CH617653A5 - Process for the preparation of cyclobutane derivatives. - Google Patents

Description

The invention relates to a process for the preparation of cyclobutanones of the general formula (I)

60

A

(

I.

i

A C C = 0 (I)

1

—C— (I)

II. 10

Cyclobutenones of the general formula (II)

A

I.

Ç 0-0 (IIJ

I I

Shark

Shark

(III)

30th

3rd

617 653

or of cyclobutenones of the general formula (II)

A

I.

A C C = 0 (II)

II c = c

wherein in both formulas A represents a halogen atom with an atomic number of not more than 35, a hydrogen atom or a substituted or unsubstituted hydrocarbon radical.

The a-halocyclo-butanones mentioned in British Pat. No. 1,194,604 are obtained by a (2 + 2) cycloaddition of halogen ketene onto olefins. Such a cycloaddition can, as described in J. A.C.S. 87 (1965) S 5257-9 and Tetrahedron Letters No. 1, pp. 135-9 (1966), are brought about by dehydrochlorination of dichloroacetyl chloride with triethylamine. The dichloroketene formed in situ reacts with an olefin to form an a-chlorocyclobutanone, which is, however, obtained in poor yield because it reacts with triethylamine itself to form a quaternary ammonium chloride.

According to J. Org. Chem. 31 (1966) 626-8, the cycloaddition can also be carried out by dehalogenating an α-haloacetyl bromide with zinc dust in an inert solvent. In the publication mentioned, only the preparation of dichlorocetenes is described, starting from dichloroacetyl bromide and zinc. The dichlorocetene is isolated in a hydrocarbon, such as hexane or octane, as a solvent and the solutions thus obtained are used as a source of dichlorocetenes (see the mentioned GB-PS, where it is stated that after the solution has been removed the undesirable by-products are removed which reacts halogen ketene with an olefin). However, nothing is mentioned in the article about the isolation of a monohalogen ketene made from di-haloacetyl halide and zinc, which suggests that such isolation is impossible because a monohalogen ketene is an unstable compound that polymerizes very easily, even at low temperature . This assumption is confirmed by a publication in Synthesis, August 1971, pp. 415-422, which shows that in the preparation of monochloroacetes by dehydrohalogenation of monochloroacetyl chloride with triethylamine in the presence of chloral, a mixture of cis- and trans -4-Trichloromethyl-2-oxäthanon receives, while the production of monochloroceten by dehalogenation of dichloroacetyl chloride with zinc in the presence of chloral only leads to ", / 3-dichlorovinyldichloroacetate. It can be concluded from this that the dehydrohalogenation and dehalogenation methods are not equivalent.

In fact, it has also been found that isolation of monochlorocetene is not possible, since dichloroacetyl chloride and zinc form a reaction mixture in diethyl ether which contains no monochloro ketene and in which no cyclobutanone is formed after the zinc has been separated off and 2,3-dimethyl-2-butene has been added forms. Surprisingly, however, it was found that the monochloro-ketene formed in situ during the dehalogenation has the ability to enter a (2 + 2) cycloaddition.

The invention therefore relates to a process for the preparation of cyclobutanones of the general formula (I)

A I

A C C = 0 (I)

or of cyclobutenones of the general formula (II)

A

A ç C = 0 (II)

l = l_

wherein A in both formulas represents a halogen atom with an atomic number of at most 35, a hydrogen atom or a substituted or unsubstituted hydrocarbon radical; the process is characterized in that a 2-haloacyl halide of the general formula

A shark

! |

A C C = 0 (III)

i

Hai wherein A has the above meaning and Hai represents a halogen atom with an atomic number of at most 35, in an inert aprotic, polar solvent at a temperature above 5 ° C in the presence of zinc and / or tin with an ethylenically unsaturated compound or an alkyne .

The 2-haloacyl halide of the general formula (III) is referred to below simply as acyl halide or acid halide, while the cyclobutanone of the general formula (I) and the cyclobutenone of the general formula (II) together as the "cyclic compound" and the ethylenic unsaturated compound and the alkyne are collectively referred to as the "unsaturated compound".

The ketene formed in situ has the general formula

A

where A has the above meaning.

The process according to the invention is preferably carried out with zinc, since this metal usually leads to higher yields of cyclic compounds than the tin.

The two symbols shark in the general formula (III) stand for fluorine, chlorine or bromine atoms in any combination.

The two atoms or groups A in the general formula (III) must not be attacked when carrying out the general process. They can be the same or different. If the symbol A represents a hydrocarbon radical, this can be an alkyl, a cycloalkyl or an aryl group or a combination thereof. The number of carbon atoms in the hydrocarbon residues is not critical. Examples of substituted hydrocarbon radicals are hydrocarbon groups, the halogen atoms or alkoxy groups with z. B. contain 1-6 carbon atoms. The alkyl groups can have a straight or a branched chain and can be up to z. B. 20 and in particular up to 6 carbon atoms. The above-mentioned surprise effect is particularly brought about by 2,2-dihaloacyl halides. Very good results are usually obtained with 2-haloalkanoyl halides, especially with 2-haloalkanoyl halides.

Examples of groups represented by A are: methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, tert-butyl,

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

617 653

Benzyl, phenethyl, trityl, cyclopentyl, cyclohexyl, phenyl, naphthyl, tolyl and xylyl groups. Examples of compounds of the general formula (III) are: monochloroacetyl chloride, dichloroacetyl chloride, trichloroacetyl chloride, 2-chloropropanoyl chloride, 2,2-dichloropropanoyl chloride, 2-chlorobutanoyl chloride, 2,2-dichlorobutanoyl chloride, monochloro-monophenylacetyl chloride, dichloromononylchloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-chloro-mono-chloro-chloro-chloro-mono-chloro-chloro-chloromethyl and the acyl halides obtained by replacing one or more chlorine atoms with bromine atoms in these compounds. Very good results have been obtained with dichloroacetyl chloride.

With respect to the double bond, asymmetric ethylenically unsaturated compounds can form two different cyclo-butanones and alkynes that are asymmetric with respect to the triple bond can form two different cyclo-butenones, depending on the regional specificity of the cycloaddition in question (to explain the term For "regional specificity" see "Methods of Organic Chemistry" [Hou-ben-Weyl], 4th edition [1971], Volume IV / 4, p. 143).

The unsaturated compounds can be hydrocarbons or they can carry substituents such as alkoxy, benzyloxy, oxo or ethoxycarbonyl groups, as is the case for example with isopropyl-3-methyl-2-butenyl ether, benzyl-3-methyl-2-butenyl ether, Ethyl 2,3,5-trimethyl-2,4-hexadienoate and 6-methyl-5-hepten-2-one. However, substituted unsaturated compounds usually give the cyclic compounds in relatively low yield, e.g. B. below 20%, calculated on the acid halide. Unsubstituted unsaturated compounds are preferred because they give higher yields of cyclic compounds. The cyclobutanones are usually obtained in a yield between 50 and 75% from the particularly preferred alkenes. The alkenes can be straight-chain or branched and can have a cis or trans structure. Examples of alkenes are: ethene, propene, 1-butene, cis-2-butene, trans-2-butene, isobutene, 2-pentene, 2-hexene, 3-hexene, 2-heptene, 3-heptene, 2-methyl -2-butene, 3-methyl-2-pentene, 3-methyl-3-hexene, 2,4-dimethyl-3-hexene, 2,3,4-trimethyl-2-pentene, 1-octene, 2-octene , 3-octene, 1-nonen, 1-decene, 1-dodecene, 1-tetradecene, 1-pentadecene, 1-hexadecene, 1-eicosen, 1-doco-sen, methylene cyclobutane, methylene cyclopentane, methylene cyclohexane, the corresponding isopropylidene cycloalkanes and 3-phenyl-l-propene. Particularly good results were obtained with 2,3-dimethyl-2-butene and 2-methyl-2-pentene.

It was found that 2,5-dimethyl-2,4-hexadiene with monochloro-ketene is stereospecific with very good selectivity to trans-2-chloro-4,4-dimethyl-3- (2-methyl-l-propenyl) cyclobu- tanone and trans-2-chloro-3,3-dimethyl-4- (2-methyl-l-propenyl) cyclobutanone reacted. For an explanation of the term “stereo specificity” see “Methods of Organic Chemistry” (Houben-Weyl), 4th edition (1971), Volume IV / 4, p. 143. The meaning of this stereospecificity is explained below.

Unsaturated compounds with an alien structure give alkylidene cyclobutanones. Examples of alleniseli unsaturated compounds are: Allen, 1,2-butadiene, 2,3-pentadiene, 2,4-dimethyl-2,3-pentadiene, 3,5-diethyl-3,4-heptadiene, 5-methyl-1 , 2-hexadiene, 2,8-dimethyl-4,5-nonadiene, 3-nonyl-1,2-dodecadiene, 1,2-pentadecadiene, allenylbenzene and tetra-phenyl allene.

If the ethylenically unsaturated compound is a (hetero) cyclic compound, bicyclic compounds with a cyclobutanone ring are formed. The cyclic starting compound can e.g. B. five-, six-, seven- or eight-membered and substituted or unsubstituted and can have a second carbon-carbon double bond. One of the ring members can be an oxygen atom. Examples of substituents are: halogen atoms, which must not be bonded to a double bonded carbon atom in a molecule with only one carbon-carbon double bond, and alkyl groups. Examples of cyclically unsaturated compounds are: cyclohexene, cycloheptene, cyclooctene, 1,2-dimethylcyclopentene, 2-methylcyclohexene, 3-methylcyclohexene, 2,5-dimethylfuren, indene, 2,3-dimethylindene and 2H-3,4-di -hydropyran.

Examples of alkyls are propynes, 1-butynes, 2-butynes, 1-pentynes, 2-pentynes, 1-hexynes, 1-heptynes, 1-dodecynes, 2-methyl-1-pentynes, phenylethynes and 3-phenyl- l-propyn.

In ethylenically unsaturated compounds and alkynes which contain only a single double or triple bond, the double or triple-bonded carbon atoms should expediently not contain any deactivating substituents (for example no halogen atoms, carboxyl or carboxyl ester groups) since these are substituted unsaturated compounds form cyclic compounds only with difficulty, if at all.

The reaction has been found to be carried out in an inert, aprotic, polar solvent in order to counteract the occurrence of side reactions if possible. It has been found that ethers, especially dialkyl ethers and alkanones, are very suitable solvents, which is particularly true for ketones in which no more than one of the carbon atoms on the carbonyl group is quaternary.

The reaction according to the invention can also be carried out in a mixture of inert, aprotic, polar solvents, for. B. perform in a mixture of diethyl ether and methyl tert-butyl ketone. Small amounts of inert solvents such as toluene or xylene can also be tolerated.

Examples of dialkyl ethers are: diethyl ether, di-n-propyl ether, n-propyl isopropyl ether, diisopropyl ether and di-n-butyl ether. Among them, the diethyl ether is preferred since the best yields of cyclic compounds are usually obtained in this solvent.

The acyl halide can be used in any concentration in the dialkyl ether, a concentration below 1 mol / 1 dialkyl ether being preferred, since the yield of cyclic compound decreases more and more at higher concentrations. A concentration in the range of 0.1-0.6 mol / l is particularly preferred.

The unsaturated compound and the acyl halide can be dissolved in the dialkyl ether in any molar ratio. The higher the molar ratio of unsaturated compound to acyl halide, the better the cyclic compounds are obtained; at a molar ratio of 4: 1, for example, the yield has reached a value of more than 90%. In view of this, the molar ratio is preferably selected in a range of 2-20, and particularly 2-10: 1.

So far ketones, especially alkanones, have proven to be particularly suitable solvents because they give high yields of cyclic compounds at concentrations of the acyl halide of well over 1 mol / l. This applies in particular to alkanones which have at least two branches in the carbon skeleton and in which no more than one of the two carbon atoms located on the carbonyl group is quaternary. Diisobutyl ketone and methyl tert-butyl ketone are preferred. In ketones, the acyl halide is partly converted into cyclic compounds and partly into polymers, while the rest remains unchanged. The presence of unchanged acyl halide is an advantage when using ketones, which cannot be achieved with dialkyl ethers; in the latter solvents the acyl halide is partially converted into the cyclic compound and the rest results in a high molecular weight material. In some

4th

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

5

617 653

Ketones form relatively high proportions of polymeric substances, which is due to the acyl halide or the unsaturated compound or both. Little or even very little polymer is formed in diisobutyl ketone and methyl tert-butyl ketone.

The yield of cyclic compounds decreases the higher the higher concentrations of acyl halide are used in a ketone. However, the yield is still very high at concentrations of up to 15 and in particular up to 10 moles per liter of ketone. The acyl halide is therefore preferably used in a concentration of 1-15 mol and in particular 3-10 mol per liter of ketone. At higher concentrations of unsaturated compound above 15 mol / 1, the yield drops rapidly regardless of the acyl halide concentration, since the zinc and tin halide formed becomes less and less soluble in the supernatant liquid. If the concentration rises above 40 mol / l, these halides are hardly or no longer soluble and the cyclic compounds are formed with great difficulty, if at all.

The selectivity for the formation of cyclic compounds when using ketones as a solvent is hardly influenced if the molar ratio of unsaturated compound to acyl halide rises above 0.5. This molar ratio is therefore preferably chosen between 0.5 and 10 and in particular between 1 and 2.

The tendency to form cyclic compounds increases with an increasing molar ratio of zinc or tin to acyl halide. This molar ratio is therefore preferably chosen in the range from 1-10 and in particular from 1-5.

A very good selectivity is usually obtained when the molar ratio is in the range 3.5-4.5. The selectivity for the formation of cyclic compounds is also favorably influenced if the zinc or tin is homogeneously distributed in the liquid. This selectivity is relatively low when zinc dust - which has a relatively large surface area - is used, on the other hand is significantly higher if the zinc particles have a relatively small specific surface area, e.g. B. when using zinc particles, the largest dimension of which is at least about 0.1 mm. The use of particles with the largest dimension between 0.5 and 5 mm leads to a high selectivity.

If the method were modified to operate at a temperature of no more than 5 ° C, no measurable cycloaddition would take place. It has been found that when the working temperature rises above 5 ° C., the yield of cyclic compounds initially increases, whereupon it reaches a maximum, which is usually 25-60 ° C. and decreases again when the temperature rises. The process according to the invention is therefore preferably carried out at temperatures of 15-100 ° C., in particular at 25-60 ° C. Particularly good results are obtained in the temperature range of 35-50 ° C.

The reactants can be contacted in any manner. So you add z. B. the acid chloride of a stirred suspension of zinc or tin in a solution of the unsaturated compound either at once (which is preferable), or over a period of e.g. B. distributed up to 5 hours. The addition of the acid halide is best done fairly quickly, e.g. B. within a quarter or three-quarter hour. Longer addition times usually reduce the yield of cyclic compound. A gradual addition of acid halide is particularly preferred in the case of 2,2-di- and 2,2,2-trihaloacyl halides, since the selectivity for the formation of cyclic compounds has a favorable effect insofar as these halides in situ mono- or Form dihalo-ketenes that are easily converted into undesirable high molecular by-products. In certain cases, however, cycloaddition can start suddenly when most or all of the acid halide is added, at the same time releasing heat and considerable polymer formation taking place. The cycloaddition usually begins suddenly and proceeds smoothly without a noticeable acid halide concentration when successively suspending zinc or tin in a solution of less than 25%, preferably 2-10% of the total amount of acid halide with stirring, the unsaturated compound in the suspension is stirred in and then the remaining acid halide is added. The desired selectivity is also favorably influenced if the zinc or tin is gradually added to a solution of the acid halide and the unsaturated compound, or in particular if the acid halide and the unsaturated compound are added together while stirring a suspension of zinc or tin in adds a solvent.

The selectivity towards the formation of cyclobutanones or cyclobutenones is usually improved by carrying out the process according to the invention in the presence of an inorganic halide. Catalytic amounts of halides are particularly suitable and are preferably in the range of 0.1-10 mol%, calculated on 2-haloacyl halide. Particularly suitable inorganic halides are mercury iodide, sodium chloride and in particular potassium iodide and ammonium chloride.

The cyclic compounds prepared with the aid of the process according to the invention can be isolated in pure form by distillation of the reaction mixture after removal of the zinc or tin and washing out with water in order to remove the zinc or tin halide formed.

If the cyclic compounds are 2-halocyclobutanones, the reaction mixture can be heated with water in the presence of a base after removal of the zinc or tin and its halides; this causes a ring contraction to form salts of cyclopropanecarboxylic acids of the general formula

H COOH

C C

I I

the yield is often 90-100%, calculated on the 2-halo-cyclobutanone. Substituted esters of this cyclopropanic acid are particularly useful insecticides because they combine high insecticidal activity with low toxicity to vertebrates.

The present invention therefore also includes a process for the preparation of cyclopropanecarboxylic acids of the general formula (V), which is characterized in that first by reacting a 2-haloacyl halide of the general formula (III) in an inert, aprotic, polar solvent with an ethylenic unsaturated compound or an alkyne at temperatures above 5 ° C in the presence of zinc and / or tin produces a compound of general formula (I) or (II) and then heated with water in the presence of a base and the salt of cyclopropanecarboxylic acid thus obtained in the free acid is transferred. (This method can also be expressed as a possible use for the compounds according to the invention.)

So you can z. B., as already explained, 2,5-dimethyl-2,4-hexadiene with monochloro-ketene formed in situ to 2-chloro-4,4-dimethyl-3- (2'-methyl-l'-propenyl) -cyclobutanone s

10th

15

20th

25th

30th

35

40

45

50

55

60

65

617 653

6

and 2-chloro-3,3-dimethyl-4- (2'-methyl-r-propenyl) cyclobutanone. The latter two compounds, when subjected to the above-mentioned ring contraction, are converted into a mixture of salts of ice and trans-chrysan-temum monocarboxylic acid (2,2-dimethyl-3-isobutenylcyclopro-pancarboxylic acid), which are easily converted into the free one Acid can be transferred. The chrysantemum monocarboxylic acid formed is 96% in the trans form, which is advantageous insofar as the trans-chrysantemum monocarboxylic acid has a significantly higher insecticidal effect than the cis-chrysanemumonocarboxylic acid.

If 2,4-dimethyl-2,3-pentadiene is reacted with monochloro-ketene formed in situ, 2-chloro-3,3-dimethyl-4-iso-propylidene-cyclobutanone and 2-chloro-4,4-dimethyl-3- isopro-pylidene cyclobutanone. The latter two compounds are converted into salts of 2,2-dimethyl-3-isopropylidene cyclopropanecarboxylic acid by the ring contraction mentioned above.

The cyclopropanecarboxylic acids can be precipitated from the aqueous solution of their salts by adding a strong mineral acid in an aqueous solution. The precipitated carboxylic acid, which is obtained by subjecting 2-halocyclobutanone to the ring contraction and releasing the acid, has a higher purity and a lighter color, the less polymer is simultaneously formed in the process according to the invention. For this reason, methyl tert-butyl ketone and diisobutyl ketone are the preferred solvents in the preparation of 2-halocyclobutanones as precursors to cyclopropanecarboxylic acids.

The cyclobutenones can be hydrogenated to the corresponding cyclobutanones, which are then used as described above.

The examples serve to explain the invention in more detail. The experiments described were carried out in a three-necked flask equipped with a stirrer, a metering funnel with a tap, a thermometer, an inlet for nitrogen and a water-cooled reflux condenser connected to a drying tube. The experiments were carried out under nitrogen.

Some of the compounds of the formulas (I), (II) or (V) are novel compounds.

The experiments described in Examples 1-5 were carried out as follows (unless stated otherwise):

The flask was charged with 2,3-dimethyl-2-butene, zinc grains and 11 dried diethyl ether. The zinc grains had a maximum diameter of 1 mm. The suspension in the flask was refluxed and dichloroacetyl chloride was added dropwise from the dropping funnel over 4 hours, after which the reaction mixture thus formed was stirred under reflux for an additional 8 hours. During the entire test period, the stirrer kept the zinc grains homogeneously distributed in the liquid. The dichloroacetyl chloride was completely used up; some of it was converted to 2-chloro-3,3,4,4-tetramethylcyclobutanone (hereinafter referred to as "Compound A"), while the rest gave high molecular weight products. The 2,3-dimethyl-2-butene, as far as it had reacted, was converted into compound A. The yield of Compound A is calculated based on the dichloroacetyl chloride used. The 2,3-dimethyl-2-butene is hereinafter referred to as DMB and the dichloroacetyl chloride as DCAC and their concentrations are expressed in moles per liter of solvent.

example 1

Five experiments were carried out, the concentrations of DMB and DCAC and the molar ratios of zinc to DCA being given in Table I. The table also contains the calculated molar ratios of DMB to DCAC and the yields of compound A.

Table I

Ver

Concentrate

Mol / 1

Molar ratio

From search tration

DCAC

DMB: DCAC

Zn: DCAC

prey

No.

from

to A

DMB

(%)

1

0.24

0.77

0.31

9.2

22

2nd

0.24

0.32

0.75

7.4

57

3rd

0.24

0.18

1.33

10th

52

4th

0.49

0.10

5

2nd

> 90

5

1.96

0.10

20th

2nd

> 90

Example 2

Five experiments were carried out again, DMB and DCAC were each used in a concentration of 0.24 mol / l and the molar ratio of zinc to DCAC is given in Table II. The yields of compound A are also shown in Table II.

Table II

Experiment molar ratio yield

Zn: DCAC anA (%)

1 1.0 17

2 1.1 27

3 1.5 58

4 2.0 62

5 4.0 64

Example 3

Five experiments were carried out again, using equimolar amounts of DMB and DCAC and the molar ratio of zinc to DCAC being 2; the concentration of DCAC can be found in Table III. In experiments 4 and 5, the DCAC was added within 16 and 24 hours instead of within 4 hours. Table III also contains the yields of compound A.

Table III

Attempting concentration of yield

No. DCAC (mol / 1) anA (%)

l1 0.24 62

2 0.42 41

3 0.84 38

4 0.42 38

5 0.84 37

1 corresponds to experiment 4 in example 2

Example 4

A mixture of DCAC and DMB (instead of just DCAC) was added with stirring to a mixture of diethyl ether and zinc grains (instead of a mixture of DMB, zinc grains and diethyl ether as above). Three experiments were carried out, the molar ratio of zinc to DCAC

2 and the molar ratios of DMB to DCAC and the concentrations of DCAC are listed in Table IV, which also contains the yields of compound A.

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

Table IV

Experiment concentration molar ratio yield

No. of DCAC. Mol / 1 DMB: DCAC at A (%)

1 0.42 1.0 53

2 0.42 1.1 52

3 0.84 1.0 42

The yields obtained in experiments 1 and 3 are higher than those from experiments 2 and 3 in example 3, in which the same concentrations of DCAC were used.

Example 5

Trial A

A molar ratio of DMB to DCAC of 0.75 and a molar ratio of zinc to DCAC of 7.4 were used for this experiment. The flask was charged with 400 ml (instead of 11) of diethyl ether. The DCAC was used in an amount of 0.16 mol, dissolved in 100 ml of diethyl ether. The reaction mixture was stirred an additional 2 (instead of 8) hours after the DCAC had been added. The yield of compound A was 57%.

Trial B

(Comparative test, does not correspond to the method according to the invention)

A mixture of 50 ml of diethyl ether, 0.012 mol of DCAC and 0.036 mol of zinc grains with a largest diameter of 1 mm was stirred vigorously at 34 ° C. under reflux. After stirring for 16 hours, the DCAC was completely used up. The zinc was then separated off by decanting and 0.012 mol of DMB was added to the liquid obtained, whereupon the mixture was stirred at 34 ° C. for a further 3 hours. At the end of this period, no more cyclobutanone was found in the mixture.

The experiments described in Examples 6-10 were carried out as follows:

A three-necked flask was charged with 10 mmol DCAC 0.6 mmol KJ, 96 mmol zinc swarf with a largest dimension of 0.841 mm and 20 ml solvent. The starting temperature of the mixture was 38 ° C. The mixture was then stirred at 43 ° C. for 1 hour, after which 48 mmol (5.7 ml) of DMB were added all at once. Then 52 mmol DCAC were added within 35 minutes and the reaction mixture was stirred for a further 1/4 hour (stirring speed 2000 rpm).

Example 6

Six experiments were carried out, using the solvents listed in Table VI, which also shows the yields of compound A, calculated on DCAC.

Table VI

Ver

solvent

yield

polymer

Search color

at A (%)

educated

Reaction

No.

mixed

1

acetone

21st

a lot of dark brown

2nd

Methyl ethyl ketone

30th

a little light brown

3rd

Methyl isobutyl ketone

38

a little light brown

4th

Diisobutyl ketone

54

very little yellow

5

Methyl tert-butyl ketone

53

little yellow

6

Di-tert-butyl

less much dark

ketone as 0.8

brown

617 653

The polymers formed in Experiments 1 and 2 were from DCAC and DMB. The DMB that had reacted in experiments 3, 4 and 5 was fully converted into compound A. The ZnCl2 formed on the surface of the zinc particles in experiment 6 did not dissolve, the more polymer is formed, the darker the color of the reaction mixture.

Example 7

Four experiments were carried out, diisobutyl ketone being used as the solvent and the concentrations of DMB and DCAC being shown in Table VII, which also contains the molar ratios of DMB to DCAC (calculated from these concentrations) and the yields of compound A.

Table VII

Ver

Concentra

Mol / 1

Molar ratio

Yield search

DCAC

DMB: DCAC

at A (%)

No.

DMB

I1

2.4

3.1

0.78

54

2nd

4.8

3.1

1.55

58

3rd

12.0

3.1

3.87

56

4th

46.5

3.1

15.0

0

1 corresponds to experiment 1 in example 1

Very little polymer was formed and, as far as it reacted, the DMB was completely converted to compound A. In experiment 3 the ZnCl2 did not dissolve completely and in experiment 4 not at all.

Example 8

Three experiments were carried out, using diisobutyl ketone and 62 mmol DCAC as solvents. The molar ratio of zinc to DCAC and the yields of compound A are shown in Table VIII. The converted DMB was completely converted into compound A.

Table VIII

Trial molar ratio yields

Zinc: DCAC at A (%)

1 1.1 51

2 1.55 70

3 3.9 75

Example 9

Three experiments were carried out, using diisobutyl ketone as solvent and the molar ratio of DMB: DCAC being 0.78. The concentration of DMB and DCAC is shown in Table IX and the yields of compound A are given.

Table IX

.Attempt

concentration

Mol / 1

Exploit

No.

DMB

DCAC

at A (%)

I1

2.4

3.1

54

2nd

4.8

6.2

50

3rd

9.6

12.3

37

1 corresponds to experiment 1 from example 7

7

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

617 653

8th

Example 10

Three experiments were carried out with diisobutyl ketone as solvent, the temperatures being given in Table X, which also contains the yield of compound A.

Table X

Experiment temperature yield polymer color of No. ° C anA (%) formed reaction mixture

1 24 36 little yellow

2 43 54 little yellow

Example 11

A suspension of 240 mmol zinc swarf (of the same dimension as in Example 6), 6 mmol ammonium chloride and 0.6 mmol potassium iodide in 20 ml diisobutyl ketone were added at 38 ° C with 10.3 mmol DCAC with stirring. The solution turned yellow within 3 minutes and an increase in temperature was observed. The temperature was kept between 40 and 45 ° C and after 10 minutes 96 mmol of 2-methyl-2-pentene was added in one portion, after which 51.7 mmol of DCAC were added within 30 minutes. The mixture was then stirred at 40-45 ° C for a further 14 hours.

The orange-yellow solution thus formed was decanted in a separatory funnel and the excess zinc was washed three times with acetone, whereupon the washing acetone was added to the orange-yellow solution and the mixture thus formed was washed out with 200 ml of water. Some precipitate formed, which dissolved again after acidification with a few drops of concentrated aqueous HCl. The acidified solution - which contained 2-chloro-3-ethyl-4,4-dimethyl-cyclobutanone and 2-chloro-4-ethyl-3,3-dimethylcyclobutanone, two novel compounds - was then left at 22 for a 3/4 hour ° C stirred with 110 ml of 1 M aqueous sodium hydroxide solution. The mixture was then separated into an aqueous and an organic layer, whereupon the aqueous layer was acidified with 7.5 l of concentrated aqueous HCl. The oil thus formed was extracted with diethyl ether and the extract was dried over anhydrous magnesium sulfate. After the diethyl ether had been driven off, 3.8 g of viscous oil remained, which contained 84% by weight of 2,2-dimethyl-3-ethylcyclopropanecarboxylic acid. The yield of this acid, which has not yet been described, was 42%, calculated on DCAC. The selectivity for this acid was higher than 50%. About 60% of the acid had the trans configuration.

Example 12

10.3 mmoles of DCAC were added at 40 ° C. to a suspension of 240 mmoles of zinc swarf (same dimensions as in Example 7), 6 mmoles of ammonium chloride and 0.6 mmoles of potassium iodide in 20 ml of diisobutyl ketone with stirring. The solution turned yellow within 3 minutes and an increase in temperature was observed. The temperature was kept between 40 and 45 ° C and after 8 minutes 96 mmol of 2,5-dimethyl-2,4-hexadiene were added all at once. Then 51.7 mmol DCAC, distributed over 30 minutes, were added, whereupon the mixture was stirred at 40-45 ° C for 1 hour. The orange-yellow solution thus obtained was decanted in a separatory funnel, the excess zinc was washed three times with acetone and the acetone washing liquids were added to the orange-yellow solution, whereupon the mixture was washed out with 150 ml of water. The mixture, which after washing the novel compounds 2-chloro-4,4-dimethyl-3- (2-methyl-l-propenyl) -cyclobutanone and 2-chloro-3,3-dimethyl-4- (2nd -methyl-l-

propenyl) -cyclobutanone was stirred with 110 ml of a 1 M aqueous sodium hydroxide solution at 22 ° C. for 3/4 hour, whereupon it was separated into an aqueous and an organic layer. The aqueous layer became 7.5 ml of concentrated aqueous The oil thus formed was extracted with chloroform and the extract dried over anhydrous magnesium sulfate, and after evaporation of the chloroform from the extract, 5.5 g of a viscous oil remained, which contained 70% by weight of chrysantemum monocarboxylic acid. The yield of this acid was 37% calculated on DCAC and about 96% of the acid was in the trans configuration.

Example 13

10.3 mmoles of DCAC were added at 40 ° C. to a suspension of 240 mmoles of zinc swarf (same dimension as in Example 6), 6 mmoles of ammonium chloride and 0.6 mmoles of potassium iodide in 20 ml of diisobutyl ketone with stirring. After 3 minutes, 48 mmol of isopropyl-3-methyl-2-butenyl ether were added all at once. Then 51.7 mmol DCAC were added within 20 minutes and the mixture was stirred at 40-45 ° C for a quarter of an hour.

The yellow solution thus formed was decanted in a separatory funnel, the excess zinc was washed three times with acetone and the acetone washing liquids were added to the yellow solution, whereupon the resulting mixture was washed out with 175 ml of water. The mixture, which contained the two novel compounds 2-chloro-4-iso-propoxymethyl-3,3-dimethylcyclobutanone and 2-chloro-3-iso-propoxymethyl-4,4-dimethylcyclobutanone after washing, was mixed with 110 ml of 1 M aqueous sodium hydroxide solution was stirred at 22 ° C for 3/4 hour, after which it was divided into an aqueous and an organic layer. The aqueous layer was acidified with 7.5 ml of concentrated aqueous HCl. The oil thus formed was extracted with chloroform and the extract was dried over anhydrous magnesium sulfate. After evaporation of the chloroform from the extract, 2.65 g of a viscous oil remained, which contained 64% by weight of 2,2-dimethyl-3-isopropoxymethyl-cyclopropanecarboxylic acid. The yield of this acid, which has not yet been described, was 15%, calculated on DCAC. About two thirds of it was in the trans configuration.

Example 14

To a suspension of 1200 mmol zinc swarf of the same dimension as in Example 6, 29.9 mmol ammonium chloride and 3.0 mmol potassium iodide in 100 ml diisobutyl ketone were added at 35 ° C 51.7 mmol DCAC with stirring. The solution turned yellow within 5 minutes and an increase in temperature was observed. The temperature was kept between 40 and 45 ° C. After 5 minutes, 240 mmoles of benzyl-3-methyl-2-butenyl ether were added all at once, resulting in a temperature rise to 50 ° C. 10 minutes later, 310 mmol DCAC was added to the mixture over 35 minutes and the mixture was stirred at a temperature of 40-45 ° C for 3/4 hour.

The solution formed was decanted in a separatory funnel, the excess zinc was washed three times with acetone and the acetone washing liquids were added to the solution, whereupon the resulting mixture was washed out with 500 ml of water. After washing, the mixture contained the two novel compounds 2-benzyloxymethyl-4-chloro-3,3-dimethylcyclobutanone and 3-benzyloxymethyl-2-chloro-4,4-dimethylcyclobutanone and became high for a 3/4 hour 22 ° C with 550 ml of 1 M aqueous sodium hydroxide solution, whereupon it was separated into an aqueous and an organic layer. The aqueous layer was acidified with 40 ml of concentrated aqueous HCl and the oil thus formed was extracted with chloroform and the extract was dried over anhydrous magnesium sulfate. After the chloroform was evaporated, the extract left

5

10th

15

20th

25th

30th

35

40

45

50

55

60

65

9

617 653

14 g of a viscous oil with a content of 53% by weight of the compound 2-benzyloxy-methyl-3,3-dimethylcyclopropanecarboxylic acid which has not previously been described. The yield of this acid was 8% calculated on the DCAC and 57% was in the trans configuration. 5

Example 15

A three-necked flask was charged with 10 ml of diethyl ether, 3 mmoles of an unsaturated compound and 6 mmoles of zinc granules, and the mixture was kept at 35 ° C. with stirring. Then 6 mmoles of DCAC were added all at once.

Seven attempts were made, each with a different unsaturated compound. Table XI shows which unsaturated compound was used and what the yield of cyclic compounds, calculated on DCAC, was at different times after the start of the experiment. The cyclic compounds formed have not been described in the literature to date, but with the exception of 2-chloro-3,3,4,4-tetramethylcyclobutanone.

Table XI

unsaturated cyclic compounds formed Yield of cyclic compounds

Connection after ... min in%

15 30 60 120 180

Propene 2-chloro-4-methylcyclobutanone and

2-chloro-3-methylcyclobutanone

28

34

35

Cis-2-butene

2-chloro-3,4-dimethylcyclobutanone

12

39

43

43

Trans-2-butene

2-chloro-3,4-dimethylcyclobutanone

45

53

54

Isobutene

2-chloro-4,4-dimethylcyclobutanone and

2-chloro-3,3-dimethylcyclobutanone

10th

21st

49

51

2-methyl-2-butene

2-chloro-3,4,4-trimethylcyclobutanone

and 2-chloro-3,3,4-trimethylcyclobutanone

50

55

55

67

2,3-dimethyl-2-butene

2-chloro-3,3,4,4-tetramethylcy clobutanone

43

59

67

36

2-butyn

4-chloro-2,3-dimethylcyclobuten-2-one

29

35

Example 16

A three-necked flask was charged with 11 dried 35 diethyl ether, 0.54 mol zinc grains with a largest diameter of 1 mm and 0.24 mol 2,3-dimethyl-2-butene. A solution of 0.24 mol of DCAC in 50 ml of dried diethyl ether was added dropwise to the refluxing suspension over the dropping funnel within four hours and the reaction mixture was stirred under reflux for a further eight hours. After cooling to 20 ° C, the mixture was washed out with an equal volume of water. The two phases were separated and the organic layer which contained the compound A was stirred with a solution of 0.5 mol of sodium hydroxide in 500 ml of water, the diethyl ether being simultaneously distilled off. 20% by weight aqueous HCl was then added to the residue until the pH had dropped to 2.5, the solution was subjected to steam distillation and the solid 2,2,3,3-tetramethylcyclopropane-carboxylic acid was distilled off from the distillate. The yield was 57%, calculated on DCAC.

Example 17

The procedure described in Example 16 was applied to four other ethylenically unsaturated compounds. Table XII shows the unsaturated compounds used, the names of the cyclobutanones and cyclopropanecarboxylic acids formed, the yield figures and the physical data of the compounds in question.

Table XII

unsaturated cyclopropanecarboxylic acid formed cyclobutanone formed physical

Connection off-off data

Label prey label prey

2,4-dimethyl-2-chloro-4,4-dimethyl-30

2,3-pentadiene 3-isopropylidene cyclo-butanone * and 4-chloro-3,3-dimethyl-2-iso-propylidene cyclobutanone

2,5-dimethyl-2-chloro-4,4-dimethyl-42

2,4-hexadiene 3- (2-methyl-l-propenyl) cyclobutanone * and 2-chloro-3,3-dimethyl-4- (2-methyl-l-propenyl) cyclobutanone *

2,2-dimethyl-3-iso-

propylidene cyclopropane

carboxylic acid

23

2,2-dimethyl-3- (2-methyl-25-propenyl) -cyclopropane-carboxylic acid (chrysanthemum monocarboxylic acid)

Kp.

70 ° / 10 mm

Mp 53 °

617 653

10th

Table XII (continued)

unsaturated cyclopropanecarboxylic acid formed cyclobutanone formed physical

Connection off-off data

Label prey label prey

EthyI-2,3,5-

trimethyl

2,4-hexadienoate

1,2-dimethyl-cyclopentene

2-chloro-3,3-dimethyl-38 4- (1-methyl-2-ethoxycarbonyl-l-propenyl) cyclobutanone *; 2-chloro-4,4-dimethyl-3 - (1-methyl-2-ethoxycarbonyl-1-propenyl) cyclobutanone *;

2-chloro-3,4-dimethyl

3-ethoxycarbonyl-4- (2-methyl-propenyl) -cyclo-butanone * and 2-chloro-3,4-dimethyl-4-ethoxy-carbonyl-3- (2-methyl-propenyl) -cyclobutanone

6-chloro-1,4-dimethyl-20 bicyclo- (3,2,0) -heptanone-5 *

(Endo- and exo-)

2- (1-methyl-2-carboxy-l-propenyl) -3,3-dimethyl-cyclopropanecarboxylic acid * and its isomers

14

1,5-dimethylbicyclo- (3,1,0) -hexane-6-carbon-

12

Mp 62 °

acid''

new connection

Example 18

When working according to Example 16, the zinc granules (0.5 mol) were replaced by 0.5 mol of tin powder. Compound A was obtained in a yield of 25%.

Claims (15)

617 653 2nd PATENT CLAIMS 1. Process for the preparation of cyclobutanones of the general formula (I) A or of which in both formulas A denotes a halogen atom with an atomic number of not more than 35, a hydrogen atom or a substituted or unsubstituted hydrocarbon radical, characterized in that a 2-haloacyl halide of the general formula (III) wherein A has the above meaning and Hai represents a halogen atom with an atomic number of not more than 35, in an inert, aprotic, polar solvent at a temperature above 5 ° C in the presence of zinc and / or tin with an ethylenically unsaturated compound or an alkyn. 2. The method according to claim 1, characterized in that dichloroacetyl chloride is used as the compound of the formula (III). 3. The method according to claim 1 or 2, characterized in that as an ethylenically unsaturated hydrocarbon is an alkene with one or two carbon-carbon double bonds, in particular 2,3-dimethyl-2-butene, the 2-methyl-2-pentene or the 2,5-dimethyl-2,4-hexadiene is used. 4. The method according to any one of claims 1-3, characterized in that a dialkyl ether, in particular diethyl ether, as solvent for the reactants, or used a ketone. 5. The method according to any one of claims 1-4, characterized in that the 2-haloacyl halide according to formula (III) in a concentration of 0.1-1 mol, preferably 0.1-0.6 mol, per liter of dialkyl ether used. 6. The method according to any one of claims 1-5, characterized in that the reactants are used in a ratio of 2-20, preferably 2-10 moles of ethylenically unsaturated compound or alkynes to 1 mole of 2-haloacyl halide according to formula (III). 7. The method according to any one of claims 1-6, characterized in that the solvent is an alkanone with at least two branches in the carbon skeleton of the molecule, in which at most one of the two carbon atoms located on the carbonyl group is quaternary, in particular diisobutyl ketone or methyl tert-butyl ketone used. 8. The method according to claim 4 or 7, characterized in that the 2-haloacyl halide of the general formula (III) is used in a concentration of 1-15 mol, preferably 3-10 mol, per liter of ketone. 9. The method according to any one of claims 4, 7 or 8, characterized in that the reactants in a quantitative ratio of 0.5-10, preferably 1-2 moles of ethylenically unsaturated compound or alkynes to 1 mole of 2-haloacyl halide of the formula ( III) used. 10. The method according to any one of claims 1-9, characterized in that the zinc or tin in a ratio of 1-10, preferably 1-5 mol of zinc or tin to 1 mol of 2-haloacyl halide according to formula (III) used. 11. The method according to any one of claims 1-10, characterized in that the zinc is used in the form of particles with a largest diameter of at least 0.1 mm. 12. The method according to any one of claims 1-11, characterized in that it is carried out at a temperature of 25-60, preferably 35-50 ° C. 13. The method according to any one of claims 1-12, characterized in that the haloacyl halide according to formula (III) is added with vigorous stirring to a suspension of zinc or tin in a solution of the ethylenically unsaturated compound or the alkyne. 14. The method according to claim 13, characterized in that a suspension of zinc or tin in a solution of less than 25% of the total amount of the 2-haloacyl halide of the general formula (III) with stirring, the ethylenically unsaturated compound or the alkyne and then the remaining 2-haloacyl halide according to formula (III). 15. The method according to any one of claims 1-14, characterized in that it is preferably in the presence of 0.1-10 mole% of an inorganic halide 35 of potassium iodide and / or ammonium chloride, calculated on the 2-haloacyl halide according to formula (III). 16. The method according to claim 1, characterized in that the compound of formula (II) obtained is catalytically hydrogenated to give the corresponding compound of formula (I) 40 received. 17. Use of the compounds of the formula (I) prepared by the process according to claim 1 for the preparation of a carboxylic acid of the general formula (V) 45 H CQOH (V) - c / —— i { 50 characterized in that a compound of the general formula (I) is heated with water in the presence of a base and the salt formed of the cyclopropanecarboxylic acid of the formula (V) in question is converted into the free acid. 55