Processes for preparing an oxyfluorfen intermediate, and the oxyfluorfen intermediate prepared, process for preparing oxyfluorfen, and the oxyfluorfen prepared

Abstract

The present disclosure relates to a process for preparing an oxyfluorfen intermediate, and the oxyfluorfen intermediate prepared by the process. The present disclosure also relates to a process for preparing oxyfluorfen, and the oxyfluorfen prepared by the process.

Description

[0001] PROCESSES FOR PREPARING AN OXYFLUORFEN INTERMEDIATE, AND THE OXYFLUORFEN INTERMEDIATE PREPARED, PROCESS FOR PREPARING OXYFLUORFEN, AND THE OXYFLUORFEN PREPARED

[0002] TECHNICAL FIELD OF THE DISCLOSURE

[0003] The present disclosure relates to a process for preparing an oxyfluorfen intermediate, and the oxyfluorfen intermediate prepared by the process. The present disclosure also relates to a process for preparing oxyfluorfen, and the oxyfluorfen prepared by the process.

[0004] FIELD AND BACKGROUND OF THE DISCLOSURE

[0005] Oxyfluorfen is a broad-spectrum, pre- and post-emergent nitrophenol ether herbicide and diphenyl ether herbicide used to control certain annual weeds in vegetables, fruit and other crops, and is first described in GB1390295A. The chemical name of oxyfluorfen is 2-chloro-a,a,a-trifluoro-p-tolyl 3 -ethoxy -4-nitrophenyl ether,

[0006] <"

[0007]

[0008] with a structural formula of The CAS registry number of oxyfluorfen is 42874-03-3.

[0009] 2-ethoxy-4-fluoro-nitrobenzene, with a structural formula of

[0010]

[0011] , is an important intermediate for preparing oxyfluorfen.

[0012] As one synthesis process in the prior art, IN476525B discloses reacting 2-hydroxy- 4-fluoro nitrobenzene with ethyl chloride gas in the presence of DMSO and K2CO3 to produce 2-ethoxy-4-fluoro-nitrobenzene. In this patent, 2-hydroxy- 4-fluoro nitrobenzene is prepared from 2,4-difluoro nitrobenzene, KOH and water. This patent also discloses a process for preparing oxyfluorfen comprising: a)... b) adding a first portion of 2-chloro-4-trifluoromethyl phenol to said solution under stirring at a temperature in the range of 25 °C to 35 °C to obtain a mixture; c) adding 2-ethoxy-4-fluoro nitrobenzene to said mixture and reacting at a first predetermined temperaturefor a first predetermined time period to obtain a reaction mass; d) adding at least two portions of 2-chloro-4-trifluoromethyl phenol in said reaction mass at a second predetermined temperature for a second predetermined time period to obtain a product mixture comprising oxyfluorfen and oxyfluorfen analogue; and e) purifying said product mixture comprising oxyfluorfen and oxyfluorfen analogue.

[0013] CN109970567A discloses reacting 2,4-difluoro nitrobenzene with sodium ethoxide in the presence of toluene to produce 2-ethoxy-4-fluoro-nitrobenzene at a yield of about 92%. No water is used in the reaction disclosed by this application. This application also discloses reacting 2-ethoxy-4-fluoro-nitrobenzene with 2-chloro-4-trifluoromethylphenol in the presence of organic solvent (DMF or DMSO) and a base (KOH or KCO3) to produce oxyfluorfen.

[0014] US4262152A discloses reacting 2,4-difluoro nitrobenzene with anhydrous sodium ethoxide prepared by dissolving sodium metal in anhydrous ethanol to produce 2-ethoxy-4-fluoro-nitrobenzene. No water is used in the reaction disclosed by this patent. This patent also discloses reacting 2-ethoxy-4-fluoro-nitrobenzene with 2-chloro-4-trifluoromethylphenol in the presence of a base to produce oxyfluorfen (Preparation 49).

[0015] The methods disclosed in the prior art for preparing 2-ethoxy-4-fluoro-nitrobenzene using 2,4-difluoro nitrobenzene with sodium ethoxide employ anhydrous environment with a yield of about 92%. In addition to the desired product 2-ethoxy-4-fluoro-nitrobenzene, these methods generally produce several undesired byproducts, such as 2- fluoro-4- ethoxy -nitrobenzene (isomer byproduct) and 2-ethoxy-4- ethoxy -nitrobenzene (di-ethoxy byproduct), which in turn result in undesired oxyfluorfen byproducts, and lowering the yield of oxyfluorfen. There is a need in the art to produce 2-ethoxy-4-fluoro-nitrobenzene in a cleaner, faster, and material-saving way with a higher selectivity.

[0016] SUMMARY OF THE DISCLOSURE

[0017] Surprisingly, it has now been found that, using a specified amount of water in the reaction of 2,4-difluoro nitrobenzene and sodium ethoxide, our inventors have successfully prepared 2-ethoxy-4-fluoro-nitrobenzene in a cleaner and faster way with a higher selectivity than the prior art processes. The process provided in the present disclosure is cleaner (i.e., less total selectivity of isomer byproduct and di-ethoxybyproduct), faster and more material-saving, has a higher selectivity for 2-ethoxy-4-fluoro-nitrobenzen than the prior art processes.

[0018] The present disclosure provides a process for preparing 2-alkoxy-4-halo-nitrobenzene of formula (I) comprising: reacting 2,4-dihalo-nitrobenzene of formula (II) with an alkoxide of Ri-O-X in the presence of an organic solvent and water,

[0019]

[0020] (I) (II) wherein:

[0021] Ri is a Ci-6 alkyl,

[0022] R2 is a halogen,

[0023] R3 is NO2,

[0024] R4 is a halogen,

[0025] X is an alkali metal.

[0026] The present disclosure also provides a process for preparing oxyfluorfen comprising the following steps:

[0027] (i) preparing 2-ethoxy-4-fluoro-nitrobenzene according to the process for preparing 2-alkoxy-4-halo- nitrobenzene of formula (I) disclosed in the present disclosure; and

[0028] (ii) reacting 2-ethoxy-4-fluoro-nitrobenzene obtained from step (i) with 2-chl oro-4-trifluorom ethylphenol .

[0029] The present disclosure also provides the 2-alkoxy-4-halo- nitrobenzene of formula (I), especially the 2-ethoxy-4-fluoro-nitrobenzene prepared by the process of the present disclosure, and the oxyfluorfen prepared by the process of the present disclosure.

[0030] Specifically, the present disclosure provides:

[0031] 1. A process for preparing 2-alkoxy-4-halo-nitrobenzene of formula (I) comprising: reacting 2,4-dihalo-nitrobenzene of formula (II) with an alkoxide of Ri-O-X in the presence of an organic solvent and water,

[0032]

[0033] (II)

[0034] wherein:

[0035] Ri is a Ci-6 alkyl,

[0036] R2 is a halogen,

[0037] R3 is NO2,

[0038] R4 is a halogen,

[0039] X is an alkali metal.

[0040] 2. The process of embodiment 1, wherein the molar ratio of water to 2,4-dihalo-nitrobenzene of formula (II) is 0.1 : 1 to 3.5 : 1.

[0041] 3. The process of embodiment 2, wherein the molar ratio of water to 2,4-dihalo-nitrobenzene of formula (II) is 0.5:l to 3:l.

[0042] 4. The process of any one of embodiments 1 to 3, wherein X is sodium or potassium.

[0043] 5. The process of any one of embodiments 1 to 4, wherein Ri is C1.3 alkyl, R2 and R4 are identical or different and independently selected from F or Cl.

[0044] 6. The process of any one of embodiments 1 to 5, wherein the alkoxide is produced by reacting an alkanol of Ri-OH with a hydroxide X-OH and Ri and X are as previously defined.

[0045] 7. The process of embodiment 6, wherein the hydroxide is added in two parts, the first part is added along with water without the alkanol, and the second part is added along with water and the alkanol.

[0046] 8. The process of embodiment 7, wherein for the first part, the hydroxide is in a water solution, and the concentration of the hydroxide in the water solution is 45wt% to 54wt%.

[0047] 9. The process of any one of embodiments 6 to 8, wherein the molar ratio of the alkanol to 2,4-dihalo-nitrobenzene of formula (II) is 1:1 to 4: 1.10. The process of embodiment 9, wherein the molar ratio of the alkanol to 2,4-dihalo-nitrobenzene of formula (II) is 1:1 to 3:1.

[0048] 11. The process of any one of embodiments 1 to 10, wherein the molar ratio of the alkoxide to 2,4-dihalo-nitrobenzene of formula (II) is 0.7:1 to 2:1.

[0049] 12. The process of embodiment 11, wherein the molar ratio of the alkoxide to 2,4-dihalo-nitrobenzene of formula (II) is 0.8:1 to 1.5:1.

[0050] 13. The process of any one of embodiments 1 to 12, wherein the 2-alkoxy-4-halo- nitrobenzene of formula (I) is 2-ethoxy-4-fluoro-nitrobenzene, and the 2,4-dihalo-nitrobenzene of formula (II) is 2,4-difluoro-nitrobenzene.

[0051] 14. The process of embodiment 13, wherein the molar ratio of water to 2,4-difluoro-nitrobenzene is 1:2 to 1.8:1.

[0052] 15. A process for preparing oxyfluorfen comprising the following steps:

[0053] (i) preparing 2-ethoxy-4-fluoro-nitrobenzene according to embodiment 13 or 14; and

[0054] (ii) reacting 2-ethoxy-4-fluoro-nitrobenzene obtained from step (i) with 2-chloro-4-trifluorom ethylphenol .

[0055] 16. The process of embodiment 15, wherein the 2-chloro-4-trifluoromethylphenol is obtained from a mixture of 2-chloro-4-trifluoromethylphenol and 2-chloro-5-trifluoromethyl-phenol.

[0056] 17. The process of embodiment 16, wherein the 2-chloro-4-trifluorom ethylphenol is present in its alkali metal salt.

[0057] 18. The process of embodiment 17, wherein the alkali metal salt is K salt. 19. The 2-alkoxy-4-halo- nitrobenzene of formula (I) prepared according to any one of embodiments 1 to 14.

[0058] 20. The 2-ethoxy-4-fluoro-nitrobenzene prepared according to embodiment 13 or 14.

[0059] 21. The oxyfluorfen prepared according to any one of embodiment 15 to 18.

[0060] DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE DISCLOSURE

[0061] Definitions

[0062] Prior to setting forth the present disclosure in detail, it may be helpful to provide definitions of certain terms to be used herein. Unless defined otherwise, all technicaland scientific terms used herein have the same meaning as is commonly understood by those skilled in the art to which this disclosure pertains.

[0063] The term “a” or “an” as used in the present disclosure includes the singular and the plural, unless specifically stated otherwise. Therefore, the term “a,” “an,” or “at least one” can be used interchangeably in this application.

[0064] It is understood that where a parameter range is provided, all integers within that range, and tenths thereof, are also provided by the disclosure as if the integers and tenths thereof are expressly described herein. For example, “0.1% to 70%” includes 0.1%, 0.2%, 0.3%, 0.4%, 0.5% etc. up to 70%.

[0065] “Alkyl” means in the present disclosure a straight or branched hydrocarbon chain radical consisting of carbon and hydrogen atoms, containing no unsaturation, having the number of carbon atoms indicated in each case, for example 1-6 carbon atoms (Ci-6), which is attached to the rest of the molecule through a single bond. For example, an alkyl group comprises 1-6 carbon atoms, typically 1-4 carbon atoms. Exemplary alkyl groups can be methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, t-butyl, or n-pentyl.

[0066] “Alkoxyl” means in the present disclosure a radical of the formula -O-alkyl, wherein alkyl has been previously defined. Exemplary alkoxyl groups are methoxy, ethoxy, or propoxy.

[0067] “Halogen” or “halo” refers in the present disclosure to -F, -Cl, -Br or -I.

[0068] “Alkali metal” refers in the present disclosure to Na, K, or Li.

[0069] “Conversion rate” measures the degree of a raw material converting to all products, and may be calculated as the remaining amount of the raw material / the initial amount of the raw material xl00%.

[0070] “Selectivity” measures the degree of a raw material converting to a specific product. In an HPLC chromatogram, aera% of a specific product is the area percent of a peak of the specific product as a percentage of the total area of all peaks, and may represent the selectivity of the specific product.

[0071] Throughout the application, descriptions of various embodiments use the term "comprising"; however, it will be understood by one of skill in the art, that in some specific instances, an embodiment can alternatively be described using the language "consisting essentially of' or "consisting of'.For purposes of better understanding the present teachings and in no way limiting the scope of the teachings, unless otherwise indicated, all numbers expressing quantities, percentages, or proportions, and other numerical values used in the specification and claims, are to be understood as being modified in all instances by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth in the following specification and attached claims are approximations that may vary depending upon the desired properties sought to be obtained. At the very least, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques. In this regard, use of the term "about" herein specifically includes ±10% from the indicated values in the range. In addition, the endpoints of all ranges directed to the same component or property herein are inclusive of the endpoints, are independently combinable, and include all intermediate points and ranges.

[0072] First Aspect

[0073] In the first aspect, the present disclosure provides a process for preparing 2-alkoxy-4-halo- nitrobenzene of formula (I), and the 2-alkoxy-4-halo- nitrobenzene of formula (I), especially the 2-ethoxy-4-fluoro-nitrobenzene prepared by the process.

[0074] The process for preparing 2-alkoxy-4-halo-nitrobenzene of formula (I) comprising: reacting 2,4-dihalo-nitrobenzene of formula (II) with an alkoxide of Ri-O-X in the presence of an organic solvent and water,

[0075]

[0076] wherein:

[0077] Ri is a Ci-6 alkyl,

[0078] R2 is a halogen,

[0079] R3 is NO2,

[0080] R4 is a halogen,

[0081] X is an alkali metal.In the process of the first aspect, Ri in formula (I) and Ri-O-X may be Ci-6 alkyl. In one embodiment of the present disclosure, Ri in formula (I) and Ri-O-X may be Ci- 4 alkyl. In one embodiment of the present disclosure, Ri in formula (I) and Ri-O-X may be Ci-3 alkyl, such as methyl, ethyl, n-propyl, or iso-propyl.

[0082] In the process of the first aspect, R2 in formulas (I) and (II) may be a halogen, that is, F, Cl, Br, or I. In one embodiment of the present disclosure, R2 in formulas (I) and (II) may be F, Cl, or Br. In one embodiment of the present disclosure, R2 in formulas (I) and (II) may be F or Cl. In one embodiment of the present disclosure, R2 in formulas (I) and (II) may be F.

[0083] In the process of the first aspect, R4 in formula (II) may be a halogen. In one embodiment of the present disclosure, R4 in formula (II) may be F, Cl, or Br. In one embodiment of the present disclosure, R4 in formula (II) may be F or Cl. In one embodiment of the present disclosure, R4 in formula (II) may be F.

[0084] In the process of the first aspect, both R2 and R4 in formulas (I) and / or (II) are halogens. In one embodiment of the present disclosure, R2 and R4 in formulas (I) and / or (II) may be the same or different from each other. In one embodiment of the present disclosure, R2 and R4 in formulas (I) and / or (II) may be the same, for example, both R2 and R4 in formulas (I) and / or (II) are F.

[0085] In the process of the first aspect, X in Ri-O-X may be an alkali metal, such as, Na, K, and Li. In one embodiment of the present disclosure, X in Ri-O-X may be Na or K. In one embodiment of the present disclosure, X in Ri-O-X may be K.

[0086] In the process of the first aspect, the molar ratio of water to 2,4-dihalo-nitrobenzene of formula (II) may be 0.1:1 to 3.5:1. Within the range of 0.1:1 to 3.5:1, the molar ratio of water to 2,4-dihalo-nitrobenzene of formula (II) may be 0.1 : 1, 0.2:1, 0.3:1, 0.4:1, 0.5:1, 0.6:1, 0.7:1, 0.8:1, 0.9:1, 1.0:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2.0:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1, 2.6:1, 2.7:1, 2.8:1, 2.9:1, 3.0:1, 3.1:1, 3.2:1, 3.3:1, 3.4:1, 3.5:1, and any ranges formed by selecting any two molar ratios mentioned above as the two limits, for example, 0.8:1 to 3:1, 1.1:1 to 2.5:1, or 1.4:1 to 1.7:1, etc.

[0087] In the process of the first aspect, the alkoxide of Ri-O-X may be produced e.g., in situ, by reacting an alkanol of Ri-OH with a hydroxide X-OH, and Ri and X are as previously defined. In one embodiment of the present disclosure, the alkanol of Ri-OH may be methanol, ethanol, n-propanol, or iso-propanol. In one embodiment of the present disclosure, the alkanol of Ri-OH may be methanol or ethanol. In oneembodiment of the present disclosure, the alkanol of Ri-OH may be ethanol. In one embodiment of the present disclosure, the hydroxide X-OH may be NaOH, KOH, or LiOH. In one embodiment of the present disclosure, the hydroxide X-OH may be NaOH or KOH. In one embodiment of the present disclosure, the hydroxide X-OH may be KOH.

[0088] In the process of the first aspect, when the alkoxide of Ri-O-X is produced e.g., in situ, by reacting an alkanol of Ri-OH with a hydroxide X-OH, and Ri and X are as previously defined, the hydroxide X-OH may be added in two parts, the first part of hydroxide is added along with water without the alkanol, and the second (remaining) part of hydroxide is added along with water and the alkanol. For the first part, no alkanol is involved, and hydroxide is added along with water. In one embodiment of the present disclosure, the first part of hydroxide and water may form a hydroxide water solution. In one embodiment of the present disclosure, the concentration of the hydroxide in the water solution may be 40 percent by weight (wt%) to 60wt%. Within the range of 40wt% to 60wt%, the concentration of the hydroxide in the water solution may be 40wt%, 41wt%, 42wt%, 43wt%, 44wt%, 45wt%, 46wt%, 47wt%, 48wt%, 49wt%, 50wt%, 51wt%, 52wt%, 53wt%, 54wt%, 55wt%, 56wt%, 57wt%, 58wt%, 59wt%, 60wt%, and any ranges formed by selecting any two concentrations mentioned above as the two limits, for example, 42wt% to 58wt%, 45wt% to 54wt%, etc.

[0089] For the second part, the remaining hydroxide is added along with the water and the alkanol. In one embodiment of the present disclosure, the second part of hydroxide, the water and alkanol may form a hydroxide water / alkanol solution. The amount of the water added along with the second part of hydroxide may be decided by the total amount of water and the amount added along with the first part of hydroxide. Therefore, the amount of the water added along with the second part of hydroxide may be equal to or less than the difference between the total amount of water and the amount added along with the first part of hydroxide. In one embodiment of the present disclosure, the amount of the water added along with the second part of hydroxide may be equal to the difference between the total amount of water and the amount added along with the first part of hydroxide. In one embodiment of the present disclosure, the amount of the water added along with the second part of hydroxide may be less than the difference between the total amount of water and the amount added along with the first part of hydroxide, and in this case, the remaining water may be added separately from the first and second parts of hydroxide.In one embodiment of the present disclosure, the first part of hydroxide may be added along with water to a reactor first, and then the second part of hydroxide, water and alkanol are added to the reactor.

[0090] In the process of the first aspect, when the alkoxide of Ri-O-X is produced e.g., in situ, by reacting an alkanol of Ri-OH with a hydroxide X-OH, and Ri and X are as previously defined, the molar ratio of the alkanol to 2,4-dihalo-nitrobenzene of formula (II) may be 1:1 to 4: 1. Within the range of 1 : 1 to 4: 1, the molar ratio of the alkanol to 2,4-dihalo-nitrobenzene of formula (II) may be 1.0:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2.0:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1, 2.6:1, 2.7:1, 2.8:1, 2.9:1, 3.0:1, 3.1:1, 3.2:1, 3.3:1, 3.4:1, 3.5:1, 3.6:1, 3.7:1, 3.8:1, 3.9:1, 4.0:1, and any ranges formed by selecting any two molar ratios mentioned above as the two limits, for example, 1.2:1 to 3.5:1, 1:1 to 3:1, or 1.8:1 to 2.5:1, etc.

[0091] In the process of the first aspect, the molar ratio of the alkoxide to 2,4-dihalo-nitrobenzene of formula (II) may be 0.7:1 to 2:1. Within the range of 0.7:1 to 2:1, the molar ratio of the alkanol to 2,4-dihalo-nitrobenzene of formula (II) may be 0.7:1, 0.8:1, 0.9:1, 1.0:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2.0, and any ranges formed by selecting any two molar ratios mentioned above as the two limits, for example, 0.8:1 to 1.5:1, or 0.9:1 to 1.1:1, etc.

[0092] In the process of the first aspect, in the preferable embodiment of the present disclosure, the 2-alkoxy-4-halo- nitrobenzene of formula (I) is 2-ethoxy-4-fluoro-nitrobenzene, and the 2,4-dihalo-nitrobenzene of formula (II) is 2,4-difluoro-nitrobenzene, that is to say, Ri is ethyl, R2 and R4 are identical and are F. In this embodiment, the molar ratio of water to 2,4-difluoro-nitrobenzene may be preferably 1:1 to 3:1. Within the range of 1:1 to 3:1, the molar ratio of water to 2,4-difluoro-nitrobenzene may be 1.0:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2.0:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1, 2.6:1, 2.7:1, 2.8:1, 2.9:1, 3.0:1, and any ranges formed by selecting any two molar ratios mentioned above as the two limits, for example, 1.2:1 to 1.8:1, or 1.4:1 to 1.7:1, etc.

[0093] In the process of the first aspect, there is no limitation for the organic solvent used in the process. Any suitable organic solvent that are conventionally used for preparing 2-ethoxy-4-fluoro-nitrobenzene are applicable. For example as the organic solvent, both polar and non-polar organic solvents can be used, among polar solvents Ci-Ce alcohols (e.g., methanol, ethanol), acetonitrile, tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide, and the like are suitable. Among non-polarsolvents benzene, toluene, xylene, chlorobenzene, dichloromethane, di chloroethane, chloroform and the like are suitable. Two or more of the above-mentioned solvents may be used as a mixture.

[0094] In the process of the first aspect, in one embodiment of the present disclosure, the organic solvent may be benzene, toluene, xylene, chlorobenzene, dichloromethane, di chloroethane, chloroform and the like. In the process of the first aspect, in one embodiment of the present disclosure, the organic solvent is preferably toluene.

[0095] In the process of the first aspect, the molar ratio of the organic solvent to 2,4-dihalo-nitrobenzene of formula (II) may be 1:1 to 15:1. Within the range of 1 : 1 to 15:1, the molar ratio of the organic solvent to 2,4-dihalo-nitrobenzene of formula (II) may be 1.0:1, 1.5:1, 2.0:1, 2.5:1, 3.0:1, 3.5:1, 4.0:1, 4.5:1, 5.0:1, 5.5:1, 6.0:1, 6.5:1, 7.0:1, 7.5:1, 8.0:1, 8.5:1, 9.0:1, 10.0:1, 11.0:1, 12.0:1, 13.0:1, 14.0:1, 15.0:1, and any ranges formed by selecting any two molar ratios mentioned above as the two limits, for example, 2.0: 1 to 12.0:1, 3.0:1 to 10.0:1, or 6.0:1 to 8.0:1, etc.

[0096] In the process of the first aspect, there is no limitation on how the organic solvent is added in the process. The organic solvent may be added in a conventional way.

[0097] As mentioned above, in one embodiment, it is possible that the alkoxide of Ri-O-X is produced (e.g., in situ) by reacting an alkanol of Ri-OH with a hydroxide X-OH, and Ri and X are as previously defined, and the hydroxide X-OH are added in two parts, the first part is added along with water without the alkanol, and the second part is added along with water and the alkanol. In this embodiment of the present disclosure, all the organic solvent may be added along with the second part of hydroxide, water and the alkanol. It is also possible that the organic solvent is added in two parts, one part is added with the first part of hydroxide, and the other part is added with the second part of hydroxide. It is still possible that the organic solvent may be added in more than two parts, one part is added along with the first part of hydroxide, the second part is added with the second part of hydroxide, and the other part(s) is / are added independently from the hydroxide.

[0098] In the process of the first aspect, there is no limitation on the reaction temperature, and the reaction of 2,4-dihalo-nitrobenzene of formula (II) and the alkoxide may be conducted at any conventional temperatures based on the actual requirements. In one embodiment of the present disclosure, the temperature for thereaction of 2,4-dihalo-nitrobenzene of formula (II) and the alkoxide may be 0 to 90 °C. Within the range of 0 to 90 °C, the temperature may be 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90 °C, and any ranges formed by selecting any two temperatures mentioned above as the two limits, for example, 15 to 80 °C, 20 to 40 °C, 25 to 35 °C, etc.

[0099] In the process of the first aspect, there is no limitation on the reaction time for the reaction of 4-dihalo-nitrobenzene of formula (II) and the alkoxide, those skilled in the art may decide the reaction time based on the actual conditions such as the reaction temperature. In one embodiment of the present disclosure, the reaction time may be 0.5 h to 40 hrs, e.g., 1 to 28 hrs, or 2 to 17 hrs. Surprisingly, it has now been found that, by adding a specified amount of water in the reaction of 2,4-dihalo-nitrobenzene of formula (II) and the alkoxide, the rection may be conducted in a faster way (shorter) than the prior art processes.

[0100] In the process of the first aspect, the selectivity of 2-alkoxy-4-halo-nitrobenzene of formula (I) (e.g., 2-ethoxy-4-fluoro-nitrobenzene) in the process of the present disclosure may be greater than 95 area%. In one embodiment of the present disclosure, the selectivity of 2-alkoxy-4-halo- nitrobenzene of formula (I) (e.g., 2-ethoxy-4-fluoro-nitrobenzene) may be greater than 96 area%, for example, greater than 97 area%, greater than 98 area%, or greater than 99 area%. Surprisingly, it has now been found that, by adding a specified amount of water in the reaction of 2,4-dihalo-nitrobenzene of formula (II) and the alkoxide, the rection may be conducted at a higher selectivity of 2-alkoxy-4-halo- nitrobenzene of formula (I) (e.g., 2-ethoxy-4-fluoro-nitrobenzene) than the prior art processes.

[0101] In the process of the first aspect, the selectivity of all the byproducts in the product mixture may be less than 5 area%. In one embodiment of the present disclosure, the selectivity of all the byproducts in the product mixture may be less than 4 area %, for example, less than 3 area %, less than 2 area %, or less than 1 area %. Surprisingly, it has now been found that, by adding a specified amount of water in the reaction of 2,4-dihalo-nitrobenzene of formula (II) and the alkoxide, the rection may be conducted in a cleaner way than the prior art processes.In the process of the first aspect, when the alkoxide of Ri-O-X is produced (e.g., in situ) by reacting an alkanol of Ri-OH with a hydroxide X-OH, and Ri and X are as previously defined, the amount of the Ri-OH used in the present disclosure may be less than 80wt% of the prior art processes. In one embodiment of the present disclosure, when the alkoxide of Ri-O-X is produced (e.g., in situ) by reacting an alkanol of Ri-OH with a hydroxide X-OH, and Ri and X are as previously defined, the amount of the Ri-OH used in the present disclosure may be less than 80wt%, less than 70wt%, less than 60wt%, less than 50wt% of the prior art processes. Surprisingly, it has now been found that, by adding a specified amount of water in the reaction of 2,4-dihalo-nitrobenzene of formula (II) and the alkoxide, the rection may be conducted in a material-saving way as compared to the prior art processes.

[0102] In the first aspect, the process may further comprise other steps in addition to the reaction of 2,4-dihalo-nitrobenzene of formula (II) and an alkoxide of Rl-O-X. For example, the process may comprise a separation step in which the organic phase comprising 2-alkoxy-4-halo- nitrobenzene of formula (I) and the organic solvent is separated from an aqueous phase. The process may comprise a drying step to dry out the organic solvent.

[0103] In the first aspect, the present disclosure also provides the 2-alkoxy-4-halo-nitrobenzene of formula (I) prepared by the process of the first aspect.

[0104] In the first aspect, the present disclosure also provides the 2-ethoxy-4-fluoro-nitrobenzene prepared by the process of the first aspect. The 2-ethoxy-4-fluoro-nitrobenzene prepared by the process of the first aspect may be used to prepare oxyfluorfen.

[0105] Second Aspect

[0106] In the second aspect, the present disclosure provides a process for preparing oxyfluorfen and the oxyfluorfen prepared by the process of the second aspect.

[0107] The process for preparing oxyfluorfen in the second aspect comprises the following steps: step (i): preparing 2-ethoxy-4-fluoro-nitrobenzene by the process as described in the first aspect; and step (ii): reacting 2-ethoxy-4-fluoro-nitrobenzene obtained in step (i) with 2-chloro-4-trifluorom ethylphenol.

[0108] In step (i) of the process of the second aspect, the 2-ethoxy-4-fluoro-nitrobenzene is prepared by the process as described in the first aspect. Therefore, all the specific descriptions made on the process for preparing 2-alkoxy-4-halo-nitrobenzene of formula (I) in the first aspects (when the 2-alkoxy-4-halo- nitrobenzene of formula (I) is 2-ethoxy-4-fluoro-nitrobenzene, and the 2,4-dihalo-nitrobenzene of formula (II) is 2,4-difluoro-nitrobenzene, that is, Ri is ethyl, R2 is a F, R3 is NO2, R4 is F) apply to the step (i) as all relevant descriptions have been copied here. For example, unless otherwise indicated, all the specific descriptions on the molar ratio of water to 2,4-dihalo-nitrobenzene of formula (II), the alkoxide of Ri-O-X, the organic solvent, the addition of the hydroxide, the concentration of the hydroxide in the water solution, the molar ratio of the alkanol to 2,4-dihalo-nitrobenzene of formula (II), the molar ratio of water to 2,4-difluoro-nitrobenzene, reaction conditions (temperature, time), and the like specified in the first aspect apply to here in the second aspect as all relevant specific descriptions have been copied here.

[0109] In step (ii) of the process of the second aspect, 2-ethoxy-4-fluoro-nitrobenzene obtained in step (i) is reacted with 2-chloro-4-trifluoromethylphenol. Any methods and conditions known in the art for preparing oxyfluorfen by reacting 2-ethoxy-4-fluoro-nitrobenzene with 2-chloro-4-trifluoromethylphenol may be adopted in the process of the second aspect. For example, the methods and conditions disclosed in US4262152A and IN476525B may be used in step (ii) of the process of the second aspect.

[0110] In the second aspect, in one embodiment of the present disclosure, 2-chloro-4-trifluoromethylphenol in step (ii) may be obtained as a by-product and / or residual waste in different manufacturing process such as described in U.S. Patent No. 4, 046,798. In the second aspect, in one embodiment of the present disclosure, as the residual waste, 2-chloro-4-trifluoromethylphenol in step (ii) may exist in a mixture with 2-chloro-5-(trifluoromethyl)-phenol .

[0111] In the second aspect, in one embodiment of the present disclosure, 2-chloro-4-trifluoromethylphenol in step (ii) may be obtained from a mixture of 2-chloro-4-trifluoromethylphenol and 2-chloro-5-trifluoromethyl-phenol. In the second aspect, in one embodiment of the present disclosure, step (ii) may comprise the steps of: (iil) combining the mixture of 2-chloro-4-trifluoromethylphenol and 2-chloro-5-trifluoromethyl-phenol with a base in the presence of at least one solvent so as to form a precipitate; and (ii2) separating the precipitate, thereby separating the 2-chloro-4-trifluoromethylphenol from the mixture.

[0112] In the second aspect, in one embodiment of the present disclosure, in step (iil), the base may be an organic base selected from the group consisting of triethylamine, trimethylamine, ammonia, ammonium hydroxide, pyridine, guanidines,tetramethylammonium hydroxide, tetrabutylammonium hydroxide, choline hydroxide, 1,4- diazabicyclo[2.2.2]octane (DABCO), or an inorganic base selected from the group consisting of an alkali metal base (such as a sodium base, lithium base, potassium base, magnesium base or calcium base), hydroxy base, alkoxy base (such as a methoxy base or an ethoxy base) or carbonate base (such as lithium carbonate, sodium carbonate, sodium bicarbonate, potassium carbonate or potassium bicarbonate). The base may contain water.

[0113] In the second aspect, in one embodiment of the present disclosure, in step (iil), at least two solvents are present, at least one of the solvents is a polar solvent selected from alcohol (methanol, ethanol or propanol), dimethyl sulfoxide (DMSO), dimethylformamide (DMF), N-Methyl-2-pyrrolidone (NMP), glycols, sulfolan, mono and di-glymes, acetamide, glycerine, acetonitrile (ACN), nitro ethane, and any combination thereof; and at least one of the solvents is a nonpolar solvent selected from toluene, xylene, mono chloro benzene (MCB), naphtha, pentane, hexane, or dichloromethane (DC ) and any combination thereof. In the second aspect, in one embodiment of the present disclosure, in step (iil), one of the solvents is water. In one embodiment of the present disclosure, in step (iil), the water is added to the reaction mixture. In one embodiment of the present disclosure, in step (iil), the water is formed during the reaction. In one embodiment of the present disclosure, in step (ii 1), the water is formed with addition of the base into the reaction mixture.

[0114] In the second aspect, in one embodiment of the present disclosure, in step (iil), the ratio of 2-chloro-4-trifluoromethylphenol to 2-chloro-5-trifluoromethyl-phenol in the mixture may be from 1 : 1000 to 1000: 1, for example, 90: 10 to 70:30, e.g., 90: 10, 85: 15, or 80:20, 75:25, or 70:30, preferably 88: 12.

[0115] In the second aspect, in one embodiment of the present disclosure, in step (iil), the mixture which comprises 2-chloro-4-trifluoromethylphenol to 2-chloro-5-trifluoromethyl-phenol may be a solution. In one embodiment of the present disclosure, in step (iil), the concentration of the 2-chloro-4-trifluoromethylphenol in the solution may be from about 1% to 99%.

[0116] In the second aspect, in one embodiment of the present disclosure, in step (iil), the resulting precipitate material may be a metal salt.

[0117] In the second aspect, in one embodiment of the present disclosure, in step (iil), the ratio of 2-chloro-4-trifluoromethylphenol to 2-chloro-5-trifluoromethyl-phenol inthe resulting precipitate material may be from 50: 1 to 1000: 1, for example 50:1 to 500:1, 50: I to 200: 1, or 50:1 to 100: 1, preferably 77:0.4, more preferably 98.15: 1.85.

[0118] In the second aspect, in one embodiment of the present disclosure, in step (iil), the resulting precipitate material may be a solid.

[0119] In the second aspect, in one embodiment of the present disclosure, in step (iil), the resulting precipitate material may be a paste.

[0120] In the second aspect, in one embodiment of the present disclosure, in step (ii2), the resulting precipitate material may be separated by filtration.

[0121] In the second aspect, in one embodiment of the present disclosure, in step (ii2), the resulting precipitate material may be separated by centrifuge.

[0122] In the second aspect, in one embodiment of the present disclosure, in step (ii2), the resulting precipitate material may be separated by decantation.

[0123] In the second aspect, in one embodiment of the present disclosure, 2-chloro-4-trifluoromethylphenol in step (ii) may be present in its alkali metal salt, e.g., K, Li, Na salt. In one embodiment of the present disclosure, 2-chloro-4-trifluoromethylphenol in step (ii) may be present in its K or Na salt. The alkali metal salt may be prepared by any methods known in the art from 2-chloro-4-trifluorom ethylphenol.

[0124] WO2018185559 discloses the details for obtaining 2-chloro-4-trifluoromethylphenol or its alkali metal salt from a mixture of 2-chloro-4-trifluoromethylphenol and 2-chloro-5-trifluoromethyl-phenol, which is incorporated herein for reference.

[0125] In the second aspect, the process may further comprise other steps after the step (ii) or (ii2). For example, the process may comprise a distillation step to distill the organic solvent. The process may comprise a filtration step to obtain crude products comprising oxyfluorfen. The process may comprise a drying step to dry out the solvent.

[0126] In the second aspect, the present disclosure also provides the oxyfluorfen prepared by the process of the second aspect. The oxyfluorfen may be a solid. The oxyfluorfen may be a solution in an organic solvent.

[0127] Each embodiment disclosed herein is contemplated as being applicable to each of the other disclosed embodiments. Thus, all combinations of the various elements described herein are within the scope of the disclosure.

[0128] This disclosure will be better understood by reference to the Examples which follow, but those skilled in the art will readily appreciate that the specific experimentsdetailed are only illustrative of the disclosure as described more fully in the claims which follow thereafter.

[0129] The disclosure is illustrated by the following examples without limiting it thereby.

[0130] EXAMPLES

[0131] Comparative Example 1 (CE1): Preparation of 2-ethoxy-4-fluoro-nitrobenzene

[0132] To a IL reactor was added with 80gr 2,4-dihalo-nitrobenzene (DFNB) and 320 gr of Toluene. To a dropping panel was added with 131.8gr of 22.5% KOH solution in ethanol. The reactor was cooled to 18°C and the KOH solution was added dropwise over 5hr. The reactor was maintained on a temperature of 20°C during the reaction. The progress of the reaction was monitored by GC as shown in Table 1 :

[0133] Table 1:

[0134] "

[0135]

[0136] Note: Ethoxy: 2-ethoxy-4-fluoro-nitrobenzene

[0137] Isomer: 2- fluoro-4- ethoxy -nitrobenzene

[0138] Di-Ethoxy: 2-ethoxy-4- ethoxy -nitrobenzene

[0139] ND: not detected

[0140] Aera%: the area percent of a peak of the specific substance as a percentage of the total area of all peaks in an HPLC chromatogram

[0141] As is seen from Table 1, after 4 hours, DFNB was not detected at the HPLC sample, that is to say the conversion rate of DFNB after 4 hours was nearly 100%. After 5 hours, the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) was present at 93.9 area % from HPLC in the product mixture , which represented a selectivity of 93.9 area%. The selectivity of the undesired product Isomer (2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 0.13 area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 5.07 area%. After 6hours, the selectivity of desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 94.48 area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy - nitrobenzene) in the product mixture was 5.01 area%.

[0142] Comparative Example 1’ (CE1’): Preparation of 2-ethoxy-4-fluoro-nitrobenzene

[0143] To a IL reactor was added with 80gr 2,4-dihalo-nitrobenzene (DFNB) and 320 gr of Toluene. To a dropping panel was added with 130gr of 22.5% KOH solution in ethanol. The reactor was heated to 29°C and the KOH solution was added dropwise over 5hr. The reactor was maintained on a temperature of 30°C during the addition, and kept stirring 1 hr to ensure the end of reaction and then overnight at 20°C. The progress of the reaction was monitored by GC as shown in Table 1’:

[0144] Table 1’:

[0145]

[0146] Note: Ethoxy: 2-ethoxy-4-fluoro-nitrobenzene

[0147] Isomer: 2- fluoro-4- ethoxy -nitrobenzene

[0148] Di-Ethoxy: 2-ethoxy-4- ethoxy -nitrobenzene

[0149] ND: not detected

[0150] O.N.: overnight

[0151] Compared CEE to CE1, the temperature was raised from 20 °C in CE1 to 30 °C in CEF, the molar ratio of ethanol to DFNB was reduced from 4.42 in CE1 to 4.37 inCE1’. As is seen from Table 1’, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 97.88area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 1.44 area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 0.39 area%. After 6 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 97.42 area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 1.49 area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 0.47 area%. After 7 hours or even over night, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 97.42 area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 1.53 area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 0.47 area%.

[0152] Comparative Example 2 (CE2): Preparation of 2-ethoxy-4-fluoro-nitrobenzene

[0153] To a IL reactor was added with 80gr 2,4-dihalo-nitrobenzene (DFNB) and 320 gr of Toluene, and the reactor was cooled to 17°C. In additional vessel 27gr KOH 89% (solid) was added to 35gr water with stirring. The KOH aq. solution was cooled to 10°C and then added to ethanol (80gr) with stirring to obtain a clear solution. The solution of KOH / water / ethanol was added to the reactor dropwise over 5hrs while the temperature was maintained at 20 °C. The progress of the reaction was monitored by GC as shown in Table 2:

[0154] Table 2

[0155]

[0156]

[0157] Note: Ethoxy: 2-ethoxy-4-fluoro-nitrobenzene

[0158] Isomer: 2- fluoro-4- ethoxy -nitrobenzene

[0159] Di-Ethoxy: 2-ethoxy-4- ethoxy -nitrobenzene

[0160] ND: not detected

[0161] Aera%: the area percent of a peak of the specific substance as a percentage of the total area of all peaks in an HPLC chromatogram

[0162] Compared CE2 to CE1, water was added in a molar ratio of water to DFNB of 4.2, and the molar ratio of ethanol to DFNB was reduced from 4.42 in CE1 to 3.46 in CE2. As is seen from Table 2, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 77.82 area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 1.81 area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 2.14 area%. After 6 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 80.04 area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 2.14 area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 2.36 area%. After even 7 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 80.69 area%, the selectivity of the undesired product Isomer ( 2-fluoro-4- ethoxy -nitrobenzene) in the product mixture was 2.37 area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 2.3 area%. It is clear that DFNB was still present significantly in the product mixture after 5, 6, or 7 hours. Without being limited to theory, with too much water, the solution phase formed by KOH, Ethanol, and water was decomposed and the reaction was stacked on 80% to 85% conversion rate for DFNB.

[0163] Example 3 (E3): Preparation of 2-ethoxy-4-fluoro-nitrobenzene

[0164] To a IL reactor was added with 640 gr of toluene and 15.4 gr water and 18.6 gr of KOH solid (90%). The solution mixture was stirred at 40°C for 1 hr and then cooled to 20°C. In an additional vessel, a clear solution of KOH, ethanol and waterwas prepared by adding 44gr KOH 90% (solid) to 100 gr ethanol and 14gr water, and stirring for 30 min. Then the DFNB (160 gr) was added to the reactor at 20°C while stirring. Following, the solution of KOH, ethanol and water was added dropwise to the reactor during 3hr and then stirred for addition 3hr with the temperature maintained at 28 to 30 °C. The progress of the reaction was monitored by GC as shown in Table 3:

[0165] Table 3:

[0166] "

[0167] """

[0168] "

[0169]

[0170] Note: Ethoxy: 2-ethoxy-4-fluoro-nitrobenzene

[0171] Isomer: 2- fluoro-4- ethoxy -nitrobenzene

[0172] Di-Ethoxy: 2-ethoxy-4- ethoxy -nitrobenzene

[0173] ND: not detected

[0174] Aera%: the area percent of a peak of the specific substance as a percentage of the total area of all peaks in an HPLC chromatogram

[0175] As is seen from Table 3, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 98.76area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 0.79area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 0.23area%. After 6 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 99.1 larea%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 0.66area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4-ethoxy -nitrobenzene) in the product mixture was 0.23area%.

[0176] Compared E3 to CEE, water was added in a molar ratio of water to DFNB of 1.66, and the molar ratio of ethanol to DFNB was reduced from 4.37 in CEF to 2.16in E3. Compared E3 to CEE, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was increased from 97.88area% in CEF to 98.76area% in E3, and after 6 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was increased from 97.42area% in CEF to 99.11area% in E3. Similarly, compared E3 to CEF, after 5 hours, the total selectivity of the undesired products Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) and Di-Ethoxy (2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was reduced from 1.83 area% in CEF to 1.02area% in El, and after 6 hours, the total selectivity of the undesired products Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) and Di-Ethoxy (2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was reduced from 1.96 area% in CEF to 0.89area% in E3.

[0177] Compared E3 to CE2, the molar ratio of water to DFNB was reduced from 3.88 in CE2 to 1.66 in E3, and the molar ratio of ethanol to DFNB was reduced from 3.46 in CE2 to 2.16 in E3. Compared E3 to CE2, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was increased from 77.82area% in CE2 to 98.76area% in E3, and after 6 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was increased from 80.04area% in CE2 to 99.1 larea% in E3.

[0178] Similarly, compared E3 to CE2, after 5 hours, the total selectivity of the undesired products Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) and Di-Ethoxy (2-ethoxy-4-ethoxy -nitrobenzene) was reduced from 3.95 area% in CE2 to 1.02area% in E3, and after 6 hours, the total selectivity of the undesired products Isomer ( 2- fluoro-4-ethoxy -nitrobenzene) and Di-Ethoxy (2-ethoxy-4- ethoxy -nitrobenzene) was reduced from 4.50 area% in CE1 to 0.89area% in E3.

[0179] Example 4 (E4): Preparation of 2-ethoxy-4-fluoro-nitrobenzene

[0180] To a IL reactor was added with 320 gr of toluene, 6.4 gr water and 9.8 gr of KOH solid (90%) (total KOH in water solution was 54.7%). The solution mixture was stirred at 40°C for 1 hr and then cooled to 20°C. In an additional vessel, a clear solution of KOH, ethanol and water was prepared by adding 22gr KOH 90% (solid) to 50 gr ethanol and 7gr water and stirring for 30 min. Then the DFNB (80 gr) was added to the reactor at 20°C while stirring. The solution of KOH, ethanol and water (25.1% KOH in water / E ethanol) was added dropwise to the reactor during 3hr and then stirred for additional 2hr with the temperature maintained at 28 to 30 °C. Thereaction was finished after 5 hr. The progress of the reaction was monitored by GC as shown in Table 4.

[0181]

[0182] Isomer: 2- fluoro-4- ethoxy -nitrobenzene

[0183] Di-Ethoxy: 2-ethoxy-4- ethoxy -nitrobenzene

[0184] ND: not detected

[0185] Aera%: the area percent of a peak of the specific substance as a percentage of the total area of all peaks in an HPLC chromatogram

[0186] As is seen from Table 4, after 4 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 99.03 area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 0.54area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 0.13 area%. After 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 99.09area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 0.68area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4-ethoxy -nitrobenzene) in the product mixture was 0.22area%.

[0187] Compared E4 to CEE, water was added in a molar ratio of water to DFNB of 1.84, and the molar ratio of ethanol to DFNB was reduced from 4.37 in CEF to 2.16 in E4. Compared E4 to CEF, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was increased from 97.88area% in CE1 ’ to 99.09area% in E4. Similarly, compared E4 to CE1 ’, after 5 hours, the total selectivity of the undesired products Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) and Di-Ethoxy (2-ethoxy-4- ethoxy -nitrobenzene) was reduced from 1.83 area% in CEE to 0.90area% in E4.

[0188] Compared E4 to CE2, the molar ratio of water to DFNB was reduced from 4.2 in CE2 to 1.84 in E4, and the molar ratio of ethanol to DFNB was reduced from 3.46 in CE2 to 2.16 in E4. Compared E4 to CE2, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) was increased from 77.82area% in CE2 to 99.09area% in E4. Similarly, compared E4 to CE2, after 5 hours, the total selectivity of the undesired products Isomer (2- fluoro-4- ethoxy -nitrobenzene) and Di-Ethoxy (2-ethoxy-4- ethoxy -nitrobenzene) was reduced from 3.95 area% in CE2 to 0.90area% in E4.

[0189] Compared E4 to E3, the molar ratio of water to DFNB was reduced from 1.84 to 1.66, and the molar ratio of ethanol to DFNB was the same. Compared E4 to E3, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) was increased from 98.76area% in E3 to 99.09area% in E4. Compared E4 to E3, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in E4 after 5 hours was 99.09area% which was almost the same as in E3 after 6 hours (99.1 larea%). Similarly, compared E4 to E3, after 5 hours, the total selectivity of the undesired products Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) and Di-Ethoxy (2-ethoxy-4- ethoxy -nitrobenzene) was 0.90area% in E4, which was almost the same as in E3 after 6 hours (0.89area%). Therefore, E4 was almost 1 hour faster than E3 to arrive at the same selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) and the same total selectivity of the undesired products Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) and Di-Ethoxy (2-ethoxy-4- ethoxy -nitrobenzene).

[0190] Example 5 (E5): Preparation of 2-ethoxy-4-fluoro-nitrobenzene

[0191] To a IL reactor was added with 80gr 2,4-dihalo-nitrobenzene (DFNB) and 320 gr of Toluene.to the reactor added 16.3 gr of KOH solution (55%) with stirring at RT. In additional vessel 22.6 gr KOH 92.6% (solid - that contained 1.67 gr water) was added to 6.1 gr water and 50 gr of ethanol with stirring to obtain a clear solution. The solution of KOH / water / ethanol was added to the reactor dropwise over 5hrs with the reaction temp maintained at 30°C. The progress of the reaction was monitored by GC as shown in Table 5:

[0192] Table 5

[0193]

[0194] Note: Ethoxy: 2-ethoxy-4-fluoro-nitrobenzene

[0195] Isomer: 2- fluoro-4- ethoxy -nitrobenzene

[0196] Di-Ethoxy: 2-ethoxy-4- ethoxy -nitrobenzene

[0197] ND: not detected

[0198] O.N.: overnight

[0199] As is seen from Table 5, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 97.66area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 0.96area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 0.35 area%. After 6 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 97.99area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 0.94area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4-ethoxy -nitrobenzene) in the product mixture was 0.39 area%. After a whole night, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 98.39area%, the selectivity of the undesired product Isomer ( 2-fluoro-4- ethoxy -nitrobenzene) in the product mixture was 0.86area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 0.52area%.

[0200] Compared E5 to CEE, water was added in a molar ratio of water to DFNB of 1.7, and the molar ratio of ethanol to DFNB was reduced from 4.37 in CEF to 2.17 in E5. Compared E5 to CEF, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 97.88 in CEF whichwas similar to 97.66area% in E5. Similarly, compared E5 to CEE, after 5 hours, the total selectivity of the undesired products Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) and Di-Ethoxy (2-ethoxy-4- ethoxy -nitrobenzene) was reduced from 1.83 area% in CEF to 1.31area% in E5.

[0201] Example 6 (E6): Preparation of 2-ethoxy-4-fluoro-nitrobenzene

[0202] To a IL reactor was added with 79.5gr 2,4-dihalo-nitrobenzene (DFNB) and 320 gr of Toluene.to the reactor added 10 gr of KOH solid (92.6%) and 1 gr of water with stirring at RT. In additional vessel 22.4 gr KOH 92.6% (solid - that contained 1.67 gr water) was added to 5.6 gr water and 50 gr of ethanol with stirring to obtain a clear solution. The solution of KOH / water / ethanol was added to the reactor dropwise over 5hrs with the reaction temp maintained at 30°C. The progress of the reaction was monitored by GC as shown in Table 6:

[0203] Table 6

[0204]

[0205] Note: Ethoxy: 2-ethoxy-4-fluoro-nitrobenzene

[0206] Isomer: 2- fluoro-4- ethoxy -nitrobenzene

[0207] Di-Ethoxy: 2-ethoxy-4- ethoxy -nitrobenzene

[0208] ND: not detected

[0209] O.N.: overnight

[0210] As is seen from Table 6, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 98.23 area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 0.87area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 0.49 area%.After 7 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 98.54area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 0.71area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4-ethoxy -nitrobenzene) in the product mixture was 0.75 area%.

[0211] Compared E6 to CEE, water was added in a molar ratio of water to DFNB of 1, and the molar ratio of ethanol to DFNB was reduced from 4.37 in CEF to 2.17 in E6. Compared E6 to CEF, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was increased from 97.88area% in CEF to 98.23area% in E6. Similarly, compared E6 to CE1, after 5 hours, the total selectivity of the undesired products Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) and Di-Ethoxy (2-ethoxy-4- ethoxy -nitrobenzene) was reduced from 1.83 area% in CEF to 1.36area% in E6.

[0212] Example 7 (E7): Preparation of 2-ethoxy-4-fluoro-nitrobenzene

[0213] To a IL reactor was added with 79.5gr 2,4-dihalo-nitrobenzene (DFNB) and 320 gr of Toluene.to the reactor added 10 gr of KOH solid (92.6%) and 5 gr of water with stirring at RT. In additional vessel 22.4 gr KOH 92.6% (solid - that contained 1.67 gr water) was added to 6.1 gr water and 50 gr of ethanol with stirring to obtain a clear solution. The solution of KOH / water / ethanol was added to the reactor dropwise over 5hrs with the reaction temp maintained at 30°C. The progress of the reaction was monitored by GC as shown in Table 7:

[0214] Table 7

[0215] "

[0216]

[0217] Note: Ethoxy: 2-ethoxy-4-fluoro-nitrobenzene

[0218] Isomer: 2- fluoro-4- ethoxy -nitrobenzene

[0219] Di-Ethoxy: 2-ethoxy-4- ethoxy -nitrobenzeneND: not detected

[0220] As is seen from Table 7, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 98.61area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 0.65area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 0.75 area%. After 6 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 98.52area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 0.52area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4-ethoxy -nitrobenzene) in the product mixture was 0.95 area%.

[0221] Compared E7 to CEE, water was added in a molar ratio of water to DFNB of 1.5, and the molar ratio of ethanol to DFNB was reduced from 4.37 in CEF to 2.17 in E7. Compared E7 to CEF, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was increased from 97.88area% in CEF to 98.61area% in E7. Similarly, compared E7 to CEF, after 5 hours, the total selectivity of the undesired products Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) and Di-Ethoxy (2-ethoxy-4- ethoxy -nitrobenzene) was reduced from 1.83area% in CEF to 1.40area% inE7.

[0222] Example 8 (E8): Preparation of 2-ethoxy-4-fluoro-nitrobenzene

[0223] To a IL reactor was added with 79.5gr 2,4-dihalo-nitrobenzene (DFNB) and 320 gr of Toluene.to the reactor added 10 gr of KOH solid (92.6%) and 10 gr of water with stirring at RT. In additional vessel 22.4 gr KOH 92.6% (solid - that contained 1.67 gr water) was added to 10.1 gr water and 50 gr of ethanol with stirring to obtain a clear solution. The solution of KOH / water / ethanol was added to the reactor dropwise over 5hrs with the reaction temp maintained at 30°C. The progress of the reaction was monitored by GC as shown in Table 8:

[0224] Table 8

[0225]

[0226]

[0227] Note: Ethoxy: 2-ethoxy-4-fluoro-nitrobenzene

[0228] Isomer: 2- fluoro-4- ethoxy -nitrobenzene

[0229] Di-Ethoxy: 2-ethoxy-4- ethoxy -nitrobenzene

[0230] ND: not detected

[0231] O.N.: overnight

[0232] As is seen from Table 8, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 96.74area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 1.14area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 0.34 area%. After a whole night, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 98.33area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 0.9area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 0.74 area%.

[0233] Compared E8 to CEE, water was added in a molar ratio of water to DFNB of 2.5, and the molar ratio of ethanol to DFNB was reduced from 4.37 in CE1 to 2.17 in E8. Compared E8 to CEF, after 6 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 97.88 area% in CEF which was similar to 97.32area% in E8. Similarly, compared E8 to CEF, after 6 hours, the total selectivity of the undesired products Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) and Di-Ethoxy (2-ethoxy-4- ethoxy -nitrobenzene) was reduced from 1.96 area% in CEF to 1.54area% in E8.

[0234] Example 9 (E9): Preparation of 2-ethoxy-4-fluoro-nitrobenzene

[0235] To a IL reactor was added with 80gr 2,4-dihalo-nitrobenzene (DFNB) and 320 gr of Toluene.to the reactor added 18.2 gr of KOH solution (49.4%) with stirring at RT. In additional vessel 22.6 gr KOH 92.6% (solid - that contained 1.67 gr water) was added to 6.8 gr water and 41.5 gr of ethanol with stirring to obtain a clearsolution. The solution of KOH / water / ethanol was added to the reactor dropwise over 5hrs with the reaction temp maintained at 30 °C. The progress of the reaction was monitored by GC as shown in Table 9:

[0236] Table 9

[0237] "

[0238] "

[0239]

[0240] Note: Ethoxy: 2-ethoxy-4-fluoro-nitrobenzene

[0241] Isomer: 2- fluoro-4- ethoxy -nitrobenzene

[0242] Di-Ethoxy: 2-ethoxy-4- ethoxy -nitrobenzene

[0243] ND: not detected

[0244] O.N.: overnight

[0245] As is seen from Table 9, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 97.3area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 0.89area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4- ethoxy -nitrobenzene) in the product mixture was 0.28 area%. After a whole night, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 98.55area%, the selectivity of the undesired product Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) in the product mixture was 0.43area%, and the selectivity of the undesired product Di-Ethoxy ( 2-ethoxy-4-ethoxy -nitrobenzene) in the product mixture was 1.03 area%.

[0246] Compared E9 to CEE, water was added in a molar ratio of water to DFNB of 2.03, and the molar ratio of ethanol to DFNB was reduced from 4.37 in CE1 to 1.8 in E9. Compared E9 to CEF, after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was 97.88area% in CE1 which was similar to 97.3area% in E9. Similarly, compared E9 to CEF, after 5hours, the total selectivity of the undesired products Isomer ( 2- fluoro-4- ethoxy -nitrobenzene) and Di-Ethoxy (2-ethoxy-4- ethoxy -nitrobenzene) was reduced from 1.83 area% in CEE to 1.17area% in E9.

[0247] Example 10 (E10): Effect of temperature on Preparation of 2-ethoxy-4-fluoro-nitrobenzene

[0248] To a IL reactor was added with 79.5gr 2,4-dihalo-nitrobenzene (DFNB) and 320 gr of Toluene.to the reactor added 18.2 gr of KOH solution (49.4%) with stirring at RT. In additional vessel 22.6 gr KOH 92.6% (solid - that contained 1.67 gr water) was added to 6.2 gr water and 50 gr of ethanol with stirring to obtain a clear solution. The solution of KOH / water / ethanol was added to the reactor dropwise over 5hrs with the reaction temp maintained at 30 to 80 °C (the temp changed in each experiments) . The progress of the reaction was monitored by GC as shown in Table 10:

[0249] Table 10

[0250]

[0251]

[0252] Note: Ethoxy: 2-ethoxy-4-fluoro-nitrobenzene

[0253] Isomer: 2- fluoro-4- ethoxy -nitrobenzene

[0254] Di-Ethoxy: 2-ethoxy-4- ethoxy -nitrobenzene

[0255] ND: not detected

[0256] O.N.: over night

[0257] As is seen from Table 10, after only 4 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was above 98area% for temperatures of 40 to 60 °C, and after 5 hours, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was above 98area% for temperatures of 30 to 60 °C, which indicated that the higher the temperature was, and fast the reaction was. However, the selectivity of the desired product Ethoxy ( 2-ethoxy-4-fluoro-nitrobenzene) in the product mixture was less than 98 area% at a temperature of 80°C, even over night, which indicated that excessively high temperature was not conducive to the reaction.

[0258] Example 11 (Ell): Preparation of 2-chloro-4-trifluoromethylphenol K salt 350gr toluene was added to a IL round bottom flask, then 90gr KOH flakes, 25gr ethanol, 15gr water were added in sequence, and the mixture in the flask was stirred for one hour. 300gr 93.6% of a mixture of 2-chloro-4-trifhroromethylphenol and 2-chloro-5-trifluoromethyl-phenol (the ratio of 2-chloro-4-trifluorom ethylphenol to 2-chloro-5-trifluoromethyl-phenol was nearly 5:95) was added dropwise at 30° to 35°C for 2hrs, and stirred for 4hrs to dissolve all KOH flakes. The resulted 2-chloro-4-trifluoromethylphenol K salt (Phenoxy-K) solid mass was filtered, the cake was suck dried, and washed with 50gr fresh toluene. Then, the Phenoxy-K was suck dried to obtain the final product with a yield of 97.4%.

[0259] Example 12 (Ell): Preparation of oxyfluorfen

[0260] 1800gr DMF was added to a 3L reactor, and 25gr K2CO3 was added the reactor.

[0261] 610 gr 2-ethoxy-4-fluoro-nitrobenzene prepared according to E4 in DMF (57.7%) was added to the reactor. 600gr Phenoxy-K (98%) prepared according to E5 was dissolved in 2400gr DMF. The reactor was heated to 108°C at 250mbar, and the Phenoxy -K / DMF solution was added dropwise for 10 hours at 108°C and 250mbat while wet DMF was distilled. The reaction was monitored until 2-ethoxy-4-fluoro-nitrobenzene was 2.4 area%. 280gr water was added at 90°C for 15mins, and stirred for 30mins. 850gr Methanol was added slowly at 90° down to 73°C for 15mins, and stirred for Ihr at 73°C. The mixture was cooled to 20°C, the resulting oxyfluorfen was filtrated, and the cake was washed with 450gr methanol / water 75 / 25 solution, and then suck dried to obtain the final product with a yield of 91.5%.

[0262] All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference.

[0263] The examples illustrate the practice of the present subject matter in some of its embodiments but should not be construed as limiting the scope of the present subject matter. Other embodiments apparent to persons of ordinary skill in the art from consideration of the specification and examples herein that fall within the spirit and scope of the appended claims are part of this disclosure. The specification, including the examples, is intended to be exemplary only, without limiting the scope and spirit of the disclosure.

Claims

CLAIMS1. A process for preparing 2-alkoxy-4-halo-nitrobenzene of formula (I) comprising: reacting 2,4-dihalo-nitrobenzene of formula (II) with an alkoxide of Ri-O-X in the presence of an organic solvent and water,(I) (II) wherein:Ri is a Ci-6 alkyl,R2 is a halogen,R3 is NO2,R4 is a halogen,X is an alkali metal.

2. The process of claim 1, wherein the molar ratio of water to 2,4-dihalo-nitrobenzene of formula (II) is 0.1 : 1 to 3.5 : 1.

3. The process of claim 2, wherein the molar ratio of water to 2,4-dihalo-nitrobenzene of formula (II) is 0.5:l to 3:l.

4. The process of any one of claims 1 to 3, wherein X is sodium or potassium.

5. The process of any one of claims 1 to 4, wherein Ri is C1.3 alkyl, R2 and R4 are identical or different and independently selected from F or Cl.

6. The process of any one of claims 1 to 5, wherein the alkoxide is produced by reacting an alkanol of Ri-OH with a hydroxide X-OH and Ri and X are as previously defined.

7. The process of claim 6, wherein the hydroxide is added in two parts, the first part is added along with water without the alkanol, and the second part is added along with water and the alkanol.

8. The process of claim 7, wherein for the first part, the hydroxide is in a water solution, and the concentration of the hydroxide in the water solution is 45wt% to 54wt%.

9. The process of any one of claims 6 to 8, wherein the molar ratio of the alkanol to 2,4-dihalo-nitrobenzene of formula (II) is 1:1 to 4:1.

10. The process of claim 9, wherein the molar ratio of the alkanol to 2,4-dihalo-nitrobenzene of formula (II) is 1:1 to 3 : 1.

11. The process of any one of claims 1 to 10, wherein the molar ratio of the alkoxide to 2,4-dihalo-nitrobenzene of formula (II) is 0.7:1 to 2:1.

12. The process of claim 11, wherein the molar ratio of the alkoxide to 2,4-dihalo-nitrobenzene of formula (II) is 0.8:1 to 1.5:1.

13. The process of any one of claims 1 to 12, wherein the 2-alkoxy-4-halo-nitrobenzene of formula (I) is 2-ethoxy-4-fluoro-nitrobenzene, and the 2,4-dihalo-nitrobenzene of formula (II) is 2,4-difluoro-nitrobenzene.

14. The process of claim 13, wherein the molar ratio of water to 2,4-difluoro-nitrobenzene is 1:1 to 2.5:1.

15. A process for preparing oxyfluorfen comprising the following steps:(i) preparing 2-ethoxy-4-fluoro-nitrobenzene according to claim 13 or 14; and (ii) reacting 2-ethoxy-4-fluoro-nitrobenzene obtained from step (i) with 2-chloro-4-trifluorom ethylphenol .

16. The process of claim 15, wherein the 2-chloro-4-trifluoromethylphenol is obtained from a mixture of 2-chloro-4-trifluoromethylphenol and 2-chloro-5-trifluoromethyl-phenol .

17. The process of claim 16, wherein the 2-chloro-4-trifluoromethylphenol is present in its alkali metal salt.

18. The process of claim 17, wherein the alkali metal salt is K salt.

19. The 2-alkoxy-4-halo- nitrobenzene of formula (I) prepared according to any one of claims 1 to 14.

20. The 2-ethoxy-4-fluoro-nitrobenzene prepared according to claim 13 or 14.

21. The oxyfluorfen prepared according to any one of claim 15 to 18.

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