A process for the preparation of an organic base catalyzed synthesis of imines
By using a DBU catalyst to catalyze the reaction of primary amines and aldehydes in an aqueous environment to prepare imines, the problems of low efficiency and environmental pollution in the production of imines from primary amines in existing technologies have been solved, and a highly efficient and environmentally friendly imine synthesis has been achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- HUBEI UNIV OF EDUCATION
- Filing Date
- 2025-03-25
- Publication Date
- 2026-05-29
AI Technical Summary
Existing technologies are difficult to efficiently catalyze the formation of imines from primary amines in an aqueous environment, and conventional methods use organic solvents, leading to environmental pollution.
Water was used as the solvent, organic base DBU as the catalyst, and primary amines and aldehydes as raw materials. The reaction temperature was 25-100℃ and the reaction time was 3-16h. The target product, imine, was separated using an ethyl acetate:petroleum ether chromatography column.
It achieves efficient catalytic conversion of primary amines to imines in an aqueous environment with a yield of over 80%, avoids organic solvent pollution, is simple to operate, and has potential for industrial application.
Smart Images
Figure CN120423978B_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a highly efficient preparation process for synthesizing imines using organic base catalysis. Background Technology
[0002] Imine structures are generally formed through the dehydration condensation of C=O and R-NH2, and their chemical structures are widely found in natural products and drug molecules. These small molecules containing imine structures possess numerous pharmacological activities, thus attracting the attention of many organic chemists and medicinal chemists. In organic synthesis, imines act as electrophiles, reacting with other reagents to form nitrogen-containing compounds. Imine synthesis methods require the participation of Lewis acids or metal catalysts. Conventional methods can synthesize imines when highly reactive carbonyl compounds or highly nucleophilic amine compounds are used as reaction substrates; however, primary amines with lower nucleophilicity are difficult to dehydrate with carbonyl compounds to form the corresponding imines.
[0003] Existing research has identified a highly efficient method for the synthesis of N-sulfinylimides and N-sulfonylimides catalyzed by pyrrolidine. In this method, an aldehyde first reacts with pyrrolidine to form an intermediate state, which then reacts with a primary amine compound to generate the target imine product, releasing pyrrolidine and one molecule of water simultaneously. Because the intermediate state is more electrophilic than the aldehyde by several orders of magnitude, even poorly nucleophilic (sulfinyl)amides can react readily with it, resulting in high-yield imine products. However, this reaction system requires the participation of the organic solvent DCM, and the large-scale use of organic solvents in industrial production can easily cause environmental pollution. Currently, no relevant literature reports on how to efficiently catalyze the formation of the corresponding imine from a primary amine in an aqueous environment. Summary of the Invention
[0004] The purpose of this invention is to address the aforementioned problems in the prior art by providing an efficient organic-base catalytic process for the synthesis of imines, which can efficiently catalyze the formation of corresponding imines from primary amines in an aqueous environment.
[0005] To achieve the above objectives, the technical solution of the present invention is as follows:
[0006] This invention provides a highly efficient process for the synthesis of imines catalyzed by an organic base. The process includes: using water as a solvent, an organic base as a catalyst, and primary amines and aldehydes as raw materials to react and obtain reaction products, and separating the target product imine from the reaction products; wherein the organic base is DBU.
[0007] The ratio of primary amine, aldehyde, organic base, and water is 1-3 mol: 1-3 mol: 0.1-0.3 mol: 1-3 L.
[0008] The ratio of primary amine, aldehyde, organic base, and water is 1 mol: 1 mol: 0.1 mol: 3 L.
[0009] The reaction temperature is 25-100℃, and the reaction time is 3-16h.
[0010] The reaction temperature is 100℃ and the reaction time is 16h.
[0011] The reaction products were separated using a chromatography column with an ethyl acetate:petroleum ether ratio of 2:1 to obtain the target product, imine.
[0012] The primary amine is p-methoxyaniline, the aldehyde is benzaldehyde, and the target product is N-benzylidene-4-methoxyaniline.
[0013] The primary amine is aniline, the aldehyde is p-bromobenzaldehyde, and the target product is N-p-bromobenzylaniline.
[0014] Compared with the prior art, the beneficial effects of the present invention are as follows:
[0015] This invention discloses a highly efficient organic-base catalytic synthesis process for imines. Using water as a solvent and an organic base as a catalyst, primary amines and aldehydes are used as raw materials to react and obtain reaction products. The target product, imine, can be separated from the reaction products. The organic base is DBU. This method utilizes water as a reaction solvent and DBU as a catalyst to achieve highly efficient preparation of imines from primary amines. It avoids the environmental pollution caused by using organic solvents in imine synthesis, and achieves a yield of over 80%. The process is high-yield, simple to operate, and has potential for industrial application. Attached Figure Description
[0016] Figure 1 The NMR spectrum of N-benzylidene-4-methoxyaniline, the target product of Example 1.
[0017] Figure 2 The NMR spectrum of the target product N-p-bromobenzylaniline in Example 2 is shown. Detailed Implementation
[0018] The present invention will now be described in further detail with reference to specific embodiments and accompanying drawings.
[0019] A highly efficient process for synthesizing imines catalyzed by an organic base includes: using water as a solvent, an organic base as a catalyst, and primary amines and aldehydes as raw materials to react and obtain reaction products, and separating the target product imine from the reaction products; wherein the organic base is DBU.
[0020] The ratio of primary amine, aldehyde, organic base, and water is 1-3 mol: 1-3 mol: 0.1-0.3 mol: 1-3 L.
[0021] The ratio of primary amine, aldehyde, organic base, and water is 1 mol: 1 mol: 0.1 mol: 3 L.
[0022] The reaction temperature is 25-100℃, and the reaction time is 3-16h.
[0023] The reaction temperature is 100℃ and the reaction time is 16h.
[0024] The reaction products were separated using a chromatography column with an ethyl acetate:petroleum ether ratio of 2:1 to obtain the target product, imine.
[0025] The primary amine is p-methoxyaniline, the aldehyde is benzaldehyde, and the target product is N-benzylidene-4-methoxyaniline.
[0026] The primary amine is aniline, the aldehyde is p-bromobenzaldehyde, and the target product is N-p-bromobenzylaniline.
[0027] Example 1:
[0028] Preparation of the target product N-benzylidene-4-methoxyaniline
[0029] 1.0 mmol of benzaldehyde and 1.0 mmol of p-methoxyaniline were placed in a 25 mL round-bottom flask, 3 mL of water was added to the flask, and then 0.1 mmol of catalyst DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) was added. The mixture was refluxed at 100 °C for 16 h. The reaction process is shown below:
[0030]
[0031] After the reaction was complete, the target product was obtained by column chromatography using ethyl acetate:petroleum ether in a 2:1 ratio, with a yield of 86%. The NMR spectrum of the target product is shown below. Figure 1 As shown, it can be verified that the target product is N-benzyl-4-methoxyaniline; 1 H NMR (400MHz, Chloroform-d) δ8.48 (s, 1H, CH=N), 7.97–7.77 (m, 2H, Ph), 7.46 (tt, J= 3.2, 2.0Hz, 3H, Ph), 7.28–7.15 (m, 2H, Ph), 6.99–6.82 (m, 2H, Ph), 3.83 (s, 3H, OCH3).
[0032] The effects of different catalyst types, catalyst amounts, reaction temperatures, and solvents on the yield of the target product N-benzyl-4-methoxyaniline were investigated below. Other experimental procedures were the same as in Example 1, and the results are shown in Table 1.
[0033] Table 1 Yield of the target product
[0034]
[0035] Experiments 5 and 6 were blank experiments without catalyst. Comparison of Experiment 7 with Experiments 5 and 6 shows that using DBU significantly increases the yield. Comparison of Experiment 7 with Experiments 1-4 shows that using DBU yields higher yields than K2CO3 (inorganic base catalyst), TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene, organic base catalyst), DABCO (1,4-diazabicyclo[2.2.2]octane, organic base catalyst), and p-TsOH (p-toluenesulfonic acid, acid catalyst). Comparison of Experiments 7 and 8 shows that only 10% mol of the raw material is needed for efficient catalysis with DBU. The possible catalytic mechanism of DBU is that the aldehyde and primary amine undergo a nucleophilic addition reaction (the nitrogen atom with a lone pair attacking the carbonyl carbon atom) to obtain an α-hydroxyamine intermediate, which then loses a water molecule to obtain an imine. In this process, the addition of DBU facilitates the removal of water molecules.
[0036] Comparing Experiment 7 and Experiments 9-10, it is evident that temperature significantly affects the yield when water is used as the solvent. Experiments were conducted at room temperature, 60℃, and 100℃, and the results show that the reaction yield is highest at the boiling point of water. Comparing Experiment 7 and Experiments 11-14, it is clear that under other organic solvent conditions (toluene, dichloromethane, DMF), the yield of the corresponding catalytic system is lower than that under water-based solvent conditions. Furthermore, the reaction yield is also lower when the reaction temperature is increased to the boiling point of the organic solvent.
[0037] Example 2:
[0038] It is basically the same as Example 1, except that:
[0039] The amounts of benzaldehyde, p-methoxyaniline, DBU, and water added were 1 mmol: 1 mmol: 0.1 mmol: 1 mL, respectively.
[0040] Example 3:
[0041] It is basically the same as Example 1, except that:
[0042] The amounts of benzaldehyde, p-methoxyaniline, DBU, and water added were 3 mmol: 3 mmol: 0.3 mmol: 1 mL, respectively.
[0043] Example 4:
[0044] Preparation of the target product N-p-bromobenzylaniline
[0045] 1.0 mmol of p-bromobenzaldehyde and 1.0 mmol of aniline were placed in a 25 mL round-bottom flask, 3 mL of water was added, and then 0.1 mmol of DBU catalyst was added. The mixture was refluxed at 100 °C for 16 h. After the reaction was complete, the target product was obtained by column chromatography using ethyl acetate:petroleum ether (1:1) with a yield of 80%. The NMR spectrum of the target product is shown below. Figure 2 As shown, it can be verified that the target product is N-p-bromobenzylaniline. 1 H NMR (400MHz, Chloroform-d) δ 8.40 (s, 1H, CH=N), 7.76 (m, 2H, Ph), 7.60 (m, 2H, Ph), 7.39 (m, 2H, Ph), 7.25 (m, 1H, Ph), 7.22-7.13 (m, 2H, Ph).
[0046] Example 5:
[0047] It is basically the same as Example 1, except that:
[0048] The amounts of p-bromobenzaldehyde, aniline, DBU, and water added were 1 mmol: 1 mmol: 0.1 mmol: 1 mL, respectively.
[0049] Example 6:
[0050] It is basically the same as Example 1, except that:
[0051] The amounts of p-bromobenzaldehyde, aniline, DBU, and water added were 1 mmol: 1 mmol: 0.1 mmol: 1 mL, respectively.
Claims
1. A process for preparing imines catalyzed by an organic base, characterized in that: The preparation process includes: using water as a solvent, an organic base as a catalyst, and primary amines and aldehydes as raw materials to react and obtain a reaction product, and separating the target product imine from the reaction product; the organic base is 1,8-diazabicyclo[5.4.0]undec-7-ene; The addition ratio of the primary amine, aldehyde, organic base, and water is 1-3 mol: 1-3 mol: 0.1-0.3 mol: 1-3 L; The primary amine is p-methoxyaniline, the aldehyde is benzaldehyde, and the target product is N-benzylidene-4-methoxyaniline.
2. The preparation process of imine catalyzed by an organic base according to claim 1, characterized in that: The ratio of primary amine, aldehyde, organic base, and water is 1 mol: 1 mol: 0.1 mol: 3 L.
3. The preparation process of imine catalyzed by an organic base according to claim 1, characterized in that: The reaction temperature is 25-100℃, and the reaction time is 3-16h.
4. The preparation process of imine catalyzed by an organic base according to claim 3, characterized in that: The reaction temperature is 100℃ and the reaction time is 16h.
5. The preparation process of imine catalyzed by an organic base according to claim 1, characterized in that: The reaction products were separated using a chromatography column with an ethyl acetate:petroleum ether ratio of 2:1 to obtain the target product, imine.