Synthetic method of benzidine

Abstract

The invention relates to the technical field of chemical synthesis, in particular to a synthetic method of benzidine, which comprises the following steps: adding p-bromoaniline, formic acid and hydrazine hydrate into a 10% sodium hydroxide aqueous solution, and heating and reacting at 70-90 DEG C for 6-10 hours under the catalysis of palladium-carbon; after the reaction is finished, filtering, dissolving the obtained filter cake with ethanol, and extracting the obtained filtrate with dichloromethane; combining the dichloromethane extracting solution and the ethanol dissolving solution, carrying out vacuum concentration until the solution is nearly dry, adding deionized water to separate out a target compound, filtering again, and drying a filter cake to obtain benzidine; by optimizing the reaction conditions and the post-treatment process, the obtained benzidine product is an off-white solid, the purity meets the requirements of various application scenes such as dye intermediates, high polymer material chain extenders and detection reagents, the problems of excessive product impurities and substandard purity caused by insufficient reaction selectivity in the prior art are avoided, and the method is suitable for industrial production. The practical value and the market applicability of the synthesis method are further guaranteed.

Description

Technical Field

[0001] This invention relates to the field of chemical synthesis technology, specifically to a method for synthesizing benzidine. Background Technology

[0002] Benzidine (CAS: 92-87-5), as a crucial basic chemical raw material, has a wide and irreplaceable application value in industrial production and scientific research. Its core uses include serving as a dye intermediate in the manufacture of various dye products such as direct dyes, acid dyes, vat dyes, ice dyes, sulfur dyes, reactive dyes, and organic pigments. In the field of polymer materials, it can be used as a chain extender in the production of polyurethane rubber and fibers. In the fields of medicine and testing, it can be used for the detection of cyanide and blood, and it is also a special chemical reagent for the determination of monoaldehydes and ammonium persulfate by thin-layer chromatography, with a consistently stable market demand.

[0003] To date, the synthesis methods of benzidine have been extensively studied, with over 200 publicly reported synthetic routes. The traditional method for large-scale industrial production involves using nitrobenzene as a starting material. Under zinc powder catalysis and strong alkaline conditions, a coupling reaction first produces azobenzene, which is then further reduced to 1,2-diphenylhydrazine. Finally, the 1,2-diphenylhydrazine undergoes a rearrangement reaction in an acidic environment and is then freed to obtain benzidine. This traditional industrial route differs fundamentally from the present invention in both its raw material system and process flow. Besides industrial-scale methods, various benzidine synthesis techniques using p-bromoaniline as a starting material have also been reported in academia: for example, [Journal of Organometallic...]. In [Chemistry, 2019, vol. 883, pp. 78-85], Rafiee, Fatemeh, Khavari, Parvaneh, et al. disclosed a synthetic method using a nano-sized palladium-on-carbon composite catalyst and solvents such as DMF. Although this method successfully synthesized benzidine, the nano-sized palladium-on-carbon composite catalyst used suffers from high cost, complex preparation process, and poor market availability, resulting in high synthesis costs and making it unsuitable for large-scale production. Similarly, in [Synlett, 2018, vol. 29, #6, pp. 779-784], Du, Fangyu, Zhou, Qifan, et al. disclosed another synthetic technique, also using p-bromoaniline as a raw material, requiring pinacol diborate as a ligand and palladium-on-carbon as a catalyst. The core drawback of this method is that the product separation and purification process requires column chromatography, which is not only cumbersome and time-consuming but also difficult to scale up industrially. Furthermore, the special nature of the ligand raw material further limits its application scenarios.

[0004] Based on existing technologies, both industrial-scale production methods and laboratory-level synthesis routes have their own technical shortcomings: traditional industrial routes involve lengthy process steps and harsh reaction conditions; existing synthesis methods using p-bromoaniline as a raw material face problems such as high catalyst costs, special ligands, and complex post-processing, and no literature or patents have disclosed the same synthesis process route as this invention.

[0005] To address the shortcomings of existing technologies, the core objective of this invention is to provide a novel method for synthesizing benzidine. This method offers significant advantages, including simple operation steps, high molecular utilization, mild reaction conditions, low operating costs, and a streamlined post-processing procedure. The purity of the obtained product meets industrial application requirements. Furthermore, all reagents involved in the preparation process are commercially available and readily available, and the one-pot synthesis strategy further simplifies the operation and reduces the complexity of the process. This synthetic route provides a practical and feasible new approach for the synthesis of benzidine, effectively filling a technological gap in the field and possessing significant practical reference and application value in both industrial production and laboratory preparation. Summary of the Invention

[0006] The purpose of this invention is to overcome the shortcomings of the prior art and propose a method for synthesizing benzidine, providing a very feasible operational approach for the synthesis of benzidine and filling a gap in the relevant technology in this field.

[0007] The specific technical solution is as follows: A method for synthesizing benzidine involves adding p-bromoaniline, formic acid, and hydrazine hydrate to a 10% sodium hydroxide aqueous solution, and heating the mixture at 70℃-90℃ for 6-10 hours under palladium-carbon catalysis; after the reaction is completed, the mixture is filtered, the resulting filter cake is dissolved in ethanol, and the resulting filtrate is extracted with dichloromethane; the dichloromethane extract and the ethanol solution are combined, concentrated under vacuum to near dryness, deionized water is added to precipitate the target compound, the mixture is filtered again, and the filter cake is dried to obtain benzidine; The synthesis circuit is as follows: .

[0008] As a further technical solution: based on p-bromoaniline, the amount of p-bromoaniline is set to 1.0 equivalent.

[0009] As a further technical solution: the amount of formic acid used is 0.7 equivalents relative to p-bromoaniline.

[0010] As a further technical solution: the amount of hydrazine hydrate used is 0.7 equivalents relative to p-bromoaniline.

[0011] As a further technical solution: the amount of the 10% sodium hydroxide aqueous solution used is 6 times the volume (v / m) of the mass of p-bromoaniline.

[0012] As a further technical solution: the reaction temperature is 70℃-90℃.

[0013] As a further technical solution: the mass fraction of palladium in the palladium on carbon is 10%, and its total amount is 0.5%-1.5% of the mass of p-bromoaniline.

[0014] As a further technical solution: the reaction time is 6-10 hours.

[0015] As a further technical solution: the amount of ethanol used is 6 times the volume (v / m) of the mass of p-bromoaniline.

[0016] As a further technical solution: the amount of dichloromethane used is 10 times the volume (v / m) of the mass of p-bromoaniline; the amount of deionized water used is 10 times the volume (v / m) of the mass of p-bromoaniline.

[0017] Compared with the prior art, the present invention has the following beneficial effects: Innovative Catalytic System for Synergistic Effect: This invention, for the first time, constructs a "formic acid-hydrazine hydrate-palladium on carbon" synergistic catalytic system. Formic acid and hydrazine hydrate react first to generate formyl hydrazine, which then forms a co-catalytic effect with palladium on carbon, driving the self-coupling reaction of p-bromoaniline, followed by reduction and rearrangement to generate benzidine. This catalytic mechanism overcomes the limitations of existing technologies that rely on a single catalyst or require specific ligands, solving the technical problems of high cost and difficulty in obtaining specific ligands in traditional nanoscale composite catalysts, significantly improving the selectivity and efficiency of the reaction. The reaction conditions are mild, and the operation is simple and controllable: The synthesis reaction of this invention is carried out within a mild temperature range of 70℃-90℃, without the need for harsh reaction conditions such as high temperature and high pressure, thus reducing the requirements for equipment and the operational safety risks. At the same time, the reaction time is controlled within 6-10 hours, which is more efficient than the lengthy reaction processes of some existing technologies. The entire synthesis process adopts a one-pot strategy, with continuous and simple operation steps. Post-processing only requires conventional operations such as filtration, extraction, concentration, and recrystallization, eliminating the need for complex separation methods such as column chromatography, greatly simplifying the process and facilitating laboratory preparation and industrial-scale production. Low raw material cost and significant industrialization potential: The reagents used in this invention, such as p-bromoaniline, formic acid, hydrazine hydrate, 10% palladium on carbon, and sodium hydroxide, are all commercially available conventional chemical raw materials. They are widely available, inexpensive, and can be used directly without complex pretreatment. This effectively avoids the problem of high production costs caused by special ligands and expensive catalysts in existing technologies, significantly reduces the synthesis cost of benzidine, and has strong economic viability for industrial applications. This invention offers a novel technical route for the synthesis of benzidine, distinct from existing industrial-scale methods and academic reports. Its core lies in the integrated coupling-reduction rearrangement process design using formyl hydrazine-palladium-carbon co-catalyzed technology. No prior art exists for this technical solution, effectively filling a technological gap in benzidine synthesis methods. This route provides a completely new technical approach for benzidine synthesis, enriching the synthetic method library of aromatic diamines and offering important insights and references for the preparation of similar structural compounds. It possesses significant technological promotion value and industry application significance. The product has reliable purity and a wide range of applications: By optimizing the reaction conditions and post-processing procedures, the benzidine product obtained by this invention is an off-white solid with purity that meets the requirements of various applications such as dye intermediates, polymer chain extenders, and detection reagents. This avoids the problems of excessive impurities and substandard purity caused by insufficient reaction selectivity in existing technologies, further ensuring the practical value and market applicability of this synthesis method. Attached Figure Description

[0018] Figure 1 This is the 1H NMR spectrum of a product synthesized using a process for synthesizing benzidine. Detailed Implementation

[0019] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0020] The raw materials, reagents, and solvents used in the examples were all purchased from Shanghai E. En Technology Co., Ltd., and were of industrial grade. Specifically, the mass fractions of p-bromoaniline and formic acid were both greater than 98%, the mass fraction of hydrazine hydrate was 80%, the mass fraction of sodium hydroxide was 85%, and the mass fraction of palladium on carbon was 10%; the mass fraction of ethanol was 95%, and the mass fraction of dichloromethane was 99%; the water used was self-made deionized water (belonging to the category of purified water).

[0021] Example 1: Under stirring, 30 mL of 10% sodium hydroxide aqueous solution, formic acid (0.77 mL, 20.35 mmol), hydrazine hydrate (1.23 mL, 20.35 mmol), and 0.05 g of 10% palladium on carbon (1% relative to p-bromoaniline) were added sequentially to a 100 mL glass reaction flask. After stirring for 30 minutes, 5 g of 4-bromoaniline (29.07 mmol) was added, and the mixture was stirred at 80 °C for 10 hours. After the reactants had reacted completely, the mixture was cooled to room temperature and filtered. The filter cake was dissolved in 30 mL of ethanol and filtered again to obtain an ethanol filtrate. 50 mL of dichloromethane was added to the filtrate for extraction. The ethanol filtrate and the dichloromethane extract were combined and concentrated under vacuum to near dryness. 100 mL of purified water (self-made deionized water) was added and stirred to precipitate the solid. The precipitate was filtered, washed, and dried to obtain 2.1 g of an off-white solid, with a yield of 78.4%.

[0022] Example 2: Under stirring, 90 mL of 10% sodium hydroxide aqueous solution, formic acid (2.3 mL, 61.04 mmol), hydrazine hydrate (3.7 mL, 61.04 mmol), and 0.15 g of 10% palladium on carbon (1% relative to p-bromoaniline) were added sequentially to a 250 mL glass reaction flask. After stirring for 30 minutes, 15 g of 4-bromoaniline (87.2 mmol) was added, and the reaction was carried out at 70 °C for 6 hours. After the reactants had reacted completely, the mixture was cooled to room temperature and filtered. The filter cake was dissolved in 100 mL of ethanol and filtered to obtain an ethanol filtrate. 150 mL of dichloromethane was added to the filtrate for extraction. The ethanol filtrate and the dichloromethane extract were combined and concentrated under vacuum to near dryness. 250 mL of purified water (self-made deionized water) was added and stirred to precipitate the solid. The precipitate was filtered, washed, and dried to obtain 6.87 g of an off-white solid, with a yield of 85.5%.

[0023] Example 3: Under stirring, 300 mL of 10% sodium hydroxide aqueous solution, formic acid (7.68 mL, 203.46 mmol), hydrazine hydrate (12.34 mL, 203.46 mmol), and 0.5 g of 10% palladium on carbon (1% relative to p-bromoaniline) were added sequentially to a 500 mL glass reaction flask. After stirring for 30 minutes, 50 g of 4-bromoaniline (290.66 mmol) was added, and the mixture was stirred at 90 °C for 8 hours. After the reactants had reacted completely, the mixture was cooled to room temperature and filtered. The filter cake was dissolved in 300 mL of ethanol and filtered again to obtain an ethanol filtrate. 500 mL of dichloromethane was added to the filtrate for extraction. The ethanol filtrate and the dichloromethane extract were combined and concentrated under vacuum to near dryness. 800 mL of purified water (self-made deionized water) was added and stirred to precipitate the solid. The precipitate was filtered, washed, and dried to obtain 23.9 g of an off-white solid, with a yield of 89.3%.

[0024] Example 4: Under stirring, 300 mL of 10% sodium hydroxide aqueous solution, formic acid (7.68 mL, 203.46 mmol), hydrazine hydrate (12.34 mL, 203.46 mmol), and 0.25 g of 10% palladium on carbon (0.5% relative to p-bromoaniline) were added sequentially to a 500 mL glass reaction flask. After stirring for 30 minutes, 50 g of 4-bromoaniline (290.66 mmol) was added, and the mixture was stirred at 90 °C for 10 hours. After the reactants had reacted completely, the mixture was cooled to room temperature and filtered. The filter cake was dissolved in 300 mL of ethanol and filtered again to obtain an ethanol filtrate. 500 mL of dichloromethane was added to the filtrate for extraction. The ethanol filtrate and the dichloromethane extract were combined and concentrated under vacuum to near dryness. 800 mL of purified water (self-made deionized water) was added and stirred to precipitate the solid. The precipitate was filtered, washed, and dried to obtain 22.8 g of an off-white solid, with a yield of 85.2%.

[0025] Figure 1 : 1HNMR (300MHz, DMSO) δ3.97 (s, 4H, NH2x2), 6.36-6.60 (m, 4H, CHx4), 7.18-7.22 (m, 4H, CHx4) Figure 1 The image shows the 1H NMR spectrum of a product synthesized using a method for synthesizing benzidine. The shift values ​​of the characteristic hydrogen atoms in the spectrum are basically consistent with the theoretical shift values ​​of the characteristic hydrogen atoms of benzidine, clearly indicating that the product is benzidine.

[0026] The preferred embodiments of the present invention disclosed above are merely illustrative of the invention. These preferred embodiments do not describe all details exhaustively, nor do they limit the invention to the specific implementations described. Clearly, many modifications and variations can be made based on the content of this specification.

Claims

1. A method of synthesizing benzidine, characterized by: The p-bromoaniline, formic acid and hydrazine hydrate are added into 10% sodium hydroxide aqueous solution, and the reaction is heated at 70-90°C under the catalysis of palladium-carbon for 6-10 hours; after the reaction is completed, the obtained filter cake is dissolved with ethanol, and the obtained filtrate is extracted with dichloromethane; the dichloromethane extraction liquid and the ethanol dissolving solution are combined, concentrated to near dryness under vacuum, and deionized water is added to precipitate the target compound, which is filtered again, and the filter cake is dried to obtain the benzidine; The synthesis line is as follows: 。 2. The method of synthesis of claim 1, wherein: The amount of p-bromoaniline is set to be 1.0 equivalent based on the p-bromoaniline.

3. The method of synthesis of claim 2, wherein: The amount of formic acid is 0.7 equivalent relative to the p-bromoaniline.

4. The method of synthesis of claim 3, wherein: The amount of hydrazine hydrate is 0.7 equivalent relative to the p-bromoaniline.

5. The method of synthesis of claim 1, wherein: The amount of 10% sodium hydroxide aqueous solution is 6 times the volume (v / m) of the mass of p-bromoaniline.

6. The method of synthesis of claim 1, wherein: The reaction temperature is 70-90°C.

7. The method of synthesis of claim 1, wherein: The mass fraction of palladium in the palladium-carbon is 10%, and the total amount is 0.5-1.5% of the mass of p-bromoaniline.

8. The method of synthesis of claim 1, wherein: The reaction time is 6-10 hours.

9. The method of synthesis of claim 1, wherein: The amount of ethanol is 6 times the volume (v / m) of the mass of p-bromoaniline.

10. The method of synthesis of claim 1, wherein: The amount of dichloromethane is 10 times the volume (v / m) of the mass of p-bromoaniline; and the amount of deionized water is 10 times the volume (v / m) of the mass of p-bromoaniline.

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