KR830002010B1 - Method for preparing substituted 1-thia-3-aza-4-one - Google Patents

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Description

Method for preparing substituted 1-thia-3-aza-4-one

The present invention relates to a process for the preparation of novel 1-thia-3-aza-4-one useful as plant fungicides and aquatic plant growth regulators.

The present invention relates to a process for preparing a thiazinone compound of formula (VIII), characterized by reacting a compound of formula (VII) with a ring closure agent.

Wherein R is C ₃ -C ₁₀ alkyl C ₃ -C ₈ cycloalkyl, metalyl, phenyl, halophenyl, trifluoromethylphenyl, benzyl, methoxy benzyl, methylbenzyl, habenzyl,, dimethylaminoethyl, methyl Cyclohexyl, C ₃ -C ₈ cycloalkyl (C ₁ -C ₈ ) alkyl, α-methyl benzyl, 2-thiazolyl, nitrophenyl, phenoxyphenyl, (tetrahydro-2-furanyl) methyl, haloaniyl , Trifluoromethylthiophenyl, methylthiophenyl, 2-norbornyl, furfuthyl, 2- (1-methoxypropyl), methoxyphenyl, fluoro (C ₁ -C ₂ ) alkoxyphenyl, 3,4- (Tilenedioxy) phenyl, xylyl, biphenylyl, tolyl or halotolyl and R ³ is hydrogen or methyl; R ⁴ is hydrogen or C ₁ to C ₆ alkyl; R ⁵ is hydrogen or methyl.

When R ³ or R ⁴ is hydrogen or R ³ is methyl and R ⁴ is C ₁ -C ₆ alkyl and R ⁵ is hydrogen, the compound of formula (VIII) is alkylated such that R ³ is methyl or R ⁴ is C ₁ General formula (VIII) compounds, which are —C ₆ alkyl, or general formula (VIII) compounds, wherein R ³ is methyl and R ⁴ is C ₁ -C ₆ alkyl and R ⁵ is methyl. It is also possible to further react the 4-keto group of formula (VIII) with P ₂ O ₅ to produce the corresponding thions.

In the prior art, Surrey describes a process for preparing 4-thiazolidone by reacting thioglycolic acid with a Schiffbase (J. Am. Chem. Soc. 69, 2911-2912 (1947)). However, no mention is made here of the utility of the compounds prepared accordingly.

Troutman et al. Describe the synthesis of 2-aryl-3-alkyl or 2-hetero-3-alkyl-4-thiazolidone that has anticonvulsive activity (J. Am. Chem. Soc. 70, 336- 3469 (1948).

Pennington et al. Describe the preparation of 2-substituted-4-thiazolidones (J. Am. Chem Soc 75, 109, 114 (1953)), according to which the compound exhibits anti-tuberculosis activity in vitro. .

Surrey et al. Also describe a process for the preparation of 2-aryl-4-thiazolidone (J. Am. Chem Soc. 76, 578-580 (1954)), and significant vimeba activity (ends in tests with hamsters). Amoeba Crisseti).

In other prior art references (J. Indian Chem. Soc., 595-597 (1976)), Xing describes the synthesis of a number of 5-methyl-3-aryl-2-arylimino-4-thiazolidinones. He and his acetoxy mercury derivatives claim to have fungicidal activity in tests using Altinary Solani as the test microorganism.

Japanese Patent No. 48-17276 discloses a method for preparing a thiazolidone derivative containing a 2-pyridyl group in its molecular structure, and accordingly, the compound has central nervous inhibitory activity.

U.S. Patent No. 4,017,628 (April 12, 1977) also describes the treatment of livestock mange using a 2-pyridyl substituted thiazolidinone compound.

Yard Harp et al. Describe the preparation of 2-methyl-2- (2-hydroxy-4, 5-dimethylphenyl) -3-aryl-4-thiazolidinone (J. Indian Chem. Soc., 424- 426 (1978) shows fungicidal activity against Helmintosporium apatarene.

The present invention includes a fungicidal composition characterized by consisting of a general formula (V) compound as an active ingredient and a fungicidally nontoxic excipient.

Wherein R ¹⁴ is C ₃ -C ₆ alkyl, C ₅ -C ₆ cycloalkyl, habenzyl, trifluoromethylphenyl, halophenyl, tolyl or methoxyphenyl, and R ¹⁵ is hydrogen or methyl.

The present invention also encompasses aquatic plant growth regulating compositions which are composed of the general formula (VI) as active ingredients and aquaticly nontoxic excipients.

이며 ; R₃는 수소 또는 메틸이고 ; R⁴는 수소 또는 C₁-C₆알킬이며 ; R₅는 수소 또는 메틸이다.In the above general formula, R ¹⁶ is C ₃ -C ₁₀ alkyl, C ₃ -C ₈ cycloalkyl, metalyl, phenyl, halophenyl, trifluoromethylphenyl, methoxybenzyl, methylbenzyl, halobenzyl, benzyl, dimethylaminoethyl, C ₃ -C ₈ cycloalkyl (C ₁ -C ₃ ) alkyl, methylcyclohexyl, 2-thiazolyl, α-methylbenzyl, phenoxyphenyl, (tetrahydro-2-furanyl) methyl, haloaniyl , Xylyl, trifluoromethyl thiophenyl, methylthiophenyl, methoxyphenyl, fluoro (C ₁ -C ₂ ) alkoxyphenyl, 3,4- (methylenedioxy) phenyl, biphenylyl, 2-norbornyl , Furfuryl, 2- (1-methoxypropyl), halotolyl, or doryl; X is oxygen or sulfur; Z is

And; R ₃ is hydrogen or methyl; R ⁴ is hydrogen or C ₁ -C ₆ alkyl; R ₅ is hydrogen or methyl.

The present invention also relates to a method for protecting plants from phytopathogenic fungi by contacting fungi with an amount of a general formula (V) compound which is fungicidally effective but does not exhibit herbicidal activity.

In the above general formula

R ¹⁴ is C ₃ -C ₆ alkyl, C ₅ -C ₆ cycloalkyl, habenzyl, trifluoromethylphenyl, halophenyl, tolyl or methoxykenyl, and R ¹⁵ is hydrogen or methyl.

The present invention also relates to a method for regulating the growth of aquatic weeds by adding growth-regulated and non-herbicidal concentrations of general formula (VI) compounds to water, including submerged and suspended aquatic weeds.

이며; R³는 수소 또는 메틸이고 ; R⁴는 수소 또는 C₁-C₆알킬이며; R⁵는 수소 또는 메틸이다.In the above general formula, R ¹⁶ is C ₃ -C ₁₀ alkyl, C ₃ -C ₈ cycloalkyl, metalyl, phenyl, halophenyl, trifluoromethylphenyl, methoxybenzyl, methylbenzyl, halobenzyl, benzyl, dimethylaminoethyl, C ₃ -C ₈ cycloalkyl (C ₁ -C ₃ ) alkyl, methylcyclohexyl, 2-thiazolyl, α-methylbenzyl, phenoxyphenyl, (tetrahydro-2-furanyl) methyl, haloaniyl xylyl , Trifluoromethylthiophenyl, methylthiophenyl, methoxyphenyl, fluoro (C ₁ -C ₂ ) alkoxyphenyl, 3,4- (methylenedioxy) phenyl, biphenylyl, 2-norbornyl, furfuryl , 2- (1-methoxypropyl), halotolyl, or tolyl; X is oxygen or sulfur; Z is

Is; R ³ is hydrogen or methyl; R ⁴ is hydrogen or C ₁ -C ₆ alkyl; R ⁵ is hydrogen or methyl.

In the general formula, C ₃ -C ₁₀ alkyl is n-propyl, isopropyl, n-butyl, secondary butyl, isobutyl, t-butyl, n-pentylisophenyl, secondary pentyl, t-pentyl, n-hexyl , Secondary hexyl, isohexyl, t-hexyl, n-heptyl, isoheptyl, secondary heptyl, n-octyl, secondary octyl, isooctyl, n-nonyl, secondary nonyl, isononyl, n-decyl, 2 Tertiary decyl and the like, C ₁ -C ₆ alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, secondary butyl, isobutyl, t-butyl, n-pentyl, isopentyl, secondary pentyl, t-pentyl, n-hexyl, secondary hexyl, isohexyl, t-hexyl and the like, C ₃ -C ₉ cycloalkyl is saturated such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like Monocyclic cycloalkyl is indicated.

Halophenyl is 0-chlorophenyl, p-chlorophenyl, p-fluorophenyl, p-bromophenyl, p-iodophenyl, m-chlorophenyl, 0-bromophenyl, 0-fluorophenyl, 2,4 -Difluorophenyl, 2,5-dichlorophenyl, 2,5-dibromophenyl, 2,4-dichlorophenyl, 2-bromo-4-chlorophenyl, 2,4-dibromophenyl, 3, 4-difluorophenyl, 4-bromo-2-chlorophenyl, 4-bromo-3-fluorophenyl, 3,4-dichlorophenyl, 3,4-dibromophenyl, 4-chloro-3- Fluorophenyl, 3,5-difluorophenyl, 3,5-dichlorophenyl, 3,5-dibromophenyl, 2,3,4-trichlorophenyl, 2,4,5-trichlorophenyl, 2 , 3,4,5-tetra chlorophenyl and the like.

Halobenzyl is 0-chlorobenzyl, p-chlorobenzyl, p-fluorobenzyl, p-bromobenzyl, p-iodobenzyl, m-chlorobenzyl, m-bromobenzyl, m-fluorobenzyl, 2,4 Dichlorobenzyl, 2-bromo-4-chloro, 3,4-dibromobenzyl, 2,5-dichlorobenzyl, 3,5-dibromobenzyl, 4-chloro-3-fluorobenzyl, 2, 5-difluorobenzyl and the like are indicated.

Haloaniline denotes p-chloroanilyl, 0-chloroanilyl, m-chloroanilyl, 2,6-dichloroanilyl, p-bromoanilyl, 0-bromoanilyl and the like.

Fluoro (C ₁ -C ₂ ) alkoxyphenyl denotes trifluoromethoxyphenyl, 1,1,2,2-tettafluoro ethoxyphenyl and pentafluoroethoxyphenyl.

C ₃ -C ₈ cycloalkyl (C ₁ -C ₃ ) alkyl is cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl, cycloheptyl Methyl cyclooctylethyl, cycloheptylmethyl, cyclooctylmethyl, cyclopropylpropyl, cyclobutylpropyl, cyclopentylpropyl, cycloheptylpropyl, cyclooctylpropyl, 1- (2-cyclopentyl-1-methyl) ethyl, 1-cyclo Hexylpropyl, and the like.

Methoxyphenyl denotes 4-methoxyphenyl, 3,4-dimethoxyphenyl, 3-methoxyphenyl and 3,5-dimethoxyphenyl.

Halo or halogen is chlorine, fluorine, urethra and fluorine. Xyline represents 3,4-dimethylphenyl, 2,3-dimethylphenyl, 3,5-dimethylphenyl, 2,4-dimethylphenyl and 2,5-dimethylphenyl.

Tolyl represents 0-, m- and p-tolyl.

Compounds of general (VI) were found to be effective when used at concentrations ranging from about 0.025 to about 10 ppm, suitably about 0.25 to about 2 ppm, for the growth control of aquatic weeds.

One aspect of the present invention is an amount of fungi that are fungicidally effective but not herbicidal in the location of the fungi (which includes plant stems, leaf stems, flowers or roots, or soils in which fungi may be present). The present invention relates to a method of protecting a plant from phytopathogenic fungi, characterized by treatment with a general formula (V) compound. Application rates vary widely depending on whether the present method of protecting plants from plant pathogenic fungi is carried out in a greenhouse or outdoors, and also to the extent of fungal infection. That is, when used in a greenhouse, the fungicidal compound is applied as a soil drencher in the form of a composition in which the concentration of the active ingredient is about 1 to about 200 ppm, preferably about 5 to about 100 ppm. As will be appreciated by those skilled in the art, application rates in the open air are usually higher than those in greenhouses, ranging from about 25 to about 1000 ppm.

The novel general formula (V) compounds of the present invention have been found to inhibit various fungi, which include the following.

Erythrope graminis triticus, a cause of wheat powdery mildew; Erysipifera cerum of cucumber powdery mildew; Ethysifen polygony of soybean flour; Helmintosporidium sativum of spots disease; Venturiina Equalis of the Apple Black Star Pattern; Plasmopara viticola of Staphylococcus aureus; Sercospora beticola of brown pattern disease; Septoria Tritici on Leaf Blight; Rizoktonia Solani of Mozalok disease.

Preferred compounds for use in the present method of protecting plants from phytopathogenic fungi are compounds of formula (V), wherein R ¹⁴ is halophenyl, cyclohexyl or tolyl, and R ¹⁵ is hydrogen or methyl.

According to the present invention, a process for preparing a tetrahydrothiazin-4-one compound, which is a compound having a 6-membered heterocycle nucleus, is performed according to the following general reaction scheme.

In the above scheme, R is as described above.

In step 1, a mixture of 3-pyridylcarboxaldehyde, an appropriately substituted amine, and an inert water-immiscible solvent (e.g., toluene, benzene, xylene) is collected to capture the water produced by the reaction under Dean-Starktrap. Reflux. The reaction mixture is cooled, filtered and concentrated in vacuo. The residue is purified by crystallization or chromatography. This step product is identified as 3-[(substituted phenylimino) methyl] pyridine, which is used in step 2.

3-[(substituted phenylimino) methyl] pyridine is mixed with β-mercaptopropionic acid and an inert water immiscible solvent (e.g. toluene, benzene, or xylene) and allowed to stand at room temperature overnight or refluxed for several hours. . The reaction mixture is concentrated in vacuo to separate the reaction product in crude form. The crude product is identified as 3- [α- (substituted anilino) -α- (3-pyridyl) methylthio] propionic acid and is used in step 3.

Reacting 3- [α- (substituted anilino) -α- (3-pyridyl) methylthio] propionic acid with N, N'-dicyclohexylcarbodiimide in an inert solvent for about 3 to about 15 hours at room temperature React until this is almost complete. [The ring closure agents that can be used in place of N, n'-dicyclohexylcarbodiimide (DCC) are N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). Other known peptide closure agents can also be used. Suitable inert solvents include methylene chloride, chloroform, carbon tetrachloride and ethylenedichloride. The separated solid is filtered off and discarded. The filtrate is concentrated to dryness in vacuo and the residue is purified according to conventional procedures such as recrystallization or column chromatography. The product is identified as the desired 3- (substituted phenyl) tetrahydro-2-(-pyridyl) -4H-1,3-thiazin-4-one.

Formula (VIII) compounds wherein R ³ , R ⁴ and R ⁵ are hydrogen or R ³ is methyl and R ⁴ and R ⁵ are hydrogen are conveniently alkylated in a manner well known to those skilled in the art. Alkylation is likely to occur at the alpha position relative to the carbonyl group of the thiazin-4-one ring.

Unlike the method of ring-closing after alkylation as described above, instead of β-mercaptopropionic acid in step 2, β-mercaptopropionic acid in which the α and / or β positions are substituted with a desired R ³ , R ⁴ or R ⁵ substituent is used. And by performing the remaining steps, an alkylation product can be obtained.

Preparation of the general formula (VIII) compound in which the carbonyl oxygen is replaced with sulfur is carried out by reacting the carbonyl oxygen compound with phosphorus pentasulfide (P ₂ S ₅ ) for about 18 hours in a suitable solvent, preferably anhydrous pyridine at about 90 ° C. By separating the latter product.

For example, 3- (4-chlorophenyl) tetrahytro-2- (3-pyridyl) -4H-1,3-thiazin-4-one is mixed with anhydrous pyridine and heated to about 90 ° C. Is generated. The solution is stirred and heated with phosphorus pentasulfide in small portions and added thereto before the reaction mixture is heated to about 90 ° C. and stirred overnight, ie for about 18 hours. The reaction mixture is cooled down and the pyridine solvent is evaporated in vacuo and the viscous oily residue is washed with water and washed. The oil is taken up in a solvent (mixture of ethanol and dimethylformamide), decolorized with carbon, filtered and ethanol removed in vacuo. Slowly pouring the dimethylformamide solution into cold water produces a solid precipitate. The solid is extracted into ethyl acetate and the extract is washed with cold sodium chloride solution. The ethyl acetate solution was concentrated in vacuo to give an oil which was chromatographed on a silica gel column using ethyl acetate as solvent and eluent. The viscous oil product obtained is crystallized with a suitable solvent (a mixture of ethyl acetate and ether) to give a product having a melting point of about 115 to 117 ° C. Elemental analysis confirmed 3- (4-chlorophenyl) tetrahydro-2- (3-pyridyl) -4H-1, 3-thiazine-4-dione.

Suitable acid addition salts of the general formula (VIII) compounds are readily prepared using acids selected from hydrochloric acid, hydrobromic acid sulfuric acid, p-toluene sulfonic acid and the like according to conventional methods known to those skilled in the art.

It should be noted that when R ⁵ is H and R ³ ≠ R ⁴ , and the general formula (VIII) compounds in which R ³ and R ⁴ are both hydrogen or both methyl and R ⁵ ≠ H exist as stereoisomers. Such stereoisomers can be isolated by the use of appropriate isolators or chromatography as is known to those skilled in the art.

The following examples further illustrate the synthesis of the general formula (VIII) compounds of the present invention, but do not limit the present invention thereto.

Example 1

3- (4-Chlorophenyl) tetrahydro-2- (3-pyridyl) -4H-1,3-thiazin-4-one This compound is prepared stepwise as follows.

Step 1

A mixture of 53.5 g of 3-pyridylcarboxaldehyde, 63.5 g of 4-chloroaniline and 600 mM of toluene is refluxed for about 4 hours using a Dean-Stark trep to collect the water produced by the reaction. All about 9mι water is collected. The reaction product mixture is cooled, filtered and the filtrate is concentrated to dryness in vacuo. The residue was recrystallized from hot ethyl ether to give 87 g of 3-[(4-chlorophenylimino) methyl] pyridine product having a melting point of about 72 ° C.

Step 2

A mixture of 15 g of 3- [4-chlorophenylimino) methyl] pyridine (prepared in step 1), 15 g of β-mercapto propionic acid and 200 mM toluene is left overnight at room temperature. The reaction mixture is concentrated in vacuo to afford 3-[[alpha]-(4-chloro anilino- [alpha]-(3-pyridyl) methylthio] propionic acid in the form of a yellow oil A portion of the yellow oil is used in the next step.

Step 3

A mixture of 6 g of the adduct from Step 2, 6 g of N, N'-dicyclohexylcarbodiimide, and 100 mι of methylene chloride is prepared at room temperature. After several hours, a white solid precipitate is formed. This solid was filtered and confirmed to be N, N'-dicyclohexylurea. The filtrate is concentrated to dryness in vacuo, and the obtained residue is again dissolved in methylene chloride to further remove N, N'-dicyclohexylurea. The filtrate is concentrated to dryness in vacuo and the remaining residue is washed with 20 mι of cold acetone, and the white solid is filtered and air dried. This solid is 3- (4-chlorophenyl) tetrahydro-2- (3-pyridyl) -4H-1,3-one with a melting point of about 149-150 ° C.

According to the step-by-step overall process of Example 1, other compounds were prepared. In some examples, the yield was improved by refluxing the reactants in step 2 but the yield was improved, the yield being shown at the end of the example. The compounds obtained, the main starting impurities used in their preparation and their weight or capacity are illustrated in later examples.

Example 2

Melting point about 178 to 180 ° C .; 3- (4-tolyl) tetrihydro-2- (3-pyridyl) -4H-1,3-thiazin-4-one with 3.21 g of 3-pyridine carboxaldehyde, 3.21 g of p-toluidine, β- Obtained from 3.18 g of mercapto propionic acid and 6.18 g of N, N'-dicyclo hexylcarbodiimide. Reflux overnight. (The intermediate produces 3- [α- (4-tolylanilino) -α- (3-pyridyl) methylthio] propionic acid.) Yield 1.6g

Analyzes for C ₁₆ H ₁₆ N ₂ OS

Example 3

3-cyclo3-carboximide having a melting point of about 162 to 164 ° C from 3.21 g of 3-pyridyl carboxaldehyde, 2.97 g of cyclohexylamine, 3.18 g of β-mercaptopropionic acid and 6.18 g of N, N'-dicyclohexyl carbodiimide Hexyltetrahydro-2- (3-pyridyl) 4H-1,3-thiazin-4-one is obtained. Reflux 4 hours. (The intermediate 3- [α- (cyclohexylanilino) -α- (3-pyridyl) methylthio] propionic acid is produced). Yield 3.58 g

Analysis of C ₁₅ H ₂₀ N ₂ OS

Example 4

3-hexyltetrahydro-2- (3-pyridyl) from 3.21 g of 3-pyridyl carboxaldehyde, 3.03 g of hexylamine, 3.18 g of β-mercaptopropionic acid and 6.18 g of N, N'-dicyclohexylcarbodiimide ) -4H-1,3-thiazin-4-one is obtained. Reflux overnight (Intermediate 3- [α-hexylarino) -α- (3-pyridyl) methylthio] propionic acid is produced.)

Analyzes for C ₁₅ H ₂₂ N ₂ OS

Example 5

3-cyclopentyl tetrahydro-2- (3-pyridyl) -4H-1,3-thiazin-4-one with a melting point of about 147 to 149 ° C., 3.21 g of 3-pyridyl carboxaldehyde, 2.55 cyclopentylamine g, β-mercaptopropionic acid 3.18g, N, N'-dicyclohexylcarbodiimide 3.21g, cyclopentylamine 2.55g, β-mercaptopropionic acid 3.18g, and N, N'-dicyclohexylcarbodiimide 6.18 Obtained from g. Reflux overnight. (The intermediate 3- [α- (cyclopentylanilino) -α- (3-pyridyl) methylthio] propionic acid is produced.) Yield 1.38 g

Example 6

3-pyridyl carboxaldehyde 3.21 g, 3,4-dichloroaniline 4.86 g, 3.18 g β-mercapto propionic acid and 6.18 g N, N'-dicyclo hexylcarbodiimide (3,4-Dichlorophenyl) tetrahydro-2- (3-pyridyl) -4H-1,3-thiazin-4-one is obtained. Reflux overnight. (Intermediate 3- [α- (3,4-dichlorophenylanilino) α- (3-pyridyl) methylthio] propionic acid is produced). Yield 6.5 g

Example 7

3- (2) having a melting point of about 111 to 113 ° C. from 9.63 g of 3-pyridyl carboxaldehyde, 11.49 g of 2-chloroaniline, 9.55 g of β-mercaptopropionic acid and 18.57 g of N.N′-dicyclohexylcarbodiimide -Chlorophenyl) tetrahydro-2- (3-pyridyl) -4H-1,3-thiazin-4-one. Reflux overnight. (The intermediate 3- [α- (2-chlorophenylanilino) -α- (3-pyridyl) methylthio] -propionic acid was produced.) Yield 6.0 g

Analysis for C ₁₅ H ₁₃ CIN ₂ OS

Example 8

3- (4) having a melting point of about 88 to 90 DEG C. from 6.24 g of 3-phyridylcarboxaldehyde, 8.50 g of 4-chlorobenzylamine, 6.4 g of β-mercaptopropionic acid and 12.37 g of N.N'-dicyclohexylcarbodiimide. -Chlorobenzyl) tetrahydro-2- (3-pyridyl) -4H-1,3-thiazin-4-one. Reflux for 6 hours. (Intermediate, 3- [α- (4-chlorobenzylanilino) -α- (3-pyridyl) methylthio] -propionic acid is produced) Yield 3.1 g

Assay for C ₁₆ H ₁₅ CIN ₂ OD

Example 9

3-pyridylcarboxaldehyde 6.43 g, 4-fluoroanilineniline 6.67 g, β-mercapto propionic acid 6.37 g and 12.4 g N, N'-dicyclohexylcarbodiimide 3 having a melting point of about 162 to 164 ° C Obtain-(4-fluorophenyl) tetrahydro 2- (3-pyridyl) -4H-1,3-thiazin-4-one. Reflux overnight. (Intermediate 3- [α- (4-fluorophenylanilinino) -α- (3-pyridyl) methylthio] propionic acid is produced) Yield 6.6 g

Analyzes for C ₁₅ H ₁₃ FN ₂ OS

Example 10

It has a melting point of about 131 to 133 DEG C from 6.43 g of 3-pyridyl carboxaldehyde, 9.66 g of 4-trifluoromethylaniline, 6.37 g of β-mercaptopropionic acid and 12.4 g of N.N'-dicyclohexylcarbodiimide. Eggplant yields tetrahydro-2- (3-pyridyl) -3- [4-trifluoromethyl) phenyl] -4H-1,3-thiazin-4-one. Reflux overnight. (Intermediate 3- {α- [4- (trifluoromethyl phenyl-anilino] -α- (3-pyridyl) methylthio} propionic acid is produced) Yield 10.6 g

Analytical Value for C ₁₆ H ₁₃ F ₃ N ₂ OS

Example 11

6.43 g of 3-pyridylcarboxaldehyde, 17.63 g of 2-cyclopentyl-1-methyl-ethylamine, 6.37 g of β-mercaptopropionic acid from 12.4 g of N, N'-dicyclo hexylcarbodiimide from about 100 to 112 ° C. 3- (2-cyclopentyl-1-methylethyl) tetrahydro-2- (3-pyridyl) -4H-1,3-thiazin-4-one having a melting point is obtained. Reflux overnight. (Intermediate 3- {α-[(2-cyclopentyl-1-methylethyl) anilino] -α- (3-pyridyl) methylthio} propionic acid is produced.) Yield 2.55 g

Analyzes for C ₁₇ H ₂₄ N ₂ OS

Example 12

3-pyridylcarboxaldehyde 6.43 g, 3,4-dimethylaniline 7.27 g, 6.37 g of β-mercapto propionic acid and 12.4 g of N, N'-dicyclohexylcarbodiimide, having a melting point of about 185 to 188 ° C. -(3,4-xylyl) tetrahydro-2- (3-pyridyl) -4H-1,3-riazin-4-one is obtained. Reflux overnight (Intermediate 3- [α- (3,4-xylylanilino) -α- (3-pyridyl) methylthio] propionic acid was produced.) Yield 8.75 g

Analyzes for C ₁₇ H ₁₈ N ₂ OS

Example 13

From 6.43 g of 3-pyridylcarboxaldehyde, from 4-methylthio aniline (obtained from 10.54 g of 4-methylenethioaniline hydrochloride), from 6.37 g of β-mercaptopropionic acid and from 8.25 g of N, N'-dicyclohexyl carbodiimide 3- (4-methylthiophenyl) tedhrahydro-2- (3-pyridyl) -4H_1,3-thiazin-4-one having a melting point of about 164 to 166 ° C is obtained.

Reflux overnight. (Intermediate produced 3- {α- [4-methylthiophenyl) anilino] -α- (3-pyridyl) -methylthio} propionic acid. Yield 5.72 g

Analyzes for C ₁₆ H ₁₆ N ₂ OS ₂

Example 14

3- (2-fluorophenyl) tetrahydro- from 6.43 g of 3-pyridylcarboxaldehyde, 6.67 g of 2-fluoroaniline, 6.37 g of β-mercaptopropionic acid and 12.4 g of N, N'-dicyclohecarbodiimide 2- (3-pyridyl) -4H-1,3-thiazin-4-one is obtained. Reflux overnight. (Intermediate 3-[(2-fluorophenyl) anilino] -α- (3-pyridylmethylthio} -propionic acid is produced.) Yield 6.93 g

NMR (CDCl ₃ / DMSO) (δ)

Example 15

3- (4-chlorophenyl) tetrahydro-5-methyl-2- (3-pyridyl) -4H-1,3-thiazin-4-one

3.05 g (0.01 mol) of 3- (4-chlorophenyl) tetrahydro-2- (3-pyridyl-4H-1,3-thiazin-4-one prepared in the same manner as in Example 1 under nitrogen atmosphere It is added to 40 mι of anhydrous tetrahydrofuran maintained with mechanical stirring and cooled to about -75 ° C. 4.28 mι of n-butyllithium 2.4 mol hexane solution is added to this cold solution for about 15 minutes to about -70 ° C. The reaction mixture is stirred for about 30 minutes at a temperature of about -75 [deg.] C. and 5mι of methyl iodide is added dropwise over about 10-15 minutes after the addition is complete. Cool overnight in the bath and stir slowly in the morning to about 0 ° C. A peachy solid precipitate forms during the night The reaction product mixture is warmed to room temperature and methylene chloride is added to form a red solution. Concentrate The residue thus obtained is redissolved in methylene chloride, the solution is washed twice with cold water and dried over anhydrous sodium sulfate, the desiccant is filtered and the filtrate is concentrated in vacuo to obtain the residue, which is dissolved in ethyl acetate. The resulting ethyl acetate solution was concentrated in vacuo to dissolve the remaining oil in methylene chloride, treated with carbon to decolorize and filtered, and the filtrate was concentrated to dryness in vacuo. After dissolving and cooling, the solid crystallizes, which is filtered, The solid has a melting point of about 128 to 130 ° C. and a yield of 1.1 g. Elemental analysis of this solid shows 3- (4-chlorophenyl) tetrahydro. It was identified as -5-methyl-2- (3-pyridyl) -4H-1,3-thiazin-4-one.

Analyzes for C ₁₆ H ₁₅ ClN ₂ OS

Following the general procedure of Example 15, the following compound was prepared.

Example 16

4-g of 3- (4-chlorophenyl) tetrahydro-5-methyl-2- (3-pyridyl) -4H-1,3-thiazin-4-one (prepared from Example 15), with 8mι of methyl iodide 3- (4-chlorophenyl) -tetrahydro-5,5-dimethyl-2- (3-pyridyl) -4H- having a melting point of about 126 to 128 ° C. from 5.4 mι of a 2.4 M hexane solution of n-butyllithium 2.60 g of 1,3-thiazin-4-one are obtained.

Analyzes for C ₁₇ H ₁₇ ClN ₂ OS

Example 17

3- (4-chlorophenyl) tetrahydro-2- (3-pyridyl) -4H-1,3-thiazine-4-thione

10 g (0.033 mole) of 3- (4-chlorophenyl) tetrahydro-2- (3-pyridyl-4H-1,3-thiazin-4-one (prepared in Example 1 above) The mixture is mechanically stirred and heated to about 90 [deg.] C. to form a solution.The resulting solution is then stirred continuously, adding 1.78 g (0.008 mole) of phosphorus sulphate in small portions over about 10 to 15 minutes. The solution turns orange After addition, the reaction mixture is stirred overnight at a temperature of about 90 ° C. The red solution is then cooled and the pyridine solvent is evaporated in vacuo The viscous oily residue is washed with water and washed. This oil is dissolved in a mixture of dimethylformamide and ethanol, decolorized with carbon, filtered and the ethanol is evaporated in vacuo The crude dimethylformamide solution is slowly added to cold orange water to give a crude orange solid precipitate. Furnace with aqueous horn Extract from water This extract is washed with cold sodium chloride solution and ethyl acetate solution and concentrated in vacuo to give a dark red oil This oil is dissolved in minimal volume of ethyl acetate and chromatographed on silica gel column to give a red viscous oil. This was crystallized from a mixture of ethyl acetate and ether to give 3.91 g of a yellow solid having a melting point of 115 to 117 ° C. The product was analyzed by elemental analysis to give 3- (4-chlorophenyl) tetrahydro-2- (3-pyridyl ) -4H-1,3-thiazine 4-thione.

Analyzes for C ₁₅ H ₁₃ ClN ₂ S ₂

Aquatic growth control is carried out by adding active-substituted 1-thia-3-aza-4-one compounds of formula (VI) to water containing aquatic or floating aquatic weeds. The compounds can be applied to water in the form of powders mixed with bentonite, Fuller's earth, diatomaceous earth or various powders of silicate such as mica, talc, feldspar and clay. The compounds can also be mixed with surfactant dispersants to produce concentrates which, when used as spray agents, can promote dispersion in water and improve wettability. If desired, the compound may be mixed with a solid powder carrier, an interfacial-active dispersing agent or applied directly on its own, or shaken with water to produce a wet powder that can be applied in the form of an aqueous dispersant. The compounds can be dissolved in oils, such as hydrocarbons or chlorinated hydrocarbon oils, and oil solutions of the compounds of the invention can be dispersed in water with the aid of an interfacial-active dispersant to produce a sprayable aqueous dispersant. Such surfactant dispersants include cationic, nonionic, or anionic surfactants. Such surfactants are known and detailed examples are described in US Pat. No. 2,614,916 to Hoffman et al. The compound of general formula (VI) can also be used by the aerosol method. The solution used by the aerosol method is prepared by directly dissolving this compound in an aerosol carrier which is a liquid under pressure and a gas at atmospheric pressure and normal temperature (eg 20 ° C.). Alternatively, an aerosol solution is prepared by first dissolving the compound in a weakly volatile solvent and then mixing the solution with a highly volatile liquid aerosol carrier. Compounds of formula (VI) are added to water with submerged or suspended weeds in an amount that exhibits growth-modulating activity but no herbicidal activity, ie, at a concentration of about 0.25 to about 10 ppm.

The optimal concentration of the active compound for a particular aquatic weed suppression problem depends on the temperature, the type of weed to be controlled and the type of water to be treated. Higher water temperatures generally require less compound at lower temperatures than necessary for a given degree of control.

When carrying out a treatment to control the plant populations anchored in the moving stream, the compound concentration used in the treatment passes through the treatment area, so that the concentration of the compound during the contact period is dependent on the water flow rate, chemical utilization rate and duration of application. Particular attention should be paid to the fact that it depends on.

The novel aquatic plant growth control method and composition therefor according to the present invention are illustrated by the following experiment.

Experiment 1

Experimental experiments were conducted to evaluate the growth control of aquatic weeds when the compound was used at a concentration of 10 ppm for representative submerged aquatic weeds. The compound of general formula (VI) used for this test was prepared by the following method.

Add 20 mg of compound to 12mι disposable vial. To the vial containing the compound, 1 ml of acetone and 9 ml of aqueous 0.1% polyoxyethylene sorbitan monooleate (Tween 80) solution are added. 4.00mι of this stock solution is added to a plastic container containing 785mι of water to obtain a test concentration of 10ppm. This flask container uses a potted plant with a bottom diameter of 9 cm, a top diameter of 11.5 cm and a height of 11.5 cm.

For the test, Florida Elodia, Hydilda Vertisilata (L.F.) (hereafter referred to as Hydila), and 10 cm long end pieces without side branches are prepared. Three cut branches are placed in each plastic container containing 785 mι of water and the test compound prepared as described above is added together with 3 mι of Hogland nutrient solution. Into each of the several control vessels containing water, add three 10 cm branches of hydrila. To each vessel is added the amount of solvent used to prepare the test compound.

After 2-3 weeks, measure the total length of each plant. The average total growth is obtained by dividing the total length by the number of test subjects. Subtract 10 cm from this to get an average increase. This difference is divided by the average increase in plant length in the solvent control (SC) and multiplied by 100 to obtain% inhibition.

=평균길이, 평균길이-10cm=평균 증가치

= Average length, average length-10 cm = average increase

)×100=% 억제율(One-

) × 100 =% inhibition rate

Each compound used in this experiment is indicated by its example number.

The experimental results observed after 3 weeks at the concentration of 10ppm of the compound are shown in Table 1. In Table 1, the first column number indicates the test compound, and the second column indicates the rate of inhibition of hydrila growth.

TABLE 1

Substituted 1-thia-3-aza-4-one derivatives

Test 2

The general procedure of Experiment 1 was repeated for Hydrila vertisilata (L.F.) using various other compounds of formula (VI). In this case the test compound concentrations are 1,0,5 and 0.25 ppm.

The test compound was prepared by the following method. 20 mg of compound is leveled into 12 ml vials. To the vial containing the compound, 1 ml of acetone and 9 ml of 0.1% aqueous solution of tolyoxyethylene sorbitan monooleate are added. This solution is referred to as stock solution A.

Prepare 1 ppm of test compound as follows. Undiluted solution 4mι was diluted with 36mι of 0.1% polyoxyethylene sorbitan monooleate aqueous solution to obtain stock solution B. Add 4mι of stock B to a plastic test container containing 785mι of water to make 1ppm of the test compound. This plastic test container is the same as used in Experiment 1.

A 0.5 ppm test compound is prepared as follows. Stock solution B 20mι was diluted with 20mι of 0.1% lyricoxyethylene sorbitan monoacetate aqueous solution. 4mι of stock solution C is added to a plastic test container containing 785mι of water, and the concentration is 0.5 ppm.

0.25 ppm of test compound is prepared as follows. Diluted Stock Solution C 20mι with 20mι of 0.1% polyoxyethylene sorbitan monooleate aqueous solution to obtain Stock Solution D. This stock solution D 4mι is added to a plastic container containing 785mι of water to a concentration of 0.25 ppm.

As in Experiment 1, the total growth of each plant was measured three weeks after the application of the test compound, and the percent inhibition was determined using the formula in Experiment 1. The results are reported in Table 2 below. Test compounds are indicated by the preparation example numbers, respectively.

TABLE 2

Substituted 1-thia-3-aza-4-one derivatives

Another aspect of the present invention is practiced by applying an effective fungicidal amount of one or more general formula (V) compounds to the location of plant pathogenic fungi. The effective dosage of the compound will vary somewhat depending on other factors such as the degree of fungal infection and the treatment environment.

The composition preferably comprises one or more additives including water, polyhydroxy compounds, petroleum distillates and other dispersion media, surfactant dispersants, emulsifiers and finely divided inert solids, in addition to substituted 1-thia-3-aza-4-one It contains. The concentration of substituted 1-thia-3-aza-4-one in the composition depends on whether it is applied directly to the plant or diluted with an additional inert carrier such as water to produce the treatment composition.

The treatment composition is most conveniently formulated as a liquid solid concentrate, which is later diluted and used to the desired concentration. Soluble liquid concentrates may be prepared by mixing in an appropriate water-immiscible organic liquid to mix about 1 to about 10% by weight of active ingredient and emulsifier. Such concentrates may be further diluted with water to produce spray mixtures in the form of tangible emulsions in water. Such spray compositions consist of the active ingredient, a water-immiscible solvent, an emulsifier and water. Suitable emulsifiers include nonionic or ionic forms or mixtures thereof, including condensation products of alkylene oxides with phenols and organic acids, polyoxyethylene derivatives of sorbitan esters, ether aralkyl complexes, arylalkyl sulfonates Ionic compounds and the like. Suitable water-immiscible organic solvents used include mixtures thereof such as aromatic hydrocarbons, aliphatic hydrocarbons, cycloaliphatic hydrocarbons and petroleum distillates.

The solid concentrate mixture contains about 10 to about 50% by weight of the substituted 1-thia-3-aza-4-one compound subdivided into solid carriers (egbentonite, fluto, diatomaceous earth, hydrated silica, diatom silica expanded mica, talc, chalk). It can be manufactured by mixing with). Such concentrates may be formulated into powder compositions and used directly, if necessary, or in some cases diluted with additional inert solid carriers containing from about 0.05 to 1% by weight of substituted 1-thia-3-aza-4-one. Powder powder may be produced. Or a surfactant, i.e. a dispersing and / or wetting agent, may be mixed with a substituted 1-thia-3-aza-4-one in the solid carrier to produce about 10 to 25% by weight of the wettable powder concentrate, which is later water or It may also be dispersed in other hydrocyclization carriers to produce a spray composition. Suitable surfactants include condensed aryl sulfonic acids and their sodium salts, sodium lignosulfates, sulfonate-oxide condensate mixtures, alkylaryl polyether alcohols, sulfonate / nonionic mixtures, anionic wetting agents and the like.

The active substance, substituted 1-thia-3-aza-4-one, can be mixed with liquids, simple dispersions, aerosol formulations and other media that can be used for plant treatment or soil application.

The fungicidal compositions of the present invention are applied to plant surfaces that are infected or susceptible by conventional methods such as spraying, spraying, dipping, or trenching. Spraying is preferred, particularly when treating a large number of plants, given the speed and uniformity of the treatment. When spraying, it is usually sufficient to completely wet the infectious or susceptible surface with the liquid dispersant used. Satisfactory results have been obtained when the spray composition is used as an emulsion or solid acid of a solid concentrate.

If fungi to be suppressed are present in the soil, as described above, the fungicidal compounds may be applied directly to the soil, or diluted with various inert solids or liquid diluents and applied to the fungal-infected areas. One application for soil is to spray the soil surface with a dispersion or emulsion of the active ingredient. Allow the application to coat the soil surface or incorporate it into the soil by disking hoeing or other methods known to those skilled in the art. Another application is to apply the active ingredient as a drencher to the soil in the form of a liquid dispersant or an emulsion. The application rate of the active ingredient for the inhibition of soil-culture fungi in the greenhouse is about 5 to about 200 ppm. When using acid addition salts of 1-thia-3-aza-4-one base, the rate of application depends, of course, on the amount of base present. Salts are mainly used because of their ease of handling and formulation.

Fungicidal active compounds of general formula (V) have also been found to be effective in the case of seed use as a seeding agent prior to sowing. When the fungicidal compound is applied as an invasive agent, an invasive composition containing the fungicidal compound and other excipients (eg ethanol-acetone mixtures, polyoxyethylene sorbitan monooleate, etc.) is prepared. When the general formula (V) compound is used as an immersion agent, a satisfactory inhibitory effect is obtained at a rate of about 50 to about 400 ppm with a substituted 1-thia-3-aza-4-one compound. The seeds are soaked in the composition for about 4 hours and then sown. The effect of the general formula (V) compound and its acid addition salts as plant acid fungicides is explained by the following procedure.

Test 3

The effect of general formula (V) compounds on fungi causing four fungal diseases of wheat was measured by drenching the test compounds in leaves and soil in a greenhouse according to the following procedure.

The seed of the Monon variety is sown in a round plastic pot of sanded soil. Prepare two experimental photos and four control ports per disease. (24 ports total). When the seedlings grew about 4-5 inches, that is, about 5-7 days after sowing depending on the season in which the test was conducted, the soil of each of the two test ports was sprayed with the same formulation test compound (approximately 400 ppm application rate) and soil treatment The soil is moistened with 10 milligrams of the same formulated test compound (application rate 12.32 kg / ha) in each of the two test ports. This procedure is carried out for each of the formulated test compounds, two methods of spray application and soil trench application for each test compound per disease in two separate ports. As a control, using a total of four control ports for each disease, the plants of the two control ports are divided into a solvent-emulsifier solution diluted with water and the soil in the two control ports is wetted with a solvent-emulsifier solution diluted with water.

Within 24 hours of application of the formulated test compound and solvent-surfactant solution, all pots are transferred into the greenhouse and inoculated with conidia of test fungi respectively. After moving the plant into the greenhouse, observe the symptoms of the disease for 4 to 8 days and record the extent.

According to the severity of the disease,

1- Severe 4-Weak

2- Slightly severe 4- Disease does not occur (100% inhibition)

3-normal

Test microorganisms are as follows;

Spot Pattern Disease (H): (Helmintosporium Sativaboom)

Red Rust (LR): (Pushnia Recondira Tritici)

Powdery mildew (PM): (Ericipe Graminis Tritici)

Leaf blight (S): (Septaria Trilish)

The results are shown in the following Table 3, wherein the compound number represents the example number thereof.

TABLE 3

Morbidity

The results obtained in the experiments described above indicate that the novel substituted 1-thia-3-aza-4-one derivatives of general formula (VIII) according to the invention are grown in aquatic and floating aquatic plants according to the method described and claimed herein. It has been shown to be effective in regulating, protecting plants from phytopathogenic fungi, and regulating growth of carnivorous plants such as wheat and barley.

Claims (1)

A process for preparing a thiazinone compound of formula (VIII), characterized by reacting a compound of formula (VII) with a ring closure agent.

Wherein R is C ₃ -C ₁₀ alkyl, C ₃ -C ₈ cycloalkyl, metalyl, phenyl, halophenyl, trifluoromethylphenyl, benzyl, methoxybenzyl, methylbenzyl, halobenzyl, dimethylaminoethyl, methyl Cyclohexyl, C ₃ -C ₈ cycloalkyl (C ₁ -C ₃ ) alkyl, α-methylbenzyl, 2-thiazolyl, nitrophenyl, phenoxyphenyl, (tetrahydro-2-furanyl) methyl, haloaniyl , Trifluoromethylthiophenyl, methylthiophenyl, 2-norbornyl, furfuthyl, 2- (1-methoxypropyl), methoxyphenyl, fluoro (C ₁ -C ₂ ) alkoxyphenyl, 3,4- (Methylenedioxy) phenyl, xylyl, biphenylyl, tolyl or halotolyl; R ³ is hydrogen or methyl; R ⁴ is hydrogen or C ₁ -C ₆ alkyl; R ⁵ is hydrogen or methyl.