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HK1088316B - Biphenyl derivatives and their use as fungicides - Google Patents

Biphenyl derivatives and their use as fungicides Download PDF

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Publication number
HK1088316B
HK1088316B HK06108652.6A HK06108652A HK1088316B HK 1088316 B HK1088316 B HK 1088316B HK 06108652 A HK06108652 A HK 06108652A HK 1088316 B HK1088316 B HK 1088316B
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Hong Kong
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cfh
ccf
formula
cme
compound
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HK06108652.6A
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Chinese (zh)
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HK1088316A1 (en
Inventor
J．埃伦弗罗因德
C.兰贝特
H．托布勒
H.瓦尔特
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辛根塔参与股份公司
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Priority claimed from GBGB0230155.4A external-priority patent/GB0230155D0/en
Application filed by 辛根塔参与股份公司 filed Critical 辛根塔参与股份公司
Publication of HK1088316A1 publication Critical patent/HK1088316A1/en
Publication of HK1088316B publication Critical patent/HK1088316B/en

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Description

Diphenyl derivatives and their use as fungicides
Technical Field
The present invention relates to novel carboxamide derivatives as active ingredients having microbiocidal activity, in particular fungicidal activity. The invention also relates to the preparation of these active ingredients, to novel diphenyl derivatives which are useful as intermediates in the preparation of these active ingredients, to the preparation of these novel intermediates, to agrochemical compositions which comprise at least one novel active ingredient, to the preparation of these compositions and to the use of the active ingredients or compositions in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.
Background
Fungicidally active carboxamide derivatives are disclosed in JP2001072510, JP2001072508, JP2001072507 and JP 2001302605.
Certain amino-or halogen-substituted diphenyl derivatives are disclosed in DE2205732 and JP 2001302605.
Disclosure of Invention
The present invention provides compounds of formula (I):
wherein Het is a 5-or 6-membered heterocyclic ring containing 1-3 heteroatoms, each heteroatom independently selected from oxygen, nitrogen and sulfur, with the proviso that: the ring being other than 1, 2, 3-triazole, the ring being substituted by 1, 2 or 3RySubstituted by groups; r1Is hydrogen, formyl, CO-C1-4Alkyl, COO-C1-4Alkyl radical, C1-4Alkoxy (C)1-4) Alkylene, CO-C1-4Alkyleneoxy (C)1-4) Alkyl, propargyl or allenyl; r2、R3、R4And R5Each independently hydrogen, halogen, methyl or CF3(ii) a Each R6Independently halogen, methyl or CF3；R7Is (Z)mC≡C(Y1)、(Z)mC(Y1)＝C(Y2)(Y3) Or three (C)1-4) An alkylsilyl group; each RyIndependently of one another, halogen, C1-3Alkyl radical, C1-3Haloalkyl, C1-3Alkoxy (C)1-3) Alkylene or cyano; x is O or S; y is1、Y2And Y3Each independently of the others is hydrogen, halogen, C1-6Alkyl [ optionally substituted with one or more substituents, each substituent independently selected from halogen, hydroxy, C1-4Alkoxy radical, C1-4Haloalkoxy, C1-4Alkylthio radical, C1-4Haloalkylthio, C1-4Alkylamino radical, di (C)1-4) Alkylamino radical, C1-4Alkoxycarbonyl radical、C1-4Alkyl carbonyl oxygen and tri (C)1-4) Alkyl silyl radical]、C2-4Alkenyl [ optionally substituted with one or more substituents, each substituent independently selected from halogen]、C2-4Alkynyl [ optionally substituted with one or more substituents, each substituent independently selected from halogen]、C3-7Cycloalkyl [ optionally substituted with one or more substituents, each substituent independently selected from halogen, C1-4Alkyl and C1-4Haloalkyl group]Or three (C)1-4) An alkylsilyl group; z is C1-4Alkylene [ optionally substituted with one or more substituents, each substituent independently selected from hydroxy, cyano, C1-4Alkoxy, halogen, C1-4Haloalkyl, C1-4Haloalkoxy, C1-4Alkylthio, COOH and COO-C1-4Alkyl radical](ii) a m is 0 or 1; and n is 0, 1 or 2.
In a particular aspect, the invention provides a compound of formula (I) as defined above, wherein Y is1、Y2And Y3Each independently of the others is hydrogen, halogen, C1-4Alkyl [ optionally substituted with one or more substituents, each substituent independently selected from halogen, hydroxy, C1-4Alkoxy radical, C1-4Haloalkoxy, C1-4Alkylthio radical, C1-4Haloalkylthio, C1-4Alkylamino radical, di (C)1-4) Alkylamino radical, C1-4Alkoxycarbonyl and tris (C)1-4) Alkyl silyl radical]、C2-4Alkenyl [ optionally substituted with one or more substituents, each substituent independently selected from halogen]、C2-4Alkynyl [ optionally substituted with one or more substituents, each substituent independently selected from halogen]、C3-7Cycloalkyl [ optionally substituted with one or more substituents, each substituent independently selected from halogen, C1-4Alkyl and C1-4Haloalkyl group]Or three (C)1-4) An alkylsilyl group.
In one aspect, the invention provides a compound of formula (I) as defined above, wherein Z is C1-4Alkylene [ optionally substituted with one or more substituents, each substituent independentlyThe tertiary amino group is selected from hydroxyl, cyano and C1-4Alkoxy radical, C1-4Haloalkoxy, C1-4Alkylthio, COOH and COO-C1-4Alkyl radical]。
In one aspect, the present invention provides a compound of formula (I) as defined above, with the proviso that: when X is O, R7Is not C2-6An alkenyl group; r1Is hydrogen; r2、R3、R4And R5One of which is fluorine and the others are all hydrogen; n is 1; and Het is
In another aspect, the present invention provides a compound of formula (I) as defined above, with the proviso that: when X is O, R7Is not C2-6An alkenyl group; r1、R2、R3、R4And R5Are all hydrogen; and Het is
In another aspect, the present invention provides a compound of formula (I) as defined above, with the proviso that: when X is O, R7Is not C2-6An alkenyl group; r1、R2、R3、R4And R5Are all hydrogen; n is 1; and Het is
In another aspect, the present invention provides a compound of formula (I) as defined above, with the proviso that: when X is O, R7Not C in the 4' position2-6An alkenyl group; r1、R3And R5Are all hydrogen; r2And R4Each independently is hydrogen or fluorine; n is 0; or n is 1; or n is 2 and 2 independent R6The substituents are in positions 2 ', 3' or 2 ', 5' or 3 ', 5'; and Het is
Halogen is fluorine, chlorine, bromine or iodine [ preferably fluorine, chlorine or bromine ].
Each alkyl moiety is straight or branched chain and is, for example, methyl, ethyl, n-propyl, n-butyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl. Similarly, each alkylene moiety is straight or branched.
Haloalkyl moieties are alkyl moieties substituted by one or more of the same or different halogen atoms and are, for example, CF3、CF2Cl、CHF2、CH2F、CCl3、CF3CH2、CHF2CH2、CH2FCH2、CH3CHF or CH3CF2。
Alkenyl and alkynyl moieties may be in the form of straight or branched chains. The alkenyl moiety may where appropriate be (E) -or (Z) -configuration. Examples are vinyl, allyl, ethynyl and propargyl.
Cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.
In III (C)1-4) Alkylsilyl and di (C)1-4) In alkylamino, each alkyl moiety is independently selected.
In the present specification, Me represents a methyl group and Et represents an ethyl group.
Preferably, Het is pyrazole, pyrrole, thiophene, furan, thiazole, isothiazole, oxazole, isoxazole, pyridine, pyrazine, pyrimidine, pyridazine, 5, 6-dihydropyran or 5, 6-dihydro-1, 4-oxathiahexadiene [ more preferably pyrazole, pyrrole, thiophene, furan, thiazole, oxazole, pyridine, pyrimidine, pyridazine or 5, 6-dihydropyran; more preferably pyrazole, pyrrole, pyridine or thiazole; and more preferably pyrazole, pyrrole or thiazole ].
In one aspect, preferably Het is pyrazole, pyrrole, thiophene, furan, thiazole, isothiazole, oxazole, isoxazole, pyrazine, pyrimidine, pyridazine, 5, 6-dihydropyran or 5, 6-dihydro-1, 4-oxathiin [ more preferably pyrazole, pyrrole, thiophene, furan, thiazole, oxazole, pyrimidine, pyridazine or 5, 6-dihydropyran, and more preferably pyrazole, pyrrole or thiazole ].
Preferably, R1Is hydrogen, propargyl, allenyl, formyl, COMe, COEt or COCH2OMe。
More preferably, R1Is hydrogen.
Preferably, R2Is hydrogen.
Preferably, R3Is hydrogen.
Preferably, R4Is hydrogen.
Preferably, R5Is hydrogen or halogen.
More preferably, R5Is hydrogen or fluorine.
More preferably, R5Is hydrogen.
In one aspect of the invention, R7Is three (C)1-4) An alkylsilyl group.
Preferably, Y1、Y2And Y3Independently of one another is hydrogen, halogen, C1-6Alkyl radical, C1-3Haloalkyl, C1-4(haloalkoxy) C1-4Alkyl radical, C1-4(haloalkylthio) C1-4Alkyl, trimethylsilyl, C2-4Alkenyl radical, C2-4Haloalkenyl or C3-6Cycloalkyl (ren)Optionally substituted with one or more substituents, each substituent independently selected from halogen and C1-2Alkyl groups).
Preferably, Z is C1-2Alkylene [ which may be optionally substituted with one or more substituents each independently selected from halogen, C1-4Haloalkyl and C1-4Halogenated alkoxy]。
Preferably, R7Is at the 4' position.
Preferably, R7Is vinyl [ optionally substituted with 1-3 substituents, each substituent independently selected from halogen, C1-4Alkyl radical, C1-3Haloalkyl, C3-6Cycloalkyl (optionally substituted with 1-5 substituents, each substituent independently selected from halogen, CH3And C1-2Haloalkyl) and trimethylsilyl]Ethynyl [ optionally substituted with 1 substituent selected from: cyclopropyl, cyclopentyl and cyclohexyl (each optionally substituted with 1-5 substituents each independently selected from halogen, CH3And C1-2Haloalkyl), halogen, C1-6Alkyl radical, C1-4Haloalkyl, C2-4Alkenyl radical, C2-4Haloalkenyl and tri (C)1-4) Alkyl silyl radical]Allyl [ optionally substituted with 1-3 substituents, each substituent independently selected from halogen, CH3、C1-2Haloalkyl and trimethylsilyl]Propargyl [ optionally substituted with 1-3 substituents each independently selected from halogen, C1-4Alkyl radical, C1-2Haloalkyl and trimethylsilyl]Or three (C)1-4) An alkylsilyl group.
In a particular aspect, R7Preferably vinyl [ optionally substituted with 1-3 substituents, each substituent independently selected from halogen, C1-4Alkyl radical, C1-3Haloalkyl, C3-6Cycloalkyl and trimethylsilyl]Ethynyl [ optionally substituted with one substituent selected from: halogen, C1-4Alkyl radical, C1-2Haloalkyl, cyclopropyl (optionally substituted1-5 substituents, each substituent independently selected from halogen, CH3、C1-2Haloalkyl and trimethylsilyl) and trimethylsilyl]Allyl [ optionally substituted with 1-3 substituents, each substituent independently selected from halogen, CH3、C1-2Haloalkyl and trimethylsilyl]Propargyl [ optionally substituted with 1-3 substituents each independently selected from halogen, CH3、C1-2Haloalkyl and trimethylsilyl]Or three (C)1-4) An alkylsilyl group.
In another specific aspect, R7Preferably vinyl [ optionally substituted with 1-3 substituents, each substituent independently selected from halogen, C1-4Alkyl radical, C1-3Haloalkyl, C3-6Cycloalkyl and trimethylsilyl]Ethynyl [ optionally substituted with one substituent selected from: halogen, C1-4Alkyl radical, C1-2Haloalkyl and trimethylsilyl]Allyl [ optionally substituted with 1-3 substituents, each substituent independently selected from halogen, CH3、C1-2Haloalkyl and trimethylsilyl]Propargyl [ optionally substituted with 1-3 substituents each independently selected from halogen, CH3、C1-2Haloalkyl and trimethylsilyl]Or three (C)1-4) An alkylsilyl group.
More preferably, R7Is CH ═ CH2、CH＝CH(CH3)、CH＝CHSiMe3、CH＝CF2、CH＝CCl2、C(CH3)＝CCl2、CH＝CBr2、C(CH3)＝CBr2、C(CH3)＝CF2、CH＝CFCl、CH＝CFBr、C(CH3)＝CFCl、C(CH3)＝CFBr、CH＝CFMe、CH＝CBrMe、CH＝CClMe、CH＝CHBr、CH＝CHF、CH＝CHCl、CF＝CF2、CCl＝CF2、CCl＝CH2、CBr＝CH2、CF＝CH2、C(CF3)＝CFBr、C(CF3)＝CFCl、C(CF3)＝CBr2、C(CF3)＝CCl2、C(CF3)＝CF2、C(CF3)＝CH2、CF＝CHF、CH＝CHCF3、CH＝CFCF2Cl、CH＝CClCF2Cl、CH＝CBrCF2Cl、CH＝C(CF3)2、CH＝CHC2F5、CH＝CHCF(CF3)2、C(CH3)＝CHCF3、C(CH3)＝CFCF3、C(CH3)＝CClCF3、C(CH3)＝CBrCF3、CH＝CClCF3、CH＝CClC2F5、CH＝CBrCF3、CH＝CFC2F5、CH＝CFCF3、CH2CH＝CH2、CH2CH＝CF2、CH2CH＝CCl2、CH2CH＝CBr2、CH2CH＝CFBr、CH2CH＝CFCl、CH2CH＝CClCF3、CH2CH＝CHSiMe3、C≡CH、C≡CSiMe3、C≡CSiEt3、C≡CSiMe2C(CH3)3、C≡CCl、C≡CBr、C≡CF、C≡CCF3、C≡CCF2H、C≡CCF2Cl、C≡CCF2Me、C≡CCF2Et、C≡CCHFCl、C≡CCF2Br、C≡CC2F5、C≡CCF(CF3)2、C≡CCHF(CF3)、C≡CCH2F、C≡CCH(Me)F、C≡CCH(Et)F、C≡CMe、C≡CCH2Me、C≡CCHMe2、C≡CCH2CHMe2、C≡CCMe3、C≡CCH2CMe3、C≡CCH2SiMe3、C≡CCMe2Cl、C≡CCMe2F、C≡CCH2OMe、C≡CCH2CF3、C≡CCMe2OMe、C≡CCMe2OH、C≡CCMe2OCOMe、C≡CC(Me)＝CH2、C≡CCF＝CF2C.ident.C (cyclopropyl), C.ident.C (cyclopentyl), C.ident.C (1-F-cyclopentyl), CH2C≡CH、CF2C≡CH、CHFC≡CH、CH(CF3)C≡CH、SiMe3、CH2C≡CCMe3Or CH2C≡CSiMe3。
In a particular aspect, R7More preferably CH ═ CH2、CH＝CH(CH3)、CH＝CHSiMe3、CH＝CF2、CH＝CCl2、C(CH3)＝CCl2、CH＝CBr2、CF＝CF2、CCl＝CH2、CBr＝CH2、CF＝CH2、CF＝CHF、CH＝CHCF3、CH＝CClCF3、CH＝CBrCF3、CH2CH＝CH2、CH2CH＝CHSiMe3、C≡CH、C≡CSiMe3、C≡CSiEt3、C≡CSiMe2C(CH3)3、C≡CCl、C≡CBr、C≡CCF3、C≡CCF2H、C≡CCF2Cl、C≡CCF2Br、C≡CCF(CF3)2C≡CMe、C≡CCHMe2、C≡CCMe3、C≡CCMe2Cl、C≡CCH2OMe, C.ident.C (Ring C)3H5) C.ident.C (Ring C)5H9)、CH2C≡CH、SiMe3Or CH2C≡CSiMe3.
More preferably, R7Is CH ═ CF2、CH＝CCl2、C(CH3)＝CCl2、CH＝CBr2、C(CH3)＝CBr2、C(CH3)＝CF2、CH＝CFCl、CH＝CFBr、C(CH3)＝CFCl、C(CH3)＝CFBr、CH＝CHBr、CH＝CHF、CH＝CHCl、CCl＝CH2、CH＝CHCF3、CH＝CFCF2Cl、CH＝CClCF2Cl、CH＝CBrCF2Cl、CH＝C(CF3)2、CH＝CHC2F5、CH＝CHCF(CF3)2、C(CH3)＝CHCF3、CH＝CClCF3、CH＝CClC2F5、CH＝CFC2F5、CH＝CBrCF3、CH＝CFCF3、CH2CH＝CClCF3、CH2CH＝CCl2、CH2CH＝CBr2、C≡CH、C≡CSiMe3、C≡CSiEt3、C≡CSiMe2C(CH3)3、C≡CCl、C≡CCF3、C≡CCF2H、C≡CCF2Cl、C≡CCHFCl、C≡CCF2Me、C≡CCF2Et、C≡CCHFEt、C≡CCF2Br、C≡CCF(CF3)2、C≡CCF2CF3、C≡CCHF(CF3)、C≡CCH2F、C≡CCH(Me)F、C≡CMe、C≡CCHMe2、C≡CCH2Me、C≡CCH2CHMe2、C≡CCMe3、C≡CCH2CMe3、C≡CCMe2F、C≡CCH2CF3C ≡ C (cyclopropyl), C ≡ C (cyclopentyl), C ≡ C (1-F-cyclopentyl), C ≡ cc (me) -CH2、C≡CCF＝CF2、C≡CCH2SiMe3、CH2C≡CH、CF2C ≡ CH or CHFC ≡ CH.
In a particular aspect, R7More preferably CH ═ CH2、CH＝CHSiMe3、CH＝CF2、CH＝CCl2、CH＝CBr2、CF＝CF2、CCl＝CH2、CBr＝CH2、CF＝CHF、CH＝CHCF3、CH＝CClCF3、C≡CH、C≡CSiMe3、C≡CCl、C≡CBr、C≡CCF3、C≡CMe、C≡CCMe3、C≡CCHMe2C.ident.C (Ring C)3H5)、CH2C≡CH、SiMe3Or CH2C≡CSiMe3。
More preferably, R7Is CH ═ CF2、CH＝CCl2、CH＝CBr2、CH＝CFCl、CH＝CFBr、CH＝CHBr、CH＝CHF、CH＝CHCl、CCl＝CH2、CH＝CHCF3、CH＝CFCF2Cl、CH＝CClCF2Cl、CH＝CBrCF2Cl、CH＝C(CF3)2、CH＝CHC2F5、CH＝CClCF3、CH＝CBrCF3、CH＝CFCF3、C≡CH、C≡CSiMe3、C≡CCl、C≡CCF3、C≡CCF2H、C≡CCHFCl、C≡CCHF(CF3)、C≡CCF2Cl、C≡CCF2Me、C≡CCF2Br、C≡CCF2CF3、C≡CCH2F、C≡CCH(Me)F、C≡CMe、C≡CCHMe2、C≡CCH2CHMe2、C≡CCMe3、C≡CCCH2CMe3、C≡CCMe2F、C≡CCH2CF3C.ident.C (cyclopropyl), C.ident.C (cyclopentyl), C.ident.C (1-F-cyclopentyl), CH2C≡CH、CF2C ≡ CH, CHFC ≡ CH or C ≡ CCH2Me。
In a particular aspect, R7More preferably CH-CHSiMe3、CH＝CF2、CH＝CCl2、CH＝CBr2、CF＝CF2、CCl＝CH2、CBr＝CH2、CF＝CHF、CH＝CHCF3、CH＝CClCF3、C≡CH、C≡CSiMe3、C≡CCl、C≡CBr、C≡CCF3、C≡CMe、C≡CCMe3、C≡CCHMe2C.ident.C (Ring C)3H5)、CH2C≡CH、SiMe3Or CH2C≡CSiMe3。
Preferably, the nitrogen atoms in the Het ring are independently unsubstituted or substituted by RyAnd (3) substituted.
When R isyWhen it is a substituent on the nitrogen atom, it is preferably C1-3Alkyl radical, C1-3Haloalkyl or methoxymethylene; more preferably C1-2Alkyl, CF3、CF2Cl、CHF2、CH2F or methoxymethylene; more preferably methyl group and CHF2Or a methoxymethylene group; more preferably methyl or methoxymethylene; most preferred is methyl.
Preferably, not bound to CXNR1The carbon atoms of the Het ring on the substituted atom being independently unsubstituted or substituted by RyAnd (3) substituted.
When R isyIs not bound to the target CXNR1When the substituent on the carbon atom of the substituted atom is a halogen, C1-3Alkyl radical, C1-3Haloalkyl or methoxymethylene; more excellentIs selected from chlorine, methoxy methylene and CH3、CHF2Or CF3(ii) a More preferably chlorine and CH3、CHF2Or CF3(ii) a More preferably CH3Or CF3. Bound to CXNR1There may be 1 or 2 carbon atoms in the Het ring on the substituted atom; preferably, such carbon atoms are independently unsubstituted or substituted by RyAnd (3) substituted.
When R isyIs bound to the quilt CXNR1When the substituent on the carbon atom of the substituted atom is a halogen, C1-3Alkyl or C1-3A haloalkyl group; more preferably chlorine, fluorine, bromine, C1-2Alkyl, CF3、CF2Cl、CHF2、CH2F; and more preferably chlorine, fluorine, bromine, methyl, CF3、CHF2Or CH2F。
More preferably, when bound to CXNR1When there is only 1 carbon atom in the Het ring on the substituted atom, that carbon atom is substituted by RyAnd (3) substituted.
More preferably, when bound to CXNR1When there are 2 carbon atoms in the Het ring on a substituted atom, one such carbon atom is substituted by RySubstituted, the other carbon atom being unsubstituted or substituted by fluorine, chlorine or methyl.
Preferably, m is 0.
Preferably, n is 0.
Preferably, X is O.
A compound of formula (II):
wherein R is1、R2、R3、R4、R5、R6、R7And n is as defined above for the compound of formula (I),is also novel [ except where R1、R2、R3、R4And R5Each is hydrogen, n is 0 and R7Is CH ═ CHCH2CO2Other than the compound of formula (II) of H]And are useful as intermediates in the preparation of compounds of formula (I).
Thus, in one aspect, the present invention provides a compound of formula (II) wherein R1、R2、R3、R4、R5、R6、R7And n is as defined above for the compound of formula (I), with the proviso that: when R is1、R2、R3、R4And R5Each is hydrogen and n is 0, R7Is not CH ═ CHCH2CO2H。
R in the Compound of formula (II)1、R2、R3、R4、R5、R6、R7And preferred values of n are as defined above for the compounds of formula (I).
Many compounds of formula (III):
wherein R is2、R3、R4、R5、R6、R7And n is as defined above for the compounds of formula (I) and Hal is bromo, chloro or iodo, are also novel and are useful as intermediates in the preparation of the compounds of formula (I).
Certain compounds of formula (III) are known; table 0 shows the known compounds of the formula (IIIa) in which Hal, R2、R3、R4And R7As defined in table 0.
TABLE 0
Hal R R R R
Cl Cl H H C(CH)＝CH-CH-OH
Br H Me H C(CF)＝CF
Br H Me Br C(CF)＝CF
Cl H H H C≡CH
Cl H H H CH＝CH-CH-CH-OH
Cl H H H C(CH)＝CH-CH-OH
Cl H H H C(CH)＝CH-C(＝O)-OCH
Cl H H H C(CH)＝CH-CH(OH)CH
Cl H H H CH＝CH-CH(OH)CH
Thus, in another aspect, the invention provides a compound of formula (III) wherein R2、R3、R4、R5、R6、R7And n is as defined above for the compound of formula (I) and Hal is bromo, chloro or iodo; with the following conditions: the compound is not a compound of formula (IIIa) according to table 0.
R in the Compound of formula (III)2、R3、R4、R5、R6、R7And preferred values of n are as defined above for the compounds of formula (I).
Preferably, Hal is bromine or chlorine.
More preferably, Hal is bromine.
The compounds of formulae (I), (II) and (III) may exist as different geometric or optical isomers, or in different tautomeric forms. For each formula, the invention includes all such isomers, tautomers, mixtures thereof in all ratios and isotopic forms, such as deuterated compounds.
The compounds of the present invention are illustrated below by the compounds in tables 1-13.
TABLE 1
Compound numbering R1 R R R R X
1.01 H C≡CH H Me CF O
1.02 H C≡CH H Me CF S
1.03 H C≡CH H Me CFH O
1.04 Propargyl group C≡CH H Me CF O
1.05 H C≡CH F Me Me O
1.06 H C≡CH H CHOMe CF O
1.07 Allenyl radical C≡CH H Me CF O
1.08 H C≡CSiMe H Me CF O
1.09 H C≡CSiMe H Me CF S
1.10 H C≡CSiMe H Me CFH O
1.11 H C≡CSiMe F Me Me O
1.12 H C≡CCl H Me CF O
1.13 H C≡CCl H Me CFH O
1.14 H C≡CCl F Me Me O
1.15 H C≡CBr H Me CF O
1.16 H C≡CBr H Me CFH O
1.17 H C≡CBr F Me Me O
1.18 H C≡CCF H Me CF O
1.19 H C≡CCF H Me CFH O
1.20 H C≡CCF F Me Me O
1.21 Allenyl radical C≡CCF H Me CF O
1.22 H CH＝CH H Me CF O
1.23 H CH＝CH H Me CF S
1.24 H CH＝CH H Me CFH O
1.25 Propargyl group CH＝CH H Me CF O
1.26 H CH＝CH F Me Me O
1.27 H CH＝CH H CHOMe CF O
1.28 Allenyl radical CH＝CH H Me CF O
1.29 H CH＝CF H Me CF O
1.30 H CH＝CF H Me CFH O
1.31 H CH＝CF F Me Me O
1.32 H CH＝CCl H Me CF O
1.33 H CH＝CCl H Me CFH O
1.34 H CH＝CCl F Me Me O
1.35 H CH＝CBr H Me CF O
1.36 H CH＝CBr H Me CFH O
1.37 H CH＝CBr F Me Me O
1.38 H CF＝CF H Me CF O
1.39 H CF＝CF H Me CFH O
1.40 H CF＝CF F Me Me O
1.41 H CCl＝CH H Me CF O
1.42 H CCl＝CH H Me CFH O
1.43 H CCl＝CH F Me Me O
1.44 H CBr＝CH H Me CF O
1.45 H CBr＝CH H Me CFH O
1.46 H CBr＝CH F Me Me O
1.47 H CF＝CHF H Me CF O
1.48 H CF＝CHF H Me CFH O
1.49 H CF＝CHF F Me Me O
1.50 H CH＝CHSiMe H Me CF O
1.51 H CH＝CHSiMe H Me CFH O
1.52 H CH＝CHSiMe F Me Me O
1.53 H CH＝CHCF H Me CF O
1.54 H CH＝CHCF H Me CFH O
1.55 H CH＝CHCF F Me Me O
1.56 H CH＝CClCF H Me CF O
1.57 H CH＝CClCF H Me CFH O
1.58 H CH＝CClCF F Me Me O
1.59 H CHC≡CH H Me CF O
1.60 H CHC≡CH H Me CFH O
1.61 H CHC≡CH F Me Me O
1.62 H CHC≡CH H CHOMe CF O
1.63 H CHC≡CSiMe H Me CF O
1.64 H CHC≡CSiMe H Me CFH O
1.65 H CHC≡CSiMe F Me Me O
1.66 H C≡CCMe H Me CF O
1.67 H C≡CCMe H Me CFH O
1.68 H C≡CCMe F Me Me O
1.69 H C≡CMe H Me CF O
1.70 H C≡CMe H Me CFH O
1.71 H C≡CMe F Me Me O
1.72 COMe C≡CH H Me CF O
1.73 H C≡CH H CFH CFH O
1.74 H C≡CH H CFH CF O
1.75 H C≡CH H Me CHF O
1.76 H C≡CSiMe H Me CHF O
1.77 H C ≡ C (cyclopropyl) H Me CF O
1.78 H C ≡ C (cyclopropyl) H Me CHF O
1.79 H SiMe H Me CHF O
1.80 H SiMe H Me CF O
1.81 H SiMe H Me CHF O
1.82 H C≡CF H Me CF O
1.83 H C≡CF H Me CFH O
1.84 H C≡CF F Me Me O
1.85 H C≡CCFCl H Me CF O
1.86 H C≡CCFCl H Me CFH O
1.87 H C≡CCFCl F Me Me O
1.88 H C≡CCFH H Me CF O
1.89 H C≡CCFH H Me CFH O
1.90 H C≡CCFH F Me Me O
1.91 H C≡CCFBr H Me CF O
1.92 H C≡CCFBr H Me CFH O
1.93 H C≡CCFBr F Me Me O
1.94 H C≡CCHF H Me CF O
1.95 H C≡CCHF H Me CFH O
1.96 H C≡CCHF F Me Me O
1.97 H C≡CCH(Me)F H Me CF O
1.98 H C≡CCH(Me)F H Me CFH O
1.99 H C≡CCH(Me)F F Me Me O
1.100 H C≡CC(Me)F H Me CF O
1.101 H C≡CC(Me)F H Me CFH O
1.102 H C≡CC(Me)F F Me Me O
1.103 H C≡CCHC(Me) H Me CF O
1.104 H C≡CCHC(Me) H Me CFH O
1.105 H C≡CCHC(Me) F Me Me O
1.106 H C≡CCH(Me) H Me CF O
1.107 H C≡CCH(Me) H Me CFH O
1.108 H C≡CCH(Me) F Me Me O
1.109 H C≡CCHCH(Me) H Me CF O
1.110 H C≡CCHCH(Me) H Me CFH O
1.111 H C≡CCHCH(Me) F Me Me O
1.112 H CHC≡CCMe H Me CF O
1.113 H CHC≡CCMe H Me CFH O
1.114 H CHC≡CCMe F Me Me O
1.115 H CFC≡CCMe H Me CF O
1.116 H CFC≡CCMe H Me CFH O
1.117 H CFC≡CCMe F Me Me O
1.118 H CFC≡CMe H Me CF O
1.119 H CFC≡CMe H Me CFH O
1.120 H CFC≡CMe F Me Me O
1.121 H CFC≡CH H Me CF O
1.122 H CFC≡CH H Me CFH O
1.123 H CFC≡CH F Me Me O
1.124 H CMeC≡CH H Me CF O
1,125 H CMeC≡CH H Me CFH O
1.126 H CMeC≡CH F Me Me O
1.127 H CHFC≡CH H Me CF O
1.128 H CHFC≡CH H Me CFH O
1.129 H CHFC≡CH F Me Me O
1.130 H CHMeC≡CH H Me CF O
1.131 H CHMeC≡CH H Me CFH O
1.132 H CHMeC≡CH F Me Me O
1.133 H CH(CF)C≡CH H Me CF O
1.134 H CH(CF)C≡CH H Me CFH O
1.135 H CH(CF)C≡CH F Me Me O
1.136 H C ≡ C (1-F-cyclopentyl) H Me CF O
1.137 H C ≡ C (1-F-cyclopentyl) H Me CHF O
1.138 H C≡CCHOMe H Me CF O
1.139 H C≡CCHOMe H Me CFH O
1.140 H C≡CCHOMe F Me Me O
1.141 H C≡CCMeOMe H Me CF O
1.142 H C≡CCMeOMe H Me CFH O
1.143 H C≡CCMeOMe F Me Me O
1.144 H C≡CCMeOCOMe H Me CF O
1.145 H C≡CCMeOCOMe H Me CFH O
1.146 H C≡CCFMe H Me CF O
1.147 H C≡CCFMe H Me CFH O
1.148 H C≡CCFMe F Me Me O
1.149 H C≡CC(Me)＝CH H Me CF O
1.150 H C≡CC(Me)＝CH H Me CFH O
1.151 H CH＝CFCl H Me CF O
1.152 H CH＝CFCl H Me CFH O
1.153 H CH＝CFCl F Me Me O
1.154 H CH＝CFBr H Me CF O
1.155 H CH＝CFBr H Me CFH O
1.156 H CH＝CFBr F Me Me O
1.157 H CH＝CHBr H Me CF O
1.158 H CH＝CHBr H Me CFH O
1.159 H CH＝CHBr F Me Me O
1.160 H CH＝CHF H Me CF O
1.161 H CH＝CHF H Me CFH O
1.162 H CH＝CHF F Me Me O
1.163 H CMe＝CHCF H Me CF O
1.164 H CMe＝CHCF H Me CFH O
1.165 H CMe＝CHCF F Me Me O
1.166 H CH＝CFCF H Me CF O
1.167 H CH＝CFCF H Me CFH O
1.168 H CH＝CFCF F Me Me O
1.169 H CH＝CBrCF H Me CF O
1.170 H CH＝CBrCF H Me CFH O
1.171 H CH＝CBrCF F Me Me O
1.172 H CH＝CHCF H Me CF O
1.173 H CH＝CHCF H Me CFH O
1.174 H CH＝CHCF F Me Me O
1.175 H CH＝CHCl H Me CF O
1.176 H CH＝CHCl H Me CFH O
1.177 H CH＝CHCl F Me Me O
1.178 H CH＝C(CF) H Me CF O
1.179 H CH＝C(CF) H Me CFH O
1.180 H CH＝C(CF) F Me Me O
1.181 H CMe＝CFCl H Me CF O
1.182 H CMe＝CFCl H Me CFH O
1.183 H CMe＝CFCl F Me Me O
1.184 H CMe＝CFBr H Me CF O
1.185 H CMe＝CFBr H Me CFH O
1.186 H CMe＝CFBr F Me Me O
1.187 H CMe＝CF H Me CF O
1.188 H CMe＝CF H Me CFH O
1.189 H CMe＝CF F Me Me O
1.190 H CMe＝CCl H Me CF O
1.191 H CMe＝CCl H Me CFH O
1.192 H CMe＝CCl F Me Me O
1.193 H CMe＝CBr H Me CF O
1.194 H CMe＝CBr H Me CFH O
1.195 H CMe＝CBr F Me Me O
1.196 H CMe＝CFCF H Me CF O
1.197 H CMe＝CFCF H Me CFH O
1.198 H CMe＝CFCF F Me Me O
1.199 H CMe＝CClCF H Me CF O
1.200 H CMe＝CClCF H Me CFH O
1.201 H CMe＝CClCF F Me Me O
1.202 H CCF＝CF H Me CF O
1.203 H CCF＝CF H Me CFH O
1.204 H CCF＝CF F Me Me O
1.205 H CCF＝CCl H Me CF O
1.206 H CCF＝CCl H Me CFH O
1.207 H CCF＝CCl F Me Me O
1.208 H CCF＝CBr H Me CF O
1.209 H CCF＝CBr H Me CFH O
1.210 H CCF＝CBr F Me Me O
1.211 H CCF＝CH H Me CF O
1.212 H CCF＝CH H Me CFH O
1.213 H CCF＝CH F Me Me O
1.214 H CCF＝CFBr H Me CF O
1.215 H CCF＝CFBr H Me CFH O
1.216 H CCF＝CFBr F Me Me O
1.217 H CCF＝CHF H Me CF O
1.218 H CCF＝CHF H Me CFH O
1.219 H CCF＝CHF F Me Me O
1.220 H CCF＝CFCl H Me CF O
1.221 H CCF＝CFCl H Me CFH O
1.222 H CCF＝CFCl F Me Me O
1.223 H CCF＝CHCl H Me CF O
1.224 H CCF＝CHCl H Me CFH O
1.225 H CCF＝CHCl F Me Me O
1.226 H CH＝CFCFCl H Me CF O
1.227 H CH＝CFCFCl H Me CFH O
1.228 H CH＝CFCFCl F Me Me O
1.229 H CH＝CClCFCl H Me CF O
1.230 H CH＝CClCFCl H Me CFH O
1.231 H CH＝CClCFCl F Me Me O
1.232 H CHCF＝CF H Me CF O
1.233 H CHCF＝CF H Me CFH O
1.234 H CHCF＝CF F Me Me O
1.235 H CF＝CFBr H Me CF O
1.236 H CF＝CFBr H Me CFH O
1.237 H CF＝CFBr F Me Me O
1.238 H CHCH＝CF H Me CF O
1.239 H CHCH＝CF H Me CFH O
1.240 H CHCH＝CF F Me Me O
1.241 H CHCH＝CCl H Me CF O
1.242 H CHCH＝CCl H Me CFH O
1.243 H CHCH＝CCl F Me Me O
1.244 H CHCH＝CBr H Me CF O
1.245 H CHCH＝CBr H Me CFH O
1.246 H CHCH＝CBr F Me Me O
1.247 H CCl＝CF H Me CF O
1.248 H CCl＝CF H Me CFH O
1.249 H CCl＝CF F Me Me O
1.250 H C≡CCMeOH H Me CF O
1.251 H C≡CCMeOH H Me CFH O
1.252 H C≡CSi(Me)CMe H Me CF O
1.253 H C≡CSi(Me)CMe H Me CFH O
1.254 H C≡CCHSiMe H Me CF O
1.255 H C≡CCHSiMe H Me CFH O
1.256 H C≡CCHSiMe F Me Me O
1.257 H C≡CCMe H CFH CF O
1.258 H C≡CCHCF H Me CF O
1.259 H C≡CCHCF H Me CFH O
1.260 H C≡CCHCF F Me Me O
1.261 H C≡CCMe H CFH CFH O
1.262 H C≡CCHCH H Me CF O
1.263 H C≡CCHCH H Me CFH O
1.264 H C≡CCHCH F Me Me O
1.265 H C≡CCF＝CF H Me CF O
1.266 H C≡CCF＝CF H Me CFH O
1.267 H C≡CCHFCl H Me CF O
1.268 H C≡CCHFCl H Me CFH O
1.269 H C≡CCHFCl F Me Me O
1.270 H CH＝CFCF H Me CF O
1.271 H CH＝CFCF H Me CFH O
1.272 H CH＝CFCF F Me Me O
1.273 H C≡CCFCHCH H Me CF O
1.274 H C≡CCFCHCH H Me CFH O
1.275 H C≡CCFCHCH F Me Me O
1.276 H C≡CCHFCHCH H Me CF O
1.277 H C≡CCHFCHCH H Me CFH O
1.278 H C≡CCHFCHCH F Me Me O
1.279 H C≡CCF(CF) H Me CF O
1.280 H C≡CCF(CF) H Me CFH O
1.281 H C≡CCF(CF) F Me Me O
1.282 H CH＝CClCF H Me CF O
1.283 H CH＝CClCF H Me CFH O
1.284 H CH＝CClCF F Me Me O
1.285 H C≡CCF H Me CF O
1.286 H C≡CCF H Me CFH O
1.287 H C≡CCF F Me Me O
Table 1 provides 287 compounds of formula (Ia):
wherein R is1、R7、R8、R9、R10And X is as defined in table 1.
Table 1 provides 287 compounds of formula (IaA):
wherein R is1、R7、R8、R9、R10And X is as defined in table 1.
Table 1 provides 287 compounds of formula (IaB), wherein R1、R7、R8、R9、R10And X is as defined in table 1.
Table 1 provides 287 compounds of formula (IaC), wherein R1、R7、R8、R9、R10And X is as defined in table 1.
Table 1 provides 287 compounds of formula (IaD), wherein R1、R7、R8、R9、R10And X is as defined in table 1.
Table 1 provides 287 compounds of formula (IaE), wherein R1、R7、R8、R9、R10And X is as defined in table 1.
Table 1 provides 287 compounds of formula (IaF), wherein R1、R7、R8、R9、R10And X is as defined in table 1.
Table 1 provides 287 compounds of formula (IaG),wherein R is1、R7、R8、R9、R10And X is as defined in table 1.
Table 1 provides 287 compounds of formula (IaH), wherein R1、R7、R8、R9、R10And X is as defined in table 1.
Table 1 provides 287 compounds of formula (IaI) wherein R1、R7、R8、R9、R10And X is as defined in table 1.
Table 1 provides 287 compounds of formula (IaJ), wherein R1、R7、R8、R9、R10And X is as defined in table 1.
TABLE 2
Compound numbering R1 R R R R X
2.01 H C≡CH H Me CF O
2.02 H C≡CH H Me CF S
2.03 H C≡CH H Me CFH O
2.04 Propargyl group C≡CH H Me CF O
2.05 H C≡CH F Me Me O
2.06 H C≡CH H CHOMe CF O
2.07 Allenyl radical C≡CH H Me CF O
2.08 H C≡CSiMe H Me CF O
2.09 H C≡CSiMe H Me CF S
2.10 H C≡CSiMe H Me CFH O
2.11 H C≡CSiMe F Me Me O
2.12 H C≡CCl H Me CF O
2.13 H C≡CCl H Me CFH O
2.14 H C≡CCl F Me Me O
2.15 H C≡CBr H Me CF O
2.16 H C≡CBr H Me CFH O
2.17 H C≡CBr F Me Me O
2.18 H C≡CCF H Me CF O
2.19 H C≡CCF H Me CFH O
2.20 H C≡CCF F Me Me O
2.21 Allenyl radical C≡CCF H Me CF O
2.22 H CH＝CH H Me CF O
2.23 H CH＝CH H Me CF S
2.24 H CH＝CH H Me CFH O
2.25 Propargyl group CH＝CH H Me CF O
2.26 H CH＝CH F Me Me O
2.27 H CH＝CH H CHOMe CF O
2.28 Allenyl radical CH＝CH H Me CF O
2.29 H CH＝CF H Me CF O
2.30 H CH＝CF H Me CFH O
2.31 H CH＝CF F Me Me O
2.32 H CH＝CCl H Me CF O
2.33 H CH＝CCl H Me CFH O
2.34 H CH＝CCl F Me Me O
2.35 H CH＝CBr H Me CF O
2.36 H CH＝CBr H Me CFH O
2.37 H CH＝CBr F Me Me O
2.38 H CF＝CF H Me CF O
2.39 H CF＝CF H Me CFH O
2.40 H CF＝CF F Me Me O
2.41 H CCl＝CH H Me CF O
2.42 H CCl＝CH H Me CFH O
2.43 H CCl＝CH F Me Me O
2.44 H CBr＝CH H Me CF O
2.45 H CBr＝CH H Me CFH O
2.46 H CBr＝CH F Me Me O
2.47 H CF＝CHF H Me CF O
2.48 H CF＝CHF H Me CFH O
2.49 H CF＝CHF F Me Me O
2.50 H CH＝CHSiMe H Me CF O
2.51 H CH＝CHSiMe H Me CFH O
2.52 H CH＝CHSiMe F Me Me O
2.53 H CH＝CHCF H Me CF O
2.54 H CH＝CHCF H Me CFH O
2.55 H CH＝CHCF F Me Me O
2.56 H CH＝CClCF H Me CF O
2.57 H CH＝CClCF H Me CFH O
2.58 H CH＝CClCF F Me Me O
2.59 H CHC≡CH H Me CF O
2.60 H CHC≡CH H Me CFH O
2.61 H CHC≡CH F Me Me O
2.62 H CHC≡CH H CHOMe CF O
2.63 H CHC≡CSiMe H Me CF O
2.64 H CHC≡CSiMe H Me CFH O
2.65 H CHC≡CSiMe F Me Me O
2.66 H C≡CCMe H Me CF O
2.67 H C≡CCMe H Me CFH O
2.68 H C≡CCMe F Me Me O
2.69 H C≡CMe H Me CF O
2.70 H C≡CMe H Me CFH O
2.71 H C≡CMe F Me Me O
2.72 COMe C≡CH H Me CF O
2.73 H C≡CH H CFH CFH O
2.74 H C≡CH H CFH CF O
2.75 H C≡CH H Me CHF O
2.76 H C≡CSiMe H Me CHF O
2.77 H C ≡ C (cyclopropyl) H Me CF O
2.78 H C ≡ C (cyclopropyl) H Me CHF O
2.79 H SiMe H Me CHF O
2.80 H SiMe H Me CF O
2.81 H SiMe H Me CHF O
2.82 H C≡CF H Me CF O
2.83 H C≡CF H Me CFH O
2.84 H C≡CF F Me Me O
2.85 H C≡CCFCl H Me CF O
2.86 H C≡CCFCl H Me CFH O
2.87 H C≡CCFCl F Me Me O
2.88 H C≡CCFH H Me CF O
2.89 H C≡CCFH H Me CFH O
2.90 H C≡CCFH F Me Me O
2.91 H C≡CCFBr H Me CF O
2.92 H C≡CCFBr H Me CFH O
2.93 H C≡CCFBr F Me Me O
2.94 H C≡CCHF H Me CF O
2.95 H C≡CCHF H Me CFH O
2.96 H C≡CCHF F Me Me O
2.97 H C≡CCH(Me)F H Me CF O
2.98 H C≡CCH(Me)F H Me CFH O
2.99 H C≡CCH(Me)F F Me Me O
2.100 H C≡CC(Me)F H Me CF O
2.101 H C≡CC(Me)F H Me CFH O
2.102 H C≡CC(Me)F F Me Me O
2.103 H C≡CCHC(Me) H Me CF O
2.104 H C≡CCHC(Me) H Me CFH O
2.105 H C≡CCHC(Me) F Me Me O
2.106 H C≡CCH(Me) H Me CFH O
2.107 H C≡CCH(Me) H Me CFH O
2.108 H C≡CCH(Me) F Me Me O
2.109 H C≡CCHCH(Me) H Me CFH O
2.110 H C≡CCHCH(Me) H Me CFH O
2.111 H C≡CCHCH(Me) F Me Me O
2.112 H CHC≡CCMe H Me CF O
2.113 H CHC≡CCMe H Me CFH O
2.114 H CHC≡CCMe F Me Me O
2.115 H CFC≡CCMe H Me CF O
2.116 H CFC≡CCMe H Me CFH O
2.117 H CFC≡CCMe F Me Me O
2.118 H CFC≡CMe H Me CF O
2.119 H CFC≡CMe H Me CFH O
2.120 H CFC≡CCMe F Me Me O
2.121 H CFC≡CH H Me CF O
2.122 H CFC≡CH H Me CFH O
2.123 H CFC≡CH F Me Me O
2.124 H CMeC≡CH H Me CF O
2,125 H CMeC≡CH H Me CFH O
2.126 H CMeC≡CH F Me Me O
2.127 H CHFC≡CH H Me CF O
2.128 H CHFC≡CH H Me CFH O
2.129 H CHFC≡CH F Me Me O
2.130 H CHMeC≡CH H Me CF O
2.131 H CHMeC≡CH H Me CFH O
2.132 H CHMeC≡CH F Me Me O
2.133 H CH(CF)C≡CH H Me CF O
2.134 H CH(CF)C≡CH H Me CFH O
2.135 H CH(CF)C≡CH F Me Me O
2.136 H C ≡ C (1-F-cyclopentyl) H Me CF O
2.137 H C ≡ C (1-F-cyclopentyl) H Me CHF O
2.138 H C≡CCHOMe H Me CF O
2.139 H C≡CCHOMe H Me CFH O
2.140 H C≡CCHOMe F Me Me O
2.141 H C≡CCMeOMe H Me CF O
2.142 H C≡CCMeOMe H Me CFH O
2.143 H C≡CCMeOMe F Me Me O
2.144 H C≡CCMeOCOMe H Me CF O
2.145 H C≡CCMeOCOMe H Me CFH O
2.146 H C≡CCFMe H Me CF O
2.147 H C≡CCFMe H Me CFH O
2.148 H C≡CCFMe F Me Me O
2.149 H C≡CC(Me)＝CH H Me CF O
2.150 H C≡CC(Me)＝CH H Me CFH O
2.151 H CH＝CFCl H Me CF O
2.152 H CH＝CFCl H Me CFH O
2.153 H CH＝CFCl F Me Me O
2.154 H CH＝CFBr H Me CF O
2.155 H CH＝CFBr H Me CFH O
2.156 H CH＝CFBr F Me Me O
2.157 H CH＝CHBr H Me CF O
2.158 H CH＝CHBr H Me CFH O
2.159 H CH＝CHBr F Me Me O
2.160 H CH＝CHF H Me CF O
2.161 H CH＝CHF H Me CFH O
2.162 H CH＝CHF F Me Me O
2.163 H CMe＝CHCF H Me CF O
2.164 H CMe＝CHCF H Me CFH O
2.165 H CMe＝CHCF F Me Me O
2.166 H CH＝CFCF H Me CF O
2.167 H CH＝CFCF H Me CFH O
2.168 H CH＝CFCF F Me Me O
2.169 H CH＝CBrCF H Me CF O
2.170 H CH＝CBrCF H Me CFH O
2.171 H CH＝CBrCF F Me Me O
2.172 H CH＝CHCF H Me CF O
2.173 H CH＝CHCF H Me CFH O
2.174 H CH＝CHCF F Me Me O
2.175 H CH＝CHCl H Me CF O
2.176 H CH＝CHCl H Me CFH O
2.177 H CH＝CHCl F Me Me O
2.178 H CH＝C(CF) H Me CF O
2.179 H CH＝C(CF) H Me CFH O
2.180 H CH＝C(CF) F Me Me O
2.181 H CMe＝CFCl H Me CF O
2.182 H CMe＝CFCl H Me CFH O
2.183 H CMe＝CFCl F Me Me O
2.184 H CMe＝CFBr H Me CF O
2.185 H CMe＝CFBr H Me CFH O
2.186 H CMe＝CFBr F Me Me O
2.187 H CMe＝CF H Me CF O
2.188 H CMe＝CF H Me CFH O
2.189 H CMe＝CF F Me Me O
2.190 H CMe＝CCl H Me CF O
2.191 H CMe＝CCl H Me CFH O
2.192 H CMe＝CCl F Me Me O
2.193 H CMe＝CBr H Me CF O
2.194 H CMe＝CBr H Me CFH O
2.195 H CMe＝CBr F Me Me O
2.196 H CMe＝CFCF H Me CF O
2.197 H CMe＝CFCF H Me CFH O
2.198 H CMe＝CFCF F Me Me O
2.199 H CMe＝CClCF H Me CF O
2.200 H CMe＝CClCF H Me CFH O
2.201 H CMe＝CClCF F Me Me O
2.202 H CCF＝CF H Me CF O
2.203 H CCF＝CF H Me CFH O
2.204 H CCF＝CF F Me Me O
2.205 H CCF＝CCl H Me CF O
2.206 H CCF＝CCl H Me CFH O
2.207 H CCF＝CCl F Me Me O
2.208 H CCF＝CBr H Me CF O
2.209 H CCF＝CBr H Me CFH O
2.210 H CCF＝CBr F Me Me O
2.211 H CCF＝CH H Me CF O
2.212 H CCF＝CH H Me CFH O
2.213 H CCF＝CH F Me Me O
2.214 H CCF＝CFBr H Me CF O
2.215 H CCF＝CFBr H Me CFH O
2.216 H CCF＝CFBr F Me Me O
2.217 H CCF＝CHF H Me CF O
2.218 H CCF＝CHF H Me CFH O
2.219 H CCF＝CHF F Me Me O
2.220 H CCF＝CFCl H Me CF O
2.221 H CCF＝CFCl H Me CFH O
2.222 H CCF＝CFCl F Me Me O
2.223 H CCF＝CHCl H Me CF O
2.224 H CCF＝CHCl H Me CFH O
2.225 H CCF＝CHCl F Me Me O
2.226 H CH＝CFCFCl H Me CF O
2.227 H CH＝CFCFCl H Me CFH O
2.228 H CH＝CFCFCl F Me Me O
2.229 H CH＝CClCFCl H Me CF O
2.230 H CH＝CClCFCl H Me CFH O
2.231 H CH＝CClCFCl F Me Me O
2.232 H CHCF＝CF H Me CF O
2.233 H CHCF＝CF H Me CFH O
2.234 H CHCF＝CF F Me Me O
2.235 H CF＝CFBr H Me CF O
2.236 H CF＝CFBr H Me CFH O
2.237 H CF＝CFBr F Me Me O
2.238 H CHCH＝CF H Me CF O
2.239 H CHCH＝CF H Me CFH O
2.240 H CHCH＝CF F Me Me O
2.241 H CHCH＝CCl H Me CF O
2.242 H CHCH＝CCl H Me CFH O
2.243 H CHCH＝CCl F Me Me O
2.244 H CHCH＝CBr H Me CF O
2.245 H CHCH＝CBr H Me CFH O
2.246 H CHCH＝CBr F Me Me O
2.247 H CCl＝CF H Me CF O
2.248 H CCl＝CF H Me CFH O
2.249 H CCl＝CF F Me Me O
Table 2 provides 249 compounds of formula (Ib) wherein R1、R7、R8、R9、R10And X is as defined in table 2.
TABLE 3
Compound numbering R1 R R R X
3.01 H C≡CH Me CF O
3.02 H C≡CH Me CF S
3.03 H C≡CH Me CFH O
3.04 Propargyl group C≡CH Me CF O
3.05 H C≡CH Me Me O
3.06 H C≡CH CHOMe CF O
3.07 Allenyl radical C≡CH Me CF O
3.08 H C≡CSiMe Me CF O
3.09 H C≡CSiMe Me CF S
3.10 H C≡CSiMe Me CFH O
3.11 H C≡CSiMe Me Me O
3.12 H C≡CCl Me CF O
3.13 H C≡CCl Me CFH O
3.14 H C≡CCl Me Me O
3.15 H C≡CBr Me CF O
3.16 H C≡CBr Me CFH O
3.17 H C≡CBr Me Me O
3.18 H C≡CCF Me CF O
3.19 H C≡CCF Me CFH O
3.20 H C≡CCF Me Me O
3.21 Allenyl radical C≡CCF Me CF O
3.22 H CH＝CH Me CF O
3.23 H CH＝CH Me CF S
3.24 H CH＝CH Me CFH O
3.25 Propargyl group CH＝CH Me CF O
3.26 H CH＝CH Me Me O
3.27 H CH＝CH CHOMe CF O
3.28 Allenyl radical CH＝CH Me CF O
3.29 H CH＝CF Me CF O
3.30 H CH＝CF Me CFH O
3.31 H CH＝CF Me Me O
3.32 H CH＝CCl Me CF O
3.33 H CH＝CCl Me CFH O
3.34 H CH＝CCl Me Me O
3.35 H CH＝CBr Me CF O
3.36 H CH＝CBr Me CFH O
3.37 H CH＝CBr Me Me O
3.38 H CF＝CF Me CF O
3.39 H CF＝CF Me CFH O
3.40 H CF＝CF Me Me O
3.41 H CCl＝CH Me CF O
3.42 H CCl＝CH Me CFH O
3.43 H CCl＝CH Me Me O
3.44 H CBr＝CH Me CF O
3.45 H CBr＝CH Me CFH O
3.46 H CBr＝CH Me Me O
3.47 H CF＝CHF Me CF O
3.48 H CF＝CHF Me CFH O
3.49 H CF＝CHF Me Me O
3.50 H CH＝CHSiMe Me CF O
3.51 H CH＝CHSiMe Me CFH O
3.52 H CH＝CHSiMe Me Me O
3.53 H CH＝CHCF Me CF O
3.54 H CH＝CHCF Me CFH O
3.55 H CH＝CHCF Me Me O
3.56 H CH＝CClCF Me CF O
3.57 H CH＝CClCF Me CFH O
3.58 H CH＝CClCF Me Me O
3.59 H CHC≡CH Me CF O
3.60 H CHC≡CH Me CFH O
3.61 H CHC≡CH Me Me O
3.62 H CHC≡CH CHOMe CF O
3.63 H CHC≡CSiMe Me CF O
3.64 H CHC≡CSiMe Me CFH O
3.65 H CHC≡CSiMe Me Me O
3.66 H C≡CCMe Me CF O
3.67 H C≡CCMe Me CFH O
3.68 H C≡CCMe Me Me O
3.69 H C≡CMe Me CF O
3.70 H C≡CMe Me CFH O
3.71 H C≡CMe Me Me O
3.72 COMe C≡CH Me CF O
3.73 H C≡CH CFH CFH O
3.74 H C≡CH CFH CF O
3.75 H C≡CH Me CHF O
3.76 H C≡CSiMe Me CHF O
3.77 H C ≡ C (cyclopropyl) Me CF O
3.78 H C ≡ C (cyclopropyl) Me CHF O
3.79 H SiMe Me CHF O
3.80 H SiMe Me CF O
3.81 H SiMe Me CHF O
3.82 H C≡CF Me CF O
3.83 H C≡CF Me CFH O
3.84 H C≡CF Me Me O
3.85 H C≡CCFCl Me CF O
3.86 H C≡CCFCl Me CFH O
3.87 H C≡CCFCl Me Me O
3.88 H C≡CCFH Me CF O
3.89 H C≡CCFH Me CFH O
3.90 H C≡CCFH Me Me O
3.91 H C≡CCFBr Me CF O
3.92 H C≡CCFBr Me CFH O
3.93 H C≡CCFBr Me Me O
3.94 H C≡CCHF Me CF O
3.95 H C≡CCHF Me CFH O
3.96 H C≡CCHF Me Me O
3.97 H C≡CCH(Me)F Me CF O
3.98 H C≡CCH(Me)F Me CFH O
3.99 H C≡CCH(Me)F Me Me O
3.100 H C≡CC(Me)F Me CF O
3.101 H C≡CC(Me)F Me CFH O
3.102 H C≡CC(Me)F Me Me O
3.103 H C≡CCHC(Me) Me CF O
3.104 H C≡CCHC(Me) Me CFH O
3.105 H C≡CCHC(Me) Me Me O
3.106 H C≡CCH(Me) Me CF O
3.107 H C≡CCH(Me) Me CFH O
3.108 H C≡CCH(Me) Me Me O
3.109 H C≡CCHCH(Me) Me CF O
3.110 H C≡CCHCH(Me) Me CFH O
3.111 H C≡CCHCH(Me) Me Me O
3.112 H CHC≡CCMe Me CF O
3.113 H CHC≡CCMe Me CFH O
3.114 H CHC≡CCMe Me Me O
3.115 H CFC≡CCMe Me CF O
3.116 H CFC≡CCMe Me CFH O
3.117 H CFC≡CCMe Me Me O
3.118 H CFC≡CMe Me CF O
3.119 H CFC≡CMe Me CFH O
3.120 H CFC≡CCMe Me Me O
3.121 H CFC≡CH Me CF O
3.122 H CFC≡CH Me CFH O
3.123 H CFC≡CH Me Me O
3.124 H CMeC≡CH Me CF O
2,125 H CMeC≡CH Me CFH O
3.126 H CMeC≡CH Me Me O
3.127 H CHFC≡CH Me CF O
3.128 H CHFC≡CH Me CFH O
3.129 H CHFC≡CH Me Me O
3.130 H CHMeC≡CH Me CF O
3.131 H CHMeC≡CH Me CFH O
3.132 H CHMeC≡CH Me Me O
3.133 H CH(CF)C≡CH Me CF O
3.134 H CH(CF)C≡CH Me CFH O
3.135 H CH(CF)C≡CH Me Me O
3.136 H C ≡ C (1-F-cyclopentyl) Me CF O
3.137 H C ≡ C (1-F-cyclopentyl) Me CHF O
3.138 H C≡CCHOMe Me CF O
3.139 H C≡CCHOMe Me CFH O
3.140 H C≡CCHOMe Me Me O
3.141 H C≡CCMeOMe Me CF O
3.142 H C≡CCMeOMe Me CFH O
3.143 H C≡CCMeOMe Me Me O
3.144 H C≡CCMeOCOMe Me CF O
3.145 H C≡CCMeOCOMe Me CFH O
3.146 H C≡CCFMe Me CF O
3.147 H C≡CCFMe Me CFH O
3.148 H C≡CCFMe Me Me O
3.149 H C≡CC(Me)＝CH Me CF O
3.150 H C≡CC(Me)＝CH Me CFH O
3.151 H CH＝CFCl Me CF O
3.152 H CH＝CFCl Me CFH O
3.153 H CH＝CFCl Me Me O
3.154 H CH＝CFBr Me CF O
3.155 H CH＝CFBr Me CFH O
3.156 H CH＝CFBr Me Me O
3.157 H CH＝CHBr Me CF O
3.158 H CH＝CHBr Me CFH O
3.159 H CH＝CHBr Me Me O
3.160 H CH＝CHF Me CF O
3.161 H CH＝CHF Me CFH O
3.162 H CH＝CHF Me Me O
3.163 H CMe＝CHCF Me CF O
3.164 H CMe＝CHCF Me CFH O
3.165 H CMe＝CHCF Me Me O
3.166 H CH＝CFCF Me CF O
3.167 H CH＝CFCF Me CFH O
3.168 H CH＝CFCF Me Me O
3.169 H CH＝CBrCF Me CF O
3.170 H CH＝CBrCF Me CFH O
3.171 H CH＝CBrCF Me Me O
3.172 H CH＝CHCF Me CF O
3.173 H CH＝CHCF Me CFH O
3.174 H CH＝CHCF Me Me O
3.175 H CH＝CHCl Me CF O
3.176 H CH＝CHCl Me CFH O
3.177 H CH＝CHCl Me Me O
3.178 H CH＝C(CF) Me CF O
3.179 H CH＝C(CF) Me CFH O
3.180 H CH＝C(CF) Me Me O
3.181 H CMe＝CFCl Me CF O
3.182 H CMe＝CFCl Me CFH O
3.183 H CMe＝CFCl Me Me O
3.184 H CMe＝CFBr Me CF O
3.185 H CMe＝CFBr Me CFH O
3.186 H CMe＝CFBr Me Me O
3.187 H CMe＝CF Me CF O
3.188 H CMe＝CF Me CFH O
3.189 H CMe＝CF Me Me O
3.190 H CMe＝CCl Me CF O
3.191 H CMe＝CCl Me CFH O
3.192 H CMe＝CCl Me Me O
3.193 H CMe＝CBr Me CF O
3.194 H CMe＝CBr Me CFH O
3.195 H CMe＝CBr Me Me O
3.196 H CMe＝CFCF Me CF O
3.197 H CMe＝CFCF Me CFH O
3.198 H CMe＝CFCF Me Me O
3.199 H CMe＝CClCF Me CF O
3.200 H CMe＝CClCF Me CFH O
3.201 H CMe＝CClCF Me Me O
3.202 H CCF＝CF Me CF O
3.203 H CCF＝CF Me CFH O
3.204 H CCF＝CF Me Me O
3.205 H CCF＝CCl Me CF O
3.206 H CCF＝CCl Me CFH O
3.207 H CCF＝CCl Me Me O
3.208 H CCF＝CBr Me CF O
3.209 H CCF＝CBr Me CFH O
3.210 H CCF＝CBr Me Me O
3.211 H CCF＝CH Me CF3 O
3.212 H CCF＝CH Me CFH O
3.213 H CCF＝CH Me Me O
3.214 H CCF＝CFBr Me CF O
3.215 H CCF＝CFBr Me CFH O
3.216 H CCF＝CFBr Me Me O
3.217 H CCF＝CHF Me CF O
3.218 H CCF＝CHF Me CFH O
3.219 H CCF＝CHF Me Me O
3.220 H CCF＝CFCl Me CF O
3.221 H CCF＝CFCl Me CFH O
3.222 H CCF＝CFCl Me Me O
3.223 H CCF＝CHCl Me CF O
3.224 H CCF＝CHCl Me CFH O
3.225 H CCF＝CHCl Me Me O
3.226 H CH＝CFCFCl Me CF O
3.227 H CH＝CFCFCl Me CFH O
3.228 H CH＝CFCFCl Me Me O
3.229 H CH＝CClCFCl Me CF O
3.230 H CH＝CClCFCl Me CFH O
3.231 H CH＝CClCFCl Me Me O
3.232 H CHCF＝CF Me CF O
3.233 H CHCF＝CF Me CFH O
3.234 H CHCF＝CF Me Me O
3.235 H CF＝CFBr Me CF O
3.236 H CF＝CFBr Me CFH O
3.237 H CF＝CFBr Me Me O
3.238 H CHCH＝CF Me CF O
3.239 H CHCH＝CF Me CFH O
3.240 H CHCH＝CF Me Me O
3.241 H CHCH＝CCl Me CF O
3.242 H CHCH＝CCl Me CFH O
3.243 H CHCH＝CCl Me Me O
3.244 H CHCH＝CBr Me CF O
3.245 H CHCH＝CBr Me CFH O
3.246 H CHCH＝CBr Me Me O
3.247 H CCl＝CF Me CF O
3.248 H CCl＝CF Me CFH O
3.249 H CCl＝CF Me Me O
3.250 H C≡CCMeOH Me CF O
3.251 H C≡CCHCH Me CFH O
3.252 H C≡CCHCH Me Me O
3.253 H C≡CCHCH Me CF O
3.254 H C≡CCF＝CF Me CF O
3.255 H C≡CCF＝CF Me CFH O
3.256 H C≡CCHFCl Me CF O
3.257 H C≡CCHFCl Me CFH O
3.258 H C≡CCHFCl Me Me O
3.259 H CH＝CFCF Me CF O
3.260 H CH＝CFCF Me CFH O
3.261 H CH＝CFCF Me Me O
3.262 H C≡CCFCHCH Me CF O
3.263 H C≡CCFCHCH Me CFH O
3.264 H C≡CCFCHCH Me Me O
3.265 H C≡CCHFCHCH Me CF O
3.266 H C≡CCHFCHCH Me CFH O
3.267 H C≡CCHFCHCH Me Me O
3.268 H C≡CCF(CF) Me CF O
3.269 H C≡CCF(CF) Me CFH O
3.270 H C≡CCF(CF) Me Me O
3.271 H CH＝CClCF Me CF O
3.272 H CH＝CClCF Me CFH O
3.273 H CH＝CClCF Me Me O
3.274 H C≡CCF Me CF O
3.275 H C≡CCF Me CFH O
3.276 H C≡CCF Me Me O
Table 3 provides 276 compounds of formula (Ic):
wherein R is1、R7、R9、R10And X is as defined in table 3.
Table 3 provides 276 compounds of formula (IcA), wherein R1、R7、R9、R10And X is as defined in table 3.
Table 3 provides 276 compounds of formula (IcB), wherein R1、R7、R9、R10And X is as defined in table 3.
Table 3 provides 276 compounds of formula (IcC), wherein R1、R7、R9、R10And X is as defined in table 3.
Table 3 provides 276 compounds of formula (IcD), wherein R1、R7、R9、R10And X is as defined in table 3.
Table 3 provides 276 compounds of formula (IcE), wherein R1、R7、R9、R10And X is as defined in table 3.
Table 3 provides 276 compounds of formula (IcF), wherein R1、R7、R9、R10And X is as defined in table 3.
Table 3 provides 276 compounds of formula (IcG), wherein R1、R7、R9、R10And X is as defined in table 3.
Table 4 provides 3 compounds of formula (Id):
wherein R is1、R7、R9And R10As defined in table 4.
TABLE 4
Compound numbering R1 R R R
4.01 H C≡CH Me CF
4.02 H C≡CSiMe Me CF
4.03 H CH＝CH Me CF
Table 5 provides 15 compounds of formula (Ie):
wherein R is1、R7、R8、R9And R10As defined in table 5.
TABLE 5
Compound numbering R1 R R R R
5.01 H C≡CH H H CF
5.02 H C≡CH Me Me Me
5.03 H C≡CH H Me CF
5.04 H C≡CH Me Me H
5.05 COMe C≡CH Me Me H
5.06 COMe C≡CH Me Me Me
5.07 COEt C≡CH Me Me Me
5.08 H C≡CSiMe H H CF
5.09 H C≡CSiMe Me Me Me
5.10 H C≡CSiMe H Me CF
5.11 H C≡CSiMe Me Me H
5.12 H C≡CSiMe H H CF
5.13 H CH＝CH Me Me Me
5.14 H CH＝CH H Me CF
5.15 H CH＝CH Me Me H
Table 6 provides 15 compounds of formula (If):
wherein R is1、R7、R8、R9And R10As defined in table 6.
TABLE 6
Compound numbering R1 R R R R
6.01 H C≡CH H H CF
6.02 H C≡CH Me Me Me
6.03 H C≡CH H Me CF
6.04 H C≡CH Me Me H
6.05 COMe C≡CH Me Me H
6.06 COMe C≡CH Me Me Me
6.07 COEt C≡CH Me Me Me
6.08 H C≡CSiMe H H CF
6.09 H C≡CSiMe Me Me Me
6.10 H C≡CSiMe H Me CF
6.11 H C≡CSiMe Me Me H
6.12 H C≡CSiMe H H CF
6.13 H CH＝CH Me Me Me
6.14 H CH＝CH H Me CF
6.15 H CH＝CH Me Me H
Table 7 provides 10 compounds of formula (Ig):
wherein R is1、R7、R8And X is as defined in table 7.
TABLE 7
Compound numbering R1 R R X
7.01 H C≡CH CF O
7.02 H C≡CH Me O
7.03 H C≡CH CF S
7.04 COMe C≡CH Me O
7.05 H C≡CSiMe CF O
7.06 H C≡CSiMe Me O
7.07 H CH＝CH CF O
7.08 H CH＝CH CF O
7.09 Propargyl group CH＝CH Me O
7.10 Allenyl radical CH＝CH Me O
Table 8 provides 10 compounds of formula (Ih):
wherein R is1、R7、R8And X is as defined in table 8.
TABLE 8
Compound numbering R1 R R X
8.01 H C≡CH CF O
8.02 H C≡CH Me O
8.03 H C≡CH CF S
8.04 COMe C≡CH Me O
8.05 H C≡CSiMe CF O
8.06 H C≡CSiMe Me O
8.07 H CH＝CH CF O
8.08 H CH＝CH CF O
8.09 Propargyl group CH＝CH Me O
8.10 Allenyl radical CH＝CH Me O
TABLE 9
Compound numbering R1 R R
9.01 H C≡CH Cl
9.02 H C≡CH CF
9.03 COMe C≡CH Cl
9.04 H C≡CH Br
9.05 COCHOMe C≡CH Cl
9.06 H C≡CSiMe Cl
9.07 H C≡CSiMe CF
9.08 H C≡CSiMe Br
9.09 H CH＝CH CF
9.10 H CH＝CH Br
9.11 H CH＝CH Cl
9.12 H CH＝CH CH
9.13 Propargyl group CH＝CH Cl
9.14 Allenyl radical CH＝CH Cl
9.15 H C≡CCl Cl
9.16 H C≡CCl CF
9.17 H C≡CCl Br
9.18 H C≡CBr Cl
9.19 H C≡CBr CF
9.20 H C≡CBr Br
9.21 H C≡CCF Cl
9.22 H C≡CCF CF
9.23 H C≡CCF Br
9.24 H CH＝CF CF
9.25 H CH＝CF Br
9.26 H CH＝CF Cl
9.27 H CCl＝CH CF
9.28 H CCl＝CH Br
9.29 H CCl＝CH Cl
9.30 H CBr＝CH CF
9.31 H CBr＝CH Br
9.32 H CBr＝CH Cl
9.33 H CF＝CHF CF
9.34 H CF＝CHF Br
9.35 H CF＝CHF Cl
9.36 H CH＝CHCF CF
9.37 H CH＝CHCF Br
9.38 H CH＝CHCF Cl
9.39 H CH＝CClCF CF
9.40 H CH＝CClCF Br
9.41 H CH＝CClCF Cl
9.42 H CHC≡CH CF
9.43 H CHC≡CH Br
9.44 H CHC≡CH Cl
9.45 H CHC≡CSiMe CF
9.46 H CHC≡CSiMe Br
9.47 H CHC≡CSiMe Cl
9.48 H C≡CMe CF
9.49 H C≡CMe Br
9.50 H C≡CMe Cl
9.51 H CH＝CCl CF
9.52 H CH＝CCl Br
9.53 H CH＝CCl Cl
9.54 H CH＝CHSiMe CF
9.55 H CH＝CHSiMe Br
9.56 H CH＝CHSiMe Cl
9.57 H C ≡ C (cyclopropyl) Cl
9.58 H SiMe Cl
9.59 H C≡CCM Cl
9.60 H CH＝CBr CF
9.61 H CH＝CBr Br
9.62 H CH＝CBr Cl
9.63 H CF＝CF CF
9.64 H CF＝CF Br
9.65 H CF＝CF Cl
9.66 H C≡CCMe CF
9.67 H C≡CCMe Br
9.68 Allenyl radical C≡CCMe Cl
9.69 H C ≡ C (cyclopropyl) CF
9.70 H C ≡ C (cyclopropyl) Br
9.71 H C≡CF CF
9.72 H C≡CF Br
9.73 H C≡CF Cl
9.74 H C≡CCFCl Cl
9.75 H C≡CCFCl CF
9.76 H C≡CCFCl Br
9.77 H C≡CCFH Cl
9.78 H C≡CCFH CF
9.79 H C≡CCFH Br
9.80 H C≡CCFBr Cl
9.81 H C≡CCFBr CF
9.82 H C≡CCFBr Br
9.83 H C≡CCHF Cl
9.84 H C≡CCHF CF
9.85 H C≡CCHF Br
9.86 H C≡CCH(Me)F Cl
9.87 H C≡CCH(Me)F CF
9.88 H C≡CCH(Me)F Br
9.89 H C≡CC(Me)F Cl
9.90 H C≡CC(Me)F CF
9.91 H C≡CC(Me)F Br
9.92 H C≡CCHCMe Cl
9.93 H C≡CCHCMe Br
9.94 H C≡CCHMe CF
9.95 H C≡CCHMe Br
9.96 H C≡CCHMe Cl
9.97 H C≡CCHCHMe CF
9.98 H C≡CCHCHMe Br
9.99 H C≡CCHCHMe Cl
9.100 H CFC≡CMe CF
9.101 H CFC≡CMe Br
9.102 H CFC≡CMe Cl
9.103 H CFC≡CH CF
9.104 H CFC≡CH Br
9.105 H CFC≡CH Cl
9.106 H CHFC≡CH CF
9.107 H CHFC≡CH Br
9.108 H CHFC≡CH Cl
9.109 H C ≡ C (1-F-cyclopentyl) CF
9.110 H C ≡ C (1-F-cyclopentyl) Br
9.111 H C ≡ C (1-F-cyclopentyl) Cl
9.112 H C≡CCHOMe Cl
9.113 H C≡CCHOMe Br
9.114 H C≡CCHOMe CF
9.115 H C≡CCMeOMe Cl
9.116 H C≡CCMeOMe Br
9.117 H C≡CCMeOMe CF3
9.118 H C≡CCMeOCOMe Cl
9.119 H C≡CCMeOCOMe Br
9.120 H C≡CCMeOCOMe CF
9.121 H C≡CCFMe Cl
9.122 H C≡CCFMe Br
9.123 H C≡CCFMe CF
9.124 H CH＝CFCl CF
9.125 H CH＝CFCl Br
9.126 H CH＝CFCl Cl
9.127 H CH＝CFBr CF
9.128 H CH＝CFBr Br
9.129 H CH＝CFBr Cl
9.130 H CH＝CHBr CF
9.131 H CH＝CHBr Br
9.132 H CH＝CHBr Cl
9.133 H CMe＝CHCF CF
9.134 H CMe＝CHCF Br
9.135 H CMe＝CHCF Cl
9.136 H CH＝CFCF CF
9.137 H CH＝CFCF Br
9.138 H CH＝CFCF Cl
9.139 H CH＝CBrCF CF
9.140 H CH＝CBrCF Br
9.141 H CH＝CBrCF Cl
9.142 H CH＝CHCF CF
9.143 H CH＝CHCF Br
9.144 H CH＝CHCF Cl
9.145 H CH＝CHCl CF
9.146 H CH＝CHCl Br
9.147 H CH＝CHCl Cl
9.148 H CH＝C(CF) Cl
9.149 H CMe＝CFCl CF
9.150 H CMe＝CFCl Br
9.151 H CMe＝CFCl Cl
9.152 H CMe＝CFBr CF
9.153 H CMe＝CFBr Br
9.154 H CMe＝CFBr Cl
9.155 H CMe＝CF CF
9.156 H CMe＝CF Br
9.157 H CMe＝CF Cl
9.158 H CMe＝CCl CF
9.159 H CMe＝CCl Br
9.160 H CMe＝CCl Cl
9.161 H CMe＝CBr CF
9.162 H CMe＝CBr Br
9.163 H CMe＝CBr Cl
9.164 H CCF＝CF CF
9.165 H CCF＝CF Br
9.166 H CCF＝CF Cl
9.167 H CCF＝CCl CF
9.168 H CCF＝CCl Br
9.169 H CCF＝CCl Cl
9.170 H CCF＝CBr CF
9.171 H CCF＝CBr Br
9.172 H CCF＝CBr Cl
9.173 H CCF＝CH CF
9.174 H CCF＝CH Br
9.175 H CCF＝CH Cl
9.176 H CCF＝CFBr CF
9.177 H CCF＝CFBr Br
9.178 H CCF＝CFBr Cl
9.179 H CCF＝CFCl CF
9.180 H CCF＝CFCl Br
9.181 H CCF＝CFCl Cl
9.182 H CH＝CFCFCl CF
9.183 H CH＝CFCFCl Br
9.184 H CH＝CFCFCl Cl
9.185 H CH＝CClCFCl Cl
9.186 H CHCF＝CF CF
9.187 H CHCF＝CF Br
9.188 H CHCF＝CF Cl
9.189 H CF＝CFBr Cl
9.190 H CHCH＝CF Cl
9.191 H CHCH＝CCl Cl
9.192 H CHCH＝CBr Cl
9.193 H CHCH＝CBr CF
9.194 H CHCH＝CBr Br
9.195 H CCl＝CF Cl
9.196 H C≡CMe CHF
9.197 H C≡CCHMe CHF
9.198 H C≡CCHCHMe CHF
9.199 H C≡CCF CHF
9.200 H C≡CH CHF
9.201 H C≡CCHSiMe Cl
9.202 H C≡CCHCF Cl
9.203 H C≡CSi(M)CMe Cl
9.204 H C≡CCHCH Cl
9.205 H C≡CCF＝CF Cl
9.206 H C≡CCHFCl Cl
9.207 H CH＝CFCF Cl
9.208 H C≡CCFCHCH Cl
9.209 H C≡CCHFCHCH Cl
9.210 H C≡CCF(CF) Cl
9.211 H CH＝CClCF Cl
9.212 H C≡CCF Cl
Table 9 provides 212 compounds of formula (Ii):
wherein R is1、R7And R8As defined in table 9.
Table 9 provides 212 compounds of formula (IiA), wherein R1、R7And R8As defined in table 9.
Table 9 provides 212 compounds of formula (IiB), wherein R1、R7And R8As defined in table 9.
Table 9 provides 212 compounds of formula (IiC), wherein R1、R7And R8As defined in table 9.
Table 9 also provides 212 compounds of formula (IiD), wherein R1、R7And R8As defined in table 9.
Table 10 provides 14 compounds of formula (Ij):
wherein R is1、R7And R8As defined in table 10.
Watch 10
Compound numbering R1 R R
10.01 H C≡CH Cl
10.02 H C≡CH CF
10.03 COMe C≡CH Cl
10.04 H C≡CH Br
10.05 COCHOMe C≡CH Cl
10.06 H C≡CSiMe Cl
10.07 H C≡CSiMe CF
10.08 H C≡CSiMe Br
10.09 H CH＝CH CF
10.10 H CH＝CH Br
10.11 H CH＝CH Cl
10.12 H CH＝CH CH
10.13 Propargyl group CH＝CH Cl
10.14 Allenyl radical CH＝CH Cl
Table 11 provides 14 compounds of formula (Ik):
wherein R is1、R7And R8As defined in table 11.
TABLE 11
Compound numbering R1 R R
11.01 H C≡CH Cl
11.02 H C≡CH CF
11.03 COMe C≡CH Cl
11.04 H C≡CH Br
11.05 COCHOMe C≡CH Cl
11.06 H C≡CSiMe Cl
11.07 H C≡CSiMe CF
11.08 H C≡CSiMe Br
11.09 H CH＝CH CF
11.10 H CH＝CH Br
11.11 H CH＝CH Cl
11.12 H CH＝CH CH
11.13 Propargyl group CH＝CH Cl
11.14 Allenyl radical CH＝CH Cl
Table 12 provides 94 compounds of formula (II) wherein R2、R3、R4And R5Each is hydrogen; n is 0; and R is1And R7As defined in table 12.
TABLE 12
Compound numbering R1 R
12.01 H C≡CH
12.02 H C≡CSiMe
12.03 H C≡CCF
12.04 H C≡CCl
12.05 H CH＝CH
12.06 H CH＝CF
12.07 H CH＝CCl
12.08 H CH＝CBr
12.09 H CF＝CF
12.10 H CCl＝CH
12.11 H CF＝CHF
12.12 H CH＝CHCF
12.13 H CH＝CClCF
12.14 H CHC≡CH
12.15 H C≡CCMe
12.16 CHO C≡CMe
12.17 H C ≡ C (cyclopropyl)
12.18 H SiMe
12.19 H C≡CBr
12.20 H CBr＝CH
12.21 H CH＝CHSiMe
12.22 H CHC≡CSiMe
12.23 H C≡CMe
12.24 H C≡CF
12.25 H C≡CCFCl
12.26 H C≡CCFH
12.27 H C≡CCFBr
12.28 H C≡CCHF
12.29 H C≡CCH(Me)F
12.30 H C≡CC(Me)F
12.31 H C≡CCHC(Me)
12.32 H C≡CCH(Me)
12.33 H C≡CCHCH(Me)
12.34 H CHC≡CCMe
12.35 H CFC≡CCMe
12.36 H CFC≡CMe
12.37 H CFC≡CH
12.38 H CMeC≡CH
12.39 H CHFC≡CH
12.40 H CHMeC≡CH
12.41 H CH(CF)C≡CH
12.42 H C ≡ C (1-F-cyclopentyl)
12.43 H C≡CCHOMe
12.44 H C≡CCMeOMe
12.45 H C≡CCMeOCOMe
12.46 H C≡CCFMe
12.47 H C≡CC(Me)＝CH
12.48 H CH＝CFCl
12.49 H CH＝CFBr
12.50 H CH＝CHBr
12.51 H CH＝CHF
12.52 H CMe＝CHCF
12.53 H CH＝CFCF
12.54 H CH＝CBrCF
12.55 H CH＝CHCF
12.56 H CH＝CHCl
12.57 H CH＝C(CF)
12.58 H CMe＝CFCl
12.59 H CMe＝CFBr
12.60 H CMe＝CF
12.61 H CMe＝CCl
12.62 H CMe＝CBr
12.63 H CMe＝CFCF
12.64 H CMe＝CClCF
12.65 H CCF＝CF
12.66 H CCF＝CCl
12.67 H CCF＝CCl
12.68 H CCF＝CCl
12.69 H CCF＝CBr
12.70 H CCF＝CH
12.71 H CCF＝CFBr
12.72 H CCF＝CHF
12.73 H CCF＝CFCl
12.74 H CCF＝CHCl
12.75 H CH＝CFCFCl
12.76 H CH＝CClCFCl
12.77 H CHCF＝CF
12.78 H CF＝CFBr
12.79 H CHCH＝CF
12.80 H CHCH＝CCl
12.81 H CHCH＝CBr
12.82 H CCl＝CF
12.83 H C≡CCHSiMe
12.84 H C≡CSiMeCMe
12.85 H C≡CCMeOH
12.86 H C≡CCHCH
12.87 H C≡CCF＝CF
12.88 H C≡CCHFCl
12.89 H CH＝CFCF
12.90 H C≡CCFCHCH
12.91 H C≡CCHFCHCH
12.92 H C≡CCF(CF)
12.93 H CH＝CClCF
12.94 H C≡CCF
Table 13 provides 1 compound of formula (III) wherein R2、R3、R4And R5Each is hydrogen; n is 0; and Hal and R7As defined in table 13.
Watch 13
Compound numbering R Hal
13.01 C≡CH Br
In this specification, the unit of temperature is; "NMR" refers to nuclear magnetic resonance spectroscopy; MS represents mass spectrum; m+-1 or M++1 is the signal in the mass spectrum, corresponding to molecular weight-1 or molecular weight +1, respectively; and "%" is weight percent unless the corresponding concentration is indicated by other units.
The following abbreviations are used in the present specification.
m.p. ═ melting point b.p. ═ boiling point
s-broad
d-doublet dd-doublet
t is triplet q is quartet
m-multiplet ppm-10 ppm-6]
Table 14 shows selected melting points, selected molecular ions and selected NMR data, all with CDCl, for the compounds in tables 1-133As solvent (unless otherwise stated; if a mixture of solvents is used, it is indicated, for example, as (CDCl)3/d6-DMSO)) (in all cases, no attempt was made to list all the characteristics). Unless otherwise indicated, the data refer to cis/trans mixtures of each compound.
TABLE 14
Compound numbering 1H-NMR data: (ppm/number of peaks/H) or MS-data m.p./(℃)
1.01 169-170
1.03 132-135
1.08 147-150
1.10 ＞200
1.12 195-197
1.13 139-144
1.15 193-194
1.16 120-125
1.18 207-209
1.19 210-212
1.22 184-187
1.24 137-141
1.29 197-198
1.30 181-182
1.32 173-176
1.33 147-150
1.35 167-169
1.36 148-150
1.38 156-157
1.39 168-170
1.41 212-213
1.42 174-176
1.50 117-124
1.53 205-206
1.54 194-195
1.56 143-145
1.57 118-121
1.59 186-190
1.60 137-139
1.66 139-143
1.67 406(M-1) 193-196
1.69 382(M-1) 221-223
1.70 364(M-1) 205-208
1.77 208-210
1.78 202-205
1.80 165-166
1.81 165-169
1.85 198-198.5
1.86 184-184.5
1.88 206-207
1.89 200-201
1.193 160-162
1.94 205-206
1.95 198-199
1.97 197-
1.98 176-177
1.100 120-121
1.101 128-129
1.106 155-158
1.107 142-143
1.109 150-153
1.110 132-140
1.137 132-133
1.138 167-169
1.139 163-165
1.141 141-142.5
1.142 155-156
1.144 1.8(s，6)；2.1(s，3)；3.95(s，3)7.2-7.6(m，7)；7.75(br.s，1)；8.25(d，1)
1.145 132-141
1.147 149-150
1.150 143-145
1.151 189-194
1.152 168-170
1.154 197-200
1.155 174-178
1.158 195
1.166 172-155
1.167 145-150
1.182 127-129
1.185 111-114
1.194 2.25(s，3)；3.9(s，3)；6.7(t，1)；7.2-7.5(m，6)；7.7(s，1)；7.72(br，1)；8.3(d，1)
1.212 176-179
1.226 152.5-153
1.227 146-147
1.250 159-162
1.251 156-161
1.252 163-165
1.254 139-140
1.255 187-187.5
1.257 177-178
2.01 145-148
2.08 148-154
2.66 160-165
3.01 145-147
3.08 103-105
3.12 122-126
3.18 160-165
3.29 146-147
3.32 125-130
3.35 120-126
3.38 122-127
3.41 169-170
3.56 132-137
3.66 129-133
3.69 159-163
3.97 133-134
3.100 127.7-129
3.109 117-119
3.136 140-142
3.141 1.55(s，6)；2.7(s，3)；3.4(s，3)；7.2-7.3(m，4)；7.4(m，1)；7.5(d，2)；7.55(br，1)；8.3(d，1)
3.146 141-142
3.157 145-157
3.166 148-150
3.193 128-132
3.211 183-184
3.250 140-143
9.01 150-152
9.06 84-86
9.15 154-157
9.21 185-189
9.38 141-142
9.41 143-145
9.50 157-159
9.53 133-138
9.58 130-132
9.59 123-125
9.62 138-139
9.65 164-167
9.68 1.8(s，9)；4.9+5，25(m，1)；6.15-8.5(m，12)
9.83 143-145
9.86 169-170
9.89 167-167.5
9.99 109-111
9.118 1.8(s，6)；2.1(s，3)；7.2-7.6(m，9)，8.1(m，1)；8.45(m，1)
9.132 162-165
9.138 172-175
9.163 167-171
9.185 119-120.5
9.201 0.0(s，9)；1.55(s，2)；7.0-7.3(m，8)；79-8.0(m，2)；8.3(m，2)
9.203 105-107
12.01 111-115
12.02 0.05(s，9)；6.5-6.7(d+t，2)；6.8-7.1(t+t，2)；7.2-7.5(m，4)
12.03 262(M+H)；303(M+MeCN+H)；
12.04 92-98
12.06 3.75(br，2)；5.35(dd，1)；6.75-6.9(m，2)；7.1-7.2(m，2)；7.35-7.5(m，4)
12.07 3.8(br，2)；6.8(d，1)；6.85(t，1)；6.9(s，1)；7.1-7.2(d+t，2)；7.45-7.65(m，4)
12.08 3.8(br，2)；6.75-6.9(m，2)；7.1-7.2(m，2)；7.5-7.7(m，5)
12.09 3.8(br, 2); 6.7-6.9(m, 2); 7.1-7.2(m, 2); 7.6 (very narrow m, 4)19F：-99.7；-114.6；-177.3
12.10 230(M+H)；371(M+MeCN+H)
12.12 84-86
12.13 298(M+H)；339(M+MeCN+H)；
12.14 208(M+H)；249(M+MeCN+H)；
12.15 66-69
12.16 91-96
12.17 0.8-0.9(m，4)；1.4-1.5(m，2)；3.7(br，2)；6.7-6.8(m，2)；7.1-7.2(m，2)；7.3-7.5(m，4)
12.18 0.15(s, 9); 2.0-2.6 (very wide, 2); 6.6-6.7(m, 2); 7.0-7.1(m, 2); 7.3-7.5(m, 4)
12.19 3.8(br，2)；6.75-6.9(m，2)；7.1-7.2(m，2)；7.35-7.55(m，4)
12.23 108-112
12.25 3.75(br，2)；6.8(m，2)；7.1-7.25(m，2)；7.5-7.7(m，4)
19F：-35.9
12.26 3.8(br，2)；6.4(t，1)；6.75-6.9(m，2)；7.1-7.25(m，2)；7.4-7.56(m，4)；19F：-105.7
12.28 69-71
12.29 1.7 (doublet, 3); 3.8(br, 2); 5.5 (doublet of fourfold, 1); 6.75-6.9(m, 2); 7.05-7.2(m, 2); 7.4-7.6(m, 4)19F：-165.6
12.30 1.75(d，6)；3.8(br，2)；6.8(m，2)；7.15(m，2)；7.4-7.6(m，4)19F：-126.0
12.32 1.3(d，6)；3.7(br，2)；6.7-6.8(d+t，2)；7.15(m，2)；7.3-7.5(m，4)
12.33 1.05(d，6)；1.9(m，1)；2.35(d，2)；3.75(br，2)；6.75-6.9(m，2)；7.1-7.2(m，2)；7.35-7.5(m，4)
12.42 1.7-2.5(m，8)；3.7(br，2)；6.7-6.8(m，2)；7.05-7.15(m，2)；7.35.7.5(m，4)；7.1-7.2(m，2)；7.4-7.6(m，4)
12.43 3.45(s，3)；3.8(br，2)；4.35(s，2)；6.7-6.8(d+t，2)；7.1-7.25(m，2)；7.4-7.6(m，4)
12.45 1.75(s，6)；2.1(s，3)；3.75(br，2)；6.75-6.85(m，2)；7.1-7.2(m，2)；7.4-7.6(m，4)
12.46 2.0(t，3)；3.75(br，2)；6.75-6.85(m，2)；7.1-7.2(m，2)；7.4-7.6(m，4)
12.47 2.0(s, 3); 3.75(br, 2); 5.3 (narrow m, 1); 5.4(s, 1); 6.75-6.85(m, 2); 7.1-7.2(m, 2); 7.4-7.55(m, 4)
12.48 3.8(br，2)；5.85+6.45(2ds，1)；6.7-6.9(m，2)；7,1-7.2(m，2)；7.4-7.65(m，4)；19F：-71.2；-73.9
12.49 4.0-4.6(br，2)；6.0+6.7(2ds，1)；6.75-6.9(m，2)；7,1-7.2(m，2)；7.4-7.65(m，4)；
12.50 86-92
12.53
12.58 2.1(2s，3)；3.8(br，2)；6.7-6.9(m，2)；7.1-7.2(m，2)；7.35-7.5(m，2)；19F：-80.1；-81.3
12.59 2.1(2s，3)；3.8(br，2)；6.7-6.9(m，2)；7.1-7.2(m，2)；7.35-7.5(m，2)；19F：-74.2；-74.6
12.62 120-129
12.70 3.75(br, 2); 5.8 (narrow m, 1); 5.95 (narrow m, 1); 6.75-6.9(m, 2); 7.1-7.2(m, 2); 7.4-7.55(m, 4)
12.75 67-68.5
12.83 0.0(s，9)；1.6(s，2)；6.6(d，1)；6.65(t，1)；7.0(m，2)；7.2-7.4(m，4)
12.84 0.0(s, 6); 0.8(s, 9); 4.25 (very wide, 2); 6.65-6.75(m, 2); 6.9-7.05(m, 2); 7.2-7.4(m, 4)
12.85 252(M+H)
15.25 131-134
15.26 Amorphous
15.28 1.3(s，9)；7.2-7.5(m，10)；8.1(m，2)；8.45(m，2)
16.7 63-64
Table 15 provides 48 compounds of formula 1(m) wherein R, X and Het are as defined in table 15.
Watch 15
Compound numbering X R Het
15.1 H C≡CH Het(1)
15.2 H C≡CH Het(2)
15.3 H C≡CH Het(3)
15.4 H C≡CH Het(4)
15.5 Cl C≡CH Het(1)
15.6 Cl C≡CH Het(2)
15.7 Cl C≡CH Het(3)
15.8 Cl C≡CH Het(4)
15.9 F C≡CH Het(1)
15.10 F C≡CH Het(2)
15.11 F C≡CH Het(3)
15.12 F C≡CH Het(4)
15.13 H C≡CMe Het(1)
15.14 H C≡CMe Het(2)
15.15 H C≡CMe Het(3)
15.16 H C≡CMe Het(4)
15.17 F C≡CMe Het(1)
15.18 F C≡CMe Het(2)
15.19 F C≡CMe Het(3)
15.20 F C≡CMe Het(4)
15.21 Cl C≡CMe Het(1)
15.22 Cl C≡CMe Het(2)
15.23 Cl C≡CMe Het(3)
15.24 Cl C≡CMe Het(4)
15.25 H C≡CCMe Het(1)
15.26 H C≡CCMe Het(2)
15.27 H C≡CCMe Het(3)
15.28 H C≡CCMe Het(4)
15.29 Cl C≡CCMe Het(1)
15.30 Cl C≡CCMe Het(2)
15.31 Cl C≡CCMe Het(3)
15.32 Cl C≡CCMe Het(4)
15.33 F C≡CCMe Het(1)
15.34 F C≡CCMe Het(2)
15.35 F C≡CCMe Het(3)
15.36 F C≡CCMe Het(4)
15.37 H CH＝CClCF Het(1)
15.38 H CH＝CClCF Het(2)
15.39 H CH＝CClCF Het(3)
15.40 H CH＝CClCF Het(4)
15.41 Cl CH＝CClCF Het(1)
15.42 Cl CH＝CClCF Het(2)
15.43 Cl CH＝CClCF Het(3)
15.44 Cl CH＝CClCF Het(4)
15.45 F CH＝CClCF Het(1)
15.46 F CH＝CClCF Het(2)
15.47 F CH＝CClCF Het(3)
15.48 F CH＝CClCF Het(4)
Table 16 provides 12 compounds of formula ii (m), wherein R and X are as defined in table 16.
TABLE 16
Compound numbering X R
16.1 H C≡CH
16.2 Cl C≡CH
16.3 F C≡CH
16.4 H C≡CMe
16.5 F C≡CMe
16.6 Cl C≡CMe
16.7 H C≡CCMe
16.8 Cl C≡CCMe
16.9 F C≡CCMe
16.10 H CH＝CClCF
16.11 Cl CH＝CClCF
16.12 F CH＝CClCF
The compounds according to the invention may be prepared according to the following reaction schemes, wherein each variable is as defined above for the compounds of formula (I), unless otherwise indicated.
There are many alternative processes for preparing compounds of formula (I).
Method A
The compounds of formula (I) may be prepared as follows: in the presence of a strong base [ e.g. NaH or sodium hexamethyldisilazane ]]In the case of (1), in an anhydrous polar solvent [ preferably THF ]]At a temperature between-10 ℃ and the boiling point of the solvent [ preferably at ambient temperature]Reacting a compound of formula (II) with a compound of formula Het-C (═ O) OR' [ whereinR' is C1-5Alkyl radical]And (3) reacting the compound. An article by wang et al Synlett2001, 1485 details a similar preparation.
Method B
The compounds of formula (I) may be prepared as follows: in an inert organic solvent [ e.g. ethyl acetate, dichloromethane, dioxane or DMF]At a temperature between-10 ℃ and the boiling point of the solvent [ preferably at ambient temperature]Reacting a compound of formula (II) with a compound of formula Het-C (═ O) R "[ wherein R" is OH or a leaving group, for example Cl, Br, F or OC (═ O) C1-4Alkyl radical]And (3) reacting the compound. If R' is OH, then an activator [ e.g., BOP-C1]And 2 equivalents of a base [ e.g. tertiary amine, inorganic carbonate or bicarbonate]The reaction was carried out. Alternatively, if R' is a leaving group, in the presence of at least 1 equivalent of a base [ e.g., pyridine, tertiary amine, inorganic carbonate or bicarbonate]The reaction was carried out.
Method C
A compound of formula (I) [ wherein R1Is as defined above, but is not hydrogen]Can be prepared as follows: in the presence of a base [ e.g., a tertiary amine, an alkali metal carbonate, an alkali metal bicarbonate, an alkali metal hydroxide, or NaH; although if L is1Is O (CO) C1-4Alkyl radical, simple heating without base is also possible]In the case of (A), in a solvent [ e.g. a halogenated solvent (e.g. dichloromethane), an ether, ethyl acetate, DMF or even water (as a biphasic mixture, optionally in the presence of a phase transfer catalyst, e.g. tert-butylammonium hydrogen sulfate ]]In (b), reacting a compound of formula (I) [ wherein R1Is hydrogen]And formula R1-L1[ wherein R1Is as defined above, but is not hydrogen; and L is1Is a leaving group such as Cl, Br, I, sulfonate (e.g. mesylate or tosylate) or OC (O) C1-4Alkyl radical]And (3) reacting the compound.
Method D
The compounds of formula (I) may be prepared as follows: in the presence of a Cu (I) compound and an aprotic solvent [ e.g.Cyclic ethers, e.g. dioxane]In the case of compounds of the formula (III) [ wherein Hal is preferably bromine or iodine ], at elevated temperature, and preferably under reflux]And of the formula Het-C (═ O) NH2And (3) reacting the compound. Preferred conditions are: CuI used in the presence of 1, 2-diamine as ligand former (e.g. 1, 2-diaminocyclohexane or ethylenediamine) and at least 1 equivalent of a base (e.g. alkali metal carbonate or alkali metal phosphate) is used in the range of 2% to 100% mol/mol relative to the compound of formula (III). Klapars et al j.am.chem.soc.123The article 7727(2001) details a similar preparation.
Method E
By converting a compound of formula (IV), a compound of formula (I):
[ wherein FG is a functional group which can be converted to R via 1 or more synthetic steps7]. Interconversion of functional groups is standard for those skilled in the art. The literature describes many methods which can be used as such or modified depending on the functionalities present; table A provides references (some of which also cite other suitable references), particularly to FG and R7To prepare the compounds of formula (I). Those skilled in the art will appreciate that the literature examples provided in Table A are not necessarily limited to the specifically mentioned R7But can also be used analogously for the preparation of other structurally related Rs7。
TABLE A
Reference to the literature FG R
Synthesis 2001，2081Tetrahedron 58，1491(2002) CHO CH＝CBrCH＝CHBrC≡CBr
Russ.Chem.Bull.50(6)，1047(2001) CHO CH＝CCl
Tetrahedron 57，7519(2001) CHO CH＝CClCFCH＝CFCFCl
Bull.Chem.Soc.Jpn.73，1691(2000)Bull.Chem.Soc.Jpn.71，2903(1998-) CHO CF＝CBrF
J.Chem.Soc.Perkin 1 2002，883 COCH C(CH)＝CHBrC(CH)＝CCl
J.Fluorine Chem.1，381(1972)J.Fluorine Chem.23，339(1983) COCHCOCF C(CH)＝CBrC(CH)＝CFBrC(CH)＝CFClC(CF)＝CFBrC(CF)＝CFClC(CF)＝CF
Tetrahedron Letters 41，8045(2000)J.Org.Chem.62，9217(1997) Halogen element CF＝CHF
Tetrahedron Letters 37，8799(1996) Halogen element CH＝CF
JP 09278688J.Fluorine Chem.31，115(1986) Halogen element CF＝CF
Zh.Org.Khim.25，1451(1989) Halogen element CF＝CFCl
J.Org.Chem.53，2714(1988) Halogen element CF＝CFCF
J.Org.Chem.56，7336(1991)Tetrahedron Letters 42，4083(2001) Halogen element C(CF)＝CH
Ukr.Khim.Zh.32，996(1966) CHBrCHCF CH＝CHCF
Bull.Chem.Soc.Jap.62，1352 CH＝CClCFCH＝CFCFCl C≡CCFC≡CCFCl
J.Org.Chem.54，5856(1989)J.Am.Chem.Soc.109，2138(1987)Tetrahedron 45，6511(1989)J.Orgmet.Chem.549，127(1997)Tetrahedron 56，10075(2000)Tetrahedron Asymmetry 6，245(1995) Halogen or trifluoromethyl sulfonate C≡CHC≡CSiMeC≡CCHC≡CCMeC≡CCHOHC≡CCHMeOHC≡CCMeOHC≡CCHOC≡CC(O)Me
J.Org.Chem.32，1674(1967) C≡CCH CHC≡CH
Synth.Comm.1989，561 CHOCHCHO C≡CHCHC≡CH
WO 01 092563 CHO CH＝CH
J.Am.Chem.Soc.123，4155(2001)Org.Lett.2，3703(2000)J.Org.Chem.57，3558(1992) Halogen or trifluoromethyl sulfonate CH＝CH
Synthesis 2001，893
GB 2 183 639 C≡CH CH＝CH
Synthesis 1996，1494J.Org.Chem.49，294(1984) CHO C≡CClC≡CHC≡CBr
US 6 159956 CHBr CHCF＝CF
Liebigs Ann.Chem.1995，2027 CHBr CH＝C(CF)
J.Am.Chem.Soc.123，4155(2001) CHBr CHC≡CSiMe
Inorg.Chim.Acta 296，37(1999) Halogen element CHC≡CMe
J.Fluorine Chem.111，185(2001)J.Chem.Soc.Perkin I 1988，921 CH＝CHBrCH＝CFBrCH＝CBr CH＝CHCFCH＝CFCFCH＝C(CF)
DE 4417441US 3976691J.Org.Chem.64，7048(1999) C≡CCHOHC≡CCHMeOHC≡CCMeOHC≡CCHOC≡CC(O)Me C≡CCHFC≡CCHMeFC≡CCMeFC≡CCHFC≡CCFMe
J.Chem.Soc.Perkin I 1994，725 C≡CCHOH C≡CCHCF
Synthesis 1997，1489Angew.Chem.Int.Ed.39，2481(2000)J.Org.Chem.47，2255(1982)J.Fluorine.Chem.113，55(2002) C≡CH C≡CCFCFCH＝CHCFCF
J.Fluorine.Chem.64，61(1993)J.Am.Chem.Soc.109，3492(1987) C≡CH C≡CCHFClC≡CCFBr
J.Am.Chem.Soc.107，5186(1985) CH＝CHBr CH＝CHCFCF
There are many alternative methods of preparing compounds of formula (II), (III) or (IV).
Process F-preparation of Compounds of formula (II) or (III)
From compounds of formula (V) [ wherein FG is as defined above for compounds of formula (IV) and T is halogen, amino, NHR1Protected amino T' (e.g. carbamates, amides, cyclic imides, N-alkyl-, N-alkenyl-, N-benzyl-, N-diphenylmethyl-or N-trityl-derivatives, imine derivatives or N-silyl-or N-disilyl-derivatives) or groups T "(that is to say, can be converted into NH by using the synthetic methods described in the literature)2Or NHR1A group of (a); t' is preferably azido, nitro, halogen, triflate, CONH2COOH, COCl or NCO)]To prepare compounds of formula (II), (III) or (VI). Starting from the compound of formula (V), the functional group FG can be converted to R by using a method analogous to method E above7. This transformation directly yields the compound of formula (II) [ when T is NHR1Time of flight]A compound of formula (III) [ when T is halogen (preferably chlorine, bromine or iodine)]Or a compound of formula (VI) [ when T is T' or T]。
In the second step, T' is converted to NH by using the method [ that is, deprotecting or converting T ] as generally described above2]A compound of the formula (VI) or (II) [ when R ] may be used1When not H]Conversion to a compound of formula (II) [ wherein R1Is H]。
Examples of general values for T' and methods of deprotection are found in T.W.Green and P.Wuts, Protective Groups in Organic Synthesis, 3 rd edition (John Wiley & Sons 1999), Chapter 7.
Compilation of useful values for T 'and conversion of T' into NH2T' or NHR1See M.B. Smith, Complex of Organic Synthetic Methods, Vols.1-10, Chapter 7 (Wiley, Vol.10: 2002).
Method G
By a coupling reaction between a compound of formula (VII) and a compound of formula (VIII) [ wherein Ra and Ra' are each independently halogen (preferably Cl, Br or I), a triflate or a metal containing functional group containing, for example, B, Sn, Mg, Zn or Cu as the metal; examples are B (OH)2Esters of boric acid, preferably esters derived from 1, 2-or 1, 3-diols, trialkyltin, preferably Sn (CH)3)3Or Sn (nBu)3) Halogen salts of Mg, halogen salts of Zn or Cu. If Ra or Ra' is a metal-containing functional group, the other substituent must be halogen or triflate]Compounds of formula (II), (III) or (VI) can be prepared.
Such coupling reactions are widely known in the literature. Particularly suitable are Pd (0), Ni (0) or copper-catalyzed couplings, which are known to the person skilled in the art, for example Stille couplings, Suzuki couplings, Negishi couplings or Ullmann reactions. For a review of these Reactions, see Metal-catalyzed Cross-Coupling Reactions; diederich and p.stang (eds); Wiley-VCH; weinheim 1998.
In the second step, the NH is converted by the method described generally above [ that is, deprotection or T2Transformation of (2)]A compound of the formula (VI) or (II) [ when R ] may be used1When not H]Conversion to a compound of formula (II) [ wherein R1Is H]。
It has now surprisingly been found that, for practical purposes, the novel compounds of the formula (I) have a very advantageous activity spectrum in protecting plants against diseases caused by fungi, bacteria and viruses.
The compounds of formula (I) can be used as active ingredients for controlling plant pests in the agricultural sector and in the related fields of application. The novel compounds are characterized in that: excellent activity at lower application rates, plant tolerance, and environmental safety. They have very useful disease-, preventive and systemic properties and are used for the protection of a wide variety of cultivated plants. The compounds of the formula I can be used for inhibiting or destroying pests which occur on different kinds of useful plants or plant parts (fruits, flowers, leaves, stems, tubers, roots) while also protecting those parts of the plants which subsequently grow, for example against phytopathogenic microorganisms.
The compounds of the formula (I) can also be used as dressings for the treatment of plant propagation material, in particular of seeds (fruits, tubers, grains) and plant cuttings (e.g. rice), to avoid fungal infections and to combat phytopathogenic fungi which occur in the soil.
Furthermore, the compounds according to the invention can be used in the relevant field for controlling fungi, for example in the protection of technical materials, including wood and technical products related to wood, in food storage, in hygiene management, etc.
The compounds of formula (I) are effective against phytopathogenic fungi, such as the following species: fungi imperfecti (e.g. Botrytis cinerea, Magnaporthe grisea, Helminthosporium elongatum, Fusarium, Septoria nodorum, Cercospora arachidicola and Neurospora alternata) and Basidiomycetes (e.g. Rhizoctonia, Russia, Puccinia). In addition, they are also effective against ascomycetes (e.g., Venturia and Erysiphe, Podosphaera, Sclerotinia, Rhizoctonia) and oomycetes (e.g., Phytophthora, Pythium, Plasmopara). Significant activity was observed for powdery mildew (powdery mildew) and rust (puccinia). Furthermore, the novel compounds of the formula I are also effective against phytopathogenic bacteria and viruses, for example against Xanthomonas spp.
Within the scope of the present invention, the target crop to be protected typically comprises the following plant species: cereals (wheat, barley, rye, oats, rice, maize, sorghum and related species); sugar beet (sugar beet and fodder beet); pomes, stone fruits and soft fruits (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries); leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olive, sunflower, coconut, castor, cocoa beans, groundnut); cucurbits (pumpkin, cucumber, watermelon); fiber plants (cotton, flax, hemp, jute); citrus fruits (oranges, lemons, grapefruit, oranges); vegetables (spinach, lettuce, asparagus, cabbage, carrot, onion, tomato, potato, pepper); lauraceae (avocado, camphora, camphor) or other plants, such as tobacco, nuts, coffee, eggplant, sugar cane, tea, pepper, vines, hops, bananas and natural rubber trees, and ornamentals.
The compounds of formula (I) are used in unmodified form or, preferably, together with adjuvants conventionally employed in the art of formulation. For this purpose, they are conventionally prepared in a known manner as emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granules and encapsulants, for example in polymers. Depending on the type of composition, the application method is chosen, for example, to spray, atomize, scatter, coat or pour, depending on the intended purpose and the prevailing circumstances. The composition may also contain other adjuvants such as stabilizers, defoamers, viscosity modifiers, binders or adhesives, fertilizers, micronutrient donors or other agents for achieving a particular effect.
Suitable carriers and adjuvants can be solid or liquid and are the substances used in formulation technology, for example natural or regenerated mineral substances, solvents, dispersants, wetting agents, adhesives, thickeners, binders or fertilizers and the like. Such vectors are described, for example, in WO 97/33890.
The compounds of formula (I) are generally used in the form of compositions and may be applied to the crop area or plant to be treated simultaneously or sequentially with other compounds. These other compounds may be, for example, fertilizers or micronutrient donors or other preparations capable of affecting plant growth. They may also be selective herbicides and insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with other carriers, surfactants or application-promoting adjuvants customarily employed in the art of formulation.
The compounds of formula (I) may be mixed with other fungicides and in some cases give rise to unexpected synergistic activity. Particularly preferred mixed components are azoles, such as, for example, azaconazole, BAY14120, bitertanol, bromuconazole, cyproconazole, difenoconazole, diniconazole, epoxiconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, hexaconazole, imazalil, imibenconazole, ipconazole, metconazole, myclobutanil, pefurazoate, penconazole, pyriproxyfen, prochloraz, propiconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triflumizole, triticonazole; pyrimidinylmethanols, such as pyrimidinol, isocitritol, fluoropyrimidinol; 2-aminopyrimidines, such as sulfopyrimethanil, metrafidine, ethirimine; morpholines, such as dodemorph, fenpropidin, fenpropimorph, spiroxamine, tridemorph; anilinopyrimidines, for example cyprodinil, mepanipyrim, pyrimethanil; azoles, such as fenpiclonil, oxazalil; phenylamides, for example benalaxyl, furalaxyl, metalaxyl, R-metalaxyl, furoylamide, oxadixyl; benzimidazoles, such as benomyl, carbendazim, diethoxymetazoline, fuberidazole, thiabendazole; diamides, such as ethidium, sclerotium, iprodione, myclol, bacteriocide, dimeticone; amides, such as carboxin, furamectin, flutolanil, propoxymetrobin, oxycarboxin, fludioxonil; guanidines, such as biguanide salts, dodine, iminoctadine; strobilurines, for example azoxystrobin, kresoxim-methyl, tolanilide, SSF-129, trifloxystrobin, picoxystrobin, BAS 500F (recommended name pyraclosterobin), BAS 520; dithiocarbamic acids such as ferbam, mancozeb, maneb, metiram, propineb, thiram, zineb, ziram; n-halogen methylthiophthalimides, such as captafol, captan, dichlofluanid, flufenapyr, folpet, tolylfluanid; copper compounds, such as bordeaux mixture, copper hydroxide, copper oxychloride, copper sulfate, cuprous oxide, manganin mixture, oxine-copper; nitrophenol derivatives, such as dinocap, iprodione; organophosphorus derivatives such as blasticidin, iprobenfos, isoprothiolane, diflufenzophos, fenamiphos and tolclofos-methyl; other examples include acibenzolar-S-methyl, trichlorfon, benthizalilrb, blasticidin, chlorfenapyr, diclofen, chlorothalonil, cyflufenamid, cymoxanil, dichloronaphthoquinone, diclofen, niclosamide, diethofencarb, dimethomorph, SYP-L190 (suggested name flumorph), dithianon, ethaboxam, clomazole, oxazolone, fenamidone, fenoxanil, tritolyl, pyrimethanil, fluazinam, flusulfamide, fenhexamid, fosetyl, hymexazol, iprovalicarb, IKF-916(cyazofamid), kasugamycin, sulbencarb, metranone, nicoblifen, pencycuron, tetrachloraz, polyoxin, thiabendazole, bervazol, fluazinone, quinazinone, quindox, penoxsulam, chlorazol, thifluazin, thifluazinam, quincloxacarb, thifluazinam.
A preferred method of applying the compound of formula (I) or the agrochemical composition containing at least one of said compounds is foliar application. The application frequency and application rate depend on the risk of infestation by the respective pathogen. However, the compounds of formula I may also penetrate into the plant from the roots through the soil (systemic action) by soaking the plant locus with a liquid formulation, or by applying the compound in solid form to the soil, for example in particulate form (soil application). In rice crops, such granules may be applied to irrigated paddy fields. The compounds of the formula I can also be applied to seeds (coatings) by soaking the seeds or tubers in a liquid formulation of the fungicide or coating them with a solid formulation.
The formulations [ that is to say, the compositions containing the compounds of formula (I) ] and, if desired, solid or liquid adjuvants are prepared in a known manner, typically by homogeneously mixing and/or grinding the compounds together with extenders, for example, solvents, solid carriers and optionally surface-active compounds (surfactants).
Agrochemical formulations generally contain 0.1 to 99% by weight, preferably 0.1 to 95% by weight, of a compound of the formula I, 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid or liquid adjuvant and 0 to 25% by weight, preferably 0.1 to 25% by weight, of a surfactant.
Advantageous application rates are generally from 5g to 2kg of active ingredient (a.i.)/hectare (ha), preferably from 10g to 1kg a.i./ha, most preferably from 20g to 600g a.i./ha. When used as seed soaking agents, a convenient dosage is from 10mg to 1g of active per kg of seed.
While commercial products are preferably formulated as concentrates, end users typically use dilute formulations.
The following non-limiting examples illustrate the invention described above in more detail.
Example 1
This example illustrates the preparation of compound No. 1.01.
2-amino-4' -ethynyl-biphenyl (0.30g) and 1-methyl-3-trifluoromethyl-4-chlorocarbonyl-pyrazole (0.33g) were mixed in THF under ice-cooling, followed by addition of pyridine (0.12 ml). After warming to ambient temperature, the suspension was stirred for 3.5 hours, poured into water and extracted 2 times with ethyl acetate. The organic phase was separated, dried over sodium sulfate, the solvent evaporated and chromatographed on silica gel (solvent: hexane: ethyl acetate 2: 1) to give 0.4g (70.2%) of compound number 1.01.
Example 2
This example illustrates the preparation of compound No. 2.01.
To 1-methyl-3-trifluoromethyl-4-pyrrolecarboxylic acid (0.22g) dissolved in 10ml of dichloromethane were added triethylamine (0.32ml) and 2-amino-4' -trimethylsilylethynyl-biphenyl (0.3g), and finally, under ice-cooling, bis (2-oxo-3-oxazolidinyl) chlorophosphinic acid (0.29 g). After stirring for 18 hours, the solvent was removed under reduced pressure and the residue was treated with ethyl acetate. Washed with water and brine, dried over sodium sulfate and the solvent evaporated to give 0.45g of a yellow oil which is chromatographed on silica gel (eluent: hexane: ethyl acetate 2: 1) to give 0.13g (26%) of Compound No. 2.01.
Example 3
This example illustrates the preparation of compound No. 1.72.
To NaH (46mg) in 5ml of anhydrous THF was added 2-N-formylamino-4' - (propyn-1-yl) -biphenyl (0.3g) in 10ml of anhydrous THF at 0-5 ℃. After 1 hour at this temperature, 1-methyl-3-trifluoromethyl-4-chlorocarbonyl-pyrazole (0.372g) was added. The resulting suspension was stirred at room temperature overnight, poured into brine and extracted with ethyl acetate. The solvent was evaporated, the residue was taken up in methanol, and sodium methoxide (10mg) was added. After 30 minutes, the mixture was neutralized with dilute HCl, extracted with ethyl acetate, and washed to neutrality. Chromatography on silica gel (eluent: ethyl acetate: hexane 1: 2) and recrystallization from toluene: hexane (4: 1) gave 0.169g of compound No. 1.72.
Example 4
This example illustrates the preparation of 2-amino-4 '- (trimethylsilyl) ethynyl-biphenyl (compound No. 12.02) and 2-amino-4' -ethynyl-biphenyl (compound No. 12.01) using method F above.
To 2.5g of 2-amino-4' -bromo-biphenyl (WO0264562) in piperidine (25ml) was added CuI (0.1g), bis (triphenylphosphino) palladium dichloride (0.35g) and trimethylsilylacetylene (2.8ml) in that order under nitrogen. The mixture was stirred at room temperature for 22 hours and then at 60 ℃ for 26 hours. After cooling, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic phase is then washed with water and dried over sodium sulfate. After evaporation of the solvent in vacuo, the mixture was chromatographed on silica gel (hexane: ethyl acetate 9: 1) to give 2-amino-4' - (trimethylsilyl) ethynyl-biphenyl (2g) (compound No. 12.02).
1.4g of this compound was dissolved in methanol (40ml), and potassium carbonate (0.9g) was added under cooling. The resulting suspension was stirred for 2 hours, poured onto ice-water, and the formed precipitate was filtered off, washed thoroughly with water, and dried to give light brown crystals of 2-amino-4' -ethynyl-biphenyl (0.9g) (compound No. 12.01).
Example 5
This example illustrates the preparation of 2-N-formylamino-4' - (propyn-1-yl) -biphenyl (compound No. 12.16).
N-formylamino-4' -bromo-biphenyl (3.5g) (J.chem.Soc.1957, 4), tributyltin (propynyl-1) (5g) (available from Aldrich), tetrakis (triphenylphosphine) palladium (0.37g) were mixed in toluene (200ml) under nitrogen and heated at reflux for 16 h. The resulting black mixture was diluted with water and extracted with ethyl acetate. The organic phase is washed with water, dried over sodium sulfate and the solvent is evaporated under reduced pressure. The residue was taken up in acetonitrile and washed repeatedly with hexane. After removing acetonitrile under reduced pressure, the residue was chromatographed on silica gel (eluent: ethyl hexane acetate 2: 1) to give 2-N-formylamino-4' - (propyn-1-yl) -biphenyl (compound No. 12.16) (1.57g) as a pale yellow powder.
Example 6
This example illustrates the preparation of 2-amino-4 '(2, 2-dichloro) ethylene-biphenyl (compound No. 12.07) and 2-amino-4' (chloroethynyl) -biphenyl (compound No. 12.04).
a) Preparation of 2-nitro-4' (2, 2-dichloro) ethylene-biphenyl
To 2-nitro-4' formyl-biphenyl (2g) (WO 9503290) (prepared by Pd-catalyzed coupling of 2-bromonitrobenzene with 4-formyl-phenyl-boronic acid) in ethanol (70ml) was added hydrazine hydrate (95%) (1.32g) and the resulting mixture was refluxed for 5 hours. The solvent was evaporated to dryness under reduced pressure, the residue was suspended in DMSO (30ml), then ammonia (25%) (3ml) and freshly prepared CuCl (80mg) were added successively, and finally carbon tetrachloride (3.8g) was added dropwise under water cooling. The mixture was stirred at room temperature for 24 hours, the resulting green suspension was poured into water, extracted with dichloromethane, washed with water and dried over sodium sulfate. The solvent was evaporated and the residue was chromatographed on silica gel (eluent: hexane: ethyl acetate 4: 1) to give 2-nitro-4' (2, 2-dichloro) ethylene-biphenyl (0.8g), m.p.58-59 ℃.
b) Preparation of 2-amino-4' (2, 2-dichloro) ethylene-biphenyl
2-Nitro-4' (2, 2-dichloro) ethylene-biphenyl (0.76g) from step (a) was dissolved in 50% ethanol (30ml) and heated under reflux. 2N HCl (0.3ml) in 50% ethanol (10ml) was then added dropwise. The reaction mixture was refluxed for 4 hours, cooled to room temperature and filtered. The filtrate was neutralized with sodium bicarbonate, extracted 2 times with ethyl acetate and the organic phase was dried over sodium sulfate. The solvent was evaporated under reduced pressure to give 2-amino-4' (2, 2-dichloro) ethylene-biphenyl (0.62g) (compound No. 12.07).
c) 2-amino-4' (2, 2-dichloro) ethylene-biphenyl (3g) was dissolved in 150ml of dimethyl sulfoxide in which 0.9g of KOH (85%, powder) had been suspended. The mixture was stirred at room temperature overnight, diluted with excess water, extracted 2 times with ethyl acetate and the organic phase dried over sodium sulfate. The solvent was evaporated under reduced pressure and the residue was chromatographed on silica gel (eluent: hexane: ethyl acetate 4: 1) to give 2.5g of 2-amino-4' (2, 2-dichloro) ethylene-biphenyl as a brown solid.
Example 7
This example illustrates the preparation of compound No. 12.18.
Step A: 2-Nitro- (4' -trimethylsilyl) -biphenyl
2-bromo-nitrobenzene (0.86g), 4- (trimethylsilyl) phenylboronic acid (1g) and bis- (triphenylphosphine) -palladium dichloride (0.3g) were dissolved in dimethoxyethane (35ml), and then a solution of sodium bicarbonate (1.3g) dissolved in water (5ml) was added dropwise. The mixture was heated for 3 hours (80 ℃ bath temperature), cooled to room temperature, poured onto ethyl acetate/water 1: 1(300ml), and filtered with suction. The organic phase was separated, dried over sodium sulfate and the solvent was removed. The residue obtained (1.58g of black oil) is chromatographed on silica gel (eluent: hexane: ethyl acetate 4: 1) to yield a yellow oil (1.12 g). This compound was used in step B.
And B: 2-amino- (4' -trimethylsilyl) -biphenyl [ compound 12.18]
The compound (0.955g) obtained in the above step A and ammonium formate (1.86g) were dissolved in methanol (30ml), and purged with nitrogen. To this solution, Pd (100 mg; 10% on carbon) was added in 2 portions. After stirring at room temperature for 15 hours, the reaction mixture was filtered and the solvent was evaporated.
Formulation examples of Compounds of formula (I)
The procedure for preparing formulations of the compounds of the formula I, for example emulsifiable concentrates, solutions, granules, dusts and wettable powders, is described in WO 97/33890.
Biological examples: fungicidal action
Example B-1: action against Puccinia recondita (brown rust of wheat) on wheat
Wheat plants cv. arina of 1 week old were treated with formulated test compound (0.02% active ingredient) in a spray booth. After 1 day of application, the test plants were inoculated by spraying a spore suspension (1X 10)5Summer spores/ml) were used to inoculate wheat plants. After 2 days of incubation at 20 ℃ and 95% relative humidity, the plants were kept in a greenhouse at 20 ℃ and 60% relative humidity for 8 days. Disease incidence was assessed 10 days after inoculation.
Infection with each compound 1.01, 1.03, 1.08, 1.10, 1.12, 1.13, 1.15, 1.16, 1.18, 1.19, 1.22, 1.24, 1.33, 1.56, 1.57, 1.60, 1.66, 1.67, 1.69, 1.70, 1.77, 1.78, 1.81, 1.106, 1.107, 1.138, 1.139, 1.151, 1.152, 1.154, 1.155, 1.182, 1.185, 1.251, 1.252, 2.01, 2.08, 2.66, 3.01, 3.08, 3.12, 3.18, 3.32, 3.56, 3.66, 3.69, 3.250, 9.01, 9.06, 9.15, 9.21, 9.41, 9.50, 9.53, 9.59, 9.25, 15.59, 15.25, 28% was actually prevented (0% complete).
Example B-2: action against Podosphaera leucotricha on apples (apple powdery mildew)
5-week-old apple seedlings cv. mcintosh were treated with the formulated test compound (0.02% active ingredient) in a spray booth. After 1 day of application, apple plants were inoculated by shaking the apple powdery mildew infected plants over the test plants. After incubation at 22 ℃ and 60% relative humidity for 14/10 hours (light/dark) for 12 days, the incidence of disease was assessed.
Infection with each compound 1.01, 1.03, 1.08, 1.10, 1.12, 1.13, 1.15, 1.16, 1.18, 1.19, 1.24, 1.33, 1.35, 1.36, 1.56, 1.57, 1.66, 1.67, 1.70, 1.77, 1.78, 1.81, 1.106, 1.107, 1.139, 1.151, 1.152, 1.154, 1.155, 1.182, 1.185, 1.251, 1.252, 2.01, 2.08, 2.66, 3.01, 3.08, 3.12, 3.18, 3.32, 3.35, 3.56, 3.66, 3.69, 3.250, 9.01, 9.06, 9.15, 9.21, 9.41, 9.50, 9.53, 9.59, 9.25, 15.25, 15.26, 28.25, 28% was completely (at virtually 0%) prevented.
Example B-3: action against Venturia inaequalis on apples (apple scab)
4-week-old apple seedlings cv. mcintosh were treated with the formulated test compound (0.02% active ingredient) in a spray booth. After 1 day of application, the test plants were sprayed with a spore suspension (4X 10)5Conidia/ml) to inoculate apple plants. At 21 ℃ and 95After incubation for 4 days at% relative humidity, the plants were placed in a greenhouse at 21 ℃ and 60% relative humidity for 4 days. Disease incidence was assessed after incubation for an additional 4 days at 21 ℃ and 95% relative humidity.
With each compound 1.01, 1.03, 1.08, 1.10, 1.12, 1.13, 1.18, 1.19, 1.24, 1.33, 1.56, 1.57, 1.66, 1.67, 1.69, 1.70, 1.77, 1.78, 1.81, 1.106, 1.107, 1.138, 1.152, 1.154, 1.155, 1.251, 1.252, 2.01, 2.08, 2.66, 3.01, 3.08, 3.12, 3.18, 3.32, 3.56, 3.66, 3.69, 9.01, 9.06, 9.15, 9.21, 9.50 and 9.59, the infestation is virtually completely prevented (0-5%).
Example B-4: action against powdery mildew on barley
Barley plants cv. regina at 1 week age were treated with formulated test compound (0.02% active ingredient) in a spray booth. After 1 day of application, barley plants were inoculated by shaking the powdery mildew-infected plants above the test plants. Disease incidence was assessed after incubation for 6 days in a greenhouse at 20 ℃/18 ℃ (day/night) and 60% relative humidity.
With each compound 1.01, 1.03, 1.08, 1.10, 1.12, 1.13, 1.15, 1.16, 1.18, 1.19, 1.24, 1.33, 1.35, 1.36, 1.56, 1.57, 1.66, 1.67, 1.70, 1.77, 1.78, 1.106, 1.107, 1.152, 1.155, 1.251, 1.252, 2.01, 2.08, 2.66, 3.01, 3.08, 3.12, 3.18, 3.32, 3.35, 3.56, 3.66, 3.69, 3.250, 9.01, 9.06, 9.15, 9.21, 9.41, 9.50 and 9.59, the infestation was virtually completely prevented (0-5% infestation).
Example B-5: action on Botrytis cinerea (grape gray mold) on grapes
Grape seedlings cv. gutedel of 5 weeks of age were treated with formulated test compound (0.02% active ingredient) in a spray chamber. After 2 days of application, the test plants were sprayed with a spore suspension (1X 10)6Conidia/ml) were used to inoculate grape plants. At 21 ℃ and 95% relative humidityAfter incubation for 4 days in a greenhouse, the incidence of disease was assessed.
With each of compounds 1.01, 1.03, 1.08 and 1.10, infection was virtually completely prevented (0-5% infection).
Example B-6: action on Botrytis cinerea (tomato Botrytis cinerea) on tomato
4-week-old tomato plants cv. rot Gnom were treated with formulated test compound (0.02% active ingredient) in a spray chamber. After 2 days of application, the test plants were sprayed with a spore suspension (1X 10)5Conidia/ml) were used to inoculate tomato plants. After incubation for 4 days in a growth chamber at 20 ℃ and 95% relative humidity, the incidence of disease was assessed.
With each of compounds 1.01, 1.03, 1.08, 1.10, 1.12, 1.13, 1.15, 1.16, 1.18, 1.19, 1.24, 1.33, 1.36, 1.56, 1.57, 1.66, 1.67, 1.69, 1.70, 1.77, 1.78, 1.106, 1.107, 1.138, 1.139, 1.152, 1.155, 1.251, 1.252, 2.01, 2.66, 3.01, 3.08, 3.12, 3.66, 3.69, 3.250, 9.06, 9.15, 9.21, 9.41, 9.50 and 9.59, the infection was virtually completely prevented (0-5% infection).
Example B-7: for septoria nodorum (bacterial glume blight of wheat) on wheat Function of
Wheat plants cv. arina of 1 week old were treated with formulated test compound (0.02% active ingredient) in a spray booth. 1 day after application, the test plants were treated by spraying with a spore suspension (5X 10)5Conidia/ml) were used to inoculate wheat plants. After incubation at 20 ℃ and 95% relative humidity for 1 day, the plants were kept in a greenhouse at 20 ℃ and 60% relative humidity for 10 days. Disease incidence was assessed 11 days after inoculation.
With each of compounds 1.01, 1.03, 1.08 and 1.10, infection was virtually completely prevented (0-5% infection).
Example B-8: on barleyAction of Helminthosporium torvum (barley net blotch)
Barley plants cv. regina at 1 week age were treated with formulated test compound (0.02% active ingredient) in a spray booth. After 2 days of application, the test plants were sprayed with a spore suspension (3X 10)4Conidia/ml) were used to inoculate barley plants. After incubation for 4 days at 20 ℃ and 95% relative humidity in a greenhouse, the incidence of disease was assessed.
Infection with each compound 1.01, 1.03, 1.08, 1.10, 1.12, 1.13, 1.15, 1.16, 1.18, 1.19, 1.22, 1.24, 1.33, 1.36, 1.35, 1.56, 1.57, 1.60, 1.66, 1.67, 1.69, 1.70, 1.77, 1.78, 1.81, 1.106, 1.107, 1.138, 1.139, 1.151, 1.152, 1.154, 1.155, 1.182, 1.185, 1.251, 1.252, 2.01, 2.08, 2.66, 3.01, 3.08, 3.12, 3.18, 3.32, 3.35, 3.56, 3.66, 3.69, 9.01, 9.06, 9.15, 9.21, 9.41, 9.50, 9.53, 9.25, 25, 25.25, 28% was completely (actual and 0% complete (at infection).
Example B-9: against Alternaria solani (tomato early blight) on tomato Function of
4-week-old tomato plants cv. rote Gnom were treated with formulated test compound (0.02% active ingredient) in a spray chamber. After 2 days of application, the test plants were sprayed with a spore suspension (2X 10)5Conidia/ml) were used to inoculate tomato plants. After incubation for 3 days in a growth chamber at 20 ℃ and 95% relative humidity, the incidence of disease was assessed.
With each compound 1.01, 1.03, 1.08, 1.10, 1.13, 1.15, 1.16, 1.19, 1.22, 1.24, 1.33, 1.35, 1.36, 1.56, 1.57, 1.67, 1.69, 1.70, 1.77, 1.78, 1.81, 1.107, 1.151, 1.152, 1.154, 1.155, 1.182, 1.185, 1.251, 1.252, 2.01, 3.01, 3.08, 3.12, 3.32, 3.35, 3.56, 3.69, 9.01, 9.06, 9.15, 9.41, 9.50, 9.62 and 15.26, the infection was virtually completely prevented (0-5% infection).
Example B-10: for grape powdery mildew of leptospirillum (grape powdery mildew) on grapes Function of
Grape seedlings cv. gutedel of 5 weeks of age were treated with formulated test compound (0.02% active ingredient) in a spray chamber. After 1 day of application, the grape plants were inoculated by shaking the plants infected with grape powdery mildew above the test plants. Disease incidence was assessed after incubation for 7 days at 26 ℃ and 60% relative humidity, on a light regime of 14/10 hours (light/dark).
Infection was virtually completely prevented (0-5% infection) with each of compounds 1.01, 1.03, 1.08, 1.10, 1.12, 1.13, 1.18, 1.19, 1.24, 1.33, 1.56, 1.57, 1.60, 1.66, 1.67, 1.70, 1.77, 1.78, 1.81, 1.106, 1.107, 1.138, 1.139, 1.151, 1.152, 1.154, 1.155, 1.182, 1.185, 1.251, 1.252, 2.01, 2.08, 2.66, 3.01, 3.08, 3.12, 3.32, 3.56, 3.66, 3.69, 3.250, 9.01, 9.06, 9.15, 9.41, 9.50, 9.53 and 9.59.
Example B-11: action on wheat septoria tritici (wheat leaf blight)
Wheat plants cv. riband 2 weeks old were treated with formulated test compound (0.2% active ingredient) in a spray chamber. 1 day after application, the test plants were treated by spraying the spore suspension (10X 10)5Conidia/ml) were used to inoculate wheat plants. After 1 day of incubation at 23 ℃ and 95% relative humidity, the plants were kept in the greenhouse for 16 days at 23 ℃ and 60% relative humidity. Disease incidence was assessed 18 days after inoculation.
In this test, compounds 1.10, 1.03, 1.09, 1.70, 1.69, 3.01, 1.67, 1.66, 3.66, 9.59, 3.69, 1.33, 2.66, 9.06, 3.08, 1.77, 1.78, 1.56, 1.57, 1.138, 1.139, 1.12, 1.18, 1.106, 1.107, 9.53, 3.32, 1.151, 1.152, 1.252, 1.155, 9.41, 3.56, 1.13, 3.12, 9.21, 1.250, 1.19 and 3.18 all showed good activity (< 20% disease incidence).

Claims (11)

1. A compound of formula (I):
wherein Het is a pyrazole, pyrrole or thiazole ring, which ring is substituted by 1, 2 or 3RySubstituted by groups;
R1is hydrogen;
R2、R3and R4Each independently hydrogen, halogen, methylOr CF3；
R5Is hydrogen or fluorine;
each R6Independently halogen, methyl or CF3；
R7Is (Z)mC≡C(Y1)；
Each RyIndependently of one another, halogen, C1-3Alkyl radical, C1-3Haloalkyl, C1-3Alkoxy (C)1-3) Alkylene or cyano;
x is 0;
Y1is hydrogen; halogen; c1-6Alkyl optionally substituted with one or more substituents, each substituent independently selected from halogen, hydroxy, C1-4Alkoxy radical, C1-4Haloalkoxy, C1-4Alkylthio radical, C1-4Haloalkylthio, C1-4Alkylamino radical, di (C)1-4) Alkylamino radical, C1-4Alkoxycarbonyl and tris (C)1-4) An alkylsilyl group; c2-4Alkenyl, optionally substituted with one or more substituents, each substituent independently selected from halogen; c2-4Alkynyl optionally substituted with one or more substituents, each substituent independently selected from halogen; c3-7Cycloalkyl optionally substituted with one or more substituents each independently selected from halogen, C1-4Alkyl and C1-4A haloalkyl group; or three (C)1-4) An alkylsilyl group;
z is C1-4Alkylene optionally substituted with one or more substituents each independently selected from hydroxy, cyano, C1-4Alkoxy radical, C1-4Haloalkoxy, C1-4Alkylthio, COOH and COO-C1-4An alkyl group;
m is 0 or 1; and is
n is 0, 1 or 2.
2. A compound of formula (I) as claimed in claim 1, wherein m-0.
3. As claimed in claim 1 or 2A compound of formula (I) wherein R7At the 4' position.
4. A compound of formula (I) as claimed in claim 1 wherein R5Is hydrogen.
5. A compound of formula (I) as claimed in claim 4 wherein R2、R3And R4Is hydrogen.
6. A compound of formula (I) as claimed in claim 1, wherein n-0.
7. A compound of formula (I) as claimed in claim 1 wherein the compound is selected from 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid [4 '- (3, 3-dimethyl-but-1-ynyl) -diphenyl-2-yl ] -amide and 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (4' -prop-1-ynyl-diphenyl-2-yl) -amide.
8. A compound of formula (II):
wherein R is1、R2、R3、R4、R5、R6、R7And n is as defined in claim 1.
9. A compound of formula (III):
wherein R is2、R3、R4、R5、R6、R7And n is as defined in claim 1 and Hal is bromine, chlorine or iodine; with the following conditions: the compound isIs a compound of the following formula (IIIa):
wherein Hal is Cl; each R2、R3And R4Is hydrogen, R7is-C.ident.CH.
10. A composition for controlling microorganisms and for preventing attack and infestation of plants by microorganisms, wherein the active ingredient is a compound of formula (I) as claimed in claim 1 together with a suitable carrier.
11. A method of controlling or preventing infestation of cultivated plants by phytopathogenic microorganisms, which comprises applying a compound of formula (I) according to claim 1 to the plants, parts thereof or the locus thereof.
HK06108652.6A 2002-12-24 2003-12-15 Biphenyl derivatives and their use as fungicides HK1088316B (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GB0230155.4 2002-12-24
GBGB0230155.4A GB0230155D0 (en) 2002-12-24 2002-12-24 Chemical compounds
PCT/EP2003/014248 WO2004058723A1 (en) 2002-12-24 2003-12-15 Biphenyl derivatives and their use as fungicides

Publications (2)

Publication Number Publication Date
HK1088316A1 HK1088316A1 (en) 2006-11-03
HK1088316B true HK1088316B (en) 2009-07-24

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