Process for the preparation of 2-halobenzoic acids
The present invention provides a process for producing 2-halobenzoic acids of the general formula (I), characterized by reacting a benzoic acid of formula (II) with a halogenating agent in the presence of Pd catalyst: (wherein A is —OH, —OM (M is alkali metal), —N(R 6 )R 7 (R 6 and R 7 are each H, C 1 –C 6 alkyl, optionally substituted phenyl, or the like); R is H, C 1 –C 6 alkyl, C 1 –C 6 alkylcarbonyl, carboxyl, C 1 –C 12 alkoxycarbonyl, optionally substituted phenylcarbonyl, or the like; n is 0 to 4; X is Cl, Br or I, or alternatively (R)n may be present on benzene-constituting carbon atoms adjacent to each other and form a C 3 –C 4 alkylene- or C 3 –C 4 alkenylene-fused ring).
1. A process for producing a 2-halobenzoic acid represented by the following formula (I):
{wherein X represents a chlorine atom, a bromine atom or an iodine atom;
A represents —OH, —OM (in this formula, M represents an alkali metal atom) or —N(R 6 )R 7 (in this formula, R 6 and R 7 which may be the same or different represent a hydrogen atom; a C 1 –C 6 alkyl group; a phenyl group; a phenyl group having at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 –C 6 alkyl group, C 1 –C 6 alkoxy group, halo C 1 –C 6 alkyl group, halo C 1 –C 6 alkoxy group, C 1 –C 6 alkylsulfinyl group and C 1 –C 6 alkylsulfonyl group; a group represented by the following formula:
(in this formula, R 1 , R 2 , R 3 and R 4 which may be the same or different represent a hydrogen atom or a C 1 –C 6 alkyl group, R 5 represents a C 1 –C 6 alkyl group, m represents an integer of 0 or 1, and k represents an integer of 1 or 2); a group represented by the following formula:
(in this formula, R 8 , R 9 and R 10 which may be the same or different represent a hydrogen atom or a C 1 –C 6 alkyl group); or a group represented by the following formula:
(in this formula, R 11 , R 12 , R 13 , R 14 , R 15 and R 16 which may be the same or different represent a hydrogen atom or a C 1 –C 6 alkyl group and I represents an integer of 1 or 2));
R which may be the same or different represents a hydrogen atom; a halogen atom; a cyano group; a nitro group; a C 1 –C 6 alkyl group; a C 1 –C 6 alkylcarbonyl group; a carboxyl group; a C 1 –C 12 alkoxycarbonyl group; a phenylcarbonyl group; a phenylcarbonyl group having at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 –C 6 alkyl group, C 1 –C 6 alkoxy group, halo C 1 –C 6 alkyl group and halo C 1 –C 6 alkoxy group; a benzylcarbonyl group; a benzylcarbonyl group having, on the ring thereof, at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 –C 6 alkyl group, C 1 –C 6 alkoxy group, halo C 1 –C 6 alkyl group and halo C 1 –C 6 alkoxy group; or —CON(R 17 )R 18 (in this formula, R 17 and R 18 which may be the same or different represent a hydrogen atom; a C 1 –C 6 alkyl group; a phenyl group; a phenyl group having at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 –C 6 alkyl group, C 1 –C 6 alkoxy group, halo C 1 –C 6 alkyl group and halo C 1 –C 6 alkoxy group; a pyridyl group; a pyridyl group having at least one, the same or different substituents selected from the group consisting of hydrogen atom, halogen atom, cyano group, nitro group, C 1 –C 6 alkyl group, C 1 –C 6 alkoxy group, halo C 1 –C 6 alkyl group and halo C 1 –C 6 alkoxy group; a benzyl group; or a benzyl group having, on the ring thereof, at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 –C 6 alkyl group, C 1 –C 6 alkoxy group, halo C 1 –C 6 alkyl group and halo C 1 –C 6 alkoxy group); and
n represents an integer of 0 to 4;
or alternatively (R)n may be linked to an adjacent carbon atom on the benzene ring to form a fused ring being a C 3 –C 4 alkylene group or a C 3 –C 4 alkenylene group, which may have at least one, the same or different substituents R (R is as defined above)};
characterized by reacting a benzoic acid represented by the following formula (II):
(wherein A, R and n are as defined above), with a halogenating agent in the presence of a palladium catalyst.
2. A process according to claim 1 , wherein A represents —OH or —OM (in this formula, M represents an alkali metal atom).
3. A process for producing a 2-halobenzoic acid represented by the following formula (I):
{wherein X represents a chlorine atom, a bromine atom or an iodine atom;
A represents —N(R 6 )R 7 (in this formula, R 6 and R 7 may be the same or different and represent a hydrogen atom; a C 1 –C 6 alkyl group; a phenyl group; a phenyl group having at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 –C 6 alkyl group, C 1 –C 6 alkoxy group, halo C 1 –C 6 alkyl group, halo C 1 –C 6 alkoxy group, C 1 –C 6 alkylsulfinyl group and C 1 –C 6 alkylsulfonyl group; or
(in this formula, R 1 , R 2 , R 3 and R 4 may be the same or different and represent a hydrogen atom or a C 1 –C 6 alkyl group , R 5 represents a C 1 –C 6 alkyl group, m represents an integer of 0 or 1, and k represents an integer of 1 or 2));
R which may be the same or different represents a hydrogen atom; a halogen atom; a cyano group; a nitro group; a C 1 –C 6 alkyl group; a C 1 –C 6 alkylcarbonyl group; a carboxyl group; a C 1 –C 12 alkoxycarbonyl group; a phenylcarbonyl group; a phenylcarbonyl group having at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 –C 6 alkyl group, C 1 –C 6 alkoxy group, halo C 1 –C 6 alkyl group and halo C 1 –C 6 alkoxy group; a benzylcarbonyl group; a benzylcarbonyl group having, on the ring thereof, at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 –C 6 alkyl group, C 1 –C 6 alkoxy group, halo C 1 –C 6 alkyl group and halo C 1 –C 6 alkoxy group; or —CON(R 17 )R 18 (in this formula, R 17 and R 18 which may be the same or different represent a hydrogen atom; a C 1 –C 6 alkyl group; a phenyl group; a phenyl group having at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 –C 6 alkyl group, C 1 –C 6 alkoxy group, halo C 1 –C 6 alkyl group and halo C 1 –C 6 alkoxy group; a pyridyl group; a pyridyl group having at least one, the same or different substituents selected from the group consisting of hydrogen atom, halogen atom, cyano group, nitro group, C 1 –C 6 alkyl group, C 1 –C 6 alkoxy group, halo C 1 –C 6 alkyl group and halo C 1 –C 6 alkoxy group; a benzyl group; or a benzyl group having, on the ring thereof, at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 –C 6 alkyl group, C 1 –C 6 alkoxy group, halo C 1 –C 6 alkyl group and halo C 1 –C 6 alkoxy group); and
n represents an integer of 0 to 4;
or alternatively (R)n may be linked to an adjacent carbon atom on the benzene ring to form a fused ring being a C 3 –C 4 alkylene group or a C 3 –C 4 alkenylene group, which may have at least one, the same or different substituents R (R is as defined above)};
characterized by reacting a benzoic acid represented by the following formula (II):
(wherein A, R and n are as defined above), with a halogenating agent in the presence of a palladium catalyst.
4. A process according to claim 3 , wherein R 6 and R 7 may be the same or different and represent a hydrogen atom or
(in this formula, R 1 , R 2 , R 3 and R 4 may be the same or different and represent a hydrogen atom or a C 1 –C 6 alkyl group, R 5 represents a C 1 –C 6 alkyl group, m represents an integer of 0 or 1, and k represents an integer of 1 or 2).
5. A process according to claim 3 , wherein R 6 and R 7 may be the same or different and represent a hydrogen atom; a phenyl group; or a phenyl group having at least one, the same or different substituents selected from the group consisting of halogen atom, cyano group, nitro group, C 1 –C 6 alkyl group, C 1 –C 6 alkoxy group, halo C 1 –C 6 alkyl group, halo C 1 –C 6 alkoxy group, C 1 –C 6 alkylsulfinyl group and C 1 –C 6 alkylsulfonyl group.