WO2014173047A1 - 生物质有机胍催化法合成光学纯l-/d-丙交酯的工艺方法 - Google Patents

生物质有机胍催化法合成光学纯l-/d-丙交酯的工艺方法 Download PDF

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WO2014173047A1
WO2014173047A1 PCT/CN2013/081710 CN2013081710W WO2014173047A1 WO 2014173047 A1 WO2014173047 A1 WO 2014173047A1 CN 2013081710 W CN2013081710 W CN 2013081710W WO 2014173047 A1 WO2014173047 A1 WO 2014173047A1
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lactide
lactic acid
catalyst
crude
washed
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PCT/CN2013/081710
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French (fr)
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李弘�
张全兴
成娜
张天荣
江伟
黄伟
潘丙才
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南京大学
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Priority to JP2016509263A priority Critical patent/JP6031213B2/ja
Priority to US14/782,627 priority patent/US9630942B2/en
Publication of WO2014173047A1 publication Critical patent/WO2014173047A1/zh

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
    • C07D319/12—1,4-Dioxanes; Hydrogenated 1,4-dioxanes not condensed with other rings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0201—Oxygen-containing compounds
    • B01J31/0205—Oxygen-containing compounds comprising carbonyl groups or oxygen-containing derivatives, e.g. acetals, ketals, cyclic peroxides
    • B01J31/0208—Ketones or ketals
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0241—Imines or enamines
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0271—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds also containing elements or functional groups covered by B01J31/0201 - B01J31/0231
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/30—Addition reactions at carbon centres, i.e. to either C-C or C-X multiple bonds
    • B01J2231/34—Other additions, e.g. Monsanto-type carbonylations, addition to 1,2-C=X or 1,2-C-X triplebonds, additions to 1,4-C=C-C=X or 1,4-C=-C-X triple bonds with X, e.g. O, S, NH/N

Definitions

  • the invention belongs to the field of optically pure monomers for synthesizing eco-friendly/biomedical degradable polylactic acid materials, in particular to a method for synthesizing optically pure L-/D-lactide using a biomass organic bismuth compound creatinine (CR) as a catalyst. . Background technique
  • Polylactic acid or polylactide is a widely used eco-friendly material and biodegradable material that can be used to prepare a variety of medical materials, such as implantable hard tissue repair materials, surgical sutures, targeting and control. Release drug carriers and the like.
  • polylactic acid can also be used to prepare various biodegradable plastic articles such as films, fibers, packaging materials and the like.
  • Commercially available high molecular weight polylactic acid is generally prepared by catalytic ring opening polymerization of lactide as a monomer. Therefore, the synthesis of lactide is of great significance for the production of polylactic acid.
  • Optically pure lactides include: L-lactide and D-lactide.
  • the object of the present invention is to solve the problem that the metal tin catalyst is easy to contaminate the product, is not easy to be regenerated, and may cause environmental pollution in the synthesis of the commercially available L-/D-lactide, and provides a biomass organic ruthenium catalytic synthesis. Process for optically pure L-/D-lactide.
  • the method provided by the invention adopts biomass organic bismuth compound creatinine (human arginine metabolite, abbreviated as CR) as a catalyst, and uses 90% of L-/D-lactic acid as raw material, and adopts reactive reduction.
  • Catalytic synthesis of optically pure L-/D-lactide by pressure distillation, the process for catalyzing the synthesis of L-/D-lactide of the present invention specifically comprises the following steps:
  • L-/D-lactic acid is first reacted under normal pressure for 1-4 hours, then slowly decompressed to 30-60 torr for 2-8 hours. , dehydration condensation polymerization into a lactic acid oligomer having a weight average molecular weight of 600-1500 Da.
  • step (2) adding the catalyst creatinine CR to the lactic acid oligomer synthesized in the step (1), controlling the reaction temperature to between 150 and 260 ° C, the degree of vacuum to between 2 and 15 torr, and reacting for 1-4 hours, collecting and distilling off White crude L-/D-lactide.
  • step (3) The crude L-/D-lactide collected in step (2) is firstly used with a base concentration of 1-10% (sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate or Wash with potassium bicarbonate) solution, then rinse to neutral with deionized water.
  • a base concentration of 1-10% sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogencarbonate or Wash with potassium bicarbonate
  • the mass ratio of the biomass organic ruthenium catalyst creatinine CR to the lactic acid oligomer is between 1:100-1:10000.
  • the crude L-/D-lactide is washed with an alkali solution to remove impurities, thereby avoiding the purification of the crude lactide by the rectification method which is usually used.
  • biomass organic ruthenium catalyst used CR, non-toxic, non-metallic, non-cytotoxic;
  • the reactor was charged with 100 g of L-lactic acid (90% by mass), heated to 130 ° C under argon atmosphere and normal pressure, dehydrated for 4 h, and then the reactor was slowly depressurized to 60 torr at 130 ° C. 8h.
  • the lactic acid oligomer OLLA was obtained, and the weight average molecular weight was 1500 Da.
  • the catalyst biomimetic organic ruthenium compound CR was added to control the mass ratio of catalyst CR to L-lactic acid to be 1:100, the reaction temperature was controlled to 180 ° C, the degree of vacuum was 2 torr, and the reaction was carried out for 1 hour, and the distilled white crude L-propane was collected. ester.
  • the reactor was charged with 100 g of L-lactic acid (90% by mass), heated to 170 ° C under an argon atmosphere and atmospheric pressure, dehydrated for 1 h, and then the reaction vessel was slowly depressurized to 30 torr at 170 ° C. 2h.
  • the lactic acid oligomer OLLA was obtained, and the weight average molecular weight was 600 Da.
  • the catalyst biomimetic organic ruthenium compound CR was added, and the mass ratio of the catalyst to the L-lactic acid was 1 : 10000, the reaction temperature was 260 Torr, the degree of vacuum was 15 torr, and the reaction was carried out for 4 hours, and the distilled white crude L-lactide was collected.
  • the collected crude L-lactide was first washed with a 10% alkali (sodium carbonate) solution, then washed with deionized water to neutrality, and dried under vacuum at 40 ° C for 36 h to obtain white needle-like L-propyl.
  • the reactor was charged with 100 g of L-lactic acid (90% by mass), heated to 150 ° C under argon atmosphere and normal pressure, dehydrated for 2 h, and then the reaction kettle was slowly depressurized to 40 torr at 150 ° C. 4h.
  • the lactic acid oligomer OLLA was obtained, and the weight average molecular weight was 1,100 Da.
  • the reactor was charged with 100 g of L-lactic acid (90% by mass), heated to 160 ° C under argon atmosphere and normal pressure, dehydrated for 2 h, and then the reaction kettle was slowly depressurized to 50 torr at 160 ° C. 4h.
  • a lactic acid oligomer OLLA was obtained with a weight average molecular weight of 1300 Da.
  • the catalyst biomimetic organic ruthenium compound CR was added, the mass ratio of the catalyst to the L-lactic acid was 1:2000, the reaction temperature was 220 ° C, the vacuum degree was 8 torr, and the reaction was carried out for 2 hours, and the distilled white crude L-lactide was collected. .
  • the reactor was charged with 100 g of L-lactic acid (90% by mass), heated to 150 ° C under argon atmosphere and normal pressure, dehydrated for 1 h, and then the reaction kettle was slowly depressurized to 30 torr at 150 ° C. 3h.
  • the lactic acid oligomer OLLA was obtained, and the weight average molecular weight was 900 Da.
  • the catalyst biomimetic organic ruthenium compound CR was added, and the mass ratio of the catalyst to the L-lactic acid was 1:5000, the reaction temperature was controlled to 240 V, the degree of vacuum was 5 torr, and the reaction was carried out for 3 hours, and the distilled white crude L-lactide was collected.
  • the reactor was charged with 100 g of L-lactic acid (90% by mass), heated to 140 ° C under argon atmosphere and normal pressure, dehydrated for 2 h, and then the reaction kettle was slowly depressurized to 30 torr at 140 ° C. 3h.
  • the catalyst biomimetic organic ruthenium compound CR was added, the mass ratio of the catalyst to the L-lactic acid was 1:2000, the reaction temperature was controlled to 250, the degree of vacuum was 3 torr, and the reaction was carried out for 4 hours, and the distilled white crude L-lactide was collected.
  • the reactor was charged with 100 g of D-lactic acid (90% by mass), heated to 130 ° C under argon atmosphere and normal pressure, dehydrated for 3 h, and then the reaction kettle was slowly depressurized to 60 torr at 130 ° C. 8h.
  • the lactic acid oligomer ODLA was obtained, and the weight average molecular weight was 1,500 Da.
  • the catalyst biomimetic organic ruthenium compound CR was added, the mass ratio of the catalyst to D-lactic acid was 1:100, the reaction temperature was controlled to 150 ° C, the degree of vacuum was 2 torr, and the reaction was carried out for 2 hours, and the distilled white crude D-lactide was collected. .
  • the reactor was charged with 100 g of D-lactic acid (90% by mass), heated to 170 ° C under argon atmosphere and normal pressure, dehydrated for 1 h, and then the reaction kettle was slowly depressurized to 30 torr at 170 ° C. 4h.
  • the lactic acid oligomer ODLA was obtained, and the weight average molecular weight was 800 Da.
  • the catalyst biomimetic organic ruthenium compound CR was added, and the mass ratio of the catalyst to D-lactic acid was 1 : 10000, the reaction temperature was 260 Torr, the degree of vacuum was 15 torr, and the reaction was carried out for 4 hours, and the distilled white crude D-lactide was collected.
  • the reactor was charged with 100 g of D-lactic acid (90% by mass), heated to 150 ° C under argon atmosphere and normal pressure, dehydrated for 2 h, and then the reaction kettle was slowly depressurized to 40 torr at 150 ° C. 4h.
  • the lactic acid oligomer ODLA was obtained, and the weight average molecular weight was 1,100 Da.
  • the catalyst biomimetic organic ruthenium compound CR was added, the mass ratio of the catalyst to D-lactic acid was 1:1000, the reaction temperature was controlled at 200 ° C, the degree of vacuum was lOtorr, and the reaction was carried out for 3 hours, and the distilled white crude D-lactide was collected. .
  • the reactor was charged with 100 g of D-lactic acid (90% by mass), heated to 160 ° C under argon atmosphere and normal pressure, dehydrated for 2 h, and then the reaction kettle was slowly depressurized to 50 torr at 160 ° C. 4h.
  • the lactic acid oligomer ODLA was obtained, and the weight average molecular weight was 1300 Da.
  • the catalyst biomimetic organic ruthenium compound CR was added, and the mass ratio of the catalyst to D-lactic acid was 1:2000, the reaction temperature was 220 Torr, the degree of vacuum was 8 torr, and the reaction was carried out for 2 hours, and the distilled white crude D-lactide was collected.
  • the reactor was charged with 100 g of D-lactic acid (90% by mass), heated to 150 ° C under argon atmosphere and normal pressure, dehydrated for 1 h, and then the reaction kettle was slowly depressurized to 30 torr at 150 ° C. 3h.
  • the lactic acid oligomer ODLA was obtained, and the weight average molecular weight was 900 Da.
  • the catalyst biomimetic organic ruthenium compound CR was added, and the mass ratio of the catalyst to D-lactic acid was 1:5000, the reaction temperature was controlled to be 240 Torr, the degree of vacuum was 5 torr, and the reaction was carried out for 3 hours, and the distilled white crude D-lactide was collected.
  • the reactor was charged with 100 g of D-lactic acid (90% by mass), heated to 140 ° C under argon atmosphere and normal pressure, dehydrated for 2 h, and then the reaction kettle was slowly depressurized to 30 torr at 140 ° C. 3h.
  • the lactic acid oligomer ODLA was obtained, and the weight average molecular weight was 1200 Da.
  • the catalyst biomimetic organic ruthenium compound CR was added, and the mass ratio of the catalyst to D-lactic acid was 1:2000, the reaction temperature was 250, the degree of vacuum was 3 torr, and the reaction was carried out for 4 hours, and the distilled white crude D-lactide was collected.

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  • Engineering & Computer Science (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
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Abstract

生物质有机胍催化法合成光学纯 L-/D-丙交酯的工艺方法。本发明方法以生物质有机胍化合物肌酐（CR）为催化剂，以 L-/D-乳酸（质量含量90%）为原料，采用反应性减压蒸馏催化法合成光学纯 L-/D-丙交酯。本发明优点为：所用催化剂为生物质有机胍化合物肌酐，无毒无金属，无细胞毒性；所合成丙交酯光学纯度高（L-丙交酯的比旋光度[α]25D= -276～-280，D-丙交酯的比旋光度[α]25D=280），而且不含任何金属；反应使用的催化剂用量少，工艺流程简化（避免了常规法粗丙交酯产品精馏提纯工艺），操作简便，易于工业化实施。

Description

生物质有机胍催化法合成光学纯 L-/D-丙交酯的工艺方法 技术领域
本发明属于生态友好 /生物医用可降解聚乳酸材料合成用光学纯单体领域， 具体说是 运用生物质有机胍化合物肌酐 （CR) 为催化剂合成光学纯 L-/D-丙交酯的工艺方法。 背景技术
聚乳酸或聚丙交酯 （PLA) 是一种有广泛用途的生态友好材料以及生物可降解材料， 可用于制备各种医用材料， 如植入性硬组织修复材料、 手术缝合线、 靶向及控释药物载体 等。 此外， 聚乳酸还可以应用于制备各种可生物降解塑料制品， 如薄膜、 纤维、 包装材料 等。 商品化的高分子量聚乳酸一般采用丙交酯为单体经催化开环聚合制备。 因此， 丙交酯 的合成对于聚乳酸的生产有着重要的意义。 光学纯的丙交酯包括： L-丙交酯和 D-丙交酯。 目前，商品化 L-/D-丙交酯的合成是以 L-/D-乳酸为原料，采用金属盐催化剂（如辛酸亚锡、 氯化亚锡等， 参见 US 5053522)。这种方法存在金属锡催化剂容易污染产品、不容易再生、 可能对环境造成污染等缺陷。 发明内容
本发明的目的解决现有商品化 L-/D-丙交酯的合成中存在金属锡催化剂容易污染产 品、 不容易再生、 可能对环境造成污染等问题， 提供一种生物质有机胍催化法合成光学纯 L-/D-丙交酯的工艺方法。
本发明提供的工艺方法是以生物质有机胍化合物肌酐（人体内精氨酸代谢产物， 英文 縮写为 CR)为催化剂， 以质量含量 90%的 L-/D-乳酸为原料， 采用反应性减压蒸馏法催化 合成光学纯 L-/D-丙交酯， 本发明催化合成 L-/D-丙交酯的工艺方法具体包括以下步骤：
( 1 ) 在加热温度范围是 130°C-170 °C条件下， 将 L-/D-乳酸先在常压条件下反应 1-4 小时， 然后缓慢减压到 30-60torr反应 2-8小时， 脱水縮聚合成重均分子量为 600-1500Da 的乳酸低聚物。
(2)在步骤（1 )合成的乳酸低聚物中加入催化剂肌酐 CR，控制反应温度至 150-260°C 之间， 真空度至 2-15torr之间， 反应 1-4小时， 收集蒸出的白色粗 L-/D-丙交酯。
( 3 )将步骤 （2) 收集到的粗 L-/D-丙交酯先用质量浓度为 1-10%的碱 （氢氧化钠、 氢 氧化钾、 碳酸钠、 碳酸钾、 碳酸氢钠或碳酸氢钾） 溶液洗涤， 再用去离子水清洗至中性， 20°C-40°C真空干燥 24-36h即得到高光学纯度的丙交酯 （L-丙交酯的比旋光度 [ct]25D= -276〜- 280， D-丙交酯的比旋光度 [a]25D=280 )。
本发明步骤（2) 中生物质有机胍催化剂肌酐 CR与乳酸低聚物的质量比为 1 : 100-1： 10000之间。 步骤 （3 ) 中将粗 L-/D-丙交酯采用碱溶液洗涤去除杂质， 避免了采用通常使 用的精馏法提纯粗丙交酯。 本发明的优点和有益效果：
1. 所用生物质有机胍催化剂 CR， 无毒无金属， 无细胞毒性；
2.所合成 L-/D-丙交酯经提纯后光学纯度高（L-丙交酯的比旋光度 [ct]25D= -276〜- 280， D-丙交酯的比旋光度 [ct]25D=280) ，而且不含任何金属；
3. 反应时间短， 催化剂用量少， 工艺流程简化， 操作简便， 易于工业化实施。 具体实施方式
实施例 1
①向反应釜中装入 100g的 L-乳酸（质量含量 90%)， 在氩气氛及常压下加热至 130°C， 脱 水反应 4h，然后将反应釜缓慢减压至 60torr在 130°C反应 8h。 得到乳酸低聚物 OLLA, 重 均分子量 1500Da。
②加入催化剂仿生有机胍化合物 CR， 控制催化剂 CR与 L-乳酸质量比为 1 : 100， 控制反 应温度为 180°C， 真空度为 2torr， 反应 1小时， 收集蒸出的白色粗 L-丙交酯。
③将收集到的粗 L-丙交酯先用浓度为 1%的碱 （氢氧化钠） 溶液洗涤， 再用去离子水清洗 至中性， 20°C真空干燥 24h，得到白色针状 L-丙交酯， 产率 35.5%， 比旋光度 [a]25D=-276。 实施例 2
①向反应釜中装入 100g的 L-乳酸 （质量含量 90%)， 在氩气氛及常压下加热至 170°C， 脱水反应 lh，然后将反应釜缓慢减压至 30torr在 170°C反应 2h。 得到乳酸低聚物 OLLA, 重均分子量 600 Da。
②加入催化剂仿生有机胍化合物 CR， 控制催化剂与 L-乳酸质量比为 1 : 10000， 控制反应 温度为 260Ό， 真空度为 15torr， 反应 4小时， 收集蒸出的白色粗 L-丙交酯。
③将收集到的粗 L-丙交酯先用浓度为 10%的碱 （碳酸钠） 溶液洗涤， 再用去离子水清洗 至中性， 40°C真空干燥 36h，得到白色针状 L-丙交酯， 产率 40.3%， 比旋光度 [a]25D=-280。 ①向反应釜中装入 lOOg的 L-乳酸（质量含量 90%)， 在氩气氛及常压下加热至 150°C， 脱 水反应 2h，然后将反应釜缓慢减压至 40torr在 150°C反应 4h。 得到乳酸低聚物 OLLA, 重 均分子量 1100 Da。
②加入催化剂仿生有机胍化合物 CR， 控制催化剂与 L-乳酸质量比为 1 : 1000， 控制反应 温度为 200°C， 真空度为 lOtorr, 反应 3小时， 收集蒸出的白色粗 L-丙交酯。
③将收集到的粗 L-丙交酯先用浓度为 8%的碱 （碳酸氢钠） 溶液洗涤， 再用去离子水清洗 至中性， 35 °C真空干燥 30h，得到白色针状 L-丙交酯， 产率 45.8%， 比旋光度 [a]25D=-277。 实施例 4
①向反应釜中装入 100g的 L-乳酸（质量含量 90%)， 在氩气氛及常压下加热至 160°C， 脱 水反应 2h，然后将反应釜缓慢减压至 50torr在 160°C反应 4h。 得到乳酸低聚物 OLLA, 重 均分子量 1300 Da。
②加入催化剂仿生有机胍化合物 CR， 控制催化剂与 L-乳酸质量比为 1 : 2000， 控制反应 温度为 220°C， 真空度为 8torr， 反应 2小时， 收集蒸出的白色粗 L-丙交酯。
③将收集到的粗 L-丙交酯先用浓度为 5%的碱 （碳酸氢钾） 溶液洗涤， 再用去离子水清洗 至中性， 30°C真空干燥 26h，得到白色针状 L-丙交酯， 产率 40.8%， 比旋光度 [a]25D=-280。 实施例 5
①向反应釜中装入 100g的 L-乳酸（质量含量 90%)， 在氩气氛及常压下加热至 150°C， 脱 水反应 lh，然后将反应釜缓慢减压至 30torr在 150°C反应 3h。 得到乳酸低聚物 OLLA, 重 均分子量 900 Da。
②加入催化剂仿生有机胍化合物 CR， 控制催化剂与 L-乳酸质量比为 1 : 5000， 控制反应 温度为 240V , 真空度为 5torr， 反应 3小时， 收集蒸出的白色粗 L-丙交酯。
③将收集到的粗 L-丙交酯先用浓度为 2%的碱 （氢氧化钾） 溶液洗涤， 再用去离子水清洗 至中性， 30°C真空干燥 35h，得到白色针状 L-丙交酯， 产率 38.8%， 比旋光度 [a]25D=-277。 实施例 6
①向反应釜中装入 100g的 L-乳酸（质量含量 90%)， 在氩气氛及常压下加热至 140°C， 脱 水反应 2h，然后将反应釜缓慢减压至 30torr在 140°C反应 3h。 得到乳酸低聚物 OLLA, 重 ②加入催化剂仿生有机胍化合物 CR， 控制催化剂与 L-乳酸质量比为 1 : 2000， 控制反应 温度为 250 , 真空度为 3torr， 反应 4小时， 收集蒸出的白色粗 L-丙交酯。
③将收集到的粗 L-丙交酯先用浓度为 1%的碱 （碳酸钾） 溶液洗涤， 再用去离子水清洗至 中性， 40°C真空干燥 24h，得到白色针状 L-丙交酯， 产率 42.4%， 比旋光度 [a]25D=-280。 实施例 7
①向反应釜中装入 100g的 D-乳酸（质量含量 90%)， 在氩气氛及常压下加热至 130°C， 脱 水反应 3h，然后将反应釜缓慢减压至 60torr在 130°C反应 8h。 得到乳酸低聚物 ODLA, 重 均分子量 1500 Da。
②加入催化剂仿生有机胍化合物 CR， 控制催化剂与 D-乳酸质量比为 1 : 100， 控制反应温 度为 150°C， 真空度为 2torr， 反应 2小时， 收集蒸出的白色粗 D-丙交酯。
③将收集到的粗 D-丙交酯先用浓度为 1%的碱 （氢氧化钾）溶液洗涤， 再用去离子水清洗 至中性， 20°C真空干燥 24h，得到白色针状 D-丙交酯， 产率 41.7%， 比旋光度 [a]25D=280。 实施例 8
①向反应釜中装入 100g的 D-乳酸（质量含量 90%)， 在氩气氛及常压下加热至 170°C， 脱 水反应 lh，然后将反应釜缓慢减压至 30torr在 170°C反应 4h。 得到乳酸低聚物 ODLA, 重 均分子量 800 Da。
②加入催化剂仿生有机胍化合物 CR， 控制催化剂与 D-乳酸质量比为 1 : 10000， 控制反应 温度为 260Ό， 真空度为 15torr， 反应 4小时， 收集蒸出的白色粗 D-丙交酯。
③将收集到的粗 D-丙交酯先用浓度为 5%的碱 （碳酸钾）溶液洗涤， 再用去离子水清洗至 中性， 40°C真空干燥 36h，得到白色针状 D-丙交酯， 产率 40.3%， 比旋光度 [a]25D=280。 实施例 9
①向反应釜中装入 100g的 D-乳酸（质量含量 90%)， 在氩气氛及常压下加热至 150°C， 脱 水反应 2h，然后将反应釜缓慢减压至 40torr在 150°C反应 4h。 得到乳酸低聚物 ODLA, 重 均分子量 1100 Da。
②加入催化剂仿生有机胍化合物 CR， 控制催化剂与 D-乳酸质量比为 1 : 1000， 控制反应 温度为 200°C， 真空度为 lOtorr, 反应 3小时， 收集蒸出的白色粗 D-丙交酯。
③将收集到的粗 D-丙交酯先用浓度为 6%的碱 （碳酸氢钾）溶液洗涤， 再用去离子水清洗 至中性， 35 °C真空干燥 30h，得到白色针状 D-丙交酯， 产率 45.6%， 比旋光度 [a]25D=280。 实施例 10
①向反应釜中装入 100g的 D-乳酸（质量含量 90%)， 在氩气氛及常压下加热至 160°C， 脱 水反应 2h，然后将反应釜缓慢减压至 50torr在 160°C反应 4h。 得到乳酸低聚物 ODLA, 重 均分子量 1300 Da。
②加入催化剂仿生有机胍化合物 CR， 控制催化剂与 D-乳酸质量比为 1 : 2000， 控制反应 温度为 220Ό， 真空度为 8torr， 反应 2小时， 收集蒸出的白色粗 D-丙交酯。
③将收集到的粗 D-丙交酯先用浓度为 1%的碱 （氢氧化钠）溶液洗涤， 再用去离子水清洗 至中性， 30°C真空干燥 26h，得到白色针状 D-丙交酯， 产率 46.8%， 比旋光度 [a]25D=280。 实施例 11
①向反应釜中装入 100g的 D-乳酸（质量含量 90%)， 在氩气氛及常压下加热至 150°C， 脱 水反应 lh，然后将反应釜缓慢减压至 30torr在 150°C反应 3h。 得到乳酸低聚物 ODLA, 重 均分子量 900 Da。
②加入催化剂仿生有机胍化合物 CR， 控制催化剂与 D-乳酸质量比为 1 : 5000， 控制反应 温度为 240Ό， 真空度为 5torr， 反应 3小时， 收集蒸出的白色粗 D-丙交酯。
③将收集到的粗 D-丙交酯先用浓度为 10%的碱 （碳酸钠） 溶液洗涤， 再用去离子水清洗 至中性， 30°C真空干燥 35h，得到白色针状 D-丙交酯， 产率 44.5%， 比旋光度 [a]25D=280。 实施例 12
①向反应釜中装入 100g的 D-乳酸（质量含量 90%)， 在氩气氛及常压下加热至 140°C， 脱 水反应 2h，然后将反应釜缓慢减压至 30torr在 140°C反应 3h。 得到乳酸低聚物 ODLA, 重 均分子量 1200 Da。
②加入催化剂仿生有机胍化合物 CR， 控制催化剂与 D-乳酸质量比为 1 : 2000， 控制反应 温度为 250 , 真空度为 3torr， 反应 4小时， 收集蒸出的白色粗 D-丙交酯。
③将收集到的粗 D-丙交酯先用浓度为 6%的碱 （碳酸氢钠）溶液洗涤， 再用去离子水清洗 至中性， 40°C真空干燥 24h，得到白色针状 D-丙交酯， 产率 43.8%， 比旋光度 [a]25D=280。

Claims

权 利 要 求 书
1. 一种生物质有机胍催化法合成光学纯 L-/D-丙交酯的工艺方法， 其特征在于该方法 以生物质有机胍化合物肌酐为催化剂， 以质量含量 90%的 L-/D-乳酸为有原料， 采用反应 性减压蒸馏法催化合成光学纯 L-/D-丙交酯， 具体合成步骤包括：
( 1 ) 在加热温度范围是 130°C-170 °C条件下， 将 L-/D-乳酸先在常压条件下反应 1-4小 时， 然后缓慢减压到 30-60torr反应 2-8小时， 脱水縮聚合成重均分子量为 600-1500Da的 乳酸低聚物；
(2) 在步骤 （1 ) 合成的乳酸低聚物中加入催化剂肌酐， 控制反应温度至 150-260°C之 间， 真空度至 2-15torr之间， 反应 1-4小时， 收集蒸出的白色粗 L-/D-丙交酯；
(3 ) 将步骤 （2) 收集到的粗 L-/D-丙交酯先用质量浓度为 1-10%的碱溶液洗涤， 再用 去离子水清洗至中性， 20°C-40°C真空干燥 24-36h， 制得高光学纯 L-/D-丙交酯。
2. 根据权利要求 1所述的方法， 其特征在于所合成的 L-/D-丙交酯中， L-丙交酯的比 旋光度 [a]25D= -276〜- 280， D-丙交酯的比旋光度 [a]25D=280。
3. 根据权利要求 1所述的方法， 其特征在于步骤（2) 中生物质有机胍催化剂肌酐与 乳酸低聚物的质量比为 1 : 100-1： 10000之间。
4. 根据权利要求 1所述的方法， 其特征在于步骤 （3 ) 中所述的质量浓度为 1-10%的 碱溶液为氢氧化钠、 氢氧化钾、 碳酸钠、 碳酸钾、 碳酸氢钠或碳酸氢钾； 将粗 L-/D-丙交 酯采用碱溶液洗涤去除杂质， 避免了采用通常使用的精馏法提纯粗丙交酯。
PCT/CN2013/081710 2013-04-24 2013-08-17 生物质有机胍催化法合成光学纯l-/d-丙交酯的工艺方法 WO2014173047A1 (zh)

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CN112250661B (zh) * 2020-11-18 2021-11-02 南京大学 一种催化合成丙交酯的方法
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