Large-steric-hindrance arylamine derivative and preparation method thereof
By constructing sterically hindered aromatic amine compounds through mild organic reaction steps, the problems of low preparation efficiency and poor economy in existing technologies have been solved, and the efficient preparation of aromatic amine derivatives with complex structures has been achieved, which is applicable to the chemical and pharmaceutical fields.
Patent Information
- Application Number
- CN202510977042.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-16
- Publication Date
- 2025-11-07
AI Technical Summary
Existing technologies for the synthesis of sterically hindered aromatic amines suffer from low preparation efficiency, poor economics, and insufficient environmental friendliness, especially when using transition metal catalysts, where the reaction conditions are harsh and there are many side reactions.
Using sodium hydride as a catalyst, sterically hindered aromatic amine compounds are constructed through a series of mild organic reaction steps, including the reaction of malonate with 3-bromopropyne, the reaction of potassium carbonate with N-bromosuccinimide, the reaction of cuprous chloride with n-butylamine, and the reaction of TEMPO, thus avoiding the use of transition metal catalysts.
This method enables the efficient preparation of sterically hindered aromatic amine derivatives under mild reaction conditions and with readily available raw materials. It utilizes substrates with different functional groups and steric hindrance, making it suitable for chemical production and clinical pharmaceutical applications.
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Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the technical field of organic synthesis, in particular to a kind of big steric hindrance arylamine derivative and preparation method thereof BACKGROUND
[0002] As an important member of nitrogen-containing organic compounds, arylamine and its derivatives exhibit indispensable value in many fields. In the field of pharmaceutical chemistry, the core skeleton of many clinically used drug molecules contains arylamine structural units. For example, fluoxetine, an antidepressant, has an arylamine structure that participates in specific binding with neurotransmitter receptors to regulate neural signal transmission. The arylamine structure of sulfonamide compounds, an antibiotic, is a key pharmacophore for antibacterial activity. In addition, many alkaloid natural products also contain arylamine structures. For example, camptothecin, which has anti-cancer activity, has an arylamine fragment that interacts with tumor cell targets, exhibiting significant biological activity.
[0003] Given the importance of arylamine and its derivatives, developing efficient and simple synthesis methods has been a research focus in the field of synthetic chemistry. Currently, Figure 1 Various classical synthetic strategies shown above play an important role in C-N bond formation and synthesis of highly steric hindered arylamines.
[0004] Reductive amination reaction uses aldehyde or ketone and amine as raw materials. Under the action of a reducing agent (such as sodium borohydride or sodium cyanoborohydride), the C-N bond is formed through the reduction of an imine intermediate. This method has problems such as difficulty in controlling selectivity and easy occurrence of side reactions (such as over-reduction). Especially in the reaction of highly steric hindered substrates, the reaction efficiency is significantly reduced due to steric hindrance.
[0005] The Buchwald-Hartwig coupling reaction catalyzed by palladium uses a palladium complex as a catalyst and aryl halides or pseudohalides as substrates. In the presence of a ligand (such as a phosphine ligand or a nitrogen heterocyclic carbene ligand), the aryl C-N bond is efficiently formed. However, the palladium catalyst is expensive, and the reaction system is sensitive to air and moisture, requiring strict anhydrous and anaerobic conditions, which limits its large-scale application.
[0006] The copper-catalyzed Ullman-type coupling reaction uses copper salt as a catalyst to form a C-N bond through the coupling reaction of aryl halide and amine. However, it usually requires high temperature and high catalyst loading, has poor selectivity, and may be accompanied by side reactions such as self-coupling, which poses challenges in the synthesis of highly steric hindered arylamines, such as low yield and difficulty in separation and purification
[0007] Therefore, it is necessary to design a preparation method for highly steric hindered arylamine derivatives to solve the problems of low preparation efficiency, poor economy, and environmental friendliness of traditional preparation methods. SUMMARY
[0008] In view of this, the present application provides a preparation method of a large steric hindrance arylamine derivative, to solve the problems of low preparation efficiency, poor economy and environmental friendliness of traditional preparation methods.
[0009] In one aspect, the present application provides a preparation method of a large steric hindrance arylamine derivative, comprising the following preparation steps:
[0010] Sodium hydride is used as a catalyst, malonic acid ester and 3-bromopropynyl are added to super dry tetrahydrofuran in an ice water bath, a first reaction is carried out, then separation and purification are carried out to obtain compound 1 in the form of yellow oil liquid;
[0011] Potassium carbonate, N-bromosuccinimide and silver carbonate are dissolved in methanol, stirred uniformly, arylethynyl is added dropwise, after dropwise addition is completed, it is transferred to an oil bath, a second reaction is carried out, then separation and purification are carried out to obtain compound 2 in the form of light yellow liquid;
[0012] After n-butylamine aqueous solution is mixed with DCM and stirred in an ice bath, cuprous chloride is added first, then hydroxylamine hydrochloride is added, then the compound 1 is added, then the compound 2 is added dropwise, a third reaction is carried out, after separation and purification, a coupling tetrayne compound 3 is obtained;
[0013] The compound 3 is added to a THF solvent to carry out a fourth reaction with TEMPO, after natural cooling to room temperature, the reaction is stopped, the product is purified and separated to obtain an arylamine derivative.
[0014] Further, the molar ratio of sodium hydride, malonic acid ester and 3-bromopropynyl is 4:1:2.5.
[0015] Further, the temperature of the first reaction is room temperature, and the reaction time is 3 hours.
[0016] Further, the molar ratio of potassium carbonate, N-bromosuccinimide, silver carbonate and arylethynyl is 0.5:2:0.1:1.
[0017] Further, the temperature of the second reaction is 50℃, and the reaction time is 2 hours.
[0018] Further, the molar ratio of cuprous chloride, hydroxylamine hydrochloride, compound 1 and compound 2 is 0.2:0.6:1:4.
[0019] Further, the temperature of the third reaction is room temperature, and the reaction time is 4 hours.
[0020] Further, the molar ratio of TEMPO and compound 3 is 2:1.
[0021] Further, the temperature of the fourth reaction is 120℃, and the reaction time is 12 hours.
[0022] In another aspect, the present application also provides a sterically hindered arylamine derivative prepared by the preparation method, and the structure of the sterically hindered arylamine derivative is as follows:
[0023]
[0024] wherein E1 and E2 are the same, CO2R, R is a linear alkane, branched alkane, saturated hydrocarbon, unsaturated hydrocarbon or aromatic hydrocarbon group; R1 is halogen, linear alkyl, linear alkyl, ester, alkoxy and its corresponding derivative.
[0025] Compared with the prior art, the present application has the beneficial effects that: the sterically hindered arylamine derivative prepared by the present application does not need to use transition metal catalytic reaction, the reaction condition is relatively mild, the raw material is cheap and easy to obtain, and the substrate with different functional groups and steric hindrance can construct complex sterically hindered arylamine compounds under heating condition, and the preparation efficiency is high. For ordinary polysubstituted arylamine derivatives, the sterically hindered arylamine derivative prepared by the present application has a polycyclic structure, and the structure is more complex and diverse, which will also have a broader application prospect in chemical production, clinical medicine and materials. BRIEF DESCRIPTION OF DRAWINGS
[0026] Various other advantages and benefits will become apparent to those of ordinary skill in the art upon reading the following detailed description of the preferred embodiments. The drawings are for purposes of illustration only and are not intended to limit the present application thereto. Moreover, the use of the same reference symbols in different drawings indicates similar or identical items. In the drawings:
[0027] Figure 1 FIG. 1 is a 1H-NMR spectrum of the sterically hindered arylamine derivative prepared in Example 1 of the present application;
[0028] Figure 2 FIG. 2 is a 1H-NMR spectrum of the sterically hindered arylamine derivative prepared in Example 2 of the present application. DETAILED DESCRIPTION
[0029] The technical solutions in the embodiments of the present application will be described clearly and completely below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments in the present application, all other embodiments obtained by those of ordinary skill in the art without creative labor fall within the scope of protection of the present application.
[0030] In the description of the present application, it needs to be understood that the terms "center", "upper", "lower", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer" and the like indicate the orientation or positional relationship shown in the drawings, which are only for the convenience of describing the present application and simplifying the description, and do not indicate or imply that the devices or elements referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as a limitation of the present application.
[0031] The terms "first", "second" are only for descriptive purposes, and cannot be understood as indicating or implying relative importance or implicitly indicating the number of the technical features indicated. Therefore, the features defined with "first", "second" can explicitly or implicitly include one or more of the features. In the description of the present application, unless otherwise specified, the meaning of "a plurality of" is two or more.
[0032] In the description of the present application, it needs to be explained that, unless otherwise explicitly specified and limited, the terms "mounting", "connection", "connection" should be understood broadly, for example, it can be fixed connection, or detachable connection, or integral connection; it can be mechanical connection, or electrical connection; it can be directly connected, or indirectly connected through intermediate medium, or the communication inside two elements. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.
[0033] In one aspect, in some embodiments of the present application, a preparation method of a large steric hindered arylamine derivative includes the following preparation steps:
[0034] Sodium hydride is used as catalyst, malonic acid ester and 3-bromopropynyl are added to super dry tetrahydrofuran in ice water bath, first reaction is carried out, then separation and purification are carried out, and yellow oily liquid compound 1 is obtained;
[0035] Potassium carbonate, N-bromosuccinimide and silver carbonate are dissolved in methanol, stirred uniformly, arylethynyl is added dropwise, after dropwise addition is completed, it is transferred to oil bath, second reaction is carried out, then separation and purification are carried out, and yellow liquid compound 2 is obtained;
[0036] After the aqueous solution of n-butylamine is mixed with DCM and stirred in ice bath, cuprous chloride is added first, then hydroxylamine hydrochloride is added, then the compound 1 is added, then the compound 2 is added dropwise, third reaction is carried out, and after separation and purification, the coupling tetrayne compound 3 is obtained;
[0037] The compound 3 is added to THF solvent and reacted with TEMPO, after the reaction is stopped by natural cooling to room temperature, the product is purified and separated, and the arylamine derivative is obtained.
[0038] Specifically, potassium carbonate, N-bromosuccinimide, silver carbonate are dissolved in methanol, and stirred uniformly, then arylethynyl is added dropwise, and after the dropwise addition is completed, it is transferred to an oil bath, and a second reaction is carried out, and then the separation and purification, the separation and purification are specifically as follows: the second reaction product is filtered to remove the salt in the reaction, and the MeOH is rotary evaporated under reduced pressure, and the crude product is washed with saturated sodium bicarbonate aqueous solution, extracted with dichloromethane, and rotary evaporated under reduced pressure. Column chromatography is used to separate the petroleum ether to obtain a light yellow liquid product, i.e. compound 2.
[0039] Specifically, sodium hydride is used as a catalyst to add malonic acid ester and 3-bromopropynyl to super-dry tetrahydrofuran in an ice water bath, and a first reaction is carried out, and then the separation and purification, the separation and purification are specifically as follows: the product of the first reaction is added to saturated ammonium chloride aqueous solution, then extracted with ethyl acetate, rotary evaporated under reduced pressure, and column chromatography is used to separate the ethyl acetate and petroleum ether in a volume ratio of 1:20 to obtain a yellow oily liquid product, i.e. compound 1.
[0040] Specifically, potassium carbonate, N-bromosuccinimide, silver carbonate are dissolved in methanol, and stirred uniformly, then arylethynyl is added dropwise, and after the dropwise addition is completed, it is transferred to an oil bath, and a second reaction is carried out, and then the separation and purification, the separation and purification are specifically as follows: the second reaction product is filtered to remove the salt in the reaction, and the MeOH is rotary evaporated under reduced pressure, and the crude product is washed with saturated sodium bicarbonate aqueous solution, extracted with dichloromethane, and rotary evaporated under reduced pressure. Column chromatography is used to separate the petroleum ether to obtain a light yellow liquid product, i.e. compound 2.
[0041] Specifically, the n-butylamine aqueous solution is mixed with DCM and stirred in an ice bath, and during the stirring, cuprous chloride is first added, then hydroxylamine hydrochloride is added, then the compound 1 is added, and then the compound 2 is added dropwise to carry out a third reaction, and then the separation and purification, the separation and purification are specifically as follows: the third reaction product is added to saturated ammonium chloride aqueous solution, then extracted with dichloromethane, rotary evaporated under reduced pressure, and column chromatography is used to separate the ethyl acetate and petroleum ether in a volume ratio of 1:20 to obtain a light yellow liquid product, i.e. compound 3.
[0042] Specifically, the n-butylamine aqueous solution is mixed with DCM and stirred in an ice bath at 0°C, and under N2 atmosphere, cuprous chloride is first added, then hydroxylamine hydrochloride is added, then the compound 1 is added, and then the compound 2 is added dropwise.
[0043] Specifically, the ratio of the n-butylamine aqueous solution to DCM is 1:2, and the concentration of the n-butylamine aqueous solution is 40%.
[0044] Specifically, the compound 3 is added to a THF solvent to carry out a fourth reaction with TEMPO, and after the reaction is completed, it is naturally cooled to room temperature to stop the reaction, and then the product is separated and purified, the separation and purification are specifically as follows: the fourth reaction product is rotary evaporated under reduced pressure, and column chromatography is used to separate the ethyl acetate and petroleum ether in a volume ratio of 1:20 to obtain a colorless liquid product, i.e. a sterically hindered arylamine derivative, and the column chromatography yield is about 95%.
[0045] Specifically, the arylamine derivative is a colorless liquid.
[0046] It can be understood that the large steric hindered arylamine derivative prepared by the application does not need to use a transition metal catalytic reaction, the reaction condition is relatively mild, the raw material is cheap and easy to obtain, the substrate has different functional groups and steric hindrance, and a complex large steric hindered arylamine compound can be constructed by heating the alkyne under the condition, and the preparation efficiency is high. For ordinary polysubstituted arylamine derivatives, the large steric hindered arylamine derivative prepared by the application has a polycyclic ring, and the structure is more complex and diverse, and will also have a more broad application prospect in chemical production, clinical medicine and materials.
[0047] In some embodiments of the application, the molar ratio of sodium hydride, malonate, and 3-bromopropynyl is 4:1:2.5.
[0048] Specifically, the malonate is dimethyl malonate, diethyl malonate, diisopropyl malonate, or the like.
[0049] In some embodiments of the application, the temperature of the first reaction is room temperature, and the reaction time is 3 hours.
[0050] In some embodiments of the application, the molar ratio of potassium carbonate, N-bromosuccinimide, silver carbonate, and arylacetylene is 0.5:2:0.1:1.
[0051] In some embodiments of the application, the temperature of the second reaction is 50°C, and the reaction time is 2 hours.
[0052] Specifically, the arylacetylene is added dropwise at room temperature.
[0053] In some embodiments of the application, the molar ratio of cuprous chloride, hydroxylamine hydrochloride, compound 1, and compound 2 is 0.2:0.6:1:4.
[0054] In some embodiments of the application, the temperature of the third reaction is room temperature, and the reaction time is 4 hours.
[0055] Specifically, the third reaction is a Cadiot-Chodkiewicz reaction.
[0056] In some embodiments of the application, the molar ratio of TEMPO and compound 3 is 2:1.
[0057] In some embodiments of the application, the temperature of the fourth reaction is 120°C, and the reaction time is 12 hours.
[0058] On the other hand, in some embodiments of the application, a large steric hindered arylamine derivative is prepared by the preparation method, and the structural formula of the large steric hindered arylamine derivative is:
[0059]
[0060] wherein E1and E2are the same and are CO2R, R is a linear alkane, branched alkane, saturated hydrocarbon, unsaturated hydrocarbon or aromatic hydrocarbon group; R1is halogen, linear alkyl, linear alkyl, ester, alkoxy and its corresponding derivatives.
[0061] The structural formula of the said sterically hindered arylamine derivative is preferably:
[0062]
[0063] Example 1
[0064] S1, (1) In a round bottom flask, 40 mmol NaH was added, vacuumed and filled with N2, 10 mmol dimethyl malonate was dissolved in 30 mL THF, stirred in ice bath at 0 °C, 25 mmol 3-bromopropyne solution (80 wt% in toluene, stab. with MgO) was added dropwise. After the addition was completed, the ice bath was removed and the reaction was carried out at room temperature for 3 h. After the completion of the reaction was monitored by TLC, a small amount of saturated NaHCO3 solution was added to quench the reaction, extracted with EtOAc, washed with saturated NaCl solution, dried with anhydrous Na2SO4, filtered, and the organic phase solution was concentrated under vacuum to obtain the crude product, which was purified by silica gel column chromatography to obtain compound 1 as a yellow oily liquid with a yield of 95%.
[0065] S2, (2) In a round bottom flask, 5 mmol K2CO3, 20 mmol equiv N-bromosuccinimide (NBS), 1 mmol Ag2CO3 were added and dissolved in an appropriate amount of CH3OH, stirred uniformly under N2 atmosphere, 10 mmol arylacetylene was added dropwise at room temperature, and after the addition was completed, the reaction was carried out in an oil bath at 50 °C for 3 h. After the completion of the reaction, the salt generated in the reaction was removed by filtration and the solvent was dried under vacuum to obtain the crude product, which was diluted with CH2Cl2, and then separated into two phases by adding saturated NaHCO3 solution, extracted with CH2Cl2, and the organic layers were combined, dried with anhydrous Na2SO4, filtered, and the organic phase solution was concentrated under vacuum to obtain the crude product, which was purified by silica gel column chromatography to obtain compound 2 as a light yellow liquid with a yield of 99%.
[0066] S3, in a round bottom flask, add 1:2 ratio of 40 n-BuNH2(3 mL / 1 mmol of substrate) and CH2Cl2, place in an ice bath at 0 °C and stir, first add 2 mmol of CuCl under N2atmosphere, the solution turns dark blue and remains unchanged, then add 6 mmol of NH2OH-HCl, the blue color immediately fades, when the solution becomes colorless, add 10 mmol of compound 1 to the reaction flask, then add 40 mmol of compound 2 dropwise, react at 0 °C for 40 min, obtain the coupled tetrayne compound by Cadiot-Chodkiewicz reaction, after the reaction is complete, dilute the reaction mixture with saturated NH4Cl solution, extract with CH2Cl2, dry over anhydrous Na2SO4, filter, concentrate under vacuum, purify the crude product by silica gel column chromatography to obtain compound 3 as a light yellow liquid, with a yield of 89%.
[0067] S4, dissolve 1 mmol of compound 3 prepared in step S3 and 2 mmol of TEMPO radical reagent in degassed THF, heat to reflux in an oil bath at 120 °C under N2atmosphere for 12 h, monitor the completion of the reaction by TLC, cool to room temperature after the reaction is complete, quench with saturated NaHCO3solution, extract with CH2Cl2, dry over anhydrous Na2SO4, concentrate the organic phase solution under vacuum to obtain the crude product, purify by silica gel column chromatography to obtain the yellow liquid product, i.e. the polysubstituted arylamine derivative, with a yield of 95%.
[0068] Example 2
[0069] S1, in a round bottom flask, add 40 mmol of NaH, vacuumize and fill with N2, add ultradry THF to dissolve (10 mmol of dimethyl malonate / 30 mL of THF), stir in an ice bath at 0 °C, slowly dropwise add 10 mmol of compound dimethyl malonate, after the dropwise addition is complete, react at 0 °C for 30 min, then transfer to room temperature for 15 min, then transfer to 0 °C for cooling, dropwise add 25 mmol of 3-bromopropyne solution (80 wt% in toluene, stab. with MgO). After the dropwise addition is complete, remove the ice bath and react at room temperature for 3 h. After the completion of the reaction is monitored by TLC, quench the reaction by adding saturated NaHCO3solution in small amounts and multiple times, extract with EtOAc, wash with saturated NaCl solution, dry over anhydrous Na2SO4, filter, concentrate the organic phase solution under vacuum to obtain the crude product, purify by silica gel column chromatography to obtain compound 1 as a yellow oily liquid, with a yield of 95%.
[0070] S2, in a round bottom flask, add 5 mmol K2CO3, 20 mmol equiv N-bromosuccinimide (NBS), 1 mmol Ag2CO3 and dissolve in appropriate amount of CH3OH, stir uniformly under N2atmosphere, drop 10 mmol aryl acetylene at room temperature, after drop completion, transfer to 50°C oil bath and react for 3h. After reaction is completed, remove the salt generated in the reaction by filtration and dry the solvent in vacuum to obtain the crude product, add CH2Cl2to dilute, then add saturated NaHCO3solution to separate into two phases, extract with CH2Cl2, combine the organic layers, dry with anhydrous Na2SO4, filter, and concentrate the organic phase solution in vacuum to obtain the crude product, then purify by silica gel column chromatography to obtain compound 2 as a light yellow liquid with a yield of 99%.
[0071] S3, in a round bottom flask, add 40 n-BuNH2(3mL / mmol substrate) and CH2Cl2in a ratio of 1:2, stir in a 0°C ice bath, first add 2 mmol CuCl under N2atmosphere, the solution turns dark blue and remains unchanged, then add 6 mmol NH2OH·HCl, the blue color immediately fades, when the solution becomes colorless, add 10 mmol compound 1 to the reaction bottle, then drop 40 mmol compound 2, react for 40 min at 0°C, obtain the coupled tetrayne compound by Cadiot-Chodkiewicz reaction, after reaction is completed, dilute the reaction mixture with saturated NH4Cl solution, extract with CH2Cl2, dry with anhydrous Na2SO4, filter, concentrate under vacuum, purify the crude product by silica gel column chromatography to obtain precursor compound 3 as a light yellow liquid with a yield of 89%.
[0072] S4, dissolve 1 mmol compound 3 prepared in step S3 and 2 mmol 4-OAc-TEMPO radical reagent in degassed THF, heat to reflux at 120°C oil bath under N2atmosphere for 12h, monitor the completion of the reaction by TLC, cool to room temperature after the reaction is completed, quench with saturated NaHCO3solution, extract with CH2Cl2, dry with anhydrous Na2SO4, concentrate the organic phase solution in vacuum to obtain the crude product, purify by silica gel column chromatography to obtain the yellow liquid product, i.e. polysubstituted arylamine derivative, with a yield of 88%.
[0073] The polysubstituted arylamine derivative prepared in Example 1 has the structural formula:
[0074]
[0075] The polysubstituted arylamine derivative prepared in Example 1 is detected by nuclear magnetic resonance (CDCl3) as shown in Figure 1 The nuclear magnetic resonance (CDCl3) data are as follows: 1H NMR: δ 7.68 (d, J = 7.5 Hz, 2H), 7.50-7.42 (m, 2H), 7.40-7.34 (m, 3H), 7.33-7.23 (m, 4H), 3.95-3.65 (m, 10H), and 1.95-0.66 (m, 8H).
[0076] The substituted arylamine derivative prepared in Example 2 has the structural formula:
[0077]
[0078] The substituted arylamine derivative prepared in Example 2 was subjected to nuclear magnetic resonance (CDCl3) detection, and the nuclear magnetic resonance (CDCl3) data thereof are shown in the following table: Figure 1 1 H NMR: δ 7.68 (d, J = 7.5 Hz, 2H), 7.50-7.42 (m, 2H), 7.40-7.34 (m, 3H), 7.33-7.23 (m, 4H), 3.95-3.65 (m, 10H), and 1.95-0.66 (m, 8H).
[0079] The above only describes the preferred embodiments of the present application, and it should be noted that those of ordinary skill in the art can make several improvements and refinements without departing from the principles of the present application, and these improvements and refinements should also be considered within the protection scope of the present application.
Claims
1. A process for the preparation of a highly hindered aromatic amine derivative, characterized by, The preparation method comprises the following steps: Sodium hydride, malonic acid ester and 3-bromopropynyl are added into ultradry tetrahydrofuran in an ice water bath to perform a first reaction, and then separated and purified to obtain compound 1 in the form of yellow oil liquid; Potassium carbonate, N-bromosuccinimide, silver carbonate are dissolved in methanol, stirred uniformly, and arylethynyl is added dropwise, and then transferred into an oil bath to perform a second reaction, and then separated and purified to obtain compound 2 in the form of light yellow liquid; n-Butylamine aqueous solution is mixed with DCM and stirred in an ice bath, and cuprous chloride is added first, followed by hydroxylamine hydrochloride, then the compound 1, and then the compound 2 is added dropwise to perform a third reaction, and then separated and purified to obtain a coupled tetrayne compound 3; The compound 3 is added into THF solvent to perform a fourth reaction with TEMPO, and then naturally cooled to room temperature to stop the reaction, and then the product is separated and purified to obtain an arylamine derivative.
2. The preparation method of the sterically hindered arylamine derivative according to claim 1, wherein a molar ratio of the sodium hydride, the malonic acid ester and the 3-bromopropynyl is 4:1:2.
5.
3. The preparation method of the sterically hindered arylamine derivative according to claim 2, wherein a temperature of the first reaction is room temperature, and a reaction time is 3 hours.
4. The preparation method of the sterically hindered arylamine derivative according to claim 3, wherein a molar ratio of the potassium carbonate, the N-bromosuccinimide, the silver carbonate and the arylethynyl is 0.5:2:0.1:
1.
5. The preparation method of the sterically hindered arylamine derivative according to claim 4, wherein a temperature of the second reaction is 50 DEG C, and a reaction time is 2 hours.
6. The preparation method of the sterically hindered arylamine derivative according to claim 5, wherein a molar ratio of the cuprous chloride, the hydroxylamine hydrochloride, the compound 1 and the compound 2 is 0.2:0.6:1:
4.
7. The preparation method of the sterically hindered arylamine derivative according to claim 6, wherein a temperature of the third reaction is room temperature, and a reaction time is 4 hours.
8. The preparation method of the sterically hindered arylamine derivative according to claim 7, wherein a molar ratio of the TEMPO and the compound 3 is 2:
1.
9. The preparation method of the sterically hindered arylamine derivative according to claim 8, wherein a temperature of the fourth reaction is 120 DEG C, and a reaction time is 12 hours. The structure of the sterically hindered arylamine derivative is as follows: wherein E1 and E2 are the same, CO2R, R is a straight chain alkyl, branched chain alkyl, saturated hydrocarbon, unsaturated hydrocarbon or aromatic hydrocarbon group; R1 is halogen, straight chain alkyl, straight chain alkyl, ester group, alkoxy and corresponding derivatives thereof. 10. A highly hindered arylamine derivative prepared according to the process of claims 1-9.