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

A method for producing a 1,3-bis(substituted phenyl)-3-substituted-3-hydroxypropan-1-one compound represented by Formula (3):

• wherein R1 represents a trifluoromethyl group;
• each of A1, A2, A3 and A4 independently represents C—Y;
• A6 represents C—H
• each of A5 and A7 independently represents C—X;
• X represents a halogen atom or a C1-C6 haloalkyl, and each X is optionally the same as or different from each other;
• R2 represents a halogen atom, cyano, —C(O)OH, —C(O)OR3, —C(O)NH2, —C(O)N(R1b)R1a, or a substituent selected from D-21 to D-36;
• R3 represents a C1-C6 alkyl, C1-C4 alkoxy (C1-C4) alkyl, or C1-C6 haloalkyl;
• Y represents a hydrogen atom, cyano, or C1-C4 alkyl, and each Y is optionally the same as or different from each other;
• two adjacent Ys optionally form A8=A9−A10=A11 together;
• each of A8, A9, A10 and A11 independently represents C—Y1;
• Y1 represents a hydrogen atom;
• R1a represents a C1-C6 alkyl optionally substituted by R8, —N(R11)R10, —C(O)OR9, —C(O)NH2, —C(O)NHR9, —C(R7)═NOR6, 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;
• R1b represents a hydrogen atom, C1-C6 alkyl, C1-C4 alkoxy (C1-C4) alkyl, cyano (C1-C6) alkyl, C3-C6 alkynyl, —C(O)R9 or —C(O)OR9,
• or represents that R1b optionally forms a 3-7 membered ring with a nitrogen atom to be bonded, by forming a C2-C6 alkylene chain together with R1a, and this alkylene chain optionally contains one oxygen atom, sulfur atom or nitrogen atom in this case;
• R6 represents a C1-C6 alkyl;
• R7 represents a hydrogen atom or C1-C6 alkyl;
• R8 represents a halogen atom, cyano, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy —C(O)N(R15)R14, —C(R7)═NOR6, 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-3 to D-5, D-7, D-9 to D-15, D-18 to D-36, and D-42 to D-49 represent aromatic heterocyclic rings represented by the following structural formulae:
• Z represents a halogen atom, cyano, nitro, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 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-5, and E-7 represent saturated heterocycles represented by the following structural formulae:
• R9 represents a C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy (C1-C4) alkyl, C1-C6 alkylthio (C1-C4) alkyl, C3-C8 cycloalkyl, C3-C6 alkenyl or C3-C6 alkynyl;
• R10 represents a C1-C6 haloalkyl, —C(O)R14, —C(O)OR14, phenyl, phenyl substituted by (Z)p1, D-3, D-4, D-18, D-42, D-45, D-46, D-48 or D-49;
• R11 represents a hydrogen atom, C1-C6 alkyl or C3-C6 alkynyl;
• R12 represents a C1-C6 alkyl;
• R13 represents a C1-C4 alkyl, and each R13 is optionally the same as or different from each other when q2, q3 or q4 represents an integer of 2 or more, wherein two R13s optionally form oxo together when two R13s are bonded to the same carbon atom;
• R14 represents a C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl (C1-C4) alkyl, C3-C6 cycloalkyl, C3-C6 alkenyl or C3-C6 alkynyl;
• R15 represents a hydrogen atom or C1-C6 alkyl;
• R16 represents a —OH, C1-C4 alkoxy or C1-C4 alkylthio;
• R17 represents a hydrogen atom, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, —C(R5)═NOR19, —C(O)OR19, —C(O)NH2, —C(O)N(R5)R19, —C(O)NHC(O)R19, —C(O)N(R5)C(O)OR19, —N(R21)R20, phenyl substituted by (Z)p1, D-9 to D-11, D-18 to D-20, D-42 to D-47 or D-48;
• R18 represents a hydrogen atom, C1-C6 alkyl, C3-C6 alkynyl, —C(O)R19a, —C(O)OR19a or C1-C6 haloalkylthio;
• R19 represents a C1-C6 alkyl, C1-C6 haloalkyl or C2-C6 alkenyl;
• R19a represents a C1-C6 alkyl, C1-C6 haloalkyl, C1-C4 alkoxy (C1-C4) alkyl, C1-C4 alkylthio (C1-C4) alkyl, C1-C4 alkylsulfinyl (C1-C4) alkyl, C1-C4 alkylsulfonyl (C1-C4) alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C1-C6 alkoxycarbonyl, phenyl, phenyl substituted by (Z)p1, D42, D43 or D44;
• R20 represents a C1-C6 haloalkyl, C1-C6 alkoxycarbonyl, phenyl, phenyl substituted by (Z)p1, D42 to D46 or D47;
• R21 represents a hydrogen atom, C1-C6 alkyl, C3-C6 alkenyl or C3-C6 alkynyl;
• 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,
• the method consisting of
• reacting an aromatic ketone compound represented by Formula (4)
• wherein R1, A5, A6 and A7 represent the same meaning as described above,
• and a substituted acetophenone compound represented by Formula (5)
• wherein R2, A1, A2, A3 and A4 represent the same meaning as described above,
• in a suspended state in the presence or absence of an additive and in the presence of a base in a solvent, wherein
• the base is selected from the group consisting of sodium acetate, potassium acetate, methylamine, ethylamine, n-propylamine, i-propylamine, n-butylamine, i-butylamine, t-butylamine, n-pentylamine, i-pentylamine, benzylamine, aniline, dimethylamine, diethylamine, di-n-propylamine, di-i-propylamine, di-n-butylamine, di-i-butylamine, di-n-pentylamine, di-i-pentylamine, pyrrolidine, piperidine, piperazine, morpholine, dibenzylamine, trimethylamine, triethylamine, tri-n-propylamine, tri-n-butylamine, tripentylamine, tribenzylamine, diisopropylethylamine, N-methylmorpholine, and combinations thereof, and
• the additive is selected from the group consisting of a C1-C6 alcohol, an aprotic polar solvent, a surfactant, a water soluble organic solvent, and combinations thereof.