CN108299272B - A method of ketone compound is coughed up in the chloro- 2,2,2- trifluoro ethylidene substitution of synthesis 1- - Google Patents
A method of ketone compound is coughed up in the chloro- 2,2,2- trifluoro ethylidene substitution of synthesis 1- Download PDFInfo
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- CN108299272B CN108299272B CN201810094947.1A CN201810094947A CN108299272B CN 108299272 B CN108299272 B CN 108299272B CN 201810094947 A CN201810094947 A CN 201810094947A CN 108299272 B CN108299272 B CN 108299272B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/36—Oxygen or sulfur atoms
- C07D207/38—2-Pyrrolones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
Abstract
The invention discloses a kind of synthesis 1- chloro- 2,2,2- trifluoro ethylidene replaces the method for coughing up ketone compound: using trifluoroacetic anhydride as reagent, to cough up ketone derivatives as substrate, using alchlor as catalyst, in a solvent, 60 DEG C are heated to, is stirred 24 hours, reaction solution post-processes to obtain 1- chloro- 2 after reaction, ketone compound is coughed up in the substitution of 2,2- trifluoro ethylidene.The advantages that generally higher, raw material is easy to get synthetic method of the invention with yield, easy to operate, and substrate is wide, has good prospects for commercial application.
Description
Technical field
The invention belongs to organic fluorine chemistries to synthesize field, and in particular to a kind of chloro- 2,2,2- trifluoro ethylidene of synthesis 1- takes
The method that generation coughs up ketone compound.
Background technique
Organic fluoride-containing compound is widely used to medicine, agriculture because having good bioactivity and stronger stability
The fields such as medicine and functional material.Therefore, the method as being selectively introducing fluorine-containing atomic radical in whither organic molecule is studied
Have become the research emphasis of current organic fluorine chemistry.For example, trifluoromethyl group, which is introduced into organic compound, can make mesh
Polarity, dipole moment, stability and the lipophilicity of mark molecule are improved.
On the other hand, coughing up ketone compounds is a kind of important heterocyclic compound, is widely present in natural products and all kinds of
In artificial synthesized bioactive compound.It is widely used in since pyrrolidones have multiple biological activities
Field of medicaments.The present invention utilizes some raw materials simple and easy to get, and assimilation is coughed up in the substitution of chloro- 2,2,2- trifluoro ethylidene of one-step synthesis 1-
Object is closed, is expected to be applied on medicine, pesticide and advanced material.
Summary of the invention
Replace the side for coughing up ketone compound the purpose of the present invention is to provide a kind of chloro- 2,2,2- trifluoro ethylidene of synthesis 1-
The advantages that method, high, raw material is easy to get with yield, easy to operate, and substrate is wide, has good prospects for commercial application.
To achieve the above object, the present invention adopts the following technical scheme:
A kind of method that ketone compound is coughed up in the substitution of chloro- 2,2,2- trifluoro ethylidene of synthesis 1-, is anti-with trifluoroacetic anhydride
Reagent is answered, to cough up ketone derivatives as reaction substrate, using alchlor as catalyst, heated reaction obtains the 1- in a solvent
Ketone compound is coughed up in chloro- 2,2,2- trifluoro ethylidene substitution；
Its reaction process are as follows:；
Its specific reaction step are as follows: in nitrogen atmosphere, to magnetic stirring apparatus container in be added alchlor,
Ketone derivatives, trifluoroacetic anhydride are coughed up, shut plug after mixing, are heated to 60 DEG C, after being stirred to react 24 h, use acetic acid
Ethyl ester extracts three times, merges organic phase, saturated sodium chloride solution is added to wash, and after anhydrous magnesium sulfate is dry, revolving removes organic
Solvent, obtained crude product are chloro- through the isolated 1- of silica gel column chromatography using pentane (n-hexane) and ethyl acetate as eluant, eluent
What 2,2,2- trifluoro ethylidene replaced coughs up ketone compounds.
Wherein, trifluoroacetic anhydride, cough up ketone derivatives, alchlor and solvent molar ratio be 0.30-3.00:0.10-
1.00:0.15-1.50:16-50。
The solvent is N,N-dimethylformamide.
The general structure for coughing up ketone derivatives are as follows:, it is specially any one in following formula 1- formula 30:
。
The chloro- 2,2,2- trifluoro ethylidene of gained 1- replaces the general structure for coughing up ketone compound are as follows:,
Any one specially in following formula 1- formula 30:
。
The beneficial effects of the present invention are:
The present invention with trifluoroacetic anhydride cheap and easy to get, cough up ketone derivatives etc. as raw material, one-step synthesis 1- chloro- 2,2,2- tri-
Ketone compound is coughed up in the substitution of fluorine ethylidene, easy to operate, universal yield with higher, and substrate spectrum is wide, is had good
Prospects for commercial application.
Detailed description of the invention
Fig. 1 is the chloro- 2,2,2- trifluoro ethylidene of (Z) -3-(1- made from embodiment 1) -1- methylpyrrolidin- 2- ketone monocrystalline
Structural schematic diagram.
Specific embodiment
In order to make content of the present invention easily facilitate understanding, With reference to embodiment to of the present invention
Technical solution is described further, but the present invention is not limited only to this.
Embodiment 1
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1- methylpyrrolidin- are added
2- ketone, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mL n,N-Dimethylformamide, in 60 DEG C of enclosed systems
After being stirred to react 24 h, it is extracted with ethyl acetate three times, merges organic phase, add saturated sodium chloride solution to wash, through anhydrous slufuric acid
After magnesium is dry, revolving removes organic solvent；Obtained crude product passes through using pentane (n-hexane) and ethyl acetate as eluant, eluent
The isolated chloro- 2,2,2- trifluoro ethylidene of (Z) -3-(1- of silica gel column chromatography) -1- methylpyrrolidin- 2- ketone (yield 93%).1H
NMR (400 MHz, CDCl3) δ 3.45 (t, J = 6.3 Hz, 2H), 3.15 - 3.05 (m, 2H), 3.01
(s, 3H). 19F NMR (376 MHz, CDCl3) δ -64.8 (t, J = 3.0 Hz, 3F). 13C NMR (101
MHz, CDCl3) δ 164.4 (s),134.3 (s), 121.4 (q, J= 38.8 Hz), 124.7 (q, J = 274.3
Hz), 45.3 (q, J = 1.6 Hz), 30.5 (s), 25.2 (q, J = 3.3 Hz)。
Embodiment 2
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1- ethyl pyrrolidines-are added
2- ketone, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mL n,N-Dimethylformamide, in 60 DEG C of enclosed systems
After being stirred to react 24 h, it is extracted with ethyl acetate three times, merges organic phase, add saturated sodium chloride solution to wash, through anhydrous slufuric acid
After magnesium is dry, revolving removes organic solvent；Obtained crude product passes through using pentane (n-hexane) and ethyl acetate as eluant, eluent
The isolated chloro- 2,2,2- trifluoro ethylidene of (Z) -3-(1- of silica gel column chromatography) -1- ethyl pyrrolidine -2- ketone (yield 95%).1H
NMR (400 MHz, CDCl3) δ 3.51 – 3.40 (m, 4H), 3.15 - 3.02 (m, 2H), 1.18 (t, J =
7.3 Hz, 3H). 19F NMR (376 MHz, CDCl3) δ -64.8 (t, J = 3.1 Hz, 3F). 13C NMR (101
MHz, CDCl3) δ163.9 (s), 134.9 (q, J = 1.9 Hz), 121.1 (q, J = 38.8 Hz), 124.7
(q, J = 274.2 Hz), 42.6 (q, J = 1.6 Hz), 38.1 (s), 25.2 (q, J = 3.3 Hz), 12.2
(s)。
Embodiment 3
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1- butyl pyrrolidines-are added
2- ketone, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mL n,N-Dimethylformamide, in 60 DEG C of enclosed systems
After being stirred to react 24 h, it is extracted with ethyl acetate three times, merges organic phase, add saturated sodium chloride solution to wash, through anhydrous slufuric acid
After magnesium is dry, revolving removes organic solvent；Obtained crude product passes through using pentane (n-hexane) and ethyl acetate as eluant, eluent
The isolated chloro- 2,2,2- trifluoro ethylidene of (Z) -1- butyl -3-(1- of silica gel column chromatography) pyrrolidin-2-one (yield 85%).1H
NMR (400 MHz, CDCl3) δ 3.42 (dd, J = 14.4, 7.2 Hz, 4H), 3.08 (ddt, J = 9.3,
6.3, 3.1 Hz, 2H), 1.62 – 1.51 (m, 2H), 1.35 (dq, J = 14.6, 7.3 Hz, 2H), 0.95
(t, J = 7.3 Hz, 3H). 19F NMR (376 MHz, CDCl3) δ -64.8 (t, J = 3.1 Hz, 3F). 13C
NMR (101 MHz, CDCl3) δ 164.1 (s), 134.81 (q, J = 1.9 Hz), 121.2 (q, J = 38.7
Hz), 124.8 (q, J = 274.2 Hz), 43.3 (dd, J = 3.3, 1.6 Hz), 43.2 (s), 29.08
(s), 25.3 (q, J = 3.3 Hz), 24.1 (s), 13.7 (s)。
Embodiment 4
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1- cyclohexyl pyrroles are added
Alkane -2- ketone, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mLN, dinethylformamide, 60 DEG C of enclosed systems
In be stirred to react 24 h after, be extracted with ethyl acetate three times, merge organic phase, add saturated sodium chloride solution to wash, through anhydrous sulphur
After sour magnesium is dry, revolving removes organic solvent；Obtained crude product leads to using pentane (n-hexane) and ethyl acetate as eluant, eluent
Cross the isolated chloro- 2,2,2- trifluoro ethylidene of (Z) -3-(1- of silica gel column chromatography) -1- cyclohexyl pyrrolidin-2-one (yield
96%).1H NMR (400 MHz, CDCl3) δ 4.08 (tt, J = 11.5, 3.6 Hz, 1H), 3.41 (t, J =
6.3 Hz, 2H),3.2- 3.0 (m, 2H), 1.85 (dd, J = 7.7, 2.6 Hz, 2H), 1.78 (d, J =
6.4 Hz, 2H), 1.75 – 1.59 (m, 2H), 1.53 – 1.34 (m, 4H). 19F NMR (376 MHz,
CDCl3) δ -64.8 (t, J = 3.1 Hz, 3F)13C NMR (101 MHz, CDCl3) δ 163.6 (s), 135.4
(q, J = 2.0 Hz), 124.8 (q, J = 38.7 Hz), 124.8 (q, J = 274.2 Hz), 51.7 (s),
39.4 (q, J = 1.6 Hz), 29.9 (s), 25.4 (s), 25.4 (s), 25.4 (t, J = 1.7 Hz)。
Embodiment 5
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1- Phenylpyrrolidines-are added
2- ketone, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mL n,N-Dimethylformamide, in 60 DEG C of enclosed systems
After being stirred to react 24 h, it is extracted with ethyl acetate three times, merges organic phase, add saturated sodium chloride solution to wash, through anhydrous slufuric acid
After magnesium is dry, revolving removes organic solvent；Obtained crude product passes through using pentane (n-hexane) and ethyl acetate as eluant, eluent
The isolated chloro- 2,2,2- trifluoro ethylidene of (Z) -3-(1- of silica gel column chromatography) -1- Phenylpyrrolidine -2- ketone (yield 92%).1H
NMR (400 MHz, CDCl3) δ 7.71 (d, J = 7.9 Hz, 2H), 7.42 (t, J = 8.0 Hz, 2H),
7.23 (t, J = 7.4 Hz, 1H), 3.87 (t, J = 6.6 Hz, 2H), 3.23-3.14 (m, J = 6.2,
2H). 19F NMR (376 MHz, CDCl3) δ -64.6 (t, J = 3.1 Hz). 13C NMR (101 MHz, CDCl3)
δ 163.1 (s), 138.7 (s), 134.9 (d, J = 1.9 Hz), 129.0 (s), 125.8 (s), 122.8
(q, J = 38.7 Hz), 124.7 (q, J = 274.5 Hz), 124.1 (s), 44.4 (d, J = 1.4 Hz),
25.0 (q, J = 3.3 Hz)。
Embodiment 6
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1-(4-tolyl is added)
Pyrrolidin-2-one, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mL n,N-Dimethylformamide, 60 DEG C closed
After being stirred to react 24 h in system, it is extracted with ethyl acetate three times, merges organic phase, add saturated sodium chloride solution to wash, through nothing
After water magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is elution with pentane (n-hexane) and ethyl acetate
Agent passes through isolated chloro- 2,2, the 2- trifluoro ethylidene of (Z) -3-(1- of silica gel column chromatography) -1-(4- tolyl) pyrrolidines -2-
Ketone (yield 96%).1H NMR (400 MHz, CDCl3) δ 7.61 (d, J = 8.2 Hz, 2H), 7.23 (d, J =
8.2 Hz, 2H), 3.89 (t, J = 6.5 Hz, 2H), 3.27-3.14 (m, 2H), 2.37 (s, 3H). 19F
NMR (376 MHz, CDCl3) δ -64.6 (t, J = 3.2 Hz, 3F). 13C NMR (101 MHz, CDCl3) δ
162.9 (s), 136.2 (s), 135.6 (s), 134.9 (d, J = 1.8 Hz), 129.6 (s), 122.6 (q,J = 38.1Hz), 120.7 (q, J = 273.5 Hz), 120.0 (s), 44.5 (d, J = 1.4 Hz), 25.0
(q, J = 3.2 Hz), 20.9 (s)。
Embodiment 7
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1-(2-tolyl is added)
Pyrrolidin-2-one, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mL n,N-Dimethylformamide, 60 DEG C closed
After being stirred to react 24 h in system, it is extracted with ethyl acetate three times, merges organic phase, add saturated sodium chloride solution to wash, through nothing
After water magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is elution with pentane (n-hexane) and ethyl acetate
Agent passes through isolated chloro- 2,2, the 2- trifluoro ethylidene of (Z) -3-(1- of silica gel column chromatography) -1-(2- tolyl) pyrrolidines -2-
Ketone (yield 92%).1H NMR (400 MHz, CDCl3) δ 7.29 (s, 1H), 7.27 (d, J = 1.9 Hz, 1H),
7.24 (dd, J = 7.2, 2.4 Hz, 1H), 3.74 (t, J = 6.4 Hz, 2H), 3.36 – 3.15 (m,
2H), 2.24 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -64.7 (t, J = 3.2 Hz, 3F). 13C
NMR (101 MHz, CDCl3) δ 163.3 (s), 136.7 (s), 135.5 (s), 134.3 (q, J = 2.0
Hz), 131.3 (s), 128.5 (s), 127.0 (s), 126.2 (s),122.9(q, J = 39 Hz) 124.7 (q,J = 274.5 Hz), 46.3 (q, J = 1.7 Hz), 26.0 (q, J = 3.3 Hz), 18.0 (s)。
Embodiment 8
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1-(3-tolyl is added)
Pyrrolidin-2-one, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mL n,N-Dimethylformamide, 60 DEG C closed
After being stirred to react 24 h in system, it is extracted with ethyl acetate three times, merges organic phase, add saturated sodium chloride solution to wash, through nothing
After water magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is elution with pentane (n-hexane) and ethyl acetate
Agent passes through isolated chloro- 2,2, the 2- trifluoro ethylidene of (Z) -3-(1- of silica gel column chromatography) -1-(3- tolyl) pyrrolidines -2-
Ketone (yield 91%).1H NMR (400 MHz, CDCl3) δ 7.63 (s, 1H), 7.45 (d, J = 8.1 Hz, 1H),
7.30 (t, J = 7.7 Hz, 1H), 7.06 (d, J = 7.5 Hz, 1H), 3.89 (t, J = 6.5 Hz, 2H),
3.25-3.15 (m, 2H), 2.40 (s, 3H). 19F NMR (376 MHz, CDCl3) δ -64.6 (t, J = 3.0
Hz, 3F). 13C NMR (101 MHz, CDCl3) δ 163.1 (s), 139.0 (s),138.6 (s), 135.0 (d,J = 1.8 Hz), 128.8 (s), 126.6 (s), 122.8 (q, J = 38.8 Hz), 120.9 (s), 120.7
(q, J = 274.6 Hz), 117.0 (s), 44.5 (d, J = 1.4 Hz), 25.0 (q, J = 3.2 Hz),
21.6 (s)。
Embodiment 9
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1-(4- methoxybenzenes are added
Base) pyrrolidin-2-one, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mL n,N-Dimethylformamide, 60 DEG C
After being stirred to react 24 h in enclosed system, it is extracted with ethyl acetate three times, merges organic phase, saturated sodium chloride solution is added to wash,
After anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is with pentane (n-hexane) and ethyl acetate
Eluant, eluent passes through isolated chloro- 2,2, the 2- trifluoro ethylidene of (Z) -3-(1- of silica gel column chromatography) -1-(4- methoxyphenyl) pyrrole
Cough up alkane -2- ketone (yield 92%).1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 9.1 Hz, 2H), 6.95
(d, J = 9.1 Hz, 2H), 3.87 (t, J = 6.5 Hz, 2H), 3.84 (s, 3H), 3.26 – 3.14 (m,
2H). 19F NMR (376 MHz, CDCl3) δ -64.5 (t, J = 3.1 Hz, 3F). 13C NMR (101 MHz,
CDCl3) δ 162.8 (s), 157.4 (s), 134.9 (q, J = 1.9 Hz), 131.9 (s), 121.7 (s),
122.4(q, J = 38), 124.7 (q, J = 274.4 Hz), 114.2 (s), 55.5 (s), 44.7 (q, J =
1.7 Hz), 25.0 (q, J = 3.4 Hz)。
Embodiment 10
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1-(3- methoxybenzenes are added
Base) pyrrolidin-2-one, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mLN, dinethylformamide, 60 DEG C are close
After being stirred to react 24 h in closure system, it is extracted with ethyl acetate three times, merges organic phase, saturated sodium chloride solution is added to wash, pass through
After anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is to wash with pentane (n-hexane) and ethyl acetate
De- agent, passes through isolated chloro- 2,2, the 2- trifluoro ethylidene of (Z) -3-(1- of silica gel column chromatography) -1-(3- methoxyphenyl) pyrroles
Alkane -2- ketone (yield 91%).1H NMR (400 MHz, CDCl3) δ 7.53 (s, 1H), 7.32 (t, J = 8.2 Hz,
1H), 7.17 (d, J = 8.2 Hz, 1H), 6.81 (d, J = 8.3 Hz, 1H), 3.91 (t, J = 6.6 Hz,
2H), 3.86 (s, 3H), 3.26-3.14 (m, 2H). 19F NMR (376 MHz, CDCl3) δ -64.6 (t, J =
3.0 Hz, 3F). 13C NMR (101 MHz, CDCl3) δ 163.1 (s), 160.1 (s), 139.9 (s), 135.0
(q, J = 2.0 Hz), 129.7 (s), 122.9 (q, J = 38.7 Hz), 125.2 – 116.3 (m), 116.6
(d, J = 0.8 Hz), 111.8 (s), 111.6 (s), 55.4 (s), 44.5 (q, J = 1.5 Hz), 24.9
(q, J = 3.3 Hz)。
Embodiment 11
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1-(3,5- dimethyl are added
Phenyl) pyrrolidin-2-one, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mL n,N-Dimethylformamide, 60
After being stirred to react 24 h in DEG C enclosed system, it is extracted with ethyl acetate three times, merges organic phase, saturated sodium chloride solution is added to wash
It washs, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is with pentane (n-hexane) and ethyl acetate
For eluant, eluent, pass through isolated chloro- 2,2, the 2- trifluoro ethylidene of (Z) -3-(1- of silica gel column chromatography) -1-(3,5- dimethyl benzene
Base) pyrrolidin-2-one (yield 98%).
Embodiment 12
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1-(4-(fluoroforms are added
Oxygroup) phenyl) pyrrolidin-2-one, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mL N, N- dimethyl formyls
Amine after being stirred to react 24 h in 60 DEG C of enclosed systems, is extracted with ethyl acetate three times, merges organic phase, add saturated sodium-chloride molten
Liquid washing, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is with pentane (n-hexane) and acetic acid
Ethyl ester is eluant, eluent, passes through isolated chloro- 2,2, the 2- trifluoro ethylidene of (Z) -3-(1- of silica gel column chromatography) -1-(4-(fluoroform
Oxygroup) phenyl) pyrrolidin-2-one (yield 80%).
Embodiment 13
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1-(4- fluorophenyls are added)
Pyrrolidin-2-one, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mL n,N-Dimethylformamide, 60 DEG C closed
After being stirred to react 24 h in system, it is extracted with ethyl acetate three times, merges organic phase, add saturated sodium chloride solution to wash, through nothing
After water magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is elution with pentane (n-hexane) and ethyl acetate
Agent passes through isolated chloro- 2,2, the 2- trifluoro ethylidene of (Z) -3-(1- of silica gel column chromatography) -1-(4- fluorophenyl) pyrrolidines -2-
Ketone (yield 82%).
Embodiment 14
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1-(3- fluorophenyls are added)
Pyrrolidin-2-one, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mL n,N-Dimethylformamide, 60 DEG C closed
After being stirred to react 24 h in system, it is extracted with ethyl acetate three times, merges organic phase, add saturated sodium chloride solution to wash, through nothing
After water magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is elution with pentane (n-hexane) and ethyl acetate
Agent passes through isolated chloro- 2,2, the 2- trifluoro ethylidene of (Z) -3-(1- of silica gel column chromatography) -1-(3- fluorophenyl) pyrrolidines -2-
Ketone (yield 63%).
Embodiment 15
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1-(4-(fluoroforms are added
Base) phenyl) pyrrolidin-2-one, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mL n,N-Dimethylformamide,
After being stirred to react 24 h in 60 DEG C of enclosed systems, it is extracted with ethyl acetate three times, merges organic phase, saturated sodium chloride solution is added to wash
It washs, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is with pentane (n-hexane) and ethyl acetate
For eluant, eluent, pass through isolated chloro- 2,2, the 2- trifluoro ethylidene of (Z) -3-(1- of silica gel column chromatography) -1-(4-(trifluoromethyl)
Phenyl) pyrrolidin-2-one (yield 61%).
Embodiment 16
It is put into polytetrafluoroethylene (PTFE) magnetite one in a 25 mL reaction tubes, 1.00 mmol 1-(2-(fluoroforms are added
Base) phenyl) pyrrolidin-2-one, 1.5 mmol alchlors, 3 mmol trifluoroacetic anhydride and 4 mL n,N-Dimethylformamide,
After being stirred to react 24 h in 60 DEG C of enclosed systems, it is extracted with ethyl acetate three times, merges organic phase, saturated sodium chloride solution is added to wash
It washs, after anhydrous magnesium sulfate is dry, revolving removes organic solvent；Obtained crude product is with pentane (n-hexane) and ethyl acetate
For eluant, eluent, pass through isolated chloro- 2,2, the 2- trifluoro ethylidene of (Z) -3-(1- of silica gel column chromatography) -1-(2-(trifluoromethyl)
Phenyl) pyrrolidin-2-one (yield 79%).
The foregoing is merely presently preferred embodiments of the present invention, all equivalent changes done according to scope of the present invention patent with
Modification, is all covered by the present invention.
Claims (3)
1. a kind of chloro- 2,2,2- trifluoro ethylidene of synthesis 1- replaces the method for coughing up ketone compound, it is characterised in that: with trifluoroacetic acid
Acid anhydride is reaction reagent, and to cough up ketone derivatives as reaction substrate, using alchlor as catalyst, heated reaction is made in a solvent
Ketone compound is coughed up in the chloro- 2,2,2- trifluoro ethylidene substitution of 1-；Ketone compound is coughed up in the chloro- 2,2,2- trifluoro ethylidene substitution of the 1-
Structural formula are as follows:, any one in following formula 1- formula 16:
；
The solvent is N,N-dimethylformamide；
The structural formula for coughing up ketone derivatives is；Its any one in following formula 1- formula 16:。
2. chloro- 2,2,2- trifluoro ethylidene of synthesis 1- according to claim 1 replaces the method for coughing up ketone compound, feature
Be: trifluoroacetic anhydride used, the molar ratio for coughing up ketone derivatives, alchlor and solvent are 0.30-3.00:0.10-1.00:
0.15-1.50:16-50。
3. chloro- 2,2,2- trifluoro ethylidene of synthesis 1- according to claim 1 replaces the method for coughing up ketone compound, feature
Be: the temperature of the heating reaction is 60 DEG C, and the reaction time is for 24 hours.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004026826A1 (en) * | 2002-09-20 | 2004-04-01 | F. Hoffmann-La Roche Ag | 4-pyrrolidino-phenyl-benzyl ether derivatives |
| WO2007127704A1 (en) * | 2006-04-24 | 2007-11-08 | Eli Lilly And Company | Cyclohexyl substituted pyrrolidinones as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004026826A1 (en) * | 2002-09-20 | 2004-04-01 | F. Hoffmann-La Roche Ag | 4-pyrrolidino-phenyl-benzyl ether derivatives |
| WO2007127704A1 (en) * | 2006-04-24 | 2007-11-08 | Eli Lilly And Company | Cyclohexyl substituted pyrrolidinones as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1 |
Non-Patent Citations (2)
| Title |
|---|
| Efficient Trifluoromethylation of Activated and Non-Activated Alkenyl Halides by Using (Trifluoromethyl)trimethylsilane;Andreas Hafner等;《Adv. Synth. Catal.》;20111020;第353卷;第3044-3048页 * |
| Simo＇n E. Lo＇pez等.Trifluoroacetic acid: Uses and recent applications in organic synthesis.《Journal of Fluorine Chemistry》.2013,第156卷第73-100页. * |
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