A furo[2,3-c]pyrrolidinedione compound and its synthesis method

Abstract

The present invention discloses a kind of furo[2,3-c]pyrrole-2,5-dione compounds and their synthesis method, belonging to the technical field of organic chemical synthesis. In the present invention, 3,4-dichloro-1-phenyl-1H-pyrrole-2,5-dione and β-dicarbonyl compounds are used as substrate raw materials, and furo[2,3-c]pyrrole-2,5-dione compounds are directly obtained by reacting in the presence of a weakly nucleophilic base. It has the advantages of high reaction efficiency, simple and easy operation, cheap and easily available raw materials, mild reaction conditions, short reaction time, good compatibility with various substituents, and high yield.

Description

Technical Field

[0001] The present invention relates to a kind of furano[2,3-c]pyrrole dione compound and its synthesis method, belonging to the technical field of organic chemical synthesis. Background Art

[0002] The maleimide skeleton is an important structural unit widely present in drugs, natural products, functional materials and bioactive molecules. Its saturated form is succinimide, which is also a structural unit with drug activity. This kind of parent nucleus exists in drugs such as Apremilast, Thalidomide, Phensuximide, Ethosuximide, and natural product antibiotic AM-2282. Besides having significant effects in aspects such as anti-tumor, anti-virus, antibacterial, and enzyme activity inhibition, it can further become an important parent nucleus for fluorescent materials and resin materials, such as non-conjugated A-PM fluorescent materials, BMI resins, etc.

[0003] Compounds with a furano[2,3-c]pyrrole parent nucleus have obvious effects in antibacterial and insecticidal aspects. For example, in the existing literature and patent supports, 5-isopropylfuran[2,3-c]pyrrole compound has been detected with antifungal activity; 2-methyl-5-phenyl-furano[2,3-c]pyrrole dione has good activity in weeding.

[0004] Currently, the main synthesis methods of this kind of compound are as follows:

[0005] (1) In 2019, Li Mengyao et al. obtained a series of furano pyrrole dione derivatives through a tandem cyclization reaction of bromo maleimide and 1,3-dicarbonyl compounds, with a yield reaching 78-93%.

[0006]

[0007] (2) In 2021, Zhao Shengyin et al. reported an oxidative cyclization reaction of maleimide and 1,3-dicarbonyl compounds catalyzed by copper salt, with the highest yield reaching 86%.

[0008]

[0009] (3) Fabio M et al. reported using 2,2,2-trichloro-1-(4,5-dihydrofuran-3-yl)ethan-1-one as the raw material, generating a cyano carboxylic acid compound through the action of NaCN, and then cyclizing with amine compounds to generate furano pyrrole compounds, with a good yield.

[0010]

[0011] (4) In 2021, Zhang Xiaomei et al. reported the enantioselective [3+2] cyclization of 3-hydroxymaleimide and quinone monoimine using chiral phosphoric acid as a catalyst. A variety of novel succinimide-fused dihydrobenzofurans with two consecutive quaternary stereocenters were obtained in moderate to excellent yields (up to 99%) and moderate to good enantioselectivities (up to 99% ee).

[0012] Summary of the Invention

[0013] In the first aspect, the present invention aims to provide a furano[2,3-c]pyrrole-2,5-dione compound.

[0014] A furano[2,3-c]pyrrole-2,5-dione compound, the structural formula of which is shown in formula (3),

[0015]

[0016] wherein, R1 is an alkyl group, a phenyl group, a benzyl group, a phenyl group with substituents on the benzene ring or a benzyl group; R2 is a methyl group or a phenyl group; R3 is a methyl group, a phenyl group or an alkoxy group.

[0017] As a preference of the above technical solution, R1 is a phenyl group with substituents on the benzene ring, and the substituents are selected from one of methyl, methoxy, halogen, and trifluoromethyl.

[0018] As a preference of the above technical solution, R1 is a phenyl group substituted by fluorine or chlorine.

[0019] As a preference of the above technical solution, R1 is a phenyl group substituted by methoxy, an ortho- or meta-methyl-substituted phenyl group, R2 is a methyl group, and R3 is a methyl group.

[0020] As another preference of the above technical solution, R1 is a p-methyl-substituted phenyl group, R2 is a phenyl group, and R3 is a phenyl group.

[0021] As still another preference of the above technical solution, R1 is a phenyl group substituted by methyl, R2 is a methyl group, and R3 is a methoxy group or an ethoxy group.

[0022] In the second aspect, the present invention aims to provide a synthesis method of the above compound.

[0023] A synthesis method of a furano[2,3-c]pyrrole-2,5-dione compound, comprising the following steps: reacting the compounds shown in general formulas (1) and (2) and a base in an organic solvent at room temperature for 2 to 5 hours, and separating and purifying the obtained reaction solution to obtain the product shown in general formula (3).

[0024]

[0025] In formula (1), R1 is an alkyl group, a phenyl group, a benzyl group, a phenyl group with substituents on the benzene ring, or a benzyl group with substituents.

[0026] In formula (2), R2 is a methyl group or a phenyl group; R3 is a methyl group, a phenyl group, or an alkoxy group.

[0027] The above reaction equation is as follows:

[0028]

[0029] In formula (3), R1 is an alkyl group, a phenyl group, a benzyl group, a phenyl group with substituents on the benzene ring, or a benzyl group with substituents; R2 is a methyl group or a phenyl group; R3 is a methyl group, a phenyl group, or an alkoxy group.

[0030] In the above technical solution of the present invention, the reaction process is monitored by TLC. When the reaction substrate (i.e., the compound shown in formula (1)) reacts completely, the reaction is ended by TLC monitoring.

[0031] In the above technical solution of the present invention, the process of separating and purifying the reaction solution is as follows:

[0032] Water is added to the reaction solution after the reaction, and it is extracted 2 - 3 times with dichloromethane. The organic phases are combined and dried with anhydrous magnesium sulfate, filtered, and the filtrate is concentrated under reduced pressure. The residue is purified by silica gel column chromatography, and the eluent containing the product is collected. The solvent is evaporated to obtain the furan[2,3-c]pyrrole dione compound. The eluent for silica gel column chromatography is a mixed solvent of petroleum ether and ethyl acetate with a volume ratio of 4:1.

[0033] As a preference of the above technical solution, the organic solvent is selected from one of dichloromethane, chloroform, toluene, acetonitrile, THF, DMF, and DMSO; the base is selected from one of triethylamine, potassium carbonate, DIPEA, and DABCO.

[0034] As a further preference of the above technical solution, the organic solvent is dichloromethane, and the base is DABCO.

[0035] In summary, the present invention has the following technical effects:

[0036] 1. The present invention uses the compounds shown in formula (1) and formula (2) as raw materials, and through a tandem cyclization reaction of a weakly nucleophilic base such as DABCO with a dicarbonyl compound, efficiently prepares furan[2,3-c]pyrrole-4,6(5H)-dione compounds.

[0037] 2. The synthesis method of this compound has the advantages of high reaction efficiency, simple and easy operation, cheap and easily available raw materials, mild reaction conditions, short reaction time, good compatibility with various substituents, and high yield.

[0038] 3. In existing patents, it has been proven that a few derivatives of maleimide have herbicidal and antibacterial activities. The present invention adopts a simpler and more efficient method to prepare furan[2,3-c]pyrrole-4,6(5H)-diones, which also have antibacterial and herbicidal activities or become the key research objects of antibacterial and herbicidal drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 1H NMR spectrum of product 3a provided in Example 1 of the present invention 1 1H NMR spectrum;

[0040] Figure 2 13C NMR spectrum of product 3a provided in Example 1 of the present invention 13 13C NMR spectrum;

[0041] Figure 3 1H NMR spectrum of product 3k provided in Example 11 of the present invention 1 1H NMR spectrum;

[0042] Figure 4 13C NMR spectrum of product 3k provided in Example 11 of the present invention 13 13C NMR spectrum;

[0043] Figure 5 1H NMR spectrum of product 3q provided in Example 17 of the present invention 1 1H NMR spectrum;

[0044] Figure 6 13C NMR spectrum of product 3q provided in Example 17 of the present invention 13 13C NMR spectrum;

[0045] Figure 7 1H NMR spectrum of product 3r provided in Example 18 of the present invention 1 1H NMR spectrum;

[0046] Figure 8 13C NMR spectrum of product 3r provided in Example 18 of the present invention 13 13C NMR spectrum;

[0047] Figure 9 1H NMR spectrum of product 3s provided in Example 19 of the present invention 1 1H NMR spectrum;

[0048] Figure 10 13C NMR spectrum of product 3s provided in Example 19 of the present invention 13 13C NMR spectrum. DETAILED DESCRIPTION OF THE INVENTION

[0049] In order to make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0050] Example 1

[0051] In a 25 mL single-necked dry flask, substrate 1a (0.3 mmol), 2a (0.33 mmol), DABCO (3 eq), and dry dichloromethane (2 mL) were added. The reaction was stirred at room temperature, and the reaction progress was monitored by TLC. After the reaction was completed, water was added, and the mixture was extracted with dichloromethane three times, washed with saturated brine, dried over anhydrous magnesium sulfate, concentrated, and purified by column chromatography. The eluent was petroleum ether:ethyl acetate (6:1), and white solid 3a was obtained with a yield of 96%.

[0052] Figure 1 The 1 1H NMR spectrum of product 3a is shown; Figure 2 The 13 13C NMR spectrum of product 3a is shown.

[0053] The 1 1H NMR 13 and 13C NMR data of the product are as follows

[0054] 1 1H NMR (500 MHz, CDCl3) δ 7.53 - 7.46 (m, 2H), 7.46 - 7.38 (m, 1H), 7.41 - 7.32 (m, 2H), 2.79 (s, 3H), 2.72 (s, 2H).

[0055] 13 13C NMR (125 MHz, CDCl3) δ 192.9, 169.3, 161.0, 156.5, 152.6, 131.3, 129.1, 128.2, 127.1, 126.9, 118.0, 31.6, 15.1.

[0056] Example 2

[0057] In a 25 mL single-necked dry flask, substrate 1b (0.3 mmol), 2b (0.33 mmol), DABCO (3 eq), and dry DMF (2 mL) were added. The reaction was stirred at room temperature, and the reaction progress was monitored by TLC. After the reaction was completed, water was added, and the mixture was extracted with dichloromethane three times, washed with saturated brine, dried over anhydrous magnesium sulfate, concentrated, and purified by column chromatography. The eluent was petroleum ether:ethyl acetate (6:1), and white solid 3b was obtained with a yield of 88%.

[0058] The 1 1H NMR 13 and 13C NMR data of the product are as follows

[0059] 11H NMR (500 MHz, CDCl3) δ 7.41 - 7.33 (m, 2H), 7.31 (td, J = 7.54, 2.25 Hz, 1H), 7.18 (dd, J = 7.9, 1.1 Hz, 1H), 2.79 (s, 2H), 2.71 (s, 3H), 2.23 (s, 3H).

[0060] 13 13C NMR (125 MHz, CDCl3) δ 192.91, 169.13, 161.03, 156.63, 152.70, 136.98, 131.12, 130.10, 129.60, 129.18, 127.34, 126.85, 118.09, 31.54, 17.96, 15.02.

[0061] Example 3

[0062] In a 25 mL single - necked dry flask, add substrate 1c (0.3 mmol), 2c (0.33 mmol), DABCO (3 eq), dry dichloromethane (2 mL), stir the reaction at room temperature, and monitor the reaction progress by TLC. After the reaction is completed, add water, extract with dichloromethane 3 times, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and perform column chromatography. The eluent is petroleum ether:ethyl acetate (6:1) to obtain white solid 3c with a yield of 91%.

[0063] The 1 1H spectrum, 13 13C spectrum data are as follows

[0064] 1 1H NMR (500 MHz, CDCl3) δ 7.37 (t, J = 7.76 Hz, 1H), 7.24 - 7.19 (m, 1H), 7.17 - 7.10 (m, 2H), 2.78 (s, 3H), 2.71 (s, 3H), 2.41 (s, 3H).

[0065] 13 13C NMR (125 MHz, CDCl3) δ 192.93, 169.26, 161.10, 156.62, 152.72, 139.21, 131.16, 129.13, 128.95, 127.58, 127.14, 124.05, 118.05, 31.58, 21.33, 15.05.

[0066] Example 4

[0067] In a 25 mL single-necked dry flask, add substrate 1d (0.3 mmol), 2d (0.33 mmol), DABCO (3 eq), and dry dichloromethane (2 mL). Stir the reaction at room temperature and monitor the reaction progress by TLC. After the reaction is completed, add water, extract with dichloromethane three times, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and perform column chromatography. The eluent is petroleum ether:ethyl acetate (6:1) to obtain white solid 3d with a yield of 61%.

[0068] The 1 1H spectrum, 13 13C spectrum data are as follows

[0069] 1 1H NMR (500 MHz, CDCl3) δ 7.29 (d, J = 8.1 Hz, 2H), 7.25 - 7.19 (m, 2H), 2.79 (s, 3H), 2.72 (s, 3H), 2.41 (s, 3H).

[0070] 13 13C NMR (125 MHz, CDCl3) δ 192.97, 169.20, 161.15, 156.71, 152.73, 138.36, 129.80, 128.62, 126.83, 118.06, 31.58, 21.15, 15.05.

[0071] Example 5

[0072] In a 25 mL single-necked dry flask, add substrate 1e (0.3 mmol), 2e (0.33 mmol), DIPEA (3 eq), and dry DMF (2 mL). Stir the reaction at room temperature and monitor the reaction progress by TLC. After the reaction is completed, add water, extract with dichloromethane three times, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and perform column chromatography. The eluent is petroleum ether:ethyl acetate (6:1) to obtain white solid 3e with a yield of 89%.

[0073] The 1 1H spectrum, 13 13C spectrum data are as follows

[0074] 1 1H NMR (500 MHz, CDCl3) δ 7.49 - 7.41 (m, 1H), 7.32 (td, J = 7.40, 1.78 Hz, 1H), 7.30 - 7.21 (m, 2H), 2.78 (s, 3H), 2.70 (s, 3H).

[0075] 1313C NMR (125 MHz, CDCl3) δ 192.7, 169.4, 160.24, 158.1 (d, J = 252.3 Hz), 155.81, 152.60, 130.95 (d, J = 8.1 Hz), 130.31, 127.59, 124.63 (d, J = 4.0 Hz), 118.93 (d, J = 13.8 Hz), 118.12, 116.68 (d, J = 20.1 Hz), 31.57, 15.06.

[0076] Example 6

[0077] In a 25 mL single-necked dry flask, add substrate 1f (0.3 mmol), 2f (0.33 mmol), DIPEA (3 eq), dry DMF (2 mL), stir the reaction at room temperature, and monitor the reaction progress by TLC. After the reaction is completed, add water, extract with dichloromethane 3 times, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and perform column chromatography. The eluent is petroleum ether:ethyl acetate (6:1) to obtain white solid 3f with a yield of 58%.

[0078] The 1 1H spectrum, 13 13C spectrum data are as follows

[0079] 1 1H NMR (500 MHz, CDCl3) δ 7.44 (td, J = 8.2, 6.3 Hz, 1H), 7.17 (dd, J = 8.0, 1.9 Hz, 1H), 7.16 - 7.06 (m, 2H), 2.78 (s, 3H), 2.70 (s, 3H).

[0080] 13 13C NMR (125 MHz, CDCl3) δ 192.6, 169.6, 162.5 (d, J = 247.3 Hz), 160.55, 155.9, 152.45, 132.66 (d, J = 10.4 Hz),, 130.19 (d, J = 8.65 Hz), 127.15, 122.25 (d, J = 3.05 Hz), 118.04, 115.05 (d, J = 21.0 Hz) 114.14 (d, J = 24.18 Hz), 31.56, 15.07.

[0081] Example 7

[0082] In a 25 mL single-necked dry flask, add 1 g (0.3 mmol) of the substrate, 2 g (0.33 mmol), DIPEA (3 eq), and dry DMF (2 mL). Stir the reaction at room temperature, and monitor the reaction progress by TLC. After the reaction is completed, add water, extract with dichloromethane three times, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and perform column chromatography. The eluent is petroleum ether:ethyl acetate (6:1) to obtain 3 g of a white solid with a yield of 56%.

[0083] The 1 1H spectrum, 13 13C spectrum data are as follows

[0084] 1 1H NMR (500 MHz, CDCl3) δ 7.37 - 7.29 (m, 2H), 7.23 - 7.14 (m, 2H), 2.80 (s, 3H), 2.72 (s, 3H).

[0085] 13 13C NMR (125 MHz, CDCl3) δ 197.5, 174.25, 166.78 (d, J = 248.8 Hz), 165.74, 161.23, 157.2, 133.55 (d, J = 9.17 Hz), 131.95, 122.85, 120.96 (d, J = 23.0 Hz), 36.38, 19.89.

[0086] Example 8

[0087] In a 25 mL single-necked dry flask, add 1 h (0.3 mmol) of the substrate, 2 h (0.33 mmol), DABCO (3 eq), and dry dichloromethane (2 mL). Stir the reaction at room temperature, and monitor the reaction progress by TLC. After the reaction is completed, add water, extract with dichloromethane three times, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and perform column chromatography. The eluent is petroleum ether:ethyl acetate (6:1) to obtain 3 h of a white solid with a yield of 40%.

[0088] The 1 1H spectrum, 13 13C spectrum data are as follows

[0089] 1 1H NMR (500 MHz, CDCl3) δ 7.57 (dd, J = 7.8, 1.8 Hz, 1H), 7.43 (dtd, J = 16.7, 7.5, 1.7 Hz, 2H), 7.35 (dd, J = 7.6, 1.9 Hz, 1H), 2.80 (s, 3H), 2.72 (s, 3H).

[0090] 1313C NMR (125 MHz, CDCl3) δ 197.54, 174.22, 165.20, 160.75, 157.33, 138.54, 136.04, 135.73, 135.18, 133.88, 132.54, 132.29, 122.91, 36.38, 19.90.

[0091] Example 9

[0092] In a 25 mL single-necked dry flask, add substrate 1i (0.3 mmol), 2i (0.33 mmol), DABCO (3 eq), and dry dichloromethane (2 mL). Stir the reaction at room temperature and monitor the reaction progress by TLC. After the reaction is completed, add water, extract with dichloromethane 3 times, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and perform column chromatography. The eluent is petroleum ether:ethyl acetate (6:1) to obtain white solid 3i with a yield of 60%.

[0093] The 1 1H spectrum, 13 13C spectrum data are as follows

[0094] 1 1H NMR (500 MHz, CDCl3) δ 7.26 - 7.28 (m, 1H), 7.36 - 7.43 (m, 3H), 2.70 (S, 3H), 2.78 (s, 3H).

[0095] 13 13C NMR (125 MHz, CDCl3) δ 192.6, 169.6, 160.5, 155.9, 152.4, 134.6, 130.0, 128.2, 127.1, 126.9, 124.8, 118.0, 31.5, 15.1.

[0096] Example 10

[0097] In a 25 mL single-necked dry flask, add substrate 1j (0.3 mmol), 2j (0.33 mmol), DABCO (3 eq), and dry dichloromethane (2 mL). Stir the reaction at room temperature and monitor the reaction progress by TLC. After the reaction is completed, add water, extract with dichloromethane 3 times, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and perform column chromatography. The eluent is petroleum ether:ethyl acetate (6:1) to obtain white solid 3j with a yield of 54%.

[0098] The 1 1H spectrum, 13 13C spectrum data are as follows

[0099] 11H NMR (500 MHz, CDCl3) δ 7.76 (d, J = 8.3 Hz, 2H), 7.54 (d, J = 8.3 Hz, 2H), 2.81 (s, 3H), 2.73 (s, 3H), 1.28 (s, 1H).

[0100] 13 13C NMR (125 MHz, CDCl3) δ 192.6, 169.8, 160.4, 155.8, 152.4, 134.5, 129.88 (q, J = 33.33 Hz), 127.2, 126.6, 126.24 (q, J = 3.54 Hz), 123.71 (q, J = 272.68 Hz), 118.1, 31.58, 15.12.

[0101] Example 11

[0102] In a 25 mL single-necked dry flask, substrate 1k (0.3 mmol), 2k (0.33 mmol), DABCO (3 eq), and dry dichloromethane (2 mL) were added. The reaction was stirred at room temperature, and the reaction progress was monitored by TLC. After the reaction was completed, water was added, and the mixture was extracted with dichloromethane three times, washed with saturated brine, dried over anhydrous magnesium sulfate, concentrated, and purified by column chromatography with a mobile phase of petroleum ether:ethyl acetate (6:1) to obtain white solid 3k with a yield of 80%.

[0103] Figure 3 The 1 1H spectrum of product 3k is shown; Figure 4 The 13 13C spectrum of product 3k is shown.

[0104] The 1 1H spectrum, 13 13C spectrum data of the product are as follows

[0105] 1 1H NMR (500 MHz, CDCl3) δ 7.42 - 7.25 (m, 5H), 4.73 (s, 2H), 2.73 (s, 3H), 2.67 (s, 3H).

[0106] 13 13C NMR (125 MHz, CDCl3) δ 192.9, 168.8, 161.6, 157.3, 152.8, 136.3, 128.7, 128.4, 127.3, 117.9, 41.8, 31.5, 14.9.

[0107] Example 12

[0108] In a 25 mL single-necked dry flask, add substrate 1l (0.3 mmol), 2l (0.33 mmol), DABCO (3 eq), and dry acetonitrile (2 mL). Stir the reaction at 50 °C, and monitor the reaction progress by TLC. After the reaction is completed, add water, extract with dichloromethane three times, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and perform column chromatography. The eluent is petroleum ether:ethyl acetate to obtain white solid 3l with a yield of 85%.

[0109] The 1 1H spectrum, 13 13C spectrum data are as follows

[0110] 1 1H NMR (500 MHz, CDCl3) δ 7.46 (d, J = 7.5 Hz, 2H), 7.35 (t, J = 7.6 Hz, 2H), 7.28 (t, J = 7.4 Hz, 1H), 5.43 (q, J = 7.3 Hz, 1H), 2.72 (s, 3H), 2.66 (s, 3H), 1.89 (d, J = 7.3 Hz, 3H).

[0111] 13 13C NMR (125 MHz, CDCl3) δ 193.0, 168.6, 161.7, 157.4, 152.7, 140.2, 128.5, 127.7, 127.2, 126.9, 117.9, 49.9, 31.5, 17.6, 14.9.

[0112] Example 13

[0113] In a 25 mL single-necked dry flask, add substrate 1m (0.3 mmol), 2m (0.33 mmol), potassium carbonate (3 eq), and dry acetonitrile (2 mL). Stir the reaction at room temperature, and monitor the reaction progress by TLC. After the reaction is completed, add water, extract with dichloromethane three times, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and perform column chromatography. The eluent is petroleum ether:ethyl acetate (6:1) to obtain white solid 3m with a yield of 98%.

[0114] The 1 1H spectrum, 13 13C spectrum data are as follows

[0115] 1 1H NMR (500 MHz, CDCl3) δ 3.55 (t, J = 7.2 Hz, 2H), 2.71 (s, 3H), 2.66 (s, 3H), 1.59 (p, J = 7.5 Hz, 2H), 1.33 (p, J = 7.4 Hz, 2H), 0.92 (t, J = 7.3 Hz, 3H).

[0116] 13 13C NMR (125 MHz, CDCl3) δ 193.0, 168.5, 162.0, 157.7, 152.9, 127.1, 117.8, 37.9, 31.4, 30.8, 19.9, 14.9, 13.5.

[0117] Example 14

[0118] In a 25 mL single-necked dry flask, substrate 1n (0.3 mmol), 2j (0.33 mmol), DABCO (3 eq), and dry dichloromethane (2 mL) were added. The reaction was stirred at room temperature, and the reaction progress was monitored by TLC. After the reaction was completed, water was added, and the mixture was extracted with dichloromethane three times, washed with saturated brine, dried over anhydrous magnesium sulfate, concentrated, and purified by column chromatography with a mobile phase of petroleum ether:ethyl acetate (6:1) to obtain white solid 3n in a yield of 93%.

[0119] The 1 1H NMR, 13 13C NMR data of the product are as follows

[0120] 1 1H NMR (500 MHz, CDCl3) δ 7.28 - 7.21 (d, J = 8.85 Hz, 2H), 7.03 - 6.96 (d, J = 8.87 Hz, 2H), 3.84 (s, 3H), 2.78 (s, 3H), 2.71 (s, 3H).

[0121] 13 13C NMR (125 MHz, CDCl3) δ 192.9, 169.1, 161.3, 159.4, 156.8, 152.6, 128.4, 127.0, 123.8, 118.0, 114.4, 55.5, 31.5, 15.0.

[0122] Example 15

[0123] In a 25 mL single-necked dry flask, substrate 1o (0.3 mmol), 2o (0.33 mmol), DABCO (3 eq), and dry dichloromethane (2 mL) were added. The reaction was stirred at room temperature, and the reaction progress was monitored by TLC. After the reaction was completed, water was added, and the mixture was extracted with dichloromethane three times, washed with saturated brine, dried over anhydrous magnesium sulfate, concentrated, and purified by column chromatography with a mobile phase of petroleum ether:ethyl acetate (6:1) to obtain white solid 3o in a yield of 52%.

[0124] The 1 1H NMR, 13 13C NMR data of the product are as follows

[0125] 11H NMR (500 MHz, CDCl3) δ 7.48 (t, J = 7.8 Hz, 2H), 7.42 - 7.36 (m, 1H), 7.37 - 7.32 (m, 2H), 4.39 (q, J = 7.2 Hz, 2H), 2.81 (s, 3H), 1.43 (t, J = 7.1 Hz, 3H).

[0126] 13 13C NMR (125 MHz, CDCl3) δ 169.59, 161.41, 159.66, 156.72, 153.40, 131.49, 129.11, 128.09, 127.92, 126.98, 111.83, 61.49, 14.55, 14.13.

[0127] Example 16

[0128] In a 25 mL single-necked dry flask, add substrate 1p (0.3 mmol), 2p (0.33 mmol), DABCO (3 eq), and dry dichloromethane (2 mL). Stir the reaction at room temperature and monitor the reaction progress by TLC. After the reaction is completed, add water, extract with dichloromethane 3 times, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and perform column chromatography. The eluent is petroleum ether:ethyl acetate (6:1) to obtain white solid 3p with a yield of 47%.

[0129] The 1 1H spectrum, 13 13C spectrum data are as follows

[0130] 1 1H NMR (500 MHz, CDCl3) δ 7.46 - 7.39 (m, 1H), 7.32 (t, J = 7.3 Hz, 1H), 7.25 (t, J = 8.4 Hz, 2H), 4.38 (q, J = 7.2 Hz, 2H), 2.81 (s, 3H), 1.41 (t, J = 7.1 Hz, 3H).

[0131] 13 13C NMR (125 MHz, CDCl3), δ 192.6, 169.6 163.5, 161.5 (d, J = 247.1 Hz), 157.2, 155.9, 130.8, 130.7 (d, J = 8.16 Hz), 130.3, 128.3, 124.59, 124.56 (d, J = 3.53 Hz), 119.19, 119.09 (d, J = 13.53 Hz), 116.72, 116.56 (d, J = 20.04 Hz), 111.8, 61.4, 14.4, 14.0.

[0132] Example 17

[0133] In a 25 mL single-necked dry flask, add substrate 1q (0.3 mmol), 2q (0.33 mmol), DABCO (3 eq), and dry dichloromethane (2 mL). Stir the reaction at room temperature and monitor the reaction progress by TLC. After the reaction is completed, add water, extract with dichloromethane three times, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and perform column chromatography. The eluent is petroleum ether:ethyl acetate (6:1) to obtain white solid 3q with a yield of 54%.

[0134] Figure 5 The 1 1H NMR spectrum of product 3q is shown; Figure 6 The 13 13C NMR spectrum of product 3q is shown.

[0135] The 1 1H NMR, 13 13C NMR data of the product are as follows

[0136] 1 1H NMR (500 MHz, CDCl3) δ 7.27 - 7.20 (m, 2H), 7.02 - 6.95 (m, 2H), 4.38 (q, J = 7.2 Hz, 2H), 3.83 (s, 3H), 2.79 (s, 3H), 1.42 (t, J = 7.1 Hz, 3H).

[0137] 13 13C NMR (125 MHz, CDCl3) δ 169.43, 161.43, 160.01, 159.32, 157.06, 153.44, 128.48, 127.86, 124.07, 114.46, 111.78, 61.45, 55.49, 14.50, 14.12.

[0138] Example 18

[0139] In a 25 mL single-necked dry flask, add substrate 1r (0.3 mmol), 2r (0.33 mmol), DABCO (3 eq), and dry dichloromethane (2 mL). Stir the reaction at room temperature and monitor the reaction progress by TLC. After the reaction is completed, add water, extract with dichloromethane three times, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and perform column chromatography. The eluent is petroleum ether:ethyl acetate (6:1) to obtain white solid 3r with a yield of 50%.

[0140] Figure 7 The 1 1H NMR spectrum of product 3r is shown; Figure 8 The 13 13C NMR spectrum of product 3r is shown.

[0141] of the product 1 1H NMR spectrum, 13 13C NMR spectrum data are as follows

[0142] 1 1H NMR (500 MHz, CDCl3) δ 7.98 - 7.91 (m, 2H), 7.84 - 7.74 (m, 2H), 7.65 - 7.59 (m, 1H), 7.59 - 7.33 (m, 4H), 7.28 (s, 1H), 7.25 - 7.16 (m, 2H), 2.39 (s, 3H).

[0143] 13 13C NMR (125 MHz, CDCl3) δ 188.53, 163.9, 159.92, 156.9, 153.3, 138.20, 136.55, 134.31, 131.02, 129.75, 128.94, 128.76, 128.71, 127.86, 127.71, 126.71, 117.09, 21.16.

[0144] Example 19

[0145] In a 25 mL single - necked dry flask, substrate 1s (0.3 mmol), 2s (0.33 mmol), DABCO (3 eq), and dry dichloromethane (2 mL) were added. The reaction was stirred at room temperature, and the reaction progress was monitored by TLC. After the reaction was completed, water was added, and the mixture was extracted with dichloromethane three times, washed with saturated brine, dried over anhydrous magnesium sulfate, concentrated, and purified by column chromatography. The eluent was petroleum ether:ethyl acetate (6:1), and white solid 3s was obtained with a yield of 74%.

[0146] Figure 9 Shown is the 1 1H NMR spectrum of product 3s; Figure 10 Shown is the 13 13C NMR spectrum of product 3s.

[0147] of the product 1 1H NMR spectrum, 13 13C NMR spectrum data are as follows

[0148] 1 1H NMR (500 MHz, CDCl3) δ 7.27 - 7.20 (m, 2H), 7.02 - 6.95 (m, 2H), 3.94 (s, 3H), 3.84 (s, 3H), 2.80 (s, 3H).

[0149] 1313C NMR (125 MHz, CDCl3) δ 169.64, 161.89, 160.01, 159.29, 157.00, 153.50, 128.40, 127.71, 124.05, 114.43, 111.32, 55.48, 52.31, 29.68, 14.54.

[0150] Example 20

[0151] In a 25 mL single-necked dry flask, add substrate 1t (0.3 mmol), 2t (0.33 mmol), potassium carbonate (3 eq), and dry acetonitrile (2 mL). Stir the reaction at 50 °C, and monitor the reaction progress by TLC. After the reaction is completed, add water, extract with dichloromethane three times, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and perform column chromatography. The eluent is petroleum ether:ethyl acetate (6:1) to obtain white solid 3t with a yield of 75%.

[0152] The 1 1H spectrum, 13 13C spectrum data are as follows

[0153] 1 1H NMR (500 MHz, CDCl3) δ 7.46 (t, J = 7.8 Hz, 2H), 7.41 - 7.31 (m, 3H), 3.92 (s, 3H), 2.79 (s, 3H).

[0154] 13 13C NMR (125 MHz, CDCl3) δ 169.79, 161.83, 159.61, 156.61, 153.45, 131.48, 129.06, 128.03, 127.74, 126.88, 111.33, 52.31, 14.53.

[0155] Example 21

[0156] In a 25 mL single-necked dry flask, add substrate 1u (0.3 mmol), 2u (0.33 mmol), potassium carbonate (3 eq), and dry acetonitrile (2 mL). Stir the reaction at 50 °C, and monitor the reaction progress by TLC. After the reaction is completed, add water, extract with dichloromethane three times, wash with saturated brine, dry over anhydrous magnesium sulfate, concentrate, and perform column chromatography. The eluent is petroleum ether:ethyl acetate (6:1) to obtain white solid 3u with a yield of 60%.

[0157] The 1 1H spectrum, 13 13C spectrum data are as follows

[0158] 11H NMR (500 MHz, CDCl3) δ 7.98 - 7.91 (m, 2H), 7.84 - 7.74 (m, 2H), 7.65 - 7.59 (m, 1H), 7.59 - 7.33 (m, 4H), 7.28 (s, 1H), 7.25 - 7.16 (m, 2H), 2.39 (s, 3H).

[0159] 13 13C NMR (125 MHz, CDCl3) δ 188.53, 164.02, 160.00, 138.20, 136.55, 134.31, 131.02, 129.75, 128.94, 128.76, 128.71, 127.86, 127.71, 126.71, 117.09, 21.16.

[0160] The product 3a prepared in Example 1 of the present invention can be further used for synthesizing the herbicidal and antibacterial 2 - methyl - 5 - phenyl - furan[2,3 - c]pyrrolidinedione compound. The present invention provides a feasible and simple synthetic reaction route as follows:

[0161]

[0162] The reaction conditions in the above - mentioned synthetic reaction route are as follows:

[0163] 2.692 grams (10 millimoles) of 3 - acetyl - 2 - methyl - 5 - phenyl - 4H - furan[2,3 - c]pyrrole - 4,6(5H) - dione was added to 10 milliliters of anhydrous ethanol, and 1.02 grams (15 millimoles) of sodium ethoxide dissolved in 10 milliliters of anhydrous ethanol was slowly added dropwise. After the reaction ended, a small amount of ice - water was added to quench the reaction, and it was rotary - evaporated under reduced pressure. The crude product was recrystallized using chloroform and petroleum ether to finally obtain the 2 - methyl - 5 - phenyl - furan[2,3 - c]pyrrolidinedione herbicide compound.

[0164] The reaction substrates, corresponding products and yields involved in Examples 1 - 21 are listed in the following table.

[0165]

[0166]

[0167]

Claims

1. A 2-methyl-5-phenyl-furo[2,3-c]pyrrolidinedione intermediate, characterized in that: The structural formula of the said compound is as shown in Formula (3), wherein, R1 is phenyl; R2 is methyl; R3 is methyl, phenyl or alkoxy group.

2. The 2-methyl-5-phenyl-furan[2,3-c]pyrrolidione intermediate according to claim 1, characterized in that, R3 is methyl.

3. A method for synthesizing the 2-methyl-5-phenyl-furan[2,3-c]pyrrole dione intermediate according to any one of claims 1 to 2, characterized in that, It includes the following steps: React the compounds shown by General Formula (1) and (2) and a base in an organic solvent at room temperature for 2 - 5 hours, and the obtained reaction solution is separated and purified to obtain the product shown by General Formula (3). In Formula (1), R1 is phenyl; In Formula (2), R2 is methyl; R3 is methyl, phenyl or alkoxy group.

4. The synthesis method of an intermediate of 2-methyl-5-phenyl-furo[2,3-c]pyrrole-2,5-dione according to claim 3, characterized in that: The said organic solvent is selected from one of methylene chloride, chloroform, toluene, acetonitrile, THF, DMF, DMSO; the said base is selected from one of triethylamine, potassium carbonate, DIPEA, DABCO.

5. The synthesis method of an intermediate of 2-methyl-5-phenyl-furan[2,3-c]pyrrole dione according to claim 3, characterized in that: The said organic solvent is methylene chloride and the said base is DABCO.

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