, isoxazolinyl, oxazolidinyl, isoxazolidinyl and morpholinyl. Suitable substituents for a substituted heterocyclic radical are the substituents specified later on below, and additionally also oxo. The oxo group may also occur on the hetero-ring atoms which are able to exist in different oxidation states, as in the case of N and S, for example.
Preferred examples of heterocyclyl are a heterocyclic radical having from 3 to 6 ring atoms from the group consisting of pyridyl, thienyl, furyl, pyrrolyl, oxiranyl, 2-oxetanyl, 3-oxetanyl, oxolanyl (=tetrahydrofuryl), pyrrolidyl, piperidyl, especially oxiranyl, 2-oxetanyl, 3-oxetanyl or oxolanyl, or is a heterocyclic radical having two or three heteroatoms, for example pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, thiazolyl, thiadiazolyl, oxazolyl, isoxazolyl, pyrazolyl, triazolyl, piperazinyl, dioxolanyl, oxazolinyl, isoxazolinyl, oxazolidinyl, isoxazolidinyl or morpholinyl.
Preferred heterocyclic radicals are also benzo-fused heteroaromatic rings, for example benzofuryl, benzisofuryl, benzothiophenyl, benzisothiophenyl, isobenzothiophenyl, indolyl, isoindolyl, indazolyl, benzimidazolyl, benzotriazolyl, benzoxazolyl, 1,2-benzisoxazolyl, 2,1-benzisoxazolyl, benzothiazolyl, 1,2-benzisothiazolyl, 2,1-benzisothiazolyl, 1,2,3-benzoxadiazolyl, 2,1,3-benzoxadiazolyl, 1,2,3-benzothiadiazolyl, 2,1,3-benzothiadiazolyl, quinolyl (quinolinyl), isoquinolyl (isoquinolinyl), quinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, naphthyridinyl, benzotriazinyl, purinyl, pteridinyl, indolizinyl, benzo-1,3-dioxylyl, 4H-benzo-1,3-dioxinyl and 4H-benzo-1,4-dioxinyl, and, where possible, N-oxides and salts thereof.
When a base structure is substituted by one or more radicals from a list of radicals (=group) or a generically defined group of radicals, this in each case includes simultaneous substitution by a plurality of identical and/or structurally different radicals.
Substituted radicals, such as a substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, phenyl, benzyl, heterocyclyl and heteroaryl radical, are, for example, a substituted radical derived from the unsubstituted base structure, where the substituents are, for example, one or more, preferably 1, 2 or 3, radicals from the group consisting of halogen, alkoxy, alkylthio, hydroxyl, amino, nitro, carboxyl, cyano, azido, alkoxycarbonyl, alkylcarbonyl, formyl, carbamoyl, mono- and dialkylaminocarbonyl, substituted amino such as acylamino, mono- and dialkylamino, and alkylsulphinyl, alkylsulphonyl and, in the case of cyclic radicals, also alkyl, haloalkyl, alkylthioalkyl, alkoxyalkyl, optionally substituted mono- and dialkylaminoalkyl and hydroxyalkyl; in the term “substituted radicals”, such as substituted alkyl, etc., substituents include, in addition to the saturated hydrocarbon radicals mentioned, corresponding unsaturated aliphatic and aromatic radicals, such as optionally substituted alkenyl, alkynyl, alkenyloxy, alkynyloxy, phenyl and phenoxy. In the case of substituted cyclic radicals having aliphatic moieties in the ring, cyclic systems with those substituents which are bonded on the ring by a double bond are also included, for example substituted by an alkylidene group such as methylidene or ethylidene.
Unless defined in more detail, optionally substituted phenyl is preferably phenyl or phenyl which is unsubstituted or substituted by one or more radicals from the group consisting of halogen, cyano, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy-(C1-C4)alkyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy, (C1-C4)-alkoxy-(C1-C4)-alkoxy, (C1-C4)-alkylthio and nitro, in particular phenyl which is optionally substituted by one or more radicals from the group consisting of halogen, (C1-C4)-alkyl, (C1-C4)-haloalkyl and (C1-C4)-alkoxy.
In the case of radicals having carbon atoms, preference is given to those having 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms. Preference is generally given to substituents from the group consisting of halogen, e.g. fluorine and chlorine, (C1-C4)-alkyl, preferably methyl or ethyl, (C1-C4)-haloalkyl, preferably trifluoromethyl, (C1-C4)-alkoxy, preferably methoxy or ethoxy, (C1-C4)-haloalkoxy, nitro and cyano. Particular preference is given here to the substituents methyl, methoxy, fluorine and chlorine.
Substituted amino, such as mono- or disubstituted amino, is a radical from the group consisting of the substituted amino radicals which are N-substituted, for example, by one or two identical or different radicals from the group consisting of alkyl, alkoxy, acyl and aryl; preferably mono- and dialkylamino, mono- and diarylamino, acylamino, N-alkyl-N-arylamino, N-alkyl-N-acylamino and N-heterocycles; preference is given to alkyl radicals having from 1 to 4 carbon atoms; aryl is preferably phenyl or substituted phenyl; acyl is as defined below, preferably (C1-C4)-alkanoyl. The same applies to substituted hydroxylamino or hydrazino.
Acyl is a radical of an organic acid which arises in a formal sense by removal of a hydroxyl group on the acid function, and the organic radical in the acid may also be bonded to the acid function via a heteroatom. Examples of acyl are the —CO—R radical of a carboxylic acid HO—CO—R and radicals of acids derived therefrom, such as those of thiocarboxylic acid, optionally N-substituted iminocarboxylic acids or the radical of carbonic monoesters, N-substituted carbamic acid, sulphonic acids, sulphinic acids, N-substituted sulphonamide acids, phosphonic acids or phosphinic acids.
Acyl is, for example, formyl, alkylcarbonyl such as [(C1-C4)-alkyl]carbonyl, phenylcarbonyl, alkyloxycarbonyl, phenyloxycarbonyl, benzyloxycarbonyl, alkylsulphonyl, alkylsulphinyl, N-alkyl-1-iminoalkyl and other radicals of organic acids. The radicals may each be substituted further in the alkyl or phenyl moiety, for example in the alkyl moiety by one or more radicals from the group consisting of halogen, alkoxy, phenyl and phenoxy; examples of substituents in the phenyl moiety are the substituents already mentioned above in general for substituted phenyl.
Acyl is preferably an acyl radical in the narrower sense, i.e. a radical of an organic acid in which the acid group is bonded directly to the carbon atom of an organic radical, for example formyl, alkylcarbonyl such as acetyl or [(C1-C4)-alkyl]carbonyl, phenylcarbonyl, alkylsulphonyl, alkylsulphinyl and other radicals of organic acids.
More preferably, acyl is an alkanoyl radical having 1 to 6 carbon atoms, in particular 1 to 4 carbon atoms. Here, (C1-C4)-alkanoyl is the radical of an alkanoic acid having 1 to 4 carbon atoms formed after removal of the OH group of the acid group, i.e. formyl, acetyl, n-propionyl, isopropionyl or n-, i-, sec- or tert-butanoyl.
The “yl position” of a radical denotes the carbon atom having the free bond.
Compounds of the formula (G) according to the invention and compounds of the formula (G) used according to the invention and/or salts thereof are in short also referred to as “compounds (G)”.
The invention also provides all stereoisomers which are encompassed by formula (G) and mixtures thereof. Such compounds of the formula (G) may contain one or more asymmetric carbon atoms or may contain double bonds which are not stated separately in the general formulae (G). The possible stereoisomers defined by their specific three-dimensional shape, such as enantiomers, diastereomers, Z- and E-isomers, are all encompassed by the formula (G) and can be obtained from mixtures of the stereoisomers by customary methods or else prepared by stereoselective reactions in combination with the use of stereochemically pure starting materials.
The present invention also relates to a compound of the formula (G) and/or a salt thereof,
in which
n is independently selected from 0, 1 or 2,
m is independently selected from 0 or 1,
P is independently selected from 0, 1, 2 or 3,
q is independently selected from 0, 1 or 2,
Y is 0 or 1,
with the proviso that:
the compound of formula (G) is not 3-amino-5-(morpholin-4-ylcarbonothioyl)-1,2-thiazole-4-carbonitrile (i.e. not the compound of formula (G), wherein R2—N-(A)y-R4 together form a morpholin-4-yl ring, W is S, R3 is CN, R4 is H and R5 is H),
and
y is 1, if R1 is a substituted 4-heptafluoroisopropylphenyl residue, a substituted 4-(nonafluoro-2-butyl)phenyl residue, a substituted 4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl residue, a 2-bromo-4-methyl-6-(heptafluoroisopropyl)pyridin-3-yl residue or a 2-bromo-4-methyl-6-(2,2,2-trifluoro-1-trifluoromethylethoxy)pyridin-3-yl residue.
Preferred compounds according to the present invention correspond to the formula (G), wherein
R3 is not hydrogen,
and wherein the other structural elements in the formula (G) each have, independently from one another, the meaning as defined above in the context of the formula (G), preferably each have, independently from one another, the meaning as defined above in one of the preferred, more preferred, or particularly preferred embodiments.
According to the present invention, compounds of the formula (G) and/or a salt thereof are preferred, in which
n is independently selected from 0, 1 or 2,
m is independently selected from 0 or 1,
P is independently selected from 0, 1 or 2,
q is independently selected from 0, 1 or 2,
Y is 0 or 1,
with the proviso that:
y is 1, if R1 is a substituted 4-heptafluoroisopropylphenyl residue, a substituted 4-(nonafluoro-2-butyl)phenyl residue, a substituted 4-(1,1,2,3,3,3-hexafluoropropoxy)phenyl residue, a 2-bromo-4-methyl-6-(heptafluoroisopropyl)pyridin-3-yl residue or a 2-bromo-4-methyl-6-(2,2,2-trifluoro-1-trifluoromethylethoxy)pyridin-3-yl residue.
Preferred compounds according to the present invention correspond to the formula (G) as defined hereinabove, wherein
y is 0,
and wherein A, W, R2, R3, R4, R5, n, m, p and q each have the meaning defined hereinabove.
Preferred compounds according to the present invention correspond to the formula (G), wherein
y is 1, if R1 is a substituted phenyl residue or a substituted pyridin-3-yl residue,
and wherein the other structural elements in the formula (G) each have, independently from one another, the meaning as defined above in the context of the formula (G), preferably each have, independently from one another, the meaning as defined above in one of the preferred, more preferred, or particularly preferred embodiments.
According to the present invention, compounds of the formula (G) and/or a salt thereof are preferred, in which
n is independently selected from 0, 1 or 2,
m is independently selected from 0 or 1,
p is independently selected from 0, 1 or 2,
q is independently selected from 0 or 1,
y is 0 or 1,
with the proviso that:
y is 1, if R1 is a substituted phenyl residue or a substituted pyridin-3-yl residue.
According to the present invention, compounds of the formula (G) and/or a salt thereof are more preferred, in which
n is independently selected from 0, 1 or 2,
m is independently selected from 0 or 1,
p is independently selected from 0, 1 or 2,
q is independently selected from 0 or 1,
y is 0 or 1,
with the proviso that:
y is 1, if R1 is a substituted phenyl residue or a substituted pyridin-3-yl residue.
According to the present invention, compounds of the formula (G) and/or a salt thereof are even more preferred, in which
R3 is halogen, trifluoromethyl or ethynyl.
According to the present invention, compounds of the formula (G) and/or a salt thereof are even more preferred, in which
R3 is F, Cl, Br, I, trifluoromethyl or ethynyl.
If R3 is Cl, in preferred compounds according to the present invention corresponding to the formula (G), then R1 is not a substituted 4-heptafluoroisopropylphenyl residue.
Particularly preferred compounds according to the present invention correspond to the formula (G), wherein y=1.
Particularly preferred compounds according to the present invention correspond to the formula (G), wherein y=1, and wherein W, R1, R2, R3, R4, R5 and A each have, independently from one another, the meaning as defined above in the context of the formula (G), preferably each have, independently from one another, the meaning as defined above in one of the preferred, more preferred, or particularly preferred embodiments.
Particularly preferred compounds according to the present invention correspond to the formula (G), wherein y=1, A is CHR1 (i.e. R6═H), wherein R2 is hydrogen or methyl, and wherein W, R1, R2, R3, R4, and R5 each have, independently from one another, the meaning as defined above in the context of the formula (G), preferably each have, independently from one another, the meaning as defined above in one of the preferred, more preferred, or particularly preferred embodiments.
In a preferred embodiment, the compounds according to the present invention correspond to the formula (G), wherein
and wherein the other structural elements in the formula (G) each have, independently from one another, the meaning as defined above in the context of the formula (G), preferably each have, independently from one another, the meaning as defined above in one of the preferred, more preferred, or particularly preferred embodiments.
Preferred compounds according to the present invention correspond to the formula (G), wherein
R2 is not methyl,
and wherein the other structural elements in the formula (G) each have, independently from one another, the meaning as defined above in the context of the formula (G), preferably each have, independently from one another, the meaning as defined above in one of the preferred, more preferred, or particularly preferred embodiments.
According to the present invention, compounds of the formula (G) and/or a salt thereof are even more preferred, wherein
R2 is H (hydrogen).
More preferred compounds according to the present invention correspond to formula the (G), wherein R2═H, and wherein W, R1, R3, R4, R5, A and y each have, independently from one another, the meaning as defined above in the context of formula the (G), preferably each have, independently from one another, the meaning as defined above in one of the preferred, more preferred, or particularly preferred embodiments.
In all of the above embodiments, preferred compounds according to the present invention correspond to the formula (G), wherein
In all of the above embodiments, more preferred compounds according to the present invention correspond to the formula (G), wherein
The following compounds of the formulae (I), (II), (III), (IV) and (V) are preferred compounds of the formula (G) according to the present invention.
Preferred compounds according to the present invention correspond to the formula (G), wherein W═O, R2═H, R4═H, R5═H, y=1, and A=CH2.
These preferred compounds of the formula (G) are compounds of the formula (I):
wherein R1 and R3 each have, independently from one another, the meaning as defined above in the context of the formula (G), preferably each have, independently from one another, the meaning as defined above in one of the preferred, more preferred, or particularly preferred embodiments.
Preferred compounds according to the present invention correspond to the formula (G), wherein W═O, R2═H, y=1, and A=CH2.
These preferred compounds of formula (G) are compounds of the formula (II):
wherein R1, R3, R4 and R5 each have, independently from one another, the meaning as defined above in the context of the formula (G), preferably each have, independently from one another, the meaning as defined above in one of the preferred, more preferred, or particularly preferred embodiments.
Preferred compounds according to the present invention correspond to the formula (G), wherein R2═H, i.e. compounds of the formula (III):
wherein R1, R3, R4, R5, A and y each have, independently from one another, the meaning as defined above in the context of the formula (G), preferably each have, independently from one another, the meaning as defined above in one of the preferred, more preferred, or particularly preferred embodiments.
Preferred compounds according to the present invention correspond to the formula (G), wherein W═S, R2═H, ═Cl, y=1, and A=CH2.
These preferred compounds of formula (G) are compounds of the formula (IV):
wherein R1, R4 and R5 each have, independently from one another, the meaning as defined above in the context of the formula (G), preferably each have, independently from one another, the meaning as defined above in one of the preferred, more preferred, or particularly preferred embodiments.
Preferred compounds according to the present invention correspond to the formula (G), wherein W═O, R3═Cl, R4═H, R5═H, y=1, and A=CH2, i.e. compounds of the formula (V):
wherein R1 and R5 each have, independently from one another, the meaning as defined above in the context of the formula (G), preferably each have, independently from one another, the meaning as defined above in one of the preferred, more preferred, or particularly preferred embodiments.
In the following Tables 1 to 5 specific and preferred definitions of R1, R2, R3, R4, R5 and A, respectively, are mentioned.
The abbreviations and numerations of the substituent positions used in the context of the present invention and in Tables 1 to 5 are explained in detail in the section Examples hereinafter.
R1 in the context of the formula (G) particularly preferably is selected from the group consisting of the moieties mentioned in Table 1, Table 2, Table 3, Table 4 and Table 5 for R1.
R2 in the context of the formula (G) particularly preferably is selected from the group consisting of H and the moieties mentioned in Table 5 for R2.
R3 in the context of the formula (G) particularly preferably is selected from the group consisting of H and the moieties mentioned in Table 1, Table 2 and Table 3 for R3.
R4 and R5 the context of the formula (G) particularly preferably are selected from the group consisting the moieties mentioned in Table 2, Table 3 and Table 4 for NR4R5.
A in the context of the formula (G) particularly preferably is selected from the group consisting of CH2 and the moieties mentioned in Table 3 for A.
Specific preferred compounds of the formula (I) are shown in Table 1.
Specific preferred compounds of the formula (II) are shown in Table 2.
Specific preferred compounds of formula (III) are shown in Table 3.
Specific preferred compounds of the formula (IV) are shown in Table 4.
Specific preferred compounds of formula (V) are shown in Table 5.
Preferably, the one or more compounds of the formulae (G), (I), (II), (III), (IV), (V), each as defined above, and the salts thereof, are used in the context of the present invention as herbicides and/or plant growth regulators, preferably in crops of useful plants and/or ornamental plants, wherein the structural elements in the formulae (G), (I), (II), (III), (IV), (V), each have, independently from one another, the meaning as defined above in the context of the meaning as defined above in one of the preferred, more preferred, or particularly preferred embodiments.
The present invention also provides processes for preparing the compounds of the general formula (G) and/or their salts. This includes processes which can be carried out analogously to known methods.
Compounds according to the invention of structure type (E-V) may, for example, can originate from compounds of type (E-IV), which bear an amino group in the 3-position of the isothiazole ring. For this purpose, alkylation, acylation or sulphonylation reactions may, inter alia, be used, in which (E-IV) in a solvent is reacted, for example, with a suitable alkyl halide, alkyl sulphonate, acyl halide, acid anhydride or sulphonyl halide. Compounds of type (E-V) are, in individual cases, also directly accessible from intermediates of type (E-II), by reacting (E-II) directly with a suitable amine of the general structure R4—NH—R5, wherein, if appropriate, a transition metal catalyst or precatalyst, possibly in combination with a suitable ligand and a base, for example K3PO4, Cs2CO3 or other bases, is required. Such reactions are usually conducted in a solvent commonly used in organic chemistry, for example dimethylformamide, toluene or other solvents, and at elevated temperature, for example between 50° C. and 200° C.
Compounds of structure type (E-IV) can be prepared either directly from the compounds (E-II) or via structure type (E-III). In the first case, (E-II) is reacted with ammonia in a solvent at elevated temperatures, wherein a suitable catalyst system may be used. In the second case, a suitable ammonia surrogate, which includes a protecting group which can be cleaved, is used in place of ammonia. Such a surrogate may be, for example, benzophenone imine or 4-methoxybenzylamine or other surrogates. The reaction must generally also be conducted with the aid of a catalyst composed of a transition metal complex and optionally one or more additional ligands. Suitable transition metal complexes are, for example, Pd(PPh3)4, Pd2dba3, PdCl2(PPh3)2, etc., and suitable ligands are, for example, XantPhos [4,5-bis(diphenylphosphino)-9,9-dimethylxanthene], Mor-DalPhos [di(1-adamantyl)-2-morpholinophenylphosphine], BrettPhos [2-(dicyclohexylphosphino)3,6-dimethoxy-2′,4′,6′-triisopropyl-1,1′-biphenyl], etc. . . . . These catalyst systems, besides a multitude of other systems and the reaction conditions required for the reactions, are described in detail in the literature, for example, in D. Surry, S. Buchwald Chem. Sci., 2011, 2, 27.
The conditions for the conversion of structure type (E-III) to structure type (E-IV) depend on the nature of the protecting group PG to be cleaved. Generally used in this connection and preferred in this context, however, are acids such as dilute mineral acids or organic acids (HCl in MeOH, trifluoroacetic acid (TFA), if PG is, for example, diphenylmethylene; 4-methoxybenzyl; benzyl, etc.) or oxidative reagents (such as dichlorodicyanoquinone, if the protecting group PG is, for example, 4-methoxybenzyl, etc.).
The synthesis of (E-II) is effected via amide bond formation between the commercially available acid (E-I) and a suitable amine (E-XXXII). In this context, a very large number of possible reaction procedures are described in the literature, for example, in V. Pattabiraman, J. Bode, Nature Vol.: 480 (2011) Issue: 7378, pp. 471-479 and literature cited therein. A very large number of the amines (E-XXXII) are commercially available.
The resulting amide compounds of type (E-V), for example, can be converted in a further step into the corresponding thioamides (E-VI) as shown in Scheme 2, by reaction with a sulphur-transferring reagent (thionation agent) such as, for example, P4S10 or Lawesson's reagent [2,4-Bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphetane-2,4-disulfide]. For this purpose, (E-V) is stirred with equimolar amounts or an excess of Lawesson's reagent in an inert solvent such as, for example, toluene or xylene at temperatures between 80° C. and 200° C. In an analogous manner, the resulting compounds of structure types (E-III), (E-IV), (E-XX), (E-XXIII), (E-XXVIII) can be converted to the corresponding thioamides.
Scheme 1 describes synthetic routes to the target compounds according to the invention, in which amide formation initially takes place and then an amino substituent is introduced into the 3-position of the isothiazole ring. The sequence of these transformations may also be changed, which results in the synthetic route shown in Scheme 3.
Compound (E-Ia) can be obtained by esterification using a conventional method from the corresponding carboxylic acid (for example compound (E-I)), wherein R1 may be (C1-C6)-alkyl, (C1-C6)-haloalkyl, (C3-C8)-cycloalkyl, (C3-C8)-cycloalkyl-(C1-C4)-alkyl or optionally substituted phenyl. The structure (E-VII) is then reacted with a suitable ammonium surrogate, comprising a cleavable protecting group PG, in an analogous manner to the reaction of (E-II) to give (E-III) described in Scheme 1. The following step is the cleavage of the ester group, which may be conveniently carried out under basic conditions, for example, by using an inorganic base such as NaOH or KOH in solvents such as MeOH, tetrahydrofuran (THF), water or other solvents, or mixtures of these solvents. The resulting acid of structure type (E-VIII) is reacted with a suitable amine (E-XXXII) to give the amide (E-IIIa), wherein again one of the many amide forming reactions described in the literature can be used.
The compounds (E-III), (E-IV) or (E-V) may in turn be used as starting points for derivatizations leading to further compounds according to the invention. For instance, the chlorine atom can be removed under reductive conditions for example, in order to afford compounds bearing a hydrogen atom in the 4-position of the isothiazole ring. This reaction may be achieved using a heterogeneous catalyst such as, for example, Pd on activated carbon in a hydrogen atmosphere at pressures between 1 bar and 50 bar in solvents such as ethyl acetate, ethanol, THF, etc.
An alternative strategy to the synthetic routes shown in Schemes 1 and 3, which is particularly suitable for the synthesis of a multitude of compounds according to the invention having different R3 substituents, is shown in Scheme 4. Compounds with R3=iodo allow an easy access to various 4-substituted isothiazole derivatives of formula (G).
The main intermediates for a broad range of derivatizations of the 4-position of the isothiazole ring (R3) may be, for example, structures of type (E-XX) or (E-XXIII), which may be obtained from the corresponding acids (E-XIX) and (E-XXII) by the common amidation reactions with suitable amines (E-XXXII), as described above. The acids in turn are available from the corresponding esters (E-XVIII) and (E-XXI) by basic ester cleavage, for example, with the aid of inorganic bases such as NaOH or LiOH or other bases in aqueous solvents or solvent mixtures.
The intermediate (E-XVIII) can be obtained, for example, from the acid (E-XVII) by Hoffman degradation, Curtius or Schmidt rearrangement or by a related reaction, wherein the tertiary butyl carbamate, which is readily isolatable, is directly obtained using a suitable reaction procedure (t-BuOH as solvent or solvent constituent). This tertiary butyl carbamate (E-XVIII) may be cleaved to the free amine (E-XXI) by treatment with acid, such as, for example, trifluoroacetic acid or dilute mineral acid.
The required acid (E-XVII) may be obtained, for example, from the tertiary butyl ester (E-XVI) by the action of acid, such as, for example, trifluoroacetic acid or dilute mineral acid. The latter may be obtained from the amino compound (E-XV) by the Sandmeyer reaction or related reactions. For instance, (E-XV) may be reacted, for example, with an alkyl nitrite, such as isoamyl nitrite, and iodine in an inert solvent, such as acetonitrile, at temperatures between 20° C. and 150° C.
The amino compound (E-XV) may be synthesized from the compound (E-XIV) by cyclization, by firstly treating the latter with a weak base, for example triethylamine or other organic bases, and directly after with ethanolic HCl.
The starting compound (E-XIV) required for the cyclization can be readily prepared in three steps from the cyanoacetic ester (E-X). For this purpose, (E-X) is initially reacted with NaNO2 in aqueous acetic acid, which forms the oxime (E-XI), which may be converted in a second step to the para-tolylsulphonate. For this purpose, (E-XI) is stirred with a suitable sulphonylating reagent, for example para-tolylsulphonyl chloride, and an organic base, for example pyridine. The resulting tosylate (E-XII) is reacted in the third step with the thioglycolate (E-XIII), forming a N—S bond, to give the cyclization precursor (E-XIV). This reaction generally takes place in a commonly used organic solvent such as ethanol, with the aid of an organic base such as pyridine.
The compounds (E-XVIII), (E-XX), and (E-XXIII) described in Scheme 4 may also be starting materials for further compounds according to the present invention, in particular having diverse R3 substituents. Reactions that may be used for this purpose, among others, are shown in Schemes 5, 6 and 7.
As shown in Scheme 5, starting from compound (E-XVIII), in a first step 5-(i) the iodine atom is removed, which may be accomplished by the action of zinc dust in acidic medium, for example by means of acetic acid as solvent. Subsequently, in step 5-(ii), a second BOC (tert.-butyloxycarbonyl) group is introduced on the nitrogen bound to the 3-position of the isothiazole, which yields compound (E-XXIV). This compound can be deprotonated in the 4-position of the isothiazole ring in step 5-(iii) using a suitable organometallic base such as TMPZnCl.LiCl (Knochel et al. Angew. Chem. Int. Ed. 2011, 50, 9794-9824), such that a heterocyclic organometallic compound is formed, which may then be reacted in a cross-coupling reaction in step 5-(iv) to afford the compound (E-XXV), wherein in R3 is not hydrogen. If the cross-coupling reaction is carried out with R3-Hal, then Hal can be chlorine, bromine or iodine.
The cross-coupling reaction in step 5-(iv) is generally carried out with the aid of a transition metal catalyst or transition metal precatalyst (Pd2dba3, PdCl2(PPh3)2, etc.) and a suitable complex-forming ligand (PPh3, P(o-furyl)3, etc.) in a suitable solvent (THF, toluene, etc.), generally at temperatures in the range of 25° C. and 120° C.
The further steps to the target compounds are firstly cleavage of the BOC groups under acidic conditions (e.g. trifluoroacetic acid) to give (E-XXVI), secondly cleavage of the methyl ester (E-XXVII) under basic conditions (e.g. NaOH in a mixture of methanol and water), and thirdly amide bond formation with amines (E-XXXII) to give the compounds (E-XXVIII).
Scheme 6 shows how 4-iodothiazoles, such as (E-XXIX), can be converted into compounds (E-XXV), wherein R3 is not iodine. 4-Iodothiazoles can be converted directly to a metallized isothiazoles via a metal-halogen exchange. For this purpose, in step 6-(i) the double tertiary butyl carbamate protected compound (E-XXIX) is metallized in the 4-position, e.g. reacted with a suitable organometallic compound, a Grignard compound for example, in an inert solvent, generally at temperatures below −50° C. The isothiazole compound metallized in the 4-position thus obtained, in addition to the cross-coupling reaction described above, can also be directly subjected to reaction with a sufficiently reactive electrophilic agent in step 6-(ii). In such a case, no catalyst is required. The electrophilic reaction partners used may be, for example, alkyl halides such as methyl iodide, isopropyl iodide, or alkenyl halides such as allyl bromide, or alkynyl halides such as propargyl bromide or any substituted arylalkyl halide such as benzyl bromide or amides such as, for example, dimethylformamide or other carbonyl compounds such as acetone, propionaldehyde or ethyl formate, etc. or also disulphide compounds such as, for example, dimethyl disulphide. A product of structural formula (E-XXV) is obtained in all cases as a result of the reactions.
However, 4-iodoisothiazoles may also participate directly in transition metal-catalyzed cross-coupling reactions, without intermediate generation of isothiazolyl metal species, whereby a multiplicity of different residues R3 residues are also accessible. Reactions which may be used in this context are, for example, the Suzuki-Miyaura reaction (reaction with arylboronic acids or heteroarylboronic acids) or the Sonogashira reaction (reaction with terminal alkynes) or numerous variants of these two reactions.
In Scheme 7, the conversion of compounds respective (E-XXI), (E-XXII) or (E-XXIII) to the respective compounds (E-XXVI), (E-XXVII) or (E-XXVIII) in step 7-(i) is shown. Depending on the desired R3 residue in compounds (E-XXVI), (E-XXVII) or (E-XXVIII), wherein in each case R3 is not iodine, different catalysts and reaction conditions in step 7-(i) may be used, e.g. when using cross-coupling reactions. Reaction conditions suitable in step 7-(i) are described in the literature and summarized in recent reviews: Chinchilla et al. Chem. Soc. Rev. 2011, 40, 5084-5121; Suzuki et al. Chem. Rev. 1995, 95, 2457-2483; Science of Synthesis, Cross Coupling and Heck-Type Reactions, 2013, Volumes 1 to 3, Editor: G. A. Molander (Volume 1), M. Larhed (Volume 2), J. P. Wolfe (Volume 3), Georg Thieme Verlag, Stuttgart, N.Y.
It may be advantageous in some cases to introduce the residue R2 independently of the residue R1 as shown in Scheme 8. For this purpose, a compound of type (E-XXX) is initially prepared by one of the routes described above, which is then converted to compound (E-XXXI), wherein R2 is not hydrogen. By this conversion compound (E-XXX) can be, for example, alkylated, acylated or sulphonylated.
It is evident that the compounds (E-III), (E-IIIa), (E-IV), (E-V), (E-VI), (E-XXIII), (E-XXVIII), and (E-XXXI), prepared by the methods described herein, may themselves in turn be starting points for further chemical reactions, which can lead to additional compounds according to the invention. This applies in particular to reactions which afford modifications or structural variations in the residues R1, R2, R3, R4 and/or R5.
The present invention further relates to a process for preparing a compound of the formulae (G) as defined hereinabove, and/or a salt thereof, characterized in that
Several intermediates were found to be particularly suitable in the processes for preparing a compound of the formulae (G) according to the present inventon as defined hereinabove, for example those described in the Schemes 1 to 8 above.
Therefore, in a further aspect, the present invention relates to a compound of the formula (Z-A), (Z-B) and/or a salt thereof,
wherein
Q is hydrogen, CN, COCl, COF, CO2H and salts thereof, CONR13R14, and CO2Rq, wherein Rq is (C1-C9)-alkyl or (C1-C9)-haloalkyl,
RZ8 is selected from the group consisting of H, F, Cl, Br, I, CH3, CH2F, CHF2 and CF3,
RZ1 and RZ2 are each independently hydrogen, CN, CH2aryl, X—C(═Y)—, wherein Y is NH, O or S and X is NH2, OH, SH, (C1-C8)-alkyl, (C1-C8)-haloalkyl, (C1-C8)-alkoxy, (C1-C8)-haloalkoxy, (C1-C6)-alkylthio, HN(C1-C8)-alkyl, or aryl, wherein each aryl is unsubstituted or is substituted by one or more residues from the group consisting of halogen, nitro, hydroxyl, cyano, NR13R14, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulphoxy, and (C1-C4)-alkylsulphonyl,
RZ3 is hydrogen, (C1-C8-alkyl, (C1-C8)-haloalkyl, (C1-C8)-alkoxy, (C1-C8)-haloalkoxy, (C1-C6)-alkylthio, or aryl, wherein aryl is unsubstituted or is substituted by one or more residues from the group consisting of halogen, nitro, hydroxyl, cyano, NR13R14, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulphoxy, and (C1-C4)-alkylsulphonyl,
RZ4 is (C1-C8)-alkyl, (C1-C8)-haloalkyl, (C1-C8)-alkoxy, (C1-C8)-haloalkoxy, (C1-C6)-alkylthio, or aryl, wherein aryl is unsubstituted or is substituted by one or more residues from the group consisting of halogen, nitro, hydroxyl, cyano, NR13R14, C4) alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulphoxy, and (C1-C4)-alkylsulphonyl,
wherein R13 and R14 in each case each independently have the meaning as defined herein, preferably the meaning as defined in one of the preferred embodiments.
Preferably, the present invention relates to compounds of the formula (Z-A) or (Z-B) as defined above, and/or a salt thereof, wherein
Q is CN, COCl, COF, CO2H and salts thereof, and CO2Rq, wherein Rq is (C1-C6)-alkyl or (C1-C6)-haloalkyl,
RZ8 is selected from the group consisting of H, F, Cl, Br, I, CH3, CH2F, CHF2 and CF3,
RZ1 and RZ2 are each independently hydrogen, CN, CH2phenyl, X—C(═Y)—, wherein Y is NH, O or S and X is NH2, OH, SH, (C1-C6)-alkyl, (C1-C6)-haloalkyl, (C1-C6)-alkoxy, (C1-C6)-haloalkoxy, (C1-C4)-alkylthio, HN(C1-C6)-alkyl, or phenyl, wherein each phenyl is unsubstituted or is substituted by one or more residues from the group consisting of halogen, nitro, hydroxyl, cyano, NR13R14, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, and (C1-C4)-haloalkoxy,
RZ3 is hydrogen, (C1-C6)-alkyl, (C1-C6)-haloalkyl, (C1-C6)-alkoxy, (C1-C6)-haloalkoxy, (C1-C4)-alkylthio, or phenyl, wherein phenyl is unsubstituted or is substituted by one or more residues from the group consisting of halogen, nitro, hydroxyl, cyano, NR13R14, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulphoxy, and (C1-C4)-alkylsulphonyl,
RZ4 is (C1-C6)-alkyl, (C1-C6)-haloalkyl, (C1-C6)-alkoxy, (C1-C6)-haloalkoxy, (C1-C4)-alkylthio, or phenyl, wherein phenyl is unsubstituted or is substituted by one or more residues from the group consisting of halogen, nitro, hydroxyl, cyano, NR13R14 (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulphoxy, and (C1-C4)-alkylsulphonyl,
wherein R13 and R14 in each case each independently have the meaning as defined herein, preferably the meaning as defined in one of the preferred embodiments.
More preferably, the present invention relates to compounds of the formula (Z-A) or (Z-B) as defined above, and/or a salt thereof, wherein
Q is CN, COCl, COF, CO2H and salts thereof, and CO2Rq, wherein Rq is (C1-C6)-alkyl,
RZ8 is selected from the group consisting of H, F, Cl, Br, I, CH3, CH2F, CHF2 and CF3,
RZ1 and RZ2 are each independently hydrogen, CN, CH2phenyl, X—C(═Y)—, wherein Y is NH, O or S and X is NH2, OH, SH, (C1-C6)-alkyl, (C1-C6)-haloalkyl, (C1-C6)-alkoxy, (C1-C4)-alkylthio, HN(C1-C6)-alkyl, or phenyl, wherein each phenyl is unsubstituted or is substituted by one or more residues from the group consisting of halogen, hydroxyl, cyano, (C1-C4)-alkyl, (C1-C4)-haloalkyl, and (C1-C4)-alkoxy,
RZ3 is hydrogen, (C1-C6)-alkyl, (C1-C6)-haloalkyl, (C1-C6)-alkoxy, (C1-C6)-haloalkoxy, (C1-C4)-alkylthio, or phenyl, wherein phenyl is unsubstituted or is substituted by one or more residues from the group consisting of halogen, hydroxyl, cyano, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, and (C1-C4)-haloalkoxy,
RZ4 is (C1-C6)-alkyl, (C1-C6)-haloalkyl, (C1-C6)-alkoxy, (C1-C6)-haloalkoxy, (C1-C4)-alkylthio, or phenyl, wherein phenyl is unsubstituted or is substituted by one or more residues from the group consisting of halogen, hydroxyl, cyano, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, and (C1-C4)-haloalkoxy.
Even more preferably, the present invention relates to compounds of the formula (Z-A) or (Z-B) as defined above, and/or a salt thereof, wherein
Q is CN, COCl, COF, CO2H and salts thereof, and CO2Rq, wherein Rq is (C1-C4)-alkyl,
RZ8 is selected from the group consisting of H, F, Cl, Br, I, CH3, CH2F, CHF2 and CF3,
RZ1 and RZ2 are each independently hydrogen, CN, CH2phenyl, X—C(═Y)—, wherein Y is NH, O or S and X is NH2, OH, SH, (C1-C6)-alkyl, HN(C1-C6)-alkyl, or phenyl, wherein each phenyl is unsubstituted or is substituted by one or more residues from the group consisting of halogen, hydroxyl, cyano, (C1-C4)-alkyl, (C1-C4)-haloalkyl, and (C1-C4)-alkoxy,
RZ3 is hydrogen, (C1-C6)-alkyl or phenyl, wherein phenyl is unsubstituted or is substituted by one or more residues from the group consisting of halogen, hydroxyl, cyano, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, and (C1-C4)-haloalkoxy,
RZ4 is (C1-C6)-alkyl or phenyl, wherein phenyl is unsubstituted or is substituted by one or more residues from the group consisting of halogen, hydroxyl, cyano, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, and (C1-C4)-haloalkoxy.
The present invention particularly preferably relates to a compound of the formula (Z-1), (Z-2), (Z-3), (Z-4), (Z-5), (Z-6) and/or a salt thereof,
wherein
A1 is selected from the group consisting of H, F, Cl, Br and I,
A2 is selected from the group consisting of F, Cl, Br and I,
A3 is H or C1,
A4 is H or Br,
E1 is selected from the group consisting of H, methyl, ethyl and iso-propyl,
E2 is selected from the group consisting of H, methyl, ethyl, iso-propyl, and tert.-butyl.
Depending on the type of reaction and the reaction conditions used, the skilled person will select suitable organic solvents, such as:
If the compounds described in the context of the present invention, in particular the intermediates and compounds (G) of the present invention, are obtained as solids, the purification can also be carried out by recrystallization or digestion.
The following acids are generally suitable for preparing the acid addition salts of the compounds of the formula (G): hydrohalic acids, such as hydrochloric acid or hydrobromic acid, furthermore phosphoric acid, nitric acid, sulphuric acid, mono- or bifunctional carboxylic acids and hydroxycarboxylic acids, such as acetic acid, maleic acid, succinic acid, fumaric acid, tartaric acid, citric acid, salicylic acid, sorbic acid, or lactic acid, and also sulphonic acids, such as p-toluenesulphonic acid and 1,5-naphthalenedisulphonic acid. The acid addition compounds of the formula (G) can be obtained in a simple manner by the customary methods for forming salts, for example by dissolving a compound of the formula (G) in a suitable organic solvent, such as, for example, methanol, acetone, methylene chloride or benzene, and adding the acid at temperatures of from 0 to 100° C., and they can be isolated in a known manner, for example by filtration, and, if appropriate, purified by washing with an inert organic solvent.
The base addition salts of the compounds of the formula (G) are preferably prepared in inert polar solvents, such as, for example, water, methanol or acetone, at temperatures of from 0 to 100° C. Examples of bases which are suitable for the preparation of the salts according to the invention are alkali metal carbonates, such as potassium carbonate, alkali metal hydroxides and alkaline earth metal hydroxides, for example NaOH or KOH, alkali metal hydrides and alkaline earth metal hydrides, for example NaH, alkali metal alkoxides and alkaline earth metal alkoxides, for example sodium methoxide or potassium tert-butoxide, or ammonia, ethanolamine or quaternary ammonium hydroxide.
What is meant by the “inert solvents” referred to in the above process variants are in each case solvents which are inert under the respective reaction conditions.
Collections of compounds of the formula (G) which can be synthesized by the aforementioned process can also be prepared in a parallel manner, it being possible for this to take place in a manual, partly automated or completely automated manner. In this connection, it is possible to automate the reaction procedure, the work-up or the purification of the products and/or intermediates. Overall, this is understood as meaning a procedure as described, for example, by S. H. DeWitt in “Annual Reports in Combinatorial Chemistry and Molecular Diversity: Automated Synthesis”, Volume 1, Verlag Escom, 1997, pages 69 to 77.
For the parallelized reaction procedure and workup it is possible to use a range of commercially available instruments, of the kind offered by, for example, the companies Stem Corporation, Woodrolfe Road, Tollesbury, Essex, CM9 8SE, England, or H+P Labortechnik GmbH, Bruckmannring 28, 85764 OberschleiBheim, Germany. For the parallel purification of compounds (G) or of intermediates produced during the preparation, there are available, inter alia, chromatography apparatuses, for example from ISCO, Inc., 4700 Superior Street, Lincoln, Nebr. 68504, USA. The apparatuses listed allow a modular procedure in which the individual process steps are automated, but between the process steps manual operations have to be carried out. This can be circumvented by using partly or completely integrated automation systems in which the respective automation modules are operated, for example, by robots. Automation systems of this type can be acquired, for example, from Zymark Corporation, Zymark Center, Hopkinton, Mass. 01748, USA.
Besides the methods described here, the preparation of compounds of the formula (G) can take place completely or partially by solid-phase supported methods. For this purpose, individual intermediates or all intermediates in the synthesis or a synthesis adapted for the corresponding procedure are bonded to a synthesis resin. Solid-phase-supported synthesis methods are described extensively in the specialist literature, for example Barry A. Bunin in “The Combinatorial Index”, Academic Press, 1998.
The use of solid-phase-supported synthesis methods permits a number of protocols, which are known from the literature and which for their part may be performed manually or in an automated manner, to be carried out. For example, the “teabag method” (Houghten, U.S. Pat. No. 4,631,211; Houghten et al., Proc. Natl. Acad. Sci, 1985, 82, 5131-5135) in which products from IRORI, 11149 North Torrey Pines Road, La Jolla, Calif. 92037, USA, are employed, may be semiautomated. The automation of solid-phase-supported parallel syntheses is performed successfully, for example, by apparatuses from Argonaut Technologies, Inc., 887 Industrial Road, San Carlos, Calif. 94070, USA or MultiSynTech GmbH, Wullener Feld 4, 58454 Witten, Germany.
The preparation according to the processes described herein produces compounds of the formula (G) in the form of substance collections or libraries. Accordingly, the present invention also provides libraries of compounds of the formula (G) which comprise at least two compounds of the formula (G), and precursors thereof.
The compounds of the formula (G) used in the context of the present invention or according to the invention (and/or their salts) have excellent herbicidal efficacy against a broad spectrum of economically important monocotyledonous and dicotyledonous annual harmful plants. The active compounds of the formula (G) also provide good control over perennial harmful plants which are difficult to control and produce shoots from rhizomes, root stocks or other perennial organs.
The present invention therefore also relates to a method for controlling unwanted plants or for regulating the growth of plants, preferably in crops of plants, where one or more compound(s) according to the invention is/are applied to the plants (for example harmful plants such as monocotyledonous or dicotyledonous weeds or undesired crop plants), to the seed (for example grains, seeds or vegetative propagules such as tubers or shoot parts with buds), to the soil in or on which the plants grow (for example the soil of cropland or non-cropland) or to the area on which the plants grow (for example the area under cultivation).
Thus, in a further aspect, the present invention relates to a method for controlling harmful plants or for regulating the growth of plants, characterized in that an effective amount of
is applied to the plants, seeds of plants, the soil in which or on which the plants grow or the area under cultivation.
The compounds according to the invention can be deployed, for example, prior to sowing (if appropriate also by incorporation into the soil), prior to emergence or after emergence. Specific examples may be mentioned of some representatives of the monocotyledonous and dicotyledonous weed flora which can be controlled by the compounds according to the invention, without the enumeration being restricted to certain species.
Monocotyledonous harmful plants of the genera: Aegilops, Agropyron, Agrostis, Alopecurus, Apera, Avena, Brachiaria, Bromus, Cenchrus, Commelina, Cynodon, Cyperus, Dactyloctenium, Digitaria, Echinochloa, Eleocharis, Eleusine, Eragrostis, Eriochloa, Festuca, Fimbristylis, Heteranthera, Imperata, Ischaemum, Leptochloa, Lolium, Monochoria, Panicum, Paspalum, Phalaris, Phleum, Poa, Rottboellia, Sagittaria, Scirpus, Setaria, Sorghum.
Dicotyledonous weeds of the genera: Abutilon, Amaranthus, Ambrosia, Anoda, Anthemis, Aphanes, Artemisia, Atriplex, Bellis, Bidens, Capsella, Carduus, Cassia, Centaurea, Chenopodium, Cirsium, Convolvulus, Datura, Desmodium, Emex, Erysimum, Euphorbia, Galeopsis, Galinsoga, Galium, Hibiscus, Ipomoea, Kochia, Lamium, Lepidium, Lindernia, Matricaria, Mentha, Mercurialis, Mullugo, Myosotis, Papaver, Pharbitis, Plantago, Polygonum, Portulaca, Ranunculus, Raphanus, Rorippa, Rotala, Rumex, Salsola, Senecio, Sesbania, Sida, Sinapis, Solanum, Sonchus, Sphenoclea, Stellaria, Taraxacum, Thlaspi, Trifolium, Urtica, Veronica, Viola, Xanthium.
The compounds of the formula (G) to be used according to the invention or the compounds of the formula (G) according to the invention and/or their salts were found to be highly effective in the control of harmful plants such as Alopecurus myosuroides, Avena fatua, Echinochloa crus-galli, Lolium multiflorum, Setaria viridis, Abutilon theophrasti, Amaranthus retroflexus, Matricaria inodora (=Tripleurospermum maritimum subsp. inodorum), Pharbitis purpurea, Polygonum convolvulus (=Fallopia convolvulus), Stellaria media, Viola tricolor, and Veronica persica.
When the compounds (G) according to the invention are applied to the soil surface before germination, either the weed seedlings are prevented completely from emerging or the weeds grow until they have reached the cotyledon stage, but then stop growing and eventually, after three to four weeks have elapsed, die completely.
If the compounds (G) are applied post-emergence to the green parts of the plants, growth stops after the treatment, and the harmful plants remain at the growth stage of the time of application, or die completely after a certain time, such that competition by the weeds, which is harmful to the crop plants, is thus eliminated very early and in a lasting manner.
Although the compounds according to the invention display an outstanding herbicidal activity against monocotyledonous and dicotyledonous weeds, crop plants of economically important crops, for example dicotyledonous crops of the genera Arachis, Beta, Brassica, Cucumis, Cucurbita, Helianthus, Daucus, Glycine, Gossypium, Ipomoea, Lactuca, Linum, Lycopersicon, Miscanthus, Nicotiana, Phaseolus, Pisum, Solanum, Vicia, or monocotyledonous crops of the genera Allium, Ananas, Asparagus, Avena, Hordeum, Oryza, Panicum, Saccharum, Secale, Sorghum, Triticale, Triticum, Zea, in particular Zea and Triticum, are damaged only to an insignificant extent, or not at all, depending on the structure of the respective compound according to the invention and its application rate. For these reasons, the present compounds are very suitable for selective control of unwanted plant growth in plant crops such as agriculturally useful plants or ornamentals.
Furthermore, it has been found that the compounds of the formula (G) to be used according to the invention or the compounds of the formula (G) according to the invention and/or their salts show excellent or very good pre-emergence and post-emergence action, and are particularly selectively in certain crops, in particular in oilseed rape, soya beans, cotton and cereals (and here in particular in maize, barley, wheat, rye, oats, triticale, millet varieties, rice).
In addition, the compounds according to the invention (depending on their particular structure and their application rate) have outstanding growth-regulating properties in crop plants. They intervene to regulate the plant's metabolism and can thus be used for controlled influence on plant constituents and to facilitate harvesting, for example by triggering desiccation and stunted growth. Moreover, they are also suitable for generally controlling and inhibiting unwanted vegetative growth without destroying the plants in the process. Inhibiting the vegetative growth plays an important role in many monocotyledonous and dicotyledonous crops since for example lodging can be reduced, or prevented completely, hereby.
By virtue of their herbicidal and/or plant growth-regulating properties, the active compounds (G) can also be used for control of harmful plants in crops of genetically modified plants or plants modified by conventional mutagenesis. In general, transgenic plants are notable for special advantageous properties, for example for resistances to certain pesticides, in particular certain herbicides, resistances to plant diseases or organisms that cause plant diseases, such as certain insects or microorganisms such as fungi, bacteria or viruses. Other specific characteristics relate, for example, to the harvested material with regard to quantity, quality, storability, composition and specific constituents. Thus, transgenic plants are known whose starch content is increased, or whose starch quality is altered, or those where the harvested material has a different fatty acid composition.
It is preferred with a view to transgenic crops to use the compounds according to the invention and/or their salts in economically important transgenic crops of useful plants and ornamentals, for example of cereals such as wheat, barley, rye, oats, millet, rice and corn or else crops of sugar beet, cotton, soybean, oilseed rape, potato, tomato, peas and other vegetables.
It is preferred to employ the compounds according to the invention as herbicides in crops of useful plants which are resistant, or have been made resistant by recombinant means, to the phytotoxic effects of the herbicides.
By virtue of their herbicidal and/or plant-growth-regulatory properties, the active compounds of the formula (G) can also be employed for controlling harmful plants in crops of known genetically modified plants or genetically modified plants still to be developed. In general, the transgenic plants are distinguished by especially advantageous properties, for example by resistances to certain pesticides, mainly certain herbicides, resistances to plant diseases or causative organisms of plant diseases, such as certain insects or microorganisms such as fungi, bacteria or viruses. Other specific characteristics relate, for example, to the harvested material with regard to quantity, quality, storability, composition and specific constituents. Thus, transgenic plants are known whose starch content is increased, or whose starch quality is altered, or those where the harvested material has a different fatty acid composition. Other particular properties may be tolerance or resistance to abiotic stressors, for example heat, low temperatures, drought, salinity and ultraviolet radication.
It is preferred to use the compounds of the formula (G) according to the invention and/or salts thereof in economically important transgenic crops of useful plants and ornamental plants, for example of cereals such as wheat, barley, rye, oats, sorghum and millet, rice, cassava and corn or else crops of sugar beet, cotton, soybean, oilseed rape, potato, tomato, peas and other vegetables.
It is preferred to employ the compounds of the formula (G) according to the invention as herbicides in crops of useful plants which are resistant, or have been made resistant by recombinant means, to the phytotoxic effects of the herbicides.
On employment of the active compounds (G) according to the invention in transgenic crops, not only do the effects toward harmful plants observed in other crops occur, but often also effects which are specific to application in the particular transgenic crop, for example an altered or specifically widened spectrum of weeds which can be controlled, altered application rates which can be used for the application, preferably good combinability with the herbicides to which the transgenic crop is resistant, and influencing of growth and yield of the transgenic crop plants.
The invention therefore also relates to the use of the compounds of the formula (G) according to the invention and/or their salts as herbicides for controlling harmful plants in crops of useful plants or ornamentals, optionally in transgenic crop plants.
Preference is given to the use by the pre- or post-emergence method in cereals such as wheat, barley, rye, oats, millet and rice, in particular in wheat by the post-emergence method.
Preference is also given to the use by the pre- or post-emergence method in corn, in particular by the pre-emergence method in corn.
Preference is also given to the use by the pre- or post-emergence method in soybeans, in particular by the post-emergence method in soybeans.
The use according to the invention for the control of harmful plants or for the growth regulation of plants also includes the case in which the active compound of the formula (G) or its salt is not formed from a precursor substance (“prodrug”) until after application on the plant, in the plant or in the soil.
The invention also provides the method (application method) for controlling harmful plants or for regulating the growth of plants which comprises applying an effective amount of one or more compounds of the formula (G) and/or salts thereof onto the plants (harmful plants, if appropriate together with the useful plants), plant seeds, the soil in which or on which the plants grow or the area under cultivation.
The compounds (G) according to the invention can be used in the form of wettable powders, emulsifiable concentrates, sprayable solutions, dusting products or granules in the customary formulations. The invention therefore also provides herbicidal and/or plant growth-regulating compositions which comprise compounds of the formula (G) and/or salts thereof.
Thus, in a further aspect, the present invention relates to a herbicidal and/or plant growth-regulating composition, characterized in that said composition comprises one or more compounds of the formula (G) and/or salts thereof as defined hereinabove, preferably in one of the preferred, more preferred or particularly preferred embodiments, and one or more further substances selected from groups (i) and/or (ii):
(i) one or more further agrochemically active substances, preferably selected from the group consisting of insecticides, acaricides, nematicides, further herbicides, fungicides, safeners, fertilizers and/or further growth regulators,
(ii) one or more formulation auxiliaries customary in crop protection.
The compounds of the formula (G) and/or salts thereof can be formulated in various ways according to which biological and/or physicochemical parameters are required. Possible formulations include, for example: wettable powders (WP), water-soluble powders (SP), water-soluble concentrates, emulsifiable concentrates (EC), emulsions (EW), such as oil-in-water and water-in-oil emulsions, sprayable solutions, suspension concentrates (SC), oil- or water-based dispersions, oil-miscible solutions, capsule suspensions (CS), dusting products (DP), seed-dressing products, granules for broadcasting and soil application, granules (GR) in the form of microgranules, sprayable granules, coated granules and adsorption granules, water-dispersible granules (WG), water-soluble granules (SG), ULV formulations, microcapsules and waxes.
These individual formulation types are known in principle and are described, for example, in: Winnacker-Küchler, “Chemische Technologie” [Chemical technology], volume 7, C. Hanser Verlag Munich, 4th ed. 1986; Wade van Valkenburg, “Pesticide Formulations”, Marcel Dekker, N.Y., 1973; K. Martens, “Spray Drying” Handbook, 3rd ed. 1979, G. Goodwin Ltd. London.
The necessary formulation auxiliaries, such as inert materials, surfactants, solvents and further additives are likewise known and are described, for example, in: Watkins, “Handbook of Insecticide Dust Diluents and Carriers”, 2nd Ed., Darland Books, Caldwell N.J., H.v. Olphen, “Introduction to Clay Colloid Chemistry”; 2nd Ed., J. Wiley & Sons, N.Y.; C. Marsden, “Solvents Guide”; 2nd Ed., Interscience, N.Y. 1963; McCutcheon's “Detergents and Emulsifiers Annual”, MC Publ. Corp., Ridgewood N.J.; Sisley and Wood, “Encyclopedia of Surface Active Agents”, Chem. Publ. Co. Inc., N.Y. 1964; Schönfeldt, “Grenzflächenaktive Äthylenoxidaddukte” [Interface-active Ethylene Oxide Adducts], Wiss. Verlagsgesell, Stuttgart 1976; Winnacker-Küchler, “Chemische Technologie”, volume 7, C. Hanser Verlag Munich, 4th ed. 1986.
Wettable powders are preparations which can be dispersed uniformly in water and, as well as the active compound, apart from a diluent or inert substance, also comprise surfactants of the ionic and/or nonionic type (wetting agents, dispersants), for example polyoxyethylated alkylphenols, polyoxyethylated fatty alcohols, polyoxyethylated fatty amines, fatty alcohol polyglycol ether sulphates, alkanesulphonates, alkylbenzenesulphonates, sodium lignosulphonate, sodium 2,2′-dinaphthylmethane-6,6′-disulphonate, sodium dibutylnaphthalenesulphonate or else sodium oleoylmethyltaurinate. To prepare the wettable powders, the herbicidally active compounds are ground finely, for example in customary apparatus such as hammer mills, blower mills and air-jet mills, and simultaneously or subsequently mixed with the formulation assistants.
Emulsifiable concentrates are produced by dissolving the active compound in an organic solvent, for example butanol, cyclohexanone, dimethylformamide, xylene or else relatively high-boiling aromatics or hydrocarbons or mixtures of the organic solvents, with addition of one or more surfactants of the ionic and/or nonionic type (emulsifiers). The emulsifiers used may, for example, be: alkylarylsulphonic calcium salts, such as calcium dodecylbenzenesulphonate, or nonionic emulsifiers such as fatty acid polyglycol esters, alkylaryl polyglycol ethers, fatty alcohol polyglycol ethers, propylene oxide-ethylene oxide condensation products, alkyl polyethers, sorbitan esters, such as, for example, sorbitan fatty acid esters, or polyoxyethylene sorbitan esters, such as, for example, polyoxyethylene sorbitan fatty acid esters.
Dusting products are obtained by grinding the active compound with finely distributed solid substances, for example talc, natural clays, such as kaolin, bentonite and pyrophyllite, or diatomaceous earth.
Suspension concentrates may be water- or oil-based. They can be produced, for example, by wet grinding by means of commercial bead mills with optional addition of surfactants as already listed above, for example, for the other formulation types.
Emulsions, e.g. oil-in-water emulsions (EW), can be prepared, for example, by means of stirrers, colloid mills and/or static mixers using aqueous organic solvents and if appropriate surfactants, as have for example already been listed above in connection with the other types of formulation.
Granules can be produced either by spraying the active compound onto adsorptive granulated inert material or by applying active compound concentrates by means of adhesives, for example polyvinyl alcohol, sodium polyacrylate or mineral oils, to the surface of carrier substances, such as sand, kaolinites or of granulated inert material. Suitable active compounds can also be granulated in the manner customary for the production of fertilizer granules—if desired as a mixture with fertilizers.
Water-dispersible granules are produced generally by the customary processes such as spray-drying, fluidized bed granulation, pan granulation, mixing with high-speed mixers and extrusion without solid inert material.
For the production of pan granules, fluidized bed granules, extruder granules and spray granules, see, for example, processes in “Spray-Drying Handbook” 3rd ed. 1979, G. Goodwin Ltd., London; J. E. Browning, “Agglomeration”, Chemical and Engineering 1967, pages 147 ff.; “Perry's Chemical Engineer's Handbook”, 5th Ed., McGraw-Hill, New York 1973, pp. 8-57.
For further details regarding the formulation of crop protection agents, see, for example, G. C. Klingman, “Weed Control as a Science”, John Wiley and Sons, Inc., New York, 1961, pages 81-96 and J. D. Freyer, S. A. Evans, “Weed Control Handbook”, 5th ed., Blackwell Scientific Publications, Oxford, 1968, pages 101-103.
The agrochemical formulations comprise generally from 0.1 to 99% by weight, in particular from 0.1 to 95% by weight, of active compound of the formula (G) and/or salts thereof.
In wettable powders, the active compound concentration is, for example, about 10 to 90% by weight; the remainder to 100% by weight consists of the customary formulation constituents. In the case of emulsifiable concentrates, the active compound concentration can be from about 1 to 90, preferably from 5 to 80, % by weight. Dust-type formulations contain from 1 to 30% by weight of active compound, preferably usually from 5 to 20% by weight of active compound; sprayable solutions contain from about 0.05 to 80% by weight, preferably from 2 to 50% by weight of active compound. In the case of water-dispersible granules, the active compound content depends partly on whether the active compound is present in liquid or solid form and on which granulation assistants, fillers, etc., are used. In the water-dispersible granules, the content of active compound is, for example, between 1 and 95% by weight, preferably between 10 and 80% by weight.
In addition, the active compound formulations mentioned optionally comprise the respective customary tackifiers, wetting agents, dispersants, emulsifiers, penetrants, preservatives, antifreeze agents and solvents, fillers, carriers and dyes, defoamers, evaporation inhibitors and agents which influence the pH and the viscosity. Examples of formulation auxiliaries are described, inter alia, in “Chemistry and Technology of Agrochemical Formulations”, ed. D. A. Knowles, Kluwer Academic Publishers (1998).
The compounds of the formula (G) and/or salts thereof can be employed as such or in the form of their preparations (formulations) combined with other pesticidally active compounds, such as, for example, insecticides, acaricides, nematicides, herbicides, fungicides, safeners, fertilizers and/or growth regulators, for example as finished formulation or as tank mixes. The combination formulations can be prepared on the basis of the abovementioned formulations, while taking account of the physical properties and stabilities of the active compounds to be combined.
The weight ratios of herbicide (mixture) to safener depend generally on the herbicide application rate and the efficacy of the safener in question and may vary within wide limits, for example in the range from 200:1 to 1:200, preferably 100:1 to 1:100, in particular 20:1 to 1:20. Analogously to the compounds (G) or mixtures thereof, the safeners can be formulated with further herbicides/pesticides and be provided and employed as a finished formulation or tankmix with the herbicides.
For application, the herbicide or herbicide/safener formulations present in commercial form are, if appropriate, diluted in a customary manner, for example in the case of wettable powders, emulsifiable concentrates, dispersions and water-dispersible granules with water. Preparations in the form of dusts, granules for soil application or granules for broadcasting and sprayable solutions are usually not diluted further with other inert substances prior to application.
The application rate of the compounds of the formula (G) and/or salts thereof can vary within wide limits. For the application as herbicide for controlling harmful plants, for example, generally the range of from 0.001 to 10.0 kg/ha of active substance is suitable, preferably the compounds of the formula (G) and/or salts thereof are applied in the range of from 0.005 to 5 kg/ha, in particular in the range of from 0.01 to 1 kg/ha. This applies both to the pre-emergence and the post-emergence application.
When used as plant growth regulator, for example as culm stabilizer for crop plants like those mentioned above, preferably cereal plants, such as wheat, barley, rye, triticale, millet, rice or corn, the application rate of the compounds of the formula (G) and/or salts thereof is, for example, in the range of from 0.001 to 2 kg/ha or more of active substance, preferably in the range of from 0.005 to 1 kg/ha, in particular in the range of from 10 to 500 g/ha of active substance. This applies both to application by the pre-emergence method and the post-emergence method, the post-emergence treatment generally being preferred.
The application as culm stabilizer may take place at various stages of the growth of the plants. Preferred is, for example, the application after the tillering phase, at the beginning of the longitudinal growth.
As an alternative, application as plant growth regulator is also possible by treating the seed, which includes various techniques for dressing and coating seed. Here, the application rate depends on the particular techniques and can be determined in preliminary tests.
In an exemplary manner, some synthesis examples of compounds of the general formula (G) are described below. In the examples, the amounts (including percentages) refer to the weight, unless especially stated otherwise.
The symbols “>” and “<” mean “greater than” and “smaller than”, respectively. The symbol “≥” means “greater than or equal to”, the symbol “≤” means “smaller than or equal to”.
If, in the context of the description and the examples, the terms “R” and “S” are given for the absolute configuration on a centre of chirality of the stereoisomers of the formula (G), this RS nomenclature follows, unless defined differently, the Cahn-Ingold-Prelog rule.
In the context of the present invention and in the Tables 1 to 5 mentioning specific and preferred compounds according to the present invention, the following abbreviations are used:
The position of a substituent, e.g. at the phenyl ring in position 2, is stated as a prefix to the symbol or the abbreviation of the radical, for example
Numerations of the substituent positions for di- or trisubstituted substitution patterns are analogously stated as a prefix, for example
Other abbreviations are to be understood analogously to the examples stated above.
In addition, the customary chemical symbols and formulae apply, such as, for example, CH2 for methylene or CF3 for trifluoromethyl or OH for hydroxyl.
Correspondingly, composite meanings are defined as composed of the abbreviations mentioned, for example
NMR-Peak lists
1H-NMR data of selected examples are written in form of 1H-NMR-peak lists. To each signal peak are listed the δ-value in ppm and the signal intensity in round brackets. Between the δ-value-signal intensity pairs are semicolons as delimiters.
The peak list of an example has therefore the form:
δ1 (intensity1); δ2 (intensity2); . . . ; δi (intensityi); . . . ; δn (intensityn)
Intensity of sharp signals correlates with the height of the signals in a printed example of a NMR spectrum in cm and shows the real relations of signal intensities. From broad signals several peaks or the middle of the signal and their relative intensity in comparison to the most intensive signal in the spectrum can be shown.
For calibrating chemical shift for 1H spectra, tetramethylsilane and/or the chemical shift of the solvent was used, especially in the case of spectra measured in DMSO (Dimethyl sulfoxide). Therefore in NMR peak lists, tetramethylsilane peak can occur, but not necessarily
The 1H-NMR peak lists are similar to classical 1H-NMR prints and contains therefore usually all peaks, which are listed at classical NMR-interpretation.
Additionally they can show like classical 1H-NMR prints signals of solvents, stereoisomers of the target compounds, which are also object of the invention, and/or peaks of impurities.
To show compound signals in the delta-range of solvents and/or water the usual peaks of solvents, for example peaks of DMSO in DMSO-D6 and the peak of water are shown in our 1H-NMR peak lists and have usually on average a high intensity.
The peaks of stereoisomers of the target compounds and/or peaks of impurities have usually on average a lower intensity than the peaks of target compounds (for example with a purity >90%).
Such stereoisomers and/or impurities can be typical for the specific preparation process. Therefore their peaks can help to recognize the reproduction of our preparation process via “side-products-fingerprints”.
An expert, who calculates the peaks of the target compounds with known methods (MestreC, ACD-simulation, but also with empirically evaluated expectation values) can isolate the peaks of the target compounds as needed optionally using additional intensity filters. This isolation would be similar to relevant peak picking at classical 1H-NMR interpretation.
Further details of NMR-data description with peak lists can be found in the publication “Citation of NMR Peaklist Data within Patent Applications” of the Research Disclosure Database Number 564025.
The compounds according to the present invention, such as described in the Tables 1 to 5, are obtained according to or analogously to the following chemical synthesis examples.
(A) Chemical synthesis examples:
730 mg of 3,4-dichloroisothiazole-5-carboxylic acid (3.7 mmol) were dissolved in 10 ml of dichloromethane and a drop of dimethylformamide was added. 1.4 g of oxalyl chloride (11.1 mmol) were added dropwise at room temperature. After stirring for 1 h at room temperature, the solution was evaporated to dryness on a rotary evaporator. The residue was taken up in 3 ml of dichloromethane and slowly added dropwise to a solution of 626 mg of 1-cyclohexylmethanamine (5.5 mmol) and 746 mg of triethylamine (7.4 mmol) in 10 ml of dichloromethane. The mixture was stirred at room temperature for 1 h. The reaction mixture was then added to water and extracted repeatedly with dichloromethane. The concentrated extracts were dried over MgSO4, concentrated and purified by column chromatography. Yield: 1.05 g (97% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 6.86 (br, 1H), 3.34 (tr, 2H), 1.77 (m, 4H), 1.66 (m, 1H), 1.58 (m, 1H), 1.3-1.15 (m, 3H), 1.0 (m, 2H).
1.27 g of 3,4-dichloro-N-(cyclohexylmethyl)isothiazole-5-carboxamide (4.3 mmol) were dissolved in 6 ml of toluene. To this solution were added consecutively 1.87 g of benzophenone imine (10 mmol), 2.8 g of caesium carbonate (8.68 mmol), 102 mg of Xantphos (0.17 mmol) and 79 mg of tri(dibenzylideneacetone)dipalladium (Pd2dba3; 0.087 mmol). The reaction vessel with the resulting solution was then briefly evacuated and immediately filled with argon three times in succession. The mixture was then heated in an oil bath preheated to 100° C. for 24 h. After cooling, the reaction solution was added to water, extracted repeatedly with ethyl acetate, dried, concentrated and purified by column chromatography. Yield: 253 mg (13% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 7.82 (d, 2H), 7.57-7.21 (m, 8H), 6.80 (br, 1H), 3.29 (tr, 2H), 1.76 (m, 4H), 1.67 (m, 1H), 1.58 (m, 1H), 1.3-1.15 (m, 3H), 1.04-0.95 (m, 2H).
184 mg of 4-chloro-N-(cyclohexylmethyl)-3-[(diphenylmethylene)amino]isothiazole-5-carboxamide were dissolved in 1.5 ml of tetrahydrofuran (THF) to which 0.5 ml of 6N hydrochloric acid was added and the mixture was stirred at room temperature until the reactant was completely consumed according to thin-layer chromatography. The reaction mixture was added to a little water and extracted with ethyl acetate. On drying the ethyl acetate phases, concentrating and chromatography, the desired product was obtained. Yield: 89 mg (77% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 6.68 (br, 1H), 4.73 (br, 2H), 3.32 (tr, 2H), 1.77 (m, 4H), 1.66 (m, 1H), 1.57 (m, 1H), 1.32-1.13 (m, 3H), 1.06-0.96 (m, 2H).
15 g of 3,4-dichloroisothiazole-5-carboxylic acid (75.7 mmol) were dissolved in 300 ml of ethanol and 8.4 ml of concentrated sulphuric acid were added. The mixture was stirred under reflux for 20 h. The reaction mixture was then concentrated to half the original volume, neutralized with saturated NaHCO3, added to water and extracted with dichloromethane. The dichloromethane phases were dried and carefully concentrated on a rotary evaporator. Yield: 15.2 g (89% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 4.44 (q, 2H), 1.42 (tr, 3H).
14.06 g of ethyl 3,4-dichloroisothiazole-5-carboxylate (62.19 mmol) were dissolved in 150 ml of toluene. To this solution were added consecutively 13.9 g of benzophenone imine (74.6 mmol), 40.5 g caesium carbonate (124.4 mmol), 1.44 g Xantphos (2.49 mmol) and 1.14 g tri(dibenzylidenaceton)dipalladium (Pd2dba3; 1.24 mmol). The reaction vessel with the resulting solution was then briefly evacuated and immediately filled with argon three times in succession. The mixture was then heated for 24 h in an oil bath which had been preheated to 100° C. After cooling, the reaction solution was filtered through a 2 cm thick layer of silica gel, which was rinsed repeatedly with dichloromethane. The filtrate was concentrated and the residue purified by column chromatography. Yield: 5.29 g (23% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 7.82 (d, 2H), 7.59-7.22 (m, 8H), 4.36 (q, 2H), 1.37 (tr, 3H).
10.1 g of ethyl 4-chloro-3-[(diphenylmethylene)amino]isothiazole-5-carboxylate (27.2 mmol) were dissolved in 200 ml of tetrahydrofuran (THF) to which 12 ml of 6N hydrochloric acid was added and the mixture was stirred at room temperature until the reactant was completely consumed according to thin-layer chromatography. The reaction mixture was added to a little water and extracted with ethyl acetate. On drying the ethyl acetate phases, concentrating and chromatography, the desired product was obtained. Yield: 4.51 g (91% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 5.0-4.5 (br, 2H), 4.40 (q, 2H), 1.39 (tr, 3H).
To 4.27 g of ethyl 3-amino-4-chloroisothiazole-5-carboxylate (20.6 mmol) in a mixture of 50 ml of ethanol and 50 ml of THF were added 26 ml of 2N sodium hydroxide solution and the mixture was stirred at room temperature for 1 h. The reaction mixture was then adjusted to pH 5 by careful addition of 2N hydrochloric acid, whereupon a portion of the product precipitated in the form of crystals. The crystals were filtered off under suction and the filtrate was extracted with ethyl acetate. The organic extracts were dried and concentrated, whereby a further batch of the product was obtained. Yield: 3.57 g (97% of theory).
1H-NMR (400 MHz, DMSO 6, ppm) 14.05 (br, 1H), 6.58 (s, 2H).
To 100 mg of 3-amino-4-chloroisothiazole-5-carboxylic acid (0.56 mmol) in 4 ml of dichloromethane were added 130 mg of 3,4,5-trifluorobenzylamine (0.78 mmol), 170 mg of triethylamine (1.68 mmol) and 0.83 ml of a 50 percent solution of n-propylphosphonic anhydride (T3P; 1.4 mmol) in THF and the mixture was stirred overnight at room temperature. The reaction mixture was then added to water and extracted repeatedly with ethyl acetate. The organic extracts were washed with saturated sodium chloride solution, dried and concentrated on a rotary evaporator. The residue was purified by column chromatography. Yield: 102 mg (57% of theory).
1H-NMR (400 MHz, DMSO 6, ppm) 9.0 (tr, 1H), 7.26 (m, 2H), 6.56 (s, 2H), 4.43 (d, 2H).
Analogously to the synthesis of compound 1-35 described above, 120 mg of 3-amino-4-chloroisothiazole-5-carboxylic acid (0.67 mmol) were reacted with 143 mg (1 mmol) of 2,4-difluorobenzylamine. Yield: 188 mg (91% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 7.41 (m, 1H), 7.03 (br, 1H), 6.86 (m, 2H), 4.73 (br, 2H), 4.66 (d, 2H).
83 mg of 3-amino-4-chloro-N-(2,4-difluorobenzyl)isothiazole-5-carboxamide (0.27 mmol) and 121 mg of 4-methoxyphenyldithiophosphonic anhydride (Lawesson's reagent; 0.3 mmol) in 2 ml of THF were stirred at room temperature for 6 h and at 50° C. for 1 h. After cooling, the mixture was added to water and extracted with dichloromethane. The dichloromethane phases were dried and concentrated. The residue was purified by column chromatography. Yield: 17.1 mg (20% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 8.67 (br, 1H), 7.48 (m, 1H), 6.90 (m, 2H), 5.02 (d, 2H).
To 70 mg of 3-amino-4-chloro-N-(cyclohexylmethyl)isothiazole-5-carboxamide (I-4; 0.25 mmol) in 3 ml of dichloromethane were added 52 mg of triethylamine (0.51 mmol), 4 mg of 4-dimethylaminopyridine and 62 mg of n-pentanoyl chloride (0.51 mmol) and the mixture was stirred for 3 h at room temperature. The mixture was then added to water and extracted with dichloromethane. The dichloromethane phases were dried and concentrated. The residue was purified by chromatography. Yield: 53 mg (57% of theory)
1H-NMR (400 MHz, CDCl3 δ, ppm) 7.68 (bs, 1H), 6.73 (bs, 1H), 3.33 (t, 2H), 2.63 (bs, 2H), 1.73 (m, 6H), 1.59 (m, 2H), 1.43 (m, 2H), 1.21 (m, 4H), 1.00 (m, 4H).
Analogously to the synthesis of compound 1-35 described above, 100 mg of 3-amino-4-chloroisothiazole-5-carboxylic acid (0.56 mmol) were reacted with 115 mg of 2,6-difluorobenzylamine (0.78 mmol). Yield: 125 mg (74% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 7.31 (m, 1H), 7.05 (bs, 1H), 6.94 (m, 2H), 4.76 (d, 2H), 4.72 (bs, 2H).
To 20 mg of 3-amino-4-chloro-N-(2,6-difluorobenzyl)isothiazole-5-carboxamide (I-24; 0.06 mmol) in 1 ml of dichloromethane were added 13 mg of triethylamine (0.13 mmol), 2 mg of 4-dimethylaminopyridine and 28 mg of trifluoroacetic anhydride (0.13 mmol) and the mixture was stirred for 3 h at room temperature. The mixture was then added to water and extracted with dichloromethane. The dichloromethane phases were dried and concentrated and the residue was purified by chromatography. Yield: 13 mg (49% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 8.29 (bs, 1H), 7.31 (m, 1H), 7.09 (bs, 1H), 6.94 (m, 2H), 4.78 (d, 2H).
To 80 mg of 3-amino-4-chloro-N-(2,4-difluorobenzyl)isothiazole-5-carboxamide (I-22; 0.26 mmol) in 4 ml of dichloromethane were added 53 mg of triethylamine (0.52 mmol), 4 mg of 4-dimethylaminopyridine and 73 mg of 1-chlorocyclopropanecarbonyl chloride (0.52 mmol) and the mixture was stirred for 2 h at room temperature. The mixture was then added to water and extracted with dichloromethane. The dichloromethane phases were dried and concentrated. The residue obtained therefrom was purified by chromatography. Yield: 24 mg (22% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 7.37 (m, 1H), 6.83 (m, 2H), 5.06 (s, 2H), 4.82 (bs, 2H), 1.66 (m, 2H), 1.30 (m, 2H).
To 650 mg (2.28 mmol) of methyl 3-amino-4-iodo-1,2-thiazole-5-carboxylate in 11 ml of DMF were added 43.6 mg (0.229 mmol) of CuI, 160 mg (0.229 mmol) of Pd(PPh3)2Cl2 and 0.638 ml (5.58 mmol) of triethylamine and the mixture was stirred at room temperature for 5 min under protective gas (argon). 0.647 ml (4.58 mmol) of ethynyltrimethylsilane were added dropwise and then the mixture was stirred for 1 h at 100° C. The mixture was then concentrated on a rotary evaporator and the residue was treated with a saturated NH4Cl solution and extracted with dichloromethane/heptane 1:9. The organic phase was dried over Na2SO4, filtered and concentrated by rotary evaporation. The residue was purified by chromatography. Yield: 486 mg (83% of theory)
1H-NMR (400 MHz, CDCl3 δ, ppm) 4.91 (br, 2H), 3.92 (s, 3H), 0.29 (s, 9H).
300 mg (1.18 mmol) of methyl 3-amino-4-[(trimethylsilyl)ethynyl]isothiazole-5-carboxylate were dissolved in 10 ml of THF/methanol 1:1. 1.77 ml (3.54 mmol) of NaOH dissolved in 2 ml of water were added dropwise. After stirring for 1 h at room temperature, the mixture was concentrated on a rotary evaporator. The residue was treated with 2M HCl and the mixture was extracted with ethyl acetate. The organic phase was dried over Na2SO4, filtered and concentrated by rotary evaporation. Yield: 197 mg (100%) of crude product.
135 mg (0.8 mmol) of 3-amino-4-ethynylisothiazole-5-carboxylic acid, 0.26 ml (2.0 mmol) of cyclohexylmethylamine, 1.27 g (2.0 mmol, 50% in THF) of n-propylphosphonic anhydride (T3P) and 0.335 ml (2.4 mmol) of triethylamine were dissolved in 8 ml of THF and the mixture was stirred at 55° C. for 1.5 h. The mixture was then concentrated on a rotary evaporator, the residue then treated with 2M NaOH and extracted repeatedly with ethyl acetate. The organic extracts were dried with Na2SO4 and concentrated on a rotary evaporator. The residue was purified by column chromatography. Yield: 156 mg (74% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 7.12 (br, 1H), 4.83 (br, 2H), 3.77 (s, 1H), 3.32 (t, 2H), 1.80-1.56 (m, 6H), 1.31-1.15 (m, 3H), 1.06-1.00 (m, 2H).
1.10 g (2.86 mmol) of methyl 3-[(tert-butoxycarbonyl)amino]-4-iodoisothiazole-5-carboxylate, 460 mg (3.44 mmol) of potassium trifluoro(vinyl)borate and 0.6 ml (4.30 mmol) of triethylamine were dissolved in 7.7 ml of ethanol and the mixture was stirred for 5 min at room temperature under protective gas (argon). 25.4 mg (0.143 mmol) of PdCl2 were added and the mixture was heated for 1 h at 100° C. in a microwave. The mixture was then concentrated and the residue extracted with NaHCO3 and ethyl acetate, separated off, dried with Na2SO4 and concentrated by rotary evaporation. The residue was purified by column chromatography. Yield: 580 mg (71% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 7.16 (br, 1H), 7.10-7.02 (dd, 1H), 5.72-5.66 (m, 2H), 3.91 (s, 3H), 1.53 (s, 9H).
680 mg (2.39 mmol) of methyl 3-[(tert-butoxycarbonyl)amino]-4-vinylisothiazole-5-carboxylate were dissolved in 35 ml of THF. 2.63 ml of a 2M NaOH solution were added dropwise. After stirring for 2 h at room temperature, the mixture was concentrated on a rotary evaporator. The residue was treated with 2M HCl and extracted with ethyl acetate. The organic phase was dried over Na2SO4, filtered and concentrated by rotary evaporation. Yield: 645 mg (100%) of crude product.
323 mg (1.20 mmol) of 3-[(tert-butoxycarbonyl)amino]-4-vinylisothiazole-5-carboxylic acid, 0.46 ml (3.59 mmol) of cyclohexylmethylamine, 950 mg (2.99 mmol, 50% in THF) of n-propylphosphonic anhydride (T3P) and 0.50 ml (3.59 mmol) of triethylamine were dissolved in 9 ml of THF and the mixture stirred at 55° C. for 1.5 h. The mixture was then concentrated on a rotary evaporator, the residue treated with 1M HCl and extracted repeatedly with dichloromethane. The organic extracts were dried with Na2SO4 and concentrated on a rotary evaporator. The residue was purified by column chromatography. Yield: 412 mg (94% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 6.94 (br, 1H), 6.83-6.76 (dd, 1H), 6.16 (br, 1H), 5.76-5.65 (m, 2H), 3.25 (t, 2H), 1.74-1.68 (m, 4H), 1.54-1.47 (m, 11H), 1.36-1.11 (m, 3H), 1.01-0.88 (m, 2H).
100 mg (0.274 mmol) of tert-butyl {5-[(cyclohexylmethyl)carbamoyl]-4-vinylisothiazol-3-yl}carbamate) were dissolved in 2.7 ml of methanol and 2.91 mg (0.027 mmol) of Pd/C (5%) were added. After stirring for 18 h at room temperature under hydrogen, the mixture was filtered and concentrated by rotary evaporation. Yield: 100 mg (99% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 6.75 (br, 1H), 5.87 (br, 1H), 3.27 (t, 2H), 2.81 (q, 2H), 1.77-1.67 (m, 4H), 1.58-1.53 (m, 11H), 1.28-1.15 (m, 6H), 1.02-0.93 (m, 2H).
75 mg (0.204 mmol) of tert-butyl {5-[(cyclohexylmethyl)carbamoyl]-4-ethylisothiazol-3-yl}carbamate) and 0.204 ml (2.65 mmol) of TFA were together dissolved in 1 ml of dichloromethane and the mixture was stirred at room temperature for 30 min. The mixture was then concentrated on a rotary evaporator, the residue treated with 2M NaOH and extracted repeatedly with dichloromethane. The organic extracts were dried with Na2SO4 and concentrated on a rotary evaporator. The residue was purified by column chromatography.
Yield: 51 mg (93% of theory).
1H-NMR (400 MHz, CDCl3 δ, ppm) 5.82 (br, 1H), 4.52 (br, 2H), 3.25 (t, 2H), 2.74 (q, 2H), 1.76-1.53 (m, 6H), 1.27-1.15 (m, 6H), 1.02-0.88 (m, 2H).
NMR Peak Lists
NMR peak lists for compounds according to formula (G) in the context of the present invention. The numbering of these compounds (called Examples in said list) refers to Tables 1 to 5 above.
1. Herbicidal pre-emergence action
Seeds of monocotyledonous and dicotyledonous weed plants and crop plants were placed in wood-fibre pots in sandy loam and covered with soil. The compounds (G) according to the invention, formulated in the form of wettable powders (WP), were then applied as aqueous suspension or emulsion at a water application rate of 600 I/ha (converted) with the addition of 0.2% of wetting agent to the surface of the covering soil.
After the treatment, the pots were placed in a greenhouse and kept under good growth conditions for the test plants. After about 3 weeks, the effect of the preparations was scored visually in comparison with untreated controls as percentages. For example, 100% activity=the plants have died, 50% herbicidal activity or damage=the plants have been reduced by 50% or the plant mass has been reduced by 50%, 0% activity=like control plants.
Compounds (G) according to the invention such as, for example, the compounds No. I-9, I-10, I-11, I-13, I-16, I-17, I-20, I-21, I-23, I-24, I-25, I-26, I-27, I-28, I-29, I-30, I-31, I-32, I-33, I-34, I-35, I-36, I-37, I-38, I-39, I-40, I-41, I-44, I-46, I-48, I-53, I-86, I-96, I-103, I-104, I-107, I-109, I-111, I-120, I-127, I-168, I-186, I-209, I-227, I-250, I-254, I-258, I-268, I-291, I-332, I-350, I-373, I-391, I-414, I-432, I-455, I-473, I-495, I-497, I-504, I-506, I-509, I-517, I-524, I-527, I-528, I-534, I-535, I-537, I-540, I-541, II-5, II-8, II-9, II-10, II-13, II-14, II-15, II-22, II-28, II-29, II-35, II-36, II-50, II-55, II-56, II-57, II-62, II-63, II-64, II-70, II-71, II-77, II-78, II-84, II-85, II-91, II-92, II-98, II-99, II-105, II-106, II-111, II-112, II-113, II-119, II-120, II-126, II-127, II-133, II-134, II-140, II-141, II-147, II-148, II-155, II-168, II-183, II-189, II-196, II-204, II-211, II-217, II-224, II-225, II-232, II-233, II-248, II-249, II-250, II-251, II-255, II-256, II-257, II-258, II-259, II-260, II-261, II-262, II-264, II-265, II-266, II-279, II-281, II-282, II-283, II-284, II-286, II-287, II-288, II-289, II-290, II-292, II-293, II-294, II-295, II-297, II-299, II-300, II-301, II-302, II-303, II-304, II-306, II-307, II-308, II-309, II-311, II-312, II-313, II-314, II-315, II-316, II-326, II-327, II-329, II-330, II-332, II-334, II-335, II-336, II-337, II-338, II-340, II-341, II-342, II-343, II-346, II-347, II-348, II-349, II-350, II-351, II-352, II-353, II-354, II-355, II-356, II-357, II-358, II-359, II-360, II-361, II-363, II-364, II-365, II-366, II-367, II-374, II-376, II-379, II-380, II-382, II-385, II-386, II-387, II-388, II-389, II-390, II-398, II-399, II-400, II-401, II-402, II-413, II-417, II-419, III-420, II-421, II-422, II-424, II-425, II-426, II-427, II-428, II-429, II-430, II-437, II-438, II-439, III-19, III-32, III-42, III-43, III-46, III-52, III-62, III-85, III-86, III-87, III-88, 111-89, III-92, III-93, III-94, III-95, III-96, IV-2, IV-3, IV-4, IV-5, IV-6, IV-7, IV-9, IV-12, IV-19, IV-23, V-8, V-9, V-10, V-11, V-12, V-13 and V-16 from the above Tables 1 to 5, have good herbicidal efficacy (70% to 100% activity) against a plurality of harmful plants at an application rate of 320 g or less of active substance per hectare when applied by the pre-emergence method, in particular against against one, two, three, four, five, six, seven, eight, nine, ten or more, or even all of the harmful plants selected from the group consisting of
ALOMY=Alopecurus myosuroides
AVEFA=Avena fatua
ECHCG=Echinochloa crus-galli
LOLMU=Lolium multiflorum
SETVI=Setaria viridis
ABUTH=Abutilon theophrasti
AMARE=Amaranthus retroflexus
MATIN=Matricaria inodora (=Tripleurospermum maritimum subsp. inodorum)
PHBPU=Pharbitis purpurea
POLCO=Polygonum convolvulus (=Fallopia convolvulus)
STEME=Stellaria media
VIOTR=Viola tricolor
VERPE=Veronica persica
What was determined was the respective herbicidal activity, in each case at the same point in time after application of the formulation in question, i.e. the damage to the respective harmful plant in % compared to untreated control plants.
The compounds No. I-9, I-17, I-20, I-21, I-23, I-25, I-27, I-32, I-33, I-34, I-35, I-36, I-38, I-44, I-86, I-109, I-209, I-227, II-15, II-22, II-29, II-36, II-50, II-57, II-64, II-70, II-71, II-78, II-84, II-85, II-91, II-92, II-98, II-99, II-105, II-106, II-112, II-113, II-119, II-120, II-126, II-127, II-133, II-134, II-140, II-141, II-147, II-148, II-155, II-183, II-196, II-204, II-211, II-217, II-225, V-8, V-9 and V-10 showed excellent activity (90-100%) against several harmful plants when applied by the pre-emergence method at an application rate of 320 g of active substance per hectare, and showed very good activity (80-100%) against several harmful plants when applied by the pre-emergence method at an application rate of 80 g of active substance per hectare, in particular against two, three, four or more harmful plants selected from the group consisting of ALOMY, AVEFA, ECHCG, LOLMU, SETVI, ABUTH, AMARE, MATIN, PHBPU, POLCO, STEME, VIOTR and VERPE.
Similarly, the compounds No. I-495, I-497, I-504, I-506, I-524, I-527, I-528, I-534, I-535, I-537, I-540, II-28, II-56, II-63, II-233, II-248, II-249, II-250, II-251, II-255, II-256, II-257, II-258, II-259, II-260, II-261, II-264, II-265, II-266, II-279, II-281, II-282, II-283, II-284, II-286, II-287, II-288, II-289, II-290, II-294, II-295, II-297, II-299, II-300, II-301, II-302, II-303, II-304, II-306, II-307, II-308, II-309, II-311, II-312, II-314, II-327, II-329, II-330, II-332, II-334, II-335, II-337, II-338, II-340, II-341, II-342, II-343, II-346, II-347, II-348, II-349, II-350, II-351, II-352, II-353, II-354, II-355, II-356, II-359, II-363, II-365, II-366, II-367, II-374, II-379, II-380, II-382, II-386, II-387, II-388, II-389, II-390, II-401, II-413, II-419, 111-420, II-421, II-422, II-424, II-425, I-427, II-428, II-429, II-430, II-437, II-438, II-439, III-85, III-89, V-12 and V-16 showed excellent activity (90-100%) against several harmful plants when applied by the pre-emergence method at an application rate of 320 g of active substance per hectare, and showed very good activity (80-100%) against several harmful plants when applied by the pre-emergence method at an application rate of 80 g of active substance per hectare, in particular against two, three, four or more harmful plants selected from the group consisting of ALOMY, AVEFA, ECHCG, LOLMU, SETVI, ABUTH, AMARE, MATIN, PHBPU, POLCO, STEME, VIOTR and VERPE.
The compounds according to the invention displayed particularly good herbicidal activity in pre-emergence application method against several harmful plants selected from the group ALOMY=Alopecurus myosuroides, ECHCG=Echinochloa crus-galli, SETVI=Setaria viridis, ABUTH=Abutilon theophrasti, AMARE=Amaranthus retroflexus, PHBPU=Pharbitis purpurea, POLCO=Polygonum convolvulus, VIOTR=Viola tricolor and VERPE=Veronica persica.
2. Herbicidal Post-Emergence Action
Seeds of monocotyledonous and dicotyledonous weeds and crop plants were placed in sandy loam in wood-fibre pots, covered with soil and cultivated in a greenhouse under good growth conditions. 2 to 3 weeks after sowing, the test plants were treated at the one-leaf stage, where the compounds (G) according to the invention, formulated in the form of wettable powders (WP), were applied by spraying as aqueous suspension or emulsion at a water application rate of 6001/ha (converted) with the addition of 0.2% of wetting agent to the green parts of the plants. After the test plants had been kept in the greenhouse under optimum growth conditions for about 3 weeks, the activity of the preparations was rated visually in comparison to untreated controls in percent (%): For example, 100% activity=the plants have died, 50% herbicidal activity or damage=the plants have been reduced by 50% or the plant mass has been reduced by 50%, 0% activity=like control plants.
Compounds (G) according to the invention such as, for example, the compounds No. I-9, I-10, I-11, I-13, I-16, I-17, I-20, I-21, I-23, I-24, I-25, I-26, I-27, I-28, I-29, I-30, I-31, I-32, I-33, I-34, I-35, I-36, I-37, I-38, I-39, I-40, I-41, I-44, I-46, I-48, I-53, I-86, I-96, I-103, I-104, I-107, I-109, I-111, I-120, I-127, I-168, I-186, I-209, I-227, I-250, I-254, I-258, I-268, I-291, I-332, I-350, I-373, I-391, I-414, I-432, I-455, I-473, I-495, I-497, I-504, I-506, I-513, I-515, I-516, I-517, I-518, I-524, I-527, I-528, I-534, I-535, I-540, I-541, II-5, II-8, II-9, II-10, II-13, II-14, II-15, II-22, II-28, II-29, II-35, II-36, II-50, II-55, II-56, II-57, II-63, II-64, II-70, II-71, II-77, II-78, II-84, II-85, II-91, II-92, II-98, II-99, II-105, II-106, II-111, II-112, II-113, II-119, II-120, II-126, II-127, II-133, II-134, II-140, II-141, II-147, II-148, II-155, II-168, II-183, II-189, II-196, II-204, II-211, II-217, II-224, II-225, II-232, II-233, II-248, II-249, II-250, II-251, II-255, II-256, II-257, II-258, II-259, II-260, II-261, II-262, II-264, II-265, II-266, II-279, II-281, II-282, II-283, II-284, II-286, II-287, II-288, II-289, II-290, II-292, II-293, II-294, II-295, II-297, II-299, II-300, II-301, II-302, II-303, II-304, II-306, II-307, II-308, II-309, II-311, II-312, II-313, II-314, II-315, II-316, II-317, II-318, II-320, II-321, II-326, II-327, II-329, II-330, II-332, II-334, II-335, II-337, II-338, II-340, II-341, II-342, II-346, II-347, II-348, II-349, II-350, II-351, II-352, II-353, II-354, II-355, II-356, II-357, II-358, II-359, II-360, II-361, II-362, II-363, II-364, II-365, II-366, II-367, II-369, II-374, II-376, II-379, II-380, II-382, II-385, II-386, II-387, II-388, II-389, II-390, II-392, II-393, II-394, II-395, II-398, II-399, II-400, II-401, II-402, II-403, II-405, II-417, II-419, II-420, II-422, II-424, II-425, II-426, II-427, II-428, II-429, II-430, II-437, II-439, III-19, III-32, III-42, III-43, III-46, III-52, III-62, III-85, III-86, III-88, III-89, III-92, III-93, III-96, IV-2, IV-3, IV-4, IV-5, IV-6, IV-7, IV-9, IV-12, IV-19, IV-23, V-8, V-9, V-10, V-11, V-12 and V-16 from the above Tables 1 to 5, have good herbicidal efficacy (70% to 100% activity) against a plurality of harmful plants at an application rate of 320 g or less of active substance per hectare when applied by the pre-emergence method, in particular against against one, two, three, four, five, six, seven, eight, nine, ten or more, or even all of the harmful plants selected from the group consisting of ALOMY, AVEFA, ECHCG, LOLMU, SETVI, ABUTH, AMARE, MATIN, PHBPU, POLCO, STEME, VIOTR and VERPE.
What was determined was the respective herbicidal activity, in each case at the same point in time after application of the formulation in question, i.e. the damage to the respective harmful plant in % compared to untreated control plants.
The compounds No. 1-9, I-20, I-23, I-25, I-26, I-32, I-33, I-35, I-36, I-38, I-86, I-104, I-109, I-209, I-227, II-22, II-29, II-50, II-57, II-70, II-71, II-78, II-84, II-85, II-91, II-92, II-98, II-99, II-105, II-106, II-112, II-113, II-119, II-120, II-126, II-127, II-133, II-140, II-147, II-148, II-183, II-196, II-211, II-217, II-225, V-8, V-9 and V-10 showed excellent activity (90-100%) against several harmful plants when applied by the post-emergence method at an application rate of 320 g of active substance per hectare, and showed very good activity (80-100%) against several harmful plants when applied by the post-emergence method at an application rate of 80 g of active substance per hectare, in particular against two, three, four or more harmful plants selected from the group consisting of ALOMY, AVEFA, ECHCG, LOLMU, SETVI, ABUTH, AMARE, MATIN, PHBPU, POLCO, STEME, VIOTR and VERPE.
Similarly, the compounds No. 1-495, I-497, I-506, I-515, I-517, I-524, I-527, I-528, I-534, I-535, I-540, I-541, II-28, II-35, II-56, II-63, II-77, II-233, II-248, II-249, II-251, II-255, II-256, II-257, II-258, II-259, II-260, II-261, II-262, II-264, II-265, II-266, II-281, II-282, II-283, II-284, II-286, II-287, II-288, II-289, II-290, II-292, II-293, II-294, II-295, II-297, II-299, II-300, II-301, II-302, II-303, II-304, II-306, II-307, II-308, II-309, II-311, II-312, II-313, II-314, II-315, II-316, II-317, II-318, II-320, II-321, II-326, II-327, II-329, II-330, II-332, II-334, II-335, II-337, II-338, II-340, II-341, II-342, II-346, II-347, II-348, II-349, II-350, II-351, II-352, II-355, II-356, II-357, II-358, II-359, II-360, II-361, II-362, II-363, II-366, II-367, II-374, II-376, II-379, II-380, II-382, II-386, II-387, II-392, II-393, II-394, II-398, II-399, II-400, II-402, II-417, II-419, II-420, II-422, II-424, II-425, II-427, II-428, II-429, II-430, II-437, II-439, III-85, III-89, III-92, III-93, III-96, V-11 and V-16 showed excellent activity (90-100%) against several harmful plants when applied by the post-emergence method at an application rate of 320 g of active substance per hectare, and showed very good activity (80-100%) against several harmful plants when applied by the post-emergence method at an application rate of 80 g of active substance per hectare, in particular against two, three, four or more harmful plants selected from the group consisting of ALOMY, AVEFA, ECHCG, LOLMU, SETVI, ABUTH, AMARE, MATIN, PHBPU, POLCO, STEME, VIOTR and VERPE. The compounds according to the invention displayed particularly good herbicidal activity in post-emergence application method against several harmful plants selected from the group ECHCG=Echinochloa crus-galli, SETVI=Setaria viridis, ABUTH=Abutilon theophrasti, AMARE=Amaranthus retroflexus, PHBPU=Pharbitis purpurea, POLCO=Polygonum convolvulus, STEME=Stellaria media, VIOTR=Viola tricolor and VERPE=Veronica persica, in some cases with a particular pronounced herbicidal activity against ABUTH, AMARE, PHBPU, POLCO, VIOTR and VERPE.
3. Herbicidal Action and Crop Plant Compatibility
In further trials in the greenhouse, seeds of crop plants are placed in pots in sandy loam soil, covered with soil and cultivated under good growth conditions and treated by the pre-emergence method and scored analogously to the harmful plants mentioned in above section (C) examples 1 and 2, respectively.
3.1 The results showed that the compounds according to the invention did not cause significant damage when applied by the pre-emergence method at the same application rates as mentioned above to monocotyledonous crops, such as
ORYSA=Oryza sativa (common rice)
TRZAS=Triticum aestivum (spring) (summer wheat)
ZEAMX=Zea mays (maize)
BRSNW=Brassica napus subsp. napus (winter) (winter oilseed rape)
Here, the observed damage to the respective useful plants was within the acceptable range and was generally assessed as low (generally in a range from 0 to 10%).
3.2 The results showed that the compounds according to the invention did not cause significant damage when applied by the post-emergence method at the same application rates as mentioned above to monocotyledonous crops, such as those mentioned in above section (C) 3.1.
Here, the observed damage to the respective useful plants was within the acceptable range and was generally assessed as low (generally in a range from 0 to 20%).
| Number | Date | Country | Kind |
|---|---|---|---|
| 14199545.6 | Dec 2014 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2015/080713 | 12/21/2015 | WO | 00 |
