WO2014106419A1 - 一种合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的方法 - Google Patents

一种合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的方法 Download PDF

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WO2014106419A1
WO2014106419A1 PCT/CN2013/088725 CN2013088725W WO2014106419A1 WO 2014106419 A1 WO2014106419 A1 WO 2014106419A1 CN 2013088725 W CN2013088725 W CN 2013088725W WO 2014106419 A1 WO2014106419 A1 WO 2014106419A1
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methyl
oxo
trioxabicyclo
octane
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刘国琴
巩凡
李琳
杨晓泉
李冰
刘新旗
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华南理工大学
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/08—Bridged systems

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  • the present invention relates to a process for the synthesis of organic compounds, and in particular to a process for the synthesis of 1-methyl-2-oxo-3,6,7-trioxabicyclo[2,2,2]octane.
  • Milk flavor is one of the most invested and most active fragrances in the field of flavors and fragrances. It is mainly used for flavoring of cold food, candy and beverages.
  • the characteristic aroma of natural cream is caused by the inclusion of some lactones, and caprolactone is an essential ingredient.
  • Both propranolactone and butanolide are the common octactone milk flavors on the market.
  • the synthesis of these fragrances requires a multi-step reaction and is therefore relatively expensive.
  • Octane is a caged octanolide with a coconut or milky aroma. Its aroma is elegant, pleasant and long-lasting, and has the potential to be used in foods and high-end cosmetics.
  • this octanolactone can be synthesized in one step using only glycerin and pyruvic acid, and the product is inexpensive, the reaction conditions are mild, and the product is simply post-treated.
  • the object of the present invention is to provide a process for synthesizing and separating 1-methyl-2-oxo-3,6,7-trioxabicyclo[2,2,2]octane, which has mild reaction conditions and a reaction condition It is fast, simple in process and easy to operate. It uses cheap and easy-to-use catalysts, water-carrying agents and solvents, and has low separation difficulty. It can meet the needs of various industries to prepare 1-methyl-2-oxo-3,6,7-trioxa Bicyclo[2,2,2]octane requirements.
  • the technical scheme adopted by the invention is: a new method for synthesizing 1-methyl-2-oxo-3,6,7-trioxabicyclo[2,2,2]octane: using raw materials pyruvic acid and triacetin
  • the amount of alcohol and glycerol is 1-10 times the molar amount of pyruvic acid, and p-toluenesulfonic acid is used as a catalyst.
  • the amount of the catalyst is 0.1%-20% of the total mass of the material, and dichloromethane is used as a water-carrying agent at 0- Esterification at 80 ° C to synthesize 1-methyl-2-oxo-3,6,7-trioxabicyclo[2,2,2]octane; input raw material pyruvic acid, glycerol, catalyst into the reactor In the middle, stirring and heating, then continuously injecting the water-carrying agent, and the water-repellent agent is separated from the water and recycled. When the water layer is no longer increased, the reaction is stopped, the sodium carbonate solution is used to neutralize the reaction system, and the dichloromethane is extracted.
  • the product was collected and washed repeatedly to remove water-soluble impurities such as sodium p-toluenesulfonate, glycerol, sodium pyruvate, sodium carbonate, etc., using anhydrous ethanol as a solvent, and recrystallization to obtain 1-methyl-2-oxo- 3,6,7-Trioxabicyclo[2,2,2]octane crystal.
  • water-soluble impurities such as sodium p-toluenesulfonate, glycerol, sodium pyruvate, sodium carbonate, etc.
  • the beneficial effects of the invention are: the raw materials used in the invention, pyruvic acid, glycerol, catalyst p-toluenesulfonic acid, water-carrying agent dichloromethane, solvent anhydrous ethanol are easily obtained, through the liquid phase An economical milk flavor can be obtained by extraction and recrystallization.
  • the method has mild reaction conditions, rapid reaction, simple process and easy operation, and uses a cheap and easily available catalyst, a water-carrying agent and a solvent, and has low separation difficulty.
  • Embodiment 1 is a diagrammatic representation of Embodiment 1:
  • a method for synthesizing 1-methyl-2-oxo-3,6,7-trioxabicyclo[2,2,2]octane the specific process is: in a 250 ml flask, adding 15 g of pyruvic acid, 47 g of propylene Alcohol, 1.8g P-toluenesulfonic acid, magnetic stirring rotor.
  • the flask was connected using a controlled flow constant pressure funnel, 120 ml of dichloromethane was added to the funnel, the flow rate was controlled to 8 ml/min, and the upper portion of the constant pressure funnel was connected to a condenser.
  • the magnetic stirring was carried out, and the temperature was raised by heating in a water bath to maintain the temperature of the water bath at 60 °C.
  • the water layer in the constant pressure funnel is no longer increased and the reaction is stopped.
  • 100 ml of dichloromethane was added, and the mixture was washed with a mass concentration of 5% sodium carbonate solution until the pH of the upper layer was 7-8, and the lower layer liquid was collected by liquid separation, washed three times with 50 ml of distilled water, respectively, and the lower layer liquid was collected by liquid separation.
  • the collected liquid was subjected to atmospheric distillation to remove the water-carrying agent, the temperature was maintained at 75 ° C, and anhydrous ethanol was slowly added until the product was completely dissolved.
  • the product was allowed to stand at room temperature to crystallize, and the mother liquor was discarded by filtration.
  • the above crystallization operation was repeated once to obtain the product 1-methyl-2-oxo-3,6,7-trioxabicyclo[2,2,2]octane.
  • Embodiment 2 is a diagrammatic representation of Embodiment 1:
  • a new method for the synthesis of 1-methyl-2-oxo-3,6,7-trioxabicyclo[2,2,2]octane the specific process is: in a 250 ml flask, adding 20 g of pyruvic acid, 47 g of C Triol, 2g P-toluenesulfonic acid, magnetic stirring rotor. The flask was connected using a controlled flow constant pressure funnel, 120 ml of dichloromethane was added to the funnel, the flow rate was controlled to 8 ml/min, and the upper portion of the constant pressure funnel was connected to a condenser. Magnetic stirring, heating in a water bath, keeping the water bath temperature at 65 °C.
  • the water layer in the constant pressure funnel is no longer increased and the reaction is stopped.
  • 100 ml of dichloromethane was added, and the mixture was washed with a mass concentration of 5% sodium carbonate solution until the pH of the upper layer was 7-8, and the lower layer liquid was collected by liquid separation, washed three times with 50 ml of distilled water, respectively, and the lower layer liquid was collected by liquid separation.
  • the collected liquid was subjected to atmospheric distillation to remove the water-carrying agent, the temperature was maintained at 75 ° C, and anhydrous ethanol was slowly added until the product was completely dissolved.
  • the product was allowed to stand at room temperature to crystallize, and the mother liquor was discarded by filtration.
  • the above crystallization operation was repeated once to obtain the product 1-methyl-2-oxo-3,6,7-trioxabicyclo[2,2,2]octane.
  • Embodiment 3 is a diagrammatic representation of Embodiment 3
  • a new method for the synthesis of 1-methyl-2-oxo-3,6,7-trioxabicyclo[2,2,2]octane the specific process is: in a 250ml flask, adding 25g pyruvic acid, 47g C Triol, 2.2g P-toluenesulfonic acid, magnetic stirring rotor.
  • the flask was connected using a controlled flow constant pressure funnel, 120 ml of dichloromethane was added to the funnel, the flow rate was controlled to 8 ml/min, and the upper portion of the constant pressure funnel was connected to a condenser.
  • Magnetic stirring heating in a water bath, keeping the water bath temperature at 70 °C. The water layer in the constant pressure funnel is no longer increased and the reaction is stopped.
  • the milk flavor was characterized by nuclear magnetic resonance carbon spectroscopy.
  • the product obtained in the above examples was dissolved in deuterated chloroform, and the carbon spectrum was obtained using a Bruker 400M nuclear magnetic resonance spectrometer as follows: As can be seen from Fig. 1, the chemical shifts of 76.75, 77.06, and 77.38 were all solvent chloroform peaks.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)

Abstract

公开一种合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的方法，所述方法采用原料丙酮酸和丙三醇，催化剂为对甲基苯磺酸，二氯甲烷作为带水剂，在0°C-80°C条件酯化合成。所述丙三醇用量是丙酮酸摩尔量1〜10倍，催化剂用量是物料总质量的0.1%〜20%。

Description

一种合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的方法
技术领域
本发明涉及有机化合物合成方法，具体涉及合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的方法。
背景技术
奶味香精是香精香料领域中投资最大、开发研究最为活跃的香精之一，主要用于冷食、糖果、饮料等的增香。天然奶油的特征香味是由于其中含有一些内酯所引起的，辛内酯就是其中必不可少的成分。丙位辛内酯和丁位辛内酯都是市场上常见的辛内酯类奶味香精，这些香精的合成需要经过多步反应，因此价格相对较高。 1- 甲基 -2- 氧代 -3,6,7- 三氧杂二环 [2,2,2] 辛烷是一种笼状辛内酯，具有椰子或奶味香气的香料，它的香气优雅、愉快且浓郁持久，有用于食品及高级化妆品中调香的潜力。不仅如此，这种辛内酯仅仅使用甘油和丙酮酸就可以一步合成，原料便宜、且反应条件温和、产物后处理简单即可得到产品。
1- 甲基 -2- 氧代 -3,6,7- 三氧杂二环 [2,2,2] 辛烷，分子式为 C6H8O4 ，（Ⅰ ）所示结构（该化合物结构以图为准，可以有不同命名）。
Figure PCTCN2013088725-appb-I000001
（Ⅰ ）
发明内容
本发明目的是提供一种合成并分离1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的方法，该方法反应条件温和、反应迅速、工艺简单、易操作，使用了廉价易得的催化剂、带水剂、溶剂，并且分离难度低，满足各行业制备1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的要求。
本发明采用的技术方案是：合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的新方法：采用原料丙酮酸和丙三醇，丙三醇用量是丙酮酸摩尔量1-10倍，使用对甲基苯磺酸作为催化剂，催化剂用量是物料总质量的0.1%-20%，二氯甲烷作为带水剂，在0-80℃下酯化合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷；将原料丙酮酸、丙三醇、催化剂投入反应器中，搅拌并升温，然后不断注入带水剂，带水剂与水分离后循环使用，当带水剂中水层不再增加即停止反应，使用碳酸钠溶液中和反应体系，二氯甲烷萃取收集产物，反复水洗去除对甲基苯磺酸钠、丙三醇、丙酮酸钠、碳酸钠等水溶性杂质，使用无水乙醇作溶剂，通过重结晶得到1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷晶体。
合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的反应路线如下：
Figure PCTCN2013088725-appb-C000001
 。
与现有技术相比，本发明的有益效果是：本发明采用的原料丙酮酸、丙三醇，催化剂对甲苯磺酸，带水剂二氯甲烷，溶剂无水乙醇均容易获得，通过液相萃取和重结晶就可以得到获得经济的奶味香精。该方法反应条件温和、反应迅速、工艺简单、易操作，使用了廉价易得的催化剂、带水剂、溶剂，并且分离难度低。
附图说明
图 1 是本发明制得的产物的 核磁共振碳谱图。
具体实施方式
下面结合具体实施例对本发明作进一步详细说明，但本发明并不局限于具体实施例。
实施例一：
合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的方法，具体工艺为：250ml烧瓶中，加入15g丙酮酸、47g丙三醇、1.8g 对甲基苯磺酸、磁力搅拌转子。使用可控流速恒压漏斗连接烧瓶，在漏斗中添加120ml二氯甲烷，控制流速为8ml/min，恒压漏斗上部连接冷凝管。磁力搅拌，水浴加热升温，保持水浴温度为60℃。待恒压漏斗中水层不再增加，停止反应。冷却至室温，加入100ml二氯甲烷，使用质量浓度5%碳酸钠溶液洗至上层液体pH为7-8，分液收集下层液体，分别使用50ml蒸馏水洗涤三次，分液收集下层液体。将收集液体常压蒸馏脱除带水剂，保持温度为75℃，缓缓加入无水乙醇直至完全溶解产物，室温静置使产物结晶，过滤弃去母液。重复上述结晶操作一次，得到产品1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷。
实施例二：
合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的新方法，具体工艺为：250ml烧瓶中，加入20g丙酮酸、47g丙三醇、2g 对甲基苯磺酸、磁力搅拌转子。使用可控流速恒压漏斗连接烧瓶，在漏斗中添加120ml二氯甲烷，控制流速为8ml/min，恒压漏斗上部连接冷凝管。磁力搅拌，水浴加热升温，保持水浴温度为65℃。待恒压漏斗中水层不再增加，停止反应。冷却至室温，加入100ml二氯甲烷，使用质量浓度5%碳酸钠溶液洗至上层液体pH为7-8，分液收集下层液体，分别使用50ml蒸馏水洗涤三次，分液收集下层液体。将收集液体常压蒸馏脱除带水剂，保持温度为75℃，缓缓加入无水乙醇直至完全溶解产物，室温静置使产物结晶，过滤弃去母液。重复上述结晶操作一次，得到产品1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷。
实施例三：
合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的新方法，具体工艺为：250ml烧瓶中，加入25g丙酮酸、47g丙三醇、2.2g 对甲基苯磺酸、磁力搅拌转子。使用可控流速恒压漏斗连接烧瓶，在漏斗中添加120ml二氯甲烷，控制流速为8ml/min，恒压漏斗上部连接冷凝管。磁力搅拌，水浴加热升温，保持水浴温度为70℃。待恒压漏斗中水层不再增加，停止反应。冷却至室温，加入100ml二氯甲烷，使用质量浓度5%碳酸钠溶液洗至上层液体pH为7-8，分液收集下层液体，分别使用50ml蒸馏水洗涤三次，分液收集下层液体。将收集液体常压蒸馏脱除带水剂，保持温度为75℃，缓缓加入无水乙醇直至完全溶解产物，室温静置使产物结晶，过滤弃去母液。重复上述结晶操作一次，得到产品1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷。
1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷结构表征：
采用核磁共振碳谱对该奶味香精进行表征。将上述个实例得到的产品溶解于氘代氯仿，使用Bruker400M核磁共振仪获得碳谱如下：由图1可知，化学位移76.75、77.06、77.38均为为溶剂氯仿峰。此外共有5个峰，化学位移值δ=19.33ppm是C（1）甲基吸收峰，δ=166.82ppm是C（3）羰基吸收峰，δ=92.64ppm是C（2）吸收峰，δ=71.07ppm是C（4）吸收峰，δ=66.34ppm是C（5）、C（6）吸收峰。由13C NMR可以证明合成的物质是1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷。

Claims (7)

  1. 一种合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的方法，所述1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的分子式为C6H8O4，结构式为
    Figure PCTCN2013088725-appb-I000002
    其特征是：采用丙酮酸和丙三醇作为原料，添加催化剂，注入带水剂，合成反应完毕后经过液相萃取、重结晶得到
    1- 甲基 -2- 氧代 -3,6,7- 三氧杂二环 [2,2,2] 辛烷。
  2. 根据权利要求1所述的合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的方法，其特征是：将原料丙酮酸、丙三醇、催化剂投入反应器中，搅拌并升温，不断注入带水剂，带水剂与水分离后循环使用，当带水剂中水层不再增加即停止反应，使用碳酸钠溶液中和反应体系，用二氯甲烷萃取收集反应产物，反复水洗去除对甲基苯磺酸钠、丙三醇、丙酮酸钠、碳酸钠，使用无水乙醇作溶剂，通过重结晶得到1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷。
  3. 根据权利要求1所述的合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的方法，其特征是：所述催化剂为对甲苯磺酸或其他磺酸基类型的化合物或离子交换树脂。
  4. 根据权利要求1所述的合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的方法，其特征是：催化剂用量是丙酮酸和丙三醇总质量的0.1%-20%。
  5. 根据权利要求1所述的合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的方法，其特征是：所述反应的温度为0℃-80℃。
  6. 根据权利要求1所述的合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的方法，其特征是：丙三醇用量是丙酮酸摩尔量1-10倍。
  7. 根据权利要求1所述的合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的方法，其特征是：带水剂为二氯甲烷，且匀速添加，循环使用。
PCT/CN2013/088725 2013-01-04 2013-12-06 一种合成1-甲基-2-氧代-3,6,7-三氧杂二环[2,2,2]辛烷的方法 WO2014106419A1 (zh)

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