Process for preparing substituted pyrazoles containing haloalkoxy- and haloalkylthio groups from alpha,alpha -dihaloalkylamines and ketimines

Patent metadata

Field	Value
Publication number	US-10273215-B2
Application number	US-201615738470-A
Country	US
Kind code	B2
Filing date	Jun 21, 2016
Priority date	Jun 26, 2015
Publication date	Apr 30, 2019
Grant date	Apr 30, 2019

Abstract

The present invention relates to a novel process for preparing 3,5-bis substituted pyrazoles containing haloalkoxy- and haloalkylthio groups.

First claim

The invention claimed is:

1. A process for preparing a 3,5-bis(haloalkyl)pyrazole of formula (Ia) or (Ib)

wherein:
R 1 is selected from the group consisting of C 1 -C 6 -haloalkyl-ether and C 1 -C 6 -haloalkyl-thioether;
R 2 is selected from the group consisting of H, halogen, COOH, (C═O)OR 5 , CN and (C═O)NR 6 R 7 ;
R 3 is C 1 -C 6 -haloalkyl;
R 4 is selected from the group consisting of H, C 1 -C 8 alkyl, aryl and pyridyl;
R 5 is selected from the group consisting of C 1-12 -alkyl, C 3-8 -cycloalkyl, C 6-18 -aryl, C 7-19 -arylalkyl and C 7-19 -alkylaryl; and
R 6 and R 7 are independently selected from the group consisting of C 1-12 -alkyl, C 3-8 -cycloalkyl, C 6-18 -aryl, C 7-19 -arylalkyl and C 7-19 -alkylaryl,
or
R 6 and R 7 are taken together with the nitrogen atom to which they are attached to form a four-, five- or six-membered ring,

comprising: step (A1), reacting an α,α-dihaloalkylamine of formula (II)

wherein:
R 1 is selected from the group consisting of C 1 -C 6 -haloalkyl-ether and C 1 -C 6 -haloalkyl-thioether;
each X is independently selected from the group consisting of F, Cl and Br; and
R 10 and R 11 are independently selected from the group consisting of C 1-6 -alkyl and C 3-8 -cycloalkyl,

in the presence of a Lewis Acid with a compound of formula (III)

wherein:
R 8 is selected from the group consisting of C 1-12 -alkyl, C 3-8 -cycloalkyl and benzyl;
R 2 is selected from the group consisting of H, halogen, COOH, (C═O)OR 5 , CN and (C═O)NR 6 R 7 ;
R 3 is C 1 -C 6 -haloalkyl;
R 5 is selected from the group consisting of C 1-12 -alkyl, C 3-8 -cycloalkyl, C 6-18 -aryl, C 7-19 -arylalkyl and C 7-19 -alkylaryl; and
R 6 and R 7 are independently selected from the group consisting of C 1-12 -alkyl, C 3-8 -cycloalkyl, C 6-18 -aryl, C 7-19 -arylalkyl and C 7-19 -alkylaryl,
or
R 6 and R 7 are taken together with the nitrogen atom to which they are attached to form a four-, five- or six-membered ring,

to form a compound of formula (V-1)

wherein:
A − is BF 4 , AlCl 3 F, AlF 2 Cl 2 or AlF 3 Cl;
R 1 is selected from the group consisting of C 1 -C 6 -haloalkyl-ether and C 1 -C 6 -haloalkyl-thioether;
R 2 is selected from the group consisting of H, halogen, COOH, (C═O)OR 5 , CN and (C═O)NR 6 R 7 ;
R 3 is C 1 -C 6 -haloalkyl;
R 5 is selected from the group consisting of C 1-12 -alkyl, C 3-8 -cycloalkyl, C 6-18 -aryl, C 7-19 -arylalkyl and C 7-19 -alkylaryl;
R 6 and R 7 are independently selected from the group consisting of C 1-12 -alkyl, C 3-8 -cycloalkyl, C 6-18 -aryl, C 7-19 -arylalkyl and C 7-19 -alkylaryl,
or
R 6 and R 7 are taken together with the nitrogen atom to which they are attached to form a four-, five- or six-membered ring;
R 8 is selected from the group consisting of C 1-12 -alkyl, C 3-8 -cycloalkyl and benzyl; and
R 10 and R 11 are independently selected from the group consisting of C 1-6 -alkyl and C 3-8 -cycloalkyl,

and step (B), cyclizing the compound of formula (V-1) in the presence of a hydrazine of formula (IV)
H 2 N—NHR 4   (IV)

wherein:
R 4 is selected from the group consisting of H, C 1 -C 8 alkyl, aryl and pyridyl, to form the compound of formula (Ia) or (Ib).

2. The process according to claim 1 , comprising step (A2), wherein the compound of formula (V-1) is further reacted with water to form a compound of formula (V-2)

wherein:
R 1 is selected from the group consisting of C 1 -C 6 -haloalkyl-ether and C 1 -C 6 -haloalkyl-thioether;
R 2 is selected from the group consisting of H, halogen, COOH, (C═O)OR 5 , CN and (C═O)NR 6 R 7 ;
R 3 is C 1 -C 6 -haloalkyl;
R 5 is selected from the group consisting of C 1-12 -alkyl, C 3-8 -cycloalkyl, C 6-18 -aryl, C 7-19 -arylalkyl and C 7-19 -alkylaryl;
R 6 and R 7 are independently selected from the group consisting of C 1-12 -alkyl, C 3-8 -cycloalkyl, C 6-18 -aryl, C 7-19 -arylalkyl and C 7-19 -alkylaryl,
or
R 6 and R 7 are taken together with the nitrogen atom to which they are attached to form a four-, five- or six-membered ring; and
R 8 is selected from the group consisting of C 1-12 -alkyl, C 3-8 -cycloalkyl and benzyl;

and step (B), wherein the compound of formula (V-2) is cyclized in the presence of the hydrazine of formula (IV)
H 2 N—NHR 4   (IV)

wherein:
R 4 is selected from the group consisting of H, C 1 -C 8 alkyl, aryl and pyridyl, to form (Ia/Ib) to form the compound of formula (Ia) or (Ib).

3. A process for preparing a 3,5-bis(haloalkyl)pyrazole of formula (Ia) or (Ib)

wherein:
R 1 is selected from the group consisting of CHF—OCF 3 (fluoro(trifluoromethoxy)methyl), CHF—OC 2 F 5 (fluoro(pentafluoroethoxy)methyl), CHF—SCF 3 (fluoro(trifluorothiomethyl)methyl), and CHF—SC 2 F 5 fluoro(pentafluorothioethyl)methyl;
R 2 is selected from the group consisting of H, F, Cl, Br, COOCH 3 , COOC 2 H 5 , COOC 3 H 7 , CN, CON(CH 3 ) 2 and CON(C 2 H 5 ) 2 ;
R 3 is selected from the group consisting of difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, tetrafluoroethyl (CF 3 CFH), pentafluoroethyl, and 1,1,1-trifluoroprop-2-yl; and
R 4 is selected from the group consisting of H, C 1 -C 8 alkyl, aryl and pyridyl,

comprising: step (A1), reacting an α,α-dihaloalkylamine of formula (II)

wherein:
R 1 is selected from the group consisting of CHF—OCF 3 (fluoro(trifluoromethoxy)methyl), CHF—OC 2 F 5 (fluoro(pentafluoroethoxy)methyl), CHF—SCF 3 (fluoro(trifluorothiomethyl)methyl), and CHF—SC 2 F 5 fluoro(pentafluorothioethyl)methyl;
each X is independently selected from the group consisting of F and Cl; and
R 10 and R 11 are independently selected from the group consisting of C 1-12 -alkyl, C 3-8 -cycloalkyl, and C 7-19 -arylalkyl,
or
R 10 and R 11 are taken together with the nitrogen atom to which they are attached to form a five-membered ring,

in the presence of a Lewis Acid with a compound of formula (III)

wherein:
R 8 is selected from the group consisting of methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, t-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, benzyl, phenylethyl, C 7-19 -alkylaryl, tolyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4-dimethylphenyl and 3,5-dimethylphenyl;
R 2 is selected from the group consisting of H, F, Cl, Br, COOCH 3 , COOC 2 H 5 , COOC 3 H 7

Assignees

• Bayer Cropscience Ag
• Centre Nat Rech Scient

Inventors

• Pazenok Sergii
• Vors Jean-Pierre
• Leroux Frédéric R
• Schmitt Etienne

Classifications

• A61P31/10

  Antimycotics · CPC title

• C07D231/16 Primary

  Halogen atoms or nitro radicals · CPC title

• C07C251/26

  having nitrogen atoms of imino groups further bound to halogen atoms · CPC title

• C07C251/30 Primary

  having nitrogen atoms of imino groups quaternised · CPC title

• C07C251/08

  being acyclic · CPC title