CN107629013A - The synthetic method of the new part of a kind of efficient catalytic CuAAC reactions - Google Patents
The synthetic method of the new part of a kind of efficient catalytic CuAAC reactions Download PDFInfo
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- CN107629013A CN107629013A CN201710764027.1A CN201710764027A CN107629013A CN 107629013 A CN107629013 A CN 107629013A CN 201710764027 A CN201710764027 A CN 201710764027A CN 107629013 A CN107629013 A CN 107629013A
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- methyl ester
- glycine methyl
- nitrine
- diine
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Abstract
The invention discloses the synthetic method of the new part of a kind of efficient catalytic CuAAC reactions, belong to the synthesis technical field of functional structure molecule.Technical scheme main points are：The synthetic method of the new part of a kind of efficient catalytic CuAAC reactions, synthesizes the synthesis of glycine methyl ester diine first, then with glycine methyl ester diine, azide compounds, K2CO3It is raw material with cuprous iodide, with acetonitrile and water as solvent, is reacted in stirring at normal temperature, reaction obtains new 1,2,3 pairs of triazoles of part glycine methyl ester through processing later after terminating and opens cyclics.The present invention provides the ligand catalyst efficient, simple and easy to get of various new for click reactions, accelerates reaction effect obvious as part, and have very actual purposes.
Description
Technical field
The invention belongs to the synthesis technical field of functional structure molecule, and in particular to a kind of efficient catalytic CuAAC reactions
The synthetic method of new part.
Background technology
The chemist Sharpless of Scripps research institutes of the Nobel chemistry Prize winner U.S. proposed " point in 2001
Hit " concept of chemistry, the concept is just wide concerned once proposing, turns into domestic outer chemical, life, medicine and material every subjects
One of focus paid close attention to jointly.How the biocompatibility of click reaction and reduction Cu (I) dosage are improved into current research
New tendency.
Two important research fields of current click chemistry work：One be no copper catalysis SPAAC reaction, another is
Can be with univalent copper ion coordination and favorable ligand compound.Part accelerate promote click reaction while pair
Reduction copper ion plays the role of very good to the toxicity of cell.The new part of efficient catalytic CuAAC reactions is to belong to monovalence
The part of cupric coordination is a kind of, either in common organic reaction system or life system, is urged as ligand catalyst
Change and accelerate to suffer from highly effective effect in terms of click reactions.
In recent years, although there is monovalence copper ligand compound to be come out by successive report, for extensively should for click reactions
For, the research and development demand to part is also far from enough.Synthesis on this kind of part in the past, the condition that it is synthesized are past
Toward the reaction raw materials for needing costliness, it is difficult to largely synthesize and reaction condition is more harsh.
The content of the invention
Present invention solves the technical problem that there is provided, a kind of raw material sources are extensive, cost is cheap and technique is simply a kind of
The synthetic method of the new part of efficient catalytic CuAAC reactions.
The present invention adopts the following technical scheme that a kind of the new of efficient catalytic CuAAC reactions is matched somebody with somebody to solve above-mentioned technical problem
The synthetic method of body, it is characterised in that concretely comprise the following steps：
(1) synthesis of glycine methyl ester diine, using glycine methyl ester hydrochloride, trimethyl silicane ethyl-acetylene, mass concentration as
37% formalin, sodium acid carbonate and stannous chloride is raw material, small in 35 DEG C of lasting stirring reactions 18 in constant temperature oil bath
When, then glycine methyl ester TMS- dialkynes are obtained by post processing, then using tetrahydrofuran as solvent, the tetrabutyl is fluorinated
Ammonium and glycine methyl ester TMS- dialkynes are reacted in normal temperature, then obtain compound glycine methyl ester two by post processing
Alkynes；
(2) glycine methyl ester 1,2,3- double triazoles open the synthesis of cyclics, with glycine methyl ester diine, nitrine class
Compound, K2CO3It is raw material with cuprous iodide, with acetonitrile and water as solvent, is reacted in stirring at normal temperature, after reaction passes through after terminating
Processing obtains the double triazoles of new part glycine methyl ester 1,2,3- and opens cyclics, and the azide compounds are to fluoroform
Base aziminobenzene, aziminobenzene, p-fluorophenyl nitrine, o-fluorophenyl nitrine, a fluorophenyl nitrine, 3,5- difluorophenyls nitrine,
3,4,5- trifluorophenyls nitrine, rubigan nitrine, p-bromophenyl nitrine, p-nitrophenyl nitrine or p-methoxyphenyl are folded
Nitrogen.
Further preferably, the mol ratio of glycine methyl ester hydrochloride, trimethyl silicane ethyl-acetylene and formaldehyde described in step (1)
For 1:2.5:2.5, the mol ratio of sodium acid carbonate and glycine methyl ester hydrochloride is 2.5:1, stannous chloride and glycine methyl ester salt
The mol ratio of hydrochlorate is 0.1:1, the mol ratio of tetrabutyl ammonium fluoride and glycine methyl ester TMS- diines is 2.5:1.
Further preferably, the mol ratio of glycine methyl ester diine and aziminobenzene described in step (2) is 1:2, iodate is sub-
The mol ratio of copper and glycine methyl ester diine is 0.1:1, K2CO3Mol ratio with glycine methyl ester diine is 1.2:1.
The present invention reacts for click provides the ligand catalyst efficient, simple and easy to get of various new, as part plus
Fast reaction effect is obvious, and has very actual purposes.
Embodiment
The above of the present invention is described in further details by the following examples, but this should not be interpreted as to this
The scope for inventing above-mentioned theme is only limitted to following embodiment, and all technologies realized based on the above of the present invention belong to this hair
Bright scope.
Embodiment 1
Glycine methyl ester TMS- diines are synthesized, glycine methyl ester hydrochloride 2mmol trimethyl silicanes are added in round-bottomed flask
Ethyl-acetylene 5mmol, formalin 5mmol, sodium acid carbonate 5mmol and the stannous chloride 0.2mmol that mass concentration is 37%, in
35 DEG C mix reaction 18 hours, and course of reaction is monitored with TLC.Reaction is used after terminating and methylene chloride/water extracts three times, is taken
Dried after organic phase cleaning, yield 92%.Product is colourless liquid.Glycine methyl ester diine is synthesized, is added in round-bottomed flask
Then in 5mL tetrahydrofuran solutions tetrabutyl ammonium fluoride 5mmol is added portionwise, in normal temperature in glycine methyl ester TMS- diines 2mmol
Reaction 3 hours is mixed, course of reaction is monitored with TLC.Reaction is used after terminating and methylene chloride/water extracts three times, is taken organic
Dried after mutually cleaning, yield 90%.Product is colourless liquid.
Embodiment 2
1mmol glycine methyl esters diine, 2mmol aziminobenzenes, 1.2mmol K are added in 10mL round-bottomed flasks2CO3With
0.1mmol cuprous iodides, reaction 10 hours is mixed in normal temperature in acetonitrile and aqueous solvent, course of reaction is detected with TLC, instead
It is extracted with ethyl acetate after should terminating, the isolated target product of silica gel column chromatography, yield 85%.
Embodiment 3
Added in 10mL round-bottomed flasks 1mmol glycine methyl esters diines, 2mmol p-trifluoromethyl phenyls nitrine,
1.2mmol K2CO3With 0.1mmol cuprous iodides, reaction 12 hours, course of reaction are mixed in normal temperature in acetonitrile and aqueous solvent
Detected with TLC, reaction is extracted with ethyl acetate after terminating, the isolated target product of silica gel column chromatography, yield 80%.
Embodiment 4
1mmol glycine methyl esters diine, 2mmol p-fluorophenyls nitrine, 1.2mmol are added in 10mL round-bottomed flasks
K2CO3With 0.1mmol cuprous iodides, reaction 8 hours is mixed in normal temperature in acetonitrile and aqueous solvent, course of reaction is examined with TLC
Survey.Reaction is extracted with ethyl acetate after terminating, the isolated target product of silica gel column chromatography, yield 87%.
Embodiment 5
1mmol glycine methyl esters diine, 2mmol 2- fluorophenyls nitrine, 1.2mmol are added in 10mL round-bottomed flasks
K2CO3With 0.1mmol cuprous iodides, reaction 10 hours, course of reaction TLC are mixed in normal temperature in acetonitrile and aqueous solvent
Detection, reaction are extracted with ethyl acetate after terminating, and clean the sterling through the isolated target product of silica gel column chromatography after organic phase,
Yield is 89%.
Embodiment 6
1mmol glycine methyl esters diine, 2mmol 3- fluorophenyls nitrine, 1.2mmol are added in 10mL round-bottomed flasks
K2CO3With 0.1mmol cuprous iodides, reaction 10 hours, course of reaction TLC are mixed in normal temperature in acetonitrile and aqueous solvent
Detection, reaction are extracted with ethyl acetate after terminating, and clean the sterling through the isolated target product of silica gel column chromatography after organic phase,
Yield is 94%.
Embodiment 7
Added in 10mL round-bottomed flasks 1mmol glycine methyl esters diines, 2mmol 3,5- difluorophenyls nitrine,
1.2mmol K2CO3With 0.1mmol cuprous iodides, reaction 10 hours is mixed in normal temperature in acetonitrile and aqueous solvent, was reacted
Journey is detected with TLC, and reaction is extracted with ethyl acetate after terminating, and is cleaned after organic phase through the isolated target product of silica gel column chromatography
Sterling, yield 89%.
Embodiment 8
Added in 10mL round-bottomed flasks 1mmol glycine methyl esters diines, 2mmol 3,4,5- trifluorophenyls nitrine,
1.2mmol K2CO3With 0.1mmol cuprous iodides, reaction 14 hours is mixed in normal temperature in acetonitrile and aqueous solvent, was reacted
Journey is detected with TLC, and reaction is extracted with ethyl acetate after terminating, and is cleaned after organic phase through the isolated target product of silica gel column chromatography
Sterling, yield 90%.
Embodiment 9
1mmol glycine methyl esters diine, 2mmol rubigan nitrine, 1.2mmol are added in 10mL round-bottomed flasks
K2CO3With 0.1mmol cuprous iodides, reaction 14 hours is mixed in normal temperature in acetonitrile and water, course of reaction is detected with TLC,
Reaction is extracted with ethyl acetate after terminating, and cleans the sterling through the isolated target product of silica gel column chromatography after organic phase, yield
For 90%.
Embodiment 10
1mmol glycine methyl esters diine, 2mmol p-bromophenyls nitrine, 1.2mmol are added in 10mL round-bottomed flasks
K2CO3With 0.1mmol cuprous iodides, reaction 14 hours, course of reaction TLC are mixed in normal temperature in acetonitrile and aqueous solvent
Monitoring, reaction are extracted with ethyl acetate after terminating, and clean the sterling through the isolated target product of silica gel column chromatography after organic phase,
Yield is 92%.
Embodiment 11
1mmol glycine methyl esters diine, 2mmol p-nitrophenyls nitrine, 1.2mmol are added in 10mL round-bottomed flasks
K2CO3With 0.1mmol cuprous iodides, reaction 14 hours, course of reaction TLC are mixed in normal temperature in acetonitrile and aqueous solvent
Detection, reaction are extracted with ethyl acetate after terminating, and clean the sterling through the isolated target product of silica gel column chromatography after organic phase,
Yield is 88%.
Embodiment 12
1mmol glycine methyl esters diine, 2mmol p-methoxyphenyls nitrine, 1.2mmol are added in 10mL round-bottomed flasks
K2CO3With 0.1mmol cuprous iodides, reaction 14 hours, course of reaction TLC are mixed in normal temperature in acetonitrile and aqueous solvent
Detection, reaction are extracted with ethyl acetate after terminating, and clean the sterling through the isolated target product of silica gel column chromatography after organic phase,
Yield is 85%.
Embodiment above describes the general principle of the present invention, main features and advantages, the technical staff of the industry should
Understand, the present invention is not limited to the above embodiments, the original for simply illustrating the present invention described in above-described embodiment and specification
Reason, under the scope for not departing from the principle of the invention, various changes and modifications of the present invention are possible, and these changes and improvements are each fallen within
In the scope of protection of the invention.
Claims (3)
1. the synthetic method of the new part of a kind of efficient catalytic CuAAC reactions, it is characterised in that concretely comprise the following steps：
（1）The synthesis of glycine methyl ester diine, using glycine methyl ester hydrochloride, trimethyl silicane ethyl-acetylene, mass concentration as 37%
Formalin, sodium acid carbonate and stannous chloride are raw material, in 35 DEG C of persistently stirring reaction 18 hours, then pass through in constant temperature oil bath
Later processing obtains glycine methyl ester TMS- dialkynes, then using tetrahydrofuran as solvent, by tetrabutyl ammonium fluoride and sweet
Propylhomoserin methyl esters TMS- dialkynes are reacted in normal temperature, then obtain compound glycine methyl ester diine by post processing；
（2）Glycine methyl ester 1,2, the double triazoles of 3- open the synthesis of cyclics, with glycine methyl ester diine, nitrine class chemical combination
Thing, K2CO3It is raw material with cuprous iodide, with acetonitrile and water as solvent, is reacted in stirring at normal temperature, reaction is handled after terminating after
Obtain the double triazoles of new part glycine methyl ester 1,2,3- and open cyclics, the azide compounds are to trifluoromethylbenzene
Base nitrine, aziminobenzene, p-fluorophenyl nitrine, o-fluorophenyl nitrine, a fluorophenyl nitrine, 3,5- difluorophenyls nitrine, 3,4,
5- trifluorophenyls nitrine, rubigan nitrine, p-bromophenyl nitrine, p-nitrophenyl nitrine or p-methoxyphenyl nitrine.
2. the synthetic method of the new part of a kind of efficient catalytic CuAAC reactions according to claim 1, it is characterised in that：
Step（1）Described in glycine methyl ester hydrochloride, trimethyl silicane ethyl-acetylene and formaldehyde mol ratio be 1:2.5:2.5, bicarbonate
The mol ratio of sodium and glycine methyl ester hydrochloride is 2.5:1, the mol ratio of stannous chloride and glycine methyl ester hydrochloride is 0.1:
1, the mol ratio of tetrabutyl ammonium fluoride and glycine methyl ester TMS- diines is 2.5:1.
3. the synthetic method of the new part of a kind of efficient catalytic CuAAC reactions according to claim 1, it is characterised in that：
Step（2）Described in the mol ratio of glycine methyl ester diine and azide compounds be 1:2, cuprous iodide and glycine methyl ester two
The mol ratio of alkynes is 0.1:1, K2CO3Mol ratio with glycine methyl ester diine is 1.2:1.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108623572A (en) * | 2018-07-11 | 2018-10-09 | 河南师范大学 | Functionalized ion liquid ligand and its preparation method and application of the one kind for CuAAC reactions |
| CN110041274A (en) * | 2019-05-13 | 2019-07-23 | 河南师范大学 | A kind of method that the multicomponent one kettle way of air oxidation prepares 5- fluoroalkylation triazole compound |
-
2017
- 2017-08-30 CN CN201710764027.1A patent/CN107629013A/en active Pending
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108623572A (en) * | 2018-07-11 | 2018-10-09 | 河南师范大学 | Functionalized ion liquid ligand and its preparation method and application of the one kind for CuAAC reactions |
| CN108623572B (en) * | 2018-07-11 | 2020-07-03 | 河南师范大学 | Functionalized ionic liquid ligand for CuAAC reaction and preparation method and application thereof |
| CN110041274A (en) * | 2019-05-13 | 2019-07-23 | 河南师范大学 | A kind of method that the multicomponent one kettle way of air oxidation prepares 5- fluoroalkylation triazole compound |
| CN110041274B (en) * | 2019-05-13 | 2022-12-13 | 河南师范大学 | Method for preparing 5-fluoroalkyl triazole compound by air oxidation multi-component one-pot method |
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Application publication date: 20180126 |