Method for synthesizing heptafluoroisopropyl substituted aniline compound through electrochemical catalysis
The electrochemical catalytic synthesis of aniline compounds containing heptafluoroisopropyl substitution solves the problems of solid waste pollution and low efficiency in traditional methods, and realizes an efficient and environmentally friendly synthesis process.
Patent Information
- Application Number
- CN202510809800.6
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-06-17
- Publication Date
- 2025-09-19
AI Technical Summary
The existing method for synthesizing 2-trifluoromethyl-4-(heptafluoroisopropyl)aniline has the problem of solid waste pollution and requires the additional addition of a phase transfer catalyst, resulting in environmental pollution and low efficiency.
An electrochemical catalytic synthesis method is adopted, using electrode materials and electrolytes to react at room temperature, avoiding the solid waste problem, and synthesizing aniline compounds containing heptafluoroisopropyl substitution through electrocatalysis.
It achieves high-yield and high-selectivity environmentally friendly synthesis with a yield much higher than traditional methods, and does not require metal catalysts, reducing solid waste pollution.
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Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of organic compound synthesis, and particularly relates to a method for electrochemically catalytically synthesizing an aniline compound containing a heptafluoroisopropyl substitution. Background Art
[0002] In agriculture, horticulture, and the cultivation of vegetables, fruit trees, and cash crops, plant diseases, insect pests, and weeds are major factors that seriously affect crop growth, leading to yield reductions, reducing product value, and causing economic losses or social harm. Therefore, the development of effective plant protection products is crucial.
[0003] Cyproflanilide, a new diamide insecticide, demonstrates excellent pest control effectiveness thanks to its high efficacy, low toxicity, broad insecticide spectrum, good penetration, rapid onset of action, and long-lasting effect. It effectively controls lepidopteran pests (such as beet armyworm, diamondback moth, Spodoptera litura, and striped stem borer), coleopteran pests (such as longhorn beetles and leaf beetles), and thrips.
[0004] 2-Trifluoromethyl-4-(heptafluoroisopropyl)aniline is an important organic synthesis intermediate, widely used in pharmaceutical intermediates (such as antiviral and anticancer drugs) and fluorinated polymer materials. In particular, in the pesticide field, it is a core intermediate in the synthesis of the novel fluorinated insecticide cyproflumizone. Through further condensation and reduction steps, the pesticide molecule is constructed, forming a fluorinated heterocyclic structure and ultimately forming the target product with insecticidal activity.
[0005] One of the classic methods for synthesizing 2-trifluoromethyl-4-(heptafluoroisopropyl)aniline involves reducing heptafluoroisopropyl bromide with hydrosulfite to generate a heptafluoroisopropyl radical, which then reacts with 2-trifluoromethylaniline. However, this method has significant drawbacks: Firstly, it generates a large amount of solid waste; secondly, because the reaction is carried out in a water-oil two-phase medium, the addition of a phase transfer catalyst is required, which introduces a new source of solid waste pollution.
[0006] Therefore, a new synthesis method is urgently needed to solve the problem of solid waste pollution. Summary of the Invention
[0007] The purpose of this section is to summarize some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the abstract and title of this application to avoid obscuring the purpose of this section, the abstract and the title of the invention, and such simplifications or omissions should not be used to limit the scope of the present invention.
[0008] In view of the above problems and / or the problems existing in the prior art, the present invention is proposed.
[0009] One of the objectives of the present invention is to provide a method for electrochemically catalytically synthesizing an aniline compound containing a heptafluoroisopropyl substitution, which uses electrocatalysis, does not require heating, and has no solid waste problem, making it more environmentally friendly than traditional synthesis methods.
[0010] In order to solve the above technical problems, the present invention provides the following technical solution: a method for electrochemically catalyzing the synthesis of aniline compounds containing heptafluoroisopropyl substitution, comprising:
[0011] The compound represented by Formula I and the compound represented by Formula II are mixed, an ultra-dry solvent is added, and the reaction mixture is stirred in an electrolyte at a constant current of 5 to 10 mA for 2 to 6 hours, while maintaining the reaction temperature at room temperature to obtain the target product, a heptafluoroisopropyl-substituted aniline compound;
[0012]
[0013] Wherein, R1 is selected from one of hydrogen, methyl and halogen; R2 is selected from one of bromine and iodine.
[0014] Preferably, the molar ratio of the compound represented by formula I to the compound represented by formula II is 1:1.3-1.8.
[0015] Preferably, the compound represented by formula I is selected from aniline, o-trifluoromethylaniline, m-toluidine, and o-bromoaniline.
[0016] Preferably, the solvent includes one or more of acetonitrile, methanol, acetone, dichloromethane, ethyl acetate, tetrahydrofuran, and dichloroethane.
[0017] Preferably, the solvent is acetonitrile.
[0018] Preferably, the electrolyte includes one or more of tetraethylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, and triethylamine tetrafluoroborate.
[0019] Preferably, the electrolyte is tetraethylammonium tetrafluoroborate.
[0020] Preferably, in the electrodes used for the constant current reaction, the cathode is an electrode material containing platinum, tin, nickel or iron, and the anode is an electrode material containing carbon or platinum.
[0021] Preferably, the cathode is an electrode material containing platinum, and the anode is an electrode material containing carbon.
[0022] Preferably, the method further comprises a step of purifying the target product.
[0023] Compared with the prior art, the present invention has the following beneficial effects:
[0024] The present invention adopts electrocatalysis, has no solid waste problem, is more environmentally friendly than the traditional sodium hydrosulfite reduction reaction, does not require a metal catalyst, and the electrocatalytic reaction yield of the present invention is much higher than that of the traditional reduction reaction, with high yield and good selectivity. DETAILED DESCRIPTION
[0025] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.
[0026] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein. Those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.
[0027] Secondly, the term "one embodiment" or "embodiment" herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in various places throughout this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive of other embodiments.
[0028] Unless otherwise specified, the raw materials used in the examples were purchased commercially.
[0029] Example 1
[0030] To a dry reaction flask, add 1.0 mmol of the electrolyte tetraethylammonium tetrafluoroborate (Et4NBF4), 1.0 mmol of 2-trifluoromethylaniline, 1.7 mmol of 2-bromoheptafluoropropane, and 3 mL of acetonitrile (CH3CN). A graphite felt anode and a platinum sheet cathode were used. After sealing, stir at 25°C and a constant current of 5 mA for 5 h. Upon completion, dilute the reaction mixture with 10 mL of water and extract with ethyl acetate (3 × 10 mL). The combined organic phases were concentrated under reduced pressure. Finally, the product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10:1).
[0031] The reaction formula is:
[0032]
[0033] The target product was characterized, and the H NMR spectrum was:
[0034] 1 H NMR (400MHz, Chloroform-d) δ7.64 (s, 1H), 7.48 (d, J = 8.7Hz, 1H), 6.82 (d, J = 8.8Hz, 1H), 4.51 (br, 2H).
[0035] According to the characterization data, the obtained reaction product is an aniline compound containing a heptafluoroisopropyl substitution (purity>99%); the product yield is calculated to be 99%.
[0036] Example 2
[0037] In Example 2, based on Example 1, the solvent type was adjusted, and other conditions remained the same as in Example 1. The results are shown in Table 2.
[0038] Table 2
[0039] solvent Yield (%) Acetonitrile 99 Methanol 83 acetone 80 dichloromethane 82 Ethyl acetate 89 Tetrahydrofuran 67 Ethylene dichloride 78
[0040] The above results show that under the same reaction conditions, the target compound can be obtained in different solvents; among them, the yield in acetonitrile solvent is the highest, reaching 99%.
[0041] Example 3
[0042] In this embodiment 3, based on embodiment 1, the cathode electrode material was adjusted, and other conditions remained the same as in embodiment 1. The results are shown in Table 3.
[0043] Table 3
[0044] cathode Yield (%) platinum sheet 99 Glassy Carbon 0 Tin electrode 80 Nickel electrode 56 Stainless steel 66
[0045] From the above results, it can be seen that using different electrode materials as the cathode has a great influence on the yield of the target compound; among them, the target compound cannot be obtained under the glassy carbon electrode; only a moderate yield can be obtained under the nickel electrode or stainless steel electrode; and the yield under the platinum sheet electrode is the highest, reaching 99%.
[0046] Example 4
[0047] In Example 4, based on Example 1, the type of electrolyte was adjusted, and other conditions remained the same as in Example 1. The results are shown in Table 4.
[0048] Table 4
[0049] electrolytes Yield (%) Tetraethylammonium tetrafluoroborate 99 Tetrabutylammonium iodide 0 Tetrabutylammonium hexafluorophosphate 78 triethylamine tetrafluoroborate 30
[0050] The above results show that different electrolyte conditions have a great influence on the yield of the target compound. Among them, the target compound cannot be obtained when tetrabutylammonium iodide is used as the electrolyte; the yield of the target compound is low when triethylamine tetrafluoroborate is used as the electrolyte; and the yield of the target compound is the highest when tetraethylammonium tetrafluoroborate is used as the electrolyte, reaching 99%.
[0051] Example 5
[0052] To a dry reaction flask, add 1.0 mmol of the electrolyte tetraethylammonium tetrafluoroborate (Et4NBF4), 1.0 mmol of o-bromoaniline, 1.7 mmol of 2-bromoheptafluoropropane, and 3 mL of acetonitrile (CH3CN). A graphite felt anode and a platinum sheet cathode were used. After sealing, stir at 25°C and a constant current of 5 mA for 5 h. Upon completion, dilute the reaction mixture with 10 mL of water and extract with ethyl acetate (3 × 10 mL). The combined organic phases were concentrated under reduced pressure. Finally, the product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10:1).
[0053] The reaction formula is:
[0054]
[0055] The target product was characterized.
[0056] 1 H NMR (400MHz, Chloroform-d) δ7.64 (d, J=2.2Hz, 1H), 7.39–7.27 (m, 1H), 6.80 (dd, J=8.7, 0.9Hz, 1H), 4.19 (s, 2H).
[0057] According to the characterization data, the obtained reaction product is 2-bromo-4-heptafluoroisopropylaniline (purity>98%); the product yield is calculated to be 92%.
[0058] Example 6
[0059] To a dry reaction flask, add 1.0 mmol of the electrolyte tetraethylammonium tetrafluoroborate (Et4NBF4), 1.0 mmol of m-toluidine, 1.7 mmol of 2-bromoheptafluoropropane, and 3 mL of acetonitrile (CH3CN). Using graphite felt as the anode and a platinum sheet as the cathode, seal the flask and stir at 5 mA at 25°C for 5 h. Upon completion, dilute the reaction mixture with 10 mL of water and extract with ethyl acetate (3 × 10 mL). Combine the organic phases and concentrate under reduced pressure. Finally, purify the product by silica gel column chromatography (petroleum ether / ethyl acetate = 10:1).
[0060] The reaction formula is:
[0061]
[0062] The target product was characterized.
[0063] 1H NMR (400MHz, Chloroform-d) δ7.30–7.19(m,1H),6.53(dt,J=4.3,2.2Hz,2H),3.80(s,2H),2.42(d,J=8.5Hz,3H).
[0064] According to the characterization data, the obtained reaction product is 3-methyl-4-heptafluoroisopropylaniline (purity>98%); the product yield is calculated to be 97%.
[0065] Example 7
[0066] To a dry reaction flask, add 1.0 mmol of the electrolyte tetraethylammonium tetrafluoroborate (Et4NBF4), 1.0 mmol of aniline, 1.7 mmol of 2-bromoheptafluoropropane, and 3 mL of acetonitrile (CH3CN). A graphite felt was used as the anode and a platinum sheet was used as the cathode. After sealing, the reaction mixture was stirred at a constant current of 5 mA at 25°C for 5 h. Upon completion, the reaction mixture was diluted with 10 mL of water and extracted with ethyl acetate (3 × 10 mL). The combined organic phases were concentrated under reduced pressure. Finally, the product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10:1).
[0067] The reaction formula is:
[0068]
[0069] The target product was characterized.
[0070] 1 H NMR (400MHz, Chloroform-d) δ7.39 (d, J = 8.4Hz, 2H), 6.73 (d, J = 8.7Hz, 2H), 3.88 (s, 2H).
[0071] According to the characterization data, the obtained reaction product is 4-heptafluoroisopropylaniline (purity>98%); the product yield is calculated to be 99%.
[0072] The present invention adopts electrocatalysis, has no solid waste problem, is more environmentally friendly than the traditional sodium hydrosulfite reduction reaction, does not require a metal catalyst, and the electrocatalytic reaction yield of the present invention is much higher than that of the traditional reduction reaction, with high yield and good selectivity.
[0073] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art should understand that the technical solutions of the present invention may be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present invention, which should all be included in the scope of the claims of the present invention.
Claims
1. A method for electrochemically catalyzing the synthesis of an aniline compound containing a heptafluoroisopropyl substitution, characterized in that: include, The compound represented by Formula I and the compound represented by Formula II are mixed, an ultra-dry solvent is added, and the reaction mixture is stirred in an electrolyte at a constant current of 5 to 10 mA for 2 to 6 hours, while maintaining the reaction temperature at room temperature to obtain the target product, a heptafluoroisopropyl-substituted aniline compound; Wherein, R1 is selected from one of hydrogen, methyl and halogen; R2 is selected from one of bromine and iodine.
2. The method for electrochemically catalytically synthesizing an aniline compound containing a heptafluoroisopropyl substitution according to claim 1, wherein: The molar ratio of the compound represented by formula I to the compound represented by formula II is 1:1.3-1.
8.
3. The method for electrochemically catalytically synthesizing an aniline compound containing a heptafluoroisopropyl substitution according to claim 1, wherein: The solvent includes one or more of acetonitrile, methanol, acetone, dichloromethane, ethyl acetate, tetrahydrofuran, and dichloroethane.
4. The method for electrochemically catalytically synthesizing an aniline compound containing a heptafluoroisopropyl substitution according to claim 3, wherein: The solvent is acetonitrile.
5. The method for electrochemically catalytically synthesizing an aniline compound containing a heptafluoroisopropyl substitution according to claim 1, wherein: The electrolyte includes one or more of tetraethylammonium tetrafluoroborate, tetrabutylammonium hexafluorophosphate, and triethylamine tetrafluoroborate.
6. The method for electrochemically catalytically synthesizing an aniline compound containing a heptafluoroisopropyl substitution according to claim 5, wherein: The electrolyte is tetraethylammonium tetrafluoroborate.
7. The method for electrochemically catalytically synthesizing an aniline compound containing a heptafluoroisopropyl substitution according to claim 1, wherein: In the electrodes used for the constant current reaction, the cathode is an electrode material containing platinum, tin, nickel or iron, and the anode is an electrode material containing carbon or platinum.
8. The method for electrochemically catalytically synthesizing an aniline compound containing a heptafluoroisopropyl substitution according to claim 7, wherein: The cathode is an electrode material containing platinum, and the anode is an electrode material containing carbon.
9. The method for electrochemically catalytically synthesizing an aniline compound containing a heptafluoroisopropyl substitution according to any one of claims 1 to 8, characterized in that: The compound represented by formula I is selected from one of aniline, o-trifluoromethylaniline, m-toluidine and o-bromoaniline.
10. The method for electrochemically catalytically synthesizing an aniline compound containing a heptafluoroisopropyl substitution according to claim 9, wherein: The method also includes the step of purifying the target product.