Method for green synthesis of DL panthenol diethyl ether

Abstract

The invention discloses a method for green synthesis of DL panthenol diethyl ether, and relates to the field of chemical synthesis, in particular to preparation of DL panthenol diethyl ether by synthesis of DL pantoic acid lactone and 3-ethoxypropylamine, dehydration treatment is respectively performed on raw materials DL pantoic acid lactone and 3-ethoxypropylamine before reaction, reaction liquid is prepared through one-step reaction after dehydration is finished, and the DL panthenol diethyl ether is prepared through one-step reaction after reaction is finished. And deaminating under reduced pressure to obtain the finished product DL panthenol diethyl ether. The yield of the prepared product is as high as 99.3%, the yield is high, the cost is low, three wastes are basically avoided, and the method belongs to green and clean production.

Description

Technical Field

[0001] The invention relates to the field of chemical synthesis, and in particular to a method for green synthesis of DL panthenol ethyl ether. Background Art

[0002] DL Panthenol Ethyl Ether, English name:

[0003] (R)-(+)-2,4-Dihydroxy-N-(3-ethoxypropyl)-3,3-dimethylbutyramide, molecular formula C 11 H 23 NO4, CAS No. 667-84-5, is a colorless to light yellow viscous transparent liquid used as a cosmetic additive.

[0004] D-panthenol ethyl ether is a physiologically active right-handed stereoisomer, mainly used in the pharmaceutical industry and the production of high-end cosmetics, while dl-panthenol ethyl ether is a racemic mixture of d-panthenol ethyl ether and l-panthenol ethyl ether, and its physiological activity is 50% of that of d-panthenol ethyl ether, and is widely used in "hair regeneration promotion composition". Panthenol ethyl ether is also widely used in skin care product compositions as one of the skin nutrition components, which has a beneficial effect on preventing skin cracking and beautifying the skin. Panthenol ethyl ether is one of the excellent pantothenic acid series products, with similar functions to panthenol, but with lower viscosity than panthenol and lower production cost.

[0005] Therefore, it is urgent to develop a green method for synthesizing DL-panthenol ethyl ether to meet market demand. Summary of the invention

[0006] The purpose of the present invention is to solve at least one of the technical problems existing in the prior art and to provide a green method for synthesizing DL panthenol ethyl ether.

[0007] The technical solution of the present invention is as follows:

[0008] A green method for synthesizing DL panthenol ethyl ether comprises the steps of dehydrating DL pantolactone and 3-ethoxypropylamine respectively, and performing a one-step synthesis reaction between the dehydrated DL pantolactone and the dehydrated 3-ethoxypropylamine to obtain DL panthenol ethyl ether.

[0009] Preferably, the method specifically comprises the following steps:

[0010] S1: dehydrating DL pantolactone until its water content is ≤0.5%;

[0011] S2: dehydrating 3-ethoxypropylamine until its water content is ≤0.5%;

[0012] S3: adding dehydrated DL pantolactone to dehydrated 3-ethoxypropylamine dropwise, wherein the molar ratio of DL pantolactone to 3-ethoxypropylamine is 1:(1.01-1.03); during the addition, the reaction temperature is controlled not to exceed 55° C., and after the addition is completed, the reaction temperature is controlled at 45-55° C. under nitrogen protection and kept warm for 6-8 hours;

[0013] S4: After the heat preservation is completed, the vacuum is turned on, and the temperature is maintained at 50-55° C. under stirring to remove the unreacted 3-ethoxypropylamine under negative pressure. After the removal of amination is completed, sampling is performed to detect the residual amount of 3-ethoxypropylamine to be ≤0.8%, and the discharged material is the finished product of DL-panthenol ethyl ether.

[0014] Preferably, step S1 is specifically as follows: before the reaction, DL pantolactone is added into a lactone distillation kettle. After the feeding is completed, the vacuum is opened to a vacuum degree of -0.098Mpa, the temperature is increased for distillation and dehydration, and the fraction with a top temperature below 130°C is collected as the front fraction. After the front fraction is extracted, the temperature is continued to be increased to collect the positive fraction, which is DL pantolactone. The moisture content of the positive fraction is required to be ≤0.5%.

[0015] Preferably, step S2 specifically comprises: putting 3-ethoxypropylamine into a dehydration kettle, opening the vacuum to -0.06 to -0.08 MPa, controlling the temperature to below 35° C., and using dry nitrogen to perform bubbling dehydration for 2 hours until the moisture content is ≤0.5%.

[0016] Preferably, in step S2 and / or S3, the moisture content is ≤ 0.2%

[0017] Preferably, in step S3, the reaction temperature is 45-50°C.

[0018] Preferably, in step S3, the molar ratio of DL pantolactone to 3-ethoxypropylamine is 1:1.01.

[0019] Preferably, in step S4, the deamination time is 2 to 4 hours.

[0020] The invention has the beneficial effects that: the invention adopts DL pantolactone and 3-ethoxypropylamine to synthesize DL panthenol ethyl ether, dehydrates the raw materials DL pantolactone and 3-ethoxypropylamine respectively before the reaction, and obtains the reaction liquid by one-step reaction after the dehydration is completed, and then obtains the finished product DL panthenol ethyl ether after deamination under reduced pressure. The product yield is as high as 99.3%, the yield is high, the cost is low, and basically no three wastes are generated, which belongs to green and clean production. DETAILED DESCRIPTION

[0021] The present invention provides a method for green synthesis of DL panthenol ethyl ether, wherein DL pantolactone and 3-ethoxypropylamine are used to synthesize DL panthenol ethyl ether in one step. In the reaction, the water content of the reaction system has a significant effect on the reaction end point. The higher the water content, the lower the reaction rate, that is, the higher the residual raw material. If the reaction temperature is too low, the reaction speed will be affected. If the reaction temperature is too high, DL panthenol ethyl ether will decompose during the reaction and the reaction end point will not be reached. If the temperature is too high, the product color will turn yellow. Specifically, the following steps are included:

[0022] S1: Before the reaction, DL pantolactone is pre-dehydrated, and the specific treatment steps are as follows: put it into the lactone distillation kettle, after the feeding is completed, open the vacuum to the vacuum degree of -0.098Mpa, heat up the distillation and dehydration, collect the fraction with the top temperature below 130°C as the front fraction, after the front fraction is collected, continue to heat up to collect the positive fraction, which is DL pantolactone, and the moisture content of the positive fraction is required to be ≤0.5%, preferably ≤0.2%. After the moisture content is qualified, keep it warm for use;

[0023] S2: 3-ethoxypropylamine is put into a dehydration kettle, the vacuum is turned on to -0.06-0.08Mpa, the temperature is controlled below 35°C, and dry nitrogen is used for bubbling dehydration for 2 hours until the moisture content is ≤0.5%, preferably ≤0.2%. After the moisture content is qualified, it is ready for use;

[0024] S3: adding DL pantolactone positive fraction to 3-ethoxypropylamine dropwise, wherein the molar ratio of DL pantolactone to 3-ethoxypropylamine is 1:1.01 to 1:1.03, preferably 1:1.01, and the temperature is controlled not to exceed 55°C during the dropping process. After the dropping is completed, the reaction temperature is controlled at 45 to 55°C under nitrogen protection and kept warm for 6 to 8 hours, preferably 7 hours, and the reaction temperature is preferably 45 to 50°C;

[0025] S4: After the heat preservation is completed, the vacuum is turned on, and the temperature is maintained at 50-55° C. under stirring to remove the unreacted 3-ethoxypropylamine under negative pressure. The deamination time is about 2-4 hours. After the deamination is completed, samples are taken to detect the residual 3-ethoxypropylamine. If it meets the standard of ≤0.8%, the discharged material is the finished DL-panthenol ethyl ether.

[0026] The embodiments of the present invention are described in detail below. The embodiments described below are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention. If no specific techniques or conditions are specified in the embodiments, the techniques or conditions described in the literature in this area or the product specifications are used. The reagents or instruments used that do not specify the manufacturer are all conventional products that can be obtained commercially.

[0027] Example 1

[0028] S1: Take three glass flasks, put in 300g DL-pantolactone, turn on the vacuum pump, distill at -0.098Mpa, after the top temperature reaches 130°C, switch to collect 260g of authentic DL-pantolactone, detect the moisture content to be 0.3%, and set aside. The fore fraction and distillation residue produced by distillation can be applied to the next batch;

[0029] S2: Take a three-necked glass flask, put in 210g of 3-ethoxypropylamine, turn on the vacuum, and perform bubbling dehydration at 35°C under -0.08Mpa for 2hr. After the dehydration is completed, the water content is 0.2%, and it is ready for use;

[0030] S3: Add 200 g of dehydrated 3-ethoxypropylamine to the amidation reactor, and add 249.8 g of dehydrated DL-pantolactone (mol ratio is 1.01) dropwise under stirring, the temperature of the addition process does not exceed 55° C., and after the addition is completed, keep the temperature at 50° C. for 7 hours under nitrogen protection;

[0031] S4: After the heat preservation is finished, the vacuum is turned on, and the deamination is carried out at 50-55°C for 3 hours to produce 449.3g of product. After sampling and testing, the moisture content is 0.23%, the specific rotation is 0.005, the content of DL panthenol ethyl ether is 99.1%, the content of 3-ethoxypropylamine is 0.3%, and the pH is 9.6, which meets the quality standard requirements. The yield is 99.3%.

[0032] Example 2

[0033] S1: Take three-necked glass flasks, put in 500g DL-pantolactone, turn on the vacuum pump, distill at -0.098Mpa, after the top temperature reaches 131°C, switch to collect 481g of authentic DL-pantolactone, and detect the water content to be 0.24%, and set aside;

[0034] S2: Take three glass flasks, put in 384g 3-ethoxypropylamine, turn on the vacuum at -0.08Mpa and 35°C for bubbling dehydration for 4 hours. After dehydration, the water content is 0.21%, and it is ready for use;

[0035] S3: Add 380g of dehydrated 3-ethoxypropylamine to the amidation reactor, and add 470g of dehydrated DL-pantolactone (mol ratio is 1.02) dropwise under stirring, the temperature of the addition process does not exceed 55°C, and after the addition is completed, keep the temperature at 52°C for 7 hours under nitrogen protection;

[0036] S4: After the heat preservation is finished, the vacuum is turned on, and the deamination is carried out at 50-55°C for 2 hours to produce 849.2g of product. After sampling and testing, the moisture content is 0.33%, the specific rotation is 0.002, the content of DL panthenol ethyl ether is 99.4%, the content of 3-ethoxypropylamine is 0.25%, and the pH is 9.4, which meets the quality standard requirements. The yield is 98.8%.

[0037] Example 3

[0038] S1: Take three glass flasks, put in 500g DL-pantolactone, turn on the vacuum pump, distill at -0.098Mpa, after the top temperature reaches 133°C, switch to collect 484g of authentic DL-pantolactone, and detect the water content to be 0.2% for standby use;

[0039] S2: Take three glass flasks, put in 384g 3-ethoxypropylamine, turn on the vacuum at -0.076Mpa and 35°C for bubbling dehydration for 3 hours. After dehydration, the water content is 0.26%, and it is ready for use;

[0040] S3: Add 380g of dehydrated 3-ethoxypropylamine to the amidation reactor, and add 465.4g of dehydrated DL-pantolactone (mol ratio is 1.03) dropwise under stirring, the temperature of the addition process does not exceed 55°C, and after the addition is completed, keep the temperature at 51°C for 8 hours under nitrogen protection;

[0041] S4: After the heat preservation is finished, the vacuum is turned on, and the deamination is carried out at 50-55°C for 2 hours to produce 844.9g of product. After sampling and testing, the moisture content is 0.36%, the specific rotation is 0.001, the content of DL panthenol ethyl ether is 99.3%, the content of 3-ethoxypropylamine is 0.4%, and the pH is 9.9, which meets the quality standard requirements. The yield is 98.3%.

[0042] Comparative Example 1:

[0043] S1: Take authentic DL pantolactone, test the water content to be 0.92%, and set aside;

[0044] S2: 380 g of 3-ethoxypropylamine (water content 0.74%) was added to an amidation reactor, and 465.4 g of DL-pantolactone (mol ratio 1.03) was added dropwise under stirring. The temperature of the addition process did not exceed 55° C. After the addition was completed, the temperature was kept at 51° C. for 8 hours under nitrogen protection;

[0045] S3: After the heat preservation is finished, the vacuum is turned on, and the deamination is carried out at 50-55°C for 2 hours to produce 843.3 g of product. After sampling and testing, the moisture content is 0.96%, the specific rotation is 0.001, the content of DL panthenol ethyl ether is 98.2%, the content of 3-ethoxypropylamine is 1.0%, and the pH is 10.8. The yield is 98.1%.

[0046] Comparative Example 2:

[0047] S1: Take authentic DL pantolactone, test the water content to be 1.8%, and set aside;

[0048] S2: 380 g of 3-ethoxypropylamine (water content 0.74%) was added to an amidation reactor, and 470 g of DL-pantolactone (mol ratio 1.02) was added dropwise under stirring, and the temperature of the addition process did not exceed 55° C. After the addition was completed, the temperature was kept at 51° C. for 8 hours under nitrogen protection;

[0049] S3: After the heat preservation is finished, the vacuum is turned on, and the deamination is carried out at 50-55°C for 2 hours. The product is 838.9g, and the sample is taken for testing. The moisture content is 1.3%, the specific rotation is 0.001, the content of DL panthenol ether is 96.7%, the content of 3-ethoxypropylamine is 1.4%, and the pH is 11.9. The yield is 97.6%. The product content and pH do not meet the requirements.

[0050] The above-mentioned embodiments only express the preferred implementation modes of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the present invention. It should be pointed out that, for ordinary technicians in this field, various other corresponding changes and deformations can be made according to the technical solutions and concepts described above, and all these changes and deformations should fall within the scope of protection of the claims of the present invention.

Claims

1. A method for green synthesis of DL panthenol ethyl ether, characterized in that: DL pantolactone and 3-ethoxypropylamine are subjected to dehydration treatment respectively, and the dehydrated DL pantolactone and the dehydrated 3-ethoxypropylamine are subjected to a one-step synthesis reaction to obtain DL panthenol ethyl ether.

2. A method for green synthesis of DL panthenol ethyl ether according to claim 1, characterized in that: The following steps are involved: S1: dehydrating DL pantolactone until its water content is ≤0.5%; S2: dehydrating 3-ethoxypropylamine until its water content is ≤0.5%; S3: adding dehydrated DL pantolactone to dehydrated 3-ethoxypropylamine dropwise, wherein the molar ratio of DL pantolactone to 3-ethoxypropylamine is 1:(1.01-1.03); during the addition, the reaction temperature is controlled not to exceed 55° C., and after the addition is completed, the reaction temperature is controlled at 45-55° C. under nitrogen protection and kept warm for 6-8 hours; S4: After the heat preservation is completed, the vacuum is turned on, and the temperature is maintained at 50-55° C. under stirring to remove the unreacted 3-ethoxypropylamine under negative pressure. After the removal of amination is completed, sampling is performed to detect the residual amount of 3-ethoxypropylamine to be ≤0.8%, and the discharged material is the finished product of DL-panthenol ethyl ether.

3. A method for green synthesis of DL panthenol ethyl ether according to claim 2, characterized in that, Step S1 is specifically as follows: before the reaction, DL pantolactone is added into the lactone distillation kettle. After the feeding is completed, the vacuum is opened to a vacuum degree of -0.098Mpa, the temperature is increased for distillation and dehydration, and the fraction with a top temperature below 130°C is collected as the front fraction. After the front fraction is extracted, the temperature is continued to be increased to collect the positive fraction, which is DL pantolactone, and the moisture content of the positive fraction is required to be ≤0.5%.

4. A method for green synthesis of DL panthenol ethyl ether according to claim 2, characterized in that, Step S2 is specifically as follows: 3-ethoxypropylamine is put into a dehydration kettle, vacuum is turned on to -0.06-0.08Mpa, the temperature is controlled below 35°C, and dry nitrogen is used for bubbling dehydration for 2 hours until the water content is ≤0.5%.

5. A green method for synthesizing DL panthenol ethyl ether according to any one of claims 2 to 4, characterized in that: In step S2 and / or S3, the moisture content is ≤0.2%.

6. A green method for synthesizing DL panthenol ethyl ether according to claim 2, characterized in that: In step S3, the reaction temperature is 45-50°C.

7. A green method for synthesizing DL panthenol ethyl ether according to claim 2, characterized in that: In step S3, the molar ratio of DL pantolactone to 3-ethoxypropylamine is 1:1.

01.

8. A green method for synthesizing DL panthenol ethyl ether according to claim 2, characterized in that: In step S4, the deamination time is 2 to 4 hours.