# US 9,751,821 B1 · 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

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- Number: US 9,751,821 B1
- Document ID: US9751821B1
- Status: Granted
- Kind: B1
- Application number: 15/586,913
- Filed: 2017-05-04
- Published: 2017-08-17
- Granted: 2017-09-05
- Earliest claimed: 2007-06-27
- Assignees: Nissan Chemical Industries, Ltd.
- Applicants: Nissan Chemical Industries, Ltd.
- Inventors: Manabu Yaosaka; Tomohisa Utsunomiya; Yuji Moriyama; Tomohiro Matsumoto; Kazutaka Matoba
- Web page: https://patentgrep.com/patent/US9751821B1

## CPC

- C07C 45/72: by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
- C07C 45/66: by dehydration
- C07C 45/74: combined with dehydration
- C07C 49/83: polycyclic
- C07C 49/835: having unsaturation outside an aromatic ring
- C07C 51/353: by isomerisation; by change of size of the carbon skeleton
- C07C 51/367: by introduction of functional groups containing oxygen only in singly bound form
- C07C 51/377: by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups {(C07C51/36 - C07C51/373 take precedence)}
- C07C 65/40: containing singly bound oxygen-containing groups
- C07C 67/327: by elimination of functional groups containing oxygen only in singly bound form
- C07C 67/343: by increase in the number of carbon atoms
- C07C 67/347: by addition to unsaturated carbon-to-carbon bonds
- C07C 69/65: of unsaturated acids
- C07C 231/12: by reactions not involving the formation of carboxamide groups
- C07C 253/30: by reactions not involving the formation of cyano groups
- C07C 319/20: by reactions not involving the formation of sulfide groups
- C07D 213/04: having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D 213/30: Oxygen atoms
- C07D 213/50: Ketonic radicals
- C07D 213/61: Halogen atoms or nitro radicals
- C07D 233/14: Radicals substituted by oxygen atoms
- C07D 233/60: with hydrocarbon radicals, substituted by oxygen or sulfur atoms, attached to ring nitrogen atoms
- C07D 249/08: 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D 261/04: having one double bond between ring members or between a ring member and a non-ring member
- C07D 401/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 413/14: containing three or more hetero rings
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

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 C1-C6 alcohol and an aprotic polar solvent in the presence of a base and water.

## Claims

### Claim 1

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.

### Claim 2 (depends on 1)

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

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 1)

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.

### Claim 5 (depends on 1)

The method according to claim 1, wherein R2 represents a halogen atom, —C(O)OH, —C(O)OR3, —C(O)NH2, —C(O)N(R1b)R1a, or a substituent selected from D-21 and D-36.

### Claim 6 (depends on 5)

The method according to claim 5, wherein R1a represents a C1-C6 alkyl optionally substituted by R8—N(R11)R10, —C(O)OR9, —C(O)NH2, —C(O)NHR9, or —C(R7)═NOR6; and
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.

### Claim 7 (depends on 6)

The method according to claim 6, wherein R1a represents a C1-C6 alkyl optionally substituted by R8; and
R1b represents a hydrogen atom, C1-C6 alkyl, C1-C4 alkoxy (C1-C4) alkyl, cyano (C1-C6) alkyl, C3-C6 alkynyl.

### Claim 8 (depends on 7)

The method according to claim 7, wherein
R1b represents a hydrogen atom;
R3 represents a C1-C6 alkyl; and
when present, R8 represents D-42.

### Claim 9 (depends on 8)

The method according to claim 8, wherein Y represents a hydrogen atom, cyano, or C1-C4 alkyl, and each Y is optionally the same as or different from each other.

### Claim 10 (depends on 1)

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.

### Claim 11 (depends on 1)

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.