Process for producing substituted phenyl urea derivatives

Abstract

The invention relates to a novel process for producing substituted phenyl urea derivatives, in particular 3-(3,4-dichlorophenyl)-1,1-dimethyl urea.

Description

[0001] Process for the preparation of substituted phenylurea derivatives

[0002] The present invention relates to a novel process for the preparation of substituted phenylurea derivatives, in particular 3-(3,4-dichlorophenyl)-1,1-dimethylurea.

[0003] State of the art

[0004] Phenylureas are a class of selective herbicides; for example, 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) is a herbicide that inhibits plant photosynthesis. It is used for the complete elimination of plants (broad-spectrum herbicide), as well as for the protection of wood and masonry and as a coating agent.

[0005] Various approaches for the preparation of phenylurea derivatives are known in the prior art, in particular the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) from 3,4-dichlorophenyl isocyanate and dimethylamine, which are carried out either in solvents or in the melt.

[0006] In the melt processes described in DE-A-2206167 and DD-A-201140, which are carried out as semi-batch processes in stirred reactors, adequate heat removal and thus temperature control must be ensured by suitable technical measures due to the highly exothermic nature of the reaction. For this purpose, both reactants are added in a controlled dosage, which leads to the formation of undesirable by-products due to the associated long residence times at temperatures above the melting point of the product. In the case of local amine deficiency caused by insufficient mixing, the isocyanate is not converted sufficiently rapidly, resulting in thermal decomposition or undesirable dimerization and trimerization (tris-(3,4-dichlorophenyl)-1,3,5-triazine-2,4,6-trione) of the isocyanate.

[0007] Solvent processes typically involve a water-immiscible solvent such as benzene, toluene, or chlorobenzene, often in combination with an aqueous solution of the amine (see, for example, DE-A 3245679 or CN-A-103539704). This has the disadvantage that this solvent must be laboriously removed after the reaction and recycled for reuse. The use of aqueous amine solutions also leads to hydrolysis of the isocyanate, which in turn causes the formation of undesirable biphenyl ureas.

[0008] HU178312 also describes a solvent process in which water serves as the solvent and the reaction of 3,4-dichlorophenyl isocyanate with dimethylamine is described as a continuous process. The amine is used in a high molar excess to minimize the formation of undesirable byproducts. However, the presence of water also leads to the formation of significant amounts of biphenyl ureas (1,3-bis(3,4-dichlorophenyl)urea), which precipitate with the target product and cannot be removed from the product without further purification steps. Furthermore, the wastewater must be intensively treated because the aforementioned compounds are highly hazardous to water bodies.

[0009] Object of the present invention

[0010] The object of the present invention was therefore to provide an efficient process for the preparation of substituted phenylurea derivatives, in particular of 3-(3,4-dichlorophenyl)-1,1-dimethylurea, which does not have the problems of the prior art, such as the complex separation and purification of the solvent and the formation of biphenylureas (1,3-bis-(3,4-dichlorophenyl)urea) or the dimerization or trimerization of the isocyanate.

[0011] Solution to the task

[0012] Surprisingly, it has now been found that the object underlying the invention is achieved by carrying out the reaction of substituted phenylurea derivatives with dimethylamine and / or N,0-dimethylhydroxylamine in a reactor having a surface area to volume ratio of 100 to 5000m 2 / m 3 has.

[0013] Subject of the invention

[0014] The invention therefore relates to a process for the preparation of substituted

[0015] Phenylurea derivatives of formula (I) with R 1 = H, methyl, F, Cl or Br,

[0016] R 2 = H, F, CI, Br, preferably CI, or Ci - C3-alkyl, or Ci - C3-alkyl substituted one or more times with F, CI or Br, preferably CF3, where R 1 and R 2 not simultaneously mean H and

[0017] R 3 = CH3or OCH3, by the reaction of compounds of formula (II) l (III) where R 1 , R 2 and R 3 have the above meaning, and wherein the reaction is carried out in a reactor having a surface to volume ratio of 100 to 5000m 2 / m 3 has.

[0018] Particularly preferably, the substituted phenylurea derivatives of formula (I) are the compounds mentioned below: and / or

[0019] The compound of formula (la) is preferably prepared by reacting 3,4-dichlorophenyl isocyanate with

[0020] Dimethylamine.

[0021] The compound of formula (Ib) is preferably prepared by reacting 3-chloro-4-methylphenyl isocyanate with dimethylamine.

[0022] The compound of formula (Ic) is preferably prepared by reacting 3-trifluoromethylphenyl isocyanate with dimethylamine.

[0023] The compound of formula (Id)

[0024] (Id), is preferably prepared by reacting 3,4-dichlorophenyl isocyanate with an amine of formula (III)

[0025] NH with R3 = OCH3.

[0026] In a preferred embodiment of the invention, the surface to volume ratio is 500 to 3500m 2 / m 3 , particularly preferred 650 to 2000m 2 / m 3 .

[0027] A reactor in the sense of the invention is preferably understood to be a tubular reactor. Tubular reactors, tube bundle reactors, or microreactors are preferred. A cooling medium, such as thermal oil, preferably flows around the preferred tubular reactor.

[0028] In a particularly preferred embodiment of the invention, the reactor, or in the case of a tube bundle reactor, the individual tubes of the reactor, have a diameter of 0.8 mm to 40 mm, particularly preferably 2 to 6 mm. The reactor length is preferably 0.4 to 3 m.

[0029] In a further preferred embodiment of the invention, the reactors are equipped with static mixers.

[0030] A static mixer is a device for mixing fluids in which the flow movement alone preferably causes mixing and which does not have any moving elements. It preferably consists of flow-influencing elements in a tube, preferably one or more differently arranged elements that alternately divide and recombine the material flow, thereby achieving mixing.

[0031] In a further preferred embodiment of the invention, the residence time in the reactor is 5-120 seconds, preferably 20-60 seconds. Furthermore, it is preferred that the proportion of water and / or organic solvents, such as preferably toluene, is 0-0.2 wt.%, based on the total mixture.

[0032] In addition, it is preferred that the preparation is carried out continuously, ie both reactants are continuously fed to the reactor in the desired molar ratio.

[0033] In a preferred embodiment of the invention, the molar ratio of amine of formula (III) to substituted phenyl isocyanate of formula (II) is 2:1 to 10:1, preferably 3:1 to 6:1. In the process according to the invention, the substituted phenyl isocyanate is preferably introduced via nozzles into the amine of formula (III), which is preferably present in excess.

[0034] In a further preferred embodiment of the invention, the process according to the invention is carried out at a pressure of 1 to 100 bar, preferably 5 to 60 bar, particularly preferably 10 to 55 bar.

[0035] In a further preferred embodiment of the invention, the process according to the invention is carried out at a temperature of 1 to 30°C above the melting point of the substituted phenylurea derivative of the formula (I), preferably at a pressure of 1 to 100 bar, in the case of 3-(3,4-dichlorophenyl)-1,1-dimethylurea thus at 160 to 190°C, preferably at a pressure of 1 to 100 bar.

[0036] The amine of formula (III), preferably used in a molar excess in the process according to the invention, is separated from the final product, the substituted phenylurea derivative of formula (I), after reaction with the substituted phenyl isocyanate of formula (II), preferably 3,4-dichlorophenyl isocyanate, and the excess amine is preferably recycled back to the reactor. This can be done, for example, by recycling it to the amine storage tank, from which it is then metered into the reactor.

[0037] Preferred embodiment of the method:

[0038] In a preferred embodiment of the invention, the process according to the invention is carried out using the example of the preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea as follows:

[0039] In an oil-tempered tubular reactor with a surface to volume ratio of 1000m 2 / m 3Dimethylamine preheated to 120–150°C is introduced into a 4mm diameter reactor equipped with static mixers. 3,4-Dichlorophenyl isocyanate preheated to 100–120°C is introduced through a nozzle installed at the beginning of the tubular reactor, ensuring a molar ratio of dimethylamine to 3,4-dichlorophenyl isocyanate of 3:1 to 10:1 is maintained. The mixing of dimethylamine with 3,4-dichlorophenyl isocyanate is ideally carried out using a static mixer. The pressure is preferably 20–50 bar, the reactor temperature 160–185°C, and the residence time of the reaction medium is approximately 30 seconds. At the end of the tubular reactor, the pressure is then released to ambient pressure, followed by separation of the 3-(3,4-dichlorophenyl)-1,1-dimethylurea from the excess dimethylamine by degassing.

[0040] For the other substituted phenylurea derivatives of formula (I), the process according to the invention is carried out analogously. The reactor temperatures are adjusted according to the melting point of the substituted phenylurea derivative of formula (I) and are preferably at a temperature of 1 to 30°C above the melting point of the substituted phenylurea derivative of formula (I).

[0041] The invention will be described below using examples and comparative examples. However, the following examples are only preferred examples of the present invention, and the present invention is not limited to the following examples.

[0042] Examples

[0043] Preparation of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (melting point: 158-159°C)

[0044] Example 1 (according to the invention):

[0045] In an oil-tempered tubular reactor with a surface area / volume ratio of 1000m 2 / m3 (Diameter 4 mm) equipped with static mixers, 262 g / h of dimethylamine preheated to 120°C were continuously introduced. Through a nozzle installed directly at the beginning of the reaction tube, 273 g / h of 3,4-dichlorophenyl isocyanate preheated to 130°C were continuously injected into the dimethylamine and mixed using static mixers. The molar ratio of dimethylamine to 3,4-dichlorophenyl isocyanate was 4:1. The maximum temperature occurring in the tubular reactor was approximately 185°C. The pressure was 55 bar, and the residence time of the reaction medium was approximately 60 s. At the end of the reaction tube, the pressure was released to ambient pressure, followed by degassing of the reaction product from the excess amine.

[0046] The conversion was >99.998% based on the isocyanate used, and the purity of the obtained product was >99.7%.

[0047] The content of the by-product 1,3-bis-(3,4-dichlorophenyl)urea, which is formed as a result of hydrolysis and thermal decomposition of the isocyanate, was below 50 ppm.

[0048] Undesired dimerization and trimerization of the isocyanate as well as critical by-products such as 3,4,3',4'-tetrachloroazobenzene and 3,4,3',4'-tetrachloroazoxybenzene were not detectable.

[0049] Example 2 (according to the invention):

[0050] The process was repeated according to Example 1 with the same molar ratio of dimethylamine to 3,4-dichlorophenyl isocyanate of 4:1, with the difference that the residence time was approximately 30 s, the pressure was 55 bar and the maximum temperature was 189 °C.

[0051] The conversion was >99.997% based on the isocyanate used, the purity was >99.7%.

[0052] The proportion of 1,3-bis-(3,4-dichlorophenyl)urea was <50 ppm, undesirable dimerization and trimerization of the isocyanate did not occur, and 3,4,3',4'-tetrachloroazobenzene and 3,4,3',4'-tetrachloroazoxybenzene were not detectable. Example 3 (according to the invention):

[0053] The procedure was repeated according to Example 1, with the difference that the pressure was reduced to 23 bar.

[0054] The conversion was >99.996%, the purity of 3-(3,4-dichlorophenyl)-1,1-dimethylurea was >99.6%.

[0055] The proportion of 1,3-bis-(3,4-dichlorophenyl)urea was <50 ppm, undesired dimerization and trimerization of the isocyanate did not occur and 3,4,3',4'-tetrachloroazobenzene and 3,4,3',4'-tetrachloroazoxybenzene were not detectable.

[0056] Example 4 (comparative example) according to HU178312

[0057] In a continuously operated stirred tank reactor with a surface / volume ratio in the order of approximately 50 m 2 / m 3 Equipped with an intensive mixer, a circulating 25% aqueous dimethylamine solution was introduced, resulting in a residence time of the reaction media of approximately 40 s. Additionally, a 58% aqueous dimethylamine solution and molten 3,4-dichlorophenyl isocyanate were added as feed in a stoichiometric ratio of 1:1. The molar ratio of the total dimethylamine added to the isocyanate was approximately 23:1. The reaction temperature was 40-45°C.

[0058] The product collected in the downstream filter within one hour was dried. The conversion was 98% based on the isocyanate used, and the purity of the resulting product was 98.5%.

[0059] The proportion of 1,3-bis-(3,4-dichlorophenyl)urea was > 1%, 3,4,3',4'-tetrachloroazobenzene and 3,4,3',4'-tetrachloroazoxybenzene were not detectable.

[0060] Example 5 (comparison example):

[0061] In a stirred oil-tempered double-jacketed pressure reactor with a surface / volume ratio of approximately 50 m 2 / m 3 34.14 g / min of 3,4-dichlorophenyl isocyanate (liquid, i.e., preheated to at least 65°C) and 33.45 g / min of dimethylamine were continuously added. The molar ratio was 4. For optimal mixing, a gassing stirrer was used at 1200 rpm. The reactor pressure was maintained at 55 bar, the internal reactor temperature was 185°C, and the oil temperature was 165°C. The average residence time was approximately 60 s.

[0062] After depressurization and cooling to room temperature of the melt leaving the reactor, the conversion of 3-(3,4-dichlorophenyl)-1,1-dimethylurea was 92%, based on the isocyanate used.

[0063] The content of unreacted isocyanate was > 6%, based on the isocyanate used.

[0064] Example 6 (comparison example):

[0065] In a microcapillary reactor heated to 185 °C with a surface / volume ratio of 6153 m 2 / m 3 2.78 g / h of 3,4-dichlorophenyl isocyanate (liquid, i.e., preheated to at least 65°C) and 2.032 g / h of dimethylamine were continuously added via a T-mixer. The molar ratio was 4, and the reactor pressure was 55 bar. The average residence time was approximately 60 s.

[0066] Continuous operation over extended periods could not be maintained due to pressure fluctuations and clogging in the capillary area. The experiments showed fluctuating yields, which were well below 90%.

[0067] Summary:

[0068] It was found that substituted phenylurea derivatives of formula (I) were obtained in high yield and purity using the process according to the invention and that the proportion of 1,3-bis-(3,4-dichlorophenyl)urea was <50 ppm and 3,4,3',4'-tetrachloroazobenzene and 3,4,3',4'-tetrachloroazoxybenzene were not detectable.

Claims

Patent claims: 1 . Process for the preparation of substituted phenylurea derivatives of formula (I) with R 1 = H, methyl, F, Cl or Br, R 2 = H, F, CI, Br, preferably CI, or Ci - C 3 -alkyl, or Ci - C mono- or polysubstituted with F, CI or Br 3 -Alkyl, preferably CF 3 , where R 1 and R 2 not simultaneously mean H and R 3 = CH 3 or OCH 3 , by the reaction of compounds of formula (II) el (III) where R 1 , R 2 and R 3 have the abovementioned meaning, characterized in that the reaction is carried out in a reactor having a surface to volume ratio of 100 to 5000m 2 / m 3 , preferably 500 to 3500m 2 / m 3 , particularly preferred 650 to 2000m 2 / m.

2. Process according to claim 1, characterized in that the compounds of formula (I) are is.

3. Process according to claim 1 to 2, characterized in that the reactor is a tubular reactor.

4. Process according to at least one of claims 1 to 3, characterized in that the tubular reactor has a diameter of 0.8 mm to 40 mm.

5. The process according to at least one of claims 1 to 4, characterized in that the tubular reactor is a tube bundle reactor or a microreactor.

6. Process according to at least one of claims 1 to 5, characterized in that the reaction is carried out continuously.

7. Process according to at least one of claims 1 to 6, characterized in that the amine according to formula (III) and the substituted phenyl isocyanate according to formula (II) are used in a molar ratio of 2:1 to 10:1, preferably 3:1 to 6:

1.

8. Process according to at least one of claims 1 to 7, characterized in that the reaction is carried out at a pressure of 1 to 100 bar, preferably 5 to 60 bar, particularly preferably 10 to 55 bar.

9. Process according to at least one of claims 1 to 8, characterized in that the reaction is carried out at a temperature of 1 to 30°C above the melting point of the substituted phenylurea derivative of the formula (I) at a pressure of 1 to 100 bar, preferably 5 to 60 bar, particularly preferably 10 - 55 bar.

10. Process according to claim 7, characterized in that the excess amine of formula (III) is returned to the reactor after the reaction.

11. Process according to at least one of claims 1 to 10, characterized in that the residence time in the reactor is 5-120 seconds.