4-propylbenzaldehyde and preparation method thereof

Abstract

The invention discloses 4-propylbenzaldehyde and a preparation method thereof.According to the preparation method, a compound which is low in price and easy to obtain serves as a raw material, high-yield and high-purity 4-propylbenzaldehyde is synthesized through short reaction steps, the production process is safe and environmentally friendly, and the cost is low.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic synthesis, and particularly relates to 4-propylbenzaldehyde and a preparation method thereof. BACKGROUND

[0002] 4-propylbenzaldehyde is an organic compound with aromatic odor. 4-propylbenzaldehyde is an important pharmaceutical intermediate, and is widely used in the pharmaceutical synthesis, perfume and cosmetic industries. 4-propylbenzaldehyde has a rich and strong odor of cumin and grass, and is naturally present in plants such as fennel, cumin, black rice and cinnamon. However, the synthesis process of 4-propylbenzaldehyde reported in the current literature has many limitations, such as harsh reaction conditions, many by-products, great difficulty in extraction and separation, low purity and the like, so that the market price is relatively high. SUMMARY

[0003] One of the purposes of the present application is to provide a preparation method of 4-propylbenzaldehyde, which uses cheap and readily available compounds as raw materials, and synthesizes 4-propylbenzaldehyde with high yield and high purity through a short reaction step, and the production process is safe, environmentally friendly and low in cost.

[0004] Another purpose of the present application is to provide 4-propylbenzaldehyde prepared by the above preparation method.

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

[0006] A preparation method of 4-propylbenzaldehyde comprises the following steps:

[0007] 4-propylphenyl lithium is obtained by dissolving 4-propylbromobenzene in a dry organic solvent under nitrogen protection, cooling to-60℃, then adding 1.05-5eq of n-butyllithium and reacting for 2-5h, and then adding 1.1-8eq of N,N-dimethylformamide and reacting for 1-10h, with the whole process controlling the system temperature to be not higher than-60℃.

[0008] In some possible implementation manners, the system temperature is-70 to-60℃.

[0009] In some possible implementation manners, the reaction time of 4-propylbromobenzene and n-butyllithium is 2.5h.

[0010] In some possible implementation manners, the addition amount of n-butyllithium is 1.25eq.

[0011] In some possible implementation manners, the reaction time of 4-propylphenyl lithium and N,N-dimethylformamide is 2h.

[0012] In some possible implementation manners, the addition amount of N,N-dimethylformamide is 2eq.

[0013] In some possible implementations, the mass-to-volume ratio of 4-propylbromobenzene to the organic solvent is 1 g: 0.2–10 mL.

[0014] In some possible implementations, the organic solvent is tetrahydrofuran, n-hexane, toluene, cyclohexane, diethyl ether, or n-heptane.

[0015] In some possible implementations, the preparation method further includes the following steps: after the reaction is complete, the reaction system is brought to room temperature and then allowed to stand or be stirred for 10–14 hours. This step is to ensure that all 4-propylphenyl lithium is consumed; otherwise, impurities may be generated in subsequent operations, affecting the purity of the product.

[0016] In some possible implementations, the preparation method further includes the following steps: after the reaction is completed, an aqueous solution of saturated ammonium chloride is added to the system for quenching, and then the system is successively washed, dried, concentrated and distilled under reduced pressure to obtain 4-propylbenzaldehyde.

[0017] In some possible implementations, the temperature for vacuum distillation is 108–112 °C.

[0018] A 4-propylbenzaldehyde was prepared by the above method.

[0019] The present invention has at least the following beneficial effects:

[0020] 1. Low production cost: This invention uses 4-propylbromobenzene, n-butyllithium, and N,N-dimethylformamide (DMF) as raw materials, which are simple and readily available;

[0021] 2. High product quality: conversion rate greater than 95%, product purity greater than 95%, and yield greater than 84%;

[0022] 3. The synthesis route and reaction steps are simple, making it suitable for industrial scale-up;

[0023] 4. Safe and environmentally friendly: The post-processing is simple and does not generate solid waste or pollutants. Attached Figure Description

[0024] Figure 1 The image shows the gas chromatogram (GC) of 4-propylbenzaldehyde prepared in Example 1.

[0025] Figure 2 The NMR spectrum of 4-propylbenzaldehyde prepared in Example 1 is shown. Detailed Implementation

[0026] The technical solution of the present invention will be further explained and described below through specific embodiments.

[0027] In the following embodiments, unless otherwise specified, the water used can be one or more of distilled water, purified water, and drinking water; the detection methods in the following embodiments are conventional detection methods unless otherwise specified; the reagents in the following embodiments are commercially available unless otherwise specified. Concentration as used in this application refers to the removal of solvent from the reaction system. In the following embodiments, the specific method of concentration is rotary evaporation. This application has no special requirements for the rotation speed and time of rotary evaporation, as long as the solvent can be removed.

[0028] Example 1

[0029]

[0030] Take a dry 1L three-necked flask, add 120g (1 eq) of 4-propylbromobenzene, then purge with nitrogen in a double-row tube. Inject anhydrous tetrahydrofuran (THF, 120mL), and cool the ethyl acetate (EA) / liquid nitrogen system to -70℃. Add dropwise a hexane solution of n-butyllithium (1.25 eq, 2.5M, 300mL), controlling the internal temperature not to exceed -60℃. After the addition is complete, the system changes from a clear solution to a white suspension. Insulate the reaction temperature for 2.5h to obtain 4-propylphenyllithium.

[0031] Anhydrous DMF (2 eq, 93 mL) was added dropwise to the system while maintaining the internal temperature no higher than -60℃. After the addition was complete, the reaction was maintained at this temperature for 1 h. Samples were taken, quenched with saturated ammonium chloride, extracted with EA, and the GC results are shown in Table 1. Figure 1 As shown, the product purity is 98.40%.

[0032] The system was quenched with saturated ammonium chloride (300 mL), then extracted sequentially with EA (100 mL × 3), washed with saturated brine (500 mL × 2), dried over anhydrous sodium sulfate, and concentrated to obtain the crude product. The crude product was then subjected to vacuum distillation at 110 °C, with the first distillate discarded and subsequent distillates collected to yield 4-propylbenzaldehyde, a pale yellow, transparent oily substance with a mass of 80.86 g and a yield of 90.53%. GC analysis showed a product purity of 99%.

[0033] The product was analyzed by hydrogen nuclear magnetic resonance, and the results are as follows: Figure 2 As shown, 1 HNMR (500MHz, CDCl3) δ9.87 (s, 1H), 7.70 (d, J = 8.1Hz, 2H), 7.23 (d, J = 8.1Hz, 2H), 2.59–2.52 (m, 2H), 1.64–1.51 (m, 2H), 0.86 (t, J = 7.4Hz, 3H).

[0034] Table 1. Gas chromatography results (signal: FID1B)

[0035]

[0036] Example 2

[0037] A dry three-necked flask was used. 79.64 g (1 eq) of 4-propylbromobenzene was added, followed by purging with nitrogen in a double-row tube. Anhydrous THF (240 mL) was then injected, and the EA / liquid nitrogen system was cooled to -70 °C. A hexane solution of n-butyllithium (200 mL, 2.5 M, 1.25 eq) was added dropwise, controlling the internal temperature to not exceed -60 °C. After the addition was complete, the system changed from a clear solution to a white suspension, with increased viscosity, making stirring difficult. The reaction was maintained at this temperature for 4.5 h to obtain 4-propylphenyllithium.

[0038] Anhydrous DMF (77 mL, 2.5 eq) was added dropwise to the system while maintaining a steady temperature. After the addition was complete, the reaction was maintained at this temperature for 1 hour. The reaction was then allowed to proceed for 12 hours after reaching room temperature. A sample was taken, quenched with a saturated ammonium chloride aqueous solution, extracted with EA, and analyzed by GC. The purity of the raw material was 3.2%, and the product purity was 95.3%, with no obvious impurities observed.

[0039] The system was quenched with saturated ammonium chloride aqueous solution (200 mL), extracted with EA (100 mL × 3), and dried over anhydrous sodium sulfate. The mixture was then distilled under reduced pressure at an external temperature of 120 °C. The first distillate, approximately 2.23 g, was discarded, and subsequent distillates were collected to yield 50.23 g of product, with a yield of 84.22%.

[0040] Comparative Example 1

[0041] Take a dry three-necked flask, add 4-propylbromobenzene (4.52 g, 1 eq), then purge with nitrogen in a double-row tube. Inject anhydrous THF (45 mL), and cool the EA / liquid nitrogen system to -70 °C. Add n-butyllithium in n-hexane solution (10 mL, 2.5 M, 1.1 eq), controlling the internal temperature at -50 to -60 °C. After addition, the system changes from a clear solution to a white suspension, with increased viscosity and difficulty in stirring. Maintain the reaction temperature for 4 h. Add anhydrous DMF (3.6 mL, 2 eq), controlling the internal temperature to remain unchanged. After addition, maintain the reaction temperature for 1 h, then raise it to room temperature and react for 12 h. Take a sample, quench with saturated ammonium chloride aqueous solution, extract with EA, and analyze by GC. The results show 16.3% raw material, 77.4% product, and 4.66% impurities.

[0042] Comparative Example 2

[0043] Take a dry three-necked flask, add 4-propylbromobenzene (4.17 g, 1 eq), then purge with nitrogen in a double-row tube. Inject anhydrous THF (50 mL), and cool the ethanol / liquid nitrogen system to -50 to -60 °C. Add n-butyllithium in n-hexane solution (10 mL, 2.5 M, 1.2 eq), controlling for no significant change in internal temperature. After addition, slowly raise the temperature to -30 °C and maintain the reaction temperature for 1.5 h. Cool the system to -78 °C, and add anhydrous DMF (3.2 mL, 2 eq), controlling for no significant change in internal temperature. After addition, maintain the reaction temperature for 1 h, then raise it to room temperature and react for 12 h. After quenching with saturated ammonium chloride aqueous solution, extract with EA, and analyze by GC. The results show 8.2% of the raw material, 29.7% of the product, and 57.6% of impurities.

[0044] Comparative Example 3

[0045] Take a dry three-necked flask, add 5 g of 4-propylbromobenzene (1 eq), then purge with nitrogen in a double-row tube. Inject 50 mL of anhydrous THF and cool the system to -25 to -20 °C. Add 13 mL of n-butyllithium in n-hexane (2.5 M, 1.3 eq), keeping the internal temperature stable, and maintain the reaction temperature for 2 h. Inject 2.7 mL of anhydrous DMF (1.4 eq) and 10 mL of anhydrous THF into a constant-pressure dropping funnel, keeping the internal temperature below -20 °C during the addition. After the addition is complete, maintain the reaction temperature for 2 h, then raise the temperature to room temperature and react for another 1 h. The system is a pale yellow transparent solution. Quench with saturated ammonium chloride aqueous solution, extract with EA, and perform GC analysis on a sample; almost no product was found.

[0046] 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 4-propylbenzaldehyde, characterized in that, Includes the following steps: Under nitrogen protection, 4-propylbromobenzene is dissolved in a dry organic solvent, cooled to -60°C, and then 1.05–5 eq of n-butyllithium is added and reacted for 2–5 h to obtain 4-propylphenyllithium. Then, 1.1–8 eq of N,N-dimethylformamide is added and reacted for 1–10 h, with the system temperature controlled not higher than -60°C throughout the process.

2. The preparation method according to claim 1, characterized in that, The system temperature is -70 to -60℃.

3. The preparation method according to claim 1, characterized in that, The reaction time between the 4-propylbromobenzene and the n-butyllithium is 2.5 h.

4. The preparation method according to claim 1, characterized in that, The amount of n-butyllithium added is 1.25 eq.

5. The preparation method according to claim 1, characterized in that, The reaction time between the 4-propylphenyllithium and the N,N-dimethylformamide is 2 hours.

6. The preparation method according to claim 1, characterized in that, The amount of N,N-dimethylformamide added is 2 eq.

7. The preparation method according to claim 1, characterized in that, The mass-to-volume ratio of the 4-propylbromobenzene to the organic solvent is 1 g: 0.2–10 mL.

8. The preparation method according to claim 1, characterized in that, It also includes the following steps: after the reaction is complete, the reaction system is brought to room temperature and then allowed to stand or be stirred for 10 to 14 hours.

9. The preparation method according to claim 1, characterized in that, The process also includes the following steps: after the reaction is complete, an aqueous solution of saturated ammonium chloride is added to the system for quenching, and then the system is successively washed, dried, concentrated and distilled under reduced pressure to obtain the 4-propylbenzaldehyde.

10. A 4-propylbenzaldehyde, characterized in that, It is prepared by the preparation method described in any one of claims 1 to 9.

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