Synthetic method of ethylhexylglycerin

Abstract

The invention belongs to the technical field of pharmaceutical chemicals, and particularly relates to a synthetic method of ethylhexylglycerin. The preparation method comprises the following steps: carrying out Williamson reaction on 2-ethylhexyl alkoxide and 4-(chloromethyl)-2, 2-dimethyl-1, 3-dioxolane to obtain 4-[((2-ethylhexyl) oxy) methyl]-2, 2-dimethyl-1, 3-dioxolane, adding an aqueous solution of acid into a system after the reaction is completed, and carrying out ketal removal reaction to obtain ethylhexyl glycerol. According to the ethylhexylglycerin prepared by the synthesis method provided by the invention, the yield is up to 95% or above, and the purity is up to 99.9% or above.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical chemical industry, and particularly relates to a method for synthesizing ethylhexylglycerol. Background Art

[0002] Ethylhexylglycerin is a new type of multifunctional nonionic surfactant. It can be used as a preservative, antibacterial agent, deodorant, emollient, synergist, emulsifier, plasticizer, octane improver, defoamer and other additives, and the product has biological efficacy. It is mainly used in the daily chemical industry and is recognized worldwide as a non-toxic and harmless organic preservative. Due to the late development and application of ethylhexylglycerin, the existing synthesis method has a long process route, complex reactions, and expensive products, which greatly limits its application.

[0003] At present, the reported synthesis methods of ethylhexylglycerol mainly include glycidyl ether method and glycidyl ester method (Hu Wei, Li Fang, Li Jian, et al. A method for preparing ethylhexylglycerol: CN201711481343.4). Among them, the glycidyl ether method is further divided into acetone carbonyl addition method (Li Chengbei, Yang Jie, Wang Heping, et al. A method for preparing high-purity ethylhexylglycerol: CN201510239933.0), acetic anhydride esterification method (Ding Shengfeng. A method for synthesizing octoxyglycerol: CN201710605563.7), sodium acetate hydrolysis method (Xin Hua, Zhong Quanfa, Shi Lihui. A synthesis process of a new cosmetic antibacterial agent octoxyglycerol: CN201410626792.3), and enzyme-catalyzed hydrolysis method (Shi Luqiu, Wang Changguo, Su Guizhen, et al. A method for preparing ethylhexylglycerol: CN201811353198.6). The glycidyl ether method uses 2-ethylhexylglyceryl ether as raw material and uses different methods to produce ethylhexyl glycerol. The main problem of this method is the high cost of raw materials and the easy polymerization under high temperature conditions, which greatly affects the yield. The glycidyl ester method uses 2-ethylhexanol and carboxylic acid glycidyl ester as raw materials, and reacts under the action of boron trifluoride ether to obtain 2-ethylhexyl carboxylic acid glyceride, and then hydrolyzes under acidic conditions to obtain ethylhexyl glycerol. This method has the disadvantages of easy polymerization, long reaction time and great separation difficulty. Cheng Xitao et al. used isooctyl alcohol, 3-chloro-1,2-propylene glycol and common inorganic bases as raw materials, prepared the target product ethylhexyl glycerol through a one-step reaction, and then separated the organic phase and molecular distillation equipment to distill the organic phase components under a vacuum of 40-50Pa to obtain a high-purity ethylhexyl glycerol product (CN202011517370.4). The total yield of this method is low, with a maximum of only 86%. The reason is that 3-chloro-1,2-propanediol generates glycidol under alkaline conditions, or reacts with sodium isooctyl to obtain ethylhexyl glycidyl ether. Both products are very easy to produce polymerization products under alkaline conditions, resulting in a decrease in yield and a significant increase in solid waste, which is not conducive to industrial application.

[0004] In view of the above situation, how to prepare ethylhexylglycerol at low cost, high yield and high purity becomes a difficult problem in its industrial preparation process. Summary of the invention

[0005] In order to solve the above technical problems, the purpose of the present invention is to provide a method for synthesizing ethylhexyl glycerol. The present invention selects 2-ethylhexyl alcohol salt and 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane to perform a Willi amson reaction to obtain 4-[((2-ethylhexyl)oxy)methyl]-2,2-dimethyl-1,3-dioxolane. After the reaction is completed, an aqueous solution of an acid is added to the system to perform a deketalization reaction to obtain ethylhexyl glycerol. The ethylhexyl glycerol prepared by the synthesis method provided by the present invention has a yield of more than 95% and a purity of more than 99.9%.

[0006] In order to achieve the above technical objectives, the present invention adopts the following technical solutions:

[0007] A method for synthesizing ethylhexylglycerol comprises the following steps:

[0008] 2-ethylhexanol is subjected to alkalization and dehydration to obtain 2-ethylhexyl alcohol salt; after the reaction is completed, 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane is added thereto to perform Williamson synthesis reaction; after the reaction is completed, the temperature is lowered, an acid aqueous solution is added to the reaction system to perform a deketalization reaction, and after the reaction is completed, ethylhexyl glycerol is fractionated to obtain ethylhexyl glycerol, and the yield of the obtained ethylhexyl glycerol is more than 95% and the purity is more than 99.9%.

[0009] Furthermore, the base used in the alkalization dehydration is a solid inorganic base.

[0010] Furthermore, the solid inorganic base is selected from potassium hydroxide and / or sodium hydroxide, preferably potassium hydroxide.

[0011] Furthermore, the acid is selected from any one of p-toluenesulfonic acid, methanesulfonic acid, sulfuric acid, phosphoric acid and hydrochloric acid, preferably hydrochloric acid.

[0012] Further, the molar ratio of 2-ethylhexanol to the inorganic base is 1.5-3:1, preferably 2-3:1.

[0013] Further, the molar ratio of 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane to the inorganic base is 1:1.1-1.5, preferably 1:1.2.

[0014] Further, the molar ratio of the acid to 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane is 4%-6%.

[0015] Furthermore, the synthesis method of ethylhexyl glycerol includes the following steps: mixing 2-ethylhexanol with a solid inorganic base, reacting at 184-186° C. for 1.5-3 hours to obtain anhydrous 2-ethylhexyl alcohol salt; after the reaction is completed, adding 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane thereto, reacting at 184-186° C. for 1-2 hours, and performing Williamson synthesis to generate 4-[((2-ethylhexyl)oxy)methyl]-2,2-dimethyl-1,3-dioxolane; after the reaction is completed, cooling to 75-85° C., adding an aqueous solution of an acid to the reaction system, reacting at 75-85° C. for 0.5-1 hour, performing a deketalization reaction, and after the reaction is completed, fractionating to obtain ethylhexyl glycerol.

[0016] Further, 3-chloro-1,2-propylene glycol and acetone are subjected to ketal reaction under anhydrous acid catalysis, and anhydrous 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane is obtained by fractionation. In the ketal reaction, the acid is selected from any one of p-toluenesulfonic acid, methanesulfonic acid, sulfuric acid, and phosphoric acid, preferably sulfuric acid; the molar ratio of 3-chloro-1,2-propylene glycol to acetone is 1:1-2, and the molar ratio of acid to 3-chloro-1,2-propylene glycol is 1%-5%; the reaction conditions are: 50-56°C for 1-2 hours.

[0017] In the present invention, 3-chloro-1,2-propylene glycol is used as a starting material, and the reaction formula for preparing ethylhexyl glycerol is as follows:

[0018]

[0019] The present invention has the following beneficial effects:

[0020] 1. Compared with the method in the prior art in which isooctyl alcohol, 3-chloro-1,2-propylene glycol and a common inorganic base are reacted in one step to prepare a target product, the method of the present invention avoids direct contact between 3-chloro-1,2-propylene glycol and isooctyl alcohol and the base, and thus overcomes the following shortcomings: the raw material 3-chloro-1,2-propylene glycol generates glycidol during the reaction, and glycidol is easily polymerized under alkaline conditions or at high temperatures, resulting in reduced yield and decreased purity; sodium isooctyl alcohol and 3-chloro-1,2-propylene glycol react to obtain ethylhexyl glycidyl ether, and this product is also easily polymerized under alkaline conditions, resulting in reduced yield and decreased purity.

[0021] 2. The present invention provides a new synthesis route of ethylhexylglycerol. The total yield of the target product ethylhexylglycerol can reach 95%-97%, the purity can reach 99.92%-99.97%, and there is no peculiar smell.

[0022] 3. The raw material 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane selected in the synthesis method of the present invention contains a five-membered ring and has a stable structure. It can be easily obtained by the ketal protection reaction of 3-chloro-1,2-propanediol and acetone. Since no by-products are generated in the entire synthesis method, the equipment requirements are low. For example, ordinary fractionation equipment can be used at the end, and there is no need to use expensive molecular distillation equipment. The operation is simple and the safety factor is high. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is the hydrogen spectrum of ethylhexylglycerol prepared in Example 1 of the present invention. DETAILED DESCRIPTION

[0024] In order to make the purpose and technical solution of the embodiment of the present invention clearer, the technical solution of the present invention will be clearly and completely described in combination with the embodiment of the present invention. Obviously, the described embodiment is a part of the embodiment of the present invention, not all of the embodiments. Based on the described embodiment of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0025] It will be understood by those skilled in the art that, unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as those generally understood by those skilled in the art in the art to which the present invention belongs. It should also be understood that terms such as those defined in common dictionaries should be understood to have meanings consistent with the meanings in the context of the prior art, and will not be interpreted with idealized or overly formal meanings unless defined as herein.

[0026] Embodiment 1 A method for synthesizing ethylhexylglycerol comprises the following steps:

[0027] 111.6 g (1.01 mol) 3-chloro-1,2-propylene glycol was mixed with 87.9 g (1.515 mol) acetone, and then 1.98 g (0.0202 mol) 100% sulfuric acid was added, and the mixture was reacted at 55°C for 1 hour. After the reaction was completed, 150.5 g 4-(Chloromethyl)-2,2-dimethyl-1,3-dioxolane, yield: 99%, purity: 99.5% (using standard substance, external standard method to determine its purity, Agilent 8860 gas chromatograph, FID detector, chromatographic column: Agilent HP-5: 30m×0.30mm×0.25um, injection port temperature: 250°C, detector temperature: 280°C, column temperature program: 60°C (maintained for 3min), temperature gradient: 10°C, endpoint temperature: 250°C (maintained for 2min), split ratio: 20:1, 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane elution time: 15.7min);

[0028] 312g (2.4mol) 2-ethylhexanol was mixed with 67.2g (1.2mol) solid potassium hydroxide, reacted at 185°C and separated water, and the reaction was completed in 1.5h to obtain a 2-ethylhexanol solution of potassium 2-ethylhexanol; then 150.5g (1mol) 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane was added to the 2-ethylhexanol solution of potassium 2-ethylhexanol, and the mixture was refluxed at 185°C to carry out a Williamson reaction, and the reaction was completed in 1 hour; the reaction system was cooled to 75-80°C, 6g (0.05mol) 30wt% hydrochloric acid was added to the reaction solution, and the mixture was reacted at 80°C for 30 minutes to remove the ketal protection, and after the reaction was completed, 199.9g colorless liquid ethylhexylglycerol (see hydrogen spectrum) was obtained by fractionation. Figure 1 ), yield 98%, purity 99.97% (using standard substances, using external standard method to determine its purity, Agilent 8860 gas chromatograph, FID detector, chromatographic column Agilent HP-5: 30m×0.30mm×0.25um, injection port temperature: 250°C, detector temperature: 280°C, column temperature program: 60°C (maintained for 3min), temperature gradient of 10°C, endpoint temperature of 250°C (maintained for 2min), split ratio: 20:1, ethylhexylglycerol elution time is 14.9min).

[0029] Embodiment 2 A method for synthesizing ethylhexylglycerol comprises the following steps:

[0030] 112.7 g (1.02 mol) of 3-chloro-1,2-propylene glycol was mixed with 88.8 g (1.53 mol) of acetone, and then 3.51 g (0.0204 mol) of p-toluenesulfonic acid powder was added, and the mixture was reacted at 55° C. for 1.5 hours. After the reaction was completed, 150.5 g of 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane was obtained by fractionation, with a yield of 98% and a purity of 99.2% (the purity was determined by using a standard substance and an external standard method);

[0031] 468g (3.6mol) of 2-ethylhexanol was mixed with 48g (1.2mol) of solid sodium hydroxide, reacted at 185°C and separated water, and the reaction was completed in 3h to obtain a 2-ethylhexanol solution of sodium 2-ethylhexanol; then 150.5g (1mol) of 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane was added to the 2-ethylhexanol solution of sodium 2-ethylhexanol, and the mixture was refluxed at 185°C for a Willi amson reaction, and the reaction was completed in 2 hours; the reaction system was cooled to 75-80°C, 6g (0.05mol) of 30wt% hydrochloric acid was added to the reaction solution, and the mixture was reacted at 80°C for 30 minutes to remove the ketal protection. After the reaction was completed, 197.9g of colorless liquid ethylhexylglycerol was obtained by fractionation, with a yield of 97% and a purity of 99.95% (the purity was determined by an external standard method using a standard substance).

[0032] Embodiment 3 A kind of synthesis method of ethylhexylglycerol

[0033] The synthesis method of ethylhexylglycerol in this embodiment is the same as that in Example 1, except that 24.5 g (0.05 mol) of 20 wt % aqueous sulfuric acid solution is added to the reaction solution after the Wil Liamson reaction is completed, and the reaction is carried out at 80° C. for 30 minutes to remove the ketal protection. After the reaction is completed, 196.8 g of colorless liquid ethylhexylglycerol is obtained by fractionation, with a yield of 96.5% and a purity of 99.97% (the purity is determined by using a standard substance and an external standard method).

[0034] The above is only an embodiment of the present invention, and its description is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that for ordinary technicians in this field, several modifications and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention.

Claims

1. A method for synthesizing ethylhexylglycerol, characterized in that: The following steps are involved: 2-ethylhexanol is subjected to alkalization and dehydration to obtain 2-ethylhexanol salt; 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane is then added thereto to carry out a Williamson synthesis reaction; the temperature is lowered, an aqueous acid solution is added to the reaction system to carry out a deketalization reaction, and ethylhexyl glycerol is obtained by fractionation.

2. The synthesis method according to claim 1, characterized in that The alkali used in the alkalization dehydration is a solid inorganic alkali.

3. The synthesis method according to claim 2, characterized in that The solid inorganic base is selected from potassium hydroxide and / or sodium hydroxide; and / or the acid is selected from any one of p-toluenesulfonic acid, methanesulfonic acid, sulfuric acid, phosphoric acid, and hydrochloric acid.

4. The synthesis method according to claim 2, characterized in that The molar ratio of 2-ethylhexanol to the inorganic base is 1.5-3:1; and / or the molar ratio of 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane to the inorganic base is 1:1.1-1.

5.

5. The synthesis method according to claim 4, characterized in that The molar ratio of 2-ethylhexanol to the inorganic base is 2-3:1; and / or the molar ratio of 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane to the inorganic base is 1:1.

2.

6. The synthesis method according to claim 1, characterized in that The molar ratio of acid to 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane is 4% to 6%.

7. The synthesis method according to any one of claims 1 to 6, characterized in that The following steps are involved: 2-ethylhexanol is mixed with a solid inorganic base, and the mixture is reacted at 184-186° C. for 1.5-3 hours to obtain anhydrous 2-ethylhexanol salt; after the reaction is completed, 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane is added thereto, and the mixture is reacted at 184-186° C. for 1-2 hours to perform a Williamson synthesis reaction to generate 4-[((2-ethylhexyl)oxy)methyl]-2,2-dimethyl-1,3-dioxolane; after the reaction is completed, the temperature is lowered to 75-85° C., an aqueous acid solution is added to the reaction system, and the mixture is reacted at 75-85° C. for 0.5-1 hour to perform a deketalization reaction, and after the reaction is completed, ethylhexylglycerol is obtained by fractionation.

8. The synthesis method according to claim 1, characterized in that 3-Chloro-1,2-propanediol and acetone are reacted in anhydrous acid catalysis to form a ketal reaction, and anhydrous 4-(chloromethyl)-2,2-dimethyl-1,3-dioxolane is obtained by fractional distillation.

9. The synthesis method according to claim 8, characterized in that The acid is selected from any one of p-toluenesulfonic acid, methanesulfonic acid, sulfuric acid, and phosphoric acid; the molar ratio of 3-chloro-1,2-propylene glycol to acetone is 1:1-2, and the molar ratio of the acid to 3-chloro-1,2-propylene glycol is 1%-5%; the reaction conditions are: 50-56° C. for 1-2 hours.

10. The synthesis method according to claim 1, characterized in that The yield of the obtained ethylhexyl glycerin is above 95%, and the purity is above 99.9%.

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