DE2130923C3 - Sulphoxide denvates and processes for their preparation - Google Patents

Description

R ²

R ¹ - SO - CH - Shark

(D

wherein Hai represents a halogen atom, with a compound the general formula

R ³ -XY (II)

wherein Y represents a hydrogen atom or an alkali metal, is reacted in an alkaline medium.

The new sulfoxides have an acaricidal effect and are the extremely effective zinc ethylene bisdithiocarbamate. a commercial product, both in terms of this property and in terms of worthy of their toxicity. In contrast to »Zineb« which is considered harmful in many publications For the description of the human skin, the sulfoxides according to the invention have this disadvantage not. Furthermore, the crystals of the well-known commercial products are subject to> easy to decompose once they have absorbed moisture, the acaricidal activity decreases with moisture absorption during storage. Also this disadvantage the compounds according to the invention do not have. Meanwhile, the total yield of zinc-ethylene bisdithiocarbars 1. Starting from Ethylenediamine. cannot carry over 63 °, they can exploit more than 90% of the compounds according to the invention, based on the starting material (e.g. dimethyl sulfoxide) The new sulfoxides can also be used to manufacture various drugs and for manufacturing agricultural chemicals are used.

Specific examples of u-halosulfoxides of Formula I are -i-chlorosulfoxides and the corresponding <z-bromosulfoxides.

The starting materials are easily accessible.

There are e.g. B. various known processes for the synthesis of u-haloene sulfoxides (M. Hojo and Z. Y o s h i d a. J. Am. Chem. Soc., 90, 4496 [1968]: G. Tsuchihashi and K. O gura, Bull. Chem Soc. Japan. 44.1726 [1971]: G. T s u c h i h a s h i et al. Synthesis, 89 [1971]: G. Tsuchihashi and S. Inuchijima. Bull. Chem. Soc. Japan.43.2271 [197 (1]: S. I riuchij ima and G. Tsuch ihashi, Synthesis, 588 [1970]).

The implementation of the, i-Halogensulfoxyds of the formula I with a compound of formula II is represented by the following equation:

R ²

R ¹ - SO - CH-Hal + R ³ - XY
R-

> R ¹ - SO - CH - X - P ³ + Y - Hai

Ej is advantageous that this reaction takes place under alkaline Conditions, d. H. for example by adding sodium hydroxide or potassium hydroxide will.

The reaction proceeds uniformly at room temperature; however, it is also possible to heat ^{to temperatures below 100 ° C., for example.} The two reactants can be used in almost equimolar proportions. The use of a reaction medium is advantageous, the presence of a solvent depending on the nature of the reactants and the products. Solvents in which both reactants are soluble are preferred. Examples of solvents useful in the present invention are water, acetonitrile, dimethylformamide.

Dimethyl sulfoxide and mixtures thereof. When the compound of formula II is an alcohol and im Excess is used, the excess portion can serve as the reaction medium.

The following examples illustrate the invention. The yield of product is based on the "-Halogensulfovyd der Rormel I. That as Ausgannsmateria! was used.

example 1

Chloromethyl methyl sulfoxide (1.00 g) was added in! 5 ml Dissolve methanol and add to this mixture 2.0g potassium hydroxide. The mixture was then heated to 50 ° C. over 15 hours. chloroform (50 mils was then added, and insoluble material was removed by nitration. The filtrate was concentrated under reduced pressure and then the Subjected to column chromatography. 720 mg of methoxymethylmethylsulfoxide were obtained in the form of a colorless liquid with a yield of 75%. A sample of the product was obtained by distillation cleaned unu analyzed. The structure of the product was determined by infrared spectrum (IR spectrum). nuclear magnetic Resonance spectrum (NMR) and mass spectrum determined.

product

boiling point

79 C 15 torr.
IR (pure)

. ■ SO 1040cm " ^1. .COC 1110cm" ¹ .
NMR (CDCl ₃ )

Λ 4.40 s (2H), 3.65 s (3H). 2.57s (3H).
Mass spectrum (12 EVj

Me 108 (M ⁺ ), 47.0 base peak. no other distinct peaks.

The product was further oxidized to the corresponding sulfone and this was analyzed.

Example 2

The procedure of Example 1 was repeated using ethanol in place of methanol. 816 mg of a colorless liquid with a boiling point of 80 to 82 C 5 Torr were obtained a yield of 76.5%. Through the IR. NMR and mass spectra of this product were found as ethoxymethylmethylsulfoxide identified.

product

IR (pure)

. • SO 1038 cm " ¹ .

. • COC, 1110 cm " ¹ .
NMR (CDCl ₃ )

f> 4.45 s (2H), 3.85 q (2H, J = 7.2 cps). 2.57 s (3 H), 1.26 t (3 H, J = 7.2 cps).

Mass spectrum (12 EV)

M / e 122 (M ⁺ ), 59 (base peak).

This product was converted into the corresponding sulfone and this was analyzed.

Example 3

The procedure of Example 1 was repeated using isopropanol in place of methanol. A colorless liquid was obtained in a yield of 55%, which had a boiling point of 71 ° C / 7 torr. This product was identified by the IR, NMR and mass spectra as methvlmethvlsulfoxvd identified.

ipropox) -

product

35

IR (pure) iSO 1035 cm " ^1. RC-OC. 1102 cm" ¹ . NMR (CCl ₄ I.

λ 4.34 s (2 Hl.) 3.97 (1 H. J = 6 cps). 2.48 s (3 H).

2.75 d (3 H. J = 6 cps), 2.68 d (3 H. .1 = 6 cpsl. Mass spectrum (12 EV)

Me 136 (M "). 106 (8%) *). 73 | 58%). 64 (52% l.

43 (basic peak). 41 (15%).

Elemental analysis for C ₅ H ₁₂ O ₂ S

Calculated ... C 44.09. H 8.88. S 23.54 ° «: found .... C 43.71, H 8.98. S 23.41%.

Example 4

Water (1 ml) was added to a mixture of 707 mg of phenol and 904 mg of bromomethylmethyl sulfoxide. 580 mg of potassium hydroxide were dissolved in this mixture under a nitrogen atmosphere. The mixture was then 11.5 hours at room temperature held. 40 ml of methylene chloride was added and then the solution became anhydrous Dried sodium sulfate and evaporated under reduced pressure. The product was column chromatography using silica gel and chloroform ethyl acetate (9: 1) as eluents subjected, 626 mg (yield: 64.2%) of a colorless liquid obtained which had a boiling point of 131 C / 2 Torr. Through the IR. NMR and mass spectra of this product were identified as phenoxymethylmethylsulfoxide identified.

product

IR (pure)

. • SO 1040 cm " ¹ ,, 'COC, 1202 cm" ¹ .

NMR (CCl ₄ )

ή 7.4-6.8 m (5H), 4.95 d (1 H. J = 9.5 cps). 4.79 d (IH, J = 9.5 cps), 2.58 s (3H). Mass spectrum (70 EV)

MIe 170 (M ⁺ ), 107 (72%), 79 (25%). 77 (100%).

51 (29%).

Example 5

460 mg potassium hydroxide were added under nitrogen to a mixture of 560 mg and 616 Chlormethylmethylsulfoxyd mgThiophenol, and then the mixture for 13.5 hours 60 ^c C was heated. To the mixture was added 3 ml of water, and then the mixture was extracted with chloroform. The extract was dried over anhydrous sodium sulfate and then chromatographed on silica gel using chloroform-ethyl acetate (9: 1) column chromatographed to give 812 mg Methylphenylthiomethylsulfoxyd having a boiling point of 148 ⁰ C / 0.5 torr and a N'O from 1.6053 obtained in the form of a colorless liquid in a yield of 87.3%.

Elemental analysis for C ₈ H ₁₀ S ₂ O.

Calculated ... C 51.57, H 5.41, S 34.43%; found .... C 51.51, H 5.75, S 34.09%.

45 *) The intensity relates to the basic peak.

one

Examples 6 to

from chloromethylphenyl sulphide

. ■, __, ";" AH-nli iinrl

■ hnnp pour 50 ml of methylene chloride solution mixture _{over anhydrous Na} .

_and dried the ^^ ^^ ^ ^ ^ ^{,. ^ tr} , urnsulfat. ω- _of methylene chloride as

° ™ ~ ^taL

table

-SOCH ₂ Cl + R ³ SH (D 1 ")

/ ~~ \ —soch _: sr ³

example

10

t-butyl

Amount of

Compound I

(mg)

l-propyl

Cl CH ₃

830

804

1026

810

Amount of connection

666 mg

830 mg

823 I 917 mg Menac
K-OH

1.0 g

400 mg

1.0 g

500 mg

500 mg

Warming

temperature

(Cl

50
50
50

Heating time ih.)

18 15 24 16.5

35

Si 1.0 '.' ". 6

'■' · ί, 5

45

In Examples 6 to 10, the following were obtained Products whose properties are also specified:

Example 6 t-Butylthiomethylphenylsulfoxide

A colorless oil; IR (film), 1042cm "¹; NMR (CCU): δ 1.38 s (9H), 3.64 d (1H, J = 13.5 Hz); 3.77 d (1H, J = 13 , 5Hz), 1.3 ~ 7.8 m (5 H). Analysis calculated for C ₁₁ H ₁₆ OS ₂ .

Calculated ... C 57.85, H 7.06, S 28.08%; found .... C 57.71, H 7.00, S 28.08%.

Example 7 Phenylthiomethylphenyl sulfoxide

A colorless oil; IR (film), 1049.745 and 690 cm NMR (CCl ₄ ): f> 3.98 d (1 H, J = 13.5 Hz), 4.03 d (1 H, J = 13.5 Hz), 7.1 ~ 7.8m (IOH).

Analysis for C ₁₃ H ₁₂ O ₂ S.

Calculated ... C 62.87, H 4.87, S 25.82%; found .... C 62.78, H 4.85, S 25.87%.

Example 8 Isopropylthiomethylphenylsulfoxide

A colorless oil; IR (FiIm), 1044cm- ¹ ; NMR (CCU); , 52.27 d (6 H, J = 6.8 Hz), 3.318 sectet (1 H, J = 6.8 Hz), 3.7 / 5 (2 H, 7.3 ~ 7.8 m (5 H).

Analysis door C ₁₀ H ₁₄ OS ₂ .

Calculated ... C 56.03, H 6.58%; Found .... C 56.12, H 6.64%.

Example 9 p-Chlorophenylthiomethylphenylsulfoxy ;;

Colorless
1040 cm- ¹ ;
(9H).
Analysis for C ₁₃ H ₁₁ OS.

(KBr), - 7.8 m

Example 10 p-Tolylthiomethylphenylsulfoxide

Fin colorless oil; IR (film), 1048 cm- ¹ ; NMR -T2 30 s (3H), 3.91 d (1 H, J = 13.5 Hz), 3.99 d = 13.5 Hz), 6.9 ~ 7.7 m (9H).

-ι.

Analysis door C ₁₄ H ₁₄ OS ₂ .

Calculated ... C 64.08, H 5.38%; found ..

C 63 ', 97, H 5.45%.

Example 11

Chloroethyl methyl sulfoxide (607 mg) was added to 3 ml of a 20% strength aqueous solution of the sodium salt of methyl mercaptan, an exothermic reaction taking place. To the reaction mixture was added 25 ml of chloroform, and then the reaction mixture was dried with anhydrous sodium sulfate and then subjected to column chromatography on silica gel using chloroform-ethyl acetate (1: 1) to give 640 mg of a colorless liquid having a boiling point of 90 ° C / 5Torr and an n'S of 1.5172

received. Through the IR. NMR and mass spectra of this product were identified as methylthiomethylmethylsulfoxide identified.

Elemental analysis for C ₃ H _B OS ₂ .

Calculated ... C 29.00. H 6.49%:
found .... C 28.97. H 6.78%.

B e i s ρ i e 1 12

Chloromethylphenylsulfoxide (270 mg) was dissolved in 3 ml of acetonitrile, then 1 ml of one was added 20% strength aqueous solution of the sodium salt of methyl mercaptan was added and the mixture was heated during 80 minutes at 60 ° C. 30 ml of chloroform were added to the reaction product, and that Product was dried with Glauber's salt and then on silica gel using chloroform column chromatographed as the eluent. 213 mg of colorless crystals were obtained with a M.p. from 61 to 61.5 ° C. From the IR. NMR and mass spectra followed that this product was methylthiomethylphenylsulfoxide was.

Elemental analysis for QH ₁₀ S ₂ O.

Calculated ... C 51.57, H 5.41. S 34.43%;
found .... C 51.62, H 5.47. S 34.37%.

B e i s ρ i e 1 13

A mixture of 30,085 g of chloromethyl-p-tolylsulfoxide and 110 ml of the sodium salt of methyl mercaptan was dissolved in 210 ml of acetonitrile, and then the solution was stirred at 40 ° C. for 13 hours. The reaction product was treated with methylene chloride extracted, dried with anhydrous sodium sulfate and concentrated to give 33.533 g of crude crystals obtained from methylthiomethyl-p-toluylsulfoxide. the Crude crystals were recrystallized from methanol and carbon tetrachloride n-hexane, whereby colorless crystals with a melting point of 60.0 to 61.0 ° C. were obtained.

Elemental analysis for CH ₁₂ OS ₂ .

Calculated ... C 53.96, H 6.04. S 32.02%:
found .... C 53.93, H 6.13, S 32.15%.

Example 14

832 mg of (l-bromoethyl) phenyl sulfoxide were dissolved in 1 ml of acetonitrile, and after adding 33 ml a 20% aqueous solution of the sodium salt of methyl mercaptan, the mixture was during Heated at 40 ° C for 10 hours. The product was extracted with 50 ml of chloroform and anhydrous Dried sodium sulfate. The solvent was removed under reduced pressure and the product was separated by column chromatography with silica gel and chloroform as the eluent. 170 mg of 1-methylthioethylphenyl sulfoxide were obtained with a yield of 75.4%.

Elemental analysis for C ₉ H ₁₂ OS ₂ .

Example 15

Calculated
found .

C 53.96, H 6.04%;
C 53.81, H 6.22%. 220 mg ((i-ChlorbencyU-phenylsulfoxide were dissolved in 5 ml of acetonitrile, and with the addition of 3 ml of a 20% strength aqueous solution of the sodium salt of methyl mercaptan, the mixture was stirred for 4 days at room temperature. Methylene chloride (50 ml) was added, and the product was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure, the product was separated by column chromatography (silica gel, chloroform) to give (u-methylthiobenzyl) phenylsulfoxide in the form of colorless crystals with a m.p. in a yield of 82.6%.

Example 16

524 mg of cis-2-chlorohiolane-1-oxide were in 1 ml Dissolved acetonitrile, and after adding 1.5 ml of a 20% strength aqueous solution of the sodium salt of methyl mercaptan, the mixture was stirred for 4 hours at room temperature. It became methylene chloride (50 ml) was added and then the product was dried over anhydrous sodium sulfate, whereby ma '. 158 mg of trans-2-methylthiothiolane-1-oxide with a boiling point of 90 C / 0.1 Torr was obtained as a colorless liquid with a yield of 56.7%.

IR (neat) 1033 cm "'.
NMR (CCU)

Λ 3.87 q (1 H. J = 3.7 Hz). 2.30 s (3H), 1.7-3.2 m (6H).

Elemental analysis for C ₅ H ₁₀ S ₂ O.

Calculated ... C 39.96. H 6.71%: found .... C 39.66. H 6.83%.

Example 17

The procedure of Example 8 was repeated using 826 mg of chloromethyl isopropyl sulfoxide Instead of chloromethylphenyl sulfoxide used. 962 mg of isopropylisopropylthiomethylsulfoxide were obtained in a yield of 90.9%.

IR (pure)

1048 cm- ¹ .
NMR (CDCl ₃ )

h 1.28 d (3H, J = 6.8 Hz), 1.32 d (3H, J = 6.8 Hz), 1.34 d (6 H. J = 6.8 Hz). 2.7-3.6 m (2H), 3.68 s (2H).

Elemental analysis for C ₇ H ₁ ^ OS ₂ .

Calculated ... C 46.62, H 8.92, S 35.56%; found .... C 46.51, H 9.00, 35.76%.

Example 18

1 ml of water was added to a mixture of 2M ethyl mercaptan and 895 mg of chloromethylethyl sulphide, and then 1.0 g of potassium hydroxide was dissolved in this mixture. The mixture was ^{heated at 50 °} C. for 15 hours. 50 ml of methylene chloride were added to this mixture and the product was dried over anhydrous sodium sulfate. Subsequently, it was distilled under reduced pressure. Ma received 1011 mg of ethylethylthiomethylsulfoxide m

309 640/4;

■

a boiling point of 95 to 97 ^c C / 2.5 Torr in the form of a colorless liquid in a yield of 95%.

IR (pure)
1042 cm- '.

NMR (CDCl ₃ )

Λ 1.32 t (3 H, J = 7.4 Hz), 1.36 t (3 H, J = 7.4 Hz). 2.5-3.3 m (4H), 3.72 s (2H).

Elemental analysis for C ₅ H ₁₂ OS ₂ .

Calculated ... C 39.43, H 7.94, S 42.12%;
found .... C 39.22, H 8.00, S 42.04%.

Example 19

The procedure of Example 9 was repeated except that 970 mg of chloromethyl p-chlorophenyl sulfoxide were obtained used in place of chloromethylphenyl sulfoxide. 1633 mg of p-chlorophenyl-p-chlorophenylthiomethylsulfoxide were obtained in a yield of 90%. Colorless crystals, col. 81 bis 82 ° C.

IR (KBr)
1036 cm- ¹ .

NMR (CDCl ₃ )
h 4.12 s (2H), 7.32A ₂ BJq (4H). 7.54 A ₂ B ^ (4H).

Atomic analysis for C ₁₃ H ₁₀ OS ₂ Cl ₂ .

Calculated ... C 49.22, H 3.18, S 20.21%;

found .... C 48.95, H 3.31, S 20.10%.

Example 20

4.004 g (19.15 mmol) of chloromethyl-p-chlorophenylsulfoxide and 2.854 g (19.15 x 1.2 mmol) of p-thiocresol were heated and dissolved in an argon atmosphere, after which 1.5 g of potassium hydroxide and 1.5 ml of water were added and the mixture 15 ¹ Z was placed _{for 2} hours in an oil bath at 74 ° C for reaction. A dark brown, viscous liquid was obtained. An appropriate amount of water was added to the reaction solution and extracted with methylene chloride. The extraction solution was dried with Glauber's salt, the solvent was removed under reduced pressure, and the residue was extracted with cyclohexane and subjected to column chromatography on 25 g of silica gel with methylene chloride as an eluent to separate the blackish brown substance to give a yellowish brown liquid. A small amount of n-hexane was added to the resulting liquid to cause crystallization, followed by recrystallization from carbon tetrachloride / cyclohexane. 0.5 g of p-chlorophenyl-p-tolylthiomethyl sulfoxide was obtained in the form of colorless crystals. The yield was 89%, F. = 62.0 to 63.5 C.

NMR (CDCl ₃ )

Λ 2.34 s (3H), 4.1Oq (2H), 7.20 A ₂ B ₂ q (4M). 7.52A ₂ B ₂ q (4H).

IR (KBr. Compact)

1046 cm- '.
Elemental analysis for C ₁₄ H ₁₃ S ₂ OCl.

Calculated ... C 56.65, H 4.41, S 21.60%;
found .... C 56.69, H 4.39, S 21.59%.

Example 21

2.552 g (13.5 mmol) of chloromethyl-p-toiylsulfoxide and 2.34 g (13.5 x 1.2 mmol) of p-chlorothiophenol were heated and dissolved in a stream of argon, after which 1.5 α potassium hydroxide and 1 ml of water were added and the obtained mixture bc 16 hours: 64 ⁰ C was placed in an oil bath for reaction a suitable amount of water was added to the reaction liquid, and extracted chloride with methylene, the extraction solution with Glauber's salt, dried and the solvent removed under reduced pressure. For crystallization, a small amount of η hexane was added to the solution obtained, 3.538 g of p-chlorophenyl-thiomethyl-p-tolylsulfoxide being obtained in the form of colorless crystallizers. The yield was 88.3%, di (analytical sample was crystallized from CCLyCyclohextin order. F. = 83.0 to 84.0 ⁰ C.

NMR (CDCl ₃ )

δ 2.40 s (3H), 4.10 s (2H), 7.10-7.62 m (8H).
IR (KBr. Compact)

1036 cm " ¹ (sulfoxide).

Elemental analysis for C ₁₄ H ₁₃ S ₂ OCl.

Calculated ... C 56.65, H 4.42, S 21.60%;
found .... C 56.66, H 4.38, S 21.49%.

Claims (2)

Patent claims: 1. Sulphoxide derivatives of the general tunnel RR ¹ - SO - CH - X - R ³ wherein R ¹ and R ^{3 represent} an alkyl group having 1 to 4 carbon atoms, the phenyl group, or a phenyl group substituted by a chlorine atom or a methyl group. R ^{2 represents} a hydrogen atom, the methyl group or the phenyl group. R ¹ and R ² together can form an alkylene group having 3 carbon atoms and X is an oxygen or a sulfur atom. 2. Process for the preparation of the sulfoxviderivate according to claim 1, characterized in that that one is a u-halosulfoxide of the general formula R ²
R ¹ - SO - CH - Hai,. wherein Hai represents a halogen atom, with a Compound of the general formula R ³ -XY where Y represents a hydrogen atom or an alkali metal, is reacted in an alkaline medium. 35 The invention relates to sulfoxide derivatives of the general formula R ² R ¹ - SO - CH - XR ³ wherein R ¹ and R ^{3 are} an alkyl group having 1 to 4 carbon atoms, the phenyl group or a phenyl group substituted by a chlorine atom or a methyl group, R ^{2 is} a hydrogen atom, the methyl group or the phenyl group, R ¹ and R ² together are an alkyl group having 3 carbon atoms can form and X is an oxygen or a sulfur atom. The invention also relates to a process for the preparation of these compounds, which is characterized is that you can use a u-halosulfoxide general formula 45