A method for the Diels - Alder reaction of a photocatalytic dienophile with a diene

Abstract

The present invention discloses a method for the Diels-Alder reaction of a photocatalytic dienophile and a diene. Using water-soluble cadmium sulfide quantum dots modified with a hole scavenger as the photocatalyst, a mixed solution of water and hexafluoroisopropanol with different volume ratios as the solvent, and the dienophile and the diene as the substrates, it realizes the visible-light-driven oxidation of the dienophile and the cycloaddition reaction with the diene to construct a six-membered ring in a green solvent system. The photocatalyst of the present invention is synthesized using cheap and easily available raw materials by a simple and easy-to-operate experimental method. This photocatalytic reaction does not require the use of explosive and dangerous solvents, and the Diels-Alder reaction can be achieved under mild conditions. The products can be applied to the synthesis of drugs and the production of chemical value-added products.

Description

Technical Field

[0001] The present invention belongs to the technical field of photocatalytic organic synthesis, and particularly relates to a method for realizing cycloaddition by using quantum dots as photocatalysts to catalyze dienophiles and dienes to carry out Diels-Alder reactions. Background Art

[0002] Organic synthesis plays a crucial role in human production and life. Using organic synthesis, we can obtain drugs, food preservatives, pesticides, fertilizers, etc. that we need in daily life. However, traditional organic synthesis reactions not only involve multiple synthesis routes, but also usually require some toxic strong oxidants or reductants. In recent years, due to the global energy and environmental crises, photocatalytic reactions have received the favor of many researchers. Photocatalytic reactions can achieve one-step synthesis of organic compounds at room temperature without high temperature and high pressure, simplifying the cumbersome steps in traditional organic synthesis, while also reducing energy consumption. After the reaction, the photocatalyst is easy to remove, and the product is easy to separate, reducing the separation cost. In addition, visible light accounts for 44% of the solar spectrum (while ultraviolet light accounts for 3%), which provides motivation for the development of visible light-driven photocatalytic systems for the synthesis of value-added or complex molecules.

[0003] The Diels-Alder reaction is a key step in the synthesis of six-membered cycloaddition compounds, natural terpene compounds, and pharmaceutical intermediates, and many reactions can be used in the synthesis of natural substances. Therefore, organocatalytic Diels-Alder reactions have received increasing attention. Traditional organic synthesis methods for Diels-Alder reactions mostly require conditions such as high temperature, high pressure, and external oxidants, with low yields and accompanied by the generation of multiple by-products, bringing great difficulties to preparation and separation. Electro-catalytic Diels-Alder reactions have the advantages of being clean and efficient, but are quite limited from an energy perspective. Photocatalytic Diels-Alder reactions have received the favor of many scholars in recent years due to their advantages of being green, clean, and sustainable. Therefore, using photocatalysis to find suitable photocatalysts, reaction conditions, and substrates for Diels-Alder reactions to achieve cycloaddition has important academic significance.

[0004] Photocatalysis can be divided into homogeneous photocatalysis and heterogeneous photocatalysis. In recent years, metals such as Ru and Cr have played important roles in the field of homogeneous catalysis of the Diels-Alder reaction. For example, in 2011, the Yoon research group selected different types of dienophiles and dienes as substrates, used ruthenium(II) polypyridyl complexes as catalysts, and dichloromethane as a solvent. Under visible light irradiation, the radical cation Diels-Alder cycloaddition reaction of the dienophile could be promoted, with a yield of up to 98% (J. Am. Chem. Soc., 2011, 133, 48, 19350-19353). However, since Ru(II) is a precious metal, the cost of a series of complex photocatalysts centered on Ru(II) is relatively high, which limits its application. Therefore, it is very important to find low-cost and highly active photocatalysts that can replace precious metals. In 2017, Susan M. Stevenson et al. first reported that Cr(III) complexes could be used as photocatalysts for organic synthesis, successfully screening a series of Diels-Alder reaction products with electron mismatch. Nitromethane was used as a solvent, and after 6 h of ultraviolet light irradiation, the yield reached 80% (Chem. Sci., 2017, 8, 654-660). However, the Diels-Alder reaction in homogeneous catalysis brings certain difficulties to the separation of the catalyst and the product. To solve the problem that the catalyst and the product are in the same phase, researchers have conducted a large number of studies on the heterogeneous photocatalytic Diels-Alder reaction. For example, in 2017, Yubao Zhao et al. realized the Diels-Alder reaction for the first time with g-C3N4, a heterogeneous photocatalyst, under visible light irradiation in an atmospheric environment, with nitromethane as a solvent, and the photonic yield of this model reaction could reach 47% (Angew. Chem. Int. Ed., 2017, 56, 32, 9336-9340). In 2019, the Yohei Okada research group successfully catalyzed the Diels-Alder reaction using TiO2, with LiClO4 / nitromethane as a solvent. After 2 h of irradiation with 365 nm ultraviolet light, the yield was as high as 90% (Org. Lett., 2019, 21, 7, 2246-2250). The heterogeneous photocatalytic method makes it easy to separate the catalyst from the product, reducing the difficulty of purifying the target product. In addition, the characteristic that the heterogeneous photocatalyst can be reused after separation reduces the reaction cost, creating conditions for its industrial application.

[0005] In the reported heterogeneous photocatalytic Diels-Alder reaction methods, the solvents used are all nitromethane, and nitromethane is an explosive solvent. Therefore, further research on the heterogeneous photocatalytic Diels-Alder reaction and exploring the development of a heterogeneous photocatalytic Diels-Alder reaction that is green, economical, and simple and safe to operate has very important theoretical and practical research significance. Summary of the Invention

[0006] The object of the present invention is to provide a method for photocatalytic cycloaddition of a dienophile and a diene to achieve cycloaddition under mild conditions using inexpensive and readily available quantum dots as catalysts without the need for dangerous and explosive solvents.

[0007] For the above object, the technical solution adopted by the present invention is: adding a water-soluble cadmium sulfide quantum dot modified with a hole scavenger, a dienophile of formula I, and a diene of formula II into a transparent reactor containing a mixed solution of hexafluoroisopropanol and water, mixing evenly, introducing oxygen for 5 to 10 minutes, and irradiating the reactor with visible light having a wavelength of 400 to 780 nm to achieve the cycloaddition reaction of the dienophile and the diene to obtain a product of formula III;

[0008]

[0009] Among them, R represents any one of C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, dimethylamino, methylthio, ester group, and halogen atom; R1 and R2 each independently represent any one of a hydrogen atom, C1-C8 alkyl, carboxyl, phenyl, acetoxy, and C2-C8 alkenyl.

[0010] In the above method, the dienophile is specifically any one of trans-anethole, 1-methoxy-2-propen-1-benzene, 1-methoxy-3-1,3,5-trimethoxy-2-propen-1-benzene, 1,2,3-trimethoxy-5-propen-1-benzene, dimethylaniline-4-propen-1-aniline, 4-(propen-1-en-1-yl)phenol, 7-methoxy-2,2-dimethylbenzene, 1-methyl-4-propen-1-benzene, methyl(4-(propen-1-enyl)phenyl)sulfane, etc. The diene is specifically any one of butadiene, isoprene, 2,3-dimethyl-1,3-butadiene, ocimene, myrcene, 1-acetoxy-1,3-butadiene, 1-phenyl-1,3-butadiene, etc.

[0011] In the above method, it is preferred that the molar ratio of the dienophile to the diene is 1:1 to 1:5, the volume ratio of hexafluoroisopropanol to water in the mixed solution is preferably 1:1 to 5:1, and the mass ratio of the added water-soluble cadmium sulfide quantum dot modified with the hole scavenger to the molar amount of the dienophile is preferably 10 to 15 mg:1 mmol.

[0012] In the above method, the hole-trapping agent-modified water-soluble cadmium sulfide quantum dots are cadmium sulfide quantum dots modified by both a hole-trapping agent and 11-mercaptoundecanoic acid, with an average particle size of 2-7 nm. The hole-trapping agent is any one of 2-ethylthiophene, 2-chlorothiophene, thiophene, 10-methylphenothiazine, 3-methoxythiophene, and 5,10-dihydrophenazine, and the doping amount of the hole-trapping agent is 10%-20% of the molar amount of cadmium sulfide. The hole-trapping agent-modified water-soluble cadmium sulfide quantum dots are synthesized by referring to the method of 3-mercaptopropionic acid-modified cadmium sulfide quantum dots (MPA-CdS QDs) reported in Patent CN111939987A (Wang Hongyan, Hu Rong, Xie Weihua. A photocatalytic material for photocatalytic reduction of CO2 to produce syngas and its method). The specific synthesis steps are as follows:

[0013] Step 1: In an N2 atmosphere, dissolve CdCl2 in distilled water, then add 11-mercaptoundecanoic acid, adjust the pH to 7 with 1 mol / L NaOH aqueous solution. Wait until the solution changes from colorless to a white turbid liquid and then to a colorless transparent solution, and then add 0.1 mol / L Na2S aqueous solution to the system. Reflux at 100 °C for 4 h. After the reaction is completed, a clear orange-yellow solution is obtained. Spin out the excess water, add isopropanol, centrifuge, and repeat twice to obtain an orange-yellow solid. Dry at 60 °C to obtain 11-mercaptoundecanoic acid-modified cadmium sulfide quantum dots; among them, the addition amount of 11-mercaptoundecanoic acid is 2-2.5 times the molar amount of CdCl2, and the addition amount of Na2S is 0.8-1.2 times the molar amount of CdCl2;

[0014] Step 2: At room temperature, dissolve the 11-mercaptoundecanoic acid-modified cadmium sulfide quantum dots in deionized water. After complete dissolution, add absolute ethanol to fully disperse the 11-mercaptoundecanoic acid-modified cadmium sulfide quantum dots, and then add the hole-trapping agent. Stir for 1 h under dark conditions. After the reaction is completed, a clear orange-yellow solution is obtained. Wash with isopropanol by centrifugation and repeat twice to obtain an orange-yellow solid. Dry at 60 °C to obtain the hole-trapping agent-modified water-soluble cadmium sulfide quantum dots; among them, the addition amount of the hole-trapping agent is 10%-20% of the molar amount of CdCl2 in Step 1. Preferably, the addition amount of the absolute ethanol is 3-6 times the volume of deionized water.

[0015] In the above method, it is preferred to irradiate the reactor with visible light having a wavelength of 400-780 nm and react at room temperature for 4-12 hours.

[0016] The beneficial effects of the present invention are as follows:

[0017] The present invention uses water-soluble cadmium sulfide quantum dots modified with hole-trapping agents as photocatalysts, and under visible light irradiation, the Diels-Alder reaction between dienophiles and dienes is realized to achieve cycloaddition. The present invention realizes the Diels-Alder reaction between dienophiles and dienes under photocatalytic conditions, uses solar energy, a clean energy source, to replace thermal reactions. The reaction conditions are simple and easy to operate, and a green and safe solvent, a mixed solution of water and hexafluoroisopropanol, is used to replace nitromethane used as a solvent in currently reported relevant literature. A good yield can be achieved with a short irradiation time. Each component used in this photocatalytic organic small molecule system is inexpensive and easily available, the photocatalytic conversion efficiency is high, the solvent is mild and safe, and the catalyst is easily separated from the product, and it can be applied to actual production. Description of the Drawings

[0018] Figure 1 is the 1H NMR spectrum of 4'-methoxy-2,4-dimethyl-1,2,3,6-tetrahydro-1,1'-biphenyl in Example 1.

[0019] Figure 2 is the 13C NMR spectrum of 4'-methoxy-2,4-dimethyl-1,2,3,6-tetrahydro-1,1'-biphenyl in Example 1.

[0020] Figure 3 is the 1H NMR spectrum of 4'-methoxy-2,4,5-trimethyl-1,2,3,6-tetrahydro-1,1'-biphenyl in Example 2.

[0021] Figure 4 is the 13C NMR spectrum of 4'-methoxy-2,4,5-trimethyl-1,2,3,6-tetrahydro-1,1'-biphenyl in Example 2.

[0022] Figure 5 is the gas chromatography-mass spectrometry data (GC-MS) of 4'-methoxy-2-methyl-4-(4-methyl-3-penten-1-yl)-1,2,3,6-tetrahydro-1,1'-biphenyl in Example 3.

[0023] Figure 6 is the gas chromatography-mass spectrometry data (GC-MS) of 4'-methoxy-2,5-dimethyl-6-(3-methylbut-2-en-1-yl)-1,2,3,6-tetrahydro-1,1'-biphenyl in Example 4.

[0024] Figure 7 is the gas chromatography-mass spectrometry data (GC-MS) of 2',4',6'-trimethoxy-2,4,5-trimethyl-1,2,3,6-tetrahydro-1,1'-biphenyl in Example 5. Detailed Embodiments

[0025] The present invention is further described in detail below in conjunction with the accompanying drawings and specific embodiments, but the protection scope of the present invention is not limited to these embodiments.

[0026] The preparation method of the MUA&ETP CdS photocatalyst used in the following examples is:

[0027] Step 1: In a N2 atmosphere, CdCl2·H2O (114.2 mg, 0.57 mmol) was dissolved in 100 mL of distilled water, and then 11-mercaptoundecanoic acid (MUA, 500 μL, 11.5 mmol) was injected, and then the pH was adjusted to 7 with 1 mol / L NaOH. During the reaction, the solution changed from colorless to white turbid liquid, and finally to a colorless transparent solution. Finally, 5 mL of 0.1 mol / L Na2S aqueous solution was added to the system and refluxed at 100 ° C for 4 h. After the reaction was completed, a clear orange-yellow solution was obtained, and the excess water was spun out, and a large amount of isopropanol was added, washed and centrifuged, and repeated twice to obtain orange-yellow solid 11-mercaptoundecanoic acid modified cadmium sulfide quantum dots, i.e., water-soluble cadmium sulfide quantum dots.

[0028] Step 2: Dissolve the prepared water-soluble cadmium sulfide quantum dots (60 mg) in 4 mL of deionized water at room temperature. After fully dissolved, add 16 mL of anhydrous ethanol to fully disperse the quantum dots. Finally, add the hole capture agent 2-ethylthiophene (ETP, 10 mg, 0.09 mmol) and stir for 1 hour in the dark. After the reaction is completed, a clear orange-yellow solution is obtained. Centrifugal washing with isopropanol is repeated twice to obtain an orange-yellow solid. Dry at 60°C to obtain water-soluble cadmium sulfide quantum dots modified with hole capture agents with an average particle size of 4 nm, which are recorded as MUA&ETP CdS photocatalysts.

[0029] Example 1

[0030]

[0031] 6 mg of MUA&ETP CdS photocatalyst with an average particle size of 4 nm, 76 μL (0.5 mmol) of trans-anethole, 150 μL (1.5 mmol) of isoprene, and 5 mL of a mixed solution of hexafluoroisopropanol and deionized water in a volume ratio of 3:2 were added to a pyrex test tube, mixed evenly, oxygen was introduced for 5 to 10 minutes until saturation and the air in the system was removed, the system was sealed, and an LED lamp with a wavelength of 420 nm was used for irradiation at room temperature for 6 hours to obtain 4'-methoxy-2,4-dimethyl-1,2,3,6-tetrahydro-1,1'-biphenyl with a yield of 84%. The structural characterization data are as follows: 11H NMR (400 MHz, CDCl3): δ 7.14 - 7.06 (m, 2H), 6.91 - 6.81 (m, 2H), 5.51 - 5.38 (m, 1H), 3.80 (s, 3H), 2.30 (td, J = 10.6, 5.3 Hz, 1H), 2.21 - 2.11 (m, 2H), 1.97 - 1.85 (m, 1H), 1.84 - 1.75 (m, 1H), 1.74 - 1.62 (m, 3H), 0.71 (d, J = 6.3 Hz, 3H), see Figure 1 ; 13 13C NMR (400 MHz, CDCl3): δ 157.79, 138.20, 133.82, 128.51, 120.93, 113.71, 55.22, 46.97, 39.87, 35.29, 33.98, 23.41, 20.26, see Figure 2 。

[0032] Example 2

[0033]

[0034] In this example, 170 μL (1.5 mmol) of 2,3 - dimethyl - 1,3 - butadiene was used to replace isoprene in Example 1, and other steps were the same as those in Example 1. 4'-Methoxy - 2,4,5 - trimethyl - 1,2,3,6 - tetrahydro - 1,1'-biphenyl was obtained with a yield of 81%. The structure characterization data are as follows: 1 1H NMR (400 MHz, Chloroform - d): δ 7.10 (dd, J = 10.0, 3.7 Hz, 2H), 6.93 - 6.77 (m, 2H), 3.81 (s, 3H), 2.43 - 2.25 (m, 1H), 2.26 - 1.98 (m, 4H), 1.95 - 1.77 (m, 2H), 0.71 (d, J = 5.6 Hz, 3H), see Figure 3 ; 13 13C NMR (400 MHz, CDCl3): δ 206.94, 157.76, 138.21, 128.46, 125.47, 125.32, 113.70, 55.22, 47.83, 41.83, 41.65, 34.27, 30.92, 20.00, 18.72, 18.64, see Figure 4 。

[0035] Example 3

[0036]

[0037] In this example, 170 μL (1.5 mmol) of myrcene was used to replace isoprene in Example 1, and the other steps were the same as those in Example 1 to obtain 4'-methoxy-2-methyl-4-(4-methylpent-3-en-1-yl)-1,2,3,6-tetrahydro-1,1'-biphenyl with a yield of 75%. The structural characterization data are shown in Figure 5 , where a) the crude product, with an elution time of 6.105 - 7.490 min, is the raw material trans-anethole with a relative molecular mass of 148; b) the crude product, with an elution time of 12.695 - 13.245 min, is the characteristic peak of the product with a relative molecular mass of 284; c) the purified product, with an elution time of 12.763 - 13.335 min, is the characteristic peak of the product with a relative molecular mass of 284.

[0038] Example 4

[0039]

[0040] In this example, 250 μL (1.5 mmol) of ocimene was used to replace isoprene in Example 1, and the other steps were the same as those in Example 1 to obtain 4'-methoxy-2,5-dimethyl-6-(3-methylbut-2-en-1-yl)-1,2,3,6-tetrahydro-1,1'-biphenyl with a yield of 63%. The structural characterization data are shown in Figure 6 , where a) the crude product, with an elution time of 5.896 - 6.731 min, is the raw material trans-anethole with a relative molecular mass of 148; b) the crude product, with an elution time of 11.834 - 12.341 min, is the characteristic peak of the product with a relative molecular mass of 284; c - d) the purified product, with elution times of 11.373 - 11.815 min and 11.945 - 12.206 min, are the characteristic peaks of the cis - trans structural products with a relative molecular mass of 284.

[0041] Example 5

[0042]

[0043] In this example, 104 mg (0.5 mmol) of 1,3,5-trimethoxy-2-propen-1-benzene was used to replace trans-anethole in Example 1, and the other steps were the same as those in Example 1 to obtain 2',4',6'-trimethoxy-2,4,5-trimethyl-1,2,3,6-tetrahydro-1,1'-biphenyl with a yield of 51%. The structural characterization data are shown in Figure 7, where a) the crude product, with an elution time of 8.745 - 9.295 min, is the raw material 1,3,5-trimethoxy-2-propen-1-benzene, with a relative molecular mass of 208; b) the crude product, with an elution time of 12.280 - 12.735 min, is the characteristic peak of the product, with a relative molecular mass of 276; c) the purified product, with an elution time of 11.763 - 11.986 min, is the characteristic peak of the product, with a relative molecular mass of 276.

Claims

1. A method for the Diels - Alder reaction of a photocatalytic dienophile with a diene, characterized in that: The water-soluble cadmium sulfide quantum dots modified with a hole-trapping agent, the dienophile of formula I, and the diene of formula II are added to a transparent reactor containing a mixed solution of hexafluoroisopropanol and water, mixed evenly, oxygen is introduced for 5-10 minutes, and the reactor is irradiated with visible light with a wavelength of 400-780 nm to achieve the cycloaddition reaction between the dienophile and the diene, and the product of formula III is obtained; wherein, R represents any one of C1-C3 alkyl, C1-C3 alkoxy, hydroxyl, dimethylamino, methylthio, and halogen atom; R1 and R2 each independently represent any one of a hydrogen atom, C1-C8 alkyl, carboxyl, phenyl, and acetoxy; or the diene of formula II is ocimene or myrcene; The water-soluble cadmium sulfide quantum dots modified with the hole-trapping agent are cadmium sulfide quantum dots modified with both a hole-trapping agent and 11-mercaptoundecanoic acid. Among them, the hole-trapping agent is any one of 2-ethylthiophene, 2-chlorothiophene, thiophene, and 3-methoxythiophene, and the doping amount of the hole-trapping agent is 10%-20% of the molar amount of cadmium sulfide; The water-soluble cadmium sulfide quantum dots modified with the hole-trapping agent are prepared by the following method: Step 1: In an N2 atmosphere, CdCl2 is dissolved in distilled water, then 11-mercaptoundecanoic acid is added, and the pH is adjusted to 7 with 1 mol / L NaOH aqueous solution. After the solution changes from colorless to a white turbid liquid and then to a colorless transparent solution, a 0.1 mol / L Na2S aqueous solution is added to the system, and the mixture is refluxed at 100 °C for 4 h. After the reaction is completed, a clear orange-yellow solution is obtained. The excess water is spun out, isopropanol is added, and centrifugation is carried out twice. An orange-yellow solid is obtained and dried at 60 °C to obtain 11-mercaptoundecanoic acid-modified cadmium sulfide quantum dots; among them, the addition amount of 11-mercaptoundecanoic acid is 2-2.5 times the molar amount of CdCl2, and the addition amount of Na2S is 0.8-1.2 times the molar amount of CdCl2; Step 2: At room temperature, the 11-mercaptoundecanoic acid-modified cadmium sulfide quantum dots are dissolved in deionized water. After complete dissolution, anhydrous ethanol is added to disperse the 11-mercaptoundecanoic acid-modified cadmium sulfide quantum dots sufficiently. Then, a hole-trapping agent is added, and stirring is carried out for 1 h under light-shielded conditions. After the reaction is completed, a clear orange-yellow solution is obtained. It is centrifuged and washed with isopropanol twice to obtain an orange-yellow solid, which is dried at 60 °C to obtain the water-soluble cadmium sulfide quantum dots modified with the hole-trapping agent; among them, the addition amount of the hole-trapping agent is 10%-20% of the molar amount of CdCl2 in Step 1.

2. The method for the Diels-Alder reaction of a photocatalytic dienophile and a diene according to claim 1, characterized in that: The diene is any one of butadiene, isoprene, 2,3-dimethyl-1,3-butadiene, 1-acetoxy-1,3-butadiene, and 1-phenyl-1,3-butadiene.

3. The method for the Diels - Alder reaction of a photocatalytic dienophile and a diene according to claim 1 or 2, characterized in that: The molar ratio of the dienophile to the diene is 1:1 to 1:

5.

4. The method for the Diels-Alder reaction of a photocatalytic dienophile and a diene according to claim 1 or 2, characterized in that: The volume ratio of hexafluoroisopropanol to water in the mixed solution is 1:1 to 5:

1.

5. The method for the Diels - Alder reaction of a photocatalytic dienophile with a diene according to claim 1 or 2, characterized in that: The average particle size of the water-soluble cadmium sulfide quantum dots modified with the hole-trapping agent is 2-7 nm, and the mass ratio of its addition to the molar amount of the dienophile is 10-15 mg:1 mmol.

6. The method for carrying out the Diels - Alder reaction between a photocatalytic dienophile and a diene according to claim 1, characterized in that: In Step 2, the addition amount of the absolute ethanol is 3 to 6 times the volume of the deionized water.

7. The method for Diels - Alder reaction of a photocatalytic dienophile and a diene according to claim 1 or 2, characterized in that: Irradiate the reactor with visible light having a wavelength of 400 to 780 nm, and carry out the reaction at room temperature for 4 to 12 hours.

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