PROCESS OF PREPARING 1,1'-DISULFANDIYLBIS(4-FLUORO-2-METHYL-5-NITROBENZOL)

Abstract

The present invention relates to a process for preparing 1,1′-disulfanediylbis(4-fluoro-2-methyl-5-nitrobenzene)

##STR00001## which serves as an intermediate for the preparation of insecticidally, acaricidally and nematicidally active phenyl sulfoxides.

Claims

1. A process for preparing 1,1′-disulfanediylbis(4-fluoro-2-methyl-5-nitrobenzene) of formula (I) ##STR00016## comprising (1) reacting, 3-fluorotoluene with chlorosulfonic acid to give a first mixture comprising 4-fluoro-2-methylbenzenesulfonyl chloride of formula (IX) and 2-fluoro-4-methylbenzenesulfonyl chloride of formula (X), ##STR00017## (2) nitrating, the first mixture from (1) with nitric acid to give a second mixture comprising 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride of formula (III), 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride of formula (XI) and 2-fluoro-4-methyl-5-nitrobenzenesulfonyl chloride of formula (XII), ##STR00018## (3), converting the second mixture from (2) to a third mixture by reducing the amount of 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride of formula (XI) by at least 50%, based on the starting amount of 4-fluoro-2-methyl-3-benzenesulfonyl chloride of formula (XI) in the second mixture, (4), reducing the third mixture from (3) to give a fourth mixture, comprising 1,1′-disulfanediylbis(4-fluoro-2-methyl-5-nitrobenzene) of formula (I) and at least one further compound (A) selected from 1,1′-disulfanediylbis(4-fluoro-2-methyl-3-nitrobenzene) of formula (XIII), ##STR00019## 1,1′-disulfanediylbis(2-fluoro-4-methyl-5-nitrobenzene) of formula (XIV), ##STR00020## 1-fluoro-4-[(4-fluoro-2-methyl-5-nitrophenyl)disulfanyl]-3-methyl-2-nitrobenzene of formula (XV), ##STR00021## 1 -fluoro-4-[(2-fluoro-4-methyl-5-nitrophenyl)disulfanyl]-5-methyl-2-nitrobenzene of formula (XVI), ##STR00022## and 1 -fluoro-4-[(2-fluoro-4-methyl-5-nitrophenyl)disulfanyl]-3-methyl-2-nitrobenzene of formula (XVII). ##STR00023##

2. The process according to claim 1, wherein (1) 3-fluorotoluene is chlorosulfonated without solvent in the presence of 2 to 5 molar equivalents of chlorosulfonic acid.

3. The process according to claim 1, wherein (1) is carried out at a temperature between −5 and 40° C.

4. The process according to claim 1, wherein three to 30 kilograms of water per kilogram of 3-fluorotoluene are added to the first mixture after process step (1), optionally without addition of a solvent, phases are separated and an organic phase is used in (2).

5. The process according to claim 1, wherein (2) is conducted in sulfuric acid as solvent.

6. The process according to claim 5, wherein sulfuric acid is present between 1 and 20 molar equivalents, based on a mixture of sulfonyl chlorides of formulae (IX) and (X).

7. The process according to claim 1, wherein in (2) 70 to 100% nitric acid is used.

8. The process according to claim 7, wherein nitric acid is present between 1 and 1.75 molar equivalents, based on the mixture of sulfonyl chlorides of formulae (IX) and (X).

9. The process according to claim 1, wherein (2) is carried out at a temperature between −5 and 70° C.

10. The process according to claim 1, wherein the second mixture after (2) is additionally a) seeded with 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride of formula (III), b) admixed with water, c) filtered, and d) washed with water.

11. The process according to claim 1, wherein the amount of 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride of formula (XI) is reduced in (3) by crystallization in a solvent.

12. The process according to claim 11, wherein the solvent is toluene, o-xylene, m-xylene, p-xylene, mesitylene, chlorobenzene, pentane, hexane, heptane, octane, isooctane, cyclopentane, cyclohexane, methylcyclohexane, decalin, special boiling point spirit 60/95, special boiling point spirit 80/110, special boiling point spirit 80/120, special boiling point spirit 100/125, special boiling point spirit 100/140, special boiling point spirit 100/155 or a mixture thereof.

13. The process according to claim 11, wherein the amount of solvent is between 1 and 10 kilograms per kilogram of second mixture.

14. The process according to claim 11, wherein crystallization is conducted at a temperature between −10 and 30° C.

15. The process according to claim 1, wherein in (4) sodium hypophosphite, sodium hypophosphite hydrate or ascorbic acid is used as reducing agent.

16. The process according to claim 1, wherein (4) is carried out in the presence of a catalyst.

17. The process according to claim 16, wherein the catalyst is an iodide, optionally potassium iodide.

18. The process according to claim 1, wherein (4) is carried out in a solvent.

19. The process according to claim 18, wherein the solvent is formic acid, acetic acid, propionic acid or a mixture thereof.

20. The process according to claim 1, wherein at least one compound (A) is selected from compound of formula (XV), and compound of formula (XVI).

21. The process according to claim 1, comprising (5) converting the fourth mixture from (4) to a fifth mixture by reducing an amount of one or more compounds (A) each by at least 50%, based on a starting amount of each compound (A) in the fourth mixture.

22. The process according to claim 21, wherein an amount of two or more compounds (A) is reduced.

23. The process according to claim 21, wherein at least one compound (A) is selected from compound of formula (XV), and compound of formula (XVI).

24. The process according to claim 21, wherein an amount of one or more compounds (A) is reduced in (5) by crystallization in a solvent.

25. The process according to claim 24, wherein the solvent is formic acid, acetic acid, propionic acid or a mixture thereof.

26. The process according to claim 24, wherein the amount of solvent is between 1 and 5 kilograms per kilogram of fourth mixture.

27. The process according to claim 24, wherein the crystallization is conducted at a temperature between 0 and 100° C.

Description

EXAMPLE 1

4-Fluoro-2-methylbenzenesulfonyl chloride (IX)

[0056] 90 g (0.749 mol) of chlorosulfonic acid (97% purity) was initially charged and cooled to from 0 to 5° C. 27.8 g (0.25 mol) of 3-fluorotoluene (99% purity) were metered in at this temperature within 80 minutes. The mixture was subsequently stirred for a further 4 hours at 0 to 5° C., left overnight to come to room temperature and then the reaction mixture was stirred into 700 g of ice-water, the temperature not rising above 10° C. The emulsion obtained was then extracted three times with 100 ml of methylene chloride each time. The combined organic phases were concentrated under a gentle vacuum. This gave 44.4 g of a yellowish oil.

[0057] Composition:

[0058] HPLC: 86.1 area % 4-fluoro-2-methylbenzenesulfonyl chloride (IX) (corresponding to 73% of theory) [0059] 8.1 area % 2-fluoro-4-methylbenzenesulfonyl chloride (X)

EXAMPLE 2

4-Fluoro-2-methylbenzenesulfonyl chloride (IX)

[0060] 72.1 g (0.6 mol) of chlorosulfonic acid (97% purity) was initially charged and cooled to from 0 to 5° C. 22.25 g (0.2 mol) of 3-fluorotoluene (99% purity) were metered in at this temperature within 120 minutes. The mixture was subsequently stirred for a further 2 hours at 10 to 12° C. The reaction mixture was subsequently metered at 45 to 50° C. into 100 g of water and the phases were separated. This gave 33.3 g of a cloudy oil.

[0061] Composition:

[0062] HPLC: 87.3 area % 4-fluoro-2-methylbenzenesulfonyl chloride (IX) (corresponding to 70% of theory) [0063] 9.0 area % 2-fluoro-4-methylbenzenesulfonyl chloride (X)

EXAMPLE 3

4-Fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III)

[0064] 35.7 ml of conc. sulfuric acid (65.38 g; 12.8 molar equivalents, based on the sum total of the isomeric fluoromethylbenzenesulfonyl chlorides) were initially charged and to this were metered in at an internal temperature of 5° C. 10.61 g (0.05 mol) of 4-fluoro-2-methylbenzenesulfonyl chloride having a purity of 90% (additionally containing 8.3% of 2-fluoro-4-methylbenzenesulfonyl chloride). Then, at an internal temperature of 0 to 5° C., 5.85 g (0.065 mol) of 70% nitric acid (1.3 molar equivalents, based on the sum total of the isomeric fluoromethylbenzenesulfonyl chlorides) were metered in within 10 minutes. After the end of the metered addition of nitric acid, the mixture was stirred further for 1 hour at 10 to 15° C. The reaction mixture (suspension) was then stirred into 200 ml of ice-water. Extraction was performed twice with 50 ml of methylene chloride, the combined organic phases were washed once with 30 ml of water, dried and concentrated under reduced pressure. This gave 12.7 g of a yellowish oil which solidified in crystalline form after some time.

[0065] Composition:

[0066] HPLC: 87.5 area % sum total of 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III) and 2-fluoro-4-methyl-5-nitrobenzenesulfonyl chloride (XII) [0067] 9.2 area % 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride (XI)

[0068] .sup.19F NMR: 83.0% 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III) (−106.2 ppm) [0069] 8.6% 2-fluoro-4-methyl-5-nitrobenzenesulfonyl chloride (XII) (−100.2 ppm) [0070] 8.3% 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride (XI) (−111.3 ppm)

EXAMPLE 4

4-Fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III)

[0071] 22.3 ml of conc. sulfuric acid (40.87 g; 4 molar equivalents, based on the sum total of the isomeric fluoromethylbenzenesulfonyl chlorides) were initially charged and to this were metered in at an internal temperature of 20° C. 21.22 g (0.1 mol) of 4-fluoro-2-methylbenzenesulfonyl chloride having a purity of 90% (additionally containing 8.3% of 2-fluoro-4-methylbenzenesulfonyl chloride). Then, at an internal temperature of 20 to 23° C., 7.88 g (0.125 mol) of 100% nitric acid (1.25 molar equivalents, based on the sum total of the isomeric fluoromethylbenzenesulfonyl chlorides) were metered in within 15 minutes. After the end of the metered addition of nitric acid, the mixture was stirred further for 2 hours at 20 to 22° C. The reaction mixture (suspension) was then stirred into 300 ml of ice-water. Extraction was performed twice with 50 ml of methylene chloride, the combined organic phases were washed once with 30 ml of water, dried and concentrated under reduced pressure. This gave 25.7 g of a yellowish oil which solidified in crystalline form after some time.

[0072] Composition:

[0073] HPLC: 86.3 area % sum total of 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III) and 2-fluoro-4-methyl-5-nitrobenzenesulfonyl chloride (XII) [0074] 10.6 area % 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride (XI)

[0075] .sup.19F NMR: 81.9% 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III) (−106.2 ppm) [0076] 8.7% 2-fluoro-4-methyl-5-nitrobenzenesulfonyl chloride (XII) (−100.2 ppm) [0077] 9.4% 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride (XI) (−111.3 ppm)

EXAMPLE 5

4-Fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III)

[0078] 51 ml of conc. sulfuric acid (57.2 g; 4 molar equivalents, based on the sum total of the isomeric fluoromethylbenzenesulfonyl chlorides) were initially charged and to this were metered in at an internal temperature of 20 to 25° C. 30.33 g (0.14 mol) of a mixture having the composition 90.0% 4-fluoro-2-methylbenzenesulfonyl chloride and 6.3% 2-fluoro-4-methylbenzenesulfonyl chloride. Then, at an internal temperature of 20 to 25° C., 11.03 g (0.175 mol) of 100% nitric acid (1.25 molar equivalents, based on the sum total of the isomeric fluoromethylbenzenesulfonyl chlorides) were metered in within 190 minutes. After the end of the metered addition of nitric acid, the mixture was stirred further for 2 hours at 30 to 35° C. The phases were then separated at this temperature. The upper phase was stirred into 140 ml of water. The precipitated solids were filtered off, washed with water and dried under reduced pressure at 40° C. This gave 31.84 g of a yellowish solid.

[0079] Composition:

[0080] HPLC: 84.9 area % sum total of 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III) and 2-fluoro-4-methyl-5-nitrobenzenesulfonyl chloride (XII) [0081] 11.0 area % 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride (XI)

[0082] .sup.19F NMR: 81.9% 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III) (−106.2 ppm) [0083] 8.0% 2-fluoro-4-methyl-5-nitrobenzenesulfonyl chloride (XII) (−100.2 ppm) [0084] 10.2% 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride (XI) (−111.3 ppm)

[0085] 31.05 g of this solid were stirred into 100 ml of methylcyclohexane (MCH) for 1 hour at room temperature.

[0086] The remaining solid was then filtered off with suction, washed with 20 ml of MCH and dried under reduced pressure at 45° C. This gave 25.77 g of colourless solid.

[0087] Composition:

[0088] HPLC: 94.8 area % sum total of 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III) and 2-fluoro-4-methyl-5-nitrobenzenesulfonyl chloride (XII) [0089] 1.8 area % 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride (XI)

[0090] .sup.19F NMR: 91.0% 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III) (−106.2 ppm) [0091] 6.5% 2-fluoro-4-methyl-5-nitrobenzenesulfonyl chloride (XII) (−100.2 ppm) [0092] 1.7% 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride (XI) (−111.3 ppm)

EXAMPLE 6

4-Fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III)

[0093] A reaction vessel was initially charged with 418.7 ml (766.2 g; 3 molar equivalents) of conc. sulfuric acid and this was cooled to 10° C. Subsequently, first 330 g (1.525 mol) of a mixture having the composition 92.4% 4-fluoro-2-methylbenzenesulfonyl chloride and 4% 2-fluoro-4-methylbenzenesulfonyl chloride and 211 g (0.979 mol) of a mixture having the composition 91.1% 4-fluoro-2-methylbenzenesulfonyl chloride and 5.7% 2-fluoro-4-methylbenzenesulfonyl chloride were metered in and thereafter 196.9 g (3.125 mol) of 100% nitric acid (1.25 molar equivalents, based on the sum total of the isomeric fluoromethylbenzenesulfonyl chlorides) were metered in within 120 minutes. After the end of the metered addition of nitric acid, the mixture was stirred further for 7 days at 20 to 25° C. The reaction mixture was then dissolved in 800 ml of methylene chloride. The solution was stirred into 1000 ml of ice-water, the phases were separated, the aqueous phase was extracted with 200 ml of methylene chloride and the combined organic phases were washed twice with 750 ml of water each time. After drying over sodium sulfate and concentrating under reduced pressure, this gave 644.8 g of a yellowish oil which later solidified.

[0094] Composition:

[0095] HPLC: 85.0 area % sum total of 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III) and 2-fluoro-4-methyl-5-nitrobenzenesulfonyl chloride (XII) [0096] 10.4 area % 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride (XI)

[0097] .sup.19F NMR: 83.1% 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III) (−106.2 ppm) [0098] 6.5% 2-fluoro-4-methyl-5-nitrobenzenesulfonyl chloride (XII) (−100.2 ppm) [0099] 8.5% 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride (XI) (−111.3 ppm)

[0100] 25 g of the product thus prepared were initially charged in 115.5 g of methylcyclohexane and the mixture was heated with stirring to 83° C., until a clear solution was formed. This solution was then slowly cooled to 20° C. and stirred at this temperature for a further 3 hours. The solid was filtered off with suction, washed with a little MCH and dried. This gave 19.2 g of a pale yellow solid.

[0101] Composition:

[0102] HPLC: 94.0 area % sum total of 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III) and 2-fluoro-4-methyl-5-nitrobenzenesulfonyl chloride (XII) [0103] 1.1 area % 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride (XI)

[0104] .sup.19F NMR: 92.2% 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III) (−106.2 ppm) [0105] 6.9% 2-fluoro-4-methyl-5-nitrobenzenesulfonyl chloride (XII) (−100.2 ppm) [0106] <0.1% 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride (XI) (−111.3 ppm)

EXAMPLE 7

1,1′-disulfanediylbis(4-fluoro-2-methyl-5-nitrobenzene) (I)

a) Synthesis

[0107] 63.0 g of crude (not purified by crystallization from MCH) of 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride having the composition according to HPLC of 84.3 area % sum total of 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III) and 2-fluoro-4-methyl-5-nitrobenzenesulfonyl chloride (XII) and 10.8 area % 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride (XI) (approx. 95.1%, sum total of the isomers, corresponding to 0.236 mol) were initially charged in 250 g of acetic acid, 3.92 g (23.6 mmol) of potassium iodide were added and then 37.56 g (0.354 mol) of sodium hypophosphite monohydrate were metered in at 60° C. within 100 minutes. The mixture was stirred at 60° C. for 5 hours, then cooled to 40° C., 100 ml of water were added, the mixture was stirred at 30° C. for 30 minutes, and the solid was filtered off, washed with 60 ml of water and dried. This gave 41.65 g of solid.

[0108] Composition:

[0109] HPLC: 64.2 area % 1,1′-disulfanediylbis(4-fluoro-2-methyl-5-nitrobenzene) (I) [0110] 13.3 area % 1-fluoro-4-[(2-fluoro-4-methyl-5-nitrophenyl)disulfanyl]-5-methyl-2-nitrobenzene (XVI) [0111] 18.1 area % 1-fluoro-4-[(4-fluoro-2-methyl-5-nitrophenyl)disulfanyl]-3-methyl-2-nitrobenzene (XV) [0112] 1.8 area % 1-fluoro-4-[(2-fluoro-4-methyl-5-nitrophenyl)disulfanyl]-3-methyl-2-nitrobenzene (XVII) [0113] 1.2 area % 1,1′-disulfanediylbis(4-fluoro-2-methyl-3-nitrobenzene) (XIII)

b) Purification

[0114] The solid from a) was dissolved in 84 g of acetic acid at approx. 80° C. The solution was left to cool to 20° C. with stirring, and the precipitated crystals were filtered off, washed with a little petroleum ether and dried. 32.5 g of solid were obtained.

[0115] Composition:

[0116] HPLC: 79.7 area % 1,1′-disulfanediylbis(4-fluoro-2-methyl-5-nitrobenzene) (I) [0117] 4.3 area % 1-fluoro-4-[(2-fluoro-4-methyl-5-nitrophenyl)disulfanyl]-5-methyl-2-nitrobenzene (XVI) [0118] 14.8 area % 1-fluoro-4-[(4-fluoro-2-methyl-5-nitrophenyl)disulfanyl]-3-methyl-2-nitrobenzene (XV) [0119] 0.4 area % 1-fluoro-4-[(2-fluoro-4-methyl-5-nitrophenyl)disulfanyl]-3-methyl-2-nitrobenzene (XVII) [0120] 0.7 area % 1,1′-disulfanediylbis(4-fluoro-2-methyl-3-nitrobenzene) (XIII)

EXAMPLE 8

1,1′-disulfanediylbis(4-fluoro-2-methyl-5-nitrobenzene) (I)

a) Synthesis

[0121] 4.1 kg of 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride having the composition according to HPLC of 93.3 area % sum total of 4-fluoro-2-methyl-5-nitrobenzenesulfonyl chloride (III) and 2-fluoro-4-methyl-5-nitrobenzenesulfonyl chloride (XII) and 2.3 area % 4-fluoro-2-methyl-3-nitrobenzenesulfonyl chloride (XI) (approx. 95.6%, sum total of isomers, corresponding to 15.45 mol) were initially charged in 30.5 kg of acetic acid, 0.25 kg (1.51 mol) of potassium iodide were added and then 2.388 kg (27.1 mol) of sodium hypophosphite were metered in at 40° C. within 100 minutes. The mixture was stirred at 40° C. for 16 hours, approx. 20 1 of acetic acid were removed by distillation, the residue was metered into 20 1 of water and this mixture was stirred at 40° C. for 1 hour. The precipitated solid was filtered off and washed with a total of 30 1 of water. After drying this gave 2.86 kg of yellow solid.

[0122] Composition:

[0123] HPLC: 81.8 area % 1,1′-disulfanediylbis(4-fluoro-2-methyl-5-nitrobenzene) (I) [0124] 10.2 area % 1-fluoro-4-[(2-fluoro-4-methyl-5-nitrophenyl)disulfanyl]-5-methyl-2-nitrobenzene (XVI) [0125] 3.4 area % 1-fluoro-4-[(4-fluoro-2-methyl-5-nitrophenyl)disulfanyl]-3-methyl-2-nitrobenzene (XV) [0126] 1.6 area % 1,1′-disulfanediylbis(2-fluoro-4-methyl-5-nitrobenzene) (XIV)

b) Purification

[0127] 4.4 kg of a solid which had been prepared analogously to example 8a) and had the following composition:

[0128] HPLC: 80.4 area % 1,1′-disulfanediylbis(4-fluoro-2-methyl-5-nitrobenzene) (I) [0129] 13.1 area % 1-fluoro-4-[(2-fluoro-4-methyl-5-nitrophenyl)disulfanyl]-5-methyl-2-nitrobenzene (XVI) [0130] 4.6 area % 1-fluoro-4-[(4-fluoro-2-methyl-5-nitrophenyl)disulfanyl]-3-methyl-2-nitrobenzene (XV) [0131] 0.3 area % 1,1′-disulfanediylbis(2-fluoro-4-methyl-5-nitrobenzene) (XIV)

[0132] were dissolved in 8.5 1 of acetic acid at 100° C. This solution was slowly cooled to 30° C., with crystallization commencing from approx. 60° C. The precipitated solid was filtered off with suction, washed with acetic acid and water and dried. This gave 3.52 kg of solid.

[0133] Composition: (sum total 97%)

[0134] HPLC: 96.9 area % 1,1′-disulfanediylbis(4-fluoro-2-methyl-5-nitrobenzene) (I) [0135] 2.7 area % 1-fluoro-4-[(2-fluoro-4-methyl-5-nitrophenyl)disulfanyl]-5-methyl-2-nitrobenzene (XVI) [0136] 0.3 area % 1-fluoro-4-[(4-fluoro-2-methyl-5-nitrophenyl)disulfanyl]-3-methyl-2-nitrobenzene (XV) [0137] <0.1 area % 1,1′-disulfanediylbis(2-fluoro-4-methyl-5-nitrobenzene) (XIV)

[0138] It is clear that the amount of compound of formula (XI), which for example is reduced compared to example 7, brings about a better purity of the compound of formula (I).