Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
  • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
  • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
  • C07D213/81—Amides; Imides
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
  • A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
  • A01N37/46—N-acyl derivatives
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
  • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
  • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
• • A—HUMAN NECESSITIES
  • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
  • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
  • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
  • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
  • A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
  • C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
  • C07C237/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having carbon atoms of carboxamide groups, amino groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
  • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
  • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
  • C07D213/81—Amides; Imides
  • C07D213/82—Amides; Imides in position 3
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
  • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
  • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
  • C07D213/83—Thioacids; Thioesters; Thioamides; Thioimides
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
  • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
  • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
  • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
  • C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
  • C07D241/28—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C2601/00—Systems containing only non-condensed rings
  • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
  • C07C2601/14—The ring being saturated

Definitions

• the present invention relates to amino esters having a high fungicidal activity; in particular, it relates to suitably substituted compounds having a high fungicidal activity and their use for the control of phytopathogenic fungi of important agricultural crops.
• Fungicidal amino esters have been described in literature and in particular are described in patent applications WO99/27783, WO01/14339, WO01/12587 and WO01/05769.
• the present invention therefore relates to new compounds having general formula (I):
• X represents a hydrogen atom or a C(O)R 6 group
• Y represents a hydrogen atom or a C(O)R 6 group or a Q group:
• Z 1 and Z 2 can represent a nitrogen atom or a CR c group
• R c represents a hydrogen atom, a halogen atom selected from fluorine, chlorine, bromine or iodine, a C 1 -C 12 alkoxyl group, a C 1 -C 12 thioalkoxyl group, a nitro group, an amino group, a formylamino group;
• M represents a halogen atom selected from fluorine, chlorine, bromine or iodine or a W 2 -
• W 1 and W 2 represent an oxygen atom or a sulfur atom;
• R d represents a hydrogen atom, a halogen atom selected from fluorine, chlorine, bromine or iodine, a nitro group, a cyano group, a C 1 -C 12 alkyl group, a C 3 -C 12 cycloalkyl group, a C 3 -C 12 cycloalkyl-C 1 - C 12 -alkyl group, a C 1 -C 12 haloalkyl group, a C 2 -C 12 alkenyl group, a C 2 -C 12 haloalkenyl group, a C 3 -C 12 cycloalkenyl group, a C 1 -C 12 alkoxyl group, a C 1 -C 12 thioalkoxyl group, a C 3 -C 12 cycloalkoxyl group, an aryl group, a phenoxy
• R 6 represents a C 1 -C 12 alkoxyl group, a benzyloxy group or a fluorenylmethoxy group
• R 7 represents a hydrogen atom, a COR group, a CH 2 OCOR group, a CH 2 OR group, aCH 2 SR 8 group;
• R 8 represents a C 1 -C 12 alkyl group, a C 3 -C 12 cycloalkyl group, a C 1 -C 12 haloalkyl group, a C 1 -C 12 alkoxyl group, said groups being optionally substituted by one or more R d groups the same as or different from each other;
• R 9 and R 10 represent a hydrogen atom, a C 1 -C 12 alkyl group, a C 1 -C 12 haloalkyl group, a C 2 -C 12 alkenyl group, a C 2 -C 12 haloalkenyl group, a C 3 -C 12 cycloalkyl group, a C 3 -C 12 halocycloalkyl group, an aryl group, an aryl- C 1 -C 12 - alkyl group, said groups being optionally substituted by one or more R d groups the same as or different from each other;
• R a , R b and R e represent a hydrogen atom, a C 1 - C 12 alkyl group, a C 1 -C 12 haloalkyl group, a C 3 -C 12 cycloalkyl group, an aryl group, an aryl-C 1 -C 12 -alkyl group, a heterocyclic group, penta- or hexa-atomic, aromatic or non- aromatic, containing at least one heteroatom selected from oxygen, sulfur, possibly oxidized to sulfoxide or sulfone, nitrogen, possibly oxidized to N-oxide, a heterocyclyl- C 1 -C 12 - alkyl group wherein the heterocyclic group is as defined above, said groups being optionally substituted by one or more R d groups;
• R a and R b together with the carbon atom to which they are bound, form a C 3 -C 12 cycloalkyl ring; or R b and R e together with the two carbon atoms to which they are bound, form a C 4 -C 12 cycloalchyl ring;
• R 1 represents a hydrogen atom, a C 1 -C 12 alkyl group, a C 1 -C 6 haloalkyl group, a C 2 -C 12 alkenyl group, a C 2 -C 12 haloalkenyl group, a C 3 -C 12 cycloalkyl group, a C 3 -C 12 cycloalkenyl gorup, a C 3 -C 12 cycloalkyl-C 1 -C 12 -alkyl group, an aryl group, an aryl-C 1 - C 12 -alkyl group, a heterocyclic group, penta- or hexa-atomic, aromatic or non-aromatic, also benzocondensed or heterobicyclic, containing at least one heteroatom selected from oxygen, sulfur, possibly oxidized to sulfoxide or sulfone, nitrogen, possibly oxidized to N-oxide or a heterocyclyl-C 1 -C 12 -al
• R 2 represents a C 1 -C 12 alkyl group, a C 1 -C 12 haloalkyl group, a C 2 -C 12 alkenyl group, a C 2 -C 12 haloalkenyl group, a C 3 -C 12 cycloalkyl group, a C 3 -C 12 cycloalkenyl group, a C 3 - C 12 cycloalkyl-C 1 -C 12 -alkyl group, an aryl group, an aryl-C 1 -C 12 -alkyl group, a heterocyclic group, penta- or hexa-atomic, aromatic or non-aromatic, also benzocondensed or heterobicyclic, containing at least one heteroatom selected from oxygen, sulfur, possibly oxidized to sulfoxide or sulfone, nitrogen, possibly oxidized to
• R 2 represents a group selected from the following T and T 1 residues:
• R 3 , R 5 represent a C 1 -C 12 alkyl group, a C 1 -C 12 haloalkyl group, a C 2 -C 12 alkenyl group, a C 2 -C 12 haloalkenyl group, a C 3 -C 12 cycloalkyl group, an aryl group, an aryl-C 1 -C 12 -alkyl group, a heterocyclic group, penta- or hexa- atomic, aromatic or non-aromatic, also benzocondensed or heterobicyclic, containing at least one heteroatom selected from oxygen, sulfur, possibly oxidized to sulfoxide or sulfone, nitrogen, possibly oxidized to N-oxide or a heterocyclyl-C 1 -C 12 -alkyl group, said groups being optionally substituted by one or more R d groups;
• R 4 represents a hydrogen atom, a hydroxyl, a halogen atom selected from fluorine, chlorine, bromine or iodine, a C 1 -C 12 alkyl group, a C 1 -C 12 haloalkyl group, a C 2 -C 12 alkenyl group, a C 2 -C 12 haloalkenyl group, a C 3 -C 12 cycloalkyl group, a C 1 -C 12 alkoxyl group;
• R 11 , R 12 and R 13 represent a hydrogen atom, a C 1 -C 12 alkyl group, a C 1 -C 12 haloalkyl group, a C 2 -C 12 alkenyl group, a C 2 -C 12 haloalkenyl group, a C 3 -C 12 cycloalkyl group, said groups being optionally substituted by one or more R d groups;
• R 1 and R 2 together with the carbon atom to which they are bound form a C 3 -C 12 cycloalkyl group or a C 3 -C 12 cycloalkenyl group, or a heterocyclic group, penta- or hexa- atomic, containing at least one heteroatom selected from oxygen, sulfur, possibly oxidized to sulfoxide or sulfone, nitrogen, possibly oxidized to N-oxide, said groups being optionally substituted by one or more R d groups;
• R a and R b different from each other, indifferently represent a hydrogen atom or a methyl, R 1 and R 2 , different from each other, cannot have the meanings of hydrogen and methyl;
• R a and R b different from each other, indifferently represent a hydrogen atom or a phenyl, R 1 and R 2 , different from each other, cannot have the meanings of hydrogen and
• the compounds having general formula (I) are preferably compounds wherein:
• - X represents a hydrogen atom or a C(O)R 6 group
• - Y represents a hydrogen atom or a C(O)R 6 group or a Q group
• Z 1 and Z 2 can represent a nitrogen atom or a CR c group
• R c represents a hydrogen atom, a halogen atom, a C 1 -C 12 alkoxyl group, a C 1 -C 12 thioalkoxyl group, a formylamine group;
• M represents a W 2 -R 7 group
• W 1 and W 2 represent an oxygen atom or a sulfur atom
• R d represents a hydrogen atom, a halogen atom selected from fluorine, chlorine, bromine or iodine, a C 1 -C 12 alkyl group, a C 1 -C 12 haloalkyl group, a C 1 -C 12 alkoxyl group, a C 1 - C 12 thioalkoxyl group;
• n a number ranging from 0 to 1 ;
• R 6 represents a C 1 -C 12 alkoxyl group, or a fluorenylmethoxy group
• R 7 represents a hydrogen atom, a COR 8 group, a CH 2 OCOR 8 group, a CH 2 SR 8 group;
• R 8 represents a C 1 -C 12 alkyl group, a C 1 -C 12 alkoxyl group, said groups being optionally substituted by one or more R d groups the same as or different from each other;
• R a , R b and R e represent a hydrogen atom, a C 1 - C 12 alkyl group, a C 1 -C 12 haloalkyl group, an aryl group, an aryl-C 1 -C 12 -alkyl group, said groups being optionally substituted by one or more R d groups;
• R a and R b together with the carbon atom to which they are bound, form a C 3 -C 12 cycloalkyl ring;
• R 1 represents a hydrogen atom, a C 1 -C 12 alkyl group, a C 1 -C 6 haloalkyl group, a C 3 -C 12 cycloalkyl group, an aryl group, said groups being optionally substituted by one or more R d groups;
• R 2 represents a C 1 -C 12 alkyl group, a C 1 -C 12 haloalkyl group, a C 3 -C 12 cycloalkyl group, a C 3 -C 12 cycloalkenyl group, a C 3 -C 12 cycloalkyl-C 1 -C 12 -alkyl group, an aryl group, an aryl- C 1 -C 12 -alkyl group, said groups being optionally substituted by one or more R d groups, or R 2 represents a group selected from the following T and T 1 residues:
• R 3 , R 5 the same as or different from each other, represent a C 1 -C 12 alkyl group, a C 3 -C 12 cycloalkyl group, an aryl group, said groups being optionally substituted by one or more R d groups;
• R 4 represents a hydrogen atom, a hydroxyl, a C 1 -C 12 alkyl group, a C 1 -C 12 alkoxyl group;
• R 11 , R 12 and R 13 represent a hydrogen atom, a C 1 -C 12 alkyl group, said groups being optionally substituted by one or more R d groups; or R 1 and R 2 together with the carbon atom to which they are bound, form a C 3 -C 12 cycloalkyl group, said groups being optionally substituted by one or more R d groups.
• C 1 -C 12 alkyls which can be linear or branched, are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, 3-methylbutyl, n-hexyl, 3,3- dimethylbutyl.
• C 1 -C 12 haloalkyls are fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, 2,2,2-trifluoroethyl, 1,1,2,2-tetrafluoroethyl, pentafluoroethyl, heptafluoropropyl, 4,4,4-trichloro-butyl, 4,4-difluoropentyl, 5,5-difluorohexyl.
• C 2 -C 12 alkenyls which can be linear or branched, are vinyl, allyl, 3-butenyl, 4-pentyl.
• C 2 -C 12 haloalkenyls are 1-(1,1,2-trifluoro)-butenyl, 1-(2,2-difluoro)-butenyl.
• C 3 -C 12 cycloalkyls are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl.
• C 3 -C 12 sono ciclopropenile, ciclopentenile, cicloesenile.
• C 3 -C 12 halocycloalkyls are 2,2-dichloro-cyclopropyl, 2,2-difluorocyclopropyl, 2,2,3,3-tetrafluorocyclobutyl, 3 ,3-difluorocyclopentyl , 2-fluorocyclohexyl.
• C 3 -C 12 cycloalkyl-C 1 -C 12 -akyls are cyclopropylmethyl, 2-cyclopentylethyl, 2- cyclohexylpropyl.
• C 1 -C 12 alkoxyls are methoxyl, ethoxyl, iso-propoxyl, tert-butoxyl.
• C 1 -C 12 thioalkoxyls are thiomethoxyl, thioethoxyl, iso-thiopropoxyl.
• C3-C12 cycloalkoxylic are cyclopropoxy, cyclopentoxyl.
• phenoxyl groups are 4-chloro-phenoxyl, 2,4-difluoro-phenoxyl, 3-methyl phenoxyl.
• aryls referring to aromatic systems consisting of carbon atoms, are phenyl, naphthyl.
• heterocyclic rings referring to cyclic systems with 5 or 6 terms, aromatic or non-aromatic, possibly benzocondensed containing from 1 to 3 heteroatoms selected from O, N, S, are: thiazole, 1,3,4 thiadiazole, pyrrolidine, piperidine, morpholine, pyrazole etc.
• Esempi di aryl-C 1 -C 12 -alkyl are benzyl, phenylethyl, 2-phenyl-propyl, 3-(2-fluoro)-phenyl- butyl.
• heterocyclyl-C 1 -C 12 -alkylene examples include 2-(1,3,4-thiadiazolyl)-methyl, 4-pyrazolyl- methyl, 2-[3-(N-methyl)-pyrrolidinyl]-propyl.
• Examples of compounds having general formula (I) with X having the meaning of hydrogen and Y representing a C(O)R 6 group are compounds wherein R a , R b , R e , R 1 , R 2 , R 6 have the meanings indicated in Table 1:
• Examples of compounds having general formula (I) with X and Y representing a hydrogen atom are compounds wherein, R a , R b , R e , R 1 , R 2 , have the meanings indicated in Table 2:
• the reaction is carried out by activating the acid by means of the corresponding chloride, for example with thionyl chloride in dichloromethane or chloroform or by using a condensing agent such as N,N'-dicyclohexylcarbodiimide or N-(3-dimethylaminopropyl)-N'- ethylcarbodiimide in tetrahydrofuran or ethyl acetate, or using 1,1-carbonyldiimidazole in tetrahydrofuran or methylene chloride or PyBOP [(1-Benzotriazolyloxy) tripyrrolidinephosphonium hexafluorophosphate], HATU (1-[Bis(dimethylamino)methylene]- 1H-1,2,3- triazole [4,5-b] pyridinium 3-oxide hexafluorophosphate) at a temperature ranging from 0°C to the reflux temperature of the solvent used, as
• the activated form of the acid in the presence of the amine having formula (lb) reacts in a suitable solvent such as methylene chloride, or dichloroethane, or chloroform at a temperature ranging from 0°C to the reflux temperature of the solvent in the presence or in the absence of a base such as triethylamine or 4-dimethylaminopyridine or diisopropylethylamine to give the compounds having general formula (I), according to what is known in literature in RC Larock "Comprehensive Organic Transformations".
• a suitable solvent such as methylene chloride, or dichloroethane, or chloroform
• a base such as triethylamine or 4-dimethylaminopyridine or diisopropylethylamine
• Z 1 has the value of CH
• Z 2 represents a CR c group wherein R c has the meaning of a formylamino group
• M represents a W 2 -R 7 group
• W 1 and W 2 are both oxygen
• n has the value of 0
• R 7 represents a COR 8 group and R 8 represents a methyl group and the use of the above compound having formula (II) as an intermediate in the preparation of compounds having formula (Ic).
• compound (V) which is condensed with a suitable alcohol having general formula (VI) in a suitable solvent such as methylene chloride, or dichloroethane, or chloroform, in the presence of a condensing agent such as N,N'-dicyclohexylcarbodiimide or N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide in tetrahydrofuran or ethyl acetate, or by using 1,1-carbonyldiimidazole in tetrahydrofuran or methylene chloride at a temperature ranging from 0°C to the reflux temperature of the solvent in the presence or absence of a base such as for example triethylamine or 4-dimethylaminopyridine or diisopropylethylamine as known in literature in RC Larock “Comprehensive Organic Transformations”.
• a suitable solvent such as methylene chloride, or dichloroethane, or chloro
• the reaction is carried out between the halide of the acid having formula (VII), wherein Alg preferably represents a chlorine atom and the N-carboxyhydride of beta amino acid (VIII) in a suitable solvent such as ethyl acetate, methylene chloride, or dichloroethane, or chloroform, at a temperature ranging from 0°C to the reflux temperature of the solvent in the presence or absence of a base such as for example triethylamine or 4-dimethylaminopyridine or diisopropyl- ethylamine according to what is known in literature in CN 108658887 to give the intermediates having formula (IX) with W 1 which has the meaning of oxygen, not known in literature.
• a suitable solvent such as ethyl acetate, methylene chloride, or dichloroethane, or chloroform
• the compounds having general formula (Ic) with W 1 having the meaning of a sulfur atom can be easily obtained from the corresponding compounds with W 1 representing an oxygen atom, by sulfonating the amides by reaction with P 4 S 10 or with the Lawesson reagent, according to what is known in literature and described in R. Larock "Comprehensive Organic Transformations " .
• the compounds having general formula (Ic) when Z 1 has the meaning of a CH group and 2 a CR c group, with R c representing an NHCHO group can be obtained by condensing the appropriate 3-nitrosalicylic acid (Ila) with beta amino ester ( lb) to give the compound having formula (Ic') and subsequent reduction reaction of the nitro group to give the compound having formula (Ic”).
• the compounds having formula (Ic") can be subjected to a formylation reaction to give the compound having general formula (Ic), according to reaction scheme 4:
• the conditions of the condensation reaction between the compounds having general formula (Ila) and (lb) are the same as those described in the previous paragraphs.
• the reduction reaction of the nitro group can be carried out according to the usual methods well-known in the art and described in RC Larock "Comprehensive Organic Transformations", such as for example catalytic hydrogenation in the presence of catalysts such as for example Pd on 5% carbon or Pd on 10% carbon in a solvent such as methanol, ethanol or tetrahydrofuran, at atmospheric pressure or under pressure and at a temperature ranging from environmental values to 80°C, or with ammonium formate in methanol at atmospheric pressure and room temperature or with metallic iron and acetic acid in a hydro alcoholic mixture at temperatures ranging from environmental values to the reflux values of the reaction mixture, or with tin chloride in ethyl acetate at the reflux temperature of the solvent.
• a solvent such as methanol, ethanol or tetrahydrofuran
• the formylation reaction of the amino group can be carried out according to the usual methods well-known in the art such as, for example, using a mixed anhydride obtained between formic acid and acetic anhydride in a solvent such as tetrahydrofuran or dioxane as described in Krishnamurthy S. " Tetrahedron Letters ", 1982, vol. 23, pages 3315-3318, or in formamide at 150°C as described in John Janetzko, Robert A. Batey, "Journal of Organic Chemistry", 2014, vol. 79, pages 7415-7424 or with zinc oxide and formic acid as written in Hosseini-Sarvari Mona, Sharghi Hashem, “Journal of Organic Chemistry", 2006, vol. 71 (17), pages 6652-6654 or cerium oxide and formic acid in the presence of ultrasounds as described in Sajadi S. Mohammad et al, “Letters in Organic Chemistry", 2014, vol.11, pages 49-54.
• the compounds having general formula (Ic) wherein R 7 has the meaning of a COR 8 group, OCOR 8 group, a CH 2 OR 8 group or a CH 2 SR 8 group, are obtained by acylation or alkylation reaction of the corresponding compounds having general formula (Ic) wherein R 7 represents a hydrogen atom using a compound having general formula L-R 7 , with R 7 different from the hydrogen atom and L which represents an outgoing group such as halogen, a mesylate or a triflate in ethyl acetate or N, N-dimethylformamide or acetone with a temperature ranging from -15°C to 70°C, in the presence of an organic or inorganic base such as potassium carbonate, or sodium carbonate, or triethylamine or pyridine or sodium hydride in the presence or absence of a catalyst such as sodium iodide, potassium iodide and a crown ether such as 15-crown-5 or 18-crown-6 according to methods well
• hydrides such as sodium borohydride, lithium aluminum hydride in suitable solvents such as tetrahydrofuran or dioxane at a temperature ranging from 0°C to the boiling point of the solvent according to methods known in literature as described in E. Tadashi, U. Norichika, Y. Masataka, et al. "Tetrahedron", 2009, vol. 65, pages 9583 - 95
• the Q1-Q4 groups when they are not commercial, can be obtained using the procedures reported in R. E. Buntrock "Review of Heterocyclic Chemistry", 5th Edition, 2012 Copyright ⁇ 2012 The American Chemical Society and Division of Chemical Education, Inc.
• the present invention also relates to reaction intermediates having general formula (IX)
• Z 1 , Z 2 , M, R a , R b , R d , R e and n have the same meanings previously defined.
• the present invention also relates to the use of the above compounds having formula (IX) as intermediates in the preparation of compounds having formula (Ic).
• the present invention further relates to the use of compounds having formula (I) for the control of phytopathogenic fungi of agricultural crops..
• the compounds having general formula (I) are in fact endowed with an extremely high fungicidal activity that is exerted against numerous phytopathogenic fungi that attack important agricultural crops.
• phytopathogenic fungi that can be effectively treated and fought against with the compounds having general formula (I) are those belonging to the classes of Basidiomycetes,
• Tilletia spp. Uromyces spp., Phakopsora spp., Rhizoctonia spp., Eryiphe spp., Sphaerotheca spp., Podosphaera spp., Uncinula spp., Helminthosporium spp., Rhynchosporium spp.,
• Pyrenophora spp. Monilinia spp., Sclerotinia spp., Septoria spp. ( Mycosphaerella spp.), Venturia spp., Botrytis spp., Alternaria spp., Fusarium spp., Cercospora spp., Cercosporella herpotrichoides, Colletotrichum spp., Pyricularia oryzae, Sclerotium spp., Phytophtora spp., Pythium spp., Plasmopara viticola, Peronospora spp., Pseudoperonospora cubensis, Bremia lactucae.
• the main crops that can be protected with the compounds according to the present invention comprise cereals (wheat, barley, rye, oats, rice, corn, sorghum, etc.), fruit-trees (apples, pears, plums, peaches, almonds, cherries, bananas, vines, strawberries, raspberries, blackberries, etc.), citrus fruits (oranges, lemons, mandarins, grapefruit, etc.), legumes (beans, peas, lentils, soybeans, etc.), vegetables (spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes, eggplants, peppers, etc.), cucurbits (pumpkins, courgettes, cucumbers, melons, watermelons, etc.), oleaginous plants (sunflower, rapeseed, peanut, castor, coconut, etc.), tobacco, coffee, tea, cocoa, sugar beet, sugar cane, cotton.
• cereals wheat, barley, rye, oats, rice, corn,
• the compounds having formula (I) have proved to be extremely effective in the control of Plasmopara viticola on grapevines, Phytophtora infestans and Botrytis cinerea on tomatoes, Puccinia recondita, Erisiphae graminis, Helminthosporium teres, Septoria nodorum, Septoria tritici and Fusarium spp. on cereals, in the control of Phakopsora pachyrhizi on soybeans, in the control of Uromyces appendiculatus on beans, in the control of Venturia inaequalis on apple-trees, in the control of Sphaerotheca fuliginea on cucumbers.
• the compounds having general formula (I) are also effective in the control of phytopathogenic bacteria and viruses, such as for example Xanthomonas spp., Pseudomonas spp., Erwinia amylovora, the tobacco mosaic virus.
• the compounds having formula (I) are capable of exerting a fungicidal action of both a curative and preventive nature and show an extremely low or zero phytotoxicity with respect to the crops treated.
• fungicidal compositions containing the compounds according to the present invention suitably formulated.
• Tthe present invention also relates to fungicidal compositions comprising one or more compounds having formula (I), a solvent and/or solid or liquid diluent, possibly a surfactant.
• the above-mentioned fungicidal compositions can be in the form of dry powders, wettable powders, emulsifiable concentrates, emulsions, micro-emulsions, pastes, granules, granules dispersible in water, solutions, suspensions, etc.: the choice of the type of composition depends on the specific use.
• the fungicidal compositions are prepared according to known methods, for example by diluting or dissolving the active substance with a solvent medium and/or a solid or liquid diluent, possibly in the presence of surfactants.
• Silica, kaolin, bentonite, talc, diatomaceous earth, dolomite, calcium carbonate, magnesia, gypsum, clays, synthetic silicates, attapulgite, seppiolite can be used, for example, as solid diluents, or carriers.
• Solvents or liquid diluents that can be used are for example, in addition to water, aromatic organic solvents (xylols or blends of alkyl benzenes, chlorobenzene, etc.), paraffins (petroleum fractions), alcohols (methanol, propanol, butanol, octanol, glycerin, etc.), esters (ethyl acetate, isobutyl acetate, alkyl carbonates, alkyl esters of adipic acid, alkyl esters of glutaric acid, alkyl esters of succinic acid, alkyl esters of lactic acid, etc.), vegetable oils (rapeseed oil, sunflower oil, soybean oil, castor oil, corn oil, peanut oil, and their alkyl esters), ketones (cyclohexanone, acetone, acetophenone, isophorone, ethylamylketone, etc.), amides (N,N-d
• Propellant gases such as butane, propane, halogenated hydrocarbons, nitrogen or carbon dioxide can be used as liquefied diluents or liquefied substances which gasify at room temperature and pressure.
• Surfactants that can be used are sodium, calcium, potassium, triethylamine or triethanolamine salts of alkylnaphthalenesulfonates, poly-naphthalenesulfonates, alkylsulfonates, arylsulfonates, alkylarylsulfonates, polycarboxylates, sulfosuccinates, alkyl-sulfosuccinates, lignin sulfonates, alkyl sulfates; and furthermore polyethoxylated fatty alcohols, polyethoxylated alkylphenols, polyethoxylated or polypropoxy-polyethoxylated arylphenols or polyethoxylated, polyproproxy-polyethoxylated esters of sorbitol (block polymers), can also be used.
• the fungicidal compositions can also contain special additives for particular purposes, for example antifreeze agents such as propylene glycol, or adhesion agents such as arabic gum, polyvinyl alcohol, polyvinylpyrrolidone, dispersing agents, for example lignin and its salts, cellulose derivatives or alginates, or stabilizers, for example antioxidants or ultraviolet-ray absorbents.
• antifreeze agents such as propylene glycol
• adhesion agents such as arabic gum, polyvinyl alcohol, polyvinylpyrrolidone
• dispersing agents for example lignin and its salts, cellulose derivatives or alginates, or stabilizers, for example antioxidants or ultraviolet-ray absorbents.
• the concentration of active compound having formula (I) in the above compositions can vary within a wide range and depends on various factors. It varies in relation to the active compound having formula (I), the applications for which said compositions are destined, the environmental conditions and type of formulation adopted. In general, the concentration of active compound having formula (I) ranges from 0.1 to 90% by weight with respect to the total weight of the composition, preferably from 0.5 to 90% by weight.
• fungicidal compositions containing the compounds having general formula (I) other active ingredients compatible with the same, such as fungicides other than those having general formula (I), phytoregulators, antibiotics, herbicides, insecticides, fertilizers, biostimulants and/or mixtures thereof.
• fungicides different from those having general formula (I) which can be included in the fungicidal compositions object of the present invention are: fluindapyr, acibenzolar, aldimorph, ametoctradin, amisulbrom, ampropylfos, anilazine, azaconazole, azithiram, azoxystrobin, benalaxyl, benalaxyl-M, benodanil, benomyl, benquinox, bentaluron, benthiavalicarb, benthoxazin, benzamacril, benzamorf, benzovindiflupyr, binapacryl, bitertanol, bixafen, blasticidin-S, boscalid, bromuconazole, bupirimate, buthiobate, captafol, captan, carbamorph, carbendazim, carboxin, carpropamid, chinomethionat,
• the present invention therefore also relates to fungicidal compositions comprising at least one compound having general formula (I) and at least one other fungicide other than the compounds having formula (I).
• Fungicidal compositions containing at least one compound having formula (I) and one or more known fungicides are those wherein one or more compounds having general formula (I) are combined with one or more known fungicides belonging to the following classes:
• azoles selected from azaconazole, bitertanol, bromuconazole, cyproconazole, difenoconazole, epoxyconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imazalil, imibenconazole, ipconazole, ipfentrifluconazole, mefentrifluconazole, metconazole, myclobutanil, penconazole, propiconazole, prochloraz, prothioconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, tricyclazole, triflumizole, triticonazole;
• amines, ergosterol biosynthesis inhibitors selected from aldimorph, dodemorph, fenpropimorph, fenpropidin, spiroxamine, tridemorph;
• succinate-dehydrogenase inhibitors selected from benzovindiflupyr, bixafen, boscalid, carboxin, fluindapyr, fluopyram, flutolanil, fluxapyroxad, furametpyr, inpyrfluxam, isopyrazam, oxycarboxin, penflufen, penthiopyrad, sedaxane, thifluzamide;
• strobilurins selected from azoxystrobin, coumoxystrobin, dimoxystrobin, enoxastrobin, fluoxastrobin, kresoxim-methyl, metominostrobin, orysastrobin, picoxystrobin, pyraclostrobin, pyrametostrobin, pyraoxostrobin, trifloxystrobin;
• aniline-pyramidines selected from pyrimethanil, mepanipyrim, cyprodinil; g) benzimidazoles and analogues thereof selected from carbendazim, benomyl, thiabendazole, thiophanate-methyl;
• dicarboxyimides selected from iprodione, procymidone
• phtalimides selected from captafol, captan, folpet;
• SAR systemic acquired resistance
• phenylpyrroles selected from fenpiclonil, fludioxonil;
• acylalanines selected from benalaxyl, benalaxyl-M, furalaxyl, metalaxyl, metalaxyl-M;
• dithiocarbamates selected from maneb, mancozeb, propineb, zineb, metiram; q) phosphorus acid and its inorganic or organic salts, fosetyl- aluminium
• cupric compounds selected from Bordeaux mixture, carpropamid, copper hydroxide, copper oxychloride, copper sulfate, copper salicylate;
• fungicides selected from chlorothalonil, fenhexamid, fenpyrazamine, fluazinam, silthiofam, tebufloquin, zoxamide, dodine, guazatine, iminoctadine, tolclofos -methyl.
• the fungicidal compounds are indicated in the present description with their international ISO name; the chemical structures and their CAS and IUPAC names are reported in Alan Wood's Website (www.alanwood.net), Compendium of Pesticide Common Names; the chemical-physical data and biological characteristics of most of these compounds are indicated in the "Pesticide Manual", C.D.S. Tomlin, 15th edition, 2009, British Crop Production Council.
• compositions containing at least one compound having formula (I) (component A) and at least one other known fungicide are those consisting of:
• C42 compound 258 + cimoxanil; C43: compound 258 + dimetomorph; C44: compound 258 + oxathiopiproline; C45: compound 258 + fluopicolide;
• Component A i.e. the compounds having general formula (I), of the previous compositions
• Et is the percentage of expected effectiveness for the composition containing compounds A and B at the doses d A + d B
• E A is the percentage of effectiveness observed for component A at the dose d A
• E B is the percentage of effectiveness observed for component B at the dose d B .
• E t E A + E B 1 + E B2 - (E A XE B1 + E A XE B2 + E B1 XE B2 )/100
• Et is the percentage of expected effectiveness for the composition containing compounds A, B1 and B2 at the doses d A + d B1 + d B2
• E A is the percentage of effectiveness observed for component A at the dose d A
• E B1 is the percentage of effectiveness observed for component B1 at the dose d B1
• E B2 is the percentage of effectiveness observed for component B2 at the dose d B2 .
• the present invention therefore also relates to the use of the compositions comprising at least one compound having general formula (I) for the control of phytopathogenic fungi in agricultural crops.
• the main crops which can be protected with the compositions comprising at least one compound having formula (I), alone or combined with at least one other known active ingredient comprise cereals (wheat, barley, rye, oats, rice, com, sorghum, etc.), fruit-trees (apples, pears, plums, peaches, almonds, cherries, bananas, grape-vines, strawberries, raspberries, blackberries, etc.), citrus fruit (oranges, lemons, mandarins, grapefruit, etc.), legumes (beans, peas, lentils, soybeans, etc.), vegetables (spinach, lettuce, asparagus, cabbage, carrots, onions, tomatoes, potatoes, eggplants, peppers, etc.), cucurbits (pumpkins, zucchini, cucumbers, melons, watermelons, etc.), oleaginous plants (sunflower, rapeseed, peanut, castor, coconut, etc.); tobacco, coffee, tea, cocoa, sugar beet, sugar cane, cotton, nuts.
• compositions of the present invention have proved to be extremely effective in the control of Plasmopara viticola on vines, Phytophtora infestans and Botrytis cinerea on tomatoes, Phytophtora infestans on potatoes, Puccinia recondita, Erysiphe graminis, Helminthosporium teres, Septoria spp and Fusarium spp. on cereals, in the control of Phakopsora pachyrhizi on soybeans, in the control of Uromyces appendiculatus on beans, in the control of Venturia inaequalis on apple trees, in the control of Sphaerotheca fuliginea on cucumbers.
• compositions of the present invention are also effective in the control of soil fungi, such as, for example, Rhizoctonia solani, Sclerotinia spp, Pythium ultimum on vegetables.
• compositions of the present invention are also effective in the control of phytopathogenic bacteria and viruses, preferably Xanthomonas spp., Pseudomonas spp., Erwinia amylovora, the tobacco mosaic vims.
• compositions object of the present invention are capable of exerting a fungicidal action which can be of a curative, preventive or eradicative nature, and, in general, exhibit a very low or zero phy to toxicity on the crops treated.
• a fungicidal action which can be of a curative, preventive or eradicative nature, and, in general, exhibit a very low or zero phy to toxicity on the crops treated.
• the compositions comprise a compound having general formula (Ic) and at least one known active ingredient
• the weight ratios in the above compositions vary according to the compounds selected and can normally range from 1: 100 to 100: 1, preferably from 1:10 to 10: 1.
• the total concentration of the active components in the above compositions can vary within a wide range; they generally range from 1% to 99% by weight with respect to the total weight of the composition, preferably from 5 to 90% by weight with respect to the total weight of the composition.
• compositions can take place on any part of the plant, for example on the leaves, stems, branches and roots, or on the seeds themselves before sowing, or on the soil in which the plant grows.
• the present invention therefore also relates to a method for controlling phytopathogenic fungi in agricultural crops, which consists in applying effective and non-phytotoxic doses of compounds comprising at least one compound having formula (I), and, optionally, one or more known active ingredients compatible with the same, on any part of the plant to be protected or on the soil.
• the concentration of the amide compounds having general formula (I) in the above- mentioned compositions can vary within a wide range; in general, it ranges from 1% to 90% by weight with respect to the total weight of the composition, preferably from 5 to 50% by weight with respect to the total weight of the composition.
• compositions can take place on any part of the plant, for example on the leaves, stems, branches and roots, or on the seeds themselves before sowing, or on the soil in which the plant grows.
• the present invention therefore also relates to a method for the control of phytopathogenic fungi in agricultural crops, which consists in applying effective doses of the compounds having formula (I), used as such or formulated in fungicidal compositions as described above.
• the quantity of compound to be applied for obtaining the desired effect can vary according to various factors such as, for example, the compound used, the crop to be preserved, the type of pathogen, the degree of infection, the climatic conditions, the method of application, the formulation adopted.
• Doses of compound ranging from 10 g to 5 kg per hectare of agricultural crop generally provide a sufficient control.
• reaction mixture was stirred at this temperature for 2 hours and then left to rise to environmental values and under stirring for a further 2 hours. After LC-MS control, the reaction mixture was concentrated in a rotavapor and then purified by silica gel chromatography using an automatic Biotage separator. 1.50 g of the desired product were obtained. Yield 85%
• the reaction mixture was stirred at this temperature for 2 hours and then left to rise to environmental values and under stirring for a further 2 hours. After LC-MS control, the reaction mixture was washed with water and the phases were separated. The aqueous phase was extracted with CH 2 CI 2 (3 x 15 ml) and the combined organic phases were washed with water (1 x 30 ml) and with a saturated solution of NaCl (1 x 30 ml). These were then dried on Na 2 SO 4 , filtered an concentrated. 2.6 g of a raw product were obtained, which was washed with ethyl ether and filtered to eliminate the by-products of the condensing agent. The ether phase was concentrated in a rotavapor and then purified by silica gel chromatography using an automatic Biotage separator. 1.11 g of the desired product were obtained Yield 62%
• reaction mixture was stirred at this temperature for 2 hours and then left to rise to environmental values and under stirring overnight. After LC-MS control, the reaction mixture was concentrated in a rotavapor and then purified by silica gel chromatography using an automatic Biotage separator. 0.53 g of the desired product were obtained. Yield 80%
• the reaction mixture was stirred at this temperature for 2 hours and then left to rise to environmental values and under stirring for a further 2 hours. After LC-MS control, the reaction mixture was washed with water and the phases were separated. The aqueous phase was extracted with CH 2 CI 2 (3 x 10 ml) and the combined organic phases were washed with water (1 x 25 ml) and with a saturated solution of NaCl (1 x 25 ml). These were then dried on Na 2 SO 4 , filtered and concentrated. 1.8 g of a raw product were obtained which was washed with ethyl ether and filtered to eliminate the by-products of the condensing agent. The ether phase was concentrated in a rotavapor and then purified by silica gel chromatography using an automatic Biotage separator. 0.75 g of the desired product were obtained Yield 64%
• the aqueous phase was extracted with CH 2 CI 2 (3 x 15 ml) and the combined organic phases were washed with water (2 x 30 ml) and with a saturated solution of NaCl (1 x 30 ml). These were then dried over anhydrous Na 2 SO 4 , filtered and concentrated. 0.94 g of a raw product were obtained, which was purified by silica gel chromatography using an automatic Biotage separator. 0.50 g of the desired product were obtained. Yield 79%
• the aqueous phase was extracted with CH 2 CI 2 (3 x 15 ml) and the combined organic phases were washed with water (2 x 30 ml) and with a saturated solution of NaCl (1 x 30 ml). These were then dried on anhydrous Na 2 SO 4 , filtered and concentrated.
• the raw product thus obtained was purified by silica gel chromatography using an automatic Biotage separator. 0.14 g of product were obtained. Yield 22%
• the reaction mixture was stirred at this temperature for 2 hours and then left to rise to environmental values and under stirring for a further 2 hours. After LC-MS control the reaction mixture was washed with water and the phases were separated. The aqueous phase was extracted with CH 2 CI 2 (3 x 20 ml) and the combined organic phases were washed with water (2 x 30 ml) and with a saturated solution of NaCl (1 x 30 ml). These were then dried on anhydrous Na 2 SO 4 , filtered and concentrated. 2.45 g of a raw product were obtained which was washed with ethyl ether and filtered to eliminate the by-products of the condensing agent. The ether phase was concentrated in a rotavapor and then purified by silica gel chromatography using an automatic Biotage separator. 1.04 g of the desired product were obtained. Yield 55%
• the reaction mixture was stirred at this temperature for 2 hours and then left to rise to environmental values and under stirring for a further 2 hours. After LC-MS control, the reaction mixture was washed with water and the phases were separated. The aqueous phase was extracted with CH 2 CI 2 (3 x 15 ml) and the combined organic phases were washed with water (2 x 30 ml) and with a saturated solution of NaCl (1 x 30 ml). These were then dried over anhydrous Na 2 SO 4 , filtered and concentrated. 3.1 g of a raw product were obtained which was washed with ethyl ether and filtered to eliminate the by-products of the condensing agent. The ether phase was concentrated in a rotavapor and then purified by silica gel chromatography using an automatic Biotage separator. 1.16 g of the desired product were obtained. Yield 57%
• the reaction mixture was stirred at this temperature for 2 hours and then left to rise to environmental values and under stirring for a further 2 hours. After LC-MS control, the reaction mixture was washed with water and the phases were separated. The aqueous phase was extracted with CH 2 CI 2 (3 x 20 ml) and the combined organic phase were washed with water (2 x 35 ml) and with a saturated solution of NaCl (1 x 35 ml), dried over anhydrous Na 2 SO 4 , filtered and evaporated. 2.3 g of a raw product were obtained which was washed with ethyl ether and filtered to eliminate the by-products of the condensing agent. The ether phase was concentrated in a rotavapor and then purified by silica gel chromatography using an automatic Biotage separator. 1.01 g of the desired product were obtained. Yield 61%
• Table 12 indicates the results of the GC-MS analyses carried out on compounds 206, 207, 209, 211, 212, 229, 234, 235, 236, 247, 263, 264, 268, 270, 272, 320 and 321.
• RH Relative Humidity
• the plants were kept in a humidity- saturated environment at a temperature ranging from 18 to 24°C for the incubation period of the fungus (1 day).
• the evaluation scale ranges from 0 (completely healthy plant) to 100 (completely necrotic plant).
• Table 13 indicates the results obtained by carrying out the test described with compounds Nr. 257, 258, 248, 262, 267.
• RH Relative Humidity
• the plants were sprayed on both sides of the leaves with an aqueous suspension of conidia of Phakopsora pachyrhizi (50 mg of urediniumspore in 100 ml of demineralized water with the addition of a drop of Tween surfactant). After spraying, the plants were kept in a humidity- saturated environment at a temperature ranging from 18 to 24°C for the incubation period of the fungus (1 day).
• Table 14 indicates the results obtained by carrying out the test described with compounds Nr. 257, 258, 248, 262, 267.
• the molecules having general formula (I) were tested to evaluate their antifungal activity in vitro against the following fungi and straminipila: Alternaria alternata, Botrytis cinerea, Cercospora beticola, Colletotrichum lindemuthianum, Drechslera graminea, Fusarium graminearum, Magnaporthe oryzaena Monilia, Parastagonospora nodorum, Phytophthora infestans, Pythium ultimum, Rhizoctonia solani, Sclerotinia sclerotiorum, Ustilago maydis, Venturia inaequalis and Zymoseptoria tritici.
• the pure culture isolates were kept and stored at 4°C in a refrigerator on agarized nutrient substrates suitable for each of them.
• the inoculum was prepared which, depending on the species of the pathogen, could be a suspension of conidia or a mycelial homogenate.
• mycelium plugs were transferred to a grinding egg containing 6 ml of Potato Dextrose Broth (PDB)2x and some metal balls.
• the suspension was homogenized with a Pulverisette 23 mini-mill (Fritsch GmbH).
• the conidic suspension was prepared starting from a culture grown on a suitable agarized medium and under suitable conditions for stimulating sporulation.
• the conidia were collected in 1 ml of PDB2x and counted under a microscope with a counting chamber in order to obtain a final inoculation of 2 x 104 conidia/ml.
• the concentrations tested for each active molecule were 0.001, 0.01, 0.1, 1,5 and 10 mg/1.
• a mother solution in dimethylsulfoxide (DMSO) at 80,000 mg/1 was prepared which was then serially diluted in sterile demineralized water to obtain the solutions to be tested in double concentrations compared to the final doses.
• the inhibition tests were carried out in 96-well plates: 50 ml of inoculum were mixed with 50 ml of the active molecule solution in each well using the Eppendorf Multipette® System E3 serial dispenser. Four wells were used as replicates for each concentration of active ingredient.
• the sensitivity to the molecules was assessed as a growth inhibition of the fungus and measured in terms of absorbance immediately before and after the incubation period.
• the absorbance was measured for each well using an Infinite® F50 Absorbance Reader (Tecan Group Ltd) spectrophotometer at 405 nm (for mycelial inoculae) and 492 nm (for conidic inoculae).
• the growth inhibition percentage (GIP) caused by each of the concentrations of the active ingredient was calculated using the following formula:
• At 72-120 and At 0 are respectively the absorbances of the treated and untreated well measured at the end and at the beginning of the incubation period.
• the GIP data were used for calculating EC 50 which are, respectively, the effective concentrations (mg/l) of active molecule that reduce mycelial growth by 50% compared to the untreated control.
• Table 15 shows the results obtained by carrying out the test described with compounds Nr.

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