A method for synthesizing trans-2-octenal

Abstract

The application belongs to the technical field of medicine and spice synthesis, and particularly relates to a synthesis method of trans-2-octenal. The synthesis method comprises the following steps: 1-octene-3-ol is subjected to isomerization reaction under the catalysis of 3,4-dinitrobenzoic acid to obtain a trans-2-octene-1-ol intermediate; and the trans-2-octene-1-ol is subjected to oxidation by interchloroiodobenzene, 4-hydroxy-TEMPO (4-hydroxy-2,2,6,6-tetramethylpiperidinooxy) and peroxoacetic acid to obtain the trans-2-octenal. The preparation method has mild reaction conditions, simple operation and does not need to use 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 high-priced raw materials such as Witting reagent, boron trifluoride and its ether complex, etc., 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 perspective 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 during storage and transportation. 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 provided by the present application 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:

[0007] A synthesis method of trans-2-octenal, comprising the following steps:

[0008]

[0009] S1, dissolving 1-octen-3-ol and a catalytic amount of 3,4-dinitrobenzoic acid in a solvent to occur isomerization reaction to obtain trans-2-octen-1-ol;

[0010] 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 nitroxide radical) and peracetic acid.

[0011] 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.

[0012] 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).

[0013] 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.

[0014] Preferably, in step S2, the solvent is one of dichloromethane, chloroform and dichloroethane.

[0015] 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.

[0016] 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).

[0017] Compared with the prior art, the present application has the following beneficial effects:

[0018] 1-octene-3-ol is subjected to isomerization reaction 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 subjected to oxidation under the action of meta-chloroiodobenzene, 4-hydroxy-TEMPO (4-hydroxy-2,2,6,6-tetramethylpiperidine nitroxide radical) and peracetic acid, to obtain trans-2-octene aldehyde. 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

[0019] The drawings constituting a part of 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 improper limitations on the present application.

[0020] Figure 1The nuclear magnetic hydrogen spectrum of trans-2-octenal synthesized in Example 1 of the present application. DETAILED DESCRIPTION

[0021] 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.

[0022] The technical solutions of the present application are further described below in combination with specific examples.

[0023] Example 1

[0024] A method for synthesizing trans-2-octenal, the synthetic route is as follows:

[0025]

[0026] At 25°C, 1-octene-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 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-octene-1-ol.

[0027] To the above-obtained dichloromethane solution of trans-2-octene-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 the mixture was stirred for 10 h. The temperature was lowered to room temperature, and the organic phase was collected by 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%.

[0028] The nuclear magnetic hydrogen spectrum data of the obtained trans-2-octenal are as follows: 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).

[0029] Example 2

[0030] To 20 mL of acetonitrile 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.

[0031] 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 reaction was cooled 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%.

[0032] Example 3

[0033] To 20 mL of acetonitrile 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.

[0034] 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 reaction was cooled 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%.

[0035] Example 4

[0036] To 20 mL of tetrahydrofuran was added 1-octen-3-ol (1.28 g, 10 mmol) at 25 °C, 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 15 h. Tetrahydrofuran was removed by rotary evaporation, 20 mL of dichloromethane was added, and the organic phase was collected by liquid-liquid extraction using 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.

[0037] To the above-obtained dichloromethane solution of trans-2-octen-1-ol was added m-chloroiodobenzene (0.12 g, 0.5 mmol) and 4-hydroxy-TEMPO (0.09 g, 0.5 mmol), 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 12 h. The temperature was lowered to room temperature, and the organic phase was collected by liquid-liquid extraction using 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 0.85 g of trans-2-octenal with a two-step yield of 67%.

[0038] Example 5

[0039] To 20 mL of tetrahydrofuran was added 1-octen-3-ol (1.28 g, 10 mmol) at 25 °C, 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 chloroform was added, and the organic phase was collected by liquid-liquid extraction using 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 chloroform solution of trans-2-octen-1-ol.

[0040] To the above-obtained chloroform solution of trans-2-octen-1-ol was added m-chloroiodobenzene (0.12 g, 0.5 mmol) and 4-hydroxy-TEMPO (0.09 g, 0.5 mmol), 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 using 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 0.76 g of trans-2-octenal with a two-step yield of 60%.

[0041] Example 6

[0042] 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 40 °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.

[0043] 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 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 0.81 g of trans-2-octenal with a two-step yield of 64%.

[0044] Comparative Example 1 (differing from Example 1 in that the solvent is tetrahydrofuran)

[0045] 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 40 °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.

[0046] 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 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 0.81 g of trans-2-octenal with a two-step yield of 64%.

[0047] Comparative Example 2 (differing from Example 1 in that 4-hydroxy-TEMPO is not added)

[0048] 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. Tetrahydrofuran was removed by rotary evaporation, 20 mL of dichloromethane was added, and the organic phase was collected by liquid-liquid extraction using 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.

[0049] To the above-obtained dichloromethane solution of trans-2-octen-1-ol, m-chloroiodobenzene (0.12 g, 0.5 mmol) was added, and the temperature was lowered to 0°C. Peroxyacetic acid (1.67 g, 20 mmol) was slowly added dropwise, and the temperature was raised to 30°C for stirring for 10 h. The temperature was lowered to room temperature, and the organic phase was collected by liquid-liquid extraction using 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 trans-2-octenal. The two-step yield was 17%.

[0050] Comparative Example 3 (differing from Example 1 in that m-chloroiodobenzene is not added)

[0051] 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. Tetrahydrofuran was removed by rotary evaporation, 20 mL of dichloromethane was added, and the organic phase was collected by liquid-liquid extraction using 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.

[0052] To the above-obtained dichloromethane solution of trans-2-octen-1-ol, 4-hydroxy-TEMPO (0.09 g, 0.5 mmol) was added, and the temperature was lowered to 0°C. Peroxyacetic acid (1.67 g, 20 mmol) was slowly added dropwise, and the temperature was raised to 30°C for stirring for 10 h. The temperature was lowered to room temperature, and the organic phase was collected by liquid-liquid extraction using 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 trans-2-octenal. The two-step yield was 8%.

[0053] Comparative Example 4 (differing from Example 1 in that peroxyacetic acid is not added)

[0054] To 20 mL of tetrahydrofuran was added 1-octene-3-ol (1.28 g, 10 mmol) at 25 °C, 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 using 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-octene-1-ol.

[0055] To the dichloromethane solution of trans-2-octene-1-ol obtained above was added m-chloroiodobenzene (0.12 g, 0.5 mmol) and 4-hydroxy-TEMPO (0.09 g, 0.5 mmol), respectively, and the reaction was carried out at 30 °C under stirring. No reaction occurred.

[0056] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Various modifications and changes can be made by those skilled in the art based on the spirit and principles of the present application. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope 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 allow them to undergo an isomerization reaction to obtain trans-2-octen-1-ol; the reaction temperature is 20~60℃ and the reaction time is 8~15h. 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 trans-2-octenal; the reaction temperature is 30~75℃ and the reaction time is 8~15h.

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.

4. The synthesis method according to claim 2, characterized in that, In step S1, the volume ratio of tetrahydrofuran or acetonitrile to water is 10:

1.

5. 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).

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

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

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

9. The synthesis method according to claim 1, characterized in that, In step S2, the reaction temperature is 30~60℃.

10. The synthesis method according to claim 1, characterized in that, In step S2, the reaction temperature is 30-40℃.

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

12. 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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