Method for synthesizing pyrazolone structure by using carbon dioxide

Abstract

The invention relates to the field of synthesis of pyrazolone, and provides a method for synthesizing a pyrazolone structure by utilizing carbon dioxide aiming at the problem that an expensive transition metal catalyst and high-toxicity carbon monoxide are needed for synthesizing pyrazolone by utilizing carbonylation reaction, and the reaction formula is as follows: # imgabs0 # reaction conditions are as follows: in the presence of carbon dioxide, in an organic solvent and under the action of alkali, the reaction is carried out for 1-3 hours, so that the pyrazolone structure is synthesized by utilizing carbon dioxide. And reacting the compound II with carbon dioxide to obtain the pyrazolone structure. According to the method, the pyrazolone structure is synthesized in a green and efficient manner by utilizing carbon dioxide.

Description

Technical Field

[0001] The invention relates to the field of pyrazolone synthesis, in particular to a method for synthesizing pyrazolone structures by utilizing carbon dioxide. Background Art

[0002] Pyrazolone compounds are valuable compounds that play an important role in medicinal chemistry, functional materials, dyes, etc. (Dye. Pigm. 2012, 95, 580; J. Saudi Chem. Soc. 2018, 22, 705; J. Mol. Liq. 2019, 288, 110994; Dye. Pigm. 2019, 160, 853; Materials 2020, 13, 5698; Appl. Organomet. Chem. 2022, 36, e6563.). Pyrazolone compounds are especially widely studied as one of the most important heterocyclic structures in medicinal chemistry. They have a variety of biological activities, including analgesia, anti-cancer, anti-diabetes, antiviral, etc. (Inorganica Chim. Acta 2010,363,289; J.Med.Chem.2010,53,8727; BioorganicMed.Chem.Lett.2015,25,3535; Chem.Cent.J.2017, 11,112; Eur.J.Med.Chem.2018,159,47; Bioorg.Chem.2018,78,103; Bioorg.Med.Chem.2021,40,116187.). At present, some reaction methodologies for synthesizing pyrazolone compounds using carbonylation reactions have been reported (Org. Lett., 2001, 3, 3651.; Tetrahedron Lett., 2016, 57, 3363.), but these reactions require the use of high equivalent and expensive transition metal catalysts and highly toxic and dangerous carbon monoxide. There has never been a report on a method for directly synthesizing pyrazolone structures using carbon dioxide. Summary of the invention

[0003] In order to overcome the problem that expensive transition metal catalysts and highly toxic carbon monoxide are required for synthesizing pyrazolone by carbonylation reaction, the present invention provides a method for synthesizing pyrazolone structures by using carbon dioxide, and synthesizes pyrazolone structures by using carbon dioxide in a green and efficient manner.

[0004] In order to achieve the above object, the present invention adopts the following technical solutions: The method of synthesizing pyrazolone structures using carbon dioxide, the reaction formula is as follows: The reaction conditions are: in an organic solvent under a carbon dioxide atmosphere, under the action of a base, compound II is reacted with carbon dioxide to obtain pyrazolone structure I.

[0005] Preferably, the R 1 , R 2 , R 3 They are independently selected from hydrogen, C1-C6 alkyl, C6-C16 aryl, and aryl with substituents, and the substituents are one or more of C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 alkoxy, C1-C10 alkylamino, C1-C10 acyl, C3-C30 cycloalkyl, halogen, halogenated C1-C6 alkyl, C6-C16 aryl, C1-C6 acyloxy, and C1-C6 amide.

[0006] As further preferred, the aryl group is a phenyl group, and the substituent is one of a C1-C10 alkyl group, a C1-C10 alkoxy group, and a halogen group.

[0007] Preferably, the pressure of the carbon dioxide is 0.1-10 atm, more preferably 1-5 atm.

[0008] Preferably, the organic solvent is one or more of N,N-dimethylformamide, dimethyl sulfoxide, N,N-dimethylacetamide, N-methylpyrrolidone, diethylene glycol dimethyl ether, 1,2-dimethoxyethane, p-xylene, m-xylene, o-xylene, mesitylene, trifluorotoluene, toluene, 1,4-dioxane, anisole, tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether and 1,2-dichloroethane.

[0009] Preferably, the amount of the organic solvent used is 0.5-10 mL / mmol of compound II.

[0010] Preferably, the base is one or more of lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, cesium fluoride, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, lithium hydroxide, sodium hydroxide, potassium hydroxide, 1,4-diazabicyclo[2.2.2]octane, triethylamine, and diisopropylethylamine.

[0011] Preferably, the molar ratio of the base to compound II is (0.1-10):1, more preferably (1-5):1.

[0012] Preferably, the reaction temperature is 80-200°C, more preferably 100-160°C.

[0013] Preferably, the reaction time is 10-96 h, more preferably 24-72 h. The reaction progress can be monitored by TLC or HPLC.

[0014] Preferably, after the reaction is completed, the product is purified by post-treatment, which comprises the following steps: adding water to the reaction solution, extracting with ethyl acetate, drying the organic phase, concentrating it, and purifying it by column chromatography.

[0015] Therefore, the beneficial effects of the present invention are: directly using carbon dioxide to synthesize pyrazolone structures, avoiding the use of expensive transition metal catalysts and highly toxic and dangerous carbon monoxide, and the preparation method is green and efficient. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 It is a reaction mechanism diagram of the present invention. DETAILED DESCRIPTION

[0017] The technical solution of the present invention is further described below through specific embodiments.

[0018] In the present invention, unless otherwise specified, the raw materials and equipment used can be purchased from the market or are commonly used in the art. The methods in the embodiments, unless otherwise specified, are all conventional methods in the art.

[0019] Example In organic chemistry, pyrazolone compounds often have important biological activities, such as antibacterial and antiviral activities, so their research is of great significance. Pyrazolone can be used as an intermediate for the preparation of pyrazolone dyes and drugs, and can also be used for the derivatization of sugars. For example, in the application of drugs: Pyrazolone (Pyrazolon Derivatives) antipyretic analgesic is a group of drugs represented by phenylbutazone, which belongs to non-steroidal anti-inflammatory drugs (NSAID). As early as 1884, antipyrine was synthesized and used as an antipyretic analgesic and anti-inflammatory drug. A few years later, aminopyrine was synthesized.

[0020] Pyrazolone compounds contain both a pyrazole ring structure and a keto group. The pyrazole ring is composed of two carbon atoms and one nitrogen atom, and the carbon atoms and nitrogen atoms are alternately connected to form a five-membered heterocyclic structure. The keto group is a group in which a carbon atom forms a double bond with an oxygen atom. The structure of pyrazolone compounds can vary depending on the specific substituents, and the difference in substituents can affect the properties and uses of the compound.

[0021] The general preparation method of pyrazolones requires the use of high equivalent and expensive transition metal catalysts and highly toxic and dangerous carbon monoxide. In addition, there is the Knorr pyrazole synthesis method. The Knorr pyrazole synthesis method involves the reaction of hydrazine or substituted hydrazine with 1,3-dicarbonyl compounds. Substituted hydrazines include alkyl hydrazines, phenyl hydrazines, heterocyclic aromatic hydrazines and acyl hydrazines. β-ketoesters react with hydrazine or substituted hydrazines to produce pyrazolones. When β-ketoesters are used to prepare pyrazolones, a base is usually added to the reaction. In addition to β-ketoesters as substrates, α-cyanoacetic acid esters can also undergo this reaction to produce pyrazolones substituted with 5-amino groups. The reaction is usually carried out at 0 to 100 ° C, and the commonly used solvents are polar protic solvents such as methanol, ethanol, isopropanol and water. There are two possible reaction mechanisms: one is that the two nitrogen atoms of hydrazine attack the two carbonyl groups at the same time, and then dehydrate to obtain pyrazole; the other is that one nitrogen atom of hydrazine first attacks one of the more electrophilic carbonyl groups to form a hydrazone, and then reacts with the other carbonyl carbon to dehydrate to obtain the product.

[0022] The present invention provides a method for synthesizing a pyrazolone structure using carbon dioxide, which uses carbon dioxide to synthesize a pyrazolone structure in a green and efficient manner. The specific method is as follows: A method for synthesizing pyrazolone structures using carbon dioxide, the reaction formula is as follows: R in compound II 1 , R 2 , R 3 They are independently selected from hydrogen, C1-C6 alkyl, C6-C16 aryl (more preferably phenyl), aryl with a substituent (more preferably phenyl). The substituent is one or more of C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 alkoxy, C1-C10 alkylamino, C1-C10 acyl, C3-C30 cycloalkyl, halogen, halogenated C1-C6 alkyl, C6-C16 aryl, C1-C6 acyloxy, C1-C6 amide; more preferably, one of C1-C10 alkyl, C1-C10 alkoxy, and halogen.

[0023] The reaction conditions of the above reaction formula are: in an organic solvent under a carbon dioxide atmosphere, under the action of a base, compound II reacts with carbon dioxide to obtain pyrazolone structure I. After the reaction is completed, the product is purified by post-treatment, and the post-treatment comprises the following steps: adding water to the reaction solution and extracting with ethyl acetate, drying the organic phase, concentrating and purifying by column chromatography. As further preferred, the drying uses anhydrous sodium sulfate. The steps and conditions of the column chromatography can be selected according to the steps and conditions of column chromatography conventional in the art.

[0024] The pressure of the carbon dioxide is 0.1-10 atm, more preferably 1-5 atm.

[0025] The organic solvent is one or more of N,N-dimethylformamide, dimethyl sulfoxide, N,N-dimethylacetamide, N-methylpyrrolidone, diethylene glycol dimethyl ether, 1,2-dimethoxyethane, p-xylene, m-xylene, o-xylene, mesitylene, trifluorotoluene, toluene, 1,4-dioxane, anisole, tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether and 1,2-dichloroethane.

[0026] The amount of the organic solvent used is 0.5-10 mL / mmol of compound II.

[0027] The base is one or more of lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, cesium fluoride, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, lithium hydroxide, sodium hydroxide, potassium hydroxide, 1,4-diazabicyclo[2.2.2]octane, triethylamine, and diisopropylethylamine.

[0028] The molar ratio of the base to compound II is (0.1-10):1, more preferably (1-5):1.

[0029] The reaction temperature is 80-200°C, more preferably 100-160°C.

[0030] The reaction time is 10-96 h, more preferably 24-72 h. The reaction progress can be monitored by TLC or HPLC.

[0031] The reaction mechanism of the present invention is as follows Figure 1 As shown, compound 1 generates intermediate 1-1 under alkaline conditions, intermediate 1-1 reacts with carbon dioxide to generate intermediate 1-2, intermediate 1-2 further reacts with carbon dioxide under reaction conditions to generate intermediate 1-3, intermediate 1-3 may be converted into intermediate 1-4 or intermediate 1-5 under the action of base, and then an intramolecular ring closure process occurs to obtain the product and its tautomers 2″′, 2′, 2″, and the final product 2 is obtained after post-treatment. Under the reaction conditions, there may be mutual conversion between intermediate I and intermediate I'.

[0032] Example 1 A method for synthesizing a pyrazolone structure using carbon dioxide, as shown in Formula 1, under 1 atm carbon dioxide atmosphere, with 2 mL of N,N-dimethylformamide (DMF) as solvent, in the presence of 4 eq (equivalent) of lithium tert-butoxide, 1 mmol of substrate 1a is reacted with carbon dioxide at 140° C. for 48 hours to obtain a pyrazolone structure 2a.

[0033] After the reaction is completed, the product is purified by post-treatment, wherein the post-treatment steps are: adding water to the reaction solution and then extracting with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, concentrating and purifying by column chromatography.

[0034] The hydrogen spectrum data of 2a is 1 H NMR (500MHz, CD3CO2D): 7.86 (d, J = 7.7Hz, 2H), 7.56-7.49 (m, 4H), 7.44-7.30 (m, 8H), 7.29-7.24 (m, 1H).

[0035] Example 2 A method for synthesizing a pyrazolone structure using carbon dioxide, as shown in Formula 1, under 1 atm carbon dioxide atmosphere, with 2 mL of N,N-dimethylformamide (DMF) as solvent, in the presence of 3 equivalents of lithium tert-butoxide, 1 mmol of substrate 1a is reacted with carbon dioxide at 140° C. for 48 hours to obtain a pyrazolone structure 2a.

[0036] After the reaction is completed, the product is purified by post-treatment, wherein the post-treatment steps are: adding water to the reaction solution and then extracting with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, concentrating and purifying by column chromatography.

[0037] Example 3 A method for synthesizing a pyrazolone structure using carbon dioxide, as shown in Formula 1, under 1 atm carbon dioxide atmosphere, with 2 mL of N,N-dimethylformamide (DMF) as solvent, in the presence of 4 eq (equivalent) of lithium tert-butoxide, 1 mmol of substrate 1a is reacted with carbon dioxide at 130° C. for 48 hours to obtain a pyrazolone structure 2a.

[0038] After the reaction is completed, the product is purified by post-treatment, wherein the post-treatment steps are: adding water to the reaction solution and then extracting with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, concentrating and purifying by column chromatography.

[0039] Example 4 A method for synthesizing a pyrazolone structure using carbon dioxide, as shown in Formula 1, under 1 atm carbon dioxide atmosphere, with 2 mL of dimethyl sulfoxide (DMSO) as solvent, in the presence of 4 eq (equivalent) of lithium tert-butoxide, 1 mmol of substrate 1a is reacted with carbon dioxide at 140° C. for 48 hours to obtain a pyrazolone structure 2a.

[0040] After the reaction is completed, the product is purified by post-treatment, wherein the post-treatment steps are: adding water to the reaction solution and then extracting with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, concentrating and purifying by column chromatography.

[0041] Comparative Example 1 A method for synthesizing a pyrazolone structure using carbon dioxide, as shown in Formula 1, under 1 atm carbon dioxide atmosphere, with 2 mL of diethylene glycol dimethyl ether as solvent, in the presence of 4 eq (equivalent) of lithium tert-butoxide, 1 mmol of substrate 1a is reacted with carbon dioxide at 140° C. for 48 hours to obtain a pyrazolone structure 2a.

[0042] After the reaction is completed, the product is purified by post-treatment, wherein the post-treatment steps are: adding water to the reaction solution and then extracting with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, concentrating and purifying by column chromatography.

[0043] Comparative Example 2 A method for synthesizing a pyrazolone structure using carbon dioxide, as shown in Formula 1, under 1 atm carbon dioxide atmosphere, with 2 mL of N,N-dimethylformamide (DMF) as solvent, in the presence of 4 eq (equivalent) of cesium fluoride (CsF), 1 mmol of substrate 1a is reacted with carbon dioxide at 140° C. for 48 hours to obtain a pyrazolone structure 2a.

[0044] After the reaction is completed, the product is purified by post-treatment, wherein the post-treatment steps are: adding water to the reaction solution and then extracting with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, concentrating and purifying by column chromatography.

[0045] Comparative Example 3 A method for synthesizing a pyrazolone structure using carbon dioxide, as shown in Formula 1, under 1 atm carbon dioxide atmosphere, with 2 mL of N,N-dimethylformamide (DMF) as solvent, in the presence of 4 eq (equivalent) of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1 mmol of substrate 1a is reacted with carbon dioxide at 140° C. for 48 hours to obtain a pyrazolone structure 2a.

[0046] After the reaction is completed, the product is purified by post-treatment, which includes the following steps: adding water to the reaction solution and extracting with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, concentrating and purifying by column chromatography.

[0047] The difference between Examples 2-4 and Comparative Examples 1-3 and Example 1 is that the reaction conditions are different. The specific differences and separation yields are summarized in Table 1. As can be seen from the table, different bases and different solvents have a great influence on the reaction yield. Example 1 uses lithium tert-butoxide as the base and N,N-dimethylformamide as the solvent, and the yield is the best, reaching 87%.

[0048] Table 1. Yield table of Examples 1-4 and Comparative Examples 1-3 Example 5-39 The difference from Example 1 is that the substrate 1 is different, and the products are 2b-2y, 2za-2zc, and 2aa-2ag in Table 2. Specifically, they are as follows: A method for synthesizing a pyrazolone structure using carbon dioxide, as shown in Formula 2, under 1 atm carbon dioxide atmosphere, with N,N-dimethylformamide (DMF) as solvent, under the action of lithium tert-butoxide, 1 mmol of substrate 1 is reacted with carbon dioxide to obtain a pyrazolone structure 2.

[0049] After the reaction is completed, the product is purified by post-treatment, wherein the post-treatment steps are: adding water to the reaction solution and then extracting with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, concentrating and purifying by column chromatography, and calculating the separation yield of the product.

[0050] Table 2. Products and yields of Examples 5-39 Note: Unless otherwise specified, the reaction conditions are 1 atm carbon dioxide atmosphere, 2 mL N,N-dimethylformamide (DMF) as solvent, 1 mmol of substrate 1 and carbon dioxide are reacted at 140°C for 48 hours in the presence of 4 mmol lithium tert-butoxide. The yields listed in the table are isolated yields. b The reaction temperature was 160°C. c The reaction conditions are as follows: 1.5 mmol of substrate 1 is reacted with carbon dioxide at 160° C. for 48 h in 1 atm carbon dioxide atmosphere with 1 mL of N,N-dimethylformamide (DMF) as solvent and 4 mmol of lithium tert-butoxide.

[0051] As can be seen from Table 2, the preparation method of the present invention can prepare pyrazolone compounds with various structures. Most of them have a yield of 70 to 80 percent, which is high. 1 There are phenyl, naphthyl, benzothiophene, vinylbenzene, benzyl, tert-butyl and phenyl with substitution, the substitution is methoxy, halogen, methyl and trifluoromethyl in the para, meta or ortho position. 2 There are hydrogen, alkyl, phenyl, naphthyl, pyridine and phenyl with substituents, and the substituents are methoxy, halogen, methyl and trifluoromethyl in the para, meta or ortho positions. 3 There are phenyl, naphthyl, alkyl and phenyl with substituents, and the substituents include alkoxy, halogen and alkyl at the para position and meta position.

[0052] Proton spectrum data of the product The hydrogen spectrum data of 2b is 1 H NMR (500MHz, CD3CO2D): δ7.85 (d, J=7.9Hz, 2H), 7.59-7.54 (m, 2H), 7.51 (t, J=7.9Hz, 2H), 7.42-7.32 (m, 5H), 7.30-7.26 (m, 1H), 7.12 (t, J=8.7Hz, 2H).

[0053] The hydrogen spectrum data of 2c is 1 H NMR (500MHz, CD3CO2D): δ7.86 (d, J = 7.8Hz, 2H), 7.54-7.48 (m, 4H), 7.42-7.27 (m, 8H).

[0054] The 2d hydrogen spectrum data is 1 H NMR (500MHz, CD3CO2D): δ7.87 (d, J=7.8Hz, 2H), 7.73-7.63 (m, 4H), 7.52 (t, J=7.9Hz, 2H), 7.41-7.28 (m, 6H).

[0055] The hydrogen spectrum data of 2e is 1 H NMR (500MHz, CD3CO2D): δ7.84(d,J=7.7Hz,2H),7.50(t,J=7.9Hz,2H),7.44-7.39 (m,4H),7.37-7.30(m,3H),7.29-7.24(m,1H),7.20(d,J=8.0Hz,2H),2.36(s,3H).

[0056] The hydrogen spectrum data of 2f is 1 H NMR (500MHz, CF3CO2D): δ7.85-7.75(m,5H),7.67-7.58(m,5H),7.56-7.49(m,2H),7.20-7.10(m,2H),4.08(s,3H).

[0057] The hydrogen spectrum data of 2g is 1 H NMR (500MHz, CD3CO2D): δ7.92(t,J=1.5Hz,1H),7.85(d,J=7.7Hz,2H),7.76(d,J=8.0Hz,1H),7.51( t,J=7.9Hz,2H),7.46(d,J=7.9Hz,1H),7.40-7.33(m,5H),7.32-7.27(m,1H),7.10(t,J=7.9Hz,1H).

[0058] The hydrogen spectrum data of 2h is 1 H NMR (500MHz, CD3CO2D): δ7.83 (d, J = 7.7Hz, 2H), 7.53-7.48 (m, 3H), 7.41-7.33 (m, 4H), 7.32-7.15 (m, 5H), 2.12 (s, 3H).

[0059] The hydrogen spectrum data of 2i is 1 H NMR (500MHz, CD3CO2D): δ7.81(d,J=7.7Hz,2H),7.50(t,J=7.9Hz,2H),7.47-7.41(m,2H),7 .38-7.33(m,3H),7.26(t,J=7.5Hz,2H),7.22-7.17(m,1H),7.03-6.97(m,2H),3.54(s,3H).

[0060] The hydrogen spectrum data of 2j is 1 H NMR (500MHz, CD3CO2D): δ8.14 (s, 1H), 7.91 (d, J = 8.1Hz, 2H), 7.88-7.81 (m, 3H), 7.57-7.49(m,5H),7.46(d,J=7.2Hz,2H),7.39-7.31(m,3H),7.30-7.26(m,1H).

[0061] The hydrogen spectrum data at 2k is 1 H NMR (500MHz, CD3CO2D): δ8.01 (d, J=8.3Hz, 1H), 7.96-7.85 (m, 4H), 7.74-7.68 (m, 1H),7.59-7.46(m,4H),7.44-7.35(m,2H),7.34-7.30(m,2H),7.13-7.03(m,3H).

[0062] The hydrogen spectrum data of 2l is 1 H NMR (500MHz, CD3CO2D): δ7.94-7.86 (m, 3H), 7.84 (s, 1H), 7.68 (d, J = 8.1Hz, 1H), 7.52 (t, J = 7.9Hz, 2H), 7.42-7.33 (m, 4H), 7.28-7.14 (m, 4H).

[0063] The hydrogen spectrum data of 2m is 1H NMR (500MHz, CD3CO2D): δ7.87 (d, J = 7.9 Hz, 2H), 7.60 (d, J = 7.4 Hz, 2H), 7.56-7.30 (m, 12H), 7.09 (d, J = 16.6 Hz, 1H).

[0064] The hydrogen spectrum data of 2n is 1 H NMR (500MHz, CF3CO2D): δ7.99-7.92(m,3H),7.91-7.84(m,5H),7.76-7.71(m,2H),7.68-7.60(m,3H),7.49(d,J=7.1Hz,2H),4.52(s,2H).

[0065] The hydrogen spectrum data of 2o is 1 H NMR (500MHz, CF3CO2D): δ7.95-7.90(m,3H),7.89-7.80(m,5H),7.75-7.70(m,2H),1.68(s,9H).

[0066] The hydrogen spectrum data of 2p is 1 H NMR (500MHz, CD3CO2D): 7.85 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 7.0 Hz, 2H), 7.50 (t, J = 7.9 Hz, 2H), 7.43-7.31 (m, 6H), 6.90 (d, J = 8.7 Hz, 2H), 3.80 (s, 3H).

[0067] The hydrogen spectrum data of 2q is 1 H NMR (500MHz, CD3CO2D): δ7.87-7.82(m,2H), 7.56-7.48(m,4H), 7.43-7.33(m,4H), 7.29(d,J=8.1Hz,2H), 7.14(d,J=7.9Hz,2H), 2.33(s,3H).

[0068] The hydrogen spectrum data of 2r is 1 H NMR (500MHz, CD3CO2D): δ7.77 (d, J = 7.8Hz, 2H), 7.61-7.51 (m, 4H), 7.50-7.44 (m, 5H), 7.42-7.33 (m, 3H).

[0069] The 2s hydrogen spectrum data is 1H NMR (500MHz, CD3CO2D): δ7.84 (d, J=7.6Hz, 2H), 7.54-7.48 (m, 4H), 7.47-7.33 (m, 6H), 7.09-7.03 (m, 2H).

[0070] The hydrogen spectrum data of 2t is 1 H NMR (500MHz, CD3CO2D): δ7.88-7.83(m,2H),7.62(t,J=1.7Hz,1H),7.57-7.49(m,4H),7.48-7.40(m,4H),7.39-7.34(m,2H),7.22(t,J=7.9Hz,1H).

[0071] The hydrogen spectrum data of 2u is 1 H NMR (500MHz, CF3CO2D): δ7.82(d,J=7.9Hz,1H),7.77(s,1H),7.70-7.63(m,5H),7 .57-7.52(m,1H),7.48-7.40(m,4H),7.33(d,J=7.7Hz,1H),7.17(t,J=7.8Hz,1H).

[0072] The hydrogen spectrum data of 2v is 1 H NMR (500MHz, CD3CO2D): δ7.90-7.84 (m, 2H), 7.51 (t, J = 8.0Hz, 2H), 7.47-7.44 (m,2H),7.40-7.30(m,4H),7.29-7.23(m,3H),7.22-7.17(m,1H),2.14(s,3H).

[0073] The hydrogen spectrum data of 2w is 1 H NMR (500MHz, CD3CO2D): δ8.01(s,1H),7.91-7.86(m,2H),7.83-7.75(m,3H),7.58-7.49(m,4H),7.48-7.34(m,7H).

[0074] The hydrogen spectrum data of 2x is 1 H NMR (500MHz, CD3CO2D): δ7.95-7.85(m,5H),7.56-7.49(m,4H),7.49-7.44(m,1H),7.43-7.35(m,4H),7.30-7.25(m,1H),7.23-7.17(m,2H).

[0075] The hydrogen spectrum data of 2y is 1H NMR (500MHz, CD3CO2D): δ9.03(s,1H),8.63(d,J=5.3Hz,1H),8.36(d,J=8.2Hz,1H),7.83(d,J=8.0H z, 2H), 7.79 (dd, J = 8.0, 5.7Hz, 1H), 7.58 (d, J = 7.0Hz, 2H), 7.54-7.44 (m, 5H), 7.38 (t, J = 7.4Hz, 1H).

[0076] The hydrogen spectrum data of 2za is 1 H NMR (400MHz, CDCl3): δ8.04-7.99(m,2H),7.81-7.76(m,2H),7.49-7.41(m,5H),7.24-7.19(m, 1H), 3.87 (dd, J = 6.0, 4.3Hz, 1H), 2.33-2.21 (m, 1H), 2.14-2.02 (m, 1H), 0.84 (t, J = 7.4Hz, 3H).

[0077] The hydrogen spectrum data of 2zb is 1 H NMR (500MHz, CD3CO2D): δ8.04 (d, J = 7.8Hz, 2H), 7.72-7.67 (m, 2H), 7.45 (t, J = 8.0Hz, 2H), 7.42-7.31 (m, 8H), 7.24 (t, J = 7.4Hz, 1H), 1.98 (s, 3H).

[0078] The hydrogen spectrum data of 2zc is 1 H NMR (500MHz, CDCl3): δ7.98 (d, J=8.0Hz, 2H), 7.81-7.75 (m, 2H), 7.50-7.40 (m, 5H), 7.22 (t, J=7.4Hz, 1H), 3.85 (s, 2H).

[0079] The hydrogen spectrum data of 2aa is 1 H NMR (500MHz, CD3CO2D): δ7.66 (d, J = 9.0 Hz, 2H), 7.49-7.43 (m, 4H), 7.42-7.23 (m, 11H), 7.09 (d, J = 9.0 Hz, 2H), 5.12 (s, 2H).

[0080] The hydrogen spectrum data of 2ab is 1 H NMR (500MHz, CF3CO2D): δ8.09 (d, J = 7.7Hz, 2H), 7.87 (d, J = 8.0Hz, 2H), 7.84-7.63 (m, 10H).

[0081] The hydrogen spectrum data of 2ac is 1 H NMR (500MHz, CD3CO2D): δ7.66 (s, 1H), 7.62 (d, J = 8.1Hz, 1H), 7.52 (d, J = 7.3Hz, 2H), 7.45-7. 35(m,6H),7.32(t,J=7.4Hz,2H),7.27(t,J=7.2Hz,1H),7.18(d,J=7.6Hz,1H),2.41(s,3H).

[0082] The hydrogen spectrum data of 2ad is 1 H NMR (500MHz, CD3CO2D): δ8.28 (s, 1H), 8.02-7.90 (m, 4H), 7.58-7.51 (m, 4H), 7.46-7.37 (m, 5H), 7.33 (t, J = 7.4Hz, 2H), 7.27 (t, J = 7.2Hz, 1H).

[0083] The hydrogen spectrum data of 2ae is 1 H NMR (500MHz, CD3CO2D): δ7.40-7.26 (m, 11H), 7.25-7.21 (m, 1H), 6.90 (d, J = 8.7Hz, 2H), 5.22 (s, 2H), 3.78 (s, 3H).

[0084] The hydrogen spectrum data of 2af is 1 H NMR(500MHz,CD3CO2D)δ7.44(d,J=7.2Hz,2H),7.34(t,J=7.6Hz,2H),7.27-7.15(m,6H ), 7.09 (d, J = 7.1Hz, 2H), 6.87 (d, J = 8.7Hz, 2H), 5.11 (s, 2H), 3.99 (s, 2H), 3.76 (s, 3H).

[0085] The hydrogen spectrum data of 2ag is 1 H NMR (600MHz, CDCl3): δ7.32(s,1H),7.26-7.19(m,3H),4.77(s,2H),3.24(s,2H),1.18(s,9H).

[0086] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment as above, it is not used to limit the present invention. Any technician familiar with this profession can make some changes or modifications to equivalent embodiments of equivalent changes using the technical contents disclosed above without departing from the scope of the technical solution of the present invention. However, any simple modification, equivalent change and modification made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A method for synthesizing a pyrazolone structure using carbon dioxide, characterized in that: The reaction formula is as follows: The reaction conditions are: in an organic solvent under a carbon dioxide atmosphere, under the action of a base, compound II is reacted with carbon dioxide to obtain pyrazolone structure I.

2. The method according to claim 1, characterized in that The R 1 , R 2 , R 3 They are independently selected from hydrogen, C1-C6 alkyl, C6-C16 aryl, and aryl with substituents, and the substituents are one or more of C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 alkoxy, C1-C10 alkylamino, C1-C10 acyl, C3-C30 cycloalkyl, halogen, halogenated C1-C6 alkyl, C6-C16 aryl, C1-C6 acyloxy, and C1-C6 amide.

3. The method according to claim 1 or 2, characterized in that: The pressure of the carbon dioxide is 0.1-10 atm.

4. The method according to claim 1, characterized in that: The organic solvent is one or more of N,N-dimethylformamide, dimethyl sulfoxide, N,N-dimethylacetamide, N-methylpyrrolidone, diethylene glycol dimethyl ether, 1,2-dimethoxyethane, p-xylene, m-xylene, o-xylene, mesitylene, trifluorotoluene, toluene, 1,4-dioxane, anisole, tetrahydrofuran, 2-methyltetrahydrofuran, methyl tert-butyl ether and 1,2-dichloroethane.

5. The method according to claim 1 or 4, characterized in that: The amount of the organic solvent used is 0.5-10 mL / mmol of compound II.

6. The method according to claim 1, characterized in that The base is one or more of lithium tert-butoxide, sodium tert-butoxide, potassium tert-butoxide, lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate, cesium fluoride, 1,8-diazabicyclo[5.4.0]undec-7-ene, 1,5-diazabicyclo[4.3.0]non-5-ene, 1,4-diazabicyclo[2.2.2]octane, lithium hydroxide, sodium hydroxide, potassium hydroxide, triethylamine, and diisopropylethylamine.

7. The method according to claim 1 or 6, characterized in that: The molar ratio of the base to compound II is (0.1-10):

1.

8. The method according to claim 1, characterized in that The reaction temperature is 80-200°C.

9. The method according to claim 1 or 8, characterized in that: The reaction time is 10-96h.

10. The method according to claim 9, characterized in that The reaction time is 24-72h.

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