Industrial preparation method of ortho-position large-steric-hindrance aniline

Abstract

The invention discloses an industrial preparation method of ortho-position large-steric-hindrance aniline, which comprises the following steps: reacting 2, 4-disubstituted aniline with benzhydrol or a derivative thereof, and performing simple post-treatment on the reaction product to obtain the ortho-position large-steric-hindrance aniline product. The method effectively solves the problem of difficulty in large-scale industrial preparation in the prior art, and has the advantages of mild reaction conditions, simplicity in operation, high efficiency and good effect.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to an industrial preparation method of ortho-position bulky sterically hindered aniline. Background Art

[0002] Ortho-large steric hindered aniline is one of the most effective catalyst ligand composition structures in the field of polymer catalysts. Its large steric hindrance can effectively regulate the molecular weight and branching degree of the polymerization product, so it is widely used in the structure composition of polymer catalysts. Ortho-large steric hindered aniline refers to an aniline derivative containing a super-large steric hindered substituent in the ortho position of the amino group, among which diphenylmethyl substituents are a relatively common representative group.

[0003] Ortho-hindered aniline is prepared by Friedel-Crafts alkylation of common aniline and benzhydrol or its derivatives in the presence of Lewis acid. Currently, diimine catalysts are increasingly used in industry, but related reports mainly focus on monoaniline or simple methyl-substituted aniline, and research on the synthesis of hindered aniline is still not given enough attention.

[0004] US4436936 uses aniline, tert-butyl alcohol, hydrochloric acid and zinc chloride to prepare large steric hindered aniline, but the patent specifically mentions that a sealed high-pressure reaction is required, and the yield is 75%; in CN116903476A, the amount of aniline used is more than twice the equivalent of benzhydrol or its derivatives, the amount of hydrochloric acid and zinc chloride used exceeds 1 equivalent, and the ortho-position large steric hindered aniline is obtained by high-temperature reaction at 150°C. The reaction system is solid in the later stage, and industrial scale-up is difficult. CN114249850A / CN114163482A uses substituted aniline and benzhydrol to prepare large steric hindered aniline, 1 equivalent of hydrochloric acid, 0.5 equivalent of zinc chloride, and the reaction is violently exothermic and bubbling during the reaction, and the reaction system gradually turns into a solid, which is difficult to scale up industrially.

[0005] Overall, the existing process has problems with low reaction conversion rate and selectivity, and the process itself is difficult to industrialize. Summary of the invention

[0006] The purpose of this section is to summarize some aspects of embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the specification abstract and the invention title of this application to avoid blurring the purpose of this section, the specification abstract and the invention title, and such simplifications or omissions cannot be used to limit the scope of the present invention.

[0007] In view of the above problems and / or the problems existing in the prior art, the present invention is proposed.

[0008] Therefore, the object of the present invention is to overcome the deficiencies in the prior art and provide an industrial preparation method for ortho-positioned bulky sterically hindered aniline.

[0009] In order to solve the above technical problems, the present invention provides the following technical solution: an industrial preparation method of ortho-large sterically hindered aniline, comprising:

[0010] Adding 2,4-disubstituted aniline, benzhydrol or its derivatives, a catalyst and an additive into a solvent and reacting at a high temperature;

[0011] After cooling and treatment, the ortho-hindered aniline is obtained;

[0012] The structural formula of the 2,4-disubstituted aniline is:

[0013]

[0014] The structural formula of the benzhydrol or its derivative is:

[0015]

[0016] The structural formula of the ortho-large sterically hindered aniline is:

[0017]

[0018] Wherein, R1 to R4 are alkyl, aromatic or halogen substituents;

[0019] The solvent includes one or more of 1,4-dioxane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, heptane, octane, nonane, decane, butyl acetate, nitrobenzene, and chlorobenzene.

[0020] As a preferred embodiment of the preparation method of the present invention, the additive comprises an inorganic acid, an organic acid or a mixture thereof.

[0021] As a preferred embodiment of the preparation method of the present invention, the inorganic acid and organic acid include at least one of hydrochloric acid, sulfuric acid, hydrobromic acid, nitric acid, phosphoric acid, hydrofluoric acid, formic acid, acetic acid, benzoic acid and p-toluenesulfonic acid.

[0022] As a preferred embodiment of the preparation method of the present invention, the catalyst comprises Lewis acid salt.

[0023] As a preferred embodiment of the preparation method of the present invention, the Lewis acid salt includes at least one of cupric chloride, ferric chloride, zinc chloride, cupric sulfate, aluminum chloride, ferrous chloride, cuprous chloride, zinc sulfate, aluminum sulfate, ferrous sulfate, ferrous sulfate, cuprous sulfate, cupric acetate, zinc acetate, cuprous acetate, ferric acetate, ferrous acetate, and cobalt acetate.

[0024] As a preferred embodiment of the preparation method of the present invention, the high temperature reaction has a reaction temperature of 90 to 200° C. and a reaction time of 3 to 7 hours.

[0025] As a preferred embodiment of the preparation method of the present invention, the molar ratio of the 2,4-disubstituted aniline, benzhydrol or its derivatives, catalyst and additive is 1:0.8-1.5:0.05-0.5:0.01-1.

[0026] As a preferred embodiment of the preparation method of the present invention, the molar ratio of the 2,4-disubstituted aniline to the solvent is 0.1 to 3:1, and more preferably 0.5 to 2:1.

[0027] As a preferred embodiment of the preparation method of the present invention, the cooling post-treatment includes desolventizing after the reaction is completed, washing the bottom liquid with dichloromethane and ammonium chloride or sodium carbonate / potassium carbonate aqueous solution, separating the liquids, concentrating the organic phase, adding a poor solvent to pulp, filtering and drying to obtain the final product.

[0028] Beneficial effects of the present invention:

[0029] (1) The present invention provides an industrial preparation method of ortho-hindered aniline, which is efficient and effective. By adding a solvent, the reaction system will not be converted into a solid phase in the later stage, which is very suitable for kettle scale-up.

[0030] (2) The post-processing of the present invention is simple. Due to the high reaction selectivity and conversion rate, after removing the catalyst and additives by water washing, the obtained organic phase only needs a simple purification treatment to obtain a product with a purity of more than 98%.

[0031] (3) The method of the present invention is green and environmentally friendly, with low cost. The reaction conditions of the present invention are mild, the amount of additives used is small, the purification efficiency is high, and the three wastes discharge and production costs are significantly reduced. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for describing the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without creative labor. Among them:

[0033] Figure 1 This is the H NMR spectrum of the product obtained in Example 1 of the present invention. DETAILED DESCRIPTION

[0034] 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.

[0035] In the following description, many specific details are set forth to facilitate a full understanding of the present invention, but the present invention may also be implemented in other ways different from those described herein, and 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.

[0036] Secondly, the term "one embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The term "in one embodiment" that appears in different places in this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive with other embodiments.

[0037] The calculation method of the product yield in the embodiment of the present invention is:

[0038] Yield (%) = (product molar amount / raw material molar amount) × 100%;

[0039] The raw materials in the embodiments of the present invention are all common commercially available products.

[0040] Example 1

[0041] This embodiment provides an industrial preparation method of ortho-hindered aniline, the main steps of which are:

[0042] (1) Weigh 26.5 g of di(4-fluorophenyl)methanol, 12.1 g of 2,4-dimethylaniline, 2.8 g of zinc chloride, 1 mL of formic acid, and 100 mL of diethylene glycol dimethyl ether, stir at 160° C. for 5 h, and then concentrate;

[0043] (2) 100 mL of dichloromethane and 100 mL of 5% sodium carbonate aqueous solution were added to the obtained bottom liquid, and the liquids were separated. After the organic phase was concentrated, methanol was added to make pulp, filtered, and the filter cake was dried to obtain the product, 29.6 g, with a yield of 92%.

[0044] The structural formula of the obtained product is:

[0045]

[0046] The H NMR spectrum of the product can be found in Figure 1 .

[0047] Example 2

[0048] This embodiment provides an industrial preparation method of ortho-hindered aniline, the main steps of which are:

[0049] (1) Weigh 26.5 g of di(4-chlorophenyl)methanol, 12.1 g of 2,4-dimethylaniline, 2.8 g of zinc chloride, 1 mL of formic acid, and 100 mL of diethylene glycol dimethyl ether, stir at 160° C. for 5 h, and then concentrate;

[0050] (2) 100 mL of dichloromethane and 100 mL of 5% sodium carbonate aqueous solution were added to the obtained bottom liquid, and the liquids were separated. After the organic phase was concentrated, n-hexane was added to make pulp, filtered, and the filter cake was dried to obtain the product, 31.2 g, with a yield of 88%.

[0051] The structural formula of the obtained product is:

[0052]

[0053] Example 3

[0054] This embodiment provides an industrial preparation method of ortho-hindered aniline, the main steps of which are:

[0055] (1) Weigh 18.4 g of benzhydrol, 18 g of 2,4-diisopropylaniline, 2 g of cuprous chloride, 4 mL of hydrochloric acid, and 100 mL of n-octane, stir at 130 °C for 6 h, and then concentrate;

[0056] (2) 100 mL of 1,2-dichloroethane and 100 mL of 5% potassium carbonate aqueous solution were added to the obtained bottom liquid, and the liquids were separated. After the organic phase was concentrated, petroleum ether was added to make pulp, filtered, and the filter cake was dried to obtain the product, 31.7 g, with a yield of 92%.

[0057] The structural formula of the obtained product is:

[0058]

[0059] Example 4

[0060] This embodiment provides an industrial preparation method of ortho-hindered aniline, the main steps of which are:

[0061] (1) Weigh 25.2 g of 3-(trifluoromethyl)diphenylmethanol, 12.1 g of 2,4-dimethylaniline, 3 g of aluminum chloride, 3 mL of hydrochloric acid, and 100 mL of 1,4-dioxane, stir at 120° C. for 7 h, and then concentrate;

[0062] (2) 100 mL of 1,2-dichloroethane and 100 mL of 5% potassium carbonate aqueous solution were added to the obtained bottom liquid, and the liquids were separated. After the organic phase was concentrated, ethanol was added to make pulp, filtered, and the filter cake was dried to obtain the product, 31.2 g, with a yield of 88%.

[0063] The structural formula of the obtained product is:

[0064]

[0065] Example 5

[0066] This embodiment provides an industrial preparation method of ortho-hindered aniline, the main steps of which are:

[0067] (1) Weigh 18.4 g of benzhydrol, 12.1 g of 2,4-dimethylaniline, 0.7 g of zinc chloride, 1 mL of hydrochloric acid, and 100 mL of diethylene glycol dimethyl ether, stir at 160° C. for 6 h, and then concentrate;

[0068] (2) 100 mL of dichloromethane and 100 mL of 5% sodium carbonate aqueous solution were added to the obtained bottom liquid, and the liquids were separated. After the organic phase was concentrated, methanol was added to make pulp, filtered, and the filter cake was dried to obtain the product, 26.1 g, with a yield of 91%.

[0069] The structural formula of the obtained product is:

[0070]

[0071] Example 6

[0072] This embodiment provides an industrial preparation method of ortho-hindered aniline, the main steps of which are:

[0073] (1) Weigh 18.4 g of benzhydrol, 12.1 g of 2,4-dimethylaniline, 2.8 g of zinc chloride, 1 mL of hydrochloric acid, and 100 mL of ethylene glycol dimethyl ether, stir at 90° C. for 6 h, and then concentrate;

[0074] (2) 100 mL of dichloromethane and 100 mL of 10% aqueous ammonium chloride solution were added to the obtained bottom liquid, and the liquids were separated. After the organic phase was concentrated, n-hexane was added to make pulp, filtered, and the filter cake was dried to obtain the product, 23.0 g, with a yield of 81%.

[0075] The structural formula of the obtained product is:

[0076]

[0077] Example 7

[0078] This embodiment provides an industrial preparation method of ortho-hindered aniline, the main steps of which are:

[0079] (1) Weigh 20 g of benzhydrol, 12.1 g of 2,4-dimethylaniline, 1.4 g of zinc chloride, 1 mL of sulfuric acid, and 100 mL of nitrobenzene, stir at 200 °C for 3 h, and then concentrate;

[0080] (2) 100 mL of dichloromethane and 100 mL of 5% potassium carbonate aqueous solution were added to the obtained bottom liquid, and the liquids were separated. After the organic phase was concentrated, petroleum ether was added to make pulp, filtered, and the filter cake was dried to obtain the product, 26.0 g, with a yield of 91%.

[0081] The structural formula of the obtained product is:

[0082]

[0083] Comparative Example 1

[0084] (1) Weigh 26.5 g of di(4-fluorophenyl)methanol, 12.1 g of 2,4-dimethylaniline, 8.2 g of zinc chloride, and 5 mL of hydrochloric acid, stir at 160°C for 4 h, and then cool;

[0085] (2) The obtained solid was added with 100 mL of dichloromethane and 100 mL of 10% ammonium chloride aqueous solution, and the liquids were separated. The organic phase was concentrated and then methanol was added to make pulp. The mixture was filtered and the filter cake was dried to obtain the product, 15.7 g, with a yield of 49%.

[0086] Comparative Example 2

[0087] Weigh 18.4 g of benzhydrol, 12.1 g of 2,4-dimethylaniline, 0.7 g of zinc chloride, 1 mL of hydrochloric acid, and 100 mL of dichloromethane. Stir at 40°C for 6 h. The gas phase measurement results show that almost no product is generated.

[0088] Comparative Example 3

[0089] (1) Weigh 26.5 g of di(4-fluorophenyl)methanol, 12.1 g of 2,4-dimethylaniline, 2.8 g of zinc chloride, and 1 mL of formic acid, stir at 160° C. for 5 h, and then concentrate;

[0090] (2) 100 mL of dichloromethane and 100 mL of 5% sodium carbonate aqueous solution were added to the obtained bottom liquid, and the liquids were separated. After the organic phase was concentrated, methanol was added to make pulp, filtered, and the filter cake was dried to obtain the product, 6.8 g, with a yield of 21%.

[0091] Comparative Example 4

[0092] Weigh 26.5 g of di(4-fluorophenyl)methanol, 12.1 g of 2,4-dimethylaniline, 2.8 g of zinc chloride, 1 mL of formic acid, and 100 mL of dichloromethane. After stirring at 40° C. for 5 h, the gas phase shows that almost no product is produced.

[0093] Comparative Example 5

[0094] (1) Weigh 26.5 g of di(4-fluorophenyl)methanol, 12.1 g of 2,4-dimethylaniline, 2.8 g of zinc chloride, 1 mL of formic acid, 50 mL of diethylene glycol dimethyl ether + 50 mL of 1,4-dioxane, stir at 160° C. for 5 h, and concentrate;

[0095] (2) 100 mL of dichloromethane and 100 mL of 5% sodium carbonate aqueous solution were added to the obtained bottom liquid, and the liquids were separated. After the organic phase was concentrated, methanol was added to make pulp, filtered, and the filter cake was dried to obtain the product, 28.8 g, with a yield of 89%.

[0096] It should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention rather than to limit it. 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 can 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 present invention.

Claims

1. An industrial preparation method of ortho-hindered aniline, characterized in that: include, Adding 2,4-disubstituted aniline, benzhydrol or its derivatives, a catalyst and an additive into a solvent and reacting at a high temperature; After cooling and treatment, the ortho-hindered aniline was obtained; The structural formula of the 2,4-disubstituted aniline is: The structural formula of the benzhydrol or its derivative is: The structural formula of the ortho-large sterically hindered aniline is: Wherein, R1 to R4 are alkyl, aromatic or halogen substituents; The solvent includes one or more of 1,4-dioxane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, heptane, octane, nonane, decane, butyl acetate, nitrobenzene, and chlorobenzene.

2. The preparation method according to claim 1, characterized in that: The additive includes an inorganic acid, an organic acid or a mixture thereof.

3. The preparation method according to claim 2, characterized in that: The inorganic acid and organic acid include at least one of hydrochloric acid, sulfuric acid, hydrobromic acid, nitric acid, phosphoric acid, hydrofluoric acid, formic acid, acetic acid, benzoic acid, and p-toluenesulfonic acid.

4. The preparation method according to any one of claims 1 to 3, characterized in that: The catalyst comprises a Lewis acid salt.

5. The preparation method according to claim 4, characterized in that: The Lewis acid salt includes at least one of cupric chloride, ferric chloride, zinc chloride, cupric sulfate, aluminum chloride, ferrous chloride, cuprous chloride, zinc sulfate, aluminum sulfate, ferrous sulfate, ferrous sulfate, cuprous sulfate, cupric acetate, zinc acetate, cuprous acetate, ferric acetate, ferrous acetate, and cobalt acetate.

6. The preparation method according to claim 1 or 5, characterized in that: The high temperature reaction, wherein the reaction temperature is 90-200° C., and the reaction time is 3-7 hours.

7. The preparation method according to any one of claims 1, 2, 3 or 5, characterized in that: The molar ratio of the 2,4-disubstituted aniline, benzhydrol or its derivatives, the catalyst and the additive is 1:0.8-1.5:0.05-0.5:0.01-1.

8. The preparation method according to claim 7, characterized in that: The molar ratio of the 2,4-disubstituted aniline to the solvent is 0.1-3:

1.

9. The preparation method according to claim 1, characterized in that: The cooling post-treatment includes: desolventizing after the reaction is completed, adding dichloromethane and ammonium chloride or sodium carbonate / potassium carbonate aqueous solution to the bottom liquid for washing, separating the liquids, concentrating the organic phase, adding a poor solvent for pulping, filtering and drying to obtain the final product.

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