Preparation method of 3-formyl-5, 6-dihydro-2, 6-dipropyl-2H-pyran

Abstract

The invention discloses a preparation method of 3-formyl-5, 6-dihydro-2, 6-dipropyl-2H-# imgabs0 # pyrans, and belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 3-formyl-5, 6-dihydro-2, 6-dipropyl-2H-# imgabs0 # pyrans. The preparation method comprises the following steps: carrying out an addition reaction on 2-hexene-aldehyde serving as a raw material and hydrogen chloride, carrying out substitution with sodium thiosulfate in the presence of a phase catalyst to prepare a Bunte salt, hydrolyzing under an acidic condition by a one-pot method, and directly carrying out condensation cyclization on the Bunte salt and 2-hexenal to obtain 3-formyl-5, 6-dihydro-2, 6-dipropyl-2, 6-dipropyl-2, 6-dipropyl-2H-# imgabs1 # pyrane. The raw materials used in the route are cheap and easy to obtain, the use safety is high, industrial production is convenient, the yield is high and can reach 89%, and the method is suitable for industrial large-scale production.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a method for preparing 3-formyl-5,6-dihydro-2,6-dipropyl-2H-furan. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] 3-Formyl-5,6-dihydro-2,6-dipropyl-2H-pyran has a strong fruity, green, minty and unique tropical aroma, and is widely used in food, chewing gum, perfume, cosmetics, oral and pharmaceutical products for flavoring and flavoring. There are few reports on its synthesis, mainly based on two patents for the synthesis of this compound.

[0004] Patent EP3025591A1 discloses the use of 3-acetylthio-1-hexanal in the presence of sodium methoxide for the cyclization synthesis of 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran. The raw material in this synthesis route is relatively expensive thioacetic acid, and column chromatography purification is required, resulting in a complicated treatment process.

[0005] Patent US4629799A discloses the synthesis of 3-formyl-5,6-dihydro-2,6-dimethyl-2H-pyran by condensation of hydrogen sulfide and olefinic aldehyde. The synthesis method can be used to prepare 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran according to the description. However, the synthesis method requires the use of highly toxic hydrogen sulfide gas, which poses a high safety risk.

[0006] Therefore, it is necessary to develop a new synthetic route for 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran, starting from low-cost raw materials, to simply, safely and efficiently synthesize 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran. Summary of the invention

[0007] In order to solve the shortcomings of the prior art, the purpose of the present invention is to provide a method for preparing 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran. The method for preparing 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran provided by the present invention has the advantages of cheap and readily available raw materials, high safety, high yield, etc.

[0008] In order to achieve the above object, the technical solution of the present invention is:

[0009] In a first aspect of the present invention, a method for preparing 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran is provided, comprising:

[0010] 3-Chloro-1-hexanal reacts with sodium thiosulfate to obtain an intermediate;

[0011] The intermediate reacts with 2-hexenal to obtain 3-formyl-5,6-dihydro-2,6-dipropyl-2H-furan;

[0012] The structure of the intermediate is:

[0013]

[0014] The synthetic route of the present invention is as follows:

[0015]

[0016] In some embodiments of the present invention, the molar ratio of 3-chloro-1-hexanal, sodium thiosulfate and 2-hexenal is 1:(1-1.5):(1-1.5).

[0017] In some embodiments of the present invention, the preparation method comprises:

[0018] Under the catalysis of a phase catalyst, 3-chloro-1-hexanal reacts with sodium thiosulfate to obtain an intermediate;

[0019] The intermediate is hydrolyzed under acidic conditions and then reacted with 2-hexenal to obtain 3-formyl-5,6-dihydro-2,6-dipropyl-2H-furan.

[0020] In some embodiments of the present invention, the intermediate may be isolated or not isolated before participating in the reaction with 2-hexenal.

[0021] In some embodiments of the present invention, the phase catalyst is selected from one of benzyltriethylammonium chloride (TEBA), tetrabutylammonium bromide (TBAB), tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, polyethylene glycol 2000 (PEG2000) or cyclodextrin, preferably TBAB, with high yield.

[0022] In some embodiments of the present invention, the amount of the catalyst is 1-5% of the amount of 3-chloro-1-hexanal, specifically 1%, 2%, 3%, 4%, 5%, etc., preferably 3%.

[0023] In some embodiments of the present invention, the acidic condition is that the pH of the reaction system is 1-2.

[0024] In some embodiments of the present invention, the preparation method further comprises the step of separating and purifying the intermediate after the reaction with 2-hexenal is completed to obtain 3-formyl-5,6-dihydro-2,6-dipropyl-2H-furan;

[0025] The separation and purification method comprises the following steps: after the reaction of the intermediate and 2-hexenal is completed, dichloromethane is added to the reaction system for liquid-liquid extraction, the organic phase is collected, washed, the solvent is removed, and distilled.

[0026] In some embodiments of the present invention, the preparation method further comprises the following steps:

[0027] 3-Chloro-1-hexanal is obtained by reacting 2-hexenal with hydrogen chloride.

[0028] In some embodiments of the present invention, the molar ratio of 2-hexenal to hydrogen chloride is 1:(1-1.5).

[0029] The beneficial effects of the present invention are:

[0030] The invention provides a novel preparation method of 3-formyl-5,6-dihydro-2,6-dipropyl-2H-furan, which uses 2-hexene-aldehyde as a raw material, first performs an addition reaction with hydrogen chloride, then performs substitution with sodium thiosulfate in the presence of a phase catalyst to prepare Bunte salt, and finally performs hydrolysis under acidic conditions by a pot method, and then directly condenses with 2-hexenal to form a ring, thereby obtaining 3-formyl-5,6-dihydro-2,6-dipropyl-2H-furan. The raw materials used in the route are cheap and easy to obtain, the use safety is high, the industrial production is convenient, the yield is high, and the yield can reach 89%, and the route is suitable for industrial large-scale production. DETAILED DESCRIPTION

[0031] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below in conjunction with specific embodiments.

[0032] Example 1

[0033] A method for preparing 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran, the synthetic route is as follows:

[0034]

[0035] The specific method includes the following steps:

[0036] (1) In a 500 mL three-necked flask equipped with a thermometer and a reflux condenser, 250 g of dichloromethane and 147 g (1.5 mol) of 2-hexenal were added, accompanied by deep cooling, and the reaction temperature was controlled at 15-20° C. 60 g (1.65 mol) of hydrogen chloride gas was introduced. After the addition was completed, the reaction was continued with stirring for 2 h. The solvent was removed to obtain 196 g of 3-chloro-1-hexanal intermediate with a purity of 97.5% and a yield of 96%, which could be directly used in the next step of synthesis.

[0037] (2) In a 1000 mL three-necked flask, add 150 g of water, 20 g of ethanol, 100 g (0.74 mol) of the intermediate 3-chloro-1-hexanal, and then add 7.2 g (0.03 eq) of the phase transfer catalyst TBAB. Control the kettle temperature at 42-46 °C and add 430 g of 30% (0.82 mol) of sodium thiosulfate aqueous solution, after completion of dropwise addition, continue to stir and react for 4 hours; add 115g (0.82 mol) of 2-hexenal dropwise, continue to add 32% hydrochloric acid dropwise, adjust the pH of the reaction solution to 1-2, after completion of dropwise addition, keep the reaction at 42-46°C for 3 hours, cool to room temperature, extract twice with 300g of dichloromethane respectively, wash once with 100g of saturated sodium bicarbonate aqueous solution, desolventize to obtain 161.6g of crude product, distill, collect the fraction at 105-108°C under 1mmHg, and obtain 146.1g of 3-formyl-5,6-dihydro-2,6-dipropyl-2H-furan with a purity of 99.2% and a yield of 93%.

[0038] H NMR

[0039] 1 H NMR (CDCl3, 400MHz): 9.32 (s, 1H), 6.79 (dd, 1H, J = 5.3, 2.8Hz), 3.51 (m, 1H), 2.92-3.05 (m, 1H), 2. 61-2.75(m,1H), 2.22-2.38(m,1H), 1.35-1.7(6m,8H), 0.95(t,3H,J=7.1Hz), 0.93(t3H,J=6.9Hz).

[0040] Example 2

[0041] A method for preparing 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran comprises the following steps:

[0042] (1) In a 500 mL three-necked flask equipped with a thermometer and a reflux condenser, 250 g of dichloromethane and 147 g (1.5 mol) of 2-hexenal were added, accompanied by deep cooling, and the reaction temperature was controlled at 15-20° C. 54.5 g (1.5 mol) of hydrogen chloride gas was introduced. After the addition was completed, the reaction was continued with stirring for 2 h. The solvent was removed to obtain 179 g of 3-chloro-1-hexanal intermediate with a purity of 95.2% and a yield of 85.6%, which could be directly used in the next step of synthesis.

[0043] (2) In a 1000 mL three-necked flask, add 150 g of water, 20 g of ethanol, 100 g (0.74 mol) of the intermediate 3-chloro-1-hexanal, and then add 7.2 g (0.03 eq) of the phase transfer catalyst TBAB. Control the kettle temperature at 42-46° C. and add dropwise 38830% (0.74 mol) of sodium thiosulfate aqueous solution. After the addition is complete, continue to stir and react for 4 h; add dropwise 104 g (0.74 mol) of 2-hexenal, and continue to add dropwise 32% of salt. Acid, adjust the pH of the reaction solution to 1-2, after dropping, keep the reaction at 42-46 ° C for 3h, cool to room temperature, extract twice with 300g of dichloromethane respectively, wash once with 100g of saturated sodium bicarbonate aqueous solution, desolventize to obtain 161.6g of crude product, distill, collect the fraction at 105-108 ° C under 1mmHg, and obtain 131g of 3-formyl-5,6-dihydro-2,6-dipropyl-2H-furan with a purity of 99.1% and a yield of 83.4%.

[0044] The H NMR spectrum of 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran obtained in Example 2 is consistent with that in Example 1.

[0045] Example 3

[0046] A method for preparing 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran comprises the following steps:

[0047] (1) In a 500 mL three-necked flask equipped with a thermometer and a reflux condenser, 250 g of dichloromethane and 147 g (1.5 mol) of 2-hexenal were added, accompanied by deep cooling, and the reaction temperature was controlled at 15-20° C. 82 g (2.25 mol) of hydrogen chloride gas was introduced. After the addition was completed, the reaction was continued with stirring for 2 h. The solvent was removed to obtain 188 g of 3-chloro-1-hexanal intermediate with a purity of 94.6% and a yield of 89.3%, which could be directly used in the next step of synthesis.

[0048] (2) In a 1000 mL three-necked flask, add 150 g of water, 20 g of ethanol, 100 g (0.74 mol) of the intermediate 3-chloro-1-hexanal, and then add 7.2 g (0.03 eq) of the phase transfer catalyst TBAB. Control the kettle temperature at 42-46 °C and add 582 g of 30% (1.11 mol) of sodium thiosulfate aqueous solution, after completion of dropwise addition, continue to stir and react for 4 hours; add 155g (1.11 mol) of 2-hexenal dropwise, continue to add 32% hydrochloric acid dropwise, adjust the pH of the reaction solution to 1-2, after completion of dropwise addition, keep the reaction at 42-46°C for 3 hours, cool to room temperature, extract twice with 300g of dichloromethane respectively, wash once with 100g of saturated sodium bicarbonate aqueous solution, desolventize to obtain 161.6g of crude product, distill, collect the fraction at 105-108°C under 1mmHg, and obtain 141g of 3-formyl-5,6-dihydro-2,6-dipropyl-2H-furan with a purity of 99.1% and a yield of 89.8%.

[0049] The H NMR spectrum of 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran obtained in Example 3 is consistent with that in Example 1.

[0050] Example 4

[0051] A method for preparing 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran is different from Example 1 in that the phase transfer catalyst is TEBA, and the remaining steps are consistent with Example 1. Finally, 139 g of 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran is obtained with a purity of 99.1% and a yield of 88.5%.

[0052] The H NMR spectrum of 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran obtained in Example 4 is consistent with that in Example 1.

[0053] Example 5

[0054] A method for preparing 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran is different from Example 1 in that the phase transfer catalyst is tetrabutylammonium chloride, and the remaining steps are consistent with Example 1. Finally, 143 g of 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran is obtained with a purity of 99.2% and a yield of 91.1%.

[0055] The H NMR spectrum of 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran obtained in Example 5 is consistent with that in Example 1.

[0056] Example 6

[0057] A method for preparing 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran is different from Example 1 in that the phase transfer catalyst is tetrabutylammonium hydrogen sulfate, and the remaining steps are consistent with Example 1. Finally, 135 g of 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran is obtained with a purity of 99.0% and a yield of 86.0%.

[0058] The H NMR spectrum of 3-formyl-5,6-dihydro-2,6-dipropyl-2H-pyran obtained in Example 6 is consistent with that in Example 1.

[0059] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A 3-formyl-5,6-dihydro-2,6-dipropyl-2H- The method for preparing fumaran is characterized in that: include: 3-Chloro-1-hexanal reacts with sodium thiosulfate to obtain an intermediate; The intermediate reacts with 2-hexenal to obtain 3-formyl-5,6-dihydro-2,6-dipropyl-2H- mumble; The structure of the intermediate is:

2. The preparation method according to claim 1, characterized in that The molar ratio of 3-chloro-1-hexanal, sodium thiosulfate and 2-hexenal is 1:(1-1.5):(1-1.5).

3. The preparation method according to claim 1, characterized in that: The preparation method comprises: Under the catalysis of a phase catalyst, 3-chloro-1-hexanal reacts with sodium thiosulfate to obtain an intermediate; The intermediate was hydrolyzed under acidic conditions and reacted with 2-hexenal to obtain 3-formyl-5,6-dihydro-2,6-dipropyl-2H- Mumble.

4. The preparation method according to claim 3, characterized in that: The intermediate can be isolated or not and then be used in the reaction with 2-hexenal.

5. The preparation method according to claim 3, characterized in that: The phase catalyst is selected from one of benzyltriethylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium chloride, tetrabutylammonium hydrogen sulfate, polyethylene glycol 2000 and cyclodextrin.

6. The preparation method according to claim 3, characterized in that: The amount of the catalyst is 1-5% of the amount of 3-chloro-1-hexanal.

7. The preparation method according to claim 3, characterized in that: The acidic condition is that the pH of the reaction system is 1-2.

8. The preparation method according to claim 3, characterized in that: The preparation method also includes separating and purifying the intermediate after the reaction with 2-hexenal to obtain 3-formyl-5,6-dihydro-2,6-dipropyl-2H- The steps of humming; The separation and purification method comprises the following steps: after the reaction of the intermediate and 2-hexenal is completed, dichloromethane is added to the reaction system for liquid-liquid extraction, the organic phase is collected, washed, the solvent is removed, and distilled.

9. The preparation method according to any one of claims 1 to 8, characterized in that: The preparation method further comprises the following steps: 3-Chloro-1-hexanal is obtained by reacting 2-hexenal with hydrogen chloride.

10. The preparation method according to claim 9, characterized in that: The molar ratio of 2-hexenal to hydrogen chloride is 1:(1-1.5).

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