Process for the preparation of chloromethyl ethyl ether

Abstract

A process for the preparation of chloromethyl ethyl ether is disclosed. The process comprises reacting paraformaldehyde with ethanol and thionyl chloride. The present invention further discloses a process for the preparation of substantially pure acetochlor comprising the step of treating a crude mixture of acetochlor and 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide with chloromethyl ethyl ether in the presence of a base and a solvent at a temperature of about 0°C to about 40°C, thereby making the process simple, economical and industrially viable and thereby providing acetochlor with reduced content of 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide.

Description

Technical Field

[0001] This invention relates to a method for preparing chloromethyl ethyl ether. Furthermore, this invention also provides a method for preparing acetochlor using chloromethyl ethyl ether. Background Technology

[0002] Chloromethyl ethyl ether or (chloromethoxy)ethane is a valuable substance for the chemical industry. It is best known as a chloromethylating agent or methoxymethylating agent in various chemical reactions and as a raw material in the preparation of various pharmaceutical and agrochemical active ingredients. It is also an important building block used in the preparation of acetochlor. Acetochlor, a well-known chloroacetanilide herbicide represented by formula (I), is mainly used as a pre-emergence or pre-planting herbicide to control annual grasses and some broadleaf weeds. It is a selective herbicide primarily absorbed through the seedlings and roots of germinating weeds. It inhibits the synthesis of very long-chain fatty acids.

[0003] .

[0004] JP02282344 describes the preparation of chloromethyl ethyl ether via the reaction of ethanol, paraformaldehyde, and hydrogen chloride gas. In this reaction, water is produced as a byproduct. Chloromethyl ethyl ether is known to be a moisture-sensitive compound. To avoid interference from water in the reaction, the method involves the use of calcium chloride. Calcium chloride ensures the removal of water / moisture from the reaction and the completion of the reaction.

[0005] The disadvantages of the methods provided in the prior art can be listed as follows:

[0006] i) Use corrosive agents, such as hydrogen chloride gas; it is difficult to handle and requires extreme caution;

[0007] ii) The use of calcium chloride, if not handled properly, can cause health hazards and may lead to corrosion of reaction vessels, especially those made of stainless steel.

[0008] To overcome these drawbacks, the inventors of this invention have developed an economical, eco-friendly, and high-yield method for preparing chloromethyl ethyl ether. Furthermore, a method for preparing acetochlor with high purity and high yield using said chloromethyl ethyl ether has also been developed. Summary of the Invention

[0009] The main objective of this invention is to provide a method for preparing chloromethyl ethyl ether.

[0010] Another object of the present invention is to provide an economical, safe and easy-to-handle method for preparing chloromethyl ethyl ether.

[0011] Another object of the present invention is to provide a method for preparing acetochlor in high yield and high purity.

[0012] Another object of the present invention is to convert 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (a byproduct formed during the preparation of acetochlor) into acetochlor by reacting it with chloromethyl ethyl ether prepared according to the present invention.

[0013] Another object of the present invention is to provide a simple, economical and industrially feasible method for preparing acetochlor (I) with reduced 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III).

[0014] According to one aspect of the present invention, a method for preparing chloromethyl ethyl ether (II) is provided, the method comprising reacting paraformaldehyde with ethanol and thionyl chloride.

[0015] .

[0016] According to another aspect of the invention, a method for converting a byproduct into acetochlor (I) is provided, the method comprising the step of treating a mixture containing acetochlor (I) and its byproduct with chloromethyl ethyl ether (II); wherein the byproduct is 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III).

[0017] .

[0018] According to another aspect of the present invention, a method for preparing acetochlor (I) is provided, the method comprising:

[0019] i. Reaction of N-(2-ethyl-6-methylphenyl)methylimine (IV) with chloroacetyl chloride (V) yields 2-chloro-N-(chloromethyl)-N-(2-ethyl-6-methylphenyl)acetamide (VI);

[0020] ii. React 2-chloro-N-(chloromethyl)-N-(2-ethyl-6-methylphenyl)acetamide (VI) with ethanol to obtain a mixture containing acetochlor and its byproduct (III);

[0021] iii. The byproduct is converted into acetochlor (I) by treating the mixture with chloromethyl ethyl ether (II);

[0022] The byproduct is 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III), and the reaction is carried out in a continuous flow reactor.

[0023]

[0024] .

[0025] According to another aspect of the present invention, a method for preparing acetochlor (I) is provided, the method comprising:

[0026] i. Reacting paraformaldehyde with ethanol and thionyl chloride to obtain chloromethyl ethyl ether (II); and

[0027] ii. Reaction of N-(2-ethyl-6-methylphenyl)methylimine (IV) with chloroacetyl chloride (V) yields 2-chloro-N-(chloromethyl)-N-(2-ethyl-6-methylphenyl)acetamide (VI), followed by reaction with ethanol to obtain acetochlor and its byproduct (III);

[0028] iii. Treat a mixture containing acetochlor and its byproducts with the chloromethyl ethyl ether (II);

[0029] The byproduct is 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III). Attached Figure Description

[0030] Figure 1 The GC chromatogram of Example 1 is shown;

[0031] Figure 2 The GC chromatogram of Example 2 is shown;

[0032] Figure 3 The GC chromatogram of Example 3 is shown;

[0033] Figure 4 The GC chromatogram of Example 4 is shown;

[0034] Figure 5 The continuous flow synthesis of acetochlor according to Example 5 of the present invention is illustrated in schematic diagram. Detailed Implementation

[0035] Those skilled in the art will recognize that the invention described herein can undergo variations and modifications beyond those specifically described. It should be understood that the invention described herein includes all such variations and modifications. The invention also includes all such steps, features, compositions, and methods individually or collectively mentioned or indicated in this specification, as well as any and all combinations of any two or more of the stated steps or features.

[0036] For convenience, certain terms used in the specification and embodiments are described herein before further description of the invention. These definitions should be interpreted in conjunction with the remainder of this disclosure and will be understood by those skilled in the art. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Unless otherwise limited in specific circumstances, the terms used throughout this specification are defined as follows.

[0037] The terminology used in this article is defined as follows:

[0038] Unless the context clearly specifies otherwise, as used in this specification and claims, the singular forms “a”, “an”, and “the” include plural indicators.

[0039] The scope of this disclosure is not limited to the specific embodiments described herein, which are intended for illustrative purposes only.

[0040] The term “approximately” should be interpreted as “close to” or “reasonably close” and any statistically insignificant variation therefrom.

[0041] As used herein, the terms “comprising,” “including,” “having,” “containing,” “involving,” etc., should be understood as open-ended, meaning including but not limited to.

[0042] The terms “preferred” and “preferred” refer to embodiments of the invention that may provide certain benefits in certain circumstances. In one embodiment, the aspects and embodiments described herein should also be interpreted as replacing the term “comprising / including” with “consisting of”, “substantially consisting of”, or “truly consisting of”.

[0043] Unless otherwise stated, the term "room temperature" essentially refers to a temperature in the range of about 20°C to about 35°C.

[0044] The term "purity" refers to the purity determined by gas chromatography (GC).

[0045] As used in this article, the abbreviation "CSTR" refers to a continuous stirred tank reactor.

[0046] As used herein, “substantially pure acetochlor” refers to acetochlor containing less than 1% by weight of 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III).

[0047] Unless otherwise stated, all quantities expressed in “%” or “weight%” refer to the weight percentage of the total composition.

[0048] The scope of this disclosure is not limited to the specific embodiments described herein, which are intended for illustrative purposes only.

[0049] As used herein, the term "mixture containing acetochlor and byproducts" refers to acetochlor obtained by synthetic methods containing more than 2% by weight of 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide as a byproduct / impurity.

[0050] As used herein, the term "substantially free of 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide" means containing less than 2% by weight, preferably less than 1% by weight, and more preferably less than 0.8% by weight of 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide.

[0051] According to one aspect of the present invention, a method for preparing chloromethyl ethyl ether (II) is provided, the method comprising reacting paraformaldehyde with ethanol and thionyl chloride.

[0052] .

[0053] According to one embodiment, the method for preparing chloromethyl ethyl ether (II) is carried out at a temperature of about 0°C to about 50°C.

[0054] According to one embodiment, the method for preparing chloromethyl ethyl ether (II) is carried out at a temperature of about 5°C to about 40°C.

[0055] According to one embodiment, the method for preparing chloromethyl ethyl ether (II) is carried out at a temperature of about 10°C to 30°C.

[0056] According to one embodiment, the molar ratio of paraformaldehyde to ethanol and thionyl chloride is about 1:1:1 to about 1:2:2.

[0057] According to one embodiment, the molar ratio of paraformaldehyde to ethanol and thionyl chloride is about 1:1:1 to about 1:1:1.5.

[0058] According to one embodiment, the molar ratio of paraformaldehyde to ethanol and thionyl chloride is 1:1:1 to 1:1:1.2.

[0059] According to one embodiment, the method for preparing chloromethyl ethyl ether (II) can be carried out as a batch process.

[0060] According to another embodiment, the method for preparing chloromethyl ethyl ether (II) can be carried out by a continuous flow method.

[0061] According to one embodiment, the obtained chloromethyl ethyl ether (II) has a purity of more than 92% by weight, preferably more than 95% by weight.

[0062] According to another embodiment, the obtained chloromethyl ethyl ether (II) has less than about 1% impurity A based on area GC.

[0063] Impurity A is characterized by a retention time of approximately 11.17 ± 0.02 minutes in GC analysis.

[0064] The method for preparing chloromethyl ethyl ether (II) described in this invention does not require the use of corrosive agents such as calcium chloride to remove moisture. Water generated during the reaction reacts with thionyl chloride to form hydrogen chloride gas, which is consumed in the reaction.

[0065] According to one aspect of the invention, a method for converting a byproduct into acetochlor (I) is provided, the method comprising the step of treating a mixture containing acetochlor and its byproduct with chloromethyl ethyl ether, wherein the byproduct is 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide.

[0066] According to one embodiment, a mixture comprising acetochlor and its byproducts is prepared by conventional methods, said mixture containing greater than 3% w / w 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III).

[0067] In one embodiment, the content of 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III) in acetochlor was analyzed by GC.

[0068] In one embodiment, the amount of chloromethyl ethyl ether (II) used is in the range of 0.5 to 4 moles relative to 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III).

[0069] According to one embodiment, the amount of chloromethyl ethyl ether (II) used is in the range of 1 to 2 moles relative to 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III).

[0070] In one embodiment, the method for converting the byproduct into acetochlor is carried out in the presence of a base.

[0071] The alkali used is selected from organic or inorganic alkalis; inorganic alkalis are preferred, such as alkali metal hydroxides, alkali metal carbonates, and alkali metal bicarbonates.

[0072] In another embodiment, the method for converting the byproduct into acetochlor is carried out in the presence of an inorganic base selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, etc.

[0073] In one embodiment, the method for converting the byproduct into acetochlor is carried out in the presence of a solvent.

[0074] The solvent is selected from halogenated solvents, such as dichloromethane, dichloroethane, chloroform, chlorobenzene; aromatic hydrocarbons, such as toluene, xylene; or mixtures thereof.

[0075] In one embodiment, the amount of base used is in the range of 1 to 10 moles relative to 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III).

[0076] In one embodiment, the amount of base used is in the range of 3 to 8 moles relative to 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III).

[0077] In one embodiment, the method for converting the byproduct into acetochlor is carried out at a temperature of 0°C to 40°C.

[0078] In one embodiment, a method for preparing substantially pure acetochlor is provided, the method comprising the step of treating a crude mixture of acetochlor and 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III) with chloromethyl ethyl ether (II) at a temperature of about 0°C to about 40°C in the presence of a base and a solvent.

[0079] According to one embodiment, the method for preparing chloromethyl ethyl ether (II) is carried out at a temperature of about 5°C to about 40°C.

[0080] According to one embodiment, the method for preparing chloromethyl ethyl ether (II) is carried out at a temperature of about 10°C to 30°C.

[0081] According to one embodiment, acetochlor obtained by converting byproducts is substantially free of 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III).

[0082] In one embodiment, the obtained acetochlor contains less than 3% by weight of 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III).

[0083] In one embodiment, the obtained acetochlor contains less than 1% by weight of 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III).

[0084] In one embodiment, the obtained acetochlor contains less than 0.5% by weight of 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III).

[0085] According to one embodiment of the present invention, a continuous flow method for preparing acetochlor is provided.

[0086] In one embodiment, the flow reactor is selected from, but is not limited to, stirred tank reactors, stirred tube reactors, rotary tube reactors, static mixer flow reactors, etc.

[0087] In one embodiment, 2-chloro-N-(chloromethyl)-N-(2-ethyl-6-methylphenyl)acetamide in a mixture comprising acetochlor and its byproducts is reacted in a flow reactor with an aqueous solution of alkali and chloromethyl ethyl ether (II) to produce acetochlor (I). The residence time of the mixture in the reactor is from about 5 seconds to about 10 minutes.

[0088] In one embodiment, the residence time of the mixture in the reactor is from about 5 seconds to about 5 minutes.

[0089] In one embodiment, the operating temperature in the reactor is from about 0°C to about 80°C.

[0090] In one embodiment, the acetochlor obtained according to the method of the present invention has a purity of over 95% and is substantially free of 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide.

[0091] According to another aspect of the present invention, a method for preparing acetochlor (I) is provided, the method comprising:

[0092] i. Reaction of N-(2-ethyl-6-methylphenyl)methylimine (IV) with chloroacetyl chloride (V) yields 2-chloro-N-(chloromethyl)-N-(2-ethyl-6-methylphenyl)acetamide (VI);

[0093] ii. Reacting 2-chloro-N-(chloromethyl)-N-(2-ethyl-6-methylphenyl)acetamide (VI) with ethanol to obtain a mixture containing acetochlor and its byproduct (III); and

[0094] iii. The byproduct is converted into acetochlor (I) by treating the mixture with chloromethyl ethyl ether (II);

[0095] The byproduct is 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III), and the reaction is carried out in a continuous flow reactor.

[0096] According to one embodiment of the present invention, acetochlor can be prepared by a continuous flow method.

[0097] In one embodiment, the flow reactor is selected from, but is not limited to, stirred tank reactors, stirred tube reactors, rotary tube reactors, static mixer flow reactors, etc.

[0098] In one embodiment, in step i, N-(2-ethyl-6-methylphenyl)methylimine is reacted with chloroacetyl chloride at a flow rate of 1 g / min to 15 g / min in a mixer for a residence time of 20 seconds to 5 minutes to obtain 2-chloro-N-(chloromethyl)-N-(2-ethyl-6-methylphenyl)acetamide.

[0099] In one embodiment, in step ii, 2-chloro-N-(chloromethyl)-N-(2-ethyl-6-methylphenyl)acetamide is reacted with ethanol at a flow rate of 1 g / min to 15 g / min in a mixer for a residence time of 20 seconds to 3 minutes.

[0100] In one embodiment, the mixer is a T-shaped mixer.

[0101] In one embodiment, step i is carried out at a reaction temperature of 50°C to 120°C.

[0102] In one embodiment, step ii is carried out at a reaction temperature of 20°C to 120°C.

[0103] In one embodiment, in step ii, the reaction mixture is treated with an alkali.

[0104] In one embodiment, in step ii, the reaction mixture is treated with an organic base.

[0105] In one embodiment, the organic base is selected from ammonia, triethylamine, pyridine, imidazole, methylamine, ethylamine, pyrrolidine, piperidine, benzimidazole, etc.

[0106] In one embodiment, in step ii, the reaction mixture is treated with an inorganic base.

[0107] In one embodiment, the inorganic base is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, etc.

[0108] In one embodiment, in step iii, 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide in a mixture containing acetochlor and its byproducts at a flow rate of 5 g / min to 40 g / min is reacted in a flow reactor with an aqueous solution of alkali at a flow rate of 0.5 g / min to 10 g / min and chloromethyl ethyl ether (II) at a flow rate of 0.1 g / min to 10 g / min to produce acetochlor (I). The residence time of the mixture in the reactor is from about 5 seconds to about 10 minutes.

[0109] In one embodiment, in step iii, the operating temperature in the reactor is from about 0°C to about 80°C.

[0110] In one embodiment, in step iii, the acetochlor obtained according to the method of the present invention has a purity of more than 95% and is substantially free of 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide.

[0111] According to another aspect of the present invention, a method for preparing acetochlor (I) is provided, the method comprising:

[0112] i. Reacting paraformaldehyde with ethanol and thionyl chloride to obtain chloromethyl ethyl ether (II); and

[0113] ii. Reaction of N-(2-ethyl-6-methylphenyl)methylimine (IV) with chloroacetyl chloride (V) yields 2-chloro-N-(chloromethyl)-N-(2-ethyl-6-methylphenyl)acetamide (VI), followed by reaction with ethanol to obtain acetochlor and its byproduct (III);

[0114] iii. Treat a mixture containing acetochlor and its byproducts with the chloromethyl ethyl ether (II);

[0115] The byproduct is 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III).

[0116] According to one embodiment, in step i, the amount of thionyl chloride used is provided in the above embodiment.

[0117] According to one embodiment, in step iii of the preparation of acetochlor, the amount of chloromethyl ethyl ether (II) is provided in the above embodiment.

[0118] Figure 5 A method for the continuous production of acetochlor according to a particularly preferred embodiment of the present invention is illustrated schematically, and the figures and description are used to further describe the invention. The following elements are arranged in... Figure 5 In the middle section: feed lines F1-F6, mixers M1-M3, feed streams 1-4, continuous flow reactors R1-R3, and continuous stirred tank reactors C1-C2. (Refer to...) Figure 5 :

[0119] In step a), N-(2-ethyl-6-methylphenyl)methylimine (from feed line F1) and chloroacetyl chloride (from feed line F2) are mixed in a mixer (M1) and then fed into a continuous flow reactor (R1), where the components are reacted to produce stream 1 containing 2-chloro-N-(chloromethyl)-N-(2-ethyl-6-methylphenyl)acetamide. Stream 1 is then mixed with ethanol (from feed line F3) in a mixer (M2) and fed into a continuous flow reactor (R2) to produce stream 2 containing acetochlor and 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide. Product stream 2 is combined with chloromethyl ethyl ether (from stream 4) and an aqueous solution of sodium hydroxide (from feed line F6) and then reacted in a continuous stirred reactor (C1) to obtain acetochlor. Product stream 3 containing chloromethyl ethyl ether is prepared by mixing paraformaldehyde (from feed line F4) in ethanol with thionyl chloride (from feed line F5) in a mixer (M3) and reacting the mixture in a continuous flow reactor (R3) to produce product stream 3 containing chloromethyl ethyl ether. This product stream is then diluted with dichloroethane in a collection container (C2). The resulting product stream 4 is fed into C1 to prepare acetochlor as discussed above.

[0120] The method for preparing chloromethyl ethyl ether of formula (II) and acetochlor (I) provided in this invention has been proven to be superior to all prior art methods. Some of the advantages are listed below:

[0121] Advantages of this invention:

[0122] 1. This invention discloses an economical and simple method for preparing acetochlor and its intermediates.

[0123] 2. The method according to the present invention is environmentally friendly.

[0124] 3. The method according to the present invention provides acetochlor in high yield and high purity.

[0125] 4. The method according to the invention relates to the use of the byproduct 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide, thereby increasing the overall yield of acetochlor.

[0126] It should be understood that this specification and embodiments are illustrative and not intended to limit the invention, and other embodiments within the spirit and scope of the invention will be apparent to those skilled in the art. Other embodiments also within the scope of the invention may be practiced. The following embodiments illustrate the invention but are in no way intended to limit the scope of the claims.

[0127] Example

[0128] Analytical methods

[0129] Method used: Gas chromatography (GC)

[0130] Microsyringe: 5μl capacity

[0131] Gas chromatograph: The SHIMADZU NEXIS (GC-2030) gas chromatograph equipped with an FID detector should be operated at the following recommended parameters. These parameters can be varied depending on the available facilities, provided they have been standardized.

[0132] GLC conditions:

[0133] A) Column: DB-624, length 30m, inner diameter 0.53mm, film thickness 3μm

[0134] B) Initial column oven temperature: 40℃

[0135] C) Holding time at 40℃: 5 minutes

[0136] D) Heating rate -1: 15℃ / min

[0137] Example 1: Preparation of chloromethyl ethyl ether using thionyl chloride (according to the present invention).

[0138] To a solution of paraformaldehyde (20 g, 0.63 mol) in ethanol (30 g, 0.64 mol) stirred at 15-25 °C, thionyl chloride (77 g, 0.63 mol) was added dropwise over 2-3 hours, and the resulting reaction mixture was stirred at 15-20 °C for 30 minutes. The organic layer was separated to give 63 g of chloromethyl ethyl ether (yield: 85%) (content (peak area percentage (A / A)): 95.41%, impurity A at retention time (RT) 11.17 min: 0.04%). Figure 1 ).

[0139] Example 2: Preparation of chloromethyl ethyl ether using dry HCl gas (comparative example).

[0140] To a solution of paraformaldehyde (44.5 g, 1.4 mol) in ethanol (66.2 g, 1.42 mol) stirred at 10-15 °C, calcium chloride (33 g, 0.28 mol) was added, and the mixture was stirred for 10-15 minutes. Hydrogen chloride gas (77.2 g, 1.5 mol) was bubbled into the mixture at 10-15 °C for 2-3 hours until a clear layer was observed. After the reaction was complete, the reaction mixture was filtered. The filtrate was dried, and the desired product was separated to give 150 g of chloromethyl ethyl ether (yield: 81.06%) (content (peak area percentage (A / A)): 90.71%, impurity A at retention time (RT) 11.18 min: 1.9%). Figure 2 ).

[0141] Example 3: Preparation of acetochlor in a flow reactor

[0142] A 100% N-(2-ethyl-6-methylphenyl)methylimine solution stream (purity: 50%, flow rate: 7.786 g / min) was combined with a chloroacetyl chloride stream (purity: 30%, flow rate: 13.54 g / min) using a T-mixer, with a residence time of 2 minutes in a plug flow reactor at an operating temperature of 80 °C. The resulting reaction stream containing the product 2-chloro-N-(chloromethyl)-N-(2-ethyl-6-methylphenyl)acetamide was combined with an ethanol stream (7.26 g / min) using a T-mixer, with a residence time of 1 minute in another plug flow reactor at an operating temperature of 80 °C. The reaction mixture was cooled to 20 °C and ammonia was bubbled in to adjust the pH to 9. The reaction mixture was filtered and washed with ethanol. The filtrate was distilled to remove the solvent. The obtained material was dissolved in dichloroethane and washed with HCl, followed by washing with NaOH. The organic layer was then distilled to obtain 33 g of crude mixture (containing acetochlor: peak area percentage (A / A) of 89.6% and 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide: peak area percentage (A / A) of 9.83%). Figure 3 ).

[0143] Example 4: Preparation of acetochlor (according to the present invention).

[0144] Sodium hydroxide (48%, 14.9 g, 178.8 mmol) was added to the crude mixture (33 g) obtained from Example 3 at 10–15 °C, followed by dropwise addition of chloromethyl ethyl ether (4.5 g, 47.60 mmol) in dichloroethane (4.5 ml). The resulting mixture was stirred at 15–20 °C for 30 minutes. After the reaction was complete, water was added to the mixture and the layers were separated. The aqueous layer was extracted with toluene and the combined organic layers were concentrated under reduced pressure to give approximately 33 g of acetochlor (containing acetochlor: peak area percentage (A / A) of 98.79% and 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide: peak area percentage (A / A) of 0.46%). Figure 4 ).

[0145] Example 5: Preparation of acetochlor in a flow reactor (according to the present invention)

[0146] exist Figure 5In the flow reactor shown, N-(2-ethyl-6-methylphenyl)methylimine solution (purity: 50%, flow rate: 7.786 g / min) from feed line F1 is mixed with chloroacetyl chloride (purity: 30%, flow rate: 13.54 g / min) from feed line F2 using a T-mixer (M1). The residence time in the plug flow reactor R-1 is 2 minutes, and the operating temperature is 80°C. The resulting feed stream 1 containing the product 2-chloro-N-(chloromethyl)-N-(2-ethyl-6-methylphenyl)acetamide is combined with ethanol (7.26 g / min) from feed line F3 via a T-mixer (M2). The residence time in the plug flow reactor (R-2) is 1 minute, and the operating temperature is 80°C. The resulting stream 2, containing the products acetochlor and 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide, was collected in a CSTR (C1) and combined with stream 4 (0.5 g / min, 5.3 mmol), containing the product chloromethyl ethyl ether, and 48% sodium hydroxide (1.5 g / min, 0.018 mol) from feed line F6. The residence time was 2 minutes, and the operating temperature was 15–20 °C. After the reaction was complete, water was added to the mixture, and the layers were separated. The aqueous layer was extracted with toluene, and the combined organic layers were concentrated under reduced pressure to obtain approximately 31.5 g of acetochlor.

[0147] The feed stream 4 containing the product chloromethyl ethyl ether was prepared as follows:

[0148] Preparation of chloromethyl ethyl ether in continuous flow: An ethanol solution of paraformaldehyde (0.15 g / min, 0.0047 mol) from feed line F4 and thionyl chloride (0.24 g / min, 0.0047 mol) from feed line F5 are combined in a T-mixer (M3). The residence time in the plug flow reactor R-3 is 2 minutes, and the operating temperature is 25-30°C. This product stream 3 is collected in collection container C2 and diluted with dichloroethane (5 ml). This solution stream 4 containing chloromethyl ethyl ether is combined in C1 to prepare acetochlor as described above.

Claims

1. A method for preparing chloromethyl ethyl ether (II), the method comprising reacting paraformaldehyde with ethanol and thionyl chloride. 。 2. The method of claim 1, wherein the reaction is carried out at a temperature of about 0°C to about 50°C.

3. The method of claim 1, wherein the molar ratio of paraformaldehyde to ethanol and thionyl chloride is about 1:1:1 to about 1:2:

2.

4. A method for preparing substantially pure acetochlor, the method comprising the step of treating a crude mixture of acetochlor (I) and 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III) with chloromethyl ethyl ether (II) at a temperature of about 0°C to about 40°C in the presence of a base and a solvent. 。 5. The method of claim 4, wherein the base used is selected from sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, and potassium bicarbonate.

6. The method of claim 4, wherein the solvent is selected from dichloromethane, dichloroethane, chloroform, chlorobenzene; aromatic hydrocarbons such as toluene, xylene; or mixtures thereof.

7. The method of claim 4, wherein the method is carried out in a continuous flow reactor.

8. The method of claim 7, wherein the residence time of the reaction in the reactor is from about 5 seconds to about 5 minutes.

9. A method for preparing acetochlor (I), the method comprising: i. Reaction of N-(2-ethyl-6-methylphenyl)methylimine (IV) with chloroacetyl chloride (V) yields 2-chloro-N-(chloromethyl)-N-(2-ethyl-6-methylphenyl)acetamide (VI); ii. React 2-chloro-N-(chloromethyl)-N-(2-ethyl-6-methylphenyl)acetamide (VI) with ethanol to obtain a mixture containing acetochlor and its byproduct (III); iii. The byproduct (III) is converted into acetochlor (I) by treating the mixture with chloromethyl ethyl ether (II); The reaction is carried out in a continuous flow reactor.

10. The method of claim 9, wherein the flow rate of N-(2-ethyl-6-methylphenyl)methylimine is about 1 g / min to about 15 g / min; the flow rate of chloroacetyl chloride is about 5 g / min to about 20 g / min; the flow rate of 2-chloro-N-(chloromethyl)-N-(2-ethyl-6-methylphenyl)acetamide is about 5 g / min to 35 g / min; the flow rate of ethanol is about 1 g / min to about 15 g / min; the flow rate of the mixture of byproduct (III) and acetochlor is about 5 g / min to about 40 g / min; the flow rate of chloromethyl ethyl ether is about 0.1 g / min to 10 g / min; and the flow rate of base is about 0.5 g / min to about 15 g / min.

11. The method of claim 9, wherein the residence time of the reaction in step i, ii, or iii in the reactor is from about 5 seconds to about 5 minutes.

12. The method of claim 9, wherein the method is performed at a temperature of about 20°C to about 120°C.

13. The method of claim 9, wherein the obtained acetochlor contains less than 1% by weight of 2-chloro-N-(2-ethyl-6-methylphenyl)acetamide (III).

14. The method of claim 9, wherein the chloromethyl ethyl ether (II) used in step iii is prepared by reacting paraformaldehyde with ethanol and thionyl chloride.

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