Difunctional N-heterocyclic carbene catalyst as well as preparation method and application thereof

Abstract

The invention discloses a difunctional N-heterocyclic carbene catalyst as well as a preparation method and application thereof. The catalyst N-heterocyclic carbene and carboxyl or hydroxyl connected with the N end have a synergistic effect, activation and coupling of reactant formaldehyde molecules can be accelerated, and high-efficiency and high-selectivity generation of a trimerization product dihydroxy acetone is promoted.

Description

Technical Field

[0001] The present application relates to a bifunctional nitrogen carbene catalyst and a preparation method and application thereof, belonging to the field of organic synthesis. Background Art

[0002] In the process of artificial starch synthesis, it is crucial to construct the carbon trimer 1,3-dihydroxyacetone from the carbon one molecule in one step. There are currently two ways to obtain dihydroxyacetone from the carbon one molecule. One is to use the modified benzaldehyde lyase to achieve the trimerization of formaldehyde molecules. This method mainly faces the problem of high enzyme and product separation; the other is to obtain the trimerization product dihydroxyacetone with high selectivity through the formaldehyde polysaccharide reaction. This process is green and meets the atomic economy, and has significant economic competitiveness. At present, only azacarbene catalysts with benzothiazole or naphthothiazole as the parent ring can obtain high selectivity for the product dihydroxyacetone. Using 5mol% of 3-ethylbenzothiazole carbene catalyst in the solvent DMF can achieve a formaldehyde conversion rate of 98% and a dihydroxyacetone selectivity of 89%. Using 2.5mol% of 3-ethylnaphthothiazole carbene catalyst in the solvent DMF can obtain a dihydroxyacetone yield of 64%, and the selectivity of the measured products is close to 85%. At present, the catalyst efficiency in this type of research is relatively low, and the TOF (calculated as the product DHA) does not exceed 10h -1 .

[0003] In order to further improve the catalytic performance of this type of catalyst, the catalyst structure needs to be further modified. Current research mainly focuses on the modification of the parent ring of nitrogen heterocyclic carbene, while there is little research on the modification of the N-terminal substituent and no obvious effect. Summary of the invention

[0004] The N substituent of azacarbene affects the catalytic performance from the aspects of electronic effect and steric hindrance. Studies have shown that some proton-carrying small molecules such as amines, alcohols, phenols, etc., help to reduce the activation energy of Breslow intermediate formation through intermolecular proton transfer and accelerate the reaction. Based on this, the present application provides a series of bifunctional azacarbene catalysts with phenolic hydroxyl and phenyl carboxyl modified N-terminal for formaldehyde polysaccharide reaction to improve the catalytic efficiency of such catalysts.

[0005] According to one aspect of the present application, a bifunctional nitrogen carbene catalyst is provided, wherein the bifunctional nitrogen carbene catalyst has a structure shown in Formula I:

[0006]

[0007] R is selected from at least one of formula II, formula III, hydroxyl, and carboxyl;

[0008]

[0009] Wherein, n is an integer between 1 and 4;

[0010] R 1 At least one selected from a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, a fluorine atom, a chlorine atom, and a nitro group;

[0011] R 2 At least one selected from a hydrogen atom, a methyl group, an ethyl group, a propyl group, and a tert-butyl group;

[0012] R 3 At least one selected from the group consisting of a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, a fluorine atom, a chlorine atom, a nitro group, and a methoxy group;

[0013] * indicates the attachment site.

[0014] According to another aspect of the present application, a method for preparing the above-mentioned bifunctional nitrogen carbene catalyst is provided, comprising the following steps:

[0015] Mixing benzothiazole, a bromine-containing raw material and an organic solvent, performing reaction I to obtain the bifunctional azacarbene catalyst precursor, and mixing the bifunctional azacarbene catalyst precursor with a base, performing reaction II to obtain the bifunctional azacarbene catalyst;

[0016] The bifunctional azacarbene catalyst precursor has a structure shown in Formula IV:

[0017]

[0018] The bromine-containing raw material is selected from at least one of formula A, formula B, formula C, and formula D;

[0019]

[0020]

[0021] The reaction I is performed without solvent or with an organic solvent selected from at least one of acetonitrile, dioxane, tetrahydrofuran, dimethyl sulfoxide and acetone.

[0022] The dosage ratio of the benzothiazole to the organic solvent is 5 to 20 mol / L;

[0023] Optionally, any value among 5 mol / L, 10 mol / L, 15 mol / L, 20 mol / L, or a range between any two of them.

[0024] The molar ratio of the bromine-containing raw material to benzothiazole is 1:1-2;

[0025] Optionally, the molar ratio of the bromine-containing raw material to benzothiazole is any value of 1:1, 1:1.5, 1:2, or a range between any two values.

[0026] The temperature of the reaction I is 80-120°C;

[0027] Optionally, the temperature of the reaction I is any value among 80°C, 90°C, 100°C, 110°C, 120°C, or any range between two of them.

[0028] The reaction time of the reaction I is 10 to 48 hours;

[0029] Optionally, the reaction time I is any value among 10h, 12h, 24h, 36h, 48h, or a range value between any two of them.

[0030] The base is selected from at least one of triethylamine, quinuclidine, cesium carbonate, potassium tert-butoxide, imidazole, and DBU;

[0031] The molar ratio of the bifunctional nitrogen carbene catalyst precursor to the base is 1:1-3.

[0032] Optionally, the molar ratio of the bifunctional azacarbene catalyst precursor to the base is any value of 1:1, 1:2, 1:3, or a range between any two values.

[0033] The reaction II uses an organic solvent selected from at least one of dioxane, tetrahydrofuran, and ethylene glycol dimethyl ether;

[0034] The temperature of the reaction II is 25-100°C;

[0035] Optionally, the temperature of the reaction II is any value among 25°C, 50°C, 75°C, 100°C, or any range therebetween.

[0036] The time of the reaction II is 12 to 24 hours;

[0037] Optionally, the time of reaction II is any value among 12h, 18h, 24h, or any range value therebetween.

[0038] Optionally, after reaction I is completed, the mixture is cooled to room temperature, the solvent is removed by rotary evaporation to obtain a brown viscous liquid, 3 volumes of ethyl acetate are added, and the mixture is vigorously stirred for 10 minutes to precipitate a viscous solid. After standing, the upper liquid is poured out, and this operation is repeated three times to obtain a light brown solid; 10 volumes of dichloromethane are added to the obtained light brown solid, and the mixture is vigorously stirred at room temperature for 10 hours. The white solid is filtered to obtain the bifunctional nitrogen carbene catalyst precursor.

[0039] According to another aspect of the present application, there is provided an application of the above-mentioned bifunctional azacarbene catalyst for formaldehyde polysaccharide reaction.

[0040] The temperature of the formaldehyde polysaccharide reaction is higher than 60°C;

[0041] Optionally, the temperature of the formaldehyde polysaccharide reaction is 60-200°C.

[0042] The beneficial effects of this application include:

[0043] The present application provides a novel bifunctional azacarbene catalyst design, synthesis and application in the preparation of dihydroxyacetone from formaldehyde (formaldehyde polysaccharide reaction). The catalyst azacarbene has a synergistic effect with the carboxyl or hydroxyl group connected to the N-terminus, which can accelerate the activation and coupling of the reactant formaldehyde molecule and promote the efficient and selective generation of the trimerization product dihydroxyacetone. BRIEF DESCRIPTION OF THE DRAWINGS

[0044] Figure 1 is the hydrogen nuclear magnetic resonance spectrum of the catalyst A1 (3-(2-(2-hydroxyphenyl)ethyl)-benzothiazole bromide) of the present invention;

[0045] Figure 2 is the carbon nuclear magnetic resonance spectrum of the catalyst A1 (3-(2-hydroxyethyl)-benzothiazole bromide) of the present invention;

[0046] Figure 3 This is a graph showing the peak results of dihydroxyacetone in gas chromatography in Example 21 of the present invention.

[0047] Figure 4 This is a comparison chart of the catalytic effect of A1 in the present invention and the catalyst effect in current research. DETAILED DESCRIPTION

[0048] The present application is described in detail below with reference to embodiments, but the present application is not limited to these embodiments.

[0049] Unless otherwise specified, the raw materials in the examples of this application were purchased through commercial channels.

[0050] Example 1

[0051] This embodiment is a method for preparing a catalyst precursor A1 (3-(2-(2-hydroxyphenyl)ethyl)-benzothiazole bromide), and the specific steps are as follows:

[0052] 1) Benzothiazole was dissolved in acetonitrile at a concentration of 10 mol / L.

[0053] 2) Add 1.2 equivalents of 2-(2-bromoethyl)phenol to the above solution and react at 100°C for 20 hours.

[0054] 3) After the reaction is completed, the mixture is cooled to room temperature and the solvent acetonitrile is removed by rotary evaporation to obtain a brown viscous liquid;

[0055] 4) Add 3 volumes of ethyl acetate to the above brown viscous liquid, stir vigorously for 10 minutes, precipitate a viscous solid, let stand and pour out the upper liquid, repeat this operation three times to obtain a light brown solid;

[0056] 5) Add 10 times the volume of dichloromethane to the obtained light brown solid, stir vigorously at room temperature for 10 hours, and filter to obtain a white solid, which is catalyst A1 (3-(2-(2-hydroxyphenyl)ethyl)-benzothiazole bromide), with a yield of 24%.

[0057] 6) The structural characterization data of the product obtained in Example 1 are as follows: 1 HNMR (400MHz, DeuteriumOxide) δ9.72 (s, 1H), δ8.22-8.15 (m, 1H), 8.08 (d, J=8.5Hz, 1H), 7.84-7.69 (m, 2H), 7.09-7.00 (m, 1H) , 6.89 (dd, J=7.6, 1.7Hz, 1H), 6.73 (dd, J=8.1, 6.8Hz, 1H), 6.61 (d, J=8.1Hz, 1H), 4.99 (t, J=6.3Hz, 2H), 3.21 (t, J=6.3Hz, 2H). 13 CNMR (101MHz, DeuteriumOxide) δ154.16, 131.05, 130.80, 129.82, 129.19, 128.75, 124.34, 122.62, 120.82, 116.47, 115.15, 53.29, 29.45.

[0058] 7) Based on the above NMR data, it is inferred that the product conforms to the following structure:

[0059]

[0060] Example 2

[0061] This embodiment is a method for preparing a catalyst precursor B1 (3-(2-hydroxyethyl)-benzothiazole bromide), and the specific steps are as follows:

[0062] 1) Benzothiazole was dissolved in acetonitrile at a concentration of 10 mol / L.

[0063] 2) Add 1.2 equivalents of 2-bromoethanol to the above solution and react at 90°C for 20 hours.

[0064] 3) After the reaction is completed, the mixture is cooled to room temperature and the solvent acetonitrile is removed by rotary evaporation to obtain a brown viscous liquid;

[0065] 4) Add 3 volumes of ethyl acetate to the above brown viscous liquid, stir vigorously for 10 minutes, precipitate a viscous solid, let stand and pour out the upper liquid, repeat this operation three times to obtain a light brown solid;

[0066] 5) Add 10 volumes of dichloromethane to the obtained light brown solid, stir vigorously at room temperature for 10 h, and filter to obtain a white solid, which is catalyst B1 (3-(2-hydroxyethyl)-benzothiazole bromide), with a yield of 76%.

[0067] 6) The structural characterization data of the product obtained in Example 2 are as follows: 1 HNMR (400 MHz, DMSO-d 6 )δ10.56 (s, 1H), 8.61-8.54 (m, 1H), 8.46 (dd, J=8.3, 1.1Hz, 1H), 7.94 (ddd, J=8.5, 7.2, 1.3 Hz, 1H), 7.86 (ddd, J=8.3, 7.2, 1.1Hz, 1H), 5.01-4.94 (m, 2H), 3.89 (dd, J=5.7, 4.3Hz, 2H). 13 CNMR (101 MHz, DMSO-d 6 )δ165.61, 140.86, 131.97, 129.89, 128.78, 125.76, 117.85, 58.80, 55.44.

[0068] 7) Based on the above NMR data, it is inferred that the product conforms to the following structure:

[0069]

[0070] Example 3

[0071] This embodiment is a method for preparing a catalyst C1 precursor (3-(2-carboxyethyl)-benzothiazole bromide), and the specific steps are as follows:

[0072] 1) Benzothiazole was dissolved in acetonitrile at a concentration of 10 mol / L.

[0073] 2) Add 1.2 equivalents of 3-bromopropionic acid to the above solution and react at 90°C for 20 hours.

[0074] 3) After the reaction is completed, the mixture is cooled to room temperature and the solvent acetonitrile is removed by rotary evaporation to obtain a brown viscous liquid;

[0075] 4) Add 3 volumes of ethyl acetate to the above brown viscous liquid, stir vigorously for 10 minutes, precipitate a viscous solid, let stand and pour out the upper liquid, repeat this operation three times to obtain a light brown solid;

[0076] 5) Add 10 volumes of dichloromethane to the obtained light brown solid, stir vigorously at room temperature for 10 h, and filter to obtain a white solid, which is catalyst C1 (3-(2-carboxyethyl)-benzothiazole bromide), with a yield of 94%.

[0077] 6) The structural characterization data of the product obtained in Example 3 are as follows: 1 HNMR (400MHz, DMSO-d6) δ12.72 (s, 1H), 10.63 (s, 1H), 8.58-8.51 (m, 1H), 8.50-8.43 (m, 1H), 7.94 (ddd, J=8.6, 7.2, 1.3Hz, 1H), 7.86 (ddd, J=8.3, 7.2, 1.1Hz, 1H), 5.06 (t, J=6.8Hz, 2H), 3.07 (t, J=6.8Hz, 2H). 13 CNMR (101MHz, DMSO-d6) δ172.05, 166.22, 140.61, 131.86, 130.07, 128.83, 125.79, 117.68, 48.67, 32.99.

[0078] 7) Based on the above NMR data, it is inferred that the product conforms to the following structure:

[0079]

[0080] Example 4

[0081] This embodiment is a method for preparing a catalyst precursor D1 (3-(2-carboxyphenyl)methyl-benzothiazole bromide), and the specific steps are as follows:

[0082] 1) Benzothiazole was dissolved in acetonitrile at a concentration of 10 mol / L.

[0083] 2) Add 1.2 equivalents of 2-bromomethylbenzoic acid to the above solution and react at 90°C for 20 hours.

[0084] 3) After the reaction is completed, the mixture is cooled to room temperature and the solvent acetonitrile is removed by rotary evaporation to obtain a brown viscous liquid;

[0085] 4) Add 3 volumes of ethyl acetate to the above brown viscous liquid, stir vigorously for 10 minutes, precipitate a viscous solid, let stand and pour out the upper liquid, repeat this operation three times to obtain a light brown solid;

[0086] 5) Add 10 times the volume of dichloromethane to the obtained light brown solid, stir vigorously at room temperature for 10 hours, and filter to obtain a white solid, which is catalyst D1 (3-(2-carboxyphenyl)methyl-benzothiazole bromide), with a yield of 35%.

[0087] 6) The structural characterization data of the product obtained in Example 2 are as follows: 1 HNMR (400MHz, DMSO-d6) δ13.44 (s, 1H), 10.41 (s, 1H), 8.63-8.53 (m, 1H), 8.33-8.23 (m, 1H), 8.1 7-8.07 (m, 1H), 7.89 (tt, J=7.3, 5.7Hz, 2H), 7.66-7.53 (m, 2H), 7.17-7.10 (m, 1H), 6.40 (s, 2H). 13 CNMR (101MHz, DMSO-d6) δ168.10, 165.83, 141.00, 133.86, 133.61, 132.02, 130.25, 130.00, 129.87, 129.05, 125.90, 117.85, 55.09.

[0088] 7) Based on the above NMR data, it is inferred that the product conforms to the following structure:

[0089]

[0090] Example 5

[0091] This embodiment is a method for preparing a catalyst A1 solution.

[0092] Under argon protection, 78 mg of catalyst precursor A1 and 28 uL of triethylamine were added to a 10 mL Schlenk tube, and then 2 mL of dioxane was added as a solvent. After sealing, the tube was reacted at room temperature for 12 hours. After the reaction was completed, the solid was filtered out under argon protection to obtain a catalyst A1 solution.

[0093] Catalyst B1, C1, and D1 solutions were prepared in the same manner.

[0094] Embodiments 6 to 9

[0095] This example shows the results of the formaldehyde polysaccharide reaction using different catalyst dosages of catalyst A1.

[0096] Under argon protection, add 0.5mmol paraformaldehyde, 15mL 1,4-dioxane and different volumes of catalyst A1 solution with a concentration of 0.1mol / L to a dry and clean 35mL pressure tube, and stir at 100℃ for 1h. After the reaction, cool quickly to room temperature, take 0.2mL of the reaction solution and react with 0.2mL pyridine, 2.3mg 1,4-butanediol, and 35mg hydroxylamine hydrochloride at 70℃ for 1h. After cooling, add 0.2mL hexamethyldisilazane and 0.2mL trimethylchlorosilane, and react at room temperature for 1h. Dilute the above-mentioned derivatization product with dichloromethane and analyze it by gas chromatography. The specific experimental results are shown in Table 1.

[0097] Table 1

[0098]

[0099] According to the results of Example 6, TOF (calculated as product molecules) is 29h -1 .

[0100] Embodiments 10 to 14

[0101] Except for using the solvents listed in Table 2 below, the formaldehyde polysaccharide reaction was carried out in the same manner as in Example 6. The specific experimental results are listed in Table 2.

[0102] Table 2

[0103]

[0104] Embodiments 15 to 19

[0105] Except for adopting the reaction temperature in Table 3 below, the formaldehyde polysaccharide reaction was carried out in the same manner as in Example 6. The specific experimental results are listed in Table 3.

[0106] Table 3

[0107]

[0108] Embodiments 20 to 22

[0109] Except for using the reactant concentrations in Table 4 below, the formaldehyde polysaccharide reaction was carried out in the same manner as in Example 6. The specific experimental results are listed in Table 4.

[0110] Table 4

[0111]

[0112]

[0113] Embodiments 23 to 25

[0114] Except for using the catalyst types listed in Table 5 below, the formaldehyde polysan reaction was carried out in the same manner as in Example 6. The specific experimental results are listed in Table 5.

[0115] Table 5

[0116]

[0117] Embodiment 26

[0118] Using conventional 3-ethylbenzothiazole bromide as a catalyst, the formaldehyde polysaccharide reaction was carried out in the same manner as in Example 6, with a formaldehyde conversion rate of 77.3% and a 1,3-dihydroxyacetone selectivity of 36.6%.

[0119] The above are only a few embodiments of the present application and do not constitute any form of limitation to the present application. Although the present application is disclosed as above with preferred embodiments, it is not intended to limit the present application. Any technician familiar with the profession, without departing from the scope of the technical solution of the present application, using the technical content disclosed above to make slight changes or modifications are equivalent to equivalent implementation cases and fall within the scope of the technical solution.

Claims

1. A bifunctional nitrogen carbene catalyst, characterized in that The bifunctional azacarbene catalyst has a structure shown in Formula I: R is selected from at least one of formula II, formula III, hydroxyl, and carboxyl; Wherein, n is an integer between 1 and 4; R1 is at least one selected from a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, a fluorine atom, a chlorine atom, and a nitro group; R2 is selected from at least one of a hydrogen atom, a methyl group, an ethyl group, a propyl group, and a tert-butyl group; R3 is at least one selected from a hydrogen atom, a methyl group, an ethyl group, an isopropyl group, a fluorine atom, a chlorine atom, a nitro group, and a methoxy group; * indicates the attachment site.

2. A method for preparing the bifunctional azacarbene catalyst according to claim 1, characterized in that: The following steps are involved: Mixing benzothiazole, a bromine-containing raw material and an organic solvent, performing reaction I to obtain the bifunctional azacarbene catalyst precursor, and mixing the bifunctional azacarbene catalyst precursor with a base, performing reaction II to obtain the bifunctional azacarbene catalyst solution; The bifunctional azacarbene catalyst precursor has a structure shown in Formula IV: The bromine-containing raw material is selected from at least one of formula A, formula B, formula C, and formula D; 3. The preparation method according to claim 2, characterized in that: The reaction I can be carried out without solvent or with an organic solvent selected from at least one of acetonitrile, dioxane, tetrahydrofuran, dimethyl sulfoxide and acetone.

4. The preparation method according to claim 2, characterized in that: When the organic solvent is used, the ratio of benzothiazole to the organic solvent is 5 to 20 mol / L; The molar ratio of the bromine-containing raw material to benzothiazole is 1:1-2.

5. The preparation method according to claim 2, characterized in that: The temperature of the reaction I is 80-120°C; The reaction time of the reaction I is 10 to 48 hours.

6. The preparation method according to claim 2, characterized in that: The reaction II uses an organic solvent selected from at least one of dioxane, tetrahydrofuran and ethylene glycol dimethyl ether.

7. The preparation method according to claim 2, characterized in that: The base is selected from one of triethylamine, quinuclidine, cesium carbonate, potassium tert-butoxide, imidazole, and DBU; The molar ratio of the bifunctional nitrogen carbene catalyst precursor to the base is 1:1-3.

8. The preparation method according to claim 2, characterized in that: The temperature of the reaction II is 25-100°C; The time of the reaction II is 12 to 24 hours.

9. Use of the bifunctional nitrogen carbene catalyst according to claim 1, characterized in that: Used for formaldehyde polysaccharide reaction.

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