DD151157A5 - PROCESS FOR THE PREPARATION OF ALKENES - Google Patents

Abstract

The invention relates to a novel process for the preparation of alkenes of the formula I, in which R & exp1 !, R & exp2 !, R & exp3! having the meaning given in the description, characterized in that alpha-hydroxyphosphonic acid esters of the formula II are reacted with phosphorus-containing olefination agents of the formula III in the presence of bases. Some of the compounds are new and can be used, for example, in the synthesis of insecticidally active pyrethroids.

Description

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2 2 0 8 O ^ 4 '

Process for the preparation of alkenes Field of application of the invention

The invention relates to a novel process for the preparation of known and novel alkenes and their intermediates which can be used in the synthesis of insecticides.

Well-known technical solutions

It is known that alkenes, such as. B, the 3- (2-methyl-2-methoxy-carbonyl-vinyl) -2,2-dimethyl-cyclopropane-1-carboxylic acid tert-butyl ester useful as an intermediate for insecticidal pyrethroids aldehydes or ketones, such as. B, 3-formyl-2,2-dimethyl-cyclopropane-l-carboxylic acid tert-butyl ester, with phosphorus ylides (phosphoryls), such as. B. (1-methoxy-carbonyl-ethylidene) phosphoric acid diethyl ester, reacted (see Organic Reactions, Vol 25 (1977), p 73-253, in particular p. 85 and p 121, and literature cited therein).

Furthermore, it is known - as a special case of the above-mentioned synthesis method - that certain 3- (2-chloro-2-phenyl-vinyl) -2,2-dimethyl-cyclopropane -! - carboxylic acid esters, such as. B. 3- (2-chloro-2-phenyl-vinyl) -2,2-dimethyl-cyclopropane-1-carboxylic acid ethyl ester, if corresponding benzyl phosphonic acid ester with a strong base such. B. butyl lithium, treated and the intermediately formed ylides with carbon tetrachloride and then with 3-formyl-2,2-dimethylcyclopropane-1-carboxylic acid esters, (see DE-OS 2,738 150)

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Although the above generally illustrated carbonyl olefination reaction has a very wide range of applications, but for example, then no longer interesting for industrial concerns, if the aldehydes (or ketones) to be used as starting materials can be produced only with great effort. Thus, according to the prior art, usable as pyrethroid intermediates 3-formyl-2 ^ -dimethyl-cyclopropane-l-carboxylic acid ester by ozonolysis of 3 ~ alkenyl-2 ^ -dimethyl-cyclopropane-l-carboxylic acid esters, eg. B. Chrysanthemumsäureethylester, which in turn are produced from naturally occurring pyrethroids (see US Patent No. 3,679,667). A technically feasible manufacturing method for 3-formyl-2,2-dimethylcyclopropane -! - carboxylic acid esters is not known.

A high cost would require the technical implementation of the above-described, known method for the synthesis of 3- (2-chloro-2-phenyl-vinyl) -2 ^ -dimethyl-cyclopropane-l-carbcnsäureestern.

The strong bases required for ylide formation from benzylphosphonic acid esters, such as. As butyllithium, are sensitive to moisture and air; therefore, the reaction is carried out in an inert gas atmosphere, for example under nitrogen or argon, and using an inert, carefully dried diluent. Since the reaction at low temperature, for example at -70 ⁰ C, has to take place, the reaction mixture must be cooled intensively. The workup to isolate the desired products, which is obtained as mixtures of isomers, is also expensive; it includes several extractions and solvent distillates

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tion and a chromatographic separation process. For these reasons, the known synthetic method is unsuitable for the preparation of 3- (2-chloro-2-phenyl-vinyl) -2,2-dimethylcyclopropane-1-carboxylic acid esters on an industrial scale.

Object of the invention

It is an object of the invention to eliminate these disadvantages.

Essence of the invention

The invention has for its object to provide processes for the preparation of new alkenes and their intermediates,

The subject of the present invention are:

(1) A process for producing alkenes of the formula (I)

> 3

C = CH-R ¹ (I),

in which

R is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aralkenyl or aryl radical or an optionally substituted heterocyclic radical,

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R * is hydrogen or halogen and

R is halogen, cyano, an optionally substituted, alkyl, alkenyl, alkynyl, cycloalkyl, aralkenyl, aryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl or aminocarbonyl radical or an optionally substituted heterocyclic radical stands,

characterized in that Ai-hydroxy-phosphonic acid ester of the formula II

(R ⁴ O) ₅ P-CH-R ¹ (II),

OH

in which

R has the meaning given above and

R represents alkyl or phenyl or the two radicals R together represent straight-chain or branched alkanediyl (alkylene),

with phosphorus-containing olefination agents of the formula III

R ³

"""* CH-Z ¹ (III),

R ² -

in which

2 3

R and R have the meanings given above, and

Z is a phosphorus-containing radical

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7 g ^{or p} ( ^R ) x * ^x

stands, where

R and R are the same or different and are individually alkyl, phenyl, alkoxy or phenoxy or together are alkanedioxy,

R is alkyl or phenyl and X is halogen,

in the presence of bases, optionally in the presence of catalysts and optionally using diluents, at temperatures between -70 and +150 ⁰ C converts ·

(2) The process for the preparation of the new OG-Hydroxyphosphonsäureester of formula II a

OH

Il ·

Z ² (Ha),

H ₃ C CH ₃

in which

R and Z have the meanings given above,

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22

^wv - 6 -

with hydride complexes of the formula V

M (M'H ₄ ) (V),

in which

M is lithium, sodium or potassium and M 'is boron or aluminum,

if appropriate in the presence of a buffering agent and if appropriate using a diluent at temperatures between -20 and + 50 ° C.

(3) The process for producing the novel QC- oxo-phosphonic acid esters of the formula IV

(R ⁴ Q) ₂ P-CO. , Z ²

(IV),

H ₃ C CH ₃

in which

R is alkyl or phenyl or the two radicals R together represent straight-chain or branched alkanediyl (alkylene) and

Z is cyano, carbamoyl, acetyl or C 1 -C 4 alkoxycarbonyl,

is that one carboxylic acid chlorides of the formula VI

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Cl-CO-, ^ - Z ²

(VI)

H ₃ C CH ₃

in which

Z has the abovementioned meaning, with phosphorous acid esters of the formula VII

R ⁸ OP (OR ⁴ J ₂ (VII),

in which R has the abovementioned meaning and R stands for methyl or ethyl,

at temperatures between -20 and +150 ⁰ C converts.

(4) The process for the preparation of the novel carboxylic acid chlorides of the formula VI

Cl-CO

H ₃ C CH ₃

in which

Z is cyano, carbamoyl, acetyl or C 1 -C 4 alkoxycarbonyl

is, is that carboxylic acids of formula VIII

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22 O 8 O 4 - H ₃ C 8th - ι Z ² I "CH ₃ In which one

(VIII)

Z has the meaning given above.,

with a chlorinating agent at temperatures between 20 and 80 ⁰ C *

(5) The process for the preparation of the novel styryl-cyclopropane derivatives of the formula XI

C = CH.

(XI)

^H 3 ^{C CH} 3

in which

R is halogen or optionally halogen-substituted radicals alkyl, alkoxy, alkylthio or alkylenedioxy and also cyano or nitro,

η is zero to 5,

R is hydrogen, halogen or optionally halogen-substituted alkyl, and

Y is acetyl, cyano or carbamoyl,

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is that benzylphosphonic the formula XII

^CH - ^p \ (XU),

in which

Q Ίο R, η and R have the meanings given above,

and the leftovers

R individually for alkyl or phenyl or together

represent alkanediyl (alkylene),

with formyl-cyclopropane derivatives of the formula XIII

OHC Y

/ \ (XIII),

H ₃ C CH ₃

in which

Y has the meaning given above,

in the presence of bases and if appropriate using diluents, at temperatures between -70 and +150 ⁰ C converts ·

(6) The process for the preparation of the novel formyl-cyclopropane derivatives of the formula XIII

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'(XIII) ₄

H ₃ C CH ₃

in which

Y is acetyl or carbamoyl;

is that for the preparation of the formyl-cyclopropane derivative of formula XIII (above),

in which

is acetyl.

2-Acetyl-3, B-dimethyl-cyclopropane-1-carboxylic acid chloride of the formula XIV

CO-CH ₃

(XIV)

H ₃ C CH ₃

with lithium tri-tert-butoxy-hydrido-aluminate, optionally using a diluent, at temperatures between -100 and + 100 ⁰ C reacted; and

(7) the process for the preparation of formyl-cyclopropane derivatives of the formula XIII (above),

in which

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Y is acetyl, cyano or oarbamoyl,

consists in that % -hydroxy-cyclopropylmethyl-phosphonic acid ester of the formula XV

0 OH

• II

(R ⁴ O) ₀ P-CH

^{2 v} '(XV),

in which

R is alkyl or phenyl or both radicals R together represent alkanediyl (alkylene), and

Y is acetyl, cyano or carbamoyl,

with aqueous alkali solutions, optionally in the presence of a water-immiscible organic solvent such. B, methylene chloride, reacted at temperatures between 0 and 100 ⁰ C.

Surprisingly, alkenes of the formula (I) can be obtained in good yields and in high purity by the novel process 1 (above), which is simple and inexpensive to carry out and for which starting compounds which are easy to prepare can be used.

Advantages of the new method are, for example, the possibility of implementation at room temperature or

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at least at temperatures which are not very different, use cheap bases such as alkali hydroxides or alcoholates and use water-containing solvents.

A particular advantage of the process according to the invention is that the preparation of aldehydes, which are generally used as reaction components in the preparation of alkenes by reacting carbonyl compounds with phosphorus-containing olefination agents, can be avoided.

If the starting materials used are, for example, dimethyl (3-MQthoxy-carbonyl-2,2-dimethyl-cycloprop-il-yl) -oC-hydroxymethanephosphonic acid dimethyl ester and oC-chlorobenzyl-phosphonic acid diethyl ester, the reaction according to the invention of these compounds can be effected by the following Outlined formula scheme:

0 OH

• I ·

CH-P (OC ₂ H ₅ ) ₂ + (CH ₃ O) ₂ P-CH Cl

O-OCH.

CO-OCH.

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The oc-hydroxy-phosphonic acid esters to be used as starting materials are defined by formula (II)

R is C "-C" _{4 "} alkyl or phenyl, or both radicals R together are 2,2-dimethyl-propane-1,3-diyl and

R is optionally halogen-substituted C.-C.-alkyl, optionally substituted by halogen, cyano, carbamoyl, C ^ -C. alkoxycarbonyl and / or phenoxybenzyl-oxy-carbonyl (which may be substituted by fluorine, cyano and / or Ethinyl is substituted) substituted Cz-Cg-cycloalkyl, for optionally chlorine-substituted benzyl or phenylethyl, or for optionally substituted by halogen, C ^ -C ^ alkyl and / or C ₁ -C ₄ -alkoxy substituted phenyl »

In a particularly preferred group of (new) starting compounds of formula (II) is in this formula

R ¹ for the rest

H ₃ C CH ₃

2 wherein Z is cyano, carbamoyl, acetyl or carbonyl and

R ^{4 is} methyl or ethyl.

Examples include:

Ε-hydroxy-3-methylbenzyl, ω-hydroxy-4-methylbenzyl,

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e ^ -hydroxy-3,4-dimethyl-benzyl,

o £-hydroxy-4-fluoro-benzyl,

06 »hydroxy-3-chloro-benzyl-,

iC-hydroxy-4-chloro-benzyl,

si-hydroxy-3,4-dichloro-benzyl,

c6 "hydroxy-3-bromo-benzyl,

<£ ~ Hydroxy-4-bromo-benzyl _#

G ~ ~ hydroxy ~ 4-methoxybenzyl and

oO-hydroxy-3,4-dimethoxy-benzyl

phosphonic acid dimethyl ester and diethyl ester; C 1-8 -hydroxy- (3-methoxycarbonyl-2,2-dimethyl-cyclo-prop-1-yl) -methanephosphonic acid dimethyl ether and diethyl ester, C 1 -hydroxy- (3-ethoxycarbonyl) 2-dimethyl-cycloprop-1-yl) -methanephosphonic acid-3-diethyl ether and diethyl ester, «C-hydroxy-c <, - (3-acetyl-2, -dimethyl-cycloprop-1-yl) -methanephosphonic acid dimethyl ester and diethyl ester, and hydroxy Oi ~ (3-cyano-2,2-dimethyl-cycloprop-l-yl) -methanphosphonsäure- dimethyl ester and diethyl ester ·

Some of the starting compounds of the formula (II) have not yet been described in the literature, but can be prepared by processes known in principle. Thus, the novel c-hydroxy-methane-phosphonic acid esters of the formula ( IIa ) are obtained by dissolving the corresponding Oxoverbindungen of formula IV (above) with a reducing agent of formula V (above), such as "B" sodium tetrahydroborate (sodium borohydride), optionally with the use of a diluent, such as. 8 "water or aqueous methanol, at temperatures between -2Ό and * 50 ⁰ C, preferably between -10 and +30 ⁰ C, and reacted by addition of a buffering agent, such as, for example, sodium hydrogen phosphate, the pH between 5 and 8 holds (compare

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Chem. Ber. 103 (1970), 2984-2986). For working up and isolation of the products are extracted with a water-immiscible solvent such. B, methylene chloride, the organic phase is dried, filtered and the solvent is distilled off under reduced pressure.

The substituted Ot-oxo-methanephosphonsäureester of formula (IV) are not described in the literature. These compounds are obtained by reacting carboxylic acid chlorides of the formula VI (above) with P ^ osphorigsäureestern of formula VII (above) (at temperatures between -20 and + 150 ⁰ C, preferably between Q and 120 ⁰ C compare 3 "Am. Chem. Soc, 86 (1964), 3862-3866 and Methods of Organic Chemistry (Houben-Weyl-Muller), 4 _e Aufl. Volume 12/1 , p. 453, Georg Thieme Verlag, Stuttgart 1963).

For isolation and purification of the products, distilled, if appropriate under reduced pressure.

An alternative route to the preparation of a part of the compounds of the formula (II) - see formula (VIII) - is described below.

Are not yet known cyclopropane carboxylic acid chlorides of the formula (VI) is obtained according to the following reaction scheme from known cyclopropane carbonsäureestern (see Figure 3, Am Chem Soc _e 89 (1957), 3912-3914;.. 3, Org Chem 32 (1967),.. 1978, 1847-1850; Bull. Soc. Chim., 87 (1978), 721-732) according to methods known per se, by first by hydrolysis, for example by reaction with aqueous-alcoholic

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Potassium hydroxide at temperatures between 20 and 100 ⁰ C and then acidifying the corresponding cyclopropanecarboxylic produces and these with halogenating agents, such as »B» thionyl chloride, at temperatures between 20 and 80 ⁰ C implemented.

Z ² -R-7-C0-Oalkyl Z ² L CO-OH Z ² __COCl

^H 2 ° _v H ^ C CH ₃ ^S0Cl 2 _y ^H 3 ^{C CH} 3

(VII) (VI)

The phosphorus-containing olefinating agents to be further used as starting materials are defined by formula (III)

R is hydrogen, chlorine or bromine,

R is phenyl, which is optionally substituted by halogen,

, C 1 -C ₆ -halogenoalkyl, C ₃ -C ₄ -alkoxy, haloalkoxy, C ₁ -C ₆ -phenyl-alkylenedioxy, C 1 -C -lo- and / or C 1 -C 6 -phenyl-haloalkylthio, and

preferably represents the rest

wherein R and R are the same or different and are individually C ₁ -C ₄ -alkoxy, phenoxy or together represent 2,2-dimethylpropan-1,3-dioxy.

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Examples include:

Dimethylbenzylphosphonic acid dimethyl ester and diethyl ester, dimethyldodecylester and diethyl ester of o-chlorobenzylphosphonic acid, dimethyl o-bromobenzylphosphonate and diethyl ester, 4-fluoro, 3-chloro, 4-chloro, 3,4- Dichloro, 3-bromo, 4-bromo, 3-methyl, 4-methyl, 3,4-dimethyl, 4-methoxy and 3,4-dimethoxybenzene] .p ^no sph ^on acid dimethyl ester and diethyl ester;

4-fluoro-, 4-chloro- _# 3-chloro-, 3,4-dichloro-, 3-bromo-, 4-bromo-, 4-Mothyl-, 3-methyl-, 3,4-dimethyl-, 4 Methoxy- and 3,4-dimethoxy-c-chloro-benzylphosphonic acid dimethyl ester and diethyl ester;

4-fluoro, 3-chloro, 4-chloro, 3,4-dichloro, 3-bromo, 4-bromo, 3-methyl, 4-methyl, 3,4-dimethyl, 4 -Methoxy- and 3,4-dimethoxy-Q-bromo-benzylphosphonic acid dimethyl ester and diethyl ester «

Some of the phosphorus-containing olefination agents of the formula (III) have not yet been described in the literature, but they can be prepared by processes which are known in principle.

Benzylphosphonsäureester unsubstituted in formula (ΙΙΪ) is obtained by reaction of benzyl halides with esters of phosphorous acid (see methods of organic chemistry (Houben-V / ayl-Muller), 4th edition, Volume 12/1, S 433-453, Georg-Thieme Verlag, Stuttgart 1963).

Under formula (III) falling qC-chloro- and * C-bromo-benzylphosphonsäureester obtained by reaction of ^ -hydroxy

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benzylphosphonic esters of the formula VIII

Il

₂ (VIII),

OH

in which

R has the meaning given above and

R is optionally substituted phenyl,

with a chlorinating agent, such as. As thionyl chloride, or »with a brominating agent, such as. B, dibromotriphenylphosphorane, optionally in the presence of an acid acceptor, such as. Pyridine, and optionally using a diluent, such as, B, methylene chloride or ethylene chloride, at temperatures between 10 and 100 ⁰ C or between -50 and +50 ⁰ C (see 0, Am. Chem. Soc. 87 ( 1965), 2777-2778; Chimia 28 (1974), 656-657) _β

The ν-hydroxybenzylphosphonsäureester of formula (VIII) are not yet known in part. They are obtained by the above-mentioned route for the preparation of compounds of the formula (II) or by reacting benzaldehydes of the formula IX

R ³ -CHO

•in which

R has the meaning just given,

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with phosphorous acid ester of the formula X.

HP (OR ⁴ J ₂ (X).

in which

R has the meaning given above,

optionally in the presence of a catalyst, such as. B. triethylamine, at temperatures between 0 and 150 ⁰ C, preferably between 20 and 100 ⁰ C (see methods of organic chemistry (Houben-Weyl-Muller), 4th Edition Volume 12/1, p 475 - 483, Georg -thieme-Verlag, Stuttgart 1963).

The aldehydes of the formula IX and the phosphorous acid esters of the formula (X) are widely known.

The process according to the invention for the preparation of alkenes of the formula (I) is preferably carried out using suitable solvents or diluents. In addition to water, virtually all inert organic sol-dients are suitable as such. These include in particular aliphatic and aromatic, optionally chlorinated hydrocarbons, such as pentane, hexane, heptane, cyclohexane, benzene, toluene, xylene, methylene chloride, ethylene chloride, chloroform, carbon tetrachloride, chlorobenzene and dichlorobenzenes, ethers, such as diethyl and dibutyl ether, tetrahydrofuran and dioxane, Alcohols such as methanol, ethanol, n- and iso-propanol, η-, iso-, sec- and tert-butanol and aprotic polar solvents such as dimethylformamide and dimethyl sulfoxide.

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When working in the two-phase medium, organic solvents such as pentane, hexane, heptane, benzene or toluene, which are immiscible with water, are used in addition to about 50% sodium hydroxide solution or potassium hydroxide solution.

When catalysts are used in carrying out the process according to the invention in multiphase reaction media - compounds which are usually used in reactions in multiphase systems as an aid for the phase transfer of reactants. In particular, as such phase transfer catalysts tetraalkyl and trialkyl-benzyl am-ammonium salts, such as. B, tetrabutylammonium bromide and trimethylbenzylammonium chloride.

As bases, in carrying out the process according to the invention, the bases customary in carbonyl olefinations can be used. Mentioned are alkali metal hydroxides, such as. For example, potassium and sodium hydroxide, alkali metal such as. For example, potassium and sodium methylate, ethylate, n- and iso-propylate, n-, iso-, sec- and tert-butoxide, alkali metal hydrides such as 2 »B, sodium hydride and alkyl lithium compounds, such as. B. Butyllithium "Preferably, the said alkali metal hydroxides and / or alcoholates are used.

The process is generally carried out at atmospheric pressure. The reaction temperatures are between -70 and +150 ⁰ C, preferably between -20 and * 50 ⁰ C.

To carry out the process according to the invention, the starting compounds of the formulas (II) and (III) are usually employed in equimolar amounts. When working in single-phase systems, two base equivalents are generally used.

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lente, when using 50% alkali metal hydroxide as secondary phases generally 5-15 times the stoichiometrically required amount.

The base and, if appropriate, the catalyst are initially introduced in a suitable reaction medium and are added simultaneously or in succession, if appropriate in one of the solvents indicated, to the starting materials of the formulas (II) and (III). To complete the reaction, the mixture is stirred for several hours.

The workup can be carried out by customary methods. For isolating distillable products can be distilled off, for example, the solvent, the residue in a water-immiscible solvent such. B. Ligroin, wash the solution with water, dry, filter and distill. For the isolation of crystalline products, the reaction mixture may optionally be poured into (ice) water and aspirated from the crystalline product or, if the solvent is immiscible with water, washed with water , dried, filtered and evaporated. According to the latter work-up method, oily, difficult-to-distillate products can be obtained relatively pure.

The products are characterized by their melting or boiling points.

Compounds of the formula (I) to be prepared by the process according to the invention can be used as intermediates for the preparation of insecticides (cf.

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DE-OS 2 738 150).

As already mentioned, the novel alkenes of the formula XI can also be prepared by the novel process 1 (above). These new compounds can also be prepared by the method 5 (above) »

Is used in process 5 (above) as starting materials, for example, ^ i-chloro-benzyl-phosphonsau re-dimethyl ester and 2-formyl-3, S-dimethyl-cyclopropane-l-carbon acid amide and sodium hydroxide as the base, the Reaction of these compounds are outlined by the following equation:

OHC-V T-CO-NH

Cl - H ₃ C CH ₃

+ NaOH

- H ₀ O

-NaO-P (OCH-) _o 0

Preferably, the novel styryl-cyclopropane derivatives of the formula XI are obtained,

in which

R represents fluorine, chlorine, B _r om, C ^ C-alkyl, trifluoromethyl,

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C ₁ -C 6 -fluoroalkoxy, C ₁ -C 4 -chlorofluoroalkoxy, C ₁ -C 4 -alkylthio, C ₁ -C 6 -fluoroalkylthio, C ₁ -C ₂ -chlorohydroboroalkylthio, C ₁ -C 4 -alkylenedioxy, C ₁ -C 6 -fluoroalkylenedioxy, cyano or nitro,

η is zero to 5,

R is hydrogen, chlorine, bromine

C 1 -C 4 alkyl or C 1 -C 6 fluoroalkyl, and

Y stands for acetyl, cyano or carbamoyl «

The process described under 5 (above) is preferably carried out using diluents.

As such, in particular polar organic solvents are suitable, These include carboxylic acid amides such as »B, dimethylformamide and N-methylpyrrolidone, sulfoxides and sulfones, such as. For example, dimethyl sulfoxide and tetramethylene sulfone, phosphoric acid amides, such as. For example, hexamethylphosphoric triamide, ethers, such as. As glycol dimethyl ether, diglycol dimethyl ether, tetrahydrofuran and dioxane, nitriles, such as. B, acetonitrile and propionitrile, as well as alcohols such as z, B, methanol, ethanol, n- and iso-propanol, n-iso-, sec- and tert-butanol. ,

In process (5), the bases common in carbonyl olefinations can be used. Mentioned are alkali metal hydroxides, such as. B, sodium and potassium hydroxide, alkali metal such as z, B, sodium and Kaiiummethylat, ethylate, n- and iso-propylate, n-, -iso-, -sek «- and tert-butoxide, alkali -

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2 2 0 8 0 A - ²⁴ ~

hydride, like ζ. For example, sodium hydride, and alkyl lithium compounds, such as. B. Butyllithium. Alcoholates are particularly preferred as bases.

The reaction temperatures are generally between -70 and +150 C, preferably between -20 and +50 C. The process is generally carried out at atmospheric pressure.

The starting compounds of the formulas (XII) and (XIII) are generally employed in equimolar amounts. In a preferred embodiment of process (5) the base is added dropwise charged to a specified dor above diluent and washed successively with a Benzylphosphonsäureestar of formula (XII) and a formylcyclopropane derivative of the formula (XIII). The reaction mixture is stirred for several hours and worked up by one of the usual methods; it is diluted with water and extracted with a water-immiscible solvent such. As methylene chloride or toluene, the extract is dried, filtered and the solvent is distilled off. The residual crude product can be purified by vacuum distillation. For characterization serve the boiling point and / or the refractive index,

The benzyl phosphonic acid esters to be used as starting materials in process (5) are defined by formula (XII). Preferably stand in it

α ίο

R and R are those radicals which have been mentioned as preferred in the definition of the radicals R and R in formula (XI),

η stands for zero to 5 and

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R ⁴ is preferably C 1 -C 4 -alkyl, phenyl

or both radicals R together represent 2,2-dimethyl-propane-1,3-diyl

Examples include:

Dimethyl benzylphosphonate and diethyl ester, dimethyl t-chlorobenzylphosphonate and diethyl ester, diethyl dimethyl ester and diethylester, 4-fluoro, 3-chloro, 4-chloro, 3,4-dichloro , 3-bromo, 4-bromo, 3-methyl, 4-methyl, 3,4-dimethyl, 4-methoxy and 3,4-dimethoxybenzylphosphonic acid dimethyl ester and diethyl ester;

4-fluoro-, 4-chloro-, 3-ehlor-, 3,4-dichloro-, 3-bromo-, 4 ~ bromo, _3-methyl-# 4-methyl-, 3,4-dimethyl-, 4 -Methoxy- and 3,4-dimethoxy- »C-chloro-benzylphosphonic acid dimethyl ester and diethyl ester;

4-fluoro, 3-chloro-j 4-chloro, 3,4-dichloro, 3-bromo, 4-bromo, 3-methyl, 4-methyl, 3,4-dimethyl, 4 -Methoxy- and 3,4-dimethoxy- - ^ -Brom-benzylphosphonsäure dimethyl ester and. diethyl.

The benzyl phosphonic acid esters of the formula (XII) are not yet described in the literature, but can be prepared by processes known in principle.

Benzylphosphonester according to formula (XII), in which R ^{10 is} hydrogen or optionally substituted alkyl, is obtained by reacting corresponding benzyl halides with esters of phosphorous acid (see Methods of

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Organic Chemistry (Houben-Weyl-Muller), 4th ed., Volume 12/1, p 433-435, Georg Thieme Verlag, Stuttgart 1963).

Benzyl phosphonic acid esters according to formula (XII), in which

10 R is chlorine or bromine, is obtained by reaction of <c ~ hydroxy-benzyl-phosphonic acid esters of the formula XVI

in which

ö Λ

R, η and R have the meanings given above,

with a chlorinating agent, such as. For example, thionyl chloride, or, with a brominating agent such as dibromo-triphenylphosphorane, optionally in the presence of an acid acceptor such. B * pyridine, and optionally using a diluent, such as. For example, methylene or ethylene chloride, at temperatures between -50 and +50 ⁰ C (see, 0 Am Chem, Soc. 87 (1965), 2777-2778, Chima 28 (1974), 656-657).

-Hydroxy-benzyl-phosphonic acid ester of the formula (XVI) is obtained by reacting benzaldehydes of the formula XVII

CHO

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in which

R and η dio have the meanings given above,

with phosphorous acid esters of the formula XVIII

^H " ^P - (XVIII),

~ 0R ⁴

in which

R has the meaning given above,

optionally in the presence of a catalyst, such as. B. triethylamine, at temperatures between 10 and 100 ⁰ C (see, Methods of Organic Chemistry (Houben-VYeyl-Müller), 4 · Aufl., Volume 12/1, S, 475-483; Georg-Thieme-Verlag, Stuttgart 1963).

Aldehydes of the formula (XVII) and phosphoric esters of the formula (XVIII) are known.

As examples of the formyl cyclopropane derivatives of the formula (XIII) to be used as further starting compounds in process (5):

2-acetyl-3, S-dimethyl-cyclopropane-1-carbaldehyde, 2-cyano-3, S-dimethyl-cyclopropane-1-carbaldehyde and 2-carbamoyl-3,3-dimethyl-cyclopropane-1-carbaldehyde.

This gives 2-acetyl-3,3-dimethyl-cyclopropane-1-carbaldehyde

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0 04

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for example, according to the method specified under (6) by reacting 2-acetyl-3, S-dimethyl-cyclopropane-l-carboxylic acid chloride (XIV) with lithium tri-tert-butoxy-hydrido-aluminate, which is optionally in situ Lithium tetrahydridoaluminat (lithium alanate) and tert-butanol has been prepared, optionally in the presence of a diluent, such as. B. tetrahydrofuran, at temperatures between -100 and +100 C, preferably between -80 and +50 C., The workup can be carried out by conventional methods, for example by pouring the reaction mixture into a mixture of hydrochloric acid and ice water, with a not with water miscible solvents, such as. B, diethyl ether, the extracts are dried, filtered and concentrated. For purification of the residual crude product is optionally distilled.

In general, formyl-cyclopropane derivatives of the formula (XIII) are obtained by the process described under (7) by reacting O- ^4- hydroxycyclopropylmethyl-phosphonic acid esters of the formula XV (supra) with aqueous alkali solutions, such as. B. with aqueous sodium hydroxide solution, optionally "in the presence of a water-immiscible solvent, such as" methylene chloride, at temperatures between 0 and 100 ⁰ C, preferably between 10 and 50 ° C (see »Chem. Ber · 103 (1979 ), 2984-2986).

For workup, the organic phase is separated, dried, filtered, concentrated and the crude product remaining as residue optionally purified by distillation.

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The hydroxyphosphonic acid esters of the formula (XV) are obtained, for example, according to the following scheme starting from known cyclopropane-carboxylic acid esters of the formula (XXIX) by saponifying them to give the corresponding acids of the formula (XXVIII), from which the acid chlorides of the formula (XXVIII ), prepared by reaction with alkyl phosphites, the Cyolopropanoyl-phosphonic acid ester of the formula (XXVI) and this reduced with Natriumtetrahydridoborat (R for C ^ -C ^ alkyl):

stands

H ₃ C CH ₃

(XXIX)

-CO-OR

CO-OH

SOCI,

(XXVIII)

(XXVII)

¹⁰ OP (0R ⁴ ) ₂ R ¹⁰ Cl

(XXVI)

By hydrolysis of known cyclopropanecarboxylic acid esters of the formula (XXIX) (compare D, Org · Chem, 32, (1967), 3351-3355; Bull, Soc. Chim, BeIg. 87 (1978), 721-732; Tetrahedron Lett. 1847 - 1850), for example by

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22080 * --so-

Reaction with aqueous-alcoholic potassium hydroxide solution at temperatures between 20 and 100 ⁰ C and subsequent acidification gives the carboxylic acids of the formula (XXVIII). These can be converted by reaction with halogenating agents, such as. As thionyl chloride, be converted at temperatures between 20 and 100 ⁰ C in the acid chlorides of the formula (XXVII).

Reaction of the acid chlorides (XXVII) with alkyl phosphites at temperatures between -20 and +150 ° C., preferably between 0 and 100 ° C., affords the cyclopropanoylphosphonic acid esters of the formula (XXVI) (cf. 0 · Am. Chem. Soc. 86 (1964) , 3862 - 3866; Methods of Organic Chemistry (Houben-Weyl-Muller), 4th Edition, Volume 12/1, p. 453, Gsorg-Thieme-Verlag, Stuttgart 1963). For isolation and purification of the products, distilled, if appropriate under reduced pressure.

The ^ -hydroxy-phosphonic acid ester of the formula (XV) is obtained by reduction of the oxo compounds of the formula (XXVI) with Natriumtetrahydridoborat, optionally using a diluent, such. As water or aqueous methanol and optionally in the presence of a water-immiscible solvent such. As methylene chloride, at temperatures between -20 and +50 C (see, Chem. Ber., 103, (1970), 2984-2986). For working up, extract with a water-immiscible solvent such. As methylene chloride, the extracts are dried, filtered and the solvent is distilled off under reduced pressure.

Since the formyl-cyclopropane derivatives used as starting compounds of the formula (XIII) as well as the styrylcyclo

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propane derivatives of the formula (XI) each have asymmetric carbon atoms, the compounds of the formulas (XI) and (XIII) can occur in a corresponding number of stereoisomeric forms. The processes according to the invention relate to the preparation of compounds of the formula (XI) which are obtained either in the form of the individual stereoisomers or as mixtures of stereoisomers.

From the styryl-cyclopropane derivatives of the formula (XI) in which Y is cyano or carbamoyl, the corresponding carboxylic acid esters of the formula (XI) in which Y is alkoxycarbonyl are obtained in a known manner, for example by reaction with alcohols, such as, for example, methanol or ethanol, in the presence of a mineral acid, such as. B, sulfuric acid, at temperatures between 80 and 200 ⁰ C (see DE-OS 2,831,555).

The compounds of the formula (XI) in which Y is acetyl can be prepared in a known manner, for example by reaction with aqueous sodium hypobromite solution, which has optionally been generated in situ from bromine and sodium hydroxide, optionally in the presence of an organic solvent, such. As dioxane, at temperatures between -20 and +50 ⁰ C, in the corresponding carboxylic acids of the formula (XI), in which then Y is carboxy, be converted (see DE-OS 2,621,833).

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2 2 O 8 O ^ - 32 -

This is an example of a game

1. Examples of Process (I) ₁

example 1

Cl-A

22.8 g (0.1 mol) of diethyl benzylphosphonate are added to a cooled to 0 to 5 ⁰ C solution of 22.4 g (0.2 mol) Kaliunwtert.-butyiat in 100 ml of tetrahydrofuran (dried over sodium) within Added dropwise for 15 minutes. The mixture is stirred for one hour; Then, while cooling to 0 to 5 ⁰ C, a solution of 28 g (0.1 mol) c ^ -hydroxy-4-chloro-benzyl-phosphonic acid diethyl ester in 50 ml of tetrahydrofuran and the mixture is stirred for 15 h * at Room temperature (about 20 ⁰ C), Then poured into 1 1 of ice water, filtered off with suction and dried. This gives 18 g (84 % of theory) of 1- (4-chlorophenyl) -2-phenyl-ethylene in the form of colorless crystals of melting point 130 ^° C.

Example 2

Cl - //

28 g (0.1 mol) of diethyl ** -hydroxy-4-chloro- benzylphosphonate and 30 g (0.1 mol) of diethyl oC-chloro-4-chlorobenzylphosphonate are dissolved in 50.degree toluene dissolved, and this solution is within 30 min, to an intense

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2 2 0 8 0

- 33 -

stirred mixture of 100 ml of toluene, 100 ml of 40% sodium hydroxide and 2 g of tetrabutyl-ammonium bromide at an internal temperature of 30 to 45 ⁰ C added dropwise »the mixture is stirred for 15 hours at room temperature (about 20 ⁰ C), separates the organic phase, washed twice with water, dried, filtered and the solvent is distilled off in vacuo. The residue is obtained crystalline from ligroin: 14 g (49 % of theory) of 1-chloro-1- (4-chlorophenyl) -2- (4-chlorophenyl) -ethylene; Melting point 89 ^° C.

Example 3

CO-OCH,

Cl- / V- C = CH

^H 3 ^{C CH} 3

30 g (0.1 mol) of oi-chloro-4-chloro-benzyl-phosphonsaurediethylester are added dropwise to a cooled to 0 to 10 ⁰ C solution of 8 # 8 g (0.2 mol) of sodium in 200 ml of tetrahydrofuran. The mixture is stirred at 0 ^° C. for 1 h. Then, at 0 to 10 ⁰ C, a solution of tC -hydroxy- © C- (3-methoxycarbonyl-2,2-dimethyl-cyclopropl-yl) -methanphosphonsäure-dimethyl ester in 50 ml of tetrahydrofuran, stir The reaction mixture is distilled for 15 hours at room temperature (about 20 ^° C.), the solvent is distilled off, the residue is taken up in ligroin, the solution is washed with ice-water, dried, filtered and distilled to give 18 g (60 % of theory). Methyl 3- (2-chloro-2- (4-chloro-phenyl) -vinyl) -2,2-dimethyl-cyclopropane-1-carboxylate of boiling point 100 ° C / 0.01 mbar.

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2 2 Q 8 0 ^ -34-

Example 4

Cl - // \ y_C = CH- ^ ^ CO-CH-.

H, C CH,

30 g (O ₁ I mole) ° & chloro-4-chloro-benzyl-phosphonic acid diethyl ester dissolved in 50 ml of tetrahydrofuran are added to a to 0 to 10 ⁰ C cooled solution of 8.8 g (0.2 mol) of sodium methylate in 200 ml of tetrahydrofuran added dropwise. The mixture is stirred for 1 h; Then, at 0 to 5 C, a solution of 25 g (0.1 mol) of oxyhydroxyC (3 * * acetyl-2,2-dimethyl-cyclo-prop-1-yl) -methanephosphonic acid dimethyl ester in 100% is added ml of tetrahydrofuran, the reaction mixture is stirred for 15 hrs. At 15 to 25 ° C, the solvent is distilled off, the residue is taken up in toluene, washed three times with water, dried, filtered and distilled.

This gives 18 g (64 % of theory) of (3- (2-chloro-2- (4-chlorophenyl) -vinyl) -2,2-dimethyl-cycloprop-l-yl) -methyl-ketone of boiling point 90 ° C. / 0.01 mbar. Analog obtained

Beis piel 5

Cl-A ^ S-C = CH-T-T-CN

_cl f \ boiling point: 94 ° C / 0 _t 01

H ₃ C CH ₃ ^mbar

As starting materials to be used "t-hydroxy phosphon-

Acid esters of the formula (II) can, for example, as

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22 0 8 O ^ -35-

2 ' _i Examples of methods (2)

(CH ₃ O) ₂ P-CH-VT-CO-CH.

OH

H ₃ CCH ₃

A solution of 50 g (0.2 mol) of oc-oxo-t- (3-acetyl-2,2-dimethyl-cycloprop-l-ylj-methanphosphonsäuredimethylester in 50 ml of methylene chloride is cooled to 0 to 5 C mixture from 2.5 g of sodium borohydride, 100 ml of water and 100 ml of methylene chloride are added dropwise, and the reaction mixture is stirred for 2 hours at 0 to 5 ⁰ C. Then, the aqueous phase is separated from the organic phase and extracted twice more with methylene chloride The organic phases are dried, filtered and evaporated. After recrystallization of the residual crude product from 200 ml of ethyl acetate / ligroin (2: 8), 31 g (62 % of theory) of α-hydroxy-ε * - (3-acetyl-2, Dimethyl 2-dimethyl-cycloprop-1-yl-yl-phosphorane acid of melting point 104 ° C

Analogously to the example above, 0 is obtained

Il

7. (CH ₃ O) ₂ P-CH ₂ -TCO-OCH ₃

OH A ^ melting point: 69 C

H ₃ C CH ₃

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β "

3 « Examples of procedures (3)

10, (CH ₃ O) ₂ P-

H ₃ C CH ₃

6 »5 g (0.05 MoI) of trimethyl phosphite are added to a warmed to 35 to 40 ⁰ C solution of 9 g (0.05 mol) of 3-acetyl-2,2-dimethyl-cyclopropane-l-carboxylic acid chloride in 20 ml of methylene chloride added dropwise and the reaction mixture is 15 hrs. At 15 to 25 ⁰ C stirred. After distilling off the solvent in vacuo, 9 g (72 % of theory) of dimethyl c-oxo- pt- (3-acetyl-2 ^ -dimethyl-cycloprop-l-ylj-methanephosphonsäure.

Analogously to the above example is obtained

H ₃ C

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12. (C ₂ H ₅ O) ₂ P-CO

CN

H ₃ C CH ₃

4. Examples of methods (4)

Cl-CO 14.

H ₃ C CH ₃

A mixture of 172 g (1 mol) of 3-methoxycarbonyl-2,2-dimethylcyclopropanl-carboxylic acid, 130 g of thionyl chloride, 2 ml of dimethylformamide and 200 ml of methylene chloride is refluxed for 4 hrs under reflux. After distillation in vacuo, 135 g (71 % of theory) of 3-methoxycarbonyl-2,2-dimethyl-cyclopropane-l-carboxylic acid chloride of boiling point 86 ° C / 15 mbar.

Analog obtained

15 »Cl-CO-rr-CO-CH

H ₃ C CH ₃

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16, Cl-CO

Boiling point: 95 to 193 ⁰ C / CH ₃ CH ₃ 10 mbar

5, Examples of Procedures (5) Example 17

H ₃ C CH ₃

To a solution of 8.9 g (0.042 mol) of sodium methylate in methanol and 80 ml of tetrahydrofuran is added dropwise at 0 to 10 C, a solution of 11.8 g (0.04 mol) of chloro (4-chlorobenzyl) - " Phosphonic acid diethylester in 20 ml of tetrahydrofuran and stirred for 1 hr. At 0 to 10 ⁰ C. Then, at 10 ⁰ C 5 g (0.04 mol) of 3, S-dimethyl - ^ - cyano-cyclopropancarb-aldehyde, stirred The reaction mixture is stirred for 1 hour without further cooling and then poured into 300 ml of water _e The aqueous solution is extracted three times with 100 ml of methylene chloride, the combined organic phases are dried over sodium sulfate and evaporated in vacuo. 89 % of theory) 3,3-dimethyl-2- (2-chloro-2- (4-chlorophenyl) -vinylj-cyclopropanecarbonitrile as a yellow oil with the

22

Refractive index n _ß: 1.5611,

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Example 18

Cl- ^ 7 - C = CH ^ r-7-CO-CH \ / \ /

To a solution of 17.8 g (O ₁ 84 mol) of sodium in methanol and 160 ml of tetrahydrofuran is added dropwise at 0 to 10 ⁰ C, a solution of 23.7 g (0.08 mol) of oo-chloro (4-chlorobenzyl ) ~ Phosphonsäurediethylester in 40 ml of tetrahydrofuran and stirred for 1 h _e at 0 to 10 ⁰ C after. Then 11.2 g (0.08 mol) of trans 3,3-dimethyl-2-acetyl-cyclopropanecarbaldehyde are added at 10 ^° C., the reaction mixture is stirred for 2 hours without further cooling and then poured into 800 ml of water » The aqueous solution is extracted three times with 200 ml of methylene chloride, the combined organic phases are dried over sodium sulfate and evaporated in vacuo. This gives 19.7 g (87 % of theory) of trans-3,3-dimethyl-2- (2-chloro-2- (4-chlorophenyl) -vinyl) -1-acetyl-cyclopropane as a yellow oil with the Boiling point 120 to 128 ° C / O, 1 mm «

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Example 19

CO-CH ₃

To a solution of 4.9 g (0.09 mole) of sodium methylate in a mixture of 20 ml of methanol and 200 ml of tetrahydrofuran at 0 ⁰ C, 24.1 g (0.09 mol) oC, chloro (4-chloro -benzyl) -phosphonic acid added dropwise. Then 12.6 g (0.09 mol) of 3 _# 3-dimethyl-> 2-acetyl-cyclopropanecarbaldehyde in 50 ml of tetrahydrofuran are added at 20 ^° C., and the reaction mixture is stirred for 5 hours.

After working up as in Example 1, 16 g (63 % of theory) of 3,3-dimethyl-2 ~ (2-chloro-2 ~ (4-chloro-phenyl) -vinyl) -1-acetyl-cyclopropane in the form of a Oil with the

20

Refractive index n _Q : 1.5698.

22 0804

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Example 20

C = CH-

COOH

H ₃ C CH ₃

To a solution of 11.5 g of sodium hydroxide in 60 ml of water is added dropwise at 5 to 10 ⁰ C, 13.8 g of bromine and then at 0 to 5 ⁰ C, a solution of 8.1 g (0.029 mol) of trans-3.3 -Dimethyl 2- (2-chloro-2- (4-chlorophenyl) -vinyl) -1-acetylcyclopropane in 30 ml of dioxane. The mixture is stirred for 3 hours without cooling, poured into 250 ml of water and extracted twice with 50 ml of ether. The aqueous phase is freed from adhering ether in vacuo and then brought to pH 2 by addition of aqueous hydrochloric acid. After crystallization, the product is filtered off with suction and washed with water. This gives 6.2 g (77 % of theory) of trans-3,3-dimethyl-2- (2-chloro-2- (4-chlorophenyl) -vinyl) -cyclopropanecarboxylic acid in the form of pale yellow crystals having the melting point of 103 to 106 ⁰ C.

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2 2 O 8 O 4 - ⁴² -

6. Examples of Method (6) Example 21

CHO

To a mixture of 6.3 g (0.165 mole) of lithium alanate and .100 ml of tetrahydrofuran is added dropwise at 20 to 30 ⁰ C within 1 hr. 36.6 g (0.495 mol) of tert-butanol. The mixture is stirred for 2 hrs. At room temperature and then it drips it at -50 to -60 C to a solution of 26.1 g (0.15 mol) of trans-3,3-dimethyl-2 ~ acetyl-cyclopropane-carboxylic acid chloride in 75 ml of tetrahydrofuran. After the addition, stirring is continued for 1 hour without cooling, poured onto a mixture of 30 ml of concentrated sodium chloride and 300 g of ice and extracted by shaking twice with 400 ml of ether each time. The organic phases are first washed with 50 ml of saturated sodium bicarbonate solution and then with 100 ml of water, dried over sodium sulphate and evaporated in vacuo. By distillation of the residue in vacuo, 12.7 g (62 % of theory) of trans-3, S-dimethyl ^ -acetyl-cyclopropane-carb aldehyde in the form of a colorless oil having a boiling point 80 to 86 ⁰ C / 10 mbar.

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2 2 O 8 O ^

7. Examples of Methods (7) Example 22

A mixture of 50 g of dimethyl hydroxyethyl (3-acetyl-2,2-dimethylcycloprop-1-ylmethanephosphonate, 8 g of sodium hydroxide, 60 ml of water and 200 ml of methylene chloride is added at room temperature for 90 minutes The organic phase is separated off, dried and distilled twice, giving 20 g (71 % of theory) of 3,3-dimethyl-2-acetylcyclopropane-carbaldehyde in the form of a colorless oil of boiling point 78 ° C./8 mbar.

Analogously to Example 22 is obtained

r · CHO

X /

Boiling point: 77 ° C / 3 mbar

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The cyclopropanecarboxylic acids of the formula (VII) to be used as starting materials in process (4) can be prepared, for example, as follows:

Example 24

COOH

A suspension of 33.4 g (0.2 mol) of 2-cyano-3,3-dimethylcyclopropan-carboxylic acid ethyl ester and 16.8 g (0.3 mol) of potassium hydroxide in 200 ml of water and'100 ml of ethanol is 15 hrs. At 20 to 25 ⁰ C stirred. Then the alcohol is drawn off, the aqueous solution is acidified with dil. Hydrochloric acid and extracted twice with 100 ml of ether (or methylene chloride). The combined organic extracts are dried over Na ₂ SO ₄ , concentrated and distilled. This gives 21.2 g (76 % of theory) of 2-cyano-3,3-dimethyl-cyclopropanecarboxylic acid in the form of an oil of boiling point 110 to 120 ⁰ C, which crystallized on cooling (mp. 101 to 106 ° C).

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22 Q8 04

- 45 -

The benzyl phosphonic acid esters of the formula (XII) to be used as starting materials in process (5) can be prepared, for example, as follows:

Example 25

^ -CH-P (0C ₂ H ₅ ) ₂ Cl

To a mixture of 20.2 g (0.0725 mol) of 4-chloro «/ -hydroxybenzylphosphonic acid diethyl ester, 65 g of dichloro-methane and 5.8 g (0.0725 mol) of pyridine at 20 to 40 ⁰ C under light water cooling within about 1 hr. Added 9.2 g (0.0768 mol) of thionyl chloride. The reaction mixture is then refluxed for 3 hours and stirred for 12 hours without further heat. The mixture is poured onto about 100 g of ice water, the organic phase separated and dried. After distilling off the solvent, the residue is concentrated at 6 Torr and 45 ⁰ C. This gives 21 g (97.7% of theory) of 4-chloro - «(- chloro-benzylphosphon-acid diethyl ester as a yellow viscous oil having a purity of 98.6% (gas chromatography) and a refractive index of 1.5250 nir t

Analogously, 0 is obtained

  Il

26 C ^) - CH-P (OC ₉ HJ ₉ "refractive index:

Cl h ²³ : 1.5117

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2 2 Q 8 Q 4 - 46 -

In a solution of 131 g (0.5 mol) of triphenylphosphine in 500 ml of methylene chloride is allowed under exclusion of moisture at 30 to 35 ⁰ C 90 g of bromine dissolved in 250 ml of methylene chloride added dropwise. The mixture is stirred for 1 h * at room temperature, then allowed at -20 ⁰ C within 1 hr. A solution of 122 g (0.5 mol) of cc-hydroxy-benzyl-phosphonic acid diethyl ester in 250 ml of methylene chloride, stirred for 1 hr -20. ⁰ C and then added dropwise within 1 h, at -20 ⁰ C 40 g of pyridine, dissolved in 250 ml of methylene chloride. The mixture is stirred for 20 hrs., The temperature rises slowly to +20 G.

The reaction mixture is transferred in a pear-shaped flask and the solvent distilled off in a water-jet vacuum. The residue is stirred with one liter of ether and filtered off with suction from the undissolved triphenylphosphine oxide (triphenylphosphine oxide 120 g = 86 % of theory). Concentrate the mother liquor in vacuo and distil the residue in a high vacuum. 112 g (72 % of theory) of diethyl cc-bromobenzylphosphonate are obtained as a pale yellow oil having a boiling point of 110 ° C./0.01 torr and a purity of 95.9 % (GC).

Analog obtained. _Q

28 Cl- ^ ~~ ^ -CH-P (0C _o H _K ) _o boiling point;

Br 2.25 ° C / 0.01 Torr.

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- 47 -

The q6-hydroxycyclobenzylphosphonic acid esters to be used as starting materials in Examples 25 to 28 can be prepared, for example, as follows

Example 29

Cl- <^ \ - CH-P (OC ^) _o

OH

, In a mixture of 20.7g (0.15 mol) of diethyl phosphite and 1.09 g (0.0109 mol) of triethylamine 21 g (0.150 mol) of chlorobenzaldehyde are introduced within 1 hr. With water cooling at 50 to 70 ⁰ C. , The reaction mixture is stirred for 1 hr. At 70 ⁰ C .. After cooling, the mixture is taken up with 40 g of toluene and washed several times with dilute hydrochloric acid and cold water. The organic layer is separated and freed from the solvent in vacuo. The solid residue melts at 70 to 72 ⁰ C. The yield is 37 g (88.5% of theory) of 4-chloro-oihydroxy-benzyl-phosphonic acid diethyl ester.

Claims (1)

24. 9. 80 AP C 07 C / 220 804 GZ 57 103 12 22 0 8 O ^ " ⁴⁸ - E r findun & sans pruch 1> Process for the preparation of alkenes of formol (I) X = CH-R ¹ (X) . R ² ' in which R is an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aralkyl, aralkenyl or aryl radical or an optionally substituted heterocyclic radical, R is hydrogen or halogen and R is halogen, cyano, an optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aralkenyl, aryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl or amino-carbonyl radical or an optionally substituted heterocyclic radical . characterized in that ⁰ C-hydroxy-phosphonic acid ester of the formula II (R ⁴ O) ₅ P-CH-R ¹ (II), c- < OH 24 · 9. 80 AP C 07 C / 220 804 GZ 57 103 12 22 - 49 - in which R has the meaning given above and R represents alkyl or phenyl or the two radicals R together represent straight-chain or branched alkanediyl (alkylene), with phosphorus-containing olefination agents of the formula III CH-Z ¹ (III), R ² in which 2 3 R and R have the meanings given above, and Z for a phosphorhaltigon rest ?> - ^r5 ₇ β ο ^ or -P (R), X stands, where ^R and R are the same or different and are individually alkyl, phenyl, alkoxy or phenoxy or together are alkanedioxy, R is alkyl or phenyl and X is halogen, 24 «9« AP C 07 C / 220 GZ 57 103 22 08 - 50 - in the presence of bases, optionally in the presence of catalysts, and optionally using diluents at temperatures between -70 and +150 ⁰ C.