Synthesis method of trans-2-octenal

Abstract

The invention belongs to the technical field of synthesis of medicines and spices, and particularly relates to a synthesis method of trans-2-octenal. The synthesis method comprises the following steps: carrying out isomerization reaction on 1-octylene-3-alcohol under the catalytic action of 3, 4-dinitrobenzoic acid to obtain a trans-2-octylene-1-alcohol intermediate; the preparation method comprises the following steps: preparing trans-2-octenal from trans-2-octylene-1-alcohol under the oxidation action of m-chloroiodobenzene, 4-hydroxy-TEMPO (4-hydroxy-2, 2, 6, 6-tetramethylpiperidine nitroxide free radical) and peracetic acid, and further preparing the trans-2-octenal from the trans-2-octylene-1-alcohol. The preparation method is mild in reaction condition, simple to operate and free of expensive reagents or catalysts.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of synthesis of medicine and perfume, and particularly relates to a synthesis method of trans-2-octenal. BACKGROUND

[0002] The information disclosed in the background of the present application is only intended to increase the understanding of the overall background of the present application, and should not necessarily be regarded as acknowledging or implying in any form that the information constitutes prior art known to those skilled in the art.

[0003] Trans-2-octenal (CAS: 2548-87-0) has the appearance of a yellowish liquid, can be dissolved in ethanol and most fixed oils, is slightly soluble in water, has a sharp green leafy aroma, has the appearance of a yellowish liquid, is easily oxidized, is a synthetic perfume with high price, and is widely used in daily chemical fragrances and food fragrances, and is mainly used for blending vegetable, fruit and other fragrances.

[0004] At present, the synthesis methods of trans-2-octenal mainly include the following three kinds: one is to use hexanal and phosphorus ylide to prepare by Witting reaction; two is to synthesize by aldol condensation reaction of hexanal and acetaldehyde; three is to obtain by addition of hexanal and vinyl ether under catalysis of boron trifluoride ether and then hydrolysis. These methods generally have the following defects: first, the reaction needs to use raw materials with high price such as Witting reagent, boron trifluoride and its ether complex, and the production cost is high. Secondly, by-products such as triphenyl phosphine oxide are produced in the reaction process, which not only increases the difficulty of separation and purification of the product, but also causes waste of resources from the angle of atomic utilization due to its large molecular weight. In addition, the method using acetaldehyde as raw material also has the safety hidden danger of operation, because it has low boiling point and strong volatility and toxicity, special protection measures need to be taken in the storage and transportation process. These factors all limit the industrial application of the existing synthesis methods. SUMMARY

[0005] Therefore, the present application provides a synthesis method of trans-2-octenal, the reagents used in the synthesis method are economical and inexpensive, the reaction conditions are mild, and the product yield is high.

[0006] In order to achieve the above purpose, the present application is realized by the following technical scheme: A synthesis method of trans-2-octenal, comprising the following steps:

[0007] S1, dissolving 1-octene-3-ol and a catalytic amount of 3,4-dinitrobenzoic acid in a solvent to occur isomerization reaction to obtain trans-2-octene-1-ol; S2, trans-2-octene-1-ol is obtained by oxidation of trans-2-octene-1-ol under the action of meta-chloroiodobenzene, 4-hydroxy-TEMPO (4-hydroxy-2,2,6,6-tetramethylpiperidine nitroxyl radical) and peracetic acid.

[0008] In step S1, the organic solvent is a mixed solvent of any one of tetrahydrofuran and acetonitrile and water, and the volume ratio of the organic solvent to water is 5-15:1, preferably 8-12:1, and more preferably 10:1.

[0009] Preferably, in step S1, the molar ratio of the 1-octene-3-ol to the 3,4-dinitrobenzoic acid is 1:(0.01-0.15).

[0010] Preferably, in step S1, the reaction temperature is 20-60℃, and more preferably 20-45℃; and the reaction time is 8-15h, and preferably 10-15h.

[0011] Preferably, in step S2, the solvent is one of dichloromethane, chloroform and dichloroethane.

[0012] In step S2, the reaction temperature is 30-75℃, preferably 30-60℃, and more preferably 30-40℃; and the reaction time is 8-15h, and preferably 10-12h.

[0013] The molar ratio of the 1-octene-3-ol, peracetic acid, meta-chloroiodobenzene and 4-hydroxy-TEMPO is 1:(2-2.5):(0.03-0.1):(0.03-0.1).

[0014] Compared with the prior art, the present application has the following beneficial effects: 1-octene-3-ol is isomerized in a mixed solvent of any one of tetrahydrofuran and acetonitrile and water under the catalysis of 3,4-dinitrobenzoic acid to obtain trans-2-octene-1-ol; and trans-2-octene-1-ol is oxidized under the action of meta-chloroiodobenzene, 4-hydroxy-TEMPO (4-hydroxy-2,2,6,6-tetramethylpiperidine nitroxyl radical) and peracetic acid to obtain trans-2-octenal. The preparation method has mild reaction conditions, simple operation, and does not need to use expensive reagents or catalysts, and has high product yield. BRIEF DESCRIPTION OF DRAWINGS

[0015] The drawings accompanying the specification of the present application serve to provide further understanding of the present application, and the illustrative embodiments of the present application and the description thereof serve to explain the present application, and do not constitute an improper limitation on the present application.

[0016] Figure 1 NMR hydrogen spectrum of trans-2-octenal synthesized in Example 1 of the present application. DETAILED DESCRIPTION

[0017] It should be noted that the following detailed description is exemplary in nature and is intended to provide further description of the application. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.

[0018] The technical solutions of the present application are further described below in conjunction with specific examples.

[0019] Example 1 A method for synthesizing trans-2-octenal, the synthetic route is as follows:

[0020] At 25°C, 1-octen-3-ol (1.28 g, 10 mmol) was added to 20 mL of tetrahydrofuran, 3,4-dinitrobenzoic acid (0.21 g, 1 mmol) was added, 2 mL of deionized water was added under stirring, and the reaction was carried out at 25°C for 12 h. The tetrahydrofuran was removed by rotary evaporation, 20 mL of dichloromethane was added, and the organic phase was collected by liquid-liquid extraction with 10 mL of saturated NaHCO3 aqueous solution and 10 mL of deionized water, respectively. The organic phase was dried with anhydrous sodium sulfate to obtain a dichloromethane solution of trans-2-octen-1-ol.

[0021] To the above-obtained dichloromethane solution of trans-2-octen-1-ol, m-chloroiodobenzene (0.12 g, 0.5 mmol) and 4-hydroxy-TEMPO (0.09 g, 0.5 mmol) were added, respectively, and the temperature was lowered to 0°C. Peroxyacetic acid (1.67 g, 20 mmol) was slowly added dropwise, and the addition was completed in 20 min. The temperature was raised to 30°C and stirred for 10 h. The temperature was lowered to room temperature, and the organic phase was collected by liquid-liquid extraction with 10 mL of saturated NaHCO3 aqueous solution and 10 mL of saturated brine, respectively. The solvent was removed by distillation under reduced pressure to obtain crude trans-2-octenal. The crude product was separated by column chromatography to obtain 0.91 g of trans-2-octenal, with a two-step yield of 72%.

[0022] The obtained trans-2-octenal had the following nuclear magnetic resonance hydrogen spectrum data: 1 H NMR (500 MHz, CDCl3) δ 9.52 (s,1H), 6.94 - 6.84 (m, 1H), 6.41 - 5.67 (m, 1H), 2.38 - 2.31 (m, 2H), 1.55 -1.50 (m, 2H), 1.37 - 1.31 (m, 4H), 0.94 - 0.89 (m, 3H).

[0023] Example 2 To 20 mL of tetrahydrofuran at 25 °C, 1-octen-3-ol (1.28 g, 10 mmol) was added, 3,4-dinitrobenzoic acid (0.21 g, 1 mmol) was added, 2 mL of deionized water was added under stirring, and the reaction was carried out at 25 °C for 12 h. Tetrahydrofuran was removed by rotary evaporation, 20 mL of dichloromethane was added, and the organic phase was collected by liquid-liquid extraction with 10 mL of saturated NaHCO3aqueous solution and 10 mL of deionized water, respectively. The organic phase was dried over anhydrous sodium sulfate to obtain a dichloromethane solution of trans-2-octen-1-ol.

[0024] To the above-obtained dichloromethane solution of trans-2-octen-1-ol, m-chloroiodobenzene (0.14 g, 0.6 mmol) and 4-hydroxy-TEMPO (0.1 g, 0.6 mmol) were added, respectively, and the temperature was lowered to 0 °C. Peroxyacetic acid (1.67 g, 20 mmol) was slowly added dropwise, and the reaction was carried out at 30 °C for 10 h. The temperature was lowered to room temperature, and the organic phase was collected by liquid-liquid extraction with 10 mL of saturated NaHCO3aqueous solution and 10 mL of saturated brine, respectively. The solvent was removed by distillation under reduced pressure to obtain a crude trans-2-octenal. The crude product was separated by column chromatography to obtain 0.79 g of trans-2-octenal with a two-step yield of 63%.

[0025] Example 3 To 20 mL of tetrahydrofuran at 25 °C, 1-octen-3-ol (1.28 g, 10 mmol) was added, 3,4-dinitrobenzoic acid (0.21 g, 1 mmol) was added, 2 mL of deionized water was added under stirring, and the reaction was carried out at 25 °C for 12 h. Tetrahydrofuran was removed by rotary evaporation, 20 mL of dichloromethane was added, and the organic phase was collected by liquid-liquid extraction with 10 mL of saturated NaHCO3aqueous solution and 10 mL of deionized water, respectively. The organic phase was dried over anhydrous sodium sulfate to obtain a dichloromethane solution of trans-2-octen-1-ol.

[0026] To the above-obtained dichloromethane solution of trans-2-octen-1-ol, m-chloroiodobenzene (0.14 g, 0.6 mmol) and 4-hydroxy-TEMPO (0.1 g, 0.6 mmol) were added, respectively, and the temperature was lowered to 0 °C. Peroxyacetic acid (1.67 g, 20 mmol) was slowly added dropwise, and the reaction was carried out at 30 °C for 10 h. The temperature was lowered to room temperature, and the organic phase was collected by liquid-liquid extraction with 10 mL of saturated NaHCO3aqueous solution and 10 mL of saturated brine, respectively. The solvent was removed by distillation under reduced pressure to obtain a crude trans-2-octenal. The crude product was separated by column chromatography to obtain 0.79 g of trans-2-octenal with a two-step yield of 63%.

[0027] Example 4 To the above obtained trans-2-octene-1-ol in chloroform solution was added m-chloroperbenzoic acid (0.12 g, 0.5 mmol) and 4-hydroxy-TEMPO (0.09 g, 0.5 mmol) respectively, the temperature was lowered to 0 °C, and peracetic acid (1.67 g, 20 mmol) was added dropwise slowly. The addition was completed in 20 min, the temperature was raised to 30 °C, and the mixture was stirred for 10 h. The temperature was lowered to room temperature, and the mixture was extracted with 10 mL of saturated NaHCO3 aqueous solution and 10 mL of saturated brine solution respectively. The organic phase was collected, and the solvent was removed by distillation under reduced pressure to obtain the crude trans-2-octenal. The crude product was separated by column chromatography to obtain 0.76 g of trans-2-octenal, with a two-step yield of 60%.

[0028] To the above obtained trans-2-octene-1-ol in chloroform solution was added m-chloroperbenzoic acid (0.12 g, 0.5 mmol) and 4-hydroxy-TEMPO (0.09 g, 0.5 mmol) respectively, the temperature was lowered to 0 °C, and peracetic acid (1.67 g, 20 mmol) was added dropwise slowly. The addition was completed in 20 min, the temperature was raised to 30 °C, and the mixture was stirred for 10 h. The temperature was lowered to room temperature, and the mixture was extracted with 10 mL of saturated NaHCO3 aqueous solution and 10 mL of saturated brine solution respectively. The organic phase was collected, and the solvent was removed by distillation under reduced pressure to obtain the crude trans-2-octenal. The crude product was separated by column chromatography to obtain 0.76 g of trans-2-octenal, with a two-step yield of 60%.

[0029] Example 5 To the above obtained trans-2-octene-1-ol in chloroform solution was added m-chloroperbenzoic acid (0.12 g, 0.5 mmol) and 4-hydroxy-TEMPO (0.09 g, 0.5 mmol) respectively, the temperature was lowered to 0 °C, and peracetic acid (1.67 g, 20 mmol) was added dropwise slowly. The addition was completed in 20 min, the temperature was raised to 30 °C, and the mixture was stirred for 10 h. The temperature was lowered to room temperature, and the mixture was extracted with 10 mL of saturated NaHCO3 aqueous solution and 10 mL of saturated brine solution respectively. The organic phase was collected, and the solvent was removed by distillation under reduced pressure to obtain the crude trans-2-octenal. The crude product was separated by column chromatography to obtain 0.76 g of trans-2-octenal, with a two-step yield of 60%.

[0030] To the above obtained trans-2-octene-1-ol in chloroform solution was added m-chloroperbenzoic acid (0.12 g, 0.5 mmol) and 4-hydroxy-TEMPO (0.09 g, 0.5 mmol) respectively, the temperature was lowered to 0 °C, and peracetic acid (1.67 g, 20 mmol) was added dropwise slowly. The addition was completed in 20 min, the temperature was raised to 30 °C, and the mixture was stirred for 10 h. The temperature was lowered to room temperature, and the mixture was extracted with 10 mL of saturated NaHCO3 aqueous solution and 10 mL of saturated brine solution respectively. The organic phase was collected, and the solvent was removed by distillation under reduced pressure to obtain the crude trans-2-octenal. The crude product was separated by column chromatography to obtain 0.76 g of trans-2-octenal, with a two-step yield of 60%.

[0031] Example 6 To the above obtained trans-2-octene-1-ol in dichloromethane solution, m-chloroperbenzoic acid (0.12 g, 0.5 mmol) and 4-hydroxy-TEMPO (0.09 g, 0.5 mmol) were added respectively, the temperature was lowered to 0 °C, and peracetic acid (1.67 g, 20 mmol) was added dropwise slowly. The addition was completed in 20 min, the temperature was raised to 30 °C, and the mixture was stirred for 10 h. The temperature was lowered to room temperature, and 10 mL of saturated NaHCO3 aqueous solution and 10 mL of saturated brine were added respectively. The organic phase was collected, and the solvent was removed by distillation under reduced pressure to obtain the crude trans-2-octenal. The crude product was separated by column chromatography to obtain 0.81 g of trans-2-octenal, with a two-step yield of 64%.

[0032] To the above obtained trans-2-octene-1-ol in dichloromethane solution, m-chloroperbenzoic acid (0.12 g, 0.5 mmol) and 4-hydroxy-TEMPO (0.09 g, 0.5 mmol) were added respectively, the temperature was lowered to 0 °C, and peracetic acid (1.67 g, 20 mmol) was added dropwise slowly. The addition was completed in 20 min, the temperature was raised to 30 °C, and the mixture was stirred for 10 h. The temperature was lowered to room temperature, and 10 mL of saturated NaHCO3 aqueous solution and 10 mL of saturated brine were added respectively. The organic phase was collected, and the solvent was removed by distillation under reduced pressure to obtain the crude trans-2-octenal. The crude product was separated by column chromatography to obtain 0.81 g of trans-2-octenal, with a two-step yield of 64%.

[0033] Comparative Example 1 (different from Example 1 in that the solvent is tetrahydrofuran) To the above obtained trans-2-octene-1-ol in dichloromethane solution, m-chloroperbenzoic acid (0.12 g, 0.5 mmol) and 4-hydroxy-TEMPO (0.09 g, 0.5 mmol) were added respectively, the temperature was lowered to 0 °C, and peracetic acid (1.67 g, 20 mmol) was added dropwise slowly. The addition was completed in 20 min, the temperature was raised to 30 °C, and the mixture was stirred for 10 h. The temperature was lowered to room temperature, and 10 mL of saturated NaHCO3 aqueous solution and 10 mL of saturated brine were added respectively. The organic phase was collected, and the solvent was removed by distillation under reduced pressure to obtain the crude trans-2-octenal. The crude product was separated by column chromatography to obtain 0.81 g of trans-2-octenal, with a two-step yield of 64%.

[0034] To the above obtained trans-2-octene-1-ol in dichloromethane solution, m-chloroperbenzoic acid (0.12 g, 0.5 mmol) and 4-hydroxy-TEMPO (0.09 g, 0.5 mmol) were added respectively, the temperature was lowered to 0 °C, and peracetic acid (1.67 g, 20 mmol) was added dropwise slowly. The addition was completed in 20 min, the temperature was raised to 30 °C, and the mixture was stirred for 10 h. The temperature was lowered to room temperature, and 10 mL of saturated NaHCO3 aqueous solution and 10 mL of saturated brine were added respectively. The organic phase was collected, and the solvent was removed by distillation under reduced pressure to obtain the crude trans-2-octenal. The crude product was separated by column chromatography to obtain 0.81 g of trans-2-octenal, with a two-step yield of 64%.

[0035] Comparative Example 2 (different from Example 1 in that 4-hydroxy-TEMPO is not added) At 25°C, 1-octen-3-ol (1.28 g, 10 mmol) was added to 20 mL of tetrahydrofuran, followed by 3,4-dinitrobenzoic acid (0.21 g, 1 mmol). 2 mL of deionized water was added while stirring, and the mixture was reacted at 25°C for 12 h. The tetrahydrofuran was removed by rotary evaporation, and 20 mL of dichloromethane was added. The mixture was extracted and separated using 10 mL of saturated NaHCO3 aqueous solution and 10 mL of deionized water, respectively. The organic phase was collected and dried over anhydrous sodium sulfate to obtain a dichloromethane solution of trans-2-octen-1-ol.

[0036] To the dichloromethane solution of trans-2-octen-1-ol obtained above, m-chloroiodobenzene (0.12 g, 0.5 mmol) was added, the temperature was lowered to 0 °C, and peracetic acid (1.67 g, 20 mmol) was slowly added dropwise over 20 min. The temperature was then raised to 30 °C and stirred for 10 hours. After cooling to room temperature, the mixture was extracted and separated using 10 mL of saturated NaHCO3 aqueous solution and 10 mL of saturated saline solution, respectively. The organic phase was collected, and the solvent was removed by vacuum distillation to obtain crude trans-2-octenal. The crude product was then separated by column chromatography to obtain trans-2-octenal. The two-step yield was 17%.

[0037] Comparative Example 3 (different from Example 1 in that it does not contain m-chloroiodobenzene) At 25°C, 1-octen-3-ol (1.28 g, 10 mmol) was added to 20 mL of tetrahydrofuran, followed by 3,4-dinitrobenzoic acid (0.21 g, 1 mmol). 2 mL of deionized water was added while stirring, and the mixture was reacted at 25°C for 12 h. The tetrahydrofuran was removed by rotary evaporation, and 20 mL of dichloromethane was added. The mixture was extracted and separated using 10 mL of saturated NaHCO3 aqueous solution and 10 mL of deionized water, respectively. The organic phase was collected and dried over anhydrous sodium sulfate to obtain a dichloromethane solution of trans-2-octen-1-ol.

[0038] Add 4-hydroxy-TEMPO (0.09 g, 0.5 mmol) to the dichloromethane solution of trans-2-octen-1-ol obtained above, cool to 0 °C, slowly add peracetic acid (1.67 g, 20 mmol) dropwise, and complete the addition in 20 min. Heat to 30 °C and stir for 10 hours. Cool to room temperature, extract and separate the liquid with 10 mL of saturated NaHCO3 aqueous solution and 10 mL of saturated saline solution, respectively. Collect the organic phase, remove the solvent by vacuum distillation, and obtain crude trans-2-octenal. Separate the crude product by column chromatography to obtain trans-2-octenal. The two-step yield is 8%.

[0039] Comparative Example 4 (different from Example 1 in that peracetic acid was not added) To 20 mL of tetrahydrofuran at 25 °C, 1-octen-3-ol (1.28 g, 10 mmol) was added, 3,4-dinitrobenzoic acid (0.21 g, 1 mmol) was added, 2 mL of deionized water was added under stirring, and the reaction was carried out at 25 °C for 12 h. The tetrahydrofuran was removed by rotary evaporation, 20 mL of dichloromethane was added, and the organic phase was collected by extraction with 10 mL of saturated NaHCO3aqueous solution and 10 mL of deionized water, respectively. The organic phase was dried over anhydrous sodium sulfate to obtain a dichloromethane solution of trans-2-octen-1-ol.

[0040] To the dichloromethane solution of trans-2-octen-1-ol obtained above, m-chloroiodobenzene (0.12 g, 0.5 mmol) and 4-hydroxy-TEMPO (0.09 g, 0.5 mmol) were added, respectively, and the reaction was carried out at 30 °C under stirring. No reaction occurred.

[0041] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. The present application can be variously changed and modified by those skilled in the art. Any modification, equivalent replacement, improvement, etc. within the spirit and principle of the present application shall be included in the scope of protection of the present application.

Claims

1. A method for synthesizing trans-2-octenal, characterized in that, include: S1. Dissolve 1-octen-3-ol and 3,4-dinitrobenzoic acid in a solvent and undergo an isomerization reaction to obtain trans-2-octen-1-ol; S2, trans-2-octen-1-ol, is oxidized by m-chloroiodobenzene, 4-hydroxy-2,2,6,6-tetramethylpiperidine nitric oxide radical, and peracetic acid to yield trans-2-octenal.

2. The synthesis method according to claim 1, characterized in that, In step S1, the solvent is a mixture of tetrahydrofuran and acetonitrile with water, and the volume ratio of tetrahydrofuran or acetonitrile to water is 5~15:

1.

3. The synthesis method as described in claim 2, characterized in that, In step S1, the volume ratio of tetrahydrofuran or acetonitrile to water is 8~12:1; preferably 10:

1.

4. The synthesis method according to claim 1, characterized in that, In step S1, the molar ratio of 1-octen-3-ol and 3,4-dinitrobenzoic acid is 1:(0.01~0.15).

5. The synthesis method according to claim 1, characterized in that, In step S1, the reaction temperature is 20~60℃, preferably 20-45℃.

6. The synthesis method according to claim 1, characterized in that, In step S1, the reaction time is 8-15 hours, preferably 10-15 hours.

7. The synthesis method according to claim 1, characterized in that, In step S2, the solvent is any one of dichloromethane, chloroform, and dichloroethane.

8. The synthesis method according to claim 1, characterized in that, In step S2, the reaction temperature is 30~75℃, preferably 30~60℃, and more preferably 30-40℃.

9. The synthesis method according to claim 1, characterized in that, In step S2, the reaction time is 8-15 hours, preferably 10-12 hours.

10. The synthesis method according to claim 1, characterized in that, The molar ratio of 1-octen-3-ol, peracetic acid, m-chloroiodobenzene and 4-hydroxy-2,2,6,6-tetramethylpiperidine nitroxide radical is 1:(2~2.5):(0.03~0.1):(0.03~0.1).

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