A method for synthesizing itaconic acid compounds

Abstract

This invention discloses a method for synthesizing itaconic acid compounds. The method directly uses allyl ester compounds as raw materials, selects oxalic acid compounds or oxalate amine compounds as acylation reagents, uses triphenylphosphine as an additive, and employs metal-free 3,6,-di-tert-butyl-9-mesethyl-10-phenylacridine-10-tetrafluoroborate as a photo-redox catalyst. Under the catalysis of this organic photo-redox catalyst, corresponding acyl radicals and allyl radicals are generated, respectively. Through radical cross-coupling, itaconic acid compounds are finally obtained. This method has a wide range of applicable substrates, low preparation cost, and simple steps. It is convenient to operate, environmentally friendly, exhibits excellent stereoselectivity, and tolerates a broad spectrum of functional groups.

Description

Technical Field

[0001] This invention belongs to the field of organic chemical synthesis technology, and particularly relates to a method for synthesizing itaconic acid compounds. Background Technology

[0002] With advancements in immunometabolism research, mounting evidence suggests that metabolic changes profoundly impact macrophage immune function. The tricarboxylic acid (TCA) cycle is a core cellular metabolic pathway. Itaconic acid, a byproduct of the TCA cycle, is an emerging small metabolic molecule that modulates macrophage inflammatory responses and has garnered significant attention in recent years due to its potent anti-inflammatory effects. Itaconic acid regulates macrophage function through multiple mechanisms, demonstrating promising therapeutic potential in various immune and inflammatory diseases.

[0003] Therefore, from an environmental and economic perspective, developing green synthetic methods for itaconic acid compounds using non-toxic, inexpensive, readily available, and relatively environmentally friendly raw materials, especially synthetic methods compatible with bioactive molecules, to obtain these specific functional groups, is of great appeal in contemporary chemical biology. Summary of the Invention

[0004] To overcome the shortcomings and deficiencies of the prior art, the primary objective of this invention is to provide a method for synthesizing itaconic acid compounds.

[0005] This invention is achieved by a method for synthesizing itaconic acid compounds, the method comprising the following steps:

[0006] (1) The allyl ester compound, acylation reagent, photo-oxidation-reduction catalyst, and additives were sequentially added to the reaction solvent, and the mixture was stirred for 30 min under an inert gas atmosphere, blue light irradiation, and room temperature to obtain a reaction solution; wherein, the chemical structural formula of the allyl ester compound is shown below:

[0007]

[0008] The chemical structural formula of the acylation reagent is shown below:

[0009]

[0010] (2) Remove the reaction solvent from the reaction solution and then purify itaconic acid compounds by thin-layer chromatography;

[0011] The chemical structural formula of the itaconic acid compounds is shown in formula (I) below:

[0012]

[0013] Among them, R 1It is selected from any one of hydrogen, alkoxy, alkyl, trifluoromethyl, fused aryl, heteroaryl, aliphatic amine, and aromatic amine;

[0014] R 2 It is selected from any one of the following groups: hydrogen-based, methoxy-based, cyano-based, nitro-based, tert-butyl-based, fluorine-based, bromo-based, chloro-based, ferrocene-based, trimethylsilane-ethynyl-based, fused aryl, heteroaryl, cycloalkyl, and straight-chain alkyl.

[0015] Specifically, the allyl ester compound is selected from methyl 2-acetoxy(phenyl)methacrylate, methyl 2-acetoxy(4-fluorobenzene)methacrylate, methyl 2-acetoxy(3-fluorobenzene)methacrylate, methyl 2-acetoxy(2-fluorobenzene)methacrylate, methyl 2-acetoxy(4-chlorobenzene)methacrylate, methyl 2-acetoxy(3-chlorobenzene)methacrylate, methyl 2-acetoxy(2-chlorobenzene)methacrylate, methyl 2-acetoxy(4-bromobenzene)methacrylate, methyl 2-acetoxy(3-bromobenzene)methacrylate, methyl 2-acetoxy(4-nitrobenzene)methacrylate, and methyl 2-acetoxy... Any one of (4-cyanophenyl) methyl methacrylate, 2-acetoxy(4-methoxyphenyl) methyl methacrylate, 2-acetoxy(4-tert-butylphenyl) methyl methacrylate, 2-acetoxy(4-formylphenyl) methyl methacrylate, 2-acetoxy(naphthyl-1-yl) methyl methacrylate, 2-acetoxy(furan-2-yl) methyl methacrylate, 2-acetoxy(phenyl) ethyl methacrylate, 2-cyano-1-phenylallyl acetate, 2-acetoxy-(2,4-dichlorophenyl) menthol methacrylate, and 2-acetoxy-(2,4-dichlorophenyl) methacrylate cholesterol ester;

[0016] The acylation reagent is an oxalate compound or an oxalate amine compound, selected from 2-oxo-2-phenylacetic acid, 2-(4-fluorophenyl)-2-oxoacetic acid, 2-(4-chlorophenyl)-2-oxoacetic acid, 2-(4-bromophenyl)-2-oxoacetic acid, 2-(4-iodophenyl)-2-oxoacetic acid, 2-(2,4,6-trimethylyl)-2-oxoacetic acid, 2-oxobutyric acid, 2-oxopentanoic acid, etc. 2-O-2-(thiophen-2-yl)acetic acid, 2-O-2-(furan-2-yl)acetic acid, 2-O-2-(phenylamino)acetic acid, 2-(cyclopentylamino)-2-oxoacetic acid, 2-(cyclohexylamino)-2-oxoacetic acid, 2-(tert-butylamino)-2-oxoacetic acid, 2-(benzylamino)-2-oxoacetic acid, 2-((2,2-difluoroethyl)amino)-2-oxoacetic acid Acids, 2-oxo-2-((2,2,2-trifluoroethyl)amino)acetic acid, 2-(adamantylamino)-2-oxoacetic acid, 2-(dehydrorosinamino)-2-oxoacetic acid, 2-((2-((2-methoxy-2-oxoethyl)amino)-2-oxoethyl)amino)-2-oxoacetic acid, (S)-2-((1-methoxy-1-oxopropane-2-yl)amino)-2-oxoethyl The acid, (S)-4-isobutyl-3,6,9,12-tetraoxo-2-oxa-5,8,11-triazatridecane-13-oleic acid, and (4S,7S,16S)-7-benzyl-4-isobutyl-16-(4-methoxybenzyl)-3,6,9,12,15,18-hexaoxo-2-oxa-5,8,11,14,17-pentazanephrine-19-oleic acid.

[0017] Preferably, the heteroaryl group is such as furanyl or thiophene; the cycloalkyl group is cyclohexyl.

[0018] Preferably, in step (1), the molar volume ratio of the allyl ester, acylation reagent, 3,6,-di-tert-butyl-9-trimethyl-10-phenylacridine-10-tetrafluoroborate, additive and reaction solvent is (0.2-0.) mmol:(0.24-0.48) mmol:(0.01-0.02) mmol:(0.04-0.08) mmol:(2-4) mL.

[0019] Preferably, in step (1), the inert gas is argon; in step (2), the purified developing solvent system is petroleum ether / ethyl acetate = 5:1.

[0020] Preferably, in step (1), the reaction solvent is selected from any one of toluene, xylene, dichloromethane, acetonitrile, 1,2-dichloroethane, tetrahydrofuran, 1,4-dioxane, and isopropanol.

[0021] Preferably, in step (1), the additive is selected from any one of triphenylphosphine, tris(4-methoxyphenyl)phosphine, 4-dimethylaminopyridine, triethylamine, and triethylenediamine.

[0022] Preferably, in step (1), the photo-oxidation-reduction catalyst is 3,6,-di-tert-butyl-9-trimethyl-10-phenylacridin-10-tetrafluoroborate.

[0023] This invention overcomes the shortcomings of existing technologies and provides a method for synthesizing itaconic acid compounds. This invention directly uses allyl ester compounds as raw materials, selects oxalic acid compounds as acylation reagents, uses triphenylphosphine as an additive, and uses metal-free 3,6,-di-tert-butyl-9-trimethyl-10-phenylacridin-10-tetrafluoroborate as a photo-oxidation-reduction catalyst. Under the catalysis of this organic photo-oxidation-reduction catalyst, the corresponding acyl radicals and allyl radicals are generated respectively, thus enabling the reaction to occur under mild conditions in an environmentally friendly manner. The reaction process is as follows:

[0024]

[0025] Compared with the shortcomings and deficiencies of the prior art, the present invention has the following beneficial effects:

[0026] (1) The allyl ester used in the preparation method of the present invention is a simple esterification raw material of Morit A-Baylis-Hillman alcohol, which is easy to synthesize and has a high conversion rate. It has a wide range of applicable substrates, such as various substituted phenyl or alkyl groups on the allyl ester, and has the characteristics of low preparation cost. In addition, the preparation method of the present invention has simple steps, is convenient to operate, green and environmentally friendly, has excellent stereoselectivity and tolerance to broad-spectrum functional groups.

[0027] (2) The itaconic acid compounds synthesized by the method of the present invention are general precursors for the preparation of related carbonyl molecules, and have potential drug activity and biological activity, which can provide new ways for the synthesis and application of biological and pharmaceutical active molecules. Attached Figure Description

[0028] Figure 1 This is the 1H NMR spectrum of compound (E)-2-benzylidene-4-oxo-4-phenylbutyrate methyl ester in Example 1 of this invention;

[0029] Figure 2 This is the carbon NMR spectrum of compound (E)-2-benzylidene-4-oxo-4-phenylbutyrate methyl ester in Example 1 of this invention; Detailed Implementation

[0030] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.

[0031] Example 1

[0032] (1) In a 10 mL Shrek tube under argon atmosphere, 0.4 mmol of 2-acetoxy(phenyl)methacrylate, 0.48 mmol of 2-oxo-2-phenylacetic acid, 0.02 mmol of 3,6,-di-tert-butyl-9-trimethyl-10-phenylacridine-10-tetrafluoroborate, and 0.08 mmol of triphenylphosphine were added to 4 mL of acetonitrile. The mixture was stirred under argon atmosphere, at room temperature, and irradiated with a 54 W blue lamp. The reaction equation is as follows:

[0033]

[0034] (2) After the reaction was complete as monitored by TLC, the solvent was removed by vacuum rotary evaporator, and the product was separated by thin-layer chromatography with petroleum ether / ethyl acetate system (5:1) as the developing solvent. The product was a colorless transparent liquid compound (E)-2-benzyl-4-oxo-4-phenylbutyrate methyl ester (compound 1) with a yield of 94%.

[0035] The compound (E)-2-benzyl-4-oxo-4-phenylbutyrate methyl ester was characterized, and the results are as follows: Figures 1-2 As shown, Figure 1 This is the 1H NMR spectrum of methyl (E)-2-benzylidene-4-oxo-4-phenylbutyrate; Figure 2 It is the carbon NMR spectrum of methyl (E)-2-benzylidene-4-oxo-4-phenylbutyrate.

[0036] Example 2

[0037] (1) In a 10 mL Shrek tube under argon atmosphere, 0.4 mmol of 2-acetoxy(4-formylphenyl)methyl methacrylate, 0.48 mmol of 2-oxo-2-phenylacetic acid, 0.02 mmol of 3,6,-di-tert-butyl-9-trimethylmethyl-10-phenylacridine-10-tetrafluoroborate, and 0.08 mmol of triphenylphosphine were added to 4 mL of acetonitrile. The mixture was stirred under argon atmosphere, at room temperature, and irradiated with a 54 W blue lamp. The reaction equation is as follows:

[0038]

[0039] (2) After the reaction was complete as monitored by TLC, the solvent was removed by vacuum rotary evaporator, and the product was separated by thin-layer chromatography. The developing solvent was a petroleum ether / ethyl acetate system (5:1). The product was a yellow solid (E)-2-(4-formylbenzyl)-4-oxo-4-phenylbutyrate methyl ester, with a yield of 92%.

[0040] Example 3

[0041] (1) Menthol was added to a dichloromethane solution at room temperature, and triethylamine was added at 0°C, and the mixture was stirred for 0.5 h. Then, a dichloromethane solution of acryloyl chloride was added dropwise to the above reaction solution at 0°C, and the mixture was stirred at room temperature for 12 h to obtain the reaction mixture; wherein the molar ratio of menthol, triethylamine, and acryloyl chloride was 1:2:1; the reaction equation is as follows:

[0042]

[0043] (2) The reaction mixture was quenched with saturated ammonium chloride solution, extracted three times with diethyl ether, the organic phases were combined, dried with anhydrous magnesium sulfate, the solvent was removed under reduced pressure, and the product was separated by column silica gel chromatography with petroleum ether / ethyl acetate system (80:1) as the developing solvent. The product was colorless liquid menthol acrylate with a yield of 93%.

[0044] (3) Under room temperature conditions, 2,4-dichlorobenzaldehyde, menthol acrylate, and triethylenediamine were dissolved in tetrahydrofuran and stirred for 1 week at room temperature to obtain a reaction mixture; wherein the molar ratio of 2,4-dichlorobenzaldehyde, menthol acrylate, and triethylenediamine was 1:1.2:0.5; the reaction equation is:

[0045]

[0046] (4) The reaction mixture was purified by column silica gel chromatography with petroleum ether and ethyl acetate (PE / EA = 30 / 1) to obtain a colorless liquid menthol 2-hydroxy-(2,4-dichlorophenyl)methacrylate in 89% yield.

[0047] (5) Menthol 2-hydroxy-(2,4-dichlorophenyl)methacrylate, acetic anhydride, and 4-dimethylaminopyridine were mixed at room temperature and stirred for 1 hour to obtain a reaction mixture; wherein the molar ratio of menthol 2-hydroxy-(2,4-dichlorophenyl)methacrylate, acetic anhydride, and 4-dimethylaminopyridine was 1:2:0.2.

[0048]

[0049] (6) The reaction mixture was purified by column silica gel chromatography with petroleum ether and ethyl acetate (PE / EA = 1 / 1) to give a white solid 2-acetoxy-(2,4-dichlorophenyl) methacrylate menthol ester, with a yield of 85%.

[0050] (7) Synthesis of itaconic acid compounds

[0051] In a 10 mL Shrek tube, under argon atmosphere, 0.4 mmol of 2-acetoxy(2,4-dichlorophenyl) menthol methacrylate, 0.48 mmol of 2-oxo-2-phenylacetic acid, 0.02 mmol of 3,6,-di-tert-butyl-9-trimethylmethyl-10-phenylacridine-10-tetrafluoroborate, and 0.08 mmol of triphenylphosphine were added to 4 mL of acetonitrile. The mixture was stirred under argon atmosphere, at room temperature, and irradiated with a 54 W blue lamp. The reaction equation is as follows:

[0052]

[0053] (8) After the reaction was complete as monitored by TLC, the solvent was removed by vacuum rotary evaporator, and the product was separated by thin-layer chromatography. The developing solvent was a petroleum ether / ethyl acetate system (5:1). The product was a colorless and transparent liquid compound (E)-2-benzylidene-4-oxo-4-phenylbutyric acid diacetone menthol ester, with a yield of 90%.

[0054] Example 4

[0055] (1) At room temperature, diacetone galactose was added to a dichloromethane solution, and triethylamine was added at 0°C. The mixture was stirred for 0.5 h. Then, a dichloromethane solution of acryloyl chloride was added dropwise to the above reaction solution at 0°C, and the mixture was stirred at room temperature for 12 h to obtain the reaction mixture; wherein the molar ratio of diacetone galactose, triethylamine, and acryloyl chloride was 1:2:1; the reaction equation is:

[0056]

[0057] (2) The reaction mixture was quenched with saturated ammonium chloride solution, extracted three times with dichloromethane, the organic phases were combined, dried with anhydrous magnesium sulfate, the solvent was removed under reduced pressure, and the product was separated by column silica gel chromatography with petroleum ether / ethyl acetate system (80:1) as the developing solvent to obtain white solid diacetone galactose ester of acrylic acid, with a yield of 87%.

[0058] (3) Under room temperature conditions, 2,4-dichlorobenzaldehyde, diacetone galactose acrylate and triethylenediamine are dissolved in tetrahydrofuran and stirred for 1 week at room temperature to obtain a reaction mixture; wherein the molar ratio of 2,4-dichlorobenzaldehyde, diacetone galactose acrylate and triethylenediamine is 1:1.2:0.5.

[0059]

[0060] (4) The reaction mixture was depressurized to remove the solvent, and the residue was purified by column silica gel chromatography with petroleum ether and ethyl acetate (PE / EA = 30 / 1) to give a white solid 2-hydroxy-(2,4-dichlorophenyl)methacrylate diacetone galactose ester, with a yield of 94%.

[0061] (5) Under room temperature conditions, diacetone galactose ester of 2-hydroxy-(2,4-dichlorophenyl)methacrylate, acetic anhydride, and 4-dimethylaminopyridine were mixed and stirred for 1 h at room temperature to obtain a reaction mixture; wherein the molar ratio of diacetone galactose ester of 2-hydroxy-(2,4-dichlorophenyl)methacrylate, acetic anhydride, and 4-dimethylaminopyridine was 1:2:0.2.

[0062]

[0063] (6) The reaction mixture was purified by column silica gel chromatography with petroleum ether and ethyl acetate (PE / EA = 30 / 1) to obtain a colorless liquid 2-acetoxy-(2,4-dichlorophenyl)methacrylate diacetone galactose ester, with a yield of 85%.

[0064] (7) Synthesis of itaconic acid compounds

[0065] In a 10 mL Shrek tube, under argon atmosphere, 0.4 mmol of 2-acetoxy(2,4-dichlorophenyl)methacrylate diacetone galactose ester, 0.48 mmol of 2-oxo-2-phenylacetic acid, 0.02 mmol of 3,6,-di-tert-butyl-9-trimethyl-10-phenylacridine-10-tetrafluoroborate, and 0.08 mmol of triphenylphosphine were added to 4 mL of acetonitrile. The mixture was stirred under argon atmosphere, at room temperature, and irradiated with a 54 W blue lamp. The reaction equation is as follows:

[0066]

[0067] (8) After the reaction was complete as monitored by TLC, the solvent was removed by vacuum rotary evaporator, and the product was separated by thin-layer chromatography. The developing solvent was a petroleum ether / ethyl acetate system (9:1). The product was a colorless and transparent liquid compound (E)-2-benzyl-4-oxo-4-phenylbutyric acid diacetone galactose ester, with a yield of 85%.

[0068] Example 5

[0069] (1) Cholesterol was added to a dichloromethane solution at room temperature, and triethylamine was added at 0°C. The mixture was stirred for 0.5 h. Then, a dichloromethane solution of acryloyl chloride was added dropwise to the above reaction mixture at 0°C, and the mixture was stirred at room temperature for 12 h to obtain the reaction mixture. The molar ratio of cholesterol, triethylamine, and acryloyl chloride was 1:2:1. The reaction equation is as follows:

[0070]

[0071] (2) The reaction mixture was quenched with saturated ammonium chloride solution, extracted three times with dichloromethane, the organic phases were combined, dried with anhydrous magnesium sulfate, the solvent was removed under reduced pressure, and the product was separated by column silica gel chromatography with petroleum ether / ethyl acetate system (80:1) as the developing solvent. The product was a white solid cholesterol acrylate with a yield of 61%.

[0072] (3) Under room temperature conditions, 2,4-dichlorobenzaldehyde, cholesterol acrylate, and triethylenediamine are dissolved in tetrahydrofuran and stirred for 1 week at room temperature to obtain a reaction mixture; wherein the molar ratio of 2,4-dichlorobenzaldehyde, cholesterol acrylate, and triethylenediamine is 1:1.2:0.5.

[0073]

[0074] (4) The reaction mixture was subjected to reduced pressure to remove the solvent. The residue was purified by silica gel column chromatography with petroleum ether and ethyl acetate (PE / EA = 30 / 1) to give a white solid 2-hydroxy-(2,4-dichlorophenyl)methacrylate cholesterol ester, in 58% yield.

[0075] (5) At room temperature, 2-hydroxy-(2,4-dichlorophenyl)methacrylate cholesterol ester, acetic anhydride, and 4-dimethylaminopyridine were mixed and stirred for 1 h at room temperature to obtain a reaction mixture; wherein the molar ratio of 2-hydroxy-(2,4-dichlorophenyl)methacrylate cholesterol ester, acetic anhydride, and 4-dimethylaminopyridine was 1:2:0.2.

[0076]

[0077] (6) The reaction mixture was purified by column silica gel chromatography with petroleum ether and ethyl acetate (PE / EA = 1 / 1) to give a white solid 2-acetoxy-(2,4-dichlorophenyl)methacrylate cholesterol ester, with a yield of 85%.

[0078] (7) Synthesis of itaconic acid compounds

[0079] In a 10 mL Shrek tube, under argon atmosphere, 0.4 mmol of 2-(acetoxy-(2,4-dichlorophenyl)meth)methacrylate cholesterol ester, 0.48 mmol of 2-oxo-2-phenylacetic acid, 0.02 mmol of 3,6,-di-tert-butyl-9-trimethylmethyl-10-phenylacridine-10-tetrafluoroborate, and 0.08 mmol of triphenylphosphine were added to 4 mL of acetonitrile. The mixture was stirred under argon atmosphere, at room temperature, and irradiated with a 54 W blue lamp. The reaction equation is as follows:

[0080]

[0081] (8) After the reaction was complete as monitored by TLC, the solvent was removed by vacuum rotary evaporator, and the product was separated by thin-layer chromatography with petroleum ether / ethyl acetate system (9:1) as the developing solvent. The product was a colorless and transparent liquid compound (E)-2-benzylidene-4-oxo-4-phenylbutyrate cholesterol ester with a yield of 90%.

[0082] Example 6

[0083] (1) In a 10 mL Shrek tube, under argon atmosphere, 0.4 mmol of 2-acetoxy(4-formylphenyl)methyl methacrylate, 0.48 mmol of (S)-2-((1-methoxy-1-oxopropyl-2-yl)amino)-2-oxoacetic acid, 0.02 mmol of 3,6,-di-tert-butyl-9-trimethylmethyl-10-phenylacridine-10-tetrafluoroborate, and 0.08 mmol of triphenylphosphine were added to 4 mL of acetonitrile. The mixture was stirred under argon atmosphere, at room temperature, and irradiated with a 54 W blue lamp. The reaction equation is as follows:

[0084]

[0085] (2) After the reaction was complete as monitored by TLC, the solvent was removed by vacuum rotary evaporator, and the product was separated by thin-layer chromatography. The developing solvent was a petroleum ether / ethyl acetate system (1:5). The product was a white solid (S,E)-2-benzylidene-4-((1-methoxy-1-oxopropyl-2-yl)amino)-4-oxobutyrate methyl ester, with a yield of 60%.

[0086] Example 7

[0087] (1) In a 10 mL Shrek tube, under argon atmosphere, first add 0.4 mmol of 2-acetoxy(4-formylphenyl) methyl methacrylate and 0.48 mmol of Leu-Gly - Glyoxam derivative, 0.02 mmol of 3,6,-di-tert-butyl-9-trimethyl-10-phenylacridin-10-tetrafluoroborate, and 0.08 mmol of triphenylphosphine were added to 4 mL of acetonitrile. The reaction was carried out under argon atmosphere, at room temperature, and irradiated with a 54 W blue lamp. The reaction equation is as follows:

[0088]

[0089] (2) After the reaction was complete as monitored by TLC, the solvent was removed by vacuum rotary evaporator, and the product was separated by thin-layer chromatography. The developing solvent was a dichloromethane / methanol system (1:5). The product was a colorless oily (E)-(3-(methoxycarbonyl)-4-phenylbut-3-enoyl)glycylglycyl-L-leucine methyl ester with a yield of 57%.

[0090] Example 8

[0091] (1) In a 10 mL Shrek tube, under argon atmosphere, 0.4 mmol of 2-acetoxy(4-formylphenyl)methyl methacrylate, 0.48 mmol of leucine enkephalin derivative, 0.02 mmol of 3,6,-di-tert-butyl-9-trimethyl-10-phenylacridine-10-tetrafluoroborate, and 0.08 mmol of triphenylphosphine were added to 4 mL of acetonitrile. The mixture was stirred under argon atmosphere, at room temperature, and irradiated by a 54 W blue lamp. The reaction equation is as follows:

[0092]

[0093] (2) After the reaction was complete as monitored by TLC, the solvent was removed by vacuum rotary evaporator, and the product was separated by thin-layer chromatography. The developing solvent was a dichloromethane / methanol system (1:5). The product was a colorless oily dimethyl (2S,5S,14S)-5-benzyl-19-((E)-benzylidene)-2-isobutyl-14-(4-methoxybenzyl)-4,7,10,13,17-pentaoxo-3,6,9,12,15-pentazaeicosanoic acid ester, with a yield of 44%.

[0094] Example 9

[0095] (1) In a 10 mL Shrek tube, under argon atmosphere, 0.4 mmol of methyl 2-(acetoxymethyl)acrylate, 0.48 mmol of 2-oxo-2-(prop-2-yn-1-ylamino)acetic acid, 0.02 mmol of 3,6,-di-tert-butyl-9-trimethyl-10-phenylacridin-10-tetrafluoroborate, and 0.08 mmol of triphenylphosphine were added to 4 mL of acetonitrile. The mixture was stirred under argon atmosphere, at room temperature, and irradiated with a 54 W blue lamp. The reaction equation is as follows:

[0096]

[0097] (2) After the reaction was complete as monitored by TLC, the solvent was removed by vacuum rotary evaporator, and the product was separated by thin-layer chromatography with dichloromethane / methanol system (1:5) as the developing solvent. The product was colorless oily methyl 2-methyl-4-oxo-4-(prop-2-yn-1-ylamino)butyrate, with a yield of 85%.

[0098] (3) Methyl 2-methyl-4-oxo-4-(prop-2-yn-1-ylamino)butyrate (0.3 mmol) was dissolved in THF (0.5 mL) and H2O (1 mL). NaOH (0.45 mmol, 1.5 equivalent) was added, and the solution was stirred at room temperature for 5 hours. The mixture was diluted with H2O (4 mL) and washed with diethyl ether (10 mL). The aqueous phase was separated and the pH was adjusted to 2-3 with 1 M HCl. The mixture was extracted three times with EtOAc (12 mL). The organic phases were combined, washed with brine, dried over anhydrous Na2SO4, filtered, and evaporated under vacuum to give a colorless oily product, 2-methyl-4-oxo-4-(prop-2-yn-1-ylamino)butyric acid, in 84% yield.

[0099]

[0100] Examples 10-17

[0101] Examples 10-17 are basically the same as Example 1 above, and the products obtained are the same. The differences are shown in Table 1 below:

[0102] Table 1 Comparison of Implementation Differences

[0103] serial number reaction solvent additive Yield Example 10 Toluene Triphenylphosphine 77％ Example 11 xylene Tris(4-methoxyphenyl)phosphine 86％ Example 12 dichloromethane 4-Dimethylaminopyridine 88％ Example 13 Acetonitrile Triethylamine 85％ Example 14 1,2-Dichloroethane Triethylenediamine 84％ Example 15 Tetrahydrofuran Triphenylphosphine 81％ Example 16 1,4-Dioxane Tris(4-methoxyphenyl)phosphine 89％ Example 17 Isopropanol 4-Dimethylaminopyridine 82％

[0104] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for synthesizing itaconic acid compounds, characterized in that, The method includes the following steps: (1) Allyl ester compound, acylation reagent, photo-oxidation-reduction catalyst, and additive are sequentially added to the reaction solvent. The reaction is stirred for 30 min under an inert gas atmosphere, blue light irradiation, and room temperature to obtain a reaction solution. The photo-oxidation-reduction catalyst is 3,6,-di-tert-butyl-9-trimethylyl-10-phenylacridine-10-tetrafluoroborate, the additive is triphenylphosphine, the reaction solvent is acetonitrile, and the chemical structural formula of the allyl ester compound is shown below: The chemical structural formula of the acylation reagent is shown below: (2) Remove the reaction solvent from the reaction solution and then purify itaconic acid compounds by thin-layer chromatography; The chemical structural formula of the itaconic acid compounds is shown in formula (I) below: Among them, R 1 It is selected from any one of hydrogen-based, alkoxy-based, alkyl-based, trifluoromethyl-based, fused aryl, and heteroaryl groups; R 2 It is selected from any one of the following groups: hydrogen-based, methoxy-based, cyano-based, nitro-based, tert-butyl-based, fluorine-based, bromo-based, chloro-based, ferrocene-based, trimethylsilane-ethynyl-based, fused aryl, heteroaryl, cycloalkyl, and straight-chain alkyl.

2. The method as described in claim 1, characterized in that, The heteroaryl group is furanyl or thiophene; the cycloalkyl group is cyclohexyl.

3. The method as described in claim 1, characterized in that, In step (1), the molar volume ratio of the allyl ester, acylation reagent, 3,6,-di-tert-butyl-9-trimethyl-10-phenylacridine-10-tetrafluoroborate, triphenylphosphine and acetonitrile is (0.2-0.4) mmol: (0.24-0.48) mmol: (0.01-0.02) mmol: (0.04-0.08) mmol: (2-4) mL.

4. The method as described in claim 1, characterized in that, In step (1), the inert gas is argon; in step (2), the purified developing solvent system is petroleum ether / ethyl acetate = 5:1.

Images