Use of a hydroxyaromatic aldehyde in photoassisted catalytic cis-isomerization of unsaturated organic compounds
By using hydroxy aromatic aldehydes as sensitizers, the problems of high cost and environmental unfriendliness of existing photocatalytic isomerization sensitizers are solved, achieving efficient and short-time cis-olefin isomerization with a high proportion of cis isomers in the product, which is applicable to a variety of unsaturated organic compounds.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- SICHUAN UNIV
- Filing Date
- 2023-09-27
- Publication Date
- 2026-06-30
AI Technical Summary
Existing photocatalytic isomerization sensitizers are expensive, environmentally unfriendly, require harsh reaction conditions, and have long reaction times, making it difficult to efficiently synthesize thermodynamically unstable cis(Z)olefins.
Hydroxy aromatic aldehydes were used as sensitizers to carry out the reaction of unsaturated organic compounds in N,N-dimethylformamide solvent via photo-assisted catalysis. The conditions were room temperature, air atmosphere, and blue light irradiation. The molar ratio of hydroxy aromatic aldehydes to unsaturated esters or their derivatives was greater than or equal to 3%, and the reaction time was greater than or equal to 5 minutes.
It achieves efficient and environmentally friendly cis-isomerization reactions with short reaction times, high proportion of cis isomers in the products, no byproducts, applicability to a variety of unsaturated organic compounds, and can be scaled up to gram-scale reactions.
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Figure CN117304027B_ABST
Abstract
Description
Technical Field
[0001] This invention belongs to the field of isomerization sensitizer technology, specifically relating to the application of a hydroxy aromatic aldehyde in photo-assisted catalytic cis-isomerization of unsaturated organic compounds. Background Technology
[0002] Alkenes are not only one of the most important functional groups in organic synthesis, but they are also widely present in many natural products and bioactive molecules, making their importance self-evident. Cis-trans isomerism is a diastereomeric phenomenon that occurs because the double bonds in alkenes cannot rotate freely, resulting in different spatial arrangements of the various groups. The cis (Z) and trans (E) configurations of alkenes have a significant impact on their physicochemical properties, biological activity, and function. For example, cis (Z) fatty acids are widely recognized as natural, healthy, and harmless foods, while trans (E) fatty acids are considered one of the hidden killers of cardiovascular and cerebrovascular diseases. Due to the uphill energy of the net process, the selective synthesis of thermodynamically stable trans (E) alkenes is currently easily achieved; however, methods for obtaining thermodynamically unstable cis (Z) alkenes remain limited. Cis (Z) alkenes are an indispensable and important component of the modern organic synthesis landscape, and their importance is immeasurable. Therefore, the development of efficient and convenient stereoselective synthesis methods for cis (Z) alkenes is urgently needed.
[0003] Traditional chemical methods for the selective synthesis of cis(Z)-olefins primarily involve the witting reaction. However, these methods suffer from limitations such as reliance on kinetic control, demanding reaction conditions (e.g., strong bases, extremely low temperatures), and poor selectivity. In recent years, photochemistry has become an indispensable part of modern organic synthesis due to the green and sustainable advantages of light. Research on photo-assisted olefin isomerization can be traced back to the early 1960s by Hammond et al., who used high-energy rays to excite sensitizers to achieve the trans-to-cis isomerization of stilbene. The principle involves using ultraviolet light to excite the sensitizer to reach an excited triplet state. The activated sensitizer then transfers the triplet energy to the trans-olefin to form an activated intermediate, which subsequently forms the cis-olefin. In recent years, many sensitizers capable of cis-trans isomerization of olefins have been developed, such as transition metal complexes (iridium, copper, ruthenium) and aromatic ketone compounds (9-fluorenone, benzophenone, benzoin). However, these sensitizers may suffer from drawbacks such as high cost, environmental incompatibility, demanding reaction conditions, and long reaction times. Therefore, there is an urgent need to develop a novel photocatalytic isomerization sensitizer that is inexpensive, environmentally friendly, and has high reaction efficiency. Summary of the Invention
[0004] To address the aforementioned shortcomings in the prior art, this invention provides an application of hydroxy aromatic aldehydes in photo-assisted catalytic cis-isomerization of unsaturated organic compounds. This is the first time that hydroxy aromatic aldehydes have been applied to photo-assisted catalytic isomerization reactions. Furthermore, sensitizers containing hydroxy aromatic aldehydes have the advantages of low cost, environmental friendliness, and high reaction efficiency.
[0005] To achieve the above objectives, the technical solution adopted by the present invention to solve its technical problem is: to provide an application of hydroxy aromatic aldehydes in photo-assisted catalytic cis-isomerization of unsaturated organic compounds.
[0006] Furthermore, the hydroxy aromatic aldehyde is 2-hydroxy-pyromellitic aldehyde.
[0007] Furthermore, unsaturated organic compounds include at least one carbon-carbon double bond.
[0008] Furthermore, the unsaturated organic compounds are unsaturated esters or their derivatives.
[0009] Furthermore, the application method involves mixing unsaturated esters or their derivatives with hydroxy aromatic aldehydes in a solvent, and then carrying out a photocatalytic reaction under light, air atmosphere, and room temperature.
[0010] Furthermore, the solvent is N,N-dimethylformamide.
[0011] Furthermore, the molar ratio of hydroxy aromatic aldehydes to unsaturated esters or their derivatives is greater than or equal to 3%.
[0012] Furthermore, the photocatalytic reaction time is greater than or equal to 5 minutes.
[0013] Going a step further, we irradiated the area with blue light at a wavelength of 450-480nm.
[0014] The present invention provides a sensitizer for photo-assisted catalytic cis-isomerization of unsaturated organic compounds, including hydroxy aromatic aldehydes.
[0015] In summary, the present invention has the following advantages:
[0016] 1. This invention is the first to apply hydroxy aromatic aldehydes to a photo-assisted catalytic isomerization reaction.
[0017] 2. The sensitizer of the present invention includes hydroxy aromatic aldehyde, which has extremely high isomerization catalytic activity and can complete the isomerization reaction in a very short time. Furthermore, the isomerization reaction catalyzed by this sensitizer has substrate universality and isomerization catalytic activity for a variety of unsaturated organic compounds.
[0018] 3. The method of the present invention has the advantages of short reaction time, low sensitizer dosage, high proportion of cis isomers in the reaction product, and no by-products are generated.
[0019] 4. The method of this invention can be successfully scaled up to gram-level reactions, and the isomerization effect remains highly efficient. Attached Figure Description
[0020] Figure 1 Optimization diagram for sensitizer addition amount;
[0021] Figure 2 This is the isomerization reaction time curve;
[0022] Figure 3 The figure shows the results of the study on the universality of isomerized substrates. Detailed Implementation
[0023] The basic conditions for the reaction in Experiment Example 1 were explored.
[0024] Using (E)-3-phenyl-2-butenoic acid ethyl ester as the raw material and 2-hydroxy-pyromellitic methyl aldehyde as the sensitizer, the basic reaction conditions were explored through a series of control experiments.
[0025] 1. Solvent screening
[0026] Nine groups of experiments were conducted using methanol, ethanol, isopropanol, acetonitrile, acetone, tetrahydrofuran, dichloromethane, dimethyl sulfoxide, and N,N-dimethylformamide as solvents. 0.019 mg (0.1 mmol) of (E)-3-phenyl-2-butenoic acid ethyl ester and 0.54 mg (3 mol%) of 2-hydroxy-pyromellitic acid methyl ester were placed in photocatalytic reaction glass tubes, followed by the addition of 2 mL of solvent. The mixture was ultrasonicated for 1 min and then subjected to photocatalytic reaction at 460 nm, 32 W, air atmosphere, and room temperature for 1 h. After the reaction, the solvent was removed, and the volume was adjusted to 10 mL with isopropanol. The Z / E ratio and mixed yield after the reaction were analyzed using high-performance liquid chromatography (HPLC). The results are shown in Table 1.
[0027] Table 1 Solvent Screening
[0028]
[0029] As shown in Table 1, all nine common solvents mentioned above can be used as reaction solvents to cis-isomerize a certain proportion of trans isomer raw materials without the generation of byproducts. N,N-dimethylformamide is the best reaction solvent, with a Z / E ratio as high as 92 / 8.
[0030] 2. Optimization of sensitizer dosage
[0031] Five groups of experiments were conducted with sensitizer additions of 0.2 mol%, 0.5 mol%, 1 mol%, 3 mol%, and 5 mol%. 0.019 mg (0.1 mmol) of (E)-3-phenyl-2-butenoic acid ethyl ester and 2 mL of N,N-dimethylformamide were placed in photocatalytic reaction glass tubes, and different amounts of 2-hydroxy-pyromellitic methylaldehyde were added. The mixture was then sonicated for 1 min and subjected to photocatalytic reaction for 1 h at 460 nm, 32 W, air atmosphere, and room temperature. After the reaction, the solvent was removed, and the volume was adjusted to 10 mL with isopropanol. The Z / E ratio and mixed yield after the reaction were analyzed by high-performance liquid chromatography (HPLC). The results are as follows: Figure 1 As shown.
[0032] Depend on Figure 1 It is known that when the addition amount of 2-hydroxy-pyromellitic aldehyde reaches 3 mol%, the Z / E ratio in the reaction product reaches a relatively high level and tends to be stable. Therefore, when using the sensitizer of this invention, the molar ratio of the hydroxy aromatic aldehyde to the trans isomer raw material in the sensitizer should be greater than or equal to 3%.
[0033] 3. Optimization of isomerization reaction time
[0034] Seven groups of experiments were conducted with reaction times of 0.5 min, 1 min, 2 min, 3 min, 5 min, 10 min, and 15 min. 0.019 mg (0.1 mmol) of (E)-3-phenyl-2-butenoic acid ethyl ester, 2 mL of N,N-dimethylformamide, and 0.54 mg (3 mol%) of 2-hydroxy-pyromellitic aldehyde were placed in a photocatalytic reaction glass tube, then sonicated for 1 min to mix. The photocatalytic reaction was carried out at 460 nm, 32 W, in air atmosphere, and at room temperature. After the reaction, the solvent was removed, and the volume was adjusted to 10 mL with isopropanol. The Z / E ratio and mixed yield were analyzed by high-performance liquid chromatography. The results are as follows: Figure 2 As shown.
[0035] Depend on Figure 2 It is known that after the reaction time reaches 5 minutes, the Z / E ratio in the reaction product reaches a relatively high level and tends to be stable. Therefore, 5 minutes is the optimal reaction time. The photocatalytic reaction time in the method of this invention should be greater than or equal to 5 minutes.
[0036] 4. Investigation of the necessary factors for isomerization reaction
[0037] The necessary factors for the reaction were further explored through a series of control experiments, and the Z / E ratio and mixed yield after the reaction were analyzed by high performance liquid chromatography. The results are shown in Table 2.
[0038] Table 2. Investigation of the necessary factors for isomerization reaction.
[0039] serial number condition Z / E Mixed yield (%) 1 Standard conditions 92 / 8 99 2 No sensitizer 1 / 99 99 3 No light 1 / 99 99 4 <![CDATA[O2 atmosphere]]> 36 / 64 99 5 <![CDATA[N2 atmosphere]]> 87 / 13 99
[0040] As shown in Table 2, the necessary factors for this reaction to occur are sensitizer and light. The reaction can be completed in air, O2 and N2 atmospheres, with air atmosphere being the best.
[0041] Experimental Example 2: Study on the Universality of Isomerization
[0042] Using a series of (E)-3-phenyl-2-butenoic acid ethyl ester derivatives as substrates and 2-hydroxy-pyromellitic tert-formaldehyde (BTA-1) as a sensitizer, the substrate universality of the photo-assisted catalytic isomerization reaction was investigated. The Z / E ratio and mixed yield after the reaction were analyzed by high-performance liquid chromatography (HPLC). The results are as follows: Figure 3 As shown.
[0043] Depend on Figure 3 It was found that using ortho, meta, and para substitutions of the benzene ring of (E)-3-phenyl-2-butenoate as the starting material for trans isomerization, 2-hydroxy-pyromellitic methyl ester exhibited good isomerization catalytic activity, with all showing high Z / E ratios within 5 min. Although the isomerization effect of some derivatives (E-16 / 17 / 20) was not ideal within 5 min, the Z / E ratio further improved when the reaction time was extended to 10 min. In addition, five / six-membered heterocyclic and naphthalene ring derivatives could also be isomerized in a short time.
[0044] Although specific embodiments of the present invention have been described in detail with reference to the accompanying drawings, this should not be construed as limiting the scope of protection of this patent. Various modifications and variations that can be made by those skilled in the art without inventive effort within the scope described in the claims are still within the scope of protection of this patent.
Claims
1. The application of a hydroxy aromatic aldehyde in photo-assisted catalytic cis-isomerization of unsaturated organic compounds; wherein the hydroxy aromatic aldehyde is 2-hydroxy-pyromellitic aldehyde; and the unsaturated organic compound is an unsaturated ester comprising at least one carbon-carbon double bond.
2. The application as described in claim 1, characterized in that, The application method involves mixing unsaturated organic compounds and hydroxy aromatic aldehydes in a solvent, and then carrying out a photocatalytic reaction under light, air atmosphere, and room temperature.
3. The application as described in claim 2, characterized in that, The solvent is N,N-dimethylformamide.
4. The application as described in claim 2, characterized in that, The molar ratio of the hydroxy aromatic aldehyde to the unsaturated organic compound is greater than or equal to 3%.
5. The application as described in claim 2, characterized in that, The photocatalytic reaction time is greater than or equal to 5 minutes.
6. The application as described in claim 2, characterized in that, Illuminate with 450-480 nm blue light.