CN116987043A - Atmospheric catalytic CO 2 Method for synthesizing oxazolidinone compound - Google Patents

Abstract

The invention discloses a method for synthesizing oxazolidinone compounds by catalyzing _CO2 under normal pressure. The method is as follows: using aziridine compounds as raw materials, MO _x (acac) _n /halogenated quaternary ammonium salt as the catalytic system, usually The reaction is stirred under pressure in a CO ₂ atmosphere to obtain oxazolidinone compounds, which include 5-substituted oxazolidinones and 4-substituted oxazolidinones. The method provided by the invention can efficiently catalyze the reaction of carbon dioxide and aziridine compounds to prepare oxazolidinone compounds under normal pressure. The method has the advantages of simple operation, no need for additional solvents, and mild reaction conditions.

Description

A method for synthesizing oxazolidinone compounds by catalyzing CO2 under normal pressure

Technical field

The invention belongs to the technical field of synthesis of oxazolidinone compounds, and particularly relates to a method for synthesizing oxazolidinone compounds using atmospheric pressure catalytic CO ₂ .

Background technique

The combustion of fossil fuels has been the heat and power basis for almost all industries and people's livelihoods for more than a hundred years. The carbon dioxide (CO ₂ ) produced by its combustion is emitted into the atmosphere, causing serious consequences for global warming and human health. had a serious impact. Regarding the _CO2 problem, its use as a renewable, cheap feedstock in organic conversion has particular appeal as it reduces the carbon footprint of new chemicals and our dependence on fossil resources [Energ.Environ.Sci.2020 ,13,1561-1567;Acs Catal.2019,9,7937-7956;Adv.Syn.Catal.2019,361,223-246.].

Oxazolidinones are a type of organic heterocyclic structure containing both oxygen and nitrogen in a five-membered ring. They are the core structure of a variety of oxazolidinone antibacterial drugs [Molecules 2021, 26, 4280] and are also important organic compounds. Synthetic intermediates and auxiliaries [Acc.Chem.Res.2021,54,2969-2990; J.Am.Chem.Soc.1981,103,2127-2129] are widely used, and people are more and more interested in the synthesis of this type of compounds. Come pay more and more attention to it. Oxazolidinones are synthesized by reacting CO ₂ as the ester group source with aziridine [RSCAdvances 2019, 9, 19465-19482; Chem.Eng.Sci.2021, 232, 116380; J.Org.Chem.2014, 79, 9771 -9777], compared with the traditional route using highly toxic reagents such as phosgene [J.Am.Chem.Soc.2003,125,2489-2506.], this method not only utilizes CO ₂ but also has an atom economy of 100% Green Chemistry Characteristics. However, limited by the high stability and catalyst activity of CO ₂ , this reaction usually requires high pressure and/or higher reaction temperature, or the catalyst synthesis is complex and costly, especially to achieve efficient conversion of CO ₂ under normal pressure. There are few studies on catalytic systems. There is an urgent need to develop efficient and low-energy catalytic systems that can reduce the cost of carbon dioxide activation.

Contents of the invention

The object of the present invention is to provide a method for catalyzing CO ₂ to synthesize oxazolidinone compounds under normal pressure, which can efficiently catalyze the reaction of carbon dioxide and aziridine compounds to prepare oxazolidinone compounds under normal pressure. The method has the operation It has the advantages of simplicity, no need for additional solvents, and mild reaction conditions.

The present invention provides the following technical solutions:

A method for synthesizing oxazolidinone compounds by catalyzing _CO2 under normal pressure. The method is as follows: using aziridine compound 1 as raw material, MO _x (acac) _n / halogenated quaternary ammonium salt as the catalytic system, under normal pressure The oxazolidinone compounds are obtained by stirring reaction in _CO2 atmosphere. The oxazolidinone compounds include 5-substituted oxazolidinone 2 and 4-substituted oxazolidinone 3. The reaction equation of the synthesis process is as follows:

Among them, R ₁ is a linear alkyl group, cycloalkyl group or benzyl group, R ₂ is an aryl group; MO _x (acac) _n is an acetylacetone metal complex or an acetylacetone metal complex oxide, and the value range of x is 0-2, the value range of n is 2-3.

The reaction mechanism of the present invention is that the metal complex and tetrabutyl halide catalyze the reaction through synergistic interaction, and the metal center of the metal complex activates the substrate through coordination with the N atoms in the aziridine.

The temperature of the reaction is 40-80°C, and the reaction time is 8-24h. When the reaction temperature is lower than 40°C, the reaction conversion rate is low; when the reaction temperature is greater than 80°C, the conversion rate is not significantly improved. Therefore, controlling the reaction temperature within this range can ensure the reaction conversion rate while having better performance. economic effects. When the reaction time is less than 8 hours, the reaction conversion rate is low; when the reaction time is greater than 24 hours, the substrate is basically completely converted, so the reaction time is controlled within this range.

In the main catalyst MO _x (acac) _n in the catalytic system, MO _x ⁿ⁺ is V ³⁺ , VO ²⁺ , La ³⁺ , MoO ₂ ²⁺ , Co ²⁺ , Fe ²⁺ , Fe ³⁺ or Ni ^{2 +} .

Preferably, MO _x n ⁺ in MO _x (acac) _n in the catalytic system is V ³⁺ , VO ²⁺ or La ³⁺ , MoO ₂ ²⁺ . When MO _x ⁿ⁺ is V ³⁺ , VO ²⁺ or La ³⁺ , MoO ₂ ²⁺ , as the main catalyst, it has stronger catalytic activity, the conversion rate of the substrate, the yield and the product 5-oxazolidinone The regional selection is relatively high.

The cocatalyst quaternary ammonium halide salt in the catalytic system is tetrabutylammonium chloride (TBAC), tetrabutylammonium bromide (TBAB) or tetrabutylammonium iodide (TBAI).

Preferably, the quaternary ammonium halide salt in the catalytic system is tetrabutylammonium chloride (TBAC) or tetrabutylammonium bromide (TBAB). As cocatalysts, TBAC and TBAB have better synergy with the above-mentioned main catalyst, which is more conducive to improving its catalytic activity and reaction selectivity.

The molar ratio of the aziridine compound, MO _x (acac) _n and quaternary ammonium halide salt is 100:0.5-5:0.5-5. By controlling the molar ratio of the three, the present invention can make it have better catalytic activity, and can make the substrate conversion rate, oxazolidinone yield and selectivity better at the same time.

Preferably, the molar ratio of the aziridine compound, MO _x (acac) _n and quaternary ammonium halide salt is 100:1-2:1-2. Limiting the molar ratio of the three to this range is more conducive to improving substrate conversion rate, oxazolidinone yield and selectivity.

Preferably, the molar ratio of MO _x (acac) _n and quaternary ammonium halide salt is 1:1. When the molar ratio of the two is 1:1, the synergistic effect of the two is best.

Preferably, R ₁ is ethyl, propyl, butyl or cyclohexyl, and R ₂ is phenyl or p-methylphenyl.

Compared with the existing technology, the present invention has the following excellent effects:

(1) The method provided by the invention can effectively catalyze the efficient conversion of aziridine compounds into oxazolidinone compounds through the synergistic catalytic reaction of metal complexes and tetrabutyl halides;

(2) The catalytic system in the method provided by the invention has good substrate applicability and can effectively catalyze the efficient conversion of a variety of substrates;

(3) The method provided by the invention can efficiently catalyze the reaction of carbon dioxide and aziridine compounds to prepare oxazolidinone compounds under normal pressure, and has the advantages of simple operation, no need for additional solvents, and mild reaction conditions.

Description of drawings

Figure 1 is the hydrogen nuclear magnetic resonance spectrum of 1-ethyl-2-phenyl-aziridine;

Figure 2 is a gas chromatogram sampled midway through the reaction mixture prepared in Example 1 (the substances corresponding to each peak in the figure were determined by gas chromatography-mass spectrometry technology);

Figure 3 is a proton nuclear magnetic resonance spectrum sampled midway of the reaction mixture prepared in Example 1.

Detailed ways

The above contents of the present invention will be further described in detail below through examples. However, this should not be understood to mean that the scope of the above subject matter of the present invention is limited to the following examples. All technologies implemented based on the above contents belong to the scope of the present invention.

The aziridine compounds used in the examples were synthesized independently, and other chemical reagents were purchased commercially and used directly without treatment. The manufacturers are Aladdin Reagent Co., Ltd. and Jiuding Chemical.

Using methyl sulfide, liquid bromine, and styrene as raw materials, the intermediate product (2-bromo-1-phenylethyl) dimethyl sulfide bromide (BPDMS) is synthesized under ice-water bath conditions; then react BPDMS with ethylamine The target product of aziridine is finally synthesized.

The reaction equation is:

Taking the synthesis of 1-ethyl-2-phenyl-aziridine as an example, the specific process is as follows:

The reaction was carried out in a 100mL round-bottomed flask, Br ₂ (16.0g, 0.1mol) was dissolved in 20mL CH ₃ CN, and in an ice water bath, the solution was added dropwise to 20mL dimethyl sulfide (6.2g, 0.1 mol)-CH ₃ CN solution, the dripping was completed within 30 minutes, and a light orange precipitate, dimethyl sulfide bromide (BDMS), was generated. In the preliminary experiment, the light orange solid was separated and analyzed by ¹ H NMR It was characterized by ^13C NMR and confirmed to be BDMS). After continuing to stir in the ice-water bath for 30 minutes, styrene (11.4g, 0.11mol) was added, the orange precipitate disappeared, and a white precipitate began to form after a while. After continuing to stir in an ice-water bath for 30 minutes, the reaction was stopped, filtered, and the filter cake was washed with CH ₃ CN and diethyl ether respectively, and then dried under vacuum overnight to obtain 13.3 g (yield, 40%) of white powder BPMDS.

BPMDS (3.26g, 10mmol) was dissolved in 20mL H ₂ O at room temperature (~27°C), and then 20mL of ethylamine (40mmol) aqueous solution was dropped into the above solution and stirred overnight. Pour the mixture into 40 ml saturated brine, extract with diethyl ether (3*30 mL), dry the extract with MgSO ₄ , filter the filtrate, and remove the solvent under reduced pressure to obtain 1.41 g of colorless liquid (yield, 96%) . The product was sampled and analyzed by nuclear magnetic resonance (as shown in Figure 1). The product was the target 1-ethyl-2-phenyl-aziridine.

Using the same method, 1-propyl-2-phenyl-aziridine, 1-butyl-2-phenyl-aziridine, 1-cyclohexyl-2-phenyl-azepine were also synthesized. Reaction substrates such as cyclopropane and 1-ethyl-2-p-tolyl-aziridine.

Example 1

In a 5 ml glass reaction bottle, add 1-ethyl-2-phenyl-aziridine (1a) (0.294g, 2mmol), 2mol% V(acac) ₃ (4*10 ^-3 mmol) based on 1a and 2 mol% TBAC based on 1a (4*10 ^-3 mmol). After replacing the gas atmosphere in the system 3 times with a balloon filled with CO ₂ (1 atm pressure), place the reaction bottle in a metal heating module at 40°C and react with magnetic stirring (about 350-400 rpm) for 24 hours. After determining the components of the reaction mixture using gas chromatography-mass spectrometry, hydrogen nuclear magnetic spectroscopy, etc., the product composition was analyzed using gas chromatography. The conversion rate of 1a was 98%, and the yield of oxazolidinone was 96%, of which 2a:3a=92 :8. The gas chromatogram is shown in Figure 2. The substances corresponding to each peak in the figure are determined by gas chromatography-mass spectrometry technology; the hydrogen nuclear magnetic resonance spectrum is shown in Figure 3.

Example 2

As in Example 1, 1a is used as the substrate, the catalyst uses 2mol% VO(acac) ₂ (4*10 ^-3 mmol) based on 1a and 2mol% TBAC (4*10 ^-3 mmol) based on 1a, and the reaction is carried out at 1atmCO ₂ pressure and 40°C for 24 hours. The conversion rate of 1a was 97%, and the oxazolidinone yield was 93%, where 2a:3a=92:8.

Example 3

As in Example 1, 1a is used as the substrate, the catalyst is 2mol% MO ₂ (acac) ₂ (4*10 ^-3 mmol) based on 1a and 2mol% TBAC (4*10 ^-3 mmol) based on 1a, and the reaction is The reaction was carried out for 24 hours under 1 atm CO ₂ pressure and 40°C. The conversion rate of 1a was 99%, and the oxazolidinone yield was 96%, where 2a:3a=91:9.

Example 4

As in Example 1, 1a is used as the substrate, the catalyst is 2mol% La(acac) ₃ (4*10 ^-3 mmol) based on 1a and 2mol% TBAC (4*10 ^-3 mmol) based on 1a, and the reaction is carried out at 1atmCO ₂ pressure and 40°C for 24 hours. The conversion rate of 1a was 91%, and the oxazolidinone yield was 88%, where 2a:3a=92:8.

Examples 5-8

As in Example 1, 1a is used as the substrate, and Examples 5-8 use acetylacetone metal complexes with different metal centers as the main catalysts (V(acac) ₃ , VO(acac) ₂ , MoO ₂ (acac) ₂ , La(acac) ₃ ) and tetrabutylammonium bromide (TBAB) were used as cocatalysts. The ratio of the three was 100:2:2. The reaction was carried out for 24 hours under 1atm CO ₂ pressure and 40°C.

Comparative Example 1-3

As in Example 5-8, Comparative Example 1 does not add a main catalyst; Comparative Example 2-3 adds Zn(acac) ₂ and Cd(acac) ₂ as main catalysts.

The substrate conversion rate, yield and regioselectivity of the oxazolidinones synthesized in Examples 5-8 and Comparative Examples 1-3 are shown in Table 1. In Examples 5-8, the combination of MO _x (acac) _n -TBAB also showed good catalytic activity, with a substrate conversion rate of 88% to 95% and an oxazolidinone yield of 74 to 86 %, the regioselectivity of the two isomers is 94:6~98:2 (Table 1, No. 5-8). In Comparative Examples 1-3, no acetylacetone metal complex was added, only cocatalyst TBAB was added, and the substrate conversion rate was only 11%; when Zn(acac) ₂ and Cd(acac) ₂ were used, the substrate conversion rate was The conversion rate is 0 (Table 1, No. 9-11), indicating that they not only fail to promote the reaction, but also prevent the reaction from proceeding.

Table 1 Substrate conversion rate, yield and regioselectivity for the synthesis of oxazolidinones in Examples 1-8 and Comparative Examples 1-3

aReaction conditions: substrate 1-ethyl-2phenyl-aziridine (2mmol), MO _x (acac) _n (0.04mmol, 2mol%), TBAX (0.04mmol, 2mol%), 1atm of CO ₂ , 40℃,24h.

b is determined by gas chromatography.

The ratio of c5-substituted oxazolidinones to 4-substituted oxazolidinones

Example 9

As in Example 1, 1a is used as the substrate, the catalyst is 1mol% V(acac) ₃ (4*10 ^-3 mmol) based on 1a and 1mol% TBAC (4*10 ^-3 mmol) based on 1a, and the reaction is carried out at 1atmCO ₂ pressure and 80°C for 8 hours. The conversion rate of 1a was 96%, and the oxazolidinone yield was 93%, where 2a:3a=90:10.

Example 10

As in Example 9, 1a is used as the substrate, the catalyst is 1mol% VO(acac) ₂ (4*10 ^-3 mmol) based on 1a and 1mol% TBAC (4*10 ^-3 mmol) based on 1a, and the reaction is carried out at 1atmCO ₂ pressure and 80°C for 8 hours. The conversion rate of 1a was 99%, and the oxazolidinone yield was 98%, where 2a:3a=91:9.

Example 11

As in Example 9, 1a is used as the substrate, the catalyst is 1mol% MO ₂ (acac) ₂ (4*10 ^-3 mmol) based on 1a and 1mol% TBAC (4*10 ^-3 mmol) based on 1a, and the reaction is The reaction was carried out for 8 hours under 1 atm CO ₂ pressure and 80°C. The conversion rate of 1a was 95%, and the oxazolidinone yield was 90%, where 2a:3a=91:9.

Example 12

As in Example 1, 1-cyclohexyl-2-phenylaziridine (1b) is used as the substrate, and the catalyst uses 1 mol% VO(acac) ₂ (2*10 ^-3 mmol) based on 1b and 1 mol based on 1b. %TBAC (2*10 ^-3 mmol), the reaction was carried out at 1atmCO ₂ pressure and 40°C for 24h. The conversion rate of 1b was 96%, and the oxazolidinone yield was 95%, where 2b:3b=100:0.

Example 13

As in Example 1, 1-ethyl-2-p-methylphenylaziridine (1c) is used as the substrate, and the catalyst uses 1 mol% VO(acac) ₂ (2*10 ^-3 mmol) based on 1c and based on 1c. 1c of 1mol% TBAC (2*10 ^-3 mmol), the reaction was carried out at _1atmCO2 pressure and 40°C for 24h. The conversion rate of 1c was 95%, and the oxazolidinone yield was 94%, where 2c:3c=97:3.

The above descriptions are only examples of the present invention and are not intended to limit the present invention. Various modifications and variations will occur to the present invention to those skilled in the art. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention shall be included in the scope of the claims of the present invention.

Claims (8)

1. A method for synthesizing oxazolidinone compounds with atmospheric catalytic _CO2 , characterized in that the method is: using aziridine compound 1 as raw material, MO _x (acac) _n / halogenated quaternary ammonium salt as catalysis System, the reaction is stirred in a CO ₂ atmosphere under normal pressure to obtain oxazolidinone compounds. The oxazolidinone compounds include 5-substituted oxazolidinones 2 and 4-substituted oxazolidinones 3. The reaction equation of the synthesis process as follows: Among them, R ₁ is a linear alkyl group, cycloalkyl group or benzyl group, R ₂ is an aryl group; MO _x (acac) _n is an acetylacetone metal complex or an acetylacetone metal complex oxide, and the value range of x is 0-2, the value range of n is 2-3. 2. The method for synthesizing oxazolidinone compounds with atmospheric pressure catalytic CO ₂ according to claim 1, characterized in that the temperature of the reaction is 40-80°C, and the reaction time is 8-24h. 3. The method for synthesizing oxazolidinone compounds from atmospheric catalytic _CO according to claim 1, characterized in that the MO _x ⁿ⁺ in MO _x (acac) _n in the catalytic system is V ³⁺ and VO ^{2 +} , La ³⁺ , MoO ₂ ²⁺ , Co ²⁺ , Fe ²⁺ , Fe ³⁺ or Ni ²⁺ . 4. The method for synthesizing oxazolidinone compounds from atmospheric catalytic _CO according to claim 3, characterized in that in the catalytic system, MO _x ⁿ⁺ in MO _x (acac) _n is V ³⁺ and VO ^{2 +} or La ³⁺ , MoO ₂ ²⁺ . 5. The method for synthesizing oxazolidinone compounds using atmospheric catalytic CO according to claim ₁ , characterized in that the halogenated quaternary ammonium salt in the catalytic system is tetrabutylammonium chloride or tetrabutylammonium bromide. Ammonium or tetrabutylammonium iodide. 6. The method for synthesizing oxazolidinone compounds with atmospheric catalytic _CO according to claim 5, characterized in that the halogenated quaternary ammonium salt in the catalytic system is tetrabutylammonium chloride or tetrabutylammonium bromide. ammonium. 7. The method for synthesizing oxazolidinone compounds by atmospheric pressure catalytic CO according to claim ₁ , characterized in that the molar ratio of the aziridine compounds, MO _x (acac) _n and halogenated quaternary ammonium salts is 100:0.5-5:0.5-5. 8. The method for synthesizing oxazolidinone compounds with atmospheric catalytic _CO according to claim 1, characterized in that, _R1 is ethyl, propyl, butyl or cyclohexyl, and _R2 is phenyl Or p-methylphenyl.