Purification method of a cooling agent N-ethyl-2,2-diisopropylbutyramide

Abstract

The present invention relates to a purification method of a cooling agent N-ethyl-2,2-diisopropylbutyramide, which comprises the following steps: The crude N-ethyl-2,2-diisopropylbutyramide undergoes melt crystallization, and after heating and sweating, high-purity N-ethyl-2,2-diisopropylbutyramide is obtained; The mother liquors generated during the crystallization process and the sweating process are collected separately. The components with a N-ethyl-2,2-diisopropylbutyramide content ≥ 70 wt% are mixed with the normal crystallization raw materials and used as crystallization raw materials for continuous use; The components with a N-ethyl-2,2-diisopropylbutyramide content lower than 70 wt% in the mother liquors filtered during the crystallization process and the sweating process, which are no longer suitable for direct purification by the melt crystallization method, are collected together and subjected to vacuum distillation, and the fractions with a purity ≥ 70% are collected. This part of N-ethyl-2,2-diisopropylbutyramide is used as a crystallization raw material for continuous use. Compared with the prior art, the product obtained by the present invention has high purity, no additional solvent needs to be added, and the fragrance of N-ethyl-2,2-diisopropylbutyramide is not affected by foreign solvents. Moreover, the crystallization process is safe and environmentally friendly.

Description

Technical Field

[0001] The present invention relates to the technical field of synthetic perfume purification, and particularly relates to a purification method for a cooling agent N-ethyl-2,2-diisopropylbutyramide. Background Art

[0002] L-menthol is the most familiar cooling agent to people. It has a cool, fresh and pleasant mint characteristic aroma and is widely used in products such as daily chemicals, food, tobacco, medicine and personal hygiene products. However, with the continuous improvement of people's requirements for cooling products, the deficiencies and disadvantages of L-menthol have been exposed, mainly as follows: (1) L-menthol is volatile and not heat-resistant, and its use is restricted in some foods and cigarettes that need to be heat-treated; (2) Since its cooling effect lasts for a short time on human skin and in the mouth while the instantaneous cooling effect is strong, it makes people uncomfortable and affects its use effect in foods (such as chewing gum) and personal skin care products. This objectively promotes the synthesis and research of new cooling agents. In the past thirty years, many kinds of cooling agents have been synthesized and are also widely used in fields such as food and cosmetics.

[0003] Amide-based cooling agents are mainly developed by Wilkinson Sword Ltd, such as WS-3, WS-5, WS-12, etc. They are extended on the basis of L-menthol with the configuration remaining unchanged. There is also a type of non-menthol cooling agent, and the most commercially successful one is WS-23 (FEMA: 3804), WS-27 (FEMA: 3804). WS-27 is a colorless crystal with high cooling activity and no side effects such as burning, numbness and irritation. It is mainly used as a cooling agent in medicines, oral care products and candies. The main advantages are low toxicity, high cooling activity, small odor and taste, stability during use, and low production cost. It is a food flavor allowed to be used in GB-2760. It can be widely used in foods, daily chemicals and medicines.

[0004] Patent CN 102260185 A reports that WS-27 is synthesized in one step by Ritter reaction using diisopropylbutyronitrile (BIPPN) as a raw material and different strong acids; but the separation basically obtains the pure product through rectification or solvent crystallization with petroleum ether or a mixed solvent, etc. The petroleum ether or mixed solvent for crystallization has a low flash point and is prone to cause safety problems; the solvent recovery is prone to loss, increasing the environmental protection treatment cost; the solvent has a strong odor, and a little residue has a great impact on the product odor. Summary of the Invention

[0005] The object of the present invention is to provide a purification method for the cooling flavorant N-ethyl-2,2-diisopropylbutyramide so as to overcome at least one of the defects existing in the above-mentioned prior art. The product obtained by this method has high purity, no additional solvent needs to be added, and the fragrance of N-ethyl-2,2-diisopropylbutyramide is not affected by foreign solvents. Moreover, the crystallization process is safe and environmentally friendly.

[0006] The object of the present invention can be achieved by the following technical solutions:

[0007] A purification method for the cooling flavorant N-ethyl-2,2-diisopropylbutyramide (WS-27) comprises the following steps:

[0008] Step 1: Add the N-ethyl-2,2-diisopropylbutyramide containing impurities into a crystallizer, rapidly heat it to above 40°C to completely dissolve the N-ethyl-2,2-diisopropylbutyramide, turn on the stirring, and slowly cool it to 5-10°C through the jacket of the crystallizer. After maintaining for 1-5 h, filter out the uncrystallized mother liquor;

[0009] Step 2: After discharging the mother liquor, slowly raise the temperature of the crystals to 39-40°C by controlling the temperature of the jacket of the crystallizer, and maintain for 30-60 min to allow partial melting and sweating of the crystals. Filter out the sweating liquid at different temperature points and collect it as mother liquor according to the purity;

[0010] Step 3: After rapidly cooling the crystallizer to 15-20°C, open the bottom side compartment door, and take out the crystallization material through stirring to obtain N-ethyl-2,2-diisopropylbutyramide with a purity greater than 99.8 wt%, wherein the impurities include ethyl 2,2-diisopropylbutyrate and N-ethyl-2-isopropylbutyramide, and the content of each single impurity is less than 0.1 wt%. The content of commercially available WS-27 is generally 99.5%, and the enterprise standard is: the content of WS-27 ≥ 99.0%. Therefore, the content of WS-27 obtained by the present invention has a significant advantage.

[0011] Further, in the N-ethyl-2,2-diisopropylbutyramide containing impurities, the content of N-ethyl-2,2-diisopropylbutyramide ≥ 70 wt%.

[0012] Further, in Step 1 and Step 3, during the crystallization process, the temperature of the crystallization material is controlled by reducing or increasing the temperature of the refrigerant, the cooling rate is controlled at: 1.0-5°C / h, and the heating rate is controlled at: 1.0-5.0°C / h.

[0013] Further, in Step 3, the single-pass crystallization yield of the crystallization process ≥ 85%.

[0014] Further, the mother liquor filtered out during the crystallization process in Step 1 and the sweating process in Step 2 is combined according to the principle of similar content. The component with the content of N-ethyl-2,2-diisopropylbutyramide ≥ 70 wt% is mixed with the normal crystallization raw material and then returned to Step 1 as the crystallization raw material for continuous use.

[0015] Further, for the component with the content of N-ethyl-2,2-diisopropylbutyramide lower than 70 wt% in the mother liquor filtered out during the crystallization process in Step 1 and the sweating process in Step 2, which is no longer suitable for direct purification by the melt crystallization method, it is combined and collected and then subjected to vacuum distillation. The fraction of N-ethyl-2,2-diisopropylbutyramide with a purity ≥ 70 wt% is collected and returned to Step 1 as the crystallization raw material for continuous use.

[0016] Further, the vacuum degree in the vacuum distillation is controlled at 2 - 5 mmHg.

[0017] Compared with the prior art, the present invention has the following beneficial effects:

[0018] (1) The present invention provides a method for purifying the cooling agent N-ethyl-2,2-diisopropylbutyramide by melt crystallization, and N-ethyl-2,2-diisopropylbutyramide with a content greater than 99.8 wt% can be obtained.

[0019] (2) The present invention adopts a melt crystallization - distillation - coupling process, which can fully recover N-ethyl-2,2-diisopropylbutyramide in the raw material.

[0020] (3) Compared with solvent crystallization, the present invention does not require additional solvents, and there is no influence of foreign solvents on the fragrance of N-ethyl-2,2-diisopropylbutyramide, and the crystallization process is safe and environmentally friendly. Description of the Drawings

[0021] Figure 1 It is the gas chromatogram of the pure product of N-ethyl-2,2-diisopropylbutyramide in Example 1. Detailed Embodiments

[0022] The present invention will be described in detail below with reference to the drawings and specific embodiments. This embodiment is implemented on the premise of the technical solution of the present invention, and the detailed implementation manners and specific operation processes are given, but the protection scope of the present invention is not limited to the following embodiments.

[0023] A method for purifying the cooling agent N-ethyl-2,2-diisopropylbutyramide includes the following steps:

[0024] Step 1: Add the N-ethyl-2,2-diisopropylbutyramide containing impurities into the crystallizer, quickly heat it to above 40 °C to completely dissolve the N-ethyl-2,2-diisopropylbutyramide, turn on the stirrer, and slowly cool it to 5 - 10 °C through the jacket of the crystallizer. After maintaining for 1 - 5 h, filter out the uncrystallized mother liquor;

[0025] Step 2: After discharging the mother liquor, slowly raise the temperature of the crystals to 39 - 40 °C by controlling the temperature of the jacket of the crystallizer, and maintain for 30 - 60 min to allow partial melting and sweating of the crystals. Filter out the sweating liquid at different temperature points and collect it as mother liquor according to purity;

[0026] Step 3: After quickly cooling the crystallizer to 15 - 20 °C, open the bottom side door, and take out the crystallized material by stirring to obtain N-ethyl-2,2-diisopropylbutyramide with a purity greater than 99.8 wt%. The impurities include ethyl 2,2-diisopropylbutyrate and N-ethyl-2-isopropylbutyramide, and the content of each single impurity is less than 0.1 wt%.

[0027] Step 4: The mother liquors filtered out during the crystallization process in Step 1 and the sweating process in Step 2 are combined according to the principle of similar content. The component with a N-ethyl-2,2-diisopropylbutyramide content ≥ 70 wt% is mixed with the normal crystallization raw material and then returned to Step 1 as the crystallization raw material for continued use.

[0028] Step 5: For the component with a N-ethyl-2,2-diisopropylbutyramide content lower than 70 wt% in the mother liquors filtered out during the crystallization process in Step 1 and the sweating process in Step 2, which is no longer suitable for direct purification by the melt crystallization method, they are combined and collected and then subjected to vacuum distillation. The vacuum degree is controlled at 2 - 5 mmHg, and the N-ethyl-2,2-diisopropylbutyramide fraction with a purity ≥ 70% is collected. This part of N-ethyl-2,2-diisopropylbutyramide is returned to Step 1 as the crystallization raw material for continued use.

[0029] Among them, in the N-ethyl-2,2-diisopropylbutyramide containing impurities, the content of N-ethyl-2,2-diisopropylbutyramide ≥ 70 wt%. In Step 1 and Step 3, the cooling rate is controlled at: 1.0 - 5 °C / h, and the heating rate is controlled at: 1.0 - 5.0 °C / h. In Step 3, the single-pass crystallization yield of the crystallization process ≥ 85%.

[0030] Example 1

[0031] Melt Crystallization

[0032] Take 1500 kg of crude WS-27. The content in the crude product is 8.59 wt% of 2,2-diisopropylbutyronitrile, 90.34 wt% of WS-27, and 1.07 wt% of N-ethyl-2-isopropylbutyramide. Place it in a 3-cubic-meter crystallizer. The jacket of the crystallizer can be passed with heating or cooling water for temperature control. Turn on the stirrer, heat the crystallizer to above 40 °C until the crystals are completely dissolved, and then cool it at a rate of 1 °C / h to 10 °C and hold for 5 h. Open the valve at the bottom of the crystallizer to discharge the uncrystallized mother liquor, and the mother liquor is used as the raw material for rectification to enrich WS-27. Then slowly heat and raise the temperature through the jacket for sweating, with a heating rate of 5.0 °C / h, heat up to 39 - 40 °C, hold for 30 min, end sweating, discharge the sweat, collect the sweating liquid, and mix it with the raw material to be used as the crystallization raw material. After cooling to 15 - 20 °C, open the side door at the bottom, and through stirring, take out 1236 kg of pure WS-23. The single-pass crystallization yield is 91.2%. Analyzed by gas chromatography, the content is 99.93 wt%, and the content of a single impurity is less than 0.1%, see Figure 1 。

[0033] Example 2

[0034] Melt crystallization

[0035] Take 1500 kg of crude WS-27. The main substance content in the crude product is 8.59 wt% of 2,2-diisopropylbutyronitrile, 90.34 wt% of WS-27, and 1.07 wt% of N-ethyl-2-isopropylbutyramide. Place it in a 3-cubic-meter crystallizer. The jacket of the crystallizer can be passed with heating or cooling water for temperature control. Turn on the stirrer, heat the crystallizer to above 40 °C until the crystals are completely dissolved, and then cool it at a rate of 5 °C / h to 5 °C and hold for 1 h. Open the valve at the bottom of the crystallizer to discharge the uncrystallized mother liquor, and the mother liquor is used as the raw material for rectification to enrich WS-27. Then slowly heat and raise the temperature through the jacket for sweating, with a heating rate of 1.0 °C / h, heat up to 39 - 40 °C, hold for 60 min, end sweating, discharge the sweat, collect the sweating liquid, and mix it with the raw material to be used as the crystallization raw material. After cooling to 15 - 20 °C, open the side door at the bottom, and through stirring, take out 1169 kg of pure WS-27. The single-pass crystallization yield is 86.2%. Analyzed by gas chromatography, the content is 99.83 wt%, and the content of a single impurity is less than 0.1%.

[0036] Example 3

[0037] Melt crystallization

[0038] Take 1500 kg of crude WS-27. The main substance contents in the crude product are 2,2-diisopropylbutyronitrile at 24.14 wt%, WS-27 at 75.23 wt%, and N-ethyl-2-isopropylbutyramide at 0.63 wt%. Place it in a 3-cubic-meter crystallizer. The jacket of the crystallizer can be passed with heating or cooling water for temperature control. Turn on the stirrer, heat up the crystallizer to above 40 °C until the crystals are completely dissolved, and then cool it down at a cooling rate of 3 °C / h to 5 °C and keep it warm for 2 h. Open the valve at the bottom of the crystallizer to discharge the uncrystallized mother liquor, and the mother liquor is used as the raw material for rectification to enrich WS-27. Then slowly heat it up through the jacket for sweating, with a heating rate of 4 °C / h, heat up to 39 - 40 °C, keep it warm for 40 min, end the sweating, discharge the sweat, collect the sweating liquid, and it can be used as the crystallization raw material after mixing with the raw material. After cooling down by 15 - 20 °C, open the side door at the bottom, and through stirring, take out 995 kg of pure WS-27. The single-pass crystallization yield is 88.2%. Analyzed by gas chromatography, the content is 99.82 wt%, and the content of a single impurity is less than 0.1%.

[0039] Example 4

[0040] Vacuum distillation

[0041] Add 1500 kg of WS-27 crystallization mother liquor to a 2-cubic-meter distillation kettle. The contents in the crystallization mother liquor are 2,2-diisopropylbutyronitrile at 41.86 wt% and WS-27 at 56.54 wt%. Conduct vacuum distillation, control the vacuum at 2 - 5 mmHg, the pre-fraction is 563 kg (2,2-diisopropylbutyronitrile at 96.56 wt%, WS-27 at 1.61 wt%), and the weight of WS-27 is 937 kg (2,2-diisopropylbutyronitrile at 8.59 wt%, WS-27 at 90.34 wt%). After accumulating the obtained crude products, take 1500 kg and operate according to Example 1 or 2.

[0042] The above are only the preferred embodiments of the present invention, and are not limitations on the present invention in other forms. Any person skilled in the art may use the technical content disclosed above to make changes or modifications into equivalent embodiments with equivalent changes. However, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the technical solution content of the present invention still belong to the protection scope of the technical solution of the present invention.

Claims

1. A purification method for the cooling agent N-ethyl-2,2-diisopropylbutyramide, characterized in that, It includes the following steps: Step 1: Add the N-ethyl-2,2-diisopropylbutyramide containing impurities into a crystallizer, quickly heat it to above 40 °C to completely dissolve the N-ethyl-2,2-diisopropylbutyramide, turn on the stirring, and slowly cool it to 5 - 10 °C through the jacket of the crystallizer. After maintaining for 1 - 5 h, filter out the uncrystallized mother liquor; Step 2: After discharging the mother liquor, slowly raise the temperature of the crystals to 39 - 40 °C by controlling the temperature of the jacket of the crystallizer and maintain for 30 - 60 min to make the crystals partially melt and sweat. Filter out the sweating liquid at different temperature points and collect it as mother liquor according to the purity; Step 3: After cooling the crystallizer to 15 - 20 °C, open the bottom side compartment door, take out the crystallization material through stirring, and obtain N-ethyl-2,2-diisopropylbutyramide with a purity greater than 99.8 wt%. The impurities include ethyl 2,2-diisopropylbutyrate and N-ethyl-2-isopropylbutyramide, and the content of each single impurity is less than 0.1 wt%.

2. The purification method of a cooling agent N-ethyl-2, 2-diisopropylbutyramide according to claim 1, characterized in that, In the N-ethyl-2,2-diisopropylbutyramide containing impurities, the content of N-ethyl-2,2-diisopropylbutyramide is ≥ 70 wt%.

3. The purification method of a cooling agent N-ethyl-2, 2-diisopropylbutyramide according to claim 1, characterized in that, In Step 1 and Step 3, the cooling rate is controlled at: 1.0 - 5 °C / h, and the heating rate is controlled at: 1.0 - 5.0 °C / h.

4. The purification method of a cooling agent N-ethyl-2, 2-diisopropylbutyramide according to claim 1, characterized in that, In Step 3, the single-pass crystallization yield of the crystallization process is ≥ 85%.

5. The purification method of a cooling agent N-ethyl-2, 2-diisopropylbutyramide according to claim 1, characterized in that, The mother liquor filtered out during the crystallization process in Step 1 and the sweating process in Step 2 are combined according to the principle of similar content. The component with a N-ethyl-2,2-diisopropylbutyramide content ≥ 70 wt% is mixed with the normal crystallization raw material and then returned to Step 1 as the crystallization raw material for continued use.

6. The purification method of a cooling agent N-ethyl-2, 2-diisopropylbutyramide according to claim 1, characterized in that, The mother liquor filtered out during the crystallization process in Step 1 and the sweating process in Step 2, which has a N-ethyl-2,2-diisopropylbutyramide content lower than 70 wt% and is no longer suitable for direct purification by the melt crystallization method, is combined and collected, and then subjected to vacuum distillation. The fraction of N-ethyl-2,2-diisopropylbutyramide with a purity ≥ 70 wt% is collected, and this part of N-ethyl-2,2-diisopropylbutyramide is returned to Step 1 as the crystallization raw material for continued use.

7. The purification method of a cooling agent N-ethyl-2,2-diisopropylbutyramide according to claim 6, characterized in that, The vacuum degree in the vacuum distillation is controlled at 2 - 5 mmHg.

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