A method for preparing malononitrile oxime ether compounds
Malonitrile oxime ether compounds are prepared by using a specific dehydrating agent and a base in one-step reaction under mild conditions, and the problems of low yield and high cost in the prior art are solved, and high efficiency and low cost malonitrile oxime ethers are achieved The industrial production of compounds of other compounds is suitable for the preparation of other compounds.
Patent Information
- Application Number
- CN202111537574.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2021-12-15
- Publication Date
- 2025-01-03
- Estimated Expiration
- 2041-12-15
AI Technical Summary
In the prior art, the yield and cost of preparing malonitrile oxime ether compounds are low and high, especially due to the large amount of three wastes and the use of high-priced raw materials, it is difficult to prepare industrially.
Malonitrile oxime ether compounds are prepared by reacting with specific dehydration agents and alkalis at 0 to 40°C. The dehydration agents used include acetic anhydride, trifluoromethyl acetic anhydride, trichloromethyl acetic anhydride, etc., alkali selection The solvent and base were recovered from potassium hydroxide, triethylamine, etc. from one step reaction and post-treatment, and further purified by crystallization.
Improves the yield and product quality of malonitrile oxime ether compounds, reduces production costs, reduces by-products and wastewater production, is suitable for industrial production, and is suitable for nitrile or cyanide of other alkyl or aromatic amides Preparation of compounds.
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Figure CN116262675B_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the field of organic synthesis, and in particular to a method for preparing malononitrile oxime ether compounds. Background Art
[0002] The existing literature provides a method for synthesizing malononitrile oxime ether compounds having good control effects on plant bacterial diseases and fungal diseases, as shown in the following formula:
[0003]
[0004] Wherein: LG represents a leaving group, selected from halogen or other conventional nucleofugal groups, such as trifluoromethyl, methanesulfonate or toluenesulfonate; M represents a cation, such as Na + , K + , C S + 、Ag + or NH4 + etc.; W represents various aryl or heteroaryl groups; L represents various bridges; W is selected from aryl or heteroaryl groups.
[0005] However, when the existing method is used to prepare the malononitrile oxime ether compound represented by the general formula I, the yield is generally lower than 60%, and the price of the raw material malononitrile for preparing the compound represented by the general formula III is relatively high, which leads to a relatively high cost of the compound represented by the general formula III.
[0006] Patent 201810771581.7 records that when malononitrile oxime ether compounds are prepared from formula (VI) as raw material, phosphorus oxychloride and the like as dehydrating agent, and toluene as solvent, the yield of formula (VII) is increased to 80%. However, this method requires too much phosphorus oxychloride, produces a large amount of phosphoric acid and hydrogen chloride wastewater, and has certain difficulties in the industrial preparation process.
[0007]
[0008] Therefore, how to develop a synthesis method that is more suitable for industrial production is a difficult problem that technicians in this field urgently need to solve. Summary of the invention
[0009] The main purpose of the present invention is to solve the problems of low product yield, large amount of three wastes and high preparation cost when using the existing method to prepare malononitrile oxime ether compounds, and to provide a method for preparing malononitrile oxime ether compounds.
[0010] In order to achieve the above object, the present invention adopts the following technical solution:
[0011] A method for preparing a malononitrile oxime ether compound, wherein the malononitrile oxime ether compound has a structure shown in formula (VII):
[0012] Said W is selected from aryl or heteroaryl;
[0013] The preparation method comprises: reacting the raw material (VI) with a dehydrating agent at 0-40° C. in the presence of a solvent to obtain a malononitrile oxime ether compound represented by formula (VII);
[0014]
[0015] The dehydration reaction is carried out under the action of a dehydrating agent and a base to obtain a malononitrile oxime ether compound represented by formula (VII).
[0016] The raw material (IV) is then reacted under the action of a solvent and a dehydrating agent in the presence of a base at 0 to 40° C. for 0.5 to 24 hours.
[0017] The dehydrating agent is selected from one or more of acetic anhydride, trifluoromethylacetic anhydride, trichloromethylacetic anhydride, trichloroacetyl chloride, methylsulfonyl chloride, trichloromethyl carbonate, thionyl chloride, phosphorus oxychloride and phosphorus pentoxide, preferably one or more of phosphorus oxychloride, trifluoroacetic anhydride and trichloroacetyl chloride.
[0018] During the dehydration reaction, the molar ratio of the raw material (VI) to the dehydrating agent is 1:1-5, preferably 1:1-2.
[0019] The solvent is selected from one or more of halogenated alkane organic matter, aromatic organic matter, nitrile organic matter and DMF, preferably dichloromethane, dichloroethane, chloroform, acetonitrile, toluene or DMF; the amount of the solvent used is 1-10 times the weight of the raw material (VI), preferably 2-5 times.
[0020] The base is one or more of potassium hydroxide, potassium carbonate, sodium carbonate, triethylamine, pyridine, piperidine, and aniline, preferably triethylamine and / or pyridine; the amount of the base is 2 to 10 times the mole of the raw material (VI), preferably 2-3 times.
[0021] The post-treatment process after the reaction is to add water to quench the reaction, and the alkali and solvent can be recovered and reused.
[0022] The reaction may be further followed by purification by crystallization.
[0023] The solvent used for crystallization is methanol, ethanol, isopropanol or the like or their aqueous solutions, and the preferred solvent is methanol or ethanol.
[0024] The amount of the recrystallization solvent used is 0.5 to 10 times the weight of the intermediate compound, and preferably 1 to 2 times.
[0025] The dehydration system used in the dehydration reaction can be applied in the reaction of preparing nitrile or cyanide from amide.
[0026] Compared with the prior art, the present invention has the following advantages:
[0027] In the preparation of malononitrile oxime ether compounds and the preparation of acyl nitrile compounds from amide compounds, a specific dehydrating agent is used in the dehydration process, or a specific dehydrating agent is combined with a base, and dehydration is performed under mild conditions to prepare malononitrile oxime ethers, nitriles or cyanide compounds. The dehydration process is simple and does not require special treatment. The desired malononitrile oxime ethers, nitriles or cyanide compounds can be obtained through only one-step reaction. Further,
[0028] 1. The dehydrating agent used in the present invention is a conventional chemical raw material, and its price is roughly within 6,000 yuan / ton, and thus the price is moderate; the present invention uses a specific dehydrating agent and dehydration in the presence of a base to prepare the malononitrile oxime ether compound, and the base acts as an acid binding agent in the reaction.
[0029] 2. The present invention has mild reaction conditions, no high temperature or high pressure reaction, and complete reaction, resulting in fewer reaction by-products and simple equipment, thereby making the yield and content of the product prepared by the present invention high and reducing production costs.
[0030] 3. The amount of three wastes in the present invention is relatively small, and the solvent and alkali can be recycled;
[0031] 4. The present invention has a wide application scope and is not only applicable to the preparation of malononitrile compounds but also to the dehydration of other alkyl or aromatic hydrocarbon amides to prepare nitrile or cyanide compounds. DETAILED DESCRIPTION
[0032] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present invention will be described in detail below in conjunction with the embodiments.
[0033] The method for preparing malononitrile oxime ether compounds of the present invention has the following synthetic route:
[0034]
[0035] In the above preparation method, the intermediate compound represented by compound (VI) is used. Then, under the action of a solvent and a dehydrating agent, the intermediate compound represented by formula (VI) is dehydrated to obtain the desired malononitrile oxime ether compound. And the desired product can be obtained by only one step of reaction. Therefore, the above preparation method is conducive to improving the product quality and yield of the preparation of malononitrile oxime ether compounds and reducing the process cost.
[0036] The above-mentioned malononitrile oxime ether compound is a compound having a good control effect on plant bacterial diseases and fungal diseases, and thus the above-mentioned preparation method provides a new and effective way for its industrial development.
[0037] The present application is further described in detail below in conjunction with specific embodiments. These embodiments should not be construed as limiting the scope of protection claimed in the present application.
[0038] Example 1
[0039] Preparation of 2-[((2-phenylthiazol-4-yl)methoxy)imino]malononitrile:
[0040]
[0041] 2-cyano-2-[((2-phenylthiazol-4-yl)methoxy)imino]acetamide (11.57 g, 40.0 mmol), trichloroacetyl chloride (10.92 g, 60.0 mmol), triethylamine (8.08 g, 80.0 mmol) and chloroform (80 mL) were added to the reaction bottle, and the temperature was raised to 40°C for 8 h of reaction, and the reaction was monitored by TLC until the reaction was complete. The reaction solution was cooled to room temperature, and water was added under stirring to fully dissolve, and the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and chloroform was evaporated under reduced pressure. The residue was recrystallized from ethanol to obtain 2-[((2-phenylthiazol-4-yl)methoxy)imino]malononitrile, 10.4 g of light yellow solid, with a content of 98.2% and a yield of 95% (based on 2-cyano-2-[((2-phenylthiazol-4-yl)methoxy)imino]acetamide).
[0042] 2-[((2-phenylthiazol-4-yl)methoxy)imino]malononitrile 1 HNMR (600MHz, CDCl3) δ7.95-7.94(m,2H),7.46-7.45(m,3H),7.40(s,1H),5.67(s,2H).
[0043] Example 2
[0044] Preparation of 2-[((3,4-dichlorophenyl)methoxy)imino]malononitrile:
[0045]
[0046] 2-cyano-2-[((3,4-dichlorophenyl)methoxy)imino]acetamide (11.00 g, 40.0 mmol), trichloroacetyl chloride (10.92 g, 60.0 mmol), dichloromethane (80 mL), triethylamine (8.16 g, 80.0 mmol) were added to the reaction bottle, and the mixture was kept at 8-10°C for 4 h. The reaction was monitored by TLC until the reaction was complete. The reaction solution was cooled to room temperature, and water was added under stirring to fully dissolve the mixture. The mixture was allowed to stand for stratification. The organic phase was washed with saturated saline, dried over anhydrous magnesium sulfate, filtered, and dichloromethane was evaporated under normal pressure. The residue was recrystallized from methanol to obtain 2-[((3,4-dichlorophenyl)methoxy)imino]malononitrile, 10.05 g of white solid, 98.5% content, and 96.5% yield (based on 2-cyano-2-[((3,4-dichlorophenyl)methoxy)imino]acetamide).
[0047] 2-[((3,4-dichlorophenyl)methoxy)imino]malononitrile 1 HNMR (600MHz, CDCl3) δ7.50(d,1H),7.48(d,1H),7.23(dd,1H),5.46(s,2H).
[0048] Example 3
[0049] Preparation of 2-[((2-(4-chlorophenyl)thiazol-4-yl)methoxy)imino]malononitrile:
[0050]
[0051] Add 2-cyano-2-[((2-(4-chlorophenyl)thiazol-4-yl)methoxy)imino]acetamide (12.96 g, 40.0 mmol), pyridine (6.95 g, 88.0 mmol), trichloroacetyl chloride (10.92 g, 60.0 mmol) and chloroform (80 mL) into the reaction bottle and react at room temperature for 5 h. Monitor by TLC until the reaction is complete. The reaction solution was cooled to room temperature, and water was added under stirring to fully dissolve the mixture. The mixture was allowed to stand for stratification. The organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and chloroform was evaporated under reduced pressure. The residue was recrystallized from isopropanol to obtain 2-[((2-(4-chlorophenyl)thiazol-4-yl)methoxy)imino]malononitrile as a light yellow solid (11.62 g). The yield was 95% (based on 2-cyano-2-[((2-(4-chlorophenyl)thiazol-4-yl)methoxy)imino]acetamide).
[0052] 2-[((2-(4-chlorophenyl)thiazol-4-yl)methoxy)imino]malononitrile 1HNMR (300MHz, CDCl3) δ7.89(d,2H),7.44(d,2H),7.42(s,1H),5.67(s,2H).
[0053] Example 4
[0054] Preparation of 2-[((4-methoxyphenyl)methoxy)imino]malononitrile:
[0055]
[0056] 2-cyano-2-[((4-methoxyphenyl)methoxy)imino]acetamide (9.43 g, 40.0 mmol), trichloroacetic anhydride (24.68 g, 80.0 mmol), pyridine (7.98 g, 100.0 mmol) and toluene (80 mL) were added to the reaction bottle, and the mixture was kept at 10°C for 6 h. The reaction was monitored by TLC until the reaction was complete. The reaction solution was cooled to room temperature, and water was added under stirring to fully dissolve the mixture. The mixture was allowed to stand for stratification, and the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and toluene was evaporated under reduced pressure. The residue was recrystallized from ethanol to obtain 8.40 g of a light yellow solid with a yield of 96.5% (based on 2-cyano-2-[((4-methoxyphenyl)methoxy)imino]acetamide).
[0057] 2-[((4-methoxyphenyl)methoxy)imino]malononitrile 1 HNMR(300MHz, CDCl3) δ7.33(dd,2H),6.93(dd,2H),5.46(s,2H),3.83(s,3H).
[0058] Example 5
[0059] Preparation of 2-[((6-chloropyridin-3-yl)methoxy)imino]malononitrile:
[0060]
[0061] Add 2-cyano-2-[((6-chloropyridin-3-yl)methoxy)imino]acetamide (9.64g, 40.0mmol), trichloroacetyl chloride (14.56g, 80.0mmol), triethylamine (8.16g, 80.0mmol) and dichloromethane (80mL) to the reaction bottle, react at room temperature for 6h, and monitor by TLC until the reaction is complete. Add water under stirring, fully dissolve, and stand to separate. Add liquid alkali to the aqueous phase for neutralization, stand to separate, add solid alkali to the upper aqueous liquid, dry and recover triethylamine for recycling. The organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and dichloromethane was evaporated. The residue was recrystallized from methanol to obtain 2-[((6-chloropyridin-3-yl)methoxy)imino]malononitrile as a pale yellow solid (8.52 g). The yield was 95.5% (based on 2-cyano-2-[((6-chloropyridin-3-yl)methoxy)imino]acetamide).
[0062] 2-[((6-chloropyridin-3-yl)methoxy)imino]malononitrile 1 HNMR (600MHz, CDCl3) δ8.45(s,1H),7.71(d,1H),7.43(d,1H),5.52(s,2H).
[0063] Example 6
[0064] Preparation of 2-[((6-chloropyridin-3-yl)methoxy)imino]malononitrile:
[0065]
[0066] 2-cyano-2-[((2-chlorothiazol-5-yl)methoxy)imino]acetamide (9.89 g, 40.0 mmol), trichloroacetyl chloride (27.3 g, 60.0 mmol), triethylamine (10.20 g, 100.0 mmol) and chloroform (80 mL) were added to the reaction bottle, and the temperature was raised to 40°C for 6 h. TLC was monitored until the reaction was complete. The reaction solution was cooled to room temperature, and water was added under stirring to fully dissolve. After standing for stratification, the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and chloroform was evaporated under reduced pressure. The residue was separated and purified by column chromatography to obtain 2-[((2-chlorothiazol-5-yl)methoxy)imino]malononitrile, 8.61 g of yellow oil, and a yield of 94.0% (based on 2-cyano-2-[((2-chlorothiazol-5-yl)methoxy)imino]acetamide).
[0067] 2-[((2-chlorothiazol-5-yl)methoxy)imino]malononitrile 1 HNMR (600MHz, CDCl3) δ7.65 (s, 1H), 5.62 (s, 2H).
[0068] Example 7
[0069]
[0070] Add intermediate 1 (38.1Kg, 0.10Kmol), trichloroacetyl chloride (27.6Kg, 0.15Kmol), triethylamine (25.5Kg, 0.25Kmol) and dichloroethane (80L) to the reactor, keep the temperature at 0-10℃ for 6h, and monitor the reaction by TLC until the reaction is complete. Cool the reaction solution to room temperature, add 100L of water under stirring, fully dissolve, and stand for stratification. Wash the organic phase with saturated brine, dry with anhydrous magnesium sulfate, filter, evaporate dichloroethane under reduced pressure, and recrystallize the residue with ethanol to obtain 35.6Kg of light yellow solid, with a content of 98.2% and a yield of 95.2%.
[0071] Example 8
[0072]
[0073] 2-(2-phenylthiazole)-4-yl)acetamide (8.81 g, 40.0 mmol), trichloroacetic anhydride (24.68 g, 80.0 mmol), pyridine (7.98 g, 100.0 mmol) and toluene (80 mL) were added to the reaction bottle, and the mixture was kept at 10°C for 6 h. The reaction was monitored by TLC until the reaction was complete. The reaction solution was cooled to room temperature, and water was added under stirring to fully dissolve the mixture. The mixture was allowed to stand for stratification, and the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and toluene was evaporated under reduced pressure. The residue was recrystallized from ethanol to obtain 2-(2-phenylthiazole)-4-yl)acetonitrile as a light yellow solid (7.72 g, yield 96.5%).
[0074] Example 9
[0075]
[0076] 3-(3, 4-dichlorophenoxy) propionamide (9.41 g, 40.0 mmol), trichloroacetic anhydride (24.68 g, 80.0 mmol), pyridine (7.98 g, 100.0 mmol) and toluene (80 mL) were added to the reaction bottle, and the mixture was kept at 10°C for 6 h. The reaction was monitored by TLC until the reaction was complete. The reaction solution was cooled to room temperature, and water was added under stirring to fully dissolve the mixture. The mixture was allowed to stand for stratification, and the organic phase was washed with saturated brine, dried over anhydrous magnesium sulfate, filtered, and toluene was evaporated under reduced pressure. The residue was recrystallized from ethanol to obtain 3-(3, 4-dichlorophenoxy) propionitrile as a light yellow solid (8.30 g) with a yield of 96.5%.
[0077] From the above description, it can be seen that the above embodiments of the present invention achieve the following technical effects:
[0078] As known from the background technology, the yield of malononitrile oxime ether compounds shown in general formula I is generally less than 80%. Comparing Examples 1 to 7, it can be seen that the yield of malononitrile oxime ether compounds shown in formula (VII) is greater than 90%. It can be seen that the preparation method provided by the present application can greatly improve the yield of malononitrile oxime ether compounds.
[0079] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.
Claims
1. A method for preparing malononitrile oxime ether compounds, characterized in that: The malononitrile oxime ether compound has a structure shown in formula (VII), Formula (VII); The preparation method comprises: a raw material (VI) undergoes a dehydration reaction at 0 to 40° C. in the presence of a solvent to obtain a malononitrile oxime ether compound represented by formula (VII); Formula (VI) Formula (VII); The starting material (VI) is selected from 2-cyano-2-[((2-phenylthiazol-4-yl)methoxy)imino]acetamide, 2-cyano-2-[((3,4-dichlorophenyl)methoxy)imino]acetamide, 2-cyano-2-[((2-(4-chlorophenyl)thiazol-4-yl)methoxy)imino]acetamide, 2-cyano-2-[((4-methoxyphenyl)methoxy)imino]acetamide, 2-cyano-2-[((6-chloropyridin-3-yl)methoxy)imino]acetamide or 2-cyano-2-[((2-chlorothiazol-5-yl)methoxy)imino]acetamide; The compound of formula (VII) is selected from 2-[((2-phenylthiazol-4-yl)methoxy)imino]malononitrile, 2-[((3,4-dichlorophenyl)methoxy)imino]malononitrile, 2-[((2-(4-chlorophenyl)thiazol-4-yl)methoxy)imino]malononitrile, 2-[((4-methoxyphenyl)methoxy)imino]malononitrile, 2-[((6-chloropyridin-3-yl)methoxy)imino]malononitrile or 2-[((6-chloropyridin-3-yl)methoxy)imino]malononitrile; The dehydration reaction is carried out under the action of a dehydrating agent and a base to obtain a malononitrile oxime ether compound represented by formula (VII); The dehydrating agent is selected from one or more of trichloroacetic anhydride and trichloroacetyl chloride.
2. The method for preparing malononitrile oxime ether compounds according to claim 1, characterized in that: The raw material (VI) is reacted in the presence of a base at 0-40° C. for 0.5-24 hours under the action of a solvent and a dehydrating agent.
3. The method for preparing malononitrile oxime ether compounds according to claim 2, characterized in that: During the dehydration reaction, the molar ratio of the raw material (VI) to the dehydrating agent is 1:1-5.
4. The method for preparing malononitrile oxime ether compounds according to claim 2, characterized in that: The solvent is selected from one or more of dichloromethane, dichloroethane, chloroform, acetonitrile, toluene or DMF; the amount of the solvent used is 1-10 times the weight of the raw material (VI).
5. The method for preparing malononitrile oxime ether compounds according to claim 2, characterized in that: The base is one or both of triethylamine and pyridine; the amount of the base is 2 to 10 times the molar ratio of the raw material (VI).
6. The method for preparing malononitrile oxime ether compounds according to claim 2, characterized in that: The post-treatment process after the reaction is to add water to quench the reaction, and the alkali and solvent can be recovered and reused.
7. The method for preparing malononitrile oxime ether compounds according to claim 1, characterized in that: The reaction may be further followed by purification by crystallization.