Method for synthesizing aromatic hydrocarbon compound by thermodynamically driving solid Suzuki-Miyaua coupling reaction

Abstract

The invention discloses a method for synthesizing an aromatic hydrocarbon compound by using thermodynamics to drive a solid Suzuki-Miyaua coupling reaction, and relates to the field of organic synthesis.The method comprises the steps that 5% Pd / C, K2CO3, a solid benzene substituted boric acid compound and solid halogenated aromatic hydrocarbon are heated to be not lower than 80 DEG C for a reaction, stirring is not needed, and the aromatic hydrocarbon compound can be synthesized, the structural formula of the benzene substituted boric acid compound is # imgabs0 # R1 represents a methoxy group; and the structural formula of the aryl halide is # imgabs1 # R2 represents methoxy, methyl or halogen substitution. According to the aromatic hydrocarbon solid-state synthesis method, no organic solvent needs to be added, the problems of serious environmental pollution, high cost budget, large potential safety hazards and the like caused by use of the solvent can be avoided, no ligand needs to be added, the cost and the product purification difficulty are reduced, and the method is suitable for industrial production. And the environmental burden caused by ligand addition is avoided.

Description

Technical Field

[0001] The present invention relates to the field of organic synthesis, and specifically to a method for synthesizing aromatic hydrocarbon compounds by using a thermodynamically driven solid-state Suzuki-Miyarua coupling reaction. Background Art

[0002] With the deepening of the concept of green chemistry, the development of efficient, environmentally friendly and economical organic synthesis methods has become one of the important goals of the modern chemical industry. As an important class of organic compounds, aromatic hydrocarbons have a wide range of applications in the fields of medicine, pesticides, spices, materials science, etc. Traditional methods for synthesizing aromatic hydrocarbons often rely on transition metal-catalyzed cross-coupling reactions. Among them, the Suzuki-Miyaura coupling reaction is favored due to its mild reaction conditions, good functional group tolerance, and the use of relatively non-toxic arylboronic acids as nucleophiles. However, this reaction usually needs to be carried out in solution, and in order to obtain a high yield, it is often necessary to add an excessive amount of catalyst and ligand, which not only increases the cost but also brings an environmental burden.

[0003] In recent years, with the pursuit of sustainable development, people have begun to explore how to further improve the efficiency and environmental friendliness of the Suzuki-Miyaura coupling reaction by changing the reaction medium or conditions. In this context, research on solid-state reactions has gradually attracted people's attention, and the development of a solid-state Suzuki-Miyarua coupling reaction method has important practical significance. However, its development is still very scarce. In fact, most of the reported studies are limited to mechanochemical means, such as mechanical ball mills, vibratory ball mills, planetary ball mills, etc., to generate solid aromatic amines. And in order to obtain a high yield, it is often necessary to add an excessive amount of catalyst and ligand, which not only increases the cost but also brings an environmental burden.

[0004] Reference: Research on Solid-State Suzuki Coupling Reaction Promoted by Magnetic Grinding.

[0005] The reference discloses a solvent-free Suzuki-Miyaura coupling reaction using an electromagnetic grinder as an experimental instrument, as well as a new method for preparing Schiff base compounds under solvent-free conditions. Although the reference has completed a solid-state Suzuki coupling reaction and is relatively environmentally friendly, the magnetic grinding in the solid-state Suzuki coupling reaction process and the ball milling of the prior art both belong to mechanochemical means, and the coupling reaction of magnetic grinding still requires the addition of ligands. Moreover, the solid-state Suzuki coupling reaction disclosed in the reference is a method for synthesizing Schiff base compounds, and there are few reports in the prior art on the technical scheme of synthesizing aromatic hydrocarbons by using a solid-state Suzuki-Miyarua coupling reaction. Summary of the Invention

[0006] The present invention aims to provide a method for synthesizing aromatic hydrocarbon compounds by using a thermodynamically driven solid-state Suzuki-Miyarua coupling reaction, so as to spontaneously realize the synthesis of aromatic hydrocarbons through the solid-state Suzuki-Miyarua coupling reaction without introducing mechanochemistry and without solvents.

[0007] To achieve the above object, the specific solution adopted by the present invention is as follows: A method for synthesizing aromatic hydrocarbon compounds by using a thermodynamically driven solid-state Suzuki-Miyarua coupling reaction, heating 5% Pd / C, K 2 CO 3 , a solid benzene-substituted boronic acid compound, and a solid haloarene to not less than 80 °C and reacting to synthesize aromatic hydrocarbon compounds. Among them, the structural formula of the benzene-substituted boronic acid compound is R 1 represents a methoxy group; the structural formula of the haloarene is R 2 represents a methoxy group, a methyl group, or a halogen substitution.

[0008] As a further optimization of the above technical solution, first mix 5% Pd / C, K 2 CO 3 , the solid benzene-substituted boronic acid compound, and the solid haloarene evenly, and then heat to not less than 80 °C and react.

[0009] As a further optimization of the above technical solution, heat 5% Pd / C, K 2 CO 3 , the solid benzene-substituted boronic acid compound, and the solid haloarene to 80 - 150 °C and react.

[0010] As a further optimization of the above technical solution, the reaction time is 4 h.

[0011] As a further optimization of the above technical solution, the molar ratio of the addition amounts of the solid benzene-substituted boronic acid compound and the solid haloarene is 1:2.

[0012] As a further optimization of the above technical solution, the molar ratio of the addition amounts of the solid benzene-substituted boronic acid and 5% Pd / C is 1:0.0001 - 0.1.

[0013] As a further optimization of the above technical solution, the molar ratio of the addition amounts of the solid benzene-substituted boronic acid and 5% Pd / C is 1:0.02.

[0014] As a further optimization of the above technical solution, the mass ratio of the addition amounts of 5% Pd / C and K 2 CO 3 is 1:1.

[0015] As a further optimization of the above technical solution, the product after the reaction is purified by column chromatography to obtain aromatic hydrocarbon compounds.

[0016] An aromatic hydrocarbon compound synthesized by the above method.

[0017] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0018] The present invention innovatively proposes a method for synthesizing aromatic hydrocarbon compounds by using thermodynamics-driven solid-state Suzuki-Miyaura coupling reaction. The Suzuki-Miyaura coupling reaction between solid phenyl-substituted boronic acid compounds and solid haloarenes is driven by thermodynamics principles, and the spontaneous synthesis of aromatic hydrocarbons is achieved without solvents, ligands, and the introduction of mechanochemistry. In the aromatic hydrocarbon synthesis method of the present invention, no organic solvents need to be added, which can avoid problems such as serious environmental pollution, high cost budget, and great safety hazards caused by the use of solvents. Moreover, no ligands need to be added in the aromatic hydrocarbon synthesis method of the present invention, which reduces the cost and avoids the environmental burden caused by the addition of ligands. Description of the Drawings

[0019] Figure 1 1H NMR spectrum of the aromatic hydrocarbon synthesized in Example 2 1 H NMR spectrum;

[0020] Figure 2 13C NMR spectrum of the aromatic hydrocarbon synthesized in Example 2 13 13C NMR spectrum. Detailed Embodiments

[0021] The technical solution of the present invention will be further elaborated in detail below in combination with specific embodiments. For parts not detailedly recorded and disclosed in the following embodiments of the present invention, they should all be understood as the prior art known or should be known to those skilled in the art.

[0022] The present invention discloses a method for synthesizing aromatic hydrocarbon compounds by using thermodynamics-driven solid-state Suzuki-Miyaura coupling reaction. In the presence of 5% Pd / C and K 2 CO 3 heating the solid phenyl-substituted boronic acid compound and the solid haloarene to 80 - 150 °C for 4 hours, without vibration and stirring during the reaction process. When the reaction is completely detected by HPLC, the aromatic hydrocarbon compounds can be obtained through column chromatography purification. Among them, the structural formula of the phenyl-substituted boronic acid compound is R 1 represents methoxy; the structural formula of the haloarene is R 2 represents methoxy, methyl or halogen substitution.

[0023] It should be noted that 5% Pd / C is a palladium-carbon catalyst in which the mass fraction of palladium (Pd) accounts for 5% of the total mass of the catalyst. Among them, palladium is the active component of the catalytic reaction, and activated carbon (C) serves as the carrier, providing a high specific surface area and a good dispersion environment for palladium, which helps to improve the activity and stability of the catalyst.

[0024] The reaction formula for synthesizing aromatic hydrocarbon compounds by the thermodynamically driven solid-state Suzuki-Miyarua coupling reaction in the present invention is as follows:

[0025]

[0026] The present invention proposes a new method for spontaneously synthesizing aromatic hydrocarbons by the thermodynamically driven solid-state Suzuki-Miyarua coupling reaction under solvent-free and ligand-free conditions, without introducing mechanochemistry. This method not only significantly reduces the requirements for reaction conditions, but also greatly improves the selectivity and yield of the reaction, providing new ideas and technical means for the green synthesis of aromatic hydrocarbon compounds. In addition, this technology is also expected to be applied to other types of organic synthesis reactions, with broad development prospects and practical application value.

[0027] Example 1

[0028] Add 0.1 mmol of compound I-01, 0.2 mmol of compound II-01, 5 mg of K 2 CO 3 , 5 mg of commercial 5% Pd / C into a 10 mL reaction flask, and then react at 100 °C. The reaction process is detected by HPLC. After 4 hours, the reaction yield is 99%. Then, the target compound III-01, a white solid, is obtained through column chromatography purification.

[0029] Among them, the structural formula of compound I-01 is as follows:

[0030]

[0031] The structural formula of II-01 is as follows:

[0032]

[0033] The structural formula of compound III-01 is as follows:

[0034] The obtained product was analyzed, and the analysis data was: White solid, 99% yield. 1 H NMR (500 MHz, CDCl 3)δ7.55–7.53(m,2H),7.35–7.33(m,2H),7.15–7.13(m,2H),6.98–6.95(m,2H),3.94(s,3H),2.44(s,3H). 13 C NMR (126 MHz, CDCl 3 )δ159.48,137.78,133.11,130.61,130.12,129.51,127.79,114.80,55.78,27.33.

[0035] Example 2

[0036] Add 0.1 mmol of compound Ⅰ-02, 0.2 mmol of compound Ⅱ-02, and 5 mg of K 2 CO 3 , 5 mg of commercial 5% Pd / C, then reacted at 130°C, HPLC detected the reaction progress, and the reaction yield was 96% after 4 hours. Then, the target compound III-02 was purified by column chromatography as a white solid.

[0037] Among them, the structural formula of compound I-02 is as follows:

[0038]

[0039] The structural formula of compound II-02 is as follows

[0040]

[0041] The structural formula of compound III-02 is as follows:

[0042]

[0043] The obtained product was analyzed, and the analytical data were: White solid, 96% yield. 1 H NMR (500MHz, DMSO) δ7.39 (d, J = 8.7Hz, 2H), 6.87 (d, J = 8.7Hz, 2H), 3.75 (s, 3H). 13 C NMR (126MHz, DMSO) δ158.73,133.51,127.77,114.20,55.37.

[0044] Figure 1 , Figure 2 of 1 H-NMR and 13 C NMR spectroscopy was able to elucidate the structure of product III-02.

[0045] Example 3

[0046] Add 0.1 mmol of compound Ⅰ-03, 0.2 mmol of compound Ⅱ-03, and 5 mg of K 2 CO 3 , 5 mg of commercial 5% Pd / C into a 10 mL reaction flask, mix them evenly, and then react at 100 °C. Monitor the reaction progress by HPLC. After 4 hours, the reaction yield is 95%. The target compound Ⅲ-01, a white solid, is obtained after purification by column chromatography.

[0047] Among them, the structural formula of compound Ⅰ-03 is as follows:

[0048]

[0049] The structural formula of compound Ⅱ-03 is as follows:

[0050]

[0051] The structural formula of compound Ⅲ-03 is as follows:

[0052]

[0053] The obtained product was analyzed, and the analysis data were: White solid, 95% yield, 1 1H NMR (500 MHz, CDCl 3 ) δ 7.53–7.36 (m, 4H), 7.30 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 3.77 (s, 3H). 13 13C NMR (126 MHz, CDCl 3 ) δ 159.39, 139.29, 132.69, 132.52, 128.86, 128.00, 127.98, 114.33, 55.39.

[0054] Example 4

[0055] The synthesis process of Example 4 is basically the same as that of Example 1, except that in this Example 4, the reaction temperature is adjusted to 80 °C, and the reaction results are as follows:

[0056] After the reaction in Example 4 ended, after calculation, the final yield was 97%.

[0057] Example 5

[0058] The synthesis process of Example 5 is basically the same as that of Example 1, except that in this Example 5, the reaction temperature is adjusted to 150 °C, and the reaction results are as follows:

[0059] After the reaction in Example 5 ended, the final yield was calculated to be 96%.

[0060] Comparative Example 1

[0061] The synthesis process of Comparative Example 1 was basically the same as that of Example 1, except that in this Comparative Example 1, the 5% Pd / C catalyst in Example 1 was replaced with 10% Pd / C. The reaction results are as follows:

[0062] After the reaction in Comparative Example 1 ended, the final yield was calculated to be 8%.

[0063] Comparative Example 2

[0064] The synthesis process of Comparative Example 2 was basically the same as that of Example 1, except that in this Comparative Example 2, the 5% Pd / C catalyst in Example 1 was replaced with Pd(PPh 3 ) 4 , and the reaction results are as follows:

[0065] After the reaction in Comparative Example 2 ended, the final yield was calculated to be 28%.

[0066] Comparative Example 3

[0067] The synthesis process of Comparative Example 3 was basically the same as that of Example 1, except that in this Comparative Example 3, the 5% Pd / C catalyst in Example 1 was replaced with Pd(OAc) 2 , and the reaction results are as follows:

[0068] After the reaction in Comparative Example 3 ended, the final yield was calculated to be 25%.

[0069] Comparative Example 4

[0070] The synthesis process of Comparative Example 4 was basically the same as that of Example 1, except that in this Comparative Example 4, the reaction temperature was adjusted to 0 °C. The reaction results are as follows:

[0071] After the reaction in Comparative Example 4 ended, the final yield was calculated to be 0%.

[0072] Comparative Example 5

[0073] The synthesis process of Comparative Example 5 was basically the same as that of Example 1, except that in this Comparative Example 5, the reaction temperature was adjusted to 25 °C. The reaction results are as follows:

[0074] After the reaction in Comparative Example 5 ended, the final yield was calculated to be 0%.

[0075] Comparative Example 6

[0076] The synthesis process of Comparative Example 6 was basically the same as that of Example 1, except that in this Comparative Example 6, the reaction temperature was adjusted to 70 °C. The reaction results are as follows:

[0077] After the reaction of Comparative Example 6 ended, after calculation, the final yield was 0%.

[0078] Comparative Example 7

[0079] The synthesis process of Comparative Example 7 was basically the same as that of Example 1, except that in this Comparative Example 7, the reaction temperature was adjusted to 180 °C, and the reaction results were as follows:

[0080] After the reaction of Comparative Example 7 ended, after calculation, the final yield was 39%.

[0081] Comparative Example 8

[0082] This comparative example was basically the same as Example 1, except that in this Comparative Example 8, 0.1 mmol of Compound I-01, 0.2 mmol of Compound II-01, 5 mg of K 2 CO 3 , 5 mg of commercial 5% Pd / C and 2.5 mg of triphenylphosphine ligand were added to a 10 mL reaction flask, and the reaction results were as follows:

[0083] After the reaction of Comparative Example 8 ended, after calculation, the final yield was 15%.

[0084] Result analysis:

[0085] Combining the reaction results of Example 1 and Comparative Examples 1-3, it can be seen that the palladium catalyst is crucial for the spontaneous synthesis of aromatic hydrocarbons in the thermodynamically driven solid-state Suzuki-Miyarua coupling reaction. In Example 1, when a 5% Pd / C catalyst was selected, the final yield could reach 99%, which was much higher than the final yields of Comparative Examples 1-3. Compared with Pd(OAc) 2 , loading palladium onto carbon increased the catalytic specific surface area of the catalyst and could significantly improve the yield of this reaction. The catalytic results of 10% Pd / C further verified this conclusion.

[0086] Combining the reaction results of Example 1 and Comparative Examples 4-7, it can be seen that the reaction temperature is crucial for the spontaneous synthesis of aromatic hydrocarbons in the thermodynamically driven solid-state Suzuki-Miyarua coupling reaction. This data indicates that in the process of synthesizing aromatic hydrocarbons by the thermodynamically driven solid-state Suzuki-Miyarua coupling reaction, there is a critical thermodynamic level, above which a higher yield can be achieved.

[0087] As is well known, the introduction of organic phosphine ligands usually can greatly increase the yield of the Suzuki-Miyaura coupling reaction in solution, which is exactly opposite to the conclusion of the spontaneous synthesis of aromatic hydrocarbons by the thermodynamically driven solid-state Suzuki-Miyarua coupling reaction of the present invention. An organic phosphine ligand was added to the raw materials of Comparative Example 8 of the present invention, but the final yield after the reaction was only 15%. It may be that the presence of the organic phosphine ligand hindered the formation of the liquid eutectic in the solid-state reaction and reduced the yield of the reaction. No ligand was added during the synthesis reaction of the present invention. By selecting a suitable catalyst and reaction temperature, the final yield can reach more than 95%. It is speculated that because the active centers of the 5% Pd / C catalyst are numerous, heating under special conditions increases the probability of reaction collisions, and the reaction can be accelerated without a ligand.

[0088] The specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art can make various deformations or modifications within the scope of the claims, which does not affect the essence of the present invention.

Claims

1. A method for synthesizing aromatic hydrocarbon compounds by thermodynamically driven solid-state Suzuki-Miyarua coupling reaction, characterized in that: 5% Pd / C, K2CO3, solid benzene-substituted boronic acid compound and solid halogenated aromatic hydrocarbon are heated to not less than 80°C for reaction to synthesize aromatic hydrocarbon compounds, wherein the structural formula of the benzene-substituted boronic acid compound is R1 represents a methoxy group; the structural formula of the halogenated aromatic hydrocarbon is R2 represents methoxy, methyl or halogen substitution.

2. A method for synthesizing aromatic hydrocarbon compounds by thermodynamically driven solid-state Suzuki-Miyarua coupling reaction according to claim 1, characterized in that: First, 5% Pd / C, K2CO3, solid benzene-substituted boric acid compound and solid halogenated aromatic hydrocarbon are uniformly mixed, and then heated to not less than 80°C for reaction.

3. A method for synthesizing aromatic hydrocarbon compounds by thermodynamically driven solid-state Suzuki-Miyarua coupling reaction according to claim 1, characterized in that: 5% Pd / C, K2CO3, solid benzene-substituted boric acid compound and solid halogenated aromatic hydrocarbon are heated to 80-150°C for reaction.

4. A method for synthesizing aromatic hydrocarbon compounds by thermodynamically driven solid-state Suzuki-Miyarua coupling reaction according to claim 1, characterized in that: The reaction time is 4h.

5. The method for synthesizing aromatic hydrocarbon compounds by thermodynamically driven solid-state Suzuki-Miyarua coupling reaction according to claim 1, characterized in that: The molar ratio of the added amount of the solid benzene-substituted boric acid compound and the solid halogenated aromatic hydrocarbon is 1:

2.

6. A method for synthesizing aromatic hydrocarbon compounds by thermodynamically driven solid-state Suzuki-Miyarua coupling reaction according to claim 1, characterized in that: The molar ratio of the added amount of solid benzene-substituted boric acid to 5% Pd / C is 1:0.0001-0.

1.

7. A method for synthesizing aromatic hydrocarbon compounds by thermodynamically driven solid-state Suzuki-Miyarua coupling reaction according to claim 1, characterized in that: The molar ratio of the added amount of solid benzene-substituted boric acid to 5% Pd / C is 1:0.

02.

8. The method for synthesizing aromatic hydrocarbon compounds by thermodynamically driven solid-state Suzuki-Miyarua coupling reaction according to claim 1, characterized in that: The mass ratio of the added amount of 5% Pd / C and K2CO3 is 1:

1.

9. The method for synthesizing aromatic hydrocarbon compounds by thermodynamically driven solid-state Suzuki-Miyarua coupling reaction according to claim 1, characterized in that: The product after the reaction is purified by column chromatography to obtain aromatic hydrocarbon compounds.

10. An aromatic hydrocarbon compound synthesized by the method according to any one of claims 1 to 9.

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