GB2095660A - A process for the preparation of oxadiazolidine derivatives - Google Patents

Abstract

A method for the continuous semi-continuous or batchwise production of oxadiazolidine derivatives having the general formula (I), <IMAGE> wherein R<1> and R<2> represent an aromatic or heteroaromatic group or a straight- chained, branched or cyclic, saturated or unsaturated C1-6 aliphatic hydrocarbyl group wherein a hydroxylamine derivative R'NHOH is first reacted with an isocyanate R<2>NCO in a water-miscible solvent at a pH of between 4 and 7.5 to form a free urea derivative HONR<1>CONHR<2> which is then reacted with an alkyl chloroformate to produce a substituted urea of the formula <IMAGE> in the presence of an aqueous solution of a base. The alkyl chloroformate is introduced either simultaneously or prior to the base such that the pH of the reaction mixture does not exceed 8. Finally the substituted urea is subjected to ring closure by adjusting the pH of the mixture between 9 and 10.5. The intermediates need not be isolated.

Description

SPECIFICATION A process for the preparation of oxadiazolidine derivatives The invention relates to a new method for the preparation of 1 2,4-oxadiazolidine derivatives. It is known that certain 1 2,4-oxadiazolidine compounds can be applied as active agents of agrochemical compositions and as intermediates in the production of dyestuffs (published German patent applications Nos. 1,542,820 and 1,695,592; Hungarian patent specifications Nos. 1 56,432 and 1 56,669).

According to the known methods for the preparation of 1 2,4-oxadiazolidine derivatives, an alkyl hydroxylamine or phenyl hydroxylamine is reacted with an isocyanate or a chloroformate, and then the resulting N-hydroxyurethane or N-hydroxyurea is treated with an isocyanate or a chloroformate to form the intermediate addition compound capable of ring closure [Archiv der Pharmazie 294, 764 (1961), 296,420 (1963), 298, 580 (1965); Hungarian patent specifications Nos. 156,669 and 156,432, etc.j.

Thus according to the above methods phenyl hydroxylamine is reacted with an alkali isocyanate in the presence of ether, benzene or dioxane, the resulting N-hydroxyurea derivative is isolated, converted into its alkali salt in an aqueous alkaline medium, and the resulting salt is reacted with a chloroformate.

The individual steps of the above process are complicated, the use of ether or benzene is hazardous and less advantageous on industrial scale, and the yields are not satisfactory. A similar method is described in the published German patent application No. 1,695,592, wherein the first step is performed in tetrahydrofuran or dioxane medium for 24 hours, the solvent is then removed, the residue is recrystallized, the resulting urea derivative is converted into its alkali salt in aqueous ethanol, and this salt is reacted with an alkyl chloroformate. The resulting product must be recrystallized to remove the by-products formed, and neither the yield nor the quality of the product is acceptable.

The desired compounds can also be prepared by reacting a phenyl hydroxylamine derivative with N-methyl-chlorocarbonyl urethane (published German patent application No. 1,670,299). A disadvantage of this method is, however, that the production of the chlorocarbonyl urethane from phosgene requires specific care and expensive apparatuses.

The hydroxylamine derivatives applied as starting substances can be prepared e.g. by reducing the corresponding nitro compounds [J.Am. Chem. Soc.41, 279 (1919), published German patent application No. 1,951,880]. Taking into account, however, that various by-products (such as nitrosobenzene, p-aminophenol, phenyl hydroxylamine, aniline, azoxybenzene, azobenzene, hydrazobenzene, etc.) form easily in this reaction, the phenyl hydroxylamines are difficult to isolate, and the reduction is not sufficiently selective. It has also been suggested to perform electrochemical reduction utilizing specific silver/amalgam electrodes and a diaphragm, and then to react the resulting phenyl hydroxylamine directly, i.e. without isolation, with N-carbomethoxy-carbaminic acid chloride described in the published German patent application No. 1 ,670.299.Applying this method, 1,2,4- oxadiazolidinedione derivatives can be prepared under nitrogen atmosphere within a period of about 24 hours. The authors also disclose (published German patent application No. 2,262,851) that nitrogen atmosphere should be appli.ed in order to suppress the formation of by-products. This method is difficult and expensive.

Now it has been found that the desired oxadiazolidine compounds can be prepared by a much simpler method with good yields. The new method can be performed easily and economically under plant conditions, if desired, under continuous operation. According to the new method of the invention the isolation of the intermediates, some of them bejng detrimental to health and having allergenic and vesicant effects, can be avoided.

The invention relates to a method for the continuous, semi-continuous or batchwise production of oxadiazolidine derivatives having the general formula (I),

wherein R1 and R2 represent an aromatic or heteroaromatic group (preferably a phenyl group, having optionally one or more halogen, C14 alkyl or C14 alkoxy (substituents) or a straight-chained or branched or cyclic, saturated or unsaturated aliphatic hydrocarbyl group having up to 6 carbon atoms, by reacting the respective hydroxylamine derivative (prepared optionally from the appropriate nitro compound by reduction) with an isocyanate derivative and a chloroformate.According to the invention one proceeds so that a hydroxylamine derivative of the general formula (II), R1-NH-0H (11) wherein R' is as defined above, is reacted with an isocyanate derivative of the general formula (III), R2--NCO (Ill) wherein R2 is as defined above, in a water-miscible solvent while maintaining the pH of the mixture between 4 and 7.5.Then an aqueous solution of a base is added to the reaction mixture, which contains the resulting free urea derivative of the general formula (IV),

wherein R1 and R2 are as defined above, and an alkyl chloroformate (introduced either simultaneously or before the base at such a rate that the pH of the reaction mixture does not exceed 8) to produce a substituted urea derivative of the general formula (V),

wherein R1 and R2 are as defined above and R3 is a C14 alkyl group. The latter is subjected to ring closure by adjusting the pH of the mixture between 9 and 10.5.

An important feature of the invention is the recognition that one of the key substances of the above synthesis is the N-hydroxyurea of the general formula (IV). According to the methods known so far this compound was isolated in free state, optionally purified, then converted into its alkali salt (generally in aqueous ethanolic medium), and the salt was reacted with an alkyl chloroformate. We have observed that certain decomposition products appear in the salt formation step: i-e. azo- and azoxy compounds are formed in alkaline medium, which are detrimental to health and cause allergic reactions.

According to the invention the isocyanate is added to the hydroxylamine of the general formula (II) in the presence of a water-miscible solvent, preferably isopropanol, while maintaining the pH of the reaction mixture between 4 and 7.5, preferably between 5 and 5.5.

The alkyl (e.g. C14 alkyl) chloroformate is reacted with the intermediate (IV) in the next step. This addition reaction can proceed only in the presence of a certain amount of an alkaline agent in the system. However, in contrast to the known methods, the alkaline agent is not introduced into the system before the introduction of the chloroformate, i.e. the urea compound of the general formula (IV) is not converted into its salt. In spite of this, the compound of the general formula (IV) is prepared while maintaining the pH of the mixture at an appropriately acidic level, by adding a mineral acid (hydrochloric acid, sulfuric acid, phosphoric acid) to the reaction mixture simultaneously with the addition of the isocyanate.Under continuous operation it is preferable to introduce a part or the total amount of the alkyl chloroformate, required in the next step, either before or simultaneously with the addition of the isocyanate. The alkyl chloroformate serves here as a pH regulating agent, i.e. it assists in ensuring the appropriate acidic medium during the carbamoylation step. In the next step, where the alkyl chloroformate is a reactant, the reaction sets in only under the effect of an alkaline agent, and, owing to the uniform feeding rate of the alkali, the reaction proceeds smoothly and selectively in the required direction. Thus a free N-hydroxyurea compound of the general formula (IV) is converted into the derivative of the general formula (V), and there is no need to isolate the urea compound of the general formula (1V) and converting it then into its alkali salt.In this way the side reactions occurring upon digesting the urea compound with an alkali and the formation of by-products detrimental to health can be avoided.

Thus, some or all of the chloroformate required should desirably be present in the reaction mixture after the feeding in the isocyanate, and the introduction of the aqueous alkali should only be started thereafter. It is preferred to use aqueous alkali metal hydroxides or carbonates, such as sodium hydroxide, sodium carbonate, potassium hydroxide or potassium carbonate.

According to a variant of the new method the synthesis is started with the preparation of the hydroxylamine of the general formula (it), applied as starting substance. In this instance it is preferred to prepare the hydroxylamine derivative by reducing a nitro compound of the general formula (VI), R1-N02 (Vi) (wherein R1 is as defined above), for example with hydrazine hydrate in the presence of a supported palladium catalyst.

As support e.g. charcoal, pumice stone or silica gel can be applied. The reaction is performed preferably in the presence of a C 1-4 alkanol, particularly isopropanol. When isopropanol is applied as reaction medium in the reduction step, all of the subsequent steps of the synthesis can be performed in one and the same solvent, although the mixture can be diluted by the water added.

Before starting the subsequent steps, the catalyst is removed from the reaction mixture by sedimentation, filtration or other appropriate methods. If the catalyst is allowed to settle, it is preferred to apply a catalyst with silica gel or pumice stone support. This enables one to perform the entire synthesis in the desired manner, i.e. either batchwise in a single apparatus, or semi-continuously in two apparatuses, or even continuously, by applying a cascade-connected system.

The synthesis steps, starting from the nitro compound or from the hydroxylamine derivative, can be performed according to the invention in a completely continuous operation as described below: It is preferred to use a C14 allcanol, particularly isopropanol, as solvent medium for the continuous procedure. The synthesis can be performed in a cascade system, in which the individual reaction steps may be performed in reaction units comprising one or more reaction vessels. Such equipment is shown diagrammatically in the drawing, which is described in more detail below, in Example 2.The reduction is performed in the first group of reactors 1-3, the reaction with isocyanate in the next unit (unit 4), the addition of chloroformate in the next unit (unit 5), the cyclization in the next unit (unit 6), and then the product is crystallized in the last unit (unit 7) of the system. Hydrazine hydrate, the catalyst and the nitro compound are fed continuously into the first reactor (1) of the first group whereas the isocyanate and, if desired, a p1-: regulator are added into the first reactor (4) of the next unit. When a chloroformate is applied as pH regulating agent, a part or the total amount of the chloroformate required in the synthesis is introduced into reactor 4.Most of the chloroformate may be fed into the next unit (unit 5), where the addition reaction of the chloroformate is performed while introducing the required amount of an aqueous alkali. Cyclization is performed in the next unit (6) by introducing additional amounts of an aqueous alkali, the reaction is complete either in the same unit or in the next reactor (unit 7), and then the product is crystallized in reactor 7.

The reaction mixture is continuously moved through the individual units by suction or pressure. If desired, a filter can be installed after the reduction unit, consisting of reactors 1, 2 and 3, to remove the catalyst. When the catalyst is removed by sedimentation, the reduction unit may consist of further vessels, in which sedimentation can also be performed. After the last unit, the crystalline product is filtered off. The individual reactors can be provided with appropriate stirrers.

The process of the invention can also be performed batchwise or semi-continuously as follows: When a nitro compound is used as starting material it is preferred to perform the synthesis in two reactor units. Starting from the hydroxylamine, the reaction sequence proceeds in a single unit.

Reduction is performed in a first reactor equipped with a stirrer. The catalyst is introduced into the apparatus at the start of the process. The nitro compound and the hydrazine hydrate are fed in parallel, as solutions in a water-miscible solvent. At the end of the reaction the catalyst is allowed to settle, and the mixture is passed into the second reactor. isocyanate, chloroformate and finally the base are introduced into the second reactor in the given sequence, and at the end of the reaction the product is crystallized in this apparatus as well. In the meantime the nitro compound and the hydrazine hydrate required in the next batch are fed onto the catalyst bed remaining in the first reactor.

The series of reactions starting with reduction can also be performed in a single apparatus by immersing the catalyst into the mixture to be reduced in a perforated vessel (filter bag), and when reduction is over, removing the catalyst from the system. With this technique the intensity of stirring should be increased.

The products obtained according to the invention are of high purity, and can be formulated directly, i.e. without any further purification step (recrystallization, precipitation, chromatography, etc.), into herbicides.

The invention is elucidated in detail by the aid of the following non-limiting Examples.

EXAMPLE 1 50 litres of isopropanol, containing 7.8 kg of 3,4-dichlorophenyl-hydroxylamine, are fed into a jacketed reactor, 150 litres in capacity, equipped with a stirrer. The pH of the mixture is checked and, if required, adjusted to 4.5 to 6 with hydrochloric acid or methyl chloroformate. 3 kg (3.3 litres) of methyl isocyanate are added to the mixture cooled to OOC, and then the mixture is stirred for 30 minutes.

Thereafter 5.55 kg (4.5 litres) of methyl chloroformate are added to the isopropanol solution o-, the resulting hydrnxyurea compound, and then a 5% aqueous solution of sodium hydroxide (75 kg) is added to the mixture over 2 hours, under cooling and stirring. The cooling efficiency is adjusted so that the reaction temperature should not rise above 1 00C. The reaction mixture is cooled then to 0 C and the product is filtered off on a centrifuge. 10.7 g of 2-(3,4-dichlorophenyl)-4-methyl-1 ,2,4-oxadiazolidina- 3,5-dione are obtained.

EXAMPLE 2 A continuous process is performed in the equipment shown schematically in the drawing. The equipment consists of the following: 1: reactor, Vu = 450 ml 1.1: heated feeder, 5 litres in volume, equipped with a stirrer 1.2: feeder, 2 litres in volume 2: reactor, Vu = 450 ml 3: reactor, Vu = 450 ml (sedimenter) 4: reactor, Vu = 450 ml 4.1: feeder, 2 litres in volume 4.2: feeder, 2 litres in volume 5: reactor, Vu = 900 ml 5.1: feeder, 5 litres in volume 6: reactor, Vu = 900 ml 7: reactor, Vu = 900 ml (Vu = useful capacity) The reactors are equipped with a cooling jacket and a TeflonR-coated stirrer, and they are connected in a cascade system.The last reactor (reactor 3) of the first reaction unit is used as a sedimenter.

Feeder 1.1 is filled with isopropanol containing 180 g/l of 3,4-dichloro-nitrobenzene and 10 gll of a silica gel-supported palladium catalyst. The homogeneous mixture is fed continuously, at a rate of 250 ml/h, into the reducing unit (unit 1). The next feeder (feeder 1.2) is filled with isopropanol containing 260 g/l of hydrazine hydrate, and the solution is fed continuously, at a rate of 50 ml/h, into the reducing unit (unit 1).

The cascade series is operated as follows: The isopropanol mixture of the catalyst and the 3,4 dichloro-nitrobenzene to be reduced is fed continuously, at a rate of 250 ml/h, from feeder 1.1 into reactor 1, in parallel with the isopropanol solution of the hydrazine hydrate, introduced from feeder 1.2 at a rate of 50 ml/h. The cooling of the reactor is adjusted so that the temperature is between 10 and 1 50C. When reactor 1 is full, the mixture is transferred into reactor 2, where reduction is completed under stirring and cooling. Thereafter the catalyst is separated from the isopropanol solution of the hydroxylamine compound in reactor 3, used as sedimenter, and the solution is fed at a rate of 300 ml/h into reactor 4. The catalyst settled is removed from reactor 3 through its lower discharge pipe end.A suspension containing 20 g of catalyst is removed in every two hour.

Methyl isocyanate is fed at a rate of 1 6 ml/h from feeder 4.1, and methyl chloroformate at a rate of 28 ml/h from feeder 4.2, into the mixture flowing into reactor 4. The cooling of the reactor is adjusted so that the temperature does not rise above 1 OOC. The mixture passes into reactor 5, where a 5% aqueous solution of sodium hydroxide is fed to the stirred and cooled mixture at a rate of 300 ml/h, from feeder 5.1, so that the pH of the mixture does not rise above 7.5. Thereafter the mixture is fed into reactor 6, where a 5% aqueous solution of sodium hydroxide is fed at a rate of 75 ml/h, adjusting thereby the pH of the reaction mixture to 10 to 10.5. The reaction mixture is cooled to O to 50C in reactor 7.

When the steady state of the reactor series is reached the product is filtered off hourly from the accumulated reaction mixture. 47 to 52 g/h of 2-(3,4-dichlorophenyi)-4-methyl-l ,2,4-oxadiazolidine- 3,5-dione are obtained.

EXAMPLE 3 30 g of 3,4-dichloro-nitrobenzene are dissolved in 100 ml of isopropanol, and 1.2 g of a 5% palladium-on-carbon catalyst are added to the solution. 9 ml of hydrazine hydrate, diluted previously with 1 5 ml of isopropanol, are added to the stirred mixture at 1 5-250C.

Stirring is continued until the evolution of nitrogen ceases, and then the catalyst is filtered off or allowed to settle. In the latter instance the clear solution is separated in known manner. The filtrate is cooled to O to 50C, and the pH of the solution is adjusted to 7 with some drops of sulfuric acid. 10.5 g of methyl isocyanate are fed into the reaction mixture under vigorous stirring. At the end of the carbamoylation 50 ml of water are added to the mixture, and 20 ml of ethyl chloroformate and a 10% aqueous solution of sodium hydroxide are introduced in parallel to the mixture so that the pH of the mixture is between 6 and 7. Thereafter an additional amount of alkali is added to the mixture to adjust its pH to 10.5, and the resulting suspension is stirred for 2 hours.The mixture is cooled to 50C, the solids are filtered off and washed with water and methanol.

38.8 g of 2-(3,4-dichlorophenyl)-4-methyl-1 ,2,4-oxadiazolidine-3,5-dione are obtained; m.p.: 123-1 240 C.

Analysis: calculated for C9H6C12N203: C: 41.41%, H: 2.31%, N: 10.73%, CI: 27.6%; found: C: 41.59%, H: 2.34%, N: 10.65%, CI: 26.94%.

EXAMPLE 4 One proceeds as described in Example 3 with the difference that in the cyclization step the total amount of methyl chloroformate is added to the mixture, and the 10% aqueous sodium hydroxide solution is fed in only thereafter. 38.65 g of 2-(3,4-dichlorophenyl)-4-methyl-1 ,2,4-oxadiazolidine-3,5- dione are obtained; m.p.: 122-1 240C.

EXAMPLE 5 2 g of a 5% palladium-on-silica gel catalyst (particle size: 0.1 to 0.2 mm are suspended in 70 ml of isopropanol, and a solution of 30 g of 3,4-dichloro-nitrobenzene in 30 ml of isopropanol and 9 ml of hydrazine hydrate in 1 5 ml of isopropanol are added dropwise, in parallel, to the suspension at 10 to 1 50C, under cooling and stirring. The progress of the reaction is monitored by thin layer chromatography. At the end of the reaction the stirrer is stopped and the catalyst is allowed to settle.

The clear supernatant is passed into another flask, the catalyst remained in the first flask is suspended again in 30 ml of isopropanol, the suspension is allowed to settle, and the isopropanol phase (wash) is added to the reaction mixture. The reaction mixture is cooled to 00C, 10.5 ml of methyl isocyanate are added, and the mixture is stirred for 1 5 minutes. Thereafter 20 ml of ethyl chloroformate are added dropwise to the mixture, and the pH of the mixture is adjusted then to 1 0.5 with 8% aqueous sodium hydroxide solution. The resulting suspension is stirred for 2 hours, then cooled to 50C, the solids are filtered off and washed with methanol and water. 37.2 g of 2-(3,4-dichlorophenyl)-4-methyl-1 ,2,4- oxadiazolidine-3,5-dione are obtained; m.p.: 122-1 240C.

EXAMPLE 6 3 g of a 5% palladium-on-silica gel catalyst are weighed into a bag made of filter cloth, and the bag is immersed into 70 ml of isopropanol. Thereafter a solution of 30 g of 3,4-dichloro-nitrobenzene in 30 ml of isopropanol and a solution of 9 ml of hydrazine hydrate in 1 5 ml of isopropanol are added dropwise, in parallel, to the vigorously stirred mixture. The reaction proceeds under vigorous nitrogen evolution. The end-point of the reaction is checked by thin layer chromatography, and then the reaction mixture is passed with nitrogen into a second reactor. The catalyst in the bag is rinsed with 30 ml of isopropanol. The catalyst can be used repeatedly in further processes.

Thereafter one proceeds as described in Example 5 to obtain 37.6 g of 2-(3,4-dichlorophenyl)-4 methyl- 1 ,2,4-'oxadiazoIidine-3,5ione; m.p.: 122-1 240 C.

EXAMPLES 7to 15 The compounds listed in Table 1 are prepared from the appropriate nitro compounds according to the methods disclosed in Examples 1 to 6.

TABLE 1 Compounds of the general formula (I) No. of Example R1 R2 M.p.OC 7 3,4-dichlorophenyl ethyl 106-108 8 3,4-dichlorophenyl isopropyl 96-98 9 3,4-dichlorophenyl butyl 68-70 10 3,4-dichlorophenyl cyclohexyl 135-137 11 2,5-dichlorophenyl methyl 134-135 1 2 phenyl methyl 98-99 1 3 4-chlorophenyl methyl 11 6-118 14 4-chlorophenyl allyl 56-57 15 3,4-dichlorophenyl methyl

Claims (12)

1. A method for the continuous, semi-continuous or batchwise production of an oxadiazolidine derivative of general formula (I),

wherein R' and R2 independently represent an aromatic or heteroaromatic group or a straight-chained, branched or cyclic, saturated or unsaturated aliphatic hydrocarbyl group having up to 6 carbon atoms, which comprises reacting a hydroxylamine derivative of general formula (II) R1-NH-OH (II) (wherein R1 is as defined above) with an isocyanate derivative of the general formula (III) R2-NCO (III) (wherein R2 is as defined above) in a water-miscible solvent while maintaing the pH of the reaction mixture at between 4 and 7.5, to produce a free urea derivative of the general formula (IV)

(wherein R' and R2 are as defined above); reacting the urea derivative of formula (IV) with an alkyl chloroformate in the presence of an aqueous solution of a base to produce a urea derivative of general formula (V)

(wherein R' and R2 are as defined above and R3 is a C14 alkyl group), the alkyl chloroformate being introduced into the reaction mixture either before or simultaneously with the base such that the pH does not exceed 8: and cyclizing the urea derivative of general formula (V) at a pH of 9 to 10.5 to produce a compound of formula (1).

2. A method as claimed in claim 1 wherein the hydroxylamine derivative of formula (II) is produced by reduction of a nitro derivative of the formula R1NO2, where R1 is as defined in claim 1.

3. A method as claimed in claim 2 wherein the hydroxylamine derivative (II) is not isolated from the reaction mixture prior to reaction with the isocyanate (III).

4. A method as claimed in claim 2 or claim 3 wherein the nitro derivative (Vl) is reduced in the presence of a palladium catalyst on a charcoal, silica gel or pumice support.

5. A method as claimed in any one of the preceding claims wherein the complete series of reactions is performed in the presence of a C14 alkanol solvent

6. A method as claimed in claim 5 wherein the alkanol is iso-propanol.

7. A method as claimed in any one of the preceding claims wherein the pH in the reaction between the hydroxyiamine derivative (II) and the isocyanate (III) is adjusted with the alkyl chloroformate or a mineral acid.

8. A method as claimed in any one of the preceding claims wherein the pH is maintained at between 5 and 5.5 during the reaction between the hydroxylamine derivative (II) and the isocyanate (Ill).

9. A method as claimed in any one of the preceding claims wherein R1 is a phenyl group, optionally substituted by one or more halogen, C14 alkyl or C14 alkoxy substituents.

10. A method as claimed in any one of the preceding claims, wherein the process is performed continuously in a cascade system comprising a series of reaction units comprising one or more reaction vessels, in which the hydroxylamine derivative (il) is in the produced by the reduction of the corresponding nitro compound in the first unit, reaction with isocyanate is performed in the next unit, the reaction with chloroformate in the next unit, cyclization in the next unit and crystallization in a further unit.

11. A method as claimed in claim 10 wherein the nitro compound and other reagents required for the reduction are fed continuously into the first unit, isocyanate and optionally a pH-regulating agent are fed continuously into the next unit, a chloroformate is fed continuously into the same unit or into the next unit, an aqueous alkali is fed into the next unit and the reaction is completed and the product is crystallized in the next unit, the reaction mixture continuously passing through the individual units.

12. A method as claimed in claim 2 and any of claims 3 to 9 when dependent on claim 2, wherein the process is performed semi-continuously in two reaction units, wherein reduction of the nitro derivative is performed in a first reaction unit by introducing a solution of a reducing agent and a solution of the nitro compound in parallel into the reaction unit; the catalyst is then allowed to settle; the reaction mixture is then passed to the second reaction unit; the isocyanate, an alkyl chloroform ate and then the base are fed into the second reaction unit; and the reaction is then completed and the product is crystallized, during which time the reagents required for the reduction of the next batch are fed onto the catalyst remaining in the first reaction unit.

1 3. A method as claimed in claim 1 substantially as described herein in any one of the Examples.

1 4. Oxadiazolidine derivatives of formula (I) as defined in claim 1 when produced by a method as claimed in any one of the preceding claims.