Process for preparation of 5-bromo-1,3-dichloro-2-fluoro-benzene

Patent metadata

Field	Value
Publication number	US-2022017439-A1
Application number	US-201917295102-A
Country	US
Kind code	A1
Filing date	Nov 25, 2019
Priority date	Dec 4, 2018
Publication date	Jan 20, 2022
Grant date	—

Abstract

The invention relates to a process for the preparation of 5-bromo-1,3-dichloro-2-fluoro-benzene by diazotization and reduction of 6-bromo-2,4-dichloro-3-fluoro-aniline, which is obtained by bromination of 2,4-dichloro-3-fluoro-aniline, which is obtained by reduction of 1,3-dichloro-2-fluoro-4-nitro-benzene, and a process for preparing active compounds of formula V (Formula V) wherein the variables are defined in the specification by further transforming 5-bromo-1,3-dichloro-2-fluoro-benzene obtained from 2,4-dichloro-3-fluoro-aniline by the process according to the invention.

First claim

1 . A process for preparing 5-bromo-1,3-dichloro-2-fluoro-benzene comprising diazotizing 6-bromo-2,4-dichloro-3-fluoro-aniline and reducing the resulting diazonium salt to yield 5-bromo-1,3-dichloro-2-fluoro-benzene.

2 . The process of claim 1 , wherein 6-bromo-2,4-dichloro-3-fluoro-aniline is obtained by brominating 2,4-dichloro-3-fluoro-aniline.

3 . The process of claim 2 , wherein 2,4-dichloro-3-fluoroaniline is obtained by reducing 1,3-dichloro-2-fluoro-4-nitro-benzene.

4 . The process of claim 3 , wherein the reduction is conducted with hydrogen on Pd/C catalyst.

5 . The process of claim 2 , wherein the bromination is conducted with bromine and an oxidation agent.

6 . The process of claim 5 , wherein the oxidation agent is H 2 O 2 .

7 . The process of claim 1 , wherein the diazotization is conducted with NaNO 2 .

8 . The process of claim 1 , wherein the reduction of the diazonium salt is effected with hypophosphoric acid.

9 . 6-bromo-2,4-dichloro-3-fluoro-aniline.

10 . A process for preparing a compound of formula V

wherein
X is CH, O, or S,
U is CH or N; each R 2 is independently H, halogen, CN, N 3 , NO 2 , SCN, SF 5 , C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, which groups are unsubstituted, partially or fully halogenated and/or substituted with one or more same or different R 8 ,
Si(R 12 ) 3 , OR 9 , S(O) n R 9 , NR 10a R 10b ,
phenyl which is unsubstituted or partially or fully substituted with R 11 , and a 3- to 10-membered saturated, partially or fully unsaturated heteromonocyclic or heterobicyclic ring containing 1, 2, 3 or 4 heteroatoms N, O, and/or S as ring members, which ring is unsubstituted, or substituted with one or more same or different R 11 ;

n is 0, 1, or 2;
G 1 , G 2 are each CR 3 , or together form a sulfur atom;
each R 3 is independently selected from the meanings mentioned for R 2 , or two R 3 bonded to adjacent carbon atoms may form a five- or sixmembered saturated, partially or fully unsaturated carbocyclic ring, or a dihydrofurane, or
R 3 bonded to carbon atom in position G 1 form a bond to the chain *-Q-Z— in group A 2 ;
A is a group A 1 , A 2 , A 3 , or A 4 ; wherein
A 1 is C(═W)Y;
W is O, or S;
Y is N(R 5 )R 6 , or OR 9 ;
A 2 is

wherein # denotes the bond of group A, and % denotes the bond to G 1 ;
Q-Z is %—CH 2 —O—*, ‘%—CH 2 —S(O) n —*, or %—C(═O)—O—*, wherein % marks the bond of Q to phenyl, and * the bond of Z to azetidin; and
R A4 is H or C(═O)R 4A , wherein
R 4A is H, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, C 1 -C 4 -alkylcarbonyl, which aliphatic groups are unsubstituted or substituted with one or more radicals R 41 ;
C 3 -C 6 -cycloalkyl, C 3 -C 6 -halocycloalkyl which cyclic groups are unsubstituted or substituted with one or more R 42 ;
C(═O)N(R 43 )R 44 , N(R 43 )R 45 , CH═NOR 46 ;
phenyl, heterocycle, or hetaryl HET which rings are unsubstituted or partially or fully substituted with R A ;

R 41 is independently OH, CN, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, S(O) n —C 1 -C 6 -alkyl, S(O) n —C 1 -C 6 -haloalkyl, C(═O)N(R 43 )R 44 ,
C 3 -C 6 -cycloalkyl, or C 3 -C 6 -halocycloalkyl which cycles are unsubstituted or substituted with one or more R 411 ; or
phenyl, heterocycle or hetaryl HET which rings are unsubstituted or partially or fully substituted with R A ;

R 411 is independently OH, CN, C 1 -C 2 -alkyl, or C 1 -C 2 -haloalkyl;
R 43 is H, or C 1 -C 6 -alkyl,
R 44 is H, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, or C 3 -C 6 -cycloalkyl, C 3 -C 6 -halocycloalkyl, C 3 -C 6 -cycloalkylmethyl, or C 3 -C 6 -halocycloalkylmethyl which rings are unsubstituted or substituted with a cyano;
R 45 H, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, CH 2 —CN, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halocycloalkyl, C 3 -C 6 -cycloalkylmethyl, C 3 -C 6 -halocycloalkylmethyl, phenyl and hetaryl HET which aromatic rings are unsubstituted or partially or fully substituted with R A ;
R 42 C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, or a group as defined for R 41 ;
R 46 is independently H, C 1 -C 6 -alkyl, or C 1 -C 6 -haloalkyl;
R A is independently selected from halogen, CN, NO 2 , C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -haloalkenyl, C 2 -C 4 -alkynyl, C 2 -C 4 -haloalkynyl, C 3 -C 6 -cycloalkyl, C 3 -C 6 -halocycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, S(O) n —C 1 -C 4 -alkyl, S(O) n —C 1 -C 4 -haloalkyl, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -haloalkylcarbonyl, C(═O)N(R 43 )R 44 ; or
two R A present on the same carbon atom of a saturated or partially saturated ring may form together ═O or ═S; or
two R A present on the same S or SO ring member of a heterocyclic ring may together form a group ═N(C 1 -C 6 -alkyl), ═NO(C 1 -C 6 -alkyl), ═NN(H)(C 1 -C 6 -alkyl) or ═NN(C 1 -C 6 -alkyl) 2 ;

A 3 is CH 2 —NR 5 C(═W)R 6 ;
A 4 is cyano;
R 5 is independently selected from the meanings mentioned for R 2 ;
R 6 is H, CN, C 1 -C 10 -alkyl, C 3 -C 8 -cycloalkyl, C 2 -C 10 -alkenyl, C 2 -C 10 -alkynyl, which groups are unsubstituted, partially or fully halogenated and/or substituted with one or more same or different R 8 ;
or S(O) n R 9 , or C(═O)R 8 ;
a 3- to 8-membered saturated, partially or fully unsaturated heterocyclic ring, which ring may contain 1, 2, 3, or 4 heteroatoms O, S, N, C═O and/or C═S as ring members, which heterocyclic ring is unsubstituted or partially or fully substituted with same or different halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio, C 3 -C 8 -cycloalkyl, C 3 -C 8 -halocycloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, which groups are unsubstituted, or partially or fully substituted with same or different R 8 , or phenyl which may be partially or fully substituted with R 11 ;

or R 5 and R 6 , together with the nitrogen atom to which they are bound, form a 3- to 8-membered saturated, partially or fully unsaturated heterocyclic ring, which ring may contain 1, 2, 3, or 4 heteroatoms O, S, N, C═O and/or C═S as ring members, which heterocyclic ring is unsubstituted or partially or fully substituted with same or different halogen, CN, C 1 -C 6 -alkyl, C 1 -C 6 -haloalkyl, C 1 -C 6 -alkoxy, C 1 -C 6 -haloalkoxy, C 1 -C 6 -alkylthio, C 1 -C 6 -haloalkylthio, C 3 -C 8 -cycloalkyl, C 3 -C 8 -halocycloalkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -haloalkenyl, C 2 -C 6 -alkynyl, C 2 -C 6 -haloalkynyl, which groups are unsubstituted, or partially or fully substituted with same or different R 8 , or phenyl which may be partially or fully substituted with R 11 ;
or R 5 and R 6 together form a group ═C(R 8 ) 2 , ═S(O) m (R 9 ) 2 , ═NR 10a , or ═NOR 9 ;
R 7a , R 7b are each independently H, halogen, CN, C 1 -C 6 -alkyl, C 3 -C 8 -cycloalkyl, C 2 -C 6 -alkenyl, or C 2 -C 6 -alkynyl, which groups are unsubstituted, partially or fully halogenated and/or substituted with same or different R 8 ;
each R 8 is independently CN, N 3 , NO 2 , SCN, SF 5 , C 3 -C 8 -cycloalkyl, C 3 -C 8 -halocycloalkyl, wherein the carbon chains may be substituted with one or more R 13 ;
Si(R 12 )

Assignees

• Basf Se

Inventors

• Koerber Karsten
• Rack Michael
• Bindschaedler Pascal
• Mclaughlin Martin John
• Gockel Birgit
• Vyas Devendra
• Soergel Sebastian

Classifications

• C07C245/20

  Diazonium compounds · CPC title

• C07D413/12

  linked by a chain containing hetero atoms as chain links · CPC title

• B01J23/44

  Palladium · CPC title

• C07C37/045

  by substitution of a group bound to the ring by nitrogen · CPC title

• C07C211/52

  the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups · CPC title