Method for directly decarboxylating and hydrogenating alkyl carboxylic acid without transition metal and photocatalyst

Abstract

The invention discloses a method for directly decarboxylating and hydrogenating alkyl carboxylic acid without transition metal and a photocatalyst, and relates to the field of synthesis of organic compounds. The method comprises the following steps: in an argon atmosphere, putting alkyl carboxylic acid, an N-hydroxyphthalimide compound, a phosphine catalyst, a hydrogen atom transfer reagent and an alkaline substance into a solvent, and carrying out free radical mediated decarboxylation hydrogenation under the driving of visible light, so as to synthesize a series of alkane compounds. The reaction conditions are mild, the operation is simple, and the method has a wide substrate range and good functional group tolerance. In addition, by means of the method, later modification of complex natural products and drug molecules can be achieved, and the practicability of the method is further proved. More importantly, the synthesis of hydrocarbon products is directly realized by innovatively using the alkyl carboxylic acid which is stable, low in toxicity, low in price and easy to obtain, additional steps for pre-activation treatment of the hydrocarbon products are not needed, meanwhile, participation of transition metals and photocatalysts is not needed, and the method is more in line with the concept of modern green chemistry.

Description

Technical Field

[0001] The invention relates to the field of organic compound synthesis, in particular to a method for direct decarboxylation and hydrogenation of alkyl carboxylic acids without transition metals and photocatalysts. Background Art

[0002] Alkane compounds are not only intermediates in organic synthesis but also indispensable basic raw materials in chemical synthesis. They also have important application value in the fields of fuel, chemical raw materials and pharmaceuticals (Chem. Commun., 2021, 57, 9956–9967). Therefore, inventing efficient methods for synthesizing alkane compounds has always been a research hotspot in the field of organic chemistry.

[0003] Alkyl carboxylic acids have the advantages of being stable, cheap, non-toxic, and abundant. Alkyl carboxylic acids are cheap, easy to obtain, low in toxicity, stable, and abundant, and are important synthetic raw materials in the field of organic synthesis (ACS Catal., 2021, 11, 1640-1683; ACS Med. Chem. Lett., 2022, 13, 1413-1420). Therefore, decarboxylation and hydrogenation based on alkyl carboxylic acids is one of the important strategies for synthesizing alkane compounds. At present, the strategies for decarboxylation and hydrogenation can be divided into indirect decarboxylation and direct decarboxylation. The indirect decarboxylation strategy requires the carboxylic acid to be pre-activated into thiohydroxamate, N-hydroxyphthalimide ester, etc., and then undergo free radical-mediated decarboxylation and hydrogenation (Chem. Soc. Chem. Commun. 1983, 939-941; Angew. Chem. Int. Ed. 2016, 55, 1–7). The strategy of direct decarboxylation is mainly based on single-electron oxidation of photocatalysts and light-induced transition metal-catalyzed ligand-to-metal charge transfer (Am.Chem.Soc.2015,137,11340-11348; Angew.Chem.Int.Ed.2023,62,e202213055). However, the above strategies require pre-activation of carboxylic acids, highly toxic reagents, photocatalysts or transition metal catalysts, which greatly increases the cost of production. Therefore, in order to meet the concept of modern green chemistry and improve the economic benefits of products, it is of great significance to develop a method for hydrogenation of alkyl carboxylic acids without the participation of transition metals and photocatalysts. Summary of the invention

[0004] In view of this, the object of the present invention is to provide a method for direct decarboxylation and hydrogenation of alkyl carboxylic acids without transition metals and photocatalysts in order to solve the above technical problems.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] A method for direct decarboxylation and hydrogenation of alkyl carboxylic acids without transition metals and photocatalysts, wherein the molar amount of the alkyl carboxylic acid is 50% to 200%. The method comprises placing the alkyl carboxylic acid, N-hydroxyphthalimide compounds, phosphine catalysts, hydrogen atom transfer agents and alkaline substances in a solvent under an argon atmosphere, and obtaining an alkane compound having the following general formula (II) through free radical-mediated decarboxylation and hydrogenation under visible light irradiation.

[0007]

[0008] Wherein, R is a substituted or unsubstituted C1-C20 alkyl group or a substituted or unsubstituted C3-C20 cycloalkyl group;

[0009] When the above-mentioned substituted or unsubstituted group has a substituent, the substituent is an ester group, a halogen, a methoxyl group, an amide or a natural product molecular fragment, and the natural product molecular fragment is any one of ibuprofen, isoxacic acid and lithocholic acid.

[0010] The photocatalyst is at least one of 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile, basic methylene blue trihydrate, bis[2-(2,4-difluorophenyl)-5-methylpyridine][2,2'-bi(tetra-tert-butylpyridine)]iridium di(hexafluorophosphate), fac-tri(2-phenylpyridine)iridium, tri(2,2'-bipyridine)ruthenium di(hexafluorophosphate), and eosin Y disodium salt.

[0011] The phosphine catalyst is at least one of 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene, 1,4-bis(diphenylphosphino)butane, 1,3-bis(diphenylphosphino)propane, 1,2-bis(diphenylphosphino)ethane and triphenylphosphine, among which 1,3-bis(diphenylphosphino)propane is preferred.

[0012] The hydrogen atom transfer reagent is selected from at least one of diphenyl disulfide, p-toluene disulfide, p-methylthiophenol, 2,4,6-triisopropylthiophenol, methyl thioglycolate, and triisopropylsilanethiol, among which diphenyl disulfide is preferred.

[0013] The alkaline substance is at least one of sodium bicarbonate, potassium carbonate, dipotassium hydrogen phosphate, 4-dimethylaminopyridine, 2,6-lutidine, and triethylamine, among which sodium bicarbonate is preferred.

[0014] The solvent is at least one of N,N-dimethylacetamide, acetonitrile, tetrahydrofuran, dichloromethane, 1,2-dichloroethane, ethyl acetate, trifluorotoluene, and dimethyl sulfoxide, among which N,N-dimethylacetamide is preferred.

[0015] The N-hydroxyphthalimide compound is at least one of N-hydroxyphthalimide, N-hydroxytetrachlorophthalimide, 2-hydroxy-5-methylisoindoline-1,3-dione, and 4-bromo-2-hydroxy-1(H)-phthalimide, among which N-hydroxyphthalimide is preferred.

[0016] The wavelength range of the visible light irradiation includes: 390-520nm; the range of the reaction temperature includes: 15-60°C; the range of the reaction time includes: 12-48 hours, wherein the wavelength of the visible light irradiation is preferably 450-455nm, the reaction temperature is preferably 30°C, and the reaction time is preferably 24 hours.

[0017] The method provides a method for directly synthesizing alkane compounds from alkyl carboxylic acids. The reaction conditions are mild, the operation is simple, and it has a wide range of substrates and good functional group tolerance. In addition, the method can achieve the late modification of complex natural products and drug molecules, further proving the practicality of the method. More importantly, the present invention innovatively uses stable, low-toxic, cheap and readily available alkyl carboxylic acids to directly achieve the synthesis of alkane compounds, without the need for additional steps to pre-activate them, and without the participation of transition metals and photocatalysts, which is more in line with the concept of modern green chemistry. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 This is the hydrogen nuclear magnetic resonance spectrum of N-propylphthalimide prepared in Example 1 of the present invention.

[0019] Figure 2 This is the carbon nuclear magnetic resonance spectrum of N-propylphthalimide prepared in Example 1 of the present invention.

[0020] Figure 3 This is the hydrogen nuclear magnetic resonance spectrum of 2-(cyclohexylmethyl)isoindoline-1,3-dione prepared in Example 10 of the present invention.

[0021] Figure 4 This is the carbon nuclear magnetic resonance spectrum of 2-(cyclohexylmethyl)isoindoline-1,3-dione prepared in Example 10 of the present invention.

[0022] Figure 5 This is the hydrogen nuclear magnetic resonance spectrum of 4-bromocyclopropylbenzene prepared in Example 13 of the present invention.

[0023] Figure 6 This is the carbon nuclear magnetic resonance spectrum of 4-bromocyclopropylbenzene prepared in Example 13 of the present invention.

[0024] Figure 7This is the hydrogen nuclear magnetic resonance spectrum of (3R,8R,9S,10S,13R,14S,17R)-17-[(R)-sec-butyl]-10,13-dimethyl-hexahydro-1H-cyclopenta[a]phenanthrene-3-ol prepared in Example 18 of the present invention.

[0025] Figure 8 This is the carbon nuclear magnetic resonance spectrum of (3R,8R,9S,10S,13R,14S,17R)-17-[(R)-sec-butyl]-10,13-dimethyl-hexahydro-1H-cyclopenta[a]phenanthrene-3-ol prepared in Example 18 of the present invention. DETAILED DESCRIPTION

[0026] The technical scheme of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only 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.

[0027] Embodiment 1:

[0028]

[0029] Compound 1a (0.2 mmol, 47 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. (The product is a white solid, 32.2 mg in total, yield 85%, eluent ethyl acetate: petroleum ether = 1:10).

[0030] The target product 2a obtained by the above synthesis method was tested by hydrogen and carbon nuclear magnetic resonance spectra, and the test results are as follows: 1H NMR (400MHz, CDCl3): δ7.82-7.78(m,2H),7.70-7.65(m,2H),3.63-3.60(m,2H),1.72-1.63(m,2H),0.91(t,J=7.4Hz,3H); 13 C{ 1 H}NMR (100MHz,CDCl3):δ168.4,133.7,132.1,123.0,39.5,21.8,11.2ppm. Its hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum are as shown in the attached Figure 1 and 2 shown.

[0031] Embodiment 2:

[0032]

[0033] Compound 1b (0.2 mmol, 36 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2b. (The product is a colorless oil, 22.9 mg in total, yield 84%, eluent ethyl acetate: petroleum ether = 1:10).

[0034] The target product 2b obtained by the above synthesis method was tested by hydrogen and carbon nuclear magnetic resonance spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.16-7.14(m,2H),6.88-6.85(m,2H),3.81(s,3H),2.63(q,J=7.6Hz,2H),1.24(t,J=7.6Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ157.6,136.4,128.7,113.7,55.2,27.9,15.9ppm.

[0035] Embodiment 3:

[0036]

[0037] Compound 1c (0.2 mmol, 33 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2c. (The product is a white solid, 18.9 mg in total, yield 77%, eluent ethyl acetate: petroleum ether = 1:10).

[0038] The target product 2c obtained by the above synthesis method was tested by hydrogen and carbon nuclear magnetic resonance spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.10-7.06(m,2H),6.80-6.76(m,2H),4.98(s,1H),2.60(q,J=7.6Hz,2H),1.22(t,J=7.6Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ153.3, 136.6, 128.9, 115.1, 27.9, 15.8ppm.

[0039] Embodiment 4:

[0040]

[0041] Compound 1d (0.2 mmol, 48 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) light. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2d. (The product is a colorless oil, 33.2 mg in total, yield 84%, eluent ethyl acetate: petroleum ether = 1:10).

[0042] The target product 2d obtained by the above synthesis method was tested by hydrogen and carbon nuclear magnetic resonance spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.36-7.28(m,4H),7.25-7.21(m,1H),7.00(d,J=8.0Hz,2H),6.80(d,J=8.1Hz,2H),4.95(s,2H),2.21(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ156.9,137.3,130.1,129.9,128.5,127.8,127.4,114.7,70.1,20.5ppm.

[0043] Embodiment 5:

[0044]

[0045] Compound 1e (0.2 mmol, 50 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was stirred continuously at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2e. (The product is a white solid, 35.4 mg in total, yield 85%, eluent ethyl acetate: petroleum ether = 1:10).

[0046] The target product 2e obtained by the above synthesis method was tested by hydrogen and carbon nuclear magnetic resonance spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.15 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 8.1 Hz, 2H), 6.41 (s, 1H), 2.20 (s, 3H), 1.43 (s, 9H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ152.9,135.7,132.4,129.4,118.7,80.2,28.3,20.6ppm.

[0047] Embodiment 6:

[0048]

[0049] Compound 1f (0.2mmol, 44mg), N-hydroxyphthalimide (0.2mmol, 33mg), 1,3-bis(diphenylphosphino)propane (0.16mmol, 66mg), sodium bicarbonate (0.24mmol, 20mg), and diphenyl disulfide (0.02mmol, 4mg) were added to a 10mL Schlenk reaction tube (10mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12W blue LED (450-455nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2f. (The product is a colorless oil, 29.6 mg in total, yield 83%, eluent ethyl acetate: petroleum ether = 1:10).

[0050] The target product 2f obtained by the above synthesis method was tested by nuclear magnetic resonance hydrogen spectrum and carbon spectrum, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.39-7.30(m,5H),5.13(s,2H),2.35(t,J=7.4Hz,2H),1.73-1.64(m,2H),0.96(t,J=7.4Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ173.5,136.1,128.5,128.1,66.0,36.2,18.4,13.6ppm.

[0051] Embodiment 7:

[0052]

[0053] Compound 1g (0.2mmol, 67mg), N-hydroxyphthalimide (0.2mmol, 33mg), 1,3-bis(diphenylphosphino)propane (0.16mmol, 66mg), sodium bicarbonate (0.24mmol, 20mg), and diphenyl disulfide (0.02mmol, 4mg) were added to a 10mL Schlenk reaction tube (10mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12W blue LED (450-455nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain 2g of product. (The product is a white solid, 43.5 mg in total, yield 74%, eluent ethyl acetate: petroleum ether = 1:10).

[0054] The target product 2g obtained by the above synthesis method was tested by nuclear magnetic resonance hydrogen spectrum and carbon spectrum, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.38-7.30(m,5H),5.22-5.07(m,3H),4.33-4.28(m,1 H),1.89-1.82(m,1H),1.72-1.65(m,1H),1.43(s,9H),0.90(t,J=7.5Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ172.6,155.3,135.4,128.5,128.3,128.2,79.7,66.8,54.6,28.2,25.8,9.5ppm.

[0055] Embodiment 8:

[0056]

[0057] Compound 1h (0.2mmol, 38mg), N-hydroxyphthalimide (0.2mmol, 33mg), 1,3-bis(diphenylphosphino)propane (0.16mmol, 66mg), sodium bicarbonate (0.24mmol, 20mg), and diphenyl disulfide (0.02mmol, 4mg) were added to a 10mL Schlenk reaction tube (10mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12W blue LED (450-455nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain the product 2h. (The product is a white solid, 25.2 mg in total, yield 87%, eluent ethyl acetate: petroleum ether = 1:10).

[0058] The target product 2h obtained by the above synthesis method was tested by nuclear magnetic resonance hydrogen spectrum and carbon spectrum, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.69(m,1H),7.53(d,J=7.8Hz,1H),7.24-7.22(m,1H),7.12-7.08( m,1H),7.05-7.01(m,1H),6.85-6.84(m,1H),2.71(q,J=7.5Hz,2H),1.25(t,J=7.5Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ136.4,127.4,121.8,120.4,119.0,118.9,118.8,111.0,18.3,14.4ppm.

[0059] Embodiment 9:

[0060]

[0061] Compound 1i (0.2 mmol, 46 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2i. (The product is a colorless oil, 27.1 mg in total, 73% yield, eluent ethyl acetate: petroleum ether = 1:10).

[0062] The target product 2i obtained by the above synthesis method was tested by hydrogen and carbon nuclear magnetic resonance spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ3.36-3.33(m,4H),1.58-1.53(m,2H),1.50-1.48(m,4H),1.45(s,9H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ154.9,79.0,44.6,28.4,25.7,24.5ppm.

[0063] Embodiment 10:

[0064]

[0065] Compound 1j (0.2 mmol, 57 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) light. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2j. (The product is a white solid, 44.7 mg in total, yield 92%, eluent ethyl acetate: petroleum ether = 1:10).

[0066] The target product 2j obtained by the above synthesis method was tested by nuclear magnetic resonance hydrogen spectrum and carbon spectrum, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.82-7.79(m,2H),7.69-7.67(m,2H),3.50(d,J=7.3Hz,2H),1.78-1.62(m,6H),1.20-1.14(m,3H),1.04-0.94(m,2H); 13 C{ 1 H}NMR (100MHz,CDCl3):δ168.6,133.8,132.0,123.1,44.0,36.9,30.7,26.2,25.6ppm. Its hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum are as shown in the attached Figure 3 and 4 shown.

[0067] Embodiment 11:

[0068]

[0069] Compound 1k (0.2mmol, 46mg), N-hydroxyphthalimide (0.2mmol, 33mg), 1,3-bis(diphenylphosphino)propane (0.16mmol, 66mg), sodium bicarbonate (0.24mmol, 20mg), and diphenyl disulfide (0.02mmol, 4mg) were added to a 10mL Schlenk reaction tube (10mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12W blue LED (450-455nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2k. (The product is a white solid, 29.1 mg in total, yield 78%, eluent ethyl acetate: petroleum ether = 1:10).

[0070] The target product 2k obtained by the above synthesis method was tested by nuclear magnetic resonance hydrogen spectrum and carbon spectrum, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.71-7.68(m,2H),7.57(s,1H),7.34(d,J=8.4Hz,1H), 7.16-7.13(m,2H),3.93(s,3H),2.80(q,J=7.6Hz,2H),1.33(t,J=7.6Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ157.1,139.4,132.9,129.2,128.9,127.5,126.7,125.4,118.6,105.6,55.3,28.8,15.6ppm.

[0071] Embodiment 12:

[0072]

[0073] Compound 11 (0.2 mmol, 49 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 21. (The product is a colorless oil, 22.1 mg in total, 55% yield, eluent petroleum ether).

[0074] The target product 21 obtained by the above synthesis method was tested by hydrogen and carbon nuclear magnetic resonance spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.57(d,J=7.7Hz,2H),7.46(t,J=7.6Hz,2H),7.37(t,J =7.7Hz,2H),7.08-7.01(m,2H),2.71(q,J=7.7Hz,2H),1.30(t,J=7.6Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ160.9,158.5,145.92,145.85,135.94,135.93,130.5,130.4,128. 94,128.92,128.4,127.4,126.3,126.1,123.84,123.81,115.5,115.2,28.4,28.3,15.2ppm.

[0075] Embodiment 13:

[0076]

[0077] Compound 1m (0.2mmol, 39mg), N-hydroxyphthalimide (0.2mmol, 33mg), 1,3-bis(diphenylphosphino)propane (0.16mmol, 66mg), sodium bicarbonate (0.24mmol, 20mg), and diphenyl disulfide (0.02mmol, 4mg) were added to a 10mL Schlenk reaction tube (10mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12W blue LED (450-455nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2m. (The product is a white solid, 25.2 mg in total, yield 84%, eluent ethyl acetate:petroleum ether=1:10).

[0078] The target product 2m obtained by the above synthesis method was tested by nuclear magnetic resonance hydrogen spectrum and carbon spectrum, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ2.52(s,2H),2.07-1.91(m,12H); 13 C{ 1 H}NMR (100MHz,CDCl3):δ218.4,46.9,39.2,36.2,27.4ppm. Its H NMR spectrum and H NMR spectrum are as shown in the attached Figure 5 and 6 shown.

[0079] Embodiment 14:

[0080]

[0081] Compound 1n (0.2mmol, 48mg), N-hydroxyphthalimide (0.2mmol, 33mg), 1,3-bis(diphenylphosphino)propane (0.16mmol, 66mg), sodium bicarbonate (0.24mmol, 20mg), and diphenyl disulfide (0.02mmol, 4mg) were added to a 10mL Schlenk reaction tube (10mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12W blue LED (450-455nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2n. (The product is a colorless oil, a total of 17.4 mg, a yield of 44%, and the eluent is petroleum ether).

[0082] The target product 2n obtained by the above synthesis method was tested by nuclear magnetic resonance hydrogen spectrum and carbon spectrum, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.36 (d, J = 8.1Hz, 2H), 6.94 (d, J = 8.1Hz, 2H), 1.89-1.82 (m, 1H), 0.99-0.94 (m, 2H), 0.68-0.64 (m, 2H); 13 C{ 1 H} NMR (100MHz, CDCl3): δ143.0, 131.2, 127.4, 118.8, 15.0, 9.3ppm.

[0083] Embodiment 15:

[0084]

[0085] Compound 1o (0.2 mmol, 49 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2o. (The product is a colorless oil, 20.6 mg in total, yield 52%, eluent ethyl acetate: petroleum ether = 1:10).

[0086] The target product 2o obtained by the above synthesis method was tested by nuclear magnetic resonance hydrogen spectrum and carbon spectrum, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ4.03 (s, 2H), 2.66 (t, J = 12.9Hz, 2H), 1.58 (d, J = 13.7Hz, 2H),1.51-1.47(m,1H),1.44(s,9H),1.11-1.02(m,2H),0.92(d,J=6.5Hz,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ154.9,79.1,44.0,34.0,30.9,28.4,21.9ppm.

[0087] Embodiment 16:

[0088]

[0089] Compound 1p (0.2 mmol, 41 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain the product 2p. (The product is a colorless oil, a total of 16 mg, a yield of 49%, and the eluent is petroleum ether).

[0090] The target product 2p obtained by the above synthesis method was tested by nuclear magnetic resonance hydrogen spectrum and carbon spectrum, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.13-7.11(m,2H),7.08-7.06(m,2H),2.64(q,J=7.6Hz,2H),2 .46(d,J=7.1Hz,2H),1.91-1.81(m,1H),1.24(t,J=7.6Hz,3H),0.92(d,J=6.6Hz,6H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ141.4,138.9,129.0,127.5,45.0,30.3,28.4,22.4,15.6ppm.

[0091] Embodiment 17:

[0092]

[0093] Compound 1q (0.2mmol, 54mg), N-hydroxyphthalimide (0.2mmol, 33mg), 1,3-bis(diphenylphosphino)propane (0.16mmol, 66mg), sodium bicarbonate (0.24mmol, 20mg), and diphenyl disulfide (0.02mmol, 4mg) were added to a 10mL Schlenk reaction tube (10mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12W blue LED (450-455nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2q. (The product is a white solid, 30.6 mg in total, yield 68%, eluent ethyl acetate: petroleum ether = 1:10).

[0094] The target product 2q obtained by the above synthesis method was tested by hydrogen and carbon nuclear magnetic resonance spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ8.03-8.02(m,1H),7.90(dd,J=7.6,1.4Hz,1H),7.55-7.51(m,1H),7.47-7.43(m ,1H),7.34(dd,J=7.5,1.3Hz,1H),7.29-7.25(m,1H),6.94(d,J=8.3Hz,1H),5.15(s,2H),2.34(s,3H); 13 C{ 1 H}NMR (100MHz, DMSO): δ191.1,159.3,140.5,136.4,135.7,132.6,131.5,131.4,129.4,129.1,127.7,125.0,120.4,73.6,20.4ppm.

[0095] Embodiment 18:

[0096]

[0097] Compound 1r (0.2 mmol, 75 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) light. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2r. (The product is a white solid, 45.4 mg in total, yield 68%, eluent ethyl acetate: petroleum ether = 1:1).

[0098] The target product 2r obtained by the above synthesis method was tested by hydrogen and carbon nuclear magnetic resonance spectra, and the test results are as follows: 1 H NMR (400MHz, DMSO): δ3.65-3.57(m,1H),1.98-1.94(m,1H),1.87-1.74(m,4H),1.68-1.47(m,5H ),1.44-1.21(m,12H),1.13-0.99(m,6H),0.91-0.88(m,5H),0.81(t,J=7.4Hz,3H),0.63(s,3H); 13 C{ 1 H}NMR (100MHz, DMSO): δ71.8, 56.5, 55.8, 42.6, 42.1, 40.5, 40.2, 37.0, 36.4, 35.8, 35.4, 34.6, 30.5, 28.3, 28.2, 27.2, 26.4, 24.2, 23.4, 20.8, 18.0, 12.0, 10.3ppm. Its hydrogen nuclear magnetic resonance spectrum and carbon nuclear magnetic resonance spectrum are as shown in the attached Figure 7 and 8 shown.

[0099] Embodiment 19:

[0100]

[0101] Compound 1s (0.2 mmol, 72 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain the product 2s. (The product is a yellow oil, 51.6 mg in total, yield 82%, eluent ethyl acetate: petroleum ether = 1:10).

[0102] The target product 2s obtained by the above synthesis method was tested by hydrogen and carbon nuclear magnetic resonance spectra, and the test results are as follows: 1 H NMR (400MHz, CDCl3): δ7.65-7.63(m,2H),7.47-7.45(m,2H),6.93-6.90(m,2H),6.68-6.65(m,1H),3.85(s,3H),2.32(s,3H),2.20(s,3H); 13 C{ 1 H}NMR (100MHz, CDCl3): δ168.1,155.9,138.8,134.3,133.7,131.9,131.0,130.8,128.9,115.3,114.9,111.1,101.2,55.6,13.2,8.7ppm.

[0103] Condition optimization

[0104] Reactive

[0105]

[0106] Examples 20 to 27

[0107] Compound 1a (0.2 mmol, 47 mg), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (0.012 mmol, 10 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthene (0.16 mmol, 93 mg), 4-dimethylaminopyridine (0.24 mmol, 29 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of the corresponding solvent was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. The specific types of reaction solvents and yields are shown in Table 4, and the corresponding numbers are 20 to 27.

[0108] Table 1: Effect of different types of solvents on the yield of decarboxylation hydrogenation of 4-(1,3-dioxoisoindole-2-yl)butanoic acid 1a.

[0109]

[0110] By comparing the test results of the examples in Table 1, it can be seen that when N,N-dimethylacetamide is used as the solvent, the yield of the decarboxylation hydrogen product of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a is the highest, which can reach 40%.

[0111] Embodiments 28 to 33

[0112] Compound 1a (0.2 mmol, 47 mg), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (0.012 mmol, 10 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 4,5-bis(diphenylphosphino)-9,9-dimethyloxanthene (0.16 mmol, 93 mg), alkaline substance (0.24 mmol), diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. The specific types of alkaline substances and yields of the reactions are shown in Table 2, and the corresponding numbers are 28 to 33.

[0113] Table 2: Effects of different types of bases on the decarboxylation yield of 4-(1,3-dioxoisoindole-2-yl)butyric acid 1a.

[0114]

[0115] By comparing the test results of each example in Table 2, it can be seen that when sodium bicarbonate is used as the base, the yield of the decarboxylation hydrogen product of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a is the highest, which can reach 62%.

[0116] Embodiments 34 to 38

[0117] Compound 1a (0.2 mmol, 47 mg), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (0.012 mmol, 10 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), phosphine catalyst (0.16 mmol or 0.32 mmol), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. The specific types of phosphine catalysts and yields of the reaction are shown in Table 3, and the corresponding numbers are 34-38.

[0118] Table 3: Effects of different types of phosphine catalysts on the decarboxylation yield of 4-(1,3-dioxoisoindole-2-yl)butanoic acid 1a.

[0119]

[0120] By comparing the test results of each example in Table 3, it can be seen that when 1,3-bis(diphenylphosphino)propane is selected as the phosphine catalyst, the yield of the decarboxylation hydrogenation product of 4-(1,3-dioxoisoindole-2-yl)butyric acid 1a is the highest, which can reach 69%.

[0121] Embodiments 39 to 44

[0122] Compound 1a (0.2 mmol, 47 mg), 2,4,5,6-tetrakis(9-carbazolyl)-isophthalonitrile (0.012 mmol, 10 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and hydrogen atom transfer reagent (0.02 mmol) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. The specific types of hydrogen atom transfer reagents and yields of the reaction are shown in Table 4, and the corresponding numbers are 39-44.

[0123] Table 4: Effects of different types of hydrogen atom transfer reagents on the decarboxylation yield of 4-(1,3-dioxoisoindole-2-yl)butanoic acid 1a.

[0124]

[0125] By comparing the test results of each embodiment in Table 4, it can be seen that when diphenyl disulfide is selected as the hydrogen atom transfer reagent, the yield of the decarboxylation hydrogen product of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a is the highest, which can reach 69%.

[0126] Embodiments 45 to 50

[0127] Compound 1a (0.2 mmol, 47 mg), photocatalyst (0.012 mmol or 0.002 mmol), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. The specific photocatalysts and yields of the reactions are shown in Table 5, and the corresponding numbers are 45-50.

[0128] Table 5: Effect of different types of photocatalysts on the decarboxylation yield of 4-(1,3-dioxoisoindole-2-yl)butyric acid 1a.

[0129]

[0130] By comparing the test results of each embodiment in Table 5, it can be seen that when alkaline methylene blue trihydrate is selected as the photocatalyst, the yield of the decarboxylation hydrogen product of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a is the highest, which can reach 81%.

[0131] Examples 51 to 56

[0132] Compound 1a (0.2 mmol, 47 mg), basic methylene blue trihydrate (0.012 mmol, 5 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (wavelength) lamp. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. The specific wavelengths and yields of different types of reactions are shown in Table 6, with corresponding numbers 51-56.

[0133] Table 6: Effects of different wavelengths on the decarboxylation yield of 4-(1,3-dioxoisoindole-2-yl)butanoic acid 1a.

[0134]

[0135] By comparing the test results of the embodiments in Table 6, it can be seen that when a wavelength of 450 to 455 nm is selected, the yield of the decarboxylation hydrogen product of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a is the highest, which can reach 81%.

[0136] Examples 57 to 61

[0137] Compound 1a (0.2 mmol, 47 mg), N-hydroxyphthalimide (0.2 mmol, 33 mg), 1,3-bis(diphenylphosphino)propane (0.16 mmol, 66 mg), sodium bicarbonate (0.24 mmol, 20 mg), and diphenyl disulfide (0.02 mmol, 4 mg) were added to a 10 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 2 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×10 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. The specific control and yield of different types are shown in Table 7, corresponding numbers 57-61.

[0138] Table 7: Effect of different types of control experiments on the decarboxylation hydrogenation yield of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a.

[0139]

[0140] By comparing the test results of each embodiment in Table 7, it can be seen that the yield of the decarboxylation hydrogen product of 4-(1,3-dioxoisoindol-2-yl)butyric acid 1a without adding a photocatalyst is the highest, which can reach 85%, which is equal to the yield with adding a photocatalyst, so it is chosen not to add a photocatalyst.

[0141] Example 63, Preparation of N-propylphthalimide (2a, 1 mmol reaction)

[0142]

[0143] Compound 1a (1 mmol, 233 mg), N-hydroxyphthalimide (1 mmol, 163 mg), 1,3-bis(diphenylphosphino)propane (0.8 mmol, 330 mg), sodium bicarbonate (1.2 mmol, 101 mg), and diphenyl disulfide (0.1 mmol, 21.8 mg) were added to a 50 mL Schlenk reaction tube (10 mL capacity, 14 / 20 grinding mouth). The air in the tube was completely replaced with argon three times, and then 10 mL of N,N-dimethylacetamide was added under argon atmosphere. The reaction system was continuously stirred at room temperature for 24 hours (stirring speed 300 rpm) under 12 W blue LED (450-455 nm) lamp irradiation. After the reaction was completed, the reaction was quenched with water, and the reaction solution was extracted with ethyl acetate (3×15 mL), and the combined organic phase was concentrated by rotary evaporation. The concentrated residue was separated by column chromatography to obtain product 2a. (The product is a white solid, 153.5 mg in total, yield 81%, eluent ethyl acetate: petroleum ether = 1:10).

[0144] Embodiment 64

[0145]

[0146] In the reaction of Example 64, 2.0 equivalents of tetramethylpiperidinium nitrogen oxide was added as a free radical scavenger, and the yield of the target product 2a of the reaction was 0%. The experiment showed that the reaction did undergo a free radical reaction process.

[0147] Embodiment 65

[0148]

[0149] In the reaction of Example 64, 1.0 equivalent of N-tert-butyloxycarbonyl-cyclopropylglycine was added, and the yield of the free radical-induced ring-opening product of the reaction was 32%. The experiment further showed that the reaction did undergo a free radical reaction process.

[0150] Based on the above embodiments, the present invention provides a method for direct decarboxylation and hydrogenation of alkyl carboxylic acids without transition metals and photocatalysts, wherein the method is to place alkyl carboxylic acids, N-hydroxyphthalimide compounds, phosphine catalysts, hydrogen atom transfer reagents and alkaline substances in a solvent under an argon atmosphere, and to undergo free radical-mediated decarboxylation and hydrogenation under visible light drive to synthesize a series of alkane compounds. The effects of different phosphine catalysts, hydrogen atom transfer reagents, alkaline substances, organic solvents and different wavelengths of illumination conditions on the yield of the reaction products are verified by specific examples. While achieving the purpose of the present invention and obtaining a technical solution for achieving the purpose of the present invention, the optimal selection of phosphine catalysts, hydrogen atom transfer reagents, alkaline substances, organic solvents and different wavelengths of illumination conditions in the technical solution is also obtained, which has strong theoretical value and practical value. The present invention innovatively uses stable, low-toxic, cheap and readily available alkyl carboxylic acids to directly realize the synthesis of hydrocarbon products, without the need for additional steps to pre-activate them, and without the participation of transition metals and photocatalysts, which is more in line with the concept of modern green chemistry.

[0151] It should be further explained that the specific embodiments described above further illustrate the purpose, technical solutions and beneficial effects of the present invention. It should be understood that the above description is only a specific embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A method for direct decarboxylation and hydrogenation of alkyl carboxylic acids without transition metals and photocatalysts, characterized in that: Under an argon atmosphere, an alkyl carboxylic acid, an N-hydroxyphthalimide compound, a phosphine catalyst, a hydrogen atom transfer agent and an alkaline substance are placed in a solvent, and under visible light irradiation, an alkane compound having the following general formula (II) is obtained through free radical-mediated decarboxylation hydrogenation. Wherein, R is a substituted or unsubstituted C1-C20 alkyl group or a substituted or unsubstituted C3-C20 cycloalkyl group; When the above-mentioned substituted or unsubstituted group has a substituent, the substituent is an ester group, a halogen, a methoxyl group, an amide or a natural product molecular fragment, and the natural product molecular fragment is any one of ibuprofen, isoxic acid or lithocholic acid.

2. The method according to claim 1, characterized in that The phosphine catalyst is selected from at least one of 4,5-bis(diphenylphosphine)-9,9-dimethylxanthene, 1,4-bis(diphenylphosphine)butane, 1,3-bis(diphenylphosphine)propane, 1,2-bis(diphenylphosphine)ethane, and triphenylphosphine; The molar amount of the phosphine catalyst is 50% to 200% of the molar amount of the alkyl carboxylic acid.

3. The method according to claim 1, characterized in that The hydrogen atom transfer reagent is selected from at least one of diphenyl disulfide, p-toluene disulfide, p-methylthiophenol, 2,4,6-triisopropylthiophenol, methyl thioglycolate, and triisopropylsilanethiol; The molar amount of the hydrogen atom transfer reagent is 5% to 25% of the molar amount of the alkyl carboxylic acid.

4. The method according to claim 1, characterized in that: The alkaline substance is selected from at least one of sodium bicarbonate, potassium carbonate, dipotassium hydrogen phosphate, 4-dimethylaminopyridine, 2,6-lutidine, and triethylamine; The molar amount of the alkaline substance is 50% to 200% of the molar amount of the alkyl carboxylic acid.

5. The method according to claim 1, characterized in that The organic solvent is selected from at least one of N,N-dimethylacetamide, acetonitrile, tetrahydrofuran, dichloromethane, 1,2-dichloroethane, ethyl acetate, trifluorotoluene, and dimethyl sulfoxide.

6. The method according to claim 1, characterized in that The N-hydroxyphthalimide compound is selected from at least one of N-hydroxyphthalimide, N-hydroxytetrachlorophthalimide, 2-hydroxy-5-methylisoindoline-1,3-dione, and 4-bromo-2-hydroxy-1(H)-phthalimide; The molar amount of the N-hydroxyphthalimide compound is 50% to 150% of the molar amount of the alkyl carboxylic acid.

7. The method according to claim 1, characterized in that The wavelength range of the visible light is 390 to 520 nm; the range of the reaction temperature is 15 to 60° C.; and the range of the reaction time is 12 to 48 hours.

8. The method according to claim 1, characterized in that The phosphine catalyst is 1,3-bis(diphenylphosphine)propane; The hydrogen atom transfer reagent is diphenyl disulfide; The alkaline substance is sodium bicarbonate; The solvent is N,N-dimethylacetamide; The N-hydroxyphthalimide compound is N-hydroxyphthalimide; The wavelength range of the visible light is 450-455nm.

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