CS227340B2 - Fungicide and method of preparing active substance thereof - Google Patents

Abstract

NEW MATERIAL:A triazolyl alcohol derivative shown by the formulI(X is H or Cl; * mask is asymmetric carbon atom), having (-) optical activity. EXAMPLE:( - )-( E )-1-( 4-Chlorophenyl )-2-( 1,2,4-triazole-1-yl )-4,4-dimethyl-1-pentene-3-ol. USE:A fungicide. Effective against blast, sheath blight of rice plant, powdery mildew, scab, pod and stem blight, brown spot, etc. of fruits, having high safety to men and beasts, fishes, having no phytotoxicity to crops. PROCESS:For example, a triazolylketone compound shown by the formula II is subjected to asymmetric reduction with a chiral modified lithium alminum hydride type reducing agent, to give a compound shown by the formulaI. The chiral modified LiAlH4 type reducing agent is obtained by decomposing partially LiAlH4 with an optical active alcohol in a solvent.

Description

The present invention relates to optically active triazolyl alcohol derivatives having either (-) or (+) optical activity and which can be represented by the general formula I

(I) where

X represents a hydrogen atom or a chlorine atom and an asterisk indicates an asymmetric carbon atom, a process for the preparation of the compound and a fungicide containing the compound as an active ingredient.

Racemic triazolyl alcohol derivatives, as well as their excellent fungicidal, plant growth-regulating and herbicidal effects, have already been described in Japanese patent application 'cocai (published) No 124 771/1980 and Japanese patent application 100 547/1980.

The triazolyl alcohol derivatives represented by the general formula (I) have optical isomers due to the presence of an asymmetric carbon atom (* C). The triazolyl alcohol derivative of general formula I with (-) optical activity as mentioned above is an optical isomer which has my optical rotation (-) as measured in chloroform with a sodium D line and hereinafter referred to as (-) - triazolyl alcohol derivative . On the other hand, the second omer which exhibits optical (+) - is hereinafter referred to as a (+) - triazolyl alcohol derivative.

The triezolyl alcohol derivatives of this invention may also be prepared in the form of salts. These salts are salts with acids that can be physiologically tolerated by plants. Examples of tonic acids include hydrohalic acid, hydrobromic acid, hydrochloric acid and hydroiodic acid, carboxylic acids such as acetic acid, trichloroacetic acid, maasic acid and succinic acid, sulfonic acids, such as. p-toluenesulfonic acid and methanesulfonic acid, nitric acid, sulfuric acid and phosphoric acid. These salts are obtained; in the usual way.

of the present invention have tested in detail the applicability of the (-) - or (-H-triazolyl alcohol) derivatives of formula (I) produced by the process of the present invention, when comparing the (-) -, (+) - and recemic triazyl alcohol derivatives. order: derivative of (-) - trisolyl8alcohol> cake of recemic triacyl alcohol> derivative of (+) - tri ^ f ^ s ^^ 1 ^ 2rlak ^^ hola, while plant growth regulating and herbicidal effect are in this order: derivative (+) - triaz 0 ^ 18 ^ 0 ^^> recemic triisolyl alcohol derivative> (-) - triazolyl alcohol derivative.

Briefly, the present inventors have discovered the unexpected new fact that a derivative of (-) - tert-butanol has an excellent fungicidal effect, while a derivative of (+) - tert-butane has an excellent fungicidal effect. The plant has an excellent plant growth-regulating and herbicidal action.

The present invention contributes greatly to the control of plant diseases or the cultivation of more resistant plants in the field of agriculture and zeto-sanitation. For example, the use of more efficient chemistry results in a reduction in the consumption of chemicals, which leads to an improvement in the economy of production, transport and in the field of use the expected reduction of environmental contamination as well as an increase in safety.

When poiužtí derivative of (-) - ^{<triazolylalkoholu} JEKO fungicide has been no way effect & sotauící poškození- plants even if it is inadvertently applied excess of the compound and therefore safely be used for controlling harmful controlled rostinnýc ¹H diseases.

Effectively suppressed by the (-) -? 8 derivative of zolac alcohol can be blighted and blighted cereal on plants. rice, cancer, gangrene, powdery mildew, scab, dullness and blotch of apple, leaf blotch, paddy, rust and gangrene of Japanese pear, mmlanose, scab, antreknozu, common green mold and blue menilrrnek mold, yellow fowl, Grapevines, oat rust, paddles, scab, stiffness, dustiness, bittersweet, anthers, black barley rust, dustiness, bittersweet, stiffness, weed, rust, weed, rust , gray rot, and ^ ^<treknózu Plevová, HLI zenith disease and anthracnose of melons rotting test, mildew e tekleaiální, skvrntost tomatoes, gray rot, wilting and ierticilioié pa <HI Liku, peppers pedl.í year, fell rot e ,! cactus, brown spot and powdery mildew of tobacco, cerespor of sugar beet and peanut spot oil.

As mentioned above, (+) - triazolyl alcohol derivatives can be used to control the growth of useful plants as growth regulators of these plants. For example, they can be applied so that rice, diaper, barley, lawn grass, hedge and fruit tree plants do not grow in height, and also to efficiently grow potato plant pots such as chrysanthemums, peanuts, Christmas, stars, azaleas , rhololandrons and the like. ,

In rice, wheat or barley plants, they are lodged when fertilizers are used in excessive imitations or in storms, and this is often an important problem. When using a derivative (O-trichloro-ol) but not rice, horseradish or barley at a suitable growth rate, the growth can be subtracted so that the plant height can be In cultivating chrysanthemums in a pot, the use of the compound causes a reduction in stem length without causing a detrimental effect on the flower, thereby increasing the commercial value of the plant.

In addition, (+) - triazolyl alcohol derivatives have a potent herbicidal action against grassy weeds such as hedgehog corn, bloody deer, fox-tail and weed-like weeds such as broad-edged weed in highland fields such as green amaranth, meel, common pests, common chickens, annual and perennial weeds in a paddy field, such as chicken leg, moooohooie, lavender rotele, Depatria junceum, water rush and thin box.

In fields at higher altitudes, the (+) - 1820 - 18 - 01 derivatives have a strong effect against the most important weeds and can be used for intermediate soil treatment as well as for foliar treatment in the early stages of growth. The compounds have the great advantage that they do not harm the basic crops such as rice, soybeans, beef, cucumber, peanut, peanut, sunflower and diabetes and can also be used safely for vegetables - such as lettuce, radish and tomato.

The compounds are therefore useful for controlling weeds in various grain fields, vegetable gardens, fruit crops, lawns, pastures, tea plantations, mulberry orchards, rubber plantations, forest stands, spheres! in the other faces β similarly. In addition, it has been discovered that the compounds are highly nontoxic to nets and fish and are essentially not harmful to plants agriculturally useful.

Methods for producing (+) - or (-) - traauoloylol greening derivatives by processes which are used to produce conventional optically active substances, such as asymmetric reduction.

Recently, the corresponding compound is obtained by reducing the summer compound of formula (II) with a complex metal-hydrogen compound, e.g. expresses the relationship:

where

(II)

Reducing agent

(I) the racemate

X is hydrogen or chlorine.

. The asymmetric reduction according to the invention is usually carried out using a minor-selective reduction which takes place when the lato compound of formula II is reduced by a chiral metal-hydrogen complex. A soft process variant is described below.

(a) It is common practice to use a reducing agent centrally as a central metal-hydrogen complex to provide a centrally-reducing liquid of the type resulting from the partial decomposition of the liquid-alcohol by the optically active alcohol (References: Tetra, Leo.

913 (1973); Bui. Soc. Chim. F ¹ .. - 1968. 3795; Org. Chem. 38 (10), 1973; Tet ^ ed ^ L ^ ters, 3565/19760.

Examples of optically active alcohols used as sources of asymmetry in the present invention include (+) - or (-) - menthol, (+) - or (-) boron, (+) - or (-) - N -meaylafafiro and (+) - or (-) - 2-N, N-dimethylamino-phenyletinol.

Of course, it is also possible to use optically active forms of other optically active alcohols, including alkaloids, carbohydrates and amino alcohols such as quinine, cis-nyrtenol, 2-N-tonsyl-N-methyl-allyl-1-methyl-tenol, and 4-dimethylanine (o-3-methyl-1- [2-diphenyl-2-butenol].

The preparation of a chirellic alcohol reducing agent using an optically active alcohol as an asymmetric source can be accomplished by adding 1 ei of 3 equivalents of optically active alcohol to one equivalent of a portion of the lithium ammonium hydroxide which is suspended in a suitable solvent. Ethers such as diethyl ether, tetrahydrofuran or dioxane are generally used as solvents, although some aliphatic hydrocarbons such as benzene or toluene or aliphatic hydrocarbons such as n-hexane or n-peotein may be used.

b) Sometimes it is preferred to use as a chiral metal-hydrogen complex a chiral modified lithium amine reducing agent formed by the reaction of one equivalent of an optically active alcohol, 2 equivalents of the N-substituted anane of formula III.

(III) where «2

R ^£ oižší represents an alkyl or phenyl group, and one equivalent part lithumnauíminiímhydridu (literature: Tetreheirdn Ltters,

21, 753 (1980). The opically active alcohol used as an asymmetric source in the present invention is exemplified by some of the optically active forms of the optically active alkotol, such as - for example, (+) - or (-) -. +) - otbo (-) - 2 - ^^ - ^^^ 1 ^: ^ 1.eminod-1-phenylethenol ·

With regard to N-substituted aniline, desirable results are obtained using a lower alkyl substituted lower alkyl such as N-α-1718011 ^ 110 ^ N-ethylmaloxyl

The preparation of such a chiefly modified lithium reductive reducing agent can be achieved by suspending one equivalent part of the lithium hexylamide of the formula LiAlH4 in a suitable solvent and mixing it with one equivalent part of the optically active alcohol and then 2 equivalent parts of the N-alcohol. aiOliou. The solvents described above under a) are κοΚου. use similarly.

The asymmetric reduction is carried out by adding the ketone compound of Formula II dissolved in a suitable solvent to the chloro-modified 11-amino-minilide prepared as described under a) or b) above. The solvent is the same as described under a). The reaction temperature is preferably 0 ° C or less, although it can be used. temperatures between -80 ° C and the boiling point of the solvent.

After completion of the reaction, the compound is quenched by addition. dilute aqueous acid solution and the reaction mixture are purified by extraction, column chromatography on silica gel or by recrystallization to give the product.

The compounds of the invention obtained as mentioned above can be used either alone without addition of other components or in admixture to make them more suitable for use as a fungicide or herbicide or plant growth regulator.

Examples of useful forms include a dusting powder, an oily powder, an oil spray, an emulsion, tablets, granules, fine granules, an aerosol and a liquid.

These compositions generally contain 0.1 to 95.0%, preferably 0.2 to 90.0% by weight of the active compound (including other active ingredients). The daily application rate is 20 to 5,000 g / ha and the preferred active compound concentration for areal application is. 0.001 to 1.0%. However, the concentration can preferably be increased or decreased without adhering to the stated range since the application rate and concentration depend on the type of composition, the time of use during the year, the method of use, the site of disease, the plant disease to be controlled and the type. crop to be treated.

For pouuití JEKO fungicide derivative (-) - triztoУylθlkohtlu formula I can Jíra with fungicides such as N- ^{(3,5-dichlsrf,} jnyl) -1,2-dimztylcykloprspan-1,2-dikerboximid, Sn-butyl / Sp-tert-butylbenzyldithiocarbonylimide (O, O-dimethyl) - O- (2,6-dichloro-4-methylphosphonic acid), (ethyl) (1-butylcyclohexyl-1H-benzieidiz-1,2-ylcarbonyl), N 'Trichlorosylthio-4-cyclohexyl-1,2-cicarbonyl, cis-N- (1,1,2,2-hexachloro-1,2-dicarbexyl), polyoxine, streptoeycin, zinc carbamate, zinc carbamate, zinc carbamate, zinc carbamate magnesium salt of zinc ethylene di-carbonyl, bis (N, N-diethythylcarbonyl) disuccinate, i.e., trisulphite-quartz, 8-hydroxy-quinoline, di-decyloxyguine diacetate, 5,6-isilyl-3-yl-4-methyl-3-isopropyl N'-Chlorofluoroethyl-thto-N, N-dimethyl-N'-phenylsulfamide, 1- (4-chlorophenyl) -3,5-dimethyl-11- (1,2,4-triazol-1-yl) 22-butene, 1,2 -bis (e-metsxykaebotyУld-this1Lweiis) be nzen, methyl / N- (2,6-diethylphenyl) -N-ethoxycyclyl-2-ethylzycinet, and zlueinium ethylphosphil.

In addition, the derivatives of formula (I) may be used in combination with other herbicidal agents and plant growth regulators.

Such a mixture does not cause a reduction in the control effect, any of the active ingredients even from the combined deserts can be expected to have a synergistic effect. Examples of such formulations are lensxyl-type herbicides such as 2,4-dichloro-tert-butyric acid, 2-ethyl-4-chlorophenoxy acid, 2-ethyl-4-chloro-4-chlorophenoxy acid and their esters and salts. diphenyl ether type herbicides such as 2,4-dichlorophen-1'-nitrile ether, 2,4,6-trichlorophenyl-4-nitrophenylethyl, 2-chloro-4-trifluoromethyl-3'-hexyloxy-4'-nitropynyl ether, 2 4-Dichloro-4'-nitro-3 * -methyloxyphenylether and 2,4-di-trifluoromethyl-4'-nitro-ethyl-4'-nitroethyl ether, such as 2-chloro-4,6-bibenzoyl-zeinol herbicides; 3,5-triazine, 2-cl-Lor-6-4detylmino isoprspylaeinnt-, 3,5-triazine, _{2-meZyllhloo4> 6-bisetylaminnt->} 3> 5 ^ -] triazine and 2-meeyl-4-hlo Urea-type herbicides such as 3- (3,4-trifluorophenyl) -1'-di-urea, 3- (3,4-dichloro-phenyl-1-ethoxy-methyl) -urea, 6-bibisopropyl-amino-113,5-riazine; - (alpha, alpha-dimethylbenzyl) -3-p-SllylII10-yeast with 1- (2-benzothiazolyl-1, ddimethyl-urea, carbonate type herbicides such as iboprspyl- · N- (3 (methylphenyl) carbamate and methyl-N-3,44 (dichlorophenyl) carbamate; thiol-aaramate-type herbicides such as S- (4-chlorobenzyl) -N, N-diethylthsocarbemate and S-ethyl-N, N-hexamethylene thiolcarramate; anilide-type herbicides such as S, 4-dichloro-3-anilide, 2-chloro-N-methoxymethyl-2 ', 6'-chloro-2-ethanone, 2-chloro-2 *, 6'-dihydro-N- (butoximethyl) acetainiii, 2-cdor-2 * N- (n-propyloxymethyl) acetyl and ethyl ester of N-chloroacetyl-N- (2,6-ethylphenyl) glycine; uracilovélo type herbicides such as 5-Rrom - з-sZ. butyld6-methylthio-uracil and _{3-cyclopropyl-ohlzyl-г} imeZylénuraeil 5.66 t; pyridine salt type herbicides such as 1,1-dimethyl-4,4 &apos;-bipyridine-iodide; phosphorous-type herbicides such as N- (loblonomeeylglycine, N, N-drs (loslsnomeeylglycine, O-zyl-O- (2-nirt-5-methylphenyl)) - N -butylphosphoramidoZhitene, S- (2-meety-1) piperidylcarronylmethyl-L, O, O-di-n-prooyl diisophosphate and S- (2-methyl-1-piperidinyl-arnaphenyl) -d, C0-diphenylphosphine; 2,6-dinitr-N, N-diproppl-p-totuidine, 5-tert-butyl-3- (2,4-dimethyl-5-isopropoxyphenyl) -1,3,4-thiazolidin-2-one, S -isoproppl-UH) -1,3,3-benzothiazin- (3H) -one- 2,2-disoxide, elle- (trans-phenoxy) -propionanide, 4- (2,4-dichloro-benzoyl) -1,5-dimethyl-pyrimidin-5-yl β-trifluorobenzenesulfate, 3- (methoxpk-erbonylpiperazinphenil-3-meeplphenilercemate) and 4-aminoo-1-methyl-66-β-1,2,4-zriazine.

For use as fungicides, the compounds of the present invention can be mixed with insecticides, herbicides and plant growth regulators. Such a mixture does not reduce the control effect of any single component, and a synergistic effect can be expected from the combined desert. .

Examples of such active ingredients include orgenophosphate insecticides such as O, O-dimethyl (O- (3-methyl-4-nitrophenyl) phosphorothioeth), O- (4-cyenophenyl) (O, O-dimethylphosphorothioate), O- (4 (cyanophenyl) - (0-1) methylphenylphosphoric acid, 0.04-dimethyl- (S- (N-methylcarbamoyl) yl) 4 phosphorodithioate, 2-nonethoxy-4H-1,3,2-benzodioxxphosphorin-2 -sulfide n 0.04 (diethyl) (S- (1-thioxycarbonyl-1-phenylphenyl) phioxyoxithioate); pyethroid insecticides, such as E, N-cyano-34-phenoxybenzyl (SU-chlorophenyl) sulfonate (3-phenoxybenzyl), 2,2-dieethoxy-3- (2,2-dichlorvinyl) cyclopropannerolyl], n elfa -cleno-3-phenoxyboniyl-2,2,2-diethyl-3- (2,2-dibromoyl) oxylopropenecarboxylate; phenoxy type herbicides such as 2,4-dichlorophenoxyacetic acid, 2-ethyl-4-chlorophenoxyacetic acid, 2-ethyl-4-chlorophenoxyoxyacetic acid and their salts; herbicides difeiyltterovtio types such г 4-iichioofenil - 4 nitroftiyléter, 2,4, 6-tricilorftnyl-4, 2-chiox-4-trifluoromethyl-3 luoгmetylfenil ^/ -ttoxχ - 4 nitrofnnyléttr 2,4-dichlorfniyl -4 ^/ -nitooзЗ - ettoxlftnχltttr e 2,4-dichlorophthyl-3 - ethoxyxylcarbonyl - * - n-triphenyl ether; herbicide! of triosine type, such as 2-chloro-4,6'-selyestino-1,3,5-triezine, 2-chloro-4'-ethylamino-6-thio-propyl-thio-1,3, - trinzii, г-теПуЩ ^ с) -, 6-018ethyleeino-1,3, - triezii e γ-eeylthio-4,6-bisisoprophylleginin, 1, 2, 3, ezine; E urea-type herbicides such as 3- (3,4-dichlorophthyl) -1,14-diethyleurea, 3- (3,44dicilorphthyl) -41-thiophthalicylic acid, 1- (elf 8,611--610161) 0111211-3 4-41 Oolylurea e 1- (2-01-4014olol1) -1,3-diethyleurea; trianate type herbicides such as isopropyl (NO-chlorophenyl) -. methylcarbemate (methyl (N-3,4-dichlorophthiyl) caremate); thiocarbate-type herbicides such as S- (4-chloroisyl) (N, N-diethylthixcarbamate (or S-ethyl) (N, N-methyl-thiocarboxylate); enildd type herbicides such as 3,4-dihydroxypropdo (n-di, 2-chloro-N-methylmethyl-1,2 ', 6'-nititylacetyl), 2-chloro-26'-parts-N- (butoxyethyl) 2-chloro-2', 6 'Ethyl - (- inpxxpxylmethyl) - β-N-4-thiooaectyl-1H-1,6-nitro-phenyl-ethyl-ester; urecil-type herbicides such as bromo-4-ene-botyl-6-methyluracil or 3-cyclxhin-4,66-trimethylenearaCl; pyridinium salt type herbicides such as 1,1 * 4-diethyl-4,4 * -piperidine-chlorine; phosphorous type herbicides such as N- (phosphonomethyl) glycine, N, N-nOs (phosphxiomeey®) glycine, O-ethyl-O- (2-nitro-5-ethylphthyl) -N-stk-butylphosphorothiothixate, S- (2- eetyl 1-piperiiylkerbonylmetyl) -0,0-di-n-propyldithiofosftt e S- (2 · -eetyl --- pipenidylkarboxnlmetn1) -) _-> Oonifennlliihiofosfát; toluidine-type herbicides such as alpha, alpha, ala-trifO42-42-i-xineX - (- N, Nidipropyl-p-toluinine; - tert -butylzZ- (2,4idCilXon-4-isorxooo) ynyl) -1,3, 4-Oxadiazolir-2-one, 3-isopropyl- (1 H) 42,1,3-bithiazole-thiadiezine (3 H) -xn-2,2-dioxide, .alpha .- (Otta-naphthoxyoxy-propionoleailide, 4- (2,4-chloroerzoool)) -1,13-diethylpyrazo-4-yl-p-toluenesulfonyl, -3-methylthiazolylilino-ethinyl-3'-ethylphenylcarbberate and 4-eeinio-3-methyl-66-phenol-1,2,4-trioline.

For use as herbicides or plant growth regulators with the compounds of the invention, they can be mixed with other fungicides and insecticides, and even an ergonomic effect is expected. Examples of fungicides such as 1,2-diethylcyclopropene-1,2-dihydrooxide, S-11-butyl- (Sp-tetrilylbenzyldithiokerbonimide), O, O-diethyl / O- (2, 1-butyl) 6-Dicilxr-4-ethylphthyl) hexylsulfonyl (ethyl) (1-benzylcarbexyl-1H-benzoyl) -ol-2-ylcarbonyl-N, N-tricilloreethylthio 44-cyclohexylhexyl-1,2-dicarboxylic acid, cis- 1,2-dicarboxieid, pxlyoxin, streptxeycin, tin (ethylene bis) ether, magnesium salt of diethyl thiokerbeeate, magnesium salt of ethylene bis (sodium carbonate), bis, x-2-methyl-14-oxo-thi-3-carboxidene, N ' -icilorofluoromethylthio-N, N-diyl) N ' -phenylsulfonyl, 1- (4-chlorophenyl) -3,3-diethyl-1- ( 1,2,4-triezol-4-yl) 424-butyne, 1,1'-bis (3-ethoxycarbonyl-2-thioureido) benzene, ethyl / N- (2,6-diethylphenyl) -N-methoxy-phenyl-11-methylggynyl / e-allyl-ethyl-thiophene .

Examples of insecticides include orthophosphoric insecticides such as 0,0-methyl 1 / 0- (4-nitro-3-ethylphenyl) phosphorothioate, O- (4-cyano-propyl) -4, 0- dieetylloofoxoOtiiOt /, O- (4-kim of el / D-O-ethylphthylphosphonoOhioOi), O, O-dieeeχУ / S - () - etxxlkerOeexχУmetet.) foofoooOiUdiOU / г-ев ^ Ух ^ Н-! 3,2-benzoodioxaphosphorin-2-sulfonate, 0,0-diethyl [S- (1-ethoxycarbboryl-1-phenylethyl) phosphorodithiol] e] pyethroid insecticides such as [alpha] -phenyl-34-phthioxyboniol] 2- (4-chlorophenyl) isomerate (1,3-Phenoxy) 2,2-dimethyl-3- (2H-dichloro-vinyl) -cyclo-propanecarboxetyl-alpha-cyano-4'-thioxybenzene; o '/ 2', 2'-ethyl-3 '- (2'-oxo-oxevin) clklopropenk8eboxχlát /.

The invention is illustrated in further detail in the Examples, Comparative Examples, Test Examples and Formulation Examples.

Example d 1

Synthesis of (-) - and (+) - (E) -1- (4-chlorophenyl) -2- (1,2,4-triazol-1-yl) -4,4-dimethyl-1-pentene-3- olu by cleavage of the diastereomeric ester

A mixture of 4.3 g of (I) - (E) -1- (4-chlorophenyl) -2- (1,2,4-triazol-1-yl) 44,4-dimethyl-1-penten-3-ol and 8 g (-) - menthyl chloride is stirred in 50 ml of pyridine at 70 ° C for 7 hours. The reaction mixture was poured into 200 ml of ice-water and extracted with 400 ml of ethyl acetate. The organic layer was washed successively with 0.5N hydrochloric acid, 200 ml of saturated aqueous sodium bicarbonate solution and 200 ml of ice-cold water, then dried over anhydrous sodium sulphate and evaporated under reduced pressure. The resulting oily crude material was purified by chromatography on a silica gel column (150 g silica gel, developing solvent: n-hexane / acetone 30: 1). 7.4 g of ((t) - / (E) -1- (4-chlorophenyl) -2- (1,2,4-tarisd-1-yl) -4,4-dimethyl-1 H- are obtained. of pnuteu-3-yl - (1) -methoxyacetate. Repeated chromatography on another silica gel column (250 g silica gel, developing solvent: n-hexane / benzene / acetone 20: 20: 1) gave 2.6 g of (-) - / (E) -1- (4). (chloro-phenyl) -2- (112,4-triazol-1-yl) -4,4-methyl-β-penten-3-yl- ⁽ - ^- methylmethoxyacetate (n - ^1, 5 ²⁶⁵⁾ as ^p RVN ⁱ ^ ^h ^ o ^ Elust 3 ^g asternomerní SMMS ester as the second eluate, and 1.2 g of (+) - / (E) -1- (4-chLcrfnny ^yl) -2- (1,2,4-trriZc ^y - ¹ - ^{yl) -4, 4-dimethyl-yl} - ^1-3- -pnutnu ^yy / - (l) mneutcx icetátu ^{y (n} = 5 ¹ 5 1 ^{28) to} the terminal I ^ e ^y u ^and TU .

A mixture of 2.6 g (-) - / (E) -1- ^(4-y crfnn У ^yl) -2- (1,2,4-tгiazc ^y -1 ^y-y) 44-1- -ddimetyl pnutnu-3-yl / - (l) mnentcxyicetátu and 40 m ^s of 95% aqueous solution of ethanedisulfonic containing 0.4 g of potassium hydroxide was stirred at 30 ° C for one hour. The reaction mixture was poured into 200 mL of ice water and extracted with 300 mL of ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure. The resulting crude crystals were recrystallized from a mixture of carbon tetrachloride and n-hexane. 1.2 g of (-) - (E) -1- (4-chhorfenuУ) -2- (1,2,4-taiizd-1-yl) ^-4,4-1 dimeeyl- -penteH -D δ (1 ^{) 2} ^ -4 6.0 ⁽ c = 1, CHCl 3); mp ^{1-70 to} 171 ° C. ^P NMR with ^the trum e is the same as described for the racemate described in Comparative Example 1st

Similarly, 1.2 g of (+) - [(E) -1- (4-chlorophenyl) -1-2 (112,4-risol-1- ^yl ) -4,4-dimethyl-1-pentene- 3-yl / - (--- meuthoxyacetate and 20 mL of 95% aqueous ethaned solution containing 0.2 g potassium hydroxide and the resulting crude crystals were recrystallized from a mixture of carbon tetrachloride and n-hexane to give 0.5 g (+ ) - (E) -1- (4-chhooaeeuУ) 2-11 ^2-L, 4 - rrizcl-1-yl) -4,4-dimethyl-1- ^yl-3 eutnu ^p-duty ^) ^ ^{+ 14.0 (} c = ^1.0 , CHOL1); mp ¹⁶⁹ and ¹⁷⁰ ° C.

Example 2

Synthesis of (-) - and (+) - (E) -1- (2,4-dichlorophenyl) -2- (1,2,4-trizzoУ-1-yУ-44, -diethylУ-1-peuteu) 3-ol by cleavage of the diastereomeric ester

A mixture of 4 g (i) - (E) -1- (2,4-drchlcrfnnul) -2- (1,2,4-trizzol-1-yl) 44 - ^1-p-iiietyl necessary to fully-3-ol and 8 g of (-) - ^y mentcx Уice lchlcrrdu · ^y are stirred in 50 ml of pyridine at 70 ° C for 7 hours. The reaction mixture was worked up in a sterile manner as in Example 1. The crude title compound was purified by column chromatography (150 g silica gel, 30: 1 n-hexane / acetone). 5 g of (i) - / (E) -1- (2,4-dichlorophenyl) ^-2 '(1,2,4-trizol-1-yl) -4,4-dimethyl-1-pentene-3 are obtained. - [(1) -Ethoxyxyacetate. After repeated chromatography on another silica gel column (250 g silica gel, developing solvent: n-hexane / benzene / acetone 20: 20: 1) diastereomeric ester mixture gave 1.6 g of (-) - / (E) -1- (2,4-drchlcafeuyУ) - ² - ^{(1, 2,4} -t ^{r c} iso ^-l-yl) - ^{4, 4} - ^{d e} IIe yl- ¹ -Pen ^u · ene-3 -vinyl / - ⁽ -) - Meuthoxyacetate ⁽ n ^{) 8 1.5172) is} the first eluate, 2 g. ester mixture as second eluate, and 0.7 g of (+) - / (E) -1- (2,4-dichorfenyH -G-2,4-yl trizzol --- 4 ^{4 4} -diInetyl-- penten-3-yl] -methyloxyacetate (u _d = 1.5102) as the final eluate.

A mixture of 1.6 g of (-) - [(E) -1- (2,4-dichlorophenyl) -2- (1,2,4-triazol-1-yl) -4,4-dimethyl-1-pentene- 3-yl / - (-) - mentoxyacetate and 30 ml of a 95% aqueous ethanol solution containing 0.2 g of potassium hydroxide are stirred at 25 ° C for 1 hour. The reaction mixture is poured into 200 ml of ice water and extracted 300 ml ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure. The resulting crude crystals were recrystallized from a mixture of carbon tetrachloride and n-hexane. There were obtained 0.8 g (-) - (E) -1- (2,4-dichlorophenyl) -2- (1,2,4-triazol-1-yl) -4 _of 4-dimethyl-1-penten-3- ol ( «) of ⁴ - 31 7 (c = 1, CHCl j), mp 160-161 ° C. The NMR spectrum is the same as that given for the racemate described in Comparative Example 2.

Similarly, 0.7 g of (+) - (E) -1- (2,4-dichlorophenyl) -2- (1,2,4-triazol-1-yl) -4,4-dimethyl-1- penten-3-yl / - (-) - mentoxyacetate with 20 ml of a 90% aqueous ethanol solution containing

0.1 g of potassium hydroxide and the resulting crude crystals were recrystallized from a mixture of carbon tetrachloride and n-hexane. 0.3 g of (+) - (E) -1- (2,4-dichlorophenyl) -2- (1,2,4-triazol-1-yl) -4,4-dimethyl-1-pentene- 3-ol, (ff) p + 26.0 (c = 1.0, CHCl 3); mp 160-161 ° C.

Example 3

Asymmetric reduction using (+) - menthol

To a mixture of 0.4 g (0.01 mol) of lithium aluminum hydride of formula LiAlH * and 30 ml of tetrahydrofuran at 10 ° C is added 30 ml of a tetrahydrofuran solution containing 4.4 g (0.028 mol) of (+) - menthol. The mixture was stirred at room temperature for 30 minutes and then 50 ml of a tetrahydrofuran solution containing 2.0 g (0.007 mol) of 1- (4-chlorophenyl) -2- (1,2- 4-triazol-1-yl) -4,4-dimethyl-1-penten-3-one The resulting mixture was stirred for 2 hours while maintaining a temperature of -5 ° C. 5 ml of 1N hydrochloric acid are added to the mixture, the insoluble matter is filtered off and the filtrate is poured into 300 ml of ice-water and extracted with 500 ml of ethyl ether. The organic layer was washed successively with 200 mL of saturated aqueous sodium bicarbonate solution * and 200 mL of ice-cooled water. The washed organic layer was dried over anhydrous sodium sulfate and evaporated under reduced pressure. This gives the crude product as an oil. The crude product was purified by silica gel chromatography (100 g silica gel, developing solvent: n-hexane / acetone 30: 1). This gave 0.5 g of unreacted ketone as a raw material, and 1.0 g of crystals (after crystallization from a mixture of carbon tetrachloride and n-hexane) was obtained for a longer time (-) - (E) -1- (4-chlorophenyl) - 2- (1,2,4-trlazol-1-yl) -4,4-dimethyl-1-penten-3-ol, 6.0 (c = 1, CHCl 3) ·

P. ř í к 1 and d 4

Asymmetric reduction using (+) - 2-N, N-dimethylamino-1-phenylethanol

To a mixture of 0.4 g of lithium aluminum hydride of formula LiAlH4 and 20 ml of ethyl ether, while cooling with ice, is added dropwise 50 ml of a solution of 1.75 g of (S) -2-dimethylamino-1-phenylethanol in ether. After the addition was complete, the mixture was stirred for 15 minutes while avoiding cooling. 20 ml of an ethyl ether solution of 2.54 g of N-ethylaniline are added dropwise to the mixture. After the addition, the mixture was stirred at room temperature for 3 hours. 50 ml of an ethyl ether solution containing 1.13 g of (E) -1- (2,4-dichlorophenyl) -2- (1,2,4-triazol-1-yl) -4 are added dropwise at -70 ° C. 4-dimethyl-1-penten-3-one. The mixture was stirred at -73 ° C for 3 hours and then allowed to stand overnight at room temperature. 110 ml of 2N hydrochloric acid is added to the mixture to cause decomposition. The organic layer was separated, washed successively with 100 mL of saturated aqueous sodium bicarbonate solution and 100 mL of ice water, then dried over anhydrous sodium sulfate and evaporated under reduced pressure. 1.26 g of crystalline triazolylalkoholu derivative, (R) p ⁴ - 16.6 (c = 1.0, CHCl?). The crystalline compound is recrystallized from a mixture of cyclohexane and methanol to give 0.4 g of (-) - (E) -1- (2,4-dichlorophenyl) -2- (1,2,4-triazol-1-yl) - 4ř4-dimethyl-1-penten-3-ol ( «) ^-4 - 28.8 (c = 1.0, CHC13), melting point 160-161 ° C.

Example 1 a d 5 '

Asymmetric reduction using (+) - 2-N-benzyl-N-methylamino-1-phenylethanol

To a solution of 1.08 g (0.0284 mol-) of lithium amine dihydride of formula (LiAlH) in 85 L of ether, while cooling with ice, was added dropwise 22 ml of an ether solution of 6.86 g (0.0284 mol) of (+) - 2-N- benzyl-N-ethylamino-1-phthalenol and then 40 ml of an ethereal solution of 6.90 g (0.0564 mol) of N-ethylanilium. The mixture is stirred at room temperature for 3 hours and then cooled to -78 ° C. Ke smis! 55 ml of an ethereal solution of 2.75 g (0.0095 mol) of (E) -1- (4-chloroetol) -2-11 &gt; 224-tri- are added dropwise. azoo-1-yl) -4,4-dimethyl-1-piperidin-3-one. The mixture was stirred at this temperature for 3 hours and then left at room temperature overnight. The organic layer was separated, washed successively with 100 ml of a saturated aqueous solution of sodium hydrogencarbonate and 100 ml of ice-water, then dried over anhydrous sodium sulphate and evaporated under reduced pressure. CIS ^{ka 2, 8} 3 ^ ^{g of} crude product, (a) p ^4-6, 44 (c = 1.05, CHCl ^). A 2.8 g portion of the crude product was crystallized three times from cyclohexane / methanol to give 0.82 g of (-) - (E) -1- (4-chlorophthyl) -2-1 (1,2,4-). triaza-l-1-yl) -4,4-dLοθ ^ ¹ - ¹ - ^p enttn 3 - ^{LU (a) P)} - ^{14.9 (c} = CH ^^.

Example 6

Asymeeric reduction using (+) - N-oeeylephedrin

To a solution of 1.25 g (0.033 mol) of lithium maloline iodide of formula (LiAlH) in 40 ml of ether, while cooling with ice, is added dropwise 100 ml of a tertiary ethyl acetate solution containing 6.1 g (0.034 mol) of (+) - N- oetyltphedriou within 30 oinuu. After the addition is complete, the mixture is stirred for 15 minutes while maintaining a constant temperature. 45 µl of an eryl ether solution (3101) containing 8.24 g (0.068 mol) of N-tylaluminum are added dropwise over 30 minutes. After the addition was complete, the mixture was stirred at room temperature for 2 hours. 60 ml of an eryl ether solution containing 2.9 g (0.01 ool) of (E) -1- (4-chlorophenol) -2- (1,2,4-trizzol-1-yl) -4- Ethyl-1-ptoteo-3-one at -70 to -60 ° C over 15 minutes The mixture was allowed to stand for 4 hours while maintaining a temperature of -73 ° C and then 110 L of 2N hydrochloric acid was added to effect decomposition. the organic layer was ^ oc ^ LLI dd, washed successively with 100 ml of saturated aqueous sodium Ιι ^^ ιοuhličitenu and 100 OL ice water, then dried over anhydrous sodium sulfate and evaporated Simi under reduced ^{TOWING eh} by T3 ^ G ^ ^k · u ZIS ^{ka 2.9 g} b-hundred tri1 ^ y ^ ^ veto Riva ^ ^{(a) p4} - ^{10.1 (c} = ^{1, 0,} CHCCl ^). Poddl crystals tmo0no Si 2.5 g-crystallized twice from a mixture of clk1-hexane and dioxane to give 0.7 g of (-) - (E) -1- (4-chlorophthyl) -2- (1,2,4-triaz-1-l-11) -4,4- dieetll 1-ptotto 3 - Lu ^(p ^ ^a) - 15.8 ^(c = ^{1, 0,} CHCCl ^ te ^ CTIA OTA ¹⁷⁰ and ¹⁷¹ ° C.

Example 7

Synthesis of (-) - (E) -1- (2,4-methyl-rfeoll) -2- (12,4'-thiis-o-1-yl-1,4-dimethyl-1-peotto-3-lu)

PREPARATIVE METHOD 1

Reaction temperature: -15 ° C

10 ml of an ethyl ether solution containing 0.84 g (4.7 oeol) of (+) - N-methylptthirin at room temperature are added dropwise to 10 ml of an ethyl ether solution containing 0.18 g (4.7 oeol) of lithium aminomethyldride of the formula LiAlH). 30 minutes and the mixture was further stirred for 20 minutes. To the ice-cooled mixture was added dropwise 10 l of a trylether solution containing 1 g (9.4 mmol) of N-meeylaniline over 30 minutes, and the mixture was stirred at 1 hour. The reaction mixture was cooled to -15 ° C and 10 µL of an ether solution containing 1 g (3.1 µm) of (E) -1- (2,4-dichlorophenyl) -2- (1,2-diol) was added over 10 minutes. 4-triaz-1-1-yl) -4,4-dimethyl-1-penren-3-one, and the mixture was stirred at -15 ° C for 2 hours, then poured onto 100 µL of 1N hydrochloric acid. The reaction mixture was extracted with 100 L of ether, successively washed with an aqueous solution of sodium hydrogen carbonate and ice water, dried with anhydrous sulfuric acid, and the solvent was stripped off under reduced pressure.

22734Q 10 afforded 0.98 g (98% yield) of the above compound, - 28 ^{to 0} (c = ^1.0, chloroform).

Preparation 2 Reaction temperature: 25 ° C

To 10 ml of an ethyl ether solution sacrificing 0.18 g (4.7 mmml) of LihAlH4 (LhAlH4) is added dropwise 10 ml of an ethyl ether solution containing 0.84 g (4.7 mimi) of (+) - N-methylphedrrh at room temperature over 30 minutes and the mixture was further stirred for 20 minutes. To the mixture was added dropwise 10 ml of an ethyl ether solution containing 1 g (9.4 mol) of N-methyl adenine over 20 minutes, and the mixture was stirred for a further 20 minutes. 10 ml of an ethyl ether solution containing 1 g (3.1 mmol) of (E) -1- (2,4-dichloro-enyl) -2- (1,2,4-triazr-1-yl) -4,4 are added dropwise to the mixture. -dimethyl-1-penten-3-one at 25 ° C for 5 minutes and stirred for 1 hour. The retention solution is poured into 100 ml of 1N hydrochloric acid and treated in the same manner as described above for Preparative Method 1. 0.98 g (98% yield) of the title compound is obtained, ⁽ α ^{) β5 27 27.0 (c} = 1) c (oro m).

Comparative Example 1

Synthesis of (E) -1- (4-chloro-enyl) -2- (1,2,4-triazol-1-yl) -4,4-dioethyl-1-pentan-3-yl racemate

2.9 g (0.01 mol) of (E) -1- (4-chlorophenyl) -2- (1,2,4-triazol-1-yl) -444-dioetil-1- (1) are dissolved in 50 ml of methanol. p-3-yl, having a melting point of 108-109 ° C and characterized by the NMR spectrum set forth below. 0.38 g (0.01 mol) of fluoroborohydride is added to the solution, while maintaining the temperature of the reaction system at 20 ° C or less, by cooling with ice. To the solution, which was maintained at 20 ° C for 3 hours, 1 ml of acetic acid was added to effect decomposition. The organic layer was extracted with 100 ml of ethyl acetate and the extract was washed with 50 ml of 5% aqueous sodium hydrogen carbonate solution and dried over anhydrous sodium sulfate. The oil was removed by distillation under reduced pressure and then the residue was recrystallized from n-hexane. This gave 2.0 g (59% yield) of the title compound, m.p. 153-155 ° C. Elemeeneal analysis and NMR spectra (determined on a solution in deuterochloroform and expressed with respect to δ) of each compound are shown below.

(E) -1- (1-Chloro-4-yl) -2- (1,2,4-triazol-1-yl) -4,4-dimethyl-1-penten-3-ol:

Elemeeneal analysis for CHigNjOCl:

calculated: 62.17% C, 5.58% H, 14.50% N, 12.23% Cl, found: 62.32% C · 5.60% H · 14> 11% N, · 12.20 % Cl.

NMR Spectrum; 8.11 (1H, singleton, triazole proton), 7.90 (1H, singleton, tx * azole proton), 7.15 (4H, Si, Oenyl proton), 6.99 (1H, single! , olefinic proton), 0.99 (9H, singlet, butyl proton).

(E) -1- (4-tert-orphenyl) -2- (1,2,4-triazol-1-yl) -4,4-dimethyl-1-penten-3-ol:

calculated: found:

analysis for

61.74% C,

61.82% C ·

C ₁₅ H ₁₈ N ₃ OC1:

6.23% H,

6338% H ·

14.40% N,

14 ^ 8% NI ·

12.15% Cl,

12.15% Cl.

NMR Spectrum: 8.52 (1H, singleton, triazole proton), 7.98 (1H, singleton, triazole proton), 7.30 (4H, singlet, Oenyl proton), 6.91 (1H, Si); years, olefinic proton), 4.56 (2H, broad singlet, hydroxyl proton and proton of the methine group bonded to the hydroxyl group), 0.66 (9H, singlet, butyl proton).

Comparative Example 2

Racemate Synthesis (E) -1- (2,4-0: 1сЬ1огГепу1) -2- (1,2,4-1г1аоо1-1-у1) 44,4-α1тегу1-1-реп1еп-3 · -ol

To 50 ml of a methanol solution containing 3,2 g of (E) -1- (2,4-dichlorophenyl) -2- (1,2,4-trizol-4-yl) -44,4-dimethyl-) penenen-3- One having a melting point of 92-93 ° C and characterized by the NMR spectrum below is added 0.5 g of sodium borohydride under ice-cooling. The mixture was then stirred at room temperature for 3 hours and worked up as in Reference Example 1. 2.6 g of the title compound of melting point 148-149 ° C were obtained.

The NMR spectra are given below with respect to the δ value measured in the deuterchlorophos solution.

(E) -1- (2j, 4- (dLclh) orOenyl) -2- (1 2,4ltriazol-) 1yl) _44> 4 dmee1yl-1-penten-3-one;

8.30 (1H, singlet, triazole proton), 8.04 (1H, singlet, triazole proton), 7.45 (1H, muttplet, phenyl proton), 7.26 (2H, muitplet, phenyl proton), 7, 22 (1H, singlet, olefinic proton), 0.97 (9H, singlet, butyl proton).

(E) -1- (2,2'-dichlorophenyl) -1,2,4,4-thienyl-11,11,114,4-methyl-11-penten-3-yl:

8.45 (1H, singlet, triazole proton), 7.97 (1H, singlet, triazole proton), 7.80 (3H, m ^ U-knit, phenyl proton), 6.80 (1H, singlet, olefinic proton) 4.35 (2H, broad sinjlet, hydroxyl proton and hydroxyl group bound to mmthin proton), 0.63 (9H, singlet, tert-butyl proton).

Example

Synthesis of (+) - (E) -1- (4-chlorophenyl) -2- (1,2,4-trizzol-11-yl) -44, lidimethyl-1-penten-3-ol by asymmetric reduction

In 40 ml of an ethyl ether solution containing 1.25 g (0.033 mol) of lithium lithium lithium lithium having the formula cooled with ice, 100 ml of an ethyl ether solution containing 6.1 g (0.034 mol) of (-) - 4 Nm are added dropwise over 30 minutes. The mixture was stirred at room temperature for 15 minutes and then 45 ml of an ethyl ether solution containing 8.24 g (0.068 mol) of N-ethylaniline was added dropwise over 30 minutes. 60 ml of an ethyl ether solution containing 2.9 g (0.01 mol) of (E) -1- (4-chlorophenyl) -2- ( 1,2,4-thiol-111-I, 44,4-dimethyl-1-pentenen-3-one over 12 at -70 to -67 ° C, and the mixture is stirred at -73 ° C for 3 hours under stirring. The mixture was allowed to stand overnight at room temperature and 110 ml of 2N hydrochloric acid was added to decompose, and the separated organic layer was washed with 100 ml of saturated aqueous sodium hydrogencarbonate solution. , then 100 m of ice water, dried over anhydrous sodium sulfate and evaporated under reduced pressure. 3.0 g of crystals of the triazolylalcoholic derivative are obtained, (o) * ⁴ + 9.0 (c = 1.0, CHOC-1).

2.5 g of crystals obtained were crystallized twice from cyclohexane and dioxane networks. To give 0.81 g of (+) - (E) -1- (4-c] h.oгfeny1) -2- (1,2,4-triizr1-1-11) -44 - ¹ - ^p i ^o1 entenl3l ^{(i)) + 4 15> 7 (c} = ^{1, 0,} CHCl ^) ^ mperature the ^{169 th} and ¹⁷⁰ ° C. ^NMR spe ^to trum identical with that of the racemate as shown in Comparative Example 1st

Example 9

Synthesis of (+) - (E) -1- (2,4-dichlorophenyl) -2- (1,2,4-triazol-1-yl) -4,4-dimethyl-1-penten-3-ol by asymmetric reduction

The chiral metal-hydrogen complex is prepared in a manner similar to Example 1 by adding 20 ml of an ethyl ether solution containing 0.63 g of LiAlH4 and 50 ml of an ethyl ether solution 3 containing 3.05 g of N-methylphedrine and then 20 ml of ethyl ether. of a solution containing 4.12 g of N-ethylaniline. 30 ml of an ethyl ether solution containing 1.62 g of (E) -1- (2,4-dichlorophenyl) -2- (1,2,4-triazole-1-) are added to the preferred solution at -70 ° C. yl) -4,4-dimethyl-1-penten-3-one. The resulting mixture was stirred at -73 ° C for 5 hours under adiabatic conditions and allowed to stand overnight at room temperature. To the mixture was added 60 mL of 2N hydrochloric acid to effect decomposition. The organic layer was washed successively with 100 mL of saturated sodium bicarbonate solution and 100 mL of ice-cooled water, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to give 1.82 g of crude crystals. These were recrystallized three times from a mixture of cyclohexane and methanol. 0.41 g of (+) - (E) -1- (2,4-dichlorophenyl) -2- (1,2,4-triazol-1-yl) -4,4-dimethyl-1-pentene- 3-ol, (R) β + 29.2 (c = 1.0, CHCl 3), mp 160-161 ° C. The NMR spectrum is identical to that of the racemate described in Comparative Example 2.

He did

Asymmetric reduction using (-) - menthol

To 0.4 g (0.01 mol) of lithium aluminum hydride of formula LiAlH 4 dissolved in 30 ml of tetrahydrofuran is added: at 10 ° C, 30 ml of a solution of 4.4 g (0.028 mol) of (-) - menthol in tetrahydrofuran · Stir at room temperature for 30 minutes. 50 ml of a solution of 2.0 g (0.007 mol) of 1- (4-chlorophenyl) -2- (1,2,4-triazol-1-yl) -4,4-dimethyl are added to the mixture at -30 ° C. Of 1-penten-3-one in tetrahydrofuran. The mixture was then stirred for 2 hours while maintaining a temperature of -5 ° C. 5 ml of 1N hydrochloric acid are then added to the mixture and insoluble materials are removed by filtration. The filtrate is poured into 300 ml of ice-water and extracted with 500 ml of ethyl ether. The organic layer was washed with 200 mL of saturated sodium bicarbonate solution, then with 200 mL of ice cold water, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to give the crude oily product. This crude product was purified by silica gel column fractionation (100 g silica gel, developing solvent: n-hexane / acetone 30: 1). 0.5 g of unreacted ketone compound is recovered and 1.3 g of (+) - (E) -1- (4-chlorophenyl) -2- (1,2,4-triazol-1-yl) crystals are recovered. -4,4-Dimethyl-1-penten-3-ol. After crystallization from a mixture of carbon tetrachloride and n-hexane: (R) + 5.0 (c = 1, CHCl 3).

They did

Asymmetric reduction using (-) - borneol

To 0.2 g (0.0053 mol) of lithium aluminum hydride of formula LiAlH4 dissolved in 30 ml of tetrahydrofuran is added at 0 DEG C. 30 ml of a solution of 2.4 g (0.0155 mol) of (+) - borneol in tetrahydrofuran. The mixture was then stirred at room temperature for 50 minutes. To the mixture is added 30 ml of a tetrahydrofuran solution containing 1.0 g (0.0034 mol) of (E) -1- (4-chlorophenyl) -2- (1,2,4-triazol-1-yl) - 4,4-dimethyl-1-penten-3-one. Then the mixture was stirred at room temperature for 3 hours. 0.5 ml of 1N hydrochloric acid is added to the mixture, and insoluble materials are filtered off, the filtrate is poured into 300 ml of ice-cold water and extracted with 500 ml of ethyl ether. The organic layer was washed with 200 mL of saturated aqueous sodium bicarbonate solution, then with 200 mL of ice-cooled water, dried over anhydrous sodium sulfate, and evaporated under reduced pressure to give a crude oily substance. Purification by column chromatography on silica gel (100 g silica gel, developing solvent: mixture of n-hexane and acetone 30M). 0.4 g of unreacted ketone compound is recovered and 0.45 g of (+) - (E) -1- (4-chlorophenyl) -2- (1,2,4-triazol-1-yl) crystals are obtained. ) -4,4-dimethyl-1-pentene 13

-3-ol. After crystallization from a mixture of carbon tetrachloride and n-hexane: () + 3.2 (c = 1, CHCl3) The useful properties of the (-) - trisoolyl alcohol derivatives of the invention are further illustrated in detail in connection with the teso examples performed on (-). - (E) - (4-Chlorophenyl) -4- (1 R, 3-triazol-1-yl) -4-dimethyl-1-penten-4-ol (Compound No. 1) obtainable in Example 1 and (-) - (E -1- (2,4-dichlorophenyl) -2- (1,2,4-thiisyl-1-yl) -4,4-dimethyl-1-penten-3-ol (Compound No. 2) obtained in Example 2, using reference samples of the corresponding (+) -triazolyl alcohol derivatives obtained in Examples 1 and 2 (compounds Nos. 3 and 4) and the racemates obtained in Comparative Examples 1 and 2 (compounds Nos. 5 and 6).

Test Example 1.

Suppression of fungal growth

Medium containing 5 g polypepton, 20 g malt extract, 20 g sucrose and 20 g agar per liter. of water is heated to form a liquid. A predetermined minus sample dilution of the test compound in the form of an emulsifiable concentrate is added to the liquefied medium so as to maintain the concentration of each sample in the medium at a predetermined level. After thorough mixing, the medium is poured onto a Petri dish to form an agar plate. After the agar solidifies, it is inoculated with a colony or conidium suspension of the test fungus. The fungus species and incubation period (time period from inoculation to observation) are given below. The incubation temperature is 20 ° l for Veenuria® and 28 ° l for other fungi.

Kind of mushroom and Incubation time (days) HelmintUžsožrium graminexm Hg 6 PenncillUim italCuum Fri 6 V ^ e ^ nt ^ u ^ ia inaequaais Vi 7 VUsa mmH In m 4 MylctpPuinenla mmeonis Mm 4 Diaporthe citri Dc 6 Ustilago nuda Un 6 They branched to albo-atum Va 7 SepOorii tritici St 7 * 7 lercospora beticola Cb 7

The inhibitory effect of test compound on 'the growth of fungi was evaluated according to the concentration which inhibits 90% growth Washer (ED ^ _o). As can be seen from the results. in Table 1, it was found that the triaztlylalcohol derivatives of the invention (Compounds Nos. 1 and 2) of the statement; a markedly better anti-angular spectrum compared to (+) - triazolylalcohol derivatives (compounds Nos. 3 and 4) and racemates (compounds Nos. 5 and 6).

Table 1

Cutaneous in ppm, which inhibits 90% colony growth (EDg ₀ ).

Fungus species Compound of the invention Reference compound

No. 1 No. 2 No. 3 No. 4 No. 5 No. 6

Hg 1.5 1.5 > 25.0 > 25.0 6.0 6.0 Fri 0.1 0.2 > 25.0 > 25.0 0.4 • 1.0 Vi <01 <0.1 25.0 25.0 0.1 0.1

227340 14 continued Table 1

Kind of mushroom A compound of the invention Reference compound no. 1 No. 2 No 3 No. 4 No 5 No. 6 In m 0.1 <0.1 > 25.0 > 25.0 0.4 0,1 ' Mn 0.3 0.2 > 25.0 > 25.0 1.3 1’0 Dc 0.4 1.0 > 25.0 > 25.0 5.0 5.0 Un 5.0 5.0 > 25.0 > 25.0 5.0 5.0 Va 0.4 0.4 > 25.0 > 25.0 3 1.3 St 0.4 0.1  > 25.0 > 25.0 1.0 0.4 Cb 0.4 0.4 > 25.0 > 25.0 1.5 1.5

Test Example 2

Controlling effect on the speckle of the oily ground

Semi-uppight is sown in 85 ml plastic pots filled with sandy loam soil in an amount of 1 seed per pot and the seeds are kinked in a greenhouse with air conditioning at 25-30 ° C for 12 days to obtain young seedlings oilseeds grown to the third leaf stage. At this stage, a 10 ml dilute solution of the emulsifiable endenate of each tattooed compound is sprayed onto the leaf per pot. After air drying, the seedlings are inoculated with Cersospora personata and then covered with a polyvinyl chloride film press to maintain moisture and stand in a greenhouse with air conditioning at 25-30 ° C. In order to develop a full infection, the seedlings are further cultivated for 10 days in a greenhouse. The leaves of each seedling are then inspected for signs of disease and the frequency is calculated as follows:

The observed changes caused by the disease on the monitored leaf are classified into 5 indicators, ie 0, 0.5, 1, 2 and 4 and the extent of the disease is calculated according to the relationship below.

Index Manifesting change caused by disease.

No colonies observed and no changes in free disease ·

0,5 · On the surface. Colonies or disease-induced changes of less than area% of the total leaf surface were observed. ,

On the leaf surface, colonies or disease-induced changes are less than 20% of the area, relative to the total leaf surface.

On the leaf surface colonies or disease-induced changes are less than% of the area relative to the total leaf surface.

On the leaf surface, colonies or disease-induced changes are observed at 50% or greater of the leaf area.

Σ (index x number of sheets)

Damage Percentage = ¹ x 100 (number of sheets checked) x 4

Then - the control value is obtained by the following equation:

damage in the treated area

Control value (%) = 100 - x 100 damage in control area

As shown in Table 2, the test results show that the (-) - triazolyl alcohol derivatives show a much greater control effect compared to the (+) - triazolyl alcohol derivatives and the racemates.

Table 2

Compound No. Active ingredient concentration (ppm) Control value (%) Compounds of the invention: 1 12.5 100 ALIGN! 3.1 100 ALIGN! 2 2.5 100 ALIGN! 3.1 100 ALIGN! Reference compounds: 3 12.5 0 3.1 0 4 12.5 0 3.1 0 5 12.5 91 3.1 40 6 12.5 97 3.1 50

Test Example 3

The control effect (curative effect) on wheat monillosis in the young seedlings test

Wheat seeds (var. Norin No. 61) in 10 to 15 seeds per pot are sown in 85 ml plastic pots filled with sandy loam soil and grown for 7 days in a greenhouse with air conditioning at 18-23 ° C. Young wheat seedlings are grown until they develop to the first leaf stage. The seedlings at this stage are infested with Puccinia recondita and left to stand in a humid chamber at 23 ° C for 16 hours to infect the fungus. The plants are then sprayed with a 10 ml dilute emulsion of the test compound per pot. The pots and seedlings are kept at a constant chamber temperature of 23 ° C, cultured under fluorescent light for 10 days and signs of disease on the first leaf are observed. The method of testing the disease symptoms and calculating the control value are the same as in Test Example 2.

As shown in Table 3, the test results show that the (-) - triazolyl alcohol derivatives exhibit a much higher control effect compared to not only the (+) - triazolyl alcohol derivatives but also the racemates.

227340 16

T a.b u lka 3

Compound No. · Účinnéομο ^ ι ^^ ι active ingredient (ppm) Hocbiota management (%) Compounds of the invention: 1 0.8 100 ALIGN! . 0.2 100 ALIGN! 2 0.8 100 ALIGN! 0.2 100 ALIGN! Reference compounds: 3 . 0.8 0 0.2 O 4 0.8 0 0.2 0 5 0.8 84. 0.2 57 6 0.8 90 0.2 70

Test Example 4

Control effect (tairative effect) on apple scab in the seedlings test

2 or 3 apple seeds are sown in a 65 ml plastic pot filled with sandy loam soil and activated in an air-conditioned chamber at 23-26 ° C for 30 days to obtain seedlings at the fourth or sixth leaf stage. The seedlings at this stage are infected with VeintuirLa intequjt.is and left to stand in a humid dark chamber (relative humidity 90% or higher) at 15 ° C to cause fungal infestation. On the fourth day afterwards, the leaves were sprinkled with a dilute aqueous solution of the test compound in the form of a 10 ml concentrate per pot. The pots were kept at constant chamber temperature for 20-21 days. 15 ° C under artificial light and humidification, the leaves are then subjected to disease symptom determination, disease infestation and control value calculation as in teso example 2.

As is clear from. Taft 4, the test results show that the control effect of the (-) - triazolyl alcohol derivatives is much greater than that of the (+) - trituolyl alcohol derivatives and also greater than that of the racemate.

Table 4

Compound No. Active ingredient concentration (ppm) Control value (%) Compounds of the invention: 1 3.1 100 ALIGN! 0.8 50 2 3.1 100 ALIGN! 0.8 100 ALIGN!

continuation of Table 4

Compound No. Concentration of the active ingredient Control value (ppm) (%) Reference compounds: 3 3.1 0 0.8 0 4 3.1 0 0.8 0 5 3.1 87 0.8 0 6 3.1 95 0.8 20 May

As a comparison, the results of the plant growth regulating and herbicidal effect tests are shown below.

Test Example 5

Wheat growth retardation test

10 to 15 seeds of wheat (var. Chikugo # 2), which were pickled in an aqueous dilute solution of the test compound as an emulsifiable concentrate and cultured at a controlled temperature of 18 to 23 ° C, were sown in a 85 ml plastic pot filled with sandy loam soil. 7 days. The leaf length is then measured and the percentage elongation compared to the leaf length from the control pot is determined.

length of plant on treated area Elongation (%) = ----------------------------------- x 100 plant length per control area

The test results are shown in Table 5. The growth retarding effect of the (-) - triazolyl alcohol derivatives was found to be much less than the effect of the (+) - triazolyl alcohol derivatives or racemate.

Table 5

Compound No. Concentration (ppm) in the treatment liquid Length of plant (mm) Elongation (%) Compounds of the invention: 1 12.5 95 69 3.1 115 83 2 12.5 133 96 3.1 1 38 100 ALIGN!

continuation of Table 5

Compound No · Concentration (ppm) in the treatment liquid Length of plant (mm) Elongation (%) Reference compounds: 3 > 2,5 45 33 3.1 61 44 4 12.5 75 54 3.1 95 69 5 > 2,5 62 45 3.1 83 60 6 12.5 90 65 3.1 105 76 Control determination (untreated) - 138 100 ALIGN!

The useful properties of (+) - triazolyl alcohol derivatives are described in detail below with respect to some examples of tests performed with (+) - (E) -1- (4-chlorophenyl) -2- (1,2,4-triazole-1-). yl) -4,4-dimethyl-1-penten-3-ol (Compound No. 3) obtained in Example 1 and (+) - (E) -1- (2,4-dichlorophenyl) - (1,2) 4-triazol-1-yl) -4,4-dimethyl-1-penten-3-ol (Compound No. 4), obtained in Example 2, using reference samples of the corresponding (-) - triazolyl alcohol derivatives obtained in the Examples 1 and 2 (compounds No. 1 and 2) and the racemates obtained in Comparative Examples 1 and 2 (compounds No. 5 and 6).

Test example 6

Sweat test on pot

Pot-mum (var · Paragon) is cultivated in a 12.2 cm earthen pot filled with 500 g of artificial soil consisting of sea sand, mountain clay and peat. Two weeks after sowing, the plants are punctured three times to observe the strain. Two weeks after the puncture, when budding has already begun, the test compound, diluted to a predetermined concentration, is applied to the plant. The results are shown in Table 6. · The effect is evaluated as follows: the difference between plant height at time of chemical use and plant height on the forty-second day after application is recorded and expressed as an elongation index, which is a percentage of that difference relative to similar The data presented in Table 6 represent mean values from triplicate.

All test compounds show carrier cell length reduction and plant length reduction, but phytotoxicity such as necrosis or chlorosis is not observed and also green leaf color becomes more saturated. (+) - Triazolyl alcohol derivatives (compounds No. 3 and 4) have much greater effect. causing stunting compared to (-) - triazolyl alcohol derivatives (compounds 1 and 2) and a stronger effect compared to racemates (compounds 5 and 6) ·

Table 6

Compound S. Concentration of the treatment solution (ppm) Extension Index (%) Compounds of the invention: 200 15 Dec 3 100 ALIGN! 23 50 39 200 48 4 100 ALIGN! 79 50 91 Reference compounds: 200 88 1 100 ALIGN! 94 50 103 200 90 2 100 ALIGN! 101 50 103 200 21 5 100 ALIGN! 42 50 78 200 63 6 100 ALIGN! 95 50 101

Test Example 7

Test of retardation of common shoots on apple seedlings

Apple seedlings (raft Golden Deeicious) planted in an 18 cm clay pot are cut and drowned in a greenhouse. Three weeks after the emergence of the normal sprouting, the grown part of the plants was completely treated with the liquid composition of the test compound at a predetermined concentration using a hand sprayer. fourteen days after treatment, the length of conventional shoots is measured and the elongation determined from the difference between said length and length at the time of chemical treatment. Two plant pots were used for each chemical treatment, and the length that increased was determined from 4 to 6 shoots. The results at an average value are shown in Table 7. The (+) - triazolylalcohol derivatives exhibit a much greater growth-inhibiting effect, compared to the (1-trisoolyl alcohol) derivatives and the racemates.

227340 20

Table 7

Apple sprout retardation test

Compound No. Liquid concentration used for treatment (ppm) Extension (mm) <%) Compounds of the invention: 100 ALIGN! 33 18 3 50 64 36 25 79 44 100 ALIGN! 120 67 4 50 147 82 25 163 91 Reference compounds: 100 ALIGN! 189 106 1 50 168 94 25 185 103 100 ALIGN! 171 96 2 50 176 98 25 180 ¹⁰¹ 100 ALIGN! 65 36 5 50 78 44 25 93 52 100 ALIGN! 160 89 6 50 172 96 25 172 96 Control determination (untreated) - 179 100 ALIGN!

Test Example 8

Grass growth retardation test on lawns

1/5 000 Wagner pot filled with mountain soil is sown with grass seeds (var · Seaside grass) * After covering the soil, the seeds are cultivated in a greenhouse · After 1 month the grass is cut at a height of 1 cm from the ground and treated with a predetermined amount of chemical agent using a hand sprayer · Two weeks after treatment, the growth of the grass is determined, then the grass is trimmed again and the cultivation is continued for another 4 weeks · Test results after 2 weeks (first trial) and four weeks (second ) from treatment are given in Table 8. Compared to (-) - triazolyl alcohol derivatives and racemates, (+) - triazolyl alcohol derivatives show a much greater effect ·

Table 8

Grass growth retardation test on lawns

Compound Quantity used (g / ha) Grass growth on grassland (cm) first period second period total Compounds according to the invention: 1 000 1.0 0.5 1.5 3 500 1.3 0.5 1.8 250 1 ' ⁵ 1.0 2.5 1 000 2,0 3.0 5.0 4 500 3.0 3.5 6.5 250 3.8 4.8 8.6 Reference compounds: 1 000 4.3 8.0 12.3 1 500 4,5 8.5 13.0 250 5.0 9.0 14.0 1 000 4,5 8.5 13.0 2 500 4,5 9.0 3,5 250 5.0 9.0 14.0 1 000 1.5 1.0 2.5 5 500 1,8 2,0 3.8 250 2,0 3.0 5.0 1 000 2.5 3.3 5.8 6 500 3.8 3.3 7.1 250 4.0 6.0 10.0 Not treated - 5.0 9.0 14.0

Test example 9

Spice test on barley naked

1/2,000 Weagmre pots were filled with rice plowed soil from a plowed layer that was sieved through a 1.5 x 1.5 cm square sieve. Urea based fertilizers are used as the basic fertilizer, when applied in the ratio NtPgO ^: KgO = 1,3: 1,3: 1,3 g pot · 12 seeds of barley (var · Mnodehadeacaa) are sown in a pot · 5 · December · Seeds are cultivated in a greenhouse · When seedlings arise and grow to a height of several centimeters, the seedlings unite to six seedlings per pot • At the beginning of the extension of the carrier (15 February), a predetermined mois of chemical agent is sprayed onto the soil surface continues and harvest time is reached (21 May) to measure plant height, ear count and husked barley · Test results are shown in Table 9 · Although all test compounds cause stunting, root growth and yield-enhancing effect, the (+) - triazvlylakquvl derivative shows a much better effect compared to the (-) - trizvoyl alkanol derivative and a stronger stunting weights compared to the racemate ·

Table 9

Root test on naked barley

Compound No. The deserted city! active substances (g / ha) Number of ears (per pot) Plant height (cm) Hnoonnst of shelled barley (g / pot) (») Compounds of the invention: 3 100 ALIGN! 58.0 64.7 71.7 118 500 60.0 50.4 66.2 109 4 100 ALIGN! 48.3 79.7 64.6 107 500 53.3 72.3 62.4 103 Reference compounds: 1 100 ALIGN! 46.7 88.7 60.0 99 500 48.7 75.3 61.2 101 2 100 ALIGN! 45.0 86.1 59.6 98 500 46.7 82.4 59.8 99 3 100 ALIGN! 57.7 76.4 74.3 123 500 60.0 54.3 67.3 111 4 100 ALIGN! 47.4 83.5 63.1 104 500 49.0 80.1 62.4 103 Not treated - 45.3 85.9 60.6 100 ALIGN!

Test Example 10

Weed suppression test in mountain soil

1/1 000 Werner pots are filled with soil mixed with the seeds of the bloody dew, green amaranth and gooseberry. The diluted aqueous emulsion containing a predetermined amount of test compound is applied by hand sprayer to the treated soil surface. After treatment, five-leaf beet seedlings (var. ΜοποΗΠΙ) grown in paper pots were transferred to (^ βη ^ ηο ^^ pots) and grown in a greenhouse. are given in Table 10.

The effect of weed control is carried out by classifying the results obtained in a six-step degree from 0 to 5.

Phytooicity is evaluated similarly.

Weed control%

0 0 to 9 1 10 to 29 2 30 to 49 3 50 to 69 4 70 to 89 5 90 to 100 ALIGN!

Table 10

Weed suppression test in mountain soil

Compound No · Amount used (g / ha) Weed suppressing effect Phytotoxicity for sugar beet Rosička Bloody Amaranth. green Merlík Compounds of the invention: 3 2 000 5 5 5 0 1 000 5 5 5 0 4 2 000 5 5 5 0 1 000 4 5 5 0 Reference compounds: 1 2 000 4 4 5 0 1 000 3 3 4 0 2 2 000 3 3 3 0 1 000 3 3 3 0 5 2 000 5 5 5 0 1 000 4 5 5 0 6 2 000 4 5 5 0 1 000 4 4 5 0

The fungicidal activity test results of the compounds of the invention are described below for information. The fungicidal activity of the (+) - triazolyl alcohol derivatives is much greater than that of the (-) - triazolyl alcohol derivatives and racemates.

Formulation example 1 Dust parts of Compound No. 1, 88 parts clay and 10 parts talc are thoroughly mixed by grinding to form a dusting composition containing 2% active ingredient.

Example of device 2

Dust parts of Compound No. 2, 67 parts clay and 30 parts talc are thoroughly mixed by grinding to form a dusting composition containing 3% active ingredient.

Formulation Example 3 Wettable powder of parts of Compound No. 1, 45 parts of diatomaceous earth, 20 parts of colloidal silica, 3 parts of wetting agent (sodium lauryl sulfate) and 2 parts of dispersant (calcium lignin sulphonate) were thoroughly mixed by grinding to form a wettable powder composition containing 30% of active substance.

Example of device 4

A wettable powder of parts of Compound No. 2, 45 parts of diatomaceous earth, 2.5 parts of a wetting agent (calcium alkylbenzene sulphonate) and 2.5 parts of a dispersant (calcium lignin sulphonate) is thoroughly mixed by grinding to form a wettable powder composition containing 50% active ingredient.

Example of device 5

An emulsifiable concentrate of parts of Compound No. 1, 80 parts of cyclohexanone and 10 parts of an emulsifier (polyoxyethylene alkylaryl ether) is mixed to form an emulsifiable concentrate containing 10% active ingredient.

Example of composition 6

The granules of parts by weight of Compound No. 2, 40 parts by weight of bentonite, 50 parts by weight of clay and 5 parts by weight of sodium lignin sulphonate are mixed thoroughly by rosemelling. The resulting mixture is ground with sufficient water, then granulated and dried to obtain a granular composition.

Example of device 7

Dust parts of Compound No. 3, 88 parts clay and 10 parts talc are thoroughly mixed by grinding to form a dusting composition containing 2% active ingredient.

Example of resource 8

Dust parts of Compound No. 4, 67 parts clay and 30 parts talc are thoroughly mixed by grinding to form a dusting composition containing 3% active ingredient.

Example of device 9

Wettable powder of parts of compound i. 3, 45 parts of diatomaceous earth, 20 parts of colloidal silica, 3 parts of a disintegrant (sodium lauryl sulfate) and 2 parts of a dispersant (calcium lime sulfonate) were thoroughly mixed by grinding to form a compatible powder. % active substance.

Add resource 10

The readable powder of parts of Compound No. 4, 45 parts of diatomaceous earth, 2.5 parts of a wetting agent (calcium alkylbenzene sulphonate) and 2.5 parts of a dispersant (calcium lignin sulphonate) were thoroughly mixed by grinding to form a powdered pulverulent composition containing 50% of active substance.

11

The emulsifiable concentrate of parts of Compound No. 3, 80 parts of cyclohexanone and 10 parts of an emulsifier (polyethyl ethylene alkyltrylether) is mixed to an emulsifiable concentrate containing 10% active ingredient.

Treasure of the asset

The granulated parts of Tasoonoot Compound No. 4, 40 parts of tanoonootic bentonites, 50 parts of tanoonootic clay and 5 parts of mono-mono-sodium ligoi-sodium phosphate were thoroughly mixed by grinding, then well ground with water, granulated and dried on the granular composition.

Example of device 13

Drip agent

0.05 parts of compound 3, 1 part of the Hprnml 1009 (surfactant) manufactured by Mats (USA) Co., 1 part of the Newcol 560 nonionic emulsion, 2.5 parts of the cyclic textures. and 95.45 parts of mono-water are mixed to form a liquid composition.

Claims (2)

A fungicidal composition, characterized in that the triazolyl alcohol of the formula I is present It contains as active substance a derivative (I) wherein ♦ X represents a hydrogen atom or a chlorine atom and an asterisk indicates an asymmetric atom having optical activity (-). к A process according to item 1 for the preparation of an active compound of the formula I, wherein X is as defined above and the asterisk indicates an asymmetric carbon atom having optical activity (-), characterized in that the triazolyl ketone derivatives of the formula II (II) X is as defined above, asymmetrically reduced by a modified lithium aluminum hydride type chiral reducing agent.