Pandan alcohol ether and preparation method thereof

Abstract

The invention discloses vanillin alcohol ether and a preparation method thereof, and the preparation method comprises the following steps: (1) by taking vanillin or ethyl vanillin and hydrogen as reactants and alcohol or ethyl acetate (EA) as a solvent, preparing a reactant solution, adding a Raney nickel catalyst as a catalyst, and reacting at the temperature of 40-70 DEG C under the reaction hydrogen pressure of 2-3 MPa for 8-10 hours; and (2) by taking vanillin alcohol or ethyl vanillin alcohol and second alcohol as reactants and lewis acid (such as magnesium chloride, aluminum chloride, calcium chloride, ferric chloride, copper sulfate and other lewis acids) as a catalyst, reacting at 80-100 DEG C to obtain vanillin alcohol ethers, the preparation method disclosed by the invention is mild in reaction condition, few in by-products, green and environment-friendly, high in product yield and suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis, specifically relating to vanillin alcohol ether and its preparation method. Background Technology

[0002] Vanillyl ethers, also known as capsicum ethers, possess a strong fragrance and aroma and are widely used in fragrances and flavorings. Vanillyl butyl ether, a component of vanillyl ethers, is an oil-soluble thermosensitive agent that produces a mild and lasting warming sensation upon application to the skin. It also effectively stimulates subcutaneous fat metabolism and promotes blood circulation. It is a safe, stable cosmetic additive with a pleasant vanilla scent and some metabolic-promoting effects. Methyl tantalize, a component of vanillyl ethers, is increasingly favored by the cosmetics industry, especially vanillyl butyl ether, which is most widely used in the food and cosmetic fields.

[0003] CN109942382B provides a method for preparing vanillin ether, using vanillin as a raw material and sodium borohydride as a reducing agent. This method is characterized by rapid reaction, mild conditions, and simple operation. However, due to the use of a metal complex hydride as a reducing agent, byproducts may be generated, requiring further post-processing. CN108658734A uses vanillin and n-butanol as raw materials, with anhydrous sodium sulfate as a catalyst, in a staged heating reaction. This method requires a long time for stepwise feeding and complex post-processing. CN101165038A uses vanillin and ethanol under reflux conditions, employing a cation exchange resin or concentrated sulfuric acid as a catalyst. Its yield is only 70.1%, and the strong acid catalyst may corrode equipment. Summary of the Invention

[0004] The purpose of this invention is to provide a vanillyl alcohol ether and its preparation method, which has the advantages of simple operation, mild conditions and high yield.

[0005] The technical solution of the present invention is as follows:

[0006] A method for preparing vanillin ether includes the following steps:

[0007] (1) Vanillin or ethyl vanillin and Raney nickel catalyst are added to an alcohol solvent or ethyl acetate solvent and reacted for 8-10 h under hydrogen pressure of 2-3 MPa and 40-70 °C to obtain vanillin or ethyl vanillin.

[0008] (2) Vanillin or ethyl vanillin reacts with a second alcohol at 80-100℃ for 12-18h under Lewis acid catalysis to obtain vanillin ether;

[0009] The mass ratio of vanillin or ethyl vanillin to the second alcohol is 1:1.5-5, and the second alcohol is a C1-C6 monool.

[0010] In some preferred embodiments, the concentration of vanillin or ethyl vanillin in step (1) is 0.2-0.5 wt%.

[0011] In some preferred embodiments, the mass ratio of vanillin or ethyl vanillin to Raney nickel catalyst is 1:0.1-0.05.

[0012] In some preferred embodiments, the Lewis acid is selected from at least one of magnesium chloride, aluminum chloride, calcium chloride, ferric chloride, and copper sulfate.

[0013] In some preferred embodiments, the molar ratio of vanillin or ethyl vanillin to Lewis acid is 1:0.05-0.5.

[0014] In some preferred embodiments, step (1) further includes the following operations: after the reaction is completed, the Raney nickel catalyst is removed by filtration, and then rotary evaporation and recrystallization are performed in sequence, and finally a white solid is obtained by filtration, wherein the white solid is vanillin or ethyl vanillin.

[0015] In some preferred embodiments, the alcohol solvent is a C1-C6 unit alcohol.

[0016] In some preferred embodiments, the alcohol solvent is the same as the second alcohol.

[0017] A vanillyl ether is prepared by the above-described preparation method.

[0018] The present invention has at least the following beneficial effects:

[0019] (1) The present invention uses a two-step synthesis method. Step (1) uses ethyl acetate or an alcohol solvent. Ethyl acetate solvent can avoid acetal byproducts. Step (2) is a solvent-free Lewis acid catalytic etherification, which can reduce raw material costs, is environmentally friendly and has a high yield, which is beneficial to industrial application.

[0020] (2) In some preferred embodiments, the alcohol solvent used is the same as the substrate second alcohol in step (2), further reducing possible impurities. Attached Figure Description

[0021] Figure 1 Vanillin prepared in Example 1 1 HNMR spectrum;

[0022] Figure 2 The vanillyl methyl ether prepared in Example 1 1 HNMR spectrum;

[0023] Figure 3 The ethyl vanillin prepared in Example 2 1 HNMR spectrum;

[0024] Figure 4 The methyl tantalizol prepared in Example 2 1 HNMR spectrum;

[0025] Figure 5 The vanillyl ethyl ether prepared in Example 3 1 HNMR spectrum;

[0026] Figure 6 The vanillyl propyl ether prepared in Example 4 1 HNMR spectrum;

[0027] Figure 7 The vanillyl butyl ether prepared in Example 5 1 HNMR spectrum;

[0028] Figure 8 The vanillylpentyl ether prepared in Example 6 1 HNMR spectrum;

[0029] Figure 9 The vanillyl hexyl ether prepared in Example 7 1 HNMR image. Detailed Implementation

[0030] The technical solution of the present invention will be further explained and described below through specific embodiments.

[0031] In the following embodiments, the water used can be one or more of distilled water, purified water, and drinking water; unless otherwise specified, the detection methods in the following embodiments are conventional detection methods; unless otherwise specified, the reagents in the following embodiments are all purchased from commercial channels.

[0032] A method for preparing vanillin ether includes the following steps:

[0033] Step (1): Prepare a reaction solution using vanillin or ethyl vanillin and hydrogen as reactants, alcohols or ethyl acetate as solvents, add Raney nickel catalyst as catalyst, reaction temperature 40-70℃, hydrogen pressure 2-3MPa, reaction time 8-10h. Step (2): Use vanillin or ethyl vanillin and C1-C6 alcohols as reactants, Lewis acids as catalysts (such as magnesium chloride, aluminum chloride, calcium chloride, ferric chloride and copper sulfate Lewis acids), reaction temperature 80-100℃, reaction time 12-18h.

[0034] The main reaction in the above steps is:

[0035]

[0036] Example 1

[0037] Step (1) Synthesis of vanillin:

[0038] 10 g of Raney nickel catalyst (dried and dehydrated with methanol), 100 g of vanillin, and 200 mL of ethyl acetate were added sequentially to a 500 mL hydrogenation reactor. After confirming the reactor's airtightness, it was purged with nitrogen three times, then purged with hydrogen at 3 MPa and reacted at 50 °C for 8 h. TLC analysis showed that the reaction proceeds were completely reacted. The Raney nickel catalyst was removed by filtration, and the filtrate was rotary evaporated to obtain a crude product. The product was dissolved in 100 mL of ethanol, and 200 mL of petroleum ether was added to precipitate the solid. The mixture was stirred for 0.5 h, and filtration yielded 92 g of a white solid, with a yield of 91.6%. Its 1H NMR spectrum is shown below. Figure 1 As shown.

[0039] 1 H NMR (500 MHz, Chloroform-d) δ 6.97 – 6.89 (m, 2H), 6.86 (dd, J =8.1, 1.9 Hz, 1H), 5.68 (s, 1H), 4.63 (d, J = 5.6 Hz, 2H), 3.92 (s, 3H), 1.71(t, J = 5.9 Hz, 1H).

[0040] Step (2) Synthesis of vanillyl methyl ether:

[0041] 100 g vanillin and 30.84 g anhydrous magnesium chloride were dissolved in 200 mL of methanol and added to a 1000 mL flask. The mixture was heated to 80 °C and stirred under reflux for 12 h. TLC analysis showed that the starting material reacted completely. The reaction was stopped, cooled to room temperature, and the product was extracted with 300 mL ethyl acetate and 300 mL water. The organic phase was collected by separation, dried over anhydrous sodium sulfate to remove water, and then dissolved by rotary evaporation to obtain 103 g of a brown liquid crude product. Vacuum distillation yielded 94 g of a colorless, transparent liquid product, vanillyl methyl ether, with a yield of 84%. Its 1H NMR spectrum is shown below. Figure 2 As shown.

[0042] 1 H NMR (500 MHz, Chloroform-d) δ 6.94 – 6.86 (m, 2H), 6.83 (dd, J =8.0, 1.9 Hz, 1H), 6.02 (s, 1H), 4.41 (s, 2H), 3.88 (s, 3H), 3.39 (s, 3H).

[0043] Example 2

[0044] Step (1) Synthesis of ethyl vanillin:

[0045] 10 g of Raney nickel catalyst (dried after dehydration with methanol), 100 g of ethyl vanillin, and 200 mL of ethyl acetate were added sequentially to a 500 mL hydrogenation reactor. After confirming the reactor's airtightness, it was purged with nitrogen three times, then purged with hydrogen at 3 MPa and reacted at 70 °C for 10 h. TLC analysis showed that the reaction proceeds were completely reacted. The Raney nickel catalyst was removed by filtration, and the filtrate was rotary evaporated to obtain a crude product. 100 mL of ethyl acetate was added to dissolve the crude product, followed by the addition of 100 mL of petroleum ether to precipitate the solid. The mixture was stirred for 0.5 h, and then filtered to obtain 86.02 g of white solid ethyl vanillin, with a yield of 85%. Its 1H NMR spectrum is shown below. Figure 3 As shown.

[0046] 1 H NMR (500 MHz, Chloroform-d) δ 6.95 – 6.88 (m, 2H), 6.85 (dd, J =8.0, 1.9 Hz, 1H), 5.74 (s, 1H), 4.61 (d, J = 4.5 Hz, 2H), 4.14 (q, J = 7.0Hz, 2H), 1.74 (d, J = 5.3 Hz, 1H), 1.47 (t, J = 7.0 Hz, 3H).

[0047] Step (2) Synthesis of methyl tantalizol:

[0048] 77 g of ethyl vanillin and 20.5 g of anhydrous magnesium chloride were dissolved in 160 mL of methanol and added to a 1000 mL flask. The mixture was heated to 80 °C and stirred for 14 h. TLC analysis showed that the starting material reacted completely. The reaction was stopped, cooled to room temperature, and the product was extracted with 210 mL of ethyl acetate and 210 mL of water. The organic phase was collected by separation, dried over anhydrous sodium sulfate to remove water, and then evaporated by rotary evaporation. The solvent was then removed to obtain 80 g of a pale yellow-brown oily compound, methyl vanillin, with a yield of 95.85%. Its 1H NMR spectrum is shown below. Figure 4 As shown.

[0049] 1 H NMR (500 MHz, Chloroform-d) δ 6.93 – 6.87 (m, 2H), 6.82 (dd, J =8.0, 1.9 Hz, 1H), 5.99 (s, 1H), 4.39 (s, 2H), 4.15 – 4.09 (m, 2H), 3.38 (d, J= 1.2 Hz, 3H), 1.44 (td, J = 7.0, 1.0 Hz, 3H).

[0050] Example 3

[0051] Step (1) Synthesis of vanillin: Refer to Example 1.

[0052] Step (2) Synthesis of vanillyl ethyl ether:

[0053] 100 g vanillin and 6.2 g anhydrous magnesium chloride were dissolved in 200 mL anhydrous ethanol and added to a 1000 mL flask. The mixture was heated to 80 °C and stirred for 12 h. TLC analysis showed that the starting material reacted completely. The reaction was stopped, cooled to room temperature, and 300 mL ethyl acetate and 300 mL water were added to extract the product. The organic phase was collected by separation, dried over anhydrous sodium sulfate to remove water, and then dissolved by rotary evaporation to obtain 119 g of a brown liquid. Vacuum distillation yielded 96 g of a colorless, transparent liquid vanillyl ether, with a yield of 84.1%. Its 1H NMR spectrum is shown below. Figure 5 As shown.

[0054] 1 H NMR (500 MHz, Chloroform-d) δ 6.96 – 6.86 (m, 2H), 6.83 (dd, J =8.0, 1.9 Hz, 1H), 6.04 (s, 1H), 4.45 (s, 2H), 3.87 (s, 3H), 3.55 (q, J = 7.0Hz, 2H), 1.26 (t, J = 7.0Hz, 3H).

[0055] Example 4

[0056] Step (1) Synthesis of vanillin: Refer to Example 1.

[0057] Step (2) Synthesis of vanillylpropyl ether:

[0058] In a 1000 mL three-necked flask, 100 g of white vanillin, 311 g of n-propanol, and 6.2 g of anhydrous magnesium chloride were added, and the mixture was reacted at 80 °C for 16 h. TLC analysis showed that the reactants had completely reacted. The reaction solution was washed with 300 mL of water three times, followed by a wash with 500 mL of saturated sodium chloride solution. After washing, the n-propanol was removed, yielding a yellow oil. The yellow oil was distilled under reduced pressure at 150 °C, and the fraction was collected to give 110 g of a transparent oily substance, vanillylpropyl ether, with a yield of 86%. Its 1H NMR spectrum is shown below. Figure 6 As shown.

[0059] 1H NMR (500 MHz, Chloroform-d) δ 6.95 – 6.86 (m, 2H), 6.84 (dd, J =8.0, 1.9 Hz, 1H), 5.96 (s, 1H), 4.45 (s, 2H), 3.88 (s, 3H), 3.44 (t, J = 6.8Hz, 2H), 1.67 (hept, J = 7.1, 6.6 Hz, 2H), 0.96 (t, J = 7.4 Hz, 3H).

[0060] Example 5

[0061] Step (1) Vanillin synthesis: Refer to Example 1

[0062] Step (2) Synthesis of vanillyl butyl ether:

[0063] In a 2000 mL three-necked reaction flask, 100 g of white vanillin, 480 g of n-butanol, and 6.2 g of anhydrous magnesium chloride were added. After adding a reflux condenser, the reaction flask was sealed, and the airtightness was checked. Nitrogen gas was purged three times, and the reaction was carried out at 80 °C for 16 h. TLC analysis showed that all the reactants had reacted. The reaction solution was washed with 500 mL of water three times, and then washed once with 500 mL of saturated sodium chloride solution. After washing, the n-butanol was removed to obtain a yellow oil. The yellow oil was distilled under reduced pressure at 165 °C, and the fraction was collected as 120 g of a transparent oily substance, vanillyl butyl ether, with a yield of 88%. Its 1H NMR spectrum is shown below. Figure 7 As shown.

[0064] 1 H NMR (500 MHz, Chloroform-d) δ 6.94 – 6.85 (m, 2H), 6.83 (dd, J =8.0, 1.8 Hz, 1H), 5.98 (s, 1H), 4.45 (s, 2H), 3.88 (d, J = 1.3 Hz, 3H), 3.48(t, J = 6.7 Hz, 2H), 1.67 – 1.55 (m, 2H), 1.42 (h, J = 7.4 Hz, 2H), 0.94 (t,J = 7.4 Hz, 3H).

[0065] Example 6

[0066] Step (1) Synthesis of vanillin: Refer to Example 1.

[0067] Step (2) Synthesis of vanillylpentyl ether:

[0068] 100g vanillin was dissolved in 285.7g n-pentanol, and then 6.2g anhydrous magnesium chloride was added to a 1000mL flask. The mixture was heated to 80℃ and refluxed with stirring for 16h. TLC analysis showed that the starting material had reacted completely. The reaction was stopped, cooled to room temperature, and 300mL of water was added, followed by 300mL of ethyl acetate extraction. The organic phase was collected, dried over anhydrous sodium sulfate, and then concentrated to remove the ethyl acetate. The n-pentanol distilled at 70℃ was removed by vacuum distillation, and then the mixture was heated to 170℃ to distill off 121g of the colorless and transparent product vanillylpentyl ether, with a yield of 84%. Its 1H NMR spectrum is shown below. Figure 8 As shown.

[0069] 1 H NMR (500 MHz, Chloroform-d) δ 6.97 – 6.86 (m, 2H), 6.86 – 6.80 (m,1H), 5.92 (d, J = 2.9 Hz, 1H), 4.45 (s, 2H), 3.89 (d, J = 1.5 Hz, 3H), 3.47(td, J = 6.7, 1.2 Hz, 2H), 1.64 (p, J = 6.7 Hz, 2H), 1.39 – 1.32 (m, J = 6.0,4.8 Hz, 4H), 0.99 – 0.86 (m, 3H).

[0070] Example 7

[0071] Step (1) Synthesis of vanillin: Refer to Example 1.

[0072] Step (2) Synthesis of vanillylpropyl ether:

[0073] In a 1000 mL three-necked flask, 100 g of white vanillin, 400 g of n-hexanol, and 6.2 g of anhydrous magnesium chloride were added. The reaction was carried out at 80 °C for 18 h. TLC analysis showed that the reactants had completely reacted. The reaction solution was washed with 300 mL of water three times, and then washed once with 500 mL of saturated sodium chloride solution. After washing, the n-hexanol was removed, yielding a pale yellow oil. The yellow oil was distilled under reduced pressure at 200 °C, and the fraction was collected to give 124 g of a transparent oil, vanillylpropyl ether, with a yield of 80.23%. Its 1H NMR spectrum is shown below. Figure 9 As shown.

[0074] 1H NMR (500 MHz, Chloroform-d) δ 6.94 – 6.86 (m, 2H), 6.84 (dd, J =8.1, 1.8 Hz, 1H), 5.77 (s, 1H), 4.45 (s, 2H), 3.90 (s, 3H), 3.47 (t, J = 6.7Hz, 2H), 1.63 (p, J = 6.9 Hz, 2H), 1.42 – 1.29 (m, 6H), 0.91 (t, J = 6.8 Hz, 3H).

[0075] Example 8

[0076] Step (1) Synthesis of vanillin in kilograms:

[0077] 200 g of Raney nickel catalyst (dried and dehydrated with methanol), 2 kg of vanillin, and 4 L of ethyl acetate were added sequentially to a 10 L hydrogenation reactor. After confirming the reactor's airtightness, it was purged with nitrogen three times, then purged with hydrogen at 3 MPa and reacted at 50 °C for 9 h. TLC analysis showed that the reaction proceeds were completely reacted. The Raney nickel catalyst was removed by filtration, and the filtrate was rotary evaporated to obtain a crude product. The product was dissolved in 2 L of ethanol, and 4 L of petroleum ether was added to precipitate the solid. The mixture was stirred for 0.5 h, and then filtered to obtain 1.9 kg of white solid, with a yield of 93.6%.

[0078] Step (2) Synthesis of kilogram-scale vanillyl butyl ether:

[0079] In a 20L reactor, 1 kg of white vanillin, 4.8 kg of n-butanol, and 62 g of anhydrous magnesium chloride were added. After adding a reflux condenser, the reaction flask was sealed, and the airtightness was checked. Nitrogen was purged three times, and the reaction was carried out at 80℃ for 16 h. TLC confirmed that all the raw materials had reacted. The reaction solution was washed with 5 L of water three times, and then washed once with 5 L of saturated sodium chloride solution. After washing, the n-butanol was removed to obtain a yellow oil. The yellow oil was distilled under reduced pressure at 165℃, and the fraction was collected as 1.23 kg of a transparent oily substance, vanillyl butyl ether, with a yield of 90.44%.

[0080] Example 9

[0081] Step (1) Synthesis of kilogram-scale ethyl vanillin:

[0082] 200 g of Raney nickel catalyst (dried and dehydrated with methanol), 2 kg of ethyl vanillin, and 4 L of ethyl acetate were added sequentially to a 10 L hydrogenation reactor. After confirming the reactor's airtightness, it was purged with nitrogen three times, then purged with hydrogen at 3 MPa and reacted at 70 °C for 10 h. TLC analysis showed that the reaction was complete. The Raney nickel catalyst was removed by filtration, and the filtrate was rotary evaporated to obtain a crude product. 100 mL of ethyl acetate was added to dissolve the crude product, followed by the addition of 100 mL of petroleum ether to precipitate the solid. The mixture was stirred for 0.5 h, and then filtered to obtain 1.601 kg of white solid ethyl vanillin, with a yield of 85%.

[0083] Step (2) Synthesis of kilogram-scale methyl tantalize:

[0084] 1 kg of ethyl vanillin and 0.283 kg of anhydrous magnesium chloride were dissolved in 2 L of methanol and added to a 20 L reactor. The mixture was heated to 80 °C and stirred for 14 h. TLC analysis showed that the reaction proceeds were complete. The reaction was stopped, cooled to room temperature, and 4 L of ethyl acetate and 4 L of water were added to extract the product. The organic phase was collected by separation, dried over anhydrous sodium sulfate to remove water, and then evaporated by rotary evaporation. The solvent was then removed to obtain 1.005 kg of a pale yellow-brown oily compound, methyl vanillin, with a yield of 93.05%.

[0085] The above description is merely a preferred embodiment of the present invention, and therefore should not be construed as limiting the scope of the present invention. All equivalent changes and modifications made in accordance with the scope of the patent and the contents of the specification should still fall within the scope of the present invention.

Claims

1. A method for preparing vanillin ether, characterized in that, Includes the following steps: (1) Vanillin or ethyl vanillin and Raney nickel catalyst are added to an alcohol solvent or ethyl acetate solvent and reacted for 8-10 h under hydrogen pressure of 2-3 MPa and 40-70 °C to obtain vanillin or ethyl vanillin. (2) Vanillin or ethyl vanillin reacts with a second alcohol at 80-100°C for 12-18 h under the catalysis of a Lewis acid to obtain the vanillin ether; Wherein, the mass ratio of vanillin or ethyl vanillin to the second alcohol is 1:1.5-5, and the second alcohol is a C1-C6 unit alcohol.

2. The preparation method according to claim 1, characterized in that, The concentration of vanillin or ethyl vanillin in step (1) is 0.2-0.5 wt%.

3. The preparation method according to claim 1, characterized in that, The mass ratio of vanillin or ethyl vanillin to the Raney nickel catalyst is 1:0.1-0.

05.

4. The preparation method according to claim 1, characterized in that, The Lewis acid is selected from at least one of magnesium chloride, aluminum chloride, calcium chloride, ferric chloride, and copper sulfate.

5. The preparation method according to claim 1 or 4, characterized in that, The molar ratio of vanillin or ethyl vanillin to the Lewis acid is 1:0.05-0.

5.

6. The preparation method according to claim 1, characterized in that, Step (1) also includes the following operations: after the reaction is completed, the Raney nickel catalyst is removed by filtration, and then rotary evaporation and recrystallization are performed in sequence. Finally, a white solid is obtained by filtration, and the white solid is vanillin or ethyl vanillin.

7. The preparation method according to claim 1, characterized in that, The alcohol solvent is a C1-C6 unit alcohol.

8. The preparation method according to claim 1, characterized in that, The alcohol solvent is the same as the second alcohol.

9. A vanillyl alcohol ether, characterized in that, It is prepared by the preparation method described in any one of claims 1-8.

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