DE2325043A1 - ORGANOPHOSPHORUS DERIVATIVES OF ISOTHIAZOLE AND METHOD OF MANUFACTURING - Google Patents

Description

Manufacturing

The present invention relates to organophosphorus derivatives of isothiazole of the formula I

OR,

(D

wherein R _{1 represents} a straight or branched chain alkyl radical having 1 to 3 carbon atoms, an alkoxy radical having 1 to 3 carbon atoms' or a radical -WR ¹ R ¹ ·, where R 'and R ¹ ', which can be identical or different, are Represents a hydrogen atom or a straight or branched-chain alkyl radical with 1 to 3 carbon atoms, R ″ represents a straight or branched-chain alkyl radical with 1 to 3 carbon atoms, R'j represents a hydrogen atom, a straight or branched-chain alkyl radical with 1 to 5 carbon atoms, one aryl radical

309849/1249

INSPECTED

with 6 to 10 carbon atoms, an aralkyl radical with 7 "to 12 carbon atoms, a cyano radical, a carbalkoxy radical with 2 to 4 carbon atoms or a radical NKR"', in which R' ^{11 represents} a hydrogen atom or an aryl radical with 6 to 10 carbon atoms, R ^ is a cyano group, an alkylthio group with 1 to 4 carbon atoms, an alkylsulfinyl group with 1 to 4 carbon atoms, an alkylsulfonyl group with 1 to 4 carbon atoms, a carbamoyl group or a carbalkoxy group with 2 to 4 carbon atoms or a group SO ₂ NR "" R "" where R "" and R ""', which may be the same or different, represent a hydrogen atom or an alkyl radical having 1 to 3 carbon atoms and X represents an oxygen or a sulfur atom.

In particular, the invention relates to organophosphorus derivatives of the formula I in which X, R3, Rp and R ₂ have the meanings given above and R ' _{x has} the meaning of R, where R is a hydrogen atom or a straight-chain or branched-chain alkyl radical 1 to 3 carbon atoms, an aryl group with 6 to 10 carbon atoms, an aralkyl group with 7 to 12 carbon atoms, a cyano group, a carbalkoxy group with 2 to 4 carbon atoms or a group NHR " ¹ , where R" represents a hydrogen atom or an aryl group with 6 means up to 10 carbon atoms.

Among the compounds of the formula I are in particular those described in the examples of the following experimental section called. '- -

The compounds of the formula I have considerable insecticidal and / or acaricidal properties that make them suitable for use in the Making agriculture suitable for combating harmful organisms and in particular insects and / or acarins.

The compounds of the formula I are particularly suitable for controlling insects which attack stored grains.

30 984 9M 249 ....... '

The compounds of the formula I "have a very low toxicity towards warm-blooded animals. For example, the product of Example 2, 3- (dimethoxy-thiophosphoryloxyH-cyano-5-methylisothiazole) has a DLcq (mouse) of 1000 to 1500 mg / It was also found that the product of Example 7 _} the 5- (dimethoxy-triopnosphoryloxy) 4-cyano-5-n-butylisothiazole has a DLc ₀ (mouse) which is above 150 mg / kg.

The invention also relates to a process for the preparation of the compounds of the formula I. The procedure is characterized in that a 3-Hydro ^ cyisothiazole the ionael II

(II)

or its salt of an alkali metal with a halogenate Phosphoric or thiophosphoric acid esters of the formula III

Shark P < ^-1 . (III)

reacted, where X, E ^ j, R ^, R ¹ ^ and R. retain the meanings given above and Hai represents a chlorine or bromine atom.

The alkali metal salt of 3-hydroxyisothiazole of the formula II can be obtained, for example, by the action of an alkali metal hydride on the 3-hydroxyisothiazole of the formula II.

As the alkali metal salt of 3-hydroxyisothiazole of the formula II one can, for example, the sodium, potassium or lithium salt. "· 30984 9 / 1.24 9

Select.

The reaction can in particular be carried out in a "basic medium in the presence of an organic solvent and" at a temperature of ⁰ ° C. to 120 ^° C. The base can be an amine or an alkali metal or alkaline earth metal carbonate, for example a carbonate of potassium or sodium. The organic solvent can be hydrocarbons such as benzene, halogenated hydrocarbons such as chloroform, ketones such as acetone, ethers such as diethyl ether and tetrahydrofuran or other solvents like the dimethylformamide and the acetonitrile use _β

The 3-Hydroxyisothiazole of the formula II, "the-beginning of the he ~ inventive method ₈ are used can be prepared in particular according to method ₈ are analogous to those described in the French patent 2,060,868" It should be "noted that these compounds can also be produced by other methods "(vglo, among other things, the production of 3-hydro: xy-4-eyano-5-phenylisothiazole in the following experimental part) ₀ . '.

The subject of the invention is also insecticidal and / or acaricidal compositions which contain at least one compound of formula I ₉ as active material, optionally mixed with one or more other pesticidal agents.,

These compounds may be in the Porm of powders, granules, suspensions, emulsions or solutions vo-rliegen, the cationic particular in addition to the active ingredients _$ anionic or nonionic surface active agents, inert powders such as talc _s' clays, silicates, · kieselguhrs US ₀ W _0s a carrier such as water alcohol, the "hydrocarbons" or other organic solvents, a mineral oil, animal or vegetable oil, etc. -

30984 9/1249

The following examples serve to illustrate the invention, without restricting them.

Manufacturing I
3-Hydroxy-4-cyano-5-niethylisothiazole:

With stirring, 100 cnr adds hydrogen peroxide (110 vol.) In 1000 cnr an aqueous solution of sodium-1,1-dicyano-2-thio-1-propylenat (*) (1 mol per liter) which is cooled to 10 ⁰ G . The mixture is stirred for 30 minutes and then acidified to pH = 1 with concentrated hydrochloric acid. The precipitate formed is filtered off with suction and washed with water. This gives 95 g of ^ -hydroxy- ^ - cyano ^ -methylisothiazole, which melts at 205 ° C. After recrystallization from ethyl acetate, the product melts at 209 ° C.

Manufacturing II
3-I ^ droxy-4-cyano-5-phenylisothiazole:

A mixture of 20 g of 3-methoxy-4- cyano-5-pkenylisothiazole (**) and 200 cm of a hydrobromic acid solution in acetic acid (25/75) is heated to 80 ° C. for one hour, while stirring. The suspension obtained is evaporated to dryness under reduced pressure. The residue is teigt with ethanol and isolated hydroxy-4-cyano-3 ~ the melt by suction 16 g 5 "-plienylisothiazol in the form of white crystals, at 234 ⁰ C.

Manufacture III

3-Hydroxy-4-cyano-5 ~ n-butylisothiazole:

Level A: ethyl iminothio-valerate hydrochloride

(*) The sodium 1,1-dicyano-2-thio-1-propylenate is according to the Method by K. Hartke [Ang.6,83 (1967) Ed., Intern) prepared.

(**) The 3-methoxy-4-cyano-5-phenyl-isothiazole is according to the Manufactured in the method described in U.S. Patent 3,476,765.

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A stream of anhydrous hydrochloric acid is passed ^{into a mixture of 85 g of valeronitrile 1000 cnr of ether and 63 g of ethylmereaptane for 6 hours at 0} ° C., the mixture is evaporated to dryness and 176 g of the expected product are obtained; F = 40 to 50 ⁰ C.

Level B: ethyl dithiovalerate

A stream of hydrogen sulfide is passed for 1 hour at ⁰ ° C. in 2,000 cur of pyridine, 172 g of ethyliminothiovalerate hydrochloride are then added and the flow is maintained for 4 hours. It is poured onto an ice-water mixture and acidified to pH 2 with chlorinated water. It is extracted with ether, dried and evaporated to dryness. 145 g of the desired product are obtained in the form of a yellow oil; Ept- = 71 C.

Stage C: Potassium salt of 3-mercapto-2-cyano-2-heptenonitrile

13.2 g of malonitrile are added to a mixture of 14 g of potassium methylate in 300 cnr of methanol and then add 35 g of ethyl dithio-valerate to, stirred for 18 hours, evaporated to dryness and obtained 41 g of the desired product in the form of a viscous oil.

Step D: 3-Hydroxy-4-cyano-5-n-butylisothiazole

25 cnr hydrogen peroxide (110 vol.) Is introduced into a solution of 41 g of the potassium salt of 3-mercapto-2-cyano-heptenonitrile in 300 ciir water and stirred at 20 ° C. for one hour, washed with ethyl acetate and then acidified Hydrochloric acid. (. 35 to 70 Kp = ⁰ G) is extracted with ethyl acetate, dried and "evaporated to dryness, the crystals are washed with petroleum ether, dried and obtained 28 g of the desired product; Έ = 118 to 120 ° C.

example 1

3 ^ (diethoxythiophosphoryloxy) 4-cyano-5-methylisothiazole

30 9 8 49./ 1 2 49

Man "brings 34.5 g of anhydrous potassium carbonate in a solution of 36 g 3 = hydroxy" = ⁱ = 5- cyano-5 ~ Bietliylisotliiazol in 1000 cm acetone ₉ is stirred for 10 minutes and then added 47 g OjQ-Mäthyl-chlorthiophosphat

Han stirring it, the Heaktionsmischung 16 hours, and removing the precipitate formed by! Filtration, Man = the solvent is evaporated at a temperature below 50 ⁰ O under reduced pressure to dryness 75 g of a und'erhält .braunen oil which was chromatographyert on silica · ( Eluent t cyclohexane / ethyl acetate % 7/3) »

This gives 29.7 S 3- (dietho ± jthiophosphorylo2qr) 4 ™ cyano ~ 5-methylisothiazole in the form of white crystals * that grow at 35 ° E melt,,

Analyzes CoH ₁₅ I ₂ O ₅ PS ₂ = 292-, 5

Calculated! C % 36 _S 98 H% 4 ₉ 48 I% 9 _S 58 P % 10 ₉ 60 Found 37 ₉ 1 "4-, 7 9 ₃ 6 '10.6

Example 2,

3- (Dimethoxythiophosphoryloxy) 4 »cyano- = 5 = methylisothiazole

Place 26 ₉ 2 g of anhydrous potassium carbonate in a solution of 26 _? 7 g of 3- hydroxy = = -4-cyano <= 5-methylisothiazole in 250 cm ^ acetonitrile, stirred for 10 minutes and then add 32 ₉ 5 0 g ^ 0-dimethylchlorothiophosphate to _o it is stirred the suspension for 5 hours, and removed the precipitate formed by filtration ,, the solvent at a temperature below 50 ⁰ C under reduced pressure are evaporated out and obtains 50 g of a brown oil which was _s chromatographed on silica gel (eluant: benzene / lthylacetat; 8/2) "thus obtained an oil that crystallizes on cooling; one takes the

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■ ■ - 8 -

Crystals into a paste in petroleum ether (bp. = 35 / 7O ⁰ C) and obtained 32.5 g of 3- (dimethoxy-thiophosphor3rloxy) of 4-cyano-5-methylisothiazole, which melts at 52 ° G.

Analysis: C ₇ HgN ₂ O ₅ PS ₂ = 264.2

Calculated: 0% 31.82 H% 3.43 N% 10.60 P% 11.72 Found: 31.9, 3.5 10.7 11.6

Example 3

3- (diethoxy-thiopho sphoryloxy) 4-carbajnoyl-5-methylisothiazole

A) Preparation of 3-hydroxy-4 ~ carbamoyl-5-methyl-isothiazole:

A mixture of 60 g of 3-hydroxy-4-cyano-5-niethylisothiazole is added and 150 cm ^ concentrated sulfuric acid (d = 1.838) during 15 minutes at 113 ° C. - - '

The mixture is left to the temperature to 45 ° 0 to return and pours stirring on ice, sucks the precipitate formed, then wash it with water _s ^ with acetone and dried. Are thus obtained 51.5 g of 3-hydro: xy-4-carbamoyl-5-iaethylisothiazol which melts at 248 to 25O ⁰ C.

B) Preparation of 3- (diethoxy-thiophosphoryloxy) 4-carbamoyl-5-methylisothiazole:

7.5 g of sodium hydride (50% in mineral oil) are added while stirring in a solution of 25 g of 3-Hydroxy-4-carbamoyl-5-Biethylisothiazole

λ ο

in 300 cnr dimethylformamide at a temperature below 45 C; One erwä-rmt it, the mixture slowly to 14O ⁰ Cj then allowed to cool and brings with stirring at a temperature of 15 to 20 ^0C 29.7 g OjO-diethyl-chlorthiophosphat a. The mixture is stirred for a further night at room temperature and the solvent is then filtered off with suction to dryness under reduced pressure. A residue is obtained which is taken up in ether, which removes the

3 0 9 8 Λ 9/1 2 4 9

Mineral salts through. Filtration and evaporate the filtrate Dry. The oil obtained is chromatographed on silica gel (eluent: B.enzol / acetone s 7/3)

This gives 35 S 3 ~ (diethoxy-thiophosphoryloxy) 4-carbamoyl-5-methylisothiazole "that melts at 68 ° C.

Analysis: O ₉ H ₁₅ N ₂ O ₄ PS ₂ = 310.33 -. ■

Calculated: 'G% 34.83 E% 4.87 N% 9.03 P% 9.98 Found: 35.1 5.1 8.7. . 9.9

Example 4-

3- (Dimethoxy-thiophosphoryloxy) 4-carbamoyl - 5-2iethylisothiazole

7.5 g of sodium hydride (50 % in mineral oil) are brought into a solution of 25 g of 3-hydroxy-4-carbamoyl-5-methylisoth.ia.zol, (prepared as in step A ) of Example 3 described) in JOO cnr dimethylformamide.

The mixture is then slowly brought to 140 ° (D and held 5 minutes at this temperature and then cools down to 20 ° C. 25.3 g of 0,0-dimethyl chlorothiophosphate are then added with stirring and stir for a further 3 hours at room temperature. The solvent is evaporated to dryness under reduced pressure and the residue is chromatographed on silica gel (Eluant: benzene / acetone: 7/3).

Are thus obtained 20 g of 3- (dimethoxy-thiophosphoryloxy) of 4-carbamoyl-5-methylisothiazole in the form of a white product melting at 80 to 82 ⁰ G.

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Analysis: O ₇ H ₁₁ K ₂ O ₄ PS ₂ - 282.28

Calculated: 0% 29.80 H% 3.91 N % 9.91 P% 10.98 Found: 29.8 4.2 9.5 11.1

Example 5

3- (diethoxy-thiophosphoyloxy) 4-cyano-5-phenylisothiazole

Add 5 g of sodium hydride (50% in mineral oil) while stirring into a solution of 24.2 g of 3-hydroxy-4-cyano-5-phenylisothiazole in 250 cm of dimethylformamide and then adds 22.5 S. OjO diethyl chlorothiophosphate one leaves for 3 hours at room stand at temperature and then pour onto ice-water. Extraction is then carried out with isopropyl ether, and the organic drys Phase over sodium sulfate and evaporate to dryness.

42 g of an oil are obtained which can be chroma on silica gel tographiert (eluent: ethyl acetate / cyclohexane 2 2/8) .- Man thus receives 28.5 g of 3- (diethoxy-thiophosphoryloxy) 4-cyano-5-phenylisothiazole in the form of a clear yellow oil;

n ^ ° - 1.5815

Analysis: G ₁₄ H ₁₅ N ₂ O ₅ PS ₂ = 354.40

Calculated: C % 47.45 H % 4.26 Έ% 7.91 P % 8.75 Found: 47.8 4.3 7.5 8.6

Example 6

3- (Dimethoxy-thiophosphoryloxy) 4-cyano-5-phenylisothiazole

3.2 g of sodium hydride (50% in mineral oil) are added while stirring in a solution of 13 g of 3-hydroxy-4-cyano-5-phenylisothiazole in 150 cnr dimethylformamide, stir for one hour at room temperature and then adds 9.6 g of 0,0-dimethyl chlorothiophosphate

309849/1249

The mixture is stirred for one hour and poured onto ice-water. The mixture is extracted with Ither, the organic phase is dried over magnesium sulfate and the solvent is evaporated to dryness. 20 g of an oil are obtained, which is chromatographed on silica gel (eluent: benzene). This gives 12.1 g of 3- (Mmethoxy-thiophosphoryloxy) 4- cyano-5-phenylisothiazole in the form of white crystals ₉ . Melt at around 40 ° C.

A sample of the product is used for microanalysis from a mixture Hexane / isopropyl ether; .8 / 2 recrystallized; F = 40 ° C.

Analysis; - - O ₁₂ H ₁₁ N ₂ O ₃ PS ₂ = 326.35

Calculated; G % 44.1? H % 3 ₉ 4O Έ% 8.58 P % 9.50 Found; 44 ^ 0 3 ₉ 4 8 ₂ 4 9 _? 2

Example 7

5- (Mmethoxy-thiophosphoryloxy) 4-cyano- = 5-n-butylisothiazole

6.4 g of OjO-dimethyl chlorothiophosphate are added to a mixture of 796 g of 3-hydroxy = 4-cyano-5-n = butylisothiazole _? 50 cm ^ acetone and 5 _S 6 g potassium carbonate, stir for 18 ... hours _? filtered, evaporated to dryness and the residue chromatographed on silica gel 5, eluting with a mixture of cyclohexane / ethyl acetate (9-1). 9.6 g of 3- (dimethoxy-thio- "phosphoryloxy) 4-cyano-5-3i-butylisothiazole are obtained in the form of an oil.

Analysis; C ₁₀ H ₁₅ N ₂ O ₅ PS ₂ = 306 ₉ 35

Calculated; C% 39 _? 20 H% 4.94 Έ% 9 _S 14 P % 10 _s 11 Found; 39.8 5.0 9.1 9.8

30984971249

study of the insecticidal properties of 3- (diethoxy- thiophosphorylox3r) 4- cyano-5-phenylisothiazole (compound A)

A) Test on Oeratitis Oapitata

This test is done by topical application. Acetonic solutions of compound A are prepared which correspond to 10000 and 100 mg of active material per liter. 1 nX of the acetone solution of compound A is applied to the dorsal thorax of Ceratitis Capitata - flies at the age of 2.5 days (± 0.5). ·

Perform the same treatment on other individuals where the active material is D.D.T. (Dichlorodiphenyltrichloro ethane) in acetone solution at a concentration of 100 mg per liter of active material.

This test is done on 50 individuals per concentration and per Compound to be investigated carried out.

One counts the flies that have remained alive as well as those through which both insecticides killed at different time intervals! flies.

The activity of compound A and of D.D.T. is expressed as a percentage Mortality expressed.

Products mg / 1 .% Mortality 24 hours link
A. 1,000 2 hours. 100 D.D.T. 100. 86.0 84-, 6 100 ' 11.5 22.4- 22.4

Compound A is very effective against oeratitis Gapitata, which is superior to that of DDT. -

309849/1249

B) Teat on Sitophilus Granarius;

This test is done by topical administration. Man

produces an acetone solution of compound A corresponding to 500 mg of active material per liter.

0.2 λα 1 of the acetone solution of compound A is applied the ventral thorax of Sitophilus Granarius.

Perform the same treatment on other individuals using the same treatment of malathion (0,0-dimethyl-phosphorodithionate from Diethyl mercaptosuccinate) in acetone solution with the same Concentration (500 mg / liter).

This test is done on 50 individuals per concentration and per compound to be investigated carried out. . ·

Count the surviving individuals and the individuals killed by the two insecticides at different time intervals.

The activity of compound A and malathion is expressed as a percentage ¹ mortality: '

Products mg / L % mortality 48 Hours. 5 Day link
A. 500 24 Hours. 16 , 5 40 , 7 Malathion 500 14, 2 2 20th 2, 0

Compound A showed activity under the test conditions which is superior to that of malathion.

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Example of a pesticidal composition based on 3- (diethoxy-thiopho spho ryloxy) 4-cyano-5-phenylisothiazole.

Mix the following ingredients intimately until one liquid, homogeneous concentrate is obtained: ■

3- (diethoxy-thiophosphoryloxy) 4-cyano-5-phenylisothiazole 25 $ Atlox 4851 (mixture of alkyl aryl sulphonate and polyoxyethylene triglycerides with a viscosity at 25 ° C from 300 to 70 ocP) _β 6.4%

Atlox 4-855 (mixture of alkylarylsulphonate and polyoxyethylene Triglycerides with a viscosity at 25 ° 0 from 1500 to 1900 cP) .3.2%

Xylene 65.4%

Mixing is used to obtain a sprayable composition this concentrate with water, the amount of water added depending on the dose of active material to be used.

309849/1249

Claims (1)

^ p at en-t claims üci, e Organophosphorus derivatives of isothiazole of the formula I (I) "in which R * is a straight or branched-chain alkyl group with: 1 to 3 carbon atoms, an alkoxy group with 1 to 3 carbon atoms or a radical -KR ¹ R", represents ₅ in which R 'and R ", which can be identical or different j denotes a hydrogen atom or a straight or branched chain alkyl group with 1 to 3 carbon atoms, R ^ denotes a straight or branched chain alkyl group with 1 to 3 carbon atoms, R ¹ ^ denotes a hydrogen atom, a straight or branched chain alkyl group with Λ to 3 Carbon atoms, an aryl radical having 6 to 10 carbon atoms, an aralkyl radical having 7 to 12 carbon atoms, an öyanorest, a carbalkoxy radical having 2 to 4 carbon atoms or a radical NBR " ¹ , where R ¹ " represents a hydrogen atom or an aryl radical having 6 to 10 Carbon atoms, Rn denotes a cyano group, an alkylthio group with 1 to 4 carbon atoms, an alkylsulfinyl group with 1 to 4 carbon atoms, an alkyl sulfonyl group with 1 to 4 carbon atoms represents enstoffatomen, a carbamoyl radical or a carbalkoxy radical with 2 to 4 carbon atoms or a radical SOJSR """E" ^nr , where R "" and R " ^HI , which can be the same or different, represent a hydrogen atom or an alkyl radical with 1 to 3 carbon atoms and X represents an oxygen or a sulfur atom. 309840/1249 2. Organophosphorus derivatives of isothiazole of the formula I according to claim 1, wherein X, R ^, Rp and R have the meanings listed in claim 1 and R 'has the meaning of R ^, where R ₇ T is a hydrogen atom, a straight or branched-chain alkyl radical with 1 to 3 carbon atoms, an aryl radical with 6 to 10 carbon atoms, an aralkyl radical with 7 to 12 carbon atoms, a cyano radical, a carbalkoxy radical with 2 to 4 carbon atoms or a radical NHR " ¹ , where R"'represents a hydrogen atom or a Means aryl radical which has 6 to 10 carbon atoms. 3. 3 - '(Diethoxy-thiophosphoryloxy) 4-cyano-5-methylisothiazole. 4 ·. 3- (Dimethoxy-thiophosphoryloxy) 4-cyano-5-niethylisothiazole. ' 5- 3- (diethoxy-thiophosphoryloxy) 4-carbamoyl-5-methylisothiazor. 6. 3- (Dimethoxy-thiophosphoryloxy) 4-carbamoyl-5-diethylisothiazole. 7. 3- (Iethoxy-thiophosphoiyloxy) 4-cyano-5-phenylisothiazole. 8. 3- (Dimethoxy4; hiophosphoryloxy) 4-cyano-5-phenylisothiazole. 9. 3- (Dimethoxy-thiophosphoryloxy) 4-cyano-5-n-butylisothiazole. 10. Process for the preparation of the organophosphorus derivatives general formula I according to claim 1, characterized-characterized, that a 3-hydroxyisothiazole of the formula II (11) or its salt with an alkali metal, with a halogenated phosphoric acid ester or thiophosphoric acid ester of the formula III 30 9 849 / 12A9 Hal (in) where X, R ,,, Rp, R '^ and R. the claims. 1 meanings given own and shark means a chlorine or bromine atom, implements. - * 11. The method according to claim 10, characterized in that the substituents X, R ^ ₉ R ₂ , R '* and R ^ have the meaning given in claim 2 and Hai has the meaning given in claim 10. . 12. Insecticidal and / or acaricidal compositions, which as an active ingredient at least one compound according to a of claims 1 to 9 contained 15. Insecticidal and / or acaricidal compositions, which as active ingredient contain at least one of the compounds according to any one of claims 2 to 8. ·. 3098 49/1249