Novel method for preparing aromatic aldehyde compound

Abstract

The invention discloses a novel method for preparing an aromatic aldehyde compound, and belongs to the technical field of chemical synthesis. The method for preparing the aromatic aldehyde compound comprises the following steps: mixing aryl acetic acid, an additive, a photosensitizer and a solvent, carrying out photocatalytic reaction, filtering the reaction system, concentrating the filtrate to obtain residues, and purifying to obtain the aromatic aldehyde compound. The invention develops a method for synthesizing the aromatic aldehyde compound by promoting decarboxylation of aryl acetic acid through visible light, the method is mild in condition, green and efficient, and has good compatibility to various functional groups, and the obtained aromatic aldehyde product is easily derived into other valuable functional structural units.

Description

Technical Field

[0001] The invention relates to the technical field of chemical synthesis, and in particular to a new method for preparing aromatic aldehyde compounds. Background Art

[0002] Aromatic aldehydes, as an important class of compounds in organic chemistry, have attracted much attention due to their wide application value and unique chemical properties. This type of compound is not only widely used in the preparation of fragrances, drugs, agrochemicals and polymers, but also becomes a key substrate for almost all types of organic transformation reactions due to its good reactivity and stability. In classic organic reactions such as Wittig, Ugi, Biginelli, Hantzsch, Henry, Mannich, Aldol and Perkin reactions, aromatic aldehydes play an irreplaceable role. In addition, with the rapid development of new catalytic technologies, aromatic aldehydes are increasingly used in the fields of organic molecular catalysis, photocatalysis and preparation of chiral reagents, showing strong application potential and development prospects.

[0003] However, despite the significant application value of aromatic aldehydes, their preparation process faces many challenges. Although traditional methods for preparing aromatic / heteroaromatic aldehydes, such as Vilsmeier-Haack reaction, Reimer-Tiemann reaction, Rieche reaction, Duff reaction, and Friedel-Crafts acylation reaction, can prepare the desired aromatic aldehydes to a certain extent, most of these methods have shortcomings that still need to be solved. For example, they are corrosive and have high requirements for reaction equipment and operating environment; they are sensitive to moisture and need to be carried out under anhydrous conditions, which increases the complexity of the operation; the reaction conditions are harsh, such as high temperature, high pressure or strong acid and strong base environment, which is not conducive to industrial production; in addition, problems such as poor selectivity, easy generation of waste by-products, and low tolerance to functional groups also limit the widespread application of these methods.

[0004] Therefore, developing a new method for preparing aromatic aldehydes that is simple, efficient, environmentally friendly and highly tolerant to functional groups is of vital importance to researchers in this field. Based on this, the present invention proposes a new method for preparing aromatic aldehyde compounds, aiming to overcome the deficiencies of the prior art and achieve efficient and green preparation of aromatic aldehydes. Summary of the invention

[0005] The object of the present invention is to provide a new method for preparing aromatic aldehyde compounds to solve the above-mentioned problems in the background technology. The present invention develops a method for synthesizing aromatic aldehyde compounds from arylacetic acid by visible light-promoted decarboxylation, which has mild conditions, is green and efficient, has good compatibility with various functional groups, and the obtained aromatic aldehyde product can be easily derived into other valuable functional structural units.

[0006] To achieve the above object, the present invention provides the following technical solutions:

[0007] One of the technical solutions of the present invention is to provide a method for preparing an aromatic aldehyde compound, comprising the following steps:

[0008] Aromatic acetic acid, additives, photosensitizer and solvent are mixed to undergo photocatalytic reaction, and then the reaction system is filtered, the filtrate is concentrated to obtain a residue, and then the residue is purified to obtain the aromatic aldehyde compound.

[0009] Preferably, the molar ratio of the arylacetic acid, the additive and the photosensitizer is 0.05-0.5:0.1-0.5:1-6.

[0010] Preferably, the ratio of the arylacetic acid to the solvent is 0.05-0.5 mmol:1-5 ml.

[0011] Preferably, the photosensitizer is Mes-Acr + -MeClO4 - , (Ir[dF(CF3)ppy]2(dtbpy))PF6, Eosin Y or 4CzIPN.

[0012] Preferably, the solvent is acetonitrile.

[0013] Preferably, the additive is cesium carbonate, sodium acetate, sodium carbonate, potassium carbonate, triethylamine or potassium phosphate.

[0014] Preferably, the wavelength of the photocatalytic reaction is 456 nm, the illumination power is 50 W, and the time is 24 h.

[0015] Preferably, the purification is performed by silica gel flash column chromatography.

[0016] The beneficial technical effects of the present invention are as follows:

[0017] In the prior art, the research on the direct photocatalytic synthesis of aromatic aldehydes from arylacetic acid compounds is still insufficient. The present invention develops a method for synthesizing aromatic aldehyde compounds from arylacetic acid by visible light-promoted decarboxylation. The method has mild conditions, is green and efficient, has good compatibility with various functional groups, and the obtained aromatic aldehyde product can be easily derived into other valuable functional structural units.

[0018] The synthesis method of the invention has strong atom economy, high yield, good selectivity and mild conditions, and the synthesized aromatic aldehyde derivatives have broad application prospects in the fields of spices, medicines, agricultural chemicals and polymers.

[0019] The present invention can not only reduce production costs and improve production efficiency, but also reduce the generation of waste, which is in line with the development concept of green chemistry. In addition, the application of the new method is expected to promote the application of aromatic aldehydes in more fields and provide strong support for the innovative development of organic chemistry and chemical industry. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. 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 paying creative work.

[0021] Figure 1 The 1-methylindole-3-carboxaldehyde prepared in Example 1 1 H NMR spectrum.

[0022] Figure 2 The 4-methylbenzaldehyde prepared in Example 2 1 H NMR spectrum.

[0023] Figure 3 The 11-oxo-6,11-dihydrodibenzo[b,e]oxazepine-2-carboxaldehyde prepared in Example 3 1 HNMR nuclear magnetic spectrum.

[0024] Figure 4 The 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-carbaldehyde prepared in Example 4 1 HNMR nuclear magnetic spectrum.

[0025] Figure 5 1-(4-chlorobenzoyl)-6-methoxy-2-methyl-1H-indole-3-carbaldehyde prepared in Example 5 1 H NMR spectrum. DETAILED DESCRIPTION

[0026] Now, various exemplary embodiments of the present invention are described in detail, and this detailed description should not be considered as a limitation of the present invention, but should be understood as a more detailed description of certain aspects, characteristics and embodiments of the present invention. It should be understood that the terms described in the present invention are only for describing specific embodiments and are not used to limit the present invention.

[0027] In addition, for the numerical range in the present invention, it is understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. The intermediate value in any stated value or stated range, and each smaller range between any other stated value or intermediate value in the range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0028] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the invention pertains. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention.

[0029] The words “include,” “including,” “have,” “contain,” etc. used in the present invention are open-ended terms, meaning including but not limited to.

[0030] The invention discloses a method for preparing an aromatic aldehyde compound, comprising the following steps:

[0031] In a sealed test tube dried in an oven, arylacetic acid (0.05-0.5 mmol), cesium carbonate (0.1-0.5 mmol), a photosensitizer (1-6 mmol) and a solvent (1-5 ml) were added, and then placed under 50 W blue light-emitting diode irradiation, stirred at room temperature in an air atmosphere for 24 hours, and then the reaction system was filtered, and the filtrate was concentrated under reduced pressure to obtain a residue;

[0032] The residue was purified by silica gel flash column chromatography (using ethyl acetate / petroleum ether as eluent) to obtain the aromatic aldehyde compound.

[0033] During the photocatalytic reaction, the reaction equation is:

[0034]

[0035] The "room temperature" in the present invention is 10-30°C unless otherwise specified.

[0036] All raw materials used in the following examples and comparative examples of the present invention are commercially available products.

[0037] Example 1

[0038] A method for preparing an aromatic aldehyde compound, comprising the following steps:

[0039] In a sealed test tube dried in an oven, N-methylindoleacetic acid (0.10 mmol), cesium carbonate (0.20 mmol), Mes-Acr + -MeClO4- (5mmol) and acetonitrile (2ml), then placed under 50W blue light emitting diode irradiation, stirred at room temperature in air atmosphere for 24h, after cooling, the reaction system was filtered, and the filtrate was concentrated under reduced pressure to obtain a residue;

[0040] The residue was purified by silica gel flash column chromatography (using ethyl acetate / petroleum ether in a volume ratio of 1:20 as eluent, R f =0.60), and a light yellow solid 1-methylindole-3-carboxaldehyde (denoted as 2a) was obtained. The yield was measured to be 52%. CDCl3 was used as solvent for testing 1 HNMR nuclear magnetic spectrum.

[0041] Figure 1 The 1-methylindole-3-carboxaldehyde prepared in Example 1 1 HNMR nuclear magnetic spectrum.

[0042] 1 HNMR(400MHz,Chloroform-d)δ9.97(s,1H),8.32(s,1H),7.64(s,1H),7.37(s,3H),3.85(s,3H).

[0043] Example 2

[0044] A method for preparing an aromatic aldehyde compound, comprising the following steps:

[0045] In a sealed test tube dried in an oven, p-methylphenylacetic acid (0.10 mmol), cesium carbonate (30 mg, 0.20 mmol), a photosensitizer (5 mmol) and acetonitrile (2 ml) were added, and then placed under 50 W blue light-emitting diode irradiation, stirred at room temperature in an air atmosphere for 24 h, and after cooling, the reaction system was filtered, and the filtrate was concentrated under reduced pressure to obtain a residue;

[0046] The residue was purified by silica gel flash column chromatography (using ethyl acetate / petroleum ether in a volume ratio of 1:20 as eluent, R f =0.60), and a pale white solid 4-methylbenzaldehyde (denoted as 2i) was obtained. The yield was 60% and the yield was 28 mg.

[0047] Figure 2 The 4-methylbenzaldehyde prepared in Example 2 1 HNMR nuclear magnetic spectrum.

[0048] 1HNMR(400MHz,Chloroform-d)δ9.88(s,1H),7.70(s,2H),7.25(s,2H),2.36(s,3H).

[0049] Example 3

[0050] A method for preparing an aromatic aldehyde compound, comprising the following steps:

[0051] In a sealed test tube dried in an oven, isoxic acid (0.10 mmol), cesium carbonate (0.20 mmol), a photosensitizer (5 mmol) and acetonitrile (2 ml) were added, and then placed under 50 W blue light emitting diode irradiation, stirred at room temperature in an air atmosphere for 24 h, and after cooling, the reaction system was filtered, and the filtrate was concentrated under reduced pressure to obtain a residue;

[0052] The residue was purified by silica gel flash column chromatography (using ethyl acetate / petroleum ether in a volume ratio of 1:20 as eluent, R f =0.60) to obtain 11-oxo-6,11-dihydrodibenzo[b,e]oxepin-2-carbaldehyde (denoted as 2y) in the form of a light yellow solid. The yield was measured to be 63%.

[0053] Figure 3 The 11-oxo-6,11-dihydrodibenzo[b,e]oxazepine-2-carboxaldehyde prepared in Example 3 1 HNMR nuclear magnetic spectrum.

[0054] 1 HNMR(500MHz,Chloroform-d)δ10.01(s,1H),8.74(d,J=2.2Hz,1H),8.03(dd,J=8.5,2.2Hz,1H),7.89(d,J= 7.7Hz,1H),7.64–7.59(m,1H),7.54–7.50(m,1H),7.42(d,J=6.2Hz,1H),7.18(d,J=8.5Hz,1H),5.29(s,2H).

[0055] Example 4

[0056] A method for preparing an aromatic aldehyde compound, comprising the following steps:

[0057] Tolmetin (0.10 mmol), cesium carbonate (0.20 mmol), photosensitizer (5 mmol) and acetonitrile (2 ml) were added to a sealed test tube dried in an oven, and then placed under 50 W blue light emitting diode irradiation, stirred at room temperature in an air atmosphere for 24 h, and after cooling, the reaction system was filtered, and the filtrate was concentrated under reduced pressure to obtain a residue;

[0058] The residue was purified by silica gel flash column chromatography (using ethyl acetate / petroleum ether in a volume ratio of 1:20 as eluent, R f =0.60) to obtain 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-carbaldehyde (referred to as 2x) as a light yellow solid. The yield was found to be 65%.

[0059] Figure 4 The 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-carbaldehyde prepared in Example 4 1 HNMR nuclear magnetic spectrum.

[0060] 1 HNMR (500MHz, Chloroform-d) δ9.80 (s, 1H), 7.76 (d, J = 8.0 Hz, 2H), 7.29 (d, J = 8. 3Hz, 2H), 6.91 (d, J = 4.2Hz, 1H), 6.65 (d, J = 4.3Hz, 1H), 4.25 (s, 3H), 2.45 (s, 3H).

[0061] Example 5

[0062] A method for preparing an aromatic aldehyde compound, comprising the following steps:

[0063] In a sealed test tube dried in an oven, indomethacin (0.10 mmol), cesium carbonate (0.20 mmol), a photosensitizer (5 mmol) and acetonitrile (2 ml) were added, and then placed under 50 W blue light emitting diode irradiation, stirred at room temperature in an air atmosphere for 24 h, and after cooling, the reaction system was filtered, and the filtrate was concentrated under reduced pressure to obtain a residue;

[0064] The residue was purified by silica gel flash column chromatography (using ethyl acetate / petroleum ether in a volume ratio of 1:20 as eluent, R f =0.60) to obtain 1-(4-chlorobenzoyl)-6-methoxy-2-methyl-1H-indole-3-carbaldehyde (denoted as 2d) as a light yellow solid. The yield was measured to be 48%.

[0065] Figure 51-(4-chlorobenzoyl)-6-methoxy-2-methyl-1H-indole-3-carbaldehyde prepared in Example 5 1 HNMR nuclear magnetic spectrum.

[0066] 1 HNMR(500MHz,Chloroform-d)δ12.40(s,1H),8.87(d,J=9.2Hz,1H),7.99–7.96(m,2H),7.48 –7.46(m,2H),7.43(d,J=3.0Hz,1H),7.19(dd,J=9.2,3.0Hz,1H),3.86(s,3H),2.69(s,3H).

[0067] In addition to the relevant data of Examples 1-5, the present invention also conducted the following experiments, and the specific data are shown in Table 1.

[0068] Table 1

[0069]

[0070] The embodiments described above are only descriptions of the preferred modes of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. A method for preparing an aromatic aldehyde compound, characterized in that: The following steps are involved: Aromatic acetic acid, additives, photosensitizer and solvent are mixed to undergo photocatalytic reaction, and then the reaction system is filtered, the filtrate is concentrated to obtain a residue, and then the residue is purified to obtain the aromatic aldehyde compound.

2. The method according to claim 1, characterized in that The molar ratio of the aromatic acetic acid, the additive and the photosensitizer is 0.05-0.5:0.1-0.5:1-6.

3. The method according to claim 1, characterized in that The ratio of the aromatic acetic acid to the solvent is 0.05-0.5 mmol:1-5 ml.

4. The method according to claim 1, characterized in that: The photosensitizer is Mes-Acr + -MeClO4 - , (Ir[dF(CF3)ppy]2(dtbpy))PF6, EosinY or 4CzIPN.

5. The method according to claim 1, characterized in that The solvent is acetonitrile.

6. The method according to claim 1, characterized in that The additive is cesium carbonate, sodium acetate, sodium carbonate, potassium carbonate, triethylamine or potassium phosphate.

7. The method according to claim 1, characterized in that The wavelength of the photocatalytic reaction is 456 nm, the illumination power is 50 W, and the time is 24 h.

8. The method according to claim 1, characterized in that The purification is performed by silica gel flash column chromatography.

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