DD144407A5 - PROCESS FOR PREPARING NEW FUNGICIDE-ACTING IMIDAZOLE DERIVATIVES - Google Patents

Description

21 3994

Yerfahren for the production of new fungicidally active imidazole derivatives,

Field of application of the invention

The invention relates to a process for the preparation of novel imidazole derivatives with fungiaider effectiveness »

Characteristic of the known technical solutions

Published Unexamined Japanese Patent Application No. 39674/77 discloses that some imidazole derivatives have fungicidal activity. The imidazole derivatives are represented by the general formula

stated

wherein E ^{1 is} alkyl, X * is halogen, ITitro, lower alkyl or lower alkoxy and η is 0.1 or 2.

In published, unexamined JP patent application 3Mr. 4ÖO71 / 77 is also disclosed that some other imidazole

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Derivatives fungicidal activity on iron. % of imidazole derivatives are represented by the general formula

shown,. : "

wherein E "is methyl, chlorine, bromine, nitro or tri fluorine thy I and η is 1 or 2.

Although these known imidaaol derivatives have fungicidal activity, the activity is insufficient and they cause phytotoxicity in plants. Therefore, these known compounds can not be used for practical use as fungicides.

Object of the invention

The aim of the invention is a process for producing fungicidal imidazole derivatives which have improved fungicidal properties and no phytotoxicity in plants *

presentation; the essence of the invention

The invention has for its object to provide a process for the preparation of new imidazole derivatives with improved fungiaideη properties.

According to the invention, the new imidazole derivatives of the general formula

wherein X is an identical or different substituent,

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which is halogen, lower alkyl, nitro or lower haloalkyl, η is 1 or 2; Y is alkoxyalkyl, lower alkenyloxyalkyl, phenoxyalkyl * substituted phenoxyalkyl or benzyl; with the proviso that Xn in the case of trifluoromethyl is in the 2-position and chlorine in the 4-position, v / o Y is benzyl, prepared by the reaction shown below.

("Hai" represents halogen.)

The reaction is carried out in an inert solvent in the presence of an alkaline condensing agent such as sodium carbonate, potassium carbonate, sodium hydroxide, sodium methyl alcoholate, trimethylamine, triethylamine, pyridine or piperidine. The inert solvent may be chloroform, dichloromethane, benzene, toluene, xylene, chlorobenzene, acetonitrile , acetone, DiinethyIsulfoxid, tetrahydrofuran, dimethylformamide or dioxane are used _o Usually, a temperature in the range of 0 ° bis- the boiling point of the reaction solution, preferably a temperature of 40 ⁰ C to the boiling point satisfactory. The reaction is usually completed in 1 to 3 hours. After completion of the reaction, the reaction solution is washed with water and dried *

The washing and drying may optionally be carried out after replacing the solvent. Then, the solvent is distilled to obtain the desired compound.

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The corresponding metal complexes can be prepared according to the following reaction equation.

(AB is an organic or inorganic metal salt, A is a divalent or trivalent metal atom, B is the anion component of salia and Z corresponds to the valence number of the metal atom s "A" in the metal salt "AB".)

As the metal salt, the chloride, sulfate, Hiträt or acetate of copper, zinc, Mckel, cobalt, manganese, iron or silver is used · copper sulfate, copper chloride, zinc chloride or zinc acetate is preferably used "^ u ^r hen carrying out the reaction for preparing the metal complexes , the imidazole derivative is dissolved in an inert solvent and a metal salt is added thereto; and the mixture is stirred to allow the reaction. The reaction is usually carried out at room temperature for several minutes. As the inert solvent, any solvents which dissolve the imidasol derivative and are miscible with water can be used.

Usually, ethyl acetate, methanol, acetonitrile, dioxane or tetrahydrofuran are used. After completion of the reaction, the reaction mixture is poured into η-hexane or water; the precipitated crystals are removed therefrom by filtration to obtain the metal complex according to the invention.

Embodiment '_'

The invention will be described in more detail below with reference to some examples

explained.

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example 1

1 ~ / N ^ (2-bromophenyl) -2-ethoxypropanimidoyl-1-imidazole (compound, Hr. 3)

11 g 2 ¹ ~ bromo-2- (etho xy) propionanilide was reacted with 8.4 g of phosphorus pentachloride in 50 ml of chloroform by heating the solution under reflux for 30 minutes. Then, the chloroform and the phosphoroxychloSide * formed as a by-product were removed by distillation, and the residue was dissolved in 40 ml of acetonitrile. To the solution were added 2.8 g of iinidazole and 4.1 g of triethylamine; then the mixture was refluxed for 3 hours. After completion of the reaction, the acetonitrile was distilled off and the residue was dissolved in 30 ml of dichloromethane. The solution was washed several times with water and dried over anhydrous magnesium sulfate. After distillation of the dichloromethane, the remaining oily product was purified by chromatography on silica gel with dichloromethane. 4 g of the desired compound were obtained (n 2 1.5870) *

Example 2

1- | N- (2,4-dichlorophenyl) -2-propoxypropanimidoyl-imidazole (Compound No. 9)

7.5 g of 2 ¹ , 4'-dichloro-2- (propoxy) propionanilide were allowed to with

5.6 g of phosphorus pentachloride in 40 ml of chloroform with heating the solution under reflux for 30 minutes. Then, the chloroform and the phosphorus oxychloride formed as a by-product were removed by distillation under reduced pressure; the residue was dissolved in 40 ml of acetonitrile. The solution is 1.9 g imidazole and 2 ,? g of triethylacin added; the mixture was heated for 3 hours under Bückfluß _o After completion of the reaction, the Eeaktionslösung was treated as in Example 1; 4 g of the desired compound were obtained (η £ 1.5δ9Ο) _β

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Example 3 -.

1 - ["" lT- (4-chloro-2-trifluoromethylphenyl) -2-allyloxy-propanimi-> doyl-imidazole (Compound No. 11)

9 * 3 S 4 ^! Chloro-2Hrifluoromethyl-2- (allyloxy) propionanilide was allowed to react with 6.3 g of phosphorus pentachloride in 40 ml of chloroform with warming of the solution or reflux for 30 minutes. Then, the chloroform and the phosphorous oxychloride were removed by distillation, and The residue was dissolved in 40 ml of acetonitrile. To the solution, 2.1 g of imidazo! and add 3 g of triethylamine; then the mixture was refluxed for 3 hours, after completion of the reaction, the reaction solution was treated as in Example 1; 5 g of the desired compound were obtained (n ² g 1.5440). , .

Example 4

1-1- L- (2,4-dichloro-phenyl) -2-butoxypropani- nido-1-yl-1-imidazole (Compound ETr. 19)

8.8 g of 2 ', 4'-dioxor-2- (butoxy) propionanilide was allowed to react with 6.4 g of phosphorus pentachloride in 40 ml of chloroform while heating the solution under reflux for 30 minutes. Then, the chloroform and the phosphorus oxychloride were removed by distillation and the residue was dissolved in 40 ml of acetonitrile. To the solution were added 2.1 g of imidazole and 3 g of triethylamine; then the mixture was refluxed for 3 hours. After completion of the reaction, the same treatment as in Example 1 was carried out to obtain 415 g of the desired compound (n ⁵ × 1.5682).

Example 5

1 ~ fH- (2,4-dichlorophenyl) -3-propoxypropanimidoyl-imidazole (Compound.Hr · 36)

6f'S g 2 ', 4'-dichloro-3- (propoxy) propionanilide and 8 g triethyl

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amine were dissolved in 30 ml of chloroform; 3.7 g of phosgene were introduced therein at 0 to 10 ^° C. with ice cooling. After raising the temperature of the solution to room temperature, the solution was stirred for 2 hours; then 2 g of imidazole were added. The mixture was refluxed for 2 hours, after which time the reaction was completed. the reaction solution cooled to room temperature, washed with water and dried over anhydrous magnesium sulfate. After removal of the chloroform from the solution by distillation, 7.7 g of the desired compound (n ^ 1.5688) were obtained. ,

Example 6 . '

1- _j [lT- (4-chloro-2-trifluoromethyl) -2-propoxy-ac et imidoyl] imidazole (compound ITr. 37)

12.6 g of 4-chloro-2 ^{1 t-trifluoromethyl-2-} (propoxy) acetanilide and 12.9 g of triethylamine were dissolved in 80 ml chloroform; the solution of 6.4 g of phosgene in 30 ml of chloroform was added dropwise.

The solution was stirred for one hour at room temperature and then, after adding 4.4 g of imidazole, the mixture was stirred for 15 hours at room temperature. After completion of the reaction, the chloroform was removed by distillation. The resulting residue was dissolved in η-hexane; the solution was washed with water and dried over anhydrous magnesium sulfate. After removal of the n-hexane by distillation, the residue was purified by chromatography on silica gel; 9.8 g of the desired compound were obtained (n ² → 1.5370),

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Example 7

imidazole (compound Ur. 39)

7 g of 4'-chloro- ⁵ -trifluoromethyl-2-butoxyacetanilide were allowed to react with 5.2 g of phosphorus penta-chloride in 50 ml of benzene while heating the solution at reflux for one hour. Then, the benzene and the phosphorus oxychloride were removed by distillation under reduced pressure, and the remaining oily product was dissolved in 50 ml of chloroform. To the solution 1.7 g of imidazole und.Triäthylamin were added and then the mixture was heated for one hour under stirring at 50 ⁰ C *

After completion of the reaction, the solution was washed with water and dried; the chloroform was removed by distillation. The residue was purified by chromatography on silica gel; 1.85 g of the desired compound were obtained (n ² → 1.5378).

Example 8 ".

1- [N- (4-chloro-2-trifluoromethylphenyl) -2-ethoxy-acetoxy] imidazole (Compound No. 40).

10 g of 4-chloro-2'-trifluoromethyl-2- (ethoxy) acetanilide and 10.8 g of triethylamine were dissolved in 80 ml of chloroform; a solution of 5.3 g of phosgene in 30 ml of chloroform was added dropwise. - ' ⁿ .

After stirring the solution for one hour at room temperature, 2.9 g of imidazole was added and the mixture was stirred for 15 hours at room temperature. After completion of the reaction, the chloroform was removed by distillation and the residue was dissolved in η-hexane. The solution was washed with water and dried over anhydrous magnesium sulfate. After removal of the n-hexane

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from the solution by distillation, 10.2 g of the desired compound (mp. 49-52 ⁰ C) were obtained

' Example 9

1-i ^ N- (2,4-dichlorophenyl) -4-chloro-2-methylphenoxy-acetinodinyl-imidazole (compound Hr, 43)

3.4 g of 2 ', 4-dichloro ^f (4-chloro-2-methylphenoxy) acetanilide was allowed to react with 2.3 g of phosphorus pentachloride in 40 ml Benaol by heating the solution under reflux for one hour. Then, the benzene and the phosphorus oxychloride were removed by distillation under reduced pressure; the remaining oily product was dissolved in 40 ml of chloroform. To the solution was added 0.75 g of imidazole and 1.1 g of triethylamine; the mixture was stirred at 50 ^° C. for one hour. After completion of the reaction, the same treatment as in Example 7 was carried out; there were obtained 1.1 g of crystals of the desired compound (mp, 84-86 ⁰ C),

Example 10

1-k "" C4-chloro-2-trifluoromethylphenyl) -3-ethoxy-propanimidoyl-1-imidazole (Compound No. * 46)

6.5 g of ^4-chloro-1 2 ^{l-trifluoromethyl-2-} (ethoxy) propionanilide was allowed with 4 »9 g of phosphorus pentachloride in 30 ml of chloroform under reflux for one hour to react. Then, the chloroform and the phosphorus oxychloride were heated by distillation under reduced pressure. To the residue was added 3-2 g of imidazole and 30 ml of acetonitrile; the mixture was refluxed for 30 minutes. After completion of the reaction, the acetonitrile was removed by distillation; the residue was dissolved in dichloromethane. The solution was washed with water and dried over anhydrous magnesium sulfate. After removal of the solvent from the solution by distillation, the residue was acidified

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leucography with alumina purified; There were obtained 3.5 g of the desired compound (mp. 61-62 ⁰ C),

Example 11

1-l-r- (4-chloro-2-trifluoromethylphenyl) -phenylacetimidoyl-imidazole (Compound Ir. 56)

3.5 g of li- (4-chloro-2-trifluoromethylphenyl) -phenylacetamide were left with 2.6 g of phosphorus pentachloride. react in 40 ml of benzene while heating the mixture under reflux. Reaction, the benzene and the phosphorus oxychloride evaporated. The resulting N- (4-chloro-2-trifluoromethyl-phenyl) -phenylacetimidoyl chloride was dissolved in 50 ml of acetonitrile; 0.85 g of imidaaol was added with stirring.

To the resulting solution, 1.3 g of triethylamine was gradually added with cooling; the solution was kept at 60 ^° C. for 30 minutes. After removal of the acetonitrile by distillation, the residue was dissolved in 60 ml of dichloromethane; the solution was washed with water and then dried. An oily product obtained by distilling the dichloromethane from the solution was purified by silica gel column chromatography; it was 2.1 g

OO

obtained the desired compound (η _β 1.5818).

In game 1 2

Bis-ε-k- (2,4-dichlorophenyl) -2-propO3-ypropanimidoyl-7-imidazole} copper chloride (Compound No. 57)

1 g of 1- {N- (2,4-dioxorophenyl) -2-propoxypropanimidoyl} -iinidazole was dissolved in 5 ml of methanol; 0.5 g of anhydrous copper chloride was added. The mixture was stirred for 5 minutes at room temperature and then poured into 100 ml of water to precipitate the crystals. The crystals separated by filtration were washed with water and then with

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Washed η-hexane. The crystals were dried under reduced pressure; 1 g of the desired complex was obtained (mp 165-169 ⁰ C).

Example 13

- {N- (2,4-dichlorophenyl) -2-propoxypropanimidoyl} -imidazo!] Zinc chloride (Compound No. 58)

The reaction of 2 g of 1- [ε] - (2,4-dichloro or phenyl) -2-propoxypropanimidoyl-imidazole with 0.5 g of anhydrous zinc chloride was carried out as in Example 12; 2 g of the desired complex were obtained (mp 157-158 ⁰ C).

Example 14

Bis-ε-iT- (4-chloro-2-trifluoromethylphenyl) -phenyl-aceto imidoyl-imidazole] copper chloride (Compound No. ₀ 82)

The reaction of 2 g of 1-E-iT- (4-chloro-2-trifluoromethylphenyl) -phenylacetimidoyl-imidazole with 0.5 g of anhydrous copper chloride was carried out as in Example 12 except that ethyl acetate was used instead of methanol as the reaction solvent; There were obtained 2 g of the desired complex · (mp. 105-108 ⁰ C).

The examples of the compounds according to the invention are summarized in Tables 1 and 2 »

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Table 1

Xn y sJl- ~ p \ Tn -GH-OC ₂ H ₅ CH ₃ physical ⁰ C 1.5585 2-F -f o-ö constant connection Y CH ₃ Mp. 1.6222 2-Br -CH-OC ₂ H ₅ / "(TT 1 -CH-O-CH, ι J ⁿ D * 1.5870 tt CH * 1.5300 2 2,4-Cl ₂ -C ₁ HOC ₂ H ₅ CH ₃ n ^{26 n} υ -CH-O-CHo .l _H n ³ 1.5833 3 η -CH-OC ₂ H ₅ Ah ₃ 1.5430 4 2-CI ₃ H-Cl ⁿ H ² y 1.5340 tf -CH-OC ₃ H * 5 3 -GH-O-CH ₉ CH = CH _{2 M} 24! ⁿ D 1.6090 6 2,4-Br ₂ ³ _n ⁿ D 1.5690 7 2,4-Cl ₂ -CH-O "" CpHr- ⁿ² D 1.5705 tt CH ₃ 1.5440 8th 2-CIU-4-C1 n ² l 1.5620 9 2-CH ₃ -rl 3, .-. 10 - ² l 11 * ² l 1 * 2 A

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13 H 2-HO ₂ 3 · CH ₃ t tt [73-763 n ² ^ · ⁵ 1.5292 15 2-Br-4-H0 ₂ tt -CH-OC ₂ H ₅ CH ₃ [160-161] 16 2-Cl tt » n ² j> · ⁵ 1.5720 17 2-GF ₃ ~ 4 ~ Ci -CH-OC ₃ H- I It V- ² J) * ⁵ 1.5300 18. 2-Br CH ₃ 11 n ² ^ · ⁵ 1.5820 19 2,4-Gl ₂ ' CH ₃ t -CH-OG ₄ H * n ² ^ · ⁵ 1.5682 20 2-CPo-4-Gl -CH-OC ₂ H ₅ ¹¹ -CH-OC ₃ H ^ r? \ * ⁵ 1,5295 21 2-Cl-5-CH ₃ CH ₃ n ² ^ 1,5668 -CH-O-CoH ^ 3 ti 22 23 2,4-Gl ₂ 2 -CP ₃ -4-Eq -GH-OC ₄ Hl ⁿ²⁷ D ⁵ 1> 57OO [86-8?] 24 2,4-Cl ₂ CH ₃ n ²⁷ ' ⁵ 1,5684 - 25 2 ~ GF ₃ -4 Cl 11 ²⁷ J ⁵ 1,5275 26 3 ₅ 4-Cl ₂ n ² ^ 1,5782 27 2-G ₂ H ₅ n ²⁷ '1,5541 28 2-lT0 ₂ -4-Cl n ²⁷ 1.5959 29 2-ITO ₂ -S-CH ₃ n ²⁷ 1.5799 30 4-Cl n ² ^ 1,5690 31 * 2-Cl ii ³¹ j ⁵ 1.5650

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'7 18

32

33 34

35 36

37 38

39

40 41 42

43 44 45 46 4748

49 50 51 52 53

2,4-Cl ₂

2-CF ₃ -4-Cl it

2,4-Cl ₂ 2,4-Cl ₂

2-CF3-4-Cl 2,4-Cl ₂

2-CF0-4-CI

2,4-Cl ₂

2,4-Cl ₂

It

2-CF ₃ -4-Cl η

ti

It

2,4-Cl ₂

2-CF0-4-CI

2,4-Cl ₂ 2-CFO-4-CI

-CH-O

-f \

CH.

-QH-O-CHC ₂ H ₅

-CH-O-CHC CH-, CH,

- (CH ₂ )

-CH ₂ -OC ₃ H ^

-CH ₂ -O-CHC ₂ H ₅

-CH ₂ -OC ₂ H ₅

CHU

-CH ₂ -O-

- (CH ₂ ) ₂ -O-C ₂ H ₅ - (CH ₂ ) ₂ -OC ₃ Hy) n " 0-C ₂ Hj-

-CH ₂ -OC ₄ H ₉ -CHO-O-CH-C

η 3 ^X1 7

CH

¹ p

24 D

1.6171

[90-93}

20 D

26

29 D

23 * 5

D 27

34 D

1.5382

1.5692 1.5688

1.5370 1.5765

1.5292

[49-52]

η η

η η

η η η η

21

D 20

1.5962

D ¹ »5875

[84-8 6J

20 D 21

23 D

22 D

22

D 22.5

D 22.5

D 22 * 5

D 22.5

1.5952 1.5463

1.5369 1.5295

1.5705 1.5765 1.5300 1.5717 1.5363

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54 2,4-Cl ₂ -CH ₂ -OC ₃ H ₇ f 52-53J 55 2, Ciy-4-Cl -CH ₂ -OC ₈ H ^ ₇ n ² pounds 1.5225 56 Il n ² l 1.5818

table

connection

Xn

Y AB

Physical constant Smp _e ⁰ C

58 59 60 61

62 63 64 65 66 67 68

2,4-Cl ₂

-CH-OC ₃ H ₇

It

2-CP ₃ -4-Cl CuCl,

ZnCl, CuSO 4 ZnCl,

It

-CH-O '

C ₂ H ₅

CH ₃

-CH ₀ -OC ₀ Hr CuSO,

- (CH ₂ )

-CF ₃ -4-Cl -CH ₂ -O-CH ₉

π -CH ₂ -OC ₃ H ₇ It η It -CH-O-CHC ₂ H ₅ CH ₃ CH ₃ η It

ZnCl,

CuSO 2 ZnCl, CuSO

C.

C.

ZnCl,

[165-169]

[90-94] [48-53] [71-75]

[52-56] 191-943

[58-64] [77-SI] [71-74] 2 * 76-78 /

£ 64-667

-16-

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70 2,4-Ci ₂ 71 Il 72 , 2-CI-4-C1 73 2,4-Cl ₂ 74 2-CF ₃ -4-Cl 75 It 76 It 77 2,4-Cl ₂ 78 2-CF ₃ -4-Cl 79 2,4-Cl 80 · It '81 ti 82 2-C]? ₃ -4-Cl 8 * 3 Il

-ο σ ττ ^η

-CH ₂ -OC

ii

-CH ₂ -OC ₃ Hy

-CH ₂ -O-CH-C

CH.

_T n

CH

CuSO,

[1I7-I20I

ZnCl,

CuSO

f 81-86] [132-138] 144-1513 [55-64] / 83-88]

PeGl ₃

Cu (CH ₃ COO) ₂ Zn (GH ₃ GOO) ₂

CuCl ₂ Zn (CH ₃ COO) ₂

[74-761 [5O-56i

[138-141] C128-I30J

[42-46J

"1" corresponds to the number of valency of the Bietallatoms "A" in the metal salt "AB"

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In Tables 1 and 2, the compounds preferred as fungicides are compounds Ho, 9; 11; 17; 22; 23; 34; 36; 37; 38; 39; 40; 56 and their metal complexes, such as compounds 57; 58; 59; 62; 63; 82 and 83 *

Most metal complexes have superior fungicidal activity and superior residual activity with respect to the corresponding free imidazole derivatives.

As previously mentioned, it has been found that the compounds of the present invention possess fungicidal activity when used in the prevention of plant damage.

Such compounds can combat fungal diseases of the foliage, fruit, stems and roots of growing plants without harming the host plant.

The fungicidal compositions of the present invention are effective against a variety of fungi mentioned in the following section, but are not intended to limit the scope thereof:

Gray mold ,. Sclerotienrost, fouling and powdery mildew of vegetables, brown rot of peaches, leaf sprouts of corn, scab of apples and pears, rust of pears, powdery mildew of apples and rust of cereals; the compounds are especially effective against powdery mildew, scab and rust

Another advantage of these compounds is that they have no plant phytotoxicity.

Claims (1)

- 48 - He is entitled to claim Process for the preparation of an imidazole compound. "of the general formula. wherein X represents an identical or different substituent selected from the group halogen, lower alkyl, nitro and lower haloalkyl, η is 1 or 2; and · . Y from the group Alkoxyniederalkyl, lower alkenyloxyalkyl, Niederphenoxyalkyl, substituted Niederphenoxyalkyl and Benzyl is selected; ' with the proviso that in this case Xn is trifluoromethyl at the 2-position and chlorine at the 4-position that 1 is for Benayl stands,.
characterized in that a compound of the formula • Hai in which X, Y and η are as defined above and Hai is a halogen atom, reacted with imidazole ·