Preparation method of 3-methoxy-4-hydroxybenzaldehyde

Abstract

The invention provides a preparation method of 3-methoxy-4-hydroxybenzaldehyde, and belongs to the technical field of organic synthesis. The preparation method comprises the following steps: taking isoeugenol as an initial raw material, carrying out electron transfer with a photocatalyst under the irradiation of visible light, taking oxygen as an oxidizing agent to form epoxide, oxidizing propenyl into aldehyde group under the irradiation of visible light, and finally breaking the epoxide to form vanillin. The synthesis method disclosed by the invention is simple in steps, the initial raw material is isoeugenol which is cheap and easy to obtain, air can be used as an oxidant, strong oxidants such as ozone are not needed, the use of high-pollution and high-toxicity reagents is reduced, and the method is safe to operate and environment-friendly; the reaction conditions are mild, strict low-temperature conditions are not needed, the reaction time is short, and the method is suitable for industrial production.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for preparing 3-methoxy-4-hydroxybenzaldehyde. Background Technology

[0002] Vanillin (chemical name 3-methoxy-4-hydroxybenzaldehyde) is an important natural aromatic compound widely used in the food, pharmaceutical, and cosmetic industries. Currently, vanillin is mainly synthesized industrially through lignin oxidation or guaiacol chemical synthesis, but these methods generally suffer from problems such as limited raw material sources, high energy consumption, or environmental pollution. Therefore, developing green and efficient synthesis methods has become a research hotspot.

[0003] Isoeugenol is a structurally stable and widely available natural compound containing a conjugated allyl group, which can be selectively oxidatively cleaved into vanillin. In recent years, systems using hydrogen peroxide, peroxyacids, or metal catalysts have been employed for this reaction, but problems remain, such as high catalyst costs, harsh reaction conditions, and numerous byproducts. In contrast, visible light photocatalysis, as a green and efficient catalytic method, can utilize oxygen from the air as an oxidant to achieve the oxidative conversion of isoeugenol under mild conditions, exhibiting good atom economy and environmental friendliness. Therefore, exploring efficient visible light photocatalytic systems to improve the selectivity and conversion rate of isoeugenol to vanillin is an important research direction in this field.

[0004] Currently, the main chemical synthesis methods for vanillin include the eugenol method, lignin method, p-cresol method, 4-methylguaiacol method, nitrosation method, glyoxylic acid method, and p-hydroxybenzaldehyde method, among which the glyoxylic acid method is the most widely used. This method uses guaiacol and glyoxylic acid as raw materials. Under alkaline conditions, they first condense to generate 3-methoxy-4-hydroxymandelic acid, which is then oxidized to 3-methoxy-4-hydroxyphenylacetoic acid under the action of a catalyst. After a deacidification reaction, vanillin is formed, and finally, high-purity vanillin is obtained through extraction, distillation, and crystallization. However, this method generates a large amount of phenol-containing wastewater during industrial production, causing environmental pollution. Furthermore, the synthesis route using eugenol as a raw material typically uses potassium permanganate as an oxidant, resulting in significant wastewater discharge during the reaction process, which also has a negative impact on the ecological environment.

[0005] Patent CN104119213A discloses a method for synthesizing vanillin from eugenol. This method employs a strong base, oxygen, and catalyst system, where the catalyst can be a cobalt salt, a mixed salt of cobalt and copper salts, or a mixed salt of cobalt and nickel salts. Compared to the traditional potassium permanganate oxidation method, this method reduces environmental pollution to some extent. However, its average vanillin yield is only about 50%, limiting the feasibility of industrial application. Although the patent claims that it does not require protection of the phenolic hydroxyl group of eugenol or isomerization of the allyl group, in practice, a much larger molar amount of sodium hydroxide than eugenol is still used, and the reaction is neutralized to neutral with hydrochloric acid after the oxidation reaction. In fact, the oxidative activity of the phenolic hydroxyl group is higher than that of the allyl group; without protection, it is difficult to effectively control the reaction selectivity, thus affecting the formation of vanillin.

[0006] In patent CN102701927A, eugenol is isomerizes to isoeugenol, which is then oxidized in water with ozone to yield vanillin. In patent CN104086390A, a mixture of sodium isoeugenol and water is oxidized with ozone to obtain ozonides, which are then decomposed with sodium sulfite solution and neutralized to obtain vanillin. However, using ozone for oxidation presents problems such as a long reaction process, low yield, and the generation of significant amounts of waste, leading to substantial environmental pollution.

[0007] Therefore, there is an urgent need for an environmentally friendly, simple, and safe method for synthesizing 3-methoxy-4-hydroxybenzaldehyde. Summary of the Invention

[0008] The purpose of this invention is to provide a method for preparing 3-methoxy-4-hydroxybenzaldehyde, which is environmentally friendly, uses simple reagents, is safe to operate, and can obtain 3-methoxy-4-hydroxybenzaldehyde with high purity and high yield.

[0009] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0010] This invention provides a method for preparing 3-methoxy-4-hydroxybenzaldehyde, comprising the following steps:

[0011] Isoeugenol, a photocatalyst, a protic acid, and an organic solvent were mixed and oxidized under visible light irradiation and oxygen-containing gas conditions to obtain 3-methoxy-4-hydroxybenzaldehyde.

[0012] Preferably, the photocatalyst comprises citric acid-derived carbon quantum dots, glucose-derived carbon quantum dots, or urea-derived carbon quantum dots.

[0013] Preferably, the protic acid includes hydrochloric acid, sulfuric acid, camphor sulfonic acid, or p-toluene sulfonic acid.

[0014] Preferably, the mass ratio of isoeugenol to photocatalyst is 40 to 200:1.

[0015] Preferably, the molar ratio of isoeugenol to protic acid is 1:0.01 to 0.05.

[0016] Preferably, the wavelength of the visible light is 450–530 nm.

[0017] Preferably, the oxygen-containing gas is air or oxygen; the flow rate of the oxygen-containing gas is 40-60 mL / min.

[0018] Preferably, the oxidation reaction is carried out at a temperature of 10–40°C for 8–24 hours.

[0019] Preferably, the organic solvent includes acetonitrile or THF; the ratio of the organic solvent to isoeugenol is 1.0–5.0 L: 1 mol.

[0020] This invention provides a method for preparing 3-methoxy-4-hydroxybenzaldehyde. The method uses isoeugenol as the starting material and performs a photocatalytic oxidation reaction under visible light irradiation using a photocatalyst in acidic conditions provided by a protic acid. Oxygen is used as the oxidant to oxidize the propenyl group to the aldehyde group, thereby obtaining vanillin.

[0021] The synthesis method of this invention is simple and efficient, using isoeugenol as a starting material, which is inexpensive and readily available. This significantly reduces the use of high-cost and highly hazardous reagents, resulting in better safety and environmental friendliness. By introducing air as an oxidant, the use of strong oxidants such as ozone is eliminated, effectively reducing dependence on other oxidants and the use of highly polluting and toxic reagents. The method is safe to operate and environmentally friendly, reducing costs and environmental pollution, and providing a feasible solution for large-scale synthesis.

[0022] The preparation method of this invention can efficiently synthesize vanillin under mild conditions, avoiding the use of high temperature or high pressure equipment, eliminating the need for strong oxidants and not relying on precious metal catalysts. By controlling the reaction time and acidic environment, it has a high yield, is suitable for large-scale industrial production, and has good application prospects.

[0023] The method of the present invention is simple to operate, the reaction process does not depend on harsh temperature control conditions, nor does it require strict low temperature conditions, and the reaction time is short, which can meet the needs of industrial production. Attached Figure Description

[0024] Figure 1 The diagram shows the apparatus for the organic photocatalytic reaction of this invention, which was purchased from the Green Instrument Studio of Huazhong Normal University as a photofluid reactor.

[0025] Figure 2The 1H NMR spectrum of 3-methoxy-4-hydroxybenzaldehyde prepared in Example 1;

[0026] Figure 3 The carbon NMR spectrum of 3-methoxy-4-hydroxybenzaldehyde prepared in Example 1;

[0027] Figure 4 The mass spectrum of 3-methoxy-4-hydroxybenzaldehyde prepared in Example 1;

[0028] Figure 5 The gas chromatogram of 3-methoxy-4-hydroxybenzaldehyde prepared in Example 1 is shown. Detailed Implementation

[0029] In this invention, unless otherwise specified, the raw materials or reagents required for preparation are all commercially available products well known to those skilled in the art.

[0030] This invention provides a method for preparing 3-methoxy-4-hydroxybenzaldehyde, comprising the following steps:

[0031] Isoeugenol, a photocatalyst, a protic acid, and an organic solvent were mixed and oxidized under visible light irradiation and oxygen-containing gas conditions to obtain 3-methoxy-4-hydroxybenzaldehyde.

[0032] In this invention, the structural formula of isoeugenol is as follows:

[0033] In this invention, the structural formula of the 4-hydroxy-3-methoxybenzaldehyde is as follows:

[0034] In this invention, the photocatalyst preferably includes citric acid-derived carbon quantum dots, glucose-derived carbon quantum dots, or urea-derived carbon quantum dots.

[0035] The present invention does not impose any particular limitation on the preparation method of the photocatalyst; it can be prepared according to methods well known in the art.

[0036] In this invention, the preferred method for preparing the citric acid-derived carbon quantum dots is as follows:

[0037] Dissolve 3.0 g of citric acid and 0.5 g of NaOH in 30 mL of deionized water and stir until a clear solution is formed. Heat the clear solution in a 750 W microwave reactor until the deionized water is completely evaporated to obtain a crude carbon quantum dot and NaOH mixed powder. Dissolve the obtained mixed powder in ethanol, centrifuge at 2000 rpm to remove excess NaOH and incompletely converted small organic molecules, and freeze-dry to obtain citric acid-derived carbon quantum dots.

[0038] In this invention, the preferred method for preparing the glucose-derived carbon quantum dots is as follows:

[0039] Weigh 5.0g of glucose and place it in a porcelain crucible. Put the crucible into a muffle furnace and dry-calcine at 300℃ for 2 hours (during the reaction, glucose undergoes dehydration condensation and carbonization, and the color gradually changes from white to dark brown, eventually forming a charred solid). Grind the carbonized solid and dissolve it in 50mL of deionized water. Disperse it ultrasonically for 30 minutes (to promote the release of carbon quantum dots). Filter the resulting suspension through a 0.22μm filter membrane to remove large carbon particles. Then, dialyze the filtrate (MWCO 3, 500Da) to remove small molecule impurities. Freeze-dry the filtrate to obtain glucose-derived carbon quantum dots.

[0040] In this invention, the preferred method for preparing the urea-derived carbon quantum dots is as follows:

[0041] 5.0 g of urea was dissolved in 20 mL of deionized water and stirred until homogeneous. The solution was then transferred to a 100 mL polytetrafluoroethylene-lined high-pressure reactor and subjected to hydrothermal reaction at 180 °C for 6 h. After the reaction was completed, the reactor was allowed to cool naturally to room temperature. The resulting brown reaction solution was filtered through a 0.22 μm filter membrane to remove large particulate impurities. The filtrate was dialyzed in deionized water for 48 hours using a dialysis bag (molecular weight cutoff 3,500 Da) to further remove unreacted small molecule impurities. The dialysate was then freeze-dried to obtain 3.8 g of urea-derived carbon quantum dots.

[0042] In this invention, the mass ratio of isoeugenol to photocatalyst is preferably 40-200:1, more preferably 51-102:1.

[0043] In this invention, the protic acid preferably includes hydrochloric acid, sulfuric acid, camphor sulfonic acid, or p-toluene sulfonic acid; the mass concentration of the hydrochloric acid is preferably 30%, and the mass concentration of the sulfuric acid is preferably 20%.

[0044] In this invention, the isoeugenol is preferably commercially available isoeugenol with a purity of 99%.

[0045] In this invention, the molar ratio of isoeugenol to protic acid is preferably 1:0.01 to 0.05, more preferably 1:0.01 to 0.02.

[0046] In this invention, the organic solvent preferably includes acetonitrile or THF (tetrahydrofuran); the ratio of the organic solvent to isoeugenol is preferably 1.0-5.0 L:1 mol, more preferably 2.0-3.0 L:1 mol.

[0047] In this invention, the wavelength of the visible light is preferably 450-530 nm, more preferably 480-500 nm, and even more preferably 490 nm.

[0048] In this invention, the temperature of the oxidation reaction is preferably 10-40°C, more preferably 20-30°C, and the time is preferably 8-24 hours, more preferably 12-14 hours.

[0049] In this invention, the oxygen-containing gas is preferably air or oxygen, more preferably air; the flow rate of the oxygen-containing gas is preferably 40-60 mL / min, more preferably 50 mL / min. During the oxidation reaction, the oxygen-containing gas is continuously supplied through a ventilation device to ensure the smooth progress of the oxidation reaction.

[0050] like Figure 1 As shown, the present invention preferably prepares a reaction solution by isoeugenol, photocatalyst, protic acid and organic solvent, introduces it into a photofluidic reactor, introduces oxygen or air into the reaction vessel, maintains a suitable reaction temperature, and carries out the reaction under visible light irradiation. After distilling and concentrating the obtained reaction solution at 40°C to remove the organic solvent, the photocatalyst is removed by diatomaceous earth filtration, and the crude product is subjected to vacuum distillation (135°C, 5 mmHg) to obtain 3-methoxy-4-hydroxybenzaldehyde.

[0051] In this invention, the flow rate of the reaction solution is preferably 3.5 to 4 mL / min, more preferably 4 mL / min.

[0052] The reaction formula for preparing 3-methoxy-4-hydroxybenzaldehyde in this invention is as follows:

[0053]

[0054] The specific embodiments of the present invention are described in detail below, but it should be understood that the scope of protection of the present invention is not limited to the specific embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention. Unless otherwise specified, the experimental methods described in the embodiments of the present invention are conventional methods.

[0055] Unless otherwise specified, the experimental and testing methods described below are conventional methods; unless otherwise specified, the reagents and raw materials described below are commercially available.

[0056] Example 1

[0057] Preparation of citric acid-derived carbon quantum dots: 3.0 g of citric acid and 0.5 g of NaOH were dissolved in 30 mL of deionized water and stirred until a clear solution was formed. The clear solution was heated in a 750 W microwave reactor for 2.5 minutes until the deionized water was completely evaporated, resulting in a crude carbon quantum dot and NaOH mixed powder. The resulting mixed powder was dissolved in ethanol, washed by centrifugation at 2000 rpm, and then freeze-dried to obtain 1.8 g of citric acid-derived carbon quantum dots.

[0058] Isoeugenol (164.1 g, 1.0 mol), citric acid-derived carbon quantum dots (1.6 g), D-camphorsulfonic acid (2.32 g, 0.01 mol), and acetonitrile (2.0 L) were prepared into a reaction solution and introduced into a photofluidic reactor at a flow rate of 4 mL / min. Oxygen was simultaneously introduced at a flow rate of 50 mL / min, and the reaction temperature was maintained at 30 °C. The reaction was carried out for 12 h under visible light irradiation at a wavelength of 480 nm. The resulting reaction solution was concentrated by vacuum distillation at 40 °C to remove the acetonitrile solvent. The carbon quantum dots were removed by diatomaceous earth filtration. The crude product was then distilled under vacuum (135 °C, 5 mmHg) to obtain 148.2 g of 3-methoxy-4-hydroxybenzaldehyde, with a yield of 97.4% and a purity of 99.95%.

[0059] The NMR and mass spectra of 3-methoxy-4-hydroxybenzaldehyde prepared in Example 1 are shown in Figure 1. Figures 2-4 The specific data is as follows: 1 H NMR (400MHz, CDCl3): δ9.82 (br s, 1H), 7.43–7.41 (m, 2H), 7.04 (d, J = 8.8Hz, 1H), 6.30 (brs, 1H), 3.96 (s, 3H); 13 C NMR (100MHz, CDCl3, ppm): δ191.1,151.8,147.2,129.8,127.6,114.5,108.9,56.1; [M+H] + (HR-ESI): m / z = 152.9641. This proves the successful synthesis of the target product 3-methoxy-4-hydroxybenzaldehyde.

[0060] The purity of 3-methoxy-4-hydroxybenzaldehyde prepared in Example 1 was determined by gas chromatography. The specific chromatographic conditions are shown in Table 1, and the analytical results are shown in Table 2.

[0061] Table 13 Gas Chromatographic Analysis Conditions for 3-Methoxy-4-hydroxybenzaldehyde

[0062]

[0063] Table 23 Gas Chromatographic Purity Results of 3-Methoxy-4-hydroxybenzaldehyde

[0064]

[0065] The results in Table 2 show that the purity of 3-methoxy-4-hydroxybenzaldehyde prepared in Example 1 is 99.94583%. Figure 5 .

[0066] Example 2

[0067] Preparation of glucose-derived carbon quantum dots: 5.0 g of glucose was weighed and placed in a porcelain crucible, which was then placed in a muffle furnace and carbonized at 300 °C for 2 h. The carbonized solid was then crushed and dissolved in 50 mL of deionized water, and ultrasonically dispersed for 30 minutes. The resulting suspension was filtered through a 0.22 μm filter membrane, and the resulting filtrate was dialyzed (MWCO 3, 500 Da) and then freeze-dried to obtain 4.1 g of glucose-derived carbon quantum dots.

[0068] Isoeugenol (164.1 g, 1.0 mol), glucose-derived carbon quantum dots (1.6 g), p-toluenesulfonic acid monohydrate (1.90 g, 0.01 mol), and acetonitrile (3.0 L) were prepared into a reaction solution and introduced into a photofluidic reactor at a flow rate of 3.5 mL / min. Oxygen was simultaneously introduced at a flow rate of 50 mL / min, and the reaction temperature was maintained at 30 °C. The reaction was carried out for 12 h under visible light irradiation at a wavelength of 500 nm. The resulting reaction solution was concentrated by vacuum distillation at 40 °C to remove the acetonitrile solvent. The carbon quantum dots were removed by diatomaceous earth filtration. The crude product was then distilled under vacuum (135 °C, 5 mmHg) to obtain 137.4 g of 3-methoxy-4-hydroxybenzaldehyde, with a yield of 90.3% and a purity of 99.72%.

[0069] Example 3

[0070] Preparation of urea-derived carbon quantum dots: 5.0 g of urea was weighed and dissolved in 20 mL of deionized water. After stirring evenly, the solution was transferred to a 100 mL polytetrafluoroethylene-lined high-pressure reactor and placed at 180 °C for hydrothermal reaction for 6 h. After the reaction was completed, the reactor was allowed to cool naturally to room temperature. The resulting brown reaction solution was filtered through a 0.22 μm filter membrane. The filtrate was dialyzed in deionized water for 48 hours using a dialysis bag (molecular weight cutoff 3,500 Da). The dialysate was freeze-dried to obtain 3.8 g of urea-derived carbon quantum dots.

[0071] Isoeugenol (164.1 g, 1.0 mol), urea-derived carbon quantum dots (1.6 g), 30% hydrochloric acid (1.22 g, 0.01 mol HCl), and tetrahydrofuran (2.0 L) were prepared into a reaction solution and introduced into a photofluidic reactor at a flow rate of 3.5 mL / min. Oxygen was simultaneously introduced at a flow rate of 50 mL / min, and the reaction temperature was maintained at 20 °C. The reaction was carried out for 12 h under visible light irradiation at a wavelength of 490 nm. The resulting reaction solution was concentrated by vacuum distillation at 40 °C to remove the tetrahydrofuran solvent. The carbon quantum dots were removed by diatomaceous earth filtration. The crude product was then distilled under vacuum (135 °C, 5 mmHg) to obtain 142.5 g of 3-methoxy-4-hydroxybenzaldehyde, with a yield of 93.7% and a purity of 99.81%.

[0072] Example 4

[0073] Isoeugenol (164.1 g, 1.0 mol), glucose-derived carbon quantum dots prepared in Example 2 (3.2 g), 30% hydrochloric acid (1.22 g, 0.01 mol HCl) and tetrahydrofuran (3.0 L) were prepared into a reaction solution and introduced into a photofluidic reactor at a flow rate of 3.5 mL / min, while oxygen was introduced at a flow rate of 50 mL / min. The reaction temperature was maintained at 30 °C, and the reaction was carried out for 14 h under visible light irradiation at a wavelength of 490 nm. The resulting reaction solution was concentrated by vacuum distillation at 40 °C to remove the tetrahydrofuran solvent. The carbon quantum dots were removed by diatomaceous earth filtration. The crude product was then distilled under vacuum (135 °C, 5 mmHg) to obtain 146.4 g of 3-methoxy-4-hydroxybenzaldehyde, with a yield of 96.3% and a purity of 99.67%.

[0074] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing 3-methoxy-4-hydroxybenzaldehyde, characterized in that, Includes the following steps: Isoeugenol, a photocatalyst, a protic acid, and an organic solvent were mixed and oxidized under visible light irradiation and oxygen-containing gas conditions to obtain 3-methoxy-4-hydroxybenzaldehyde.

2. The preparation method according to claim 1, characterized in that, The photocatalyst includes citric acid-derived carbon quantum dots, glucose-derived carbon quantum dots, or urea-derived carbon quantum dots.

3. The preparation method according to claim 1, characterized in that, The protic acid includes hydrochloric acid, sulfuric acid, camphor sulfonic acid, or p-toluene sulfonic acid.

4. The preparation method according to claim 1, characterized in that, The mass ratio of isoeugenol to photocatalyst is 40–200:

1.

5. The preparation method according to claim 1 or 4, characterized in that, The molar ratio of isoeugenol to protic acid is 1:0.01 to 0.

05.

6. The preparation method according to claim 1, characterized in that, The wavelength of the visible light is 450–530 nm.

7. The preparation method according to claim 1 or 6, characterized in that, The oxygen-containing gas is air or oxygen; the flow rate of the oxygen-containing gas is 40-60 mL / min.

8. The preparation method according to claim 7, characterized in that, The oxidation reaction is carried out at a temperature of 10–40°C for a duration of 8–24 hours.

9. The preparation method according to claim 1, characterized in that, The organic solvent includes acetonitrile or THF; the ratio of the organic solvent to isoeugenol is 1.0–5.0 L: 1 mol.

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