Method for synthesizing amide compound by utilizing visible light / benzothiazoline derivative to synergistically induce triazine ester

Abstract

The invention discloses a method for synthesizing an amide compound by utilizing visible light / benzothiazoline derivative synergistic induction triazine ester, which comprises the following steps: by taking the triazine ester and a nitrobenzene compound as reaction substrates and the benzothiazoline derivative as a light reducing agent, carrying out a reaction on the triazine ester and the nitrobenzene compound in the presence of organic alkali, and carrying out a reaction to obtain the amide compound. Triazine ester and a benzothiazoline derivative form a donor-acceptor compound through intermolecular interaction, a single electron transfer process is triggered through visible light excitation, and then acyl radicals are generated; a nitrobenzene compound can be changed into free radical nitro aromatic hydrocarbon under the reaction system, an acyl free radical addition process is carried out, nitrosobenzene and N-(benzoyloxy)-N-phenylaniline are sequentially changed, and finally the target product amide 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 amide compounds, and particularly relates to a method for synthesizing amide compounds by the synergistic induction of triazine esters with visible light and benzothiazoline derivatives without the participation of metals. Background Art

[0002] Due to their unique structural characteristics, small-molecule amide compounds exhibit important application values in multiple fields. In the pharmaceutical field, such compounds constitute the core structural units of many important drugs, such as the β-lactam ring structure of penicillin antibiotics and antipyretic and analgesic drugs such as paracetamol. In the chemical industry, N,N-disubstituted amide compounds (such as DMF, DMAC) have become important industrial solvents and reaction media due to their excellent aprotic polarity and solubility properties. In agricultural applications, urea, as a typical amide compound, its applications have expanded from traditional nitrogen fertilizers to multiple links in modern agriculture. At the same time, in industrial production, urea also plays multiple roles: it is an important additive in animal feed, a raw material for manufacturing high-efficiency explosives, and can also be used to produce polymer materials such as urea-formaldehyde resins. These diverse applications fully demonstrate the versatility and broad application prospects of small-molecule amide compounds.

[0003] Traditional methods for synthesizing small-molecule amide compounds usually require strong condensing agents or highly reactive acylating reagents, with harsh reaction conditions and often accompanied by the generation of a large number of by-products. With the rise of the concept of green chemistry, the development of new synthesis modes with high atom utilization and wide substrate compatibility has attracted much attention. In recent years, photocatalytic technology has gradually been applied to the field of amide synthesis, but existing systems mostly rely on noble metal complexes or organic dyes as photosensitizers, with high catalyst costs and potential metal residue risks. Therefore, the development of efficient synthesis strategies for new small-molecule amide compounds shows important theoretical value and practical needs in the field of organic synthetic chemistry. Summary of the Invention

[0004] The object of the present invention is to overcome the disadvantages of existing methods for synthesizing amide compounds, and to provide a synthesis method for amide 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 amide compounds by the synergistic induction of triazine esters with visible light / benzothiazoline derivatives. The method is as follows: under the protection of an inert gas, a triazine ester shown in Formula I and a nitrobenzene compound shown in Formula II are added to an organic solvent, and a benzothiazoline derivative 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 an amide compound shown in Formula III; the reaction equation is as follows:

[0006]

[0007] In the formula, Ar represents any one of aryl and substituted aryl, specifically such as phenyl, naphthyl, etc., or any one of the foregoing substituents substituted by C1-C6 alkyl, C1-C6 alkoxy, phenyl, halogen, etc. R represents any one of H, C1-C6 alkyl, C1-C6 alkoxy, and halogen.

[0008] In the above method, preferably, the addition amount of the triazine ester is 3 to 4 times the molar amount of the nitrobenzene compound.

[0009] In the above method, preferably, the benzothiazoline derivative is selected from any one of 2-naphthyl-2-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 derivative is 1.5 to 3 times the molar amount of the nitrobenzene compound.

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

[0013] Furthermore, preferably, the addition amount of the organic base is 0.8 to 2 times the molar amount of the nitrobenzene compound.

[0014] In the above method, preferably, the organic solvent is any one of ethyl acetate, acetonitrile, tetrahydrofuran, dichloromethane, 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 triazine ester and nitrobenzene compounds as reaction substrates, 2-naphthyl-2-benzothiazoline compounds or 2-(4-(trifluoromethyl)phenyl)-benzothiazoline as photoreductants, and in the presence of an organic base N,N-diisopropylethylamine or N-methylmorpholine, uses visible light and photoreductants to synergistically induce the reaction of triazine ester and nitrobenzene compounds to synthesize amide compounds. The present invention uses the intermolecular interaction of triazine ester and photoreductant in the presence of an organic base to form a donor-acceptor (EDA) complex, which is excited by visible light to initiate a single electron transfer (SET) process, thereby generating acyl radicals; nitrobenzene compounds will become free radical nitroaromatics in this reaction system, undergo an acyl radical addition process, and sequentially become nitrosobenzene and N-(benzoyloxy)-N-phenylaniline, and finally synthesize the target product amide compounds. The method of the invention has the advantages of being green, safe and easy to operate, and the reaction conditions are mild and efficient, the reaction time is short, the atom economy is high, the yield of the target product is high, the substrate applicability is wide, and it has broad application prospects. DETAILED DESCRIPTION

[0019] The present invention is further described in detail below in conjunction with the embodiments, but the protection scope of the present invention is not limited to these embodiments.

[0020] Example 1

[0021] Synthesize N-phenylbenzamide with the following structural formula

[0022]

[0023] 2-naphthyl-2-benzothiazoline (0.4mmol, 0.1052g) and 4,6-dimethoxy-1,3,5-triazine-2-benzoate (0.7mmol, 0.1827g) were added to the reaction tube, and the gas in the reaction tube was vacuumed and filled with nitrogen three times using a photoreactor to fully exclude the air in the tube. Subsequently, nitrobenzene (0.2mmol, 20μL), N,N-diisopropylethylamine (0.2mmol, 34μL) and ultra-dry ethyl acetate solvent (1.0mL) were added to the reaction tube in sequence in the glove box. After the reactants were added, the reaction tube was taken out of the glove box and placed on the photoreactor. The reaction system was irradiated with a blue LED lamp (390nm, 10W) ​​at room temperature for 4 hours, and the solvent was removed by vacuum rotary evaporation. N-phenylbenzamide was purified by column chromatography (PE / EA=10:1) with a yield of 83%. The spectral data of the product are: 11H NMR (400 MHz, Chloroform-d) δ 7.95 - 7.83 (m, 3H), 7.65 (d, J = 8.0 Hz, 2H), 7.55 (t, J = 7.2 Hz, 1H), 7.48 (t, J = 7.6 Hz, 2H), 7.37 (t, J = 7.6 Hz, 2H), 7.15 (t, J = 7.2 Hz, 1H); 13 13C NMR (101 MHz, Chloroform-d) δ 165.9, 138.0, 135.1, 132.0, 129.2, 128.9, 127.2, 124.7, 120.3.

[0024] Example 2

[0025] Synthesize 4-fluoro-N-phenylbenzamide with the following structural formula

[0026]

[0027] In this example, equimolar 4,6-dimethoxy-1,3,5-triazine-2-(4-fluoro)-benzoate was used to replace 4,6-dimethoxy-1,3,5-triazine-2-benzoate used in Example 1, and other steps were the same as those in Example 1. 4-Fluoro-N-phenylbenzamide was obtained with a yield of 81%. The spectral data of the yield are as follows: 1 1H NMR (400 MHz, Dimethylsulfoxide-d6) δ 10.29 (s, 1H), 8.04 (dd, J = 8.0, 5.6 Hz, 2H), 7.77 (d, J = 8.0 Hz, 2H), 7.36 (q, J = 7.6 Hz, 4H), 7.10 (t, J = 7.2 Hz, 1H); 13 13C NMR (101 MHz, Dimethyl sulfoxide-d6) δ 165.5, 164.6, 163.0, 139.2, 131.6, 130.6, 130.5, 128.8, 123.9, 120.6, 115.6, 115.4.

[0028] Example 3

[0029] Synthesize 4-chloro-N-phenylbenzamide with the following structural formula

[0030]

[0031] In this example, 4,6-dimethoxy-1,3,5-triazine-2-(4-chloro)-benzoate was used to replace 4,6-dimethoxy-1,3,5-triazine-2-benzoate used in Example 1 in an equimolar amount. Other steps were the same as those in Example 1, and 4-chloro-N-phenylbenzamide was obtained with a yield of 95%. The spectral data of the product are as follows: 1 H NMR(400MHz,Dimethylsulfoxide-d6)δ10.34(s,1H),7.99(d,J=8.4Hz,2H),7.77(d,J=8.0Hz,2H),7.61(d,J=8.4Hz,2H),7.36(t,J=8.0Hz,2H),7.18-7.05(m,1H); 13 C NMR(101MHz,Dimethylsulfoxide-d6)δ164.6,139.1,136.5,133.8,129.8,128.8,128.6,124.0,120.6.

[0032] Example 4

[0033] Synthesize 4-bromo-N-phenylbenzamide with the following structural formula

[0034]

[0035] In this example, 4,6-dimethoxy-1,3,5-triazine-2-(4-bromo)-benzoate was used to replace 4,6-dimethoxy-1,3,5-triazine-2-benzoate used in Example 1 in an equimolar amount. Other steps were the same as those in Example 1, and 4-bromo-N-phenylbenzamide was obtained with a yield of 91%. The spectral data of the product are as follows: 1 H NMR(400MHz,Dimethylsulfoxide-d6)δ10.34(s,1H),7.91(d,J=8.4Hz,2H),7.76(t,J=9.6Hz,4H),7.35(t,J=7.6Hz,2H),7.11(t,J=7.2Hz,1H); 13 C NMR(101MHz,Dimethyl sulfoxide-d6)δ164.7,139.1,134.1,131.5,130.0,128.8,125.5,124.0,120.5.

[0036] Example 5

[0037] Synthesize 4-methyl-N-phenylbenzamide with the following structural formula

[0038]

[0039] In this example, 4,6-dimethoxy-1,3,5-triazine-2-(4-methyl)-benzoate with an equimolar amount was used to replace 4,6-dimethoxy-1,3,5-triazine-2-benzoate used in Example 1. Other steps were the same as those in Example 1, and 4-methyl-N-phenylbenzamide was obtained with a yield of 50%. The spectral data of the product are as follows: 1 HNMR(400MHz,Dimethylsulfoxide-d6)δ10.22(s,1H),7.91(d,J=8.0Hz,2H),7.82(d,J=7.6Hz,2H),7.40-7.30(m,4H),7.09(t,J=7.2Hz,1H),2.37(s,3H); 13 C NMR(101MHz,Dimethyl sulfoxide-d6)δ165.5,141.7,139.4,132.2,129.0,128.7,127.9,123.7,120.5,21.2.

[0040] Example 6

[0041] Synthesize 3-methyl-N-phenylbenzamide with the following structural formula

[0042]

[0043] In this example, 4,6-dimethoxy-1,3,5-triazine-2-(3-methyl)-benzoate with an equimolar amount was used to replace 4,6-dimethoxy-1,3,5-triazine-2-benzoate used in Example 1. Other steps were the same as those in Example 1, and 3-methyl-N-phenylbenzamide was obtained with a yield of 80%. The spectral data of the product are as follows: 1 HNMR(400MHz,Dimethylsulfoxide-d6)δ10.24(s,1H),7.78(t,J=8.8Hz,4H),7.47-7.31(m,4H),7.10(t,J=7.6Hz,1H),2.40(s,3H); 13 C NMR(101MHz,Dimethyl sulfoxide-d6)δ165.8,139.4,137.8,135.1,132.3,128.8,128.4,128.3,125.0,123.7,120.4,21.1.

[0044] Example 7

[0045] Synthesize 2-methyl-N-phenylbenzamide with the following structural formula

[0046]

[0047] In this example, 4,6-dimethoxy-1,3,5-triazine-2-(2-methyl)-benzoate with an equimolar amount was used to replace 4,6-dimethoxy-1,3,5-triazine-2-benzoate used in Example 1. Other steps were the same as those in Example 1, and 2-methyl-N-phenylbenzamide was obtained with a yield of 55%. The spectral data of the product are as follows: 1 HNMR(400MHz,Dimethylsulfoxide-d6)δ10.33(s,1H),7.75(d,J=8.0Hz,2H),7.45(d,J=7.2Hz,1H),7.41-7.28(m,5H),7.08(t,J=7.6Hz,1H),2.38(s,3H); 13 C NMR(101MHz,Dimethyl sulfoxide-d6)δ168.0,139.4,137.4,135.3,130.7,129.8,128.8,127.3,125.8,123.6,119.7,19.5.

[0048] Example 8

[0049] Synthesize 4-methoxy-N-phenylbenzamide with the following structural formula

[0050]

[0051] In this example, 4,6-dimethoxy-1,3,5-triazine-2-(4-methoxy)-benzoate with an equimolar amount was used to replace 4,6-dimethoxy-1,3,5-triazine-2-benzoate used in Example 1. Other steps were the same as those in Example 1, and 4-methoxy-N-phenylbenzamide was obtained with a yield of 40%. The spectral data of the product are as follows: 1 H NMR(400MHz,Dimethylsulfoxide-d6)δ10.08(s,1H),7.96(d,J=8.8Hz,2H),7.77(d,J=8.4Hz,2H),7.34(t,J=7.6Hz,2H),7.08-7.05(m,3H),3.84(s,3H); 13 C NMR(101MHz,Dimethyl sulfoxide-d6)δ165.0,162.0,139.4,129.7,128.6,127.1,123.5,120.4,113.7,55.5.

[0052] Example 9

[0053] Synthesize 4-tert-butyl-N-phenylbenzamide with the following structural formula

[0054]

[0055] In this example, 4,6-dimethoxy-1,3,5-triazine-2-(4-tert-butyl)-benzoate with equimolar amount was used to replace 4,6-dimethoxy-1,3,5-triazine-2-benzoate used in Example 1, and other steps were the same as those in Example 1 to obtain 4-tert-butyl-N-phenylbenzamide with a yield of 62%. The spectral data of the product are as follows: 1 H NMR(400MHz,Dimethylsulfoxide-d6)δ10.21(s,1H),7.89(d,J=8.4Hz,2H),7.78(d,J=8.0Hz,2H),7.54(d,J=8.4Hz,2H),7.34(t,J=7.6Hz,2H),7.14-7.04(m,1H),1.31(s,9H); 13 C NMR(101MHz,Dimethyl sulfoxide-d6)δ165.6,154.5,139.4,132.4,128.7,127.7,125.3,123.7,120.4,34.8,31.1。

[0056] Example 10

[0057] Synthesize 4-phenyl-N-phenylbenzamide with the following structural formula

[0058]

[0059] In this example, 4,6-dimethoxy-1,3,5-triazine-2-(4-phenyl)-benzoate with equimolar amount was used to replace 4,6-dimethoxy-1,3,5-triazine-2-benzoate used in Example 1, and other steps were the same as those in Example 1 to obtain 4-phenyl-N-phenylbenzamide with a yield of 30%. The spectral data of the product are as follows: 1 HNMR(400MHz,Dimethylsulfoxide-d6)δ10.33(s,1H),8.07(d,J=8.4Hz,2H),7.83(dd,J=12.0,8.4Hz,4H),7.76(d,J=7.6Hz,2H),7.51(t,J=7.6Hz,2H),7.43(d,J=7.2Hz,1H),7.37(t,J=8.0Hz,2H),7.11(t,J=7.6Hz,1H); 13CNMR (101 MHz, Dimethyl sulfoxide-d6) δ 165.3, 143.2, 139.3, 139.2, 133.8, 129.2, 128.8, 128.5, 128.3, 127.1, 126.7, 123.8, 120.5。

[0060] Example 11

[0061] Synthesize N-phenyl-1-naphthamide with the following structural formula

[0062]

[0063] In this example, equimolar 4,6-dimethoxy-1,3,5-triazine-2-(1-naphthyl) acid ester was used to replace the 4,6-dimethoxy-1,3,5-triazine-2-benzoic acid ester used in Example 1. Other steps were the same as in Example 1, and N-phenyl-1-naphthamide was obtained with a yield of 73%. The spectral data of the product are as follows: 1 H NMR (400 MHz, Dimethyl sulfoxide-d6) δ 10.62 (s, 1H), 8.24 - 8.16 (m, 1H), 8.09 (d, J = 8.0 Hz, 1H), 8.06 - 7.99 (m, 1H), 7.84 (d, J = 8.0 Hz, 2H), 7.77 (d, J = 6.8 Hz, 1H), 7.64 - 7.58 (m, 3H), 7.39 (t, J = 7.6 Hz, 2H), 7.13 (t, J = 7.2 Hz, 1H); 13 C NMR (101 MHz, Dimethyl sulfoxide-d6) δ 167.4, 139.5, 134.9, 133.3, 130.2, 129.8, 128.9, 128.5, 127.2, 126.5, 125.6, 125.3, 125.2, 123.8, 119.9。

[0064] Example 12

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

[0066] Example 13

[0067] In this example, equimolar N-methylmorpholine was used to replace N,N-diisopropylethylamine in Example 1. Other steps were the same as in Example 1, and N-phenylbenzamide was obtained with a yield of 80%.

[0068] In the above Example 1, without adding 2-naphthyl-2-benzothiazoline and without visible light irradiation, and other steps being the same as in Example 1, no target product was generated, indicating that 2-naphthyl-2-benzothiazoline and visible light are necessary conditions for the formation of amide compounds. At the same time, acyl radicals were captured by TEMPO, and the presence of the intermediate N-(benzoyloxy)-N-phenylaniline was found. From this, we speculate that in the presence of N,N-diisopropylethylamine, the formation of an EDA complex between the 2-naphthyl-2-benzothiazoline compound and the triazine ester compound is the key to generating acyl radicals. Subsequently, nitrobenzene will become radical nitroarene in this reaction system, and an acyl radical addition process will occur, successively becoming nitroso benzene and N-(benzoyloxy)-N-phenylaniline, and finally synthesizing the target product amide compounds.

Claims

1. A method for synthesizing amide compounds by synergistically inducing triazine esters with visible light / benzothiazoline derivatives, characterized in that: Under the protection of inert gas, the triazine ester shown in Formula I and the nitrobenzene compound shown in Formula II are added into an organic solvent, and a benzothiazoline derivative 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 the amide compound shown in Formula III; In the formula, Ar represents any one of aryl and substituted aryl; R represents any one of H, C1-C6 alkyl, C1-C6 alkoxy, and halogen; The benzothiazoline derivative is selected from any one of 2-naphthyl-2-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,N-diisopropylethylamine and N-methylmorpholine.

2. The method for synthesizing amide compounds by synergistically inducing triazine esters with visible light / benzothiazoline derivatives according to claim 1, wherein: The Ar represents any one of phenyl and naphthyl, or the aforementioned substituents substituted by any one of C1-C6 alkyl, C1-C6 alkoxy, phenyl, and halogen.

3. The method for synthesizing amide compounds by using visible light / benzothiazoline derivatives to synergistically induce triazine esters according to claim 1, wherein: The addition amount of the triazine ester is 3-4 times the molar amount of the nitrobenzene compound.

4. The method for synthesizing amide compounds by synergistically inducing triazine esters with visible light / benzothiazoline derivatives according to claim 1, characterized in that: The addition amount of the benzothiazoline derivative is 1.5-3 times the molar amount of the nitrobenzene compound.

5. The method for synthesizing amide compounds by synergistically inducing triazine esters with visible light / benzothiazoline derivatives according to claim 1, wherein: The addition amount of the organic base is 0.8-2 times the molar amount of the nitrobenzene compound.

6. The method for synthesizing amide compounds by using visible light / benzothiazoline derivatives to co-induce triazine esters according to claim 1, characterized in that: The organic solvent is any one of ethyl acetate, acetonitrile, tetrahydrofuran, dichloromethane, and dichloroethane.

7. The method for synthesizing amide compounds by using visible light / benzothiazoline derivatives to synergistically induce triazine esters according to claim 1, wherein: The reaction is carried out at room temperature for 3-5 hours under visible light irradiation.

8. The method for synthesizing amide compounds by using visible light / benzothiazoline derivatives to synergistically induce triazine esters according to claim 1 or 7, characterized in that: The visible light irradiation uses a 5-20W 380-400nm blue LED lamp.

Images