Use of zirconium hydroxide as catalyst for the preparation of n-phenylformamides or derivatives thereof from aniline or derivatives thereof
By using zirconium hydroxide catalyst to catalyze the formation of CN bonds between aniline and N,N-dimethylformamide under normal pressure, the environmental and cost issues of amide bond construction in traditional methods are solved, and a highly efficient and safe amidation reaction is achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- LANZHOU UNIV
- Filing Date
- 2022-10-06
- Publication Date
- 2026-04-17
AI Technical Summary
Existing methods suffer from low atom economy, generation of corrosive and volatile gases, complex operation, and difficulty in separating and recovering catalysts when constructing amide bonds. Furthermore, traditional catalysts are costly and environmentally unfriendly.
Zirconium hydroxide was used as a catalyst, and aniline and N,N-dimethylformamide were double-activated at a mild catalytic center to form CN bonds. Inexpensive and readily available oxygen was used as the oxidant, and the reaction was carried out at atmospheric pressure.
This method achieves efficient, safe, and low-cost catalytic conversion of aniline to N,N-dimethylformamide, with reusable catalyst, high yield of target product, and environmental friendliness.
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis technology, specifically relating to the application of zirconium hydroxide as a catalyst in the preparation of N-phenylformamide or its derivatives from aniline or its derivatives. Technical Background
[0002] Amide bonds are widely found in pharmaceutical intermediates (valsartan, captopril, diltiazem, lidocaine, bupivacaine, acetazolamide, leucovorin, glucosamine, etc.), pesticides, fuels, fragrances, and natural products; approximately 25% of known clinical drugs contain at least one amide bond. Traditionally, the construction of amide compounds has focused on the acylation of amines with acyl chlorides, carboxylic acids, acid anhydrides, and esters. However, these methods suffer from low atom economy, primarily resulting in significant waste, release of corrosive and volatile gases, complex experimental procedures, and poor stability of acyl halides. Furthermore, these methods mostly employ homogeneous catalysts, utilizing formic acid and its derivatives, as well as organometallic carbonyl compounds, and require strong acids (such as AlCl3 or SnCl4) or strong bases (such as NaOH or NaOCH3) as catalysts or additives to activate the amine or formication reagent. In addition, the addition of homogeneous acids or bases during subsequent separation processes increases the difficulty of separation.
[0003] In recent years, transamidation has become a simple and effective method for establishing new CN bonds. Numerous articles have reported on the N-amidation of amines with N,N-disubstituted amides. Wang Feng et al. developed a CeO2 catalyst that exhibited high reactivity for transamidation reactions (see *Chem. Commun.*, 2014, Vol. 50, No. 19, 2438-2441). This catalyst has broad substrate applicability and requires no additives during the reaction. Akbar Heydari et al. developed superparamagnetic Fe3O4 nanoparticles loaded with Fe(OH)3 for transamidation reactions (see *RSC Adv.*, 2016, Vol. 6, No. 29, 24684-24689). This catalyst is advantageous because it is inexpensive, recyclable, and environmentally friendly. Basudeb Basu et al. even used metal-free graphene oxide (GO) nanosheets. The carboxylic acid groups present on the edges of GO nanosheets act as active acid centers, activating the weakly electrophilic amide groups and promoting further attack by the amine nucleophile through hydrogen bonding. The reaction is carried out under solvent-free conditions, and the catalyst can be recovered and reused more than three times (see *Tetrahedron Lett*, 2018, Vol. 59, No. 10, 899-903). However, the conversion rate and selectivity of the above methods need to be improved.
[0004] Therefore, we considered a novel approach to generate amides by using a Zr(OH)4 catalyst and forming new CN bonds on a solid catalyst through dual activation of an amine and N,N-dimethylformamide (DMF) at a relatively mild catalytic center. This catalyst exhibits excellent catalytic activity and selectivity. Summary of the Invention
[0005] This invention discovers that zirconium hydroxide or a composition containing zirconium hydroxide can catalyze the transamidation reaction of aniline and N,N-dimethylformamide. Therefore, this invention provides a method for the transamidation of aniline and N,N-dimethylformamide catalyzed by a zirconium hydroxide catalyst. This method is simple, low-cost, safe, and yields a high rate of change. Specifically, it includes the following:
[0006] In a first aspect, the present invention provides an application of zirconium hydroxide or a composition containing zirconium hydroxide as a catalyst for catalyzing the preparation of N-phenylformamide or a derivative thereof from aniline or its derivative and N,N-dimethylformamide.
[0007] Preferably, the structural formula of aniline or its derivatives is shown in formula (I) below, and the structural formula of N-phenylformamide or its derivatives is shown in formula (II) below:
[0008]
[0009] R1-R5 are selected from any one of hydrogen, halogen, hydroxyl, sulfonic acid group, nitro group, substituted or unsubstituted straight-chain or branched alkyl, alkoxy, carbonyl, alkenyl, alkynyl, substituted or unsubstituted aryl, amide, and cyano groups.
[0010] Preferably, R1-R5 are selected from hydrogen, methyl, chlorine, bromine, and methoxy, respectively.
[0011] Preferably, the aniline or its derivatives include: aniline, o-methylaniline, m-methylaniline, p-methylaniline, p-chloroaniline, p-bromoaniline, and p-methoxyaniline.
[0012] In a second aspect, the present invention provides a method for preparing N-phenylformamide or its derivatives, the method being: using aniline or its derivatives as shown in formula (I) as raw material, using N,N-dimethylformamide as reaction solvent, using zirconium hydroxide or a composition containing zirconium hydroxide as catalyst, and using oxygen as oxidant, to catalytically oxidize and synthesize N-phenylformamide or its derivatives as shown in formula (II).
[0013]
[0014] R1 to R5 are selected from any one of hydrogen, halogen, hydroxyl, sulfonic acid group, nitro group, substituted or unsubstituted straight-chain or branched alkyl, alkoxy, carbonyl, alkenyl, alkynyl, substituted or unsubstituted aryl, amide, and cyano groups, but are not limited to the above substituents.
[0015] Preferably, R1 to R5 are selected from hydrogen, methyl, chlorine, bromine, and methoxy, respectively.
[0016] Preferably, the aniline or its derivatives include: aniline, o-methylaniline, m-methylaniline, p-methylaniline, p-chloroaniline, p-bromoaniline, and p-methoxyaniline.
[0017] Preferably, the ratio of the catalyst to aniline or its derivative is 1-150 g: 1 mol.
[0018] Preferably, the ratio of the catalyst to aniline or its derivative is 10-100 g: 1 mol.
[0019] Preferably, the ratio of the catalyst to aniline or its derivative is 40-60 g: 1 mol.
[0020] Preferably, the ratio of the catalyst to aniline or its derivative is 50 g: 1 mol.
[0021] Preferably, the mass ratio of the reaction solvent to aniline or its derivative is 10 to 500:1.
[0022] Preferably, the mass ratio of the reaction solvent to aniline or its derivative is 100 to 400:1.
[0023] Preferably, the mass ratio of the reaction solvent to aniline or its derivative is 200–350:1.
[0024] Preferably, the mass ratio of the reaction solvent to aniline or its derivative is 300:1.
[0025] Preferably, the reaction solvent is N,N-dimethylformamide.
[0026] Preferably, the catalyst is zirconium hydroxide.
[0027] Preferably, the method includes the following steps:
[0028] (1) Add zirconium hydroxide catalyst, aniline or its derivative, and N,N-dimethylformamide to a three-necked flask;
[0029] (2) Insert the condenser into the three-necked flask, insert an oxygen-filled balloon into the condenser opening, and ensure the entire system is sealed. React at 170°C for 3 hours.
[0030] (3) Filter, distill, and recrystallize to obtain N-phenylformamide or its derivatives.
[0031] Preferably, the reaction temperature is 100–200°C.
[0032] Preferably, the reaction temperature is 170°C.
[0033] Preferably, the reaction time is 1 to 36 hours.
[0034] Preferably, the reaction time is 3 hours.
[0035] Compared with the prior art, the technical solution of the present invention has the following advantages:
[0036] (1) The zirconium hydroxide or a composition containing zirconium hydroxide used in this invention is a catalyst with low commercial cost, high activity, good selectivity, and can be purchased directly or prepared by a simple precipitation method. Compared with the traditional method of using catalyst, it greatly reduces the catalyst preparation process, significantly reduces the catalyst cost, and is green and environmentally friendly.
[0037] (2) The aniline or its derivatives used in this invention are common basic raw materials in industry, and are inexpensive and readily available.
[0038] (3) The present invention uses cheap and readily available oxygen as an oxidant and reacts under normal pressure conditions. Compared with traditional methods, it significantly reduces the cost of oxidant and solves the problems of toxic emissions and production safety caused by the use of oxidants.
[0039] (4) The method described in this invention can catalyze the transamidation reaction of aniline or its derivatives with N,N-dimethylformamide to generate N-phenylformamide or its derivatives. It has good substrate applicability and a high yield of the target product. Attached Figure Description
[0040] Figure 1 Mass spectrum of N-phenylformamide synthesized by the method described in Example 1;
[0041] Figure 2 Mass spectrum of N-phenylformamide synthesized by the method described in Example 2;
[0042] Figure 3 Mass spectrum of N-phenylformamide synthesized by the method described in Example 3;
[0043] Figure 4 Mass spectrum of N-phenylformamide synthesized by the method described in Example 4;
[0044] Figure 5 Mass spectrum of N-phenylformamide synthesized by the method described in Example 5;
[0045] Figure 6 Mass spectrum of N-(2-toluene)formamide synthesized by the method described in Example 6;
[0046] Figure 7 Mass spectrum of N-(3-toluene)formamide synthesized by the method described in Example 6;
[0047] Figure 8 Mass spectrum of N-(4-toluene)formamide synthesized by the method described in Example 6;
[0048] Figure 9 Mass spectrum of N-(4-chlorobenzene)formamide synthesized by the method described in Example 6;
[0049] Figure 10 Mass spectrum of N-(4-bromobenzamide) synthesized by the method described in Example 6;
[0050] Figure 11 Mass spectrum of N-formyl-4-methoxyaniline synthesized by the method described in Example 6; Detailed Implementation
[0051] The present invention will be further described in detail below with reference to specific embodiments. The scope of protection of the present invention is not limited thereto. Unless otherwise specified, all raw materials used in the following embodiments can be purchased commercially.
[0052] Example 1: Synthesis of N-phenylformamide using different amounts of reaction solvent
[0053] 1. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 100 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and insert an oxygen-filled balloon into the condenser to ensure that the entire system is sealed and leak-proof. Change the gas 5 to 6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 170 °C for 3 hours. Then, filter, distill and recrystallize to obtain the product N-phenylformamide.
[0054] 2. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 200 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 170 °C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0055] 3. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 170 °C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0056] 4. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 400 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 170 °C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0057] 5. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 500 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to create an oxygen atmosphere. Heat and stir the reaction at 170 °C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0058] The yields of N-phenylformamide products obtained by the preparation methods described in 1 to 5 above were calculated, and the results are shown in Table 1 below:
[0059] Table 1. Process parameters and yield of N-phenylformamide as described in Example 1.
[0060]
[0061] The mass spectrum of the main product obtained from the above reaction is shown below. Figure 1 As shown (the mass spectra of the main products of the above 5 reactions are the same, so only one mass spectrum is provided), the structural formula is shown in Formula 1 below. The above results indicate that using N,N-dimethylformamide as the reaction solvent (N,N-dimethylformamide to aniline mass ratio of 100–500:1), oxygen as the oxidant, and zirconium hydroxide as the catalyst, the transamidation reaction of aniline and N,N-dimethylformamide can be catalyzed to synthesize N-phenylformamide; simultaneously, when the mass ratio of N,N-dimethylformamide to aniline is 200–400:1, the yield of N-phenylformamide obtained is above 70%, and when the mass ratio of N,N-dimethylformamide to aniline is 300:1, the yield of N-phenylformamide obtained can reach 93%.
[0062]
[0063] Example 2: Synthesis of N-phenylformamide with different reaction times
[0064] 1. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and insert an oxygen-filled balloon into the condenser to ensure that the entire system is sealed and leak-proof. Change the gas 5 to 6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 170 °C for 1 hour. Then, filter, distill and recrystallize to obtain the product N-phenylformamide.
[0065] 2. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and insert an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 170 °C for 2 h. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0066] 3. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 170 °C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0067] 4. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 170 °C for 12 h. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0068] 5. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 170 °C for 36 h. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0069] The yields of N-phenylformamide products obtained by the preparation methods described in 1 to 5 above were calculated, and the results are shown in Table 2 below:
[0070] Table 2. Process parameters and yield of N-phenylformamide as described in Example 2.
[0071]
[0072] The mass spectrum of the main product obtained from the above reaction is shown below. Figure 2 As shown (the mass spectra of the main products of the above 5 reactions are the same, so only one mass spectrum is provided), the structural formula is shown in Formula 2 below. The above results indicate that, with a reaction time of 1–36 h, using N,N-dimethylformamide as the reaction solvent, oxygen as the oxidant, and zirconium hydroxide as the catalyst, the transamidation reaction of aniline with N,N-dimethylformamide can be catalyzed to synthesize N-phenylformamide; simultaneously, the yield of N-phenylformamide obtained from the reaction is above 90% when the reaction time is 3–36 h; and when the reaction time is 36 h, the yield of N-phenylformamide obtained from the reaction is as high as 99%.
[0073]
[0074] Example 3: Synthesis of N-phenylformamide with different catalyst addition amounts
[0075] 1. Add 1.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and insert an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 170 °C for 3 h. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0076] 2. Add 2.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 170 °C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0077] 3. Add 3.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 170 °C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0078] 4. Add 4.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to create an oxygen atmosphere. Heat and stir the reaction at 170 °C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0079] 5. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 170 °C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0080] The yields of N-phenylformamide obtained by the preparation methods described in 1 to 5 above were calculated, and the results are shown in Table 3 below:
[0081] Table 3. Process parameters and yield of N-phenylformamide as described in Example 3.
[0082]
[0083]
[0084] The mass spectrum of the main product obtained from the above reaction is shown below. Figure 3 As shown (the mass spectra of the main products of the above 5 reactions are the same, so only one mass spectrum is provided), the structural formula is shown in Formula 3 below. The above results indicate that, with a catalyst addition of 1.0–5.0 g, using N,N-dimethylformamide as the reaction solvent, oxygen as the oxidant, and zirconium hydroxide as the catalyst, the transamidation reaction of aniline and N,N-dimethylformamide can be catalyzed to synthesize N-phenylformamide; simultaneously, when the catalyst addition is 4.0–5.0 g, the yield of N-phenylformamide obtained from the reaction is above 80%; and when the catalyst addition is 5.0 g, the yield of N-phenylformamide obtained from the reaction can reach 93%.
[0085]
[0086] Example 4: Synthesis of N-phenylformamide at different reaction temperatures
[0087] 1. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and insert an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 100°C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0088] 2. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 110 °C for 3 h. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0089] 3. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 130 °C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0090] 4. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 150 °C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0091] 5. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 170 °C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0092] 6. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 190 °C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0093] 7. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 200°C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0094] The yields of N-phenylformamide products obtained by the preparation methods described in 1 to 7 above were calculated, and the results are shown in Table 4 below:
[0095] Table 4. Process parameters and yield of N-phenylformamide as described in Example 4.
[0096]
[0097] The mass spectrum of the main product obtained from the above reaction is shown below. Figure 4 As shown (the mass spectra of the main products of the above 7 reactions are the same, so only one mass spectrum is provided), the structural formula is shown in Formula 4 below. The above results show that at a reaction temperature of 100-200℃, using N,N-dimethylformamide as the reaction solvent, oxygen as the oxidant, and zirconium hydroxide as the catalyst, the transamidation reaction of aniline and N,N-dimethylformamide can be catalyzed to synthesize N-phenylformamide; at the same reaction temperature of 150-200℃, the yield of N-phenylformamide obtained by the reaction is above 70%; and at a reaction temperature of 170-200℃, the yield of N-phenylformamide obtained by the reaction can reach above 90%.
[0098]
[0099] Example 5: Synthesis of N-phenylformamide under different atmospheres
[0100] 1. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place a rubber stopper with a needle in the condenser to maintain pressure balance. Heat and stir the reaction at 170 °C for 3 h. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0101] 2. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 9.3 g of aniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is sealed and leak-proof. Change the gas 5-6 times to make the system an oxygen atmosphere. Heat and stir the reaction at 170 °C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-phenylformamide.
[0102] The yields of N-phenylformamide obtained by the preparation methods described in 1-2 above were calculated, and the results are shown in Table 5 below:
[0103] Table 5. Process parameters and yield of N-phenylformamide as described in Example 5.
[0104]
[0105] The mass spectrum of the main product obtained from the above reaction is shown below. Figure 5 As shown in Figure 5 (the main products of the two reactions above have the same mass spectrum, so only one mass spectrum is provided), the structural formula is shown in Formula 5 below. The above results indicate that, under air, oxygen, and nitrogen atmospheres, using N,N-dimethylformamide as the reaction solvent and zirconium hydroxide as the catalyst, the transamidation reaction of aniline with N,N-dimethylformamide can be catalyzed to synthesize N-phenylformamide; simultaneously, when the reaction atmosphere is oxygen, the yield of N-phenylformamide obtained from the reaction can reach over 90%.
[0106]
[0107] Example 6: Synthesis of N-phenylformamide using different aniline derivatives
[0108] 1. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 10.72 g of o-methylaniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is airtight. Change the gas 5-6 times to create an oxygen atmosphere. Heat and stir the reaction at 170 °C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-(2-toluene)formamide. The mass spectrum of the product is shown below. Figure 6 As shown, the structural formula is shown in Equation 6 below.
[0109]
[0110] 2. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 10.72 g of m-methylaniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is airtight. Change the gas 5-6 times to create an oxygen atmosphere. Heat and stir the reaction at 170°C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-(3-toluene)formamide. The mass spectrum of the product is shown below. Figure 7 As shown, the structural formula is shown in Equation 7 below.
[0111]
[0112] 3. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 10.72 g of p-methylaniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is airtight. Change the gas 5-6 times to create an oxygen atmosphere. Heat and stir the reaction at 170°C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-(4-toluene)formamide. The mass spectrum of the product is shown below. Figure 8 As shown, the structural formula is shown in Equation 8 below.
[0113]
[0114] 4. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 12.76 g of p-chloroaniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is airtight. Change the gas 5-6 times to create an oxygen atmosphere. Heat and stir the reaction at 170°C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-(4-chlorobenzene)formamide. The mass spectrum of the product is shown below. Figure 9 As shown, the structural formula is shown in Equation 9 below.
[0115]
[0116] 5. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 17.20 g of p-bromoaniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is airtight. Change the gas 5-6 times to create an oxygen atmosphere. Heat and stir the reaction at 170°C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-(4-bromobenzene)formamide. The mass spectrum of the product is shown below. Figure 10 As shown, the structural formula is shown in Equation 10 below.
[0117]
[0118] 6. Add 5.0 g of zirconium hydroxide catalyst to a three-necked flask, then add 12.32 g of p-methoxyaniline and 300 mL of N,N-dimethylformamide. Insert a condenser into the three-necked flask and place an oxygen-filled balloon into the condenser to ensure the entire system is airtight. Change the gas 5-6 times to create an oxygen atmosphere. Heat and stir the reaction at 170°C for 3 hours. Then, filter, distill, and recrystallize to obtain the product N-formyl-4-methoxyaniline. The mass spectrum of the product is shown below. Figure 11 As shown, the structural formula is shown in Equation 11 below.
[0119]
[0120] The yields of the N-phenylformamide derivatives obtained by the preparation methods described in 1 to 6 above were calculated, and the results are shown in Table 6 below:
[0121] Table 6. Process parameters and product yield of the preparation method described in Example 6.
[0122]
[0123]
[0124] The mass spectra of the main products in reactions 1-6 above are as follows: Figures 6-11 As shown above, the results indicate that using N,N-dimethylformamide as the reaction solvent, oxygen as the oxidant, and zirconium hydroxide as the catalyst, the synthesis of N-(2-toluene)formamide from o-methylaniline can be catalyzed with a yield of 39%; the synthesis of N-(3-toluene)formamide from m-methylaniline with a yield of 72%; the synthesis of N-(4-toluene)formamide from p-methylaniline with a yield of 93%; the synthesis of N-(4-chlorobenzene)formamide from p-chloroaniline with a yield of 47%; the synthesis of N-(4-bromobenzene)formamide from p-bromoaniline with a yield of 36%; and the synthesis of N-formyl-4-methoxyaniline from p-methoxyaniline with a yield of 94%. Therefore, the method described in this invention can catalyze the synthesis of N-phenylformamide or its derivatives from aniline or its derivatives, and the yield of the target product is quite considerable.
[0125] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.
Claims
1. A process for the preparation of N-phenylcarboxamide or a derivative thereof, characterized in that, The method is as follows: using aniline or its derivatives as shown in formula (I) as raw material, N,N-dimethylformamide (DMF) as reaction solvent, zirconium hydroxide as catalyst, and oxygen as oxidant to carry out catalytic oxidation reaction to synthesize N-phenylformamide or its derivatives as shown in formula (II); R1 to R5 are selected from any one of hydrogen, halogen, hydroxyl, sulfonic acid group, nitro, substituted or unsubstituted straight-chain or branched alkyl, alkoxy, carbonyl, alkenyl, alkynyl, substituted or unsubstituted aryl, amide, and cyano. The ratio of the catalyst to aniline or its derivative is 1~150 g : 1 mol; The mass ratio of the reaction solvent to aniline or its derivative is 10~500:1; The reaction temperature is 100~200 ℃; The reaction time is 1~36 h.
2. The production method according to claim 1, wherein R1 to R5 are selected from hydrogen, methyl, chlorine, bromine, and methoxy, respectively.
3. The production method according to claim 2, wherein The aniline or its derivatives include: aniline, o-methylaniline, m-methylaniline, p-methylaniline, p-chloroaniline, p-bromoaniline, and p-methoxyaniline.
4. The production method according to claim 1, wherein The catalyst is used in a ratio of 50 g to 1 mol of aniline or its derivative; the reaction solvent is used in a ratio of 300 to 1 mol of aniline or its derivative; the reaction temperature is 170 °C; and the reaction time is 3 h.