CN109422665A - A kind of synthetic method of fluorine-containing imine compound and its derivative - Google Patents
A kind of synthetic method of fluorine-containing imine compound and its derivative Download PDFInfo
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Abstract
The present invention provides a kind of synthetic methods for synthesizing fluorine-containing imine compound and its derivative: using substitution nitrine end vinyl compound shown in formula I as starting material, with 1- chloromethyl -4- fluoro- 1, two (tetrafluoro boric acid) salt of 4- diazabicyclo [2.2.2] octane is Fluorine source, under the action of alkaline matter, in organic solvent, it is reacted 8~24 hours at 0~50 DEG C, gained reaction solution is post-treated to obtain fluorine-containing imine compound and its derivative shown in formula II；Substitution nitrine end vinyl compound and the ratio between Fluorine source, the amount of substance of alkaline matter shown in the formula I are 1:1~3:1~3；Method safety environmental protection of the present invention, does not generate exhaust gas waste water；Substrate adaptability is good, and various substituent groups can have good reaction；Reaction condition is mild, easy to operate.
Description
Technical field
The present invention relates to a kind of synthetic method of organic compound, a kind of fluorine-containing imine compound is related in particular to
Synthetic method.
Background technique
Imine compound is a kind of very important nitrogenous compound, this kind of Hao Alto reactivity of compound Ju You Liang and latent
Bioactivity, be a kind of important chemical intermediate, important angle all play in the synthesis process of many compounds
Color.Such as: imines reacts to obtain aminal with another molecular amine, such as: in synthetic nitrogen hetero-Diels-Alder reaction, imines
Tetrahydropyridine is obtained with diene hydrocarbon reaction.Imines can occur oxidation reaction with metachloroperbenzoic acid (mCPBA) and obtain oxa- nitrogen
Heterocycle propane.In Povarov reaction, aromatic imine reacts to obtain quinoline with enol ether.It is anti-in azepine-Baylis-Hillman
Ying Zhong, tolysulfonyl imines and α, beta-unsaturated carbonyl compound react to obtain allyl amine.Eschweiler-Clarke is anti-
Ying Zhong, amine and formic acid are alkylated in reaction process, and imines exists as intermediate.Imines can be used as intermediate and participate in saccharification
Rearrangement reaction in, such as: Amadori rearrangement reaction.Methylene group-transfer can occur for imines anti-by unstable sulfonium ylides
It should be to prepare aziridine derivative.
At the same time, fluorochemical also plays important role.Fluorine medicine has spy due to fluorinated organic compound
The curative effect of different bioactivity and organism adaptability, Drugs Containing Fluorine is several times stronger than general drug, develops the most active.
China has started the research of fluoro-containing pesticide since fluorine pesticide seventies, successively develops fluometuron, trefanocide, Oxyfluorfen etc.
The insecticides such as herbicide and fluorine aphid locust, diflubenzuron, fluorine-containing pyrethroid, wherein trefanocide realizes industrialized production, if so,
Hu Wei, diflubenzuron etc. also have batch production.The introducing of difluoride dye fluorine element can enhance the gloss and gorgeous degree of dyestuff, and it is resistance to improve its
It shines, water-fast, organic solvent-resistant performance.Organic fluoride intermediate Organic fluoride intermediate mainly includes fluoro-aromatic compounds and aliphatic
Fluoride, wherein again based on fluoro-aromatic compounds.Fluorine-containing surfactant and fluorochemical inorganic agent fluorine-containing surfactants
Agent has been widely used as electronic component cleaning agent, antifoggant, release agent and the levelling agent of silk textile industry, metallic luster processing adds
Add agent etc..Fluorine inert fluid (fluorocarbon oil, fluorine rouge) fluothane base class compound has the chemical stability and thermal stability of height.
The method of the fluorine-containing imine compound of one-step synthesis is less at present, is typically necessary separately two steps and is synthesized, i.e.,
First synthesizing imine first carries out fluoro.Therefore, a kind of side of imine compound that simple, general synthesis is fluorine-containing is developed
Method be very it is necessary to.
Summary of the invention
In view of the deficiencies of the prior art, the purpose of the present invention is to provide a kind of a kind of general, easy, efficient fluorine-containing Asias
The synthetic method of aminated compounds and its derivative.
In order to achieve the above objectives, the technical scheme is that
A method of synthesize fluorine-containing imine compound and its derivative, the method specifically in accordance with the following steps into
Row:
It is double with the fluoro- Isosorbide-5-Nitrae-diaza of 1- chloromethyl -4- as starting material using substitution nitrine end vinyl compound shown in formula I
Two (tetrafluoro boric acid) salt of ring [2.2.2] octane is Fluorine source, under the action of alkaline matter, in organic solvent, at 0~50 DEG C
Reaction 8~24 hours, gained reaction solution is post-treated to obtain fluorine-containing imine compound and its derivative shown in formula II；It is described
Formula I shown in substitution nitrine end vinyl compound and the ratio between Fluorine source, the amount of substance of alkaline matter be 1:1~3:1~3,
In formula I or formula II,
R is H or H by Br ,-CH3O orIt is monosubstituted or polysubstituted.
Further, the alkaline matter be sodium carbonate, sodium acetate, sodium hydroxide or sodium tert-butoxide one kind or it is a kind of with
On mixture.
Further, the organic solvent be one of acetonitrile, tetrahydrofuran, methylene chloride or toluene or more than one
Mixed solvent, preferably acetonitrile.
Further, the additional amount of the organic solvent is with the substance of substitution nitrine end vinyl compound shown in formula I
Amount is calculated as 3~17ml/mmol.
Further, the preferably described reaction temperature is 25 DEG C, and the reaction time is 12 hours.
Further, the substance of substitution nitrine end vinyl compound and Fluorine source, alkaline matter shown in the preferably described formula I
The ratio between amount be 1:2:2.
Further, recommend the post-processing approach of gained reaction solution are as follows: after reaction, be added into gained reaction solution
The column chromatography silica gel of 100-200 mesh is simultaneously evaporated under reduced pressure removing solvent, gained crude product is carried out silica gel column chromatography separation, and with body
For product than being that the petrol ether/ethyl acetate mixed liquor of 5:1 is eluted as eluant, eluent, TLC tracks elution process, and collection contains mesh
The eluent for marking product, merge the eluent be evaporated off solvent obtain fluorine-containing imine compound shown in the formula II and
Its derivative.
Further, method of the present invention is recommended specifically to carry out in accordance with the following steps:
It is double with the fluoro- Isosorbide-5-Nitrae-diaza of 1- chloromethyl -4- as starting material using substitution nitrine end vinyl compound shown in formula I
Two (tetrafluoro boric acid) salt of ring [2.2.2] octane is Fluorine source, under the action of sodium carbonate, in organic solvent acetonitrile, at 25 DEG C
Reaction 12 hours, after reaction, into gained reaction solution be added 100-200 mesh column chromatography silica gel and be evaporated under reduced pressure remove it is molten
Agent, by gained crude product carry out silica gel column chromatography separation, and using volume ratio for 5:1 petrol ether/ethyl acetate mixed liquor as
Eluant, eluent is eluted, and TLC tracks elution process, collects the eluent containing target product, is merged the eluent and is evaporated off
Solvent obtains fluorine-containing imine compound and its derivative shown in formula II；Replace nitrine end alkenes shown in the formula I
Closing object and the ratio between Fluorine source, the amount of substance of alkaline matter is 1:2:2, and the additional amount of the organic solvent acetonitrile is shown in formula I
The amount of substance of substitution nitrine end vinyl compound be calculated as 3~17ml/mmol.
Compared with prior art, the beneficial effects of the present invention are:
(1) safety and environmental protection does not generate exhaust gas waste water；
(2) substrate adaptability is good, and various substituent groups can have good reaction；
(3) reaction condition is mild, easy to operate.
Specific embodiment
Invention is further described in detail combined with specific embodiments below, but protection scope of the present invention is not limited to
This:
Embodiment 1
Bromo- α-azido-the styrene of 0.3mmol (67.2mg) 4-, 0.6mmol (212.4mg) 1- chloromethyl -4- is fluoro-
Two (tetrafluoro boric acid) salt of 1,4- diazabicyclo [2.2.2] octane, that 0.6mmol (63.6mg) sodium carbonate is added to 15mL heavy wall is resistance to
It presses in reaction tube, adds 3mL acetonitrile as solvents.Then, magnetic agitation 12 hours at room temperature.After being cooled to room temperature, anti-
It answers and is added in liquid two spoon column chromatography silica gels (100-200 mesh), and solvent is removed by vacuum distillation, gained crude product is carried out
Silica gel column chromatography separation, and is eluted for the petrol ether/ethyl acetate mixed liquor of 5:1 as eluant, eluent using volume ratio, TLC with
Track elutes process, collects the eluent containing target product, merges the eluent solvent is evaporated off and obtain target product.The object
Matter is white-yellowish solid, yield 70%.
Characterize data:1H NMR(500MHz,CDCl3): δ 7.77 (d, J=8.5Hz, 2H), 7.66-7.63 (m, 2H),
5.53(s,1H),5.44(s,1H).13C NMR(125MHz,CDCl3): δ 165.31 (d, J=16.25Hz), 132.45,
132.26,129.44 (d, J=3.75Hz), 129.40,83.54 (d, J=182.5Hz)
Embodiment 2
Bromo- α-azido-the styrene of 0.3mmol (67.2mg) 4-, 0.3mmol (106.2mg) 1- chloromethyl -4- is fluoro-
Two (tetrafluoro boric acid) salt of 1,4- diazabicyclo [2.2.2] octane, that 0.6 (63.6mg) mmol sodium carbonate is added to 15mL heavy wall is resistance to
It presses in reaction tube, adds 1mL toluene and make solvent.Then, magnetic agitation 12 hours at room temperature.After being cooled to room temperature, anti-
It answers and is added in liquid two spoon column chromatography silica gels (100-200 mesh), and solvent is removed by vacuum distillation, gained crude product is carried out
Silica gel column chromatography separation, and is eluted for the petrol ether/ethyl acetate mixed liquor of 5:1 as eluant, eluent using volume ratio, TLC with
Track elutes process, collects the eluent containing target product, merges the eluent solvent is evaporated off and obtain target product.The object
Matter is white-yellowish solid, yield 63%.
Characterize data:1H NMR(500MHz,CDCl3): δ 7.77 (d, J=8.5Hz, 2H), 7.66-7.63 (m, 2H),
5.53(s,1H),5.44(s,1H).13C NMR(125MHz,CDCl3): δ 165.31 (d, J=16.25Hz), 132.45,
132.26,129.44 (d, J=3.75Hz), 129.40,83.54 (d, J=182.5Hz)
Embodiment 3
Bromo- α-azido-the styrene of 0.3mmol (67.2mg) 4-, 0.6mmol (212.4mg) 1- chloromethyl -4- is fluoro-
Two (tetrafluoro boric acid) salt of 1,4- diazabicyclo [2.2.2] octane, 0.6mmol (48mg) sodium acetate are added to 15mL heavy wall pressure resistance
In reaction tube, 3mL acetonitrile as solvents is added.Then, magnetic agitation 12 hours at room temperature.After being cooled to room temperature, reacting
It is added in liquid two spoon column chromatography silica gels (100-200 mesh), and solvent is removed by vacuum distillation, gained crude product is subjected to silicon
Plastic column chromatography separation, and eluted using volume ratio for the petrol ether/ethyl acetate mixed liquor of 5:1 as eluant, eluent, TLC tracking
Elution process collects the eluent containing target product, merges the eluent solvent is evaporated off and obtain target product.The substance
For white-yellowish solid, yield 43%.
Characterize data:1H NMR(500MHz,CDCl3): δ 7.77 (d, J=8.5Hz, 2H), 7.66-7.63 (m, 2H),
5.53(s,1H),5.44(s,1H).13C NMR(125MHz,CDCl3): δ 165.31 (d, J=16.25Hz), 132.45,
132.26,129.44 (d, J=3.75Hz), 129.40,83.54 (d, J=182.5Hz)
Embodiment 4
Bromo- α-azido-the styrene of 0.3mmol (67.2mg) 2-, 0.6mmol (212.4mg) 1- chloromethyl -4- is fluoro-
Two (tetrafluoro boric acid) salt of 1,4- diazabicyclo [2.2.2] octane, that 0.6mmol (63.6mg) sodium carbonate is added to 15mL heavy wall is resistance to
It presses in reaction tube, adds 3mL acetonitrile as solvents.Then, magnetic agitation 12 hours at room temperature.After being cooled to room temperature, anti-
It answers and is added in liquid two spoon column chromatography silica gels (100-200 mesh), and solvent is removed by vacuum distillation, gained crude product is carried out
Silica gel column chromatography separation, and is eluted for the petrol ether/ethyl acetate mixed liquor of 5:1 as eluant, eluent using volume ratio, TLC with
Track elutes process, collects the eluent containing target product, merges the eluent solvent is evaporated off and obtain target product.The object
Matter is white-yellowish solid, yield 67%.
Characterize data:1H NMR(500MHz,CDCl3): δ 8.57 (s, 1H), 8.40 (dd, J1=8.5Hz, J2=1.5Hz,
1H), 7.59 (dd, J1=8H, J2=1.5Hz, 1H), 7.38-7.35 (m, 1H), 7.07-7.04 (m, 1H), 5.03 (s, 1H),
4.93(s,1H).13C NMR(125MHz,CDCl3): δ 165.61 (d, J=17.5Hz), 134.50,132.49,128.50,
125.98,121.87,113.72,80.27 (d, J=187.5Hz)
Embodiment 5
Bromo- α-azido-the styrene of 0.3mmol (67.2mg) 2-, 0.6mmol (212.4mg) 1- chloromethyl -4- is fluoro-
Two (tetrafluoro boric acid) salt of 1,4- diazabicyclo [2.2.2] octane, that 0.3 (31.8mg) mmol sodium carbonate is added to 15mL heavy wall is resistance to
It presses in reaction tube, adds 3mL acetonitrile as solvents.Then, magnetic agitation 12 hours at 0 DEG C.After being cooled to room temperature, reacting
It is added in liquid two spoon column chromatography silica gels (100-200 mesh), and solvent is removed by vacuum distillation, gained crude product is subjected to silicon
Plastic column chromatography separation, and eluted using volume ratio for the petrol ether/ethyl acetate mixed liquor of 5:1 as eluant, eluent, TLC tracking
Elution process collects the eluent containing target product, merges the eluent solvent is evaporated off and obtain target product.The substance
For white-yellowish solid, yield 55%.
Characterize data:1H NMR(500MHz,CDCl3): δ 8.57 (s, 1H), 8.40 (dd, J1=8.5Hz, J2=1.5Hz,
1H), 7.59 (dd, J1=8H, J2=1.5Hz, 1H), 7.38-7.35 (m, 1H), 7.07-7.04 (m, 1H), 5.03 (s, 1H),
4.93(s,1H).13C NMR(125MHz,CDCl3): δ 165.61 (d, J=17.5Hz), 134.50,132.49,128.50,
125.98,121.87,113.72,80.27 (d, J=187.5Hz)
Embodiment 6
Bromo- α-azido-the styrene of 0.3mmol (67.2mg) 2-, 0.9mmol (318.6mg) 1- chloromethyl -4- is fluoro-
Two (tetrafluoro boric acid) salt of 1,4- diazabicyclo [2.2.2] octane, that 0.6 (63.6mg) mmol sodium carbonate is added to 15mL heavy wall is resistance to
It presses in reaction tube, adds 3mL acetonitrile as solvents.Then, magnetic agitation 12 hours at room temperature.After being cooled to room temperature, anti-
It answers and is added in liquid two spoon column chromatography silica gels (100-200 mesh), and solvent is removed by vacuum distillation, gained crude product is carried out
Silica gel column chromatography separation, and is eluted for the petrol ether/ethyl acetate mixed liquor of 5:1 as eluant, eluent using volume ratio, TLC with
Track elutes process, collects the eluent containing target product, merges the eluent solvent is evaporated off and obtain target product.The object
Matter is white-yellowish solid, yield 58%.
Characterize data:1H NMR(500MHz,CDCl3): δ 8.57 (s, 1H), 8.40 (dd, J1=8.5Hz, J2=1.5Hz,
1H), 7.59 (dd, J1=8H, J2=1.5Hz, 1H), 7.38-7.35 (m, 1H), 7.07-7.04 (m, 1H), 5.03 (s, 1H),
4.93(s,1H).13C NMR(125MHz,CDCl3): δ 165.61 (d, J=17.5Hz), 134.50,132.49,128.50,
125.98,121.87,113.72,80.27 (d, J=187.5Hz)
Embodiment 7
By 0.3mmol (52.5mg) 2- methoxyl group-α-azido-styrene, 0.6 (212.4mg) mmol 1- chloromethyl-
Fluoro- 1,4- diazabicyclo [2.2.2] octane two (tetrafluoro boric acid) salt of 4-, 0.6 (63.6mg) mmol sodium carbonate are added to 15mL
In heavy wall pressure resistance reaction tube, 3mL acetonitrile as solvents is added.Then, magnetic agitation 12 hours at room temperature.It is cooled to room temperature
Afterwards, it is added in reaction solution two spoon column chromatography silica gels (100-200 mesh), and solvent is removed by vacuum distillation, gained is thick
Product carries out silica gel column chromatography separation, and is washed using volume ratio for the petrol ether/ethyl acetate mixed liquor of 5:1 as eluant, eluent
De-, TLC tracks elution process, collects the eluent containing target product, merges the eluent solvent is evaporated off and obtain target
Product.The substance is white-yellowish solid, yield 74%.
Characterize data:1H NMR(500MHz,CDCl3): δ 8.62 (s, 1H), 8.38 (dd, J1=8Hz, J2=1.5Hz,
1H), 7.13-7.10 (m, 1H), 7.01-, 6.98 (m, 1H), 6.92 (dd, J1=8Hz, J2=1Hz, 1H), 4.98 (s, 1H),
4.89(s,1H),3.91(s,3H).13C NMR(125MHz,CDCl3): δ 165.31 (d, J=16.25Hz), 148.22,
(126.34,124.62,121.05,120.01,110.12,80.26 d, J=187.5Hz), 55.74.
Embodiment 8
By 0.3mmol (52.5mg) 2- methoxyl group-α-azido-styrene, 0.6 (212.4mg) mmol 1- chloromethyl-
Fluoro- 1,4- diazabicyclo [2.2.2] octane two (tetrafluoro boric acid) salt of 4-, 0.6mmol (24mg) sodium hydroxide are added to 15mL
In heavy wall pressure resistance reaction tube, adds 3mL methylene chloride and make solvent.Then, magnetic agitation 12 hours at room temperature.It is cooled to room
Wen Hou is added two spoon column chromatography silica gels (100-200 mesh) in reaction solution, and removes solvent by vacuum distillation, by gained
Crude product carries out silica gel column chromatography separation, and is carried out using volume ratio for the petrol ether/ethyl acetate mixed liquor of 5:1 as eluant, eluent
Elution, TLC track elution process, collect the eluent containing target product, merge the eluent solvent is evaporated off and obtain mesh
Mark product.The substance is white-yellowish solid, yield 47%.
Characterize data:1H NMR(500MHz,CDCl3): δ 8.62 (s, 1H), 8.38 (dd, J1=8Hz, J2=1.5Hz,
1H), 7.13-7.10 (m, 1H), 7.01-, 6.98 (m, 1H), 6.92 (dd, J1=8Hz, J2=1Hz, 1H), 4.98 (s, 1H),
4.89(s,1H),3.91(s,3H).13C NMR(125MHz,CDCl3): δ 165.31 (d, J=16.25Hz), 148.22,
(126.34,124.62,121.05,120.01,110.12,80.26 d, J=187.5Hz), 55.74.
Embodiment 9
By 0.3mmol (52.5mg) 2- methoxyl group-α-azido-styrene, 0.6mmol (212.4mg) 1- chloromethyl -4-
Fluoro- two (tetrafluoro boric acid) salt of 1,4- diazabicyclo [2.2.2] octane, 0.6mmol (63.6mg) sodium carbonate are added to 15mL thickness
In wall pressure resistance reaction tube, adds 3mL tetrahydrofuran and make solvent.Then, magnetic agitation 8 hours at room temperature.It is cooled to room temperature
Afterwards, it is added in reaction solution two spoon column chromatography silica gels (100-200 mesh), and solvent is removed by vacuum distillation, gained is thick
Product carries out silica gel column chromatography separation, and is washed using volume ratio for the petrol ether/ethyl acetate mixed liquor of 5:1 as eluant, eluent
De-, TLC tracks elution process, collects the eluent containing target product, merges the eluent solvent is evaporated off and obtain target
Product.The substance is white-yellowish solid, yield 38%.
Characterize data:1H NMR(500MHz,CDCl3): δ 8.62 (s, 1H), 8.38 (dd, J1=8Hz, J2=1.5Hz,
1H), 7.13-7.10 (m, 1H), 7.01-, 6.98 (m, 1H), 6.92 (dd, J1=8Hz, J2=1Hz, 1H), 4.98 (s, 1H),
4.89(s,1H),3.91(s,3H).13C NMR(125MHz,CDCl3): δ 165.31 (d, J=16.25Hz), 148.22,
(126.34,124.62,121.05,120.01,110.12,80.26 d, J=187.5Hz), 55.74.
Embodiment 10
By 0.3mmol (66.3mg) 2- phenyl-α-azido-styrene, 0.6mmol (212.4mg) 1- chloromethyl -4-
Fluoro- two (tetrafluoro boric acid) salt of 1,4- diazabicyclo [2.2.2] octane, 0.6mmol (63.6mg) sodium carbonate are added to 15mL thickness
In wall pressure resistance reaction tube, 3mL acetonitrile as solvents is added.Then, magnetic agitation 12 hours at room temperature.After being cooled to room temperature,
It is added in reaction solution two spoon column chromatography silica gels (100-200 mesh), and solvent is removed by vacuum distillation, by gained crude product
Silica gel column chromatography separation is carried out, and is eluted using volume ratio for the petrol ether/ethyl acetate mixed liquor of 5:1 as eluant, eluent,
TLC tracks elution process, collects the eluent containing target product, merges the eluent solvent is evaporated off and obtain target production
Object.The substance is white-yellowish solid, yield 68%.
Characterize data:1H NMR(500MHz,CDCl3): δ 8.40 (d, J=10Hz, 1H), 8.15 (s, 1H), 7.51 (t, J
=7.5Hz, 2H), 7.46-7.39 (m, 4H), 7.32 (dd, J1=10Hz, J2=5Hz, 1H), 7.27-7.24 (m, 1H), 4.87
(s,1H),4.77(s,1H).13C NMR(125MHz,CDCl3): δ 165.35 (d, J=16.25Hz), 137.50,133.46,
132.57,130.20,129.11,129.08,128.49,128.15,124.96,121.11 80.01 (d, J=183.75Hz)
Embodiment 11
By 0.3mmol (66.3mg) 2- phenyl-α-azido-styrene, 0.6mmol (212.4mg) 1- chloromethyl -4-
Fluoro- two (tetrafluoro boric acid) salt of 1,4- diazabicyclo [2.2.2] octane, 0.6 (63.6mg) mmol sodium carbonate are added to 15mL thickness
In wall pressure resistance reaction tube, 3mL acetonitrile as solvents is added.Then, magnetic agitation 12 hours at 50 DEG C.After being cooled to room temperature,
It is added in reaction solution two spoon column chromatography silica gels (100-200 mesh), and solvent is removed by vacuum distillation, by gained crude product
Silica gel column chromatography separation is carried out, and is eluted using volume ratio for the petrol ether/ethyl acetate mixed liquor of 5:1 as eluant, eluent,
TLC tracks elution process, collects the eluent containing target product, merges the eluent solvent is evaporated off and obtain target production
Object.The substance is white-yellowish solid, yield 62%.
Characterize data:1H NMR(500MHz,CDCl3): δ 8.40 (d, J=10Hz, 1H), 8.15 (s, 1H), 7.51 (t, J
=7.5Hz, 2H), 7.46-7.39 (m, 4H), 7.32 (dd, J1=10Hz, J2=5Hz, 1H), 7.27-7.24 (m, 1H), 4.87
(s,1H),4.77(s,1H).13C NMR(125MHz,CDCl3): δ 165.35 (d, J=16.25Hz), 137.50,133.46,
132.57,130.20,129.11,129.08,128.49,128.15,124.96,121.11 80.01 (d, J=183.75Hz)
Embodiment 12
By 0.3mmol (66.3mg) 2- phenyl-α-azido-styrene, 0.6mmol (212.4mg) 1- chloromethyl -4-
Fluoro- two (tetrafluoro boric acid) salt of 1,4- diazabicyclo [2.2.2] octane, 0.9 (95.4mg) mmol sodium carbonate are added to 15mL thickness
In wall pressure resistance reaction tube, 3mL acetonitrile as solvents is added.Then, magnetic agitation 24 hours at room temperature.After being cooled to room temperature,
It is added in reaction solution two spoon column chromatography silica gels (100-200 mesh), and solvent is removed by vacuum distillation, by gained crude product
Silica gel column chromatography separation is carried out, and is eluted using volume ratio for the petrol ether/ethyl acetate mixed liquor of 5:1 as eluant, eluent,
TLC tracks elution process, collects the eluent containing target product, merges the eluent solvent is evaporated off and obtain target production
Object.The substance is white-yellowish solid, yield 60%.
Characterize data:1H NMR(500MHz,CDCl3): δ 8.40 (d, J=10Hz, 1H), 8.15 (s, 1H), 7.51 (t, J
=7.5Hz, 2H), 7.46-7.39 (m, 4H), 7.32 (dd, J1=10Hz, J2=5Hz, 1H), 7.27-7.24 (m, 1H), 4.87
(s,1H),4.77(s,1H).13C NMR(125MHz,CDCl3): δ 165.35 (d, J=16.25Hz), 137.50,133.46,
132.57,130.20,129.11,129.08,128.49,128.15,124.96,121.11 80.01 (d, J=183.75Hz).
Claims (9)
1. a kind of method for synthesizing fluorine-containing imine compound and its derivative, it is characterised in that: the method specifically according to
Following steps carry out:
Using substitution nitrine end vinyl compound is starting material shown in formula I, with the fluoro- Isosorbide-5-Nitrae-diazabicyclo of 1- chloromethyl -4-
Two (tetrafluoro boric acid) salt of [2.2.2] octane is Fluorine source, in organic solvent, anti-at 0~50 DEG C under the action of alkaline matter
It answers 8~24 hours, gained reaction solution is post-treated to obtain fluorine-containing imine compound and its derivative shown in formula II；Described
Substitution nitrine end vinyl compound and the ratio between Fluorine source, the amount of substance of alkaline matter shown in formula I are 1:1~3:1~3,
In formula I or formula II,
R is H or H by Br ,-CH3O orIt is monosubstituted or polysubstituted.
2. the synthetic method of fluorine-containing imine compound as described in claim 1 and its derivative, it is characterised in that: described
Alkaline matter is one or more kinds of mixtures of sodium carbonate, sodium acetate, sodium hydroxide or sodium tert-butoxide.
3. the synthetic method of fluorine-containing imine compound as described in claim 1 and its derivative, it is characterised in that: described
Organic solvent is one of acetonitrile, tetrahydrofuran, methylene chloride or toluene or more than one mixed solvent.
4. the synthetic method of fluorine-containing imine compound as described in claim 1 and its derivative, it is characterised in that: described
The additional amount of organic solvent is to replace the amount of the substance of nitrine end vinyl compound to be calculated as 3~17ml/mmol shown in formula I.
5. the synthetic method of fluorine-containing imine compound as claimed in claim 3 and its derivative, it is characterised in that: described
Organic solvent is acetonitrile.
6. the synthetic method of fluorine-containing imine compound as described in claim 1 and its derivative, it is characterised in that: described anti-
Answering temperature is 25 DEG C, and the reaction time is 12 hours.
7. the synthetic method of fluorine-containing imine compound as described in claim 1 and its derivative, it is characterised in that: described
Substitution nitrine end vinyl compound and the ratio between Fluorine source, the amount of substance of alkaline matter shown in formula I are 1:2:2.
8. the synthetic method of fluorine-containing imine compound and its derivative as described in claim 1~7, it is characterised in that: institute
Obtain the post-processing approach of reaction solution are as follows: after reaction, the column chromatography silica gel of 100-200 mesh is added into gained reaction solution and subtracts
Solvent is distilled off in pressure, gained crude product is carried out silica gel column chromatography separation, and be petroleum ether/acetic acid second of 5:1 with volume ratio
Ester mixed liquor is eluted as eluant, eluent, TLC tracking elution process, eluent of the collection containing target product, described in merging
Eluent solvent be evaporated off obtain fluorine-containing imine compound and its derivative shown in the formula II.
9. the synthetic method of fluorine-containing imine compound as described in claim 1 and its derivative, it is characterised in that: described
Method specifically carries out in accordance with the following steps:
Using substitution nitrine end vinyl compound is starting material shown in formula I, with the fluoro- Isosorbide-5-Nitrae-diazabicyclo of 1- chloromethyl -4-
Two (tetrafluoro boric acid) salt of [2.2.2] octane is Fluorine source, anti-at 25 DEG C in organic solvent acetonitrile under the action of sodium carbonate
Answer 12 hours, after reaction, be added into gained reaction solution the column chromatography silica gel of 100-200 mesh and being evaporated under reduced pressure remove it is molten
Agent, by gained crude product carry out silica gel column chromatography separation, and using volume ratio for 5:1 petrol ether/ethyl acetate mixed liquor as
Eluant, eluent is eluted, and TLC tracks elution process, collects the eluent containing target product, is merged the eluent and is evaporated off
Solvent obtains fluorine-containing imine compound and its derivative shown in formula II；Replace nitrine end alkenes shown in the formula I
Closing object and the ratio between Fluorine source, the amount of substance of alkaline matter is 1:2:2, and the additional amount of the organic solvent acetonitrile is shown in formula I
The amount of substance of substitution nitrine end vinyl compound be calculated as 3~17ml/mmol.
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Citations (2)
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| US7115767B2 (en) * | 2003-07-18 | 2006-10-03 | Abbott Laboratories | Tetraline derivatives as ghrelin receptor modulators |
| WO2007022529A3 (en) * | 2005-08-19 | 2009-04-16 | Array Biopharma Inc | Method of treating inflammatory diseases |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7115767B2 (en) * | 2003-07-18 | 2006-10-03 | Abbott Laboratories | Tetraline derivatives as ghrelin receptor modulators |
| WO2007022529A3 (en) * | 2005-08-19 | 2009-04-16 | Array Biopharma Inc | Method of treating inflammatory diseases |
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| GEOFFROY HERVÉ LONCA，等: "Gold(I)-Catalyzed 6-endo-dig Azide-Yne Cyclization: an Efficient Access to 2H-1,3-Oxazines", 《CHEMICAL COMMUNICATIONS》 * |
| YI-FENG WANG，等: "Linking of Alcohols with Vinyl Azides", 《ORG. LETT.》 * |
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