Synthesis method of amino-substituted aniline compound

Abstract

The invention relates to the technical field of organic chemical synthesis preparation, in particular to a synthesis method of an amino-substituted aniline compound, which comprises the following steps: carrying out nitration reaction on a diphenol compound with two phenol functional groups to obtain a first intermediate compound as shown in a formula (III) or a formula (IV); then carrying out condensation reaction on the first intermediate compound and an organic compound with sulfonyl in an alkaline environment to obtain a second intermediate compound as shown in a formula (V) or a formula (VI); s3, carrying out substitution reaction on the second intermediate compound and an organic compound with a single primary amine group to obtain a third intermediate compound as shown in a formula (VII) or a formula (VIII); s4, carrying out reduction reaction on the third intermediate compound to obtain the amino-substituted aniline compound as shown in a formula (IX) or X; the synthesis method is simple in synthesis process, environment-friendly, low in cost and beneficial to industrial large-scale production.

Description

Technical Field

[0001] The present application relates to the technical field of organic chemical synthesis and preparation, and in particular to a method for synthesizing amino-substituted aniline compounds. Background Art

[0002] Amino-substituted aniline compounds can be used as raw materials for dye manufacturing, plastics, and rubber, and are particularly suitable as vulcanizing agents for rubber products such as rubber seals. During the rubber product production process, rubber undergoes a series of complex chemical reactions, transforming from a linear structure to a three-dimensional structure. This structure loses the plasticity of the compound rubber and acquires the high elasticity of cross-linked rubber, thereby obtaining excellent physical and mechanical properties, heat resistance, solvent resistance, and corrosion resistance, thereby increasing the use value and application range of rubber products. In semiconductor equipment, rubber seals need to adapt to higher temperatures and harsh chemical environments, which places higher demands on the rubber vulcanization process. However, the existing synthesis methods of amino-substituted aniline compounds are complex, require harsh conditions, and are expensive, making them unsuitable for large-scale industrial production. Furthermore, the vulcanization effect is poor. Therefore, it is necessary to develop an improved amino-substituted aniline vulcanizing agent to improve the above-mentioned problems. Summary of the Invention

[0003] In response to the above problems in the prior art, the present application provides a method for synthesizing amino-substituted aniline compounds. The specific technical solution is as follows:

[0004] In one aspect, the present application provides a method for synthesizing an amino-substituted aniline compound, the method comprising:

[0005] S1, subjecting a diphenol compound having two phenol functional groups in formula (I) or formula (II) to a nitration reaction to obtain a first intermediate compound in formula (III) or formula (IV);

[0006] S2, condensing the first intermediate compound with an organic compound having a sulfonyl group in an alkaline environment to obtain a second intermediate compound of formula (V) or formula (VI);

[0007] S3, subjecting the second intermediate compound to a substitution reaction with an organic compound having a monoprimary amine group to obtain a third intermediate compound of formula (VII) or formula (VIII);

[0008] S4, subjecting the third intermediate compound to a reduction reaction to obtain an amino-substituted aniline compound of formula (IX) or formula (X);

[0009]

[0010]

[0011] Wherein, R is an alkyl group or a halogenated alkyl group, X is an aryl group or a hydrocarbon group, and Y is an aryl group, an alkyl group or an alcohol group.

[0012] In a possible implementation manner, the S1 includes:

[0013] In a first organic solvent, the diphenol compound of formula (I) or formula (II) and dilute nitric acid are added, and the mixture is reacted at a first temperature for a first time. The liquid is separated, and the solvent layer is subjected to low-temperature rotary evaporation and drying to obtain the first intermediate compound of formula (III) or formula (IV).

[0014] In a possible implementation manner, the first temperature is 40-50°C.

[0015] In a possible implementation manner, the first duration is 4-24 hours.

[0016] In a possible implementation manner, the rotary evaporation temperature of the low-temperature rotary evaporation in S1 is 35-40°C.

[0017] In a possible implementation manner, the concentration of the dilute nitric acid is 18-23%.

[0018] In a possible implementation manner, the first organic solvent includes dichloromethane.

[0019] In a possible implementation manner, the S2 includes:

[0020] In a second organic solvent, using pyridine as an alkaline environment regulator, the first intermediate compound and the organic compound having a sulfonyl group are reacted under condensation reflux at a second temperature for a second time, and then filtered, washed, and dried to obtain the second intermediate compound of formula (V) or formula (VI).

[0021] In a possible implementation manner, the second temperature is 40-50°C.

[0022] In a possible implementation manner, the second duration is 3-4 hours.

[0023] In a possible embodiment, the ratio of the first intermediate compound to the organic compound having a sulfonyl group is less than 1:2; and pyridine is added in excess.

[0024] In a possible implementation manner, the second organic solvent includes dichloromethane.

[0025] In a possible implementation manner, the S3 includes:

[0026] Under the protection of inert gas, the second intermediate compound and the organic compound having a monoprimary amine group are reacted at a third temperature and refluxed for a third time in a third organic solvent, and a viscous substance is obtained by low-temperature rotary evaporation. After recrystallization, the third intermediate compound as described in formula (VII) or formula (VIII) is obtained.

[0027] In a possible implementation manner, the third temperature is 80-130°C.

[0028] In a possible implementation manner, the third duration is 4-16 hours.

[0029] In a possible embodiment, the low-temperature rotary evaporation temperature in S3 is below 60°C.

[0030] In a possible implementation manner, the amount ratio between the second intermediate compound and the organic compound having a monoprimary amine group is 1:(3-40).

[0031] In a possible implementation manner, the third organic solvent includes one or more of 1,4-dioxane, ethanol, and dichloromethane.

[0032] In a possible implementation manner, the S4 includes:

[0033] In a fourth solvent, the third intermediate compound is reacted with hydrazine hydrate at a fourth temperature for a fourth time in the presence of a palladium-carbon catalyst. After filtering, the filtrate is rotary evaporated at low temperature, dried, and recrystallized to obtain the amino-substituted aniline compound as described in formula (IX) or formula (X).

[0034] In a possible implementation manner, the fourth temperature is 45-55°C.

[0035] In a possible implementation manner, the fourth duration is 1.5-2.5 hours.

[0036] In a possible embodiment, the rotary evaporation temperature of the low-temperature rotary evaporation in S4 is below 60° C.

[0037] In a possible implementation manner, the amount ratio between the third intermediate compound and hydrazine hydrate is less than 2:1.

[0038] In a possible implementation manner, the fourth organic solvent includes one or more of 1,4-dioxane, ethanol, and dichloromethane.

[0039] In a possible implementation manner, the reducing agent used in S4 is hydrazine hydrate.

[0040] In a possible embodiment, R is methylene, isopropylene or hexafluoroisopropylene.

[0041] In a possible embodiment, the aryl group of Y is a phenyl group or a phenyl group having a substituent.

[0042] In a possible implementation manner, the diphenol compound having two phenol functional groups is 4,4′-(hexafluoroisopropylidene)diphenol, bisphenol A, bisphenol F or biphenol.

[0043] In a possible implementation manner, the organic compound having a sulfonyl group is p-toluenesulfonyl chloride, p-toluenesulfonic acid, alkylsulfonic acid or alkylsulfonyl chloride.

[0044] In a possible implementation manner, the organic compound having a monoprimary amine group is aniline, aniline substituents, alkylamine or monoethanolamine.

[0045] Based on the above technical solution, this application has the following beneficial effects:

[0046] In the present application, a diphenol compound having two phenol functional groups is subjected to a nitration reaction to obtain a first intermediate compound such as in formula (III) or (IV); the first intermediate compound is then subjected to a condensation reaction with an organic compound having a sulfonyl group in an alkaline environment to obtain a second intermediate compound such as in formula (V) or (VI); the second intermediate compound is subjected to a substitution reaction with an organic compound having a monoprimary amine group to obtain a third intermediate compound such as in formula (VII) or (VIII); the third intermediate compound is subjected to a reduction reaction to obtain an amino-substituted aniline compound such as in formula (IX) or (X); the above-mentioned synthesis method has a simple and easy synthesis process, consistent conditions and high reaction safety, simple processes for collecting and purifying intermediate products and final products, is environmentally friendly, low-cost and conducive to industrial large-scale production, the obtained amino-substituted aniline compound has excellent rubber vulcanization effect, and the resulting rubber products can be used in harsh chemical environments such as high temperature and acid and alkali.

[0047] It should be appreciated that all combinations of the foregoing concepts, as well as additional concepts described in greater detail below, to the extent such concepts are not mutually inconsistent, can be considered to be part of the inventive subject matter of this application.

[0048] The foregoing and other aspects, embodiments, and features of the present application will be more fully understood from the following description in conjunction with the accompanying drawings. Other additional aspects of the present application, such as features and / or beneficial effects of the exemplary embodiments, will become apparent from the following description or through practice of specific embodiments according to the teachings of the present application. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] To more clearly illustrate the technical solution of this application, the following briefly introduces the drawings required for use in the embodiments or descriptions of the prior art. Obviously, the drawings described below are merely some embodiments of this application, and those skilled in the art can derive other drawings based on these drawings without inventive effort.

[0050] Figure 1 : A schematic flow chart of a method for synthesizing amino-substituted aniline compounds provided in an embodiment of the present application;

[0051] Figure 2: The nuclear magnetic resonance spectrum of an amino-substituted aniline compound product provided in the examples of the present application; DETAILED DESCRIPTION

[0052] The following will be combined with the accompanying drawings in the embodiments of this application to clearly and completely describe the technical solutions in the embodiments of this application. Obviously, the embodiments described are only part of the embodiments of this application, not all of the embodiments. Based on the embodiments of this application, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of this application.

[0053] For the terms defined below, these definitions shall apply unless a different definition is given in the claims or elsewhere in this specification. All numerical values, whether or not explicitly indicated, are defined herein as being modified by the term "about." The term "about" generally refers to a numerical range that one of ordinary skill in the art would consider equivalent to the stated values ​​to produce substantially the same properties, functions, results, etc. A numerical range indicated by a lower value and an upper value is defined to include all numerical values ​​within that numerical range and all subranges within that numerical range. It should be noted that the terms "first," "second," etc. in the specification and claims of this application and the accompanying drawings are used to distinguish similar objects and are not necessarily used to describe a specific order or sequential sequence. It should be understood that the numbers used in this manner are interchangeable where appropriate so that the embodiments of the application described herein can be implemented in an order other than those illustrated or described herein. In addition, the terms "including," "having," and any variations thereof are intended to cover non-exclusive inclusions.

[0054] The following describes a method for synthesizing amino-substituted aniline compounds provided in the examples of this application. The method comprises steps S1-S4: S1, a diphenol compound having two phenol functional groups in formula (I) or (II) is subjected to a nitration reaction to obtain a first intermediate compound in formula (III) or (IV). The specific reaction route is shown below:

[0055]

[0056] wherein R is an alkyl group or a halogenated alkyl group.

[0057] In some embodiments, the chemical structure of the diphenol compound used in S1 has axial symmetry, and the two phenol functional groups are symmetrical about the central axis. Optionally, R is a methylene (-CH2-), an isopropylidene (-CH3CCH3-) or a hexafluoroisopropylidene (-CF3CCF3-); accordingly, the diphenol compound having two phenol functional groups is 4,4′-(hexafluoroisopropylidene)diphenol, bisphenol A, bisphenol F or biphenol. Due to the electron displacement effect, the ortho position of the hydroxyl group in the diphenol compound is easily replaced by a nitro group, and accordingly, the organic product obtained by the nitration reaction tends to have axial symmetry.

[0058] In some embodiments, S1 comprises: adding a diphenol compound of formula (I) or (II) and dilute nitric acid to a first organic solvent, reacting at a first temperature for a first time, separating the liquids, and rotary evaporating and drying the solvent layer to obtain a first intermediate compound of formula (III) or (IV). Specifically, the first organic solvent and the diphenol compound of formula (I) or (II) are first added and uniformly mixed, with no particular order of addition, and the dilute nitric acid is added last to enhance the reaction effect.

[0059] In this way, using dilute nitric acid for the nitration reaction improves reaction safety while reducing the stringent requirements for reaction temperature and operation. The reaction temperature can be appropriately increased, thereby improving preparation efficiency, and there is no need to add dropwise, reducing operation and time costs, which is conducive to industrial production. In addition, the product is dried by low-temperature rotary evaporation to avoid product denaturation.

[0060] In some embodiments, the first organic solvent includes dichloromethane.

[0061] In some embodiments, the concentration of dilute nitric acid is 18-23%, preferably 20-22%. Using dilute nitric acid at these concentrations reduces reaction risk while ensuring the efficiency and completeness of the nitration reaction of the binary compounds.

[0062] In some embodiments, the first temperature is 40-50°C, preferably 45°C; the first time is 4-24 hours, preferably 4-15 hours. Using the above preparation method, the reaction temperature can be lower than 50°C, and the reaction conditions are relatively mild.

[0063] In some embodiments, the low-temperature rotary evaporation temperature in S1 is 35-40° C. to ensure drying efficiency while avoiding product denaturation.

[0064] After the nitration reaction step S1, the yield of the first intermediate compound is greater than 90% and the purity is greater than 95%. S2, the first intermediate compound is subjected to a condensation reaction with an organic compound having a sulfonyl group in an alkaline environment to obtain a second intermediate compound as shown in Formula (V) or Formula (VI). The specific reaction route is shown below:

[0065]

[0066] Wherein, X is an aromatic or hydrocarbon group, such as p-tolyl or an alkyl group. The condensation of a sulfonyl structure with a hydroxyl group allows for the grafting of a sulfonyl group at a relatively low temperature and in a relatively short time. Furthermore, the sulfonyl group is easily substituted, which helps reduce the temperature and time requirements for the subsequent substitution reaction. Furthermore, the sulfonic acid generated after the substitution reaction is readily soluble in water, facilitating the separation, cleaning, and collection of the final product.

[0067] Optionally, the organic compound having a sulfonyl group is p-toluenesulfonyl chloride, p-toluenesulfonic acid, alkylsulfonic acid or alkylsulfonyl chloride. The use of the above-mentioned low-toxic and environmentally friendly substances reduces pollution and has high reactivity with the first intermediate compound substituted with a nitro group.

[0068] In some embodiments, S2 comprises reacting the first intermediate compound with an organic compound having a sulfonyl group in a second organic solvent under condensation reflux at a second temperature for a second time using pyridine as an alkaline environmental conditioner, followed by filtration, washing, and drying to obtain a second intermediate compound of Formula (V) or Formula (VI). After completion of the condensation reaction in S2, only filtration and washing are required to obtain the purified second intermediate compound, simplifying the separation and purification process and facilitating large-scale production.

[0069] In some embodiments, the second organic solvent includes dichloromethane.

[0070] In some embodiments, the second temperature is 40-50°C, preferably, the second temperature is 45°C; the second time is 3-4 hours, preferably, the second time is 4 hours; it can be seen that the reaction temperature is mild and easy to control and the reaction efficiency is high.

[0071] In some embodiments, the ratio of the first intermediate compound to the organic compound having a sulfonyl group is less than 1:2. Preferably, the ratio of the first intermediate compound to the organic compound having a sulfonyl group is less than 1:5. By controlling the above ratio, the reaction is ensured to completely avoid the waste of raw materials while reducing side reaction products.

[0072] In some embodiments, pyridine is added in excess to further increase conversion and reduce side reactions. Since pyridine and sulfonyl groups are relatively low in cost and easy to separate and clean, excessive addition does not significantly increase costs. The corresponding increase in conversion avoids waste of the first intermediate compound and can reduce the cost of the primary raw material. Preferably, the ratio of the first intermediate compound to pyridine is 1:(2-8).

[0073] After the condensation reaction step S2, the yield of the second intermediate compound is greater than 60%, and can reach 60% to 70%, with a purity greater than 95%. S3, the second intermediate compound is subjected to a substitution reaction with an organic compound having a monoprimary amine group to obtain a third intermediate compound as shown in Formula (VII) or Formula (VIII). The specific reaction route is shown below:

[0074]

[0075] Wherein, Y is an aryl group, an alkyl group or an alcohol group. Optionally, the aryl group of Y is a phenyl group or a phenyl group having a substituent. Accordingly, in some embodiments, the organic compound having a monoprimary amine group is aniline, an aniline substituent, an alkylamine or monoethanolamine, which replaces the sulfonyl group to obtain an amino-substituted third intermediate compound.

[0076] In some embodiments, S3 includes: under the protection of inert gas, in a third organic solvent, condensing and refluxing the second intermediate compound and the organic compound having a monoprimary amine group at a third temperature for a third time, rotary evaporating at a low temperature to obtain a viscous substance, and recrystallizing to obtain a third intermediate compound as in formula (VII) or formula (VIII).

[0077] In some embodiments, the third organic solvent includes one or more of 1,4-dioxane, ethanol, and dichloromethane.

[0078] In some embodiments, the third temperature is 80-130° C., preferably, the third temperature is 80-95° C.; the third time is 4-16 hours, preferably, the third time is 4-10 hours.

[0079] In some embodiments, the low-temperature rotary evaporation temperature in S3 is below 60°C.

[0080] In some embodiments, the amount ratio between the second intermediate compound and the organic compound having a monoprimary amine group is 1:(3-20). By adding an excessive amount of the organic compound having a monoprimary amine group, the conversion rate of the second intermediate compound can be improved and the output of the side reaction product can be reduced. The latter has a lower cost and can significantly reduce the waste of the main raw material.

[0081] After the substitution reaction step S3, the yield of the third intermediate compound is greater than 30% and the purity is greater than 95%. S4, the third intermediate compound is subjected to a reduction reaction to obtain an amino-substituted aniline compound as shown in Formula (IX) or Formula (X). The specific reaction route is shown below:

[0082]

[0083] In some embodiments, S4 comprises: reacting a third intermediate compound with hydrazine hydrate at a fourth temperature for a fourth time in a fourth solvent in the presence of a palladium-carbon catalyst, filtering, rotary evaporating the filtrate at low temperature, drying, and recrystallizing to obtain an amino-substituted aniline compound as in formula (IX) or formula (X). The nitro group is reduced to an amino group through the reduction reaction of S4 to obtain an amino-substituted amino-substituted aniline compound. The reaction conditions of S4 are mild and the reaction efficiency is high, and the product cleaning and collection methods are simple, further improving the large-scale productivity of the reaction and facilitating process application. In addition, the use of a palladium-carbon catalyst facilitates catalyst recovery and reuse, thereby reducing reaction costs.

[0084] In some embodiments, the fourth organic solvent includes one or more of 1,4-dioxane, ethanol, and dichloromethane.

[0085] In some embodiments, the reducing agent used in S4 is hydrazine hydrate.

[0086] In some embodiments, the fourth temperature is 45-55° C., preferably, the fourth temperature is 50° C.; in some embodiments, the fourth time period is 1.5-2.5 hours, preferably, the fourth time period is 2 hours.

[0087] In some embodiments, the rotary evaporation temperature of the low-temperature rotary evaporation in S4 is below 60°C.

[0088] In some embodiments, the ratio of the third intermediate compound to hydrazine hydrate is less than 2: 1, preferably less than 1: 1. By adding an excess of the lower-cost hydrazine hydrate, the conversion rate of the third intermediate compound is synergistically improved and the cost is reduced.

[0089] The yield of the second intermediate compound obtained by the condensation reaction step S4 is greater than 30%, and the purity is greater than 95%. In summary, the amino-substituted aniline compound of the present application has an overall yield of greater than 56%, and an overall conversion rate of greater than 90%, which can significantly improve the conversion rate of the main raw material while reducing process complexity and reducing the cost of reaction raw materials.

[0090] The following describes specific examples of the present application in conjunction with the above-mentioned synthesis method of amino-substituted aniline compounds. The raw materials and reagents used in the examples of the present application are all commercially available.

[0091] Example 1

[0092] This embodiment provides a method for synthesizing amino-substituted aniline compounds, comprising:

[0093] 1.1 Nitration Reaction: Add 46 g of 4,4'-(hexafluoroisopropylidene)diphenol (designated BPAF1) and 480 ml of 22% dilute nitric acid to 480 ml of DCM as solvent and react at 45°C for 4-24 hours. Separate the mixture using a separatory funnel, remove the DCM layer, rotary evaporate at 40°C, and dry in a reduced pressure vacuum oven to obtain a solid powder product, 2,2-bis(3-nitro-4-hydroxyphenyl)hexafluoropropane, designated BPAF2. The yield of BPAF2 is approximately 92% or greater.

[0094] 1.2 Condensation Reaction: In a 150ml three-necked flask, add 4.26g of BPAF2, 7.56g of p-toluenesulfonyl chloride, and 2.2g of pyridine. In 30ml of DCM as the solvent, react at 45°C under condensation reflux for 4 hours. After completion, filter the reaction using a Buchner funnel to obtain a white solid. Rinse the sample again with DCM, filter it, and vacuum dry it to obtain 2,2-bis-(3-nitro-4-toluenesulfonyloxyphenyl)hexafluoropropane, designated BPAF3. The yield is 60%-70%.

[0095] 1.3 Substitution Reaction: Add 4g BPAF-3, 8g aniline, and 40ml dioxane (or ethanol, DMF) to a 150ml three-necked flask. Connect a condenser reflux tube and nitrogen protection. React at 80-130°C for 4-16h. Rotary evaporation yields a yellow viscous substance, which is recrystallized from ethanol to precipitate an orange-yellow solid to obtain 2,2-bis-(3-nitro-4-anilinophenyl)hexafluoropropane, designated BPAF4, with a yield of over 30%. Multiple reactions can be performed to accumulate the product.

[0096] 1.4 Reduction Reaction: Combine 430g of BPAF, 15ml of hydrazine hydrate, 0.1g of Pd-C, and 100ml of dioxane (or ethanol, DMF), and react at 50°C for 2h. Recover the Pd-C by filtration, and rotary evaporate the filtrate. Dry the filtrate in a vacuum oven and recrystallize it from ethanol to obtain a solid powder product, 2,2-bis-(3-amino-4-anilinophenyl)hexafluoropropane, designated BPAF5. The yield is greater than 30% and the purity is greater than 95%.

[0097] The H NMR spectrum of the product 2,2-bis-(3-amino-4-anilinophenyl)hexafluoropropane is as follows Figure 2 shown.

[0098] The specific synthetic route is as follows:

[0099]

[0100]

[0101] Example 2

[0102] This embodiment provides a method for synthesizing amino-substituted aniline compounds, comprising:

[0103] 1.1 Nitration Reaction: Add 32 g of bisphenol A (2,2-bis(4-hydroxyphenyl)propane) and 480 ml of 22% dilute nitric acid to 480 ml of DCM as solvent and react at 40°C for 4-24 hours. Separate the mixture using a separatory funnel, remove the DCM layer, rotary evaporate at 40°C, and dry in a vacuum oven to obtain a solid powder product, 2,2-bis(3-nitro-4-hydroxyphenyl)propane, designated BPAF6. The yield of BPAF6 is approximately 90% or greater.

[0104] 1.2 Condensation Reaction: In a 150ml three-necked flask, add 3.18g of BPAF6, 15.12g of p-toluenesulfonyl chloride, and 4.4g of pyridine. In 30ml of DCM as the solvent, react at 40°C under condensation reflux for 4 hours. After completion, filter the product through a Buchner funnel, rinse the sample again with DCM, filter it, and vacuum dry it to obtain 2,2-bis-(3-nitro-4-toluenesulfonyloxyphenyl)propane, designated BPAF7. The yield is 60%-70%.

[0105] 1.3 Substitution Reaction: Add 2g BPAF7, 8g aniline, and 40ml dioxane (or ethanol, DMF) to a 150ml three-necked flask, connect a condenser reflux tube and nitrogen protection, and react at 80-110°C for 8-16h. Rotary evaporate the collected product and recrystallize it from ethanol to obtain 2,2-bis-(3-nitro-4-anilinophenyl)propane, named BPAF8, with a yield of over 30%. Multiple reactions can be performed to accumulate the product.

[0106] 1.4 Combine 816g of BPAF, 15ml of hydrazine hydrate, 0.1g of Pd-C, and 100ml of dioxane (or ethanol, DMF), and react at 50°C for 2h. Recover the Pd-C by filtration, and rotary evaporate the filtrate. Dry the filtrate in a vacuum oven and recrystallize it from ethanol to obtain a solid powder product, 2,2-bis-(3-amino-4-anilinophenyl)propane, designated BPAF9. The yield is over 40% and the purity is over 97%.

[0107] The specific synthetic route is as follows:

[0108]

[0109]

[0110] Example 3

[0111] This embodiment provides a method for synthesizing amino-substituted aniline compounds, comprising:

[0112] 1.1 Nitration Reaction: Add 480 ml of 22% dilute nitric acid and 25 g of bisphenol F (bis-(hydroxyphenyl)methane) to 480 ml of DCM as the solvent and react at 45°C for 4-24 hours. Separate the mixture using a separatory funnel, remove the DCM layer, rotary evaporate it at 40°C, and dry it in a vacuum oven to obtain a solid powder product, bis(3-nitro-4-hydroxyphenyl)methane, designated BPAF10. The yield of BPAF10 is approximately 90% or greater.

[0113] 1.2 Condensation Reaction: In a 150ml three-necked flask, add 2.9g of BPAF10, 9.5g of p-toluenesulfonyl chloride, and 4.5g of pyridine. In 30ml of DCM as the solvent, react at 40°C under condensation reflux for 4 hours. After completion, filter the reaction using a Buchner funnel, rinse the sample again with DCM, filter it again, and vacuum dry it to obtain bis-(3-nitro-4-toluenesulfonyloxyphenyl)methane, designated BPAF11. The yield is 60%-70%.

[0114] 1.3 Substitution Reaction: To a 150 ml three-necked flask, add 2.5 g BPAF11, 8 g aniline, and 40 ml dioxane (or ethanol, DMF). Connect a condenser reflux tube and nitrogen protection, and react at 90-130°C for 8-16 h. Rotary evaporate the collected product and recrystallize it from ethanol to obtain bis-(3-nitro-4-anilinophenyl)methane, designated BPAF12, with a yield of over 35%. Multiple reactions can be performed to accumulate the product.

[0115] 1.4 Combine 15g of BPAF12, 15ml of hydrazine hydrate, 0.1g of Pd-C, and 100ml of dioxane (or ethanol, DMF), and react at 55°C for 2.5 hours. Recover the Pd-C by filtration, and rotary evaporate the filtrate. Dry the filtrate in a vacuum oven and recrystallize it from ethanol to obtain a solid powder product, bis-(3-amino-4-anilinophenyl)methane, designated BPAF13. The yield is over 30% and the purity is over 97%.

[0116] The specific synthesis route is as follows:

[0117]

[0118]

[0119] Example 4

[0120] This embodiment provides a method for synthesizing amino-substituted aniline compounds, comprising:

[0121] 1.1 Nitration reaction: 480 ml of DCM was used as solvent, 22 g of diphenol (4,4'-diphenol) and 22% dilute nitric acid were added.

[0122] 480ml, react at 45°C for 4-24 hours. Separate the liquid using a separatory funnel, remove the DCM layer, rotary evaporate at 40°C, and dry in a vacuum oven to obtain a solid powder product, 4,4'-dihydroxy-3,3'-dinitrobiphenyl, named BPAF14. The yield of BPAF14 is approximately 92% or more.

[0123] 1.2 Condensation Reaction: In a 150ml three-necked flask, add 2.76g of BPAF14, 9.56g of p-toluenesulfonyl chloride, and 6g of pyridine. In 50ml of DCM, react at 45°C under reflux for 4 hours. After completion, filter the reaction using a Buchner funnel, rinse the sample again with DCM, filter it again, and vacuum dry it to obtain 4,4'-ditoluenesulfonyloxyphenyl-3,3'-dinitrobiphenyl, designated BPAF15. The yield is 60%-70%.

[0124] 1.3 Substitution Reaction: Add 2.92 g BPAF15, 8 g aniline, and 40 ml dioxane (or ethanol, DMF) to a 150 ml three-necked flask. Connect a condenser reflux tube and nitrogen atmosphere. React at 90-120°C for 9-16 h. Rotary evaporate the collected product and recrystallize it from ethanol to obtain 4,4'-diphenylamino-3,3'-dinitrobiphenyl, designated BPAF16, with a yield of over 35%. Repeat the reaction to accumulate the product.

[0125] 1.4 Combine 1619g of BPAF, 20ml of hydrazine hydrate, 0.1g of Pd-C, and 100ml of dioxane (or ethanol, DMF), and react at 55°C for 2.5 hours. Recover the Pd-C by filtration, and rotary evaporate the filtrate. Dry the filtrate in a vacuum oven and then recrystallize it from ethanol to obtain a solid powder product, 4,4'-diphenylamino-3,3'-diphenylenediamine, designated BPAF17. The yield is over 30% and the purity is over 97%.

[0126] The specific synthetic route is as follows:

[0127]

[0128]

[0129] In summary, the synthesis method of the present application has a simple and easy synthesis process, consistent conditions and high reaction safety, simple processes for collecting and purifying intermediates and final products, is environmentally friendly, low-cost and conducive to industrial large-scale production, and the obtained amino-substituted aniline compounds have excellent rubber vulcanization effects, and the resulting rubber products can be used in harsh chemical environments such as high temperature and acid and alkali.

[0130] The above description has fully disclosed the specific embodiments of this application. It should be noted that any changes made by those skilled in the art to the specific embodiments of this application do not depart from the scope of the claims of this application. Accordingly, the scope of the claims of this application is not limited to the above specific embodiments.

Claims

1. A method for synthesizing amino-substituted aniline compounds, characterized in that: The synthesis method comprises: S1, subjecting a diphenol compound having two phenol functional groups of formula (I) or formula (II) to a nitration reaction to obtain a first intermediate compound of formula (III) or formula (IV); S2, performing a condensation reaction between the first intermediate compound and an organic compound having a sulfonyl group in an alkaline environment to obtain a second intermediate compound of formula (V) or formula (VI); S3, subjecting the second intermediate compound to a substitution reaction with an organic compound having a monoprimary amine group to obtain a third intermediate compound of formula (VII) or formula (VIII); S4, subjecting the third intermediate compound to a reduction reaction to obtain an amino-substituted aniline compound of formula (IX) or formula (X); Wherein, R is a hydrocarbon group, a halogenated alkyl group or an aryl group, X is an aryl group or a hydrocarbon group, and Y is an aryl group, an alkyl group or an alcohol group.

2. The synthesis method according to claim 1, wherein Said S1 comprises: In a first organic solvent, the diphenol compound of formula (I) or formula (II) and dilute nitric acid are added, and the mixture is reacted at a first temperature for a first time. The liquid is separated, and the solvent layer is subjected to low-temperature rotary evaporation and drying to obtain the first intermediate compound of formula (III) or formula (IV).

3. The synthesis method according to claim 2, wherein The S1 satisfies at least one of the following conditions: The first temperature is 40-50°C; The first duration is 4-24 hours; The rotary evaporation temperature of the low-temperature rotary evaporation in S1 is 35-40°C; The concentration of the dilute nitric acid is 18-23%; The first organic solvent includes dichloromethane.

4. The synthesis method according to claim 1, wherein The S2 includes: In a second organic solvent, using pyridine as an alkaline environment regulator, the first intermediate compound and the organic compound having a sulfonyl group are reacted under condensation reflux at a second temperature for a second time, and then filtered, washed, and dried to obtain the second intermediate compound of formula (V) or formula (VI).

5. The synthesis method according to claim 4, wherein S2 satisfies at least one of the following conditions: The second temperature is 40-50°C; The second duration is 3-4 hours; The amount ratio between the first intermediate compound and the organic compound having a sulfonyl group is less than 1:2; The second organic solvent includes dichloromethane.

6. The synthesis method according to claim 1, wherein The S3 includes: Under the protection of inert gas, the second intermediate compound and the organic compound having a monoprimary amine group are reacted at a third temperature and refluxed for a third time in a third organic solvent, and a viscous substance is obtained by low-temperature rotary evaporation. After recrystallization, the third intermediate compound as described in formula (VII) or formula (VIII) is obtained.

7. The synthesis method according to claim 6, characterized in that S3 satisfies at least one of the following conditions: The third temperature is 80-130° C. The third duration is 4-16 hours; The rotary evaporation temperature of the low-temperature rotary evaporation in S3 is below 60°C; The amount ratio of the second intermediate compound to the organic compound having a monoprimary amine group is 1:(3-40); the third organic solvent includes one or more of 1,4-dioxane, ethanol, and dichloromethane.

8. The synthesis method according to claim 1, wherein The S4 includes: In a fourth solvent, the third intermediate compound is reacted with hydrazine hydrate at a fourth temperature for a fourth time in the presence of a palladium-carbon catalyst. After filtering, the filtrate is rotary evaporated at low temperature, dried, and recrystallized to obtain the amino-substituted aniline compound as described in formula (IX) or formula (X).

9. The synthesis method according to claim 8, characterized in that The S4 satisfies at least one of the following conditions: The fourth temperature is 45-55°C; The fourth duration is 1.5-2.5 hours; The rotary evaporation temperature of the low-temperature rotary evaporation in S4 is below 60°C; The amount ratio between the third intermediate compound and hydrazine hydrate is less than 2:1; The fourth organic solvent includes one or more of 1,4-dioxane, ethanol, and dichloromethane; The reducing agent used in S4 is hydrazine hydrate.

10. The synthesis method according to any one of claims 1 to 9, characterized in that The synthesis method satisfies at least one of the following characteristics: R is methylene, isopropylidene or hexafluoroisopropylidene; The aryl group of Y is a phenyl group or a phenyl group having a substituent.

11. The synthesis method according to any one of claims 1 to 9, characterized in that The synthesis method satisfies at least one of the following characteristics: The diphenol compound having two phenol functional groups is 4,4′-(hexafluoroisopropylidene)diphenol, bisphenol A, bisphenol F or biphenyl diphenol; The organic compound having a sulfonyl group is p-toluenesulfonyl chloride and p-toluenesulfonic acid; The organic compound having a monoprimary amine group is aniline, aniline substituents, alkylamine or monoethanolamine.

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