Use of Chromene or Chroman Derivatives as Herbicides

Abstract

The present invention is useful for controlling undesirable plants. In particular, the present invention relates to the use of at least one compound derived from chromene or chromane as a herbicide, to phytotoxic compositions comprising said compounds, and to methods of treating and / or controlling plants using said compounds.

Description

[Technical field]

[0001] The present invention is in the field of herbicides useful for combating undesirable plant growth. In particular, the present invention relates to the use of at least one chromene or chromane derivative compound as a herbicide, to phytotoxic compositions comprising said compounds, and thus to plant treatment and / or control methods implementing such compounds. [Background technology]

[0002] Weeds are considered one of the hazards that cause the greatest losses in agricultural production worldwide, accounting for more than 30% of yield and crop quality losses. Weeds appear throughout the crop growing season, causing particular damage at sowing and harvesting. Over the past 60 years, weeds have mostly been controlled by spraying with non-natural herbicides, but resistance to these herbicides is on the rise. For example, more than 50 "weeds" that have demonstrated resistance to glyphosate, a broad-spectrum systemic herbicide widely used in agricultural and non-agricultural applications, are now confirmed as "superweeds" according to the international "Herbicide-Resistant Weeds Database."

[0003] Research teams are therefore looking for sustainable solutions and alternatives, especially based on natural materials.

[0004] Among the new synthetic molecules based on natural substances, we can mention triketones (mesotrione, topramezone, tembotrione) based on leptospermone isolated from the plants Callistemon citrinus or lemon bottlebrush, which inhibit the enzyme p-hydroxyphenylpyruvate dioxygenase; cinmethylin, based on isocineole, a terpene found in cardamom or some pepper species, which inhibits tyrosine aminotransferase; and endosar, based on cantharidin, a powerful defensive toxin produced by insects, which inhibits plant protein phosphatases. In particular, leptospermone was discovered in the late 1970s after it was noted that lemon bottlebrush inhibited the growth of other plants in the environment, indicating the presence of a substance with allelopathic properties.

[0005] The literature also presents natural substances such as glufosinate, also known as phosphinothricin, often sold as its ammonium salt, obtained from the degradation of bialaphos (or biranaphos), a tripeptide isolated from bacteria. However, it was withdrawn from the market in 2017, since it was classified as a potentially reproductively toxic chemical. Other natural substances, such as fatty acids, are sold as biopesticides (e.g. pelargonic acid, sold under the reference name Beloukha® or as acetic acid) that act as foliar defoliants. Their activity is therefore time-limited.

[0006] Other research teams have focused on synthetic chromene or chromane based molecules. In particular, US5053071 describes broad spectrum herbicides containing a chromane unit having one of the following formulae: [C1] JPEG2025505715000001.jpg55170

[0007] Some compounds of US5053071 contain stereoisomers that can be problematic with respect to synthesis strategies, purification, and characterization of biological activity. Furthermore, the synthetic routes starting from the phenol ring involve multiple steps using conditions (complex phenol allylation, high temperature Clasen rearrangement, hydroboration, cyclization, and functionalization) that are difficult to carry out on a large scale.

[0008] International application WO2019 / 005484 describes herbicides that include a chromene unit having the formula: [Case 2] JPEG2025505715000002.jpg52170

[0009] However, some compounds of WO2019 / 005484 have asymmetric centers, resulting in enantiomers, diastereoisomers and / or atropisomers, which may be problematic in terms of synthesis strategies, purification and, above all, characterization of biological activity. Synthetic routes are not clearly described. Summary of the Invention [Problem to be solved by the invention]

[0010] Thus, there is a need for new herbicides that are effective against undesirable plants, are easy to prepare, and have significantly reduced environmental side effects compared to those previously mentioned.

[0011] Therefore, the object of the present invention is to overcome the above-mentioned drawbacks of the prior art and to provide a herbicide having good performance in terms of herbicidal activity and / or selectivity, which is easy to prepare and has reduced toxicity.

[0012] The objects of the present invention are achieved by the chromene and chroman derivative compounds described below. [Means for solving the problem]

[0013] A first object of the present invention is the use, as a herbicide, of at least one compound selected from the group consisting of a compound corresponding to formula (I), one of its isomers, and one of its organic and inorganic salts, said compound (I) having the following structure: [C3] JPEG2025505715000003.jpg54170, wherein * R 1 , R 2 and R 3 are each independently a hydrogen atom, a halogen atom, a C1-C5 alkyl or cycloalkyl radical, or -OH, -COOH, -COOR 5 , -OR 5 and -SO2R 5 R represents a group selected from 5 is a C1-C5 alkyl or cycloalkyl radical, said C1-C5 alkyl or cycloalkyl radical being optionally substituted with one or more substituents selected from halogen atoms and hydroxy groups; * X is a part of a six-membered heterocycle and is selected from the group consisting of an oxygen atom, a sulfur atom, a divalent SO group, a divalent SO2 group, and a divalent NR 6 represents a group, R 6 is a hydrogen atom, a C1-C5 alkyl or cycloalkyl radical, or a C2-C8 aryl or heteroaryl radical, TIFF2025505715000004.tif9170 represents a single bond or a double bond at the 2,3 or 3,4 positions of a six-membered heterocycle having a heteroatom or a divalent group X, and thus the six-membered heterocycle includes either two single bonds at the 2,3 and 3,4 positions, or a single bond at the 2,3 positions and a double bond at the 3,4 positions, or a double bond at the 2,3 positions and a single bond at the 3,4 positions; * L represents a linking arm selected from linear and branched alkylene chains having at least one carbon atom, said linear or branched alkylene chains being optionally interrupted and / or terminated with one or more heteroatoms selected from oxygen, sulfur or substituted nitrogen atoms; *Ar represents an aromatic group selected from the group consisting of phenyl, naphthyl, furyl, thiophenyl, pyrrolyl, pyridinyl, indolyl, isoindolyl, benzofuryl, benzothiophenyl, quinolyl and isoquinolyl, imidazolyl, oxazolyl, thiazolyl, pyrimidyl, pyridazyl, pyrazyl, pyrazolyl and triazolyl groups, said aromatic group being selected from the group consisting of halogen atoms, C1-C5 alkyl or cycloalkyl radicals, -OH groups, -COOH groups, -COOR groups, 7 Group, -OR 7 Group, and -SO2R 7 group, and R 7 is a C1-C5 alkyl or cycloalkyl radical, said C1-C5 alkyl or cycloalkyl radical being optionally substituted with one or more substituents selected from halogen atoms and hydroxy groups; * n is an integer ranging from 4 to 6, and the same or different substituents R 4 represents the number of * R 4 is a hydrogen atom, a halogen atom, a C1-C5 alkyl or cycloalkyl radical, or -OH, -COOH, -COOR 8 , -OR 8 and -SO2R 8 R represents a group selected from 8 is a C1-C5 alkyl or cycloalkyl radical, said C1-C5 alkyl or cycloalkyl radical being optionally substituted with one or more substituents selected from halogen atoms and hydroxy groups.

[0014] The compounds (I) of the present invention are derivatives based on chromene (2H-chromene or 4H-chromene) or chromane (3,4-dihydro-2H-1-benzopyran), including compounds naturally occurring in Hepatiques, a moss plant that lives in particular in forests and wetlands, and compounds suggested by such compounds naturally occurring in Hepatiques. Thus, the inventors have found that such compounds according to the first object of the present invention have significant herbicidal activity. Moreover, these compounds are easy to prepare and some can be extracted directly from the natural environment.

[0015] For the purposes of the present invention, by "herbicide" is intended a chemical product in the form of an active substance or phytosanitary composition that is effective in combating the growth of undesirable plants.

[0016] A herbicide may be said to be comprehensive, if it specifically kills all types of plants, or selective, if it kills only one or more categories of undesirable plants. It may also be described in terms of its mode of action, e.g., root penetrating, systemic, or post-emergence.

[0017] "Root-systemic herbicides" are herbicides that act by being absorbed by the roots of the plant, whereas "foliar herbicides" are absorbed by the leaves of the plant.

[0018] In contrast to "contact herbicides," which destroy only the surface to which they are applied and therefore come into contact with, "systemic herbicides" act by spreading throughout the plant via the sap.

[0019] Finally, "post-emergence herbicides" act on plants after the initial seedling emergence, while "pre-emergence herbicides" can act shortly after emergence.

[0020] In the present invention, "isomers" is understood to mean stereoisomers and optical isomers, said isomers having the same molar mass as the compound of formula (I) and the structural variations are limited to the following: - the position of X on the six-membered heterocycle, - the position of the tetrahedral carbon when the six-membered heterocycle contains a double bond; - R on the phenyl group 1 , R 2 , R 3 and the position of the L-Ar group, and - n groups R on a six-membered heterocycle 4 Location.

[0021] Examples of inorganic salts of the compounds of formula (I) and their isomers include the alkali metal salts and alkaline earth metal salts of the compounds of formula (I) and their isomers.

[0022] Examples of organic salts of the compounds of formula (I) and their isomers include ammonium salts of the compounds of formula (I) and their isomers.

[0023] In the present invention, a C1-C5 alkyl or cycloalkyl radical can be straight-chain or branched, preferably straight-chain.

[0024] For the purposes of the present invention, halogen is selected from F, Cl, Br and I, particularly preferably F and C.

[0025] Definition of X

[0026] base R 6 An alkyl or cycloalkyl radical as is preferably an alkyl radical, particularly preferably a straight-chain alkyl radical, very particularly preferably a straight-chain C1-C3 alkyl radical.

[0027] base R 6 The aryl radical as is preferably a C5-C6 aryl radical, particularly preferably a phenyl radical.

[0028] base R6 The heteroaryl radical as may be an indole or triazole radical.

[0029] R as a C2-C8 aryl or heteroaryl radical 6 is preferably a C5-C6 aryl radical.

[0030] base R 6 is preferably a hydrogen atom, or an alkyl or cycloalkyl radical.

[0031] According to one particularly preferred embodiment of the invention, X represents an oxygen atom.

[0032] R 1 、R 2 、R 3 and R 5 Definition of

[0033] base R 1 , R 2 or R 3 An alkyl or cycloalkyl radical as is preferably an alkyl radical, particularly preferably a straight-chain alkyl radical, very particularly preferably a straight-chain C1-C3 alkyl radical.

[0034] base R 5 An alkyl or cycloalkyl radical as is preferably an alkyl radical, particularly preferably a straight-chain alkyl radical, very particularly preferably a straight-chain C1-C3 alkyl radical.

[0035] base R 1 , R 2 , R 3 or R 5 Said alkyl or cycloalkyl radical as may be optionally substituted with one or more substituents selected from halogen atoms and hydroxy groups.

[0036] According to one particularly preferred embodiment of the invention, the group R 1 , R 2 and R 3 at least one of them represents an -OH group, advantageously a group R 3 represents an -OH group. This makes it easier to obtain the compound of the present invention and enhance its herbicidal activity.

[0037] In this embodiment, the other two groups R 1 and R 2 , or R 1 and R 3 , or R 2 and R 3 and advantageously the other two groups R 1 and R 2 are each independently a hydrogen atom, a -COOH group, or a -COOR 5 represents a group, R 5 is a C1-C5 alkyl radical, preferably a methyl radical.

[0038] Furthermore, in this embodiment, the group R 1 represents a hydrogen atom or a -COOH group, more particularly preferably a hydrogen atom.

[0039] Furthermore, in this embodiment, the group R 2 is a hydrogen atom, a -COOH group or a -COOR 5 represents a group, R 5 is a C1-C5 alkyl radical, preferably a methyl radical, more particularly preferably a hydrogen atom or a -COOH group.

[0040] Six-membered heterocycle

[0041] The six-membered heterocycle having a heteroatom or a divalent group X preferably contains two single bonds at the 2,3-position and the 3,4-position, or a single bond at the 2,3-position and a double bond at the 3,4-position, particularly preferably a single bond at the 2,3-position and a double bond at the 3,4-position.

[0042] Definition of L

[0043] L preferably represents a linear or branched alkylene chain having 1 to 6 carbon atoms, more preferably a linear alkylene chain having 2 to 3 carbon atoms, and even more preferably a linear alkylene chain having 2 carbon atoms.

[0044] The straight or branched alkylene chain as the linking arm L may be interrupted and / or terminated with one or more heteroatoms selected from oxygen, sulfur and substituted nitrogen atoms, preferably one or more oxygen atoms.

[0045] The nitrogen may be substituted with a C1-C5, preferably a C1-C3 alkyl group, said alkyl radical being preferably a straight chain alkyl radical.

[0046] Definition of Ar

[0047] Alkyl or cycloalkyl radicals as substituents of the Ar group are preferably alkyl radicals, particularly preferably straight-chain alkyl radicals, very particularly preferably straight-chain C1-C3 alkyl radicals.

[0048] base R 7 Alkyl or cycloalkyl radical as denotes preferably an alkyl radical, particularly preferably a straight-chain alkyl radical, very particularly preferably a straight-chain C1-C3 alkyl radical.

[0049] Group Ar or group R 7 Said alkyl or cycloalkyl radical as a substituent of may be substituted with one or more substituents selected from halogen atoms and hydroxy groups.

[0050] Ar preferably represents a phenyl group, said phenyl group being optionally substituted with one or more of the substituents defined in the present invention for the aromatic group Ar.

[0051] Among the substituents of the aromatic group Ar, the -OH group is preferred.

[0052] n and R 4 Definition of

[0053] A six-membered heterocycle having a divalent group or a heteroatom X may have at least four substituents R depending on the presence or absence of a double bond in the heterocycle. 4 , at most six substituents R 4 Includes.

[0054] base R 4 An alkyl or cycloalkyl radical as is preferably an alkyl radical, particularly preferably a straight-chain alkyl radical, more particularly preferably a C1-C3 straight-chain alkyl radical.

[0055] base R 8 An alkyl or cycloalkyl radical as is preferably an alkyl radical, particularly preferably a straight-chain alkyl radical, very particularly preferably a straight-chain C1-C3 alkyl radical.

[0056] base R 4 or R 8 Said alkyl or cycloalkyl radical as may be optionally substituted with one or more substituents selected from halogen atoms and hydroxy groups.

[0057] According to a first option, the heterocycle contains a double bond and therefore the compound has the following formula (Ia) or (Ib): [C4] JPEG2025505715000005.jpg56170, wherein * A, L, R 1 , R 2 , R 3 and X is as defined herein, and * R 4a , R 4b , R 4c and R 4dmay be the same or different and represent a hydrogen atom or a C1-C5 alkyl or cycloalkyl radical, said C1-C5 alkyl or cycloalkyl radical being optionally substituted with one or more halogen atoms.

[0058] According to a particularly preferred embodiment of this first option, R 4a represents a C1-C5 alkyl radical, optionally substituted with one or more halogen atoms; R 4b represents a hydrogen atom or a C1-C5 alkyl radical optionally substituted with one or more halogen atoms, R 4c and R 4d represents a hydrogen atom.

[0059] R 4a represents a C1-C3 alkyl radical, optionally substituted with one or more halogen atoms, and even more preferably a methyl radical, which thus allows for improved herbicidal efficacy.

[0060] R 4b represents a C1-C5 alkyl radical optionally substituted with one or more halogen atoms, preferably a C1-C3 alkyl radical optionally substituted with one or more halogen atoms, and even more preferably a methyl radical.

[0061] According to a second option, the heterocycle does not contain a double bond and therefore the compound has the following formula (Ic): [5] JPEG2025505715000006.jpg64170, wherein * A, L, R 1 , R 2 , R 3 and X is as defined herein, and * R 4a , R 4b , R 4c , R 4d , R 4e , and R4f may be the same or different and represent a hydrogen atom or a C1-C5 alkyl or cycloalkyl radical, said C1-C5 alkyl or cycloalkyl radical being optionally substituted with one or more halogen atoms.

[0062] According to one particularly preferred embodiment of this second option, R 4a and R 4b represents a methyl radical, and R 4c , R 4d , R 4e and R 4f represents a hydrogen atom.

[0063] According to one preferred embodiment of the invention, the compound of formula (I) is selected from the following compounds:

[0064] [Table 1] JPEG2025505715000007.jpg220170

[0065] Due to their herbicidal biological activity, the compounds defined in the first object of the invention are useful in the agricultural, horticultural and transport sectors, in particular for weed control on tarmacs or railway tracks.

[0066] The compounds defined in the first object of the present invention may be practiced in isolated or non-isolated form, and / or in natural or synthetic form.

[0067] According to one embodiment, the compound defined in the first object of the present invention is embodied in isolated form.

[0068] According to the present invention, the term "isolated form" means that the compound defined in the first object of the present invention is embodied in a pure form, i.e. in a form that is distinct from a mixture with other compounds, which may be, for example, a plant extract containing it in combination with other substances.

[0069] Thus, these compounds as defined in the first object of the invention may be isolated from plant extracts, but may also be prepared synthetically, in particular as illustrated in the examples below.

[0070] According to another embodiment, the compound defined in the first object of the invention is embodied in the form of a natural extract containing it, in particular of plant origin.

[0071] The natural origin allows for attempts to reduce the impact on the environment.

[0072] In particular, some of the compounds as defined in the first object of the present invention may be embodied in the form of extracts of bryophytes containing them, in particular but not limited to extracts of Radula laxiramea, Radula variabilis, Radula complanata, Radula buccinifera, Radula japonica, Radula oyamensis, Radula tokiensis, Radula perrottetii, Radula kojana, Radula javanica, which may generally contain mixtures of these compounds as defined in the first object of the present invention with other related compounds. The embodiment may include the plant directly, or any other biological agent that allows for the production, drying, and powderization of the compounds of the invention.

[0073] For example, compound (Ia1) was isolated from the plant Radulla kojana [Asakawa et al., Phytochemistry, 1991, 30, 219-234].

[0074] The extract can in particular be obtained by mechanical extraction, for example by pressing, or by chemical extraction, in particular by percolation, maceration or decoction. If necessary, the extraction can be followed by a chromatographic purification step or by crystallization.

[0075] According to yet another exemplary embodiment, the compounds defined in the first object of the present invention may be generated in situ or immediately prior to use from precursors, for example by hydrolysis, in particular hydrolysis of esters.

[0076] Naturally, different compounds as defined in the first object of the present invention can be used in mixtures as herbicidal active substances according to the invention.

[0077] According to the invention, a "herbicide" corresponds to any compound or any composition having the property of killing so-called undesirable vegetation, in particular plants.

[0078] These so-called "undesirable" plants are generally mosses, algae or weeds, and in particular, but not limited to, anthemis, amaranth, orchard grass, artemisia, arrowroot, cornflower, shepherd's purse, lacegrass, cardamom, thistle, gooseberry, creeping quackgrass, poppy, American morning glory, Euphorbia, trichomes, Cleome, Aster, geranium, field ryegrass, sowweed, lamb's paw, vetch, bindweed, chickweed, wild mustard, forget-me-not, nettle, oxalis, shepherd's purse, violets, dandelions, plantains, radishes, ryegrass, buttercups, knotweed, groundsel, clover, stagweed and vetch.

[0079] For example, the so-called undesirable plants may be those listed in HYPPA (HYpermedia pour la Protection des Plantes - Adventices), an encyclopedic database developed by INRAe Dijon that contains data on 580 "weeds" of Western European crops.

[0080] As will become apparent from the examples which follow, the compounds defined in the first object of the invention are particularly highly advantageous as post-emergence herbicides.

[0081] They are particularly advantageous as root-systemic herbicides, on the one hand, and as systemic herbicides, on the other hand.

[0082] In particular, the compounds defined in the first object of the present invention are used as herbicides on plants at the seedling, ie emerged young plant development stage which contains only a few leaves.

[0083] The compounds defined in the first object of the present invention are employed in a formulation suitable for application to the area to be treated.

[0084] Generally, formulations for this application are liquid, generally aqueous formulations.

[0085] This liquid formulation may be provided to the user in its pure, i.e. ready-to-use form.

[0086] It may also be a concentrated liquid formulation that must be diluted by the user immediately prior to use.

[0087] The composition may also be in the form of a solid preparation, such as granules, which the user applies as is or disperses in an aqueous medium before use.

[0088] In general, diluted application, especially in an aqueous medium, is advantageous.

[0089] The compound defined in the first object of the present invention may be embodied as the compound defined in the first object of the present invention in a concentration range of 1 μg / mL to 200 μg / mL, preferably 5 μg / mL to 150 μg / mL, and even more preferably 10 μg / mL to 100 μg / mL.

[0090] Naturally, this effective concentration may vary as a function of the chemical nature of the compound defined in the first object of the invention, the method of formulation, and the variety and developmental stage of the undesirable plants to be treated.

[0091] It is also advantageous for the formulation to be suitable for nebulization.

[0092] The compound according to the invention is R 3 =OH, X=O, R 4c =H and R 4d =H (the compound is hereinafter referred to as formula (Ia')), they can be prepared by condensation reaction of α,β-unsaturated aldehyde of formula (II) with diphenol of formula (III) in the presence of ethylenediaminediacetic acid (EDDA); Lewis acid such as Yb(OTf)3, ZnCl2; and acidic catalyst selected from NHOAc, TFA, or AcOH; polar aprotic solvent or acidic solvent in a closed reactor (e.g., sealed tube) under reflux under inert atmosphere, according to the steps shown in the following scheme. [C10] JPEG2025505715000008.jpg54170

[0093] The polar aprotic solvent may be toluene, xylene, benzene or dichloromethane.

[0094] The acidic solvent may be acetic acid.

[0095] Aldehydes of formula (II), especially if not commercially available, can be obtained according to the three steps depicted in the following scheme. [C11] JPEG2025505715000009.jpg50170The first step involves reacting a ketone of formula (IV) with triethyl phosphonoacetate in the presence of a strong base such as NaH, potassium tert-butylate or sodium methylate, and an aprotic polar solvent such as tetrahydrofuran, methyltetrahydrofuran or toluene to form compound (V); The second step involves reducing the ester functionality of compound (V) to an alcohol functionality in the presence of a reducing agent such as diisobutylaluminum hydride (DIBALH), lithium aluminium hydride or lithium borohydride under an inert atmosphere to form compound (VI); and The third step involves oxidizing the alcohol functionality of compound (VI) to an aldehyde functionality in the presence of an oxidizing agent such as MnO2, NaOCI, in the presence of TEMPO, or DMSO, in the presence of oxalyl chloride or another electrophilic agent under an inert atmosphere to form compound (II).

[0096] A second object of the present invention is a phytotoxic composition comprising at least one compound as defined under the first object of the present invention as herbicidal active substance in combination with one or more formulation additives for improving water solubility and / or penetration into plant tissues, such as, for example, anionic, cationic, zwitterionic or non-ionic surfactants.

[0097] The phytotoxic composition may further comprise one or more other active substances selected from fertilizers, growth regulators and additional herbicides.

[0098] The phrase "additional herbicide" according to the present invention refers to a herbicide that is different from the compound defined in the first object of the present invention.

[0099] Indeed, it may be advantageous to combine the compounds defined in the first object of the invention with an additional herbicide whose efficacy may be complementary to that of the compounds defined in the first object of the invention, however this additional herbicide is preferably a compound selected so as to have a lower impact on the environment.

[0100] Additional herbicides include ammonium nonanoate, nonanoic acid (=pelargonic acid), medium chain length (i.e., C8-C 12 ) fatty acids and their salts, urea derivatives, borax, copper sulfate, carboxylic acids (especially acetic acid) and their salts, nitrogen compounds, calcium salts, and mixtures thereof.

[0101] The fertilizer is preferably a nitrogen fertilizer and may be selected from urea; ammonium salts; in particular ammonium chloride, ammonium nitrate or ammonium sulfate; ammonium and potassium phosphates; leather meal; bone meal, vegetable meal; and mixtures thereof.

[0102] The growth regulator may be selected from maleic hydrazide, chloromequat-chloride (eg Cyclocel®), auxin derivatives, growth regulators of natural origin, and mixtures thereof.

[0103] Advantageously, the growth regulator of natural origin is salicylic acid, a salicylate such as ammonium salicylate, jasmonic acid, an auxin, a gibberellin, a cytokinin, lunuralic acid, abscisic acid, or a mixture thereof.

[0104] The compositions according to the invention may also contain other conventional additional additives such as surfactants, antifoaming agents, disintegrants, stabilizers, moisturizing agents, thickeners or pH adjusters.

[0105] The selection of these additives is usually made with regard to the form in which the composition is intended.

[0106] The phytotoxic composition may contain compound (I) in the pure state or in the form of a plant extract or plant powder containing it.

[0107] The phytotoxic compositions according to the invention may be in the form of a solid composition, in particular in the form of a powder or granules that are particularly suitable for aqueous dilution. The solid composition may also be dispersed directly on the area to be weeded and solubilized by wetting.

[0108] The phytotoxic compositions according to the invention may be in the form of a liquid composition, in particular in a concentrated form or in a ready-to-use form, in particular in the form of a solution or emulsion. Likewise, liquid compositions in concentrated form may also be diluted before use by adding auxiliary substances, if necessary.

[0109] A third object of the present invention is a method for controlling and / or treating undesirable vegetation on the surface of a target area, comprising contacting said target area with an effective amount of a compound as defined in the first object of the present invention or at least one phytotoxic composition as defined in the second object of the present invention.

[0110] Preferably, the compound as defined in the first object of the present invention is supplied to the plant via the cultivation substrate.

[0111] This cultivation substrate may be soil, but may also be any medium considered for hydroponic cultivation.

[0112] Advantageously, the compounds are applied directly in contact with the cultivation substrate on the surface on which the plants to be treated are growing.

[0113] Advantageously, said contacting is carried out by spraying at least one compound as defined in the first object of the invention or at least one composition as defined in the second object of the invention.

[0114] The compound as defined in the first object of the invention, the phytotoxic composition as defined in the second object of the invention or the method as defined in the third object of the invention causes the death of undesirable plants in less than 96 hours, preferably in less than 48 hours, even more preferably in less than 24 hours after application.

[0115] Further features, options and advantages of the uses, phytotoxic compositions or methods according to the invention will become apparent on reading the following exemplary embodiments, which are given by way of illustration of the invention and do not constitute a limitation thereof.

[0116] EXAMPLES

[0117] Toluene, acetonitrile and benzene were distilled over calcium hydride before use and degassed by bubbling nitrogen gas as necessary.

[0118] Analytical thin-layer chromatography (TLC) was performed on aluminized silica gel plates (silica gel 60, F254, Merck) and monitored by exposure to ultraviolet light and / or basic potassium permanganate solution or p-anisaldehyde staining solution followed by heating.

[0119] Flash column chromatography was performed on silica 60 (40-63 pm).

[0120] Nuclear magnetic resonance spectrum ( 1 H NMR and 13 C NMR) was performed on a Bruker Avance 400 spectrometer (400 MHz). 1 H NMR, 100 MHz 13 C NMR was recorded at 25 °C using CDCl as the reference solvent for residual CHCl (δH = 7.26 ppm, δC = 77.1 ppm). Chemical shifts are given in ppm and coupling constants (J) are given in Hertz. 1 H NMR spectral data are reported as follows: chemical shift ppm (br s = broad singlet, s = singlet, d = doublet, t = triplet, q = quartet, dd = double doublet, td = triple doublet, ddd = double double doublet, m = multiplet, coupling constant, integral).

[0121] High resolution mass spectra (HRMS) were obtained using a JEOL JMS-GCmate II spectrometer and are reported in m / z.

[0122] Infrared spectra were recorded on a PerkinElmer FTIR spectrometer using the attenuated total reflectance (ATR) technique. max ) is the wave number (cm -1 ) to report.

[0123] Example 1: Synthesis of compound Ia1

[0124] Preparation of dihydropinosylvin of formula (IIIa1)

[0125] Dihydropinosylvin was prepared according to the steps shown in the diagram below. [C12] JPEG2025505715000010.jpg82170

[0126] 1.1 Step 1: Preparation of (E)-3,5-dimethoxystilbene

[0127] The first step is the Horner-Wadsworth-Emmons reaction. In an inert atmosphere, potassium tert-butylate (t-BuOK) (10.8 g, 96.3 mmol) and anhydrous tetrahydrofuran (THF) (120 mL) were added to a flame-dried 500 mL flask equipped with a magnetic stir bar. The mixture was cooled in an ice bath, then diethylbenzyl phosphonate (20.6 mL, 90.3 mmol) was added dropwise over 30 min, followed by 3,5-dimethoxybenzaldehyde (10.0 g, 60.2 mmol) in small portions. The mixture was allowed to warm to room temperature and then stirred for 2 h. The THF was removed in vacuo, then a mixture of water and methanol (HO:MeOH) (2:1, ca. 60 mL) was added until the product precipitated. Filtration and drying in vacuum gave (E)-3,5-dimethoxystilbene as a white solid (13.5 g, 56.0 mmol, 93% yield).

[0128] 1 H NMR (400MHz, CDCl3): δ=7.53-7.49(m,2H),7.39-7.33(m,2H),7.29-7.23(m,1H),7.09(d,J= 16.3Hz, 1H), 7.04 (d, J = 16.3Hz, 1H), 6.69-6.66 (m, 2H), 6.40 (t, J = 2.3Hz, 1H), 3.83 (s, 6H).

[0129] 1.2. Step 2: Preparation of 1,3-dimethoxy-5-phenethylbenzene

[0130] The second step is the catalytic hydrogenation of the double bond to embody ammonium formate. Thus, the use of hydrogen gas is avoided. (E)-3,5-Dimethoxystilbene (14.0 g, 58.2 mmol) prepared in the previous step and 10% Pd / C (1.40 g, 10 wt%) were added to a flame-dried 500 mL flask, followed by ethyl acetate (243 mL, 0.245 M). Ammonium formate (18.4 g, 291 mmol) was added and the mixture was stirred overnight at room temperature. The reaction mixture was then filtered through a Celite pad and evaporated in vacuum. The remaining ammonium formate was precipitated by adding dichloromethane, and the mixture was filtered again and evaporated in vacuum to give the expected 1,3-dimethoxy-5-phenethylbenzene as a pale yellow oil (12.7 g, 52.4 mmol, 90% yield).

[0131] 1 H NMR (400MHz, CDCl3): δ=7.32-7.25(m,2H),7.23-7.17(m,3H),6.36-6.30(m,3H),3.76(s,6H),2.95-2.82(m,4H).

[0132] 1.3. Step 3: Preparation of dihydropinosylvin

[0133] The third step is the demethylation of phenol in an acidic aqueous medium. To a 250 mL flask equipped with a magnetic stir bar, the 1,3-dimethoxy-5-phenethylbenzene (2.03 g, 8.38 mmol) prepared in the previous step was added, followed by hydrobromic acid (HBr) (24.6 mL, 48 wt % in water) and glacial acetic acid (24.6 mL, HBr:AcOH 1:1 v / v, final concentration 0.15 M). The reaction mixture was then heated under reflux for 4 h and cooled to room temperature. The reaction mixture was diluted with water (50 mL) and extracted with diethyl ether (Et2O) (3 x 50 mL). The organic phase was treated with activated charcoal, filtered and reduced in vacuo to give dihydropinosylvin as a white solid (1.68 g, 7.86 mmol, 94%).

[0134] 1H NMR (400MHz, CDCl3): δ = 7.33-7.25 (m, 2H), 7.24-7.15 (m, 3H), 6.31-6.18 (m, 3H), 4.71 (br s, 2H), 2.93-2.75 (m, 4H).

[0135] Preparation of 2,2-dimethyl-7-phenethyl-2H-chromen-5-ol (compound Ia1)

[0136] In an inert atmosphere, a flame-dried sealed tube equipped with a magnetic stir bar was charged with the dihydropinosylvin obtained in the previous step (4.00 g, 18.7 mmol-1 equiv.), followed by anhydrous toluene (0.1 M) and 3-methyl-2-butenal (prenal) (1.5 equiv.). Ethylenediaminediacetic acid (EDDA, ​​5 mol%) was then added. The vessel was sealed and heated to 115°C for 1 h. This procedure (addition of EDDA and heating) was repeated three times (total of 15 mol% EDDA added), then cooled to room temperature, after which a small amount of silica was added and the solvent removed under vacuum. The crude mixture was purified by flash silica column chromatography (dry loading) eluting with hexane / ethyl acetate to give the expected 2,2-dimethyl-7-phenethyl-2H-chromen-5-ol (compound 6) as a viscous brown liquid (4.28 g, 15.3 mmol, 82% yield).

[0137] 1 H NMR (400MHz, CDCl3): δ=7.31-7.24(m,2H),7.22-7.15(m,3H),6.58(d,J=10.0,1H),6.32-6.29(m,1H),6.14-6.10 (m,1H),5.55(d,J=10.0,1H),4.59(br s,1H),2.92-2.83(m,2H),2.80-2.73(m,2H),1.42(s,6H).

[0138] Example 2: Synthesis of compound Ia1

[0139] Preparation of 2-methyl-7-phenethyl-2H-chromen-5-ol

[0140] In an inert atmosphere, a flame-dried sealed tube equipped with a magnetic stir bar was charged with compound (IIIa1) (300 mg, 1.4 mmol, 1 equiv.) previously prepared in Example 1, followed by anhydrous toluene (0.1 M) and (2E)-but-2-enal (1.5 equiv.). Ethylenediaminediacetic acid (EDDA, ​​5 mol%) was then added. The vessel was sealed and heated to 115° C. for 1 h. This procedure (addition of EDDA and heating) was repeated three times (total of 15 mol% EDDA added), then cooled to room temperature, after which a small amount of silica was added and the solvent removed under vacuum. The crude mixture was purified by flash silica column chromatography (dry loading) eluting with hexane / EtOAc to give the corresponding chromene (Ia2) as a viscous brown liquid (13 mg, 0.0488 mmol, 3% yield).

[0141] 1 H NMR (400MHz, CDCl3): δ=7.32-7.13(m,5H),6.65(d,J=9.8,1H),6.33-6.28(m,1H),6.15-6 .08(m,1H),5.58(d,J=9.8,1H),5.02-4.88(m,2H),2.95-2.69(m,4H),1.43(d,J=6.8,3H).

[0142] Example 3: Synthesis of compound Ia3

[0143] Preparation of aldehydes of formula (IIa3)

[0144] Aldehydes of formula (IIa3) were prepared according to the procedure depicted in the following scheme. [C13] JPEG2025505715000011.jpg37170

[0145] 3.1 Step 1: Preparation of (E / Z) ethyl 3-methylpent-2-enoate

[0146] To a flame-dried round-bottom flask equipped with a magnetic stir bar under an argon atmosphere was added NaH (60% dispersion in mineral oil, 1.4 equiv.) and anhydrous THF (final concentration: 0.26 M). The resulting suspension was cooled to 0° C., then triethyl phosphonoacetate (1.5 equiv.) was added dropwise via syringe over 30 min, followed by butanone of formula (IVa3) (1.25 mL, 13.9 mmol, 1 equiv.). The mixture was allowed to warm to room temperature and stirred overnight, then quenched with saturated aqueous NH4CI. The aqueous phase was extracted three times with EtO, and the combined organic phase was dried over magnesium sulfate (MgSO), evaporated in vacuo, and purified by column chromatography using CHCl as an eluent to obtain compound (Va3) (E / Z) ethyl 3-methylpent-2-enoate as a viscous yellow liquid (E / Z=78:22, 1.94 g, 13.6 mmol, 98% yield). E isomer: 1 H NMR (400MHz, CDCI3): δ=5.67-5.65(m,1H),4.15(q,J=7.2Hz,2H),2.21-2.12(m,5H,H-4),1.28(t,J=7.2Hz,3H),1.07(t,J=7.5Hz,3H).

[0147] 3.2 Second step: Preparation of (E / Z)-3-methylpent-2-en-1-ol

[0148] Compound (Va3) obtained in the previous step (3.88 g, 27.3 mmol, 1 eq.) was added to a flame-dried round-bottom flask equipped with a magnetic stir bar under an inert atmosphere, followed by dry CHCl (final concentration: 1.12 M). The solution was cooled to 0° C., then DIBALH (1 M in CHCl, 2.1 eq.) was added via syringe, and the mixture was stirred for 2 h. The reaction was quenched at 0° C. by the addition of MeOH (2.5 eq.) and allowed to warm to room temperature. Then, a saturated NaCI solution was added, followed by EtO, and the mixture was filtered through Celite. The phases were separated, the organic phase was dried over MgSO4, and concentrated in vacuo. The crude mixture was purified by flash column chromatography using the mixture Et2O:CH2Cl2 (5% Et2O:CH2Cl2) as eluent to give compound (VIa3) (E / Z)-3-methylpent-2-en-1-ol as a colorless liquid (E / Z=78:22, 1.39 g, 13.9 mmol, 51% yield).

[0149] E isomer: 1 H NMR (400MHz, CDCI3): δ = 5.44-5.35 (m, 1H), 4.20-4.10 (m, 2H), 2.14-2.00 (m, 2H), 1.76-1.66 (m, 3H), 1.05-0.98 (m, 3H).

[0150] 3.3 Third step: Preparation of (E / Z)-3-methylpent-2-enal

[0151] In an inert atmosphere, a flame-dried round-bottom flask equipped with a magnetic stir bar was charged with MnO2 (5 equiv.) and anhydrous CHCl. 12 (0.49M) and then compound (VIa3) obtained in the previous step (930 mg, 9.29 mmol, 1 equiv.) were added. A condenser was connected and the mixture was heated under reflux overnight. The mixture was then cooled to room temperature and filtered through a pad of Celite. The solvent was removed in vacuum and the crude mixture was purified by flash column chromatography using a (1:1) CHCl / pentane mixture as eluent to give compound (IIa3) (E / Z)-3-methylpent-2-enal as a colorless liquid (E / Z=78:22, 400 mg, 13.9 mmol, 44% yield).

[0152] E isomer: 1 H NMR (400MHz, CDCl3): δ=9.97(d,J=8.2,1H,H-1),5.86-5.81(m,1H,H-2),2 .60(q,J=7.5,2H,H-3),1.98(d,J=1.3,3H,H-4),1.17(t,J=7.6,3H,H-5).

[0153] Preparation of 2-ethyl-2-methyl-7-phenethyl-2H-chromen-5-ol (compound Ia3)

[0154] In an inert atmosphere, a flame-dried sealed tube equipped with a magnetic stir bar was charged with compound (IIIa1) (50 mg, 0.233 mmol, 1 eq.) previously prepared in Example 1, followed by anhydrous toluene (0.1 M) and aldehyde (IIa3) (1.5 eq.) previously prepared in Example 3. Ethylenediaminediacetic acid (EDDA, ​​5 mol%) was then added. The vessel was sealed and heated to 115° C. for 1 h. This procedure (addition of EDDA and heating) was repeated three times (total of 15 mol% EDDA added) and then cooled to room temperature, after which a small amount of silica was added and the solvent removed under vacuum. The crude mixture was purified by flash silica column chromatography (dry loading) eluting with hexane / EtOAc (95:5, Rf=0.28) to give the corresponding chromene (Ia3) as a yellow viscous liquid (27 mg, 0.0017 mmol, 39%).

[0155] 1 H NMR (400MHz, CDCl3): δ=7.30-7.24(m,2H),7.22-7.14(m,3H),6.26(d,J=10.1, 1H),6.30-6.27(m,1H),6.11-6.08(m,1H),5.49(d,J=10.1,1H),4.85-4.68(br s,1H),2.90-2.81(m,2H),2.80-2.71(m,2H),1.79-1.62(m,2H),1.36(s,3H),0.95(t,J=7.5,3H).

[0156] 13C NMR (101MHz, CDCI3): δ=154.2,151.1,143.5,141.7,128.4,128.3,127.4,125.9,116.9,109.1,107.7,107.3,78.6,37.9,37.4,33.7,25.8,8.2.

[0157] IR(ATR):3404,2972,2929,2869,1623,1576,1496,1434,1136,1062,829.

[0158] HRMS(ESI+):C 20 H 23 O2 + [MH + ]Theoretical value: 295.1693; Actual value: 295.1686.

[0159] Example 4: Synthesis of compound IC1

[0160] Compound (Ia1) (100 mg, 0.36 mmol) and 10% Pd / C (10 mg, 10% by weight) were added to a flame-dried sealed tube equipped with a magnetic stir bar under an inert atmosphere, followed by ethyl acetate (1.52 mL, 0.245 M). Ammonium formate (115 mg, 1.82 mmol) was then added and the mixture was stirred overnight at room temperature. 10 wt% Pd / C (10 mg) and ammonium formate (68.09 mg, 1.08 mmol) were then added again. The reaction mixture was stirred for 3 hours, then filtered through a Celite pad and evaporated in vacuum. Residual ammonium formate was precipitated by the addition of dichloromethane, and the mixture was filtered again and evaporated in vacuum to give the expected compound (IC1) as a pale yellow liquid (97.2 mg, 0.34 mmol, 97% yield).

[0161] 1 H NMR (400MHz, CDCI3): δ=7.32-7.24(m,2H),7.22-7.14(m,2H),6.33(d,1H),6.19(d,1H),4.63-4.59(br s, 1H), 2.92-2.70 (m, 2H), 2.63 (t, 1H), 1.81 (t, 1H), 1.33 (s, 6H).

[0162] Example 5: Use of compounds (la1), (Ia2), (Ia3) and (IC1) as herbicides

[0163] Arabidopsis thaliana ecotype Col-0 seedlings were grown hydroponically at the cotyledon stage and biological tests were performed under sterile conditions. Sterilized seeds were sown in microplates (10 seeds per well with 200 μL of distilled water) and incubated for 10–13 days at 22 °C under illumination with a 16 h / 8 h (day / night) photoperiod. Treatments were performed by replacing the culture medium with an equal volume of water containing the test molecule dissolved in DMSO. The maximum DMSO concentration in the treatment wells was 1% by volume. Therefore, a control was set up in which this concentration of DMSO was present. Phytotoxicity of the treatments was evaluated by visual analysis of induced chlorosis after 48 h of incubation.

[0164] For comparison, assay tests were also carried out under the same conditions as for compounds (Ia1), (Ia2), (Ia3) and (IC1) with two comparative compounds which do not form part of the present invention: - compounds (2) containing a diphenol ring instead of a chromene ring, and - Compounds containing a chromene ring but no -L-Ar group (3). All compounds were tested at a concentration of 125 pM.

[0165] The results are shown in Table 2 below.

[0166] Herbicidal activity is indicated by an A for Active when the plant is dead, ie, when both cotyledons have lost all their green color 48 hours after application of the product.

[0167] Lack of herbicidal activity is indicated by "N" for Not active when no biological activity is observed.

[0168] [Table 2] JPEG2025505715000012.jpg235170

[0169] As is evident from the above table, compounds 2 and 3, which are not according to the invention, do not exhibit herbicidal activity at the concentrations tested.

[0170] These studies highlight the following: the presence of a heterobicyclic ring is mandatory (compare compound of formula Ia1 according to the invention with compound (2) not according to the invention), - it is also mandatory that this heterobicyclic ring is substituted with a group of the type -L-Ar (compare the compound of formula la1 according to the invention with compound (3) not according to the invention).

Claims

1. Formula (I) having the following structure: [C20] [In the formula, ＊ R １ , R ２ and R ３ are each independently a hydrogen atom, a halogen atom, or C １ -C ５ Alkyl or cycloalkyl radicals, or -OH, -COOH, -COOR ５ , -OR ５ and -SO ２ R ５ represents a group selected from ５ is C １ -C ５ is an alkyl or cycloalkyl radical, １ -C ５ The alkyl or cycloalkyl radicals may be substituted with one or more substituents selected from halogen atoms and hydroxy groups; ＊ X is a part of a six-membered heterocycle and is an oxygen atom, a sulfur atom, a divalent SO group, a divalent SO ２ Groups and divalent NR ６ represents a group, and R ６ is a hydrogen atom, C １ -C ５ an alkyl or cycloalkyl radical, or C ２ -C ８ is an aryl or heteroaryl radical, represents a single bond or a double bond at the 2,3 or 3,4 positions of a six-membered heterocycle having a heteroatom or a divalent group X, and therefore the six-membered heterocycle contains either two single bonds at the 2,3 and 3,4 positions, or a single bond at the 2,3 positions and a double bond at the 3,4 positions, or a double bond at the 2,3 positions and a single bond at the 3,4 positions; ＊ L represents a linking arm selected from linear and branched alkylene chains having at least one carbon atom, said linear or branched alkylene chains being optionally interrupted and / or terminated with one or more heteroatoms selected from oxygen, sulfur or substituted nitrogen atoms; ＊ Ar represents an aromatic group selected from phenyl, naphthyl, furyl, thiophenyl, pyrrolyl, pyridinyl, indolyl, isoindolyl, benzofuryl, benzothiophenyl, quinolyl and isoquinolyl, imidazolyl, oxazolyl, thiazolyl, pyrimidyl, pyridazyl, pyrazyl, pyrazolyl and triazolyl groups, said aromatic group being free of halogen atoms, C １ -C ５ Alkyl or cycloalkyl radical, —OH group, —COOH group, —COOR ７ group, -OR ７ group, and —SO ２ R ７ group, and R ７ is C １ -C ５ is an alkyl or cycloalkyl radical, １ -C ５ The alkyl or cycloalkyl radicals may be substituted with one or more substituents selected from halogen atoms and hydroxy groups; ＊ n is an integer ranging from 4 to 6, and the same or different substituents R ４ represents the number of ＊ R ４ represents a hydrogen atom, a halogen atom, or C １ -C ５ Alkyl or cycloalkyl radicals, or -OH, -COOH, -COOR ８ , -OR ８ and -SO ２ R ８ represents a group selected from ８ is C １ -C ５ is an alkyl or cycloalkyl radical, １ -C ５ The alkyl or cycloalkyl radicals may be substituted with one or more substituents selected from halogen atoms and hydroxy groups.

1. Use of at least one compound selected from compounds having the formula:

2. 2. Use according to claim 1, characterized in that X represents an oxygen atom.

3. group R １ , R ２ and R ３ 2. The method according to claim 1, wherein at least one of the groups represents an —OH group.

4. group R ３ represents an —OH group, and the other two groups R １ and R ２ are each independently a hydrogen atom, a —COOH group or a —COOR ５ represents a group, and R ５ is C １ -C ５ 2. The use according to claim 1, characterized in that it is an alkyl radical.

5. 2. Use according to claim 1, characterized in that L represents a linear alkylene chain having 1 to 6 carbon atoms.

6. 2. Use according to claim 1, characterized in that Ar represents a phenyl group, said phenyl group being optionally substituted with one or more of the substituents defined in claim 1.

7. The heterocycle may contain a double bond, and therefore the compound of formula (I) may have the following formula (Ia) or (Ib): [C21] [In the formula, ＊ Ar, L, R １ , R ２ , R ３ and X are as defined in claim 1, and ＊ R ４ａ , R ４ｂ , R ４ｃ and R ４ｄ may be the same or different, and are a hydrogen atom or C １ -C ５ represents an alkyl or cycloalkyl radical, １ -C ５ The alkyl or cycloalkyl radical may be substituted with one or more halogen atoms.

2. The use according to claim 1, characterized in that it has

8. R ４ａ C optionally substituted with one or more halogen atoms １ -C ３ represents an alkyl radical, R ４ｂ is a hydrogen atom or C optionally substituted with one or more halogen atoms １ -C ３ represents an alkyl radical, and R ４ｃ and R ４ｄ 8. Use according to claim 7, characterized in that represents a hydrogen atom.

9. The heterocycle does not contain a double bond, and therefore the compound of formula (I) has the following formula (Ic): [C22] [In the formula, ＊ Ar, L, R １ , R ２ , R ３ and X are as defined in claim 1, and ＊ R ４ａ , R ４ｂ , R ４ｃ , R ４ｄ , R ４ｅ , and R ４ｆ may be the same or different, and are a hydrogen atom or C １ -C ５ represents an alkyl or cycloalkyl radical, １ -C ５ The alkyl or cycloalkyl radical may be substituted with one or more halogen atoms.

2. The use according to claim 1, characterized in that it has

10. R ４ａ and R ４ｂ represents a methyl radical, and R ４ｃ , R ４ｄ , R ４ｅ , and R ４ｆ 10. The use according to claim 9, characterized in that represents a hydrogen atom.

11. The compound of formula (I) is the compound: [Table 3] 2. The use according to claim 1, characterized in that it is selected from:

12. Phytotoxic composition, characterized in that it comprises at least one compound as defined in claim 1 as herbicidally active substance in combination with one or more formulation additives to improve water solubility and / or penetration into plant tissues.

13. 13. The phytotoxic composition according to claim 12, further comprising one or more other active ingredients selected from fertilizers, growth regulators and additional herbicides.

14. 14. A method for controlling and / or treating undesirable vegetation on the surface of a target area, the method comprising contacting the target area with an effective amount of at least one compound as defined in any one of claims 1 to 11, or at least one phytotoxic composition as defined in claim 12 or 13.

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