Process for preparing triazolyl-o,n-acetals

Trityl imidazoles and 1,2,4-triazoles, such as triphenylimidazole and triphenyl-1,2,4-triazole, are known to have good fungicidal activity (cf. U.S. Pat. No. 3,321,366 and Belgian Pat. No. 738,095). · However, their performance is not always quite satisfactory, especially in the case of low application rates and concentrations. It is further known that zinc ethylene-1,2-bis-dithiocarbamidate has good fungicidal activity against Phycomycetes species, e.g. against Phytophtora infestans, which causes potato stem and tuber plague and tomato rot, as well as against various soil fungi. However, its effectiveness when used as a seed dressing is not always entirely satisfactory.

Surprisingly, the active compounds according to the invention have a significantly higher fungicidal activity than the compounds known from the prior art, triphenylimidazole, triphenyl-1,2,4-triazole and zinc ethylene-1,2-bis-dithiourea. The active ingredients according to the invention thus enrich the field of technology.

The compounds according to the invention have a very strong fungicidal effect and are more effective than the compounds known from Finnish patent 54,115.

The compounds of formula I have two asymmetric carbon atoms and can therefore exist in both erythro and threo forms; in either case, they are primarily racemates.

Compounds of formula I are obtained when the formula

<img file="FI55835C_D0001.tif" />

where

4 . . . . .. ...

R, R and Az are as defined above, the tetrazole derivatives according to the invention are reduced with (a) hydrogen in the presence of a catalyst and optionally a polar solvent, or (h) aluminum isopropylate in the presence of a solvent, or and alkali metal hydroxide, optionally in the presence of a polar solvent; or that (e) the triazole derivatives of formula II are reacted in the presence of an inert solvent with organometallic compounds of formula

Me-R³ (III) where. ....

R has the same meaning as above and

We mean alkali metal or residue X-Mg, where

X is chlorine, bromine or iodine.

If 1-phenoxy-1- [1,2,4-triazolyl- (1 *)] -3,3-dimethylbutan-2-one and hydrogen are used as starting materials, the reaction can be shown in the following scheme (process option (a)):

<img file="FI55835C_D0002.tif" />

If 1-phenoxy-1- [1,2,4-triazolyl- (1 ')] - 3,3-dimethylbutan-2-one and aluminum isopropylate are used as starting materials, the reaction can be shown by the following scheme (process option (b)) :

<img file="FI55835C_D0003.tif" />

<img file="FI55835C_D0004.tif" />

+ (h *) ​​h₂or \

<img file="FI55835C_D0005.tif" />

OH

I

O-CH-CH-C (CH₃)₃

<img file="FI55835C_D0006.tif" />

Used as starting material 1-phenoxy-1- [1,2,4-triazolyl- (1 ')] - 3_t3 dimethylbutan-2-one and sodium borohydride, the reaction can be shown by the following scheme (process option (c)):

<img file="FI55835C_D0007.tif" />

<img file="FI55835C_D0008.tif" />

^XCH-0 O-CH \

Na t O-CH-fcH-C (CH 2) ₅ f

N - + 2 H₂0 ?^B fi \ _O-qH-CH-C (CH₃) ₃

- NaBO₂

<img file="FI55835C_D0009.tif" />

When 1-phenoxy-1- [1,2,4-triazolyl- (1 ')] - 3,3-dimethylbutan-2-one and formamidine sulphinic acid are used as starting materials, the reaction can be shown by the following scheme (process option (d)):

B₂OF^e= C-S0₂^e/ 20H '

<img file="FI55835C_D0010.tif" />

- H ~ NC-NH₀² II ²

O

- SO,

2e

<img file="FI55835C_D0011.tif" />

Used as starting material 1-phenoxy-1- [1,2,4-triateolyl- (1 ')]

3,3-dimethylbutan-2-one and methylmagnesium iodide, the reaction procedure can be shown by the following reaction scheme (method (e)):

<img file="FI55835C_D0012.tif" />

- MgBr (OH)

The triazole derivatives of formula II used as starting materials in the preparation of the compounds of the invention are not known in the art; however, in part they are the subject of an earlier Finnish patent 54,115 (priority January 11, 1972. They can be prepared, for example, by reacting a haloetherketone with 1,2,4-triazole in a stoichiometric ratio, optionally in the presence of a solvent or diluent and an acid scavenger, preferably at a temperature in the range of 80-120 ° C; other production methods include the reaction of hydroxyether ketones with 1,2,4-triazoles in the presence of a water-binding agent and optionally in the presence of a diluent, preferably at a temperature in the range of 140 to 200 ° C. Depending on the production method and production conditions, the tautomeric nature of 1,2,4-triazole is obtained

<img file="FI55835C_D0013.tif" />

H, respectively, are skeletal triazole derivatives of the formula II, either as 1,2,4-triazolyl (4) derivatives or 1,2,4-triazolyl (1) derivatives; often a mixture of both forms is formed.

Suitable salts of the compounds of the formula I are salts with physiologically tolerable acids. These include, in particular, hydrohalic acids, such as, for example, hydrochloric acid and hydrobromic acid, in particular hydrochloric acid; phosphoric acid, mono- and bifunctional carboxylic acids and hydroxycarboxylic acids, such as acetic acid, maleic acid, succinic acid, fumaric acid, tartaric acid, citric acid, salicylic acid, sorbic acid, lactic acid,

1,5-Naphthalenedisulfonic acid.

In process variant (a) according to the invention, polar organic solvents are suitable as diluents.

These are preferably alcohols such as methanol and ethanol and nitriles such as acetonitrile. The reaction is carried out in the presence of a catalyst. Precious metal oxide (or precious metal hydroxide) or Raney catalysts, especially platinum, platinum oxide and nickel, are preferably used. Reaction temperatures can be varied over a wide range. In general, work is in the range of 2O to 50 ° C, preferably in the range of 2O to 40 ° C. The reaction can be carried out at normal pressure, but also at elevated pressure (1-2 aty). In the process of option (a), one mole of the compound of formula II is used per mole of about 1 mole of water and 0.1 mole of catalyst; to isolate the compounds, the catalyst is removed by filtration, the solvent is evaporated off under reduced pressure and the products of formula I obtained are purified by recrystallization. If desired, salts of the compounds of the invention may be obtained by conventional methods.

When working according to option (b), alcohols, such as isopropanol, or inert hydrocarbons, such as benzene, are preferred diluents in the reaction according to the invention. Reaction temperatures can again be varied over a wide range; generally between 20 and 120 ° C, preferably between 50 and 10 ° C. The reaction uses about 1 to 2 moles of aluminum isopropylate per mole of the compounds of the formula II. To isolate the compounds of formula I, the excess solvent is removed by distillation under reduced pressure and the aluminum compound formed is decomposed with dilute sulfuric acid or sodium hydroxide. Further processing is performed in the usual way.

When working according to option (c), polar organic solvents are suitable as diluents in the reaction according to the invention. These are preferably alcohols such as methanol, ethanol, butanol, isopropanol; and ethers such as diethyl ether or tetrahydrofuran. The reaction is generally carried out at 0 to 30 ° C, preferably at 0 to 20 ° C. About 1 mole of a complex hydride such as sodium borohydride or lithium aluminum hydride is used per mole of the compounds of formula II. To isolate the compounds of formula I, the residue is taken up in dilute hydrochloric acid, then taken up in an alkali mixture and extracted as an organic solvent. Further processing takes place in the usual way.

Suitable diluents for the process variant (d) according to the invention are polar organic solvents, preferably alcohols, such as methanol and ethanol, but also water. The reaction temperatures can also be varied within a wide range; working at temperatures of 20-100 ° C, preferably 50-100 ° C. About 1 to 3 moles of formamidine sulfinic acid and 2 to 3 moles of alkali hydroxide are used per mole of the compounds of formula II. To isolate the final products, the solvent is removed from the reaction mixture and the residue is extracted with water and organic solvents, worked up and purified in the usual manner; possibly preparing a salt.

According to the process variant (e) according to the invention, such are obtained

...... 3 .

compounds of general formula I in which R is not hydrogen. In contrast, the reactions of alternatives (a) and (h) are reduction reactions in which the compounds of formula I obtained are secondary alcohols in which 3

R is hydrogen only.

In addition to the triazole derivatives of formula II, organometallic compounds of formula III are required in the process of option (e).

Me in formula III preferably means lithium, sodium and the so-called Grignard group Mg-X, where X is chlorine, bromine or iodine. The organometallic compounds of formula III are well known (a summary and review comprising numerous publications is given, for example, in Coates, GE, Organometallic Compounds, 2nd ed. Methuen &amp; Co., London 1960).

Reaction option (e) according to the invention preferably includes ethers such as diethyl ether, dibutyl ether. Reaction temperatures may range from 0 to 80 ° C, preferably from 30 to 60 ° C. In carrying out the process according to the invention according to option (e), about 1 mole of the organometallic compound of the formula III is used per mole of the compounds of the formula II. The reaction mixture obtained in the reaction of the organometallic compound is further worked up in a conventional and generally known manner.

The active ingredients according to the invention have a strong fungicidal effect. They do not damage crops at concentrations necessary to control fungi. For these reasons, they are suitable for use in k, plant protection9

835 as substances in the control of fungi. Fungicides are used in plant protection against Archimycetes, Phycomymycetes, Ascomycetes and Basidomycetes and Fungi imperfect.

The active compounds according to the invention have a very broad spectrum of action and can be used against parasitic fungi which infect the above-ground parts of plants or are transmitted from the soil to the plant, as well as against seed-borne pathogens.

They are particularly effective against parasitic fungi living on terrestrial plant parts, such as Erysiphe species, Podosphaera species, Sphaerotheca species and Venturia species, further against Pirioularia and Pellicularia species. They are also very effective against rust and soot fungi, e.g. against the causative agent of wheat stench. It should be emphasized that the active ingredients according to the invention have not only a prophylactic effect but also a fungicidal effect, i.e. they can also be used after an infection has already taken place. The systemic effect of the substance needs to be further emphasized. Thus, the protection of plants against fungal infection is achieved when the active ingredient is applied to the above-ground parts of the plant via soil, seedlings or seeds. · As plant protection products, the substances according to the invention can be used for soil treatment, seed treatment or treatment of above-ground parts.

The substances according to the invention are well tolerated by plants. Warm-blooded animals have only low toxicity and are not uncomfortable to handle because they have a low odor and are well tolerated by human skin.

The active compounds according to the invention can be converted into the customary forms of use, such as solutions, emulsions, suspensions, powders, pastes and granules. These are prepared in a conventional manner, e.g. by mixing the active ingredients with diluents, non-liquid solvents, liquefied gases under pressure and / or solid carriers, optionally using surfactants, i.e. emulsifiers and / or dispersants and / or blowing agents. When using water as a diluent, it is also possible to use, for example, organic solvents as co-solvents. Suitable liquid solvents are, in particular, aromatic hydrocarbons, such as xylene, toluene, benzene or alkylnaphthalenes, chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzenes, chloroethylenes or methylene chloride, aliphatic hydrocarbons, or cyclohexane, such as cyclohexane. petroleum fractions, alcohols such as butanol or glycol and their ethers and esters, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, highly polar solvents such as dimethylformamide and dimethyl sulfoxide as well as water; by liquefied gaseous diluents and carriers are meant substances which are gaseous at normal temperature and pressure, e.g. aerosol propellants such as halogenated hydrocarbons, e.g. freon; as solid carriers: natural mineral powders such as kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite and diatomaceous earth, and synthetic rock powders such as highly dispersed silica, alumina and silicates; as emulsifying and / or foaming agents: nonionic and anionic emulsifiers, such as polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, e.g. alkylaryl polyglycol ether, alkyl sulfonates, alkyl sulfates, aryl sulfonates and protein hydrolysates; as dispersants: e.g. lignin, sulphite waste liquor and methylcellulose.

The active compounds according to the invention can be used in mixtures with other known active compounds, such as fungicides, insecticides, acaricides, nematicides, herbicides, bird-eating protection agents, growing areas, plant structures and soil improvers.

The formulations generally contain from 1 to 95% by weight, preferably from 5 to 90%, of active ingredient.

The active ingredients can be used as such, in preparations containing them or in forms prepared from them by further dilution, such as ready-to-use solutions, emulsions, suspensions, powders, pastes and granules. They are used in the usual way, e.g. by wetting »spraying, spraying, dusting, sprinkling, dry-coating, wet-coating, wet-coating, slurry-coating or frosted tamal1a.

When the active ingredients are used as foliar fungicides, their concentrations in the forms of application can vary within wide limits. The content is usually between 0.1 and 0.00001% by weight, preferably between 0.05 and 0.0001%.

In the treatment of seeds, amounts of active ingredient of 0.001 to 50 g per seed are generally required, preferably 0.01 to 10 g.

In soil treatment, amounts of active ingredient of 1 to 1000 g, preferably 10 to 2000 g, per cubic meter of soil are required.

Furthermore, the active ingredients according to the invention have a good antimicrobial effect.

The following examples illustrate the wide range of applications

Example A:

Erysiphe test / protective

Solvent: 4 * 7 parts by weight of acetone

Emulsifier: 0.3 part by weight of alkylaryl polyglycol ether

Water: 95 parts by weight

The amount of active ingredient required to achieve the desired active ingredient concentration in the spray liquid is mixed with a given amount of solvent and the concentrate is diluted with a given amount of water containing said additives.

The spray liquid is used to spray young throat seedlings with about three stems. The throat seedlings are left to dry for 24 hours in the greenhouse. They are then pollinated to induce fungal infection with the spores of the fungus Erysiphe cichoreacearum. The plants are then placed in a greenhouse at 23 to 24 ° C, where the relative humidity of the air is $ 75. 0% means that there are no cases, 100% means that the morbidity of the seedlings is equal to that of the control plants.

The active substances, active substance concentrations and results are shown in the following table:

Active substance

Table A

Brysiphe test

Percentage of morbidity in untreated comparators with active substance concentration $ 0.0002%

<img file="FI55835C_D0014.tif" />

Example Β:

Erysiphe test / systemic

Solvent: 4 »7 parts by weight of acetone

Dispersant: 0.3 part by weight of alkylaryl polyglycol ether

Water: 95 parts by weight

The amount of active ingredient required to achieve the desired active ingredient content of the irrigation liquid is mixed with a given amount of solvent and the concentrate is diluted with a given amount of water containing said additives.

Throat seedlings planted in homogeneous soil are irrigated three times a week with 20 cm of irrigation fluid of the specified active ingredient content, calculated per 100 cm 2 of soil.

The seedlings thus treated are infected after treatment with the fungus o

Erysiphe cichoracearum with spores. The plants are then placed in a greenhouse at 23 to 24 C with a relative humidity of $ 70. After 12 days, the incidence of throat seedlings is determined as a percentage of untreated control plants which, however, have been infected in the same way.

% means that there is no disease, 100 means that the disease is the same as in the control plants.

The active substances, active substance concentrations and results are shown in the following table:

Table B Eryslphe test / cytemic

Morbidity Morbidity as a percentage of morbidity in untreated control plants at active substance concentration

<img file="FI55835C_D0015.tif" />

<img file="FI55835C_D0016.tif" />

Example C:

Podosphaera test (apple powdery mildew) / protective

Solvent: 4.7 parts by weight of acetone

Emulsifier: 0.3 part by weight of alkylaryl polyglycol ether

Water: 95 parts by weight

The amount of active ingredient required to achieve the desired active ingredient content of the rolling liquid is mixed with a given amount of solvent and the concentrate is diluted with a given amount of water containing said additives.

The spray liquid is used to spray young, 4-6 leaf apple seedlings. The seedlings are left for 24 hours in a greenhouse with a relative humidity of 70% at 20 ° C. They are then infected by pollination with the spores of apple powdery mildew (Podosphaera leucotricha Salm.) And placed at a temperature of 21 to 23 ° C in a greenhouse with a relative humidity of approx. 70 % days after infection, the morbidity of the seedlings is determined as a percentage of the morbidity of untreated seedlings which, however, have been infected in the same way.

means that the disease does not occur, 100% means that the morbidity is the same as in the control plants.

The active substances, active substance concentrations and results are shown in the following table:

Table C Podosphaera test / protective

Active substance Morbidity ($) of morbidity of untreated control plants

Active substance content (%): 0.00002 0.00033 0.00031

<img file="FI55835C_D0017.tif" />

<img file="FI55835C_D0018.tif" />

(known from Finnish patent 54 115)

Table C (cont.)

Podosphaera test / protective

Active substance Morbidity (%) of morbidity of untreated control plants

Active substance content: 0.00062 0.00033 0.00031

<img file="FI55835C_D0019.tif" />

O-CH-CH c^(ch3)₃

OH

Ίί

I ¹¹ j I

CH,

Cl- / Λ- O-CH-CH-C-CH_o \ _Γ »» \ ³ r ^CH'

- 16

Ίι

JJ

<img file="FI55835C_D0020.tif" />

treo shape

<img file="FI55835C_D0021.tif" />

erythro form

<img file="FI55835C_D0022.tif" />

Example D:

Ore treatment test / cereal mildew / protective (leaf-destroying fungus)

To prepare a suitable active ingredient preparation, 0.25 parts by weight of active ingredient are mixed with 25 parts by weight of dimethylformamide and 0.06 parts by weight of emulsifier W and 973 parts by weight of water are added. The concentrate is diluted with water to the desired final concentration of the spray solution.

To test the protective effect, single barley needles of the barley variety Amsel are sprayed with the active ingredient preparation. After drying, barley groats are pollinated with the fungus Erysiphe graminis var. hoedei with spores.

K_un plants have been kept for 6 days at a temperature of 21 - 22 ° C and a humidity of SO - 90%, the number of colostrum colonies in the plants is studied. The morbidity rate is expressed as a percentage of the morbidity of untreated control plants. In this case, 0% means that the disease is absent and 100% means the same degree of disease as in the untreated control plants. The lower the presence of rust, the more effective the active ingredient.

The active substances, the active substance concentrations in the spray solution and the morbidity rates are shown in the following table:

Table D

Ore treatment test / grain h fungus f protective

Active ingredients

Spray solution active ingredient content by weight%

Morbidity% of untreated control scrubs

Unprocessed oo

CH 0 -NH-CS-S ^ 0.3

Zn o, 1

Afig-KH-CS-s / * (known)

64,0

8o, 5

CH

<img file="FI55835C_D0023.tif" />

O-CH-OH-C-CH

II \ o, o1 o, oo1 o, O o, O /

<img file="FI55835C_D0024.tif" />

<img file="FI55835C_D0025.tif" />

o, o1 o, oo1

6.3 1 o, 8

<img file="FI55835C_D0026.tif" />

o, o1

0.001 o, 0 o, Ö ^CMO

OH CH_O . I 3

O-CH-CH-C-CH, II, Ns CH₃ li

0,01 0,0

0,001 0,0

Active substance

Table D (continued) Ora processing test / cereal powdery mildew /

The active ingredient content of the spray solution is% by weight protective

Morbidity% of untreated control plants

<img file="FI55835C_D0027.tif" />

o, o1 o, oo1 o, o1 o, oo1 o, o1 o, oo1

0,0

0,0

0.0 o, O o, O

23,8

<img file="FI55835C_D0028.tif" />

_{/ 0H}

-C-CH 2 ho, o1 o, oo1 o, 0 o, O

<img file="FI55835C_D0029.tif" />

o, o1 o, oo1 o, 0

6,3

Example E:

Barley powdery mildew test (Erysiphe graminis var, hordei) / systemic (cereal fungal disease)

The active ingredients are used as powdered seed treatment agents. These are attenuated by diluting the respective active ingredient with a mixture of equal parts by weight of talc and diatomaceous earth to a fine powder mixture with the desired active ingredient content.

To treat the seeds, barley seeds are shaken in a closed glass bottle with the diluted active ingredient. The seeds are sown 3 x 12 grains in flower pots to a depth of 2 cm in a mixture with of one volume of Fruhstorfer standard soil and one volume of quartz sand. Germination and germination take place under favorable conditions in the greenhouse. 7 days after sowing, when the barley seedlings have opened their first leaves, they are pollinated with fresh spores of the fungus Erysiphe graminis var hordei and further grown at 21-22 ° C and 80-90% humidity under 16 hours of illumination. Within 6 days, typical colostrum colonies form on the leaves.

The morbidity rate is expressed as a percentage of the morbidity of untreated control plants. Thus, 0% means no disease and 100% means the same degree of morbidity as untreated control plants. The less active the mildew, the more effective the active ingredient.

The active substances, the active substance concentrations and application rates of the seed treatment agent and the percentage of fungal infections are shown in the following table:

Table E

Barley powdery mildew test (Erysiphe graminis var.hordei) / systemic

Active ingredients

Active substance content in the pickling agent% by weight

Application rate of pickling agent g / kg seed

Morbidity% of untreated control plants unpainted

100

<img file="FI55835C_D0030.tif" />

10 100 ^C6^B5 (known)

CH.-NH-CS-S 2 \

Zn

CH 2 -NH-CS-S 2

10 100 (known)

Barley powdery mildew test (Erysiphe graminis.var.hordei) / systemic

Pickling Disease # application rate of untreated g / kg of seed of reference plants

Table E (cont.)

Active ingredients

Active ingredient content in the pickling agent by weight #

<img file="FI55835C_D0031.tif" />

100 (known from Finnish patent 54 115)

<img file="FI55835C_D0032.tif" />

0,0

0,0

<img file="FI55835C_D0033.tif" />

0,0

0,0

0,0

0,0

0,0

<img file="FI55835C_D0034.tif" />

0,0

0,0

0,0

Example F:

Fusicladium test (apple scab) / protective

Solvent: 4.7 parts by weight of acetone

Emulsifier: 0.3 part by weight of alkylaryl polyglycol ether

Water: 95 parts by weight

The amount of active ingredient required for the desired active ingredient concentration of the spray liquid is mixed with a given amount of solvent and the concentrate is diluted with a given amount of water containing said additives.

The spray liquid is used to spray young apple seedlings, which are 4-6 leaves, into a drip. The seedlings are left for 24 hours in a greenhouse at 20 ° C with a relative humidity of 70%. They are then infected with an aqueous suspension of spores of the apple fungus (Fusicladium dendriticum Fuck) and incubated for 18 hours in a humidified room at 18-20 ° C and 100% relative humidity.

The seedlings are then taken back to the greenhouse for 14 days.

days after infection, the morbidity of the seedlings is determined as a percentage of the morbidity of untreated but similarly infected control plants.

% means no disease, 100% means that the incidence is as high as in control plants.

The active substances, active substance concentrations and results are shown in the following table

Table F Fusicladium test / protective

Active substance Morbidity (%) of morbidity of untreated control plants

Active ingredient content (%): 0.025 0.00156, 0.00125

<img file="FI55835C_D0035.tif" />

(known from Finnish patent 54 115)

<img file="FI55835C_D0036.tif" />

(known from Finnish patent 54 115)

Table? (cont.).

Fusicladium test / protective

Active substance

Morbidity of control plants

Active substance content (%) (%) of untreated morbidity 0.025 0.00156 0.00125

<img file="FI55835C_D0037.tif" />

c (ch₃)₃

<img file="FI55835C_D0038.tif" />

O-CH-CH II IC OH

L3 ο (οη₃)₃

Br

O-CH-CH

OH

<img file="FI55835C_D0039.tif" />

Example G:

Grain Pickling Test / Barley Flycatcher · (Ustilago nuda) (Seed Mycosis)

To prepare a dry pickling agent preparation, the active ingredient is mixed with a mixture of talc and diatomaceous earth (1: 1).

The pickling product is used to pick up barley with a natural barley fly agglomeration in a closed glass bottle. Barley grains are sown (2 x 100 pieces) in seed boxes at a depth of 2 cm in a peat soil-quartz sand mixture (1: 1), and the boxes are kept in a greenhouse at 18 ° C at normal humidity; exposure 16 hours a day. After about 10-12 weeks, the barley blooms and healthy and diseased cones are observed.

Determine the percentage of disease; 0% means that no diseased cones were detected, and 100% means that all cones were diseased.

The active substances, the active substance concentrations in the pickling agent, and the amounts of pickling agent, as well as the number of diseased cones (=% morbidity) are shown in the following table:

TableG

Grain Pickling Test (Barley Flycatch)

Active ingredient Pickling agent Pickling agent amount Morbidity active ingredient content 3 kg grain% by weight%

<img file="FI55835C_D0040.tif" />

7,2

<img file="FI55835C_D0041.tif" />

7,8

0,0

0,0

0,0

0,0

Manufacturing examples

Example 1:

<img file="FI55835C_D0042.tif" />

OH f

CH

<img file="FI55835C_D0043.tif" />

II

OF

31.4 g (10 mol) of α-β-chlorophenoxy (U-β-triateolyl-Cl ')] acetophenol are dissolved in 300 parts of Matan Ol and 3 δ (θ .08 mol) of sodium borohydride are added to this solution under stirring and ice-cooling. For 1 hour at room temperature and the solvent is distilled off in vacuo. The residue is taken up in dilute hydrochloric acid, heated briefly and filtered. The filtrate is then made alkaline with sodium hydroxide solution. The precipitate formed is filtered off and taken up in ethyl acetate. When the vinegar ester is distilled off, an oil remains which crystallizes when triturated with naphtha. Recrystallization from ligroin / isopropanol gives 25 g (9% of theory) of 1- (4'-chlorophenoxy) -1- [1,2,4-triazolyl- (1 ')] - 2-phenylethanol with a melting point of 117 ° C.

Intermediate preparations

32.5 g (0.1 mol) of (i) -bromo-N- (4'-chlorophenoxy) acetophenone and g (0.44 mol) of 1,2,4-triateol are dissolved in 240 g of acetonitrile and heated under reflux for 48 hours. After the solvent has been distilled off, the residue 800 is taken up in any water. This aqueous solution is extracted several times with methylene chloride and the methylene chloride solution is washed twice with water using 200 ml each time, then dried over sodium sulfate and the solvent is distilled off in vacuo. The residue crystallizes, can be recrystallized from ligroin / isopropanol (2: 1), melting point 98-100 ° C.

The starting material a) -bromo-ww (4'chlorophenoxy) acetophenone required for the preparation of the intermediate is prepared in a conventional manner by condensing 4-chlorophenone with ω-chloroethophenone and brominating the formed ω (4'-chlorophenoxy) acetophenone and has a melting point of 71 ° 0.

Example 2

OH OH, 5

<img file="FI55835C_D0044.tif" />

587 g (2 moles) of 1- (4'-chlorophenoxy) -1- [1,2,4-triazolyl- (1 ·)] - 3,3-dimethylbutan-2-one are dissolved in 3 parts of methanol. A total of 80 g (2 moles) of sodium borohydride is added in 5 g portions under stirring and ice-cooling at 0 to 10 ° C, followed by stirring for 2 hours at 5 to 10 ° C, then for 12 hours at room temperature. It is then cooled to 10 [deg.] C. and 300 g (3 mol) of concentrated aqueous hydrochloric acid are added at 10-20 [deg.] C. After stirring for 6 hours at room temperature, the resulting suspension is diluted with 3 * 3 1: 11 of water containing 400 g (4 * 3 moles) of sodium bicarbonate. The precipitate formed is filtered off to give 502 g (85% of theory) of 1- (4'-chlorophenoxy) -1- [1,2,4-triazolyl- (1 ')] - 3,3-methyl-6'-ylbutan-2-ol , having a melting point of 112-117 ° C.

Example 3

OH CHj

Cl— / V- O-CH-C - C - CH,

<img file="FI55835C_D0045.tif" />

A suspension of 4 * 3 g (0.22 mol) of magnesium turnings in 50 ml of anhydrous ether is added dropwise with stirring and refluxing to 31.2 g (0.22 mol) of methyl iodide dissolved in 100 ml of anhydrous ether, whereupon the solvent begins to boil. Kim addition is added dropwise to this Grignard solution 29 29 g (0.1 mol) of 1- (4'-chlorophenoxy) 1- [1,2,4-triazolyl- (1 ')] - 3,3-dimethylbutane -2-one dissolved in 100% anhydrous ether and refluxed for 16 hours. After cooling, the reaction mixture is taken up in a solution of 80 g of ammonium chloride in 600 ml of water, 250 ml of ethyl acetate are added and the mixture is stirred for 15 minutes. The organic phase is separated off and the aqueous phase is extracted once more with ethyl acetate. Wash both batches of the vinegar ester used in the shaking twice with 100 ml of water each time.

8 The mixture is dried over sodium sulfate and the solvent is removed in vacuo. The crystalline precipitate is taken up in hot petroleum ether, leaving it insoluble, and filtered hot. 11 g (36% of theory) of 1- (4'-chlorophenoxy) -1- [1,2,4-triazolyl- (1 ')] - 2,3,3-trimethylbutanol with a melting point of 158-160 ° C are obtained .

Example 4

<img file="FI55835C_D0046.tif" />

33 * 6 g (0.1 mol of 1- (4^,-bromophenoxy) -1- [1,2,4-triazolyl- (1 *)] 3.3^-Dimethylbutan-2-one is dissolved in 300 ml of ethanol and 8 g (0.2 mol) of sodium hydroxide in 40 ml of aqueous sodium hydroxide are added, followed by 32.4 g (0.3 mol) of formamidine sulphinic acid. The reaction mixture is refluxed for 3 hours, filtered and the solvent is removed by distillation in vacuo. the oily residue is taken up in 100 ml of water and extracted twice with methylene chloride, using 100 ml each time. The combined organic phases are washed twice with 100 ml of water each time, dried over sodium sulfate and the solvent is removed in vacuo. The resulting oil is boiled with petroleum ether to crystallize. Filtration gives 26.5 g (79% of theory) of 1- (4'-bromophenoxy) -1- [1,2,4-triazolyl- (1 ')] - 3,3-dimethylbutan-2-ol, m.p. 115-118 ° C.

Example 5

OH CH 2

Ö-O-CH-CH-C-CH,

I · ⁵

N. CH_

X ⁵ j_ [| (erythro and threo form)

29.5 g (0.114 mol) of 1-phenoxy-1- [1,2,4-triazolyl- (1 ')] - 3,3'-dimethylbutan-2-one are dissolved in 250 ml of methanol and 0- 5 θ g (0.15 moles) of sodium borohydride with stirring at 5 ° C and reflux. After stirring for 12 hours at room temperature, 20 ml of concentrated hydrochloric acid and 250 ml of saturated sodium bicarbonate solution are treated as shown in Example 2. The sodium bicarbonate suspension is extracted twice with 150 ml of methylene chloride each time. The combined organic phases are washed neutral with two 100 ml portions of water, dried and the solvent is removed in vacuo. The resulting oil is boiled with hot petroleum ether. This leaves a crystalline residue (i) which is filtered off while hot and dried. The solvent is removed from the filtrate in vacuo and this residue (II) is triturated with petroleum ether and a small amount of ether. A total of 23.4 g (79% of theoretical) of 1-phenoxy-1- [1,2,4-triazolyl- (1 ')] is obtained.

3,3-dimethylbutan-2-one, of which 4 to 1 g (¹) the erythro form with a melting point of 132 ° C and 19 »3 g of the (II) threo form with a melting point of 88 to 94 ° C ·

Similarly, the following, of the formula, saadaan^Η

R 0-C-Cj

Compounds according to L:

Se im.

Well.

RAz Melting point (° C)

1o

<img file="FI55835C_D0047.tif" />

c (ch₃)₃ c (ch₃)₅

<img file="FI55835C_D0048.tif" />

I

194 - 196

113 - 117 c (ch₃)₃ c (ch₃)₃ c (ch₃)₃

<img file="FI55835C_D0049.tif" />

123 - 127

<img file="FI55835C_D0050.tif" />

1o7 - 112

114 - 115

First no.

R

R

R

Az Melting point (° C)

<img file="FI55835C_D0051.tif" />

HHC (CH₅)₃

HHC (CH₃)₃

HHC (CH₃)₃

HHC (CH₅)₅

HHC (CH₅)₅

<img file="FI55835C_D0052.tif" />

- 11 o

- 1oo

OF-

<img file="FI55835C_D0053.tif" />

HHC (CH₃)₃

<img file="FI55835C_D0054.tif" />

treo115-117 erytro186-190 treo114-116 erytro

161-164

107-110

153-135

E.g. _R1 _r2 _r3 Well

<img file="FI55835C_D0055.tif" />

Cl

<td>E *¹</td><td>That</td><td>Melting point</td>

<td>c (ch₃)₃</td><td>O 1</td><td> 137-144</td>

<td>c (ch₃)₃</td><td>o 1</td><td> 185-187</td>

<td>CH₃</td><td>^OF—Il H '1 1</td><td> 84-90</td>

<td>c (ch₃)₃</td><td>ΐΐ 'i M 1</td><td> 101-103</td>

<td>c (ch₃)₃</td><td>N-il 1</td><td> 113-116</td>

<td>C (CH₃)₃</td><td>ΐι ¹¹</td><td> 136-138</td>

<td>o</td><td>ΓΊ</td><td> 171-173</td>

<td></td><td>'ί J 1</td><td></td>

<td>c (ch₃)₃</td><td>o 1</td><td> 95-98</td>

<td>c (ch_q)_</td><td rowspan="2">ΓΗ! s. /</td><td> 142-144</td>

<td> 3 3</td><td></td>

t