Process for producing 6-aryloxyquinoline derivative and intermediate therefor
View Patent ↗Disclosed is a process for producing 6-aryloxyquinoline derivatives useful as insecticides or fungicides for agricultural and horticultural use. The process comprises a cyclization reaction step of reacting an anthranilic acid derivative represented by general formula (1) with a kenone in the presence of an acid to obtain a quinolone derivative and a condensation reaction step of reacting the quinolone derivative with a halogen compound or an acid anhydride to obtain a quinoline derivative.
1. A process for producing a quinoline derivative, the process comprising:
(i) a cyclization reaction step (C) of reacting an anthranilic acid derivative represented by general formula (1):
wherein
R 1 , R 2 , and R 3 each independently represent a hydrogen atom, a halogen atom, C 1-4 alkyl optionally substituted by a halogen atom(s), or C 1-4 alkoxy optionally substituted by a halogen atom(s), provided that R 1 , R 2 , and R 3 do not simultaneously represent a hydrogen atom,
R 4 represents a hydrogen atom or a protecting group of carboxylic acid, and
R 5 , R 6 , R 7 , R 8 , and R 9 each independently represent a hydrogen atom, a halogen atom, C 1-8 alkyl optionally substituted by a halogen atom(s), C 1-8 alkoxy optionally substituted by a halogen atom(s), C 1-8 alkylthio optionally substituted by a halogen atom(s), C 2-4 alkenyloxy optionally substituted by a halogen atom(s), C 2-4 alkenylthio optionally substituted by a halogen atom(s), or C 2-4 alkynyloxy optionally substituted by a halogen atom(s),
or any two adjacent substituents of R 5 , R 6 , R 7 , R 8 , and R 9 together represent —O—(CH 2 ) n —O— wherein n is 1 or 2, optionally substituted by one or more halogen atoms,
with a ketone represented by general formula (2):
wherein R 10 and R 11 each independently represent a hydrogen atom or C 1-4 alkyl optionally substituted by a halogen atom(s),
or R 10 and R 11 together represent —(CH 2 ) m — wherein m is 3 or 4, provided that R 10 and R 11 do not simultaneously represent a hydrogen atom,
in the presence of an acid to obtain a quinolone derivative of general formula (3):
wherein R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined above; and
(ii) a condensation reaction step (D) of reacting the quinolone derivative of general formula (3) with a halogen compound represented by general formula (4):
wherein R 12 represents C 1-8 alkyl optionally substituted by a halogen atom(s), C 3-6 cyclic alkyl optionally substituted by a halogen atom(s), C 2-4 alkenyl optionally substituted by a halogen atom(s), OR 13 wherein R 13 represents C 1-8 alkyl optionally substituted by a halogen atom(s); C 3-6 cyclic alkyl optionally substituted by a halogen atom(s); or C 2-4 alkenyl optionally substituted by a halogen atom(s), or SR 14 wherein R 14 represents C 1-8 alkyl optionally substituted by a halogen atom(s); C 3-6 cyclic alkyl optionally substituted by a halogen atom(s); or C 2-4 alkenyl optionally substituted by a halogen atom(s), and
Y represents any one of fluorine, chlorine, bromine, and iodine,
or an acid anhydride represented by general formula (5):
wherein R 12 is as defined above,
to obtain a quinoline derivative represented by general formula (6):
wherein R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 are as defined above.
2. The process according to claim 1 , wherein R 4 represents a hydrogen atom, C 1-8 alkyl optionally substituted by a halogen atom(s) or optionally substituted by C 1-4 alkoxy optionally substituted by a halogen atom(s), C 3-8 cyclic alkyl optionally substituted by a halogen atom(s), C 1-4 alkoxymethyl, benzoylmethyl optionally substituted by a halogen atom(s), or C 7-14 aralkyl optionally substituted by a halogen atom(s), C 1-4 alkyl, or C 1-4 alkoxy.
3. The process according to claim 1 , wherein R 1 , R 2 , and R 3 each independently represent a hydrogen atom, a chlorine atom, a bromine atom, a fluorine atom, methyl, ethyl, methoxy, ethoxy, or trifluoromethyl, provided that R 1 , R 2 , and R 3 do not simultaneously represent a hydrogen atom; R 4 represents C 1-8 alkyl optionally substituted by a halogen atom(s) or optionally substituted by C 1-4 alkoxy optionally substituted by a halogen atom(s), C 3-8 cyclic alkyl optionally substituted by a halogen atom(s), or C 7-14 aralkyl optionally substituted by a halogen atom(s), C 1-4 alkyl, or C 1-4 alkoxy; R 5 , R 6 , R 7 , R 8 , and R 9 each independently represent a hydrogen atom, a chlorine atom, a bromine atom, a fluorine atom, methyl, ethyl, methoxy, ethoxy, trifluoromethyl, pentafluoroethyl, trifluoromethoxy, or 1,1,2,2-tetrafluoroethoxy, or R 6 and R 7 together represent —OCF 2 CF 2 O—; R 10 and R 11 each independently represent a hydrogen atom or C 1-4 alkyl optionally substituted by a halogen atom(s), provided that R 10 and R 11 do not simultaneously represent a hydrogen atom; and R 12 represents C 1-4 alkyl optionally substituted by a halogen atom(s) or OR 13 wherein R 13 represents C 1-4 alkyl optionally substituted by a halogen atom(s).
4. The process according to claim 1 , wherein any one of R 1 , R 2 , and R 3 represents methyl, ethyl, or trifluoromethyl with the other two representing a hydrogen atom, R 4 represents C 1-4 alkyl optionally substituted by a halogen atom(s), any one of R 5 , R 6 , R 7 , R 8 , and R 9 represents methoxy, ethoxy, trifluoromethoxy, or 1,1,2,2-tetrafluoroethoxy with the other four representing a hydrogen atom, R 10 and R 11 each independently represent C 1-4 alkyl optionally substituted by a halogen atom(s), and R 12 represents OR 13 wherein R 13 represents C 1-4 alkyl.
5. The process according to claim 1 , wherein R 10 represents —CH 2 —R 15 , R 11 represents R 15 , and R 15 represents C 1-3 alkyl.
6. The process according to claim 1 , wherein the acid used in the cyclization reaction step (C) is an organic sulfonic acid or Lewis acid.
7. The process according to claim 6 , wherein the organic sulfonic acid is benzenesulfonic acid or p-toluenesulfonic acid.
8. The process according to claim 6 , wherein the Lewis acid is zinc chloride, iron chloride, titanium chloride, or aluminum chloride.
9. An anthranilic acid derivative represented by general formula (1a):
wherein
any one of R 1a , R 2a , and R 3a represents C 1-4 alkyl optionally substituted by a halogen atom(s) with the other two representing a hydrogen atom,
R 4a represents C 1-4 alkyl optionally substituted by a halogen atom(s), and
any one of R 5a , R 6a , R 7a , R 8a , and R 9a represents C 1-8 alkoxy optionally substituted by a halogen atom(s) with the other four representing a hydrogen atom.
10. A process for producing an anthranilic acid derivative, the process comprising:
(i) an etherification step (A) of reacting a nitrobenzoic acid derivative represented by general formula (7):
wherein
R 1 , R 2 , and R 3 each independently represent a hydrogen atom, a halogen atom, C 1-4 alkyl optionally substituted by a halogen atom(s), or C 1-4 alkoxy optionally substituted by a halogen atom(s), provided that R 1 , R 2 , and R 3 do not simultaneously represent a hydrogen atom,
R 4 represents a hydrogen atom or a protecting group of carboxylic acid, and
X represents any one of fluorine, chlorine, bromine, and iodine,
with a phenol derivative represented by general formula (8):
wherein
R 5 , R 6 , R 7 , R 8 , and R 9 each independently represent a hydrogen atom, a halogen atom, C 1-8 alkyl optionally substituted by a halogen atom(s), C 1-8 alkoxy optionally substituted by a halogen atom(s), C 1-8 alkylthio optionally substituted by a halogen atom(s), C 2-4 alkenyloxy optionally substituted by a halogen atom(s), C 2-4 alkenylthio optionally substituted by a halogen atom(s), or C 2-4 alkynyloxy optionally substituted by a halogen atom(s),
or any two adjacent substituents of R 5 , R 6 , R 7 , R 8 , and R 9 together represent —O—(CH 2 ) n —O—, wherein n is 1 or 2, optionally substituted by one or more halogen atoms,
in the presence or absence of a base to obtain an ether derivative represented by general formula (9):
wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are as defined above; and
(ii) a reduction step (B) of reducing the ether derivative of general formula (9) to obtain an anthranilic acid derivative represented by general formula (1):
wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are as defined above.
11. The process according to claim 10 , wherein R 4 represents a hydrogen atom, C 1-8 alkyl optionally substituted by a halogen atom(s) or optionally substituted by C 1-4 alkoxy optionally substituted by a halogen atom(s), C 3-8 cyclic alkyl optionally substituted by a halogen atom(s), C 1-4 alkoxymethyl, benzoylmethyl optionally substituted by a halogen atom(s), or C 7-14 aralkyl optionally substituted by a halogen atom(s), C 1-4 alkyl, or C 1-4 alkoxy.
12. The process according to claim 10 , wherein R 1 , R 2 , and R 3 each independently represent a hydrogen atom, a chlorine atom, a bromine atom, a fluorine atom, methyl, ethyl, methoxy, ethoxy, or trifluoromethyl, provided that R 1 , R 2 , and R 3 do not simultaneously represent a hydrogen atom; R 4 represents C 1-8 alkyl optionally substituted by a halogen atom(s) or optionally substituted by C 1-4 alkoxy optionally substituted by a halogen atom(s), C 3-8 cyclic alkyl optionally substituted by a halogen atom(s), or C 7-14 aralkyl optionally substituted by a halogen atom(s), C 1-4 alkyl, or C 1-4 alkoxy; and R 5 , R 6 , R 7 , R 8 , and R 9 each independently represent a hydrogen atom, a chlorine atom, a bromine atom, a fluorine atom, methyl, ethyl, methoxy, ethoxy, trifluoromethyl, pentafluoroethyl, trifluoromethoxy, or 1,1,2,2-tetrafluoroethoxy, or R 6 and R 7 together represent —OCF 2 CF 2 O—.
13. The process according to claim 10 , wherein any one of R 1 , R 2 , and R 3 represents methyl, ethyl, or trifluoromethyl with the other two representing a hydrogen atom, R 4 represents C 1-4 alkyl optionally substituted by a halogen atom(s), and any one of R 5 , R 6 , R 7 , R 8 , and R 9 represents methoxy, ethoxy, trifluoromethoxy, or 1,1,2,2-tetrafluoroethoxy with the other four representing a hydrogen atom.
14. The process according to claim 10 , wherein the reduction in the reduction step (B) is carried out by either hydrogenation in the presence of palladium, or using iron powder.
15. A process for producing a quinoline derivative, the process comprising:
(i) an etherification step (A) of reacting a nitrobenzoic acid derivative represented by general formula (7):
wherein
R 1 , R 2 , and R 3 each independently represent a hydrogen atom, a halogen atom, C 1-4 alkyl optionally substituted by a halogen atom(s), or C 1-4 alkoxy optionally substituted by a halogen atom(s), provided that R 1 , R 2 , and R 3 do not simultaneously represent a hydrogen atom,
R 4 represents a hydrogen atom or a protecting group of carboxylic acid, and
X represents any one of fluorine, chlorine, bromine, and iodine,
with a phenol derivative represented by general formula (8):
wherein
R 5 , R 6 , R 7 , R 8 , and R 9 each independently represent a hydrogen atom, a halogen atom, C 1-8 alkyl optionally substituted by a halogen atom(s), C 1-8 alkoxy optionally substituted by a halogen atom(s), C 1-8 alkylthio optionally substituted by a halogen atom(s), C 2-4 alkenyloxy optionally substituted by a halogen atom(s), C 2-4 alkenylthio optionally substituted by a halogen atom(s), or C 2-4 alkynyloxy optionally substituted by a halogen atom(s),
or any two adjacent substituents of R 5 , R 6 , R 7 , R 8 , and R 9 together represent —O—(CH 2 ) n —O—, wherein n is 1 or 2, optionally substituted by one or more halogen atoms,
in the presence or absence of a base to obtain an ether derivative represented by general formula (9):
wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are as defined above;
(ii) a reduction step (B) of reducing the ether derivative of general formula (9) to obtain an anthranilic acid derivative represented by general formula (1):
wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , and R 9 are as defined above;
(iii) a cyclization reaction step (C) of reacting an anthranilic acid derivative represented by general formula (1) with a ketone represented by general formula (2):
wherein R 10 and R 11 each independently represent a hydrogen atom or C 1-4 alkyl optionally substituted by a halogen atom(s),
or R 10 and R 11 together represent —(CH 2 ) m — wherein m is 3 or 4, provided that R 10 and R 11 do not simultaneously represent a hydrogen atom,
in the presence of an acid to obtain a quinolone derivative of general formula (3):
wherein R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11 are as defined above; and
(iv) a condensation reaction step (D) of reacting the quinolone derivative of general formula (3) with a halogen compound represented by general formula (4):
wherein R 12 represents C 1-8 alkyl optionally substituted by a halogen atom(s), C 3-6 cyclic alkyl optionally substituted by a halogen atom(s), C 2-4 alkenyl optionally substituted by a halogen atom(s), OR 13 wherein R 13 represents C 1-8 alkyl optionally substituted by a halogen atom(s); C 3-6 cyclic alkyl optionally substituted by a halogen atom(s); or C 2-4 alkenyl optionally substituted by a halogen atom(s), or SR 14 wherein R 14 represents C 1-8 alkyl optionally substituted by a halogen atom(s); C 3-6 cyclic alkyl optionally substituted by a halogen atom(s); or C 2-4 alkenyl optionally substituted by a halogen atom(s), and
Y represents any one of fluorine, chlorine, bromine, and iodine, or an acid anhydride represented by general formula (5):
wherein R 12 is as defined above,
to obtain a quinoline derivative represented by general formula (6):
wherein R 1 , R 2 , R 3 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 are as defined above.
16. The process according to claim 15 , wherein R 4 represents a hydrogen atom, C 1-8 alkyl optionally substituted by a halogen atom(s) or optionally substituted by C 1-4 alkoxy optionally substituted by a halogen atom(s), C 3-8 cyclic alkyl optionally substituted by a halogen atom(s), C 1-4 alkoxymethyl, benzoylmethyl optionally substituted by a halogen atom(s), or C 7-14 aralkyl optionally substituted by a halogen atom(s), C 1-4 alkyl, or C 1-4 alkoxy.
17. The process according to claim 15 , wherein R 1 , R 2 , and R 3 each independently represent a hydrogen atom, a chlorine atom, a bromine atom, a fluorine atom, methyl, ethyl, methoxy, ethoxy, or trifluoromethyl, provided that R 1 , R 2 , and R 3 do not simultaneously represent a hydrogen atom; R 4 represents C 1-8 alkyl optionally substituted by a halogen atom(s) or optionally substituted by C 1-4 alkoxy optionally substituted by a halogen atom(s), C 3-8 cyclic alkyl optionally substituted by a halogen atom(s), or C 7-14 aralkyl optionally substituted by a halogen atom(s), C 1-4 alkyl, or C 1-4 alkoxy; R 5 , R 6 , R 7 , R 8 , and R 9 each independently represent a hydrogen atom, a chlorine atom, a bromine atom, a fluorine atom, methyl, ethyl, methoxy, ethoxy, trifluoromethyl, pentafluoroethyl, trifluoromethoxy, or 1,1,2,2-tetrafluoroethoxy, or R 6 and R 7 together represent —OCF 2 CF 2 O—; R 10 and R 11 each independently represent a hydrogen atom or C 1-4 alkyl optionally substituted by a halogen atom(s), provided that R 10 and R 11 do not simultaneously represent a hydrogen atom; and R 12 represents C 1-4 alkyl optionally substituted by a halogen atom(s) or OR 13 wherein R 13 represents C 1-4 alkyl optionally substituted by a halogen atom(s).
18. The process according to claim 15 , wherein any one of R 1 , R 2 , and R 3 represents methyl, ethyl, or trifluoromethyl with the other two representing a hydrogen atom, R 4 represents C 1-4 alkyl optionally substituted by a halogen atom(s), any one of R 5 , R 6 , R 7 , R 8 , and R 9 represents methoxy, ethoxy, trifluoromethoxy, or 1,1,2,2-tetrafluoroethoxy with the other four representing a hydrogen atom, R 10 and R 11 each independently represent C 1-4 alkyl optionally substituted by a halogen atom(s), and R 12 represents OR 13 wherein R 13 represents C 1-4 alkyl.
19. The process according to claim 15 , wherein R 10 represents —CH 2 —R 15 , R 11 represents R 15 , and R 15 represents C 1-3 alkyl.
20. The process according to claim 15 , wherein the reduction in the reduction step (B) is carried out either by hydrogenation in the presence of palladium, or using iron powder.
21. The process according to claim 15 , wherein the acid used in the cyclization reaction step (C) is an organic sulfonic acid or Lewis acid.
22. The process according to claim 21 , wherein the organic sulfonic acid is benzenesulfonic acid or p-toluenesulfonic acid.
23. The process according to claim 21 , wherein the Lewis acid is zinc chloride, iron chloride, titanium chloride, or aluminum chloride.