CN107628980A - A kind of pyrrolidones of 3H 2 and its synthetic method - Google Patents
A kind of pyrrolidones of 3H 2 and its synthetic method Download PDFInfo
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Abstract
The invention provides a kind of pyrrolidones of 3H 2 and its synthetic method, this method promotes enamine compound as oxidant using persulfate and is cyclized rearrangement reaction, so that prepare the simple to operate of the pyrrolidones of 3H 2, it is relatively low to prepare cost, yield advantage and purity are higher, low in the pollution of the environment.In addition, the pyrrolidones of 3H 2 provided by the invention are that a series of structures are novel, have the compound of potential using value, the important chemicals such as substituted azole, butyrolactam, pyrrolidines, γ ketone acids and butanoic acid derivative can be converted into, are important organic synthesis intermediates.
Description
Technical field
The invention belongs to chemosynthesis technical field, in particular to a kind of 3H-2- pyrrolidones and its
Synthesis, purification process.
Background technology
More hydrogen pyrrolidones are a kind of special azepine 5-membered ring compounds, have physiological function, pharmaceutical active a variety of
Or have in the molecule synthesis of optical property important application (Journal of Medicinal Chemistry, 2005,48,
5412；Journal of Natural Products,2014,77,983).The pyrrolidones special as one kind,
It is important that 3H-2- pyrrolidones can also be converted into substituted azole, butyrolactam, pyrrolidines, γ -one acid and butanoic acid derivative etc.
Chemicals, be important organic synthesis intermediate (Advanced Synthesis＆Catalysis, 358,3010；Organic
Letters,2017,19,1172).But the synthetic method of 3H-2- pyrrolidones is extremely limited, particularly containing special function
Group or the 3H-2- pyrrolidones of substituent, because it is synthesized, difficulty is big, the low method report still without cost is prepared
Road.
The content of the invention
In view of the shortcomings of the prior art, the present inventor establishes a kind of simple and practical 3H-2- by many experiments
Pyrrolidones preparation method, a series of 3H-2- pyrrolidinone compounds for having synthesized reacted through tropic rearrangement and having generated
Compound.
Based on inventor's experimental result, of the invention first purpose is to provide a series of 3H-2- pyrrolidinone compounds
Compound, general structure are as follows：
Wherein R1=aryl or methyl, R2=ester group or ketone carbonyl.
It is further preferred that 3H-2- pyrrolidones as described above, aryl therein is to contain substituent
C6-C18Phenyl, biphenyl or simultaneously PAH and C4-C9Heterocyclic aryl.
Still further preferably, 3H-2- pyrrolidones as described above, aryl therein are selected from following one
Kind：Phenyl containing one or more substituents, 4- xenyls, 2- furyls, 2- thienyls, 3- thienyls.
It is further preferred that 3H-2- pyrrolidones as described above, ester group therein is-CO2R, R C1-
C6Alkyl, benzyl, pi-allyl, C6-C12Aryl.
Still further preferably, 3H-2- pyrrolidones as described above, ester group therein are selected from following one
Kind：-CO2Me,-CO2Et,-CO2 tBu,-CO2CH2Ph。
It is further preferred that 3H-2- pyrrolidones as described above, ketone carbonyl therein is-COAr, and Ar is
C4-C12Aromatic hydrocarbons, including the phenyl containing substituent, biphenyl and heterocyclic aryl.
Still further preferably, 3H-2- pyrrolidones as described above, ketone carbonyl therein are selected from following
It is a kind of：Benzoyl containing one or more substituents, 1- naphthoyls, 2- furanylcarbonyls, 2- Thenoyls, 3- thiophenes
Fen formoxyl.
In addition, second object of the present invention is the provision of a kind of synthesis of above-mentioned 3H-2- pyrrolidones
Method, this method comprise the following steps：This method is using enamine ester or enamine ketone compound as raw material, using persulfate as oxygen
Agent, additive is added, back flow reaction 6-20h obtains crude material in a solvent, and its specific reaction equation is as follows：
It is further preferred that the synthetic method of 3H-2- pyrrolidones as described above, wherein described oxidant
For potassium peroxydisulfate, sodium peroxydisulfate or ammonium persulfate, described additive is 2,2,6,6- tetramethyl piperidines-NO free radical, institute
The solvent stated is glycol dimethyl ether or tetrahydrofuran.
It is further preferred that the synthetic method of 3H-2- pyrrolidones as described above, wherein：Enamine ester or
Ketones with Enamino-esters, persulfate, the mol ratio of 2,2,6,6- tetramethyl piperidines-NO free radical are 1：(1-1.2)：(1-1.2) model
In enclosing.
Furthermore the invention provides a kind of purification process of 3H-2- pyrrolidones crude product, this method includes：
The 3H-2- pyrrolidones crude materials that above-mentioned synthetic method obtains are taken, add saturated sodium carbonate solution washing, then
Ethyl acetate extracts, and extract purifies through silica gel column chromatography, and eluent is that volume ratio is (3-10):1 petroleum ether：Acetic acid second
Ester.
Compared with prior art, the present invention creatively promotes enamine compound cyclisation weight by oxidant of persulfate
Row's reaction so that prepare the simple to operate of 3H-2- pyrrolidones, preparation cost is relatively low, and yield advantage and purity are more
Height, low in the pollution of the environment, ideal effect has been arrived in acquirement, is that the 3H-2- pyrrolidone-2 compounds reported at present synthesize most
One of directly efficient method.In addition, 3H-2- pyrrolidones provided by the invention be a series of structures it is novel,
Compound with potential using value, substituted azole, butyrolactam, pyrrolidines, γ -one acid and butyric acid can be converted into and derived
The important chemicals such as thing, it is important organic synthesis intermediate.
Embodiment
It is the specific embodiment of the present invention below, technical scheme is done and is further described, but it is of the invention
Protection domain be not limited to these embodiments.It is every to be included in this hair without departing substantially from the change of present inventive concept or equivalent substitute
Within bright protection domain.
Embodiment 1：The synthesis of 3H-2- pyrrolidones (2a), its structural formula are specific as follows：
1mmol enamines ester (1a) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 155mg, be computed yield as 88%.
Its main physical and chemical is as follows：
White solid, 144-145 DEG C of fusing point；1H NMR(400MHz,CDCl3):δ8.01(br,1H),7.65-7.68(m,
2H),7.56-7.59(m,2H),7.47-7.53(m,3H),7.34-7.39(m,3H),3.74(s,3H),3.58(s,3H)；13C
NMR(100MHz,CDCl3):δ174.6,167.8,163.3,153.2,134.6,131.3,128.9,128.8,128.6,
128.5,128.4,128.3,109.6,66.1,53.5,51.6；HRMS(ESI):m/z C20H17NNaO5[M+Na]+
374.1005。
Embodiment 2：The synthesis of 3H-2- pyrrolidones (2b), its structural formula are specific as follows：
1mmol enamines ester (1b) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 170mg, be computed yield as 90%.
Its main physical and chemical is as follows：
Yellow oil；1H NMR(400MHz,CDCl3):δ8.61(br,1H),7.64-7.67(m,2H),7.57-7.59
(m,2H),7.43-7.50(m,3H),7.33-7.37(m,3H),4.19-4.31(m,2H),4.03-4.09(m,2H),1.24
(t, J=7.1Hz, 3H), 1.04 (t, J=7.1Hz, 3H)；13C NMR(100MHz,CDCl3):δ175.3,167.2,162.8,
153.1,134.7,131.1,129.0,128.9,128.7,128.4,128.3,128.2,110.0,66.3,62.3,60.3,
14.1,14.0；HRMS(ESI):m/z C22H21NNaO5[M+Na]+402.1314。
Embodiment 3：The synthesis of 3H-2- pyrrolidones (2c), its structural formula are specific as follows：
1mmol enamines ester (1c) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 145mg, be computed yield as 72%.
Its main physical and chemical is as follows：
White solid, fusing point：166-168℃；1H NMR(400MHz,CDCl3):δ 8.02 (br, 1H), 7.57 (d, J=
8.2Hz, 2H), 7.46 (d, J=8.3Hz, 2H), 7.29 (d, J=8.0Hz, 2H), 7.17 (d, J=8.1Hz, 2H), 3.77 (s,
3H),3.58(s,3H),2.43(s,3H),2.34(s,3H)；13C NMR(100MHz,CDCl3):δ174.8,168.0,163.4,
153.4,141.8,138.3,131.7,129.2,129.1,128.9,128.4,125.9,109.2,65.8,53.4,51.5,
21.7,21.2；HRMS(ESI):m/z C22H21NNaO5[M+Na]+402.1313。
Embodiment 4：The synthesis of 3H-2- pyrrolidones (2d), its structural formula are specific as follows：
1mmol enamines ester (1d) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 133mg, be computed yield as 70%.
Its main physical and chemical is as follows：
White solid, fusing point：98-100℃；1H NMR(400MHz,CDCl3):δ8.32(br,1H),7.47-7.51(m,
2H), 7.31-7.40 (m, 4H), 7.23 (d, J=7.8Hz, 1H), 7.16 (d, J=7.5Hz, 1H), 3.78 (s, 3H), 3.59
(s,3H),2.43(s,3H),2.36(s,3H)；13C NMR(100MHz,CDCl3):δ174.9,167.9,163.3,153.4,
138.3,138.0,134.5,132.0,129.4,129.3,128.8,128.4,128.2,126.2,125.5,109.5,66.1,
53.4,51.5,27.1,21.8,21.5；HRMS(ESI):m/z C22H21NNaO5[M+Na]+402.1317。
Embodiment 5：The synthesis of 3H-2- pyrrolidones (2e), its structural formula are specific as follows：
1mmol enamines ester (1e) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 154mg, be computed yield as 76%.
Its main physical and chemical is as follows：
White solid, fusing point：173-175℃；1H NMR(400MHz,CDCl3):δ7.45(br,1H),7.28(s,2H),
7.16(s,2H),7.15(s,1H),6.98(s,1H),3.80(s,3H),3.59(s,3H),2.39(s,6H),2.32(s,6H)
；13C NMR(100MHz,CDCl3):δ174.3,168.0,163.4,153.2,138.3,137.8,134.4,132.9,130.3,
128.9,126.5,126.2,109.6,66.0,53.4,51.5,21.7,21.4；HRMS(ESI):m/z C24H25NNaO5[M+
Na]+430.1625。
Embodiment 6：The synthesis of 3H-2- pyrrolidones (2f), its structural formula are specific as follows：
1mmol enamines ester (1f) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 160mg, be computed yield as 79%.
Its main physical and chemical is as follows：
White solid, fusing point：173-175℃；1H NMR(400MHz,CDCl3):δ7.45(br,1H),7.28(s,2H),
7.16(s,2H),7.15(s,1H),6.98(s,1H),3.80(s,3H),3.59(s,3H),2.39(s,6H),2.32(s,6H)
；13C NMR(100MHz,CDCl3):δ174.3,168.0,163.4,153.2,138.3,137.8,134.4,132.9,130.3,
128.9,126.5,126.2,109.6,66.0,53.4,51.5,21.7,21.4；HRMS(ESI):m/z C24H25NNaO5[M+
Na]+430.1625.
Embodiment 7：The synthesis of 3H-2- pyrrolidones (2g), its structural formula are specific as follows：
1mmol enamines ester (1g) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 170mg, be computed yield as 83%.
Its main physical and chemical is as follows：
Faint yellow solid, fusing point：156-158℃；1H NMR(400MHz,CDCl3):δ 8.26 (br, 1H), 7.67 (d, J=
8.8Hz, 2H), 7.49 (d, J=9.0Hz, 2H), 6.98 (d, J=8.9Hz, 2H), 6.89 (d, J=9.0Hz, 2H), 3.88 (s,
3H),3.80(s,3H),3.76(s,3H),3.59(s,3H)；13C NMR(100MHz,CDCl3):δ175.2,168.3,163.6,
162.0,159.7,153.2,130.9,129.8,126.8,120.8,113.9,113.8,108.4,65.5,55.6,55.4,
53.3,51.5；HRMS(ESI):m/z C22H21NNaO7[M+Na]+434.1225。
Embodiment 8：The synthesis of 3H-2- pyrrolidones (2h), its structural formula are specific as follows：
1mmol enamines ester (1h) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 146mg, be computed yield as 71%.
Its main physical and chemical is as follows：
Weak yellow liquid；1H NMR(400MHz,CDCl3):δ 9.33 (br, 1H), 7.35 (t, J=7.9Hz, 1H), 7.25-
7.29(m,2H),7.20-7.23(m,2H),7.09-7.12(m,1H),7.01-7.04(m,1H),6.87-6.90(m,1H),
3.81(s,3H),3.78(s,3H),3.77(s,3H),3.59(s,3H)；13C NMR(100MHz,CDCl3):δ175.4,
167.6,163.1,159.3,159.2,153.3,135.8,129.6,129.3,129.0,121.5,120.5,117.4,
114.8,113.8,113.7,109.5,66.1,55.4,55.2,53.2,51.4；HRMS(ESI):m/z C22H21NNaO7[M+
Na]+434.1215.
Embodiment 9：The synthesis of 3H-2- pyrrolidones (2i), its structural formula are specific as follows：
1mmol enamines ester (1i) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 154mg, be computed yield as 79%.
Its main physical and chemical is as follows：
Weak yellow liquid；1H NMR(400MHz,CDCl3):δ9.08(br,1H),7.39(m,1H),7.27-7.32(m,
2H), 6.92-6.98 (m, 2H), 6.79 (d, J=8.6Hz, 1H), 3.93 (d, J=10.6Hz, 6H), 3.84 (s, 6H), 3.76
(s,3H),3.61(s,3H)；13C NMR(100MHz,CDCl3):δ175.7,168.2,163.6,153.1,151.6,149.3,
148.6,148.6,127.0,122.9,120.7,120.3,112.9,112.2,110.6,110.6,108.5,65.8,56.2,
56.1,56.1,55.9,53.3,51.5；HRMS(ESI):m/z C24H25NNaO9[M+Na]+494.1427。
Embodiment 10：The synthesis of 3H-2- pyrrolidones (2j), its structural formula are specific as follows：
1mmol enamines ester (1j) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 202mg, be computed yield as 80%.
Its main physical and chemical is as follows：
Faint yellow solid, fusing point：169-171℃；1H NMR(400MHz,CDCl3):δ8.52(br,1H),7.80-7.82
(m,2H),7.65-7.73(m,6H),7.58-7.61(m,4H),7.42-7.51(m,5H),7.33-7.37(m,1H),3.82
(s,3H),3.64(s,3H)；13C NMR(100MHz,CDCl3):δ175.0,167.9,163.4,153.2,144.2,141.4,
140.7,140.1,133.6,129.6,129.1,129.0,128.9,128.3,127.6,127.4,127.3,127.2,
127.1,127.1,109.5,66.0,53.5,51.6；HRMS(ESI):m/z calcd for C32H25NNaO5[M+Na]+
526.1624.
Embodiment 11：The synthesis of 3H-2- pyrrolidones (2k), its structural formula are specific as follows：
1mmol enamines ester (1k) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 141mg, be computed yield as 72%.
Its main physical and chemical is as follows：
Faint yellow solid, fusing point：164-166℃；1H NMR(400MHz,CDCl3):δ8.16(br,1H),7.69(m,
2H), 7.53 (m, 2H), 7.18 (t, J=8.6Hz, 2H), 7.05 (t, J=8.7Hz, 2H), 3.78 (s, 3H), 3.59 (s, 3H)
；13C NMR(100MHz,CDCl3):δ174.5,167.6,164.4(d,JC-F=251Hz), 163.1,162.9 (d, JC-F=
246Hz),152.5,131.3(d,JC-F=8.8Hz), 130.4 (d, JC-F=8.2Hz), 130.2 (d, JC-F=3.3Hz),
124.6(d,JC-F=3.6Hz), 115.9 (d, JC-F=22.1Hz), 115.3 (d, JC-F=21.6Hz), 109.5,65.4,
63.6,51.7；HRMS(ESI):m/z C20H15F2NNaO5[M+Na]+410.0811.
Embodiment 12：The synthesis of 3H-2- pyrrolidones (2l), its structural formula are specific as follows：
1mmol enamines ester (1l) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 169mg, be computed yield as 81%.
Its main physical and chemical is as follows：
White solid, fusing point：88-90℃；1H NMR(400MHz,CDCl3):δ 8.10 (br, 1H), 7.62 (d, J=
8.6Hz, 2H), 7.48 (m, 4H), 7.34 (d, J=8.7Hz, 2H), 3.79 (s, 3H), 3.59 (s, 3H)；13C NMR(100MHz,
CDCl3):δ174.2,167.3,162.9,152.4,137.7,134.8,132.8,130.4,130.0,129.0,128.6,
126.9,109.7,65.6,53.7,51.7；HRMS(ESI):m/z C20H15Cl2NNaO5[M+Na]+442.0239。
Embodiment 13：The synthesis of 3H-2- pyrrolidones (2m), its structural formula are specific as follows：
1mmol enamines ester (1m) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 116mg, be computed yield as 55%.
Its main physical and chemical is as follows：
White solid, fusing point：175-177℃；1H NMR(400MHz,CDCl3):δ8.09(br,1H),7.68-7.69(m,
1H),7.50-7.56(m,3H),7.42-7.46(m,2H),7.28-7.35(m,2H),3.80(s,3H),3.61(s,3H)；13C
NMR(100MHz,CDCl3):δ173.9,167.1,162.7,152.0,136.1,134.7,134.3,131.5,130.3,
130.0,129.1,128.9,128.8,127.1,126.8,110.0,65.7,53.7,51.8；HRMS(ESI):m/z
C20H15Cl2NNaO5[M+Na]+442.0220.
Embodiment 14：The synthesis of 3H-2- pyrrolidones (2n), its structural formula are specific as follows：
1mmol enamines ester (1n) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 190mg, be computed yield as 75%.
Its main physical and chemical is as follows：
White solid, fusing point：192-195℃.1H NMR(400MHz,CDCl3):δ 8.10 (br, 1H), 7.63 (d, J=
8.6Hz, 2H), 7.54 (d, J=8.7Hz, 2H), 7.49 (d, J=8.8Hz, 2H), 7.41 (d, J=8.8Hz, 2H), 3.78 (s,
3H),3.59(s,3H).13C NMR(100MHz,CDCl3):δ174.1,167.2,162.9,152.4,133.3,131.9,
131.6,130.5,130.3,127.4,126.1,123.0,109.7,65.6,53.7,51.8.HRMS(ESI):m/z
C20H15Br2NNaO5[M+Na]+531.9186.
Embodiment 15：The synthesis of 3H-2- pyrrolidones (2o), its structural formula are specific as follows：
1mmol enamines ester (1o) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 108mg, be computed yield as 44%.
Its main physical and chemical is as follows：
White solid, fusing point：105-108℃；1H NMR(400MHz,CDCl3):δ8.37(br,1H),7.75-7.80(m,
4H),7.62-7.69(m,4H),3.81(s,3H),3.60(s,3H)；13C NMR(100MHz,CDCl3):δ174.0,166.9,
162.7,152.2,138.0,133.3(q,JC-F=32.9Hz), 132.0,130.9 (q, JC-F=32.6Hz), 129.5,
129.1,125.6(q,JC-F=3.8Hz), 125.4 (q, JC-F=3.7Hz), 124.1 (d, JC-F=271.0Hz), 123.6 (d,
JC-F=270.8Hz), 110.5,65.9,53.9,51.9；HRMS(ESI):m/z C22H15F6NNaO5[M+Na]+510.0747.
Embodiment 16：The synthesis of 3H-2- pyrrolidones (2p), its structural formula are specific as follows：
1mmol enamines ester (1p) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 194mg, be computed yield as 83%.
Its main physical and chemical is as follows：
Yellow solid, fusing point：75-77℃；1H NMR(400MHz,CDCl3):δ 8.43 (br, 1H), 8.36 (d, J=
8.8Hz, 2H), 8.21 (d, J=9.0Hz, 2H), 7.85 (d, J=8.8Hz, 2H), 7.75 (d, J=9.0Hz, 2H), 4.24-
4.36 (m, 2H), 4.05-4.11 (m, 2H), 1.27 (t, J=7.1Hz, 3H), 1.05 (t, J=7.1Hz, 3H)；13C NMR
(100MHz,CDCl3):δ173.3,165.7,161.8,151.3,149.3,147.9,141.0,134.6,130.3,129.9,
123.7,123.3,111.4,66.0,63.2,61.2,14.2,14.0；HRMS(ESI):m/z C22H19N3NaO9[M+Na]+
492.1011.
Embodiment 17：The synthesis of 3H-2- pyrrolidones (2q), its structural formula are specific as follows：
1mmol enamines ester (1q) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 104mg, be computed yield as 57%.
Its main physical and chemical is as follows：
Faint yellow solid, fusing point:160-162℃；1H NMR(400MHz,CDCl3):δ9.68(br,1H),7.88-7.89
(m,1H),7.69-7.70(m,1H),7.30-7.32(m,1H),7.20-7.22(m,2H),6.97-6.99(m,1H),3.78
(s,3H),3.71(s,3H)；13C NMR(100MHz,CDCl3):δ174.3,167.2,146.3,136.4,133.2,133.0,
129.0,127.6,126.9,126.6,126.4,108.2,63.6,53.7,51.7；HRMS(ESI):m/z C16H13NNaO5S2
[M+Na]+386.1034.
Embodiment 18：The synthesis of 3H-2- pyrrolidones (2r), its structural formula are specific as follows：
1mmol enamines ester (1r) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 106mg, be computed yield as 58%.
Its main physical and chemical is as follows：
White solid, fusing point:170-171℃；1H NMR(400MHz,CDCl3):δ9.10(br,1H),8.30-8.31(m,
1H),7.65-7.67(m,1H),7.41-7.44(m,2H),7.29-7.34(m,2H),3.77(s,3H),3.67(s,3H)；13C
NMR(100MHz,CDCl3):δ174.8,167.5,163.4,147.1,134.3,131.2,128.8,128.1,127.9,
126.2,125.2,124.2,109.1,63.9,53.5,51.7；HRMS(ESI):m/z C16H13NNaO5S2[M+Na]+
386.0124.
Embodiment 19：The synthesis of 3H-2- pyrrolidones (2s), its structural formula are specific as follows：
1mmol enamines ester (1s) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 102mg, be computed yield as 62%.
Its main physical and chemical is as follows：
Brown solid, fusing point:201-202℃；1H NMR(400MHz,CDCl3):δ8.18-8.19(m,1H),7.92(br,
1H),7.60-7.61(m,1H),7.36-7.36(m,1H),6.69-6.70(m,1H),6.66-6.68(m,1H),6.38-6.40
(m,1H),3.79(s,3H),3.71(s,3H)；13C NMR(100MHz,CDCl3):δ170.7,166.1,162.9,146.8,
145.0,142.6,142.5,141.3,120.8,113.8,110.8,110.3,104.9,62.2,53.6,51.7；HRMS
(ESI):m/z C16H13NNaO7[M+Na]+354.0585.
Embodiment 20：The synthesis of 3H-2- pyrrolidones (4a), its structural formula are specific as follows：
1mmol enamines ester (3a) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 108mg, be computed yield as 87%.
Its main physical and chemical is as follows：
Brown solid, fusing point:145-147℃；1H NMR(400MHz,CDCl3):δ8.45(br,1H),3.72(s,3H),
3.70(s,3H),2.42(s,3H),1.61(s,3H)；13C NMR(100MHz,CDCl3):δ177.6,168.8,163.8,
152.6,111.7,57.4,53.1,51.3,19.3,13.8；HRMS(ESI):m/z C10H13NNaO5[M+Na]+250.0691.
Embodiment 21：The synthesis of 3H-2- pyrrolidones (4b), its structural formula are specific as follows：
1mmol enamines ester (3b) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=10: 1), obtain product 66mg, be computed yield as 52%.
Its main physical and chemical is as follows：
Brown solid, fusing point:104-105℃；1H NMR(400MHz,CDCl3):δ8.78(br,1H),4.11-4.20(m,
4H), 2.41 (s, 3H), 1.58 (s, 3H), 1.24 (t, J=7.1Hz, 3H), 1.19 (t, J=7.1Hz, 3H)；13C NMR
(100MHz,CDCl3):δ178.0,168.4,163.3,152.6,111.9,61.9,60.0,57.5,19.3,14.3,14.1,
13.6；HRMS(ESI):m/z C12H17NNaO5[M+Na]+278.1000.
Embodiment 22：The synthesis of 3H-2- pyrrolidones (4c), its structural formula are specific as follows：
1mmol enamines ester (3c) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=3: 1), obtain product 24mg, be computed yield as 24%.
Its main physical and chemical is as follows：
Brown liquid；1H NMR(400MHz,CDCl3):δ9.23(br,1H),2.46(s,3H),2.28(s,3H),2.07
(s,3H),1.54(s,3H)；13C NMR(100MHz,CDCl3):δ200.7,192.0,177.9,151.9,123.1,64.8,
29.7,26.2,18.6,15.0；HRMS(ESI):m/z C10H13NNaO3[M+Na]+562.1681.
Embodiment 23：The synthesis of 3H-2- pyrrolidones (4d), its structural formula are specific as follows：
1mmol enamines ester (3d) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=3: 1), obtain product 106mg, be computed yield as 67%.
Its main physical and chemical is as follows：
Brown solid, fusing point:178-180℃；1H NMR(400MHz,CDCl3):δ 9.05 (br, 1H), 7.63 (d, J=
7.2Hz,2H),7.44-7.49(m,2H),7.31-7.38(m,6H),1.81(s,3H),1.79(s,3H)；13C NMR
(100MHz,CDCl3):δ194.0,190.5,178.6,149.8,140.2,137.7,132.3,131.9,128.6,128.5,
127.9,127.2,124.1,63.7,21.4,15.1；HRMS(ESI):m/z C20H17NNaO3[M+Na]+342.1102.
Embodiment 24：The synthesis of 3H-2- pyrrolidones (4e), its structural formula are specific as follows：
1mmol enamines ester (3e) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=3: 1), obtain product 139mg, be computed yield as 79%.
Its main physical and chemical is as follows：
Brown solid, fusing point:225-227℃；1H NMR(400MHz,DMSO-d6):δ11.00(br,1H),7.48(d,J
=7.8Hz, 2H), 7.21-7.30 (m, 6H), 2.33 (s, 3H), 2.32 (s, 3H), 1.81 (s, 3H), 1.54 (s, 3H)；13C
NMR(100MHz,DMSO-d6):δ192.8,189.2,177.3,152.1,142.7,141.6,137.4,134.1,129.1,
128.9,127.9,127.0,122.4,62.3,21.0,20.9,14.8；HRMS(ESI):m/z C22H21NNaO3[M+Na]+
370.1408.
Embodiment 25：The synthesis of 3H-2- pyrrolidones (4f), its structural formula are specific as follows：
1mmol enamines ester (3f) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=3: 1), obtain product 130mg, be computed yield as 75%.
Its main physical and chemical is as follows：
Brown solid, fusing point:201-203℃；1H NMR(400MHz,DMSO-d6):δ11.09(br,1H),7.40(s,
1H), 7.34 (s, 3H), 7.26-7.30 (m, 2H), 7.12 (d, J=9.4Hz, 2H), 2.30 (d, J=8.4Hz, 6H), 1.78
(s,3H),1.59(s,3H)；13C NMR(100MHz,DMSO-d6):δ193.7,189.6,177.1,152.9,140.3,
137.8,137.7,136.9,133.0,131.9,128.4,128.3,127.9,127.3,124.7,123.8,122.4,62.5,
20.9,20.8,20.7,14.7；HRMS(ESI):m/z C22H21NNaO3[M+Na]+370.1412.
Embodiment 26：The synthesis of 3H-2- pyrrolidones (4g), its structural formula are specific as follows：
1mmol enamines ester (3g) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=3: 1), obtain product 116mg, be computed yield as 67%.
Its main physical and chemical is as follows：
Faint yellow solid, fusing point:192-195℃；1H NMR(400MHz,DMSO-d6):δ11.08(br,1H),7.33-
7.37(m,1H),7.25-7.30(m,2H),7.13-7.21(m,3H),7.06-7.08(m,1H),6.66(s,1H),2.33(s,
3H),1.62(s,6H),1.42(s,3H)；13C NMR(100MHz,DMSO-d6):δ197.0,190.4,176.4,155.4,
140.8,137.5,136.9,133.5,131.6,130.4,130.4,129.1,125.7,125.4,124.8,123.5,
122.8,62.7,20.5,19.3,17.4,13.0；HRMS(ESI):m/z C22H21NNaO3[M+Na]+370.1399.
Embodiment 27：The synthesis of 3H-2- pyrrolidones (4h), its structural formula are specific as follows：
1mmol enamines ester (3h) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=3: 1), obtain product 108mg, be computed yield as 52%.
Its main physical and chemical is as follows：
Brown solid, 153-155 DEG C of fusing point；1H NMR(400MHz,DMSO-d6):δ10.98(br,1H),7.37(s,
1H),7.28-7.31(m,1H),7.16-7.21(m,2H),7.11-7.12(m,2H),2.24(s,3H),2.23(s,3H),
2.22(s,3H),2.21(s,3H),1.80(s,3H),1.54(s,3H)；13C NMR(100MHz,DMSO-d6):δ192.8,
189.4,177.4,151.8,141.6,140.3,137.8,136.4,136.3,134.5,129.5,129.3,128.8,
128.1,125.4,124.4,122.5,62.4,21.0,19.43,19.40,19.37,19.1,14.8；HRMS(ESI):m/z
C20H15F2NNaO3[M+Na]+398.1718.
Embodiment 28：The synthesis of 3H-2- pyrrolidones (4i), its structural formula are specific as follows：
1mmol enamines ester (3i) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=3: 1), obtain product 161mg, be computed yield as 84%.
Its main physical and chemical is as follows：
Brown solid, 181-182 DEG C of fusing point；1H NMR(400MHz,CDCl3):δ 9.46 (br, 1H), 7.68 (d, J=
9.0Hz, 2H), 7.45 (d, J=8.8Hz, 2H), 6.83 (m, 4H), 3.81 (s, 3H), 3.77 (s, 3H), 1.87 (s, 3H),
1.73(s,3H)；13C NMR(100MHz,CDCl3):δ191.6,189.3,179.2,162.9,162.8,148.3,132.3,
132.1,130.6,129.8,129.7,124.0,113.7,63.3,55.4,55.3,21.6,15.0；HRMS(ESI):m/z
C22H21NNaO5[M+Na]+402.1297.
Embodiment 29：The synthesis of 3H-2- pyrrolidones (4j), its structural formula are specific as follows：
1mmol enamines ester (3j) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=3: 1), obtain product 128mg, be computed yield as 68%.
Its main physical and chemical is as follows：
Brown solid, fusing point:131-133℃；1H NMR(400MHz,DMSO-d6):δ11.13(br,1H),7.39(t,J
=8.0Hz, 1H), 7.33 (t, J=7.9Hz, 1H), 7.13-7.15 (m, 2H), 7.06-7.09 (m, 2H), 6.91 (d, J=
7.5Hz,1H),6.79(s,1H),3.75(s,3H),3.73(s,3H),1.59(s,3H)；13C NMR(100MHz,DMSO-d6):
δ193.3,189.2,177.1,159.1,159.1,153.2,141.7,138.0,129.8,129.7,122.3,119.7,
119.0,118.3,117.3,112.0,111.7,62.4,55.2,55.1,20.9,14.7；HRMS(ESI):m/z
C22H21NNaO5[M+Na]+402.1293.
Embodiment 30：The synthesis of 3H-2- pyrrolidones (4k), its structural formula are specific as follows：
1mmol enamines ester (3k) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=3: 1), obtain product 156mg, be computed yield as 71%.
Its main physical and chemical is as follows：
Faint yellow solid, fusing point:109-111℃；1H NMR(400MHz,DMSO-d6):δ10.95(br,1H),7.22-
7.26(m,2H),7.10-7.13(m,1H),6.95-7.03(m,3H),3.80(s,6H),3.74(s,3H),3.73(s,3H),
1.89(s,3H),1.53(s,3H)；13C NMR(100MHz,DMSO-d6):δ191.0,188.3,177.7,152.5,151.9,
150.9,148.4,148.3,132.4,129.0,122.6,122.3,121.3,111.0,110.8,110.1,62.2,55.7,
55.6,55.5,55.3,21.2,14.9；HRMS(ESI):m/z C24H25NNaO7[M+Na]+463.1529.
Embodiment 31：The synthesis of 3H-2- pyrrolidones (4l), its structural formula are specific as follows：
1mmol enamines ester (3l) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=3: 1), obtain product 86mg, be computed yield as 49%.
Its main physical and chemical is as follows：
Faint yellow solid, 219-220 DEG C of fusing point；1H NMR(400MHz,DMSO-d6):δ11.12(br,1H),7.64(m,
2H),7.49(m,2H),7.23-7.31(m,4H),1.83(s,3H),1.56(s,3H)；13C NMR(100MHz,DMSO-d6):δ
192.0,188.1,177.0,164.3(d,JC-F=249Hz), 163.9 (d, JC-F=249Hz), 153.2,136.4 (d, JC-F=
3.0Hz),133.2(d,JC-F=3.0Hz), 130.6 (d, JC-F=9.0Hz), 129.8 (d, JC-F=9.4Hz), 122.0,
115.7(d,JC-F=22.0Hz), 115.5 (d, JC-F=21.8Hz), 62.3,20.9,14.9.HRMS (ESI):m/z
C20H15F2NNaO3[M+Na]+378.0903.
Embodiment 32：The synthesis of 3H-2- pyrrolidones (4m), its structural formula are specific as follows：
1mmol enamines ester (3m) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=3: 1), obtain product 112mg, be computed yield as 58%.
Its main physical and chemical is as follows：
Faint yellow solid, 227-228 DEG C of fusing point；1H NMR(400MHz,DMSO-d6):δ11.17(br,1H),7.52-
7.56(m,4H),7.48-7.51(m,2H),7.41-7.43(m,2H),1.82(s,3H),1.55(s,3H)；13C NMR
(100MHz,DMSO-d6):δ192.6,188.1,176.8,153.8,138.6,137.3,136.3,135.3,129.7,
128.8,128.7,128.6,121.8,62.3,20.8,15.0；HRMS(ESI):m/z C20H15Cl2NNaO3[M+Na]+
410.0239.
Embodiment 33：The synthesis of 3H-2- pyrrolidones (4n), its structural formula are specific as follows：
1mmol enamines ester (3n) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=3: 1), obtain product 136mg, be computed yield as 57%.
Its main physical and chemical is as follows：
Faint yellow solid, 104-105 DEG C of fusing point；1H NMR(400MHz,DMSO-d6):δ11.15(br,1H),7.67(d,J
=8.7Hz, 2H), 7.63 (d, J=8.5Hz, 2H), 7.46 (d, J=8.6Hz, 2H), 7.35 (d, J=8.5Hz, 2H), 1.83
(s,3H),1.55(s,3H)；13C NMR(100MHz,DMSO-d6):δ192.8,188.2,176.7,153.8,138.9,
135.6,131.8,131.5,129.8,128.8,126.3,125.2,121.7,62.3,20.7,15.0；HRMS(ESI):m/z
C20H15Br2NNaO3[M+Na]+499.9298.
Embodiment 34：The synthesis of 3H-2- pyrrolidones (4o), its structural formula are specific as follows：
1mmol enamines ester (3o) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=3: 1), obtain product 106mg, be computed yield as 47%.
Its main physical and chemical is as follows：
Faint yellow solid, 243-245 DEG C of fusing point；1H NMR(400MHz,DMSO-d6):δ11.29(br,1H),7.85(d,J
=8.2Hz, 2H), 7.78 (d, J=8.1Hz, 2H), 7.70 (d, J=8.2Hz, 2H), 7.54 (d, J=8.1Hz, 2H), 1.78
(s,3H),1.60(s,3H)；13C NMR(100MHz,DMSO-d6):δ193.5,188.1,176.4,155.3,143.6,
140.2,131.8(d,JC-F=32.1Hz), 131.1 (d, JC-F=32.2Hz), 128.3,127.4,125.7 (q, JC-F=
3.8Hz),125.5(q,JC-F=3.7Hz), 125.1 (d, JC-F=9.1Hz), 122.3 (d, JC-F=8.9Hz), 121.4,
62.5,20.4,14.9；HRMS(ESI):m/z C22H15F6NNaO3[M+Na]+478.0852.
Embodiment 35：The synthesis of 3H-2- pyrrolidones (4p), its structural formula are specific as follows：
1mmol enamines ester (3p) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=3: 1), obtain product 114mg, be computed yield as 54%.
Its main physical and chemical is as follows：
Brown solid, fusing point:128-130℃；1H NMR(400MHz,DMSO-d6):δ10.69(br,1H),8.11(d,J
=7.8Hz, 1H), 8.03 (d, J=7.6Hz, 1H), 7.91-7.94 (m, 2H), 7.81 (d, J=8.4Hz, 1H), 7.67-7.69
(m,1H),7.54-7.64(m,4H),7.47-7.51(m,1H),7.39-7.43(m,1H),7.32-7.36(m,1H),6.98
(m,1H),2.45(s,3H),1.60(s,3H)；13C NMR(100MHz,DMSO-d6):δ196.7,190.0,189.9,181.9,
138.7,134.4,133.2,133.0,130.9,129.6,129.2,129.1,128.3,128.1,127.3,126.5,
126.3,125.7,125.0,124.9,124.8,124.7,124.2,123.1,109.8,77.8,19.5,17.4；HRMS
(ESI):m/z C28H21NNaO3[M+Na]+442.1424.
Embodiment 36：The synthesis of 3H-2- pyrrolidones (4q), its structural formula are specific as follows：
1mmol enamines ester (3q) and 1mmol 2,2,6,6- tetramethyl piperidines-NO free radical are added to 5mL ethylene glycol
In dimethyl ether, 1mmol potassium peroxydisulfates, back flow reaction 12h are then added.After reaction terminates, reaction solution adds 10mL unsaturated carbonates
Sodium solution washs, and is then extracted with ethyl acetate (10mL × 2), anhydrous sodium sulfate drying, is concentrated under reduced pressure after filtering, crude product is fast
Fast silica gel column chromatography (VEthyl acetate∶VPetroleum ether=3: 1), obtain product 110mg, be computed yield as 66%.
Its main physical and chemical is as follows：
Brown solid, 132-134 DEG C of fusing point；1H NMR(400MHz,DMSO-d6):δ11.00(br,1H),7.93-7.95
(m,1H),7.88-7.90(m,1H),7.73-7.74(m,1H),7.55-7.56(m,1H),7.17-7.19(m,1H),7.13-
7.15(m,1H),2.18(s,3H),1.48(s,3H)；13C NMR(100MHz,DMSO-d6):δ184.8,180.9,176.9,
152.2,143.9,141.0,134.2,133.8,133.5,131.5,128.5,128.0,121.5,62.5,19.0,15.3；
HRMS(ESI):m/z C16H13NNaO3S2[M+Na]+354.0238.
Claims (10)
1. a kind of 3H-2- pyrrolidones, its general structure are as follows：
Wherein R1=aryl or methyl, R2=ester group or ketone carbonyl.
2. 3H-2- pyrrolidones according to claim 1, it is characterised in that described aryl is containing taking
Dai Ji C6-C18Phenyl, biphenyl or simultaneously PAH or C4-C9Heterocyclic aryl.
3. 3H-2- pyrrolidones according to claim 2, it is characterised in that described aryl is selected from as follows
One kind：Phenyl containing one or more substituents, 4- xenyls, 2- furyls, 2- thienyls, 3- thienyls.
4. 3H-2- pyrrolidones according to claim 1, it is characterised in that described ester group is-CO2R,R
For C1-C6Alkyl, benzyl, pi-allyl, C6-C12Aryl.
5. 3H-2- pyrrolidones according to claim 4, it is characterised in that described ester group is selected from as follows
One kind：-CO2Me,-CO2Et,-CO2 tBu,-CO2CH2Ph。
6. 3H-2- pyrrolidones according to claim 1, it is characterised in that described ketone carbonyl is that carbon is former
Subnumber 6-18-COAr, Ar C4-C12Aromatic hydrocarbons, described aromatic hydrocarbons include the phenyl containing substituent, biphenyl and heterocyclic aryl.
7. 3H-2- pyrrolidones according to claim 6, it is characterised in that described ketone carbonyl is selected from such as
Under one kind：Benzoyl containing one or more substituents, 1- naphthoyls, 2- furanylcarbonyls, 2- Thenoyls,
3- Thenoyls.
A kind of 8. synthetic method of the 3H-2- pyrrolidones as described in claim any one of 1-7, it is characterised in that
This method is using enamine ester or enamine ketone compound as raw material, using persulfate as oxidant, adds or be added without additive,
Back flow reaction 6-20h obtains crude material in a solvent, and its specific reaction equation is as follows：
9. the synthetic method of 3H-2- pyrrolidones according to claim 8, it is characterised in that described oxidation
Agent persulfate is potassium peroxydisulfate, and described additive is 2,2,6,6- tetramethyl piperidines-NO free radical, and described solvent is
Glycol dimethyl ether or tetrahydrofuran.
10. a kind of purification process of 3H-2- pyrrolidones crude product, it is characterised in that this method includes：Weighting profit will
The 3H-2- pyrrolidones crude materials that 8 or 9 synthetic methods obtain are sought, add saturated sodium carbonate solution washing,
Then ethyl acetate extracts, and extract purifies through silica gel column chromatography, and eluent is that volume ratio is (3-10):1 petroleum ether：Acetic acid
Ethyl ester.
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| CN108409625A (en) * | 2018-02-07 | 2018-08-17 | 宁波大学 | A kind of preparation method of 2-Pyrrolidone class compound |
| CN111087338A (en) * | 2020-01-09 | 2020-05-01 | 常州大学 | Sulfonamide-substituted pyrrolidones derivative and preparation method thereof |
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Non-Patent Citations (3)
| Title |
|---|
| MALCOLM W. MOON: "Synthesis and Acylation of Pyrrolinones", 《J. ORG. CHEM.》 * |
| PENG GAO等: "K2S2O8/TEMPO-Induced Cascade Oxidative Cyclization/1,2-Migration of Electron-Deficient Groups: Strategy for the Construction of 1H‑Pyrrol-2(3H)‑ones", 《ORG. LETT.》 * |
| SIYU GUO等: "Nickel-catalyzed asymmetric transfer hydrogenation of conjugated olefins", 《CHEM. COMMUN》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108409625A (en) * | 2018-02-07 | 2018-08-17 | 宁波大学 | A kind of preparation method of 2-Pyrrolidone class compound |
| CN108409625B (en) * | 2018-02-07 | 2021-02-02 | 宁波大学 | Preparation method of 2-pyrrolidone compound |
| CN111087338A (en) * | 2020-01-09 | 2020-05-01 | 常州大学 | Sulfonamide-substituted pyrrolidones derivative and preparation method thereof |
| CN111087338B (en) * | 2020-01-09 | 2021-03-02 | 常州大学 | Sulfonamide-substituted pyrrolidones derivative and preparation method thereof |
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