Process for the preparation of halo-substituted benzenes
View Patent ↗The invention relates to a process for the preparation of compound of formula (I) wherein R 1 is halogen and R 2 is halogen or hydrogen; comprising a) reacting the compound of formula (II) in an aprotic organic solvent in the presence of an aprotic polar co-solvent with a magnesium amide base followed by a halogenating agent, to the compound of formula I wherein R 1 is halogen and R 2 is hydrogen, and b) reacting the compound of formula (I), wherein R 1 is chloro and R 2 is hydrogen, in an aprotic organic solvent in the presence of an aprotic polar co-solvent with a magnesium amide base followed by a halogenating agent to a compound of formula I, wherein R 1 is chloro and R 2 is halogen.
1. A process for the preparation of a compound of formula I
wherein
R 1 is halogen and R 2 is hydrogen or
R 1 is chloro and R 2 is halogen; comprising
a) for the preparation of a compound of formula I, wherein R 1 is halogen and R 2 is hydrogen, reacting the compound of formula II
in an aprotic organic solvent in the presence of an aprotic polar co-solvent, different from the aprotic organic solvent, with a magnesium amide base followed by a halogenating agent, to the compound of formula I
wherein R 1 is halogen and R 2 is hydrogen; and
b) for the preparation of a compound of formula I, wherein R 1 is chloro and R 2 is halogen, reacting the compound of formula I, wherein R 1 is chloro and R 2 is hydrogen, in an aprotic organic solvent in the presence of an aprotic polar co-solvent, different from the aprotic organic solvent, with a magnesium amide base followed by a halogenating agent to a compound of formula I, wherein R 1 is chloro and R 2 is halogen.
2. A process according to claim 1 , characterized in that in step a) the magnesium amide base is a compound of formula IV
complexed with lithium chloride;
wherein
R 3 and R 4 are, independently from each other, C 1 -C 6 alkyl, C 4 -C 7 cycloalkyl or C 1 -C 6 alkoxylalkyl;
and X is halogen.
3. A process according to claim 1 , characterized in that in step b) the magnesium amide base is a compound of formula IV
complexed with lithium chloride;
wherein
R 3 and R 4 are, independently from each other, C 1 -C 6 alkyl, C 4 -C 7 cycloalkyl or C 1 -C 6 alkoxylalkyl;
and X is halogen.
4. A process according to claim 1 , characterized in that the magnesium amide base of reaction steps a) and b) is identical.
5. A process according to claim 1 , characterized in that the aprotic polar co-solvent in reaction step a) is selected from the group consisting of the compounds of formula V
wherein R 5 , R 6 and R 7 are, independently from each other, C 1 -C 6 alkyl, C 4 -C 7 cycloalkyl or C 1 -C 6 alkoxylalkyl; or R 5 , R 6 or R 7 together form a C 4 -C 7 carbocycle;
the compounds of formula VI
wherein R 8 and R 9 are, independently from each other, C 1 -C 6 alkyl, C 4 -C 7 cycloalkyl or C 1 -C 6 alkoxylalkyl and both R 10 together represent a —CH 2 —CH 2 — or —CH 2 —CH 2 —CH 2 — chain;
and the compounds of formula VII
wherein R 11 and R 12 are, independently from each other, C 1 -C 6 alkyl, C 4 -C 7 cycloalkyl or C 1 -C 6 alkoxylalkyl;
or both R 11 or both R 12 together represent a —CH 2 —CH 2 —CH 2 —CH 2 — or —CH 2 —CH 2 —CH 2 —CH 2 —CH 2 -chain.
6. A process according to claim 1 , characterized in that the aprotic polar co-solvent in reaction step b) is selected from the group consisting of the compounds of formula V
wherein R 5 , R 6 and R 7 are, independently from each other, C 1 -C 6 alkyl, C 4 -C 7 cycloalkyl or C 1 -C 6 alkoxylalkyl; or R 5 , R 6 or R 7 together form a C 4 -C 7 carbocycle;
the compounds of formula VI
wherein R 8 and R 9 are, independently from each other, C 1 -C 6 alkyl, C 4 -C 7 cycloalkyl or C 1 -C 6 alkoxylalkyl and both R 10 together represent a —CH 2 —CH 2 — or —CH 2 —CH 2 —CH 2 — chain;
and the compounds of formula VII
wherein R 11 and R 12 are, independently from each other, C 1 -C 6 alkyl, C 4 -C 7 cycloalkyl or C 1 -C 6 alkoxylalkyl; or both R 11 or both R 12 together represent a —CH 2 —CH 2 —CH 2 —CH 2 — or —CH 2 —CH 2 —CH 2 —CH 2 —CH 2 — chain.
7. A process according to claim 1 , characterized in that the halogenating agent in step a) is chlorine, bromine, iodine, N-halogen amides, sulfonyl chlorides, polyhalogenated hydrocarbons, sulfuryl chloride or hexachloroacetone.
8. A process according to claim 1 , characterized in that the halogenating agent in step b) is chlorine, bromine, iodine, N-halogen amides, sulfonyl chlorides, polyhalogenated hydrocarbons, sulfuryl chloride or hexachloroacetone.
9. A process according to claim 1 , characterized in that the aprotic organic solvent and the aprotic polar co-solvent are identical for steps a) and b).
10. A process according to claim 1 , comprising
a) reacting the compound of formula II
in an aprotic organic solvent comprising organic ethers in the presence of an aprotic polar co-solvent selected from the group consisting of compounds of formulae Va and VIa
with a magnesium amide base selected from the group consisting of compounds of formulae IVa and IVb,
followed by a halogenating agent selected from chlorine, bromine, iodine, N-halogen amides, sulfonyl chlorides, polyhalogenated hydrocarbons, sulfuryl chloride and hexachloroacetone;
to the compound of formula I, wherein R 1 is halogen and R 2 is hydrogen
and
b) reacting the compound of formula I wherein R 1 is chloro and R 2 is hydrogen in an aprotic organic solvent comprising organic ethers in the presence of an aprotic polar co-solvent selected from the group consisting of compounds of formulae Va and VIa
with a magnesium amide base selected from the group consisting of compounds of formulae IVa and IVb,
followed by a halogenating agent selected from the group consisting of chlorine, bromine, iodine, N-halogen amides, sulfonyl chlorides, polyhalogenated hydrocarbons, sulfuryl chloride and hexachloroacetone; to a compound of formula I, wherein R 1 is chloro and R 2 is halogen.