CS215362B1 - 1-substituted imidazoles and triazoles and method of making the same - Google Patents

Description

The invention relates to 1-substituted imidazoles and triazoles of the general formula I,

Ri CHR-N

CH ₂ CH — R ³ (I) (CH) n

R ² where denotes

R is hydrogen, alkyl of 3 to 5 carbon atoms, preferably tertiary butyl,

R ¹ alkyl of 3 to 5 carbon atoms, preferably tertiary butyl, or aryl of 6 to 10 carbon atoms, optionally substituted with 1 to 3 substituents selected from the group consisting of fluoro, chloro, bromo, trifluoromethyl, trichloromethyl, nitro, cyano -, ethoxy group,

R ² is hydrogen or alkyl containing 1-3 carbon atoms;

R ³ is hydrogen or alkyl containing 1 to 4 carbon atoms, n is 0 or 1,

X CH or nitrogen.

The compounds of formula (I) show high activity in controlling and eradicating fungal diseases on plants. In this group of compounds, effective fungicides have been found, particularly against Puccinia recondita and other rust on wheat, barley and other host plants, against powdery mildew (Erysiphe graminis) on wheat, barley and the like. Some of the compounds of the formula I are active on Botrytis cinerae on tomatoes, strawberries and some of the compounds according to the invention are effective against fungal diseases in the post-harvest period, i.e. during storage. In this class of compounds, active compounds have been found for the treatment of cereal seed, e.g. against the Tilletia type.

The compounds of the invention may be administered as such or in the form of compositions. The compounds or compositions may be applied as sprays, dusts or in the form of vapors. They can be applied to any part of the plant, ie leaves, seeds, roots and soil surrounding the roots. The compounds according to the invention are preferably used in the form of compositions for agricultural and horticultural purposes, the type of composition used depending on the particular application. The compositions may take the form of powders, granules, e.g. in admixture with kaolin, bentonite, calcium carbonate, talc. For seed dressing, the compositions may contain seed adhesion promoters such as mineral oils, carboxymethylcellulose, polyvinyl alcohol, polyvinyl acetate, acacia, or in the form of a solution such as dimethylforamide. These compositions may further comprise fillers and suspending agents. The compositions may be in the form of dispersing or emulsions containing the active ingredient in the presence of one or more wetting, dispersing, emulsifying or suspending agents such as cationic, anionic and nonionic surfactants. The compositions thus prepared are used in the form of surfactants. The formulations thus prepared are used in the form of concentrates or diluted with water before use.

The process according to the invention is based on the known and readily available (Bull. Soc. Chim. France 1363 (1955), US Pat. 3,679,697) haloketones of the general formula II,

R ¹ —CO — CH — Hlg (II)

Wherein R ¹ and R ¹ are as defined above and H 1g is halogen, preferably chlorine or bromine, by reaction with a heteroaromatic amine of formula

III,

HN ---- II - (IM)

X N where X is as defined above, in a biphasic aqueous solution of an alkaline hydroxide or carbonate solution and a water-immiscible organic solvent in the presence of a phase transfer catalyst in a high yield of 60-80% yield a product of formula IV,

R ¹ —CO — CH — N -

I II (IV)

RXN wherein R, R ¹ are as defined above. The reaction is preferably carried out by heating a mixture of haloketones of formula II and a heteroaromatic amine of formula III in a molar ratio of 1: 1 to 2, an aqueous solution of potash or sodium hydroxide and a chlorinated solvent such as chlorobenzene or benzene and its alkyl homologs. to 110 ° C. After completion of the reaction, the aqueous phase is separated, extracted with the same solvent, the combined organics are washed with a small amount of saturated sodium chloride solution, dried over sodium or magnesium sulphate and, after evaporation of the solvent, the product obtained is purified by crystallization or distillation. Preferred phase transfer catalysts are the quaternary ammonium or phosphonium salts of formula IV-,

R «

R ⁷ —Z — R ⁴

R ⁵

Λ / v / - / (knows) where denotes

R ⁴ , R ⁵ , R ° C 1 -C 8 alkyl,

R ^{7 is} C 1 -C 16 alkyl or C 1 -C 5 phenylalkyl in the aliphatic chain,

Y is nitrogen or phosphorus.

The process according to the invention also provides a novel process for the preparation of the compounds of the general formula IV.

The compounds of formula 1 according to the method of the invention are prepared by reacting a compound of formula IV with the corresponding 1,2-alkanediol or 1,3-alkanediol of formula V,

HO-CH ₂ - (CH) _n -CH-R ³ (V)

I |

R ² OH wherein R ² and R ³ are as hereinbefore defined, in the presence of acidic reactants at elevated temperature and concomitant removal of the reaction water, preferably by means of -azotropic distillation, after which the desired product of formula I is isolated by conventional methods.

An advantage of the present invention is the easy and simple preparation of the compounds of formula IV, which does not require complex plant equipment.

The invention and its effects are illustrated by the following examples.

Example 1 o> - (Imidazol-1-yl) -acetophenone (compound I)

A mixture of 0.68 g of imidazole, 20 ml of benzene, 0.1 trioctylmethylammonium chloride, 2.2 g of phenacyl bromide was stirred for 20 minutes at room temperature, and then 1.38 g of potash was added and stirred again for 1 hour at 30 to 50 ° C. After cooling again, 5 ml of water was added, stirred for 30 minutes and then the solids were aspirated. The aqueous phase was separated from the organic layer, the solvents were removed by rotary evaporation, and the combined solids were crystallized from alcohol-cyclohexane to give 1.05 g of product, m.p. 101-102 ° C. The following significant ionic species m / e (%. Ri) were found in the mass spectrum: 187 (1.76), 186 ^M (7.65), 105 (48.5), 85 (100), 84 (48, 2), 77 (31.2), 55 (84.3). The proton NMR spectrum (CDCl _a) TMS internal standard were found the following signals (ppm): 5.39 <5 (2H) corresponds to CH _2; 6.97 and 7.06 d (1H, 1H) correspond to imidazole ring protons, two multiplets centered at 7.58 and 7.95 δ (6H) correspond to aromatic and imidazole ring protons. α- (Imidazol-1-yl) -acetophenone hydrobromide mp 260-262 ° C / ethanol.

Example 2 (t) - (Imidazol-1-yl) -4-bromoacetophenone (compound 2)

To a solution of 0.68 g of imidazole, 0.1 g of trioctylmethylammonium chloride in 20 ml of dichloromethane was added 1.5 g of potash and 5 ml of water. After stirring the reaction mixture at room temperature for 30 minutes, 2.78 g of 4-bromophenacyl bromide dissolved in 10 ml of the same solvent was added in 4 portions. After stirring for another 3 hours at room temperature, the reaction mixture was heated to boiling for 2 hours, cooled, and after solids were filtered off, the aqueous layer was separated and the solvents were distilled from the organic phase in vacuo. Crystallization of the solid residue from ethanol-cyclohexane gave 2.1 g of product, m.p.

165 [deg.] C. Mass Spectrum m / e (% rel. Int.): 264/266 (15.1 / 14.9), 183/185 (100 / 98.3), 155/157 (29.2 / 28.9), 120 (24.3), 93 (44.5), 79 (71.2), 78 (72.5). In the proton NMR spectrum (CDCl ₃ , TMS ppm): 5.42 δ (singlet, 2H), 6.98 δ (doublet, 1H, ³ Jhh = 1.5 and 7.53 δ (singlet, 1H) corresponds to protons in the imidazole ring, 7.72 <5 (doublet, 2H, ³ Jhh = θ Hz) and 7.88 <5 (doublet, 2H, ³ <Ιηη = θ Hz) protons of the aromatic nucleus.

Example 3 cu- (Imidazol-1-yl) -4-nitroacetonphenone (compound 3)

To a solution of 3.45 g of imidazole, 0.4 g of triethylbenzylammonium chloride and 6.5 g of potash in 100 ml of dichloromethane, after stirring for 20 minutes, 12.5 g of 4-nitrophenacyl bromide in 40 ml of the same solvent was added. After the reaction time and work-up as in Example 2, 6.3 g of product were isolated, which after recrystallization from ethanol-ethyl acetate had mp 168-171 ° C. Mass Spectrum m / e (% rel. Int.) 232 (8.4), 231 (63.1), 150 (100), 134 (7.9), 120 (21.0), 104 (52.6) ), 92 (14.5), 81 (55/7), 76 (25.3), 54 (19.5), 50 (14.7), 43 (26.8), in the NMR spectrum (CI) C1 ₃ , TMS internal standard ppm) 5.46 δ (singlet, 2H) RDH ₂ -group, 6.96 and 7.53 δ (3H) imidazole protons. ring, 7.70 < 5 (doublet, 2H) and 7.82 < 5 (doublet 2H) aromatics protons.

Example 4 1- (3,3-1) Imethylbutan-2-one-1-yl) imidazole (Compound 4)

The procedure of Example 1 was followed. From 3.45 g of imidazole, 8.95 g of 1-bromo-3,3-dimethylbutan-2-one, 7.5 g of potash, 0.4 g of trioctylmethylammonium chloride yielded 5.8 g. g of product mp 216-217 ° C / ethyl acetate. MS m / e (% rel. Int.) 167 (4.1), 166 (36.0), 85 (21.6), 82 (35.2), 81 (33.6), 68 (38, 4), 57 (100), 45 (24.0), 44 (58.4), 43 (41.6), 41. (57.6).

Example 5 ω Methyl-co- (imidazol-1-yl) -acetophenone (compound 5)

A mixture of 680 mg of imidazole, 100 mg of trioctylmethylammonium chloride, 1.5 g of potash, 2.4 g of 1-bromoethylphenyl ketone gave after treatment 950 mg of the product, mp 96-98 ° C, whose spectral characteristics are in accordance with the proposed structure.

Example 6 m- (Imidazol-1-yl) -4-bromoacetone phenone (compound 2)

To a mixture of 0.68 g of imidazole, 0.1 g of triethylbenzylammonium chloride (TEBA), 20 ml of dichloromethane and 5 ml of 2N-NaOH, after stirring for 1/2 hour, 2.78 g of 4-bromophenacyl bromide dissolved in 10 ml of the same were added. solvents. Following the usual procedure (see Example 2), 1.96 g of product were obtained, m.p. 163-165 ° C.

Example 7 co- (1,2,4-Triazol-1-yl) -2,3-dichloroacetophenone (compound 6)

To a mixture of 0.69 g of 1,2,4-triazole, 0.1 g of tributylcetylphosphonium bromide, 20 ml of dichloromethane, 1.5 g of potash and 5 ml of water, after stirring at room temperature for 1/2 hour, 2.67 g of 2,4-dichlorophenacyl bromide dissolved in 10 ml of the same solvent. After stirring at room temperature for 2 hours, the reaction mixture was heated to reflux for 1 hour. After the usual work-up, 2.68 g of the product was crystallized from a mixture of melting point 116-117 ° C. Mass Spectrum - m / e (% rel. / 229 (7.3 / 4.9),

173/175/177 (100 / 65.3 / 11.2), 145 (22.4), 105 (17.8). In the proton NMR spectrum (CD ₃ SOCD ₃ , ppm from TMS) 5.40 <5 (2H) - CH ₂ N, 7.16, 7.25 and 7.40 δ protons in the aromatic nucleus, 7.80 and 8, 24 δ corresponds to protons in the triazole nucleus.

Example 8

2- (2,4-Dichlorophenyl) -2- (1,2,4-triazol-1-ylmethyl) -4-propyl-1,3-dioxolane (Compound 7)

From a mixture of 5.1 g of N- (1,2,4-triazol-1-yl) -2,4-dichloroacetophenone, 2.3 g of 1,2-pentanediol, 50 mg of p-toluenesulfonic acid and 50 ml of benzene, azeotropic distillation removes the water reaction. After 6 hours, the heating was discontinued, the mixture was cooled and washed successively with 3 ml of saturated sodium bicarbonate solution and 3 ml of saturated sodium chloride solution. After drying the organic layer with magnesium sulfate, the solvents were distilled off on a rotary evaporator. 6.8 g of an oily product were obtained, the structure of which was confirmed by spectral methods. Mass Spectrum - m / e (% rel. Int.): 264 (8.1), 263 (7.2), 261 (39.0), 260 (10.0), 259 (58.9), 193 (10) 0, 191 (16.1), 175 (31.2), 173 (48.9), 128 (18.1), 70 (8.0), 69 (100), 55 (11.2), 41 (36.6). The proton NMR spectrum are found signals (C _E D ₆ NO ₂₎ ppm, TMS internal standard: 0.82 <) (3H) CH _3; 1.32 δ (4H) -C-CH ₂ -0- 4.86 δ (2H) _CH ₂ N; 3.1 <5 4.1 to <5 (3H), -CHO and -CH ₂ O-; 7.15 δ, 7.20 <5, 7.37 δ (SH) correspond to protons in the aromatic nucleus, 7.99 <5 and 8.43 δ correspond to protons in the triazole nucleus.

Example 9

2- (4-Bromophenyl) -2- (imidazol-1-ylmethyl) -4-propyl-1,3-dioxolane (Compound 8)

Reaction water was removed from a mixture of 2.64 g of o0- (imidazol-1-yl) -4-bromoacetophenone, 1.3 g of 1,2-pentadiol, 35 mg of p-toluenesulfonic acid and 30 ml of toluene by azeotropic distillation. After heating for 5 hours, the reaction mixture was worked up in the usual manner. 3.6 g of an oily product are obtained, the structure of which is in accordance with the ¹ H-NMR spectrum.

Example 10

2-Phenyl-2- (imidazol-1-yl-methyl) -4-ethyl-5-methyl-1,3-dioxane (Compound 9)

A mixture of 1.86 g of (N - (imidazol-1-yl) -aeetophenone, 1.4 g of 2-methyl-1,3-pentadiol, 30 mg of p-toluenesulfonic acid and 30 ml of toluene was heated to boiling while removing the reaction mixture). After 6 hours of heating, the reaction mixture was cooled, washed with 3 ml of saturated sodium bicarbonate solution, 3 ml of saturated sodium chloride solution and finally dried over magnesium sulphate. agrees with the proposed structure.

Example 11

2- (4-Nitrophenyl) -2-imidazol-1-ylmethyl) -4-propyl-1,3-dioxolane (Compound 10)

The procedure was as in Example 9. From a mixture of 2.3 g of N- (imidazol-1-yl) -4-nitroacetophenone, 1.4 g of 1,2-pentahdiol and 35 mg of p-toluenesulfonic acid in 30 ml of toluene was Example 9 yielded 3.2 g of an oily product whose structure was confirmed by spectral methods.

Example 12

2-tert-Butyl-2- (imidazol-1-ylmethyl) -4-propyl-1,3-dioxolane (Compound 11)

A mixture of 4.98 g of 1- (3,3-dimethylbutan-2-on-1-yl) imidazole, 2.7 g of 2-propyloxirane, 0.9 g of tetrabutylammonium bromide in 35 ml of toluene was heated to reflux for 10 hours. The product was then isolated as in Example 9. 7.3 g of a pale yellow oil were obtained, the structure of which was consistent with the interpretation of the spectra.

Example 13

This example illustrates five examples of compositions according to the invention a) Seed dressing powder

Compound 7 250 g / kg dodecylbenzene 30 g / kg talc do lkg Emulsified concentrate Compound 6 200 g / kg ethylenoxidated alkylphenol 100 g / kg sodium alkylanylsulfonate 200 g / kg dimethylforamide do lkg Aqueous suspension Compound 7 250 g / l sodium alkylanylsulfonate 30 g / l bentonite 15 g / l polysaccharide 1 g / l water to 1 1

d) Granulate

Compound 8 5-10% by weight starch kaolin

e) Solution in solvent Compound 7 dimethylformamide to% by weight to 100% by weight

200 g / l

1

Example 14

The following technique was used to test compounds against various foliar fungi:

The test plants are grown in 0-4 cm micro-pots in John Jonnes No. 1 compost by placing a layer of fine sand on the bottom of the pot. The test composition is applied by preparing a stock solution of the test compound in ethanol or ethanol-acetone and diluting to the desired concentration just prior to use. In leaf diseases, a solution or suspension of 100 ppm active ingredient is sprayed onto the leaves, applied to the maximum containment, and the substance is introduced to the roots via soil to a final concentration of about 40 ppm based on dry soil.

Treatment of plants, both leaves and soil, is carried out by applying the test compound 1-2 days prior to inoculation of the plants with diseases, only in the case of the Erysiphe graminis test, the plants are inoculated 24 hours before treatment. After inoculation, the plants are placed in an appropriate environment to allow the disease to progress in order to evaluate the disease. The time between inoculation and evaluation varies between 4 and 14 days and depends on both the environment and the disease.

When used as foliar fungicides, their concentrations may range from 0.5 to 0.0005% by weight, preferably 0.2 to 0.001% by weight. When applied to the seed, 0.01 to 50 g of compound, preferably 0.5 to 5 g, are used per kilogram.

In the following Table i, disease control results are characterized by the following scale:

..... in more than 60% of plants, the disease has developed,

..... 26 to 60% of plants have a disease,

..... 6 to 25% of the plants have a disease,

..... n 1 'to 5% of plants have a disease,

..... there was no case of disease in the file,

Table I

Compound number

9

Puccinia recondita on wheat

2— 3 4

3— 4 2—3

Erysiphe graminis on barley

2— 3 4

3— 4

Botrytis cinerae on tomatoes

1 2 3

2—3 2

Example 15

Seed dressing test - gooey mildew (seed-borne mycosis).

The active ingredient is mixed into the mixture of equal parts by weight of talc and diatomaceous earth at the desired concentration. Wheat seed is contaminated with chlamydospores of Tilletia caries at a rate of 5 g spores / kg seed. The seeds are then shaken in a sealed glass container with mordant, the seeds are decomposed on moist clay, covered with 1 layer of mule and 2 cm of medium-moist compost soil and left in a thermostatic container for 10 days at 10

Evaluation of germinated spores on experimental wheat grains is performed microscopically (each grain carries about 1.10 ^B spores), the less germinating the spore, the more effective the substance.

An overview of the results is shown in Table 11. ''

Table II

Seed pickling dough

Compound concentration used germination number effective amount of spores in% mordant compound in mordant g / kg seed

(% by weight) infested - - 10 ch ₂ nhcs ₂ \ Zn 10 1 0.5 ch ₂ nhgs ₃ / known compound 6 . 10 1 0.05 7 10 1 0.005 8 10 1 0.05 9 10 1 0.05 ''

SUBJECT

Claims (7)

1. I-substituted imidazoles and triazoles of formula 1: R ¹ CHR-N- CH ₂ CH-R ^{3 '} (CH)' R ² where denotes R is hydrogen, alkyl of 3 to 5 carbon atoms, preferably tert. butyl, R ^{1 is} C 3 -C 5 alkyl, preferably tert. butyl or aryl of 6 to 10 carbon atoms, optionally substituted with 1 to 3 substituents selected from the group consisting of fluoro, chloro, bromo, trifluoromethyl, trichloromethyl, nitro-, cyano-, methoxy-, ethoxy, ^And R is hydrogen or alkyl containing 1-3 carbon atoms; R ^{3 is} hydrogen or C 1 -C 4 alkyl, n is 0 or 1; X CH or nitrogen. 2. A process for the preparation of 1-substituted imidazoles and triazoles of formula (I) according to claim 1, characterized in that the haloketones of formula (II) are: Ri — CO — CH — Hlg (II) R where R and R ¹ have the abovementioned meaning and H1g denotes chlorine or bromine, acts by a heteroaromatic amine of formula III, HNI II Where X is as defined above, in a two-phase system of an aqueous alkali metal hydroxide or carbonate solution and a water-immiscible organic solvent in the presence of a phase transfer catalyst at a molar ratio of reactants of 1: 1 to 2 at 30 to 110 ° C; the organic phase is separated off, the solvents are distilled off in vacuo and the residue is crystallized to give the product of formula IV, R 1 -CO-CH-N- (IV) I I II RXN \ z wherein R, R ¹ and X are as defined above, which by treatment with 1,2-alkanediol or 1,3-alkanediol of the general formula V, HO-CH ₂ - (CH) "- CH-R ³ (V) R ² OH where R ² and R ^a are as defined above and n is 0 or 1, in the presence of acidic reactants at a temperature of 60 to 140 ° C and at the same time removing the reaction water to convert to the desired product of formula I after washing with saturated sodium chloride solution or aqueous sodium bicarbonate solution and evaporation of the organic solvent in vacuo and isolation. 3. The process of claim 2 wherein the alkali carbonate or hydroxide is a potash or sodium hydroxide. 4. A process according to claim 2, wherein the non-water-miscible organic solvent is a chlorinated alkane having from 1 to 4 carbon atoms or benzene, chlorobenzene, 1,2-dichlorobenzene, toluene and xylenes, or a mixture thereof and ethyl acetate. 5. A process according to claim 2, wherein the quaternary ammonium or phosphonium salt of formula VI is used as the phase transfer catalyst, (') Y (-) (VI) wherein R ⁴ , R ⁵ , R ^e is alkyl of 1 to 8 carbon atoms and R ⁷ is alkyl of 1 to 16 carbon atoms or phenylalkyl of 1 to 5 carbon atoms in the alkyl chain, Z represents a nitrogen or phosphorus atom, Y represents halogen, in particular chlorine or bromine or hydrogen sulphate. 6. The process of claim 2 wherein the reaction water is removed by azeotropic distillation. 7. Process according to claim 2, characterized in that arylsulphonic acids, preferably p-toluenesulphonic acids or inorganic exchangers, are used as acidic reactants. R ⁶ R ⁷ —Z — R ⁴ R ^e