WO2021253305A1 - 一种dl-赖氨酸的制备方法 - Google Patents

一种dl-赖氨酸的制备方法 Download PDF

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WO2021253305A1
WO2021253305A1 PCT/CN2020/096708 CN2020096708W WO2021253305A1 WO 2021253305 A1 WO2021253305 A1 WO 2021253305A1 CN 2020096708 W CN2020096708 W CN 2020096708W WO 2021253305 A1 WO2021253305 A1 WO 2021253305A1
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lysine
liquid
effluent
solid
water
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PCT/CN2020/096708
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English (en)
French (fr)
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张小峰
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苏州园方生物科技有限公司
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Priority to CN202080001050.5A priority Critical patent/CN111886220A/zh
Priority to PCT/CN2020/096708 priority patent/WO2021253305A1/zh
Publication of WO2021253305A1 publication Critical patent/WO2021253305A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C07C227/18—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof by reactions involving amino or carboxyl groups, e.g. hydrolysis of esters or amides, by formation of halides, salts or esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/38—Separation; Purification; Stabilisation; Use of additives
    • C07C227/40—Separation; Purification
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/38—Separation; Purification; Stabilisation; Use of additives
    • C07C227/40—Separation; Purification
    • C07C227/42—Crystallisation

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  • the invention relates to the field of biotechnology, in particular to a method for preparing DL-lysine.
  • DL-Lysine is one of the main raw materials for synthesizing lysine.
  • the processing technology of DL-lysine in the prior art has many processing steps and requires a lot of manpower and material resources during the processing, which is not convenient for industrial operation. The production cycle is long, the production cost is increased, and the quality of the prepared DL-lysine is poor, and the market competitiveness is poor.
  • the processing technology of DL-lysine in the prior art is also likely to cause too much product impurities, yellow color, and not meet the quality requirements. Subsequent processing is required for products that do not meet the quality standards, resulting in excessive processing costs.
  • the embodiment of the present invention provides a method for preparing DL-lysine, which has simple processing technology, is convenient for industrial operation, and has a short reaction time, which greatly improves the output of DL-lysine products. And quality, has better market competitiveness.
  • the invention discloses a method for preparing DL-lysine, which comprises the following steps:
  • the collected effluent during the elution of liquid caustic soda is distilled under reduced pressure at 55°C to 60°C, and then left to stand in an oxygen-free environment until the crystals are completely precipitated, and DL-lysine is obtained after the crystals are dried.
  • the weight ratio of L-lysine hydrochloride, glacial acetic acid and water is 1 :(2 ⁇ 2.6):(0.4 ⁇ 1).
  • the weight ratio of L-lysine hydrochloride, glacial acetic acid and water is 1 :2.6:0.4.
  • the solid rinsing method is: using 95% ethanol twice the volume of the solid to stir and wash the solid for 10-15 minutes, and centrifuge The liquid is removed, and the solid is stirred and washed with 95% ethanol of 0.5-1 times the volume of the solid for 10-15 minutes, and the liquid is removed by centrifugation.
  • the drying temperature is 70°C to 80°C.
  • the weight ratio of DL-lysine hydrochloride to water is 1:( 2 ⁇ 4).
  • the pH value is adjusted by using a 12%-15% dilute hydrochloric acid solution.
  • the step "add the upper column liquid to the cation exchange column, elute with water until the effluent does not contain chloride ions, then eluate with liquid caustic soda, and collect the effluent from the liquid caustic elution” add the upper column liquid to the cation exchange column.
  • the column solution is added to the cation exchange column and kept for 0.5h-1h before subsequent elution.
  • the concentration of liquid caustic soda is 7%-8%.
  • the effluent of the liquid caustic soda elution is vacuum distilled under reduced pressure to a solid content of 60% ⁇ 63%.
  • the DL-lysine preparation method of the invention has simple processing technology, convenient industrial operation, short reaction time, greatly improves the output and quality of DL-lysine products, and has better market competitiveness.
  • Figure 1 is a reaction schematic diagram of the preparation method of the present invention
  • Figure 2 is a flow chart of the preparation method of the present invention.
  • the color of L-lysine hydrochloride used in Examples 1 to 4 and Comparative Example 1 needs to be white or off-white to be qualified. If the color of the material is yellow or other, it is unqualified.
  • reaction solution consisting of 100Kg of L-lysine hydrochloride, 40Kg of pure water and 260Kg of glacial acetic acid into a 1000L reaction kettle, stir and heat up to 70°C ⁇ 80°C, and heat and stir for 2h, the process of heat preservation and stirring,
  • the L-lysine hydrochloride in the reaction solution fully undergoes a racemization reaction to produce DL-lysine hydrochloride.
  • the optical rotation value of the reaction solution is zero.
  • the reaction liquid after the racemization reaction in the previous step was cooled to 25° C., and the solid in the reaction liquid was suction-filtered into a clean turnover kettle using a plastic suction filter bucket.
  • Use a small amount of 95wt% ethanol to rinse the solids into the washing tank add 2 times the solid volume of 95wt% ethanol to the washing tank to wash the solids for 10-15 minutes, centrifuge to remove the washing liquid, and then add 0.5 times the solid volume of 95wt% ethanol Rinse the solid for 10-15 minutes, remove the washing liquid by centrifugation after rinsing, place the solid in a desiccator, and dry at 70°C to 80°C to obtain DL-lysine hydrochloride.
  • the upper column liquid into the cation exchange column first keep it for 0.5h so that the upper column liquid is fully absorbed by the resin particles in the cation exchange column, and then eluted with tap water until the pH value of the effluent is 6-7, and then rinsed with pure water
  • the cation exchange column makes the chloride ions in the effluent eluted and removed, that is, no chloride ions can be detected in the effluent.
  • the cation exchange column is eluted with 8% liquid caustic soda, and the effluent of the liquid caustic elution is collected.
  • the collected effluent from the elution of liquid caustic soda was distilled under reduced pressure at 55°C to 60°C to a solid content of 60% to 63%, and then placed in a clean plastic bucket, and allowed to stand at 25°C in an oxygen-free environment. The crystals were completely precipitated, the excess liquid was removed by centrifugation, and the DL-lysine sample 1 was obtained after the crystals were dried at 65°C.
  • the quality indicators of DL-lysine sample 1 prepared in this example are as follows:
  • reaction liquid consisting of 100Kg of L-lysine hydrochloride, 40Kg of pure water and 200Kg of glacial acetic acid was put into a 1000L reactor, stirred and heated to 75°C, and kept warm and stirred for 2h.
  • the reaction liquid after the racemization reaction in the previous step was cooled to 25° C., and the solid in the reaction liquid was suction-filtered into a clean turnover kettle using a plastic suction filter bucket.
  • Use a small amount of 95wt% ethanol to rinse the solids into the washing tank add 2 times the solid volume of 95wt% ethanol to the washing tank to wash the solids for 10-15 minutes, centrifuge to remove the washing liquid, and then add 0.5 times the solid volume of 95wt% ethanol Rinse the solid for 10-15 minutes, centrifuge to remove the washing liquid after rinsing, place the solid in a desiccator, and dry at 70-80°C to obtain DL-lysine hydrochloride.
  • the cation exchange column is eluted with 8% liquid caustic soda to collect the effluent from the liquid caustic elution.
  • the collected effluent from the elution of liquid caustic soda was distilled under reduced pressure at 55°C to 60°C to a solid content of 60% to 63%, and then placed in a clean plastic bucket, and allowed to stand at 25°C in an oxygen-free environment. The crystals were completely precipitated, the excess liquid was removed by centrifugation, and the DL-lysine sample 2 was obtained after the crystals were dried at 65°C.
  • the quality index of DL-lysine sample 2 prepared in this example is as follows:
  • reaction liquid consisting of 100Kg of L-lysine hydrochloride, 40Kg of pure water and 260Kg of glacial acetic acid was put into a 1000L reactor, stirred and heated to 75°C, and kept warm and stirred for 1h.
  • the reaction liquid after the racemization reaction in the previous step was cooled to 25° C., and the solid in the reaction liquid was suction-filtered into a clean turnover kettle using a plastic suction filter bucket.
  • Use a small amount of 95wt% ethanol to rinse the solids into the washing tank add 2 times the solid volume of 95wt% ethanol to the washing tank to wash the solids for 10-15 minutes, centrifuge to remove the washing liquid, and then add 0.5 times the solid volume of 95wt% ethanol Rinse the solid for 10-15 minutes, centrifuge to remove the washing liquid after rinsing, place the solid in a desiccator, and dry at 70-80°C to obtain DL-lysine hydrochloride.
  • the effluent collected during the elution of liquid caustic soda was distilled under reduced pressure at 55°C to 60°C to a solid content of 60% to 63%, and then placed in a clean plastic bucket, and allowed to stand at 25°C in an oxygen-free environment. The crystals were completely precipitated, the excess liquid was removed by centrifugation, and the DL-lysine sample 3 was obtained after the crystals were dried at 65°C.
  • the quality index of DL-lysine sample 3 prepared in this embodiment is as follows:
  • a reaction solution consisting of 100Kg of L-lysine hydrochloride, 100Kg of pure water and 260Kg of glacial acetic acid was put into a 1000L reactor, stirred and heated to 75°C, and kept warm and stirred for 6h.
  • the reaction liquid after the racemization reaction in the previous step was cooled to 25°C, and the solid in the reaction liquid was suction-filtered into a clean turnover kettle using a plastic suction filter bucket.
  • Use a small amount of 95wt% ethanol to rinse the solids into the washing tank add 95wt% ethanol of 2 times the solid volume to the washing tank to wash the solids for 10-15 minutes, centrifuge to remove the washing liquid, and then add 0.5 times the solid volume of 95wt% ethanol Rinse the solid for 10-15 minutes, remove the washing liquid by centrifugation after rinsing, place the solid in a desiccator, and dry at 70-80°C to obtain DL-lysine hydrochloride.
  • the collected effluent from the elution of liquid caustic soda was distilled under reduced pressure at 55°C to 60°C to a solid content of 60% to 63%, and then placed in a clean plastic bucket, and allowed to stand at 25°C in an oxygen-free environment. The crystals were completely precipitated, the excess liquid was removed by centrifugation, and the DL-lysine sample 4 was obtained after the crystals were dried at 65°C.
  • the quality index of DL-lysine sample 4 prepared in this embodiment is as follows in Table 5:
  • Example 1 The difference between this comparative example and Example 1 is that when preparing DL-lysine, the effluent when the collected liquid caustic soda is eluted is vacuum distilled under reduced pressure at 80°C to 85°C.
  • reaction liquid consisting of 100Kg of L-lysine hydrochloride, 40Kg of pure water and 260Kg of glacial acetic acid was put into a 1000L reactor, stirred and heated to 75°C, and kept warm and stirred for 2h.
  • the reaction liquid after the racemization reaction in the previous step was cooled to 25° C., and the solid in the reaction liquid was suction-filtered into a clean turnover kettle using a plastic suction filter bucket.
  • Use a small amount of 95wt% ethanol to rinse the solids into the washing tank add 95wt% ethanol of 2 times the solid volume to the washing tank to wash the solids for 10-15 minutes, centrifuge to remove the washing liquid, and then add 0.5 times the solid volume of 95wt% ethanol Rinse the solid for 10-15 minutes, remove the washing liquid by centrifugation after rinsing, place the solid in a desiccator, and dry at 70-80°C to obtain DL-lysine hydrochloride.
  • the collected effluent from the elution of liquid caustic soda is distilled under reduced pressure at 80°C to 85°C to a solid content of 60% to 63%, then placed in a clean plastic bucket, and allowed to stand at 25°C in an oxygen-free environment. The crystals were completely precipitated, the excess liquid was removed by centrifugation, and the DL-lysine sample 5 was obtained after the crystals were dried at 65°C.
  • the quality indicators of DL-lysine sample 5 prepared in this embodiment are as follows in Table 6:
  • Example 2 Example 3
  • Example 4 Comparative example 1 Yield 67.2% 50.2% 49.5% 66.2% 60.4%
  • the DL-lysine prepared in Examples 1 to 4 of the present invention has good quality.
  • the preparation method in Example 1 is the optimal method, and the DL-lysine prepared by the preparation method in Example 1 has better quality and a higher yield.
  • the color of L-lysine hydrochloride used in Examples 1 to 4 and Comparative Example 1 of the present invention is white or off-white, which ensures that the color indicators of the products are qualified. If the raw material L-lysine hydrochloride is yellow or other, it is unqualified.
  • the use of L-lysine hydrochloride after moisture absorption, oxidation and discoloration will affect the appearance and absorbance of the finished product, resulting in unqualified color indicators of the finished product.
  • Example 2 of the present invention reduces the dosage of glacial acetic acid, so that the racemization reaction of L-lysine hydrochloride is incomplete, resulting in a 17% lower yield of the final product. The quality has no effect.
  • Example 3 of the present invention reduces the time of the racemization reaction, and only 1 hour of the racemization reaction results in incomplete racemization reaction and reduced product yield, but has no effect on the quality of the product.
  • Example 4 of the present invention increases the dosage of pure water when L-lysine hydrochloride is racemized to prepare DL-lysine hydrochloride.
  • the optical rotation value of the reaction solution was tracked, and it was found that after the reaction time reached 6 hours, the optical rotation value of the reaction solution was 0, that is, the reaction was completed. Therefore, if the amount of pure water is input too much, it will increase the reaction time and reduce the production efficiency, but it will have no effect on the quality and yield of the product.
  • Example 1 of the present invention when preparing DL-lysine, the collected liquid caustic soda elution effluent was distilled under reduced pressure at 80°C to 85°C. Due to the high temperature, DL -The lysine sample turns yellow due to oxidation, and the final color is light yellow. During the high-temperature distillation process, the DL-lysine sample produces more derivatives, such as miscellaneous acids, which leads to product quality indicators that do not meet the requirements and reduce the product The yield. In Examples 1 to 4 of the present invention, the collected liquid caustic elution effluent was distilled under reduced pressure and vacuum at 55°C-60°C, and the DL-lysine samples obtained had good quality indicators.
  • the liquid caustic soda with a concentration of 8% is used to elute the product.
  • Sodium ions in the liquid caustic can replace the DL-lysine in the cation exchange column. If the concentration of the liquid caustic is too low , Will lead to insufficient elution, incomplete material collection, and excessively high concentration of liquid caustic soda will damage the resin particles in the cation exchange column.
  • the concentration of liquid caustic soda is selected to be 8%, which can fully elute DL-lysine in the cation exchange column without damaging the cation exchange column.
  • the collected liquid caustic elution effluent was distilled under reduced pressure at 55°C to 60°C, and then left to stand in an oxygen-free environment until the crystals were completely precipitated, and the crystals were dried.
  • DL-Lysine During the preparation process, the contact between DL-lysine and oxygen is reduced, which can prevent DL-lysine from being oxidized and turn yellow, and ensure that the finished product has better quality.
  • Examples 1 to 4 of the present invention in the elution process, tap water was used to elute the effluent to a pH of 6 to 7, and then pure water was used to rinse the cation exchange column. Dosage, thereby reducing the time required to prepare a large amount of pure water.
  • the tap water is eluted to the pH of the effluent is 6-7, a large amount of chloride ions have been removed, and then pure water is used to continue to rinse the cation exchange column until the chloride ions are completely removed, so that the production results are more accurate.

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Abstract

一种DL-赖氨酸的制备方法，包括以下步骤：将L-赖氨酸盐酸盐、冰醋酸和水搅拌升温至70℃～80℃，继续保温搅拌1～6h后，抽滤出固体，将固体进行漂洗、干燥，得到DL-赖氨酸盐酸盐。将DL-赖氨酸盐酸盐溶于水中，并调节pH值至5.0，得到上柱液。将上柱液加入阳离子交换柱中，用水洗脱至流出液中不含氯离子，再用液碱洗脱，收集液碱洗脱时的流出液。将收集的液碱洗脱时的流出液在55℃～60℃减压真空蒸馏，再于无氧环境中静置至晶体完全析出，将晶体干燥后即得DL-赖氨酸。DL-赖氨酸的制备方法，加工工艺简单，便于工业化操作，反应时间短，大大提高了DL-赖氨酸产品的产量和品质，具有较好的市场竞争力。

Description

一种DL-赖氨酸的制备方法 技术领域
本发明涉及了生物技术领域，具体的是一种DL-赖氨酸的制备方法。
背景技术
DL-赖氨酸是合成赖氨匹林的主要原料之一。现有技术中DL-赖氨酸的加工工艺，其加工步骤繁多，在加工过程中需要投入大量人力物力，不便于工业化操作。生产周期较长，增加了生产成本，并且制备得到的DL-赖氨酸品质较差，市场竞争力差。现有技术中DL-赖氨酸的加工工艺还容易造成产品杂质偏多，颜色变黄，不符合质量要求，对质量不达标的产品还需要进行后续处理，造成加工成本过高。
因此，有必要提出一种新的DL-赖氨酸的制备方法，以简化加工步骤，提高加工效率，降低加工成本。
发明内容
为了克服现有技术中的缺陷，本发明实施例提供了一种DL-赖氨酸的制备方法，其加工工艺简单，便于工业化操作，反应时间短，大大提高了DL-赖氨酸产品的产量和品质，具有较好的市场竞争力。
本发明公开了一种DL-赖氨酸的制备方法，包括以下步骤：
将L-赖氨酸盐酸盐、冰醋酸和水搅拌升温至70℃～80℃，继续保温搅拌1～6h后，抽滤出固体，将固体进行漂洗、干燥，得到DL-赖氨酸盐酸盐；
将DL-赖氨酸盐酸盐溶于水中，并调节pH值至5.0，得到上柱液；
将上柱液加入阳离子交换柱中，用水洗脱至流出液中不含氯离子，再用液碱洗脱，收集液碱洗脱时的流出液；
将收集的液碱洗脱时的流出液在55℃～60℃减压真空蒸馏，再于无氧环境中静置至晶体完全析出，将晶体干燥后即得DL-赖氨酸。
作为优选，所述步骤“将L-赖氨酸盐酸盐、冰醋酸和水搅拌升温至70℃～80℃”中，L-赖氨酸盐酸盐、冰醋酸和水的重量比为1:(2～2.6):(0.4～1)。
作为优选，所述步骤“将L-赖氨酸盐酸盐、冰醋酸和水搅拌升温至70℃～80℃”中，L-赖氨酸盐酸盐、冰醋酸和水的重量比为1:2.6:0.4。
作为优选，所述步骤“将固体进行漂洗、干燥，得到DL-赖氨酸盐酸盐”中，固体漂洗方法为：采用固体体积2倍的95％乙醇对固体进行搅拌洗涤10～15min，离心去除液体，再用固体体积0.5～1倍的95％乙醇对固体进行搅拌洗涤10～15min，离心去除液体。
作为优选，所述步骤“将固体进行漂洗、干燥，得到DL-赖氨酸盐酸盐”中，干燥温度为70℃～80℃。
作为优选，所述步骤“将DL-赖氨酸盐酸盐溶于水中，并调节pH至5.0，得到上柱液”中，DL-赖氨酸盐酸盐和水的重量比为1:(2～4)。
作为优选，所述步骤“将DL-赖氨酸盐酸盐溶于水中，并调节pH至5.0，得到上柱液”中，采用12％～15％的稀盐酸溶液调节pH值。
作为优选，所述步骤“将上柱液加入阳离子交换柱中，用水洗脱至流出液中不含氯离子，再用液碱洗脱，收集液碱洗脱时的流出液”中，将上柱液加入阳离子交换柱中，保持0.5h～1h后再进行后续洗脱。
作为优选，所述步骤“将上柱液加入阳离子交换柱中，用水洗脱至流出液中不含氯离子，再用液碱洗脱，收集液碱洗脱时的流出液”中，所述液碱的浓度为7％-8％。
作为优选，所述步骤“将收集的液碱洗脱时的流出液在55℃～60℃减压真空蒸馏”中，将液碱洗脱时的流出液减压真空蒸馏至固形物含量60％～63％。
本发明的有益效果如下：
本发明DL-赖氨酸的制备方法加工工艺简单，便于工业化操作，反应时间短，大大提高了DL-赖氨酸产品的产量和品质，具有较好的市场竞争力。
为让本发明的上述和其他目的、特征和优点能更明显易懂，下文特举较佳实施例，并配合所附图式，作详细说明如下。
附图说明
为了更清楚地说明本发明实施例或现有技术中的技术方案，下面将对实施例或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图仅仅是本发明的一些实施例，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1是本发明制备方法的反应示意图；
图2是本发明制备方法的流程图。
具体实施方式
下面将结合本发明实施例中的附图，对本发明实施例中的技术方案进行清楚、完整地描述，显然，所描述的实施例仅仅是本发明一部分实施例，而不是全部的实施例。基于本发明中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本发明保护的范围。
实施例1～4以及对比例1中所用的原辅材料的质量指标如下表1：
表1
Figure PCTCN2020096708-appb-000001
实施例1～4以及对比例1中所用的L-赖氨酸盐酸盐的颜色需要为白色或类白色才为合格。如果物料颜色为黄色或其他，则为不合格。
实施例1
制备DL-赖氨酸盐酸盐：
将由100Kg的L-赖氨酸盐酸盐、40Kg的纯水以及260Kg的冰醋酸构成的反应液投入1000L的反应釜中，搅拌升温至70℃～80℃，并保温搅拌2h，保温搅拌过程，反应液中的L-赖氨酸盐酸盐充分发生消旋反应，生成DL-赖氨酸盐酸盐，此时，反应液的旋光值为0。
将上步消旋反应后的反应液冷却至25℃，采用塑料抽滤桶，将反应液中的固体抽滤至洁净的周转釜中。用少量的95wt％乙醇将固体漂洗抽入洗涤釜中，向洗涤釜中加入固体体积2倍的95wt％乙醇对固体洗涤10～15min，离心去除洗涤液，再加入固体体积0.5倍的95wt％乙醇对固体漂洗10～15min，漂洗后离心去除洗涤液，将固体置于干燥器中，70℃～80℃烘干得到DL-赖氨酸盐酸盐。
制备DL-赖氨酸：
在1000L的搪玻璃反应釜中投入自来水275Kg、DL-赖氨酸盐酸盐100Kg，搅拌至全溶，用12％～15％的稀盐酸调节pH值至5.0，得到上柱液。
将上柱液加入阳离子交换柱中，先保持0.5h使得上柱液被阳离子交换柱中的树脂颗粒充分吸附，然后用自来水洗脱至流出液的pH值为6～7，再用纯水冲洗阳离子交换柱，使得流出液中的氯离子被洗脱去除，即流出液中检测不到氯离子。
氯离子被去除完全后，再用8％的液碱洗脱阳离子交换柱，收集液碱洗脱时的流出液。
将收集的液碱洗脱时的流出液在55℃～60℃减压真空蒸馏至固形物含量60％～63％，再放置于洁净塑料桶中，于25℃、无氧环境中静置至晶体完全析出，离心去除多余液体，将晶体65℃干燥后即得DL-赖氨酸样品1。
本实施例制备得到的DL-赖氨酸样品1的质量指标如下表2：
表2
质量指标 指标值
外观： 类白色结晶体。
比旋度： +0.5°～-0.5°
吸光度： ≤0.10
比重： 1.120～1.135
pH： 9.9～10.3(5％v/v)
氯化物： ＜500ppm
含量： 49.0～51.0％
TLC：(单一杂酸) ≤0.4％
(总杂酸)： ≤1％
实施例2
制备DL-赖氨酸盐酸盐：
将由100Kg的L-赖氨酸盐酸盐、40Kg的纯水以及200Kg的冰醋酸构成的反应液投入1000L的反应釜中，搅拌升温至75℃，并保温搅拌2h。
将上步消旋反应后的反应液冷却至25℃，采用塑料抽滤桶，将反应液中的固体抽滤至洁净的周转釜中。用少量的95wt％乙醇将固体漂洗抽入洗涤釜中，向洗涤釜中加入固体体积2倍的95wt％乙醇对固体洗涤10～15min，离心去除洗涤液，再加入固体体积0.5倍的95wt％乙醇对固体漂洗10～15min，漂洗后离心去除洗涤液，将固体置于干燥器中， 70～80℃烘干得到DL-赖氨酸盐酸盐。
制备DL-赖氨酸：
在1000L的搪玻璃反应釜中投入自来水275Kg、DL-赖氨酸盐酸盐100Kg，搅拌至全溶，用12％～15％的稀盐酸调节pH值至5.0，得到上柱液。
将上柱液加入阳离子交换柱中，先保持0.5h使得上柱液被阳离子交换柱中的树脂颗粒充分吸附，然后用自来水洗脱至流出液的pH值为6～7，再使用纯水冲洗阳离子交换柱至流出液中检测不到氯离子。
氯离子被去除完全后，再用8％的液碱对阳离子交换柱洗脱，收集液碱洗脱时的流出液。
将收集的液碱洗脱时的流出液在55℃～60℃减压真空蒸馏至固形物含量60％～63％，再放置于洁净塑料桶中，于25℃、无氧环境中静置至晶体完全析出，离心去除多余液体，将晶体65℃干燥后即得DL-赖氨酸样品2。
本实施例制备得到的DL-赖氨酸样品2的质量指标如下表3：
表3
质量指标 指标值
外观： 类白色结晶体。
比旋度： +0.5°～-0.5°
吸光度： ≤0.10
比重： 1.120～1.135
pH： 9.9～10.3(5％v/v)
氯化物： ＜500ppm
含量： 49.0～51.0％
TLC：(单一杂酸) ≤0.4％
(总杂酸)： ≤1％
实施例3
制备DL-赖氨酸盐酸盐：
将由100Kg的L-赖氨酸盐酸盐、40Kg的纯水以及260Kg的冰醋酸构成的反应液投入1000L的反应釜中，搅拌升温至75℃，并保温搅拌1h。
将上步消旋反应后的反应液冷却至25℃，采用塑料抽滤桶，将反应液中的固体抽滤至洁净的周转釜中。用少量的95wt％乙醇将固体漂洗抽入洗涤釜中，向洗涤釜中加入固 体体积2倍的95wt％乙醇对固体洗涤10～15min，离心去除洗涤液，再加入固体体积0.5倍的95wt％乙醇对固体漂洗10～15min，漂洗后离心去除洗涤液，将固体置于干燥器中，70～80℃烘干得到DL-赖氨酸盐酸盐。
制备DL-赖氨酸：
在1000L的搪玻璃反应釜中投入自来水275Kg、DL-赖氨酸盐酸盐100Kg，搅拌至全溶，用12％～15％的稀盐酸调节pH值至5.0，得到上柱液。
将上柱液加入阳离子交换柱中，先保持0.5h使得上柱液被阳离子交换柱中的树脂颗粒充分吸附，然后用自来水洗脱至流出液的pH值为6～7，再使用纯水冲洗阳离子交换柱至流出液中检测不到氯离子。
氯离子被去除完全后，再用8％的液碱洗脱，收集液碱洗脱时的流出液。
将收集的液碱洗脱时的流出液在55℃～60℃减压真空蒸馏至固形物含量60％～63％，再放置于洁净塑料桶中，于25℃、无氧环境中静置至晶体完全析出，离心去除多余液体，将晶体65℃干燥后即得DL-赖氨酸样品3。
本实施例制备得到的DL-赖氨酸样品3的质量指标如下表4：
表4
质量指标 指标值
外观： 类白色结晶体。
比旋度： +0.5°～-0.5°
吸光度： ≤0.10
比重： 1.120～1.135
pH： 9.9～10.3(5％v/v)
氯化物： ＜500ppm
含量： 49.0～51.0％
TLC：(单一杂酸) ≤0.4％
(总杂酸)： ≤1％
实施例4
制备DL-赖氨酸盐酸盐：
将由100Kg的L-赖氨酸盐酸盐、100Kg的纯水以及260Kg的冰醋酸构成的反应液投入1000L的反应釜中，搅拌升温至75℃，并保温搅拌6h。
将上步消旋反应后的反应液冷却至25℃，采用塑料抽滤桶，将反应液中的固体抽滤 至洁净的周转釜中。用少量的95wt％乙醇将固体漂洗抽入洗涤釜中，向洗涤釜中加入固体体积2倍的95wt％乙醇对固体洗涤10～15min，离心去除洗涤液，再加入固体体积0.5倍的95wt％乙醇对固体漂洗10～15min，漂洗后离心去除洗涤液，将固体置于干燥器中，70～80℃烘干得到DL-赖氨酸盐酸盐。
制备DL-赖氨酸：
在1000L的搪玻璃反应釜中投入自来水275Kg、DL-赖氨酸盐酸盐100Kg，搅拌至全溶，用12％～15％的稀盐酸调节pH值至5.0，得到上柱液。
将上柱液加入阳离子交换柱中，先保持0.5h使得上柱液被阳离子交换柱中的树脂颗粒充分吸附，然后用自来水洗脱至流出液的pH值为6～7，再使用纯水冲洗阳离子交换柱至流出液中检测不到氯离子。
氯离子被去除完全后，再用8％的液碱洗脱，收集液碱洗脱时的流出液。
将收集的液碱洗脱时的流出液在55℃～60℃减压真空蒸馏至固形物含量60％～63％，再放置于洁净塑料桶中，于25℃、无氧环境中静置至晶体完全析出，离心去除多余液体，将晶体65℃干燥后即得DL-赖氨酸样品4。
本实施例制备得到的DL-赖氨酸样品4的质量指标如下表5：
表5
质量指标 指标值
外观： 类白色结晶体。
比旋度： +0.5°～-0.5°
吸光度： ≤0.10
比重： 1.120～1.135
pH： 9.9～10.3(5％v/v)
氯化物： ＜500ppm
含量： 49.0～51.0％
TLC：(单一杂酸) ≤0.4％
(总杂酸)： ≤1％
对比例1
本对比例与实施例1的区别在于，制备DL-赖氨酸时，将收集的液碱洗脱时的流出 液在80℃～85℃减压真空蒸馏。
制备DL-赖氨酸盐酸盐：
将由100Kg的L-赖氨酸盐酸盐、40Kg的纯水以及260Kg的冰醋酸构成的反应液投入1000L的反应釜中，搅拌升温至75℃，并保温搅拌2h。
将上步消旋反应后的反应液冷却至25℃，采用塑料抽滤桶，将反应液中的固体抽滤至洁净的周转釜中。用少量的95wt％乙醇将固体漂洗抽入洗涤釜中，向洗涤釜中加入固体体积2倍的95wt％乙醇对固体洗涤10～15min，离心去除洗涤液，再加入固体体积0.5倍的95wt％乙醇对固体漂洗10～15min，漂洗后离心去除洗涤液，将固体置于干燥器中，70～80℃烘干得到DL-赖氨酸盐酸盐。
制备DL-赖氨酸：
在1000L的搪玻璃反应釜中投入自来水275Kg、DL-赖氨酸盐酸盐100Kg，搅拌至全溶，用12％～15％的稀盐酸调节pH值至5.0，得到上柱液。
将上柱液加入阳离子交换柱中，先保持0.5h使得上柱液被阳离子交换柱中的树脂颗粒充分吸附，然后用自来水洗脱至流出液的pH值为6～7，再使用纯水冲洗阳离子交换柱至流出液中检测不到氯离子。
氯离子被去除完全后，再用8％的液碱洗脱，收集液碱洗脱时的流出液。
将收集的液碱洗脱时的流出液在80℃～85℃减压真空蒸馏至固形物含量60％～63％，再放置于洁净塑料桶中，于25℃、无氧环境中静置至晶体完全析出，离心去除多余液体，将晶体65℃干燥后即得DL-赖氨酸样品5。
本实施例制备得到的DL-赖氨酸样品5的质量指标如下表6：
表6
质量指标 指标值
外观： 类白色结晶体。
比旋度： +0.5°～-0.5°
吸光度： 0.80
比重： 1.120～1.135
pH： 9.9～10.3(5％v/v)
氯化物： ＜500ppm
含量： 43.8～45.8％
TLC：(单一杂酸) 2.08％
(总杂酸)： 5.2％
实施例1～4和对比例1中样品的收率如下表7。
表7
  实施例1 实施例2 实施例3 实施例4 对比例1
收率 67.2％ 50.2％ 49.5％ 66.2％ 60.4％
本发明实施例1～4中所制备的DL-赖氨酸具有较好的品质。其中，实施例1中的制备方法为最优方法，由实施例1中制备方法制备得到的DL-赖氨酸具有较好的品质，并且具有较高的收率。
本发明实施例1～4以及对比例1中所用的L-赖氨酸盐酸盐的颜色为白色或类白色，保证了产品的颜色指标合格。如果所用的原料L-赖氨酸盐酸盐为黄色或其他，则为不合格。采用吸潮氧化变色后的L-赖氨酸盐酸盐会影响成品的外观和吸光度，导致成品的颜色指标不合格。
本发明实施例2与实施例1相比，减少了冰醋酸的投量，从而使L-赖氨酸盐酸盐消旋反应不完全，导致最终产品的收率偏低17％，但对产品的品质无影响。
本发明实施例3与实施例1相比，减少消旋反应的时间，仅消旋反应1h，导致消旋反应不完全，降低了产品的收率，但对产品的品质无影响。
本发明实施例4与实施例1相比，对L-赖氨酸盐酸盐消旋以制备DL-赖氨酸盐酸盐时，增加了纯水的投量。在消旋反应过程中，跟踪反应液的旋光值，发现反应时间达到6小时后，反应液旋光值才为0，即反应才完全。因此，如果将纯水的量投入太多，会增加反应时间，降低生产效率，但对产品的品质和收率均无影响。
本发明对比例1与实施例1相比，制备DL-赖氨酸时，将收集的液碱洗脱时的流出液在80℃～85℃减压真空蒸馏，由于温度过高，会导致DL-赖氨酸样品氧化发黄，最终颜色为淡黄色，在高温蒸馏过程中，DL-赖氨酸样品产生较多的衍生物，如杂酸，导致产品质量指标不符合规定，并且降低了产品的收率。而本发明实施例1～4中将收集的液碱洗脱时的流出液在55℃～60℃减压真空蒸馏，得到的DL-赖氨酸样品均有较好的质量指标。
本发明实施例1～4中，采用浓度为8％的液碱对产品进行洗脱，液碱中钠离子可以对阳离子交换柱中的DL-赖氨酸进行置换，液碱的浓度如果太低，会导致洗脱不充分， 收料不完全，液碱的浓度过高会伤害阳离子交换柱中的树脂颗粒。本发明选择液碱浓度为8％，可以对阳离子交换柱中的DL-赖氨酸充分洗脱，同时不会破坏阳离子交换柱。
本发明实施例1～4中，将收集的液碱洗脱时的流出液在55℃～60℃减压真空蒸馏，再于无氧环境中静置至晶体完全析出，将晶体干燥后即得DL-赖氨酸。在制备过程中，减少了DL-赖氨酸与氧气的接触，能够避免DL-赖氨酸发生氧化而变黄，保证成品具有较好的质量。
本发明实施例1～4中，在洗脱过程中，用自来水洗脱至流出液的pH值为6～7，再使用纯水冲洗阳离子交换柱，先用自来水洗脱，可以减少纯水的用量，从而减少了制备大量纯水所需的时间。当自来水洗脱至流出液的pH值为6～7，已经去除大量的氯离子，再使用纯水继续冲洗阳离子交换柱至氯离子完全被去除，以使生产结果更加精确。
本发明中应用了具体实施例对本发明的原理及实施方式进行了阐述，以上实施例的说明只是用于帮助理解本发明的方法及其核心思想；同时，对于本领域的一般技术人员，依据本发明的思想，在具体实施方式及应用范围上均会有改变之处，综上所述，本说明书内容不应理解为对本发明的限制。

Claims (9)

  1. 一种DL-赖氨酸的制备方法，其特征在于，包括以下步骤：
    将L-赖氨酸盐酸盐、冰醋酸和水搅拌升温至70℃～80℃，继续保温搅拌1～6h后，抽滤出固体，将固体进行漂洗、干燥，得到DL-赖氨酸盐酸盐；
    将DL-赖氨酸盐酸盐溶于水中，并调节pH值至5.0，得到上柱液；
    将上柱液加入阳离子交换柱中，用水洗脱至流出液中不含氯离子，再用液碱洗脱，收集液碱洗脱时的流出液；
    将收集的液碱洗脱时的流出液在55℃～60℃减压真空蒸馏，再于无氧环境中静置至晶体完全析出，将晶体干燥后即得DL-赖氨酸。
  2. 根据权利要求1所述的DL-赖氨酸的制备方法，其特征在于，所述步骤“将L-赖氨酸盐酸盐、冰醋酸和水搅拌升温至70℃～80℃”中，L-赖氨酸盐酸盐、冰醋酸和水的重量比为1:(2～2.6):(0.4～1)。
  3. 根据权利要求1所述的DL-赖氨酸的制备方法，其特征在于，所述步骤“将L-赖氨酸盐酸盐、冰醋酸和水搅拌升温至70℃～80℃”中，L-赖氨酸盐酸盐、冰醋酸和水的重量比为1:2.6:0.4。
  4. 根据权利要求1所述的DL-赖氨酸的制备方法，其特征在于，所述步骤“将固体进行漂洗、干燥，得到DL-赖氨酸盐酸盐”中，固体漂洗方法为：采用固体体积2倍的95％乙醇对固体进行搅拌洗涤10～15min，离心去除液体，再用固体体积0.5～1倍的95％乙醇对固体进行搅拌洗涤10～15min，离心去除液体。
  5. 根据权利要求1所述的DL-赖氨酸的制备方法，其特征在于，所述步骤“将固体进行漂洗、干燥，得到DL-赖氨酸盐酸盐”中，干燥温度为70℃～80℃。
  6. 根据权利要求1所述的DL-赖氨酸的制备方法，其特征在于，所述步骤“将DL-赖氨酸盐酸盐溶于水中，并调节pH至5.0，得到上柱液”中，DL-赖氨酸盐酸盐和水的重量比为1:(2～4)。
  7. 根据权利要求1所述的DL-赖氨酸的制备方法，其特征在于，所述步骤“将DL-赖氨酸盐酸盐溶于水中，并调节pH至5.0，得到上柱液”中，采用12％～15％的稀盐酸溶液调节pH值。
  8. 根据权利要求1所述的DL-赖氨酸的制备方法，其特征在于，所述步骤“将上柱液加入阳离子交换柱中，用水洗脱至流出液中不含氯离子，再用液碱洗脱，收集液碱洗脱时的流出液”中，将上柱液加入阳离子交换柱中，保持0.5h～1h后再进行后续洗脱。
  9. 根据权利要求1所述的DL-赖氨酸的制备方法，其特征在于，所述步骤“将上柱液加入阳离子交换柱中，用水洗脱至流出液中不含氯离子，再用液碱洗脱，收集液碱洗脱时的流出液”中，所述液碱的浓度为7％～8％。
    根据权利要求1所述的DL-赖氨酸的制备方法，其特征在于，所述步骤“将收集的液碱洗脱时的流出液在55℃～60℃减压真空蒸馏”中，将液碱洗脱时的流出液减压真空蒸馏至固形物含量60％～63％。
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