DE1295567B - Process for the preparation of 9-thiabicyclononane derivatives - Google Patents

Description

The invention relates to a process for the preparation of 9-thiabicyclononane derivatives of the general formula

[4,2,1] nonane

in which X can be identical or different and have bromine, iodine, fluorine or hydrogen atoms or a hydroxyl, alkoxy, hydroxyalkoxy, aryloxy, halogen-substituted alkoxy, amino, aryl, alkyl and cycloalkyl-substituted amino, Halogen-substituted aryl, pyridinyl, cyano, isothiocyano, chloroisothiocyano, acyloxy, aryl mercapto, halogen-substituted aryl mercapto, acyl mercapto, alkylthiocarbamyl mercapto, alkyl carbamyl mercapto, alkylcarbamyl mercapto group and t = 0, 1 or 2 means that which consists of a group and t = 0, 1 or 2 Implementation of dichloro-9-thiabicyclononane or its 9-oxide or 9,9-dioxide of the formula

These two isomers can easily be converted into one another. Simply by dissolving in an ionizing solvent, due to the known tendency of / i-chlorosulfides to be in equilibrium with the corresponding sulfonium chlorides with a three-membered ring, as described by F us ο η and coworkers, J. Org. Chem., 11 , 476, and by Marvel and Weil, J. Am. Chem. Soc, 76, 61.
The balance seems to be as follows:

Cl

Cl

Cl

in an inert solvent at a temperature of -40 to about 150 ^° C. with compounds of the general formula MX, in which M denotes a hydrogen atom, a metal cation, an ammonium or alkyl-substituted ammonium ion and X has one of the meanings given above, either directly both Chlorine atoms or these are replaced one after the other and, if appropriate, 9-thiabicyclononane derivatives obtained in this way are oxidized in a manner known per se to give 9-oxide or 9,9-dioxide.

The ^, ß'-dichloro ^ -thiabicyclononane is produced by a ring bridging reaction, a sulfur chloride, preferably sulfur dichloride, with a cyclooctadiene, such as cyclooctadiene (1.5), cyclooctadiene (1,4) and cyclooctadiene (l, 3), which leads to the formation of a ^, // '- dichloro ^ -thiabicyclononane. The chlorine atoms in β and 'positions to the sulfide bond give rise to exchange reactions with the desired substituents on treatment with nucleophilic reagents.

It is believed that the product of sulfur dichloride with cyclooctadione- (1,5) is mainly is one isomer, with small amounts of another isomer also being present. It therefore, two likely structures come into consideration, as represented by the following formulas are shown.

2,6-dichloro-9-thiabicyclo [3,3,1] nonane

Accordingly, any exchange reaction of the parent dichloro compound can be either a 2,6-disubstituted 9-thiabicyclo [3,3,1] nonane or a 2,5-disubstituted 9-thiabicyclo [4,2,1] nonane or both result. Because of this convertibility of the two ring systems into one another, it is difficult, if not impossible to ascribe any product to the [3,3,1] or [4,2,1} system, and many of the Crude products show that they are mixtures of both isomers, even if one isomer is predominant can.

According to the invention, the 9-oxides or 9,9-dioxides are produced by oxidation of the corresponding sulfides manufactured, ζ. B '. with hydrogen peroxide, peracetic acid, perbenzoic acid, perphthalic acid or others organic peroxide acids, nitric acid, nitrogen dioxide or nitrogen tetroxide, permanganates, Chromic acid or dichromates, bromic acid or bromates, hypochlorous acid (or chlorine + water), Ozone or molecular oxygen (preferably using a catalyst such as for example vanadium oxide or nitrogen oxide). The sulfoxide group is also easily introduced by introduction formed by 1 molar equivalent of chlorine or bromine in the sulfide. The S-dihalo adduct obtained is then hydrolyzed or treated with an organic carboxylic acid to make the two To replace halogen atoms with an oxygen atom, whereby hydrogen halide is also formed. Suitable solvents are e.g. B. alcohols such as methanol or ethanol, ketones such as acetone or Methyl ethyl ketone, aliphatic acids such as glacial acetic acid, amides such as formamide or dimethylformamide, Nitriles such as acetonitrile, nitro hydrocarbons such as nitrobenzene or nitromethane, ethers such as dioxane, Tetrahydrofuran, dimethoxyethane or diethyl ether, tertiary amines such as pyridine, and other polar ones Solvent.

If the reaction is carried out with ammonia or a primary amine, 3 moles of these or better 1 mol plus 1 or 2 mol of an acid acceptor (e.g. 2,6-lutidine, sodium carbonate or Di-tert-butylamine) per mole of dichloro-9-thiabicyclononane can be used, so new poly-

cyclic heterocyclic systems of the following type are formed in which the two substituents X coincide:

In general, the compounds obtainable according to the invention have fungicidal activity, some of them being exceedingly effective and the previous fungicides far in this regard are superior. The compounds of the invention are also useful as herbicides, bacteriostatic agents, Insecticides, miticides, nematocides and useful as chemical intermediates. the bifunctional derivatives are useful for the polymerization.

In the examples, parts mean parts by weight, unless otherwise specified.

example 1
Dibromo-9-thiabicyclononane

First, to prepare dichloro-9-thiabicyclononane, 1296 parts of cyclooctadiene (1.5) and 1236 parts of sulfur dichloride were added simultaneously from separate vessels to 1500 parts of hexane with stirring and cooling to about 10-20 ° C. When the addition was complete, the mixture was stirred for 1 hour. The solids were removed by filtration, and it was found after drying that they contained 1295 parts of product, mp 100-101 ⁰ C. Further fractions, a total of an additional 725 parts, were recovered by partial evaporation and cooling. These fractions melting in the range 89-98 ⁰ C. Recrystallization from benzene-heptane to give a colorless crystalline solid, mp 102-103 ° C.

A solution of 21.1 parts of the dichloro-9-thiabicyclononane obtained in this way in 100 by volume parts of glacial acetic acid was saturated with gaseous hydrogen bromide and then left to stand in a sealed vessel for 12 hours. The solution was then poured into water, causing the product to precipitate. 26 parts of a colorless solid substance with a melting point of 131 to 134.5 "C were obtained.

Analysis: C ₈ Hi ₂ SBr ₂ . ^

Calculated ... Br 53.3%, Cl 0.0%;
found ... Br 51.5%, Cl 0.96%.

Example 2
Diiodo-9-thiabicyclononane

25 parts of sodium iodide in 250 parts by volume of acetone were added to a solution of 10 parts of dichloro-9-thiabicyclononane added in 100 parts by volume of acetone. After 3 hours at 25 ° C, the solution became concentrated and filtered to remove solids. The solids were washed salt-free with water, 14 parts of a colorless crystalline product remained which, after recrystallization from heptane melted at 139.5 to 140 ° C.

Analysis: C ₈ Hi ₂ SJ ₂ .

) Calculated ... J 64.5%;
found ... J 63.8%.

Example 3

Difluoro-9-thiabicyclononane

42.2 parts of dichloro-9-thiabicyclononan and 50 parts of potassium fluoride were heated for 18 hours at 12O ⁰ C in 400 parts of dimethylformamide. The solution was then concentrated to half its volume and cooled to precipitate the product, which was then recrystallized from benzene. This gave 12 parts of a colorless solid substance with a melting point of 159 ° to 166 ° C. (decomposition).

Analysis: C ₈ Hi ₂ SF ₂ .

Calculated ... Cl 0.00%, S 18.00%;
found ... Cl 0.00%, S 18.17%.

Example 4
Dihydroxy-9-thiabicyclononane

A mixture of 42.2 parts dichloro-9-thiabicyclononane, 200 parts by volume of 10% aqueous sodium hydroxide and 200 parts of dimethoxyethane was Heated under reflux for 3 days. The mixture was then concentrated in vacuo until the crystals precipitated. The crystals were filtered off and recrystallized from ethanol. The product (24 parts) was one colorless solid that was moderately soluble in water and melted at 217 to 218 ° C (certain Approaches melted at 249.5 to 250 ° C, and it is therefore to be assumed dimorphism).

Analysis: C ₈ Hi ₂ S (OH) ₂ .

Calculated ... S 18.40%;
found ... S 18.68%.

Example 5
Dihydroxy-9-thiabicyclononane-9,9-dioxide

To 8.7 parts dihydroxy-9-thiabicyclononan and 100 parts by volume of acetic acid 13 parts by volume of 30% hydrogen peroxide at 25 to 33 ⁰ C. The reaction mixture was then slowly heated to 100 ° C., cooled and partially evaporated, and the precipitated crystals were recrystallized from methanol-butyl acetate. A crystalline, water-soluble solid substance with a temperature of> 300 ° C. was obtained.

Analysis: C ₈ Hi ₄ SO ₂ (OH) ₂ .

Calculated ... S 15.5%;
found ... S 15.4%.

Example 6
Di- (2-hydroxyethoxy) -9-thiabicyclononane

22.4 parts of potassium hydroxide and 500 parts by volume of ethylene glycol were heated to reflux

Drive off water and thus form the potassium salt of glycol. The solution was cooled, 21.1 parts of dichloro-9-thiabicyclononane were added, and the mixture was then briefly refluxed again. After cooling, the glycol was ^{stripped off to 100 °} C. (0.2 mm), then water was added, which caused the separation of the organic product in the form of a viscous oil. It was determined by determining the alcohol number that it was the desired diol.

Example 7

Di- (2-hydroxyethoxy) -9-thiabicyclononane-9,9-dioxide

24.3 parts of dichloro-9-thiabicyclononane-9,9-dioxide, 22.4 parts of potassium hydroxide and 500 parts by volume of ethylene glycol were refluxed for 3 hours. The glycol was then placed under 0.4 mm vacuum stripped, leaving a dry residue which was then dissolved in 500 parts of water. These Solution separated upon concentration from potassium chloride. The last traces of potassium chloride were found to be The precipitate was separated off by adding methanol and hydrochloric acid and then filtering. Evaporation of the filtrate and washing of the residue with acetone gave 15.5 parts a colorless crystalline solid substance which is soluble in water and insoluble in acetone, from F. 133 to 134 ° C.

Analysis: C ₈ Hi ₂ SO ₂ (OC ₂ H ₄ OH) ₂ .

Calculated ... S 10.9%, Cl 0.0%;
found ... S 10.2%, Cl 0.0%.

Example 8

Methoxychlor-9-thiabicyclononane and
Dimethoxy-9-thiabicyclononane

50 parts of dichloro-9-thiabicyclononane were left to stand with 300 parts by volume of methanol for a day and then refluxed for 24 hours and then the excess alcohol was distilled off. The residual product was an amber syrup from Kp.i _2142-145 ⁰ C. The infrared spectrum showed the presence of methoxy groups (-CH ₃ - and C - O - C-bands). Chlorine analysis showed that the product was a mixture of 26% monomethoxy-monochloro- and 74% dimethoxy-9-thiabicyclononane.

Example 9
Dianilino-9-thiabicyclononane

A mixture of 10.5 parts of dichloro-9-thiabicyclononane and 9.7 parts by volume of aniline in 200 parts of 1,2-dimethoxyethane was refluxed for 16 hours. Excess alcoholic potassium hydroxide was added to the partially crystallized mixture. The mixture was then briefly refluxed, diluted with a large excess of water, filtered and the solids washed with water. The dried solids (10 parts) melting at 225 to 226.5 ⁰ C.

Analysis: Ci ₈ Hi ₂ S (NHC ₆ Hs) ₂ .

Calculated ... N 8.62%;
found ... N 8.76%.

Example 10

N-cyclohexylimino-9-thiabicyclononane (Hydrochloride)

A mixture of 21.1 parts of dichloro-9-thiabicyclononane, 9.9 parts of cyclohexylamine, 22.3 parts of N-methylmorpholine and 50 parts of dimethoxyethane was refluxed for 20 hours and then filtered, 4 parts of a colorless crystalline substance from F. 276 ^C C (decomposition) which was soluble in a large volume of water.

Analysis: Ci ₄ H ₂₃ SN • HCl.

Calculated ... Cl 18.8%, N 4.72%, S 10.6%; found ... Cl 18.7%, N 4.7%, S 10.6%.

Examples 11 and 12

lO-aza-9-thiatricyclodecane and aminobis- (amino-9-thiabicyclononane)

A solution of 211 parts of dichloro-9-thiabicyclononane in 1000 parts by volume of 1,2-dimethoxyethane was with 1000 parts of a 10% ethanol Ammonia solution mixed. After standing for 4 days, the mixture became more aqueous with 3000 parts of 10% strength Sodium hydroxide solution diluted and filtered and the solids washed with water until they were devoid of strong base. After drying in air, 70 parts of a high-melting point were obtained Solid substance that was insoluble in water and soluble in dilute hydrochloric acid.

Analysis: C ₈ Hi ₃ SN.
Calculated ... N 9.0%;
found ... N 9.5%.

The filtrate was neutralized with carbon dioxide and evaporated to dryness. The residue was extracted with hot methanol, which after evaporation 30 parts of solid substance of undefined melting point, apparently a mixture of isomers.

Analysis: NH ₂ (C ₈ Hi ₂ S) NH (C ₈ Hi ₂ S) NH ₂ .

Calculated ... N 12.8%;
found ... N 12.76%.

Example 13 (chlorophenyl) chloro-9-thiabicyclononane

10 parts of aluminum chloride were added to 21.1 parts of dichloro-9-thiabicyclononane in 100 parts of chlorobenzene admitted. The mixture was then heated on a steam bath with stirring for 6 hours. The reaction mixture was added to ice water, the organic Layer washed with hydrochloric acid, filtered and evaporated under aspirator vacuum, leaving a viscous Syrup remained.

Analysis: C ₈ Hi ₂ SCl (C ₆ H ₄ Cl).

Calculated ... Cl 19.5%;
found ... Cl 19.5%.

B e i s ρ i e 1 14 bis (pyridinium) -9-thiabicyclononane dichloride

A mixture of 42.2 parts of dichloro-9-thiabicyclqnonan and 200 parts by volume of pyridine was heated for 65 hours at 90 to 100 ⁰ C. The mixture was

cooled and the precipitated solid substance isolated by filtration. The product was colorless microcrystalline water-soluble solid of undefined melting point, which allows a correct analysis (Determination of ionic chloride by Volhard titration) for the desired product.

Example 15

Bis-itrimethylammonium ^ -thiabicyclononane dichloride

A mixture of 21.1 parts of dichloro-9-thiabicyclononane, 98 parts of trimethylamine and 200 parts by volume of 95% ethanol was used for 20 hours Stirred at room temperature. The precipitated solids were filtered off and air dried. The product was a colorless, water-soluble solid with an undefined melting point.

Analysis: Ci ₄ H ₃₀ SN ₂ Cl ₂ · 2 H ₂ O.

Calculated ... Cl (ionic) 19.4%;
found ... Cl (ionic, by Volhard titration) 19.8%.

Example 16
Diphenoxy-9-thiabicyclononane

A solution of 20.7 parts of phenol and 8.8 parts of sodium hydroxide in 200 parts of water was under Reflux with a solution of 21.1 parts of dichloro-9-thiabicyclononane stirred vigorously in 100 parts of methylene chloride. After 46 hours the organic Separated solution, partially evaporated and filtered, a colorless crystalline product from M.p. 161-162 ° C.

Analysis: C ₈ H ₁₂ S (OC ₆ Hs) ₂ .

Calculated
found

S 9.8%;
S 9.9%.

Example 17
Di- (p-chlorophenoxy) -9-thiabicyclononane

The procedure of the previous example was followed using an equivalent amount p-chlorobenzene repeated in place of phenol. The product was a colorless solid from M.p. 148 to 149 ° C.

Analysis: C ₈ Hi ₂ S (OC ₆ H ₄ Cl) ₂ .

Calculated
found

Cl 18.0%;
Cl 17.8%.

Example 18
Diacetoxy-9-thiabicyclononane

A solution of 98 parts of anhydrous sodium acetate, 105.5 parts of dichloro-9-thiabicyclononan and 500 parts by volume of glacial acetic acid was maintained for 2 hours at 90 to 100 ⁰ C. Then, the precipitated salts were filtered off, water was added to the filtrate to precipitate the product, which was filtered off, washed with water and air-dried. Thus 103 parts of a colorless crystalline solid was obtained, melting at 100-101 ⁰ C. The product melted after recrystallisation from methanol at 102 to 103 ° C.

Analysis: C ₈ Hi ₂ S (OCOCHs) ₂ .

Calculated ... S 12.4%;
found ... S 12.4%.

Example 19
Dicyano-9-thiabicyclononane

To a stirred, refluxing solution of 10.8 parts of sodium cyanide in 200 parts 90% aqueous ethanol was added to 21.1 parts of dichloro-9-thiabicyclononane and the mixture Heated under reflux for 2 hours. Then the mixture was cooled and diluted with water, a precipitate was obtained which, after filtering off and washing with additional quantities Water melted at 163-164 ° C.

Analysis: C ₈ Hi ₂ S (CN) ₂ .

Calculated ... Cl 0.0%, N 14.6%, S 16.7%;
found ... Cl 0.2%, N 14.5%, S 16.9%.

After refluxing for 2 hours with 50% aqueous sulfuric acid, the dinitrile was converted into dicarboxy ^ -thiabicyclononane, a high-melting, colorless solid substance which is almost insoluble in water and soluble in aqueous sodium hydroxide and has a neutralization equivalent of 165. After refluxing the dinitrile for 5 hours excess of potassium hydroxide in ethanol crystallized from the diamide of this acid on cooling in the form of a colorless solid substance having a melting point above 200 ⁰ C.

Example 20
Diisothiocyano-9-thiabicyclononane

A mixture of 38 parts of ammonium thiocyanate, 42.2 parts of dichloro-9-thiabicyclononane and 400 parts by volume Methyl ethyl ketone was refluxed for 14 hours. Then water was added causing the precipitation of solids. These solids were filtered off and it was found that they consisted of 39 parts of a colorless crystalline product with a melting point of 149 ° C.

Analysis: C ₈ Hi ₂ S (NCS) ₂ .

Calculated ... N 10.95%;
found ... N 11.00%.

Example 21
Chloroisothiocyano-9-thiabicyclononane

A mixture of 19.4 parts of potassium thiocyanate, 42.2 parts of dichloro-9-thiabicyclononane and 2600 parts of methyl ethyl ketone was refluxed for 3 ¹ As hours and then evaporated almost to dryness. 400 parts of water were added. The salts dissolved leaving a viscous organic oil. The latter was freed of residual water and ketone under 10 mm vacuum at 100 ⁰ C. The product was a viscous oil that solidified on standing.

Analysis: C ₈ Hi ₂ SCl (NCS).

Calculated ... Cl 15.2%, N 6.0%;
found ... Cl 14.8%, N 5.8%.

909521/564

Claims (2)

Example 22 (Phenylmercapto) chloro-9-thiabicyclononane 21 parts of dichloro-9-thiabicyclononane were added to 13 parts of sodium thiophenolate in 100 parts of dimethylformamide admitted. After one day, the "precipitated sodium chloride" was filtered off removed. The filtrate was added to water, the mixture extracted with benzene and the benzene washed with water, dried over magnesium sulfate and evaporated in vacuo, with a yellow oil remained, which partially crystallized on further standing and 8% hydrolyzable Contained chlorine, indicating that it was the desired product in an impure state. Example 23 Di- (phenylmercapto) -9-thiabicyclononane 21 parts of dichloro-9-thiabicyclononane were added to 26 parts of sodium thiophenylate in 100 parts of dimethylformamide. After one day, the reaction mixture was worked up as in the previous example, an oil and crystals being obtained. The crystals melted after recrystallization from hot heptane at 144 to 145.5 ⁰ C. Analysis: C ₈ Hi ₂ S (SC ₆ Hs). ₂ Calculated ... S26.8%;
found ... S 25.0%. Example 24 Di- (p-chlorophenylmercapto) -9-thiabicyclononane A solution of 10.6 parts of dichloro-9-thiabicyclononane in 200 parts by volume of acetone was added 28.9 parts of p-chlorothiophenol and 11.2 parts of potassium hydroxide added in methyl alcohol. A mildly exothermic reaction was observed. 2 hours later the precipitated salts were filtered off. During partial evaporation of the filtrate were 14 parts of a colorless solid product with a melting point of 81.5 to 85 "C were obtained. Analysis: C ₈ Hi ₂ S (SC ₆ H ₄ Cl). Calculated ... S 22.5%;
found ... S 21.7%. Example 25 (p-Chlorophenylmercapto) chloro-9-thiabicyclononane The above procedure was repeated using half the amount of p-chlorophenyl mercaptide, a yellow oil was obtained which had practically the correct chlorine analysis for (p-chlorophenylmercapto) -chloro-9-thiabicyclononane showed. Example 26 Bis- (O, O-diethoxythiophosphinyImercapto) - 9-thiabicyclononane. To a refluxing solution of 10.45 parts of dichloro-9-thiabicyclononan in 300 parts of toluene were diäthylphosphordithiolat Ο-added with stirring 22 parts of sodium Ο,. The reflux was continued for 1/2 hour, then the mixture was filtered, the filtrate was washed with water and then the solvent was evaporated. The remaining solid substance was recrystallized from ethanol, 22 g of a pale yellowish substance with a melting point of 54 to 57 ° C. being obtained. Analysis: Ci ₈ Hi ₂ O ₄ P ₂ Ss. Calculated ... P 12.1%, S 31.4%; found ... P 12.2%, S 31.4%. Example 27 Bis- (O, O-dimethoxythiophosphinylmercapto) -9-thiabicyclononane The procedure of the previous example was carried out using sodium O, O-dimethyl phosphorodithiolate in place of the ethyl ester repeated, the desired product as a cream-colored Solid substance with a temperature of 126 to 128 ° C. Example 28 O, O-diethyl chloro-9-thiabicyclononyl phosphorodithionate A solution of 42.2 parts of dichloro-9-thiabicyclononane, 36 parts of sodium O, O-diethyl phosphorodithiolate and 21 parts of triethylamine in 180 parts Benzene was refluxed for 10 hours, cooled and removed to remove the triethylamine hydrochloride filtered. The benzene was evaporated to give the product as a reddish syrup. Analysis: Ci ₂ H ₂₂ O ₂ ClPS ₃ .
Calculated ... Cl 9.8%;
found ... Cl 9.0%. Example 29 Bis- (N, N-dimethylthiocarbamylmercapto) -9-thiabicyclononane A mixture of 21.1 parts of dichloro-9-thiabicyclononane and 141 parts of 20% strength aqueous sodium dimethyldithiocarbamate was heated at 95 ° C. for 1 hour with stirring. The mixture was then filtered, the solids were taken up in hot benzene (some salts remained undissolved), filtered, diluted with hexane and cooled to give 19 parts of crystalline solid were obtained, melting at 209-210 ⁰ C. Analysis: C ₁₄ H ₂₄ N ₂ S ₅ . Calculated ... Cl 0.0%, S 42.1%; found ... Cl 0.0%, S 41.6%. _o Patent claim: Process for the preparation of 9-thiabicyclononane derivatives the general formula in which X can be identical or different and have bromine, iodine, fluorine or hydrogen atoms or a hydroxyl, alkoxy, hydroxyalkoxy, aryloxy, halogen-substituted alkoxy, amino, Aryl, alkyl and cycloalkyl-substituted amino, halogen-substituted aryl, pyridinyl, cyano, Isothiocyano-, chloroisothiocyano-, acyloxy-, arylmercapto-, halogen-substituted arylmercapto-, Acyl mercapto-, alkylthiocarbamylmer- capto, alkylcarbamyl mercapto group and t = 0, 1 or 2, characterized in that the reaction of dichloro-9-thiabicyclononane or its 9-oxide or 9,9-dioxide of the general formula Cl Cl in an inert solvent at a temperature of -40 to about 150 ^° C. with compounds of the general formula MX, in which M denotes a hydrogen atom, a metal cation, an ammonium or alkyl-substituted ammonium ion and X has one of the meanings given above, either directly both Chlorine atoms or these are replaced one after the other, and the 9-thiobicyclonone derivatives obtained in this way are optionally oxidized in a manner known per se to give the 9-oxide or 9,9-dioxide.