A process for the preparation of N-decyl oxazolidinone

Abstract

The application belongs to a preparation method of N-decyl oxazolidinone and belongs to the field of organic synthesis. N-decyl oxazolidinone is obtained by heating, dehydrating and condensing ethylene carbonate and 1-decylamine as raw materials under the action of Na-Y molecular sieve, potassium carbonate and triphenyl boron as three catalysts. The catalytic system of the application is simple and easy to obtain, the reaction condition is mild, the selectivity problem of single substitution and double substitution is solved, the separation yield is high, two main raw materials can be used under the condition of equivalent, the method of the application is more green and environmental protection, and the process is suitable for scale-up production.

Description

Technical Field

[0001] This invention relates to a novel method for preparing N-decyloxazolidinone, belonging to the field of organic synthesis. Background Technology

[0002] Oxazolidinones have wide applications in antibacterial drugs due to their unique mechanism of action, enabling their use in novel, fully synthetic antibacterial agents. Compared to isothiazolinones, oxazolidinones exhibit advantages such as greater stability and lower irritation. N-decyloxazolidinones are highly lipid-soluble oxazolidinones that can be used in the synthesis of antibacterial drugs and as additives in daily chemical products to exert antibacterial effects. For example, they are frequently used in cosmetics as antibacterial agents, emollients, and plasticizers.

[0003] The literature [Chemistry of Heterocyclic Compounds, 1976, 12, 642-645][KhimiyaGeterotsiklicheskikh Soedinenii, 1976, 12, 768-771] reports the preparation of N-decyloxazolidinone by reacting 2-azolidinone, decyl bromide, and potassium hydroxide in DMF with heating.

[0004] The reaction route is shown below:

[0005]

[0006] Patent CN115974801,2023,A discloses a method for preparing N-decyloxazolidinone by mixing 2-(decylamino)ethanol with sodium hexafluorophosphate and tetramethylurea at 0°C and then adding a solution of triphosgene dropwise, with a yield of 99%. However, this reaction uses triphosgene, a highly toxic and hazardous substance, and 2-(decylamino)ethanol is expensive, making it unsuitable for industrial production.

[0007] The reaction route is shown below:

[0008]

[0009] To address the aforementioned issues, it is necessary to develop an alternative reaction route that utilizes the more readily available raw material ethylene carbonate to resolve the cost and safety concerns, thereby providing more process options for this type of product. Summary of the Invention

[0010] To address the problems existing in the prior art, this invention provides a method for preparing N-decyloxazolidinone. Using ethylene carbonate and 1-decylamine as raw materials, N-decyloxazolidinone is obtained through heating and dehydration condensation in the presence of Na-Y molecular sieve, potassium carbonate, and triphenylboron as catalysts. The catalysts in this invention are all common reagents, the reaction exhibits good selectivity for mono- and di-substitution, and the two main raw materials can be reacted under equisional conditions. Furthermore, this method is more environmentally friendly.

[0011] To achieve the purpose of the invention, the technical solution adopted by the present invention is: a method for preparing N-decyloxazolidinone, comprising the following steps: mixing ethylene carbonate and an organic solvent, adding 1-decylamine under the action of a mixed catalyst, and refluxing at high temperature to remove water, thereby obtaining N-decyloxazolidinone.

[0012] The reaction equation is as follows:

[0013]

[0014] Furthermore, in the above technical solution, the organic solvent is selected from DMSO, DMF, sulfolane, or toluene.

[0015] Furthermore, in the above technical solution, the temperature is selected from 100-110℃.

[0016] Furthermore, in the above technical solution, the catalyst is selected from a mixture of Na-Y molecular sieve, potassium carbonate, and triphenylborane. In actual reactions, it was found that when using only the Na-Y molecular sieve and potassium carbonate mixed catalyst, the reaction requires a molar ratio of ethylene carbonate to 1-decylamine of 4-6 / 1. When the ratio is 1-3 / 1, the disubstituted amination product increases significantly. With the addition of triphenylborane, it is speculated that due to the complexation of boron atoms with oxygen, the reaction can be maintained at approximately a 1 / 1 ratio, yielding a good monosubstituted product.

[0017] Furthermore, in the above technical solution, the molar ratio of ethylene carbonate to 1-decylamine is 1-1.2:1.

[0018] Furthermore, in the above technical solution, the reaction is carried out under nitrogen protection.

[0019] The three-component catalytic system of this invention is simple and readily available, with raw materials commonly found in the market. The reaction conditions are mild, solving the selectivity problem of mono- and di-substituted products. It has a high separation yield and the process is suitable for scale-up production. Attached Figure Description

[0020] Figure 1 The GC chromatogram of the product N-decyloxazolidinone in Example 6 is shown below.

[0021] Figure 2The image shows the GC-MS spectrum of the product N-decyloxazolidinone from Example 6. Detailed Implementation

[0022] The present invention will be further described below with reference to specific embodiments, but the present invention is not limited to these specific embodiments.

[0023] Examples 1-5

[0024]

[0025] Under nitrogen protection, 44 g (0.5 mol) of ethylene carbonate and 165 mL of organic solvent (toluene or DMF) were added to a four-necked flask equipped with a stirrer, water separator, condenser, dropping funnel, and nitrogen outlet tube. While stirring, a catalyst (5.0 g Na-Y molecular sieve, 1.6 g potassium carbonate, and 3.2 g BPh3) was added, followed by stirring. Then, 78.6 g (0.5 mol) of 1-decylamine was added dropwise. The reaction was controlled within 30 min, and the mixture was heated to 100-110 °C and refluxed for 2.5-3 h. After the reaction was completed by TLC monitoring, the catalyst was filtered off, the solvent was removed by vacuum concentration, and the product was dissolved in dichloromethane. The product was then washed with saturated ammonium chloride and saturated brine, respectively. After concentration of the organic phase, a crude product was obtained, which was purified by column chromatography to obtain N-decyloxazolidinone.

[0026]

[0027] Example 6

[0028] Under nitrogen protection, 44 g (0.5 mol) of ethylene carbonate and 165 mL of DMF were added to a four-necked flask equipped with a stirrer, water separator, condenser, dropping funnel, and nitrogen outlet tube. The catalyst (5.0 g Na-Y molecular sieve / 1.6 g anhydrous potassium carbonate / 3.2 g BPh3) was added with stirring, followed by the addition of 78.6 g (0.5 mol) of 1-decylamine. The reaction was controlled to proceed within 30 min, and the mixture was heated to 110 °C and refluxed for 3 h. After the reaction was completed by TLC monitoring, the catalyst was filtered off, the solvent was removed by vacuum concentration, and the product was dissolved in dichloromethane. The solution was then washed with saturated ammonium chloride and saturated brine, respectively. The organic phase was concentrated to obtain the crude product, which was purified by column chromatography to yield 109.1 g of N-decyloxazolidinone, with a yield of 96.0% and a GC ratio of 98.8%. 1 HNMR(400MHz, DMSO-d6):4.64-4.49(t,2H),3.24(t,2H),2.94(t,2H),1.52-1.51(m,2H),1.33-1.21(s,14H),0.88-0.85(t,3H).

[0029] Example 7

[0030]

[0031] Under nitrogen protection, 44 g (0.5 mol) of ethylene carbonate and 165 mL of DMF were added to a four-necked flask equipped with a stirrer, water separator, condenser, dropping funnel, and nitrogen outlet tube. The catalyst (4.0 g Na-Y molecular sieve / 1.6 g anhydrous potassium carbonate / 2.2 g BPh3) was added with stirring, followed by the addition of 63.0 g (0.4 mol) of 1-decylamine. The reaction was controlled within 30 min and refluxed at 110 °C for 3 h. After the reaction was completed by TLC monitoring, the catalyst was filtered off, the solvent was removed by vacuum concentration, and the product was dissolved in dichloromethane. The product was then washed with saturated ammonium chloride and saturated brine, respectively. After concentration of the organic phase, a crude product was obtained. Purification by column chromatography yielded 77.4 g of N-decyloxazolidinone, with a yield of 85.3% and a GC content of 97.1%.

[0032] Example 8

[0033]

[0034] Under nitrogen protection, 88 g (1.0 mol) of ethylene carbonate and 350 mL of DMF were added to a four-necked flask equipped with a stirrer, water separator, condenser, dropping funnel, and nitrogen outlet tube. The catalyst (10.0 g Na-Y molecular sieve / 3.2 g anhydrous potassium carbonate / 6.4 g BPh3) was added with stirring, followed by the addition of 157 g (1.0 mol) of 1-decylamine. The reaction was controlled to proceed within 30 min, and the mixture was heated to 110 °C and refluxed for 4 h. After the reaction was completed by TLC monitoring, the catalyst was filtered off, the solvent was removed by vacuum concentration, and the product was dissolved in dichloromethane. The solution was then washed with saturated ammonium chloride and saturated brine, respectively. The organic phase was concentrated to obtain the crude product, which was purified by column chromatography to yield 215.6 g of N-decyloxazolidinone, with a yield of 95.2% and a GC content of 98.5%.

[0035] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing N-decyloxazolidinone, characterized in that, Includes the following steps: ； Ethyl carbonate and an organic solvent are mixed, and 1-decylamine is added under the action of a mixed catalyst. The mixture is then refluxed at high temperature to remove water. After post-treatment, N-decyloxazolidinone is obtained. The catalyst is selected from a mixture of Na-Y molecular sieve, potassium carbonate, and triphenylboron. The molar ratio of ethylene carbonate to 1-decylamine is 1-1.2:1.

0.

2. The method for preparing N-decyloxazolidinone according to claim 1, characterized in that: The organic solvent is selected from DMSO, DMF, sulfolane, or toluene.

3. The method for preparing N-decyloxazolidinone according to claim 1, characterized in that: The reaction temperature is selected from 100-110℃.

4. The method for preparing N-decyloxazolidinone according to claim 1, characterized in that: The reaction was carried out under nitrogen protection.

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