A method for synthesizing β-amino alcohol using 1,2-butylene oxide

Abstract

The invention discloses a method for synthesizing β-amino alcohol using 1,2-butylene oxide, and relates to the technical field of β-amino alcohol synthesis. The present invention uses amylamine and 1,2-butylene oxide as raw materials, deionized water and alcohol as mixed solvents, and prepares β-amino alcohol through a ring-opening reaction by the protective effect of CO2 on the reaction product without any catalyst. The present invention has the characteristics of high conversion rate and high yield, belongs to the category of "green chemistry", has the characteristics of mild conditions, simple operation, short reaction time, high economic benefits, and is suitable for large-scale production.

Description

Technical Field

[0001] The invention belongs to the technical field of beta-amino alcohol synthesis, and particularly relates to a method for synthesizing beta-amino alcohol by utilizing 1,2-butylene oxide. Background Art

[0002] β-Amino alcohol is a widely used organic synthesis intermediate, playing a very important role in synthetic chemicals, pharmaceutical chemistry and biochemistry. In synthetic chemicals, β-amino alcohol can be used to catalyze a variety of asymmetric catalytic reactions such as asymmetric addition reaction of diethylzinc and aldehyde, asymmetric epoxidation reaction and asymmetric catalytic Henry reaction; in pharmaceutical chemistry and biochemistry, β-amino alcohol is an ideal chiral building block in asymmetric synthesis, and the structural units of β-amino alcohol are contained in the synthesis of drugs such as adrenalin, β-receptor blockers and amino sugars. Therefore, the preparation and research of β-amino alcohol has a very broad prospect in organic synthesis, and people are committed to finding the most effective and simple method for synthesizing β-amino alcohol.

[0003] The ring-opening amination reaction of epoxy compounds is the most common method for preparing β-amino alcohols. The ring-opening reaction of epoxy compounds requires the use of an excess of amine compounds, which will lead to uneven reactions. At the same time, the reaction needs to be carried out at high temperatures. Some sensitive functional groups will be affected during the reaction, resulting in the generation of side reactions, and some weakly nucleophilic and sterically hindered amines are difficult to react. Therefore, current research often adds a large amount of catalysts to improve the reaction efficiency, but this will not only increase the synthesis cost, but also use toxic catalysts for the reaction, which is also prone to environmental pollution and other problems. Summary of the invention

[0004] In view of the deficiencies of the prior art, the present invention provides a method for synthesizing β-amino alcohol using 1,2-butylene oxide, which uses pentylamine and 1,2-butylene oxide as raw materials, deionized water and alcohols such as methanol and / or ethanol as mixed solvents, and uses CO2 to protect the reaction product, and a ring-opening reaction to prepare β-amino alcohol without any catalyst. The present invention has the characteristics of high conversion rate and high yield, belongs to the category of "green chemistry", has the characteristics of mild conditions, simple operation, short reaction time, high economic benefits, and is suitable for large-scale production.

[0005] The present invention is achieved through the following technical solutions:

[0006] A method for synthesizing β-amino alcohol using 1,2-butylene oxide comprises the following steps:

[0007] (1) preparing a mixed solution of pentylamine and a solvent, wherein the weight ratio of pentylamine to solvent in the mixed solution is 1:2.2-4.2, and then stirring and heating are started, wherein the heating temperature is controlled between 40-60° C.; the solvent is a mixture of deionized water and alcohol;

[0008] (2) introducing carbon dioxide gas into the mixed solution to adjust the pH value to between 7.1 and 7.9;

[0009] (3) then adding 1,2-butylene oxide dropwise to the mixed solution, wherein the molar ratio of the amount of 1,2-butylene oxide added to pentylamine is 1:1-15, stirring is maintained during the addition process and the temperature is controlled between 40 and 60° C., and after the addition is complete, the temperature is lowered to 0 to 30° C., and the reaction is carried out at a constant temperature for 3 to 50 hours;

[0010] (4) removing the alcohol solvent in the reaction solution by distillation under reduced pressure;

[0011] (5) adding ether to extract the reaction solution, and collecting the ether layer;

[0012] (6) removing the ether from the ether layer to obtain a crude product, and then purifying the crude product.

[0013] Preferably, the alcohol in step (1) is methanol or ethanol.

[0014] Preferably, the pH value of the mixed solution in step (2) is between 7.3 and 7.5.

[0015] Preferably, the purification method includes but is not limited to column chromatography purification.

[0016] Preferably, the eluent used in the column chromatography purification treatment is a mixed solution of methanol and dichloromethane in a volume ratio of 1 to 3:97 to 99.

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

[0018] The present invention uses 1,2-butylene oxide and pentylamine to carry out ring-opening aminolysis reaction to synthesize β-amino alcohol, and the reaction raw materials are easy to obtain and have strong coordination ability. Secondly, the present invention is relatively easy to obtain more monosubstituted products by reacting and synthesizing in a mixed solvent of deionized water and alcohols. At the same time, the protective effect of CO2 on the reaction product pentylamine makes the substitution mainly occur on the terminal carbon, and the β-amino alcohol can be prepared efficiently and environmentally friendly. The β-amino alcohol prepared by the present invention has good induction ability and coordination ability, and has high stereoselectivity and catalytic activity after forming a complex with various elements. The present invention also has the characteristics of simple process operation, short reaction time, and high product yield. It belongs to the category of "green chemistry", has high economic benefits, and is suitable for large-scale production. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 Schematic diagram of the protection mechanism of CO2 on amine compounds in the present invention;

[0020] Figure 2 Schematic diagram of the synthesis route of β-amino alcohol of the present invention;

[0021] Figure 3 This is the mass spectrum of the β-amino alcohol prepared in Example 1;

[0022] Figure 4 This is the mass spectrum of the β-amino alcohol prepared in Example 2;

[0023] Figure 5 This is the mass spectrum of the β-amino alcohol prepared in Example 3;

[0024] Figure 6 This is the mass spectrum of the β-amino alcohol prepared in Example 4. DETAILED DESCRIPTION

[0025] In order to make the purpose, features and advantages of the present invention more obvious and easy to understand, the specific embodiments of the present invention are described in detail below in conjunction with the accompanying drawings. The reaction synthesis route diagram of the present invention and several embodiments are provided in the accompanying drawings. However, the present invention can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present invention more thorough and comprehensive.

[0026] Example 1

[0027] In a reactor (100mL) with a magnetic stirrer, add 2mL of deionized water, 0.3mL of methanol and 693μL of pentylamine, turn on the magnetic stirring and heat to 50°C. After stirring into a homogeneous phase, introduce carbon dioxide into the mixed solution until the pH value is measured to be 7.2; maintain the temperature and slowly add 522μL of 1,2-butylene oxide to the reactor under stirring. After the addition is completed, react at room temperature (25°C) for 6h; after the reaction is completed, remove the methanol in the reaction solution by vacuum distillation, and then add 10mL of ether for extraction; remove the ether in the ether layer, then concentrate to obtain the crude product, and finally purify by column chromatography to obtain a series of β-amino alcohols. It was found through detection that the monosubstituted organic phase ( Figure 2 C) and a very small amount of organic phase ( Figure 2 D), in addition to a small amount of disubstituted impurity organic phase ( Figure 2 E).

[0028] The crude product was purified by column chromatography to give β-amino alcohol in 49% yield.

[0029] Example 2

[0030] In a reactor (100mL) with a magnetic stirrer, add 2mL of deionized water, 0.3mL of methanol and 693μL of pentylamine, turn on the magnetic stirring and heat to 50℃, stir to form a homogeneous phase, and then introduce carbon dioxide into the mixed solution until the pH value is measured to be 7.5; maintain the temperature and slowly add 104.4μL of 1,2-butylene oxide to the reactor under stirring, and react at room temperature (25℃) for 6h after the addition is completed; after the reaction is completed, remove the methanol in the reaction solution by vacuum distillation, and then add 10mL of ether for extraction; remove the ether in the ether layer, then concentrate to obtain the crude product, and finally purify by column chromatography to obtain a series of β-amino alcohols. It was found through detection that the monosubstituted organic phase ( Figure 2 C) and a very small amount of organic phase ( Figure 2 D), in addition to a small amount of disubstituted impurity organic phase ( Figure 2 E).

[0031] The crude product was purified by column chromatography to give β-amino alcohol in 63% yield.

[0032] Example 3

[0033] In a reactor (100mL) with a magnetic stirrer, add 2mL of deionized water, 0.3mL of methanol and 693μL of pentylamine, turn on the magnetic stirring and heat to 50℃, stir to form a homogeneous phase, and then introduce carbon dioxide into the mixed solution until the pH value is measured to be 7.3; maintain the temperature and slowly add 52.2μL of 1,2-butylene oxide to the reactor under stirring, and react at room temperature (25℃) for 6h after the addition is completed; after the reaction is completed, remove the methanol in the reaction solution by vacuum distillation, and then add 10mL of ether for extraction; remove the ether in the ether layer, then concentrate to obtain the crude product, and finally purify by column chromatography to obtain a series of β-amino alcohols. It was found through detection that the monosubstituted organic phase ( Figure 2 C) and a very small amount of organic phase ( Figure 2 D), in addition to a small amount of disubstituted impurity organic phase ( Figure 2 E).

[0034] The crude product was purified by column chromatography to give β-amino alcohol in 80% yield.

[0035] Example 4

[0036] In a reactor (100mL) with a magnetic stirrer, add 2mL of deionized water, 0.3mL of methanol and 693μL of pentylamine, turn on the magnetic stirring and heat to 50℃, stir to form a homogeneous phase, and then introduce carbon dioxide into the mixed solution until the pH value is measured to be 7.4; maintain the temperature and slowly add 34.8μL of 1,2-butylene oxide to the reactor under stirring, and react at room temperature (25℃) for 6h after the addition is completed; after the reaction is completed, remove the methanol in the reaction solution by vacuum distillation, and then add 10mL of ether for extraction; remove the ether in the ether layer, then concentrate to obtain the crude product, and finally purify by column chromatography to obtain a series of β-amino alcohols. It was found through detection that the monosubstituted organic phase ( Figure 2 C) and a very small amount of organic phase ( Figure 2 D), in addition to a small amount of disubstituted impurity organic phase ( Figure 2 E).

[0037] The crude product was purified by column chromatography to give β-amino alcohol in 88% yield.

[0038] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. A method for synthesizing β-amino alcohol using 1,2-butylene oxide, characterized in that: The following steps are involved: (1) preparing a mixed solution of pentylamine and a solvent, wherein the pentylamine in the mixed solution is 693 µL, and then stirring and heating are started, wherein the heating temperature is controlled at 50° C.; the solvent is a mixture of deionized water and alcohol, wherein the deionized water is 2 mL and the methanol is 0.3 mL; (2) introducing carbon dioxide gas into the mixed solution to adjust the pH value of the mixed solution to 7.4; (3) Then, 1,2-butylene oxide was added dropwise to the mixed solution, wherein the amount of 1,2-butylene oxide added was 34.8 μL, stirring was maintained during the addition, and the temperature was controlled at 50° C. After the addition was complete, the temperature was lowered to 25° C. and the reaction was continued at a constant temperature for 6 hours; (4) removing alcohols from the reaction solution by distillation under reduced pressure; (5) adding ether to extract the reaction solution, and collecting the ether layer; (6) removing the ether from the ether layer to obtain a crude product, which is then purified by column chromatography.

2. The method for synthesizing β-amino alcohol using 1,2-butylene oxide according to claim 1, characterized in that: The eluent used in the column chromatography purification treatment is a mixed solution of methanol and dichloromethane in a volume ratio of 1-3:97-99.

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