CN108341755A - A method of it prepares containing bifunctional compound - Google Patents
A method of it prepares containing bifunctional compound Download PDFInfo
- Publication number
- CN108341755A CN108341755A CN201710059775.XA CN201710059775A CN108341755A CN 108341755 A CN108341755 A CN 108341755A CN 201710059775 A CN201710059775 A CN 201710059775A CN 108341755 A CN108341755 A CN 108341755A
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- bpo
- reaction
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 0 C(C1C2)C1=*2C1CCCC1 Chemical compound C(C1C2)C1=*2C1CCCC1 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N C1CCCCC1 Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- AHTQPOGWCCTNPO-UHFFFAOYSA-N CC(C)C1C2CCC1C2 Chemical compound CC(C)C1C2CCC1C2 AHTQPOGWCCTNPO-UHFFFAOYSA-N 0.000 description 1
- YBIRGONNHKHHFC-UHFFFAOYSA-N CC(NC(CCC#N)c(cc1)cc(OC)c1OC(C)=O)=O Chemical compound CC(NC(CCC#N)c(cc1)cc(OC)c1OC(C)=O)=O YBIRGONNHKHHFC-UHFFFAOYSA-N 0.000 description 1
- FTBUUBIPWKNBRF-UHFFFAOYSA-N CC(Oc(ccc(C=C)c1)c1OC)=O Chemical compound CC(Oc(ccc(C=C)c1)c1OC)=O FTBUUBIPWKNBRF-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B43/00—Formation or introduction of functional groups containing nitrogen
- C07B43/06—Formation or introduction of functional groups containing nitrogen of amide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/42—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms
- C07C255/44—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms at least one of the singly-bound nitrogen atoms being acylated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
This application discloses a kind of preparation methods of compound I, which is characterized in that in the presence of catalyst and radical initiator, by including that the compound II containing carbon-carbon double bond is reacted with the raw material of the compound III containing itrile group and is prepared.This method is with copper-based catalysts, with the compound of nitrile group-containing for Bifunctionalized reagent, realizes olefin(e) compound for the first time simultaneously by aminating reaction and cyanomethylation, the core skeleton of gamma aminobutyric acid derivative is prepared.
Description
Technical field
The method containing bifunctional compound is prepared this application involves a kind of, belongs to organic synthesis field.
Background technology
The intermolecular carbon aminating reaction of alkene is effective synthesis strategy that is a kind of while building C-C keys and C-N keys.
The carbon aminate of alkene includes the core skeleton in aminated compounds, amino acid, natural products and drug.Although this synthesis
Strategy is very useful, and the intermolecular carbon aminating reaction of alkene is but still very challenging and report is seldom.In addition, alkene
Intermolecular carbon amination generally require special reagent, such as NFSI, Togni reagent obtain high chemo-selective and region choosing
Selecting property.
γ-aminobutyric acid is inhibitory neurotransmitter critically important in central nervous system, can inhibit the activity of animal,
Reduce the consumption of energy.Research shows that GABA is related with the formation of certain diseases, in patient's Parkinson spinal cord the concentration of GABA compared with
Low, the GABA concentration in epileptic's spinal fluid is also below normal level.In addition, in nerve fiber the reduction of GABA also with
The formation of the neural disease of decaying such as Huntington choreas, Alzheimer disease, senile dementia is related.Many, which has, improves blood brain
The gamma-aminobutyric acid derivative of Barrier Permeability has been applied to clinical treatment these diseases.Many gamma-aminobutyric acid analogs
Also it is paid high attention to, the drug as treatment neural class disease.Therefore quickly and easily synthesis has γ-aminobutyric acid structure
Compound can promote the development of medicinal chemistry art.Currently, the carbon amination of alkene can be effectively synthesized a-amino acid and beta-amino
Acid, however but gamma-aminobutyric acid derivative is synthesized without method.
Invention content
According to the one side of the application, the method containing bifunctional compound of preparation is provided.This method is urged with copper-based
Agent realizes olefin(e) compound simultaneously by amination and cyanomethylation for the first time with the compound of nitrile group-containing for Bifunctionalized reagent,
The core skeleton of gamma-aminobutyric acid derivative is prepared.
A kind of preparation method of the compound I, which is characterized in that in the presence of catalyst and radical initiator,
By including that the compound II containing carbon-carbon double bond is reacted with the raw material of the compound III containing itrile group and is prepared;
The compound I is at least one of the compound containing structural unit shown in Formulas I;
The compound II containing carbon-carbon double bond in the compound with structural unit shown in Formula II at least one
Kind;
The compound III containing itrile group is selected from least one of the compound with structural formula shown in formula III;
R3- CN formula IIIs
Wherein, R1、R2One in alkyl, substituted hydrocarbon radical, heteroaryl, substituted heteroaryl, non-hydrocarbons substituent group
Kind;
R3Selected from C1~C20Alkyl in one kind;
A1For R3It loses a hydrogen atom and is formed by subunit.
Preferably, R1、R2Independently selected from hydrogen, C1~C20Alkyl, C1~C20In substituted hydrocarbon radical, non-hydrocarbons substituent group extremely
Few one kind.
Preferably, R3Selected from C1~C10Alkyl in one kind.
Preferably, the compound II containing carbon-carbon double bond, which is selected from, has the compound of structural formula, tool shown in Formula II -1
There are the compound of structural formula shown in Formula II -2, the compound with structural formula shown in Formula II -3, with structural formula shown in Formula II -4
At least one of compound:
In Formula II -1, R4、R5、R6、R7Independently selected from hydrogen, alkyl, substituted hydrocarbon radical, heteroaryl, substituted heteroaryl, nonhydrocarbon
One kind in class substituent group;
Wherein, n1, n2, n3, m1, m2 are independently selected from 0,1,2,3 or 4;, m3 be selected from 0,1,2 or 3;
R8、R9、R10、R11、R12、R13Independently selected from least one of alkyl, substituted hydrocarbon radical, non-hydrocarbons substituent group.
Preferably, in Formula II -1, R4、R5、R6、R7In contain aromatic rings and/or hetero-aromatic ring at least one structural formula.
Preferably, R8, R9, R10, R11, R12, R13Independently selected from C1~C20Alkyl, C1~C20Substituted hydrocarbon radical, non-hydrocarbons take
At least one of Dai Ji.
In the application, the substituent group in the substituted hydrocarbon radical, substituted heteroaryl is non-hydrocarbon substituents;The non-hydrocarbons take
Dai Ji be selected from oxygen, halogen, with the group of structural formula shown in formula (1), with the group of structural formula shown in formula (2), with formula (3)
The group of shown structural formula, at least one of the group with structural formula shown in formula (4):
In formula (1), M11Selected from hydrogen, C1~C10Alkyl;
In formula (2), M21Selected from hydrogen, C1~C10Alkyl;
M31- O- formulas (3)
In formula (3), M31Selected from hydrogen, C1~C10Alkyl.
The preferably described catalyst is selected from least one of the compound containing copper.It is further preferred that described
Catalyst is selected from four acetonitrile copper Cu (CH of hexafluorophosphoric acid3CN)4PF6, copper trifluoromethanesulfcomposite Cu (OTf)2, copper acetate Cu (OAc)2, iodine
Change cuprous CuI, stannous chloride CuCl, cuprous bromide CuBr, cupric oxalate CuC2O4At least one of.
Those skilled in the art can select suitable radical initiator according to actual needs.Preferably, the free radical
Initiator is selected from least one of organic peroxide.It is further preferred that the radical initiator is selected from acyl class peroxide
In compound, hydroperoxides, dialkyl peroxide, esters peroxide, ketone peroxide, two carbonic ester peroxide
It is at least one.It is further preferred that the radical initiator is selected from benzoyl peroxide, lauroyl peroxide, isopropylbenzene
Hydrogen peroxide, tert-butyl hydroperoxide, di-t-butyl peroxide, cumyl peroxide, peroxidized t-butyl perbenzoate, peroxide
Change trimethylacetic acid tertiary butyl ester, methyl ethyl ketone peroxide, cyclohexanone peroxide, di-isopropyl peroxydicarbonate, dicetyl peroxydicarbonate
At least one of dicyclohexyl maleate.Again it is further preferred that the radical initiator is benzoyl peroxide.
Those skilled in the art can select the ratio of each raw material in reaction according to actual needs.Preferably, described to contain carbon
The compound II of carbon double bond, the compound III containing itrile group, radical initiator and catalyst molar ratio be:
Compound II containing carbon-carbon double bond:Compound III containing itrile group:Radical initiator:Catalyst=1:2~
5:1~2:0.15~0.007.
As an implementation, the reaction temperature of the reaction is 50 DEG C to 90 DEG C, and the reaction time is 10h to 25h;
Preferably, the temperature of the reaction is 60 DEG C to 80 DEG C, and the reaction time is 15h to 18h.
As an implementation, organic solvent can be contained in the reaction system;The organic solvent is selected from nitrile
Solvent, such as acetonitrile, propionitrile, butyronitrile, isobutyronitrile, valeronitrile etc..Preferably, organic solvent (volume) and the chemical combination containing carbon-carbon double bond
The ratio of object II (molal quantity) is 4mL/mmol~60mL/mmol.It is further preferred that organic solvent (volume) with contain carbon carbon
The ratio of the compound II (molal quantity) of double bond is 10mL/mmol~30mL/mmol.
Preferably, contain inorganic acid in the reaction system.It is further preferred that the inorganic acid selects hexafluorophosphoric acid
HPF6, sulfuric acid H2SO4, at least one of trifluoromethanesulfonic acid HOTf.
As an implementation, the molar ratio of the inorganic acid and the compound II containing carbon-carbon double bond is:
Compound II containing carbon-carbon double bond:Inorganic acid=1:0.2~0.7.
As a preferred embodiment, the preparation method, at least includes the following steps:
A) it will include the compound II containing carbon-carbon double bond, the compound III containing itrile group, catalyst, free radical initiation
The mixture of agent and inorganic acid is placed in reaction vessel, and 10~25 hours postcoolings are stirred at 50 DEG C~90 DEG C to room temperature;
B) it is filtered with diatomite after ethyl acetate dilution is added, solvent, pillar layer separation is removed to get change through vacuum distillation
Close object I.
In the application, C1~C10、C1~C20Etc. referring both to carbon atom number included in group.
In the application, " alkyl " is to be formed by group by losing any one hydrogen atom on hydrocarbon molecules;Institute
It includes alkane compound, olefin(e) compound, acetylene hydrocarbon compound and aromatic compound to state hydrocarbon compound.As toluene loses on phenyl ring
The hydrogen atom of methyl contraposition is formed by p-methylphenyl or toluene loses the benzyl that any one hydrogen atom is formed on methyl
Deng.
In the application, " alkyl " is to be formed by group by losing any one hydrogen atom on alkane compound molecule.
In the application, " aryl " is to lose a hydrogen atom on aromatic rings on aromatic compound molecule to be formed by base
Group;It is formed by p-methylphenyl as toluene loses the hydrogen atom that methyl aligns on phenyl ring.
In the application, " heteroaryl " is to contain O, N, S heteroatomic aromatic compound (abbreviation heteroaryl in aromatic rings
Compound) any one hydrogen atom on aromatic rings is lost on molecule is formed by group;As lost any one hydrogen on piperazine ring
The formed piperazinyl of atom.
In the application, " halogen " refers at least one of fluorine, chlorine, bromine, iodine.
In the application, " the non-hydrocarbons substituent group " refers to containing other elements (such as halogen, S, O, P, N) in addition to H and C
Compound lose any one hydrogen atom and be formed by group.
In the application, the carbon atom of " substituted hydrocarbon radical ", " substituted arene base " and " substituted heteroaryl " is limited, refers to
The contained carbon atom number of alkyl, aryl, heteroaryl itself, and it is non-substituted after carbon atom number.Such as C1~C10Substituted hydrocarbon radical,
Finger carbon atom number is C1~C10Alkyl on, at least one hydrogen atom is substituted with a substituent.Such as a hydrogen quilt-C on adamantyl
≡ N replace the group for being 11 containing carbon atom number to be formed.
In the application, when the substituent group is oxygen, refers to two H atoms in group on any one C atom and is substituted by O,
Form C=O keys.
The advantageous effect of the application includes but not limited to:
(1) method provided herein, with raw material and catalyst are cheap, reaction condition is mild, easy to operate, reaction
The advantages that efficient.
(2) method provided herein realizes olefin(e) compound and is contained simultaneously by amination and cyanomethylation preparation for the first time
There is bifunctional compound, has obtained the core skeleton of gamma-aminobutyric acid derivative.
Specific implementation mode
The application is described in detail with reference to embodiment, but the application is not limited to these embodiments.
In embodiment, benzoyl peroxide is abbreviated as BPO.
In embodiment, nuclear magnetic resonance spectroscopy1400AVANCE III type spectroscopes of the H-NMR in Brooker company (Bruker)
(Spectrometer) it is measured on, 400MHz, CDCl3;Carbon is composed13C-NMR, 400MHz, CDCl3.Product separation uses
The full-automatic combiflash companion system of RF+UV-VIS types of Teledyne Isco.Electron impact mass spectra MS (EI) is used
The 6224TOF type mass spectrographs of AGILENT companies.
The yield of compound IV is calculated by the following formula on the basis of the amount of the compound I containing carbon-carbon double bond
It arrives:
Yield %=(quality that the quality ÷ target products that target product actually obtains should theoretically obtain) × 100%.
Embodiment 1
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 1-3, altogether
101mg, yield 78%.
The nuclear-magnetism detection data of Product samples 1-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.33 (d, J=8.3Hz, 2H), 7.15 (d, J=8.3Hz, 2H), 5.91 (d, J
=8.0Hz, 1H), 4.98-4.90 (m, 1H), 2.31-2.34 (m, 2H), 2.22-2.12 (m, 1H), 2.12-2.02 (m, 1H),
1.92(s,3H),1.24(s,9H)。13C NMR(100MHz,CDCl3)δ169.78,151.37,136.80,126.28,
126.10,119.41,52.52,34.60,31.67,31.29,23.38,14.56。HRMS(ESI)calcd for
[C16H22N2ONa]+([M+Na]+):281.1624,found:281.1624。
Embodiment 2
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 2-3, altogether
72mg, yield 66%.
The nuclear-magnetism detection data of Product samples 2-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.13-7.06 (m, 4H), 6.06 (d, J=7.8Hz, 1H), 4.95-4.88 (m,
1H),2.27(s,3H),2.26–2.21(m,2H),2.19–2.11(m,1H),2.08–1.99(m,1H),1.91(s,3H)。13C
NMR(100MHz,CDCl3)δ169.84,138.09,136.95,129.81,126.48,119.38,52.59,31.67,
23.34,21.09,14.51。HRMS(ESI)calcd for[C13H16N2ONa]+([M+Na]+):239.1155,found:
239.1156。
Embodiment 3
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 3-3, altogether
86mg, yield 79%.
The nuclear-magnetism detection data of Product samples 3-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.28-7.22 (m, 1H), 7.15-7.04 (m, 3H), 6.23 (d, J=7.9Hz,
1H),5.02–4.94(m,1H),2.35(s,3H),2.34–2.29(m,2H),2.28–2.19(m,1H),2.15–2.06(m,
1H),1.99(s,3H)。13C NMR(100MHz,CDCl3)δ168.96,139.04,137.82,127.97,127.90,
126.33,122.42,118.39,51.77,30.71,22.24,20.42,13.49。HRMS(ESI)calcd for
[C13H16N2ONa]+([M+Na]+):239.1155,found:239.1158。
Embodiment 4
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 4-3, altogether
89mg, yield 77%.
The nuclear-magnetism detection data of Product samples 4-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.09 (d, J=8.2Hz, 1H), 7.03 (d, J=6.7Hz, 1H), 7.02 (s,
1H), 5.89 (d, J=8.0Hz, 1H), 5.29-5.22 (m, 1H), 2.40-2.37 (m, 2H), 2.34-2.31 (m, 6H), 2.28-
2.22(m,1H),2.15–2.07(m,1H),1.98(s,3H)。13C NMR(100MHz,CDCl3)δ168.73,136.83,
135.17,132.10,130.08,127.77,124.49,118.45,47.64,30.41,22.22,20.10,17.88,
13.58。HRMS(ESI)calcd for[C14H18N2ONa]+([M+Na]+):253.1311,found:253.1312。
Embodiment 5
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 5-3, altogether
100mg, yield 84%.
The nuclear-magnetism detection data of Product samples 5-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.35 (d, J=8.4Hz, 2H), 7.24 (d, J=8.4Hz, 2H), 6.15 (d, J
=7.9Hz, 1H), 5.07-4.99 (m, 1H), 2.36 (t, J=7.4Hz, 2H), 2.25-2.07 (m, 2H), 2.00 (s, 3H).13C
NMR(100MHz,CDCl3)δ169.92,138.65,134.06,129.30,127.94,119.15,52.19,31.49,
23.31,14.56。HRMS(ESI)calcd for[C12H13ClN2ONa]+([M+Na]+):259.0609,found:
259.0610。
Embodiment 6
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 6-3, altogether
89mg, yield 80%.
The nuclear-magnetism detection data of Product samples 6-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.27-7.14 (m, 2H), 7.05-6.92 (m, 2H), 6.16 (d, J=7.9Hz,
1H), 5.00-4.92 (m, 1H), 2.28 (t, J=7.4Hz, 2H), 2.19-1.09 (m, 1H), 2.07-1.99 (m, 1H), 1.92
(s,3H)。13C NMR(100MHz,CDCl3) δ 169.91,162.38 (d, J=247.2Hz), 136.00 (d, J=3.3Hz),
128.27 (d, J=8.1Hz), 119.20,116.03 (d, J=21.6Hz) 52.14,31.64,23.30,14.57.19F NMR
(376MHz,CDCl3)δ-113.59。HRMS(ESI)calcd for[C12H13FN2ONa]+([M+Na]+):243.0904,
found:243.0904。
Embodiment 7
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 7-3, altogether
93mg, yield 79%.
The nuclear-magnetism detection data of Product samples 7-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.05-6.97 (m, 2H), 6.96-6.88 (m, 1H), 6.04 (d, J=7.9Hz,
1H), 5.02-4.94 (m, 1H), 2.28 (t, J=7.3Hz, 2H), 2.20 (s, 3H), 2.16-1.96 (m, 2H), 1.92 (s,
3H)。13C NMR(100MHz,CDCl3) δ 169.83,160.93 (d, J=246.0Hz), 135.58 (d, J=3.7Hz),
129.82 (d, J=5.3Hz), 125.71 (d, J=17.6Hz), 125.32 (d, J=8.2Hz), 119.24,115.60 (d, J=
22.6Hz) 52.23,31.78,23.33,14.64 (d, J=3.5Hz), 14.56.19F NMR(376MHz,CDCl3)δ-
117.86。HRMS(ESI)calcd for[C13H15FN2ONa]+([M+Na]+):257.1061,found:257.1060。
Embodiment 8
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 8-3, altogether
91mg, yield 72%.
The nuclear-magnetism detection data of Product samples 8-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.32 (d, J=8.1Hz, 2H), 7.21 (d, J=8.1Hz, 2H), 6.30 (d, J
=8.2Hz, 1H), 5.01-4.92 (m, 1H), 4.50 (s, 2H), 2.27 (t, J=7.4Hz, 2H), 2.17-1.99 (m, 2H),
1.91(s,3H)。13C NMR(100MHz,CDCl3)δ170.00,140.45,137.49,129.34,126.96,119.47,
52.44,45.67,31.56,23.29,14.56。HRMS(ESI)calcd for[C13H15ClN2ONa]+([M+Na]+):
273.0765,found:273.0764。
Embodiment 9
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 9-3, altogether
94mg, yield 72%.
The nuclear-magnetism detection data of Product samples 9-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.23 (d, J=8.6Hz, 2H), 7.02 (d, J=8.6Hz, 2H), 6.18 (d, J
=8.3Hz, 1H), 5.00-4.92 (m, 1H), 2.27 (t, J=7.4Hz, 2H), 2.23 (s, 3H), 2.14-1.99 (m, 2H),
1.90(s,3H)。13C NMR(100MHz,CDCl3)δ169.97,169.57,150.33,137.74,127.73,122.26,
119.27,52.16,31.52,23.26,21.14,14.56。HRMS(ESI)calcd for[C14H16N2O3Na]+([M+Na]+):
283.1053,found:283.1053。
Embodiment 10
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 10-3, altogether
98mg, yield 67%.
The nuclear-magnetism detection data of Product samples 10-3 is as follows:
1H NMR(400MHz,CDCl3) δ 6.93 (d, J=8.1Hz, 1H), 6.82 (s, 1H), 6.77 (d, J=8.1Hz,
1H), 6.52 (d, J=8.3Hz, 1H), 4.95-4.87 (m, 1H), 3.73 (s, 3H), 2.26 (t, J=7.3Hz, 2H), 2.23
(s,3H),2.08–1.96(m,2H),1.88(s,3H)。13C NMR(100MHz,CDCl3)δ170.20,169.26,151.38,
139.36,139.29,123.20,119.41,118.27,111.29,55.99,52.50,31.53,23.16,20.68,
14.54。HRMS(ESI)calcd for[C15H18N2O4Na]+([M+Na]+):313.1164,found:313.1159。
Embodiment 11
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 11-3, altogether
69mg, yield 59%.
The nuclear-magnetism detection data of Product samples 11-3 is as follows:
1H NMR(400MHz,CDCl3)δ7.24–7.15(m,1H),6.82–6.69(m,3H),6.54–6.40(m,1H),
4.96-4.87 (m, 1H), 3.72 (s, 3H), 2.26 (t, J=7.4Hz, 2H), 2.18-2.10 (m, 1H), 2.04-1.98 (m,
1H),1.91(s,3H)。13C NMR(100MHz,CDCl3)δ170.10,160.06,141.72,130.21,119.41,
118.68,113.09,112.74,55.31,52.76,31.70,23.25,14.50。HRMS(ESI)calcd for
[C13H16N2O2Na]+([M+Na]+):255.1104,found:255.1104。
Embodiment 12
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 12-3, altogether
80mg, yield 65%.
The nuclear-magnetism detection data of Product samples 12-3 is as follows:
1H NMR(400MHz,d6- DMSO) δ 12.91 (s, 1H), 8.44 (d, J=8.3Hz, 1H), 7.92 (d, J=
8.2Hz, 2H), 7.43 (d, J=8.2Hz, 2H), 4.95-4.86 (m, 1H), 2.61-2.45 (m, 2H), 2.04-1.92 (m,
2H),1.88(s,3H)。
13C NMR(100MHz,d6-DMSO)δ169.49,167.57,147.97,130.06,130.00,127.04,
120.56,51.89,31.76,23.13,14.43。
HRMS(ESI)calcd for[C13H14N2O3Na]+([M+Na]+):269.0897,found:269.0897。
Embodiment 13
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 13-3, altogether
59mg, yield 52%.
The nuclear-magnetism detection data of Product samples 13-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.38-7.32 (m, 2H), 7.32-7.22 (m, 3H), 6.21 (d, J=7.7Hz,
1H),5.03–4.96(m,1H),2.54–2.38(m,2H),2.09–2.02(m,2H),1.96(s,3H)。13C NMR(100MHz,
CDCl3)δ169.70,131.77,128.95,128.47,121.75,119.21,85.69,84.95,41.43,31.36,
23.09,13.78。HRMS(ESI)calcd for[C14H14N2ONa]+([M+Na]+):249.0998,found:249.0996。
Embodiment 14
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 14-3, altogether
56mg, yield 44%.
The nuclear-magnetism detection data of Product samples 14-3 is as follows:
1H NMR(400MHz,CDCl3)δ7.88–7.79(m,3H),7.73(s,1H),7.53–7.47(m,2H),7.37
(dd,J1=8.5Hz, J2=1.6Hz, 1H), 6.22 (d, J=6.6Hz, 1H), 5.24-5.16 (m, 1H), 2.38-2.27 (m,
3H),2.24–2.16(m,1H),2.01(s,3H)。13C NMR(100MHz,CDCl3)δ170.02,137.14,133.29,
133.02,129.23,127.92,127.63,126.73,126.50,125.63,124.20,119.33,52.92,31.50,
23.36,14.58。HRMS(ESI)calcd for[C16H16N2ONa]+([M+Na]+):275.1155,found:275.1156。
Embodiment 15
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 15-3, altogether
101mg, yield 78%.
The nuclear-magnetism detection data of Product samples 15-3 is as follows:
1H NMR(400MHz,CDCl3)δ7.63–7.54(m,4H),7.48–7.42(m,2H),7.40–7.33(m,3H),
5.91 (d, J=8.0Hz, 1H), 5.15-5.06 (m, 1H), 2.43-2.34 (m, 2H), 2.33-2.24 (m, 1H), 2.24-2.15
(m,1H),2.03(s,3H)。13C NMR(100MHz,CDCl3)δ169.80,141.35,140.29,138.80,128.90,
127.92,127.64,127.09,127.02,119.30,52.60,31.62,23.44,14.60。HRMS(ESI)calcd for
[C18H18N2ONa]+([M+Na]+):301.1311,found:301.1312。
Embodiment 16
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 16-3, altogether
98mg, yield 90%.
The nuclear-magnetism detection data of Product samples 16-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.30-7.14 (m, 5H), 6.58 (d, J=8.0Hz, 1H), 4.90 (t, J=
8.0Hz, 0.23H), 4.74 (t, J=8.0Hz, 0.76H), 2.54-2.44 (m, 0.84H), 2.28-2.15 (m, 2H), 2.06-
2.01 (m, 0.35H), 1.93 (s, 0.69H), 1.90 (s, 2.22H), 1.09 (d, J=8.0Hz, 0.65H), 0.89 (d, J=
4.0Hz,2.37H)。13C NMR(100MHz,CDCl3)δ170.14,170.07,139.83,139.60,129.02,129.00,
128.03,127.03,119.34,118.58,57.93,57.04,36.26,35.88,23.30,22.22,21.82,17.28,
15.76。HRMS(ESI)calcd for[C13H16N2ONa]+([M+Na]+):239.1155,found:239.1152。
Embodiment 17
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 17-3, altogether
99mg, yield 71%.
The nuclear-magnetism detection data of Product samples 17-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.25-7.14 (m, 6H), 7.07-6.97 (m, 4H), 6.05 (d, J=8.9Hz,
1H),5.38–5.31(m,1H),3.50–3.36(m,1H),3.01–2.90(m,1H),2.76–2.64(m,1H),2.04(s,
3H)。13C NMR(100MHz,CDCl3)δ170.08,138.72,138.19,128.73,128.70,128.01,127.78,
127.30,119.08,57.62,48.35,23.51,22.04。HRMS(ESI)calcd for[C18H18N2ONa]+([M+Na
]+):301.1311,found:301.1313。
Embodiment 18
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 18-3, altogether
88mg, yield 56%.
The nuclear-magnetism detection data of Product samples 18-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.86 (d, J=7.3Hz, 2H), 7.56 (t, J=7.4Hz, 1H), 7.42 (t, J
=7.8Hz, 2H), 7.31-7.17 (m, 3H), 7.15-7.08 (m, 2H), 6.97 (d, J=8.2Hz, 1H), 5.54 (dd, J=
8.3,4.5Hz, 1H), 4.45 (td, J=7.0,4.5Hz, 1H), 2.86-2.62 (m, 2H), 2.05 (s, 3H).13C NMR
(100MHz,CDCl3)δ199.91,170.31,137.50,139.95,134.29,128.93,128.66,128.33,
126.39,117.97,54.94,46.44,23.36,17.45。HRMS(ESI)calcd for[C19H18N2O2Na]+([M+Na
]+):239.1260,found:239.1260。
Embodiment 19
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 19-3, altogether
130mg, yield 73%.
The nuclear-magnetism detection data of Product samples 19-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.33-7.15 (m, 5H), 6.22 (d, J=9.3Hz, 1H), 5.01-4.94 (m,
1H), 2.41-2.26 (m, 2H), 2.18-2.09 (m, 1H), 1.94 (s, 3H), 1.26-1.07 (m, 20H), 0.81 (t, J=
6.8Hz,3H)。13C NMR(100MHz,CDCl3)δ169.97,140.01,129.06,127.96,126.78,119.68,
56.22,40.88,31.90,30.78,29.59,29.49,29.45,29.33,26.05,23.39,22.68,18.53,
14.12。HRMS(ESI)calcd for[C23H36N2ONa]+([M+Na]+):379.2720, found:379.2718.
Embodiment 20
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 20-3, altogether
74mg, yield 57%.
The nuclear-magnetism detection data of Product samples 20-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.38-7.30 (m, 3H), 7.23-7.22 (m, 2H), 6.84 (d, J=8.6Hz,
1H),5.42–5.35(m,1H),3.67(s,1.73H),3.62(s,1.14H),3.31–3.22(m,1H),2.75–2.64(m,
1H),2.61–2.51(m,1H),2.05(s,1.73H),2.00(s,1.27H)。13C NMR(100MHz,CDCl3)δ171.62,
170.76,170.00,169.87,138.11,137.62,129.10,129.06,128.57,128.41,126.83,126.32,
117.91,117.14,54.15,53.71,52.72,52.61,47.44,46.83,23.31,23.26,18.19,17.20。
HRMS(ESI)calcd for[C14H16N2O3Na]+([M+Na]+):283.1053,found:283.1056。
Embodiment 21
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 21-3, altogether
68mg, yield 63.
The nuclear-magnetism detection data of Product samples 21-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.25-7.10 (m, 4H), 5.91 (d, J=7.9Hz, 0.84H), 5.77 (d, J=
7.9Hz,0.13H),5.44–5.39(m,0.14H),5.17–5.09(m,0.86H),3.24–3.12(m,1H),2.78–2.72
(m,1H),2.72–2.66(m,1H),2.56–2.49(m,1H),2.44–2.34(m,1H),1.99(s,2.47H),1.98(s,
0.39H)。13C NMR(100MHz,CDCl3)δ170.63,170.60,141.58,141.26,140.84,140.71,129.02,
128.61,127.54,127.57,123.63,118.58,59.13,56.40,45.73,39.36,36.03,35.82,23.30,
23.11,20.98,18.04。HRMS(ESI)calcd for[C13H14N2ONa]+([M+Na]+):237.0998,found:
237.0999。
Embodiment 22
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg,
0.25mmol), it reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to room temperature, is revolved
Turn after evaporation under reduced pressure boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 22-3, altogether
56mg, yield 48%.
The nuclear-magnetism detection data of Product samples 22-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.15-7.11 (m, 3H), 7.06-7.02 (m, 1H), 5.77 (d, J=9.0Hz,
1H), 4.94-4.86 (m, 1H), 2.84-2.78 (m, 2H), 2.57 (dd, J=17.0,4.8Hz, 1H), 2.24 (dd, J=
17.0,9.2Hz,1H),2.14–2.08(m,1H),2.02(s,3H),1.78–1.60(m,2H)。13C NMR(100MHz,
CDCl3)δ170.51,136.39,135.00,129.04,127.94,127.68,126.73,118.79,52.20,38.79,
27.72,26.52,23.41,21.24。HRMS(ESI)calcd for[C14H16N2ONa]+([M+Na]+):251.1155,
found:251.1156。
Embodiment 23
Under nitrogen protection, by Cu (CH3CN)4PF6(9.15mg, 5mol%), BPO (61mg, 0.25mmol) are added
It in the Xiu Langke pipes of 100mL, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene under nitrogen protection
(0.5mmol), hexafluorophosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO
(61mg, 0.25mmol) reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to
Room temperature, after Rotary Evaporators decompression boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as
23-3, total 42mg, yield 36%.
The nuclear-magnetism detection data of Product samples 23-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.32-7.27 (m, 2H), 7.24-7.12 (m, 3H), 5.38 (d, J=8.9Hz,
1H), 4.11-3.96 (m, 1H), 2.73-2.61 (m, 2H), 2.38 (t, J=7.4Hz, 2H), 1.97 (s, 3H), 1.87-1.69
(m,4H)。13C NMR(100MHz,CDCl3)δ170.42,141.00,128.62,128.28,126.24,119.77,48.93,
36.54,32.40,31.37,23.36,14.24。HRMS(ESI)calcd for[C14H18N2ONa]+([M+Na]+):
253.1311,found:253.1311。
Embodiment 24
Under nitrogen protection, by Cu (CH3CN)4PF6(9.15mg, 5mol%), BPO (61mg, 0.25mmol) are added
It in the Xiu Langke pipes of 100mL, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene under nitrogen protection
(0.5mmol), hexafluorophosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO
(61mg, 0.25mmol) reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to
Room temperature, after Rotary Evaporators decompression boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as
24-3, total 73mg, yield 48%.
The nuclear-magnetism detection data of Product samples 24-3 is as follows:
1H NMR(400MHz,CDCl3) δ 6.96 (d, J=8.0Hz, 1H), 6.77 (s, 1H), 6.72 (d, J=8.0Hz,
1H), 5.85-5.73 (m, 1H), 4.29-4.12 (m, 1H), 3.81 (s, 3H), 2.85 (dd, J=13.9,6.6Hz, 1H), 2.73
(dd, J=13.9,7.0Hz, 1H), 2.37 (t, J=7.3Hz, 2H), 2.31 (s, 3H), 1.98-1.89 (m, 4H), 1.79-
1.65(m,1H)。13C NMR(100MHz,CDCl3)δ170.48,169.27,151.11,138.56,136.11,122.79,
121.33,119.73,113.13,55.95,49.79,40.67,29.97,23.33,20.72,14.38。HRMS(ESI)calcd
for[C16H20N2O4Na]+([M+Na]+):327.1315,found:327.1317。
Embodiment 25
Under nitrogen protection, by Cu (CH3CN)4PF6(9.15mg, 5mol%), BPO (61mg, 0.25mmol) are added
It in the Xiu Langke pipes of 100mL, vacuumizes, nitrogen is replaced three times, sequentially adds n-Butyronitrile (12mL), styrene under nitrogen protection
(58 μ L, 0.5mmol), hexafluorophosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, then add
Enter BPO (61mg, 0.25mmol), reacts 2 hours, add BPO (61mg, 0.25mmol).After completion of the reaction, liquid cooling will be reacted
But to room temperature, after Rotary Evaporators decompression boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample
It is denoted as 25-3, total 82mg, yield 63%.
The nuclear-magnetism detection data of Product samples 25-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.43-7.22 (m, 5H), 5.94 (d, J=7.8Hz, 1H), 5.20-5.13 (m,
1H), 2.53-2.37 (m, 1H), 2.26-2.09 (m, 4H), 1.75-1.63 (m, 4H), 1.08 (t, J=7.4Hz, 3H), 0.93
(t, J=7.4Hz, 3H).13C NMR(100MHz,CDCl3)δ172.52,140.31,129.14,128.12,126.53,
121.97,51.37,38.67,37.84,29.93,25.05,18.99,13.76,11.39。HRMS(ESI)calcd for
[C16H22N2ONa]+([M+Na]+):281.1624,found:281.1625。
Embodiment 26
Under nitrogen protection, by Cu (CH3CN)4PF6(9.15mg, 5mol%), BPO (61mg, 0.25mmol) are added
It in the Xiu Langke pipes of 100mL, vacuumizes, nitrogen is replaced three times, sequentially adds isobutyronitrile (30mL), styrene under nitrogen protection
(58 μ L, 0.5mmol), hexafluorophosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, then add
Enter BPO (61mg, 0.25mmol), reacts 2 hours, add BPO (61mg, 0.25mmol).After completion of the reaction, liquid cooling will be reacted
But to room temperature, after Rotary Evaporators decompression boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample
It is denoted as 26-3, total 61mg, yield 47%.
The nuclear-magnetism detection data of Product samples 26-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.40-7.23 (m, 5H), 6.09 (d, J=8.5Hz, 1H), 5.29 (td, J=
10.2,4.7Hz, 1H), 2.41 (hept, J=6.9Hz, 1H), 2.20 (dd, J=14.6,10.5Hz, 1H), 1.87 (dd, J=
14.6,4.6Hz, 1H), 1.42 (d, J=2.1Hz, 6H), 1.19 (d, J=6.9Hz, 3H), 1.14 (d, J=6.9Hz, 3H).13C
NMR(100MHz,CDCl3)δ176.42,142.00,128.94,127.77,126.21,125.40,49.86,46.33,
35.68,30.27,28.62,25.24,19.53,19.15。HRMS(ESI)calcd for[C16H22N2ONa]+([M+Na]+):
281.1624,found:281.1625。
Embodiment 27
Under nitrogen protection, by Cu (CH3CN)4PF6(18.3mg, 10mol%), BPO (61mg, 0.20mmol) are added
It in the Xiu Langke pipes of 100mL, vacuumizes, nitrogen is replaced three times, sequentially adds isobutyronitrile (30mL), styrene under nitrogen protection
(58 μ L, 0.5mmol), hexafluorophosphoric acid (60% aqueous solution) (29uL, 0.4mmol), tube sealing are reacted 2 hours at 70 DEG C, are added
BPO (61mg, 0.20mmol) reacts 2 hours, adds BPO (61mg, 0.20mmol).After completion of the reaction, reaction solution is cooled down
To room temperature, after Rotary Evaporators decompression boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample note
For 27-3, total 76mg, yield 75%.
The nuclear-magnetism detection data of Product samples 27-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.42-7.24 (m, 5H), 6.09 (d, J=7.7Hz, 1H), 5.08-4.99 (m,
1H),2.39–2.29(m,2H),2.29–2.19(m,1H),2.19–2.07(m,1H),2.00(s,3H)。13C NMR(100MHz,
CDCl3)δ169.85,139.95,129.19,128.30,126.56,119.31,52.86,31.68,23.35,14.53。HRMS
(ESI)calcd for[C12H14N2ONa]+([M+Na]+):225.0998,found:225.0999。
Embodiment 28
Under nitrogen protection, by Cu (OTf)2100mL is added in (18.1mg, 10mol%), BPO (61mg, 0.20mmol)
Xiu Langke pipes in, vacuumize, nitrogen replace three times, sequentially add isobutyronitrile (30mL), styrene (58 μ under nitrogen protection
L, 0.5mmol), hexafluorophosphoric acid (60% aqueous solution) (29uL, 0.4mmol), tube sealing reacts 2 hours at 70 DEG C, adds BPO
(61mg, 0.20mmol) reacts 2 hours, adds BPO (61mg, 0.20mmol).After completion of the reaction, reaction solution is cooled to
Room temperature, after Rotary Evaporators decompression boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as
28-3, total 71mg, yield 70%.
The nuclear-magnetism detection data of sample 28-3 is the same as sample 27-3.
Embodiment 29
Under nitrogen protection, by Cu (OAc)2(9.1mg, 10mol%), BPO (61mg, 0.20mmol), is added 100mL's
In Xiu Langke pipes, vacuumizing, nitrogen is replaced three times, sequentially adds isobutyronitrile (30mL) under nitrogen protection, styrene (58 μ L,
0.5mmol), hexafluorophosphoric acid (60% aqueous solution) (29uL, 0.4mmol), tube sealing react 2 hours at 70 DEG C, add BPO
(61mg, 0.20mmol) reacts 2 hours, adds BPO (61mg, 0.20mmol).After completion of the reaction, reaction solution is cooled to
Room temperature, after Rotary Evaporators decompression boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as
29-3, total 73mg, yield 72%.
The nuclear-magnetism detection data of sample 29-3 is the same as sample 27-3.
Embodiment 30
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
In gram pipe, vacuumizing, nitrogen is replaced three times, sequentially adds acetonitrile (30mL) under nitrogen protection, styrene (58 μ L,
0.5mmol), hexafluorophosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO
(61mg, 0.25mmol) reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled to
Room temperature, after Rotary Evaporators decompression boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as
30-3, total 89mg, yield 88%.
The nuclear-magnetism detection data of sample 30-3 is the same as sample 27-3.
Embodiment 31
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.20mmol)
In gram pipe, vacuumizing, nitrogen is replaced three times, sequentially adds acetonitrile (30mL) under nitrogen protection, styrene (58 μ L,
0.5mmol), hexafluorophosphoric acid (60% aqueous solution) (44.1uL, 0.3mmol), tube sealing react 2 hours at 70 DEG C, add BPO
(61mg, 0.20mmol) reacts 2 hours, adds BPO (61mg, 0.20mmol).After completion of the reaction, reaction solution is cooled to
Room temperature, after Rotary Evaporators decompression boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as
31-3, total 81mg, yield 80%.
The nuclear-magnetism detection data of sample 31-3 is the same as sample 27-3.
Embodiment 32
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
In gram pipe, vacuumizing, nitrogen is replaced three times, sequentially adds acetonitrile (30mL) under nitrogen protection, styrene (58 μ L,
0.5mmol), H2SO4(11uL, 0.2mmol), tube sealing react 2 hours at 70 DEG C, add BPO (61mg, 0.20mmol), instead
It answers 2 hours, adds BPO (61mg, 0.20mmol).After completion of the reaction, reaction solution is cooled to room temperature, Rotary Evaporators decompression
After boiling off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample is denoted as 32-3, total 30mg, and yield is
29%.
The nuclear-magnetism detection data of sample 32-3 is the same as sample 27-3.
Embodiment 33
Under nitrogen protection, the Xiu Lang of 100mL is added in CuI (4.75mg, 5mol%), BPO (61mg, 0.25mmol)
It in gram pipe, vacuumizes, nitrogen is replaced three times, sequentially adds acetonitrile (30mL), alkene (0.5mmol), hexafluoro under nitrogen protection
Phosphoric acid (60% aqueous solution) (11uL, 0.1mmol), H2O (18ul, 2equiv), tube sealing are reacted 2 hours at 70 DEG C, are added
BPO (61mg, 0.25mmol) reacts 2 hours, adds BPO (61mg, 0.25mmol).After completion of the reaction, reaction solution is cooled down
To room temperature, after Rotary Evaporators decompression boils off acetonitrile, column chromatography for separation (PE/EA=10/1~1/10), products therefrom sample note
For 33-3, total 85mg, yield 42%.
The nuclear-magnetism detection data of Product samples 33-3 is as follows:
1H NMR(400MHz,CDCl3) δ 7.31 (d, J=8.1Hz, 1H), 7.05 (d, J=8.1Hz, 1H), 6.99 (s,
1H), 5.86 (d, J=8.2Hz, 1H), 5.01-4.93 (m, 1H), 2.90-2.80 (m, 2H), 2.61 (s, 1H), 2.42-2.31
(m,4H),2.28–2.22(m,2H),2.18–2.10(m,2H),2.07-2.02(m,1H),2.00(s,3H),1.94–1.86
(m,2H),1.78–1.72(m,3H),1.52–1.35(m,4H),0.90(s,0.38H),0.88(s,2.39H)。13C NMR
(100MHz,CDCl3)δ169.77,140.57,137.73,136.99,127.33,126.29,123.74,119.45,87.48,
79.80,74.13,52.62,49.50,47.07,43.90,39.08,38.94,32.72,31.67,29.61,27.07,
26.16,23.45,22.81,14.59,12.69。HRMS(ESI)calcd for[C26H32N2O2Na]+([M+Na]+):
427.2356,found:427.2353。
The above is only several embodiments of the application, not does any type of limitation to the application, although this Shen
Please disclosed as above with preferred embodiment, however not to limit the application, any person skilled in the art is not taking off
In the range of technical scheme, makes a little variation using the technology contents of the disclosure above or modification is equal to
Case study on implementation is imitated, is belonged in technical proposal scope.
Claims (10)
1. a kind of preparation method of compound I, which is characterized in that in the presence of catalyst and radical initiator, by including
Compound II containing carbon-carbon double bond is reacted with the raw material of the compound III containing itrile group to be prepared;
The compound I is at least one of the compound containing structural unit shown in Formulas I;
The compound II containing carbon-carbon double bond is selected from least one of the compound containing structural unit shown in Formula II;
The compound III containing itrile group is selected from least one of the compound with structural formula shown in formula III;
R3- CN formula IIIs
Wherein, R1、R2One kind in alkyl, substituted hydrocarbon radical, heteroaryl, substituted heteroaryl, non-hydrocarbons substituent group;
R3Selected from C1~C20Alkyl in one kind;
A1For R3It loses a hydrogen atom and is formed by subunit.
2. preparation method according to claim 1, which is characterized in that the compound II containing carbon-carbon double bond is selected from tool
There are the compound of structural formula shown in Formula II -1, the compound with structural formula shown in Formula II -2, with structural formula shown in Formula II -3
Compound, at least one of the compound with structural formula shown in Formula II -4:
In Formula II -1, R4、R5、R6、R7Independently selected from hydrogen, alkyl, substituted hydrocarbon radical, heteroaryl, substituted heteroaryl, non-hydrocarbons substitution
One kind in base;
Wherein, n1, n2, n3, m1, m2 are independently selected from 0,1,2,3 or 4;, m3 be selected from 0,1,2 or 3;
R8、R9、R10、R11、R12、R13Independently selected from least one of alkyl, substituted hydrocarbon radical, non-hydrocarbons substituent group.
3. method according to any one of claims 1 to 4, which is characterized in that in the substituted hydrocarbon radical, substituted heteroaryl
Substituent group is non-hydrocarbon substituents;
The non-hydrocarbons substituent group be selected from oxygen, halogen, with the group of structural formula shown in formula (1), with structural formula shown in formula (2)
Group, with the group of structural formula, at least one of the group with structural formula shown in formula (4) shown in formula (3):
In formula (1), M11Selected from hydrogen, C1~C10Alkyl;
In formula (2), M21Selected from hydrogen, C1~C10Alkyl;
M31- O- formulas (3)
In formula (3), M31Selected from hydrogen, C1~C10Alkyl.
4. preparation method according to claim 1, which is characterized in that the catalyst is selected from the compound containing copper
At least one of;
Preferably, the catalyst is selected from four acetonitrile copper of hexafluorophosphoric acid, copper trifluoromethanesulfcomposite, copper acetate, cuprous iodide, protochloride
At least one of copper, cuprous bromide, cupric oxalate.
5. preparation method according to claim 1, which is characterized in that the radical initiator is selected from organic peroxide
At least one of;
Preferably, the radical initiator is benzoyl peroxide.
6. preparation method according to claim 1, which is characterized in that the compound II containing carbon-carbon double bond, contain
The molar ratio of the compound III of itrile group, radical initiator and catalyst is:
Compound II containing carbon-carbon double bond:Compound III containing itrile group:Radical initiator:Catalyst=1:2~5:1
~2:0.15~0.007.
7. preparation method according to claim 1, which is characterized in that the reaction temperature of the reaction is 50 DEG C to 90 DEG C,
Reaction time is 10h to 25h;
Preferably, the temperature of the reaction is 60 DEG C to 80 DEG C, and the reaction time is 15h to 18h.
8. preparation method according to claim 1, which is characterized in that contain inorganic acid in the reaction system;
Preferably, the inorganic acid is selected from least one of hexafluorophosphoric acid, sulfuric acid, trifluoromethanesulfonic acid.
9. preparation method according to claim 8, which is characterized in that the inorganic acid and the compound containing carbon-carbon double bond
The molar ratio of II is:
Compound II containing carbon-carbon double bond:Inorganic acid=1:0.5~0.7.
10. preparation method according to claim 8, which is characterized in that at least include the following steps:
A) will include the compound II containing carbon-carbon double bond, the compound III containing itrile group, catalyst, radical initiator and
The mixture of inorganic acid is placed in reaction vessel, and 10~25 hours postcoolings are stirred at 50 DEG C~90 DEG C to room temperature;
B) it is filtered with diatomite after ethyl acetate dilution is added, solvent, pillar layer separation is removed to get compound through vacuum distillation
I。
Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710059775.XA CN108341755A (en) | 2017-01-24 | 2017-01-24 | A method of it prepares containing bifunctional compound |
PCT/CN2017/073325 WO2018137260A1 (en) | 2017-01-24 | 2017-02-13 | Method for preparing compound having bifunctional group |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710059775.XA CN108341755A (en) | 2017-01-24 | 2017-01-24 | A method of it prepares containing bifunctional compound |
Publications (1)
Publication Number | Publication Date |
---|---|
CN108341755A true CN108341755A (en) | 2018-07-31 |
Family
ID=62962319
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710059775.XA Pending CN108341755A (en) | 2017-01-24 | 2017-01-24 | A method of it prepares containing bifunctional compound |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN108341755A (en) |
WO (1) | WO2018137260A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112979399A (en) * | 2019-12-02 | 2021-06-18 | 中国科学院福建物质结构研究所 | Method for alkyl-arylation of olefin compound and application |
CN114276223A (en) * | 2021-12-24 | 2022-04-05 | 江南大学 | Synthetic method of alpha-iodine-alpha-trifluoromethyl arylethanone |
CN114805123A (en) * | 2021-01-27 | 2022-07-29 | 中国科学院大连化学物理研究所 | Method for preparing gamma-aminobutyric acid and derivatives thereof by Ritter reaction of photocatalytic olefin |
-
2017
- 2017-01-24 CN CN201710059775.XA patent/CN108341755A/en active Pending
- 2017-02-13 WO PCT/CN2017/073325 patent/WO2018137260A1/en active Application Filing
Non-Patent Citations (3)
Title |
---|
GUI-JUAN CHENG ET AL.: "Computational Organic Chemistry: Bridging Theory and Experiment in Establishing the Mechanisms of Chemical Reactions", 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》 * |
NADEEM BASHIR ET AL.: "On The Mechanism of the Tetrathiafulvalene-Mediated Radical-Polar Crossover Reactions", 《TETRAHEDRON LETTERS》 * |
YOUGUI LI ET AL.: "Copper-Catalyzed Regioselective 1,2-Alkylesterification of Dienes to Allylic Esters", 《ORGANIC LETTERS》 * |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112979399A (en) * | 2019-12-02 | 2021-06-18 | 中国科学院福建物质结构研究所 | Method for alkyl-arylation of olefin compound and application |
CN112979399B (en) * | 2019-12-02 | 2022-07-19 | 中国科学院福建物质结构研究所 | Method for alkyl-arylation of olefin compound and application |
CN114805123A (en) * | 2021-01-27 | 2022-07-29 | 中国科学院大连化学物理研究所 | Method for preparing gamma-aminobutyric acid and derivatives thereof by Ritter reaction of photocatalytic olefin |
CN114805123B (en) * | 2021-01-27 | 2023-11-21 | 中国科学院大连化学物理研究所 | Method for preparing gamma-aminobutyric acid and derivatives thereof through Ritter reaction of photocatalytic olefin |
CN114276223A (en) * | 2021-12-24 | 2022-04-05 | 江南大学 | Synthetic method of alpha-iodine-alpha-trifluoromethyl arylethanone |
CN114276223B (en) * | 2021-12-24 | 2022-12-20 | 江南大学 | Synthetic method of alpha-iodine-alpha-trifluoromethyl arylethanone |
Also Published As
Publication number | Publication date |
---|---|
WO2018137260A1 (en) | 2018-08-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105418460B (en) | Intermediate of pimavanserin and similar compound thereof, and preparation method thereof, and method for preparing pimavanserin and similar compound thereof | |
CN108341755A (en) | A method of it prepares containing bifunctional compound | |
Pindi et al. | N‐Phosphinyl Imine Chemistry (I): Design and Synthesis of Novel N‐Phosphinyl Imines and their Application to Asymmetric aza‐Henry Reaction | |
JP6045320B2 (en) | Continuous process for alkylating cyclic tertiary amines | |
CN102617434B (en) | Process for preparing Vildagliptin by one-pot method | |
JP4913077B2 (en) | Process for producing optically active homoallyl hydrazino esters | |
FR2617836A1 (en) | SYNTHESIS OF PERFLUOROALKYL BROMIDES | |
EP3360861A1 (en) | Method for synthesizing bipyridine compound and method for manufacturing pyridine compound | |
KR20220051168A (en) | Method for preparing heterocyclideneacetamide derivatives | |
JP6000257B2 (en) | Method for producing 2-alkenylamine compound | |
Lohier et al. | tert-Butyl 6-bromo-1, 4-dimethyl-9H-carbazole-9-carboxylate | |
CN112279765B (en) | Preparation method of chiral alpha-fluoroketone compound | |
CN104860975B (en) | A kind of preparation method of bortezomib synthetic intermediate | |
CN102936219B (en) | Chiral 6, 6'-2 carbazole base binaphthol | |
JP5434919B2 (en) | Method for producing carbamate compound | |
CN112299996B (en) | Synthesis method of chiral alpha-deuterated ketone | |
CN107915587A (en) | A kind of alkyl alkoxylated method of olefin(e) compound | |
WO2011031764A2 (en) | Compounds and related methods of use | |
JP4732180B2 (en) | Stereoselective production method of 1,3-aminoalcohol derivatives | |
Fang | Studies on selectively fluorinated cycloalkanes | |
CN101707952A (en) | Preparation method of rivastigmine and its intermediates | |
CN105330615B (en) | A kind of preparation method of Vortioxetine | |
JP4917721B2 (en) | Method for producing imidazolidinone derivative | |
CN106316880B (en) | A kind of synthetic method of N dichloromethylenes amino benzenes derivates | |
KR20240066852A (en) | A process of preparing bis(chloromethyl)naphthalene |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20180731 |
|
RJ01 | Rejection of invention patent application after publication |