Method for synthesizing 1, 4-dicarbonyl compound by utilizing visible light to induce benzoic anhydride compound

Abstract

The invention discloses a method for synthesizing a 1, 4-dicarbonyl compound by utilizing visible light to induce a benzoic anhydride compound, which comprises the following steps: by taking the benzoic anhydride compound and methyl acrylate as reaction substrates and a benzothiazoline compound as a light reducing agent, carrying out a reaction on the benzoic anhydride compound and the methyl acrylate in the presence of organic alkali, and carrying out a reaction to obtain the 1, 4-dicarbonyl compound. The benzoic anhydride compound and the benzothiazoline compound form a donor-acceptor compound through intermolecular interaction, and the donor-acceptor compound is excited by visible light to initiate a single electron transfer process, so that the generation of an acyl radical intermediate is effectively induced. The intermediate and methyl acrylate are subjected to a free radical beta-position addition reaction, and finally the target product 1, 4-dicarbonyl compound is synthesized. The method has the advantages of being green, safe and easy to operate, the reaction condition is mild and efficient, the reaction time is short, the atom economy is high, the target product yield is high, the substrate applicability is wide, and the wide application prospect is achieved.

Description

Technical Field

[0001] The present invention belongs to the technical field of the synthesis of 1,4-dicarbonyl compounds, and particularly relates to a method for synthesizing 1,4-dicarbonyl compounds by the synergistic induction of visible light and benzothiazoline compounds without metal participation for benzoic anhydride compounds. Background Art

[0002] 1,4-Dicarbonyl compounds have become key intermediates in organic synthesis due to their unique conjugated polarization effect of the double carbonyl group and the intramolecular electron delocalization characteristics. Such compounds are not only key structural units in many natural active molecules and drug lead compounds, but also core precursors for constructing polysubstituted carbocyclic and heteroaromatic ring systems due to their unique reactivity. Through selective transformation, heteroaromatic ring systems with important biological activities such as furan, thiophene, pyrrole, and pyridazine can be efficiently constructed.

[0003] The synthetic strategies of 1,4-dicarbonyl compounds have been systematically described in many literatures, including the Stetter reaction of aldehydes and Michael acceptors, the acylation reaction of Michael acceptors, the cross-coupling reaction of α-haloketones and enolates, the coupling reaction of enolates or olefins, the reaction for extending the carbon chain of 1,3-dicarbonyl compounds, etc. In the photoredox reaction system, the acylation reaction based on Michael acceptors has become an important strategy for constructing ketone skeletons, but its core challenge still focuses on the efficient activation mechanism of acyl radical precursors. At present, most methods still have certain limitations, such as being limited by the requirement of substrate pre-functionalization or insufficient functional group tolerance. Therefore, it is very important to promote the development of photocatalytic acylation towards atom economy and step simplicity through mechanism innovation. Summary of the Invention

[0004] The object of the present invention is to overcome the disadvantages of the existing methods for synthesizing 1,4-dicarbonyl compounds, and provide a synthetic method for 1,4-dicarbonyl compounds with a green reaction process, mild reaction conditions, short reaction time, safety and high efficiency, and high yield.

[0005] To achieve the above object, the present invention provides a method for synthesizing 1,4-dicarbonyl compounds by using visible light to induce benzoic anhydride compounds. The method is as follows: under the protection of an inert gas, a benzoic anhydride compound shown in formula I and methyl acrylate are added to an organic solvent, and a benzothiazoline compound and an organic base are added, and the reaction is carried out under visible light irradiation. After the reaction is completed, separation and purification are carried out to obtain a 1,4-dicarbonyl compound shown in formula II; the reaction equation is as follows:

[0006]

[0007] In the formula, Ar represents an aryl group or a substituted aryl group, specifically such as: phenyl, naphthyl, etc., or a substituted group substituted by any 1 to 3 of C1-C6 alkyl, C1-C6 alkoxy, phenyl, and halogen.

[0008] In the above method, preferably, the addition amount of the benzoic anhydride compound is 1.5 to 3 times the molar amount of methyl acrylate.

[0009] In the above method, preferably, the benzothiazoline compound is selected from any one of 2-phenyl-benzothiazoline shown in formula A and 2-(4-(trifluoromethyl)phenyl)-benzothiazoline shown in formula B.

[0010]

[0011] Furthermore, preferably, the addition amount of the benzothiazoline compound is 1.5 to 3 times that of methyl acrylate.

[0012] In the above method, preferably, the organic base is selected from any one of N-methylmorpholine and N,N-dimethylbenzylamine.

[0013] Furthermore, preferably, the addition amount of the organic base is 1 to 2 times the molar amount of methyl acrylate.

[0014] In the above method, preferably, the organic solvent is any one of acetonitrile, ethyl acetate, tetrahydrofuran, and dichloroethane.

[0015] In the above method, preferably, the reaction is carried out at room temperature for 3 to 5 hours under visible light irradiation.

[0016] Furthermore, preferably, the visible light irradiation uses a 5-20W 380-400nm blue LED lamp.

[0017] The beneficial effects of the present invention are as follows:

[0018] The present invention uses a benzoic anhydride compound and methyl acrylate as reaction substrates, a benzothiazoline compound as a photoreducing agent. In the presence of an organic base, the benzoic anhydride compound and the benzothiazoline compound form a donor-acceptor (EDA) complex through intermolecular interaction. Upon visible light excitation, a single electron transfer process is initiated, effectively inducing the formation of an acyl radical intermediate. This intermediate then undergoes a radical β-position addition reaction with methyl acrylate, ultimately synthesizing the target product 1,4-dicarbonyl compound. The present invention has the advantages of being green, safe, and easy to operate, and has mild and efficient reaction conditions, short reaction time, high atom economy, high yield of the target product, and wide substrate applicability, and has broad application prospects. Detailed implementation manners

[0019] The following further details the present invention in conjunction with examples, but the protection scope of the present invention is not limited to these examples.

[0020] Example 1

[0021] Synthesize methyl 4 - oxo - 4 - phenylbutyrate with the following structural formula

[0022]

[0023] Add 2-(4-(trifluoromethyl)phenyl)-benzothiazoline (0.36 mmol, 101.16 mg) and benzoic anhydride (0.36 mmol, 81.36 mg) into the reaction tube. Conduct three evacuations and three purgings of the gas in the reaction tube through a photoreactor, and then transfer the reaction tube under N₂ to the glove box. First, add methyl acrylate (0.2 mmol, 18 μL) dissolved in anhydrous acetonitrile (0.5 mL), and then add N - methylmorpholine (0.28 mmol, 31 μL) dissolved in anhydrous acetonitrile (0.5 mL). After adding all the reactants, take the reaction tube out of the glove box and place it on the photoreactor. Irradiate the reaction system with a blue - light LED lamp (390 nm, 10 W) at room temperature for 4 hours, then remove the solvent by rotary evaporation under reduced pressure, and purify by column chromatography (PE / EA = 10:1) to obtain methyl 4 - oxo - 4 - phenylbutyrate with a yield of 80%. The spectral data of the product are as follows: 1 H NMR(400MHz,Chloroform - d)δ7.98(d,J = 7.2Hz,2H),7.56(t,J = 7.2Hz,1H),7.46(t,J = 8.0Hz,2H),3.70(s,3H),3.32(t,J = 6.8Hz,2H),2.77(t,J = 6.8Hz,2H); 13 CNMR(101MHz,Chloroform - d)δ198.2,173.5,136.7,133.3,128.7,128.1,51.9,33.5,28.1。

[0024] Example 2

[0025] Synthesize methyl 4-(4 - chlorophenyl)-4 - oxobutyrate with the following structural formula

[0026]

[0027] In this example, replace the benzoic anhydride used in Example 1 with an equimolar amount of 4 - chlorobenzoic anhydride, and keep other steps the same as in Example 1 to obtain methyl 4-(4 - chlorophenyl)-4 - oxobutyrate with a yield of 65%. The spectral data of the yield are as follows: 1HNMR(400MHz, Chloroform-d) δ 7.92 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 3.70 (s, 3H), 3.28 (t, J = 6.8 Hz, 2H), 2.76 (t, J = 6.4 Hz, 2H); 13 C NMR(101MHz, Chloroform-d) δ 197.0, 173.4, 139.8, 135.0, 129.6, 129.1, 52.0, 33.5, 28.1.

[0028] Example 3

[0029] Synthesize 4-methyl-4-(p-tolyl)-4-oxobutyrate with the following structural formula

[0030]

[0031] In this example, equimolar 4-methylbenzoic anhydride was used to replace the benzoic anhydride used in Example 1, and the other steps were the same as those in Example 1 to obtain 4-methyl-4-(p-tolyl)-4-oxobutyrate with a yield of 64%. The spectral data of the yield are as follows: 1 H NMR(400MHz, Chloroform-d) δ 7.88 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 8.0 Hz, 2H), 3.70 (s, 3H), 3.29 (t, J = 6.4 Hz, 2H), 2.75 (t, J = 6.4 Hz, 2H), 2.40 (s, 3H); 13 C NMR(101MHz, Chloroform-d) δ 197.8, 173.6, 144.2, 134.2, 129.4, 128.3, 52.0, 33.4, 28.2, 21.8.

[0032] Example 4

[0033] Synthesize methyl 4-oxo-4-(p-tolyl)butyrate with the following structural formula

[0034]

[0035] In this example, equimolar 2-methylbenzoic anhydride was used to replace the benzoic anhydride used in Example 1, and the other steps were the same as those in Example 1 to obtain methyl 4-oxo-4-(p-tolyl)butyrate with a yield of 50%. The spectral data of the yield are as follows: 11H NMR (400 MHz, Chloroform-d) δ 7.71 (d, J = 7.6 Hz, 1H), 7.37 (t, J = 7.2 Hz, 1H), 7.29 - 7.22 (m, 2H), 3.70 (s, 3H), 3.22 (t, J = 6.4 Hz, 2H), 2.74 (t, J = 6.4 Hz, 2H), 2.49 (s, 3H); 13 13C NMR (101 MHz, Chloroform-d) δ 202.1, 173.5, 138.4, 137.5, 132.1, 131.6, 128.6, 125.8, 51.9, 36.2, 28.4, 21.4.

[0036] Example 5

[0037] Synthesize methyl 4-(4-methoxyphenyl)-4-oxobutyrate with the following structural formula

[0038]

[0039] In this example, equimolar 4-methoxybenzoic anhydride was used to replace the benzoic anhydride used in Example 1, and the other steps were the same as those in Example 1 to obtain methyl 4-(4-methoxyphenyl)-4-oxobutyrate, with a yield of 70%. The spectral data of the yield are as follows: 1 1H NMR (400 MHz, Chloroform-d) δ 7.95 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H), 3.85 (s, 3H), 3.69 (s, 3H), 3.26 (t, J = 6.4 Hz, 2H), 2.73 (t, J = 6.8 Hz, 2H); 13 13C NMR (101 MHz, Chloroform-d) δ 196.6, 173.6, 163.7, 130.4, 129.7, 113.8, 55.6, 51.9, 33.1, 28.2.

[0040] Example 6

[0041] Synthesize methyl 4-(3-methoxyphenyl)-4-oxobutyrate with the following structural formula

[0042]

[0043] In this example, equimolar 3-methoxybenzoic anhydride was used to replace the benzoic anhydride used in Example 1, and the other steps were the same as those in Example 1 to obtain methyl 4-(3-methoxyphenyl)-4-oxobutyrate, with a yield of 32%. The spectral data of the yield are as follows: 11H NMR (400 MHz, Chloroform-d) δ 7.57 (d, J = 7.6 Hz, 1H), 7.50 (s, 1H), 7.37 (t, J = 8.0 Hz, 1H), 7.11 (dd, J = 8.0, 2.0 Hz, 1H), 3.85 (s, 3H), 3.71 (s, 3H), 3.31 (t, J = 6.4 Hz, 2H), 2.76 (t, J = 6.8 Hz, 2H); 13 13C NMR (101 MHz, Chloroform-d) δ 198.0, 173.5, 160.0, 138.0, 129.8, 120.8, 119.9, 112.3, 55.6, 52.0, 33.7, 28.2.

[0044] Example 7

[0045] Synthesize methyl 4-(2-methoxyphenyl)-4-oxobutyrate with the following structural formula

[0046]

[0047] In this example, equimolar 2-methoxybenzoic anhydride was used to replace the benzoic anhydride used in Example 1, and the other steps were the same as those in Example 1 to obtain methyl 4-(2-methoxyphenyl)-4-oxobutyrate with a yield of 45%. The spectral data of the yield are as follows: 1 1H NMR (400 MHz, Chloroform-d) δ 7.76 (d, J = 7.6 Hz, 1H), 7.46 (t, J = 8.4 Hz, 1H), 7.03 - 6.94 (m, 2H), 3.91 (s, 3H), 3.69 (s, 3H), 3.33 (t, J = 6.8 Hz, 2H), 2.71 (t, J = 6.8 Hz, 2H); 13 13C NMR (101 MHz, Chloroform-d) δ 200.0, 173.8, 159.0, 133.9, 130.7, 120.8, 111.7, 55.6, 51.8, 38.9, 28.6.

[0048] Example 8

[0049] Synthesize methyl 4-(4-(tert-butyl)phenyl)-4-oxobutyrate with the following structural formula

[0050]

[0051] In this example, equimolar 4-tert-butylbenzoic anhydride was used to replace the benzoic anhydride used in Example 1, and the other steps were the same as those in Example 1 to obtain methyl 4-(4-(tert-butyl)phenyl)-4-oxobutyrate with a yield of 54%. The spectral data of the yield are as follows:1 1H NMR (400 MHz, Chloroform-d) δ 7.92 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 3.70 (s, 3H), 3.30 (t, J = 6.8 Hz, 2H), 2.76 (t, J = 6.8 Hz, 2H), 1.34 (s, 9H); 13 13C NMR (101 MHz, Chloroform-d) δ 197.8, 173.6, 157.1, 134.1, 128.1, 125.7, 51.9, 35.2, 33.4, 31.2, 28.2.

[0052] Example 9

[0053] Synthesize 4-methyl-4-(1,1'-biphenyl)-4-oxobutyrate with the following structural formula

[0054]

[0055] In this example, equimolar 4-phenylbenzoic anhydride was used to replace the benzoic anhydride used in Example 1, and the other steps were the same as those in Example 1 to obtain 4-methyl-4-(1,1'-biphenyl)-4-oxobutyrate, with a yield of 42%. The spectral data of the yield are as follows: 1 1H NMR (400 MHz, Chloroform-d) δ 8.06 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 7.6 Hz, 2H), 7.47 (t, J = 7.2 Hz, 2H), 7.41 (d, J = 7.2 Hz, 1H), 3.72 (s, 3H), 3.35 (t, J = 6.8 Hz, 2H), 2.79 (t, J = 6.4 Hz, 2H); 13 13C NMR (101 MHz, Chloroform-d) δ 197.8, 173.5, 146.0, 139.9, 135.3, 129.1, 128.7, 128.4, 127.4, 52.0, 33.5, 28.2.

[0056] Example 10

[0057] Synthesize 4-naphthalen-2-ylmethyl-4-oxobutyrate with the following structural formula

[0058]

[0059] In this example, equimolar 2-naphthoic anhydride was used to replace the benzoic anhydride used in Example 1, and the other steps were the same as those in Example 1 to obtain 4-naphthalen-2-ylmethyl-4-oxobutyrate, with a yield of 47%. The spectral data of the yield are as follows:1 1H NMR (400 MHz, Chloroform-d) δ 8.51 (s, 1H), 8.04 (d, J = 9.6 Hz, 1H), 7.97 (d, J = 8.4 Hz, 1H), 7.89 (t, J = 8.4 Hz, 2H), 7.62 - 7.54 (m, 2H), 3.73 (s, 3H), 3.47 (t, J = 6.4 Hz, 2H), 2.83 (t, J = 6.4 Hz, 2H); 13 13C NMR (101 MHz, Chloroform-d) δ 198.1, 173.6, 135.8, 134.0, 132.6, 129.9, 129.7, 128.6, 128.6, 127.9, 126.9, 123.9, 52.0, 33.6, 28.3.

[0060] Example 11

[0061] Synthesize methyl 4 - oxo - 4-(3,4,5 - trimethoxyphenyl)butyrate with the following structural formula

[0062]

[0063] In this example, equimolar 3,4,5 - trimethoxybenzoic anhydride was used to replace the benzoic anhydride used in Example 1, and the other steps were the same as those in Example 1. Methyl 4 - oxo - 4-(3,4,5 - trimethoxyphenyl)butyrate was obtained with a yield of 60%. The spectral data of the yield are as follows: 1 1H NMR (400 MHz, Chloroform-d) δ 7.24 (s, 2H), 3.91 (s, 9H), 3.71 (s, 3H), 3.29 (t, J = 6.8 Hz, 2H), 2.76 (t, J = 6.4 Hz, 2H); 13 13C NMR (101 MHz, Chloroform-d) δ 197.0, 173.6, 153.2, 142.8, 131.9, 105.6, 61.1, 56.4, 52.0, 33.3, 28.3.

[0064] Example 12

[0065] In this example, equimolar 2 - phenyl - benzothiazoline was used to replace 2-(4 - (trifluoromethyl)phenyl)-benzothiazoline in Example 1, and the other steps were the same as those in Example 1. Methyl 4 - oxo - 4 - phenylbutyrate was obtained with a yield of 75%.

[0066] Example 13

[0067] In this example, N-methylmorpholine in Example 1 was replaced with an equal mole of N,N-dimethylbenzylamine, and the other steps were the same as in Example 1 to obtain methyl 4-oxo-4-phenylbutyrate with a yield of 76%.

[0068] In the above Example 1, 2-(4-(trifluoromethyl)phenyl)-benzothiazoline is not added and visible light is not irradiated. The other steps are the same as in Example 1, and no target product is generated, which indicates that 2-(4-(trifluoromethyl)phenyl)-benzothiazoline and visible light are necessary conditions for the generation of 1,4-dicarbonyl compounds. At the same time, acyl radicals and ester anions are captured by TEMPO, from which we speculate that in the presence of an organic base, benzoic anhydride and 2-(4-(trifluoromethyl)phenyl)-benzothiazoline construct an EDA complex through non-covalent bond interactions. The complex triggers the SET process under visible light irradiation conditions, effectively inducing the generation of acyl radical intermediates. The intermediate then undergoes a free radical β-addition reaction with methyl acrylate to finally synthesize the target product 1,4-dicarbonyl compound.

Claims

1. A method for synthesizing 1,4-dicarbonyl compounds by using visible light to induce benzoic anhydride compounds, characterized in that: Under an inert gas protection, add the benzoic anhydride compound shown in Formula I and methyl acrylate into an organic solvent, and then add a benzothiazoline compound and an organic base, and react under visible light irradiation. After the reaction, separate and purify to obtain the 1,4-dicarbonyl compound shown in Formula II; wherein Ar represents an aryl group or a substituted aryl group; The benzothiazoline compound is selected from any one of 2-phenyl-benzothiazoline shown in Formula A and 2-(4-(trifluoromethyl)phenyl)-benzothiazoline shown in Formula B. The organic base is selected from any one of N-methylmorpholine and N,N-dimethylbenzylamine.

2. The method for synthesizing 1,4-dicarbonyl compounds by using visible light to induce benzoic anhydride compounds according to claim 1, wherein: Ar represents a phenyl group or a naphthyl group, or the aforementioned substituents substituted by any 1 to 3 of C1-C6 alkyl, C1-C6 alkoxy, phenyl, and halogen.

3. The method for synthesizing 1,4-dicarbonyl compounds by using visible light to induce benzoic anhydride compounds according to claim 1, wherein: The addition amount of the benzoic anhydride compound is 1.5 to 3 times the molar amount of methyl acrylate.

4. The method for synthesizing 1,4-dicarbonyl compounds by using benzoic anhydride compounds induced by visible light according to claim 1, wherein: The addition amount of the benzothiazoline compound is 1.5 to 3 times the molar amount of methyl acrylate.

5. The method for synthesizing 1,4-dicarbonyl compounds by using visible light to induce benzoic anhydride compounds according to claim 1, wherein: The addition amount of the organic base is 1 to 2 times the molar amount of methyl acrylate.

6. The method for synthesizing 1,4-dicarbonyl compounds by using benzoic anhydride compounds induced by visible light according to claim 1, characterized in that: The organic solvent is any one of acetonitrile, ethyl acetate, tetrahydrofuran, and dichloroethane.

7. The method for synthesizing 1,4-dicarbonyl compounds by using visible light to induce benzoic anhydride compounds according to claim 1, wherein: React at room temperature for 3 to 5 hours under visible light irradiation.

8. The method for synthesizing 1,4-dicarbonyl compounds by using benzoic anhydride compounds induced by visible light according to claim 1 or 7, characterized in that: The visible light irradiation uses a 5-20W 380-400nm blue LED lamp.

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