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

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

wherein R 1 represents a trifluoromethyl group;

each of A 1 , A 2 , A 3 and A 4 independently represents C—Y;

each of A 5 , A 6 and A 7 independently represents C—X;

X represents a hydrogen atom or a halogen atom, and each X is optionally the same as or different from each other;

R 2 represents a halogen atom, cyano, —C(O)OH, —C(O)OR 3 , —C(O)NH 2 , —C(O)N(R 1b )R 1a , or a substituent selected from D-21 to D-36;

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;

Y represents a hydrogen atom, cyano, or C 1 -C 4 alkyl, 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 C—Y 1 ;

Y 1 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;

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-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, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, 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-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, wherein two R 13 s optionally form oxo together when 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 , D-9 to D-11, D-18 to D-20, D-42 to D-47 or D-48;

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;

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 R 1 , X, A 5 , A 6 and A 7 represent the same meaning as described above, and a substituted acetophenone compound represented by Formula (5)

wherein R 2 , A 1 , A 2 , A 3 and A 4 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 C 1 -C 6 alcohol, an aprotic polar solvent, a surfactant, a water soluble organic solvent, and combinations thereof.

2. The method according to claim 1 , wherein the solvent is an organic solvent and the reaction is conducted in the absence of the additive.

3. The method according to claim 1 , wherein the solvent is water and the reaction is conducted in the presence of a water-soluble organic solvent as the additive.

4. The method according to claim 1 , wherein the solvent is water and the reaction is conducted in the presence of a surfactant as the additive.

5. The method according to claim 1 , wherein R 2 represents a halogen atom, —C(O)OH, —C(O)OR 3 , —C(O)NH 2 , —C(O)N(R 1b )R 1a , or a substituent selected from D-21 and D-36.

6. The method according to claim 5 , wherein 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 , or —C(R 7 )═NOR 6 ; and

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 .

7. The method according to claim 6 , wherein R 1a represents a C 1 -C 6 alkyl optionally substituted by R 8 ; and

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.

8. The method according to claim 7 , wherein

R 1b represents a hydrogen atom;

R 3 represents a C 1 -C 6 alkyl; and

when present, R 8 represents D-42.

9. The method according to claim 8 , wherein Y represents a hydrogen atom, cyano, or C 1 -C 4 alkyl, and each Y is optionally the same as or different from each other.

10. The method according to claim 1 , wherein the base is selected from the group consisting of diethylamine, di-i-propylamine, di-n-propylamine, di-n-butylamine, pyrrolidine, triethylamine, tri-n-butylamine, and combinations thereof.

11. The method according to claim 1 , wherein the base is selected from the group consisting of methylamine, ethylamine, n-propylamine, i-propylamine, n-butylamine, i-butylamine, t-butylamine, n-pentylamine, i-pentylamine, and combinations thereof.