Method for green synthesis of aromatic ketone and biphenyl based on quartz sand solid phase system

Abstract

The invention discloses a method for green synthesis of aromatic ketone and biphenyl based on a quartz sand solid phase system, relates to the technical field of organic synthesis, and aims to solve the technical problem of lack of a solvent-free method for synthesis of aromatic ketone and biphenyl in the prior art. The method for green synthesis of aromatic ketone and biphenyl based on the quartz sand solid-phase system comprises the following steps: uniformly mixing anhydride, aryl or alkyl boric acid, a catalyst, alkali and a solid-phase system medium to obtain a reaction mixture; in a nitrogen atmosphere, heating the reaction mixture to 110 DEG C for reaction, and after the reaction is completed, performing post-treatment to obtain diarylketone or alkylaryl ketone, in an air atmosphere, heating the reaction mixture to 150 DEG C for reaction to obtain biphenyl; a reaction equation is as follows: # imgabs0 #, a substituent R1 is at least one of hydrogen, alkyl, alkoxy and halogen, R2 is alkyl, and a catalyst is a palladium catalyst.

Description

Technical Field

[0001] The present application relates to the technical field of organic synthesis, and in particular to a method for green synthesis of aromatic ketones and biphenyls based on a quartz sand solid phase system. Background Art

[0002] Benzophenone, also known as benzophenone, is the simplest diaryl ketone. It is a colorless prismatic crystal at room temperature with a sweet and rose scent. Its melting point is 47℃-49℃, its relative density is 1.1146, and its refractive index is 1.6077. It is soluble in organic solvents and monomers such as ethanol, ether, and chloroform, but insoluble in water. It is a free radical photoinitiator, mainly used in free radical UV curing systems such as coatings, inks, adhesives, etc. It is also an intermediate for organic pigments, medicines, spices, and pesticides. In the pharmaceutical industry, it is mainly used to produce dicyclohexyl piperidine, benztropine hydrobromide, diphenhydramine hydrochloride, etc. Benzophenone is also a styrene polymerization inhibitor and a fragrance fixative for spices. It can give spices a sweet smell and is widely used in perfumes and soap flavors.

[0003] The traditional method for synthesizing diaromatic ketone compounds is mainly through the Friedel-Crafts acylation reaction of aromatic groups with acylating agents such as anhydrides, acyl halides, and carboxylic acids under the catalysis of aluminum chloride. This method will produce a large amount of highly corrosive by-products, causing environmental pollution. At the same time, the more complicated product separation steps also further lead to the limitations of this method in application.

[0004] At present, the common preparation methods of benzophenone include phosgene method, benzoyl chloride method, carbon tetrachloride method, benzyl chloride method, etc., but they also have problems such as low conversion rate, harsh reaction conditions or high production cost, so industrial production is limited. Due to the shortage of resources and the improvement of environmental protection requirements, not only the full utilization of organic raw materials in chemical processes, energy saving and consumption, and the development of environmentally friendly processes are increasingly concerned, but also the demand for green chemical processes is increasing.

[0005] Direct acylation is one of the fundamental methods in organic synthesis and is one of the most common transformations used in the synthesis of pharmaceuticals, agrochemicals, and functional materials. The intrinsic value of acyl transfer reactions is that the product ketones are widely used in various aspects of organic synthesis, including bioactive natural products and pharmaceuticals, while the position of the carbonyl and substituent groups makes these methods efficient pathways to many important products in academic and industrial research. These methods rely heavily on the use of liquid organic solvents, which raises environmental, health, and safety issues. Although the choice of solvent is often critical to the chemical process, recent surveys have shown that solvents account for more than 85% of non-aqueous waste in the pharmaceutical industry. Therefore, the development of solvent-free methods is a key goal to minimize waste, reduce environmental impact, and open up new pathways that cannot be exploited by solvents. Summary of the invention

[0006] The present application provides a method for green synthesis of aromatic ketones and biphenyls based on a quartz sand solid phase system, aiming to solve the technical problem of the lack of a solvent-free method for synthesizing aromatic ketones and biphenyls in the prior art.

[0007] In order to solve the above technical problems, the present application provides a method for green synthesis of aromatic ketones and biphenyl based on a quartz sand solid phase system, comprising the following steps:

[0008] The acid anhydride, the aromatic or alkyl boronic acid, the catalyst, the base and the solid phase system medium are uniformly mixed to obtain a reaction mixture;

[0009] In a nitrogen atmosphere, the reaction mixture is heated to 110° C. for reaction, and after the reaction is completed, a post-treatment is performed to obtain a diaryl ketone or an alkyl aryl ketone;

[0010] In an air atmosphere, the reaction mixture is heated to 150° C. to react to obtain biphenyl;

[0011] The reaction equation is as follows:

[0012]

[0013] Wherein, the substituent R1 is at least one of hydrogen, alkyl, alkoxy and halogen, R2 is an alkyl, and the catalyst is a palladium catalyst.

[0014] In some preferred embodiments, at a specified temperature, no stirring is required whether the reaction is carried out in a nitrogen atmosphere or in an air atmosphere; the yield of the reaction in a nitrogen atmosphere as described above is 64%-94%, and the yield of the reaction in an air atmosphere as described above is 61%-71%.

[0015] As some optional embodiments of the present application, the solid phase system medium is at least one of quartz sand, table salt, river sand, sodium chloride, potassium chloride and anhydrous sodium sulfate.

[0016] As some optional embodiments of the present application, the palladium catalyst is at least one of bis(triphenylphosphine)palladium dichloride, palladium acetate, palladium chloride, [1,1-bis(diphenylphosphino)ferrocene]palladium dichloride and palladium on carbon.

[0017] As some optional embodiments of the present application, the base is at least one of potassium carbonate, potassium phosphate, sodium carbonate, sodium bicarbonate, sodium fluoride, potassium fluoride and cesium fluoride.

[0018] As some optional embodiments of the present application, the reaction temperature for preparing the aryl ketone is room temperature to 150°C, and the reaction time is 8 hours. In some preferred embodiments, the reaction temperature is 90°C-130°C, preferably 100°C-120°C; the reaction temperature for preparing biphenyl is 130°C-170°C, preferably 140°C-160°C.

[0019] As some optional embodiments of the present application, the molar ratio of the acid anhydride to the catalyst is 1:0.01.

[0020] As some optional embodiments of the present application, the post-processing refers to:

[0021] After the reaction is completed, the reaction system is cooled to room temperature, ethyl acetate is added to the reaction system, stirred at room temperature for 15 minutes, filtered to separate the organic phase solution and the solid mixture, the organic phase is concentrated under reduced pressure to obtain a crude product, the crude product is recrystallized with ethyl acetate and n-hexane to obtain the target product diaryl ketone, and purified by column chromatography to obtain alkyl aryl ketone.

[0022] As some optional embodiments of the present application, after the reaction is completed and the diaryl ketone or alkyl aryl ketone is obtained through post-treatment, the method further comprises:

[0023] The solid mixture obtained when separating the crude product is dried at 90°C to recover the solid phase system medium and the catalyst, and then it is re-reacted. During this process, it is not necessary to add the catalyst and the solid phase system medium again.

[0024] As some optional embodiments of the present application, after the reaction is completed and the diaryl ketone or alkyl aryl ketone is obtained through post-treatment, the method further comprises:

[0025] The filtered solid mixture is added to ethanol, stirred at room temperature for 2 hours, filtered to separate the solid waste and the ethanol solution, and the ethanol solution is concentrated under reduced pressure to obtain a crude potassium benzoate product. The crude potassium benzoate product is recrystallized from dichloromethane, and then the solvent is removed to obtain potassium benzoate.

[0026] As some optional embodiments of the present application, after the solid phase system medium and catalyst are recycled twice, the yield of the third reaction is 61%.

[0027] Compared with the prior art, the method for green synthesis of aromatic ketones and biphenyls based on a quartz sand solid phase system described in the embodiment of the present application includes uniformly mixing anhydride, aromatic or alkyl boric acid, catalyst, base and solid phase system medium, reacting at 110°C in a nitrogen atmosphere, and obtaining diaromatic ketone or alkyl aromatic ketone through post-treatment after the reaction is completed; that is, by using the solid phase system medium as the reaction medium, avoiding the use of organic solvents, and using chemical principles to reduce and eliminate the pollution of the environment caused by the use of organic solvents in industrial production from the source. At the same time, the solid phase system medium and catalyst can be recycled twice to achieve the recycling of resources, thereby achieving "cost saving, less pollution, and cost reduction". BRIEF DESCRIPTION OF THE DRAWINGS

[0028] In order to more clearly illustrate the specific implementation of the present application or the technical solution in the prior art, the following is a brief introduction to the drawings required for the specific implementation or the prior art description. In all drawings, similar elements or parts are generally identified by similar reference numerals. In the drawings, each element or part is not necessarily drawn according to the actual scale.

[0029] Figure 1 Schematic diagram of the experimental process of the quartz sand solid phase system involved in this application;

[0030] Figure 2 A schematic diagram of the recycling of the quartz sand solid phase reaction medium and the catalyst involved in this application;

[0031] Figure 3 This is a schematic diagram of the technical route for the solvent-free green synthesis of aromatic ketones using anhydride in a quartz sand solid phase system involved in this application;

[0032] Figure 4 The product synthesized in Example 1 of this application 1 H NMR spectra;

[0033] Figure 5 The product synthesized in Example 2 of this application 1 H NMR spectra;

[0034] Figure 6 The product synthesized in Example 3 of this application 1 H NMR spectra;

[0035] Figure 7 The product synthesized in Example 4 of the present application 1 H NMR spectra;

[0036] Figure 8 The product synthesized in Example 5 of this application 1 H NMR spectra;

[0037] Fig. 9The product synthesized in Example 6 of the present application 1 H NMR spectra;

[0038] Fig.10 The product synthesized in Example 7 of this application 1 H NMR spectra;

[0039] Fig.11 The product synthesized in Example 8 of this application 1 H NMR spectra;

[0040] Fig.12 The product synthesized in Example 9 of this application 1 H NMR spectra;

[0041] Fig.13 The product synthesized in Example 10 of this application 1 H NMR spectra;

[0042] Fig.14 The product synthesized in Example 11 of the present application 1 H NMR spectra;

[0043] Fig.15 The product synthesized in Example 12 of the present application 1 H NMR spectra;

[0044] Fig.16 The product synthesized in Example 13 of the present application 1 H NMR spectra;

[0045] Fig.17 The product synthesized in Example 14 of this application 1 H NMR spectra;

[0046] Fig.18 The product synthesized in Example 15 of the present application 1 H NMR spectra;

[0047] Fig.19 The product synthesized in Example 16 of this application 1 H NMR spectra;

[0048] Fig. 20 The product synthesized in Example 17 of this application 1 H NMR spectra;

[0049] Fig.21 The product synthesized in Example 18 of this application 1 H NMR spectra;

[0050] Fig. 22 The product synthesized in Example 19 of this application 1H NMR spectra;

[0051] Fig.23 The product synthesized in Example 20 of this application 1 H NMR spectra;

[0052] Fig.24 The product synthesized in Example 21 of this application 1 H NMR spectra;

[0053] Fig.25 The product synthesized in Example 23 of the present application 1 H NMR spectra;

[0054] Fig.26 The product synthesized in Example 24 of the present application 1 H NMR spectra;

[0055] Fig. 27 The product synthesized in Example 25 of the present application 1 H NMR spectra.

[0056] The realization of the purpose, functional features and advantages of this application will be further explained in conjunction with embodiments and with reference to the accompanying drawings. DETAILED DESCRIPTION

[0057] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0058] In 2001, Lukas J. Gooβen et al. first converted carboxylic anhydrides and organoboron compounds into ketones using expensive palladium acetate catalysis and flammable tetrahydrofuran, which is very easy to produce peroxides, with a yield of 48-90%. In this process, different phosphine ligands need to be selected according to the stereo and electronic properties of the anhydride. Trimethoxyphenylphosphine is generally suitable for all carboxylic anhydrides and is also a good choice for most alkyl derivatives. However, for aryl derivatives with poor electron content, triphenylphosphine or diphenylferrocenylphosphine is more effective. However, the yield of diaryl ketones synthesized by general methods is generally not high (Angew. Chem. Int. Ed. 2001, 40, No. 18). In 2011, Li-Xiong Shao et al. used a self-made palladium catalyst proline-derived imidazole-coordinated monodentate NHC-Pd(II) complex to catalyze the synthesis of diaryl ketones from carboxylic anhydrides and organoboron compounds at room temperature and in aqueous phase, with a yield of 66-98%. The reaction time was 36 hours, which was too long, and the cost of the self-made catalyst was too high, limiting the application of the reaction (Appl. Organometal. Chem. 2011, 25, 497–501). In 2013, Yangjie Wu et al. used a self-made catalyst [NaL]+[PdCl3]-form palladium-tetraethyl tetra-t-butylcalixarene-tetra(oxyacetate) complex to show high catalytic efficiency for the acyl borylation reaction of arylboronic acid with benzoyl chloride or acetic anhydride, and the corresponding ketones were generated in excellent yields under mild reaction conditions. This method can tolerate a variety of arylboronic acids, benzoyl chlorides and acetic anhydride. In addition, a typical method for synthesizing acetylaryl ketones was obtained, but this method requires the use of carcinogenic toluene as a solvent, uses a specific complex palladium catalyst, has a large molecular weight, and has low atom economy (ARKIVOC 2013 (iv) 251-271). In 2014, Lian-Ming Yang et al. first demonstrated the feasibility of nickel-catalyzed acylation of arylboronic acid with carboxylic anhydride. This process provides an efficient, cheap and convenient way to synthesize aromatic ketones, but this method uses toluene, which is harmful to the human body, as a solvent and the dosage of arylboronic acid and potassium phosphate is too high, and it is impossible to prepare products with large steric hindrance, and the product yield is generally not high (39-88%) (RSC Adv, 2014, 4, 53885). In 2022, Michal Szostak et al. developed the first solvent-free mechanochemical method using a ball mill for the highly chemically selective synthesis of ketones from anhydrides and arylboronic acids. The notable features of this process include avoiding the use of harmful solvents and short reaction time, but the reaction yield is only 40% (Org. Lett. 2022, 24, 2338-2343).

[0059] Based on this, the present application provides a method for the green synthesis of aromatic ketones and biphenyls based on a quartz sand solid phase system, that is, by using the solid phase system medium as the reaction medium, avoiding the use of organic solvents, and using chemical principles to reduce and eliminate the pollution of the environment caused by the use of organic solvents in industrial production from the source. At the same time, the solid phase system medium and catalyst can be recycled twice to achieve the recycling of resources, thereby achieving "cost saving, less pollution, and cost reduction". For example: The experimental process of the solvent-free preparation of diaromatic ketones and alkyl aromatic ketones using anhydrides as raw materials in a quartz sand solid phase system is as follows Figure 1 shown.

[0060] In order to make the technical solution clearer, the present invention is further described below in conjunction with embodiments, but the protection scope of the present invention is not limited thereto.

[0061] Example 1

[0062] Synthesis of Benzophenone

[0063]

[0064] Benzoic anhydride (0.1mmol), phenylboric acid (0.11mmol), bis(triphenylphosphine)palladium dichloride (1%mol), powdered potassium carbonate (0.165mmol), quartz sand (2.5g) and magnet were added to a 25ml two-necked flask. After mixing evenly under a nitrogen atmosphere, the system was placed at 110°C for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product benzophenone was obtained by recrystallization with ethyl acetate and n-hexane with a yield of 84%.

[0065] After testing, such as Figure 4 As shown, 1 H NMR (600MHz, CDCl3) δ7.83–7.79(m,2H),7.59(t,1H),7.48(t,J=10.8,4.7Hz,2H).

[0066] Example 2

[0067] Synthesis of 4-methoxybenzophenone

[0068]

[0069] Benzoic anhydride (0.1mmol), 4-methoxyphenylboronic acid (0.11mmol), bis(triphenylphosphine)palladium dichloride (1%mol), powdered potassium carbonate (0.165mmol), quartz sand (2.5g), and a magnet were added to a 25ml two-necked flask. After mixing evenly under a nitrogen atmosphere, the system was placed at 110°C for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4-methoxybenzophenone was obtained by recrystallization with ethyl acetate and n-hexane with a yield of 90%.

[0070] After testing, such as Figure 5 As shown, 1 H NMR (600MHz, CDCl3) δ7.86–7.81(m,2H),7.78–7.73(m,2H),7.57(tt,1H),7.47(t,J=7.6Hz,2H),6.99–6.95(m,2H),3.89(s,3H).

[0071] Example 3

[0072] Synthesis of 4-Chlorobenzophenone

[0073]

[0074] Benzoic anhydride (0.1mmol), 4-chlorophenylboric acid (0.11mmol), bis(triphenylphosphine)palladium dichloride (1%mol), powdered potassium carbonate (0.165mmol), quartz sand (2.5g), and a magnet were added to a 25ml two-necked flask. After mixing evenly under a nitrogen atmosphere, the system was placed at 110°C for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4-chlorobenzophenone was obtained by recrystallization with ethyl acetate and n-hexane with a yield of 82%.

[0075] After testing, such as Figure 6 As shown, 1 H NMR (600MHz, CDCl3) δ7.79–7.74(m,4H),7.63–7.58(m,1H),7.51–7.44(m,4H).

[0076] Example 4

[0077] Synthesis of 4,4'-dimethylbenzophenone

[0078]

[0079] In a 25 ml two-necked flask, p-toluic anhydride (0.1 mmol), 4-methylphenylboronic acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4,4′-dimethylbenzophenone was obtained by recrystallization with ethyl acetate and n-hexane with a yield of 91%.

[0080] After testing, such as Figure 7 As shown, 1 H NMR (600MHz, CDCl3) δ7.73–7.68 (m, 2H), 7.27 (d, J = 7.9Hz, 2H), 2.44 (s, 3H).

[0081] Example 5

[0082] Synthesis of 4-methoxy-4'-methyl-dimethylbenzophenone

[0083]

[0084] In a 25 ml two-necked flask, p-toluic anhydride (0.1 mmol), 4-methoxyphenylboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4-methyl-4′-dimethylbenzophenone was obtained by recrystallization with ethyl acetate and n-hexane in a yield of 94%.

[0085] After testing, such as Figure 8 As shown, 1 H NMR (600MHz, CDCl3) δ7.81 (d, J = 8.8 Hz, 2H), 7.68 (d, J = 8.1 Hz, 2H), 7.27 (d, J = 7.9 Hz, 2H), 6.96 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 2.44 (s, 3H).

[0086] Example 6

[0087] Synthesis of 4-Methyl-4'-nitro-dimethylbenzophenone

[0088]

[0089] In a 25 ml two-necked flask, p-toluic anhydride (0.1 mmol), 4-nitrobenzeneboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product, 4-methyl-4′-nitro-dimethylbenzophenone, was obtained by recrystallization with ethyl acetate and n-hexane. The yield was 81%.

[0090] After testing, such as Fig. 9 As shown, 1 H NMR (600MHz, CDCl3) δ8.33 (d, J = 8.7 Hz, 2H), 7.91 (d, J = 8.7 Hz, 2H), 7.71 (d, J = 8.1 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 2.46 (s, 3H).

[0091] Example 7

[0092] Synthesis of 4-Fluorobenzophenone

[0093]

[0094] In a 25 ml two-necked flask, p-fluorobenzoic anhydride (0.1 mmol), phenylboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4-fluorobenzophenone was obtained by recrystallization with ethyl acetate and n-hexane with a yield of 88%.

[0095] After testing, such as Fig.10 As shown, 1 H NMR (600MHz, CDCl3) δ7.88–7.82(m,2H),7.77(dt,J=8.4,1.5Hz,2H),7.63–7.58(m,1H),7.52–7.47(m,2H),7.19–

[0096] 7.14 (m, 2H).

[0097] Example 8

[0098] Synthesis of 4-Fluoro-2′-methoxybenzophenone

[0099]

[0100] In a 25 ml two-necked flask, p-fluorobenzoic anhydride (0.1 mmol), 2-methoxyphenylboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4-fluoro-4′-methoxybenzophenone was obtained by recrystallization with ethyl acetate and n-hexane in a yield of 64%.

[0101] After testing, such as Fig.11 As shown, 1 H NMR (600MHz, CDCl3) δ7.87–7.81(m,2H),7.51–7.45(m,1H),7.36(dd,J=7.4,1.7H z,1H),7.13–7.07(m,2H),7.04(t,J=13.6,6.2Hz,1H),6.99(d,1H),3.73(s,3H).

[0102] Example 9

[0103] Synthesis of 4-Fluoro-3′-methoxybenzophenone

[0104]

[0105] In a 25 ml two-necked flask, p-fluorobenzoic anhydride (0.1 mmol), 3-methoxyphenylboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4-fluoro-4′-methoxybenzophenone was obtained by recrystallization with ethyl acetate and n-hexane with a yield of 76%.

[0106] After testing, such as Fig.12 As shown, 1H NMR (600MHz, CDCl3) δ7.89–7.80(m,2H),7.38(t,1H),7.33–7.28(m,2H),7.19–7.12(m,3H),3.86(s,3H).

[0107] Example 10

[0108] Synthesis of 4-Fluoro-4′-methoxybenzophenone

[0109]

[0110] In a 25 ml two-necked flask, p-fluorobenzoic anhydride (0.1 mmol), 4-methoxyphenylboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4-fluoro-4′-methoxybenzophenone was obtained by recrystallization with ethyl acetate and n-hexane in a yield of 93%.

[0111] After testing, such as Fig.13 As shown, 1 H NMR (600MHz, CDCl3) δ7.83–7.77(m,4H),7.18–7.12(m,2H),6.99–6.95(m,2H),3.89(s,3H).

[0112] Embodiment 11

[0113] Synthesis of 4,4'-difluorobenzophenone

[0114]

[0115] In a 25 ml two-necked flask, p-fluorobenzoic anhydride (0.1 mmol), 4-fluorophenylboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4,4′-difluorobenzophenone was obtained by recrystallization with ethyl acetate and n-hexane with a yield of 86%.

[0116] After testing, such as Fig.14 As shown,1 H NMR (600MHz, CDCl3) δ7.85–7.78(m,2H),7.20–7.14(m,2H).

[0117] Example 12

[0118] Synthesis of 4-Fluoro-4′-nitrobenzophenone

[0119]

[0120] In a 25 ml two-necked flask, p-fluorobenzoic anhydride (0.1 mmol), 4-nitrobenzeneboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4-fluoro-4′-nitrobenzophenone was obtained by recrystallization with ethyl acetate and n-hexane in a yield of 83%.

[0121] After testing, such as Fig.15 As shown, 1 H NMR (600MHz, CDCl3) δ8.38–8.34(m,2H),7.93–7.89(m,1H),7.88–7.83(m,1H),7.81–7.77(m,1H),7.23–7.18(m,1H).

[0122] Example 13

[0123] Synthesis of 4-Trifluoromethylbenzophenone

[0124]

[0125] In a 25 ml two-necked flask, p-trifluoromethylbenzoic anhydride (0.1 mmol), phenylboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. without stirring for 8 hours. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4-trifluoromethylbenzophenone was obtained by recrystallization with ethyl acetate and n-hexane in a yield of 87%.

[0126] After testing, such as Fig.16 As shown, 1H NMR (600MHz, CDCl3) δ7.90 (d, J = 8.0 Hz, 2H), 7.81 (d, J = 8.2, 1.1 Hz, 2H), 7.76 (d, J = 8.2 Hz, 2H), 7.63 (t, J = 10.6, 4.3 Hz, 1H), 7.51 (t, J = 7.8 Hz, 2H).

[0127] Embodiment 14

[0128] Synthesis of 4-methoxy-4'-trifluoromethylbenzophenone

[0129]

[0130] In a 25 ml two-necked flask, p-trifluoromethylbenzoic anhydride (0.1 mmol), 4-methoxyphenylboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4-methoxy-4′-trifluoromethylbenzophenone was obtained by recrystallization with ethyl acetate and n-hexane in a yield of 89%.

[0131] After testing, such as Fig.17 As shown, 1 H NMR (600MHz, CDCl3) δ7.87–7.80 (m, 4H), 7.74 (d, J = 8.1Hz, 2H), 7.00–6.97 (m, 2H), 3.90 (s, 3H).

[0132] Embodiment 15

[0133] Synthesis of (4-methylphenyl)-(2-thiophene)methanone

[0134]

[0135] In a 25 ml two-necked flask, p-toluic anhydride (0.1 mmol), 2-thiopheneboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110°C for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product, (4-methylphenyl)-(2-thiophene)methanone, was obtained by recrystallization with ethyl acetate and n-hexane. The yield was 79%.

[0136] After testing, such as Fig.18 As shown, 1 H NMR (600MHz, CDCl3) δ7.79(d,2H),7.70(dd,J=4.9,1.1Hz,1H),7.65(dd,J=3. 8,1.1Hz,1H),7.30(d,J=7.9Hz,2H),7.16(dd,J=4.9,3.8Hz,1H),2.45(s,3H).

[0137] Example 16

[0138] Synthesis of (4-Fluorophenyl)-(2-thiophene)methanone

[0139]

[0140] In a 25 ml two-necked flask, p-fluorobenzoic anhydride (0.1 mmol), 2-thiopheneboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product (4-fluorophenyl)-(2-thiophene)methanone was obtained by recrystallization with ethyl acetate and n-hexane in a yield of 85%.

[0141] After testing, such as Fig.19 As shown, 1 H NMR (600MHz, CDCl3) δ7.94–7.89(m,2H),7.73(dd,J=4.9,1.1Hz,1H),7.63(dd,J=3.8,1.1Hz,1H),7.20–7.15(m,3H).

[0142] Embodiment 17

[0143] Synthesis of (4-trifluoromethylphenyl)-(2-thiophene)methanone

[0144]

[0145] In a 25 ml two-necked flask, p-fluorobenzoic anhydride (0.1 mmol), 2-thiopheneboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product (4-fluorophenyl)-(2-thiophene)methanone was obtained by recrystallization with ethyl acetate and n-hexane in a yield of 83%.

[0146] After testing, such as Fig. 20 As shown, 1 H NMR (600MHz, CDCl3) δ7.96 (d, J = 8.0 Hz, 2H), 7.80–7.75 (m, 3H), 7.63 (dd, J = 3.8, 1.0 Hz, 1H), 7.19 (dd, J = 4.9, 3.8 Hz, 1H).

[0147] Embodiment 18

[0148] Synthesis of acetophenone

[0149]

[0150] Benzoic anhydride (0.1mmol), methylboric acid (0.11mmol), bis(triphenylphosphine)palladium dichloride (1%mol), powdered potassium carbonate (0.165mmol), quartz sand (2.5g) and a magnet were added to a 25ml two-necked flask. After mixing evenly under a nitrogen atmosphere, the system was placed at 110°C for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product, acetophenone, was separated and purified by petroleum ether / ethyl acetate column chromatography to obtain the target product, acetophenone, with a yield of 78%.

[0151] After testing, such as Fig.21 As shown, 1 H NMR (600MHz, CDCl3) δ7.98–7.95(m,2H),7.59–7.55(m,1H),7.49–7.44(m,2H),2.61(s,3H).

[0152] Embodiment 19

[0153] Synthesis of 4-methylacetophenone

[0154]

[0155] In a 25 ml two-necked flask, p-toluic anhydride (0.1 mmol), methylboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4-methylacetophenone was obtained by separation and purification using petroleum ether / ethyl acetate column chromatography. The yield was 80%.

[0156] After testing, such as Fig. 22 As shown, 1 H NMR (600MHz, CDCl3) δ7.86 (d, J = 8.2 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 2.57 (s, 3H), 2.41 (s, 3H).

[0157] Embodiment 20

[0158] Synthesis of 4-Fluoroacetophenone

[0159]

[0160] In a 48 ml thick-walled pressure bottle, p-fluorobenzoic anhydride (0.1 mmol), methylboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4-fluoroacetophenone was obtained by separation and purification using petroleum ether / ethyl acetate column chromatography. The yield was 85%.

[0161] After testing, such as Fig.23 As shown, 1 H NMR (600MHz, CDCl3) δ8.02–7.95(m,2H),7.16–7.10(m,2H),2.59(s,3H).

[0162] Embodiment 21

[0163] Synthesis of Potassium 4-Fluorobenzoate

[0164]

[0165] In a 25 ml two-necked flask, p-fluorobenzoic anhydride (0.1 mmol), 4-methoxyboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and stirred for another 15 minutes. The solid mixture was filtered to obtain a solid mixture. The solid mixture was added to a 100 ml round-bottom flask containing 30 ml of ethanol, stirred at room temperature for 3 hours, and desolventized to obtain a crude product of potassium 4-fluorobenzoate. The crude product was recrystallized from dichloromethane and desolventized to obtain the target product potassium 4-fluorobenzoate in a yield of 85%.

[0166] After testing, such as Fig.24 As shown, 1 H NMR(600MHz,D2O)δ7.91–7.86(m,2H),7.20–7.13(m,2H).

[0167] Embodiment 22

[0168] Circulation of Quartz Sand Solid Phase Reaction Medium and Catalyst

[0169] The solid mixture obtained when separating the crude product was dried at 90°C, transferred to a 25ml two-necked flask, and benzoic anhydride (0.1mmol), 4-methoxyphenylboric acid (0.11mmol), powdered potassium carbonate (0.165mmol), and a magnet were added. After mixing evenly under a nitrogen atmosphere, the system was placed at 110°C without stirring for 8 hours. After the reaction was completed, it was cooled to room temperature, ethyl acetate (10ml) was added to the reaction system, and stirred for another 15 minutes. The organic phase and the solid mixture were filtered to obtain the organic phase and the solid mixture. After the solid mixture was dried at 90°C, the above steps were repeated to react and feed again. In this process, it was not necessary to add quartz sand and catalyst again. The quartz sand and catalyst could be recycled twice. The yield of the third reaction could be maintained at 61%. The experimental process is as follows: Figure 2 shown.

[0170] Embodiment 23

[0171] Synthesis of 4-Methylbiphenyl

[0172]

[0173] In a 25 ml two-necked flask, benzoic anhydride (0.1 mmol), 4-methylboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing well, 1.0 g of activated carbon with a water content of 55% was added and stirred well. The system was placed at 150° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4-methylbiphenyl was obtained by separation and purification using petroleum ether / ethyl acetate column chromatography. The yield was 65%.

[0174] After testing, such as Fig.25 As shown, 1 H NMR(600MHz, CDCl3)δ7.59(dd,J=7.0,1.5Hz,2H),7.53–7.48(m,2H),7.46–7.41(m,2H),7.36–7.30(m,1H),7.28–

[0175] 7.24(m,2H),2.41(s,3H).

[0176] Embodiment 24

[0177] Synthesis of 4-methoxybiphenyl

[0178]

[0179] In a 25 ml two-necked flask, benzoic anhydride (0.1 mmol), 4-methoxyboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing well, 1.0 g of activated carbon with a water content of 55% was added and stirred well. The system was placed at 150° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and it was stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4-methoxybiphenyl was obtained by separation and purification using petroleum ether / ethyl acetate column chromatography. The yield was 71%.

[0180] After testing, such as Fig.26 As shown, 1 H NMR (600MHz, CDCl3) δ7.59–7.51(m,4H),7.42(t,J=7.7Hz,2H),7.30(t,J=14.0,6.6Hz,1H),7.01–6.96(m,2H),3.86(s,3H).

[0181] Embodiment 25

[0182] Synthesis of 4-iodobiphenyl

[0183]

[0184] In a 25 ml two-necked flask, benzoic anhydride (0.1 mmol), 4-iodoboric acid (0.11 mmol), bis(triphenylphosphine)palladium dichloride (1% mol), powdered potassium carbonate (0.165 mmol), quartz sand (2.5 g), and a magnet were added. After mixing well, 1.0 g of activated carbon with a water content of 55% was added and stirred well. The system was placed at 150° C. for 8 hours without stirring. After the reaction was completed, it was cooled to room temperature. Ethyl acetate (10 ml) was added to the reaction system, and stirred for another 15 minutes. The organic phase was filtered to obtain the organic phase, and the solvent was removed. The target product 4-iodobiphenyl was obtained by separation and purification using petroleum ether / ethyl acetate column chromatography. The yield was 61%.

[0185] After testing, such as Fig. 27 As shown, 1 H NMR (600MHz, CDCl3) δ7.79–7.75(m,2H),7.57–7.53(m,2H),7.44(t,2H),7.37(t,1H),7.35–7.31(m,2H).

[0186] It can be seen that the technical route of the synthesis method described in this application is as follows Figure 3 As shown, including:

[0187] After the reactant and the reaction medium are fed, they are mixed evenly under a nitrogen atmosphere, and the system is placed at 110°C without stirring for 8 hours. After the reaction is completed, it is cooled to room temperature, ethyl acetate (10ml) is added to the reaction system, and stirred for 15 minutes, and then filtered to obtain an organic phase and a solid mixture. After the organic phase is desolvated, the solid product is purified by recrystallization, while the liquid product (such as acetophenone, 4-methylacetophenone, 4-fluoroacetophenone) is purified by column chromatography. After the solid mixture is dried at 90°C, quartz sand and catalyst can be recycled twice, and quartz sand and catalyst do not need to be added again in this process. After the third reaction, the solid mixture obtained by filtering is washed with ethanol and filtered to obtain solid waste and an ethanol solution of potassium benzoate. The ethanol solution of potassium benzoate is desolvated and washed with dichloromethane, and then desolvated and dried to obtain potassium benzoate.

[0188] The above are only preferred embodiments of the present application, and are not intended to limit the patent scope of the present application. Any equivalent structure or equivalent process transformation made using the contents of the present application specification and drawings, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present application.

Claims

1. A method for green synthesis of aromatic ketones and biphenyl based on a quartz sand solid phase system, characterized in that: The following steps are involved: The acid anhydride, the aromatic or alkyl boronic acid, the catalyst, the base and the solid phase system medium are uniformly mixed to obtain a reaction mixture; In a nitrogen atmosphere, the reaction mixture is heated to 110° C. for reaction, and after the reaction is completed, a post-treatment is performed to obtain a diaryl ketone or an alkyl aryl ketone; In an air atmosphere, the reaction mixture is heated to 150° C. to react to obtain biphenyl; The reaction equation is as follows: Wherein, the substituent R1 is at least one of hydrogen, alkyl, alkoxy and halogen, R2 is an alkyl, and the catalyst is a palladium catalyst.

2. A method for green synthesis of aromatic ketones and biphenyl based on quartz sand solid phase system according to claim 1, characterized in that: The solid phase system medium is at least one of quartz sand, table salt, river sand, sodium chloride, potassium chloride and anhydrous sodium sulfate.

3. The method for green synthesis of aromatic ketones and biphenyl based on quartz sand solid phase system according to claim 1, characterized in that: The palladium catalyst is at least one of bis(triphenylphosphine)palladium dichloride, palladium acetate, palladium chloride, [1,1-bis(diphenylphosphino)ferrocene]palladium dichloride and palladium carbon.

4. The method for green synthesis of aromatic ketones and biphenyl based on quartz sand solid phase system according to claim 1, characterized in that: The base is at least one of potassium carbonate, potassium phosphate, sodium carbonate, sodium bicarbonate, sodium fluoride, potassium fluoride and cesium fluoride.

5. The method for green synthesis of aromatic ketones and biphenyl based on quartz sand solid phase system according to claim 1, characterized in that: The reaction temperature for preparing aryl ketone is room temperature to 150°C, the reaction temperature for preparing biphenyl is room temperature to 180°C, and the reaction time is 8 hours.

6. The method for green synthesis of aromatic ketones and biphenyl based on quartz sand solid phase system according to claim 1, characterized in that: The molar ratio of the acid anhydride to the catalyst is 1:0.

01.

7. The method for green synthesis of aromatic ketones and biphenyl based on quartz sand solid phase system according to claim 1, characterized in that: The post-processing refers to: After the reaction is completed, the reaction system is cooled to room temperature, ethyl acetate is added to the reaction system, stirred at room temperature for 15 minutes, filtered to separate the organic phase solution and the solid mixture, the organic phase is concentrated under reduced pressure to obtain a crude product, the crude product is recrystallized with ethyl acetate and n-hexane to obtain the target product diaryl ketone, and purified by column chromatography to obtain alkyl aryl ketone.

8. The method for green synthesis of aromatic ketones and biphenyl based on quartz sand solid phase system according to claim 1, characterized in that: After the reaction is completed and the diaryl ketone or alkyl aryl ketone is obtained through post-treatment, the method further comprises: The solid mixture obtained when separating the crude product is dried at 90°C to recover the solid phase system medium and the catalyst, and then it is re-reacted. During this process, it is not necessary to add the catalyst and the solid phase system medium again.

9. The method for green synthesis of aromatic ketones and biphenyl based on quartz sand solid phase system according to claim 1, characterized in that: After the reaction is completed and the diaryl ketone or alkyl aryl ketone is obtained through post-treatment, the method further comprises: The filtered solid mixture is added to ethanol, stirred at room temperature for 2 hours, filtered to separate the solid waste and the ethanol solution, and the ethanol solution is concentrated under reduced pressure to obtain a crude potassium benzoate product. The crude potassium benzoate product is recrystallized from dichloromethane, and then the solvent is removed to obtain potassium benzoate.

10. The method for green synthesis of aromatic ketones and biphenyl based on quartz sand solid phase system according to claim 8, characterized in that: After the solid phase system medium and catalyst were recycled twice, the yield of the third reaction was 61%.

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