DE3225605C2 - - Google Patents

Description

Certain cyclopropane derivatives have extreme insecticides Properties on. Accordingly, many studies have been carried out with regard to the synthesis possibilities for the representation of Compounds with suitable substituted cyclopropyl groups carried out. Many works deal with the Reaction of sulfur ylides and olefins to form the cyclopropane ring. For example, G.B. describes Payne in the Journal of Organic Chemistry 32 33 51 (1967) the use of ylides, the derived from dimethyl sulfide, and other research groups already have the same or similar ones Ylide uses. Indeed, these ylids work well for Representations on a laboratory scale, however, they are suitable for generally not for large-scale representations their - and their precursors, the sulfonium salts - low thermal stability. In addition, the Handling of dimethyl sulfides on an industrial scale due to problems of volatility.

GB-PS 15 53 153 describes one Attempt to solve these problems and revealed that certain Cyclopropane derivatives by reaction of thiolan with m-phenoxybenzyl or a C (1-4) alkyl ester of Chloro or bromoacetic acid can be represented by the resulting sulfonium salt into the corresponding one  Ylid converted by reaction with a base and with an appropriately substituted olefin is implemented. This process shows several advantages compared to the originally proposed method of Payne. However, problems remain. It exists Data showing that thermal decomposition of the sulfonium salt derived from thiolan reversible runs, but a closer look shows this Data (Example 2 of this description) that only half of the original starting material after heating preserved in acetone for one hour.

One of the problems in the reaction of thiolan with haloacetic acid esters is that always a ring opening for Connection I is made. In addition, especially at Presence of thiolan in excess, compound II educated.

Hal- (CH₂) ₄-S-CH₂-CO₂R (I)

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

Furthermore, it is found that when using mesityl oxide as an olefin to prepare an ester of 2,2-dimethyl 3-acetylcyclopropanecarboxylic acid, which is a precursor of insecticides of the pyrethroid type with a 2,2-dimethyl 3- (2,2-dihalovinyl) cyclopropyl part is (see see the example in DE-OS 26 39 777), in practice Difficulties arise when trying to do this To carry out the process on an industrial scale in an economical manner. Thiolan is used during the reaction of the ylide with mesityl oxide recovered and because of its high price  economic circumstances force it for the reaction is fed again with the halogen acetate. As well it is desirable to add unreacted mesityl oxide recycle. In practice it is not possible to do that recovered thiolane from unreacted mesityl oxide to separate because their boiling points are very high at 120 and 129 ° C lie close together so that a mixture of thiolan and mesityl oxide must be recycled. However found that in the presence of mesityl oxide the reaction rate of thiolan with halogen acetate decreases significantly and in addition the selectivity for the desired product is reduced. This problem naturally occurs Use any olefin if difficult to be separated from thiolan.

The object of the invention is to provide a method with a favorable reaction rate and selectivity leads to the desired products under conditions can be carried out where an economic Recycling of the reactants is possible.

The inventive method is in claim 1 above characterized. Special designs are Subject of the subclaims.  

Preferably R1 and R2 are independently a hydrogen atom or a lower alkyl group. Still R1 and R2 in the form of a methyl group are more suitable.

Preferably Z 1 and Z 2 stand together with the neighboring one Carbon atom for a cyclopentadienyl or benzocyclopentadienyl group or Z¹ represents a hydrogen atom and Z² for a CO₂R³ or COR⁴ group, wherein R³ and R⁴ have the meaning given above and preferably represent lower alkyl groups. Particularly preferred are Z¹ as a hydrogen atom and Z² as an acetyl group.

Therefore, a particularly preferred olefin of formula VI for use in the process according to the invention mesityl oxide, in particular R¹ and R² methyl groups mean and Z¹ for a hydrogen atom and Z² for one Acetyl group stand.

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

The direct reaction product after reaction a) can be a sulfonium salt (VII) or a zwitterionic compound (VIII) plus HX, which of course depends on the basicity of the anion X ^- and the pH of the reaction mixture.

Suitable leaving groups X are organic sulfonyl groups, for example methylsulfonyl, phenylsulfonyl or p-toluenesulfonyl groups, hydroxyl groups and especially chlorine or bromine atoms.

Here, the term "lower" means the alkyl group or one 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 at a temperature range between 0 and 100 ° C, in particular performed between 30 and 80 ° C. The molar ratio the reactant is not critical. To Increasing the reaction rate is generally an excess used on one of the reactants. This lies usually in a range of 0.1 to 3 moles of excess per mole of other reactant. Other reactants can also be used in excess.  

However, the α- substituted acetic acid is preferably used in excess.

The reaction is suitably carried out in the acidic pH range Presence of a solvent, especially one highly polar solvent, for example water, one Carboxylic acid - like acetic acid -, an alcohol - like Methanol - or a cyanide - such as acetonitrile - performed. Aqueous reaction media are particularly suitable, taking the water alone or in a mixture with one water-miscible cosolvent, for example one low alkanol, such as methanol, is used. Conveniently becomes an excess of one of the reactants used as a solvent.

The esterification reaction b) can be carried out with any suitable Method, for example by direct Reaction with an alcohol or an olefin, or by a transesterification with an ester in the presence of a acid catalyst. A sulfonium salt VII correspondingly Reaction a) has been presented, is of course one Acid and can therefore act as an acid catalyst itself, however, this acid becomes during the course of the reaction removed so that additional acid is preferably added becomes. Suitable acids include organic acids, such as p-toluenesulfonic acid, mineral acids, such as hydrogen halide and sulfuric acid, and solid acidic ion exchange resins and molecular sieves. Lower alkanols, especially methanol, are used for esterification prefers. The reaction is without essential Amounts of water carried because the water is a Balance shift from the ester side to the side free acid. Water is of course used in the Esterification reaction released when an alcohol as Reactant is used. Therefore, it becomes desirable  be this water during the course of the reaction remove.

The reaction is carried out in the presence of a suitable solvent, for example a low alkanol, carried out. Where it appears desirable, the Reaction with an excess of the esterifying agent as Solvents or cosolvents are carried out for example with methanol. The reaction temperature should be in the range of 0 to 100 ° C, especially between 30 and 80 ° C.

Any suitable base for conversion can be used for reaction c) of the sulfonium salt used in the corresponding ylide will. The base can be organic in nature, for example a tertiary amine such as triethylamine, or an alkali organo oxide, for example sodium or Potassium t-butoxide, but also of an inorganic nature, for example can it be an alkali hydroxide or -carbonate. Basic ion exchange resins can can also be used. Alkali metal hydroxides are preferred, low alkoxides and carbonates. Preferably becomes relative at least an equivalent amount of base used to that of the sulfonium salt. The number the equivalents of base per mole of the sulfonium salt preferably in the range of 1 to 5, especially it ranges from 1.2 to 3. The appropriate temperature range is between 0 and 100 ° C, in particular between 0 and 40 ° C. The reaction is in the presence 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 in the reaction medium  be soluble, but it can also be a solid be used. Water can, if desired, in the reaction mixture will be present, however, in general the reaction was carried out in the non-aqueous phase. In particular, the use of alcoholic is preferred Solvents. When using an alcohol as a solvent or an alkoxide as a base, one Transesterification of the ester group take place in the sulfonium salt, so that the ester group, which is according to the invention Procedure does not necessarily result is the same as introduced by reaction b) of the process has been.

Reaction c) is preferably carried out under a protective gas atmosphere, for example, carried out under nitrogen.

In reaction d), the result of reaction c) is Ylid implemented with an olefin VI. The molar ratio from olefin to ylid is not critical and, if the olefin is liquid, this can be in excess can be used as a solvent for the reaction. Prefers however, becomes a molar ratio of olefin to ylide in the range from 1: 1 to 6: 1, in particular 1.05: 1 to 2: 1. As a suitable solvent those are used which have already been described in reaction c) are. The reaction temperature moves favorably in a range from 0 to 100 ° C, in particular between 30 and 90 ° C, the reaction also under a protective gas atmosphere is carried out.

The ylide obtained in accordance with reaction c) can before Carrying out the reaction d), are first worked up, however, the ylide is preferred in situ with the olefin VI implemented. This can be done by reaction of the sulfonium salt with a base in one to convert the  Most of the salt at ylid adequate time be carried out, then the olefin of the reaction mixture is added. Alternatively, that will Olefin preferably to the sulfonium salt at the same time, or before the base is added, so that it can react directly with the ylid formed.

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

After completion of the reaction of the ylide with the olefin the reaction mixture worked up. The recovered cyclic Sulfide is returned to reaction a). Using a sulfide and an olefin with similar boiling points, like this when using thiolan and mesityl oxide the case is, it turns out to be cheap, one Not trying to separate the two connections at all but instead to immediately return them to reaction a). When using a sulfide and an olefin with different Boiling points can separate these Components are made at this point; is in general however, this is not necessary. In contrast to the reaction of a thiolane with a haloacetic acid ester the presence of an olefin in step a) of the reaction no adverse effects.

After reaction a) is complete, residual cyclic sulfide and olefin can be evaporated or extracted from the reaction mixture, worked up and completely or partially recycled for use in reaction d) if an olefin is present. Unreacted α- substituted acetic acid and the sulfonium salt product can then be separated from one another, for example by precipitation of the sulfonium salt from the solution.

example

a) a mixture of chloroacetic acid (295 g, 3.12 mol), Thiolan (90 g, 1.02 mol) and water (100 ml) were added Stirred at 50 ° C for 2 hours and then the water deducted under reduced pressure. Then was Acetone added. The remaining precipitation was with Using NMR spectroscopy as the desired product Hydroxycarbonylmethyltetramethylene sulfonium chloride identified and isolated in 81% yield. The formula the connection is:

When replacing the thiolane with 1,4-oxathian and stirring the Reaction mixture overnight at 55 ° C was obtained corresponding sulfonium salt in a yield of 95%.

Repeating this general method when used of thiolan in the presence of an equimolar amount of Mesityl oxide gave the desired reaction product after 4 hours with 82% yield.

Analog processes can be used to manufacture the corresponding Bromide salts are used.  

b) A solution of hydroxycarbonylmethyltetramethylene sulfonium chloride (5.0 g, 28 mmol) in 20 ml of methanol was added dry HCl saturated at room temperature and at 50 ° C stirred for 45 minutes. The volatile substances were removed under reduced pressure, with a oily residue remained. NMR images showed that the Product methoxycarbonylmethyltetramethylene sulfonium chloride was. The yield was 87%.

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

Analog procedures can be used to represent the corresponding Ethyl ester and for the production of bromide salts be used.

c) A mixture of ethoxycarbonylmethyltetramethylene sulfonium bromide (7.7 g, 30 mmol), chloroform (25 ml) and saturated aqueous potassium carbonate solution (18 ml) was added 0 to 5 ° C with simultaneous dropping of 50% aqueous sodium hydroxide solution (2.4 ml, 30 mmol) touched. The temperature was then raised to 20 ° C and stirred for a further 15 minutes. The mixture was filtered, the upper chloroform layer over Potassium carbonate dried and evaporated under reduced pressure. The NMR recording showed that the residue was the ylid:

Yield: 67%.  

d) A mixture of this ylide (1.20 g, 5.2 mmol), mesityl oxide (1.0 g, 10.3 mmol) and toluene (2.5 ml) was at 80 ° C Stirred for 6 hours. Like the quantitative gas chromatographic Analysis of the reaction mixture showed passed this with 83% yield from ethyl 2,2-dimethyl-3-acetylcyclopropanecarboxylate, the predominantly in its transisomeric Form was present. When repeating this procedure using chloroform and t-butanol as A solvent was obtained instead of toluene of 69% and 60%.

Repeating the above two reactions below Use of 1,4-oxathian compound as a starting material gave the corresponding ylide in 85% yield and the cyclopropane compound in 71% yield.

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

A mixture of ethoxycarbonylmethyltetramethylene sulfonium chloride (1.05 g, 5 mmol), mesityl oxide (1.45 g, 15 mmol) and t-butanol (1.3 ml) were on an ice / water bath stirred while potassium t-butoxide (0.56 g) within of 4 minutes was added. Subsequently, for stirred for a further 15 minutes and then the temperature increased to 50 ° C over a period of one hour. The Mixture was then stirred at 50 ° C for an additional 12 hours. After cooling, toluene was added and the Filtered mixture. The quantitative gas chromatographic Analysis showed that the filtrate in 60% yield consisted of ethyl 2,2-dimethyl-3-acetylcyclopropane carboxylate.

Claims (6)

1. Process for the preparation of a cyclopropanecarboxylic acid ester of the general formula in which R represents C (1-6) alkyl, R¹ and R² independently of one another represent hydrogen, C (1-8) alkyl, benzyl, phenyl, alkylphenyl or halophenyl or R¹ and R² together represent a C (2-7) alkylene group represent and in which each Z¹ and Z² independently represent CO₂R³, COR⁴, CHO, CN, NO₂ or SO₂R⁵ or in which one of the groups of Z¹ and Z² has this meaning and the other means R⁶, or in which Z¹ and Z² together with the intermediate carbon atom represents a cyclopentadienyl or benzocyclopentadienyl group in which R³, R⁴ and R⁵ independently of one another are C (1-8) alkyl, phenyl, alkylphenyl or halophenyl and R⁶ is hydrogen, C (1-8) alkyl, phenyl, alkylphenyl or Halophenyl, characterized in that

• a) a cyclic sulfide of the general formula in which A represents a direct CC bond, a CH₂ group or an oxygen atom, with an α- substituted acetic acid of the general formula X-CH₂-CO₂H, (V) in the X an organic sulfonyl group, a hydroxyl group or a chlorine or bromine atom is implemented
• b) the sulfonium salt of the general formula obtained or the zwitterionic compound of the general formula obtained in which A and X have the meaning given above, esterified with a lower C (1-6) alkanol,
• c) the ester obtained is treated with a base and
• d) the ylide obtained with an olefin of the general formula in which R¹, R², Z¹ and Z² have the same meaning as in the general formula III.

2. The method according to claim 1, characterized in that R¹ and R² are methyl groups, Z¹ and Z² together with the one in between Carbon atom is a cyclopentadienyl or benzocyclopentadienyl group represent, or Z¹ represents a hydrogen atom and Z² are a CO₂R³ or COR⁴ group. 3. The method according to claim 2, characterized in that the olefin general formula VI is mesityl oxide. 4. The method according to claim 3, characterized in that the connection of the general formula IV is thiolane and that one in reaction d) Regraded thiolane for use in the reaction step a) recycled with unreacted mesityl oxide. 5. The method according to claim 4, characterized in that after the reaction a) any excess thiolane and mesityl oxide is evaporated or extracted from the reaction mixture and the converted α- substituted acetic acid of the general formula V and the sulfonium salt of the general formula VII by precipitation of the Separates sulfonium salt from the solution. 6. The method according to any one of claims 1 to 5, characterized in that between the Reaction steps c) and d) not worked up and you do that Olefin to the sulfonium salt formed in reaction step b) adds simultaneously with or in front of the base.