# US 6,720,428 B2 · Method for producing 2-(1,2,4-triazol-1-yl)-ethanols > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 6,720,428 B2 - Document ID: US6720428B2 - Status: Granted - Kind: B2 - Application number: 10/203,148 - Filed: 2002-08-06 - Published: 2003-01-23 - Granted: 2004-04-13 - Earliest claimed: 2000-02-09 - Assignees: Bayer Aktiengesellschaft - Inventors: Thomas Himmler - Web page: https://patentgrep.com/patent/US6720428B2 ## CPC - C07D 231/12: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms - A61P 31/10: Antimycotics - C07D 233/56: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms - C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract According to a novel process, microbicidally active 2-(1,2,4-triazol-1-yl)-ethanols of the formula in which A1, A2, R1, R2, R3 and R4 are as defined in the description, can be prepared by reacting hydrazine derivatives of the formula with N-dihalogenomethyl-formamidinium halide of the formula in which X represents chlorine or bromine, if appropriate in the presence of a diluent. ## Claims ### Claim 1 A process for preparing a 2-(1,2,4-triazol-1-yl)-ethanol of the formula (I) wherein A1 and A2 independently of one another represent a direct bond, represent optionally halogen-substituted alkanediyl, represent optionally halogen-substituted alkenediyl, represented optionally halogen-substituted alkinediyl or represent alkanediyl in which a methylene group is replaced by oxygen, R1 and R2 independently of one another represent hydrogen, represent optionally substituted cycloalkyl or represent optionally substituted aryl and R3 and R4 independently of one another represent hydrogen or represent optionally substituted alkyl or R3 and R4 together with the carbon atom to which they are attached represent optionally substituted cycloalkyl, or R1, A1 and R3 together with the carbon atoms to which they are attached represent cycloalkyl, A2 represents a direct bond, represents optionally halogen-substituted alkanediyl, represents optionally halogen-substituted alkenediyl, represents optionally halogen-substituted alkinediyl or represents alkanediyl in which one methylene group has been replaced by oxygen, R2 represents hydrogen, represents optionally substituted cycloalkyl or represents optionally substituted aryl and R4 represents hydrogen or represents optionally substituted alkyl, or R3 and R4 represent hydrogen and the groups R1—A1— and R2—A2— together with the carbon atom to which they are attached represent a radical of the formula said process comprising the step of reacting a hydrazine derivative of the formula (II) wherein A1, A2, R1, R2, R3 and R4 are as defined above with an N-dihalogenomethyl-formamidinium halide of the formula (III) wherein X represents chlorine or bromine, optionally in the presence of a diluent. ### Claim 2 (depends on 1) The process according to claim 1, wherein in said hydrazine derivative of the formula (II) A1 represents a direct bond, represents optionally halogen-substituted, straight-chain or branched alkanediyl having 1 to 4 carbon atoms, represents optionally halogen-substituted, straight-chain or branched alkenediyl having 2 to 4 carbon atoms, represents optionally halogen-substituted straight-chain or branched alkinediyl having 2 to 4 carbon atoms or represents straight-chain or branched alkanediyl in which one methylene group has been replaced by oxygen, having 2 to 4 chain members, A2 represents a direct bond, represents optionally halogen-substituted straight-chain or branched alkanediyl having 1 to 6 carbon atoms represents optionally halogen-substituted straight-chain or branched alkenediyl having 2 to 6 carbon atoms or represents optionally halogen-substituted straight-chain or branched alkinediyl having 2 to 6 carbon atoms, R1 represents cycloalkyl having 3 to 7 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine and/or alkyl having 1 to 4 carbon atoms or represents aryl having 6 to 10 carbon atoms which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, alkyl having 1 to 4 carbon atoms, cyano, nitro, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon atoms, halogenoalkyl having 1 to 4 carbon atoms and 1 to 9 fluorine, chlorine and/or bromine atoms, halogenoalkoxy having 1 to 4 carbon atoms and 1 to 9 fluorine, chlorine and/or bromine atoms or halogenoalkylthio having 1 to 4 carbon atoms and 1 to 9 fluorine, chlorine and/or bromine atoms, R2 represents hydrogen or represents cycloalkyl having 3 to 7 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine and alkyl having 1 to 4 carbon atoms or represents aryl having 6 to 10 carbon atoms which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, alkyl having 1 to 4 carbon atoms, cyano, nitro, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon atoms, halogenoalkyl having 1 to 4 carbon atoms and 1 to 9 fluorine, chlorine and/or bromine atoms, halogenoalkoxy having 1 to 4 carbon atoms and 1 to 9 fluorine, chlorine and/or bromine atoms and halogenoalkylthio having 1 to 4 carbon atoms and 1 to 9 fluorine, chlorine and/or bromine atoms, and R3 and R4 independently of one another represent hydrogen or alkyl having 1 to 4 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine and alkoxy having 1 or 2 carbon atoms or R3 and R4 together with the carbon atom to which they are attached represent cycloalkyl having 3 to 6 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine and alkyl having 1 to 4 carbon atoms, or R1, A1 and R3 together with the carbon atoms to which they are attached represent cycloalkyl having 3 to 6 carbon atoms, A2 represents a direct bond, R2 represents hydrogen or represents cycloalkyl having 3 to 7 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine and alkyl having 1 to 4 carbon atoms or represents aryl having 6 to 10 carbon atoms which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, alkyl having 1 to 4 carbon atoms, cyano, nitro, alkoxy having 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon atoms, halogenoalkyl having 1 to 4 carbon atoms and 1 to 9 fluorine, chlorine and/or bromine atoms, halogenoalkoxy having 1 to 4 carbon atoms and 1 to 9 fluorine, chlorine and/or bromine atoms or halogenoalkylthio having 1 to 4 carbon atoms and 1 to 9 fluorine, chlorine and/or bromine atoms, and R4 represents hydrogen or represents alkyl having 1 to 4 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine and alkoxy having 1 or 2 carbon atoms, or R3 and R4 represent hydrogen and the groups R1—A1— and R2—A2— together with the carbon atoms to which they are attached represent a radical of the formula ### Claim 3 (depends on 1) The process according to claim 1, wherein in said hydrazine derivative of the formula (II) A1 represents a single bond, represents methylene, ethane-1,1-diyl, ethane-1,2-diyl, ethene-1,2-diyl, ethine-1,2-diyl or —O—CH2, where the CH2 group is attached to the carbinol carbon atom, A2 represents a direct bond or represents methylene, ethane-1,1-diyl, ethane-1,2-diyl, propane-1,1-diyl, propane-1,2-diyl, propane-1,3-diyl, propane-2,2-diyl, butane-1,1-diyl, butane-1,2-diyl, butane-1,3-diyl, butane-1,4-diyl, butane-2,2-diyl, 2-methyl-propane-1,2-diyl, ethylene-1,2-diyl or ethine-1,2-diyl, each of which is optionally mono- or disubstituted by fluorine and/or chlorine, R1 represents cycloalkyl having 3 to 6 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, methyl, ethyl, n-propyl, i-propyl, n-butyl, iso-butyl, sec-butyl and tert-butyl or represents phenyl or naphthyl, each of which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, methoxy, ethoxy, methylthio, ethylthio, trifluoromethyl, trifluoromethoxy, difluoromethoxy, trifluoromethylthio and difluoromethylthio, R2 represents hydrogen or represents cycloalkyl having 3 to 6 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, methyl, ethyl, n-propyl, i-propyl, n-butyl, iso-butyl, sec-butyl and tert-butyl or represents phenyl or naphthyl, each of which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, methoxy, ethoxy, methylthio, ethylthio, trifluoromethyl, trifluoromethoxy, difluoromethoxy, trifluoromethylthio and difluoromethylthio, R3 and R4 independently of one another represent hydrogen, methyl or ethyl or R3 and R4 together with the carbon atom to which they are attached represent cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl or R1, A1 and R3 together with the carbon atoms to which they are attached represent cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, A2 represents a direct bond R2 represents hydrogen or represents cycloalkyl having 3 to 6 carbon atoms which is optionally mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, methyl, ethyl, n-propyl, i-propyl, n-butyl, iso-butyl, sec-butyl and tert-butyl, or represents phenyl or naphthyl, each of which may be mono- to trisubstituted by identical or different substituents from the group consisting of fluorine, chlorine, bromine, cyano, nitro, methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, methoxy, ethoxy, methylthio, ethylthio, trifluoromethyl, trifluoromethoxy, difluoromethoxy, trifluoromethylthio and difluoromethylthio and R4 represents hydrogen, methyl or ethyl, or R3 and R4 represent hydrogen and the groups R1—A1— and R2—A2— together with the carbon atom to which they are attached represent a radical of the formula ### Claim 4 (depends on 1) The process according to claim 1, wherein said hydrazine derivative of the formula (II) is employed in the form of an acid addition salt. ### Claim 5 (depends on 1) The process according to claim 1, wherein a reaction component of the N-dihalogenomethyl-formamidinium halide of the formula (III) is N-dichloromethyl-formamidinium hydrochloride. ### Claim 6 (depends on 1) The process according to claim 1, wherein said process is carried out at temperatures between 20° C. and 200° C. ### Claim 7 A process for preparing 2-(1-chloro-cyclopropyl)-1-(2-chlorophenyl)-3-(1,2,4-triazol-1-yl)-propan-2-ol comprising: reacting 2-(1-chloro-cycloprop-1-yl)-3-(2-chlorophenyl)-2-hydroxy-propyl-1-hydrazine hydrochloride with N-dichloromethyl-formamidinium chloride.