Carboxylic acid esterification method and gas-liquid mixed flow photochemical device

Abstract

The invention provides a method for carrying out carboxylic acid esterification by adopting a gas-liquid mixed flowing photochemical device. The gas-liquid mixed flowing photochemical device comprises a liquid and gas injection part and a four-way mixer which are connected in sequence, the method comprises the following steps: placing an alcohol compound, a carboxylic acid compound, an organic solvent, a photocatalyst and alkali in a liquid injection part to obtain a liquid raw material, placing sulfur hexafluoride gas in a gas injection part, injecting the liquid raw material and the gas into a four-way mixer, fully mixing, and carrying out a photochemical reaction in a photoreactor, the ester compound is obtained. According to the method, the sulfur hexafluoride SF6 gas can be turned into wealth, and the simple, safe, green and efficient carboxylic acid esterification reaction can be carried out.

Description

Technical Field

[0001] The invention relates to the technical field of organic intermediate synthesis, and in particular to a method for esterifying carboxylic acid by using a gas-liquid mixed flow photochemical device. Background Art

[0002] As a common group, ester group is widely present in many drug molecules. It can not only increase the lipophilicity of drugs, but also is a necessary structure-effect group in many drug molecules. Ester compounds are also an important class of chemical products in the chemical industry and indispensable in our lives. Ester compounds are also an important class of solvents. They play a very obvious role in dissolving cellulose and also play a very important role in the field of food additives and spices. Therefore, promoting the condensation esterification reaction of alcohol and carboxylic acid has important use value. At present, the methods of esterification are:

[0003] Method 1: Fischer-Speier esterification reaction is the most classic esterification reaction. Under the action of acidic catalysts (sulfuric acid, sulfonic acid, phosphoric acid, hydrochloric acid, etc.), carboxylic acid and alcohol undergo a reversible reaction to generate ester compounds. Because it is a reversible reaction, it is often necessary to add an excess of one of the raw materials, or use a Dean-Stark device to remove water.

[0004]

[0005] This method uses an acidic catalyst, which has the characteristics of high catalytic activity, low price and easy preparation. However, the disadvantage is that the yield in the esterification of secondary and tertiary alcohols is low and the raw materials are wasted (or additional equipment is required to remove water).

[0006] Method 2: Esterification reaction catalyzed by N,N-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine

[0007]

[0008] This method has the advantages of mild reaction conditions, high yield, good selectivity, etc., but it produces a by-product, dicyclohexylurea, and the post-processing is cumbersome.

[0009] Method 3: Use elemental iodine alone to catalyze the esterification reaction of carboxylic acid and alcohol.

[0010]

[0011] The advantages of this reaction system are simple operation, non-toxicity, strong applicability, relatively mild conditions and high yield; however, the post-processing is complicated and the reactant alcohol is in excess, resulting in great waste.

[0012] Therefore, there is still a need to develop a carboxylic acid esterification method that has simple and readily available raw materials, simple operation, high reaction yield, good functional group tolerance, environmental friendliness, and is easy to promote in industrial production.

[0013] And for the following reasons: SF6 gas is a colorless, odorless, non-toxic, non-combustible, non-corrosive gas at room temperature and pressure. It is an inert gas with high stability. It does not decompose at high temperatures of 500-600°C, and does not react with acids, alkalis, water, etc. It is also an insulating gas with excellent insulating properties. The gas can adsorb free discrete electrons in the electric field, effectively reducing ionization collisions in the gas, which actually has an insulating effect and can be used to eliminate high-voltage arcs. Therefore, SF6 is widely used in the power sector, but SF6 has a strong greenhouse effect, and its climate warming power is 23,900 times that of CO2. Secondly, because SF6 is an artificially synthesized gas with quite stable chemical properties, SF6 is extremely difficult to decompose, and its natural lifespan in the atmosphere can be as long as more than 3,000 years. With continuous accumulation in the atmosphere, the greenhouse effect it brings is also continuously increasing. SF6 is currently subject to strict emission restrictions, and the treatment of large amounts of SF6 stored in the power sector faces difficulties.

[0014] SF6 itself has a high potential for utilization. One SF6 molecule contains one sulfur atom and six fluorine atoms. The decomposition products of SF6 contain high-valent sulfur-fluorine intermediates, which can be used as condensation reagents in the field of organic synthesis.

[0015] At the same time, in recent years, photochemical reactions have been favored by domestic and foreign universities, research institutes and industries. This is because compared with traditional chemical reactions, photochemical reactions use light energy to excite molecules to participate in chemical reactions, which has the advantages of high efficiency, energy saving and environmental protection. Photochemical reactions mainly involve excited molecules, which can produce a variety of active substances, and can achieve highly selective and efficient reactions through photosensitizers, catalysts and other means, often allowing the reaction to occur under mild conditions.

[0016] At present, photochemical reactions have broad application prospects in the fields of organic synthesis, drug synthesis, energy conversion, etc. On the other hand, continuous flow reactions have higher production efficiency and better heat and mass transfer performance than batch reactions. The reaction materials held in a continuous flow reactor are significantly less than those in a batch reaction, so the danger of some flammable and highly toxic reactions can be reduced, thereby reducing the safety hazards of the reaction. Continuous flow reactions generally have a smaller amplification effect and are easier to achieve expanded production. Summary of the invention

[0017] The technical problem to be solved by the present invention is how to use a gas-liquid mixed flow photochemical device to perform simple, safe, green and efficient carboxylic acid esterification.

[0018] The present invention solves the above technical problems through the following technical means:

[0019] The present invention provides a method for esterification of carboxylic acid, which is carried out in a gas-liquid mixed flow photochemical device, wherein the gas-liquid mixed flow photochemical device comprises a liquid and gas injection part and a four-way mixer connected in sequence;

[0020] The method specifically comprises placing alcohol compounds, carboxylic acid compounds, organic solvents, photocatalysts and alkalis in a liquid injection section to obtain a liquid raw material, placing sulfur hexafluoride gas in a gas injection section, injecting the liquid raw material and the gas into the four-way mixer for full mixing, and then introducing them into the photoreactor for photochemical reaction to obtain an ester compound.

[0021] Furthermore, the four-way mixer comprises: a gas input port, a liquid input port and a mixture output port; the gas input port is connected to the gas push injection part and the circulation part; the liquid input port is connected to the liquid push injection part; the mixture output port is connected to the photoreactor; the interior of the four-way mixer is a hollow sphere, the outer wall of the sphere is evenly distributed with millimeter-level small holes, and the outer wall is tightly connected to the input and output ports;

[0022] The liquid raw material and the gas are pushed into the four-way mixer for full mixing as follows: the gaseous sulfur hexafluoride enters through the gas input port of the four-way mixer through the millimeter-level small holes evenly distributed on the outer wall of the inner sphere, filling the entire sphere; the liquid raw material expands along the outer wall of the inner sphere through the liquid input port of the four-way mixer, enters the sphere through the millimeter-level small holes evenly distributed on the outer wall, and is evenly divided into fine liquid flows, which are in full contact with the gas filling the inside of the sphere; and when leaving the four-way mixer, it is squeezed and divided into fine liquid flows again through the millimeter-level small holes evenly distributed on the outer wall of the sphere.

[0023] The present invention is a carboxylic acid esterification method with a wide range of applications. The method is suitable for synthesizing various ester compounds and their derivatives, and has good tolerance to aromatic carboxylic acids, alkyl carboxylic acids, substituted alkyl carboxylic acids, and heteroaryl carboxylic acids. Therefore, there is actually no particularly strict restriction on the number and type of substituents in alcohol compounds, carboxylic acid compounds, and their derivatives.

[0024] Preferably, the structural formula of the carboxylic acid compound is Wherein, R is one of aryl or substituted aryl, alkyl or substituted alkyl.

[0025] Preferably, the aryl group is one of biphenyl, phenyl, pyrazolyl, benzyl, benzalkenyl, and benzofuranyl.

[0026] Preferably, the substituents in the substituted aryl and substituted alkyl are C1-C 20Alkyl, C2-C 20 Alkenyl, C1-C 20 Hydrocarbyloxy, C6-C 20 Aryl, 5-10 membered heteroaryl containing 1-3 O, N, S heteroatoms or one or more thereof, C2-C 30 The invention further comprises one of an ester group, a cycloalkyl group having 2 to 20 carbon atoms and containing 1 to 5 one or more heteroatoms of O, N, and S, a trifluoromethyl group, a halogen group, a dimethylamino group, a cyano group, an amino group, and a carboxyl group.

[0027] Preferably, the substituted aryl group is one of a substituted phenyl group, a substituted pyrazolyl group, a substituted benzyl group, a substituted biphenyl group, and a substituted benzalkenyl group.

[0028] Preferably, the substituted alkyl group is a substituted methyl group.

[0029] Preferably, the carboxylic acid compound is one of 4-phenylbenzoic acid, benzoic acid, 4-vinylbenzoic acid, 2-iodobenzoic acid, 4-(N,N-dimethylamino)benzoic acid, 4-methoxybenzoic acid, 4-bromobenzoic acid, 4-trifluoromethylbenzoic acid, 4-cyanobenzoic acid, monomethyl isophthalate, 1-benzofuran-5-carboxylic acid, 1-(pyridin-3-yl)-1H-pyrazole-4-carboxylic acid, p-methoxyphenylacetic acid, 4-biphenylacetic acid, 4-methoxycinnamic acid, and phthalic acid.

[0030] Preferably, the structural formula of the alcohol compound is Wherein, R1 and R2 are respectively one of H, alkyl or substituted alkyl, and aryl or substituted aryl.

[0031] Preferably, the alcohol compound is one of ethanol, 1-naphthylethanol, isopropanol, diethylaminoethanol, isopentanol, benzyl alcohol and methanol.

[0032] Preferably, the photocatalyst is an organic photocatalyst or a transition metal photocatalyst, or a mixture of both.

[0033] Preferably, the organic photocatalyst is 4CZIPN, Mes-Acr + ClO4 — 、Mes-Acr-Me + ClO4 - A mixture of one or more of.

[0034] Preferably, the transition metal photocatalyst is one or a mixture of Ir[dF(CF3)ppy]2(dtbbpy)PF6, Ir(dtbbpy)ppy2PF6.

[0035] Preferably, the photocatalyst is Ir[dF(CF3)ppy]2(dtbbpy)PF6.

[0036] Preferably, the alkaline substance is an organic base.

[0037] Preferably, the organic base is a tertiary amine, preferably N,N-diisopropylethylamine. When the base is N,N-diisopropylethylamine, the yield of the ester compound is the highest.

[0038] Preferably, the wavelength of the light source is 365-480 nm.

[0039] Preferably, the power of the light source is 15-25W.

[0040] Preferably, the molar ratio of the alcohol compound to the carboxylic acid compound is 1:1 to 20:1.

[0041] Preferably, the molar ratio of the alcohol compound to the carboxylic acid compound is 10:1.

[0042] Preferably, the molar ratio of the alkaline substance to the carboxylic acid compound is 1:1 to 10:1.

[0043] Preferably, the molar ratio of the alkaline substance to the carboxylic acid compound is 5:1.

[0044] Preferably, the molar ratio of the photocatalyst to the carboxylic acid compound is 0.010:1 to 0.002:1.

[0045] Preferably, the molar ratio of the photocatalyst to the carboxylic acid compound is 0.005:1.

[0046] Preferably, during the reaction, the pressure of sulfur hexafluoride gas is 1 to 3 atm.

[0047] Preferably, during the reaction, the sulfur hexafluoride gas pressure is 1 atm. When the pressure is 1 atm, the yield of the ester compound is the highest.

[0048] Preferably, the reaction temperature is 0 to 50° C., and the reaction time is 5 to 48 hours.

[0049] Preferably, the reaction temperature is 25° C. and the reaction time is 20 h.

[0050] The reaction temperature and reaction time of the present invention can be determined by technicians according to different alcohol compounds and carboxylic acid compounds and actual needs.

[0051] Preferably, the reaction solvent is a mixture of one or more of tetrahydrofuran, acetonitrile, dichloromethane and N,N-dimethylformamide.

[0052] The present invention is carried out in a system with a single organic solvent; if necessary, other organic solvents may also be present in the system, but from the perspective of reaction yield and simplicity of operation, it is preferred not to add other organic solvents, that is, to use a single organic solvent as the reaction solvent.

[0053] Preferably, the usage ratio of the carboxylic acid compound to the reaction solvent is 0.5-0.1 mmol:1 mL.

[0054] Preferably, the usage ratio of the carboxylic acid compound to the reaction solvent is 0.17 mmol:1 mL; when the usage ratio is 0.17 mmol:1 mL, the yield of the ester compound is the highest.

[0055] The present invention also provides a gas-liquid mixed flow photochemical device using the above-mentioned carboxylic acid esterification method, the device comprising a liquid and gas injection part, a four-way mixer, a photoreactor, a gas-liquid separator, a collection part and a circulation part connected in sequence;

[0056] The four-way mixer comprises: a gas input port, a liquid input port and a mixture output port; the gas input port is connected to the gas push injection part and the circulation part; the liquid input port is connected to the liquid push injection part; the mixture output port is connected to the photoreactor;

[0057] The interior of the four-way mixer is a hollow sphere, and millimeter-level small holes are evenly distributed on the outer wall of the sphere, and the outer wall is tightly connected with the input and output ports.

[0058] The advantages of the present invention are:

[0059] (1) In the present invention, amines and carboxylic acid compounds that are easily available are used as reaction substrates, commercially available Ir[dF(CF3)ppy]2(dtbbpy)PF6 and the like are used as photocatalysts, and cheap and easily available N,N-diisopropylethylamine and the like are used as bases, and ester compounds are synthesized simply and efficiently under SF6 gas. Compared with other methods for synthesizing ester compounds, the reaction conditions of the present invention are mild, the reaction raw materials used (including alcohol compounds and carboxylic acid compounds, N,N-diisopropylethylamine) are cheap and easily available, and the method has the characteristics of cost saving, environmental friendliness, and industrial promotion. The method effectively activates and utilizes SF6, a greenhouse gas, and fully utilizes the decomposition products of SF6 to realize the esterification reaction of carboxylic acids, turning SF6 into treasure. The required raw materials are simple and easily available, the reaction conditions are simple, and the method is green and energy-saving, and has a high application value.

[0060] (2) The present invention is applicable to a variety of carboxyl-containing compounds and has successfully synthesized a variety of ester drug molecules. It can be widely used in drug synthesis and total synthesis of natural products in industry and academia, and has high application value.

[0061] (3) The present invention increases the gas-liquid mixing area and the mixing pressure inside the mixer by setting a four-way mixer with a unique structure in the device for gas-liquid mixing continuous flow photoreaction using the carboxylic acid esterification reaction method; the mixing efficiency of liquid and gas is improved for the chemically stable and non-polar gas such as sulfur hexafluoride SF6 used in the method. At the same time, by constructing a cyclic reaction path for the continuous flow photochemical reaction, the gas raw material is fully utilized, achieving the purpose of zero emission of SF6 gas, which has a serious impact on the greenhouse effect. BRIEF DESCRIPTION OF THE DRAWINGS

[0062] Figure 1 [1,1'-biphenyl]-4-carboxylic acid ethyl ester described in Example 1 of the present invention 1 H NMR nuclear magnetic spectrum;

[0063] Figure 2 [1,1'-biphenyl]-4-carboxylic acid ethyl ester described in Example 1 of the present invention 13 C NMR nuclear magnetic spectrum;

[0064] Figure 3 1-Benzofuran-5-carboxylic acid ethyl ester described in Example 2 of the present invention 1 H NMR nuclear magnetic spectrum;

[0065] Figure 4 1-Benzofuran-5-carboxylic acid ethyl ester described in Example 2 of the present invention 13 C NMR nuclear magnetic spectrum;

[0066] Figure 5 It is the ethyl p-methoxyphenylacetate described in Example 3 of the present invention 1 H NMR nuclear magnetic spectrum;

[0067] Figure 6 It is the ethyl p-methoxyphenylacetate described in Example 3 of the present invention 13 C NMR nuclear magnetic spectrum;

[0068] Figure 7 This is a schematic structural diagram of a gas-liquid mixed flow photochemical device for performing carboxylic acid esterification reaction according to Example 4 of the present invention;

[0069] Figure 8 This is a schematic diagram of a four-way mixer of a gas-liquid mixed flow photochemical device for performing a carboxylic acid esterification reaction in Example 4 of the present invention.

[0070] in:

[0071] 1-gas supply bottle; 2-gas pipe; 3-liquid pipe; 4-liquid storage bottle; 5-liquid injection pump; 6-pressure reducing valve; 7-gas flow meter; 8-check valve I; 9-four-way mixer; 10-mixing tube; 11-photoreactor; 12-gas-liquid separator; 13-gas outlet pipe; 14-gas collecting bottle; 15-gas injection pump; 16-gas flow meter; 17-check valve II; 18-liquid outlet pipe; 19-circulating material bottle. DETAILED DESCRIPTION

[0072] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0073] Unless otherwise specified, the test materials and reagents used in the following examples can be obtained from commercial sources.

[0074] If no specific techniques or conditions are specified in the examples, they can be carried out according to the techniques or conditions described in the literature in the art or according to the product instructions.

[0075] In the present invention, "ester compound" has the meaning commonly understood by those skilled in the art, that is, a substance containing an ester group.

[0076] In the present invention, "alcohol compounds" have the meaning commonly understood by those skilled in the art, that is, compounds containing a hydroxyl group connected to a carbon atom on an alkyl group, such as methanol, ethanol or various substituted derivatives thereof.

[0077] In the present invention, "carboxylic acid compounds" have the meaning commonly understood by those skilled in the art, i.e., compounds containing a carboxyl group connected to a carbon atom on an aromatic group or an alkyl group, such as benzoic acid, 4-biphenylacetic acid or various substituted derivatives thereof.

[0078] The raw materials used in the following specific examples are all commercially available, and each reagent is purified by means known in the art before use when necessary.

[0079] Example 1

[0080] This embodiment provides a method for synthesizing [1,1'-biphenyl]-4-carboxylic acid ethyl ester using a gas-liquid mixed flow photochemical device. The method is specifically as follows:

[0081] The raw material 4-phenylbenzoic acid (99.0 mg, 1 equiv.), the photocatalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6 (2.8 mg), ethanol (291.8 μL, 10 equiv.), N,N-diisopropylethylamine (434.6 μL), and 3.0 mL of anhydrous tetrahydrofuran were added to the liquid storage bottle 4 (25.0 mL) equipped with a perforated rubber stopper and a magnetic stirring bar, and added to the liquid storage bottle 4 through a syringe, and the solution was stirred until clear by the magnetic stirring bar. The pipette of the injection pump 5 was placed in the hole of the rubber stopper. After the preparation was completed, the gas supply bottle 1 and the pressure reducing valve 6 were opened, and the SF6 gas entered the four-way mixer 9 through the one-way valve I8. At the same time, the injection pump 5 is started. The solution expands along the outer wall of the inner sphere through the liquid input port of the four-way mixer 9 under the thrust of the liquid injection pump 5, and enters the sphere through the millimeter-level holes evenly distributed on the outer wall. The solution is evenly divided into fine liquid flows, which are fully in contact with the SF6 gas filling the inside of the sphere, thereby increasing the contact area between the solution and the gas. At the same time, when the solution leaves the mixing output port of the four-way mixer 9, it is squeezed and divided into fine liquid flows again through the millimeter-level holes evenly distributed on the outer wall of the sphere, thereby increasing the mixing pressure inside the mixer. Thus, the mixing efficiency of the solution and the gas is improved.

[0082] The raw material solution and SF6 gas are fully mixed through a four-way mixer and then enter the photoreactor. The photoreactor 11 is turned on, and the gas-liquid mixture undergoes a continuous flow reaction in the photoreactor 11. The gas-liquid mixture after the reaction is separated into gas and liquid in the gas-liquid separator 12. After the reaction is completed, the organic solvent is removed under vacuum, and [1,1'-biphenyl]-4-carboxylic acid ethyl ester is obtained by silica gel column chromatography (petroleum ether: ethyl acetate volume ratio = 20:1).

[0083] The NMR spectrum of the product [1,1'-biphenyl]-4-carboxylic acid ethyl ester is as follows Figure 1-2 The specific data are as follows: 1 H NMR (400MHz, CDCl3) δ8.15–8.13(m,2H),7.68–7.63(m,4H),7.49–7.46(m,2H),7.42–7.39(m,1H),4.42(q,J=7.2Hz,2H),1.43(t,J=7.2Hz,3H)ppm. 13 C NMR (101MHz, CDCl3) δ166.4,145.4,139.9,130.0,129.1,128.8,128.0,127.2,127.0,60.9,14.3ppm.

[0084] Example 2

[0085] This embodiment provides a method for synthesizing ethyl 1-benzofuran-5-carboxylate using a gas-liquid mixed flow photochemical device.

[0086] This example uses the same apparatus and process as Example 1, and the reaction raw materials use 1-benzofuran-5-carboxylic acid (81.7 mg, 1 equiv.), photocatalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6 (2.8 mg), ethanol (291.8 μL, 10 equiv.), N,N-diisopropylethylamine (434.6 μL, 5 equiv.), 3.0 mL of anhydrous tetrahydrofuran, and SF6 gas. 1-Benzofuran-5-carboxylic acid ethyl ester is obtained.

[0087] The NMR spectrum of the product 1-benzofuran-5-carboxylic acid ethyl ester is as follows Figure 3 and 4 The specific data are as follows: 1 H NMR (400MHz, CDCl3) δ7.68–7.66(m,1H),7.60–7.58(m,1H),7.53–7.52(m,1H),7.4 6–7.42(m,1H),7.32–7.28(m,1H),4.44(q,J=7.2Hz,2H),1.43(t,J=6.8Hz,3H)ppm. 13 C NMR (101MHz, CDCl3) δ159.6,155.6,145.7,127.5,126.9,123.7,122.7,113.7,112.3,61.5,14.3ppm.

[0088] Example 3

[0089] This embodiment provides a method for synthesizing ethyl p-methoxyphenylacetate using a gas-liquid mixed flow photochemical device.

[0090] This example uses the same apparatus and process as Example 1, and the reaction raw materials use p-methoxyphenylacetic acid (83.1 mg, 1 equiv.), photocatalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6 (2.8 mg), ethanol (291.8 μL, 10 equiv.), N,N-diisopropylethylamine (434.6 μL, 5 equiv.), 3.0 mL of anhydrous tetrahydrofuran, and SF6 gas to obtain ethyl p-methoxyphenylacetate.

[0091] The NMR spectrum of the product ethyl p-methoxyphenylacetate is as follows Figure 5 and 6 The specific data are as follows: 1H NMR (400MHz, CDCl3) δ7.21–7.19(m,2H),6.87–6.85(m,2H),4.14(q,J=7.2Hz,2H),3.79(s,3H),3.55(s,2H),1.25(t,J=6.8Hz,3H)ppm. 13 C NMR (101MHz, CDCl3) δ171.9,158.5,130.2,126.1,113.9,60.7,55.1,40.4,14.1ppm.

[0092] As can be seen from Examples 1-3, the present invention uses easily available carboxylic acids and alcohol compounds as reaction substrates, commercially available Ir[dF(CF3)ppy]2(dtbbpy)PF6 as a photocatalyst, cheap and easily available N,N-diisopropylethylamine as a base, and the gas-liquid mixed flow photochemical device for reaction, thereby synthesizing ester compounds simply and efficiently. This method has good reactivity to different alcohol compounds. Therefore, there are actually no particularly strict restrictions on the number and type of substituents in alcohols and carboxylic acids. Furthermore, there are no particularly strict restrictions on the number and type of substituents in ester compounds and their derivatives. Therefore, it is a general method for synthesizing ester compounds with mild conditions, simple operation, and easy industrial promotion. In addition, this method effectively activates and utilizes SF6, a greenhouse gas, and makes full use of the decomposition products of SF6 to realize the esterification reaction of carboxylic acids, turning SF6 into treasure.

[0093] Example 4

[0094] This embodiment discloses a gas-liquid mixed flow photochemical device used in the carboxylic acid esterification reaction in the above embodiments 1-3, such as Figure 7 As shown, the gas-liquid mixed flow photochemical device includes: a liquid and gas push injection unit, a four-way mixer, a photoreactor, a gas-liquid separator, a collection unit and a circulation unit connected in sequence. The liquid push injection unit includes a liquid storage bottle 4, a liquid injection pump 5 and a liquid pipe 3 connected in sequence. The gas push injection unit includes a gas supply bottle 1, a gas pipe 2, a pressure reducing valve 6, a gas flow meter 7, and a one-way valve Ⅰ8 connected in sequence;

[0095] The four-way mixer 9 is as follows Figure 8 As shown, it includes: two gas input ports, a liquid input port and a mixture output port; the gas input port is connected to the gas push injection part and the circulation part; the liquid input port is connected to the liquid push injection part; the mixture output port is connected to the photoreactor 11;

[0096] The interior of the four-way mixer 9 is a hollow sphere, and the outer wall of the sphere is evenly distributed with millimeter-level holes, and the outer wall is tightly connected to the input and output ports;

[0097] Furthermore, the reaction solid raw materials and liquid solvent are prepared into a solution and placed in a liquid storage bottle 4. By stirring, the solution is ensured to be clear and will not cause clogging of the pipeline; the solution flows in the liquid pipe 3 through the liquid injection pump 5 and is transported to the liquid input port of the four-way mixer 9.

[0098] The gas raw material in the gas supply bottle 1 is transported to the gas input port of the four-way mixer 9 through the gas pipe 2, the pressure reducing valve 6, the gas flow meter 7, and the one-way valve I8.

[0099] The gas enters through the gas input port of the four-way mixer 9 through the evenly distributed millimeter-sized holes on the outer wall of the inner sphere, filling the entire sphere;

[0100] The solution expands along the outer wall of the inner sphere through the liquid input port of the four-way mixer 9 under the thrust of the liquid injection pump 5, and enters the sphere through the millimeter-level small holes evenly distributed on the outer wall. The solution is evenly divided into fine liquid flows, which are fully in contact with the gas filling the inside of the sphere, thereby increasing the contact area between the solution and the gas. At the same time, when the solution leaves the mixing output port of the four-way mixer 9, it is squeezed and divided into fine liquid flows again through the millimeter-level small holes evenly distributed on the outer wall of the sphere, thereby increasing the mixing pressure inside the mixer. Thus, the mixing efficiency of liquid and gas is improved.

[0101] The solution and gas are uniformly and fully mixed in the four-way mixer 9 and then transported to the photoreactor 11 through the mixing tube 10 for chemical reaction. The photoreactor includes: a reaction hose, a light source module, and a temperature control module; the reaction hose is connected to the mixing tube 10, and is wound into a column and placed inside the photoreactor 11; the photoreactor 11 chemically reacts the system in the reaction hose. The separation part adopts a gas-liquid separator; the input port of the gas-liquid separator 12 is connected to the above-mentioned reaction hose, and the output port is connected to the circulation part. The collection part includes a gas collection bottle 14 and a circulation material bottle 19; the gas collection bottle 14 collects the remaining gas; the circulation material bottle 19 collects the solution after the reaction. The circulation part includes: an outlet path 13 and a liquid outlet path 18; the outlet path 13 passes through the gas collection bottle 14, the gas injection pump 15, the gas flowmeter 16 and the one-way valve II 17, and is connected to the input port of the four-way mixer 9; the liquid outlet path 18 passes through the circulation material bottle 19 and the liquid injection pump 5 and is connected to the input port of the four-way mixer 9.

[0102] Furthermore, in actual operation, Figure 7As shown, the reaction solid raw materials and liquid raw materials are prepared into a solution and placed in a liquid storage bottle 4. By stirring, the solution is ensured to be clear and will not cause the pipeline to be blocked. Preferably, a suction filter head can also be installed at the inlet of the hose. The solution is transported in the liquid pipe 3 by the liquid injection pump 5 and enters the four-way mixer 9; the liquid injection pump 5 can set the liquid flow rate, which can make the liquid flow evenly in the pipeline, which is simple, convenient and easy to operate. The gas raw material in the gas supply bottle 1 passes through the pressure reducing valve 6, the gas pipe 2 and the gas flow meter 7, and the one-way valve I8, and enters the four-way mixer 9; the gas flow meter 7 can control the gas flow rate to match the liquid flow rate; the one-way valve I8 can prevent the liquid from flowing back into the gas path.

[0103] Furthermore, the four-way mixer 9 connects the gas pipe 2 and the liquid pipe 3, where the gas and liquid are evenly and fully mixed. The gas raw material is evenly mixed with the solution through the four-way mixer 9 and then transported to the photoreactor 11 through the mixing tube 10 for chemical reaction; the photoreactor 11 includes a reaction hose, a light source module, and a temperature control module. The reaction hose is wound into a ring in the photoreactor so that the light source can evenly illuminate the gas-liquid mixed system therein, increase the illumination area, and improve the reaction efficiency; the light source module provides light energy to make the reactants enter an excited state. The temperature control module can heat or cool the reaction system to reach the optimal temperature required for the chemical reaction. By setting the temperature by yourself, it is simple and easy to operate.

[0104] Further, the outlet of the photoreactor is connected to the gas-liquid separator 12. An outlet pipe 13 is arranged at the upper end of the gas-liquid separator 12, a liquid outlet pipe 18 is arranged at the bottom of the gas-liquid separator 12, and a TLC spot plate is arranged at the input port of the gas-liquid separator 12. Through the TLC spot plate observation, the solution raw material is detected. If the raw material in the solution is completely converted, the reaction solution is transported to the circulating material bottle 19 for collection, and the gas is transported to the gas collecting bottle 14 for collection; if the raw material in the solution is not completely converted, the reaction system is separated into gas and liquid at the gas-liquid separator 12 and transported to the circulation part, that is, the gas returns to the four-way mixer 9 after passing through the outlet pipe 13, the gas collecting bottle 14, the gas injection pump 15, the gas flow meter 16, and the one-way valve II 17, and the end of the outlet pipe 13 is connected to the four-way mixer 9; the gas injection pump 15 can well control the flow rate of the unreacted gas, better participate in the subsequent reaction, and also achieve the purpose of zero gas emission. The gas flow meter 16 can more intuitively observe the cumulative flow and instantaneous flow. At the same time, the unreacted solution, raw materials and target products are returned to the circulating material bottle 19 for storage after passing through the liquid outlet pipe 18; when the liquid injection pump 5 has delivered the original material, the solution stored in the circulating material bottle 19 is re-injected into the four-way mixer 9 to be fully mixed with the gas, and then delivered to the photoreactor for reaction again. This cycle is repeated until the raw materials in the solution are completely converted through TLC spot plate observation, and the product is collected through the circulating material bottle 19.

[0105] Preferably, in this embodiment, the raw material solution is limited, while the supply of gas can be unlimited. The gas raw material always circulates in the device until the solution raw material is completely converted, the chemical reaction stops, and the solution product is collected for subsequent operations. Therefore, zero emission of reaction gas can be achieved.

[0106] Preferably, in the above-mentioned cyclic reaction, the flow rate can be set, the liquid flow rate is controlled by the liquid injection pump 5, and the gas flow rate is controlled by the gas injection pump 15, so as to achieve the material ratio designed in the experiment.

[0107] Preferably, when all the solution raw materials in this experiment have reacted completely, the gas supply is stopped, and the remaining gas in the system is transported to the gas collecting bottle 14 for collection, thereby further achieving the purpose of zero gas emission.

[0108] Preferably, the gas-liquid separator 12 described in the embodiment of the present invention can accurately control the collection amount or circulation amount of the solution when the solution product is collected or the solution is circulated again through the liquid outlet path, thereby ensuring that a certain volume of solution is always maintained in the gas-liquid separator to avoid gas leakage when the solution product is collected.

[0109] The above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit the same. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that the technical solutions described in the aforementioned embodiments may still be modified, or some of the technical features may be replaced by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for esterification of carboxylic acid, characterized in that: The method is carried out using a gas-liquid mixed flow photochemical device, which includes a liquid and gas injection part and a four-way mixer connected in sequence; the method specifically includes placing an alcohol compound, a carboxylic acid compound, an organic solvent, a photocatalyst and a base in the liquid injection part to obtain a liquid raw material, placing sulfur hexafluoride gas in the gas injection part, and injecting the liquid raw material and the gas into the four-way mixer for sufficient mixing before performing a photochemical reaction to obtain an ester compound.

2. The method for carboxylic acid esterification according to claim 1, characterized in that: The four-way mixer comprises: a gas input port, a liquid input port and a mixture output port; the gas input port is connected to the gas push injection part and the circulation part; the liquid input port is connected to the liquid push injection part; the mixture output port is connected to the photoreactor; the interior of the four-way mixer is a hollow sphere, the outer wall of the sphere is evenly distributed with millimeter-level small holes, and the outer wall is tightly connected to the input and output ports; The liquid raw material and the gas are pushed into the four-way mixer for full mixing as follows: the gaseous sulfur hexafluoride enters through the gas input port of the four-way mixer through the millimeter-level small holes evenly distributed on the outer wall of the inner sphere, filling the entire sphere; the liquid raw material expands along the outer wall of the inner sphere through the liquid input port of the four-way mixer, enters the sphere through the millimeter-level small holes evenly distributed on the outer wall, and is evenly divided into fine liquid flows, which are in full contact with the gas filling the inside of the sphere; and when leaving the four-way mixer, it is squeezed and divided into fine liquid flows again through the millimeter-level small holes evenly distributed on the outer wall of the sphere.

3. The method for carboxylic acid esterification according to claim 1, characterized in that: The structural formula of the carboxylic acid compound is Wherein, R is one of aryl or substituted aryl, alkyl or substituted alkyl.

4. The method for carboxylic acid esterification according to claim 1, characterized in that: The carboxylic acid compound is one of 4-phenylbenzoic acid, benzoic acid, 4-vinylbenzoic acid, 2-iodobenzoic acid, 4-(N,N-dimethylamino)benzoic acid, 4-methoxybenzoic acid, 4-bromobenzoic acid, 4-trifluoromethylbenzoic acid, 4-cyanobenzoic acid, monomethyl isophthalate, 1-benzofuran-5-carboxylic acid, 1-(pyridin-3-yl)-1H-pyrazole-4-carboxylic acid, p-methoxyphenylacetic acid, 4-biphenylacetic acid, 4-methoxycinnamic acid, and phthalic acid.

5. The method for carboxylic acid esterification according to claim 1, characterized in that: The structural formula of the alcohol compound is Wherein, R1 and R2 are respectively one of H, alkyl or substituted alkyl, and aryl or substituted aryl.

6. The method for carboxylic acid esterification according to claim 1, characterized in that: The alcohol compound is one of ethanol, 1-naphthylethanol, isopropanol, diethylaminoethanol, isopentanol, benzyl alcohol and methanol.

7. The method for carboxylic acid esterification according to claim 1, characterized in that: The photocatalyst is an organic photocatalyst or a transition metal photocatalyst, or a mixture of the two.

8. The method for carboxylic acid esterification according to claim 1, characterized in that: The alkaline substance is an organic base.

9. The method for carboxylic acid esterification according to claim 1, characterized in that: The wavelength of the light source is 365-480nm.

10. The method for carboxylic acid esterification according to claim 1, characterized in that: The molar ratio of the alcohol compound to the carboxylic acid compound is 1:1 to 20:

1.

11. The method for carboxylic acid esterification according to claim 1, characterized in that: The molar ratio of the alkaline substance to the carboxylic acid compound is 1:1 to 10:

1.

12. The method for carboxylic acid esterification according to claim 1, characterized in that: The molar ratio of the photocatalyst to the carboxylic acid compound is 0.010:1 to 0.002:

1.

13. The method for carboxylic acid esterification according to claim 1, characterized in that: The reaction solvent is a mixture of one or more of tetrahydrofuran, acetonitrile, dichloromethane and N,N-dimethylformamide.

14. The carboxylic acid esterification method according to any one of claims 1 to 21, characterized in that: The usage ratio of the carboxylic acid compound and the reaction solvent is 0.5-0.1 mmol:1 mL.

15. A gas-liquid mixed flow photochemical device using the carboxylic acid esterification method according to claims 1 to 14, characterized in that: The device comprises a liquid and gas injection part, a four-way mixer, a photoreactor, a gas-liquid separator, a collection part and a circulation part which are connected in sequence; The four-way mixer comprises: a gas input port, a liquid input port and a mixture output port; the gas input port is connected to the gas push injection part and the circulation part; the liquid input port is connected to the liquid push injection part; the mixture output port is connected to the photoreactor; The interior of the four-way mixer is a hollow sphere, and millimeter-level small holes are evenly distributed on the outer wall of the sphere, and the outer wall is tightly connected with the input and output ports.

Images