METHOD FOR PRODUCING SUBSTITUTED N-ARYL PYRAZOLES

Abstract

The present invention relates to a process for preparing compounds of the formula (I)

##STR00001##

starting from compounds of the formula (II)

##STR00002##

in which R.sup.1, R.sup.2 and R.sup.3 have the abovementioned meaning and where R.sup.1 and R.sup.3 are not simultaneously hydrogen in any compound.

The invention further provides the compounds of the formulae (IVa), (IVb), (V) and (VI) in which R.sup.1, R.sup.2, R.sup.3, R.sup.5, M and n have the abovementioned meaning.

##STR00003##

Claims

1: A process for preparing a compound of formula (I) ##STR00019## wherein R.sup.1 is hydrogen, cyano, halogen, C.sub.1-C.sub.4-alkyl optionally substituted by halogen or CN, or C.sub.1-C.sub.4-alkoxy optionally substituted by halogen, R.sup.2 is trifluoromethylsulfonyl, trifluoromethylsulfinyl, trifluoromethylsulfanyl, halogen, C.sub.1-C.sub.4-alkyl optionally substituted by halogen, or C.sub.1-C.sub.4-alkoxy optionally substituted by halogen, and R.sup.3 is hydrogen, cyano, halogen, C.sub.1-C.sub.4-alkyl optionally substituted by halogen or CN, or C.sub.1-C.sub.4-alkoxy optionally substituted by halogen, where R.sup.1 and R.sup.3 are not simultaneously hydrogen in any compound, starting from a compound of formula (II) wherein R.sup.1, R.sup.2 and R.sup.3 are as defined for formula (I) and wherein R.sup.1 and R.sup.3 are not simultaneously hydrogen in any compound, ##STR00020## comprising the following steps (1) to (3) (1) diazotization with of the compound of formula (II) with a compound of formula RNO.sub.2 or M(NO.sub.2).sub.n, wherein R is (C.sub.1-C.sub.6)-alkyl, n is one or two and M is ammonium, an alkali metal (with n=1) or an alkaline earth metal (with n=2), and at least one acid selected from mineral acids, sulfonic acids or carboxylic acids, wherein the carboxylic acids have a pKa of ≤2, (2) reduction with ascorbic acid; and (3) cyclization with a 1,1,3,3-tetra(C.sub.1-C.sub.4)alkoxypropane in a polar solvent in the presence of at least one acid selected from mineral acids, sulfonic acids or carboxylic acids, where the carboxylic acids have a pKa ≤2.

2: The process according to claim 1, wherein, after step (2), a base is added in a further step (2-a) and compounds of the formula (V) are precipitated out as a result ##STR00021## where R.sup.1, R.sup.2, R.sup.3 are defined according to claim 1, where R.sup.1 and R.sup.3 are not simultaneously hydrogen in any compound, n is one or two and M is ammonium, an alkali metal (with n=1) or an alkaline earth metal (with n=2).

3: The process according to claim 1, wherein, after step (2), or step (2-a), in a further step (2-b), at least one compound of the formula R.sup.5—OH is added, as a result of which, in the presence of at least one acid selected from mineral acids or sulfonic acids, compounds of the formula (VI) are formed, ##STR00022## where R.sup.1, R.sup.2, R.sup.3 are defined according to claim 1, where R.sup.1 and R.sup.3 are not simultaneously hydrogen in any compound and R.sup.5 is C.sub.1-C.sub.4-alkyl.

4: The process according to claim 1, wherein, after step (1), diazonium salts of the formula (III) are formed and these are then further reacted in step (2), ##STR00023## where R.sup.1, R.sup.2, R.sup.3 are defined according to claim 1, where R.sup.1 and R.sup.3 are not simultaneously hydrogen in any compound and X.sup.n− is a corresponding base of the acids according to claim 1, step (1), and n is 1 or 2.

5: The process according to claim 1, wherein, after step (2), a reaction mixture comprising intermediate compounds of the formula (IVa) and/or (IVb) is formed and this is then further reacted in step (3), (2-a) or (2-b) ##STR00024## where R.sup.1, R.sup.2, R.sup.3 are defined according to claim 1, where R.sup.1 and R.sup.3 are not simultaneously hydrogen in any compound.

6: The process according to claim 1, wherein R.sup.2 is halogen-substituted C.sub.1-C.sub.4-alkyl or halogen-substituted C.sub.1-C.sub.4-alkoxy.

7: The process according to claim 1, wherein R.sup.1 and R.sup.3 in each case independently of one another are a substituent selected from hydrogen, Cl, Br, F, C.sub.1-C.sub.3-alkyl, halogen-substituted C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-alkoxy or halogen-substituted C.sub.1-C.sub.3-alkoxy.

8: The process according to claim 1, wherein R.sup.1 is halogen or (C.sub.1-C.sub.3)-alkyl, R.sup.2 is fluorine-substituted C.sub.1-C.sub.4-alkyl or fluorine-substituted C.sub.1-C.sub.4-alkoxy and R.sup.3 is halogen, C.sub.1-C.sub.3-alkyl or fluorine-substituted C.sub.1-C.sub.3-alkyl, C.sub.1-C.sub.3-alkoxy or fluorine-substituted C.sub.1-C.sub.3-alkoxy.

9: The process according to claim 2, wherein the base in step (2-a) is selected from hydrogencarbonates, in particular NaHCO.sub.3 or KHCO.sub.3, carbonates, in particular Na.sub.2CO.sub.3 or K.sub.2CO.sub.3, or hydroxides, in particular NaOH or KOH.

10: The process according to claim 1, wherein the acid in step (1) is used in pure form or as an aqueous solution at concentrations from 10-99% by weight.

11: The process according to claim 3, wherein the alcohol R.sup.5—OH in step (2-b) is used simultaneously as solvent and reagent.

12: The process according to claim 3, wherein the compound R.sup.5—OH from step (2-b) is used as solvent for step (2-b) and step (3).

13: The process according to claim 1, wherein the said process comprises or consists of the steps (1), (2), (2-a), (2-b) and (3).

14: The process according to claim 1, wherein the said process comprises or consists of the steps (1), (2), (2-b) and (3).

15: The process according to claim 1, wherein the steps (1) and (2) are carried out together in a “one-pot” reaction, wherein the diazonium salt (III) formed after step (1) from compound (II) is not isolated or purified.

16: The process according to claim 3, wherein the steps (2-b) and (3) are carried out together in a “one-pot” reaction, wherein the compound (VI) formed after step (2-b) is not isolated or purified.

17: The process according to claim 1, wherein the said process is carried out as a “one-pot” reaction.

18: The process according to claim 17, wherein the conversion of a compound of the formula (II) over steps (1), (2) and (3), and optionally (2-b), into a compound of the formula (I) meets at least one of the following conditions: i) there is no isolation of the diazonium salt (III) from the reaction mixture of step (1); ii) there is no purification of the diazonium salt (III) from the reaction mixture of step (1); iii) there is no isolation of compounds of the formula (IVa), (IVb), (VI) or of any compounds of the formula (VIII) formed from the reaction mixture of step (2) or (2-b); ##STR00025## iv) there is no purification of compounds of the formula (IVa), (IVb), (VI) or of any compounds of the formula (VIII) formed from the reaction mixture of step (2) or (2-b); v) all steps (1), (2) and (3) and optionally (2-b) take place in the same reaction vessel; vi) from the solvent of step (1) only a small proportion of the solvent is removed prior to the start of step (2) or prior to the start of step (2-b) or (3), preferably less than 50% by volume (percent by volume based on the volume of solvent used), preferably less than 30% by volume, more preferably less than 10% by volume, even more preferably at most 5% by volume of the solvent (e.g. by evaporation, for example at a reaction temperature of about 40° C., or active removal, e.g. by distillation and/or reduced pressure based on 1013 hPa), preferably no solvent is actively removed by the solvent exchange between step (1) and step (2), between step (2), any step (2-b), and (3) and, if present, between step (2) and (2-b) (e.g. by distillation and/or reduced pressure based on 1013 hPa); vii) there is only a small exchange, preferably no exchange, of solvent between step (1) and (2) and between step (2) and (3) and, if present, between step (2) and (2-b) and between step (2-b) and (3), particularly preferably at most 50% by volume, preferably at most 40% by volume, more preferably at most 30% by volume, even more preferably at most 20% by volume, of the solvent used in step 1 is replaced by a new solvent (the new solvent can be the same solvent or another solvent).

19: The process according to claim 17, wherein neither the diazonium salt (III) formed after step (1) from compound (II) nor compounds of the formula (IVa), (IVb), (VI) or any compounds of the formula (VIII) formed are isolated or purified during the reaction sequence that leads to compound (I).

20: A compound of formula (V) ##STR00026## where R.sup.1, R.sup.2, R.sup.3 are defined according to claim 1, wherein R.sup.1 and R.sup.3 are not simultaneously hydrogen in any compound, n is one or two and M is ammonium, an alkali metal (with n=1) or an alkaline earth metal (with n=2).

21: A compound of formula (VI) ##STR00027## wherein R.sup.1 and R.sup.3 are defined according to claim 1, wherein R.sup.1 and R.sup.3 are not simultaneously hydrogen in any compound, R.sup.2 is halogen-substituted C.sub.1-C.sub.4-alkyl or halogen-substituted C.sub.1-C.sub.4-alkoxy and R.sup.5 is C.sub.1-C.sub.4-alkyl.

22: A compound of formula (IVa) or (IVb) ##STR00028## wherein R.sup.1 and R.sup.3 are defined according to claim 1, wherein R.sup.1 and R.sup.3 are not simultaneously hydrogen in any compound and R.sup.2 is halogen-substituted C.sub.1-C.sub.4-alkyl or halogen-substituted C.sub.1-C.sub.4-alkoxy.

Description

EXAMPLES

[0253] The following examples explain the process according to the invention in more detail without limiting the invention thereto.

[0254] Methods:

[0255] The NMR data of the examples are listed in conventional form (6 values, multiplet splitting, number of hydrogen atoms).

[0256] The solvent and the frequency in which the NMR spectrum was recorded are stated in each case.

[0257] .sup.a) HPLC (High Performance Liquid Chromatography) on a reversed-phase column (C18), Agilent 1100 LC system; Phenomenex Prodigy 100×4 mm ODS3; eluent A: acetonitrile (0.25 ml/1); eluent B: water (0.25 ml TFA/1); linear gradient from 5% acetonitrile to 95% acetonitrile in 7.00 min, then 95% acetonitrile for a further 1.00 min; oven temperature 40° C.; flow rate: 2.0 ml/min.

1) Step 1 and 2: Preparation of a Product Mixture Containing N-Arylhydrazino-2-Oxoacetic Acids (IVa)

Example 1-1) 2-[2-[2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazino]-2-oxoacetic acid (from Precursor of the General Formula (II)) (IVa-1)

[0258] 25.0 g (74.5 mmol, 1.0 eq) of 2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]aniline were initially charged in 75 ml of acetonitrile and 75 ml of 50% by weight sulfuric acid and admixed at 0-5° C. with a solution of 5.65 g of sodium nitrite (82.0 mmol, 1.1 eq) in 10.0 ml of water over 30 min. After addition was complete, the reaction mixture was stirred for 15 min at this temperature and a solution of 14.4 g (82.0 mmol, 1.1 eq) of ascorbic acid in 50 ml of water was metered in over 1 h. After addition was complete, the reaction mixture was warmed to room temperature over 1.5 h. The reaction mixture was subsequently stirred for 5 h at 40° C. and, after cooling to room temperature and addition of 150 ml of water, the product was filtered and, after drying under reduced pressure at 40° C., obtained as a yellow-orange solid: yield 26.4 g (65% of theory)

[0259] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=9.21 (d, J=4.0 Hz, 1H), 7.54 (s, 2H), 6.82 (d, J=4.8 Hz, 1H).

Example 1-2) 2-[2-[2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazino]-2-oxoacetic acid (from Precursor of the General Formula (II)) (IVa-1)

[0260] 53.4 g (136.0 mmol, 1.0 eq) of 2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]aniline were initially charged in 300 ml of glacial acetic acid and 150 ml of 50% by weight sulfuric acid and admixed at 0-5° C. with a solution of 11.3 g of sodium nitrite (163.0 mmol, 1.2 eq) in 20.0 ml of water over 30 min.

[0261] After addition was complete, the reaction mixture was stirred for 15 min at this temperature and a solution of 28.7 g (163.0 mmol, 1.2 eq) of ascorbic acid in 100 ml of water was metered in over 1 h. After addition was complete, the reaction mixture was warmed to room temperature over 1.5 h and washed with 200 ml of n-heptane. After addition of 500 ml of water, the product mixture was extracted with 500 ml of methyl tert-butyl ether, the organic phase was washed with 20% by weight NaCl solution and the crude product, after removal of the solvent under reduced pressure, was used directly in the next stage.

Example 1-3) 2-[2-[2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazino]-2-oxoacetic acid (from Precursor of the General Formula (II)) (IVa-1)

[0262] 53.4 g (136.0 mmol, 1.0 eq) of 2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]aniline were initially charged in 300 ml of glacial acetic acid and 150 ml of 50% by weight sulfuric acid and admixed at 0-5° C. with a solution of 11.3 g of sodium nitrite (163.0 mmol, 1.2 eq) in 20.0 ml of water over 30 min.

[0263] After addition was complete, the reaction mixture was stirred for 15 min at this temperature and a solution of 28.7 g (163.0 mmol, 1.2 eq) of ascorbic acid in 100 ml of water was metered in over 1 h. After addition was complete, the reaction mixture was warmed to room temperature over 1.5 h and washed with 200 ml of n-heptane. After addition of 500 ml of water, the product mixture was filtered and the crude product, after drying under reduced pressure at 40° C., was used directly in the next stage.

Step 2-a: Preparation of Sodium N-Arylhydrazino-2-Oxoacetate (V)

Example 1-4) sodium 2-[2-[2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazino]-2-oxoacetate (from Precursor Containing Compounds of the General Formula (IVa) and/or (IVb) from Step 2) (V-1)

[0264] 2.84 g (68.0 mmol, 1.0 eq) of the 2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazine derivative product mixture from step (2) were dissolved in 40 ml of acetone and admixed with 100 ml of water at room temperature. While monitoring the pH by means of a pH meter, the suspension is admixed dropwise with aqueous NaOH (10% by weight, approximately 37 ml) while stirring vigorously until a pH of 7.0 is reached. By adding 45.0 ml of saturated aqueous NaHCO.sub.3 solution, the pH is adjusted to 7.5 and the suspension is stirred at this pH and room temperature for 12 h. After addition of a further 100 ml of water, the solid was filtered and the filter cake was washed with 200 ml of water and subsequently washed three times with in each case 50 ml of methyl tert-butyl ether. After drying under reduced pressure at 40° C., the product was obtained as a light beige solid: yield 11.6 g (78% of theory).

[0265] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=9.8 (br s, 1H), 7.70 (s, 1H), 7.49 (s, 2H).

2) Step 2-b: Preparation of the Alkyl N-Arylhydrazino-2-Oxoacetates (VI)

Example 2-1) methyl 2-[2-[2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazino]-2-oxoacetate (from Precursor of the General Formula (V) from step 2-a) (VI-1)

[0266] 0.25 g (0.57 mmol, 1.0 eq) of sodium 2-[2-[2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazino]-2-oxoacetate were dissolved in 2.5 ml of methanol and admixed dropwise with 0.06 g (0.57 mmol, 1.0 eq) of 96% by weight sulfuric acid at 0-5° C. After addition was complete, the solution was heated to 65° C. and stirred at this temperature for 3.5 h. After cooling to room temperature, the solution was stirred into 5 ml of water, the solid formed was filtered off and the product, after drying under reduced pressure at 40° C., was isolated as a colourless solid: yield 0.24 g (89% of theory).

[0267] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=9.05 (br d, J=5.0 Hz, 1H), 7.51 (s, 2H), 6.85 (d, J=5.0 Hz, 1H), 3.93 (s, 3H).

Example 2-2) methyl 2-[2-[2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazino]-2-oxoacetate (from Precursor Containing Compounds of the General Formula (IVa) and/or (IVb) from Step 2) (VI-1)

[0268] 2.83 g (6.8 mmol, 1.0 eq) of the 2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazine derivative product mixture from step (2) were dissolved in 15 ml of methanol and admixed dropwise with 0.74 g of 96% by weight sulfuric acid (6.8 mmol, 1.0 eq) at 0-5° C. After addition was complete, the solution was heated to 65° C. and stirred at this temperature for 3.5 h.

[0269] After cooling to room temperature, the solution was stirred into 50 ml of water, the solid formed was filtered off and the product, after drying under reduced pressure at 40° C., was isolated as a colourless solid: yield 2.3 g (80% of theory).

3) Step 3: Preparation of the N-Arylpyrazoles (I)

Example 3-1) 1-[2,6-dichloro-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)phenyl]-1H-pyrazole (from Precursor Containing Compounds of the General Formula (IVa) and/or (Vb) from Step 2) (I-1)

[0270] 1.25 g (3.0 mmol, 1.0 eq) of the 2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazine derivative product mixture from step (2) were initially charged in 2.5 ml of acetonitrile and 2.0 ml of water and admixed dropwise with 1.8 g of 50% by weight sulfuric acid (79.2 mmol, 3.0 eq) at 0-5° C. After addition was complete, the suspension was heated to 40° C., then admixed with 0.54 g (3.3 mmol, 1.1 eq) of 1,1,3,3-tetramethoxypropane and the reaction was stirred at 60° C. for 6 h. After cooling to room temperature, the mixture was extracted twice with 20 ml of n-heptane, the combined organic phases were washed with 20 ml of saturated sodium hydrogencarbonate solution and, after removal of the solvent under reduced pressure, the product was obtained as a yellow oil: yield: 0.5 g (30% of theory).

Example 3-2) 1-[2,6-dichloro-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)phenyl]-1H-pyrazole (from Precursor of the General Formula (V) from Step 2-a) (I-1)

[0271] 11.6 g (26.4 mmol, 1.0 eq) of sodium 2-[2-[2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazino]-2-oxoacetate were initially charged in 80 ml of methanol and admixed dropwise with 8.10 g (79.2 mmol, 3.0 eq) of 96% by weight sulfuric acid at 0-5° C. After addition was complete, the suspension was heated to 65° C. and, after stirring at this temperature for 1 h, admixed with 4.34 g (26.4 mmol, 1.0 eq) of 1,1,3,3-tetramethoxypropane. The reaction was stirred at this temperature for a further 7 h. After cooling to room temperature, after addition of 80 ml of water, the mixture was extracted once with 80 ml of n-heptane, and once more with 40 ml of n-heptane, the combined organic phases were washed with 80 ml of water and, after removal of the solvent under reduced pressure, the product was obtained as a yellow-orange oil: yield: 9.6 g (92% of theory).

[0272] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=7.85 (d, J=1.8 Hz, 1H), 7.71 (s, 2H), 7.61 (d, J=2.5 Hz, 1H), 6.55 (dd, J=1.8/2.5 Hz, 1H).

Example 3-3) 1-[2,6-dichloro-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)phenyl]-1H-pyrazole (from Precursor of the General Formula (VI) from Step 2-b) (I-1)

[0273] 25.6 g (45%, 27.0 mmol, 1.0 eq) of methyl 2-[2-[2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazino]-2-oxoacetate from step (2-b) were initially charged in 100 ml of acetonitrile and admixed dropwise with 1.3 g (13.5 mmol, 0.5 eq) of 96% by weight sulfuric acid and 1.7 g (54.0 mmol, 2.0 eq) of methanol. After addition was complete, 4.4 g (27.0 mmol, 1.0 eq) of 1,1,3,3-tetramethoxypropane were added and the reaction was heated to 60° C. The reaction was stirred at this temperature for 8 h. After cooling to room temperature, the solvent was removed under reduced pressure and the residue was separated between 150 ml of n-heptane and 100 ml of 10% by weight NaOH. The aqueous phase was extracted twice with 50 ml of n-heptane and the combined organic phases were washed with 100 ml of 10% by weight HCl and, after removal of the solvent under reduced pressure, the product was obtained as a dark yellow oil: yield: 10.1 g (90% of theory).

4) Preparation of the N-Arylpyrazoles (I), Step 2-b Together with Step 3

Example 4-1) 1-[2,6-dichloro-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)phenyl]-1H-pyrazole (from Precursor Containing Compounds of the General Formula (IVa) and/or (IVb) from Step 2) (I-1)

[0274] 28.4 g (68.0 mmol, 1.0 eq) of the 2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazine derivative product mixture from step (2) were initially charged in 150 ml of methanol and admixed dropwise with 13.89 g of 96% by weight sulfuric acid (136.0 mmol, 2.0 eq) at 0-5° C. After addition was complete, the solution was heated to 65° C. and, after stirring at this temperature for 0.5 h, admixed with 10.05 g (61.2 mmol, 0.9 eq) of 1,1,3,3-tetramethoxypropane. The reaction mixture was stirred at this temperature for a further 7 h. After cooling to room temperature, after addition of 100 ml of water, the mixture was extracted once with 100 ml of n-heptane and once more with 40 ml of n-heptane. The combined organic phases were washed with 150 ml of aqueous NaOH (10% by weight) and, after removal of the solvent under reduced pressure, the product was obtained as a yellow oil: yield: 21.8 g (80% of theory).

Example 4-2) 1-[2,6-dichloro-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)phenyl]-1H-pyrazole (from Precursor of the General Formula (II): One-Pot Method with Step 1, Step 2 and Step 3) (I-1)

[0275] 27.9 g (68.0 mmol, 1.0 eq) of 2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]aniline were initially charged in 150 ml of glacial acetic acid and 75 ml of sulfuric acid (50% by weight) and admixed with a solution of 5.4 g of sodium nitrite (78.2 mmol, 1.15 eq) in 10.0 ml of water over 30 min at 0-5° C. After addition was complete, the reaction mixture was stirred for 15 min at this temperature and then 14.0 g (78.2 mmol, 1.15 eq) of ascorbic acid were added in one portion. The reaction mixture was warmed to room temperature over 2 h, then heated to 65° C., and 11.3 g (68.0 mmol, 1.0 eq) of 1,1,3,3-tetramethoxypropane were added at this temperature. The reaction was stirred at this temperature for a further 5 h. After cooling to room temperature and addition of 250 ml of water, the mixture was extracted once with 200 ml of n-heptane and once with 100 ml of n-heptane, the combined organic phases were washed with 150 ml of 10% by weight aqueous NaOH and the product was obtained, after removal of the solvent under reduced pressure, as an orange-red oil: yield 22.6 g (85% of theory).

[0276] The following N-arylpyrazoles of the general formula (I) were preparable analogously to example (4-1):

1-[2-Bromo-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-6-(trifluoromethoxy)phenyl]-1H-pyrazole (I-2)

[0277] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=7.92 (d, J=1.8 Hz, 1H), 7.84 (d, J=1.8 Hz, 1H), 7.62 (s, 1H), 7.61 (d, J=2.5 Hz, 1H), 6.54 (dd, J=1.8/2.5 Hz, 1H).

1-[2-Chloro-4-(1,1,1,2,3,3,3-heptafluoropropan-2-yl)-6-(trifluoromethoxy)phenyl]-1H-pyrazole (I-3)

[0278] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=7.85 (d, J=1.9 Hz, 1H), 7.76 (d, J=1.9 Hz, 1H), 7.62 (d, J=2.5 Hz, 1H), 7.59 (s, 1H), 6.54 (dd, J=1.9/2.5 Hz, 1H).

1-[2-Chloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]-1H-pyrazole (I-4)

[0279] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=8.43 (br s, 1H), 8.14 (d, J=2.5 Hz, 1H), 8.03 (br s, 1H), 7.86 (d, J=1.8 Hz, 1H), 6.69 (dd, J=1.8/2.5 Hz, 1H).

1-[2-Bromo-6-chloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]-1H-pyrazole (I-5)

[0280] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=8.12 (dd, J=0.6/2.5 Hz, 1H), 8.10 (br d, J=1.8 Hz, 1H), 8.06 (br d, J=1.8 Hz, 1H), 7.84 (dd, J=0.6/2.5 Hz, 1H), 6.59 (dd, J=1.8/2.5 Hz, 1H).

1-[2-Bromo-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]-1H-pyrazole (I-6)

[0281] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=8.50 (br s, 1H), 8.13 (d, J=2.5 Hz, 1H), 8.06 (br s, 1H), 7.84 (dd, J=1.8/2.5 Hz, 1H), 6.59 (dd, J=1.8/2.5 Hz, 1H).

1-[2-Methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]-1H-pyrazole (I-7)

[0282] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=7.87 (br s, 1H), 7.80 (d, J=1.8 Hz, 1H), 7.77 (br s, 1H), 7.56 (dd, J=0.7/1.8 Hz, 1H), 6.52 (dd, J=0.7/1.8 Hz, 1H), 2.09 (s, 3H).

[0283] The following intermediates of the general formula (IVa) were preparable analogously to example (4-1):

2-[2-[2-Chloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethoxy)phenyl]hydrazino]-2-oxoacetic acid (IVa-2)

[0284] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=14.2 (br s, 1H), 11.04 (s, 1H), 8.42 (s, 1H), 7.63 (d, J=2.0 Hz, 1H), 7.39 (s, 1H).

2-[2-[2-Bromo-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethoxy)phenyl]hydrazino]-2-oxoacetic acid (IVa-3)

[0285] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=14.1 (br s, 1H), 11.04 (s, 1H), 8.23 (s, 1H), 7.74 (d, J=2.0 Hz, 1H), 7.42 (s, 1H).

2-[2-[2-Chloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]hydrazino]-2-oxoacetic acid (IVa-4)

[0286] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=8.07 (br s, 1H), 7.84 (d, J=1.9 Hz, 1H), 7.58 (d, J=1.6 Hz, 1H).

2-[2-[2-Methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]hydrazino]-2-carboxylic acid (IVa-5)

[0287] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=10.84 (s, 1H), 7.75 (s, 1H), 7.60 (s, 1H), 7.51 (s, 1H).

2-[2-[2-Bromo-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]hydrazino]-2-oxoacetic acid (IVa-6)

[0288] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=11.0 (s, 1H), 8.13 (s, 1H), 8.01 (s, 1H), 7.66 (s, 1H).

[0289] The following intermediates of the general formula (V) were preparable analogously to example (1-4):

Sodium 2-[2-[2-chloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethoxy)phenyl]hydrazino]-2-oxoacetate (V-2)

[0290] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=9.92 (br s, 1H), 8.10 (s, 1H), 7.56 (s, 1H), 7.34 (s, 1H).

Sodium 2-[2-[2-bromo-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethoxy)phenyl]hydrazino]-2-oxoacetate (V-3)

[0291] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=9.90 (br s, 1H), 7.88 (s, 1H), 7.69 (s, 1H), 7.38 (s, 1H).

Sodium 2-[2-[2-chloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]hydrazino]-2-oxoacetate (V-4)

[0292] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=11.00 (s, 1H), 8.38 (s, 1H), 7.90 (s, 1H), 7.62 (s, 1H).

Sodium 2-[2-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]hydrazino]-2-oxoacetate (V-5)

[0293] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=7.53 (s, 1H), 7.47 (s, 1H), 7.41 (s, 1H).

Sodium 2-[2-[2-bromo-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]hydrazino]-2-oxoacetate (V-6)

[0294] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=7.97 (s, 1H), 7.84 (s, 1H), 7.63 (s, 1H).

[0295] The following intermediates of the general formula (VI) were preparable analogously to examples (2-1) and (2-2):

Ethyl 2-[2-[2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazino]-2-oxoacetate (VI-2)

[0296] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=11.15 (d, J=1.1 Hz, 1H), 8.12 (d, J=1.1 Hz, 1H), 7.56 (s, 2H), 4.27 (q, J=7.1 Hz, 2H), 1.27 (t, J=7.1 Hz, 3H).

Isopropyl 2-[2-[2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazino]-2-oxoacetate (VI-3)

[0297] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=11.11 (br s, 1H), 8.11 (br s, 1H), 7.56 (s, 1H), 5.05 (sept., J=6.2 Hz, 1H), 1.27 (d, J=6.2 Hz, 6H).

Methyl 2-[2-[2-chloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethoxy)phenyl]hydrazino]-2-oxoacetate (VI-4)

[0298] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=8.95 (d, J=4.6 Hz, 1H), 7.54 (d, J=1.9 Hz, 1H), 7.38 (s, 1H), 6.75 (d, J=4.6 Hz, 1H), 3.94 (s, 3H).

Ethyl 2-[2-[2-chloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethoxy)phenyl]hydrazino]-2-oxoacetate (VI-5)

[0299] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=8.98 (br s, 1H), 7.54 (s, 1H), 7.38 (s, 1H), 6.75 (s, 1H), 4.37 (q, J=7.2 Hz, 2H), 1.38 (t, J=7.2 Hz, 3H).

Methyl 2-[2-[2-bromo-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethoxy)phenyl]hydrazino]-2-oxoacetate (VI-6)

[0300] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=8.99 (d, J=4.6 Hz, 1H), 7.65 (d, J=1.9 Hz, 1H), 7.42 (s, 1H), 6.75 (d, J=4.6 Hz, 1H), 3.94 (s, 3H).

Ethyl 2-[2-[2-bromo-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethoxy)phenyl]hydrazino]-2-oxoacetate (VI-7)

[0301] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=8.98 (d, J=4.6 Hz, 1H), 7.69 (d, J=1.9 Hz, 1H), 7.42 (s, 1H), 6.75 (d, J=4.6 Hz, 1H), 4.37 (q, J=7.2 Hz, 2H), 1.37 (t, J=7.2 Hz, 3H).

Methyl 2-[2-[2-chloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]hydrazino]-2-oxoacetate (as 1:1 mixture of rotamers) (VI-8)

[0302] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=11.21 (s, 1H), 8.43 (s, 1H), 7.90 (d, J=1.9 Hz, 1H), 7.70 (d, J=1.9 Hz, 1H), 7.62 (d, J=1.9 Hz, 1H), 7.58 (d, J=1.9 Hz, 1H), 3.82 (s, 3H).

Ethyl 2-[2-[2-chloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]hydrazino]-2-oxoacetate (VI-9)

[0303] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=11.12 (s, 1H), 8.42 (s, 1H), 7.91 (d, J=1.9 Hz, 1H), 7.63 (d, J=1.6 Hz, 1H), 7.15 (q, J=7.2 Hz, 2H), 1.27 (t, J=7.2 Hz, 3H).

Methyl 2-[2-[2-bromo-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]hydrazino]-2-oxoacetate (VI-10)

[0304] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=11.02 (s, 1H) 8.18 (s, 1H), 8.02 (s, 1H), 7.66 (s, 1H), 3.82 (s, 3H).

Methyl 2-[2-[2-bromo-6-chloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazino]-2-oxoacetate (VI-11)

[0305] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=11.12 (s, 1H) 7.88 (s, 1H), 7.68 (s, 1H), 7.59 (s, 1H), 3.82 (s, 3H).

Methyl 2-[2-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]hydrazino]-2-oxoacetate (VI-12)

[0306] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=8.74 (br s, 1H), 7.68 (s, 1H), 7.55 (s, 1H), 6.27 (br s, 1H), 3.93 (s, 3H).

Ethyl 2-[2-[2-methyl-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]hydrazino]-2-oxoacetate (VI-13)

[0307] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=8.75 (br d, J=3.0 Hz, 1H), 7.68 (s, 1H), 7.52 (s, 1H), 6.27 (br d, J=3.0 Hz, 1H), 4.38 (q, J=7.2 Hz, 2H), 1.38 (t, J=7.2 Hz, 3H).

Ethyl 2-[2-[2-bromo-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]hydrazino]-2-oxoacetate (VI-14)

[0308] .sup.1H-NMR (DMSO-d.sub.6, 400 MHz) δ (ppm)=7.95 (s, 1H), 7.68 (s, 1H), 7.42 (br s, 1H), 4.27 (q, J=7.1 Hz, 2H), 1.25 (t, J=7.1 Hz, 3H).

Comparative Examples with Respect to the Adverse Effect of Water in the Case of Small Amounts of Acid

2-[2-[2,6-Dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazino]-2-oxoacetic acid (from Precursor of the General Formula (II)) (IVa-1)

[0309] 6.2 g (13.6 mmol, 1.0 eq) of 2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]aniline were initially charged in 30 ml of acetonitrile and 30 ml of 10% by weight sulfuric acid and admixed at 0-5° C. with a solution of 1.3 g of sodium nitrite (16.3 mmol, 1.2 eq) in 2.0 ml of water over 15 min. After addition was complete, the reaction mixture was stirred for 15 min at this temperature and a solution of 2.8 g (16.3 mmol, 1.2 eq) of ascorbic acid in 10 ml of water was metered in over 1 h. After addition was complete, the reaction mixture was heated to room temperature over 1.5 h. 37% of unreacted starting material was still detected by means of HPLC.sup.a, as was the formation of approximately 30% of undesired secondary components. The product was not isolated.

2-[2-[2,6-Dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]phenyl]hydrazino]-2-oxoacetic acid (from Precursor of the General Formula (II)) (IVa-1)

[0310] 8.0 g (17.2 mmol, 1.0 eq) of 2,6-dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]aniline were initially charged in 20 ml of acetonitrile and 8.0 g (41.3 mmol, 2.4 eq) of 50% by weight sulfuric acid and admixed at 0-5° C. with a solution of 1.4 g of sodium nitrite (19.7 mmol, 1.15 eq) in 2.5 ml of water over 15 min. After addition was complete, the reaction mixture was stirred for 15 min at this temperature and then 3.8 g (21.5 mmol, 1.25 eq) of ascorbic acid were added. After addition was complete, the reaction mixture was warmed to room temperature over 1.5 h. 17% of unreacted starting material was still detected by means of HPLC.sup.a, as was the formation of approximately 8% of secondary components. The product was not isolated.

Preparation of the Precursors of the Formula (II)

4-[1,2,2,2-Tetrafluoro-1-(trifluoromethyl)ethyl]aniline

[0311] 60.0 g (0.64 mol, 1.0 eq) of aniline were initially charged in 450 ml each of water and ethyl acetate and admixed successively with 4.5 g (13.0 mmol, 0.02 eq) of tetra-n-butylammonium hydrogensulfate and 144.0 g (0.70 mol, 1.1 eq) of sodium dithionite. 214.0 g (0.70 mol, 1.1 eq) of heptafluoroisopropyl iodide were metered in at room temperature over 3 h and the pH was maintained at 6.0-7.0 during the metering by adding 40% by weight aqueous K.sub.2CO.sub.3. After addition was complete, stirring was carried out for a further 3 h at approximately 21° C., then the phases were separated and the organic phase was washed with a solution of 40 ml each of 20% by weight NaCl and 2.5% by weight HCl. After removal of the solvent under reduced pressure, the product was obtained as a reddish oil: yield: 180.0 g (98% of theory).

[0312] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=7.35 (d, J=8.9 Hz, 2H), 6.72 (d, J=7.7 Hz, 2H), 3.91 (br s, 2H).

2,6-Dichloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]aniline

[0313] 180.0 g (0.64 mmol, 1.0 eq) of 4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]aniline were initially charged in 600 ml of ethyl acetate and 100 ml of water and admixed with 96.0 g (128.0 mmol, 2.0 eq) of chlorine gas over 5 h at 0-5° C. The phases were subsequently separated and the aqueous phase was extracted successively with a mixture of 100 ml of ethyl acetate and 50 ml of n-heptane and also a mixture of 50 ml of ethyl acetate and 25 ml of n-heptane. The combined organic phases were washed twice with 100 ml each time of 20% by weight NaCl solution and the product, after removal of the solvent, was obtained as a red-brown oil: yield 200.0 g (95% of theory).

[0314] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=7.41 (s, 2H), 4.76 (br s, 2H).

4-[1,2,2,2-Tetrafluoro-1-(trifluoromethyl)ethyl]-2-(trifluoromethoxy)aniline

[0315] 40.0 g (0.22 mol, 1.0 eq) of 2-trifluoromethoxyaniline were initially charged in 400 ml of water and 250 ml of ethyl acetate and admixed successively with 1.55 g (4.4 mmol, 0.02 eq) of tetra-n-butylammonium hydrogensulfate and 68.0 g (0.33 mol, 1.5 eq) of sodium dithionite. 100.2 g (0.33 mol, 1.5 eq) of heptafluoroisopropyl iodide were metered in at room temperature over 2.5 h and the pH was maintained at 4.0-5.0 during the metering by adding 40% by weight aqueous K.sub.2CO.sub.3. After addition was complete, stirring was carried out for a further 1 h at approximately 21° C., then the phases were separated. The organic phase was diluted with 100 ml of n-heptane, then washed with 250 ml of 20% by weight HCl, with 250 ml of saturated NaCl solution and with 250 ml of water. After removal of the solvent under reduced pressure, the product was obtained as a yellow oil: yield 76.4 g (92% of theory).

[0316] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=7.36 (s, 1H), 7.30 (d, J=8.6 Hz, 1H), 6.85 (d, J=8.6 Hz, 1H), 4.18 (br s, 2H).

2-Chloro-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethoxy)aniline

[0317] 30.0 g (79.7 mmol, 1.0 eq) of 4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-2-(trifluoromethoxy)aniline were dissolved in 120 ml of DMF and heated to 80° C. 14.2 g (79.7 mmol, 1.0 eq) of N-chlorosuccinimide were added in portions over 2 h at this temperature. After addition was complete, further stirring was carried out for 30 min at this temperature and, after cooling to room temperature, the mixture was separated between 200 ml of water and 100 ml of n-heptane and the organic phase was subsequently washed with 100 ml of water. After removal of the solvent under reduced pressure, the product was obtained as a brown oil: yield 30.3 g (99% of theory)

[0318] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=7.45 (s, 1H), 7.30 (s, 1H), 4.59 (s, 2H).

2-Bromo-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethoxy)aniline

[0319] 30.0 g (79.7 mmol, 1.0 eq) of 4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-2-(trifluoromethoxy)aniline were dissolved in 120 ml of DMF and heated to 80° C. 10.9 g (79.7 mmol, 1.0 eq) of N-bromosuccinimide were added in portions over 2 h at this temperature. After addition was complete, further stirring was carried out for 30 min at this temperature and, after cooling to room temperature, the mixture was separated between 200 ml of water and 100 ml of n-heptane and the organic phase was subsequently washed with 100 ml of water. After removal of the solvent under reduced pressure, the product was obtained as a brown oil: yield 31.6 g (93% of theory)

[0320] .sup.1H-NMR (CDCl.sub.3, 400 MHz) δ (ppm)=7.59 (s, 1H), 7.34 (s, 1H), 4.65 (br s, 2H).