CS214707B2 - Method of making the esters of styrylcyclopropancarboxyl acids - Google Patents

Abstract

Die Erfindung betrifft ein neues Verfahren zur Herstellung von Styryl-cyclopropan-carbonsäureestern der Formel in welcher R, R¹, R² und R³ die in der Beschreibung angegebene Bedeutung besitzen, das dadurch gekennzeichnet ist, daß man 1-Aryl-4-methyl-penta-1,3-diene mit Diazoessigsäureestern umsetzt sowie Zwischenprodukte zur Durchführung dieses Verfahrens und Verfahren zur Herstellung dieser Zwischenprodukte.

Description

The present invention relates to a novel process for the preparation of styrylcyclopropanecarboxylic acid esters, intermediates used in the process and the preparation of these intermediates.

It is already known that certain 3- (2-chloro-4-arylpynyl) -2,2-trimethylcyclopropane-1-carboxylic acid esters such as 3- (2-chloro-2-phenylvinyl) -2,2-dimethylcyclopropane-1-carboxylic acid ethyl ester acids are obtained by treating the corresponding arylmethosphonic acid esters with a strong base, for example butyllithium and then sequentially with carbon tetrachloride and a 3-formyl-2,2-dimethylcyclopropane-1-carboxylic acid ester (cf. DOS No. 2,738,150) .

However, this process for the preparation of 3- (2-chloro-2-arylvinyl) -2,2-dimethylcyclopropane-T-carboxylic acid esters has a number of disadvantages.

The strong foams, such as butyllithium, required to deprotonate arylmethanephosphonic acid esters are sensitive to moisture and air, and therefore the conventional procedure in which they are used should be carried out in an inert gas atmosphere such as nitrogen or argon and using inert, carefully dried solvents or diluents. Since the reaction is carried out at a very low temperature, about -70 ° C, the reaction mixture must also be vigorously cooled. Processing of the reaction mixture to isolate the desired products, which are obtained as mixtures of isomers, is also expensive. This treatment involves multiple extractions and distillations of solvents, as well as chromnophagic separation. Thus, the above synthesis is not very suitable for the preparation of 3- (2-chloro-2-arylvinyl) -2,2-dimethylcyclopropane-1-carboxylic acid esters on an industrial scale and should be replaced by a more easily feasible process.

The present invention provides a process for the preparation of styrylcyclopropanecarboxylic acid esters of formula (I)

AND

-C = CH CO-O-R X

H ₃ C CH ₃ (i)

in which

R is C 1 -C 4 alkyl or phenoxybenzyl optionally substituted with fluorine,

R 1 is C 1 -C 4 alkoxy, and

R ² is hydrogen or chlorine, characterized in that the l-aryl-4-methylpent.a-1,3-dienes of the formula II

The invention further provides a process for the preparation of 1-aryl-4-methylpenta-1,3-dienes of the above-mentioned general formula (II), wherein R 1 and R 2 are as defined above, characterized in that the arylmethanephosphonic acid esters of the general formula

in which

R 1 and R 2, as defined above, are reacted with diazoacetic acid esters of the general formula III-CH 2 -COO-R (III). which

R '' has the above meaning in the presence of a catalyst at a temperature between 50 and 200 ° C.

The starting 1-aryl-4-methylpenta-1,3-dienes used in formula (II) above, in which R 1 and R 2 are as defined above, are novel and can be prepared, for example, by the following processes.

Accordingly, the invention also provides a process for the preparation of 1-aryl-4-methylpenta-1,3-dienes of the above formula (II) wherein R 1 is as defined above and R 2 is chloro, wherein: 3-Methylbuten-2-ylaryl ketones of general formula. ,, IVa in which

R 1 and R 2 are as defined above and

R 4 represents an alkyl or phenyl group, or the radicals R 4 taken together form a straight or branched alkanediyl group, reacted with a dimethylacrolein of formula VI

HsC \

C = CH-CHO 2

НзС

VII), in the presence of a base and optionally using a diluent, at a temperature between -70 and + 150 ° C [process (4)].

The invention also relates to a process for the preparation of 1-allyl-4-methylpenta-1,3-dienes of the above general formula (II) in which R1 and R2 are as defined above, characterized in that: The compounds of formula VII

and / or with them isomeric 3-methylbuten-1-ylaryl ketones of formula IVb

CO-CH = CH-Ch ' ^{x X,} 1.3 (IVb) in which

R 1 is as defined above, reacted with phosphorus pentachloride, optionally using inert diluents, at a temperature between -40 ° C and + 30 ° C, after which the reaction mixture is treated with an acid binding agent at the same temperature, optionally in the presence of a catalyst [ procedure (3)].

in which

R1 and R2 are as defined above, reacted with triphenyl-isopropylphosphorane of formula VIII

CH3 Phases (C6H5) 3P — Ch

CH 3 (VIII), optionally using diluents, at a temperature between -70 and + 50 ° C [Procedure (5)].

The invention further provides a process for the preparation of i-aryl-4-methylpenta-1,3-dienes of the above-mentioned general formula II, wherein R 1 and R ² are as defined above, characterized in that the i-aryracroleins of the above-mentioned general formula VII, wherein R 1 and R 2 and m 2 14707 are as defined above, are reacted with isopropylmagnesium chloride of formula IX

H3C \

CH-Mg-Cl

OF

HsC (IX), optionally in the presence of diluents, at a temperature between -70 and + 50 ° C, and the products thus formed are dehydrated by treatment with acids at a temperature between 0 and 50 ° C (process (6)).

The invention also provides a process for the preparation of the α-aryl-acroleins of the above-mentioned general formula (VII), wherein R ¹ is as defined above and R- represents a chlorine atom, characterized in that the aryl methyl ketones of the general formula (X)

in which

R1 is as defined above, reacted with dimethylformamide and phosphorus oxychloride at a temperature between 0 ° C and 0 ° C without the addition of an additional diluent, and the reaction products are isolated without distillation [process (7)].

Surprisingly, the novel process according to the invention, which can be carried out at a lower cost than the known process and using readily obtainable starting materials, yields 3- (2-arylvinyl) -2,2-dimethylcyclopropane-1-carboxylic acid esters. in good yields.

Formula I includes a wide variety of isomers and mixtures thereof.

If, for example, 1-chloro-1 is used as starting material in the process according to the invention. - (4‘-Methoxyphenyl) -4-methylpenta-1,3-diene. and ethyl ester of diazoacetic acid, the reaction may be described as follows:

CHjO

C-CH-CO-OC3

W CH

The diazoacetic acid esters of formula (III) are known in the literature and are exemplified by the methyl ester and the ethyl ester of the diazoacetic acid.

The novel 1-aryl-4-methylpenta-1,3-dienes of formula II can be prepared as described above.

If, for example, a mixture of 2-methyl-5-oxo-5- (4-methoxyphenyl) -2-pentene and 2-methyl-5-oxo-5 is used as starting material in the process [3], - (.alpha.-methoxyfunyl) pentene, the reaction of these compounds with phosphorus pentachloride and the subsequent elimination of hydrogen chloride can be described by the following scheme:

+ PCts

-на

-> СН, 0

CH,

Ct

The starting materials of the formulas IVa and IVb used in this process are known and / or can be prepared in a manner known per se [see J. Org. Chem. 25 (1960) 2721]. The compounds of formulas IVa and IVb are obtained, for example, by reacting the arylmethyl ketones of the above formula X with isobutyraldehyde and distilling the reaction product in the presence of sodium acetate.

The reaction according to process (3) is carried out by adding phosphorus pentachloride to the starting material of formula IVa or IVb, or to a mixture thereof, in a diluent. In contrast to the general and well-known working methods in the reaction of ketones with phosphorus pentachloride (see Houben-Weyl, Methoden der organischen Chemie, vol. 5/3, p. 912), the reaction of process (3) is preferably carried out in the presence of a diluent. . Suitable diluents are, for example, hydrocarbons such as gasoline, petroleum ether, pentane, hexane, cyclohexane, benzene, toluene or xylene, chlorinated hydrocarbons such as methylene chloride, carbon tetrachloride, dichloroethane or chlorobenzene, as well as nitriles such as acetonitrile. Toluene and / or cyclohexane is preferably used as the diluent. The reaction of unsaturated ketones with phosphorus pentachloride is virtually always problematic and can cause a large number of side reactions. Thus, for example, chlorination can occur in the allyl position or in the α-position with respect to the carbonyl group. Hydrogen chloride produced here, as well as during elimination, can be re-added to the double bond. In addition, chlorination of the double bonds can also occur with phosphorus pentachloride.

It has been found that these side reactions can be virtually completely eliminated by working in the presence of diluents and at a relatively low temperature and then adding a base at the same or a lower temperature so as to avoid the presence of hydrogen chloride at higher temperatures. The reaction is generally carried out at a temperature between -40 ° C and -30 ° C, preferably between -10 ° C and + 20 ° C.

Practically all technically useful bases, such as hydroxides such as sodium and potassium hydroxides, carbonates such as sodium and potassium carbonates, as well as alkoxides such as methoxide or alkali metal may be used as acid binders in the process of process (3). sodium ethoxide. Aqueous solutions of alkali metal hydroxides or alkali metal carbonates are preferably used in the presence of phase transfer catalysts. All conventional phase transfer catalysts may be used for this purpose, but preferably tetraalkyl or aralkyl-dialkylammonium salts, for example benzyltriethylammonium chloride or tetrabutylammonium bromide, are used.

The 1-aryl-4-methylpenta-1,3-dienes prepared according to process (3) can generally be purified by distillation. If these dienes cannot be distilled without decomposition, they are purified by so-called "distillation", ie by longer heating to moderate elevated temperature under reduced pressure.

If, for example, 4-trifluoromethoxyphenyl-.alpha.-chlorobenzylphosphonic acid diethyl ester and dimethylacrolein are used as starting materials in process (4), the reaction of these compounds can be described as follows:

СН-Р (ОСН ₅ ) _Д 1a

CH $ \ = CH-CHO— /

CHj,

/ CH ₃ '' CH ₃

The starting materials used in the process (4) are defined by formulas V and VI. The dimethylacrolein of formula VI is a literature known compound.

Some of the α-chloro-arylmethanephosphonic esters of formula (V) are known. These compounds can be obtained by reacting the N-hydroxy-aryl-methanesulfonic acid esters of formula XI

1 4 7 O '7 in which

R1 and ^R4 are as defined above, with a chlorinating agent, for example thionyl chloride at temperatures between 0 and 100 ° C, preferably between 20 and 80 C [see Chim-28 and [1974)

63.6 - 657; J. Am. Chem. Soc. 87 (19'65), 2777-2778],

The α-hydroxy-arylmethanephosphonic esters of formula XI are known in some cases. These compounds are prepared in a known manner, generally by reacting the aldehydes of the general formula (XII):

R1 is as defined above, with phosphorous acid esters of formula (XIII)

O

II

H - P (OR4) 2 (ΧΙΙΙ), in which

R 4 is as defined above, optionally in the presence of a catalyst such as triethylamine, at a temperature between 0 ° and 150 ° C, preferably between 20 ° and 100 ° C [see HoubenWeyl, Methoden der organischen Chemie, 4th edition (1963), St. 12/1, pp. 475-483).

The reaction of process (4) is a variant of the Wittig-Horner reaction. Very few examples are known from the literature for this variant. The base used in the prior art is sodium hydride, which is an expensive reagent that is difficult to handle. In accordance with the new process, on the other hand, it is possible to work considerably simpler and less costly. The reaction can be carried out at room temperature in an aqueous reaction medium, and cheaper bases can be used instead of sodium hydride.

The reaction of process (4) is preferably carried out using diluents. Suitable diluents include virtually all inert organic solvents, including in particular aliphatic and aromatic and / or chlorinated hydrocarbons, such as benzine, benzene, toluene, xylene, methylene chloride, chloroform, carbon tetrachloride, chlorobenzene and o-dichlorobenzene, ethers, such as diethyl ether, dibutyl ether, tetrahydrofuran and dioxane, alcohols such as methanol, ethanol, n- and isopropanol, η-, iso-, sec-, and tert-butanol as well as dimethyl sulfoxide.

When operating in a two-phase system, in addition to 50% aqueous sodium hydroxide solution, practically water-immiscible solvents such as petrol, benzene or toluene are used.

Bases which are commonly used in the olefinization of carbonyl derivatives can be used. Examples of such bases ¹ include alkali metal hydroxides such as sodium and potassium hydroxide, alkali metal alkoxides such as methoxide, ethoxide, isopropoxide, n- and, η-, iso-, sec- and tert-butoxide and potassium alkali metal hydrides such as sodium hydride as well as alkyllithium compounds such as butyllithium. Sodium and potassium hydroxide as well as sodium methoxide and ethoxide are preferably used as bases. *

Reaction temperatures are generally between -70 and + 150 ° C, preferably between -10 and + 50 ° C. The reaction is generally carried out under normal pressure. When working according to process (4), the reaction components of the lead are used in equimolar amounts, only the bases are usually used in a larger excess, when operating in a single-phase system in excess of up to 30 mol. %, preferably up to 15 mol. If 50% sodium hydroxide is used as the second phase, a quantity of 5 to 15 times the stoichiometric amount is generally used.

The necessary alkoxides are optionally prepared in situ from alcohols and alkali metals.

In general, the base and optionally the catalyst are introduced into one or more of the above solvents and the reaction components, i.e., the .alpha.-chlorobenzylphosphonic acid ester of formula V and the dimethylacrolein of formula VI, optionally dissolved in any of the above, are added. solvents. To complete the reaction, the mixture was stirred at the above temperature for several hours. For working up, the reaction mixture was diluted with water, optionally acidified with hydrochloric acid and extracted with methylene chloride. The organic phase is dried and the solvent is distilled off in vacuo. Where appropriate, the product resulting from the evaporation process is purified by vacuum distillation or, in the case of a product which cannot be distilled without decomposition, by so-called 'distillation', ie by prolonged heating under reduced pressure to moderate temperature. The boiling point or refractive index is used to characterize these products.

The starting materials used in the process (5) are defined by formulas VII and VIII.

A process for the production of phosphorous VIII is known.

The acrolein derivatives of formula VII are known in some cases. A new method for their production, referred to as process (7), will be described below.

The reaction according to process (5) is carried out according to the usual methods used for olefinating the carbonyl group of Wittig.

If the starting materials 4-chloro-4-methoxyphenyl acrolein and isopropylmagnesium chloride are used as starting materials in process (6), the reaction of these compounds can be described as follows:

ai

2147Ď7

& CH-CHO & Cl

/ x

----? CH.O- \ ⁷ YC-CH = C * \ = 7 L-CH.

Cl 3

Isopropylmagnesium chloride can be prepared by a known method [see Chem. Ber. 69 (1936), 1766].

The starting materials used in the process (6) are defined by formulas VII and IX.

Process (6) consists of a Grignard reaction followed by dehydration. The Grignard reaction can be carried out in a manner known per se. The fact that:. It is possible to eliminate water relatively easily from the intermediate secondary alcohol formed. The dehydration is carried out by treatment with acids, preferably sulfuric acid, at a temperature between 0 and 50 ° C, preferably between 20 and 45 ° C. After pouring into water, the reaction mixture is worked up by usual extraction.

If, for example, 4-methoxyacetophenone, dimethylformamide and phosphorus oxychloride are used as starting materials in process (7), the reaction is described as follows:

POCl ₃ - "->

H-CO-N (CH 3);

CHO

The aryl methyl ketones used in the process (7) as starting material are defined by formula X.

Process (7) yields the β-chloro-β-arylacroleins of the formula III particularly easily and in an improved yield and quality if, contrary to the data recommended by the literature (see Proc. Chem. Soc. (London) 1958) , 227; Angew, Chem. 71 (1959), 573; Chem. Ber. 93 (1960 ·), 2746 and Chem. Ber. 98 (1965), 3554], does not add diluent, and distillation treatment associated with significant losses is not performed. and the product is isolated in crystalline form after gentle hydrolysis at low temperature The reaction according to process (7) is carried out by dissolving the ketone of formula X in dimethylformamide, to a solution at a temperature between 0 and 100 ° C, preferably between 20 and 60 ° C, phosphorous oxychloride is added and the mixture is stirred at the same temperature for 1 to 5 hours The reaction mixture is poured into ice-water and the pH is adjusted to ca 5 with caustic soda. that the temperature does not exceed 25 ° C. After mixing the product is sucked off, washed with water and dried in vacuo.

The reaction according to the invention is carried out in the presence of catalysts. Possible catalysts are copper and copper compounds in various oxidation stages, as well as mixtures thereof. Examples include copper (such as powder or bronze), cuprous chloride and cuprous chloride, cuprous oxide and cuprous oxide, as well as cuprous sulfate. The reaction temperature can be varied within wide limits. In general, the reaction is carried out at a temperature of between 50 and 200 ° C, preferably between 80 and 150 ° C.

The process according to the invention is generally carried out under atmospheric pressure and, in the case of needles, the weight ratio of the starting materials can be varied within wide limits. In general, a weight ratio of diazoacetic acid ester to 1-aryl-4-methylpenta-1,3-diene of between 1: 1 and 1:20 is employed. Usually the procedure is such that 2/3 of the total amount of l-Chloro ^ - ^: l-aryl-4-m (^ 1: hylpe] ^{^!} Ta-l, 3-diene of the formula II together with the catalyst is heated to the necessary The diazoacetic acid ester of formula III diluted with the remaining one-third of the diene of formula II is then added dropwise to the reaction mixture, after the nitrogen evolution ceases, the reaction mixture is cooled, diluted with a water-immiscible solvent such as methylene chloride and filtered. It is washed with water, dried and worked up by distillation.

The compounds of the formula (I) prepared according to the process of the invention can be used as intermediates for the preparation of antisepticidal active compounds (cf. DOS No. 2,738,150).

The styrylcyclopropanecarboxylic acid esters of the above general formula (I), when esterified with a fluorine-substituted phenoxybenzyl group, are suitable for controlling pests, in particular insects and spider mites, in agriculture, forestry, because of their good plant compatibility and favorable toxicity to ¹ warm-blooded animals. in the protection of stocks and materials, as well as in the field of hygiene. These compounds are active against both normally sensitive and resistant species and all or only individual developmental pests.

The above mentioned pests include:

from the order of the Isopods, for example Oniscus asellus, Armadillidium vulgare, Porcellio scaber;

from the class of the Diplopoda, for example Blaniulus guttulatus;

from the Chilopoda class, for example Geophilus carpophagus, Scutigera spec .;

from the centipede class (Symphyla), for example

Scutigerella immaculata;

of the order Thysanura, for example Lepisma saccharina, of the order Gollembola, for example Onychiurus armatus;

Orthoptera, for example Blatta orientalis, Periplaneta americana, Leucophaea maderae, Blatella germanica, Cricket (Acheta domesticus), Gryllotalpa spec., Locusta migratoria migratorioides),

Melanoplus differentialis, Schistocera gregaria;

from the order of the Dermaptera, for example Forficula auricularia;

from the order of the Isoptera, for example Reticulitermes spec.

from the order of the lice (Auoplura), such as the aphid (Phyllcxera vastatarix), the louse (Pemphigus spec.), the louse (Pediculus humanus corporis), Haematopinus spec.,

Linognathus spec .;

from the order of the Mallopliaga, for example, Trichodectes spec., Damalinea spec .;

from the order of the Thysanoptera, for example Hercinothrips femoralis, Thrips tabaci;

of the order Heteroptera, for example, Eurygaster spec., Dysdercus intermedius, Piema quadrata, Cimex lectularius, Rhodnius prolixus,

Triatoma spec .;

from the order of the Homoptera, for example, Aleurodes brassicae, Bemisia tabaci, Trialeurodes vaporariorum, A.phis gossypii, Brevicoryne brassicae, Cryptomysus ribis (Doralis fabae), Apple aphid (Doralis porni), Eriosoima lanigerum, Hyalopterus arundinis, Marcosiphum avenae,

Myzus spec., Phorodon humuli, Rhopalosiphum padi, Empoasca spec., Euscelis bilobatus,

Nepho-tettix cincticeps

Lecanium corni, Saissetia oleae,

Laodelphax striatellus, Nilaparvata lugens, Aonidiella aurantii, Aspidiotus hederae, Pseudococcus spec., Mera (Psyla spec.);

from the order of the butterflies (Lepi dopit era), for example

Pectinophora gossyplella, Dark-spot Carpet (Bupalus piniaruis),

Cheimatobia brumata, Lithocolletis blancardella, Hyponomeuta padella, Plutella maculipennis, Malocosoma neustria, Euproctis chrysorrhoea, Lyman.

1S

BLicculatrix thurberlella, Phyllocnistis citrella, Agrotis spec., Euxoa spec.

Feltia spec.,

Earias insulana, Heliothis spec., Laphygma exigua, Mametra brassicae, Panolis flammea, Prodenia litura, Spodcptera spec., Trichoplusia ni,

Carpocapsa pomonella, White (Pieris spec.), Chilo spec., Corn borer (Pyrausta nubilalis), Moth moth (Ephestia kuhniella), Wax moth (Galleria mellonella), Fruit moth (Cadoecia podana),

Capua reticulana, Curistoneura fumiferana, Clysia ambiguella, Homona magnanima, Ttotrix viridana;

from the order of the beetles (Coleoptera), for example, Anobium punctatum, Rhizopertha dominica, Bruchidius obtectus, Acanthoscelides obtectus, Hylo-trupes bajulus, Agelastelotis alni, decemlineata), Phaedon cochleariae, Diabrotica spec., Psylliodes chrysocephala, Epilachna varivestis, Atomaria spec., Sus. ), Greater Lobe (Otiorrhynchus sulcatus),

Cosmopolites sordidus, Ceuthorrhynchus assimilis,

Hypera postica, Dermestes spec., Trogoderma spec., Anthremus spec., Attagenus spec., Lyctus spec., Meligethes aeneus, Ptinus spec. fern (Niptus hololeucus), Gibbium psyloides, darkling beetle (Tribolium spec.), darkling beetle (Tenebrio molitor), click beetle (Agriotes spec.),

Conoderus spec., Common Cockchafer (Melolontha melolontha), Summer Chafer (Amphimallon solstitialis), Costelytra zealandica;

from the order of the Hymenoptera, for example Diprion spec., Hoplocampa spec., Lasius spec., Monomorium pharaonis, Vespa spec.

from the order of the diptera (Diptera), for example, the mosquito (Aedes spec.), anofeles (Anopheles spec.), mosquito (Culex spec.), fruit fly (Drosophila melanogaster), fly (Musea spec.), sunflower (Fannia spec.), Calliphora erythrocephala, Lucilia spec., Chrysomyia spec.

Cuterebra spec., Gastrophilus spec.

Hyppobosca spec., Stomoxys spec., Oestrus spec., Hypoderma spec.

Tahnia spec., Garden Fly (Bibio hortulanus), Barberry (Oscinella frit),

Phcrbia spec., Pegomyia hyoscyami, Ceratitis capitata, Dacus oleae, Tipula paludosa;

from the order of the Siphonaptera, for example, Xenopsylla cheopis, Ceratophyllus spec.

from the order of Arachnida, for example

Sccrpio maurus, Latrodectus mactans;

from the order of the Acarina mites, for example Acarus sulfur, Argas spec.

Ornithodoros spec., Dermanyssus gallinae, Eriophyes ribis, Phyllocoptruta oleivora, Boophilus spec., Rhipicephalus spec., Amblyomma spec.

Hyalomma spec., Tick (Ixodes spec.), Psoroptes spec., Scab (Chorioptes spec.),

Sarcoptes spec.

2147 0 7 mites (Tarsonemus spec.), Currant spider (Bryobia praetiosa], spider mite (Panonychus spec.), Spider mite (Tetranychus spec.).

The active compounds according to the invention can be applied in the form of commercial preparations and / or from them by further dilution of the prepared dosage forms.

The active compound content of the dosage forms prepared from the commercial preparations can be varied within wide limits, for example from 0.0000001 to 100% by weight, preferably from 0.01% to 10% by weight.

The application is carried out in a customary manner adapted to the application form used.

When used against hygiene pests and against storage pests, the active compounds according to the invention are distinguished by an excellent residual effect on wood and clay, and good stability to alkali on lime substrates.

Example A

Test for leaf beetle larvae (Phaedon cochleariae) solvent:

parts by weight of acetone emulsifier:

part by weight of alkylaryl polyglycol ether

To prepare a suitable active ingredient, 1 part by weight of the active ingredient is mixed with the indicated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.

Leaves of kale (Brassica oleracea). is treated by immersion in a formulation containing the active substance at the desired concentration and then occupied while still wet with the larvae of the leaf beetle Phaedon cochleariae).

After a given period of time, mortality was found in%. 100% means that all the leaf beetle larvae have been killed, · 0 ^{: O} / o means that no larvae have been killed.

In this test, for example, the following compound of the Examples shows a better effect than the prior art preparations:

The following examples illustrate the preparation of the active compounds according to the invention and intermediates, but are not intended to limit the scope of the invention in any way.

Example 1

Н ₃ с сн _ъ (process according to the invention)

A mixture of 44.4 g (0.2 mol) of 1- (4-methoxyphenyl) -1-chloro-4-methylpentan-1,3-diene, 1.2 g of copper powder and 1.5 g of anhydrous copper sulfate. Heat to 110 ° C and then add 22.2 g (0.1 mol) of 1- (4-methoxyphenyl) -1-chloro-4 dropwise very slowly over 5 hours with stirring at 110 ° C. methyl penta-1,3-diene and 34.2 g (0.3 mol) of diazoacetic acid ethyl ester. After nitrogen evolution ceased, the mixture was cooled, diluted with 500 mL of methylene chloride and filtered. The filtrate is shaken with 500 ml of water, the organic phase is separated, dried over magnesium sulphate and the solvent is distilled off under a water pump vacuum. The oily residue is fractionally distilled under vacuum to give two fractions:

fraction 1: boiling point 124-145 ° C / 267 Pa fraction 2: boiling point 155-175 ° C / 267 Pa.

Fraction 1 consists of unreacted 1- (4-methoxyphenyl) -1-chloro-4-methylpenta-1,3-dlene. Fraction 2 was distilled again to give 11.2 g of 2,2-dimethyl-3- [2-chloro-2- (4-methoxyphenyl) vinyl] cyclopropanecarboxylic acid ethyl ester (mixture of isomers) as a yellow oil. 160 ^; to 172 ° C / 267 Pa.

Example 2

[Procedure (3)] g of potassium hydroxide is dissolved in 12.5 ml of water and 125 ml of methanol, 150 g of 4-methoxyacetophenone are added to the solution, and 80 g is added dropwise at 50 DEG C. over a period of 1.5 hours. -obutyraldehyde. After 3.5 hours, the mixture was cooled to room temperature and neutralized with about 20 mL of acetic acid. The dimeric condensation product is filtered off with suction, washed with methanol and air-dried. 175 g of a solid are obtained, which is mixed with 5 g of sodium acetate and distilled under a water pump vacuum. 165 g of a yellow oil solidifying at room temperature are obtained, consisting of a mixture of 2-methyl-5-O.XO-5- (4-methoxyphenyl) -2-pentene and 2-methyl-5-oxo-5- (4-methoxyphenyl) - 3-pentene. This mixture of isomers has a boiling point of 158-165 ° C / 1700 Pa.

102 g of the mixture of isomers prepared above are dissolved in 500 ml of toluene and 104 g of phosphorus pentachloride are slowly added to the solution at 0 ^° C. The mixture is stirred at 0 to 10 ° C until all of the phosphorus pentachloride is dissolved, then 5 g of tetrabutylammonium bromide are added thereto and 224 g (2 mol) of 50% caustic is added dropwise thereto at 0 to 10 ° C with efficient cooling. The toluene phase is then immediately separated, washed until neutral and evaporated on a rotary evaporator.The crude pulp is distilled (boiling point 125-165 ° C / 10 mm Hg) and then purified by a second distillation to give 75 g of 1- (4-methoxyphenyl) -1-chloro 4-methylpenta-1,3-diene, bp 112-119 ° C / 27 Pa.

Example 3 g of 1- (4-methoxyphenyl) -1-chloro-4-methylpenta-1,3-diene (mixture of isomers) in the form of a yellow oil which partially crystallizes after some time. The product has a boiling point of 130-145 degrees Celsius.

The desired α-hydroxybenzylphosphonic acid ester of the formula needed as starting material

O

СН ₅ О- £ Уси-Р (ОС _г Н ₅ ) _г.

OH can be prepared as follows:

To a mixture of 20.7 g (0.15 mol) diethylphosphite and 1.09 g (0.1019 mol) triethylamine, 20.4 g (0.150 mol) was added over 1 hour while cooling with water at 50-70 ° C. The reaction mixture was stirred at 70 ° C for 1 h, cooled, shaken with 40 g of toluene, washed several times with dilute hydrochloric acid and cold water, and the organic layer was separated and the solvent was removed in vacuo. -methoxy-α-hydroxybenzylphosphonic acid is 37 g.

o ct

CH ₅ O

C = CH-CH-C ^X

AND

Ct си ₃

C _H> [procedure (4)]

4.6 g (0.2 mol) of sodium are dissolved in portions in 100 ml of dry ethanol. After dissolution of all sodium, 100 ml of anhydrous tetrahydrofuran was added and 58.4 g (0.2 mol) of diethyl 4-methoxy-α-chlorobenzylphosphonic acid dissolved in 50 ml of anhydrous tetrahydrofuran was added dropwise at 0 ° C with stirring. The resulting mixture was stirred at 0-10 ° C for 1 h, then 16.8 g (0.2 mol) of (R) -dimethylmethyrodeine dissolved in 30 ml of anhydrous tetrahydrofuran was added dropwise with stirring. After 12 hours of stirring at room temperature, 600 ml of water are added and the mixture is extracted twice with 300 ml of methylene chloride each time, the organic phase is separated, dried over magnesium sulphate, the solvent is distilled off under water pump vacuum and the residue is distilled under vacuum. It is obtained

To a mixture of 20 g (0.073 mol) of 4-methoxy-α-hydroxybenzylphosphonic acid diethyl ester, 65 g of dichloromethane and 5.8 g (0.0725 mol) of pyridine are added at 20-40 ° C with gentle water cooling over about 1 hour. Thionyl chloride (9.2 g, 0.0768 mol) The reaction mixture was heated at reflux for 3 hours and then stirred for 12 hours without further heating. The resulting mixture was poured into about 100 g of ice-water, the organic phase After distilling off the solvent, the residue is evaporated under a pressure of 800 Pa at 45 DEG C. 21 g of 4-methoxy-.alpha.-chlorobenzylphosphonic acid diethyl ester are obtained in the form of a yellow viscous oil of 98.6% purity (according to gas chromatography). ) and the refractive index n _D ²⁴ = 1.5188.

Example 4

CH 2) ~

C = CH-CH-C

AND

Cl [procedure [5]]

To a suspension of 22.7 g (0.0625 mol) triphenylisopropylphosphonium iodide in 100 mL of tetrahydro214707

At 0 DEG C., n-butyllithium (0.055 mol) in hexane (30 ml) was added dropwise. The mixture is stirred for 1 hour at 0 ° C, then a solution of 10 g (0.05 mol) of β- (4-methoxyphenyl) - / Tchloracrolein in 100 ml of tetrahydrofuran is added in one portion and the resulting mixture Stir 10 hours at 20 ° C. The reaction mixture is evaporated, 100 ml of water are added to the residue, and the mixture is extracted twice with 50 ml of ether each time. The combined ether extracts were dried over sodium sulfate and evaporated. The residue crystallizes after the addition of about 50 ml of petroleum ether. The crystals are filtered off with suction and recrystallized again from petroleum ether.

8 g of 1- (4-methoxyphenyl) -1-chloro-4-methylpenta-1,3-diene are obtained in the form of pale yellow crystals.

Example 5 сн _ь о

c = cw-cw = c ^x !

CA / ₃

CH _b [procedure (6)]

To a solution of 0.4 mol of isopropylmagnesium chloride in 40 ml of isopropyl chloride [prepared according to the procedure described by J. Houben et al. in Chem. Ber. 69 (1936), 1766] 39.3 g (0.2 mol) of β-chloro-4- (4-methoxyphenyl) acrolein in 200 ml of tetrahydrofuran was added dropwise at 20 ° C. The reaction mixture is stirred for a further 12 hours and then poured into a mixture of 500 g of ice and 100 ml of sulfuric acid with stirring. The resulting mixture was extracted twice with 100 ml of ether each time, the combined ether extracts were dried over sodium sulfate and concentrated on a rotary evaporator at 50 ° C. The residue is taken up in 1 ml of glacial acetic acid and 2 ml of concentrated sulfuric acid is added dropwise thereto at a rate such that the temperature does not exceed 46 ° C. The resulting mixture was stirred at 20 ° C for 4 hours and then poured into water. The aqueous mixture was extracted twice with 100 ml of ether each time, the combined ether extracts were dried over sodium sulfate, evaporated and the residue was distilled. 22 g of 1-diene are obtained in the form of a yellow oil which partially crystallizes in o- (4-methoxyphenyl) -1-chloro-4-methylpenta-1,3-cooling. The product boils at 140-145 ° C / 533 Pa.

Example 6

CH ₂ O-Q-C-CH-CHO ct [Procedure [7] 1

750 g (5 mol) of 4-methoxyacetophenone are dissolved in 2.5 liters of dimethylformamide and 1570 g of phosphorus oxychloride are added dropwise to the solution at 40 DEG-45 DEG C. with gentle cooling over 2 hours. The mixture is stirred for 1 hour, then poured into 25 liters of ice water and the pH is adjusted to 5 by dropwise addition of approximately 2.1 liters of concentrated sodium hydroxide solution. During neutralization, the temperature is maintained by dropping pieces of ice at 25 ° C. The resulting mixture was stirred at pH 5 for a further 1 hour and below 25 ° C. The pale crystalline precipitate is filtered off with suction, washed thoroughly with water and dried under vacuum at 50 ° C. Yield 730 g.

CH ₅ O

Example 7

(preparation of active ingredient according to the invention)

4.4 g (0.02 mol) of 3-phenoxy-4-fluorobenzyl alcohol and 7.1 g (0.02 mol) of 2,2-dimethyl-3- (2-chloro-2- (4-methoxyphenyl) chloride) (nyl) cyclopropanecarboxylic acid is dissolved in 100 ml of anhydrous toluene and 2.5 g of pyridine dissolved in 50 ml of anhydrous toluene is added dropwise while stirring at 20-25 ° C. The reaction mixture is stirred at 25-35 ° C for 3 hours, then poured into 150 ml of water containing 10 ml of concentrated hydrochloric acid, the organic phase is separated and washed again with 100 ml of water. The toluene phase is dried over sodium sulfate and the solvent is distilled off under a water pump vacuum. The last residual solvent was removed by brief distillation at 1 mmHg and a bath temperature of 60 ° C. There was obtained 8-gram (84.5% of theory) of 2,2-dimethyl-3- (2-chloro-2- (4-trifluoromethoxyphenyl) vinyl) cyclopropanecarboxylic acid 4-fluoro-3-phenoxybenzyl ester.

Claims (1)

A process for the preparation of styrylcyclopropanecarboxylic acid esters of general formula (I) R s = s - c = s R ² (II) wherein R ¹ and R ² have the abovementioned meaning, are reacted with diazoacetic acid esters of the general formula III R is C 1 -C 4 alkyl or phenoxybenzyl optionally substituted by fluorine, R ¹ is C 1 -C 4 alkoxy; R ² is hydrogen or chlorine, characterized in that the l-aryl-4-methylpent-1,3-dienes of the formula II N ₂ CH-COO-R (Ш) in which R is as defined above, in the presence of a copper catalyst and compounds thereof, at a temperature between 50 and 20-0 ° C.