DE3225605A1 - METHOD FOR PRODUCING CYCLOPROPAN DERIVATIVES - Google Patents

Description

Process for the preparation of cyclopropane derivatives

The invention relates to a process for the preparation of cyclopropane derivatives. Certain cyclopropane derivatives show extremely effective insecticidal properties. Accordingly, much research has been conducted into the Synthesis possibilities for the preparation of compounds with suitable substituted cyclopropyl groups carried out. Many papers describe the reaction of swine felyliden with olefins to form the cyclopropane ring. For example, G.B. Payne describes in Journal of Organic Chemistry 32 3351 (1967) the use of ylides derived from dimethyl sulfide and other research groups have also used the same or similar ylids. These ylids work well for indeed Laboratory-scale representations, however, are generally unsuitable for large-scale representations due to their and their precursors, the sulfonium salts, have poor thermal stability. In addition, the Handling of dimethyl sulfides on an industrial scale causes considerable problems because of their volatility.

UK Patent Specification No. 1,553,153 describes an attempt to solve these problems and discloses that certain Cyclopropane derivatives by reaction of thiolane with m-phenoxybenzyl or a C (1-4) alkyl ester of Chloric or bromoacetic acid can be prepared by converting the resulting sulfonium salt into the corresponding

56 124

Ylid converted by reaction with a base and with an olefin is reacted with a corresponding substitution pattern. There are several advantages to this method versus Payne's originally proposed method. However, problems continue to arise. It exists Data showing that thermal decomposition of the thiolane-derived sulfonium salt is reversible runs, but closer examination of these data (Example 2 of this description) shows that only half of the original starting material is retained after heating in acetone for one hour.

One of the problems with the reaction of thiolane with haloacetic acid esters is that there is always a ring opening to connection I. In addition, especially at Presence of thiolane in excess, the compound II is formed.

Shark - (CH ₂ ) 4 - S - CH ₂ - CO ₂ R (I)

r ~ \.

^ S ⁺ - (CH ₂ ) 4 - S - CH ₂ - CO ₂ R (II)

Shark "

Here, shark means a chlorine or bromine atom and R stands for m-phenoxybenzyl or C (1-4) alkyl.

It is also found that when using mesityl oxide as an olefin to prepare an ester of 2,2-dimethyl-3-acetylcyclopropanecarboxylic acid, which is a precursor to pyrethroid-type insecticides having a 2,2-dimethyl-3- (2,2-dihalovinyl) cyclopropyl moiety is (see

see the example in DE-OS 2,639,777), difficulties arise in practice when attempting this To carry out the process on an industrial scale in an economical manner. Thiolane is formed during the reaction of the ylid with mesityl oxide recovered and due to its high price

56 124

economic factors force it to be fed back in for the reaction with the haloacetate. It is also desirable to recycle unreacted mesityl oxide. In practice it is not possible to separate the recovered thiolane unreacted mesityl oxide, since their boiling points of 120 ° and 129 ⁰ C are very close, so that a mixture of thiolan and mesityl oxide to be recycled. However, it has been found that, in the presence of mesityl oxide, the reaction rate of thiolane with haloacetate decreases significantly and, in addition, the selectivity for the desired product is reduced. This problem naturally arises when any olefin is used if it is difficult to separate from thiolane.

The object of the invention is to create a process that has a favorable reaction rate and favorable selectivity leads to the desired products, and that can be carried out under conditions in which an economical Recycling the reactants is possible.

The invention provides a process for the preparation of an ester of an acid of the general formula

(III)

R.
30th

1 2
in which each of the radicals R and R independently of one another is hydrogen, C (1-8) alkyl, benzyl, phenyl, alkylphenyl

1 2 or halophenyl, or where R and R together represent a C (2-7) alkylene group in which

^ '56 124

12 3 4

Z and Z independently of one another CO ₇ R, COR, CHO, CN,

5 12

NO ₉ or SO ₉ R, or in the case of Z and Z this

6 1

has meaning and represents an R or in the case of Z

and Z together with the carbon atom in between a cyclopentadienyl or benzocyclopentadienyl

3 4 5 represent a group in which R, R and R are independent

from one another C (1-8-alkyl, phenyl, alkylphenyl or halophenyl and R is hydrogen, C (1-8) alkyl, phenyl, alkylphenyl or halophenyl. 10

The procedure includes the following steps

a) reaction of a cyclic sulfide of the general formula

CH ₂ - CH ₂

f ^ ^{S (IV)}

CH ₂ - CH ₂ ^

in which A stands for a direct CC bond, a CH ₉ group, a sulfur atom or an oxygen atom, with an o (-substituted acetic acid of the general formula

X - CH ₂ - CO ₂ H (V)

in which X represents the leaving group; b) converting the resulting compound into a Ester;

c) reaction of the resulting compound with a base to produce the corresponding ylide and

d) Reacting the ylide with an olefin of the general formula

R.
\ - C ^ CVD

V ^% '56 124

12 1 2
in which R, R, Z and Z have the same meaning as in general formula III.

Any suitable ester group can be present in the compound prepared by the process of the invention will be present. For example, the compound can be an optionally substituted alkyl ester such as a benzyl or m-phenoxybenzyl ester. Preferably however, an unsubstituted lower alkyl ester is synthesized.

1 2
Preferably, R and R independently of one another are

a hydrogen atom or a lower alkyl group. Yet 15th

1 2

R and R in the form of a methyl group are better suited.

1 2

Preferably Z and Z 'stand together with the neighboring one Carbon atom for a cyclopentadienyl or benzocyclopentadienyl group, or Z stands for a water

2 3 4

substance atom and Z for a CO ₀ R * or COR group, where R and R have the meaning given above and preferably represent lower alkyl groups. Particularly

1 2

Z as a hydrogen atom and Z as an acetyl group are preferred.

Therefore, a particularly preferred olefin of the formula VI for use in the process according to the invention is Me-

1 2 sityloxid, in which in particular R and R are methyl groups

1 2

mean and Z for a hydrogen atom and Z for one

Acetyl group.
30th

In the compound of the formula IV, A preferably represents a direct C-C bond or an oxygen atom.

The direct reaction product after reaction a) can be a sulphonium salt (VII) or a zwitterionic compound

56 124

(VIII) plus HX, which naturally depends on the Basicity of the anion X and the pH of the reaction mixture depends.

CH ₂ - CH ₂ X®

A ~> S® - CH ₂ - CO ₂ H (VII) I s ^

CH ₂ - CH ₂

A J ^ S © - CH ₂ - C0 ₂ ® (VIII)

CH ₂ - CH ₂

X represents any group that can be removed by the sulfide under the reaction conditions. 15th

Suitable leaving groups X are organic sulfonyl groups, such as methylsulfonyl, phenylsulfonyl or p-toluenesulfony groups, hydroxyl groups and especially chlorine or bromine atoms. 20th

Throughout this specification and claims, the term "lower" means the alkyl group or an Alkanol group that up to 6, preferably up to 4 carbon atoms should be present. Particularly preferred Alkyl groups are methyl and ethyl groups.

The substitution reaction a) is suitably carried out at a temperature range between 0 and 100 ^° C., in particular between 30 and 80 ^° C. The ratio of the molecular weights of the reactants. is not critical. An excess of one of the reactants is generally used to increase the rate of reaction. This is usually in a range from 0.1 to -3 mol excess per mol of other reactant. Other reactants can also be used in excess.

- 40 * 56 124

However, the f ^ -substituted acetic acid is preferred Used excess.

The reaction is suitably in the acidic pH range in the presence of a solvent, especially one highly polar solvent, for example water, a carboxylic acid - like acetic acid - an alcohol - like Methanol - or a cyanide - such as acetonitrile - carried out. Aqueous reaction media are particularly suitable, wherein the water alone or in a mixture with a water-miscible cosolvent, for example a lower alkanol, such as methanol, is used. An excess of one of the reactants is expedient used as a solvent.

The esterification reaction b) can be carried out by any suitable method, for example by direct Reaction with an alcohol or an olefin, or by transesterification with an ester in the presence of one acid catalyst. A sulfonium salt VII, which was prepared according to reaction a), is of course one Acid and can therefore act as an acidic catalyst itself, but this acid becomes during the course of the reaction removed so that additional acid is preferably added. Suitable acids include organic acids, such as p-toluenesulfonic acid, mineral acids, such as hydrohalic and sulfuric acid, as well as solid acidic ion exchange resins and molecular sieves. Lower alkanols, especially methanol, are preferred for the esterification. The response will be without substantial Quantities of water carried out because the water had an equilibrium shift from the ester side to the side the free acid causes. Water is natural at the Esterification reaction released when an alcohol is used as a reactant. Hence it becomes desirable

- / ti. 56 124

be to this water during the course of the reaction remove.

The reaction is carried out in the presence of a suitable solvent such as a lower alkanol. Wherever desirable, the reaction can be carried out with an excess of the esterifying agent as a solvent or cosolvent, such as methanol. The reaction temperature. should be in a range from 0 to 100 ^° C., in particular between 30 and 80 ^° C.

Any suitable base for converting the sulfonium salt into the corresponding ylide can be used for reaction c) will. The base can be organic in nature, for example a tertiary amine such as triethylamine, or an alkali metal oxide such as sodium or potassium t-butoxide, but also of an inorganic nature, for example it can be an alkaline metal hydroxide or a carbonate. Basic ion exchange resins can can also be used. Alkali metal hydroxides, lower alkoxides and carbonates are preferred. Preferably at least an equivalent amount of base is used relative to that of the sulfonium salt. The number the equivalents of base per mole of the sulfonium salt is preferably in the range from 1 to 5, in particular it moves between 1.2 to 3. The suitable temperature range is between 0 and 100 "C, in particular between 0 and 40 ° C. The reaction is carried out in the presence of an inert solvent, for example a hydrocarbon compound such as toluene, a halogenated hydrocarbon compound such as dichloromethane, an ether such as diethyl ether or dimethoxyethane or an alcohol, especially a lower alkanol, such as methanol. The base can be

tion medium be soluble, but it can also be used as a solid. Water can, if desired, in be present in the reaction mixture, but the reaction is generally carried out in the non-aqueous phase. The use of alcoholic solvents is particularly preferred. When using an alcohol as a solvent or an alkoxide as a base, a transesterification of the ester group in the sulfonium salt can take place, so that the ester group that results from the process of the invention is not necessarily is the same as that introduced by reaction b) of the process.

Reaction c) is preferred under a protective gas atmosphere, for example under nitrogen.

In reaction d) the ylide resulting from reaction c) is reacted with an olefin VI. The molar weight ratio of olefin to ylide is not critical and, if the olefin is liquid, it can be used in excess as a solvent for the reaction. However, a molar weight ratio of olefin to ylide in the range from 1: 1 to 6: 1, in particular 1.05: 1 to 2: 1, is preferred. Suitable solvents which can be used are those which have already been described in reaction c). The reaction temperature is expediently in a range from 0 to 100 ^° C., in particular between 30 and 90 ^° C., the reaction also being carried out under a protective gas atmosphere.

The ylide obtained in accordance with reaction c) can first be worked up before reaction d) is carried out, however, the ylide is preferably reacted in situ with the olefin VI. This can be done by reacting the sulfonium salt with a base in one, to convert the

- A3 . 56

Main part of the salt to the ylid are carried out for an adequate period of time, after which the olefin of the reaction mixture is admitted. Alternatively, the olefin is preferably converted to the sulfonium salt at the same time or before the base is added so that it can react with the ylide immediately after it is formed.

According to a particularly preferred embodiment of the process according to the invention, reactions b), c) are and d) all in the presence of the same solvent without intermediate isolation of the reaction products carried out. Lower alkanols are particularly suitable for this process.

Upon completion of the reaction of the ylid with the Olefin, the reaction mixture is worked up by means of a suitable method. The recovered cyclic Sulphide is fed back into reaction a). When using a sulfide and an olefin with similar boiling points, as is the case with the use of thiolane and mesityl oxide, it proves beneficial to have a Not to attempt to separate the two compounds, but to return them to reaction a) immediately. If a sulfide and an olefin with different boiling points are used, these can be separated Components are done at this point, but generally this is not necessary. In contrast to the reaction of a thiolane with a haloacetic acid ester results in the presence of an olefin in step a) of the reaction no serious detrimental effects.

After the reaction a) remaining cyclic sulfide and olefin evaporated or from the Reaction mixture extracted, worked up and fully or partially for use in reaction d) re

56 124

be cyclized, - if an olefin is present. Unreacted, cK -substituted acetic acid and the sulfonium salt product can then be separated from one another, for example by precipitating the sulfonium salt from the solution.

example 1

Step a) of the method according to the invention.

A mixture of chloroacetic acid (295 g, 3.12 mol), thiolane (90 g, 1.02 mol) and water (100 ml) are stirred at 5O ⁰ C for 2 hours, and the water is then removed under reduced pressure. Acetone is then added. The remaining precipitate was identified as the desired product hydroxycarbonylmethyltetramethylene sulphonium chloride with the aid of NMR spectroscopy and isolated in 81% yield. The formula of the compound is:

\ ⁺ CH2- CO ₂ H Cl®

By replacing the Thiolans by 1,4-oxathiane and stirring the reaction mixture overnight at 55 ⁰ C is obtained the corresponding sulfonium salt in'einer yield of 95%. 25th

Repeating this general method using thiolane in the presence of an equimolar amount of Mesityl oxide gives the desired reaction product in 82% yield after a reaction time of 4 hours. 30th

Analogous processes can be used for the preparation of the corresponding bromide salts.

Example 2
Step b) of the method according to the invention.

56

A solution of hydroxycarbonylmethyltetramethylensialfonium chloride (5.0 g, 28 mmol) in 20 ml of methanol is saturated with dry HCl at room temperature and ^{stirred at 50 °} C. for 45 minutes. The volatile substances are stripped off under reduced pressure, leaving an oily residue. NMR recordings show that the product is methoxycarbonylmethyltetramethylene sulfonium chloride. The yield was 87%.

Using a similar procedure, the 1,4-oxathiansulfonium salt converted into its methyl ester with 75% yield.

Analogous processes can be used for the preparation of the corresponding ethyl esters and for the preparation of bromide salts be used.

Example 3

Steps c) and d) of the method according to the invention.

A mixture of Ethoxycarbonylmethyltetramethylensulfoniumbromid (7.7 g, 30 mmol), chloroform (25 ml) and saturated aqueous potassium carbonate solution (18 ml) is ml at 0 to 5 ⁰ C with simultaneous dropwise addition of 50% aqueous sodium hydroxide solution (2.4, 30 mmol) stirred. The temperature is then increased to 2O ⁰ C and it is stirred for another 15 minutes. The mixture is filtered and the upper chloroform layer is dried over potassium carbonate and evaporated under reduced pressure. The residue, as the NMR recording shows, is the ylid:

J) S® - ⁹ CH - CO ₂ C ₂ H ₅ Yield: 67 %.

56

A mixture of this ylide (1.20 g, 5.2 mmol), mesityl oxide (1.0 g, 10.3 mmol) and toluene (2.5 ml) is added at 80 ° C Stirred for 6 hours. As the quantitative gas chromatographic analysis of the reaction mixture shows, there is this with 83% yield from ethyl 2,2-dimethyl ~ 3-acetylcyclopropancafbonxylat, which is predominantly in its trans isomeric form. When repeating this procedure using chloroform and t-butanol as solvents in place of toluene gives a yield of 69% and 60% respectively.

The repetition of the two reactions mentioned above using the 1,4-oxathiane compound as starting material gives the corresponding ylide with 85% yield and the cyclopropane compound with 71% yield.

Analogous procedures can be used for the corresponding chloride salts and the methyl esters.

A mixture of ethoxycarbonylmethyltetramethylene sulfonium chloride (1.05 g, 5 mmol), mesityl oxide (1.45 g, 15 mmol) and t-butanol (1.3 ml) is stirred on an ice / water bath while potassium t-butoxide (0 , 56 g) is added within 4 minutes. Is stirred for another 15 minutes then, after the temperature to 5O ⁰ C over a period of time is increased by one hour. The mixture is then stirred ^{at 50 °} C. for a further 12 hours. After cooling, toluene is added and the mixture filtered. The quantitative analysis by gas chromatography shows that the filtrate consists of ethyl 2,2-dimethyl-3-acetylcyclopropanecarboxylate with a yield of 60%.

XI12 8

Claims (7)

Claims 10 15 20 25 C (1-8) alkyl, benzyl, phenyl, alkylphenyl or halophe 1 2
nyl or R and R together are a C (2-7) alkylene group, and in which each Z 3 4
depending on each other CO ₂ R, COR, CHO, CH, and Z NO ₂ or independent 5 SO ₂ R and represent, or in one of the groups of Z ζ have this meaning and the other means R, 1 2
or in which Z and Z together with the carbon atom in between is a cyclopentadienyl or benzo 3 4 represent the cyclopentadieny group in which R, R and R is independently C (1-8) alkyl _f phenyl, alkylphenyl or halophenyl, and R is hydrogen, C (1-8) alkyl, phenyl, alkylphenyl or halophenyl and has the following reaction steps: a) reaction of a cyclic sulfide the general formula CH ₂ - CH ₂ A "^ S (IV) CH ₂ - CH ₂ - 2 - 56 124 at A a direct C-C bond, a CH “group Represents a sulfur atom or an oxygen atom, with a -substituted acetic acid of the general formula X- CH ₂ - CO ₂ H (V) with X as the leaving group. b) conversion of the resulting compound into an ester,
c) Implementation of the resulting compound with a base to produce the corresponding ylide and d) reaction of the ylide with an olefin of the general formula Λ / C = Ό (VI) 12 1 2
where R, R, Z and Z have the same meaning as in general formula III. 2. The method according to claim 1, characterized in that X is an organic sulfonyl group, a hydroxyl group or is a chlorine or bromine atom. 3. The method according to any one of claims 1 or 2, characterized in that 12 12 that R and R a methyl group, Z and Z together with the carbon atom in between a cyclopentadienyl or represent benzocyclopentadienyl group, 1 2 3 or Z is a hydrogen atom and Z is a CO "R - or 4th
COR group. - 3 - 56 124 4. The method according to claim 3, characterized in that the olefin of formula VI is mesityl oxide. 5. The method according to claim 4, characterized in that the compound of formula IV is a thiolane and that thiolane recovered in reaction d) for use in reaction a) with the addition of unreacted mesityl oxide is recycled. 6. The method according to claim 5,
characterized , that after the end of the reaction a) any thiolane and mesityl oxide are evaporated or extracted from the reaction mixture and unreacted compounds of the formula V and the sulfonium salt product are separated from one another by precipitating the sulfonium salt from the solution.
20th 7. The method according to any one of claims 1 to 6, characterized in that no work-up between reaction steps c) and d) takes place and the olefin to the sulfonium salt formed from reaction step b) simultaneously or is added before the base. 91X1128