CN116178136B - Preparation method of 2-hexyl decanoic acid - Google Patents
Preparation method of 2-hexyl decanoic acid Download PDFInfo
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- CN116178136B CN116178136B CN202310473215.4A CN202310473215A CN116178136B CN 116178136 B CN116178136 B CN 116178136B CN 202310473215 A CN202310473215 A CN 202310473215A CN 116178136 B CN116178136 B CN 116178136B
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- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/377—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by splitting-off hydrogen or functional groups; by hydrogenolysis of functional groups
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- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
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- C07C53/00—Saturated compounds having only one carboxyl group bound to an acyclic carbon atom or hydrogen
- C07C53/126—Acids containing more than four carbon atoms
- C07C53/128—Acids containing more than four carbon atoms the carboxylic group being bound to a carbon atom bound to at least two other carbon atoms, e.g. neo-acids
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- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
- C07C69/67—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of saturated acids
- C07C69/716—Esters of keto-carboxylic acids or aldehydo-carboxylic acids
Abstract
The application relates to the technical field of compound synthesis, and particularly discloses a preparation method of 2-hexyl decanoic acid. The preparation method of the 2-hexyl capric acid provided by the application comprises the following steps: s1: ethyl acetoacetate or methyl acetoacetate is used as a starting material, and is subjected to alkylation reaction with halogenated octane and halogenated hexane for two times in an anhydrous solution of sodium methoxide or sodium ethoxide in sequence to obtain an intermediate B; s2: decomposing the intermediate B in 30-50 mass% alkaline water solution to obtain 2-hexyl capric acid. The preparation method of the 2-hexyl decanoic acid has the advantages of mild reaction conditions, simplicity in operation, low production cost and the like, and can obtain the 2-hexyl decanoic acid with high purity and high yield.
Description
Technical Field
The application relates to the technical field of compound synthesis, in particular to a preparation method of 2-hexyl decanoic acid.
Background
The ascorbyl tetraisopalmitate is a derivative of vitamin C, has the effects of whitening, resisting aging, promoting cell regeneration and the like, and therefore has good application prospect in cosmetics. The main raw material for preparing the ascorbyl tetraisopalmitate is 2-hexyl capric acid, however, the 2-hexyl capric acid in China mainly depends on foreign import, so that the production and popularization of the ascorbyl tetraisopalmitate are greatly limited.
At present, the production process of 2-hexyl decanoic acid disclosed at home and abroad is more, and the following modes are reported to be adopted for obtaining 2-hexyl decanoic acid: the method for preparing 2-hexyl capric acid by using diethyl malonate as a starting raw material through two-step alkylation reaction, hydrolysis reaction and high Wen Tuosuo has various defects in industrialization, such as high raw material cost, long reaction route, high-temperature operation involved in decarboxylation step, severe production conditions and difficulty in realizing large-scale production. There are also reports that suggest: the 2-hexyl capric acid is obtained by a one-step method through alkylation reaction of caprylate serving as a starting material and methanol serving as a solvent with bromo-n-octane in the presence of sodium hydroxide, however, the yield is extremely low when the method is used for large-scale production, so that the production cost is too high for industrial scale, and the market popularization is not facilitated. There are also documents mentioning: the method uses LDA and NaH as catalysts, but the catalysts are explosive chemicals, and the obtained product can obtain the 2-hexyl capric acid with higher purity by adopting column chromatography in the purification process, so that the method has the danger of inflammability and explosiveness during industrialization, and the column chromatography purification involves high-cost chromatographic columns, so that the production cost is overhigh.
Therefore, at present, a preparation method of 2-hexyl decanoic acid with mild reaction conditions, simple operation and low production cost is needed to obtain high-purity and high-yield 2-hexyl decanoic acid so as to meet the domestic and foreign market demands.
Disclosure of Invention
In order to obtain 2-hexyl decanoic acid with high purity and high yield, the application provides a preparation method of 2-hexyl decanoic acid.
In a first aspect, the present application provides a method for preparing 2-hexyl decanoic acid, which adopts the following technical scheme:
a method for preparing 2-hexyl decanoic acid, comprising the following steps:
s1: ethyl acetoacetate or methyl acetoacetate is used as a starting material, and is subjected to alkylation reaction with halogenated octane and halogenated hexane for two times in an anhydrous solution of sodium methoxide or sodium ethoxide in sequence to obtain an intermediate B;
s2: decomposing the intermediate B in 30-50 mass% alkaline water solution to obtain 2-hexyl capric acid.
The application provides a preparation method of 2-hexyl decanoic acid, which only obtains the 2-hexyl decanoic acid with the purity of more than or equal to 99.00 percent and the yield of more than or equal to 80.0 percent through two-step alkylation reaction and decomposition reaction. Compared with the related art, the preparation method of the 2-hexyl decanoic acid does not need high-temperature operation, does not need dangerous chemicals such as inflammable and explosive substances, and can obtain the high-purity and high-yield 2-hexyl decanoic acid only through simple and low-cost extraction in the purification process, so that the preparation method has the advantages of mild reaction conditions, low raw material cost, simplicity in operation, short reaction route and the like, and is suitable for industrial mass production.
The preparation of 2-hexyl decanoic acid in the related art requires high Wen Tuosuo (160-200 ℃) and generates a large amount of CO after decarboxylation 2 Therefore, it is energy-consuming and there is a risk of generating a large amount of gas. On the one hand, the preparation method of the 2-hexyl capric acid does not need decarboxylation step and does not generate CO 2 Thus the risk of production is less; on the other hand, the reaction process is only carried out under the heating of steam at 60-110 ℃, so that the energy consumption is low. In addition, the raw material adopted in the preparation method of the 2-hexyl decanoic acid is ethyl acetoacetate or methyl acetoacetate, the raw material cost is low, and the yield and purity of the obtained 2-hexyl decanoic acid are high, so that the preparation method is very suitable for large-scale industrial production.
In this application, the two alkylation reactions are carried out continuously, i.e., after the first alkylation reaction is completed, the reaction mixture is directly subjected to the second alkylation reaction without treatment.
The alkylation reaction of the present application is carried out in the presence of sodium methoxide or sodium ethoxide. The starting materials of the alkylation reaction are ethyl acetoacetate and methyl acetoacetate, and the existence of sodium methoxide or sodium ethoxide can make alpha-H in the raw materials more active so as to promote the alkylation reaction; in addition, the alkylation reaction is preferably carried out in an anhydrous environment because ethyl acetoacetate and methyl acetoacetate as raw materials are susceptible to hydrolysis in the presence of water, and therefore, the presence of water in the system of the alkylation reaction or the formation of water during the reaction is disadvantageous in carrying out the reaction.
In the application, when the sodium methoxide is used, sodium methoxide solid is dissolved in anhydrous methanol to obtain sodium methoxide methanol solution; the sodium methoxide methanol solution thus obtained is anhydrous and is used for carrying out the alkylation reaction.
In the application, when sodium ethoxide is used, sodium ethoxide solid is dissolved in absolute ethyl alcohol to obtain sodium ethoxide ethanol solution; the sodium ethoxide ethanol solution thus obtained is also anhydrous for carrying out the alkylation reaction.
Therefore, the sodium methoxide methanol solution or the sodium ethoxide ethanol solution is a strongly alkaline anhydrous system, and can provide an anhydrous strongly alkaline environment for the alkylation reaction, so that the alkylation reaction can be smoothly carried out.
Preferably, the alkaline aqueous solution is an aqueous sodium hydroxide solution or an aqueous potassium hydroxide solution.
In this application, the decomposition reaction of intermediate B in an alkaline aqueous solution, which takes place in a reaction, on the one hand, to convert carboxylic acid groups to sodium carboxylate and, on the other hand, to provide a strong alkaline environment for the acid decomposition of intermediate B, is known in the art as an acid decomposition reaction. Thus, in the acid decomposition of the present application, an excess amount of the basic aqueous solution needs to be added.
Preferably, the molar ratio of the base in the basic aqueous solution to the intermediate B is 3.5-6.5.
In some embodiments, the molar ratio of base in the basic aqueous solution to the intermediate B may be (3.8-4.4), (3.8-5), (3.8-5.6), (3.8-6.3), (4.4-5), (4.4-5.6), (4.4-6.3), (5-5.6), (5-6.3), or (5.6-6.3).
In a specific embodiment, the molar ratio of base in the basic aqueous solution to the intermediate B may be 3.8, 4.4, 5, 5.6 or 6.3.
In the application, the reaction route of the preparation method of the 2-hexyl capric acid is as follows:
using ethyl acetoacetate as a starting material:
methyl acetoacetate is used as a starting material:
in some embodiments, the aqueous alkaline solution has a mass concentration of 30-35%, 30-40%, 30-45%, 35-40%, 35-45%, 35-50%, 40-45%, 40-50%, or 45-50%.
In a specific embodiment, the aqueous alkaline solution has a mass concentration of 30%, 35%, 40%, 45% or 50%.
Preferably, the concentration of the alkaline aqueous solution is 35 to 45 mass%.
The present application further controls the concentration of the alkaline aqueous solution within the above-mentioned range, so that the decomposition reaction in step S2 can be more sufficient, and the yield and purity of the obtained 2-hexyldecanoic acid can be higher.
Preferably, the molar ratio of the starting material to the halooctane is 1: (0.9-1.3), the molar ratio of the starting material to the halohexane being 1: (0.9-1.3).
Preferably, the molar ratio of the starting material to the halooctane is 1: (1-1.2) a molar ratio of the starting material to the halohexane of 1: (1-1.2).
The present application has been experimentally found that when the molar ratio of starting material to halooctane/halohexane is > 1:1, the reaction of the starting materials is incomplete, and the yield of the reaction is low; when the molar ratio of starting material to halooctane/halohexane is < 1:1.2, the reaction yield is high, but the purity of the target product is poor. Thus, the present application controls the molar ratio of starting material to halooctane/halohexane to 1: and (1-1.2), the obtained target product has good yield and high purity.
In some embodiments, the molar ratio of the starting material to the halooctane is 1: (1-1.1) or 1: (1-1.2).
In some embodiments, the molar ratio of the starting material to the halohexane is 1: (1-1.1) or 1: (1-1.2).
In a specific embodiment, the molar ratio of the starting material to the halooctane is 1:1. 1:1.1 or 1:1.2.
in a specific embodiment, the molar ratio of the starting material to the halohexane is 1:1. 1:1.1 or 1:1.2.
preferably, the halogen of the halogenated octane and halogenated hexane is selected from chlorine, bromine and iodine.
Further preferably, the halooctane is bromooctane and the halohexane is bromohexane.
Preferably, the anhydrous solution is an anhydrous methanol solution or an anhydrous ethanol solution.
Preferably, the preparation method further comprises a purification step, wherein the purification step is extraction.
The purification steps of the preparation method of the 2-hexyl capric acid provided by the application are extraction, and the 2-hexyl capric acid with the purity of more than 99.00% can be obtained; no purification operations such as reduced pressure distillation and column chromatography are required in the related art. Therefore, the purification process in this method is simple in operation, short in process, low in cost, and excellent in purification effect, as compared with the related art.
Preferably, the step S1 specifically includes: ethyl acetoacetate or methyl acetoacetate is used as a starting material, firstly reacts with halogenated octane, is heated and refluxed for 2-3 hours, and is cooled to room temperature to obtain a reaction mixture (comprising an intermediate A); then the reaction mixture is directly reacted with halogenated hexane without treatment, heated and refluxed for 2-3 hours, the solvent is evaporated to dryness, and water is added for extraction, thus obtaining the intermediate B.
Preferably, the step S2 specifically includes: adding the intermediate B into 30-50 mass% alkaline aqueous solution, and heating and refluxing for 1.5-2.5h; regulating the pH value of the system to 1.8-2.3, and extracting to obtain the 2-hexyl capric acid.
Preferably, the temperature of the heated reflux is 60-110 ℃.
In a second aspect, the present application provides 2-hexyldecanoic acid produced by the above-described process for producing 2-hexyldecanoic acid.
The purity of the 2-hexyl decanoic acid prepared by the preparation method of the 2-hexyl decanoic acid is more than or equal to 99.00 percent.
The 2-hexyl decanoic acid obtained by the method provided by the application has high purity and good yield, the purity can reach more than 99.00%, and the yield can reach more than 80.0%.
In summary, the present application has the following beneficial effects:
1. the preparation method of the 2-hexyl capric acid provided by the application takes ethyl acetoacetate or methyl acetoacetate as a starting raw material, and prepares the 2-hexyl capric acid through two-step alkylation reaction and decomposition reaction. On one hand, the starting material adopted by the preparation method is ethyl acetoacetate or methyl acetoacetate, so the cost of the raw material is low; on the other hand, the preparation method has the advantages of less reaction route, no use of dangerous reagents such as inflammable and explosive reagents, low production cost, simple operation, little pollution, easy control of reaction conditions and the like.
2. The reaction temperature of the preparation method of the 2-hexyl decanoic acid is lower, the heating reflux temperature is only 60-110 ℃, the step Wen Tuosuo in the related technology is effectively avoided, the energy consumption is low, and CO is not generated 2 Therefore, the conditions are easy to control, the energy consumption is low, the production cost is low, and the reaction risk is low.
3. The preparation method of the 2-hexyl decanoic acid provided by the application can obtain the 2-hexyl decanoic acid with the yield of more than or equal to 80.0% and the purity of more than or equal to 99.00%, is very suitable for large-scale industrial production, and meets the market demand.
4. The present application further controls the molar ratio of acetoacetic ester to bromooctane/bromohexane at 1: in the range of (1-1.2), the concentration of the sodium hydroxide aqueous solution is controlled within the range of 35-45 mass percent, and the yield and purity of the obtained 2-hexyl decanoic acid are higher, and the yield is more than or equal to 86.0 percent, and the purity is more than or equal to 99.50 percent.
Drawings
FIG. 1 is a flow chart of a preparation method of 2-hexyl decanoic acid.
FIG. 2 is a nuclear magnetic resonance spectrum of 2-hexyldecanoic acid obtained in example 8 of the present application.
FIG. 3 is a gas phase detection spectrum of 2-hexyldecanoic acid obtained in example 8 of the present application.
Detailed Description
The application provides a preparation method of 2-hexyl decanoic acid, which specifically comprises the following steps:
s1: under the protection of nitrogen, putting ethyl acetoacetate or methyl acetoacetate into a flask filled with a mixed solution of sodium alkoxide alcohol solution (sodium methoxide methanol solution or sodium ethoxide ethanol solution) and halogenated octane, heating the system to 60-110 ℃, refluxing for 2-3h, and cooling to room temperature to obtain a reaction mixture (comprising an intermediate A); then the reaction mixture is directly added into a flask filled with a mixed solution of sodium alkoxide and halogenated hexane without treatment, the system is heated to 60-110 ℃, the heating reflux is carried out for 2-3 hours, then the solvent in the reaction system is evaporated to dryness, then water is added into the reaction system, then the reaction system is extracted for 2-3 times by using an organic solvent, and the extracts are combined and rotary evaporated to obtain an intermediate B. Wherein, the mol ratio of the starting materials to the halogenated octane is 1: (0.9-1.3), the molar ratio of starting material to halogenated hexane is 1: (0.9-1.3).
S2: adding the intermediate B into 30-50 mass% sodium hydroxide aqueous solution, heating the system to 60-110 ℃, refluxing for 1.5-2.5h, stopping the reaction, regulating the pH of the system to 1.8-2.3, extracting for 2-3 times by using an organic solvent, combining the extracts, and performing rotary evaporation to obtain the 2-hexyl capric acid. Further, the concentration of the aqueous sodium hydroxide solution is 35 to 45 mass%.
In the application, the CAS number of the acetoacetic acid ethyl ester is 141-97-9; methyl acetoacetate has a CAS number of 105-45-3; the CAS number of the bromooctane is 111-83-1; the CAS number of bromohexane is 111-25-1; the remaining reagents, solvents, etc. are commercially available.
The present application will be described in further detail with reference to examples, comparative examples, performance test and accompanying drawings.
Example 1
Example 1 provides a process for the preparation of 2-hexyldecanoic acid, comprising the steps of:
s1: under the protection of nitrogen, 13g of ethyl acetoacetate was put into a flask containing 37.5g of a mixed solution of 20% sodium ethoxide and ethanol (anhydrous ethanol) and 19.3g of bromooctane, the system was heated to 80 ℃, heated under reflux for 2.5h, and then cooled to room temperature to obtain a reaction mixture (containing intermediate a); the reaction mixture was then directly added without treatment to a flask containing 37.5g of a mixed solution of 20% sodium ethoxide and 16.5g of bromohexane, and the system was heated to 80 ℃ and refluxed for 2.5 hours, then the solvent in the reaction system was evaporated to dryness, then 40g of water was added to the reaction system, extracted with 50mL of ethyl acetate for 2 times (50 ml×2), the extracts were combined and distilled by a rotary evaporator to obtain 32.7g of an oily viscous liquid as a crude intermediate B, whose purity was 98.6% by gas phase detection.
S2: the above 32.7g of intermediate B and 10mL of ethanol were added to 50g of 40% by mass aqueous sodium hydroxide solution, the system was heated to reflux, the reaction was stopped after refluxing for 2 hours, the pH of the system was adjusted to 2 with dilute hydrochloric acid, then extracted 2 times with 50mL of ethyl acetate (50 mL. Times.2), the extracts were combined and distilled on a rotary basis to obtain a colorless oily liquid, which was 2-hexyldecanoic acid.
Example 2
Example 2 provides a process for the preparation of 2-hexyldecanoic acid, comprising the steps of:
s1: under the protection of nitrogen, 11.6g of methyl acetoacetate was put into a flask containing 20g of a mixed solution of 30% sodium methoxide methanol solution (anhydrous methanol solution) and 19.3g of bromooctane, the system was heated to 65℃and heated under reflux for 2.5 hours, followed by cooling to room temperature to obtain a reaction mixture (containing intermediate A); the reaction mixture was then directly added without treatment to a flask containing 20g of a mixed solution of 30% sodium methoxide in methanol and 16.5g of bromohexane, and the system was heated to 65℃under reflux for 2.5 hours, then the solvent in the reaction system was evaporated to dryness, then 40g of water was added to and into the reaction system, followed by extraction with 50mL of ethyl acetate for 2 times (50 mL. Times.2), and the extracts were combined and distilled in a rotary manner to obtain 30.8g of oily viscous liquid as crude intermediate B, whose purity was 98.1% by gas phase detection.
S2: 30.8g of intermediate B and 10mL of methanol were added to 50g of 40% by mass aqueous sodium hydroxide solution, the system was heated to reflux, the reaction was stopped after 2 hours of heating reflux, the pH of the system was adjusted to 2 with dilute hydrochloric acid, then 2 times (50 mL. Times.2) extraction was performed with 50mL of ethyl acetate, and the extracts were combined and distilled on a rotary basis to obtain a colorless oily liquid, which was 2-hexyldecanoic acid.
Examples 3 to 6
Examples 3-6 were carried out according to the preparation method of example 1, except that: the concentration of the aqueous sodium hydroxide solution in step S2 of the process for producing 2-hexyldecanoic acid is shown in table 1 below.
TABLE 1 concentration of aqueous sodium hydroxide solution in example 1, examples 3-6
Examples 7 to 10
Examples 7-10 were performed as in example 1, except that: the molar ratio of starting material to bromooctane/bromohexane is shown in Table 2.
TABLE 2 molar ratio of starting materials to bromooctane/bromohexane in example 1, examples 7-10
Example 11
Example 11 provides a process for the preparation of 2-hexyldecanoic acid which differs from example 8 in that: the dosage of each raw material; the method specifically comprises the following steps:
s1: under the protection of nitrogen, 13kg of ethyl acetoacetate is put into a reaction kettle filled with 37.5kg of 20% sodium ethoxide ethanol solution and 21.23kg of bromooctane mixed solution, the system is heated to 80 ℃, and after heating and refluxing for 2.5h, the system is cooled to room temperature, thus obtaining an intermediate A; then, the intermediate A was charged into a 200L reactor containing 37.5kg of a mixed solution of 20% sodium ethoxide and 18.15kg of bromohexane, and the system was heated to 80℃and refluxed for 2.5 hours, then the solvent in the system was evaporated to dryness, and 40kg of water was added to the system, followed by extraction 3 times with 50L of ethyl acetate, and the extracts were combined and distilled by a rotary evaporator to obtain 31.5kg of intermediate B having a purity of 98.8%.
S2: 31.5kg of intermediate B and 10L of ethanol are added into 50kg of 40 mass percent sodium hydroxide aqueous solution, the system is heated to reflux, the reaction is stopped after the reflux is heated for 2 hours, the pH value of the system is regulated to 2 by dilute hydrochloric acid, then the mixture is extracted for 3 times by 50L of ethyl acetate, and the extracts are combined and distilled in a rotary way, thus obtaining 2-hexyl capric acid.
Comparative example 1
Comparative example 1 was conducted according to the preparation method of example 1 except that: in the preparation method of 2-hexyl decanoic acid, the concentration of the sodium hydroxide aqueous solution in the step S2 is 5 mass percent, and the molar ratio of sodium hydroxide to the intermediate B is 0.6.
Comparative example 2
Comparative example 2 was conducted according to the preparation method of example 1 except that: in the preparation method of 2-hexyl decanoic acid, the concentration of the sodium hydroxide aqueous solution in the step S2 is 60 mass percent, and the molar ratio of sodium hydroxide to the intermediate B is 7.5.
Comparative example 3
Comparative example 3 provides a process for the preparation of 2-hexyldecanoic acid, comprising the steps of:
s1: under the protection of nitrogen, adding 16g diethyl malonate and 30mL absolute ethyl alcohol into a 100mL three-necked round bottom flask, adding 37.5g 20% sodium ethoxide at room temperature, slowly adding 19.3g bromooctane, heating and refluxing after the addition is finished, and reacting for 3h; cooling to room temperature, adding 37.5g of 20% sodium ethoxide, slowly adding 16.5g of bromohexane, and heating for reflux reaction for 3h. Cooling to room temperature, removing solvent, adding 1mol/L sulfuric acid water solution to neutralize the system until the pH value is about 7, washing the organic phase with water, and distilling under reduced pressure to obtain an intermediate 1.
S2: adding 1, 55mL of sodium hydroxide aqueous solution (the concentration of sodium hydroxide is 4 mol/L) and 10mL of ethanol into a 100mL round-bottomed flask, heating and refluxing for 12h, cooling to room temperature, adding 4mol/L of sulfuric acid to adjust the pH value to about 1.9, standing, separating white solid by chromatography on the aqueous solution, filtering, washing, and recrystallizing acetone to obtain a hydrolysate, namely the intermediate 2.
S3: and adding the intermediate 2 into a 10mL round-bottom flask, heating to 160 ℃ under the protection of nitrogen, stopping reacting until no more gas is discharged, and cooling to obtain the 2-hexyl decanoic acid.
Comparative example 4
Comparative example 4 provides a process for the preparation of 2-hexyldecanoic acid, comprising the steps of:
s1: under the protection of nitrogen, 13g of ethyl acetoacetate and 30mL of absolute ethyl alcohol are put into a 100mL three-necked round bottom flask, 37.5g of 20% sodium ethoxide is added at room temperature, then 19.3g of bromooctane is slowly added, and after the addition is finished, the temperature is raised, the reflux is carried out, and the reaction is carried out for 3 hours; cooling to room temperature, adding 37.5g of 20% sodium ethoxide, slowly adding 16.5g of bromohexane, and heating for reflux reaction for 3h. Cooling to room temperature, removing solvent, adding 1mol/L sulfuric acid water solution to neutralize the system until the pH value is about 7, washing the organic phase with water, and distilling under reduced pressure to obtain an intermediate 1.
S2: adding 1, 55mL of sodium hydroxide aqueous solution (the concentration of sodium hydroxide is 4 mol/L) and 10mL of ethanol into a 100mL round-bottomed flask, heating and refluxing for 12h, cooling to room temperature, adding 4mol/L of sulfuric acid to adjust the pH value to about 1.9, standing, separating white solid by chromatography on the aqueous solution, filtering, washing, and recrystallizing acetone to obtain a hydrolysate, namely the intermediate 2.
S3: intermediate 2 was added to a 10mL round bottom flask and heated to 160 ℃ under nitrogen protection, with no evolution of gas.
Comparative example 5
Comparative example 5 provides a process for the preparation of 2-hexyldecanoic acid, comprising the steps of:
s1: under the protection of nitrogen, putting 16g diethyl malonate into a flask filled with 37.5g of a mixed solution of 20% sodium ethoxide and ethanol (anhydrous ethanol) and 19.3g of bromooctane, heating the system to 80 ℃, refluxing for 2.5h, and cooling to room temperature to obtain a reaction mixture (comprising an intermediate A); the reaction mixture was then directly added, without treatment, to a flask containing 37.5g of a mixed solution of 20% sodium ethoxide and 16.5g of bromohexane, and the system was heated to 80℃under reflux for 2.5 hours, then the solvent in the reaction system was evaporated to dryness, then 40g of water was added to the reaction system, extracted with 50mL of ethyl acetate, extracted 2 times (50 mL. Times.2), the extracts were combined, and rotary distilled to obtain intermediate B.
S2: intermediate B and 10mL of ethanol are added into 50g of 40 mass percent sodium hydroxide aqueous solution, the system is heated to reflux, the reaction is stopped after the heating and the reflux are carried out for 2 hours, the pH value of the system is regulated to 2 by dilute hydrochloric acid, then the mixture is extracted for 2 times by 50mL of ethyl acetate (50 mL multiplied by 2), and the extracts are combined and distilled in a rotary way to obtain the product.
Performance test
Nuclear magnetic structure identification
Nuclear magnetic resonance analysis was performed on the product obtained in example 8, and the obtained detection spectrum was shown in FIG. 2. Figure 2 shows that in the case of the figure, 1 HNMR（DMSO）δ＝11.930（OH，1H）；2.206（CH，1H）；1.513（CH 2 ，2H）；1.477（CH 2 ，2H）；1.332（CH 2 ，20H）；0.863（CH 3 6H). As a result, the product obtained in example 8 was 2-hexyldecanoic acid.
Gas chromatography detection
The products of examples 1 to 11 and comparative examples 1 to 5 were subjected to gas chromatography using chromatographic methanol, and the detection results are shown in Table 3.
The gas chromatography detection conditions are as follows: chromatographic column: inertOap WAX 30m 0.32mm 0.25 μm; injector temperature: 280 ℃; detector temperature: 280 ℃; column temperature: initial temperature 100 ℃, initial temperature retention time 2min, heating rate 20 ℃/min, final temperature 280 ℃ and final temperature retention time 5min. Sample injection volume: 0.3 μl (2-hexyldecanoic acid: methanol=1:1)
The gas phase detection spectrum of 2-hexyldecanoic acid obtained in example 8 is shown in FIG. 3, and it can be seen from FIG. 3 that the purity of 2-hexyldecanoic acid is as high as 99.79%.
Yield and purity detection
The yields of the preparation methods of 2-hexyldecanoic acid provided in examples 1 to 11 and comparative examples 1 to 5 were calculated, and the results are shown in Table 3.
TABLE 3 results of the yield and purity tests for examples 1-11 and comparative examples 1-5
According to the detection results of Table 3, the yield of the preparation method of 2-hexyl decanoic acid provided in examples 1-11 of the application is more than or equal to 80.0%, and the purity of the obtained 2-hexyl decanoic acid is more than or equal to 99.00%;
comparative example 1 was conducted with a 5 mass% aqueous sodium hydroxide solution, and it was found by gas phase detection of the reaction product that the gas chromatogram did not show a peak at the retention time of 9.3min, thereby indicating that the objective product 2-hexyldecanoic acid could not be obtained under the reaction conditions.
Comparative example 2 was conducted using an aqueous sodium hydroxide solution having a concentration of 60% by mass, and the yield of 2-hexyldecanoic acid obtained was only 80.1%, the purity was 97.38%, and the purity was low. Therefore, in order to further increase the purity of 2-hexyl decanoic acid, the present application further carried out distillation under reduced pressure to obtain 19.43g of a fraction, and the purity of the fraction was 98.66%, which revealed that the person skilled in the art was not only required to expend labor and equipment, but also required a large amount of energy, and the purity of the product was 98.66%. Therefore, it was demonstrated that it was difficult to obtain 2-hexyldecanoic acid having a purity of 99.00% or more with a 60% by mass aqueous sodium hydroxide solution.
The yield of the preparation method of 2-hexyl decanoic acid provided in comparative example 3 is only 76.5%, and the purity of the obtained 2-hexyl decanoic acid is 97.34%, which indicates that the purity of the product obtained by the preparation method of comparative example 3 is good, but the yield is lower; in addition, the preparation method has long reaction route, high-temperature decarboxylation is needed in the last reaction step, energy consumption is high, and a large amount of gas is generated at a certain risk, so the method of comparative example 3 is not suitable for industrial production.
The preparation method of 2-hexyl decanoic acid provided in comparative example 4 adopts ethyl acetoacetate as a raw material, and the reaction product is detected by gas chromatography, and no peak appears when the reaction product is kept for 9.3min, which indicates that the target product 2-hexyl decanoic acid cannot be obtained under the reaction condition. It is presumed that since the dicarboxylic group is not present in the raw material, a high-temperature decarboxylation reaction cannot occur, and thus 2-hexyldecanoic acid cannot be obtained.
The raw material adopted in the preparation method of the 2-hexyl decanoic acid provided in the comparative example 5 is diethyl malonate, and the reaction product is detected by gas chromatography, and no peak appears when the reaction product is kept for 9.3min, which indicates that the target product 2-hexyl decanoic acid cannot be obtained under the reaction condition. It is presumed that the reaction condition of comparative example 5 did not reach the temperature required for the decarboxylation reaction, resulting in failure of the decarboxylation reaction to occur, and thus 2-hexyldecanoic acid could not be obtained.
In addition, the raw material diethyl malonate used in comparative example 3 was much more expensive than ethyl acetoacetate/methyl acetoacetate. Thus, from the viewpoint of cost in industrialization, ethyl acetoacetate/methyl acetoacetate is more suitable as a raw material on an industrial scale.
In examples 1 and 3 to 6, example 3 uses a 30 mass% aqueous sodium hydroxide solution to obtain 2-hexyl decanoic acid with a yield of only 81.8% and a purity of only 99.01%; example 6 using 50 mass% aqueous sodium hydroxide solution, the yield of 2-hexyl decanoic acid obtained was only 85.3% and the purity was only 99.58%; examples 1 and 4 to 5 used aqueous sodium hydroxide solution having a concentration of 35 to 45 mass%, and the yield of 2-hexyldecanoic acid was 86.2 to 87.9% and the purity was 99.63 to 99.71%.
Clearly, when the concentration of the aqueous sodium hydroxide solution is controlled within the range of 35 to 45 mass%, 2-hexyldecanoic acid can be obtained in higher yield and purity.
From the results of the tests of example 1 and examples 7 to 10, the molar ratio of acetoacetic ester to bromohexane/bromooctane in example 7 was controlled to be 1: at 0.9, the yield of 2-hexyldecanoic acid obtained was 84.2% and the purity was 99.20%; example 10 the molar ratio of acetoacetate to bromohexane/bromooctane was controlled to 1:1.3, the yield of 2-hexyl decanoic acid obtained was 85.1% and the purity was 99.18%; examples 1, 8-9 the molar ratio of acetoacetoxyethyl to bromohexane/bromooctane was controlled to 1: (1-1.2), the yield of 2-hexyldecanoic acid obtained was 87.9-89.3% and the purity was 99.52-99.79%.
From this, the present application further controls the molar ratio of acetoacetoxyethyl to bromohexane/bromooctane to be 1: in the range of (1-1.2), 2-hexyldecanoic acid having excellent yield and purity can be obtained.
In summary, the present application has the following beneficial effects:
according to the method, ethyl acetoacetate or methyl acetoacetate is used as a starting material, alkylation reaction is sequentially carried out with bromooctane and bromohexane, and then the reaction is carried out with sodium hydroxide aqueous solution, so that 2-hexyl decanoic acid with the yield of more than or equal to 80% and the purity of more than or equal to 99.00% can be obtained.
Through a large number of experimental studies, in the preparation method of 2-hexyl decanoic acid, the molar ratio of the acetyl ethyl acetate to the bromooctane/bromohexane is further controlled to be 1: in the range of (1-1.2), the concentration of the aqueous sodium hydroxide solution is controlled within the range of 35-45 mass%, and the yield and purity of the obtained 2-hexyl decanoic acid are higher, the yield is up to 86.0% and above, and the purity is up to 99.50% and above.
The preparation method of 2-hexyl decanoic acid has the advantages of low production cost, simple operation, easy control of reaction conditions, small energy consumption and low reaction risk, and is very suitable for large-scale industrialized use.
While the invention has been described in detail in the foregoing general description and with reference to specific embodiments thereof, it will be apparent to one skilled in the art that modifications and improvements can be made thereto. Accordingly, such modifications or improvements may be made without departing from the spirit of the invention and are intended to be within the scope of the invention as claimed.
Claims (5)
1. The preparation method of the 2-hexyl decanoic acid is characterized by comprising the following steps of:
s1: ethyl acetoacetate or methyl acetoacetate is used as a starting material, in anhydrous solution of sodium methoxide or sodium ethoxide, the two alkylation reactions are sequentially carried out with halogenated octane and halogenated hexane, and then ethyl acetate is used for extraction to obtain an intermediate B; the molar ratio of the starting material to the halooctane is 1: (1-1.2) a molar ratio of the starting material to the halohexane of 1: (1-1.2);
s2: the intermediate B is decomposed in an alkaline aqueous solution with a concentration of 30-50 mass percent, and then extracted with ethyl acetate to obtain 2-hexyl decanoic acid.
2. The method for producing 2-hexyldecanoic acid according to claim 1, wherein the alkaline aqueous solution is an aqueous sodium hydroxide solution or an aqueous potassium hydroxide solution.
3. The method for producing 2-hexyldecanoic acid according to claim 1, wherein the concentration of the alkaline aqueous solution is 35 to 45% by mass.
4. A process for the preparation of 2-hexyldecanoic acid according to any one of claims 1 to 3, wherein the halogen of the halooctane and halohexane is selected from chlorine, bromine, iodine.
5. A process for the preparation of 2-hexyldecanoic acid according to any one of claims 1 to 3, wherein the anhydrous solution is an anhydrous methanol solution or an anhydrous ethanol solution.
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