Patent Application
20080103049
The present invention relates to benzoyl-substituted serineamides of the formula I
in which the variables are as defined below:
Moreover, the invention relates to processes and intermediates for preparing compounds of the formula I, to compositions comprising them and to the use of these derivatives or of the compositions comprising them for controlling harmful plants.
Benzoyl-substituted serineamides having pharmaceutical activity which carry a tetrazolyl radical in the β-position are described, inter alia, in JP 03/294253.
Also known from the literature, for example from WO 03/066576, are herbicidally active phenylalanine derivatives which are unsubstituted in the β-position or may carry un-substituted or halogen-substituted alkyl, alkenyl or alkynyl radicals.
However, the herbicidal properties of the prior-art compounds and/or their compatibility with crop plants are not entirely satisfactory. Accordingly, it is an object of the present invention to provide novel, in particular herbicidally active, compounds having improved properties.
We have found that this object is achieved by the benzoyl-substituted serineamides of the formula I and their herbicidal action.
Furthermore, we have found herbicidal compositions which comprise the compounds I and have very good herbicidal action. Moreover, we have found processes for preparing these compositions and methods for controlling unwanted vegetation using the compounds I.
Depending on the substitution pattern, the compounds of the formula I comprise two or more centers of chirality, in which case they are present as enantiomers or diastereomer mixtures. The invention provides both the pure enantiomers or diastereomers and their mixtures.
The compounds of the formula I may also be present in the form of their agriculturally useful salts, the nature of the salt generally being immaterial. Suitable salts are, in general, the cations or the acid addition salts of those acids whose cations and anions, respectively, have no adverse effect on the herbicidal action of the compounds I.
Suitable cations are in particular the ions of the alkali metals, preferably lithium, sodium and potassium, of the alkaline earth metals, preferably calcium and magnesium, and of the transition metals, preferably manganese, copper, zinc and iron, and also ammonium, where, if desired, 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, furthermore phosphonium ions, sulfonium ions, preferably tri(C1-C4-alkyl)sulfonium, and sulfoxonium ions, preferably tri(C1-C4alkyl)sulfoxonium.
Anions of useful acid addition salts are primarily chloride, bromide, fluoride, hydrogensulfate, sulfate, dihydrogenphosphate, hydrogenphosphate, nitrate, bicarbonate, carbonate, hexafluorosilicate, hexafluorophosphate, benzoate, and the anions of C1-C4-alkanoic acids, preferably formate, acetate, propionate and butyrate.
The organic moieties mentioned for the substituents R1-R11 or as radicals on phenyl, aryl, heteroaryl or heterocyclyl rings are collective terms for individual enumerations of the specific group members. All hydrocarbon chains, i.e. all alkyl, alkylsilyl, alkenyl, alkynyl, cyanoalkyl, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, haloalkoxy, alkoxyalkyl, alkoxyalkoxyalkyl, alkylcarbonyl, alkenylcarbonyl, alkynylcarbonyl, alkoxycarbonyl, alkenyloxycarbonyl, alkynyloxycarbonyl, alkylamino, alkylsulfonylamino, haloalkylsulfonylamino, alkylalkoxycarbonylamino, alkylaminocarbonyl, alkenylaminocarbonyl, alkynylaminocarbonyl, alkylsulfonylaminocarbonyl, dialkylaminocarbonyl, N-alkenyl-N-alkylaminocarbonyl, N-alkynyl-N-alkylaminocarbonyl, N-alkoxy-N-alkylaminocarbonyl, N-alkenyl-N-alkoxyaminocarbonyl, N-alkynyl-N-alkoxyaminocarbonyl, dialkylaminothiocarbonyl, alkylcarbonylalkyl, alkoximinoalkyl, N-(alkylamino)iminoalkyl, N(dialkylamino)iminoalkyl, phenylalkyl, phenylcarbonylalkyl, N-alkyl-N-phenylaminocarbonyl, phenylalkylcarbonyl, arylalkyl, heterocyclylalkyl, heterocyclylcarbonylalkyl, N-alkyl-N-heterocyclylaminocarbonyl, heterocyclylalkylcarbonyl, alkylthio and alkylcarbonyloxy moieties may be straight-chain or branched.
Unless indicated otherwise, halogenated substituents preferably carry one to five identical or different halogen atoms. The term halogen denotes in each case fluorine, chlorine, bromine or iodine.
Examples of other meanings are:
C1-C6-alkoxy and also the alkoxy moieties of hydroxycarbonyl-C1-C6-alkoxy, C1-C6-alkoxycarbonyl-C1-C6-alkoxy, N—(C1-C6-alkoxy)-N—(C1-C6-alkyl)aminocarbonyl, N—(C3-C6-alkenyl)-N—(C1-C6-alkoxy)aminocarbonyl, N—(C3-C6-alkynyl)-N—(C1-C6-alkoxy)aminocarbonyl and C1-C6-alkoxyimino-C1-C6-alkyl: C1-C4-alkoxy as mentioned above, and also, for example, pentoxy, 1-methylbutoxy, 2-methylbutoxy, 3-methoxylbutoxy, 1,1-dimethylpropoxy, 1,2-dimethylpropoxy, 2,2-dimethylpropoxy, 1-ethylpropoxy, hexoxy, 1-methylpentoxy, 2-methylpentoxy, 3-methylpentoxy, 4-methylpentoxy, 1,1-dimethylbutoxy, 1,2-dimethylbutoxy, 1,3-dimethylbutoxy, 2,2-dimethylbutoxy, 2,3-dimethylbutoxy, 3,3-dimethylbutoxy, 1-ethylbutoxy, 2-ethylbutoxy, 1,1,2-trimethylpropoxy, 1,2,2-trimethylpropoxy, 1-ethyl-1-methylpropoxy and 1-ethyl-2-methylpropoxy;
All phenyl and aryl rings or heterocyclyl and heteroaryl radicals and all phenyl components in phenyl-C1-C6-alkyl, phenylcarbonyl, phenylcarbonyl-C1-C6-alkyl, phenoxycarbonyl, phenylaminocarbonyl, phenylsulfonylaminocarbonyl, N—(C1-C6-alkyl)-N-phenylaminocarbonyl and phenyl-C1-C6-alkylcarbonyl, all aryl components in aryl(C1-C4-alkyl), all heteroaryl components in mono- or bicyclic heteroaryl and all heterocyclyl components in heterocyclyl-C1-C6-alkyl, heterocyclylcarbonyl, heterocyclylcarbonyl-C1-C6-alkyl, heterocyclyloxycarbonyl, heterocyclylaminocarbonyl, heterocyclylsulfonylaminocarbonyl, N—(C1-C6-alkyl)-N-heterocyclylaminocarbonyl and heterocyclyl-C1-C6-alkylcarbonyl are, unless indicated otherwise, preferably unsubstituted or carry one to three halogen atoms and/or one nitro group, one cyano radical and/or one or two methyl, trifluoromethyl, methoxy or trifluoromethoxy substituents.
In a particular embodiment, the variables of the benzoyl-substituted serineamides of the formula I are as defined below, these definitions being, both on their own and in combination with one another, particular embodiments of the compounds of the formula I:
Preference is given to the benzoyl-substituted serineamides of the formula I in which
Particular preference is given to the benzoyl-substituted serineamides of the formula I in which Het is Het-1 to Het-6
where the arrow indicates the point of attachment and
Preference is given to the benzoyl-substituted serineamides of the formula I in which
Preference is likewise given to the benzoyl-substituted serineamides of the formula I in which
Preference is likewise given to the benzoyl-substituted serineamides of the formula I in which
Preference is likewise given to the benzoyl-substituted serineamides of the formula I in which
Preference is likewise given to the benzoyl-substituted serineamides of the formula I in which
Preference is likewise given to the benzoyl-substituted serineamides of the formula I in which
R8 is C1-C6-alkyl or C1-C6-haloalkyl;
Preference is likewise given to the benzoyl-substituted serineamides of the formula I in which
cyano, hydroxyl, C3-C6-cycloalkyl, C1-C4-alkoxy, C1-C4-alkylthio, di-(C1-C4-alkyl)amino, C1-C4-alkylcarbonyl, hydroxycarbonyl, C1-C4-alkoxycarbonyl, aminocarbonyl, C1-C4-alkylaminocarbonyl, di-(C1-C4-alkyl)aminocarbonyl or C1-C4-alkylcarbonyloxy;
Preference is likewise given to the benzoyl-substituted serineamides of the formula I in which
cyano, hydroxyl, C3-C6-cycloalkyl, C1-C4-alkoxy, C1-C4-alkylthio, di-(C1-C4-alkyl)amino, C1-C4-alkylcarbonyl, hydroxycarbonyl, C1-C4-alkoxycarbonyl, aminocarbonyl, C1-C4-alkylaminocarbonyl, di-(C1-C4-alkyl)aminocarbonyl or C1-C4-alkylcarbonyloxy; or
Preference is likewise given to the benzoyl-substituted serineamides of the formula I in which
Preference is likewise given to the benzoyl-substituted serineamides of the formula I in which
Preference is likewise given to the benzoyl-substituted serineamides of the formula I in which
Particular preference is given to the benzoyl-substituted serineamides of the formula I in which
Most preference is given to the compounds of the formula I.a.1 (corresponds to formula I where Het=Het-1, R1=CF3, R2, R3, R4, R5, R6, R7 and R10=H; R8═CH3), in particular to the compounds of the formulae I.a.1.1 to I.a.1.192 of Table 1, where the definitions of the variables R1 to R14 are of particular importance for the compounds according to the invention not only in combination with one another, but in each case also on their own.
Most preference is likewise given to the compounds of the formula I.a.2, in particular to the compounds of the formulae I.a.2.1 to I.a.2.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that R2 is fluorine.
Most preference is likewise given to the compounds of the formula I.a.3, in particular to the compounds of the formulae I.a.3.1 to I.a.3.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that R3 is fluorine.
Most preference is likewise given to the compounds of the formula I.a.4, in particular to the compounds of the formulae I.a.4.1 to I.a.4.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that R4 is fluorine.
Most preference is likewise given to the compounds of the formula I.a.5, in particular to the compounds of the formulae I.a.5.1 to I.a.5.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that R2 is chlorine.
Most preference is likewise given to the compounds of the formula I.a.6, in particular to the compounds of the formulae I.a.6.1 to I.a.6.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that R3 is chlorine.
Most preference is likewise given to the compounds of the formula I.a.7, in particular to the compounds of the formulae I.a.7.1 to I.a.7.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that R3 and R4 are fluorine.
Most preference is likewise given to the compounds of the formula I.a.8, in particular to the compounds of the formulae I.a.8.1 to I.a.8.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that R1 is chlorine and R2 is CF3.
Most preference is likewise given to the compounds of the formula I.a.9, in particular to the compounds of the formulae I.a.9.1 to I.a.9.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that R1 and R2 are chlorine.
Most preference is likewise given to the compounds of the formula I.a.10, in particular to the compounds of the formulae I.a.10.1 to I.a.10. 192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that R1 and R3 are chlorine.
Most preference is likewise given to the compounds of the formula I.b.1, in particular to the compounds of the formulae I.b.1.1 to I.b.1.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-2.
Most preference is likewise given to the compounds of the formula I.b.2, in particular to the compounds of the formulae I.b.2.1 to I.b.2.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-2 and R2 is fluorine.
Most preference is likewise given to the compounds of the formula I.b.3, in particular to the compounds of the formulae I.b.3.1 to I.b.3.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-2 and R3 is fluorine.
Most preference is likewise given to the compounds of the formula I.b.4, in particular to the compounds of the formulae I.b.4.1 to I.b.4.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-2 and R4 is fluorine.
Most preference is likewise given to the compounds of the formula I.b.5, in particular to the compounds of the formulae I.b.5.1 to I.b.5.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-2 and R2 is chlorine.
Most preference is likewise given to the compounds of the formula I.b.6, in particular to the compounds of the formulae I.b.6.1 to I.b.6.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-2 and R3 is chlorine.
Most preference is likewise given to the compounds of the formula I.b.7, in particular to the compounds of the formulae I.b.7.1 to I.b.7.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-2 and R3 and R4 are fluorine.
Most preference is likewise given to the compounds of the formula I.b.8, in particular to the compounds of the formulae I.b.8.1 to I.b.8.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-2 and R1 is chlorine and R2 is CF3.
Most preference is likewise given to the compounds of the formula I.b.9, in particular to the compounds of the formulae I.b.9.1 to I.b.9.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-2 and R1 and R2 are chlorine.
Most preference is likewise given to the compounds of the formula I.b.10, in particular to the compounds of the formulae I.b.10.1 to I.b.10.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-2 and R1 and R3 are chlorine.
Most preference is likewise given to the compounds of the formula I.c.1, in particular to the compounds of the formulae I.c.1.1 to I.c.1.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-3.
Most preference is likewise given to the compounds of the formula I.c.2, in particular to the compounds of the formulae I.c.2.1 to I.c.2.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-3 and R2 is fluorine.
Most preference is likewise given to the compounds of the formula I.c.3, in particular to the compounds of the formulae I.c.3.1 to I.c.3.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-3 and R3 is fluorine.
Most preference is likewise given to the compounds of the formula I.c.4, in particular to the compounds of the formulae I.c.4.1 to I.c.4.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-3 and R4 is fluorine.
Most preference is likewise given to the compounds of the formula I.c.5, in particular to the compounds of the formulae I.c.5.1 to I.c.5.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-3 and R2 is chlorine.
Most preference is likewise given to the compounds of the formula I.c.6, in particular to the compounds of the formulae I.c.6.1 to I.c.6.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-3 and R3 is chlorine.
Most preference is likewise given to the compounds of the formula I.c.7, in particular to the compounds of the formulae I.c.7.1 to I.c.7.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-3 and R3 and R4 are fluorine.
Most preference is likewise given to the compounds of the formula I.c.8, in particular to the compounds of the formulae I.c.8.1 to I.c.8.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-3 and R1 is chlorine and R2 is CF3.
Most preference is likewise given to the compounds of the formula I.c.9, in particular to the compounds of the formulae I.c.9.1 to I.c.9.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-3 and R1 and R2 are chlorine.
Most preference is likewise given to the compounds of the formula I.c.10, in particular to the compounds of the formulae I.c.10.1 to I.c.10.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-3 and R1 and R3 are chlorine.
Most preference is likewise given to the compounds of the formula I.d.1, in particular to the compounds of the formulae I.d.1.1 to I.d.1.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-4.
Most preference is likewise given to the compounds of the formula I.d.2, in particular to the compounds of the formulae I.d.2.1 to I.d.2.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-4 and R2 is fluorine.
Most preference is likewise given to the compounds of the formula I.d.3, in particular to the compounds of the formulae I.d.3.1 to I.d.3.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-4 and R3 is fluorine.
Most preference is likewise given to the compounds of the formula I.d.4, in particular to the compounds of the formulae I.d.4.1 to I.d.4.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-4 and R4 is fluorine.
Most preference is likewise given to the compounds of the formula I.d.5, in particular to the compounds of the formulae I.d.5.1 to I.d.5.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-4 and R2 is chlorine.
Most preference is likewise given to the compounds of the formula I.d.6, in particular to the compounds of the formulae I.d.6.1 to I.d.6.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-4 and R3 is chlorine.
Most preference is likewise given to the compounds of the formula I.d.7, in particular to the compounds of the formulae I.d.7.1 to I.d.7.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-4 and R3 and R4 are fluorine.
Most preference is likewise given to the compounds of the formula I.d.8, in particular to the compounds of the formulae I.d.8.1 to I.d.8.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-4 and R1 is chlorine and R2 is CF3.
Most preference is likewise given to the compounds of the formula I.d.9, in particular to the compounds of the formulae I.d.9.1 to I.d.9.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-4 and R1 and R2 are chlorine.
Most preference is likewise given to the compounds of the formula I.d.10, in particular to the compounds of the formulae I.d.10.1 to I.d.10.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-4 and R1 and R3 are chlorine.
Most preference is likewise given to the compounds of the formula I.e.1, in particular to the compounds of the formulae I.e.1.1 to I.e.1.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-5.
Most preference is likewise given to the compounds of the formula I.e.2, in particular to the compounds of the formulae I.e.2.1 to I.e.2.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-5 and R2 is fluorine.
Most preference is likewise given to the compounds of the formula I.e.3, in particular to the compounds of the formulae I.e.3.1 to I.e.3.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-5 and R3 is fluorine.
Most preference is likewise given to the compounds of the formula I.e.4, in particular to the compounds of the formulae I.e.4.1 to I.e.4.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-5 and R4 is fluorine.
Most preference is likewise given to the compounds of the formula I.e.5, in particular to the compounds of the formulae I.e.5.1 to I.e.5.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-5 and R2 is chlorine.
Most preference is likewise given to the compounds of the formula I.e.6, in particular to the compounds of the formulae I.e.6.1 to I.e.6.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-5 and R3 is chlorine.
Most preference is likewise given to the compounds of the formula I.e.7, in particular to the compounds of the formulae I.e.7.1 to I.e.7.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-5 and R3 and R4 are fluorine.
Most preference is likewise given to the compounds of the formula I.e.8, in particular to the compounds of the formulae I.e.8.1 to I.e.8.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-5 and R1 is chlorine and R2 is CF3.
Most preference is likewise given to the compounds of the formula I.e.9, in particular to the compounds of the formulae I.e.9.1 to I.e.9.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-5 and R1 and R2 are chlorine.
Most preference is likewise given to the compounds of the formula I.e.10, in particular to the compounds of the formulae I.e.10.1 to I.e.10.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-5 and R1 and
Most preference is likewise given to the compounds of the formula I.f.1, in particular to the compounds of the formulae I.f.1.1 to I.f.1.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-6.
Most preference is likewise given to the compounds of the formula I.f.2, in particular to the compounds of the formulae I.f.2.1 to I.f.2.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-6 and R2 is fluorine.
Most preference is likewise given to the compounds of the formula I.f.3, in particular to the compounds of the formulae I.f.3.1 to I.f.3.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-6 and R3 is fluorine.
Most preference is likewise given to the compounds of the formula I.f.4, in particular to the compounds of the formulae I.f.4.1 to I.f.4.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-6 and R4 is fluorine.
Most preference is likewise given to the compounds of the formula I.f.5, in particular to the compounds of the formulae I.f.5.1 to I.f.5.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-6 and R2 is chlorine.
Most preference is likewise given to the compounds of the formula I.f.6, in particular to the compounds of the formulae I.f.6.1 to I.f.6.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-6 and R3 is chlorine.
Most preference is likewise given to the compounds of the formula I.f.7, in particular to the compounds of the formulae I.f.7.1 to I.f.7.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-6 and R3 and R4 are fluorine.
Most preference is likewise given to the compounds of the formula I.f.8, in particular to the compounds of the formulae I.f.8.1 to I.f.8.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-6 and R1 is chlorine and R2 is CF3.
Most preference is likewise given to the compounds of the formula I.f.9, in particular to the compounds of the formulae I.f.9.1 to I.f.9.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-6 and R1 and R2 are chlorine.
Most preference is likewise given to the compounds of the formula I.f.10, in particular to the compounds of the formulae I.f.10.1 to I.f.10.192, which differ from the corresponding compounds of the formulae I.a.1.1 to I.a.1.192 in that Het is Het-6 and R1 and R3 are chlorine.
The benzoyl-substituted serineamides of the formula I can be obtained by different routes, for example by the following processes:
Serine derivatives of the formula V are initially reacted with benzoic acids/benzoic acid derivatives of the formula IV to give the corresponding benzoyl derivatives of the formula III which are then reacted with amines of the formula II to give the desired benzoyl-substituted serineamides of the formula I:
The reaction of the serine derivatives of the formula V with benzoic acids/benzoic acid derivatives of the formula IV where L2 is hydroxyl to give benzoyl derivatives of the formula III is carried out in the presence of an activating reagent and a base, usually at temperatures of from 0° C. to the boiling point of the reaction mixture, preferably from 0° C. to 110° C., particularly preferably at room temperature, in an inert organic solvent (cf. Bergmann, E. D.; et al., J Chem Soc 1951, 2673; Zhdankin, V. V.; et al., Tetrahedron Lett. 2000, 41 (28), 5299-5302; Martin, S. F. et al., Tetrahedron Lett.1998, 39 (12), 1517-1520; Jursic, B. S. et al., Synth Commun 2001, 31 (4), 555-564; Albrecht, M. et al., Synthesis 2001, (3), 468-472; Yadav, L. D. S. et al., Indian J. Chem B. 41(3), 593-595 (2002); Clark, J. E. et al., Synthesis (10), 891-894 (1991)].
Suitable activating reagents are condensing agents, such as, for example, polystyrenebound dicyclohexylcarbodiimide, diisopropylcarbodiimide, carbonyldiimidazole, chloroformic esters, such as methyl chloroformate, ethyl chloroformate, isopropyl chloroformate, isobutyl chloroformate, sec-butyl chloroformate or allyl chloroformate, pivaloyl chloride, polyphosphoric acid, propanephosphonic anhydride, bis(2-oxo-3-oxazolidinyl)phosphoryl chloride (BOPCl) or sulfonyl chlorides, such as methanesulfonyl chloride, toluenesulfonyl chloride or benzenesulfonyl chloride.
Suitable solvents are aliphatic hydrocarbons, such as pentane, hexane, cyclohexane and mixtures of C5-C8-alkanes, aromatic hydrocarbons, such as benzene, toluene, o-, m- and p-xylene, halogenated hydrocarbons, such as methylene chloride, chloroform and chlorobenzene, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran (THF), nitriles, such as acetonitrile and propionitrile, ketones, such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, and also dimethyl sulfoxide, dimethylformamide (DMF), dimethylacetamide (DMA) and N-methylpyrrolidone (NMP), or else in water; particular preference is given to methylene chloride, THF and water.
It is also possible to use mixtures of the solvents mentioned.
Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydroxides, such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide, alkali metal and alkaline earth metal oxides, such as lithium oxide, sodium oxide, calcium oxide and magnesium oxide, alkali metal and alkaline earth metal hydrides, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride, alkali metal and alkaline earth metal carbonates, such as lithium carbonate, potassium carbonate and calcium carbonate, and also alkali metal bicarbonates, such as sodium bicarbonate, moreover organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine, N-methylmorpholine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to sodium hydroxide, triethylamine and pyridine.
The bases are generally employed in equimolar amounts. However, they can also be used in excess or, if appropriate, as solvent.
The starting materials are generally reacted with one another in equimolar amounts. It may be advantageous to use an excess of IV, based on V.
The reaction mixtures are worked up in a customary manner, for example by mixing with water, separating the phases and, if appropriate, chromatographic purification of the crude products. Some of the intermediates and end products are obtained in the form of viscous oils which are purified or freed from volatile components under reduced pressure and at moderately elevated temperatures. If the intermediates and end products are obtained as solids, purification can also be carried out by recrystallization or digestion.
The reaction of the serine derivatives of the formula V with benzoic acids/benzoic acid derivatives of the formula IV where L2 is halogen, C1-C6-alkylcarbonyl, C1-C6-alkoxycarbonyl, C1-C4-alkylsulfonyl, phosphoryl or isoureyl to give benzoyl derivatives of the formula III is carried out in the presence of a base, usually at temperatures of from 0° C. to the boiling point of the reaction mixture, preferably at from 0° C. to 100° C., particularly preferably at room temperature, in an inert organic solvent [cf. Bergmann, E. D.; et al., J Chem Soc 1951, 2673; Zhdankin, V. V.; et al., Tetrahedron Lett. 2000, 41 (28), 5299-5302; Martin, S. F. et al., Tetrahedron Lett.1998, 39 (12), 1517-1520; Jursic, B. S. et al., Synth Commun 2001, 31 (4), 555-564; Albrecht, M. et al., Synthesis 2001, (3), 468-472; Yadav, L. D. S. et al., Indian J. Chem B. 41(3), 593-595 (2002); Clark, J. E. et al., Synthesis (10), 891-894 (1991)].
Suitable solvents are aliphatic hydrocarbons, such as pentane, hexane, cyclohexane and mixtures of C5-C8-alkanes, aromatic hydrocarbons, such as benzene, toluene, o-, m- and p-xylene, halogenated hydrocarbons, such as methylene chloride, chloroform and chlorobenzene, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran (THF), nitriles, such as acetonitrile and propionitrile, ketones, such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, and also dimethyl sulfoxide, dimethylformamide (DMF), dimethylacetamide (DMA) and N-methylpyrrolidone (NMP), or else in water; particular preference is given to methylene chloride, THF and water.
It is also possible to use mixtures of the solvents mentioned.
Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydroxides, such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide, alkali metal and alkaline earth metal oxides, such as lithium oxide, sodium oxide, calcium oxide and magnesium oxide, alkali metal and alkaline earth metal hydrides, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride, alkali metal and alkaline earth metal carbonates, such as lithium carbonate, potassium carbonate and calcium carbonate, and also alkali metal bicarbonates, such as sodium bicarbonate, moreover organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine, N-methylmorpholine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to sodium hydroxide, triethylamine and pyridine.
The bases are generally employed in equimolar amounts. However, they can also be used in excess or, if appropriate, as solvent.
The starting materials are generally reacted with one another in equimolar amounts. It may be advantageous to use an excess of IV, based on V.
Work-up and isolation of the products can be carried out in a manner known per se.
It is, of course, also possible to initially react the serine derivatives of the formula V in an analogous manner with amines of the formula II to give the corresponding amides which are then reacted with benzoic acids/benzoic acid derivatives of the formula IV to give the desired benzoyl-substituted serineamides of the formula I.
The serine derivatives of the formula V (for example where L1=hydroxyl or C1-C6-alkoxy) required for preparing the benzoyl derivatives of the formula III are known from the literature, even in enantiomerically and diastereomerically pure form, or they can be prepared in accordance with the literature cited:
The benzoic acids/benzoic acid derivatives of the formula IV required for preparing the benzoyl derivatives of the formula III are commercially available or can be prepared analogously to procedures known from the literature from the corresponding halide by a Grignard reaction [for example A. Mannschuk et al., Angew. Chem. 100, 299 (1988)].
The reaction of the benzoyl derivatives of the formula III where L1=hydroxyl or salts thereof with amines of the formula II to give the desired benzoyl-substituted serineamides of the formula I is carried out in the presence of an activating reagent and, if appropriate, in the presence of a base, usually at temperatures of from 0° C. to the boiling point of the reaction mixture, preferably at from 0° C. to 100° C., particularly preferably at room temperature, in an inert organic solvent [cf. Perich, J. W., Johns, R. B., J. Org. Chem. 53 (17), 4103-4105 (1988); Somlai, C. et al., Synthesis (3), 285-287 (1992); Gupta, A. et al., J. Chem. Soc. Perkin Trans. 2, 1911 (1990); Guan et al., J. Comb. Chem. 2, 297 (2000)].
Suitable activating reagents are condensing agents, such as, for example, polystyrenebound dicyclohexylcarbodiimide, diisopropylcarbodiimide, carbonyldiimidazole, chloroformic esters, such as methyl chloroformate, ethyl chloroformate, isopropyl chloroformate, isobutyl chloroformate, sec-butyl chloroformate or allyl chloroformate, pivaloyl chloride, polyphosphoric acid, propanephosphonic anhydride, bis(2-oxo-3-oxazolidinyl)phosphoryl chloride (BOPCl) or sulfonyl chlorides, such as methanesulfonyl chloride, toluenesulfonyl chloride or benzenesulfonyl chloride.
Suitable solvents are aliphatic hydrocarbons, such as pentane, hexane, cyclohexane and mixtures of C5-C8-alkanes, aromatic hydrocarbons, such as benzene, toluene, o-, m- and p-xylene, halogenated hydrocarbons, such as methylene chloride, chloroform and chlorobenzene, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran (THF), nitriles, such as acetonitrile and propionitrile, ketones, such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, alcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, and also dimethyl sulfoxide, dimethylformamide (DMF), dimethylacetamide (DMA) and N-methylpyrrolidone (NMP), or else in water; particular preference is given to methylene chloride, THF, methanol, ethanol and water.
It is also possible to use mixtures of the solvents mentioned.
Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydroxides, such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide, alkali metal and alkaline earth metal oxides, such as lithium oxide, sodium oxide, calcium oxide and magnesium oxide, alkali metal and alkaline earth metal hydrides, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride, alkali metal and alkaline earth metal carbonates, such as lithium carbonate, potassium carbonate and calcium carbonate, and also alkali metal bicarbonates, such as sodium bicarbonate, moreover organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine, N-methylmorpholine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to sodium hydroxide, triethylamine, ethyldiisopropylamine, N-methylmorpholine and pyridine.
The bases are generally employed in catalytic amounts; however, they can also be employed in equimolar amounts, in excess or, if appropriate, as solvent.
The starting materials are generally reacted with one another in equimolar amounts. It may be advantageous to use an excess of II, based on III.
Work-up and isolation of the products can be carried out in a manner known per se.
The reaction of the benzoyl derivatives of the formula III where L1=C1-C6-alkoxy with amines of the formula II to give the desired benzoyl-substituted serineamides of the formula I is usually carried out at temperatures of from 0° C. to the boiling point of the reaction mixture, preferably from 0° C. to 10° C., particularly preferably at room temperature, in an inert organic solvent, if appropriate in the presence of a base [cf. Kawahata, N. H. et al., Tetrahedron Lett. 43 (40), 7221-7223 (2002); Takahashi, K. et al., J. Org. Chem. 50 (18), 3414-3415 (1985); Lee, Y. et al., J. Am. Chem. Soc.121 (36), 8407-8408 (1999)].
Suitable solvents are aliphatic hydrocarbons, such as pentane, hexane, cyclohexane and mixtures of C5-C8-alkanes, aromatic hydrocarbons, such as benzene, toluene, o-, m- and p-xylene, halogenated hydrocarbons, such as methylene chloride, chloroform and chlorobenzene, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran (THF), nitriles, such as acetonitrile and propionitrile, ketones, such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, alcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, and also dimethyl sulfoxide, dimethylformamide (DMF), dimethylacetamide (DMA) and N-methylpyrrolidone (NMP), or else in water; particular preference is given to methylene chloride, THF, methanol, ethanol and water.
It is also possible to use mixtures of the solvents mentioned.
The reaction may, if appropriate, take place in the presence of a base. Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydroxides, such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide, alkali metal and alkaline earth metal oxides, such as lithium oxide, sodium oxide, calcium oxide and magnesium oxide, alkali metal and alkaline earth metal hydrides, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride, alkali metal and alkaline earth metal carbonates, such as lithium carbonate, potassium carbonate and calcium carbonate, and also alkali metal bicarbonates, such as sodium bicarbonate, moreover organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine, N-methylmorpholine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to sodium hydroxide, triethylamine, ethyldiisopropylamine, N-methylmorpholine and pyridine.
The bases are generally employed in catalytic amounts; however, they can also be employed in equimolar amounts, in excess or, if appropriate, as solvent.
The starting materials are generally reacted with one another in equimolar amounts. It may be advantageous to use an excess of II, based on III.
Work-up and isolation of the products can be carried out in a manner known per se.
The amines of the formula II required for preparing the benzoyl-substituted serineamides of the formula I are commercially available.
Benzoyl derivatives of the formula III where R9=hydrogen can also be obtained by condensing acylated glycine derivatives of the formula VIII where the acyl group may be a cleavable protective group, such as benzyloxycarbonyl (cf. VIIIa where Σ=benzyl) or tert-butyloxycarbonyl (cf. VIIIa where Σ=tert-butyl), with heterocyclylcarbonyl compounds VII to give the corresponding aldol products VI. The protective group is then cleaved and the resulting serine derivatives of the formula V where R9=hydrogen are acylated using benzoic acids/benzoic acid derivatives of the formula IV.
Analogously, it is also possible to convert an acylated glycine derivative of the formula VIII where the acyl group is a substituted benzoyl radical (cf. VIIIb) in the presence of a base with a heterocyclylcarbonyl compound VII into the benzoyl derivative III where R9=hydrogen:
L1 is a nucleophilically displaceable leaving group, for example hydroxyl or C1-C6-alkoxy.
L2 is a nucleophilically displaceable leaving group, for example hydroxyl, halogen, C1-C6-alkylcarbonyl, C1-C6-alkoxycarbonyl, C1-C4-alkylsulfonyl, phosphoryl or isoureyl.
The reaction of the glycine derivatives VIII with heterocyclyl compounds VII to give the corresponding aldol product VI or benzoyl derivative III where R9=hydrogen is usually carried out at temperatures of from −100° C. to the boiling point of the reaction mixture, preferably at from −80° C. to 20° C., particularly preferably at from −80° C. to −20° C., in an inert organic solvent in the presence of a base [cf. J.-F. Rousseau et al., J. Org. Chem. 63, 2731-2737 (1998)].
Suitable solvents are aliphatic hydrocarbons, such as pentane, hexane, cyclohexane and mixtures of C5-C8-alkanes, aromatic hydrocarbons, such as toluene, o-, m- and p-xylene, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, and also dimethyl sulfoxide, dimethylformamide and dimethylacetamide, particularly preferably diethyl ether, dioxane and tetrahydrofuran.
It is also possible to use mixtures of the solvents mentioned.
Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydrides, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride, alkali metal azides, such as lithium hexamethyldisilazide, organometallic compounds, in particular alkali metal alkyls, such as methyllithium, butyllithium and phenyllithium, and also alkali metal and alkaline earth metal alkoxides, such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, potassium tert-pentoxide and dimethoxymagnesium, moreover organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to sodium hydride, lithium hexamethyldisilazide and lithium diisopropylamide.
The bases are generally employed in equimolar amounts; however, they can also be used catalytically, in excess or, if appropriate, as solvents.
The starting materials are generally reacted with one another in equimolar amounts. It may be advantageous to employ an excess of base and/or heterocyclylcarbonyl compounds VII, based on the glycine derivatives VIII.
Work-up and isolation of the products can be carried out in the manner known per se.
The glycine derivatives of the formula VIII required for preparing the compounds I are commercially available, known from the literature [for example H. Pessoa-Mahana et al., Synth. Comm. 32, 1437 (2002] or can be prepared in accordance with the literature cited.
The protective group is cleaved off by methods known from the literature, giving serine derivatives of the formula V where R9=hydrogen [cf. J.-F. Rousseau et al., J. Org. Chem. 63, 2731-2737 (1998)); J. M. Andres, Tetrahedron 56, 1523 (2000)]; in the case of Σ=benzyl by hydrogenolysis, preferably using hydrogen and Pd/C in methanol; in the case of Σ=tert-butyl using acid, preferably hydrochloric acid in dioxane.
The reaction of the serine derivatives V where R9=hydrogen with benzoic acids/benzoic acid derivatives IV to give benzoyl derivatives III where R9=hydrogen is usually carried out analogously to the reaction of the serine derivatives of the formula V with benzoic acids/benzoic acid derivatives of the formula IV to give benzoyl derivatives III mentioned in process A.
Analogously to process A, the benzoyl derivatives of the formula III where R9=hydrogen can then be reacted with amines of the formula II to give the desired benzoyl-substituted serineamides of the formula I where R9=hydrogen which can then be derivatized with compounds of the formula IX to give benzoyl-substituted serineamides of the formula I [cf., for example, Yokokawa, F. et al., Tetrahedron Lett. 42 (34), 5903-5908 (2001); Arrault, A. et al., Tetrahedron Lett. 43(22), 4041-4044 (2002)].
It is also possible to initially derivatize the benzoyl derivatives of the formula III where R9=hydrogen with compounds of the formula IX to give further benzoyl derivatives of the formula III [cf., for example, Troast, D. et al., Org. Lett. 4 (6), 991-994 (2002); Ewing W. et al., Tetrahedron Lett., 30 (29), 3757-3760 (1989); Paulsen, H. et al., Liebigs Ann. Chem. 565 (1987)], followed by reaction with amines of the formula II analogously to process A, giving the desired benzoyl-substituted serineamides of the formula I:
L1 is a nucleophilically displaceable leaving group, for example hydroxyl or C1-C6-alkoxy.
L3 is a nucleophilically displaceable leaving group, for example halogen, hydroxyl, or C1-C6-alkoxy.
The reaction of the benzoyl derivatives of the formula III (where, if appropriate, R9=hydrogen) with amines of the formula II to give benzoyl-substituted serineamides of the formula I (where, if appropriate, R9=hydrogen) is usually carried out analogously to the reaction of the benzoyl derivatives of the formula III with amines of the formula II described in process A.
The reaction of the benzoyl derivatives of the formula III where R9=hydrogen or of the benzoyl-substituted serineamides of the formula I where R9=hydrogen with compounds of the formula IX to give benzoyl derivatives of the formula III or benzoyl-substituted serineamides of the formula I is usually carried out at temperatures of from 0° C. to 100° C., preferably from 10° C. to 50° C., in an inert organic solvent in the presence of a base [cf., for example, Troast, D. et al., Org. Lett. 4 (6), 991-994 (2002); Ewing W. et al., Tetrahedron Lett., 30 (29), 3757-3760 (1989); Paulsen, H. et al., Liebigs Ann. Chem. 565 (1987)].
Suitable solvents are aliphatic hydrocarbons, such as pentane, hexane, cyclohexane and mixtures of C5-C8-alkanes, aromatic hydrocarbons, such as toluene, o-, m- and p-xylene, halogenated hydrocarbons, such as methylene chloride, chloroform and chlorobenzene, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, nitriles, such as acetonitrile and propionitrile, ketones, such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, alcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, and also dimethyl sulfoxide, dimethylformamide and dimethylacetamide, particularly preferably dichloromethane, tert-butyl methyl ether, dioxane and tetrahydrofuran.
It is also possible to use mixtures of the solvents mentioned.
Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydroxides, such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide, alkali metal and alkaline earth metal oxides, such as lithium oxide, sodium oxide, calcium oxide and magnesium oxide, alkali metal and alkaline earth metal hydrides, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride, alkali metal amides, such as lithium amide, sodium amide and potassium amide, alkali metal and alkaline earth metal carbonates, such as lithium carbonate, potassium carbonate and calcium carbonate, and also alkali metal bicarbonates, such as sodium bicarbonate, organometallic compounds, in particular alkali metal alkyls, such as methyllithium, butyllithium and phenyllithium, alkylmagnesium halides, such as methylmagnesium chloride, and also alkali metal and alkaline earth metal alkoxides, such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, potassium tert-pentoxide and dimethoxymagnesium, moreover organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to sodium hydroxide, sodium hydride and triethylamine.
The bases are generally employed in equimolar amounts; however, they can also be employed catalytically, in excess or, if appropriate, as solvents.
The starting materials are generally reacted with one another in equimolar amounts. It may be advantageous to use an excess of base and/or IX, based on III or 1.
Work-up and isolation of the products can be carried out in a manner known per se.
The required compounds of the formula VIII are commercially available.
Benzoyl derivatives of the formula III where R9=hydrogen can also be obtained by initially acylating aminomalonyl compounds of the formula XI with benzoic acids/benzoic acid derivatives of the formula IV to give the corresponding N-acylaminomalonyl compounds of the formula X, followed by condensation with a heterocyclylcarbonyl compound of the formula VII with decarboxylation:
L1 is a nucleophilically displaceable leaving group, for example hydroxyl or C1-C6-alkoxy.
L2 is a nucleophilically displaceable leaving group, for example hydroxyl, halogen, C1-C6-alkylcarbonyl, C1-C6-alkoxycarbonyl, C1-C6-alkylsulfonyl, phosphoryl or isoureyl.
L4 is a nucleophilically displaceable leaving group, for example hydroxyl or C1-C6-alkoxy.
The acylation of the aminomalonyl compounds of the formula XI with benzoic acids/benzoic acid derivatives of the formula IV to give the corresponding N-acylaminomalonyl compounds of the formula X is usually carried out analogously to the reaction, mentioned in process A, of the serine derivatives of the formula V with benzoic acids/benzoic acid derivatives of the formula IV to give the corresponding benzoyl derivatives of the formula III.
The reaction of the N-acylaminomalonyl compounds of the formula X with heterocyclylcarbonyl compounds of the formula VII to give benzoyl derivatives of the formula III where R9=hydrogen is usually carried out at temperatures of from 0° C. to 100° C., preferably from 10° C. to 50° C., in an inert organic solvent in the presence of a base [cf., for example, U.S. Pat. No. 4,904,674; Hellmann, H. et al., Liebigs Ann. Chem. 631, 175-179 (1960)].
If L4 in the N-acylaminomalonyl compounds of the formula X is C1-C6-alkoxy, it is advantageous to initially convert L4 by ester hydrolysis [for example Hellmann, H. et al., Liebigs Ann. Chem. 631, 175-179 (1960)] into a hydroxyl group.
Suitable solvents are aliphatic hydrocarbons, such as pentane, hexane, cyclohexane and mixtures of C5-C8-alkanes, aromatic hydrocarbons, such as toluene, o-, m- and p-xylene, halogenated hydrocarbons, such as methylene chloride, chloroform and chlorobenzene, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, nitriles, such as acetonitrile and propionitrile, ketones, such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, alcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, and also dimethyl sulfoxide, dimethylformamide and dimethylacetamide, particularly preferably diethyl ether, dioxane and tetrahydrofuran.
It is also possible to use mixtures of the solvents mentioned.
Suitable bases are, in general, inorganic compounds, such as alkali metal and alkaline earth metal hydroxides, such as lithium hydroxide, sodium hydroxide, potassium hydroxide and calcium hydroxide, alkali metal and alkaline earth metal oxides, such as lithium oxide, sodium oxide, calcium oxide and magnesium oxide, alkali metal and alkaline earth metal hydrides, such as lithium hydride, sodium hydride, potassium hydride and calcium hydride, alkali metal amides, such as lithium amide, sodium amide and potassium amide, alkali metal and alkaline earth metal carbonates, such as lithium carbonate, potassium carbonate and calcium carbonate, and also alkali metal bicarbonates, such as sodium bicarbonate, organometallic compounds, in particular alkali metal alkyls, such as methyllithium, butyllithium and phenyllithium, alkylmagnesium halides, such as methylmagnesium chloride, and also alkali metal and alkaline earth metal alkoxides, such as sodium methoxide, sodium ethoxide, potassium ethoxide, potassium tert-butoxide, potassium tert-pentoxide and dimethoxymagnesium, moreover organic bases, for example tertiary amines, such as trimethylamine, triethylamine, diisopropylethylamine and N-methylpiperidine, pyridine, substituted pyridines, such as collidine, lutidine and 4-dimethylaminopyridine, and also bicyclic amines. Particular preference is given to triethylamine and diisopropylethylamine.
The bases are generally employed in catalytic amounts; however, they can also be used in equimolar amounts, in excess or, if appropriate, as solvents.
The starting materials are generally reacted with one another in equimolar amounts. It may be advantageous to employ an excess of base, based on X.
Work-up and isolation of the products can be carried out in a manner known per se.
According to process A or B mentioned above, the resulting benzoyl derivatives of the formula III where R9=hydrogen can then be converted into the desired benzoyl-substituted serineamides of the formula I.
The required aminomalonyl compounds of the formula XI are commercially available and/or known from the literature [for example U.S. Pat. No. 4,904,674; Hellmann, H. et al., Liebigs Ann. Chem. 631, 175-179 (1960)], or they can be prepared in accordance with the literature cited.
The required heterocyclic compounds of the formula VII are commercially available.
Benzoyl derivatives of the formula III where R9 and R10=hydrogen can also be obtained by initially acylating keto compounds of the formula XIII with benzoic acids/benzoic acid derivatives of the formula IV to give the corresponding N-acyl keto compounds of the formula XII, followed by reduction of the keto group [Girard A, Tetrahedron Lett. 37(44), 7967-7970 (1996); Nojori R., J. Am. Chem. Soc.111(25), 9134-9135 (1989); Schmidt U., Synthesis (12),1248-1254 (1992); Bolhofer, A.; J. Am. Chem. Soc.75, 4469 (1953)]:
L1 is a nucleophilically displaceable leaving group, for example hydroxyl or C1-C6-alkoxy.
L2 is a nucleophilically displaceable leaving group, for example hydroxyl, halogen, C1-C6-alkylcarbonyl, C1-C6-alkoxycarbonyl, C1-C6-alkylsulfonyl, phosphoryl or isoureyl. The acylation of the keto compounds of the formula XIII with benzoic acids/benzoic acid derivatives of the formula IV to give N-acyl keto compounds of the formula XII is usually carried out analogously to the reaction, mentioned in process A, of the serine derivatives of the formula V with benzoic acids/benzoic acid derivatives of the formula IV to give the corresponding benzoyl derivatives of the formula III.
The keto compounds of the formula XIII required for preparing the benzoyl derivatives of the formula III where R9 and R10=hydrogen are known from the literature [WO 02/083111; Boto, A. et al., Tetrahedron Letters 39 (44), 8167-8170 (1988); von Geldern, T. et al., J. of Med. Chem. 39(4), 957-967 (1996); Singh, J. et al., Tetrahedron Letters 34 (2), 211-214 (1993); ES 2021557; Maeda, S: et al., Chem. & Pharm. Bull. 32 (7), 2536-2543 (1984); Ito, S. et al., J. of Biol. Chem. 256 (15), 7834-4783 (1981); Vinograd, L. et al., Zhurnal Organicheskoi Khimii 16 (12), 2594-2599 (1980); Castro, A. et al., J. Org. Chem. 35 (8), 2815-2816 (1970); JP 02-172956; Suzuki, M. et al., J. Org. Chem. 38 (20), 3571-3575 (1973); Suzuki, M. et al, Synthetic Communications 2 (4), 237-242 (1972)] or can be prepared according to the literature cited.
The reduction of the N-acyl keto compounds of the formula XII to benzoyl derivatives of the formula III where R9 and R10=hydrogen is usually carried out at temperatures of from 0° C. to 100° C., preferably from 20° C. to 80° C., in an inert organic solvent in the presence of a reducing agent.
Suitable solvents are aliphatic hydrocarbons, such as pentane, hexane, cyclohexane and mixtures of C5-C8-alkanes, aromatic hydrocarbons, such as toluene, o-, m- and p-xylene, halogenated hydrocarbons, such as methylene chloride, chloroform and chlorobenzene, ethers, such as diethyl ether, diisopropyl ether, tert-butyl methyl ether, dioxane, anisole and tetrahydrofuran, nitriles, such as acetonitrile and propionitrile, ketones, such as acetone, methyl ethyl ketone, diethyl ketone and tert-butyl methyl ketone, alcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol, and also dimethyl sulfoxide, dimethylformamide and dimethylacetamide, particularly preferably toluene, methylene chloride or tert-butyl methyl ether.
It is also possible to use mixtures of the solvents mentioned.
Suitable reducing agents are, for example, sodium borohydride, zinc borohydride, sodium cyanoborohydride, lithium triethylborohydride (Superhydrid®), lithium tri-secbutylborohydride (L-Selectrid®), lithium aluminum hydride or borane [cf., for example, WO 00/20424; Marchi, C. et al., Tetrahedron 58 (28), 5699 (2002); Blank, S. et al., Liebigs Ann. Chem. (8), 889-896 (1993); Kuwano, R. et al., J. Org. Chem. 63 (10), 3499-3503 (1998); Clariana, J. et al., Tetrahedron 55 (23), 7331-7344 (1999)].
Furthermore, the reduction can also be carried out in the presence of hydrogen and a catalyst. Suitable catalysts are, for example, [Ru(BINAP)C[2] or Pd/C [cf. Noyori, R. et al., J. Am. Chem. Soc.111 (25), 9134-9135 (1989); Bolhofer, A. et al., J. Am. Chem. Soc.75, 4469 (1953)].
In addition, the reduction can also be carried out in the presence of a microorganism. The suitable microorganism is, for example, Saccharomyces rouxii [cf. Soukup, M. et al., Helv. Chim. Acta 70, 232 (1987)].
The N-acyl keto compounds of the formula XII and the reducing agent in question are generally reacted with one another in equimolar amounts. It may be advantageous to employ an excess of reducing agent, based on XII.
Work-up and isolation of the products can be carried out in the manner known per se.
The resulting benzoyl derivatives of the formula III where R9 and R10=hydrogen can then, according to the processes A and B mentioned above, be converted into the desired benzoyl-substituted serineamides of the formula I.
Benzoyl derivatives of the formula III
where Het, R1 to R6 and R9 and R10 are as defined above and L1 is hydroxyl or C1-C6-alkoxy also form part of the subject-matter of the present invention.
The particularly preferred embodiments of the intermediates with respect to the variables correspond to those of the radicals Het, R1 to R6 and R9 and R10 of the formula I.
Particular preference is given to benzoyl derivatives of the formula III in which
The examples below serve to illustrate the invention.
Under an atmosphere of protective gas, 20.2 g (0.180 mol) of potassium tert-butoxide were suspended in THF and cooled with a mixture of acetone and dry ice. 21.8 g (0.082 mol) of ethyl N-(diphenylmethylene)glycinate, dissolved in THF, were then added dropwise. After 40 min, the solution was transferred into a cooled dropping funnel and added dropwise to a cooled solution of 11.9 g (0.082 mol) of thiophene-3-carbonyl chloride in THF. After 1 h of stirring, the reaction mixture was allowed to warm to 0° C. The mixture was hydrolyzed using 10% strength hydrochloric acid, and stirring was continued. The solvents were then removed and the residue was taken up in water and washed with methyl tert-butyl ether. The aqueous phase was removed and concentrated, methanol was added to the residue and the mixture was filtered. Concentration of the filtrate gave 22.0 g (97% of theory) of the title compound as a colorless oil. 1H-NMR (DMSO): δ=9.2 (br, 3H); 8.90 (s, 1H); 7.70 (m, 1H); 7.65 (m, 1H); 6.05 (s, 1H); 4.25 (m, 2H); 1.15 (t, 3H).
15.0 g (0.060 mol) of ethyl rac-2-amino-3-oxo-3-thiophen-3-ylpropionate hydrochloride were dissolved in methylene chloride, and 18.2 g (0.096 mol) of triethylamine were added. At 0° C., 13.6 g (0.060 mol) of 4-fluoro-2-trifluoromethylbenzoyl chloride, dissolved in methylene chloride, were added dropwise. The mixture was stirred at room temperature for 1 h, and 5% strength hydrochloric acid was then added. The organic phase was separated off, washed and dried, and the solvent was removed. This gave 13.8 g (57% of theory) of the title compound as colorless crystals. 1H-NMR (DMSO): δ=9.65 (d, 1H); 8.65 (s, 1H); 7.5-7.8 (m, 5H); 6.20 (d, 1H); 4.15 (m, 2H); 1.15 (t, 3H).
Initially, a catalyst mixture was prepared from 390 mg of dichloro(p-cymene)ruthenium(II) dimer (RuCl2Cy) and 690 mg of R-BINAP in methylene chloride and ethanol by heating the mixture at 50° C. for 1 h and then removing the solvents. 13.0 g (0.0322 mol) of ethyl rac-2-(4-fluoro-2-trifluoromethylbenzoylamino)-3-oxo-3-thiophen-3-ylpropionate were then dissolved in methylene chloride. The solution was degassed in an ultrasonic bath, and 1.0 g of the catalyst mixture was added. The reaction mixture was heated at 50° C. and under a hydrogen pressure of 100 bar for 100 h. Removal of the solvents and chromatographic purification (silica gel column, cyclohexane/ethyl acetate) gave 9.5 g (73% of theory) of the title compound as colorless crystals.
1H-NMR (DMSO): δ=8.80 (d, 1H); 7.6 (m, 2H); 7.40 (m, 1H); 7.35 (s, 1H); 7.25 (q, 1H); 7.15 (d, 1H); 5.80 (d, 1H); 5.25 (t, 1H); 4.70 (q, 1H); 4.2 (m, 2H); 1.20 (t, 3H).
9.50 g (0.0234 mol) of ethyl (2S,3R)-threo-2-(4-fluoro-2-trifluoromethylbenzoylamino)-3-hydroxy-3-thiophen-3-ylpropionate were dissolved in 200 ml of methanol. At room temperature, methylamine gas was introduced over a period of 3 h. Removal of the solvents and trituration of the residue with diisopropyl ether/pentane 1:1 gave 8.0 g (88% of theory) of the title compound as colorless crystals (m.p. 190° C.).
0.50 g (0.0013 mol) of (2S,3R)-threo-4-fluoro-N-(2-hydroxy-1-methylcarbamoyl-2-thiophen-3-ylethyl)-2-trifluoromethylbenzamide was dissolved in methylene chloride. At 0° C., 0.25 g (0.00144 mol) of N-Boc-glycine, 0.063 g (0.00052 mol) of dimethylaminopyridine and 0.28 g (0.0015 mol) of 1,3-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride were added. The solution was stirred at RT for 14 h and then washed with water, 10% strength hydrochloric acid and saturated NaHCO3 solution. The organic phase was then dried and concentrated. Stirring of the residue with pentane/diisopropyl ether gave 0.17 g (24% of theory) of the title compound as a colorless powder (m.p. 100° C.).
8.0 g (0.0205 mol) of (2S,3R)-threo-4-fluoro-N-(2-hydroxy-1-methylcarbamoyl-2-thiophen-3-ylethyl)-2-trifluoromethylbenzamide were dissolved in dimethylformamide, 3.60 g (0.0524 mol) of imidazole were added and 3.66 g (0.0243 mol) of triethylchlorosilane were added dropwise. The solution was stirred at 40° C. for 6 h, stirred into water and extracted with MTBE/ethyl acetate 1:1. The organic phase was dried and concentrated. Chromatographic purification (silica gel column, cyclohexane/ethyl acetate) gave 5.8 g (58% of theory) of the title compound as a colorless powder (m.p. 104° C.).
5.00 g (23.6 mmol) of diethyl aminomalonate hydrochloride were dissolved in 2M NaHCO3 solution and dioxane. At 0° C., 6.30 g (28.0 mmol) of 4-fluoro-2-trifluoromethylbenzoyl chloride were then added dropwise. The mixture was stirred at RT for 14 h and then concentrated and extracted with ethyl acetate. The organic phase was dried and concentrated. This gave 9.50 g (99% of theory) of the title compound as a colorless powder.
1H-NMR (DMSO): δ=9.55 (d, 1H); 7.7 (m, 3H); 5.30 (d, 1H); 4.20 (m, 4H); 1.20 (t, 6H).
9.00 g (24.6 mmol) of diethyl 2-(4-fluoro-2-trifluoromethylbenzoylamino)malonate were dissolved in dioxane. 30 ml of 1 M NaOH were then added dropwise. The solution was stirred for 14 h and then concentrated slightly and extracted with diethyl ether. Ethyl acetate was then added to the aqueous phase, and 15 ml of 1 M H2SO4 were added dropwise at 0° C. The organic phase was removed and the aqueous phase was extracted. The combined organic phases were then dried, and the solvent was removed. This gave 7.80 g (94% of theory) of the title compound as a colorless powder. 1H-NMR (DMSO): 9.30 (d, 1H); 7.7 (m, 3H); 5.10 (d, 1H); 4.10 (m, 2H); 1.20 (t, 3H).
1.99 g (5.90 mmol) of monoethyl rac-2-(4-fluoro-2-trifluoromethylbenzoylamino)malonate were dissolved in THF, and 0.63 g (5.90 mmol) of pyridin-3-aldehyde and 0.60 g (5.90 mmol) of triethylamine were added dropwise. The mixture was then stirred at RT for 14 h. The solvent was then removed, and the residue was taken up in methylene chloride. The reaction mixture was washed with saturated NaHCO3 solution and dried, and the solvent was removed. This gave 0.31 g (13% of theory) of the title compound as a colorless powder.
1H-NMR (DMSO): δ=9.05 (d, 1H); 8.55 (s, 1H); 8.50 (d, 1H); 7.80 (d, 1H); 7.70 (d, 1H); 7.60 (t, 1H); 7.40 (m, 1H); 7.10 (m, 1H); 6.05 (d, 1H); 4.95 (q, 1H); 4.65 (t, 1H); 4.15 (m, 2H); 1.15 (t, 3H).
0.30 g (0.75 mmol) of ethyl rac-erythro-2-(4-fluoro-2-trifluoromethylbenzoylamino)-3-hydroxy-3-pyridin-3-ylpropionate was dissolved in methanol. For a period of 3 h, methylamine was then introduced into the solution. The reaction solution was then concentrated using a rotary evaporator. This gave 0.25 g (87% of theory) of the title compound as a colorless powder which contained about 25% of the threo compound (m.p. 181° C.).
In addition to the above compounds, further benzoyl derivatives of the formula III and benzoyl-substituted serineamides of the formula I which were prepared or are preparable in a manner analogously to the processes described above are listed in Tables 2 and 3 below.
1H-NMR, 400 MHz, DMSO-d6, δ [ppm]
The benzoyl-substituted serineamides of the formula I and their agriculturally useful salts are suitable, both in the form of isomer mixtures and in the form of the pure isomers, as herbicides. The herbicidal compositions comprising compounds of the formula I control vegetation on non-crop areas very efficiently, especially at high rates of application. They act against broad-leaved weeds and grass weeds in crops such as wheat, rice, maize, soya and cotton without causing any significant damage to the crop plants. This effect is mainly observed at low rates of application.
Depending on the application method in question, the compounds of the formula I, or herbicidal compositions comprising them, can additionally be employed in a further number of crop plants for eliminating undesirable plants. Examples of suitable crops are the following:
Allium cepa, Ananas comosus, Arachis hypogaea, Asparagus officinalis, Beta vulgaris spec. altissima, Beta vulgaris spec. rapa, Brassica napus var. napus, Brassica napus var. napobrassica, Brassica rapa var. silvestris, Camellia sinensis, Carthamus tinctorius, Carya illinoinensis, Citrus limon, Citrus sinensis, Coffea arabica (Coffea canephora, Coffea liberica), Cucumis sativus, Cynodon dactylon, Daucus carota, Elaeis guineensis, Fragaria vesca, Glycine max, Gossypium hirsutum, (Gossypium arboreum, Gossypium herbaceum, Gossypium vitifolium), Helianthus annuus, Hevea brasiliensis, Hordeum vulgare, Humulus lupulus, Ipomoea batatas, Juglans regia, Lens culinaris, Linum usitatissimum, Lycopersicon lycopersicum, Malus spec., Manihot esculenta, Medicago sativa, Musa spec., Nicotiana tabacum (N. rustica), Olea europaea, Oryza sativa, Phaseolus lunatus, Phaseolus vulgaris, Picea abies, Pinus spec., Pisum sativum, Prunus avium, Prunus persica, Pyrus communis, Ribes sylvestre, Ricinus communis, Saccharum officinarum, Secale cereale, Solanum tuberosum, Sorghum bicolor (S. vulgare), Theobroma cacao, Trifolium pratense, Triticum aestivum, Triticum durum, Vicia faba, Vitis vinifera and Zea mays.
In addition, the compounds of the formula I may also be used in crops which tolerate the action of herbicides owing to breeding, including genetic engineering methods.
The compounds of the formula I, or the herbicidal compositions comprising them, can be used for example in the form of ready-to-spray aqueous solutions, powders, suspensions, also highly concentrated aqueous, oily or other suspensions or dispersions, emulsions, oil dispersions, pastes, dusts, materials for broadcasting, or granules, by means of spraying, atomizing, dusting, spreading or watering. The use forms depend on the intended purpose; in any case, they should ensure the finest possible distribution of the active ingredients according to the invention.
The herbicidal compositions comprise a herbicidally effective amount of at least one compound of the formula I or an agriculturally useful salt of I, and auxiliaries which are customary for the formulation of crop protection agents.
Suitable as inert auxiliaries are essentially the following:
mineral oil fractions of medium to high boiling point, such as kerosene and diesel oil, furthermore coal tar oils and oils of vegetable or animal origin, aliphatic, cyclic and aromatic hydrocarbons, for example paraffins, tetrahydronaphthalene, alkylated naphthalenes and their derivatives, alkylated benzenes and their derivatives, alcohols such as methanol, ethanol, propanol, butanol and cyclohexanol, ketones such as cyclohexanone, strongly polar solvents, for example amines such as N-methylpyrrolidone, and water.
Aqueous use forms can be prepared from emulsion concentrates, suspensions, pastes, wettable powders or water-dispersible granules by adding water. To prepare emulsions, pastes or oil dispersions, the substrates, either as such or dissolved in an oil or solvent, can be homogenized in water by means of a wetting agent, tackifier, dispersant or emulsifier. Alternatively, it is also possible to prepare concentrates comprising active substance, wetting agent, tackifier, dispersant or emulsifier and, if desired, solvent or oil, which are suitable for dilution with water.
Suitable surfactants (adjuvants) are the alkali metal salts, alkaline earth metal salts and ammonium salts of aromatic sulfonic acids, for example ligno-, phenol-, naphthalene- and dibutylnaphthalenesulfonic acid, and of fatty acids, alkyl- and alkylarylsulfonates, alkyl sulfates, lauryl ether sulfates and fatty alcohol sulfates, and salts of sulfated hexa-, hepta- and octadecanols, and also of fatty alcohol glycol ethers, condensates of sulfonated naphthalene and its derivatives with formaldehyde, condensates of naphthalene or of the naphthalenesulfonic acids with phenol and formaldehyde, polyoxyethylene octylphenol ether, ethoxylated isooctyl-, octyl- or nonylphenol, alkylphenyl or tributylphenyl polyglycol ether, alkylaryl polyether alcohols, isotridecyl alcohol, fatty alcohol/ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl ethers or polyoxypropylene alkyl ethers, lauryl alcohol polyglycol ether acetate, sorbitol esters, lignosulfite waste liquors or methylcellulose.
Powders, materials for broadcasting and dusts can be prepared by mixing or grinding the active substances together with a solid carrier.
Granules, for example coated granules, impregnated granules and homogeneous granules, can be prepared by binding the active ingredients to solid carriers. Solid carriers are mineral earths such as silicas, silica gels, silicates, talc, kaolin, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate, magnesium sulfate and magnesium oxide, ground synthetic materials, fertilizers such as ammonium sulfate, ammonium phosphate, ammonium nitrate and ureas, and products of vegetable origin, such as cereal meal, tree bark meal, wood meal and nutshell meal, cellulose powders, or other solid carriers.
The concentrations of the compounds of the formula I in the ready-to-use preparations can be varied within wide ranges. In general, the formulations comprise approximately from 0.001 to 98% by weight, preferably 0.01 to 95% by weight of at least one active ingredient. The active ingredients are employed in a purity of from 90% to 100%, preferably 95% to 100% (according to NMR spectrum).
The formulation examples below illustrate the preparation of such compositions:
The compounds of the formula I or the herbicidal compositions can be applied pre- or post-emergence. If the active ingredients are less well tolerated by certain crop plants, application techniques may be used in which the herbicidal compositions are sprayed, with the aid of the spraying equipment, in such a way that as far as possible they do not come into contact with the leaves of the sensitive crop plants, while the active ingredients reach the leaves of undesirable plants growing underneath, or the bare soil surface (post-directed, lay-by).
The rates of application of the compound of the formula I are from 0.001 to 3.0, preferably 0.01 to 1.0, kg/ha of active substance (a.s.), depending on the control target, the season, the target plants and the growth stage.
To widen the spectrum of action and to achieve synergistic effects, the benzoyl-substituted serineamides of the formula I may be mixed with a large number of representatives of other herbicidal or growth-regulating active ingredient groups and then applied concomitantly. Suitable components for mixtures are, for example, 1,2,4-thiadiazoles, 1,3,4-thiadiazoles, amides, aminophosphoric acid and its derivatives, aminotriazoles, anilides, (het)aryloxyalkanoic acids and their derivatives, benzoic acid and its derivatives, benzothiadiazinones, 2-(het)aroyl-1,3-cyclohexanediones, hetaryl aryl ketones, benzylisoxazolidinones, meta-CF3-phenyl derivatives, carbamates, quinolinecarboxylic acid and its derivatives, chloroacetanilides, cyclohexenone oxime ether derivatives, diazines, dichloropropionic acid and its derivatives, dihydrobenzofurans, dihydrofuran-3-ones, dinitroanilines, dinitrophenols, diphenyl ethers, dipyridyls, halocarboxylic acids and their derivatives, ureas, 3-phenyluracils, imidazoles, imidazolinones, N-phenyl-3,4,5,6-tetrahydrophthalimides, oxadiazoles, oxiranes, phenols, aryloxy- and hetaryloxyphenoxypropionic esters, phenylacetic acid and its derivatives, 2-phenylpropionic acid and its derivatives, pyrazoles, phenylpyrazoles, pyridazines, pyridinecarboxylic acid and its derivatives, pyrimidyl ethers, sulfonamides, sulfonylureas, triazines, triazinones, triazolinones, triazolecarboxamides and uracils. It may furthermore be beneficial to apply the compounds of the formula I alone or in combination with other herbicides, or in the form of a mixture with other crop protection agents, for example together with agents for controlling pests or phytopathogenic fungi or bacteria. Also of interest is the miscibility with mineral salt solutions, which are employed for treating nutritional and trace element deficiencies. Non-phytotoxic oils and oil concentrates may also be added.
The herbicidal activity of the benzoyl-substituted serineamides of the formula I was demonstrated by the following greenhouse experiments:
The culture containers used were plastic flowerpots containing loamy sand with approximately 3.0% of humus as the substrate. The seeds of the test plants were sown separately for each species.
For the pre-emergence treatment, the active ingredients, which had been suspended or emulsified in water, were applied directly after sowing by means of finely distributing nozzles. The containers were irrigated gently to promote germination and growth and subsequently covered with transparent plastic hoods until the plants had rooted. This cover causes uniform germination of the test plants, unless this has been impaired by the active ingredients.
For the post-emergence treatment, the test plants were first grown to a height of 3 to 15 cm, depending on the plant habit, and only then treated with the active ingredients which had been suspended or emulsified in water. For this purpose, the test plants were either sown directly and grown in the same containers, or they were first grown separately as seedlings and transplanted into the test containers a few days prior to treatment. The rate of application for the post-emergence treatment was 1.0 or 0.5 kg/ha of a.s. (active substance).
Depending on the species, the plants were kept at 10-25° C. or 20-35° C. The test period extended over 2 to 4 weeks. During this time, the plants were tended, and their response to the individual treatments was evaluated.
Evaluation was carried out using a scale from 0 to 100. 100 means no emergence of the plants, or complete destruction of at least the aerial parts, and 0 means no damage, or normal course of growth.
The plants used in the greenhouse experiments belonged to the following species:
Amaranthus retroflexus
Chenopodium album
Setaria viridis
At application rates of 0.5 kg/ha, the compound 3.10 (Table 3) showed very good post-emergence action against the unwanted plants pig weed, lambsquarters and green foxtail.
Furthermore, compound 3.11 (Table 3), applied by the post-emergence method, effected, at application rates of 1.00 kg/ha, very good control of the harmful plants pig weed, lambsquarters and green foxtail.
The activity of compound 3.13 (Table 3), applied by the post-emergence method, at application rates of 1.00 kg/ha, against the unwanted plants pig weed, lambsquarters and green foxtail was very good.
At application rates of 0.5 kg/ha, the compounds 3.21, 3.28, 3.36, 3.41, 3.53, 3.56, 3.57, 3.59, 3.63, 3.65, 3.66, 3.69, 3.71, 3.74 and 3,75 (Table 3) showed very good post-emergence action against the unwanted plants pig weed, lambsquarters and green foxtail.
Furthermore, compounds 3.14, 3.20, 3.35, 3.39, 3.40 and 3.79 (Table 3), applied by the post-emergence method, effected, at application rates of 1.0 kg/ha, very good control of the harmful plants pig weed, lambsquarters and green foxtail.
| Number | Date | Country | Kind |
|---|---|---|---|
| 10 2004 045 300.4 | Sep 2004 | DE | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/EP05/09855 | 9/14/2005 | WO | 00 | 3/13/2007 |
