Patent Application
20200054011
The invention relates to the technical field of the herbicides, especially that of the herbicides for selective control of weeds and weed grasses in crops of useful plants.
WO 2015/058519 A1 describes quinazolinedione-6-carbonylcyclohexanediones as herbicides. However, the compounds known from these documents do not always have adequate herbicidal efficacy and/or compatibility with crop plants.
It has now been found that quinazolinedione-6-carbonyl derivatives which differ from the compounds known from the prior art in that they bear other cyclohexanedione radicals than those described in WO 2015/058519 A1 are of particularly good suitability as herbicides.
The present invention thus provides quinazolinedione-6-carbonyl derivatives of the formula (I) and salts thereof
in which
X is nitro, halogen, cyano, formyl, thiocyanato, (C1-C6)-alkyl, (C1-C6)-haloalkyl, (C2-C6)-alkenyl, (C2-C6)-haloalkenyl, (C2-C6)-alkynyl, (C3-C6)-haloalkynyl, (C3-C6)-cycloalkyl, (C3-C6)-halocycloalkyl, (C3-C6)-cycloalkyl-(C1-C6)-alkyl, (C3-C6)-halocycloalkyl-(C1-C6)-alkyl, COR1, OR1, OCOR1, OSO2R2, S(O)nR2, SO2OR1, SO2N(R1)2, NR1SO2R2, NR1COR1, (C1-C6)-alkyl-S(O)nR2, (C1-C6)-alkyl-OR1, (C1-C6)-alkyl-OCOR1, (C1-C6)-alkyl-OSO2R2, (C1-C6)-alkyl-COOR1, (C1-C6)-alkyl-SO2OR1, (C1-C6)-alkyl-CON(R1)2, (C1-C6)-alkyl-SO2N(R1)2, (C1-C6)-alkyl-NR1COR1, (C1-C6)-alkyl-NR1SO2R2 or NR1R2,
W is hydrogen, nitro, halogen, cyano, (C1-C4)-alkyl, (C1-C4)-haloalkyl or (C1-C4)-alkoxy,
R1 is (C1-C10)-alkyl, (C2-C10)-alkenyl, (C2-C10)-alkynyl, halo-(C1-C10)-alkyl, halo-(C2-C10)-alkenyl, halo-(C2-C10)-alkynyl, (C3-C10)-cycloalkyl, halo-(C3-C10)-cycloalkyl, (C1-C4)-alkyl-(C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C6)-alkyl, (C3-C7)-cycloalkyl-(C3-C7)-cycloalkyl, halo-(C3-C7)-cycloalkyl-(C1-C6)-alkyl, (C1-C6)-alkyl-(C3-C7)-cycloalkyl-(C1-C6)-alkyl, (C3-C12)-cycloalkenyl, halo-(C3-C12)-cycloalkenyl, (C1-C6)-alkoxy-(C1-C6)-alkyl, (C1-C6)-alkoxy-(C2-C6)-alkenyl, (C1-C6)-alkyl-(C3-C7)-cycloalkyl, (C1-C6)-alkoxy-(C3-C7)-cycloalkyl, di-(C1-C6)-alkoxy-(C3-C7)-cycloalkyl, (C3-C7)-cycloalkoxy-(C1-C6)-alkyl, (C3-C7)-cycloalkoxy-(C1-C6)-alkoxy-(C1-C6)-alkyl, (C1-C6)-alkoxy-(C1-C6)-alkoxy-(C1-C6)-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C1-C6)-alkylsulfinyl-(C1-C6)-alkyl, (C1-C6)-alkylsulfonyl-(C1-C6)-alkyl, (C1-C6)-alkylamino-(C1-C6)-alkyl, di-(C1-C6)-alkylamino-(C1-C6)-alkyl, halo-(C1-C6)-alkylamino-(C1-C6)-alkyl, (C3-C7)-cycloalkylamino-(C1-C6)-alkyl, (C1-C6)-alkylcarbonyl, halo-(C1-C6)-alkylcarbonyl, (C3-C7)-cycloalkylcarbonyl, (C1-C6)-alkoxycarbonyl, (C3-C7)-cycloalkoxycarbonyl, (C3-C7)-cycloalkyl-(C1-C6)-alkoxycarbonyl, (C1-C6)-alkylaminocarbonyl, di-(C1-C6)-alkylaminocarbonyl, (C3-C7)-cycloalkylaminocarbonyl, cyano-(C1-C6)-alkyl, hydroxy-(C1-C6)-alkyl, (C3-C7)-cycloalkenyl-(C1-C6)-alkyl, halo-(C1-C6)-alkoxy-(C1-C6)-alkyl, (C1-C6)-alkoxyhalo-(C1-C6)-alkyl, halo-(C1-C6)-alkoxyhalo-(C1-C6)-alkyl, halo-(C3-C7)-cycloalkoxy-(C1-C6)-alkyl, (C3-C7)-cycloalkenyloxy-(C1-C6)-alkyl, halo-(C3-C7)-cycloalkenyloxy-(C1-C6)-alkyl, di-(C1-C6)-alkoxy-(C1-C6)-alkyl, (C1-C6)-alkoxy-(C1-C6)-alkylcarbonyl, (C1-C6)-alkoxycarbonyl-(C1-C6)-alkyl, halo-(C1-C6)-alkoxycarbonyl, (C1-C10)-alkoxy, halo-(C1-C10)-alkoxy, (C3-C12)-cycloalkoxy, halo-(C3-C7)-cycloalkoxy, (C3-C7)-cycloalkyl-(C1-C6)-alkoxy, (C2-C12)-alkenyloxy, halo-(C2-C10)-alkenyloxy, (C2-C10)-alkynyloxy, halo-(C3-C10)-alkynyloxy, (C1-C6)-alkoxy-(C1-C6)-alkoxy, (C1-C6)-alkylcarbonyloxy, halo-(C2-C12)-alkylcarbonyloxy, (C3-C7)-cycloalkylcarbonyloxy, (C1-C6)-alkylcarbonyl-(C1-C6)-alkoxy, (C1-C6)-alkylamino, di-(C1-C6)-alkylamino, halo-(C1-C6)-alkylamino, halodi-(C1-C6)-alkylamino, (C3-C12)-cycloalkylamino, (C1-C6)-alkylcarbonylamino, halo-(C1-C6)-alkylcarbonylamino, (C1-C10)-alkylsulfonylamino, halo-(C1-C10)-alkylsulfonylamino, (C3-C7)-cycloalkyl-(C1-C6)-alkylamino, hydroxyl, amino, NHCHO, or
R1 is phenyl, phenylsulfonyl, W1-(phenyl), W1—(O-phenyl), W1—(S-phenyl), W1—(SO2-phenyl), W2—(SO2CH2-phenyl) or W2—(SCH2-phenyl), where the phenyl rings of the eight aforementioned radicals each bear s R3 substituents,
R2 is hydrogen, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C2-C6)-alkenyl, (C2-C6)-haloalkenyl, (C2-C6)-alkynyl, (C2-C6)-haloalkynyl, (C3-C6)-cycloalkyl, (C3-C6)-halocycloalkyl, (C1-C6)-alkyl-O—(C1-C6)-alkyl, (C3-C6)-cycloalkyl-(C1-C6)-alkyl, phenyl, phenyl-(C1-C6)-alkyl, pyridyl or (C1-C6)-alkylpyridyl, where the phenyl or pyridyl rings of the four aforementioned radicals each bear s R3 substituents,
Q is a Q1, Q2, Q3, Q4 or Q5 radical,
Rc1 is hydroxyl or SR4,
Rc2, Rc3, Rc4, Rc5, Rc6 and Rc7 are each independently hydrogen or (C1-C4)-alkyl,
Rp1 is hydrogen, (C1-C6)-alkylsulfonyl, (C1-C4)-alkoxy-(C1-C6)-alkylsulfonyl, or phenylsulfonyl, thiophenyl-2-sulfonyl, benzoyl, benzoyl-(C1-C6)-alkyl or benzyl, each of which is substituted by n identical or different radicals from the group consisting of halogen, (C1-C4)-alkyl and (C1-C4)-alkoxy,
Rp2 is (C1-C4)-alkyl,
Rp3 is hydrogen, (C1-C4)-alkyl, (C3-C8)-cycloalkyl, (C1-C4)-alkyl-(C3-C6)-cycloalkyl or (C3-C6)-halocycloalkyl,
Rn1 is (C1-C4)-alkyl, (C3-C8)-cycloalkyl, (C1-C4)-alkyl-(C3-C8)-cycloalkyl or (C3-C6)-halocycloalkyl,
Rn2 is hydrogen, CO2(C1-C6)-alkyl or S(O)n(C1-C6)-alkyl,
Y1 is an ethylene or vinylene group,
Y2 is O, CO or CH2,
W1 is (C1-C10)-alkylene, (C2-C6)-alkenylene or (C2-C6)-alkynylene,
W2 is (C1-C10)-alkylene,
R3 is halogen, cyano, hydroxyl, amino, nitro, —C(═O)R3a, —C(═O)OR3a,
—C(═O)(NR3a)2, —C(═S)NH2, —C(═O)NHCN, —C(═O)NHOH, —SH, —SO2(NR3a)2, —SO2NHCN, —SO2NHOH, —OCN, —SCN, —SF5, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, halo-(C1-C6)-alkyl, halo-(C2-C6)-alkenyl, halo-(C2-C6)-alkynyl, (C3-C8)-cycloalkyl, halo-(C3-C8)-cycloalkyl, (C1-C6)-alkyl-(C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C6)-alkyl, (C3-C8)-cycloalkenyl, halo-(C3-C8)-cycloalkenyl, (C1-C6)-alkoxy-(C1-C6)-alkyl, (C3-C7)-cycloalkoxy-(C1-C6)-alkyl, (C1-C6)-alkoxy-(C1-C6)-alkoxy-(C1-C6)-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C1-C8)-alkylsulfinyl-(C1-C6)-alkyl, (C1-C8)-alkoxyhalo-(C1-C6)-alkyl, cyano-(C1-C6)-alkyl, hydroxy-(C1-C6)-alkyl, (C1-C6)-alkoxy, halo-(C1-C6)-alkoxy, (C3-C8)-cycloalkoxy, halo-(C3-C8)-cycloalkoxy, (C3-C8)-cycloalkyl-(C1-C6)-alkoxy, (C2-C6)-alkenyloxy, halo-(C2-C6)-alkenyloxy, (C1-C6)-alkoxy-(C1-C6)-alkoxy, (C2-C6)-alkylcarbonyloxy, (C1-C6)-alkylthio, halo-(C1-C6)-alkylthio, (C3-C8)-cycloalkylthio, (C1-C6)-alkylsulfinyl, halo-(C1-C6)-alkylsulfinyl, (C1-C6)-alkylsulfonyl, halo-(C1-C6)-alkylsulfonyl, (C3-C8)-cycloalkylsulfonyl, (C1-C6)-alkylamino, di-(C1-C6)-alkylamino, halo-(C1-C6)-alkylamino, halodi-(C3-C8)-alkylamino or (C3-C8)-cycloalkylamino, or two vicinal R3 radicals together with the two carbon atoms to which they are bonded form a 5- to 7-membered ring which contains v carbon atoms and p identical or different atoms from the group of oxygen, sulfur and nitrogen, and bears t oxo groups,
R3a is hydrogen, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, (C3-C6)-cycloalkyl, (C3-C6)-cycloalkyl-(C1-C6)-alkyl or phenyl,
R4 is (C1-C4)-alkyl, or phenyl substituted by p radicals from the group of halogen, nitro, cyano, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy and (C1-C4)-haloalkoxy,
n is 0, 1 or 2,
p is 0, 1, 2, 3 or 4,
s is 0, 1, 2, 3, 4 or 5,
t is 0, 1, 2, 3 or 4,
v is 2, 3, 4, 5, 6 or 7.
In the formula (I) and all the formulae which follow, alkyl radicals having more than two carbon atoms may be straight-chain or branched. Alkyl radicals are, for example, methyl, ethyl, n-propyl or isopropyl, n-, iso-, t- or 2-butyl, pentyls, hexyls such as n-hexyl, isohexyl and 1,3-dimethylbutyl. Analogously, alkenyl is, for example, 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 and 1-methylbut-2-en-1-yl. Alkynyl is, for example, propargyl, but-2-yn-1-yl, but-3-yn-1-yl, 1-methylbut-3-yn-1-yl. The multiple bond may be in any position in each unsaturated radical. Cycloalkyl is a carbocyclic saturated ring system having three to six carbon atoms, for example cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. Analogously, cycloalkenyl is a monocyclic alkenyl group having three to six carbon ring members, for example cyclopropenyl, cyclobutenyl, cyclopentenyl and cyclohexenyl, where the double bond may be in any position. (C1-C10)-Alkylene is correspondingly a methylene group, an ethylene group, or a propylene, butylene, pentylene, hexylene, heptylene, octylene, nonylene or decylene group, in each case unbranched.
Halogen is fluorine, chlorine, bromine or iodine.
If a group is polysubstituted by radicals, this should be understood to mean that this group is substituted by one or more identical or different radicals selected from the radicals mentioned. The same applies to the formation of ring systems by different atoms and elements. At the same time, the scope of the claims shall exclude those compounds known by the person skilled in the art to be chemically unstable under standard conditions.
Depending on the nature of the substituents and the manner in which they are attached, the compounds of the general formula (I) may be present as stereoisomers. If, for example, one or more asymmetric carbon atoms are present, enantiomers and diastereomers may occur. Stereoisomers likewise occur when n is 1 (sulfoxides). Stereoisomers can be obtained from the mixtures obtained in the preparation by customary separation methods, for example by chromatographic separation processes. It is likewise possible to selectively prepare stereoisomers by using stereoselective reactions with use of optically active starting materials and/or auxiliaries. The invention also relates to all the stereoisomers and mixtures thereof that are encompassed by the general formula (I) but are not defined specifically. Owing to the oxime ether structure, the compounds of the invention may also occur as geometric isomers (E/Z isomers). The invention also relates to all the E/Z isomers and mixtures thereof that are encompassed by the general formula (I) but are not defined specifically.
The compounds of the formula (I) are capable of forming salts. Suitable bases are, for example, organic amines, such as trialkylamines, morpholine, piperidine or pyridine, and also ammonium, alkali metal or alkaline earth metal hydroxides, carbonates and hydrogencarbonates, especially sodium hydroxide and potassium hydroxide, sodium carbonate and potassium carbonate and sodium hydrogencarbonate and potassium hydrogencarbonate. These salts are compounds in which the acidic hydrogen is replaced by an agriculturally suitable cation, for example metal salts, especially alkali metal salts or alkaline earth metal salts, in particular sodium and potassium salts, or else ammonium salts, salts with organic amines or quaternary ammonium salts, for example with cations of the formula [NRR′R″R″′]+ in which R to R″′ each independently of one another represent an organic radical, in particular alkyl, aryl, aralkyl or alkylaryl. Also suitable are alkylsulfonium and alkylsulfoxonium salts, such as (C1-C4)-trialkylsulfonium and (C1-C4)-trialkylsulfoxonium salts.
The compounds of the formula (I) can form salts through adduct formation of a suitable inorganic or organic acid, for example mineral acids such as HCl, HBr, H2SO4, H3PO4 or HNO3, or organic acids, for example carboxylic acids such as formic acid, acetic acid, propionic acid, oxalic acid, lactic acid or salicylic acid or sulfonic acids such as p-toluenesulfonic acid, with a basic group such as amino, alkylamino, dialkylamino, piperidino, morpholino or pyridino. In such a case, these salts will comprise the conjugate base of the acid as the anion.
Preference is given to compounds of the general formula (I) in which X is halogen, (C1-C6)-alkyl, (C1-C6)-haloalkyl, (C2-C6)-alkenyl, (C3-C6)-cycloalkyl, (C3-C6)-halocycloalkyl, OR1, S(O)nR2, SO2N(R1)2, NR1SO2R2, NR1COR1, (C1-C6)-alkyl-S(O)nR2 or (C1-C6)-alkyl-OR1,
W is hydrogen, Cl, MeO, methyl or ethyl,
R1 is (C1-C10)-alkyl, (C2-C10)-alkenyl, (C2-C10)-alkynyl, halo-(C1-C10)-alkyl, halo-(C2-C10)-alkenyl, halo-(C2-C10)-alkynyl, (C3-C10)-cycloalkyl, halo-(C3-C10)-cycloalkyl, (C1-C4)-alkyl-(C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C6)-alkyl, (C1-C6)-alkoxy-(C1-C6)-alkyl, (C1-C6)-alkyl-(C3-C7)-cycloalkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C1-C6)-alkylsulfinyl-(C1-C6)-alkyl, (C1-C6)-alkylsulfonyl-(C1-C6)-alkyl, cyano-(C1-C6)-alkyl, (C1-C10)-alkoxy, halo-(C1-C10)-alkoxy, (C1-C6)-alkoxy-(C1-C6)-alkoxy, (C1-C6)-alkylamino or di-(C1-C6)-alkylamino,
R1 is phenyl bearing s R3 substituents,
R2 is (C1-C4)-alkyl,
Q is a Q1, Q2, Q3, Q4 or Q5 radical,
Rc1 is hydroxyl,
Rc2, Rc3, Rc4, Rc5, Rc6 and Rc7 are each independently hydrogen or methyl,
Rp1 is hydrogen,
Rp2 is (C1-C4)-alkyl,
Rp3 is hydrogen, (C1-C4)-alkyl or cyclopropyl,
Rn1 is cyclopropyl,
Rn2 is hydrogen,
Y1 is an ethylene or vinylene group,
Y2 is CH2,
R3 is halogen, cyano, hydroxyl, amino, nitro, —C(═O)R3a, C(═O)OR3a, —C(═O)(NR3a)2, —C(═S)NH2, —C(═O)NHCN, —C(═O)NHOH, —SH, —SO2NH2, —SO2NHCN, —SO2NHOH, —OCN, —SCN, —SF5, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, halo-(C1-C6)-alkyl, halo-(C2-C6)-alkenyl, halo-(C2-C6)-alkynyl, (C3-C8)-cycloalkyl, halo-(C3-C8)-cycloalkyl, (C1-C6)-alkyl-(C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C6)-alkyl, (C3-C8)-cycloalkenyl, halo-(C3-C8)-cycloalkenyl, (C1-C6)-alkoxy-(C1-C6)-alkyl, (C3-C7)-cycloalkoxy-(C1-C6)-alkyl, (C1-C6)-alkoxy-(C1-C6)-alkoxy-(C1-C6)-alkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C1-C8)-alkylsulfinyl-(C1-C6)-alkyl, (C1-C8)-alkoxyhalo-(C1-C6)-alkyl, cyano-(C1-C6)-alkyl, hydroxy-(C1-C6)-alkyl, (C1-C6)-alkoxy, halo-(C1-C6)-alkoxy, (C3-C8)-cycloalkoxy, halo-(C3-C8)-cycloalkoxy, (C3-C8)-cycloalkyl-(C1-C6)-alkoxy, (C2-C6)-alkenyloxy, halo-(C2-C6)-alkenyloxy, (C1-C6)-alkoxy-(C1-C6)-alkoxy, (C2-C6)-alkylcarbonyloxy, (C1-C6)-alkylthio, halo-(C1-C6)-alkylthio, (C3-C8)-cycloalkylthio, (C1-C6)-alkylsulfinyl, halo-(C1-C6)-alkylsulfinyl, (C1-C6)-alkylsulfonyl, halo-(C1-C6)-alkylsulfonyl, (C3-C8)-cycloalkylsulfonyl, (C1-C6)-alkylamino, di-(C1-C6)-alkylamino, halo-(C1-C6)-alkylamino, halodi-(C1-C8)-alkylamino, (C3-C8)-cycloalkylamino or methylenedioxo,
R3a is hydrogen or (C1-C6)-alkyl,
n is 0, 1 or 2,
s is 0, 1, 2, 3, 4 or 5.
Particular preference is given to compounds of the general formula (I) in which
X is F, Cl, Br, methyl, ethyl, cyclopropyl, trifluoromethyl, methoxy, methoxymethyl, methoxyethoxymethyl, SMe or SO2Me,
W is hydrogen,
R1 is (C1-C10)-alkyl, (C2-C10)-alkenyl, (C2-C10)-alkynyl, halo-(C1-C10)-alkyl, halo-(C2-C10)-alkenyl, halo-(C2-C10)-alkynyl, (C3-C10)-cycloalkyl, halo-(C3-C10)-cycloalkyl, (C1-C4)-alkyl-(C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(C1-C6)-alkyl, (C1-C6)-alkoxy-(C1-C6)-alkyl, (C1-C6)-alkyl-(C3-C7)-cycloalkyl, (C1-C6)-alkylthio-(C1-C6)-alkyl, (C1-C6)-alkylsulfinyl-(C1-C6)-alkyl, (C1-C6)-alkylsulfonyl-(C1-C6)-alkyl, or R1 is phenyl bearing s R3 substituents,
R2 is methyl or ethyl,
Q is a Q1, Q2, Q3, Q4 or Q5 radical,
Rc1 is hydroxyl,
Rc2, Rc3, Rc4, Rc5, Rc6 and Rc7 are each independently hydrogen or methyl,
Rp1 is hydrogen,
Rp2 is (C1-C4)-alkyl,
Rp3 is hydrogen, (C1-C4)-alkyl or cyclopropyl,
Rn1 is cyclopropyl,
Rn2 is hydrogen,
Y1 is an ethylene or vinylene group,
Y2 is CH2,
R3 is halogen, cyano, nitro, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, halo-(C1-C6)-alkyl, (C3-C6)-cycloalkyl, (C1-C6)-alkoxy, halo-(C1-C6)-alkoxy, (C1-C6)-alkoxy-(C1-C6)-alkyl, (C1-C6)-alkylthio, (C1-C6)-alkylsulfinyl, (C1-C6)-alkylsulfonyl, phenyl or methylenedioxo,
s is 0, 1, 2, 3, 4 or 5.
In all the formulae specified hereinafter, the substituents and symbols have the same meaning as described in formula (I), unless defined differently.
Inventive compounds with Q=Q1, Q2, Q3, Q4 or Q5 can be prepared, for example, inter alia, according to Scheme 1 analogously to the methods cited in WO 2009/018925 A1.
The quinazolinedione-6-carbonyl chlorides (II) and their parent quinazolinedione-6-carboxylic acids (III) can be prepared, for example, by the methods described in WO2015058519.
It may be appropriate to alter the sequence of the reaction steps. For instance, benzoic acids bearing a sulfoxide cannot be converted directly to their acid chlorides. One option here is first to prepare the amide at the thioether stage, and then to oxidize the thioether to the sulfoxide.
Collections of compounds of the formula (I) and/or salts thereof which can be synthesized by the abovementioned reactions can also be prepared in a parallelized manner, in which case this may be accomplished in a manual, partly automated or fully automated manner. It is possible, for example, to automate the conduct of the reaction, the workup or the purification of the products and/or intermediates. Overall, this is understood to mean a procedure as described, for example, by D. Tiebes in Combinatorial Chemistry—Synthesis, Analysis, Screening (editor: Giinther Jung), Wiley, 1999, on pages 1 to 34.
For the parallelized conduct of the reaction and workup, it is possible to use a number of commercially available instruments, for example Calypso reaction blocks from Barnstead International, Dubuque, Iowa 52004-0797, USA or reaction stations from Radleys, Shirehill, Saffron Walden, Essex, CB11 3AZ, England, or MultiPROBE Automated Workstations from Perkin Elmer, Waltham, Mass. 02451, USA. For the parallelized purification of compounds of the general formula (I) and salts thereof or of intermediates which occur in the course of preparation, available apparatuses include chromatography apparatuses, for example from ISCO, Inc., 4700 Superior Street, Lincoln, Nebr. 68504, USA.
The apparatuses detailed lead to a modular procedure in which the individual working steps are automated, but manual operations have to be carried out between the working steps. This can be circumvented by using partly or fully integrated automation systems in which the respective automation modules are operated, for example, by robots. Automation systems of this type can be obtained, for example, from Caliper, Hopkinton, Mass. 01748, USA.
The implementation of single or multiple synthesis steps can be supported by the use of polymer-supported reagents/scavenger resins. The specialist literature describes a series of experimental protocols, for example in ChemFiles, Vol. 4, No. 1, Polymer-Supported Scavengers and Reagents for Solution-Phase Synthesis (Sigma-Aldrich).
Aside from the methods described here, compounds of the general formula (I) and salts thereof can be prepared 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 bound to a synthesis resin. Solid-phase-supported synthesis methods are described adequately in the technical literature, for example Barry A. Bunin in “The Combinatorial Index”, Academic Press, 1998 and Combinatorial Chemistry—Synthesis, Analysis, Screening (editor: Giinther Jung), Wiley, 1999. 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. The reactions can be performed, for example, by means of IRORI technology in microreactors from Nexus Biosystems, 12140 Community Road, Poway, CA92064, USA.
Both in the solid and in the liquid phase, the implementation of individual or several synthesis steps may be supported by the use of microwave technology. The specialist literature describes a series of experimental protocols, for example in Microwaves in Organic and Medicinal Chemistry (editor: C. O. Kappe and A. Stadler), Wiley, 2005.
The preparation by the processes described here gives compounds of the formula (I) and salts thereof in the form of substance collections, which are called libraries. The present invention also provides libraries comprising at least two compounds of the formula (I) and salts thereof.
The compounds of the invention have excellent herbicidal efficacy against a broad spectrum of economically important mono- and dicotyledonous annual harmful plants. The active ingredients also act efficiently on perennial weeds which produce shoots from rhizomes, root stocks and other perennial organs and which are difficult to control.
The present invention therefore also provides a method for controlling unwanted plants or for regulating the growth of plants, preferably in plant crops, in which one or more compound(s) of the invention is/are applied to the plants (for example harmful plants such as monocotyledonous or dicotyledonous weeds or unwanted crop plants), the seed (for example grains, seeds or vegetative propagules such as tubers or shoot parts with buds) or the area on which the plants grow (for example the area under cultivation). The compounds of 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 of some representatives of the monocotyledonous and dicotyledonous weed flora which can be controlled by the compounds of the invention are as follows, though there is no intention to restrict the enumeration to particular 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 and 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 and Xanthium.
If the compounds of the invention are applied to the soil surface before germination, either the emergence of the weed seedlings is prevented completely or the weeds grow until they have reached the cotyledon stage, but then they stop growing and ultimately die completely after three to four weeks have passed.
If the active ingredients 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 at the time of application, or they die completely after a certain time, so that in this manner competition by the weeds, which is harmful to the crop plants, is eliminated very early and in a sustained manner.
Although the compounds of the invention have 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, will be damaged to a negligible extent only, if at all, depending on the structure of the particular compound of 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 ornamental plants.
In addition, the compounds of the invention, depending on their particular chemical structure and the application rate deployed, have outstanding growth-regulating properties in crop plants. They intervene in the plants' own metabolism with regulatory effect, and can thus be used for the controlled influencing of plant constituents and to facilitate harvesting, for example by triggering desiccation and stunted growth. In addition, they are also suitable for general control and inhibition of unwanted vegetative growth without killing the plants. Inhibition of vegetative growth plays a major role for many mono- and dicotyledonous crops since, for example, this can reduce or completely prevent lodging.
By virtue of their herbicidal and plant growth regulatory properties, the active ingredients can also be used to control harmful plants in crops of genetically modified plants or plants modified by conventional mutagenesis. In general, the transgenic plants are characterized by particular advantageous properties, for example by resistances to certain pesticides, in particular certain herbicides, resistances to plant diseases or pathogens 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. For instance, there are known transgenic plants with an elevated starch content or altered starch quality, or those with a different fatty acid composition in the harvested material.
It is preferable with a view to transgenic crops to use the compounds of the invention in economically important transgenic crops of useful plants and ornamentals, for example of cereals such as wheat, barley, rye, oats, millet/sorghum, rice and corn or else crops of sugar beet, cotton, soybean, oilseed rape, potato, manioc, tomato, peas and other vegetables.
Preferably, the compounds of the invention can be used as herbicides in crops of useful plants which are resistant, or have been made resistant by genetic engineering, to the phytotoxic effects of the herbicides.
Conventional ways of producing novel plants which have modified properties in comparison to existing plants consist, for example, in traditional cultivation methods and the generation of mutants. Alternatively, novel plants with modified properties can be generated with the aid of recombinant methods (see, for example, EP-A-0221044, EP-A-0131624). For example, there have been descriptions in several cases of:
Numerous molecular biology techniques which can be used to produce novel transgenic plants with modified properties are known in principle; see, for example, I. Potrykus and G. Spangenberg (eds.) Gene Transfer to Plants, Springer Lab Manual (1995), Springer Verlag Berlin, Heidelberg, or Christou, “Trends in Plant Science” 1 (1996) 423-431.
For such recombinant manipulations, nucleic acid molecules which allow mutagenesis or sequence alteration by recombination of DNA sequences can be introduced into plasmids. With the aid of standard methods, it is possible, for example, to undertake base exchanges, remove parts of sequences or add natural or synthetic sequences. To join the DNA fragments with one another, adapters or linkers can be placed onto the fragments, see, for example, Sambrook et al., 1989, Molecular Cloning, A Laboratory Manual, 2nd edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., or Winnacker “Gene und Klone” [Genes and clones], VCH Weinheim 2nd edition 1996.
For example, the generation of plant cells with a reduced activity of a gene product can be achieved by expressing at least one corresponding antisense RNA, a sense RNA for achieving a cosuppression effect, or by expressing at least one suitably constructed ribozyme which specifically cleaves transcripts of the abovementioned gene product. To this end, it is firstly possible to use DNA molecules which encompass the entire coding sequence of a gene product inclusive of any flanking sequences which may be present, and also DNA molecules which only encompass portions of the coding sequence, in which case it is necessary for these portions to be long enough to have an antisense effect in the cells. It is also possible to use DNA sequences which have a high degree of homology to the coding sequences of a gene product, but are not completely identical to them.
When expressing nucleic acid molecules in plants, the protein synthesized may be localized in any desired compartment of the plant cell. However, to achieve localization in a particular compartment, it is possible, for example, to join the coding region to DNA sequences which ensure localization in a particular compartment. Such sequences are known to those skilled in the art (see, for example, Braun et al., EMBO J. 11 (1992), 3219-3227, Wolter et al., Proc. Natl. Acad. Sci. USA 85 (1988), 846-850; Sonnewald et al., Plant J. 1 (1991), 95-106). The nucleic acid molecules can also be expressed in the organelles of the plant cells.
The transgenic plant cells can be regenerated by known techniques to give rise to entire plants. In principle, the transgenic plants may be plants of any desired plant species, i.e. not only monocotyledonous but also dicotyledonous plants.
Thus, transgenic plants can be obtained whose properties are altered by overexpression, suppression or inhibition of homologous (=natural) genes or gene sequences or expression of heterologous (=foreign) genes or gene sequences.
The compounds of the invention can be used with preference in transgenic crops which are resistant to growth regulators, for example dicamba, or to herbicides which inhibit essential plant enzymes, for example acetolactate synthases (ALS), EPSP synthases, glutamine synthases (GS) or hydroxyphenylpyruvate dioxygenases (HPPD), or to herbicides from the group of the sulfonylureas, the glyphosates, glufosinates or benzoylisoxazoles and analogous active ingredients.
When the active ingredients of the invention are employed in transgenic crops, not only do the effects toward harmful plants observed in other crops occur, but frequently 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 provides for the use of the compounds of the invention as herbicides for control of harmful plants in transgenic crop plants.
The compounds of the invention can be applied 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 plant-growth-regulating compositions which comprise the compounds of the invention.
The compounds of the invention can be formulated in various ways, according to the biological and/or physicochemical parameters 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), dispersions based on oil or water, oil-miscible solutions, capsule suspensions (CS), dusting products (DP), dressings, granules for scattering and soil application, granules (GR) in the form of microgranules, spray granules, absorption 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-Kichler, “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 formulation auxiliaries required, 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; Schonfeldt, “Grenzflachenaktive Athylenoxidaddukte” [Interface-active Ethylene Oxide Adducts], Wiss. Verlagsgesellschaft, Stuttgart 1976; Winnacker-KiUchler, “Chemische Technologie” [Chemical Engineering], volume 7, C. Hanser Verlag Munich, 4th Ed. 1986.
On the basis of these formulations, it is also possible to produce combinations with other pesticidally active substances, for example insecticides, acaricides, herbicides, fungicides, and also with safeners, fertilizers and/or growth regulators, for example in the form of a finished formulation or as a tankmix. Suitable safeners are, for example, mefenpyr-diethyl, cyprosulfamide, isoxadifen-ethyl, cloquintocet-mexyl and dichlormid.
Wettable powders are preparations uniformly dispersible in water which, alongside the active ingredient apart from a diluent or inert substance, also comprise surfactants of an ionic and/or non-ionic type (wetting agent, dispersant), e.g. polyethoxylated alkylphenols, polyethoxylated fatty alcohols, polyethoxylated fatty amines, fatty alcohol polyglycolethersulfates, alkanesulfonates, alkylbenzenesulfonates, sodium lignosulfonate, sodium 2,2′-dinaphthylmethane-6,6′-disulfonate, sodium dibutylnaphthalenesulfonate or else sodium oleoylmethyltaurate. To produce the wettable powders, the active herbicidal ingredients are finely ground, for example in customary apparatuses such as hammer mills, blower mills and air-jet mills, and simultaneously or subsequently mixed with the formulation auxiliaries.
Emulsifiable concentrates are produced by dissolving the active ingredient 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 ionic and/or nonionic surfactants (emulsifiers). Examples of emulsifiers which may be used are: calcium alkylarylsulfonates such as calcium dodecylbenzenesulfonate, 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, for example sorbitan fatty acid esters, or polyoxyethylene sorbitan esters, for example polyoxyethylene sorbitan fatty acid esters.
Dusting products are obtained by grinding the active ingredient with finely distributed solids, for example talc, natural clays, such as kaolin, bentonite and pyrophyllite, or diatomaceous earth.
Suspension concentrates may be water- or oil-based. They may be prepared, for example, by wet-grinding by means of commercial bead mills and optional addition of surfactants as have, for example, already been listed above for the other formulation types.
Emulsions, for example oil-in-water emulsions (EW), can be produced, for example, by means of stirrers, colloid mills and/or static mixers using aqueous organic solvents and optionally surfactants as already listed above, for example, for the other formulation types.
Granules can be produced either by spraying the active ingredient onto adsorptive granular inert material or by applying active ingredient concentrates to the surface of carriers, such as sand, kaolinites or granular inert material, by means of adhesives, for example polyvinyl alcohol, sodium polyacrylate or else mineral oils. Suitable active ingredients 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, fluidized-bed, extruder and spray granules, see e.g. 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 compositions, 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 preparations contain generally 0.1 to 99% by weight, especially 0.1 to 95% by weight, of compounds of the invention.
In wettable powders, the active ingredient concentration is, for example, about 10 to 90% by weight, the remainder to 100% by weight consisting of customary formulation constituents. In emulsifiable concentrates, the active ingredient concentration may be about 1% to 90% and preferably 5% to 80% by weight. Dust-type formulations contain 1% to 30% by weight of active ingredient, preferably usually 5% to 20% by weight of active ingredient; sprayable solutions contain about 0.05% to 80% by weight, preferably 2% to 50% by weight of active ingredient. In the case of water-dispersible granules, the active ingredient content depends partially on whether the active compound is in liquid or solid form and on which granulation auxiliaries, fillers, etc., are used. In the water-dispersible granules, the content of active ingredient is, for example, between 1% and 95% by weight, preferably between 10% and 80% by weight.
In addition, the active ingredient formulations mentioned optionally comprise the respective customary stickers, wetters, dispersants, emulsifiers, penetrants, preservatives, antifreeze agents and solvents, fillers, carriers and dyes, defoamers, evaporation inhibitors and agents which influence the pH and the viscosity.
On the basis of these formulations, it is also possible to produce combinations with other pesticidally active substances, for example insecticides, acaricides, herbicides, fungicides, and also with safeners, fertilizers and/or growth regulators, for example in the form of a finished formulation or as a tankmix.
For application, the formulations 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. Dust-type preparations, granules for soil application or granules for scattering and sprayable solutions are not normally diluted further with other inert substances prior to application.
The required application rate of the compounds of the formula (I) varies with the external conditions, including, inter alia, temperature, humidity and the type of herbicide used. It can vary within wide limits, for example between 0.001 and 1.0 kg/ha or more of active substance, but it is preferably between 0.005 and 750 g/ha.
The examples listed in the tables below were prepared analogously to the methods mentioned above or can be obtained analogously to the methods mentioned above. These compounds are very particularly preferred.
The abbreviations used mean:
Ph=phenyl Me=methyl Et=ethyl
Seeds of monocotyledonous and dicotyledonous weed plants and crop plants are laid out in sandy loam in wood-fiber pots and covered with soil. The compounds of the invention, formulated in the form of wettable powders (WP) or as emulsion concentrates (EC), are then applied to the surface of the covering soil in the form of an aqueous suspension or emulsion at a water application rate equating to 600 to 800 l/ha, with addition of 0.2% wetting agent. After the treatment, the pots are placed in a greenhouse and kept under good growth conditions for the trial plants. The damage to the test plants is scored visually after a test period of 3 weeks by comparison with untreated controls (herbicidal activity in percent (%): 100% activity=the plants have died, 0% activity=like control plants). For example, inventive compound nos. 1-2, 1-3, 1-4, 1-5, 1-8, 1-19, 2-2, 2-3, 2-4, 2-7, 3-2, 3-3, 3-4, 4-2 and 5-2, at an application rate of 0.32 kg or less per hectare, showed at least 80% efficacy against Setaria viridis und Matricaria inodora.
At the same time, inventive compounds leave Gramineae crops such as barley, wheat, rye, millet/sorghum, corn or rice virtually undamaged when applied pre-emergence, even at high active ingredient dosages. In addition, some substances are also harmless to dicotyledonous crops such as soya, cotton, oilseed rape, sugar beet or potatoes. Some of the inventive compounds exhibit high selectivity and are therefore suitable for controlling unwanted vegetation in agricultural crops by the pre-emergence method.
Seeds of monocotyledonous and dicotyledonous weed and crop plants are laid out in sandy loam soil in wood-fiber pots, covered with soil and cultivated in a greenhouse under good growth conditions. 2 to 3 weeks after sowing, the test plants are treated at the one-leaf stage. The compounds of the invention, formulated in the form of wettable powders (WP) or as emulsion concentrates (EC), are then sprayed onto the green parts of the plants in the form of an aqueous suspension or emulsion at a water application rate equating to 600 to 800 l/ha, with addition of 0.2% wetting agent. After the test plants have been left to stand in the greenhouse under optimal growth conditions for about 3 weeks, the action of the preparations is assessed visually in comparison to untreated controls (herbicidal action in percent (%): 100% activity=the plants have died, 0% activity=like control plants). For example, inventive compound nos. 1-2, 1-3, 1-4, 1-5, 1-8, 1-19, 2-2, 2-3, 2-4, 2-7, 3-2, 3-3, 3-4, 4-2 and 5-2, at an application rate of 0.08 kg or less per hectare, showed at least 80% efficacy against Abuthilon theophrasti and Amaranthus retroflexus. At the same time, inventive compounds leave Gramineae crops such as barley, wheat, rye, millet/sorghum, corn or rice virtually undamaged when applied post-emergence, even at high active ingredient dosages. In addition, some substances are also harmless to dicotyledonous crops such as soya, cotton, oilseed rape, sugar beet or potatoes. Some of the compounds of the invention have high selectivity and are therefore suitable for controlling unwanted vegetation in agricultural crops by the post-emergence method.
