Method for production of 3-hydroxypropan-1-one compound, method for production of 2-propen-1-one compound and method for production of isoxazoline compound
There is provided a novel intermediate for producing pesticides. A method for producing the compound of Formula (3) comprises reacting an aromatic ketone compound of Formula (4) and a substituted acetophenone compound of Formula (5) as starting raw materials in an organic solvent or water in the presence or absence of an additive in the presence of a base in a suspended state. A method may comprise dehydrating the compound of Formula (3). A method for producing compound (2) in one step comprises reacting compound (4) and compound (5) to obtain compound (3). Further, a method for producing an isoxazoline compound of Formula (1) comprises reacting compound (2) and a hydroxylamine in an aliphatic or an aromatic hydrocarbon solvent which is optionally substituted by a halogen atom by adding an additive selected from a phase-transfer catalyst, a C 1 -C 6 alcohol and an aprotic polar solvent in the presence of a base and water.
1. A method for producing an isoxazoline compound represented by Formula (1):
wherein R 1 , R 2 , X, A 1 , A 2 , A 3 , A 4 , A 5 , A 6 and A 7 represent the same meaning as described below), the method comprising reacting a 1,3-bis(substituted phenyl)-3-substituted-2-propen-1-one compound represented by Formula (2):
wherein R 1 represents a C 1 -C 6 haloalkyl;
each of A 1 , A 2 , A 3 and A 4 independently represents N or C—Y;
each of A 5 , A 6 and A 7 independently represents N or C—X;
X represents a hydrogen atom, halogen atom, or C 1 -C 6 haloalkyl; and each X is optionally the same as or different from each other;
R 3 represents a C 1 -C 6 alkyl, C 1 -C 4 alkoxy (C 1 -C 4 ) alkyl, or C 1 -C 6 haloalkyl;
R 2 represents a C 1 -C 6 alkyl, halogen atom, cyano, nitro, —NH 2 , —N(R 5 )R 4 , —OH, —OR 3 , benzyloxy, —OSO 2 R 3 , phenylsulfonyloxy, phenylsulfonyloxy substituted by (Z) p1 , —C(O)OH, —C(O)OR 3 , —C(O)NH 2 , —C(O)N(R 1b ) R 1a , -L-Q, -L-N(R 1c )R 1d , —S(O) r -L 2 -Q 2 and substituent selected from D-1 to D-50;
Y represents a hydrogen atom, halogen atom nitro, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and each Y is optionally the same as or different from each other;
two adjacent Ys optionally form A 8 =A 9 -A 10 =A 11 together;
each of A 8 , A 9 , A l0 and A 11 independently represents N or C—Y 1 ;
Y 1 represents a hydrogen atom, halogen atom, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, —NH 2 , or —N(R 5 )R 4 , and each Y 1 is optionally the same as or different from each other;
R 4 represents a —CHO, C 1 -C 6 alkylcarbonyl, or C 1 -C 6 alkoxycarbonyl;
R 5 represents a hydrogen atom;
R 1a represents a C 1 -C 6 alkyl optionally substituted by R 8 , —N(R 11 )R 10 , —C(O)OR 9 , —C(O)NH 2 , —C(O)NHR 9 , —C(R 7 )═NOR 6 , phenyl, phenyl substituted by (Z) p1 , D-5, D-7, D-10, D-11, D-12, D-14, D-15, D-18, D-31, D-32, D-42, D-43, D-45, D-46, D-48, E-1 or E-7;
R 1b represents a hydrogen atom, C 1 -C 6 alkyl, C 1 -C 4 alkoxy (C 1 -C 4 ) alkyl, cyano (C 1 -C 6 ) alkyl, C 3 -C 6 alkynyl, —C(O)R 9 or —C(O)OR 9 ,
or represents that R 1b optionally forms a 3-7 membered ring with a nitrogen atom to be bonded, by forming a C 2 -C 6 alkylene chain together with R 1a , and this alkylene chain optionally contains one oxygen atom, sulfur atom or nitrogen atom in this case;
L represents —C(R 2a )(R 2b )—, —C(R 2a )(R 2b )CH 2 —, —CH 2 C(R 2a )(R 2b )— or —N(R 2c )—;
Q represents a hydrogen atom, halogen atom, cyano or nitro;
R 1c represents a hydrogen atom, —C(O)R 3a , —C(O)OR 3a , —C(O)SR 3a , —C(O)N(R 3b )R 3a , —C(S)N(R 3b )R 3a or —S(O) 2 R 3a ;
R 1d represents a hydrogen atom, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 4 alkoxy (C 1 -C 4 ) alkyl, C 1 -C 4 haloalkoxy (C 1 -C 4 ) alkyl, C 1 -C 4 alkylthio (C 1 -C 4 ) alkyl, C 1 -C 4 alkylsulfonyl (C 1 -C 4 ) alkyl, cyano (C 1 -C 6 ) alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl (C 1 -C 4 ) alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, —C(O)R 3c , —C(O)OR 3c , —C(O)SR 3c , C 1 -C 6 haloalkylthio or C 1 -C 6 alkylsulfonyl,
or represents that R 1c optionally forms a 5-7 membered ring with a nitrogen atom to be bonded, by forming a C 4 -C 6 alkylene chain together with R 1d , and this alkylene chain optionally contains one oxygen atom, sulfur atom or nitrogen atom in this case and is optionally substituted by a C 1 -C 6 alkyl group, —CHO group, C 1 -C 6 alkylcarbonyl group, C 1 -C 6 haloalkylcarbonyl group, C 1 -C 6 alkoxycarbonyl group, C 1 -C 6 haloalkoxycarbonyl group, C 1 -C 6 alkylaminocarbonyl group, C 1 -C 6 haloalkylaminocarbonyl group, oxo group or thioxo group;
R 2a represents a hydrogen atom, cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxycarbonyl, —C(O)NH 2 or —C(S)NH 2 ;
R 2b represents a hydrogen atom or C 1 -C 6 alkyl, or represents that R 2b optionally forms a 3-6 membered ring with a carbon atom to be bonded, by forming a C 2 -C 5 alkylene chain together with R 2a , and this alkylene chain optionally contains one to three oxygen atom(s), sulfur atom(s) or nitrogen atom(s) in this case;
R 2c represents a hydrogen atom, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl or C 1 -C 6 alkoxycarbonyl;
R 3a represents a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, (C 1 -C 4 ) alkyl optionally substituted by R 4a , C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, E-1, E-2, E-4, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, phenyl, phenyl substituted by (V) p1 , D-3, D-4, D-12 to D-14, D-42 or D-43;
R 3b represents a hydrogen atom or C 1 -C 6 alkyl;
R 3c represents a hydrogen atom, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 6 cycloalkyl (C 1 -C 4 ) alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 alkenyl or C 3 -C 6 alkynyl, or represents that R 3c optionally forms a 5-7 membered ring with a nitrogen atom, carbon atom, oxygen atom or sulfur atom to be bonded, by forming an ethylene chain or benzene ring bonded at an ortho-position together with R 3a ;
R 4a represents a halogen atom, cyano, nitro, C 3 -C 6 cycloalkyl, C 1 -C 4 alkoxy, C 1 -C 6 alkoxycarbonyl, S(O) r R 5a , D-42 or D-43;
R 5a represents a C 1 -C 4 alkyl;
V represents a halogen atom, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —OH, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylsulfonyloxy, C 1 -C 6 haloalkylsulfonyloxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, —NH 2 , C 1 -C 6 alkylamino, di(C 1 -C 6 alkyl) amino, C 1 -C 6 alkoxycarbonyl, —C(O)NH 2 , C 1 -C 6 alkylaminocarbonyl, C 1 -C 6 haloalkylaminocarbonyl, di(C 1 -C 6 alkyl) aminocarbonyl, —C(S)NH 2 , —S(O) 2 NH 2 , C 1 -C 6 alkylaminosulfonyl or di(C 1 -C 6 alkyl) aminosulfonyl, and each V is optionally the same as or different from each other when p1 represents an integer of 2 or more;
moreover, when two Vs are adjacent, the two adjacent Vs optionally form a 5-membered ring or a 6-membered ring with carbon atoms bonding to each of the two Vs by forming —OCH 2 O— or —OCH 2 CH 2 O—, and hydrogen atoms bonding to each carbon atom forming the ring are optionally substituted by halogen atoms in this case;
R 6 represents a C 1 -C 6 alkyl;
R 7 represents a hydrogen atom or C 1 -C 6 alkyl;
R 8 represents a halogen atom, cyano, C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, —C(O)N(R 15 )R 14 —C(R 7 )═NOR 6 , phenyl, phenyl substituted by (Z) p1 , D-11 to D-14, D-18, D-19, D-25, D-26, D-31, D-32, D-36, D-42, D-45, D48, D49, E-1, E-2, or E-5;
D-1 to D-50 represent aromatic heterocyclic rings represented by the following structural formulae:
Z represents a halogen atom, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 haloalkoxy, and each Z is optionally the same as or different from each other when p1, p2, p3 or p4 represents an integer of 2 or more;
E-1, E-2, E-4, E-5, and E-7 represent saturated heterocycles represented by the following structural formulae:
R 9 represents a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy (C 1 -C 4 ) alkyl, C 1 -C 6 alkylthio (C 1 -C 4 ) alkyl, C 3 -C 8 cycloalkyl, C 3 -C 6 alkenyl or C 3 -C 6 alkynyl;
R 10 represents a C 1 -C 6 haloalkyl, —C(O)R 14 , —C(O)OR 14 , phenyl, phenyl substituted by (Z) p1 , D-3, D-4, D-18, D-42, D-45, D-46, D-48 or D-49;
R 11 represents a hydrogen atom, C 1 -C 6 alkyl or C 3 -C 6 alkynyl;
R 12 represents a C 1 -C 6 alkyl;
R 13 represents a C 1 -C 4 alkyl, and each R 13 is optionally the same as or different from each other when q1, q2, q3 or q4 represents an integer of 2 or more, and moreover represents that two R 13 s optionally form oxo together when the two R 13 s are bonded to the same carbon atom;
R 14 represents a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl (C 1 -C 4 ) alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 alkenyl or C 3 -C 6 alkynyl;
R 15 represents a hydrogen atom or C 1 -C 6 alkyl;
R 16 represents a —OH, C 1 -C 4 alkoxy or C 1 -C 4 alkylthio;
R 17 represents a hydrogen atom, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 alkenyl, C 3 -C 6 haloalkenyl, C 3 -C 6 alkynyl, —C(R 5 )═NOR 19 , —C(O)OR 19 , —C(O)NH 2 , —C(O)N(R 5 )R 19 , —C(O)NHC(O)R 19 , —C(O)N(R 5 )C(O)OR 19 , —N(R 21 )R 20 , phenyl substituted by (Z) p1 , D9 to D11, D18 to D20, D42 to D47 or D48;
R 18 represents a hydrogen atom, C 1 -C 6 alkyl, C 3 -C 6 alkynyl, —C(O)R 19a , —C(O)OR 19a or C 1 -C 6 haloalkylthio;
R 19 represents a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or C 2 -C 6 alkenyl;
R 19a represents a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 4 alkoxy (C 1 -C 4 ) alkyl, C 1 -C 4 alkylthio (C 1 -C 4 ) alkyl, C 1 -C 4 alkylsulfinyl (C 1 -C 4 ) alkyl, C 1 -C 4 alkylsulfonyl (C 1 -C 4 ) alkyl, C 3 -C 6 cycloalkyl, C 2 -C 6 alkenyl, C 1 -C 6 alkoxycarbonyl, phenyl, phenyl substituted by (Z) p1 , D42, D43 or D44;
R 20 represents a C 1 -C 6 haloalkyl, C 1 -C 6 alkoxycarbonyl, phenyl, phenyl substituted by (Z) p1 , D42 to D46 or D47;
R 21 represents a hydrogen atom, C 1 -C 6 alkyl, C 3 -C 6 alkenyl or C 3 -C 6 alkynyl;
L 2 represents a single bond or C 1 -C 6 alkylene chain;
Q 2 represents a hydrogen atom, C 1 -C 6 haloalkyl, C 2 -C 6 alkynyl, —N(R 23 )R 22 , —C(O)N(R 23 )R 22 , phenyl, phenyl substituted by (Z) p1 , D18 to D20, D42 to D46 or D47;
R 22 represents a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, phenyl or phenyl substituted by (Z) p1 ;
R 23 represents a hydrogen atom or C 1 -C 6 alkyl;
p1 represents an integer of 1 to 2;
p2 represents an integer of 0 to 1;
p3 represents an integer of 0 to 1;
p4 represents an integer of 0 to 1;
p5 represents an integer of 0 or 1;
q2 represents an integer of 0 to 2;
q3 represents an integer of 0 to 2;
q4 represents an integer of 0 to 2;
r represents an integer of 0 to 2;
t represents an integer of 0 or 1,
and a hydroxylamine in a two-phase system comprising an aliphatic or an aromatic hydrocarbon solvent which is optionally substituted by a halogen atom, a base and water.
2. The method for producing an isoxazoline compound according to claim 1 , wherein the hydrocarbon solvent is selected from the group consisting of benzene, toluene, xylene, chlorobenzene, o-dichlorobenzene, mesitylene, n-pentane, n-hexane, n-heptane, n-octane, cyclopentane, cyclohexane, methylene chloride, 1,2-dichloroethane, methylcyclohexane, any of the foregoing substituted by a halogen atom, and mixtures thereof.
3. The method for producing an isoxazoline compound according to claim 1 , wherein the hydrocarbon solvent is toluene.
4. A method for producing an isoxazoline compound represented by Formula (1):
wherein R 1 , R 2 , X, A 1 , A 2 , A 3 , A 4 , A 5 , A 6 and A 7 represent the same meaning as described below), the method comprising reacting a 1,3-bis(substituted phenyl)-3-substituted-2-propen-1-one compound represented by Formula (2):
wherein R 1 represents a C 1 -C 6 haloalkyl;
each of A 1 , A 2 , A 3 and A 4 independently represents N or C—Y;
each of A 5 , A 6 and A 7 independently represents N or C—X;
X represents a hydrogen atom, halogen atom, or C 1 -C 6 haloalkyl; and each X is optionally the same as or different from each other;
R 3 represents a C 1 -C 6 alkyl, C 1 -C 4 alkoxy (C 1 -C 4 ) alkyl, or C 1 -C 6 haloalkyl;
R 2 represents a C 1 -C 6 alkyl, halogen atom, cyano, nitro, —NH 2 , —N(R 5 )R 4 , —OH, —OR 3 , benzyloxy, —OSO 2 R 3 , phenylsulfonyloxy, phenylsulfonyloxy substituted by (Z) p1 , —C(O)OH, —C(O)OR 3 , —C(O)NH 2 , —C(O)N(R 1b )R 1a , -L-Q, -L-N(R 1c )R 1d , —S(O) r -L 2 -Q 2 and substituent selected from D-1 to D-50;
Y represents a hydrogen atom, halogen atom, nitro, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, and each Y is optionally the same as or different from each other;
two adjacent Ys optionally form A 8 =A 9 -A 10 =A 11 together;
each of A 8 , A 9 A 10 and A 11 independently represents N or C—Y 1 ;
Y 1 represents a hydrogen atom, halogen atom, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy, C 1 -C 4 haloalkoxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, —NH 2 , or —N(R 5 )R 4 , and each Y 1 is optionally the same as or different from each other;
R 4 represents a —CHO, C 1 -C 6 alkylcarbonyl, or C 1 -C 6 alkoxycarbonyl;
R 5 represents a hydrogen atom;
R 1a represents a C 1 C 6 alkyl optionally substituted by R 8 , —N(R 11 )R 10 , —C(O)OR 9 , —C(O)NH 2 , —C(O)NHR 9 , —C(R 7 )═NOR 6 , phenyl, phenyl substituted by (Z) p1 , D-5, D-7, D-10, D-11, D-12, D-14, D-15, D-18, D-31, D-32, D-42, D-43, D-45, D-46, D-48, E-1 or E-7;
R 1b represents a hydrogen atom, C 1 -C 6 alkyl, C 1 -C 4 alkoxy (C 1 -C 4 ) alkyl, cyano (C 1 -C 6 ) alkyl, C 3 -C 6 alkynyl, —C(O)R 9 or —C(O)OR 9 ,
or represents that R 1b optionally forms a 3-7 membered ring with a nitrogen atom to be bonded, by forming a C 2 -C 6 alkylene chain together with R 1a , and this alkylene chain optionally contains one oxygen atom, sulfur atom or nitrogen atom in this case;
L represents —C(R 2a )(R 2b )—, —C(R 2a )(R 2b )CH 2 —, —CH 2 C(R 2a )(R 2b )— or —N(R 2c )—;
Q represents a hydrogen atom, halogen atom, cyano or nitro;
R 1c represents a hydrogen atom, —C(O)R 3a , —C(O)OR 3a , —C(O)SR 3a , —C(O)N(R 3b )R 3a , —C(S)N(R 3b )R 3a or —S(O) 2 R 3a ;
R 1d represents a hydrogen atom, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 4 alkoxy (C 1 -C 4 ) alkyl, C 1 -C 4 haloalkoxy (C 1 -C 4 ) alkyl, C 1 -C 4 alkylthio (C 1 -C 4 ) alkyl, C 1 -C 4 alkylsulfonyl (C 1 -C 4 ) alkyl, cyano (C 1 -C 6 ) alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 cycloalkyl (C 1 -C 4 ) alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, —C(O)R 3c , —C(O)OR 3c , —C(O)SR 3c , C 1 -C 6 haloalkylthio or C 1 -C 6 alkylsulfonyl,
or represents that R 1c optionally forms a 5-7 membered ring with a nitrogen atom to be bonded, by forming a C 4 -C 6 alkylene chain together with R 1d , and this alkylene chain optionally contains one oxygen atom, sulfur atom or nitrogen atom in this case and is optionally substituted by a C 1 -C 6 alkyl group, —CHO group, C 1 -C 6 alkylcarbonyl group, C 1 -C 6 haloalkylcarbonyl group, C 1 -C 6 alkoxycarbonyl group, C 1 -C 6 haloalkoxycarbonyl group, C 1 -C 6 alkylaminocarbonyl group, C 1 -C 6 haloalkylaminocarbonyl group, oxo group or thioxo group;
R 2a represents a hydrogen atom, cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxycarbonyl, —C(O)NH 2 or —C(S)NH 2 ;
R 2b represents a hydrogen atom or C 1 -C 6 alkyl, or represents that R 2b optionally forms a 3-6 membered ring with a carbon atom to be bonded, by forming a C 2 -C 5 alkylene chain together with R 2a , and this alkylene chain optionally contains one to three oxygen atom(s), sulfur atom(s) or nitrogen atom(s) in this case;
R 2c represents a hydrogen atom, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl or C 1 -C 6 alkoxycarbonyl;
R 3a represents a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, (C 1 -C 4 ) alkyl optionally substituted by R 4a , C 3 -C 6 cycloalkyl, C 3 -C 6 halocycloalkyl, E-1, E-2, E-4, C 2 -C 6 alkenyl, C 2 -C 6 haloalkenyl, C 2 -C 6 alkynyl, phenyl, phenyl substituted by (V) p1 , D-3, D-4, D-12 to D-14, D-42 or D-43;
R 3b represents a hydrogen atom or C 1 -C 6 alkyl;
R 3c represents a hydrogen atom, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 6 cycloalkyl (C 1 -C 4 ) alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 alkenyl or C 3 -C 6 alkynyl, or represents that R 3 optionally forms a 5-7 membered ring with a nitrogen atom, carbon atom, oxygen atom or sulfur atom to be bonded, by forming an ethylene chain or benzene ring bonded at an ortho-position together with R 3a ;
R a represents a halogen atom, cyano, nitro, C 3 -C 6 cycloalkyl, C 1 -C 4 alkoxy, C 1 -C 6 alkoxycarbonyl, S(O),R 5 a , D-42 or D-43;
R 5a represents a C 1 -C 4 alkyl;
V represents a halogen atom, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, —OH, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 6 alkylsulfonyloxy, C 1 -C 6 haloalkylsulfonyloxy, C 1 -C 6 alkylthio, C 1 -C 6 haloalkylthio, C 1 -C 6 alkylsulfinyl, C 1 -C 6 haloalkylsulfinyl, C 1 -C 6 alkylsulfonyl, C 1 -C 6 haloalkylsulfonyl, —NH 2 , C 1 -C 6 alkylamino, di(C 1 -C 6 alkyl) amino, C 1 -C 6 alkoxycarbonyl, —C(O)NH 2 , C 1 -C 6 alkylaminocarbonyl, C 1 -C 6 haloalkylaminocarbonyl, di(C 1 -C 6 alkyl) aminocarbonyl, —C(S)NH 2 , —S(O) 2 NH 2 , C 1 -C 6 alkylaminosulfonyl or di(C 1 -C 6 alkyl) aminosulfonyl, and each V is optionally the same as or different from each other when p1 represents an integer of 2 or more;
moreover, when two Vs are adjacent, the two adjacent Vs optionally form a 5-membered ring or a 6-membered ring with carbon atoms bonding to each of the two Vs by forming —OCH 2 O— or —OCH 2 CH 2 O—, and hydrogen atoms bonding to each carbon atom forming the ring are optionally substituted by halogen atoms in this case;
R 6 represents a C 1 -C 6 alkyl;
R 7 represents a hydrogen atom or C 1 -C 6 alkyl;
R 8 represents a halogen atom, cyano C 3 -C 6 cycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, —C(O)N(R 15 )R 14 , —C(R 7 )═NOR 6 , phenyl, phenyl substituted by (Z) p1 , D-11 to D-14, D-18, D-19, D-25, D-26, D-31, D-32, D-36, D-42, D-45, D-48, D-49, E-1, E-2, or E 5;
D-1 to D-50 represent aromatic heterocyclic rings represented by the following structural formulae:
Z represents a halogen atom, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 haloalkoxy, and each Z is optionally the same as or different from each other when p1, p2, p3 or p4 represents an integer of 2 or more;
E-1, E-2, E-4, E-5, and E-7 represent saturated heterocycles represented by the following structural formulae:
R 9 represents a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy (C 1 -C 4 ) alkyl, C 1 -C 6 alkylthio (C 1 -C 4 ) alkyl, C 3 -C 8 cycloalkyl, C 3 -C 6 alkenyl or C 3 -C 6 alkynyl;
R 10 represents a C 1 -C 6 haloalkyl, —C(O)R 14 , —C(O)OR 14 , phenyl, phenyl substituted by (Z) p1 , D-3, D-4, D-18, D-42, D-45, D-46, D-48 or D-49;
R 11 represents a hydrogen atom, C 1 -C 6 alkyl or C 3 -C 6 alkynyl;
R 12 represents a C 1 -C 6 alkyl;
R 13 represents a C 1 -C 4 alkyl, and each R 13 is optionally the same as or different from each other when q1, q2, q3 or q4 represents an integer of 2 or more, and moreover represents that two R 13 s optionally form oxo together when the two R 13 s are bonded to the same carbon atom;
R 14 represents a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl (C 1 -C 4 ) alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 alkenyl or C 3 -C 6 alkynyl;
R 15 represents a hydrogen atom or C 1 -C 6 alkyl;
R 16 represents a —OH, C 1 -C 4 alkoxy or C 1 -C 4 alkylthio;
R 17 represents a hydrogen atom, C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 alkenyl, C 3 -C 6 haloalkenyl, C 3 -C 6 alkynyl, —C(R 5 )═NOR 19 , —C(O)OR 19 , —C(O)NH 2 , —C(O)N(R 5 )R 19 , —C(O)NHC(O)R 19 , —C(O)N(R 5 )C(O)OR 19 , —N(R 21 )R 20 , phenyl substituted by (Z) p1 , D9 to D11, D18 to D20, D42 to D47 or D48;
R 18 represents a hydrogen atom, C 1 -C 6 alkyl, C 3 -C 6 alkynyl, —C(O)R 19a , —C(O)OR 19a or C 1 -C 6 haloalkylthio;
R 19 represents a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl or C 2 -C 6 alkenyl;
R 19a represents a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 4 alkoxy ( C1-C4 ) alkyl, C 1 -C 4 alkylthio (C 1 -C 4 ) alkyl, C 1 -C 4 alkylsulfinyl (C 1 -C 4 ) alkyl, C 1 -C 4 alkylsulfonyl (C 1 -C 4 ) alkyl, C 3 -C 6 cycloalkyl, C 2 -C 6 alkenyl, C 1 -C 6 alkoxycarbonyl, phenyl, phenyl substituted by (Z) p1 , D42, D43 or D44;
R 20 represents a C 1 -C 6 haloalkyl, C 1 -C 6 alkoxycarbonyl, phenyl, phenyl substituted by (Z) p1 , D42 to D46 or D47;
R 21 represents a hydrogen atom, C 1 -C 6 alkyl, C 3 -C 6 alkenyl or C 3 -C 6 alkynyl;
L 2 represents a single bond or C 1 -C 6 alkylene chain;
Q 2 represents a hydrogen atom, C 1 -C 6 haloalkyl, C 2 -C 6 alkynyl, —N(R 23 )R 22 , —C(O)N(R 23 )R 22 , phenyl, phenyl substituted by (Z) p1 , D18 to D20, D42 to D46 or D47;
R 22 represents a C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 cycloalkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, phenyl or phenyl substituted by (Z) p1 ;
R 23 represents a hydrogen atom or C 1 -C 6 alkyl;
p1 represents an integer of 1 to 2;
p2 represents an integer of 0 to 1;
p3 represents an integer of 0 to 1;
p4 represents an integer of 0 to 1;
p5 represents an integer of 0 or 1;
q2 represents an integer of 0 to 2;
q3 represents an integer of 0 to 2;
q4 represents an integer of 0 to 2;
r represents an integer of 0 to 2;
t represents an integer of 0 or 1
and a hydroxylamine in a two-phase system comprising an aliphatic or an aromatic hydrocarbon solvent, wherein the hydrocarbon solvent is selected from the group consisting of benzene, toluene, xylene, chlorobenzene, o-dichlorobenzene, mesitylene, n-pentane, n-hexane, n-heptane, n-octane, cyclopentane, cyclohexane, methylene chloride, 1,2-dichloroethane, methylcyclohexane, any of the foregoing substituted by a halogen atom and mixtures thereof, a base and water.
5. The method for producing an isoxazoline compound according to claim 1 ,
wherein the aliphatic or the aromatic hydrocarbon solvent is optionally substituted by a halogen atom by adding an additive selected from a phase-transfer catalyst, a C 1 -C 6 alcohol and an aprotic polar solvent, a base and water.
6. The method for producing an isoxazoline compound according to claim 5 , wherein the additive is a phase-transfer catalyst.
7. The method for producing an isoxazoline compound according to claim 5 , wherein the additive is a C 1 -C 6 alcohol.
8. The method for producing an isoxazoline compound according to claim 5 , wherein the additive is an aprotic polar solvent.
9. The method for producing an isoxazoline compound according to claim 5 , wherein the 1,3-bis(substituted phenyl)-3-substituted-2-propen-1-one compound represented by Formula (2) is produced by reacting, in the presence of a dehydration agent and a base, 1,3-bis(substituted phenyl)-3-substituted-3-hydroxypropan-1-one compound represented by Formula (3):
wherein R 1 , R 2 , X, A 1 , A 2 , A 3 , A 4 , A 5 , A 6 and A 7 represent the same meaning as described above.