CN111196794A - Synthesis method of food additive butylidenephthalide and application of butylidenephthalide in seasoning aspect - Google Patents
Synthesis method of food additive butylidenephthalide and application of butylidenephthalide in seasoning aspect Download PDFInfo
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- CN111196794A CN111196794A CN202010052585.7A CN202010052585A CN111196794A CN 111196794 A CN111196794 A CN 111196794A CN 202010052585 A CN202010052585 A CN 202010052585A CN 111196794 A CN111196794 A CN 111196794A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
- C07D307/88—Benzo [c] furans; Hydrogenated benzo [c] furans with one oxygen atom directly attached in position 1 or 3
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L27/00—Spices; Flavouring agents or condiments; Artificial sweetening agents; Table salts; Dietetic salt substitutes; Preparation or treatment thereof
- A23L27/20—Synthetic spices, flavouring agents or condiments
- A23L27/205—Heterocyclic compounds
- A23L27/2052—Heterocyclic compounds having oxygen or sulfur as the only hetero atoms
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Abstract
The invention discloses a synthesis method of a food additive, namely butylidene phthalide and application thereof in seasoning, wherein the synthesis method comprises the steps of dripping bromobutane into a mixed system of magnesium chips and anhydrous ether to obtain a Grignard reagent; reacting phthalic anhydride with a Grignard reagent of bromobutane, synthesizing by acidification and cyclization to obtain an intermediate 3-hydroxy-3-butyl-1 (3H) -isobenzofuranone, and hydrolyzing to obtain 3-n-butyl phenyl phthalide; the synthesized product is used as a spice for flavoring food; the synthetic process of the invention has less waste water, high yield, and utilizes the classical Grignard reaction, thus having good stability, low requirement on production equipment and easy industrialization; the butylidene phthalide is the main effective component of the medicinal plant volatile oil of angelica, ligusticum wallichii and the like and is the main fragrance component of the two natural plants, so the butylidene phthalide can replace a large amount of natural plants or natural plant extracts, and the cost is greatly reduced.
Description
[ technical field ] A method for producing a semiconductor device
The invention belongs to the field of food additives, and particularly relates to a synthesis method of a food additive of butylidene phthalide and application of the butylidene phthalide in seasoning.
[ background of the invention ]
Perfume (Perfume), also known as a fragrance raw material, is a substance that smells odor or smells fragrance, and is a raw material for preparing essence. Most of the perfumes cannot be used alone except for individual species. The perfume is divided into natural perfume and artificial perfume, wherein the natural perfume comprises animal natural perfume and plant natural perfume; artificial flavors include both isolated flavors and synthetic flavors.
Butylidenephthalide, also known as 3-n-butylidenephthalide, is a phthalide derivative, has a five-membered ring lactone structure, is a main effective component of volatile oil of medicinal plants such as angelica, ligusticum wallichii and the like, has the effects of spasmolysis, asthma relief, convulsion resistance, pain relief and the like, can be used as a flavoring agent in food, but has extremely low content in natural plants such as angelica, ligusticum wallichii and the like. Therefore, the chemical synthesis thereof is very important. Although there are several synthetic methods for butylidephthalide, these synthetic methods are not very low in yield, and the separation of reaction products is difficult; the raw materials are not easy to obtain, and the raw materials can be synthesized only through a plurality of steps of reactions, so that the methods have high cost and troublesome operation.
At present, the selling price of the butylidenephthalide in France is 2500 yuan/ton, the selling price in America is 3600 yuan/ton, the selling price in Japan is 3000 yuan/ton, the selling price is generally higher, and the production cost is high due to smaller demand, complex production process and very high requirement on production equipment.
[ summary of the invention ]
The invention aims to provide a synthesis method of a food additive of butylphthalide and application thereof in seasoning, so as to solve the problems of complex synthesis process of the butylphthalide, high equipment requirement, high processing cost and high cost of aroma-enhancing components in the food additive.
The invention adopts the following technical scheme: a synthesis method of a food additive of butylidene phthalide comprises the steps of dripping bromobutane into a mixed system of magnesium chips and anhydrous ether to obtain a Grignard reagent; reacting phthalic anhydride with a Grignard reagent of bromobutane, synthesizing by acidification and cyclization to obtain an intermediate 3-hydroxy-3-butyl-1 (3H) -isobenzofuranone, and hydrolyzing to obtain 3-n-butyl phenyl phthalide.
Further, the method comprises the following steps:
under the catalysis of iodine, reacting magnesium chips with anhydrous ether, dropwise adding anhydrous ether containing bromobutane, stirring, refluxing and cooling to obtain a Grignard reagent;
under the catalysis of cuprous iodide and the protection of nitrogen, completely reacting phthalic anhydride with anhydrous ether, dropwise adding a Grignard reagent for reaction, adjusting the pH to 1, synthesizing by acidification and cyclization, washing and drying to obtain an intermediate 3-hydroxy-3-butyl-1 (3H) -isobenzofuranone, extracting by using ether and combining organic phases;
hydrolyzing 3-hydroxy-3-butyl-1 (3H) -isobenzofuranone to obtain a crude product of 3-n-butyl phenylphthalide;
purifying the crude product of the 3-n-butyl alkenyl phthalide to obtain a pure product of the 3-n-butyl alkenyl phthalide;
wherein the molar ratio of the raw materials is as follows: magnesium chips: bromobutane: phthalic anhydride 10:10: 9.
Further, the hydrolysis process is as follows: adding toluene and toluenesulfonic acid into the intermediate 3-hydroxy-3-butyl-1 (3H) -isobenzofuranone, refluxing, carrying out water separation reaction, washing with a saturated solution of sodium bicarbonate, drying, filtering, and removing toluene to obtain a crude product of 3-n-butyl phenylphthalide.
Further, dropwise adding anhydrous ether containing bromobutane into the reaction kettle to obtain two steps, firstly dropwise adding a mixed solution of a mol of bromobutane and anhydrous ether, and after initiating the reaction, slowly dropwise adding a mixed solution of b mol of bromobutane and anhydrous ether, wherein a: b is 1: 9.
Further, the time of stirring reflux was 3 hours.
Further, the reaction temperature of the magnesium chips and the anhydrous ether is 40 ℃, and the reaction time is 5 min.
Further, the duration of the dropwise addition of the grignard reagent was 0.5h, and the reaction time after the dropwise addition of the grignard reagent was 12 h.
Further, HCl was used for pH adjustment.
Further, the duration of the refluxing water-splitting reaction was 3 hours.
The application of food additive butylidene phthalide is used as spice for flavoring food.
The invention has the beneficial effects that: the synthetic process of the invention has less waste water, high yield, and utilizes the classical Grignard reaction, thus having good stability, low requirement on production equipment and easy industrialization; the butylidene phthalide is the main effective component of the medicinal plant volatile oil of angelica, ligusticum wallichii and the like and is the main fragrance component of the two natural plants, so the butylidene phthalide can replace a large amount of natural plants or natural plant extracts, and the cost is greatly reduced.
[ detailed description ] embodiments
The present invention will be described in detail with reference to the following embodiments.
The structural formula of the butylidenephthalide is shown in the specification
The chemical name of the butylidenephthalide is as follows: 3-n-butenylphthalide with the molecular formula C12H12O2English name 3-Butylidenphthalaid, CAS No.: 551-08-6.
The invention discloses a synthesis method of a food additive of butylidene phthalide, which comprises the following steps: dropwise adding bromobutane to obtain a Grignard reagent; reacting phthalic anhydride with a Grignard reagent of bromobutane, synthesizing by acidification and cyclization to obtain an intermediate 3-hydroxy-3-butyl-1 (3H) -isobenzofuranone, and hydrolyzing to obtain a crude product of 3-n-butyl phthalide.
The method specifically comprises the following steps:
step 1: reacting magnesium chips with anhydrous ether under the catalysis of iodine, cooling, dropwise adding anhydrous ether containing bromobutane, stirring and refluxing for 3h, and cooling to obtain the Grignard reagent.
Step 2: under the catalysis of cuprous iodide and the protection of nitrogen, phthalic anhydride and anhydrous ether react completely, Grignard reagent is added dropwise and reacts for 12 hours, the pH value is adjusted to 1, the intermediate 3-hydroxy-3-butyl-1 (3H) -isobenzofuranone is obtained after acidification cyclization synthesis, washing and drying, and the organic phase is extracted and combined by utilizing ether.
And step 3: 3-hydroxy-3-butyl-1 (3H) -isobenzofuranone is hydrolyzed to obtain 3-n-butyl phenyl phthalide, and the hydrolysis process comprises the following steps: adding toluene and toluenesulfonic acid into the intermediate 3-hydroxy-3-butyl-1 (3H) -isobenzofuranone, refluxing, carrying out water separation reaction, washing with a saturated solution of sodium bicarbonate, drying, filtering, and removing toluene to obtain a crude product of 3-n-butyl phenylphthalide.
And 4, step 4: and purifying the crude product of the 3-n-butyl alkenyl phthalide to obtain a pure product of the 3-n-butyl alkenyl phthalide.
Wherein the molar ratio of the raw materials is as follows: magnesium chips: bromobutane: the phthalic anhydride is 10:10:9, the waste water generated in the synthetic process is less, the yield is high, and the classical Grignard reaction is utilized, so the method has good stability and low requirement on production equipment, and is easy to industrialize.
The synthetic route of the butylphthalide in the invention is as follows:
in step 1, under the catalysis of iodine, reacting magnesium chips with anhydrous ether in a three-necked flask, cooling to room temperature, dropwise adding anhydrous ether containing bromobutane, and dropwise adding anhydrous ether containing bromobutane to separate into two steps, firstly dropwise adding a mol of mixed solution of bromobutane and anhydrous ether, after initiating reaction, slowly dropwise adding b mol of mixed solution of bromobutane and anhydrous ether, wherein a: b is 1: 9. The separation of the anhydrous ether containing bromobutane into two steps is mainly intended to form intermediates or transition states, since in chemical reactions the reaction from reactant to product is often not done in one step, but rather undergoes several steps in which very unstable reaction intermediates, generally called organic reactive intermediates, are formed. These reactive intermediates all share common features: they are very active, react with other substances immediately after generation, and have short existence time. Therefore, the addition is divided into two steps, which can promote the formation of an intermediate and accelerate the reaction.
In the prior art, the butylidene phthalide has high selling price, low yield and high requirement on synthetic equipment, so that the synthetic cost is high, the invention utilizes cheap magnesium chips, bromobutane and phthalic anhydride to synthesize the butylidene phthalide with high purity under the catalytic action of iodine and cuprous iodide, the requirement on equipment is low, the synthetic process is simple, only 2 steps are needed, and the obtained butylidene phthalide has good stability and is easy to industrialize by utilizing the classical Grignard reaction.
The invention also discloses the application of the butylphthalide, which is used as a spice for flavoring and perfuming food, and the butylphthalide is the main effective component of the volatile oil of medicinal plants such as angelica, ligusticum wallichii and the like and is the main fragrant component of the two natural plants, so that the butylphthalide can replace a large amount of natural plants or natural plant extracts, and the cost is greatly reduced.
Example 1
A250 mL three-neck flask is added with 7.2g (0.3mol) of magnesium chips, a small piece of iodine and 30mL of anhydrous ether, slowly heated to about 40 ℃, continuously reacted for 5min after iodine vapor fills the whole flask, and cooled to room temperature. A mixture of 6.75mL (0.03mol) of bromobutane and 23.25mL of anhydrous ether was added dropwise, after the initiation of the reaction, a mixture of 61.5mL (0.27mol) of bromobutane and 58.5mL of anhydrous ether was added dropwise slowly, the mixture was stirred under reflux for 3.0h, and the Grignard reagent was obtained after cooling.
Pouring 60 ml of anhydrous ether into a 500 ml three-neck flask, adding 29.6g (0.2mol) of phthalic anhydride and 0.3g of cuprous iodide serving as a catalyst into the three-neck flask, dropwise adding a Grignard reagent at normal temperature under the protection of nitrogen, reacting for 12 hours after about half an hour, adding 130 ml of 2mol/L HCl until the pH value of a water layer is 1, stopping the reaction, extracting with 50 ml of ether for three times, combining organic phases, washing the organic phase for 3 times with saturated sodium bicarbonate solution, drying with anhydrous magnesium sulfate, and evaporating the solvent to obtain 29.8g of a crude product of the 3-hydroxy-3-butyl-1 (3H) -isobenzofuranone.
And (2) taking 29.8g of the product 3-hydroxy-3-butyl-1 (3H) -isobenzofuranone obtained in the previous step, adding 100mL of toluene, adding 15g of p-toluenesulfonic acid, refluxing, dividing water for reaction for 3H, washing the reaction solution for 2 times by using a small amount of saturated sodium bicarbonate solution, drying by using anhydrous sodium sulfate, filtering, evaporating to remove toluene to obtain a crude product of the 3-n-butenylphthalide, and rectifying to obtain 26.8g of a pure product of the 3-n-butenylphthalide, wherein the yield is 71.28%, and the purity is 99.2% by gas chromatography.
Claims (10)
1. The synthesis method of the food additive of the butylidene phthalide is characterized in that bromobutane is dripped into a mixed system of magnesium chips and anhydrous ether to obtain a Grignard reagent; reacting phthalic anhydride with a Grignard reagent of bromobutane, synthesizing by acidification and cyclization to obtain an intermediate 3-hydroxy-3-butyl-1 (3H) -isobenzofuranone, and hydrolyzing to obtain 3-n-butyl phenyl phthalide.
2. The method for synthesizing the food additive of butylidene phthalide according to claim 1, comprising the following steps:
under the catalysis of iodine, reacting magnesium chips with anhydrous ether, dropwise adding anhydrous ether containing bromobutane, stirring, refluxing and cooling to obtain a Grignard reagent;
under the catalysis of cuprous iodide and the protection of nitrogen, completely reacting phthalic anhydride with anhydrous ether, dropwise adding a Grignard reagent for reaction, adjusting the pH to 1, synthesizing by acidification and cyclization, washing and drying to obtain an intermediate 3-hydroxy-3-butyl-1 (3H) -isobenzofuranone, extracting by using ether and combining organic phases;
hydrolyzing 3-hydroxy-3-butyl-1 (3H) -isobenzofuranone to obtain a crude product of 3-n-butyl phenylphthalide;
purifying the crude product of the 3-n-butyl alkenyl phthalide to obtain a pure product of the 3-n-butyl alkenyl phthalide;
wherein the molar ratio of the raw materials is as follows: magnesium chips: bromobutane: phthalic anhydride 10:10: 9.
3. The method for synthesizing the food additive of butylidene phthalide according to claim 2, wherein the hydrolysis process comprises: adding toluene and toluenesulfonic acid into the intermediate 3-hydroxy-3-butyl-1 (3H) -isobenzofuranone, refluxing, carrying out water separation reaction, washing with a saturated solution of sodium bicarbonate, drying, filtering, and removing toluene to obtain a crude product of 3-n-butyl phenylphthalide.
4. The method for synthesizing the food additive of butylidene phthalide according to any one of claims 1 to 3, wherein the dropwise addition of the anhydrous ether containing bromobutane is divided into two steps, wherein the step of dropwise addition of the mixed solution of amol bromobutane and anhydrous ether is first performed, and after the initiation of the reaction, the mixed solution of b mol of bromobutane and anhydrous ether is slowly added dropwise, wherein a: b is 1: 9.
5. The method for synthesizing the food additive of butylidene phthalide as claimed in claim 2, wherein the time of stirring and refluxing is 3 h.
6. The method for synthesizing the food additive of butylphthalide according to claim 5, wherein the reaction temperature of magnesium chips and anhydrous diethyl ether is 40 ℃ and the reaction time is 5 min.
7. The method for synthesizing the food additive of butylidenephthalide according to claim 6, wherein the duration of the dropwise addition of Grignard reagent is 0.5h, and the reaction time after the dropwise addition of Grignard reagent is 12 h.
8. The method for synthesizing the food additive of butylidene phthalide according to claim 7, wherein HCl is used for adjusting pH.
9. The method for synthesizing the food additive of butylidenephthalide according to claim 8, wherein the duration of the reflux water separation reaction is 3 h.
10. The application of the food additive of the butylidene phthalide is characterized in that the butylidene phthalide is used as a spice to carry out flavoring and aroma enhancement on food.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1865256A (en) * | 2006-06-15 | 2006-11-22 | 兰州大学 | 6,7-dihydroligustilide and alkylidene phthalide synthesis method |
| CN105367526A (en) * | 2015-10-14 | 2016-03-02 | 济南诚汇双达化工有限公司 | Preparation method of high-purity n-butylphthalide |
| EP3400937A1 (en) * | 2016-01-07 | 2018-11-14 | Everfront Biotech Inc. | Use of butylidenephthalide |
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- 2020-01-17 CN CN202010052585.7A patent/CN111196794A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1865256A (en) * | 2006-06-15 | 2006-11-22 | 兰州大学 | 6,7-dihydroligustilide and alkylidene phthalide synthesis method |
| CN105367526A (en) * | 2015-10-14 | 2016-03-02 | 济南诚汇双达化工有限公司 | Preparation method of high-purity n-butylphthalide |
| EP3400937A1 (en) * | 2016-01-07 | 2018-11-14 | Everfront Biotech Inc. | Use of butylidenephthalide |
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