Method for producing bis(3-aminophenyl)disulfides and 3-aminothiols

Abstract

The present invention relates to a novel method for preparing bis(3-aminophenyl) disulphides of the general formula (I) and 3-aminothiols of the general formula (II), ##STR00001##
where X,Y have the meanings stated in the description,
which serve as intermediates for the preparation of phenyl sulphoxides having insecticidal, acaricidal and nematicidal activity.

Claims

1. A bis(3-nitrophenyl) disulphide of the formula (IV) ##STR00012## in which the residues X and Y are each independently methyl, ethyl, methoxy, ethoxy, or fluorine.

2. A compound of the formula (IV) according to claim 1, wherein the compound is 1,1-disulfandiylbis(4-fluoro-2-methyl-5-nitrobenzene), 1,1-disulfandiylbis(2-fluoro-4-methyl-5-nitrobenzene), 1,1-disulfandiylbis(4-fluoro-2-methyl-3-nitrobenzene), 1-fluoro-4-[(4-fluoro-2-methyl-5-nitrophenyl)disulfanyl]-3-methyl-2-nitrobenzene, 1fluoro-4-[(2-fluoro-4-methyl-5-nitrophenyl)disulfanyl]-5-methyl-2-nitrobenzene, or 1-fluoro-4-[(2-fluoro-4-methyl-5-nitrophenyl)disulfanyl]-3-methyl-2-nitrobenzene.

3. A compound of the formula (IV) according to claim 1 that is 1,1-disulfandiylbis(4-fluoro-2-methyl-5-nitrobenzene).

4. A compound of the formula (IV) according to claim 1 that is 1,1-disulfandiylbis(2-fluoro-4-methyl-5-nitrobenzene).

5. A compound of the formula (IV) according to claim 1 that is 1,1-disulfandiylbis(4-fluoro-2-methyl-3-nitrobenzene).

6. A compound of the formula (IV) according to claim 1 that is 1-fluoro-4-[(4-fluoro-2-methyl-5-nitrophenyl)disulfanyl]-3-methyl-2-nitrobenzene.

7. A compound of the formula (IV) according to claim 1 that is 1-fluoro-4-[(2-fluoro-4-methyl-5-nitrophenyl)disulfanyl]-5-methyl-2-nitrobenzene.

8. A compound of the formula (IV) according to claim 1 that is 1-fluoro-4-[(2-fluoro-4-methyl-5-nitrophenyl)disulfanyl]-3-methyl-2-nitrobenzene.

9. A bis(3-aminophenyl) disulphide of the formula (I) ##STR00013## in which the residues X and Y are each independently methyl, ethyl, or fluorine, with the proviso that at least one of X and Y in each ring is not fluorine.

10. A compound of the formula (I) according to claim 9, wherein the compound is 3,3-disulfandiylbis(6-fluoro-4-methylaniline), 3,3-disulfandiylbis(4-fluoro-6-methylaniline), 3,3-disulfandiylbis(2-fluoro-6-methylaniline), 3-[(5-amino-4-fluoro-2-methylphenyl)disulfanyl]-6-fluoro-2-methylaniline, 5-[(5-amino-2-fluoro-4-methylphenyl)disulfanyl]-2-fluoro-4-methylaniline, or 3-[(5-amino-2-fluoro-4-methylphenyl)disulfanyl]-6-fluoro-2-methylaniline.

11. A compound that is 3-amino-2-fluoro-4-methylbenzenethiol or 5-amino-2-fluoro-4-methylbenzenethiol.

12. A compound according to claim 11 that is 3-amino-2-fluoro-4-methylbenzenethiol.

13. A compound according to claim 11 that is 5-amino-2-fluoro-4-methylbenzenethiol.

Description

EXAMPLE 1

1,1-Disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene)

(1) 3.32 g [20 mmol] of potassium iodide are added to a solution of 50.7 g [200 mmol] of 4-fluoro-2-methyl-5-nitrobenzenesulphonyl chloride in 350 ml of acetic acid and the mixture is heated to 40-45 C. At this temperature, 30.39 g [345 mmol] of sodium hypophosphite are added portionwise over the course of about 50 minutes. The mixture is stirred for 8 hours at 40-45 C., cooled to room temperature and the majority of the acetic acid is distilled off. The residue is stirred with 150 ml of water. The precipitated solid is collected under suction, washed with water and dried. 36.75 g of solid are obtained with a purity of 97.4% (w/w) (96.1% of theory).

(2) .sup.1H-NMR (600 MHz, CD.sub.3CN): =2.50 (s, 6H), 7.34 (d, J=12.0 Hz, 2H), 8.13 (d, J=7.5 Hz, 2H) ppm.

(3) .sup.19F-NMR (566 MHz, CDCl.sub.3): =118.6 ppm.

EXAMPLE 2

1,1-Disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene)

(4) 1.66 g [10 mmol] of potassium iodide and 10 g [75.8 mmol] of 50% aqueous hypophosphorous acid are added to a solution of 12.7 g [50 mmol] of 4-fluoro-2-methyl-5-nitrobenzenesulphonyl chloride in 100 ml of acetic acid. The mixture is heated to 60-95 C. for 6 hours, cooled to room temperature and is concentrated on a rotary evaporator. The residue is taken up in 100 ml of water and is extracted with 100 ml of ethyl acetate. The organic phase is washed with 20 ml of semiconcentrated sodium bisulphite solution, 50 ml of water and 100 m of sodium bicarbonate solution, and is then dried and concentrated. 8.8 g of solid are obtained with a purity of 92.1% (87% of theory).

EXAMPLE 3

1,1-Disulphanediylbis(2-fluoro-4-methyl-5-nitrobenzene)

(5) Analogous to the procedure for example 1.

(6) .sup.19F-NMR (566 MHz, CDCl.sub.3): =101.6 ppm.

1,1-Disulphanediylbis(4-fluoro-2-methyl-3-nitrobenzene)

(7) Analogous to the procedure for example 1.

(8) .sup.19F-NMR (566 MHz, CDCl.sub.3): =122 ppm.

EXAMPLE 5

1,1-Disulphanediylbis(2,4-dichloro-5-nitrobenzene)

(9) Analogous to the procedure for example 1.

(10) log P(HCOOH): 5.69; log P (neutral): 5.64

(11) .sup.1H-NMR (d-DMSO. 400 MHz) =8.33 (s, 2H), 8.21 (s, 2H) ppm.

EXAMPLE 6

1-Fluoro-4-[(2-fluoro-4-methyl-5-nitrophenyl)disulphanyl]-5-methyl-2-nitrobenzene

(12) Analogous to the procedure for example 1.

(13) .sup.19F-NMR (566 MHz, CDCl.sub.3): =101.6 and 118.4 ppm.

EXAMPLE 7

3,3-Disulphanediylbis(6-fluoro-4-methylaniline)

(14) 1.96 g [5.27 mmol] of 1,1-disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene) in 50 ml of tetrahydrofuran are hydrogenated over 0.4 g of Raney cobalt (Actimet) for 19 hours at 65 C. and 30 bar hydrogen pressure. After filtering off the catalyst, the solvent is removed on a rotary evaporator. 1.7 g of solid are obtained comprising 81.3% 3,3-disulphanediylbis(6-fluoro-4-methylaniline) and 13.3% 5-amino-4-fluoro-2-methylbenzenethiol (97.5% of theory) by HPLC analysis.

(15) LC/MS: 5-amino-4-fluoro-2-methylbenzenethiol: m/e=158 (MH.sup.+)

(16) 3,3-disulphanediylbis(6-fluoro-4-methylaniline): m/e=313 (MH.sup.+)

(17) GC/MS (silylated): 5-amino-4-fluoro-2-methylbenzenethiol: m/e=301 (M.sup.+, 2silyl, 50%), 286 (<5%), 181 (60%), 73 (100%).

(18) 3,3-disulphanediylbis(6-fluoro-4-methylaniline): m/e=456 (M.sup.+, 2silyl, 100%), 441 (5%), 228 (100%), 73 (100%).

(19) .sup.1H-NMR (600 MHz, d-DMSO): =2.16 (s, 6H), 2.5 (m, 4H), 6.9-7 (m, 4H) ppm.

(20) .sup.19F-NMR (566 MHz, CDCl.sub.3): =134.5 ppm.

EXAMPLE 8

3,3-Disulphanediylbis(6-fluoro-4-methylaniline)

(21) 152 g [408 mmol] of 1,1-disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene) in 810 ml of tetrahydrofuran are hydrogenated over 16 g of Raney cobalt (Actimet) for 19 hours at 65 C. and 30 bar hydrogen pressure. After filtering off the catalyst, the solvent is removed on a rotary evaporator. 134.5 g of solid are obtained comprising 19.8% 3,3-disulphanediylbis(6-fluoro-4-methylaniline) and 75.1% 5-amino-4-fluoro-2-methylbenzenethiol (99.6% of theory) by HPLC analysis.

EXAMPLE 9

3,3-Disulphanediylbis(6-fluoro-4-methylaniline)

(22) 2.91 g [7.8 mmol] of 1,1-disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene) in 35 ml of tetrahydrofuran are hydrogenated over 0.3 g of Raney nickel (A 4000) for 19 hours at 65 C. and 30 bar hydrogen pressure. After filtering off the catalyst, the solvent is removed on a rotary evaporator. 2.6 g of solid are obtained comprising 67.3% 3,3-disulphanediylbis(6-fluoro-4-methylaniline) and 12.6% 5-amino-4-fluoro-2-methylbenzenethiol (85% of theory) by HPLC analysis.

EXAMPLE 10

3,3-Disulphanediylbis(6-fluoro-4-methylaniline)

(23) 34.2 g [91.8 mmol] of 1,1-disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene) in 180 ml of methyl tertiary butyl ether are hydrogenated over 1.8 g of Raney cobalt (Actimet) for 19 hours at 65 C. and 30 bar hydrogen pressure. After filtering off the catalyst, the solvent is removed on a rotary evaporator. 29.7 g of solid are obtained comprising 8.3% 3,3-disulphanediylbis(6-fluoro-4-methylaniline) and 89.5% 5-amino-4-fluoro-2-methylbenzenethiol (92% of theory) by HPLC analysis.

EXAMPLE 11

3,3-Disulphanediylbis(6-fluoro-4-methylaniline)

(24) 34.2 g [91.8 mmol] of 1,1-disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene) in 180 ml of acetic acid are hydrogenated over 1.8 g of Raney cobalt (Actimet) for 19 hours at 65 C. and 30 bar hydrogen pressure. After filtering off the catalyst, the solvent is removed on a rotary evaporator. 30.1 g of solid are obtained comprising 8.9% 3,3-disulphanediylbis(6-fluoro-4-methylaniline) and 89.3% 5-amino-4-fluoro-2-methylbenzenethiol by HPLC analysis.

EXAMPLE 12

3,3-Disulphanediylbis(6-fluoro-4-methylaniline)

(25) 34.2 g [91.8 mmol] of 1,1-disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene) in 180 ml of isobutyl alcohol are hydrogenated over 1.8 g of Raney cobalt (Actimet) for 19 hours at 65 C. and 30 bar hydrogen pressure. After filtering off the catalyst, the solvent is removed on a rotary evaporator. 30 g of solid are obtained comprising 16% 3,3-disulphanediylbis(6-fluoro-4-methylaniline) and 80.7% 5-amino-4-fluoro-2-methylbenzenethiol by HPLC analysis.

EXAMPLE 13

3,3-Disulphanediylbis(6-fluoro-4-methylaniline)

(26) 0.97 g [2.6 mmol] of 1,1-disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene) in 9 ml of tetrahydrofuran is hydrogenated over 44 mg of 5% Pt/C (Evonik F 105 NC/W) for 19 hours at 65 C. and 60 bar hydrogen pressure. After filtering off the catalyst, the solvent is removed on a rotary evaporator. 0.87 g of solid is obtained comprising 8% 3,3-disulphanediylbis(6-fluoro-4-methylaniline) and 88.3% 5-amino-4-fluoro-2-methylbenzenethiol by HPLC analysis.

EXAMPLE 14

3,3-Disulphanediylbis(4,6-dichloroaniline)

(27) Analogous to the procedure for example 9.

(28) log P (HCOOH): 5.14; log P (neutral): 4.95

(29) .sup.1H-NMR (d-DMSO, 400 MHz) =7.41 (s, 2H), 6.95 (s, 2H), 5.78 (broad, 4H) ppm.

(30) GC-MS: EI-Mass (m/z): 386 (4 Cl) [M].sup.+

(31) The examples and comparative examples below relate to configurations of method step (A) of the method according to the invention. The product preferably obtained is therefore a bis(3-nitrophenyl) disulphide of the general formula (IV).

EXAMPLE 15

1,1-Disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene)

(32) 1.66 g [10 mmol] of potassium iodide are added to a solution of 25.4 g [100 mmol] of 4-fluoro-2-methyl-5-nitrobenzenesulphonyl chloride in 50 g (47.7 ml) of acetic acid and the mixture is heated to 60 C. At this temperature, 15.9 g [150 mmol] of sodium hypophosphite monohydrate (corresponds to 2.7 g of water or 5.1% by weight) are added portionwise over the course of about 100 minutes. The mixture is stirred for 6 hours at 60-62 C., cooled to 40 C., 50 ml of water are added thereto and the mixture is stirred for 30 minutes at 40 C. The mixture is then cooled to 10 C., the precipitated solid is filtered off, washed with 60 ml of ice water and dried. 16.99 g of solid are obtained.

(33) HPLC analysis: 92.9 area % (IV), <0.1 area % (V); <0.1 area % (VI), <0.1 area % (VII)

(34) Yield: 85% of theory.

(35) .sup.1H-NMR (600 MHz, CD.sub.3CN): =2.50 (s, 6H), 7.34 (d, J=12.0 Hz, 2H), 8.13 (d, J=7.5 Hz, 2H) ppm.

(36) .sup.19F-NMR (566 MHz, CDCl.sub.3): =118.6 ppm.

EXAMPLE 16

1,1-Disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene)

(37) 1.66 g [10 mmol] of potassium iodide are added to a solution of 25.4 g [100 mmol] of 4-fluoro-2-methyl-5-nitrobenzenesulphonyl chloride in 50 g (47.7 ml) of acetic acid and 0.54 g of water (corresponds to 1.07% by weight) and the mixture is heated to 60 C. At this temperature, 13.2 g [150 mmol] of sodium hypophosphite having a water content of about 0.4% are added portionwise over the course of about 100 minutes. The mixture is stirred for 6 hours at 60-62 C., cooled to 40 C., 50 ml of water are added thereto and the mixture is stirred for 30 minutes at 40 C. The mixture is then cooled to 10 C., the precipitated solid is filtered off, washed with 60 ml of ice water and dried. 17.34 g of solid are obtained.

(38) HPLC analysis: 91.6 area % (IV), <0.1 area % (V); <0.1 area % (VI), <0.1 area % (VII)

(39) Yield: 85% of theory.

Comparative Example 1

1,1-Disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene)

(40) 1.66 g [10 mmol] of potassium iodide are added to a solution of 25.4 g [100 mmol] of 4-fluoro-2-methyl-5-nitrobenzenesulphonyl chloride in 50 g (47.7 ml) of acetic acid and the mixture is heated to 60 C. At this temperature, 13.2 g [150 mmol] of anhydrous sodium hypophosphite having a water content of about 0.4% are added portionwise over the course of about 100 minutes. The mixture is stirred for 6 hours at 60-62 C., cooled to 40 C., 50 ml of water are added thereto and the mixture is stirred for 30 minutes at 40 C. The mixture is then cooled to 10 C., the precipitated solid is filtered off, washed with 60 ml of ice water and dried. 17.14 g of solid are obtained.

(41) HPLC analysis: 8.7 area % (IV), 83.7 area % (V); 2.2 area % (VI), 0.3 area % (VII)

(42) Yield: 8% of theory of (IV), 74.6% of theory of (V).

EXAMPLE 17

1,1-Disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene)

(43) 1.66 g [10 mmol] of potassium iodide are added to a solution of 25.4 g [100 mmol] of 4-fluoro-2-methyl-5-nitrobenzenesulphonyl chloride in 96.5 g (92 ml) of acetic acid and 3 g of water (corresponds to 3.0% by weight) and the mixture is heated to 60 C. At this temperature, 13.2 g [150 mmol] of anhydrous sodium hypophosphite are added portionwise over the course of about 100 minutes. The mixture is stirred for 5 hours at 58-62 C., cooled to 40 C., 50 ml of water are added thereto and the mixture is stirred for 30 minutes at 40 C. The mixture is then cooled to 10 C., the precipitated solid is filtered off, washed with 60 ml of ice water and dried. 16.54 g of solid are obtained.

(44) HPLC analysis: 92.9 area % (IV), <0.1 area % (V); <0.1 area % (VI), <0.1 area % (VII)

(45) Yield: 83% of theory.

EXAMPLE 18

1,1-Disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene)

(46) Procedure as in example 17, but using 98.1 g (93:5 ml) of acetic acid and 1.5 g of water (corresponds to 1.5% by weight). 16.91 g of solid are obtained.

(47) HPLC analysis: 92.1 area % (IV), <0.1 area % (V); <0.1 area % (VI), <0.1 area % (VII)

(48) Yield: 84% of theory.

EXAMPLE 19

1,1-Disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene)

(49) Procedure as in example 17, but using 98.85 g (94.2 ml) of acetic acid and 0.75 g of water (corresponds to 0.38% by weight). 17.31 g of solid are obtained.

(50) HPLC analysis: 90.9 area % (IV), <0.1 area % (V); <0.1 area % (VI), <0.1 area % (VI)

(51) Yield: 84% of theory.

EXAMPLE 20

1,1-Disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene)

(52) Procedure as in example 17, but using 99.2 g (94.6 ml) of acetic acid and 0.375 g of water (corresponds to 0.38% by weight). 17.20 g of solid are obtained.

(53) HPLC analysis: 92 area % (IV), <0.1 area % (V); <0.1 area % (VI), <0.1 area % (VII)

(54) Yield: 86% of theory.

EXAMPLE 21

1,1-Disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene)

(55) Procedure as in example 17, but using 99.4 g (94.8 ml) of acetic acid and 0.188 g of water (corresponds to 0.19% by weight). 16.97 g of solid are obtained.

(56) HPLC analysis: 94.6 area % (IV), <0.1 area % (V); <0.1 area % (VI), <0.1 area % (VII)

(57) Yield: 86% of theory.

Comparative Example 2

1,1-Disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene)

(58) Procedure as in example 17, but using 99.5 g (94.9 mil) of acetic acid and 0.094 g of water (corresponds to 0.09% by weight). 16.37 g of solid are obtained.

(59) HPLC analysis: 37.8 area % (IV), 49.5 area % (V); 8.7 area % (VI), 0.9 area % (VII)

(60) Yield: 33.2% of theory of (IV), 43.3% of theory of (V).

Comparative Example 3

1,1-Disulphanediylbis(4-fluoro-2-methyl-5-nitrobenzene)

(61) Procedure as in example 17, but using 100 g (95.3 ml) of acetic acid without addition of water. 15.96 g of solid are obtained.

(62) HPLC analysis: 5.0 area % (IV), 89.3 area % (V); 2.2 area % (VI), 0.4 area % (VII)

(63) Yield: 4.3% of theory of (IV), 75.8% of theory of (V).