阅读说明：本技术 一种γ-壬烯内酯的合成方法 (Method for synthesizing gamma-nonene lactone ) 是由 王天义 范一义 汪洋 张政 吴旭 何云飞 汪炎 于 2021-07-26 设计创作，主要内容包括：本发明涉及一种γ-壬烯内酯的合成方法,属于香料合成技术领域,第一步、将丙二酸加入装有冷凝管和分水器的四口烧瓶中,加入哌啶,然后在95-105℃条件下,加入庚醛,升温,反应得到中间体1；第二步、将乙酸和双氧水混合,搅拌滴加中间体1,控制温度为40℃,反应得到中间体2；第三步、将中间体2、二氯甲烷和三乙胺混合,滴加乙酰氯,滴加结束后,反应得到γ-壬烯内酯。本发明的第一步中未使用溶剂,减少反应成本；中间体1在乙酸和双氧水的作用下关环,采用双氧水作氧化剂,具有环境友好的优点；用乙酰氯代替甲烷磺酰氯,在保证了产率的情况下,减少了甲烷磺酰氯的使用,更加安全,整个反应过程简单,路线较短,原料易得。(The invention relates to a method for synthesizing gamma-nonene lactone, which belongs to the technical field of perfume synthesis, and comprises the following steps of firstly, adding malonic acid into a four-neck flask provided with a condenser and a water separator, adding piperidine, then adding heptaldehyde at the temperature of 95-105 ℃, heating, and reacting to obtain an intermediate 1; secondly, mixing acetic acid and hydrogen peroxide, stirring and dropwise adding the intermediate 1, controlling the temperature to be 40 ℃, and reacting to obtain an intermediate 2; and thirdly, mixing the intermediate 2, dichloromethane and triethylamine, dropwise adding acetyl chloride, and reacting to obtain the gamma-nonene lactone after dropwise adding. In the first step of the method, a solvent is not used, so that the reaction cost is reduced; the intermediate 1 is subjected to ring closing under the action of acetic acid and hydrogen peroxide, and hydrogen peroxide is used as an oxidant, so that the method has the advantage of environmental friendliness; the acetyl chloride is used for replacing methane sulfonyl chloride, so that the use of methane sulfonyl chloride is reduced under the condition of ensuring the yield, the method is safer, the whole reaction process is simple, the route is shorter, and the raw materials are easy to obtain.)

1. A method for synthesizing gamma-nonene lactone is characterized by comprising the following steps:

step one, adding malonic acid into a four-neck flask provided with a condenser and a water separator, adding piperidine, then adding heptaldehyde at the temperature of 95-105 ℃, heating to 145 ℃ after adding, and reacting to obtain an intermediate 1;

secondly, mixing acetic acid and hydrogen peroxide, stirring for 10min, dropwise adding the intermediate 1, controlling the temperature to be 40 ℃ after dropwise adding, and reacting for 5h to obtain an intermediate 2;

and thirdly, mixing the intermediate 2, dichloromethane and triethylamine, dropwise adding acetyl chloride at 0 ℃, heating to 25 ℃ after dropwise adding, and reacting for 5 hours to obtain the gamma-nonene lactone.

2. The method for synthesizing gamma-nonenolactone according to claim 1, wherein in the first step, the reaction is stopped until the water content in the water separator is not increased any more.

3. The method for synthesizing gamma-nonenolactone according to claim 1, wherein the temperature is controlled within a range of 20 to 40 ℃ during the dropwise addition of the intermediate 1 in the second step.

4. The method for synthesizing gamma-nonenolactone according to claim 1, wherein the dropping speed is controlled so that the temperature of the system is maintained at 0 to 5 ℃ during the dropping of acetyl chloride in the third step.

5. The method for synthesizing gamma-nonenolactone according to claim 1, wherein the molar ratio of the malonic acid to the heptanal to the piperidine is 2.5 mol: 1 mol: 1 mmol.

6. The method for synthesizing gamma-nonenolactone according to claim 1, wherein the dosage ratio of acetic acid, hydrogen peroxide and intermediate 1 is 100 mL: 35mL of: 22-25 g; the mass fraction of the hydrogen peroxide is 30 percent.

7. The method for synthesizing gamma-nonenolactone according to claim 1, wherein the amount ratio of the intermediate 2, acetyl chloride, dichloromethane and triethylamine is 24-25 g: 0.21 mol: 100mL of: 44 mL.

Technical Field

The invention belongs to the technical field of perfume synthesis, and particularly relates to a synthesis method of gamma-nonene lactone.

Background

Gamma-nonene lactone, 2-nonene-gamma-lactone, is present in volatile components of various foods and plant extracts, such as beef/vegetable soup, sunflower seed oil, noodles, watermelon, potato chips, lard, mushroom, french fries, primrose, flue-cured tobacco leaves, etc., and has coconut flavor and sweet flavor; is a very important edible flavor and is widely used in various beverages, baked goods and desserts.

The gamma-nonene lactone belongs to alpha, beta-unsaturated gamma-lactone, the alpha, beta-unsaturated gamma-lactone is a structural unit of a plurality of natural products with biological activity, and a plurality of documents report the synthetic methods of the gamma-nonene lactone, and the methods have defects of different degrees, such as long route, difficult obtainment of reaction raw materials, low yield and the like, so the preparation method of the gamma-nonene lactone with simple operation, high yield and low cost still needs to be further explored.

Disclosure of Invention

The invention aims to provide a method for synthesizing gamma-nonene lactone.

The purpose of the invention can be realized by the following technical scheme:

a method for synthesizing gamma-nonene lactone comprises the following steps:

step one, adding malonic acid into a four-neck flask provided with a condenser and a water separator, adding piperidine, then adding heptaldehyde at the temperature of 95-105 ℃, after the addition is finished, heating to 145 ℃, and stopping the reaction until the water content in the water separator is not increased any more, so as to obtain an intermediate 1; carrying out condensation reaction on malonic acid and heptaldehyde serving as raw materials to prepare an intermediate 1; wherein the molar ratio of the use amount of the malonic acid to the use amount of the heptaldehyde to the use amount of the piperidine is 2.5 mol: 1mo l: 1mmo l.

The reaction process is as follows:

step two, mixing acetic acid and 30 mass percent hydrogen peroxide, stirring for 10m in, dropwise adding the intermediate 1, controlling the temperature to be 20-40 ℃ in the dropwise adding process, controlling the temperature to be 40 ℃ after dropwise adding, reacting for 5h, cooling reaction liquid to be 0-5 ℃ after reaction, adjusting the pH value to be 9 by using 40 mass percent sodium hydroxide solution, extracting by using ether and deionized water, washing an organic phase by using saturated saline solution, drying by using anhydrous magnesium sulfate, concentrating under reduced pressure to remove a solvent, distilling under reduced pressure, and collecting 114-; the intermediate 1 is subjected to ring closure under the oxidation action of acetic acid and hydrogen peroxide to obtain an intermediate 2; wherein the dosage ratio of the acetic acid, the hydrogen peroxide and the intermediate 1 is 100 mL: 35mL of: 22-25 g.

The reaction process is as follows:

thirdly, mixing the intermediate 2, dichloromethane and triethylamine, dropwise adding acetyl chloride at 0 ℃, controlling the dropwise adding speed in the dropwise adding process to maintain the temperature of the system between 0 and 5 ℃, heating to 25 ℃ after dropwise adding, reacting for 5 hours, washing with saturated saline water for three times after the reaction is finished, drying with anhydrous magnesium sulfate, concentrating under reduced pressure to remove the solvent after drying is finished, and then distilling and collecting 104-plus material 106 ℃/0.4kPa fraction to obtain the gamma-nonene lactone. And carrying out elimination reaction on the intermediate 2 to obtain the gamma-nonene lactone. Wherein the dosage ratio of the intermediate 2, acetyl chloride, dichloromethane and triethylamine is 24-25 g: 0.21mo l: 100mL of: 44 mL.

The reaction process is as follows:

the invention has the beneficial effects that:

according to the invention, malonic acid and heptaldehyde are used as raw materials to perform condensation reaction to prepare the intermediate 1, and no solvent is used in the first step of the reaction process, so that the reaction cost is reduced; the intermediate 1 is subjected to ring closure under the oxidation action of acetic acid and hydrogen peroxide to obtain an intermediate 2, and hydrogen peroxide is used as an oxidant, so that the method has the advantage of environmental friendliness; the intermediate 2 undergoes elimination reaction to obtain gamma-nonene lactone, acetyl chloride is used for replacing methane sulfonyl chloride, the use of methane sulfonyl chloride is reduced under the condition of ensuring the yield, the method is safer, the whole reaction process is simple, the route is shorter, and the raw materials are easy to obtain.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Example 1

The preparation method of the gamma-nonene lactone comprises the following steps:

step one, adding malonic acid into a four-neck flask provided with a condenser pipe and a water separator, adding piperidine, then adding heptaldehyde at 95 ℃, after the addition is finished, heating to 145 ℃, and stopping the reaction until the water content in the water separator is not increased any more, so as to obtain an intermediate 1; wherein the molar ratio of the use amount of the malonic acid to the use amount of the heptaldehyde to the use amount of the piperidine is 2.5 mol: 1mo l: 1mmo l; yield: 82 percent.

Step two, mixing acetic acid and 30% by mass of hydrogen peroxide, stirring for 10m in, dropwise adding the intermediate 1, controlling the dropwise adding speed in the dropwise adding process, controlling the temperature to be 40 ℃ after dropwise adding, reacting for 5h, cooling the reaction liquid to 0 ℃ after the reaction is finished, adjusting the pH value to be 9 by using 40% by mass of sodium hydroxide solution, extracting by using ether and deionized water, washing an organic phase by using saturated saline solution, drying by using anhydrous magnesium sulfate, concentrating under reduced pressure to remove a solvent, distilling under reduced pressure, and collecting 114-; wherein the dosage ratio of the acetic acid, the hydrogen peroxide and the intermediate 1 is 100 mL: 35mL of: 22g of the total weight of the mixture; yield: 86 percent.

And thirdly, mixing the intermediate 2, dichloromethane and triethylamine, dropwise adding acetyl chloride at 0 ℃, controlling the dropwise adding speed in the dropwise adding process to maintain the system temperature at 0 ℃, heating to 25 ℃ after dropwise adding, reacting for 5 hours, washing with saturated saline water for three times after the reaction is finished, drying with anhydrous magnesium sulfate, concentrating under reduced pressure to remove the solvent after drying is finished, and then distilling under reduced pressure to collect 104-fold organic solvent at 106 ℃/0.4kPa fraction to obtain the gamma-nonene lactone. Wherein the dosage ratio of the intermediate 2, acetyl chloride, dichloromethane and triethylamine is 24 g: 0.21mo l: 100mL of: 44 mL. Yield: 89 percent.

Example 2

The preparation method of the gamma-nonene lactone comprises the following steps:

step one, adding malonic acid into a four-neck flask provided with a condenser pipe and a water separator, adding piperidine, then adding heptaldehyde at 100 ℃, after the addition is finished, heating to 145 ℃, and stopping the reaction until the water content in the water separator is not increased any more, so as to obtain an intermediate 1; wherein the molar ratio of the use amount of the malonic acid to the use amount of the heptaldehyde to the use amount of the piperidine is 2.5 mol: 1mo l: 1mmo l; yield: 82 percent.

Step two, mixing acetic acid and hydrogen peroxide with the mass fraction of 30%, stirring for 10m & lti & gt n, dropwise adding the intermediate 1, controlling the temperature to be 30 ℃ in the dropwise adding process, controlling the temperature to be 40 ℃ after dropwise adding, reacting for 5 hours, cooling the reaction liquid to be 0 ℃ after the reaction is finished, adjusting the pH value to be 9 by using a sodium hydroxide solution with the mass fraction of 40%, extracting by using ether and deionized water, washing an organic phase by using saturated saline solution, drying by using anhydrous magnesium sulfate, concentrating under reduced pressure to remove a solvent, distilling under reduced pressure, and collecting 114-; wherein the dosage ratio of the acetic acid, the hydrogen peroxide and the intermediate 1 is 100 mL: 35mL of: 24g of a mixture; yield: 88 percent.

And thirdly, mixing the intermediate 2, dichloromethane and triethylamine, dropwise adding acetyl chloride at 0 ℃, controlling the dropwise adding speed in the dropwise adding process to maintain the system temperature at 0 ℃, heating to 25 ℃ after dropwise adding, reacting for 5 hours, washing with saturated saline water for three times after the reaction is finished, drying with anhydrous magnesium sulfate, concentrating under reduced pressure to remove the solvent after drying is finished, and then distilling under reduced pressure to collect 104-fold organic solvent at 106 ℃/0.4kPa fraction to obtain the gamma-nonene lactone. Wherein the dosage ratio of the intermediate 2, acetyl chloride, dichloromethane and triethylamine is 24 g: 0.21mo l: 100mL of: 44 mL. Yield: 90 percent.

Example 3

The preparation method of the gamma-nonene lactone comprises the following steps:

step one, adding malonic acid into a four-neck flask provided with a condenser and a water separator, adding piperidine, then adding heptaldehyde at 105 ℃, after the addition is finished, heating to 145 ℃, and stopping the reaction until the water content in the water separator is not increased any more, so as to obtain an intermediate 1; wherein the molar ratio of the use amount of the malonic acid to the use amount of the heptaldehyde to the use amount of the piperidine is 2.5 mol: 1mo l: 1mmo l; yield: 82 percent.

Step two, mixing acetic acid and 30% by mass of hydrogen peroxide, stirring for 10m in, dropwise adding the intermediate 1, controlling the temperature to be 40 ℃ in the dropwise adding process, controlling the temperature to be 40 ℃ after dropwise adding, reacting for 5 hours, cooling reaction liquid to 5 ℃ after reaction, adjusting the pH value to be 9 by using 40% by mass of sodium hydroxide solution, extracting by using ether and deionized water, washing an organic phase by using saturated saline solution, drying by using anhydrous magnesium sulfate, concentrating under reduced pressure to remove a solvent, distilling under reduced pressure, and collecting 114-; wherein the dosage ratio of the acetic acid, the hydrogen peroxide and the intermediate 1 is 100 mL: 35mL of: 25g of the total weight of the mixture; yield: 87 percent.

And thirdly, mixing the intermediate 2, dichloromethane and triethylamine, dropwise adding acetyl chloride at 0 ℃, controlling the dropwise adding speed in the dropwise adding process to maintain the system temperature at 5 ℃, heating to 25 ℃ after dropwise adding, reacting for 5 hours, washing with saturated saline water for three times after the reaction is finished, drying with anhydrous magnesium sulfate, concentrating under reduced pressure to remove the solvent after drying is finished, and then distilling under reduced pressure to collect 104-fold organic solvent at 106 ℃/0.4kPa fraction to obtain the gamma-nonene lactone. Wherein the dosage ratio of the intermediate 2, acetyl chloride, dichloromethane and triethylamine is 25 g: 0.21mo l: 100mL of: 44 mL. Yield: 89 percent.

Comparative example 1

Compared with example 2, xylene was added as a solvent in the first step, and the rest of the raw materials and the preparation process were kept unchanged. Yield in the first step: 82 percent.

Comparative example 2

Compared with example 2, the acetic acid in the second step was changed to formic acid, and the rest of the raw materials and the preparation process remained unchanged. Yield of the second step: 86 percent.

Comparative example 3

In comparison with example 2, the acetyl chloride in the third step was exchanged for methanesulfonyl chloride, the remaining starting materials and the preparation were kept unchanged. Yield in the third step: 88 percent.

In the description herein, references to the description of "one embodiment," "an example," "a specific example" or the like are intended to mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.

The foregoing is illustrative and explanatory only and is not intended to be exhaustive or to limit the invention to the precise embodiments described, and various modifications, additions, and substitutions may be made by those skilled in the art without departing from the scope of the invention or exceeding the scope of the claims.