Method for the preparation of substituted phenylurea derivatives
The described process addresses the issue of impurities in phenylurea derivative production by using a reactor with controlled temperature and pressure, followed by atomization, resulting in high-purity products with minimized byproducts.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- LANXESS DEUTSCHLAND GMBH
- Filing Date
- 2025-12-15
- Publication Date
- 2026-06-25
AI Technical Summary
Existing methods for producing substituted phenylurea derivatives, such as 3-(3,4-dichlorophenyl)-1,1-dimethylurea, face issues with high byproduct formation due to insufficient temperature control and mixing, leading to impurities and thermal decomposition, despite achieving high yields.
A process involving a reactor with a specific surface area to volume ratio, operating at temperatures above the melting point and high pressure, followed by atomization and depressurization of the reaction mixture to below the melting point, using nozzles to form droplets, which promotes crystallization and purity.
This method results in high-purity substituted phenylurea derivatives with reduced byproducts, achieved through efficient and simple process conditions.
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Abstract
Description
[0001] P001 01251 Abroad - 1 -
[0002] Methods for the production of substituted phenylurea derivatives
[0003] The present invention relates to a new process for the production of substituted phenylurea derivatives, in particular of 3-(3,4-dichlorophenyl)-1,1-dimethylurea.
[0004] State of the art
[0005] Phenylureas are a class of selectively acting herbicides; for example, 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) inhibits plant photosynthesis. It is used for the complete eradication of plants (broad-spectrum herbicide) as well as for the protection of wood and masonry and as a coating agent.
[0006] Various approaches for the production of phenylurea derivatives are known in the prior art, in particular the production 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.
[0007] In the melting processes described in DE-A-2206167 and DD-A-201140, which are carried out as semi-batch processes in stirred reactors, sufficient heat removal and thus temperature control must be ensured by suitable technical measures due to the high exothermicity of the reaction. For this purpose, both reactants are added in a metered manner, which, due to the associated long residence times at temperatures above the melting point of the product, leads to the formation of undesirable byproducts. In the case of a local amine deficiency caused by insufficient mixing, the isocyanate is not converted quickly enough, leading to thermal decomposition or undesired dimerization and trimerization (tris-(3,4-dichlorophenyl)-1,3,5-triazine-2,4,6-trione) of the isocyanate.
[0008] From EP23210489.3 a melting process for the production of substituted phenylurea derivatives is known, in which the reaction of substituted phenylurea derivatives with dimethylamine and / or N,0-dimethylhydroxylamine is carried out in a reactor having a surface area to volume ratio of 100 to 5000m² 2 / m 3 exhibits.
[0009] The aforementioned reaction conditions do indeed lead to the high yield of the substituted phenylurea derivatives; however, it is desirable to further increase the purity of the product using a time-efficient and technically simple method. P001 01251 Abroad - 2 -
[0010] Object of the present invention
[0011] The object of the present invention was therefore to provide an efficient process for the production of substituted phenylurea derivatives, in particular of 3-(3,4-dichlorophenyl)-1,1-dimethylurea, in high purity, which can be carried out in a time-efficient and technically simple manner.
[0012] Solution to the task
[0013] Surprisingly, it has now been found that the problem underlying the invention is solved by producing substituted phenylurea derivatives, in particular 3-(3,4-dichlorophenyl)-1,1-dimethylurea, in a reactor with a surface area to volume ratio of 100 to 5000 m². 2 / m 3at temperatures 1 to 30°C above the melting point of the substituted phenylurea derivative of formula (I) and at a pressure of 5 to 100 bar, which is characterized by the fact that the reaction mixture is atomized after the reaction by means of a nozzle and is depressurized to a pressure < 5 bar, wherein the temperature after atomization is below the melting point of the substituted phenylurea derivative.
[0014] Subject matter of the invention
[0015] The invention thus relates to a process for the production of substituted phenylurea derivatives of formula (I) with R 1 = H, Methyl, F, CI or Br,
[0016] R 2 = H, F, CI, Br, preferably CI, or Ci-C3-alkyl, or Ci-C3-alkyl simply or multiply substituted with F, CI or Br, preferably CF3, wherein R 1 and R 2 do not mean H at the same time and
[0017] R 3= CH3 or OCH3, P001 01251 Abroad - 3 - which are produced by the implementation of compounds of formula (II) el (III) where R 1 , R 2 and R 3 the aforementioned meaning in a reactor with a surface area to volume ratio of 100 to 5000 m² 2 / m 3 at temperatures 1 to 30°C above the melting point of the substituted phenylurea derivative of formula (I) and at a pressure of 5 to 100 bar, wherein the reaction mixture is atomized by means of a nozzle after the reaction and depressurized to a pressure of 1 to < 5 bar, preferably 1 bar, and wherein the temperature after atomization is below the melting point of the substituted phenylurea derivative of formula (I).
[0018] For the purposes of this invention, a nozzle is preferably a component of any shape, preferably a tubular one, which has a cross-sectional constriction and atomizes liquids. Single-fluid nozzles, such as hollow cone nozzles or hollow cone pressure nozzles, or two-fluid nozzles and / or pneumatic atomizers are preferred.
[0019] In another preferred embodiment of the invention, the nozzle is heated to temperatures of 1 to 30°C above the melting point of the substituted phenylurea derivative of formula (I).
[0020] The nozzle diameter is preferably in the range of 0.05 mm to 1 mm, preferably 0.1 mm to 0.25 mm. The flow rate through the nozzles is preferably from 0.3 l / h to 2.4 l / h. A pressure differential from the reactor outlet to the nozzle outlet of 5 to 60 bar is also preferred.
[0021] The atomization according to the invention preferably takes place from the reaction mixture in the form of a melt into droplets.
[0022] Preferably, lowering the temperature leads to the crystallization of the substituted phenylurea derivative of formula (I). P001 01251 Abroad - 4 -
[0023] The substituted phenylurea derivatives of formula (I) are particularly preferred as the following compounds:
[0024] The combination of formula (1a) P001 01251 Abroad - 5 - is preferably produced by the reaction of 3,4-dichlorophenyl isocyanate with dimethylamine.
[0025] The connection of formula (Ib) It is preferably produced by reacting 3-chloro-4-methylphenyl isocyanate with dimethylamine.
[0026] The connection of the formula (Ic) It is preferably produced by reacting 3-trifluoromethylphenyl isocyanate with dimethylamine.
[0027] The connection of the formula (Id)
[0028] (Id) is preferably prepared by reacting 3,4-dichlorophenyl isocyanate with an amine of formula (III) with R 3 = OCH3. P001 01251 Abroad - 6 -
[0029] In one embodiment of the invention, the reaction is carried out in a reactor at temperatures that are 1 to 30°C above the melting point of the substituted phenylurea derivative of formula (I).
[0030] In a preferred embodiment of the invention, the surface area to volume ratio in the reactor is 500 to 3500 m². 2 / m 3 , especially preferred 650 to 2000m 2 / m 3 .
[0031] For the purposes of this invention, a reactor is preferably a tubular reactor. Tubular reactors, especially tube bundle reactors, or microreactors are preferred. The preferred tubular reactor is preferably surrounded by a cooling medium, such as thermal oil.
[0032] 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.
[0033] In another preferred embodiment of the invention, the reactors are equipped with static mixers.
[0034] A static mixer is a device for mixing fluids in which, preferably, the mixing is effected solely by the flow motion and which has no moving elements. It preferably consists of flow-influencing elements in a pipe, more preferably of one or more differently arranged elements that alternately divide and recombine the fluid flow, thereby achieving mixing.
[0035] In another preferred embodiment of the invention, the residence time in the reactor is 5-120 seconds, preferably 20-60 seconds.
[0036] 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.
[0037] Furthermore, it is preferred that the production is carried out continuously, i.e., that both reactants are continuously fed into the reactor in the desired molar ratio.
[0038] In a preferred embodiment of the invention, the molar ratio of amine of formula (III) to the 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 into the amine of formula (III), which is preferably present in excess, via nozzles. P001 01251 Foreign - 7 -
[0039] In a further preferred embodiment of the invention, the method according to the invention is carried out at a pressure of 5 to 60 bar, particularly preferably 10 to 55 bar.
[0040] 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 formula (I), preferably at a pressure of 1 to 100 bar, i.e. in the case of 3-(3,4-dichlorophenyl)-1,1-dimethylurea at 160 to 190°C, preferably at a pressure of 1 to 100 bar.
[0041] In the process according to the invention, the amine of formula (III), preferably used in molar excess, is separated from the end 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 into the reactor. This can be done, for example, by recycling it back into the amine storage container, from which it is then added to the reactor.
[0042] In the process according to the invention, at the end of the reaction tube, the pressure is reduced to 1 to < 5 bar and the reaction mixture, preferably the melt, is atomized by means of a nozzle, preferably in droplets.
[0043] In one embodiment of the invention, the nozzle is heated to temperatures of 1 to 30°C above the melting point of the substituted phenylurea derivative of formula (I). The expansion then takes place into a container in which the temperature after atomization is below the melting point of the substituted phenylurea derivative.
[0044] The product preferably forms immediately after the nozzle as a white, finely powdered solid.
[0045] Preferred embodiment of the method:
[0046] In a preferred embodiment of the invention, the inventive process is carried out using the example of the production of 3-(3,4-dichlorophenyl)-1,1-dimethylurea as follows:
[0047] In an oil-temperature pipe reactor with a surface area to volume ratio of 1000m³ 2 / m 3Dimethylamine preheated to 120–150°C is introduced into a 4 mm diameter reactor equipped with static mixers. Preheated 3,4-dichlorophenyl isocyanate (100–120°C) is introduced through a nozzle installed at the beginning of the tubular reactor, maintaining a molar ratio of dimethylamine to 3,4-dichlorophenyl isocyanate of 3:1 to 10:1. The mixing of dimethylamine with 3,4-P001 01251 Abroad - 8 -
[0048] Dichlorophenyl isocyanate is ideally reacted 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 approximately 30 s. At the end of the reaction tube, the reaction mixture, preferably a melt, is depressurized, preferably via a heated valve with a downstream heated nozzle, into a cooled conical spray tower, whereby the excess amine is preferably separated as a gas phase. The product is collected immediately after the nozzle as a white, finely powdered solid, which is collected in an attached receiving container.
[0049] The process according to the invention is carried out analogously for the other substituted phenylurea derivatives according to formula (I). 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).
[0050] The invention is 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.
[0051] P001 01251 Abroad - 9 -
[0052] Examples
[0053] Example 1 (comparative example) according to EP23210489.3:
[0054] For the continuous production of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (diuron), 262 g / h of pre-heated dimethylamine (pre-tempered to 120°C) was introduced into an oil-temperature-controlled reaction tube with an inner diameter of 4 mm, equipped with static mixers. 273 g / h of 3,4-dichlorophenyl isocyanate (molar ratio DMA / 3,4-DCPI: 4), pre-heated to 130°C, was injected into the dimethylamine via a nozzle installed directly at the beginning of the reaction tube and rapidly mixed using the static mixers. The system pressure was 53 bar, the oil temperature was 163°C, and the residence time of the reaction medium was approximately 60 s.
[0055] At the end of the reaction tube, the solution was depressurized to ambient pressure via a heated valve into a pressure relief vessel. The molten reaction product was then separated from the excess amine in the pressure relief vessel, which was heated to 165°C. The residence time in the vessel ranged from 30 minutes to 1 hour.
[0056] After cooling the reaction mixture (melt), the product showed distinct brownish discoloration and still exhibited a noticeable amine odor. The exhaust pipes of the system downstream of the expansion tank showed significant fouling, which in some cases led to blockages.
[0057] The conversion rate was >99.9% based on the isocyanate used, and the purity of the recovered product was >99.7%. Critical byproducts such as 3,4,3',4'-tetrachloroazobenzene and 3,4,3',4'-tetrachloroazoxybenzene were not detectable.
[0058] Example 2 (according to the invention):
[0059] For the continuous production of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (diuron), 262 g / h of pre-heated dimethylamine (pre-tempered to 120°C) was introduced into an oil-temperature-controlled reaction tube with an inner diameter of 4 mm, equipped with static mixers. 273 g / h of 3,4-dichlorophenyl isocyanate (molar ratio DMA / 3,4-DCPI: 4), pre-heated to 130°C, was injected into the dimethylamine via a nozzle installed directly at the beginning of the reaction tube and rapidly mixed using the static mixers. The system pressure was 53 bar, the oil temperature 163°C, and the residence time of the reaction medium approximately 60 s. P001 01251 Abroad - 10 -
[0060] After the reaction, the reaction mixture (melt) at the end of the reaction tube was transferred via a heated valve with a downstream heated nozzle (nozzle diameter of 0.1 mm at a flow rate of 600 ml / h and a pressure differential of 52 bar) into a cooled conical spray tower and depressurized to 1 bar. The temperature after atomization was between 20°C and 40°C, preferably 30°C. During depressurization, excess amine escaped as a gas. The product formed immediately after the nozzle as a white, finely powdered solid, which was collected in an attached collection container. The residence time in the collection container was 30 minutes to 1 hour. The resulting product was white and no longer exhibited any amine odor. The exhaust pipes of the system downstream of the spray tower showed no further fouling.
[0061] The conversion rate was >99.9% based on the isocyanate used, and the purity of the recovered product was >99.7%. Critical byproducts such as 3,4,3',4'-tetrachloroazobenzene and 3,4,3',4'-tetrachloroazoxybenzene were not detectable.
Claims
P001 01251 Abroad - 11 - Patent claims:
1. Method for the preparation of substituted phenylurea derivatives of formula (I) with R 1 = H, Methyl, F, CI or Br, R 2 = H, F, CI, Br, preferably CI, or Ci-C3-alkyl, or Ci-C3-alkyl simply or multiply substituted with F, CI or Br, preferably CF3, wherein R 1 and R 2 do not mean H at the same time and R 3 = CH3 or OCH3, by the reaction of compounds of formula (II) el (III) where R 1 , R 2 and R 3 the aforementioned meaning in a reactor with a surface area to volume ratio of 100 to 5000 m² 2 / m 3at temperatures 1 to 30°C above the melting point of the substituted phenylurea derivative of formula (I) and at a pressure of 5 to 100 bar, characterized in that the reaction mixture is atomized after the reaction by means of a nozzle and is depressurized to a pressure of 1 to < 5 bar, wherein the temperature after atomization is below the melting point of the substituted phenylurea derivative of formula (I). P001 01251 Abroad - 12 - 2. The method according to claim 1, characterized in that the Compounds of formula (I) around it.
3. Method according to claims 1 to 2, characterized in that the reactor is a tubular reactor.
4. Method 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. P001 01251 Abroad - 13 - 5. Method 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. Method according to at least one of claims 1 to 5, characterized in that the reaction is carried out continuously.
7. Method 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. Method according to at least one of claims 1 to 7, characterized in that the conversion is carried out at a pressure of 5 to 100 bar, preferably 5 to 60 bar, particularly preferably 10 to 55 bar.
9. Method according to at least one of claims 1 to 8, characterized in that the nozzle is a tubular component which has a cross-sectional narrowing and atomizes liquids.
10. Method according to claim 9, characterized in that the nozzle is a single-component nozzle, preferably a hollow cone nozzle or hollow cone pressure nozzle, or a two-component nozzle and / or pneumatic atomizer.
11. Method according to at least one of claims 1 to 9, characterized in that the residence time in the reactor is 5 to 120 seconds.