Process for the preparation of halo-substituted benzenes

Patent metadata

Field	Value
Publication number	US-10087126-B2
Application number	US-201515516110-A
Country	US
Kind code	B2
Filing date	Oct 8, 2015
Priority date	Oct 14, 2014
Publication date	Oct 2, 2018
Grant date	Oct 2, 2018

Abstract

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.

First claim

The invention claimed is:

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.

Assignees

• Syngenta Participations Ag

Inventors

• Smits Helmars
• Knochel Paul
• Klatt Thomas
• Becker Matthias

Classifications

• C07C17/383

  by distillation · CPC title

• C07C17/35

  by reactions not affecting the number of carbon or of halogen atoms in the reaction · CPC title

• C07C17/38

  Separation; Purification; Stabilisation; Use of additives · CPC title

• C07C17/013

  by addition of halogens · CPC title

• C07C17/12 Primary

  in the ring of aromatic compounds · CPC title