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

Abstract

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

Claims

1. A process for preparing a 3,5-bis(haloalkyl)pyrazole of formula (Ia) or (Ib) ##STR00012## wherein: R.sup.1 is selected from the group consisting of C.sub.1-C.sub.6-haloalkyl-ether and C.sub.1-C.sub.6-haloalkyl-thioether; R.sup.2 is selected from the group consisting of H, halogen, COOH, (CO)OR.sup.5, CN and (CO)NR.sup.6R.sup.7; R.sup.3 is C.sub.1-C.sub.6-haloalkyl; R.sup.4 is selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, aryl and pyridyl; R.sup.5 is selected from the group consisting of C.sub.1-12-alkyl, C.sub.3-8-cycloalkyl, C.sub.6-18-aryl, C.sub.7-19-arylalkyl and C.sub.7-19-alkylaryl; and R.sup.6 and R.sup.7 are independently selected from the group consisting of C.sub.1-12-alkyl, C.sub.3-8-cycloalkyl, C.sub.6-18-aryl, C.sub.7-19-arylalkyl and C.sub.7-19-alkylaryl, or R.sup.6 and R.sup.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 ,-dihaloalkylamine of formula (II) ##STR00013## wherein: R.sup.1 is selected from the group consisting of C.sub.1-C.sub.6-haloalkyl-ether and C.sub.1-C.sub.6-haloalkyl-thioether; each X is independently selected from the group consisting of F, Cl and Br; and R.sup.10 and R.sup.11 are independently selected from the group consisting of C.sub.1-6-alkyl and C.sub.3-8-cycloalkyl, in the presence of a Lewis Acid with a compound of formula (III) ##STR00014## wherein: R.sup.8 is selected from the group consisting of C.sub.1-12-alkyl, C.sub.3-8-cycloalkyl and benzyl; R.sup.2 is selected from the group consisting of H, halogen, COOH, (CO)OR.sup.5, CN and (CO)NR.sup.6R.sup.7; R.sup.3 is C.sub.1-C.sub.6-haloalkyl; R.sup.5 is selected from the group consisting of C.sub.1-12-alkyl, C.sub.3-8-cycloalkyl, C.sub.6-18-aryl, C.sub.7-19-arylalkyl and C.sub.7-19-alkylaryl; and R.sup.6 and R.sup.7 are independently selected from the group consisting of C.sub.1-12-alkyl, C.sub.3-8-cycloalkyl, C.sub.6-18-aryl, C.sub.7-19-arylalkyl and C.sub.7-19-alkylaryl, or R.sup.6 and R.sup.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) ##STR00015## wherein: A.sup. is BF.sub.4, AlCl.sub.3F, AlF.sub.2Cl.sub.2 or AlF.sub.3Cl; R.sup.1 is selected from the group consisting of C.sub.1-C.sub.6-haloalkyl-ether and C.sub.1-C.sub.6-haloalkyl-thioether; R.sup.2 is selected from the group consisting of H, halogen, COOH, (CO)OR.sup.5, CN and (CO)NR.sup.6R.sup.7; R.sup.3 is C.sub.1-C.sub.6-haloalkyl; R.sup.5 is selected from the group consisting of C.sub.1-12-alkyl, C.sub.3-8-cycloalkyl, C.sub.6-18-aryl, C.sub.7-19-arylalkyl and C.sub.7-19-alkylaryl; R.sup.6 and R.sup.7 are independently selected from the group consisting of C.sub.1-12-alkyl, C.sub.3-8-cycloalkyl, C.sub.6-18-aryl, C.sub.7-19-arylalkyl and C.sub.7-19-alkylaryl, or R.sup.6 and R.sup.7 are taken together with the nitrogen atom to which they are attached to form a four-, five- or six-membered ring; R.sup.8 is selected from the group consisting of C.sub.1-12-alkyl, C.sub.3-8-cycloalkyl and benzyl; and R.sup.10 and R.sup.11 are independently selected from the group consisting of C.sub.1-6-alkyl and C.sub.3-8-cycloalkyl, and step (B), cyclizing the compound of formula (V-1) in the presence of a hydrazine of formula (IV)
H.sub.2NNHR.sup.4(IV) wherein: R.sup.4 is selected from the group consisting of H, C.sub.1-C.sub.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) ##STR00016## wherein: R.sup.1 is selected from the group consisting of C.sub.1-C.sub.6-haloalkyl-ether and C.sub.1-C.sub.6-haloalkyl-thioether; R.sup.2 is selected from the group consisting of H, halogen, COOH, (CO)OR.sup.5, CN and (CO)NR.sup.6R.sup.7; R.sup.3 is C.sub.1-C.sub.6-haloalkyl; R.sup.5 is selected from the group consisting of C.sub.1-12-alkyl, C.sub.3-8-cycloalkyl, C.sub.6-18-aryl, C.sub.7-19-arylalkyl and C.sub.7-19-alkylaryl; R.sup.6 and R.sup.7 are independently selected from the group consisting of C.sub.1-12-alkyl, C.sub.3-8-cycloalkyl, C.sub.6-18-aryl, C.sub.7-19-arylalkyl and C.sub.7-19-alkylaryl, or R.sup.6 and R.sup.7 are taken together with the nitrogen atom to which they are attached to form a four-, five- or six-membered ring; and R.sup.8 is selected from the group consisting of C.sub.1-12-alkyl, C.sub.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.sub.2NNHR.sup.4(IV) wherein: R.sup.4 is selected from the group consisting of H, C.sub.1-C.sub.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) ##STR00017## wherein: R.sup.1 is selected from the group consisting of CHFOCF.sub.3 (fluoro(trifluoromethoxy)methyl), CHFOC.sub.2F.sub.5 (fluoro(pentafluoroethoxy)methyl), CHFSCF.sub.3 (fluoro(trifluorothiomethyl)methyl), and CHFSC.sub.2F.sub.5 fluoro(pentafluorothioethyl)methyl; R.sup.2 is selected from the group consisting of H, F, Cl, Br, COOCH.sub.3, COOC.sub.2H.sub.5, COOC.sub.3H.sub.7, CN, CON(CH.sub.3).sub.2 and CON(C.sub.2H.sub.5).sub.2; R.sup.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.sub.3CFH), pentafluoroethyl, and 1,1,1-trifluoroprop-2-yl; and R.sup.4 is selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, aryl and pyridyl, comprising: step (A1), reacting an ,-dihaloalkylamine of formula (II) ##STR00018## wherein: R.sup.1 is selected from the group consisting of CHFOCF.sub.3 (fluoro(trifluoromethoxy)methyl), CHFOC.sub.2F.sub.5 (fluoro(pentafluoroethoxy)methyl), CHFSCF.sub.3 (fluoro(trifluorothiomethyl)methyl), and CHFSC.sub.2F.sub.5 fluoro(pentafluorothioethyl)methyl; each X is independently selected from the group consisting of F and Cl; and R.sup.10 and R.sup.11 are independently selected from the group consisting of C.sub.1-12-alkyl, C.sub.3-8-cycloalkyl, and C.sub.7-19-arylalkyl, or R.sup.10 and R.sup.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) ##STR00019## wherein: R.sup.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.sub.7-19-alkylaryl, tolyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4-dimethylphenyl and 3,5-dimethylphenyl; R.sup.2 is selected from the group consisting of H, F, Cl, Br, COOCH.sub.3, COOC.sub.2H.sub.5, COOC.sub.3H.sub.7, CN, CON(CH.sub.3).sub.2 and CON(C.sub.2H.sub.5).sub.2; and R.sup.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.sub.3CFH), pentafluoroethyl, and 1,1,1-trifluoroprop-2-yl, to form a compound of formula (V-1) ##STR00020## wherein: A.sup. is BF.sub.4, AlCl.sub.3F, AlF.sub.2Cl.sub.2 or AlF.sub.3Cl; R.sup.1 is selected from the group consisting of CHFOCF.sub.3 (fluoro(trifluoromethoxy)methyl), CHFOC.sub.2F.sub.5 (fluoro(pentafluoroethoxy)methyl), CHFSCF.sub.3 (fluoro(trifluorothiomethyl)methyl), and CHFSC.sub.2F.sub.5 fluoro(pentafluorothioethyl)methyl; R.sup.2 is selected from the group consisting of H, F, Cl, Br, COOCH.sub.3, COOC.sub.2H.sub.5, COOC.sub.3H.sub.7, CN, CON(CH.sub.3).sub.2 and CON(C.sub.2H.sub.5).sub.2; R.sup.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.sub.3CFH), pentafluoroethyl, and 1,1,1-trifluoroprop-2-yl; R.sup.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.sub.7-19-alkylaryl, tolyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4-dimethylphenyl and 3,5-dimethylphenyl; and R.sup.10 and R.sup.11 are independently selected from the group consisting of C.sub.1-12-alkyl, C.sub.3-8-cycloalkyl, and C.sub.7-19-arylalkyl, or R.sup.10 and R.sup.11 are taken together with the nitrogen atom to which they are attached to form a five-membered ring, and step (B), cyclizing the compound of formula (V-1) in the presence of a hydrazine of formula (IV)
H.sub.2NNHR.sup.4(IV) wherein: R.sup.4 is selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, aryl and pyridyl, to form the compound of formula (Ia) or (Ib).

4. The process according to claim 3, wherein the radicals in formula (Ia), (Ib), (II), (III), (IV), and (V-1) are: R.sup.1 is selected from the group consisting of fluoro(trifluoromethoxy)methyl and fluoro(pentafluoroethoxy)methyl; R.sup.2 is selected from the group consisting of H, Cl, CN and COOC.sub.2H.sub.5; R.sup.3 is selected from the group consisting of trifluoromethyl, difluoromethyl, difluorochloromethyl and pentafluoroethyl; R.sup.4 is selected from the group consisting of H, methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, n-hexyl, 1,3-dimethylbutyl, 3,3-dimethylbutyl and aryl; R.sup.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, benzyl and C.sub.7-C.sub.19-alkylaryl; each X is independently selected from the group consisting of F and Cl; and R.sup.10 and R.sup.11 are independently selected from the group consisting of C.sub.1-12-alkyl and C.sub.3-8-cycloalkyl.

5. A process for preparing a 3,5-bis(haloalkyl)pyrazole of formula (Ia) or (Ib) ##STR00021## wherein: R.sup.1 is selected from the group consisting of CHFOCF.sub.3 (fluoro(trifluoromethoxy)methyl), CHFOC.sub.2F.sub.5 (fluoro(pentafluoroethoxy)methyl), CHFSCF.sub.3 (fluoro(trifluorothiomethyl)methyl), and CHFSC.sub.2F.sub.5 fluoro(pentafluorothioethyl)methyl; R.sup.2 is selected from the group consisting of H, F, Cl, Br, COOCH.sub.3, COOC.sub.2H.sub.5, COOC.sub.3H.sub.7, CN, CON(CH.sub.3).sub.2 and CON(C.sub.2H.sub.5).sub.2; R.sup.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.sub.3CFH), pentafluoroethyl, and 1,1,1-trifluoroprop-2-yl; and R.sup.4 is selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, aryl and pyridyl, comprising: step (A1), reacting an ,-dihaloalkylamine of formula (II) ##STR00022## wherein: R.sup.1 is selected from the group consisting of CHFOCF.sub.3 (fluoro(trifluoromethoxy)methyl), CHFOC.sub.2F.sub.5 (fluoro(pentafluoroethoxy)methyl), CHFSCF.sub.3 (fluoro(trifluorothiomethyl)methyl), and CHFSC.sub.2F.sub.5 fluoro(pentafluorothioethyl)methyl; each X is independently selected from the group consisting of F and Cl; and R.sup.10 and R.sup.11 are independently selected from the group consisting of C.sub.1-12-alkyl, C.sub.3-8-cycloalkyl, and C.sub.7-19-arylalkyl, or R.sup.10 and R.sup.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) ##STR00023## wherein: R.sup.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.sub.7-19-alkylaryl, tolyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4-dimethylphenyl and 3,5-dimethylphenyl; R.sup.2 is selected from the group consisting of H, F, Cl, Br, COOCH.sub.3, COOC.sub.2H.sub.5, COOC.sub.3H.sub.7, CN, CON(CH.sub.3).sub.2 and CON(C.sub.2H.sub.5).sub.2; and R.sup.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.sub.3CFH), pentafluoroethyl, and 1,1,1-trifluoroprop-2-yl, to form a compound of formula (V-1) ##STR00024## wherein: A.sup. is BF.sub.4, AlCl.sub.3F, AlF.sub.2Cl.sub.2 or AlF.sub.3Cl; R.sup.1 is selected from the group consisting of CHFOCF.sub.3 (fluoro(trifluoromethoxy)methyl), CHFOC.sub.2F.sub.5 (fluoro(pentafluoroethoxy)methyl), CHFSCF.sub.3 (fluoro(trifluorothiomethyl)methyl), and CHFSC.sub.2F.sub.5 fluoro(pentafluorothioethyl)methyl; R.sup.2 is selected from the group consisting of H, F, Cl, Br, COOCH.sub.3, COOC.sub.2H.sub.5, COOC.sub.3H.sub.7, CN, CON(CH.sub.3).sub.2 and CON(C.sub.2H.sub.5).sub.2; R.sup.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.sub.3CFH), pentafluoroethyl, and 1,1,1-trifluoroprop-2-yl; R.sup.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.sub.7-19-alkylaryl, tolyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4-dimethylphenyl and 3,5-dimethylphenyl; and R.sup.10 and R.sup.11 are independently selected from the group consisting of C.sub.1-12-alkyl, C.sub.3-8-cycloalkyl, and C.sub.7-19-arylalkyl, or R.sup.10 and R.sup.11 are taken together with the nitrogen atom to which they are attached to form a five-membered ring, step (A2), reacting the compound of formula (V-1) with water to form a compound of formula (V-2) ##STR00025## wherein: R.sup.1 is selected from the group consisting of CHFOCF.sub.3 (fluoro(trifluoromethoxy)methyl), CHFOC.sub.2F.sub.5 (fluoro(pentafluoroethoxy)methyl), CHFSCF.sub.3 (fluoro(trifluorothiomethyl)methyl), and CHFSC.sub.2F.sub.5 fluoro(pentafluorothioethyl)methyl; R.sup.2 is selected from the group consisting of H, F, Cl, Br, COOCH.sub.3, COOC.sub.2H.sub.5, COOC.sub.3H.sub.7, CN, CON(CH.sub.3).sub.2 and CON(C.sub.2H.sub.5).sub.2; R.sup.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.sub.3CFH), pentafluoroethyl, and 1,1,1-trifluoroprop-2-yl; and R.sup.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.sub.7-19-alkylaryl, tolyl, 2,3-dimethylphenyl, 2,4-dimethylphenyl, 2,5-dimethylphenyl, 2,6-dimethylphenyl, 3,4-dimethylphenyl and 3,5-dimethylphenyl, and step (B), cyclizing the compound of formula (V-2) in the presence of a hydrazine of formula (IV)
H.sub.2NNHR.sup.4(IV) wherein: R.sup.4 is selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, aryl and pyridyl, to form the compound of formula (Ia) or (Ib).

6. The process according to claim 5, wherein the radicals in formula (Ia), (Ib), (II), (III), (IV), (V-1) and (V-2) are: R.sup.1 is selected from the group consisting of fluoro(trifluoromethoxy)methyl and fluoro(pentafluoroethoxy)methyl; R.sup.2 is selected from the group consisting of H, Cl, CN and COOC.sub.2H.sub.5; R.sup.3 is selected from the group consisting of trifluoromethyl, difluoromethyl, difluorochloromethyl and pentafluoroethyl; R.sup.4 is selected from the group consisting of H, methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, t-butyl, n-pentyl, n-hexyl, 1,3-dimethylbutyl, 3,3-dimethylbutyl and aryl; R.sup.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, benzyl and C.sub.7-C.sub.19-alkylaryl; each X is independently selected from the group consisting of F and Cl; and R.sup.10 and R.sup.11 are independently selected from the group consisting of C.sub.1-12-alkyl and C.sub.3-8-cycloalkyl.

Description

EXAMPLE 1

N,N-dimethyl-1,1,2-trifluoro-2-(trifluoromethoxy)-ethanamine (II-1)

(1) 1,1,2-trifluoro-2-(trifluoromethoxy)ethene (0.44 mL, 3.97 mmol) was liquefied at 78 C. into a sealed tube equipped with a magnetic stirbar under inert atmosphere using a dry ice/acetone bath. A solution of dimethylamine (2M in THF, 2 mL, 4 mmol) was added via syringe, the mixture was raised to max. 20 C. over 20 min to avoid polymerization of THF. The formed product was used for further transformation without purification.

EXAMPLE 2

3-(fluoro(trifluoromethoxy)methyl)-5-(trifluoromethyl)-1H-pyrazole (I-1)

(2) To the mixture solution of the N,N-dimethyl-1,1,2-trifluoro-2-(trifluoromethoxy)-ethanamine (II-1) (3.95 mmol) was added BF.sub.3-Et.sub.2O (0.5 mL, 3.95 mmol) via syringe. The solution was vigorously stirred for 15 min. The resulting biphasic mixture was then added onto a solution of N-benzyl-1,1,1-trifluoropropan-2-imine (660 mg, 3.28 mmol) in distilled THF (4 mL) under inert atmosphere into a Schlenk vessel via syringe. The mixture was stirred at room temperature for 30 min. Hydrazine hydrate (0.24 mL, 4.89 mmol) was added via syringe, rapidly followed by conc. H.sub.2SO.sub.4 (0.08 mL, 1.5 mmol), both via syringe. The mixture was further stirred 1 h at room temperature. The mixture was then evaporated in vacuo (>200 mbar, 45 C. max).

(3) The crude product was purified by flash chromatography (Et.sub.2O in pentane 0 to 20%).

(4) Yield: 500 mg, 60%; brown oil.

(5) .sup.1H NMR (400 MHz, CDCl.sub.3; Me.sub.4Si): =12.2 (s. br, NH), 6.78 (d, CHFOCF.sub.3, .sup.2J.sub.H-F=57.5 Hz), 6.77 (s, CH.sub.arom), ppm.

(6) .sup.19F NMR (376 MHz, CDCl.sub.3; CFCl.sub.3): =60.0 (d, CHFOCF.sub.3, .sup.4J.sub.H-F=5 Hz), 62.3 (s, CF.sub.3), 121.7 (qd, CHFOCF.sub.3, .sup.2J.sub.H-F=57 Hz, .sup.4J.sub.H-F=5 Hz) ppm.

(7) .sup.13C NMR (100 MHz, CDCl.sub.3; Me.sub.4Si): =140.8 (m, CCF.sub.3 and CCHFOCF.sub.3), 120.3 and 121.0 (CF.sub.3 and OCF.sub.3, .sup.1J.sub.C-F=269 and 262 Hz), 104.0 (CH.sub.arom), 99.1 (dd, CHFOCF.sub.3, .sup.1J.sub.C-F=230 Hz, .sup.3J.sub.C-F=3.5 Hz) ppm.

(8) HRMS (ESI) calcd for C.sub.6H.sub.4F.sub.7N.sub.2O [M+H]: 253.0206. Found: 253.0213.

EXAMPLE 3

3-(fluoro(trifluoromethoxy)methyl)-5-(perfluoroethyl)-1H-pyrazole (I-2)

(9) (preparation see Example 2 using N-benzyl-3,3,4,4,4-pentafluorobutan-2-imine (500 mg, 1.73 mmol) and II-1 (2.08 mmol)).

(10) Yield: 99% (by .sup.19F NMR); yellow oil.

(11) .sup.1H NMR (400 MHz, CDCl.sub.3; Me.sub.4Si): =12.59 (s. br, NH), 6.82 (s, CH.sub.arom), 6.79 (d, CHFOCF.sub.3, .sup.2J.sub.H-F=57.5 Hz) ppm.

(12) .sup.19F NMR (376 MHz, CDCl.sub.3; CFCl.sub.3): =59.9 (d, CHFOCF.sub.3, .sup.4J.sub.H-F=5 Hz), 85.1 (s, CF.sub.2CF.sub.3), 113.6 (s, CF.sub.2CF.sub.3), 121.8 (dq, CHFOCF.sub.3, .sup.2J.sub.H-F=57.4 Hz, .sup.4J.sub.H-F=4.9 Hz) ppm.

(13) .sup.13C NMR (100 MHz, CDCl.sub.3; Me.sub.4Si): =140.9 and 139.2 (m, CCHFOCF.sub.3 and CC.sub.2F.sub.5), 120.7 (q, CHFOCF.sub.3, J=263 Hz), 118.4 (qt, CF.sub.2CF.sub.3, .sup.1J.sub.C-F=286 Hz, .sup.2J.sub.C-F=40 Hz), 109.8 (tq, CF.sub.2CF.sub.3, .sup.1J.sub.C-F=252 Hz, .sup.2J.sub.C-F=40 Hz), 105.2 (CH.sub.arom), 98.8 (dd, CHFOCF.sub.3, .sup.1J.sub.C-F=230 Hz, .sup.3J.sub.C-F=2.5 Hz) ppm.

(14) HRMS (ESI) calcd for C.sub.7H.sub.4F.sub.9N.sub.2O [M+H]: 303.0174. Found: 303.0168. b.p. 80-82 C.

EXAMPLE 4

Mixture 3-(difluoromethyl)-5-(fluoro(trifluoromethoxy)methyl)-1-methyl-1H-pyrazole and 5-(difluoromethyl)-3-(fluoro(trifluoromethoxy)methyl)-1-methyl-1H-pyrazole (7:3)

(15) (preparation see Example 2, using N-benzyl-1,1-difluoropropan-2-imine (3.35 mmol) and II-1 (3.97 mmol))

(16) Yield: 84% (by .sup.19F NMR, 7/3 I-3:I-4, both isomers separated by chromatography); both yellow oils.

3-(difluoromethyl)-5-(fluoro(trifluoromethoxy)methyl)-1-methyl-1H-pyrazole (I-3)

(17) .sup.1H NMR (400 MHz, CDCl.sub.3; Me.sub.4Si): =6.71 (dt, CHF.sub.2, .sup.2J.sub.H-F=53.5 Hz, .sup.4J.sub.H-F=1.2 Hz), 6.70 (d, CHFOCF.sub.3, .sup.2J.sub.H-F=57 Hz), 4.00 (s, NCH.sub.3), 6.68 (s, CH.sub.arom) ppm.

(18) .sup.19F NMR (376 MHz, CDCl.sub.3; CFCl.sub.3): =59.3 (m, OCF.sub.3), 113.4 (m, CHF.sub.2, .sup.2J.sub.H-F=53.5 Hz), 119.8 (d, CHFOCF.sub.3, .sup.2J.sub.H-F=57.5 Hz) ppm.

(19) .sup.13C NMR (100 MHz, CDCl.sub.3; Me.sub.4Si): =144.8 (d, CCHFOCF.sub.3, .sup.2J.sub.C-F=29 Hz), 136.9 (t, CCHF.sub.2, .sup.2J.sub.C-F=26 Hz), 121.1 (q, OCF.sub.3, 1J.sub.C-F=261 Hz), 108.3 (t, CHF.sub.2, .sup.1J.sub.C-F=237 Hz), 105.3 (t, CH.sub.arom), 101.0 (qd, CHFOCF3, .sup.1J.sub.C-F=227 Hz, .sup.3J.sub.C-F=4 Hz), 38.5 (NCH.sub.3), ppm.

(20) HRMS (ESI) calcd for C.sub.7H.sub.7F.sub.6N.sub.2O [M+H]: 249.0457. Found: 249.0460.

5-(difluoromethyl)-3-(fluoro(trifluoromethoxy)methyl)-1-methyl-1H-pyrazole (I-4)

(21) .sup.1H NMR (400 MHz, CDCl.sub.3; Me.sub.4Si): =6.76 (d, CHFOCF.sub.3, .sup.2J.sub.H-F=56 Hz), 6.68 (s, CH.sub.arom), 6.64 (t, CHF.sub.2, .sup.2J.sub.H-F=55 Hz), 3.98 (s, NCH.sub.3) ppm.

(22) .sup.19F NMR (376 MHz, CDCl.sub.3; CFCl.sub.3): =59.6 (d, OCF.sub.3, .sup.4J.sub.H-F=5.5 Hz), 112.2 (d, CHF.sub.2, .sup.2J.sub.H-F=55 Hz), 121.6 (qd, CHFOCF.sub.3, .sup.2J.sub.H-F=56 Hz, .sup.4J.sub.H-F=5.5 Hz) ppm.

(23) .sup.13C NMR (100 MHz, CDCl.sub.3; Me.sub.4Si): =145.7 (t, CCHF.sub.2, .sup.2J.sub.C-F=30 Hz), 135.5 (d, CCHFOCF.sub.3, .sup.2J.sub.C-F=26 Hz), 120.8 (q, OCF.sub.3, 1J.sub.C-F=263 Hz), 110.5 (t, CHF.sub.2, 1J.sub.C-F=234 Hz), 104.8 (CH.sub.arom), 98.5 (qd, CHFOCF.sub.3, .sup.1J.sub.C-F=228 Hz, .sup.3J.sub.C-F=4 Hz), 38.5 (NCH.sub.3), ppm.

(24) HRMS calcd for C.sub.7H.sub.7F.sub.6N.sub.2O [M+H]: 249.0457. Found: 249.0458.

EXAMPLE 5

3-(fluoro(trifluoromethoxy)methyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole (I-5)

(25) (preparation according to example 2, using N-benzyl-1,1,1-trifluoropropan-2-imine (3.35 mmol) and II-1 (3.97 mmol))

(26) Yield: 66% (by .sup.19F NMR); yellow oil.

(27) .sup.1H NMR (400 MHz, CDCl.sub.3; Me.sub.4Si): =6.84 (s, CH.sub.arom), 6.71 (d, CHFOCF.sub.3, .sup.2J.sub.H-F=57 Hz), 4.02 (s, NCH.sub.3) ppm.

(28) .sup.19F NMR (376 MHz, CDCl.sub.3; CFCl.sub.3): =59.3 (d, CHFOCF.sub.3, .sup.4J.sub.H-F=5 Hz), 60.9 (s, CF.sub.3), 120.1 (qd, CHFOCF.sub.3, .sup.2J.sub.H-F=57 Hz, .sup.4J.sub.H-F=5.4 Hz) ppm.

(29) .sup.13C NMR (100 MHz, CDCl.sub.3; Me.sub.4Si): =144.8 (d, CCHFOCF.sub.3, .sup.1J.sub.C-F=30 Hz), 133.6 (CCF.sub.3, .sup.2J.sub.C-F=40 Hz), 121.0 and 119.6 (q, OCF.sub.3 and CF.sub.3, .sup.1J.sub.C-F=261 and 269 Hz), 105.8 (CH.sub.arom), 100.8 (qd, CHFOCF.sub.3, .sup.1J.sub.C-F=227 Hz, .sup.3J.sub.C-F=4 Hz), 38.6 (NCH.sub.3) ppm.

(30) HRMS (ESI) calcd for C.sub.7H.sub.6F.sub.7N.sub.2O [M+H]: 267.0363. Found: 267.0347.

EXAMPLE 6

3-(fluoro(trifluoromethoxy)methyl)-1-methyl-5-(perfluoroethyl)-1H-pyrazole (I-6)

(31) (preparation according to example 2, using N-benzyl-1,1,1-trifluoropropan-2-imine (3.35 mmol) and II-1 (3.97 mmol))

(32) Yield: 81% (by .sup.19F NMR); yellow oil.

(33) .sup.1H NMR (400 MHz, CDCl.sub.3; Me.sub.4Si): =6.84 (s, CH.sub.arom), 6.72 (d, CHFOCF.sub.3, .sup.2J.sub.H-F=57.2 Hz), 4.04 (s, NCH.sub.3) ppm.

(34) .sup.19F NMR (376 MHz, CDCl.sub.3; CFCl.sub.3): =59.3 (d, CHFOCF.sub.3, .sup.2J.sub.H-F=5.4 Hz), 83.9 (s, CF.sub.2CF.sub.3), 110.7 (CF.sub.2CF.sub.3), 120.3 (dq, CHFOCF.sub.3, .sup.2J.sub.H-F=57.2 Hz, .sup.4J.sub.H-F=5.3 Hz) ppm.

(35) .sup.13C NMR (100 MHz, CDCl.sub.3; Me.sub.4Si): =145.2 (d, CCHFOCF.sub.3, .sup.2J.sub.C-F=29.5 Hz), 131.6 (t, CC.sub.2F.sub.5, .sup.2J.sub.C-F=28.7 Hz), 121.1 (q, CHFOCF.sub.3, .sup.1J.sub.C-F=262 Hz), 118.6 (qt, CF.sub.2CF.sub.3, .sup.1J.sub.C-F=286.3 Hz, .sup.2J.sub.C-F=37.2 Hz), 109.9 (tq, CF.sub.2CF.sub.3, .sup.1J.sub.C-F=253.5 Hz, .sup.2J.sub.C-F=40 Hz), 107.4 (CH.sub.arom), 100.7 (dd, CHFOCF.sub.3, .sup.1J.sub.C-F=227.4 Hz, .sup.4J.sub.C-F=4.3 Hz), 39.5 (NCH.sub.3) ppm.

(36) HRMS (ESI) calcd for C.sub.8H.sub.6F.sub.9N.sub.2O [M+H]: 317.0331. Found: 317.0298.

EXAMPLE 7

(E/Z)N-(4-(benzylamino)-1,5,5-trifluoro-1-(trifluoromethoxy)pent-3-en-2-ylidene)-N-methylmethanaminium tetrafluoroborate (V-1-1)

(37) 1,1,2-trifluoro-2-(trifluoromethoxy)ethene (0.44 mL, 3.97 mmol) was liquefied at 78 C. into a sealed tube equipped with a magnetic stirbar under inert atmosphere using a dry ice/acetone bath. A solution of dimethylamine (2M in THF, 2 mL, 4 mmol) was added via syringe, the mixture was raised to max. 20 C. over 20 min. BF.sub.3-Et.sub.2O (0.51 mL, 4.02 mmol) was added via syringe, the solution was vigorously stirred for 15 min. The resulting biphasic mixture was then added onto a solution of N-benzyl-1,1-difluoropropan-2-imine (728 mg, 3.97 mmol) in distilled THF (0.8-1 mol/L) under inert atmosphere into a Schlenk vessel via syringe. The mixture was stirred at room temperature for 30 min. The mixture was directly concentrated in vacuo, to yield the vinamidinium intermediate as thick orange oil (1.62 g, 92%).

(38) .sup.1H NMR (400 MHz, CD.sub.3CN; Me.sub.4Si): =8.33 (s. br, NH), 7.47 to 7.35 (m, 5H, arom), 6.81 (d, CHFOCF.sub.3, .sup.2J.sub.H-F=54.1 Hz), 6.64 (t, CHF.sub.2, .sup.2J.sub.H-F=52.6 Hz), 5.14 (s, CHCN(Me).sub.2), 4.56 (d, CH.sub.2NH), 3.35 (s. br, CN(CH.sub.3).sub.2) ppm.

(39) .sup.19F NMR (376 MHz, CD.sub.3CN; CFCl.sub.3): =59.8 (d, CHFOCF.sub.3, .sup.4J.sub.H-F=4.8 Hz), 120.6 (d, CHF.sub.2, .sup.2J.sub.H-F=53.1 Hz), 129.1 (d, CHFOCF.sub.3, .sup.2J.sub.H-F=54.5 Hz), 151.5 (s, BF.sub.4.sup.) ppm.

(40) .sup.13C NMR (100 MHz, CD.sub.3CN; Me.sub.4Si): =164.6 (d, COCHFOCF.sub.3, .sup.2J.sub.C-F=25.4 Hz), 159.9 (t, CCHF.sub.2, .sup.2J.sub.C-F=23.3 Hz), 135.4, 130.0, 129.5, 129.0 (arom.), 121.6 (q, OCF.sub.3, 1J.sub.C-F=263.3 Hz), 111.0 (td, CHF.sub.2, .sup.1J.sub.C-F=244.8 Hz, .sup.5J.sub.C-F=4.3 Hz), 100.9 (d, CHFOCF.sub.3, 1J.sub.C-F=238.3 Hz), 87.3 (CHCN.sup.+(Me).sub.2), 49.8 (CH.sub.2NH) ppm.

EXAMPLE 8

(E/Z)-4-(benzylamino)-1,5,5-trifluoro-1-(trifluoromethoxy)pent-3-en-2-one (V-2-1)

(41) (E/Z)N-(4-(b enzylamino)-1,5,5-trifluoro-1-(trifluoromethoxy)pent-3-en-2-ylidene)-N-methylmethanaminium tetrafluoroborate (V-1-1) (1.62 g, 3.66 mmol) was dissolved in 10 ml of Et.sub.2O before 1 ml of water and 1 mL of 1N HCl were added followed by a vigorous stirring of the mixture (pH of the solution between 3-4). The mixture was stirred for 1 h at RT, and the organic layer was separated, dried over Na.sub.2SO.sub.4, filtered and evaporated in vacuo, to yield (V-2-1) as orange oil (1.08 g, 3.30 mmol, 83%).

(42) .sup.1H NMR (400 MHz, CDCl.sub.3; Me.sub.4Si): =10.64 (s. br, NH), 7.40 to 7.28 (m, 5H, arom), 6.18 (t, CHF.sub.2, .sup.2J.sub.H-F=53.2 Hz), 5.81 (d, CHFOCF.sub.3, .sup.2J.sub.H-F=56.9 Hz), 5.68 (s, CHCO), 4.65 (d, CH.sub.2NH) ppm.

(43) .sup.19F NMR (376 MHz, CDCl.sub.3; CFCl.sub.3): =59.3 (d, CHFOCF.sub.3, .sup.4J.sub.H-F=4.7 Hz), 119.3 (d, CHF.sub.2, .sup.2J.sub.H-F=53.1 Hz), 135.5 (dq, CHFOCF.sub.3, .sup.2J.sub.H-F=56.6 Hz, .sup.4J.sub.H-F=4.6 Hz) ppm.

(44) .sup.13C NMR (100 MHz, CDCl.sub.3; Me.sub.4Si): =185.5 (d, CO, .sup.2J.sub.C-F=25.3 Hz), 157.3 (t, CCHF.sub.2, .sup.2J.sub.C-F=22.0 Hz), 136.1, 129.2, 128.4, 127.3 (arom), 121.2 (q, OCF.sub.3, .sup.1J.sub.C-F=261 Hz), 111.0 (t, CHF.sub.2, .sup.1J.sub.C-F=245 Hz), 101.3 (dq, CHFOCF.sub.3, .sup.1J.sub.C-F=245 Hz, .sup.3J.sub.C-F=2.5 Hz), 87.8 (t, CHCO, .sup.3J.sub.C-F=77.2 Hz), 48.1 (CH.sub.2NH) ppm.

(45) An interaction of (V-2-1) with hydrazine-hydrate according to the example 2 gave 5-(difluoromethyl)-3-(fluoro(trifluoromethoxy)methyl)-1H-pyrazole in 85% yield.