Method for synthesizing pyrazolone structures using carbon dioxide

Abstract

The present invention relates to the field of pyrazolones synthesis. To address the problem that synthesizing pyrazolones using carbonylation reactions requires expensive transition metal catalysts and highly toxic carbon monoxide, a method for synthesizing pyrazolones using carbon dioxide is provided. The reaction formula is as follows: Compound II reacts with carbon dioxide in an organic solvent under a carbon dioxide atmosphere in the presence of a base to obtain a pyrazolones structure. The present invention utilizes carbon dioxide to synthesize pyrazolones in an environmentally friendly and efficient manner.

Description

Technical Field

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

[0002] Pyrazolones 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.). Pyrazolones are particularly widely studied as one of the most important heterocyclic structures in medicinal chemistry. They have a variety of biological activities, including analgesia, anticancer, antidiabetes, and antiviral (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.). Several carbonylation methodologies have been reported for synthesizing pyrazolones (Org. Lett., 2001, 3, 3651; Tetrahedron Lett., 2016, 57, 3363). However, these reactions require the use of high-equivalent and expensive transition metal catalysts and highly toxic and hazardous carbon monoxide. Direct synthesis of pyrazolones from carbon dioxide has never been reported. 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 pyrazolones by carbonylation reaction, the present invention provides a method for synthesizing pyrazolones by using carbon dioxide, thereby utilizing carbon dioxide to synthesize pyrazolones in a green and efficient manner.

[0004] In order to achieve the above object, the present invention adopts the following technical solutions:

[0005] The method of synthesizing pyrazolone structures using carbon dioxide, the reaction formula is as follows:

[0006]

[0007] The reaction conditions 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.

[0008] Preferably, the R 1 、R 2 、R 3 They are independently selected from hydrogen, C1-C6 alkyl, C6-C16 aryl, and aryl with substituents, wherein 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.

[0009] As a further preference, 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.

[0010] Preferably, the pressure of the carbon dioxide is 0.1-10 atm, more preferably 1-5 atm.

[0011] 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.

[0012] Preferably, the amount of the organic solvent used is 0.5-10 mL / mmol of compound II.

[0013] 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.

[0014] Preferably, the molar ratio of the base to compound II is (0.1-10):1, more preferably (1-5):1.

[0015] Preferably, the reaction temperature is 80-200°C, more preferably 100-160°C.

[0016] Preferably, the reaction time is 10-96 h, more preferably 24-72 h. The reaction progress can be monitored by TLC or HPLC.

[0017] Preferably, after the reaction is completed, the product is purified by post-treatment, which comprises the following steps: adding water to the reaction solution and extracting with ethyl acetate, drying the organic phase, concentrating it, and then purifying it by column chromatography.

[0018] 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

[0019] Figure 1 It is a reaction mechanism diagram of the present invention. DETAILED DESCRIPTION

[0020] The technical solution of the present invention is further described below through specific embodiments.

[0021] 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.

[0022] Example

[0023] In organic chemistry, pyrazolone compounds often possess important biological activities, such as antibacterial and antiviral properties, making their study of them of great significance. Pyrazolones can be used as intermediates in the preparation of pyrazolone dyes and drugs, as well as in the derivatization of carbohydrates. For example, in pharmaceutical applications, pyrazolone derivatives (Pyrazolone Derivatives) are a group of antipyretic and analgesic drugs, represented by phenylbutazone, that belong to the class of nonsteroidal anti-inflammatory drugs (NSAIDs). As early as 1884, antipyrine was synthesized and used as an antipyretic, analgesic, and anti-inflammatory drug. A few years later, aminopyrine was synthesized.

[0024] Pyrazolones contain both a pyrazole ring structure and a keto group. The pyrazole ring consists of two carbon atoms and a nitrogen atom, with the carbon and nitrogen atoms alternately linked to form a five-membered heterocyclic ring. A keto group is a group consisting of a carbon atom and an oxygen atom forming a double bond. The structure of pyrazolones can vary depending on the specific substituents, which can affect the properties and uses of the compound.

[0025] The typical preparation method for pyrazolones requires the use of high equivalents of expensive transition metal catalysts and the highly toxic and hazardous presence of carbon monoxide. Another method, the Knorr pyrazole synthesis, involves the reaction of hydrazine or substituted hydrazines with 1,3-dicarbonyl compounds. Substituted hydrazines include alkyl hydrazines, phenyl hydrazines, heterocyclic aryl hydrazines, and acyl hydrazines. β-ketoesters react with hydrazine or substituted hydrazines to produce pyrazolones. When using β-ketoesters to prepare pyrazolones, a base is typically added. In addition to β-ketoesters as substrates, α-cyanoacetic acid esters can also undergo this reaction to produce pyrazolones substituted at the 5-amino group. The reaction is typically carried out at temperatures between 0 and 100°C, using polar protic solvents such as methanol, ethanol, isopropanol, and water. There are two possible reaction mechanisms: one in which both nitrogen atoms of the hydrazine simultaneously attack both carbonyl groups, followed by dehydration to produce the pyrazole; the other in which one nitrogen atom of the hydrazine first attacks one of the more electrophilic carbonyl groups, forming a hydrazone, which then reacts with the carbonyl carbon of the other carbonyl group and dehydrates to produce the product.

[0026] The present invention provides a method for synthesizing pyrazolone structures using carbon dioxide, which uses carbon dioxide to synthesize pyrazolone structures in a green and efficient manner. The specific method is as follows:

[0027] A method for synthesizing pyrazolone structures using carbon dioxide, the reaction formula is as follows:

[0028]

[0029] R in compound II 1 、R 2 、R 3 Each of the substituents is independently selected from hydrogen, a C1-C6 alkyl group, a C6-C16 aryl group (more preferably a phenyl group), and a substituted aryl group (more preferably a phenyl group). The substituent is one or more of a C1-C10 alkyl group, a C2-C10 alkenyl group, a C2-C10 alkynyl group, a C1-C10 alkoxy group, a C1-C10 alkylamino group, a C1-C10 acyl group, a C3-C30 cycloalkyl group, a halogen, a halogenated C1-C6 alkyl group, a C6-C16 aryl group, a C1-C6 acyloxy group, and a C1-C6 amide group; more preferably, one of a C1-C10 alkyl group, a C1-C10 alkoxy group, and a halogen group.

[0030] The reaction conditions in the above reaction formula are as follows: Compound II reacts with carbon dioxide in an organic solvent in the presence of a base under a carbon dioxide atmosphere to obtain the pyrazolone structure I. After completion of the reaction, 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. More preferably, the drying is performed using anhydrous sodium sulfate. The steps and conditions for the column chromatography can be selected according to conventional column chromatography steps and conditions in the art.

[0031] The pressure of the carbon dioxide is 0.1-10 atm, more preferably 1-5 atm.

[0032] 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.

[0033] The amount of the organic solvent used is 0.5-10 mL / mmol of compound II.

[0034] 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.

[0035] The molar ratio of the base to compound II is (0.1-10):1, more preferably (1-5):1.

[0036] The reaction temperature is 80-200°C, more preferably 100-160°C.

[0037] The reaction time is 10-96 h, more preferably 24-72 h. The reaction progress can be monitored by TLC or HPLC.

[0038] 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, followed by intramolecular ring closure to obtain the product and its tautomers 2″′, 2′, 2″, which are then post-treated to obtain the final product 2. Under the reaction conditions, there may be mutual conversion between intermediate I and intermediate I'.

[0039] Example 1

[0040]

[0041] A method for synthesizing pyrazolone structures using carbon dioxide, as shown in Formula 1, comprises reacting 1 mmol of substrate 1a with carbon dioxide at 140°C for 48 hours in 2 mL of N,N-dimethylformamide (DMF) as a solvent in the presence of 4 eq (equivalent) of lithium tert-butoxide under 1 atm carbon dioxide atmosphere to obtain pyrazolone structure 2a.

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

[0043] The proton 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).

[0044] Example 2

[0045] A method for synthesizing pyrazolone structures using carbon dioxide, as shown in Formula 1, comprises reacting 1 mmol of substrate 1a with carbon dioxide at 140°C for 48 hours in 2 mL of N,N-dimethylformamide (DMF) as a solvent in the presence of 3 equivalents of lithium tert-butoxide under 1 atm carbon dioxide atmosphere to obtain pyrazolone structure 2a.

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

[0047] Example 3

[0048] A method for synthesizing pyrazolone structures using carbon dioxide, as shown in Formula 1, comprises reacting 1 mmol of substrate 1a with carbon dioxide at 130°C for 48 hours in 2 mL of N,N-dimethylformamide (DMF) as a solvent in the presence of 4 eq (equivalent) of lithium tert-butoxide under 1 atm carbon dioxide atmosphere to obtain pyrazolone structure 2a.

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

[0050] Example 4

[0051] A method for synthesizing pyrazolone structures using carbon dioxide, as shown in Formula 1, comprises reacting 1 mmol of substrate 1a with carbon dioxide at 140°C for 48 hours in 2 mL of dimethyl sulfoxide (DMSO) as a solvent under 1 atm carbon dioxide atmosphere in the presence of 4 eq (equivalent) of lithium tert-butoxide to obtain pyrazolone structure 2a.

[0052] After the reaction is completed, the product is purified by post-treatment, wherein the post-treatment steps include: adding water to the reaction solution and extracting with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, concentrating, and then purifying by column chromatography.

[0053] Comparative Example 1

[0054] A method for synthesizing pyrazolone structures using carbon dioxide, as shown in Formula 1, comprises reacting 1 mmol of substrate 1a with carbon dioxide at 140°C for 48 hours in the presence of 4 eq (equivalent) of lithium tert-butoxide in 2 mL of diethylene glycol dimethyl ether as a solvent under 1 atm carbon dioxide atmosphere to obtain pyrazolone structure 2a.

[0055] After the reaction is completed, the product is purified by post-treatment, wherein the post-treatment steps include: adding water to the reaction solution and extracting with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, concentrating, and then purifying by column chromatography.

[0056] Comparative Example 2

[0057] A method for synthesizing pyrazolone structures using carbon dioxide, as shown in Formula 1, comprises reacting 1 mmol of substrate 1a with carbon dioxide at 140°C for 48 hours in 2 mL of N,N-dimethylformamide (DMF) as a solvent in the presence of 4 eq (equivalent) of cesium fluoride (CsF) under a 1 atm carbon dioxide atmosphere to obtain pyrazolone structure 2a.

[0058] After the reaction is completed, the product is purified by post-treatment, wherein the post-treatment steps include: adding water to the reaction solution and extracting with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, concentrating, and then purifying by column chromatography.

[0059] Comparative Example 3

[0060] A method for synthesizing pyrazolone structures using carbon dioxide, as shown in Formula 1, comprises reacting 1 mmol of substrate 1a with carbon dioxide at 140°C for 48 hours in 2 mL of N,N-dimethylformamide (DMF) as a solvent in the presence of 4 eq (equivalent) of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) under a 1 atm carbon dioxide atmosphere to obtain pyrazolone structure 2a.

[0061] 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 then purifying by column chromatography.

[0062] The difference between Examples 2-4 and Comparative Examples 1-3 and Example 1 lies in the different reaction conditions. The specific differences and the isolated yields are summarized in Table 1. As can be seen from the table, different bases and different solvents have a significant impact 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%.

[0063] Table 1. Yield table of Examples 1-4 and Comparative Examples 1-3

[0064]

[0065] Example 5-39

[0066] 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. The details are as follows:

[0067]

[0068] A method for synthesizing a pyrazolone structure using carbon dioxide, as shown in Formula 2, comprises reacting 1 mmol of substrate 1 with carbon dioxide in a 1 atm carbon dioxide atmosphere in the presence of lithium tert-butoxide using N,N-dimethylformamide (DMF) as a solvent to obtain a pyrazolone structure 2.

[0069] After the reaction is completed, the product is purified by post-treatment. The post-treatment steps are: 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, and calculating the separation yield of the product.

[0070] Table 2. Products and yields of Examples 5-39

[0071] Note: Unless otherwise noted, reactions were performed under 1 atm CO2 atmosphere, with 2 mL of N,N-dimethylformamide (DMF) as solvent. 1 mmol of substrate 1 was reacted with CO2 at 140°C in the presence of 4 mmol of lithium tert-butoxide for 48 hours. 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 mL of N,N-dimethylformamide (DMF) as solvent and 4 mmol of lithium tert-butoxide under 1 atm carbon dioxide atmosphere.

[0072] As can be seen from Table 2, the preparation method of the present invention can prepare pyrazolone compounds with various structures. And most of the yields are between 70% and 80%, which is high. 1 There are phenyl, naphthyl, benzothiophene, vinylbenzene, benzyl, tert-butyl and phenyl with substituents, the substituents are 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 position. 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.

[0073] Proton spectrum data of the product

[0074] 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).

[0075] 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).

[0076] 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).

[0077] 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).

[0078] The hydrogen spectrum data of 2f is 1H 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).

[0079] 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).

[0080] 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).

[0081] 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).

[0082] 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).

[0083] The hydrogen spectrum data at 2k is 1H 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).

[0084] 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).

[0085] The hydrogen spectrum data of 2m is 1 H 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).

[0086] 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).

[0087] 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).

[0088] 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).

[0089] The hydrogen spectrum data of 2q is 1H 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).

[0090] 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).

[0091] The 2s hydrogen spectrum data is 1 H 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).

[0092] 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).

[0093] 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).

[0094] 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).

[0095] The hydrogen spectrum data of 2w is 1H 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).

[0096] 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).

[0097] The hydrogen spectrum data of 2y is 1 H 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).

[0098] 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).

[0099] 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).

[0100] The hydrogen spectrum data of 2zc is 1H 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).

[0101] 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).

[0102] The proton 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).

[0103] 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).

[0104] 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).

[0105] 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).

[0106] The hydrogen spectrum data of 2af is 1H 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).

[0107] 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).

[0108] The above description is merely a preferred embodiment of the present invention and does not constitute any form of limitation to the present invention. Although the present invention has been disclosed as a preferred embodiment, it is not intended to limit the present invention. Any technician familiar with the present 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 modifications, equivalent changes and modifications 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 are still within the scope of the technical solution of the present invention.

Claims

1. A method for synthesizing pyrazolone structures using carbon dioxide, characterized in that include: Under a carbon dioxide atmosphere, in an organic solvent, under the action of a base, compound II reacts with carbon dioxide to obtain pyrazolone structure I; The reaction formula is as follows: R 1 、R 2 、R 3 Independently selected from hydrogen, C1-C6 alkyl, C6-C16 aryl, and substituted phenyl; 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, and triethylamine; The substituent is one of a C1-C10 alkyl group, a C1-C10 alkoxy group, and a halogen group.

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

3. The method according to claim 2, characterized in that The pressure of the carbon dioxide is 1-1 / 5 atm.

4. The method according to claim 1, wherein 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, wherein The molar ratio of the base to compound II is (0.1-10):

1.

7. The method according to claim 6, characterized in that The molar ratio of the base to compound II is (1-5):

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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