CN108503601A - The synthetic method of 1- alkyl -5- arylthio -1,2,3- triazole compounds - Google Patents
The synthetic method of 1- alkyl -5- arylthio -1,2,3- triazole compounds Download PDFInfo
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Abstract
The invention discloses a kind of 5 arylthios 1 of 1 alkyl, 2, the synthetic method of 3 triazole compounds, with 1 benzyl, 4 TMS, 5 I 1,2,3 3-triazole compounds/1 benzyl, 5 I 1,2,3 3-triazole compounds and benzenethiol/be raw material to methylbenzene phenyl-sulfhydrate, acetonitrile be solvent, cuprous iodide or cuprous bromide be catalyst, 2 oxocyclohex alkane Ethyl formates are ligand and cesium carbonate is accelerating agent, 1 alkyl, 5 arylthios 1 are made in 70 DEG C of reactions, 2,3 triazole compounds.Raw material sources of the present invention are extensive, prepare simply, cheap.
Description
The present invention is that number of patent application is 201410788419.8, applying date 2014.12.19, entitled difunctional
The divisional application of 4-TMS-5-I-1,2,3- triazole compounds and its preparation method and application.
Technical field
The invention belongs to synthesize 1,2,3- triazole compound intermediate technical fields of 5 hetero atoms substitution, specifically
It is related to a kind of difunctional 4-TMS-5-I-1,2,3- triazole compounds and its preparation method and application.
Background technology
1,2,3- triazoles have as pharmacophoric group and functional structure in medicine, pesticide, dyestuff, chiral catalysis etc.
Very extensive application.Therefore, 1, the modification of 2,3- triazole structures and derivatization have had many people to do a large amount of research
Work.Report that the lower nitrine of copper catalysis effect and end alkynes can generate respectively from Sharpless and Medal work groups in 2002
Since the five-membered ring (CuAAC reactions) of triazole, a large amount of CuAAC reactions are closed under conditions of different copper catalysts and solvent
It is reported out in succession at 1,4 disubstituted 1,2,3- triazoles.But about 1,5 disubstituted 1, the report of 2,3- triazoles is but
It is rarely found.Report about 1,5 disubstituted 1,2,3- triazoles has nitrine under ruthenium catalytic condition to selectively produce 1,5 with end alkynes
Disubstituted triazole (RuAAC reactions), the catalytic conditions such as magnesium, bismuth, alkynyl lithium synthesize 1,5 disubstituted triazoles.But these sides
Compared with method and CuAAC reaction, need expensive transition-metal catalyst, reaction substrate selection is very limited, reaction condition compared with
For harshness.Importantly, the triazole of 5 hetero atoms substitution has very extensive purposes in bioactive molecule, and it is above-mentioned
Method cannot be used for provide 5 be hetero atom substituents 1,2,3- triazoles.
Invention content
The technical problem to be solved by the present invention is to provide a kind of difunctional 4-TMS-5-I-1,2,3- triazole chemical combination
Object is to pass through silylation end as the intermediate for providing polysubstituted 1,2,3- triazole with the 1 of silylation, 2,3- triazole
The 1,2,3- triazoles with silylation that alkynes and organic nitrine generate can be further by sloughing, taking to the orderly of silylation
1,5- disubstituted 1,2,3- triazole of the generation to be needed.
Another technical problem that the present invention solves there is provided a kind of raw material sources it is extensive, cheap and prepare it is convenient
Difunctional 4-TMS-5-I-1,2,3- triazole compounds preparation method and by difunctional 4-TMS-5-I-1,2,
3- triazole compounds are the method that intermediate further synthesizes the disubstituted 1,2,3- triazole compounds of 1,5-.
In order to solve the above technical problems, the present invention adopts the following technical scheme that：Difunctional 4-TMS-5-I-1,2,3- tri-
Nitrogen azole compounds, it is characterised in that it is solvent to be using trimethyl silicane ethyl-acetylene and nitrine as raw material, acetonitrile, cuprous iodide is to urge
Agent, N- chloro butyryl diimines (NCS) are oxidant, N- diisopropyl ethyl amines (DIPEA) are alkali, are made at normal temperatures
, difunctional 4-TMS-5-I-1,2,3- triazole compounds have the following structure：Wherein R is
Difunctional 4-TMS-5-I-1 of the present invention, the preparation method of 2,3- triazole compounds, feature exist
In the specific steps are：Solvent acetonitrile, raw material nitrine and trimethyl silicane ethyl-acetylene, alkali N- diisopropyls are sequentially added in the reaction vessel
Base ethylamine, catalyst cuprous iodide and oxidant N- chloro butyryl diimines, reaction vessel is placed under room temperature and is stirred, entirely
Reaction process is detected with thin-layer chromatography TLC, is extracted with ethyl acetate after reaction, pillar layer separation obtains after organic phase is cleaned
To sterling difunctional 4-TMS-5-I-1,2,3- triazole compounds.
Further preferably, the difunctional 4-TMS-5-I-1, the preparation method Central Plains of 2,3- triazole compounds
Expect that the molar ratio of nitrine and trimethyl silicane ethyl-acetylene is 1:1.2, catalyst cuprous iodide, oxidant N- chloro butyryl diimines and
The dosage of alkali N- diisopropyl ethyl amines is respectively 1.2 times of nitrine mole.
The chemical principle reaction equation of foundation of the present invention is as follows：
1- alkyl -5-I-1 of the present invention, 2,3- triazole compounds, it is characterised in that be with difunctional 4-
TMS-5-I-1,2,3- triazole compounds are raw material, methanol is solvent and potassium carbonate is deprotection agent, in 40 DEG C of selectivity
Made from deprotection, the 1- alkyl -5-I-1,2,3- triazole compounds have the following structure：Wherein R is
The reaction equation that the present invention is deprotected process is as follows：
Difunctional 4-TMS-5-I-1,2,3- triazole compounds or 1- alkyl -5-I-1,2,3- of the present invention
Triazole compound is applied in synthesis 1,5- disubstituted 1,2,3- triazole compounds, specially in synthesis 1- alkane
Base -5- aryloxy group -1,2,3- triazole compounds, 1- alkyl -5- arylthio -1,2,3- triazole compounds, 1- alkyl -
5- aryl -1,2,3- triazole compounds or 1- alkyl -5- alkynyls -1,2, the application in 3- triazole compounds are corresponding
Reaction equation be：
Wherein R isR1、R2、
R3For aryl, R4For aryl or alkyl.
Further preferably, the difunctional 4-TMS-5-I-1,2,3- triazole compounds or 1- alkyl -5-I-
Application of 1,2, the 3- triazole compound in synthesis 1- alkyl -5- aryloxy group -1,2,3- triazole compounds, specific side
Method is with difunctional 4-TMS-5-I-1,2,3- triazole compounds or 1- alkyl -5-I-1,2,3- triazole compounds
With phenolic compound be raw material, acetonitrile is solvent, cuprous bromide is catalyst, 2- oxocyclohex alkane Ethyl formates are ligand and carbon
Sour caesium is accelerating agent, 1- alkyl -5- phenoxy groups -1,2,3- triazole compounds is made in 70 DEG C of reactions, reaction equation is：
Wherein R ' is hydrogen, alkyl, nitro, chlorine, alkoxy or benzoyl.
Further preferably, the difunctional 4-TMS-5-I-1,2,3- triazole compounds or 1- alkyl -5-I-
Application of 1,2, the 3- triazole compound in synthesis 1- alkyl -5- arylthios -1,2,3- triazole compounds, specific side
Method is with difunctional 4-TMS-5-I-1,2,3- triazole compounds or 1- alkyl -5-I-1,2,3- triazole compounds
With phenyl-sulfhydrate compounds be raw material, acetonitrile is solvent, cuprous bromide is catalyst, 2- oxocyclohex alkane Ethyl formates be ligand and
Cesium carbonate is accelerating agent, is then solvent and potassium carbonate as deprotection agent using methanol in 70 DEG C of reactions, in 40 DEG C of selective remove-insurances
Shield 1- alkyl -5- contrapositions substitution thiophenyl -1,2 obtained, 3- triazole compounds, reaction equation are：
Wherein R " is hydrogen, alkyl, chlorine or bromine.
Further preferably, the difunctional 4-TMS-5-I-1,2,3- triazole compounds or 1- alkyl -5-I-
Application of 1,2, the 3- triazole compound in synthesis 1- alkyl -5- aryl -1,2,3- triazole compounds, specific method
Be with difunctional 4-TMS-5-I-1,2,3- triazole compounds or 1- alkyl -5-I-1,2,3- triazole compounds and
Aryl boric acid is raw material, tetrahydrofuran be solvent, palladium bichloride bi triphenyl phosphine composition be catalyst and potassium hydroxide is rush
Into agent, in 70 DEG C of reactions, tetrabutyl ammonium fluoride is then added, 1- alkyl -5- phenyl -1,2 obtained, 3- triazoles is stirred at room temperature
Class compound, reaction equation are：
Further preferably, the difunctional 4-TMS-5-I-1,2,3- triazole compounds or 1- alkyl -5-I-
Application of 1,2, the 3- triazole compound in synthesis 1- alkyl -5- alkynyls -1,2,3- triazole compounds, specific method
Be with difunctional 4-TMS-5-I-1,2,3- triazole compounds or 1- alkyl -5-I-1,2,3- triazole compounds and
Acetylene compound is raw material, tetrahydrofuran be solvent, palladium bichloride bi triphenyl phosphine composition be catalyst and potassium hydroxide is
Then accelerating agent is added tetrabutyl ammonium fluoride and 1- alkyl -5- alkynyls -1,2 obtained, tri- nitrogen of 3- is stirred at room temperature in 70 DEG C of reactions
Azole compounds, reaction equation are：
Wherein R " ' is alkyl or aryl.
The difunctional 4-TMS-5-I-1 provided according to the present invention, the synthesis of 2,3- triazoles, key problem in technology are to utilize
Excessive cuprous iodide provides iodine for 5 iodide ions of reaction product 1,2,3- triazoles again as the catalyst of the reaction
Source, and then difunctional 4-TMS-5-I-1,2,3- triazoles can be used as serial coupling reaction substrate by iodide ion and carry out 1,
The derivative of 5 disubstituted 1,2,3- triazoles.
The present invention the advantage is that compared with existing synthetic technology：(1) raw material sources are extensive, prepare simply, price is low
It is honest and clean；(2) the catalyst cuprous iodide that reaction uses, while being reactant, price wants cheap more, simple and easy to get；(3) it reacted
Journey is normal temperature and pressure, avoids harsh reaction condition, is a kind of efficient synthesis difunctional 4-TMS-5-I-1,2,3- tri-
Nitrogen azole compounds, 1- alkyl -5-I-1,2,3- triazole compounds, 1- alkyl -5- aryloxy group -1,2,3- triazoles
Close object, 1- alkyl -5- arylthio -1,2,3- triazole compounds, 1- alkyl -5- aryl -1,2,3- triazole compounds
With 1- alkyl -5- alkynyls -1,2, the method for 3- triazole compounds is conducive to large-scale industrial production.
Specific implementation mode
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 range for inventing above-mentioned theme is only limitted to embodiment below, and all technologies realized based on the above of the present invention belong to this hair
Bright range.
Embodiment 1
In 10ml round-bottomed flasks, 1mmol benzyl azides, 1.2mmol trimethyl silicanes ethyl-acetylene, 1.2mmol are sequentially added
DIPEA, 1.2mmol cuprous iodide and 1.2mmol NCS are mixed 12 hours under room temperature, and reaction process is monitored with TLC.Instead
It is extracted with ethyl acetate after answering, cleans the sterling through the isolated target product of silica gel column chromatography after organic phase, yield is
85%, product is light tan solid .96-98 DEG C of fusing point.1H NMR(CDCl3,400MHz):δ7.36-7.28(m,5H),5.62
(s,2H),0.40(s,9H).13C NMR(CDCl3,101MHz):δ133.7,127.9,127.4,127.3,126.9,83.7,
52.6,-0.9,-2.23.HRMS(ESI)m/z calculate for(M+H+)C12H17IN3Si+:358.0236,Found:
358.0231,calculate for(M+Na+)C12H16IN3NaSi+:380.0050,Found:380.0052。
Embodiment 2
In 10ml round-bottomed flasks, sequentially add 1mmol to methoxy-benzyl nitrine, 1.2mmol trimethyl silicanes ethyl-acetylene,
1.2mmol DIPEA, 1.2mmol cuprous iodides and 1.2mmol NCS are mixed 12 hours under room temperature, and reaction process is used
TLC is monitored.It is extracted with ethyl acetate, is cleaned after organic phase through the pure of the isolated target product of silica gel column chromatography after reaction
Product, yield 83%, product are viscous fluid.1H NMR(400MHz,CDCl3) δ 7.34-7.12 (m, 2H), 6.85 (d, J=
8.5Hz, 2H), 5.52 (d, J=16.2Hz, 2H), 3.78 (s, 3H), 0.38 (s, 7H), 0.25 (s, 2H)13C NMR
(101MHz,CDCl3)δ159.6,151.2,129.5,126.6,125.9,114.2,84.4,77.4,77.1,76.8,55.3,
54.3,53.1.HRMS(ESI)m/z calculate for(M+H+)C13H19IN3OSi+:388.0337,Found:
388.0336。
Embodiment 3
In 10ml round-bottomed flasks, sequentially add 1mmol anthracenes methyl azide, 1.2mmol trimethyl silicanes ethyl-acetylene,
1.2mmol DIPEA, 1.2mmol cuprous iodides and 1.2mmol NCS are mixed 12 hours under room temperature, and reaction process is used
TLC is monitored.It is extracted with ethyl acetate, is cleaned after organic phase through the pure of the isolated target product of silica gel column chromatography after reaction
Product, yield 81%, product are viscous fluid.1H NMR(400MHz,CDCl3) δ 7.73 (s, 1H), 7.24 (d, J=2.1Hz,
1H),6.92-6.81(m,2H),5.54(s,2H),3.79(s,3H),0.07(s,3H).13C NMR(101MHz,CDCl3)δ
131.4,131.2,129.7,129.5,129.3,127.3,127.0,125.1,124.0,123.6,84.0,47.2,29.5,
27.2,-0.30,-1.33.HRMS(ESI)m/z calculate for(M+H+)C20H21IN3Si+:458.0544,Found:
458.0551。
Embodiment 4
In 10ml round-bottomed flasks, sequentially add 1mmol phenylalanines nitrine, 1.2mmol trimethyl silicanes ethyl-acetylene,
1.2mmol DIPEA, 1.2mmol cuprous iodides and 1.2mmol NCS are mixed 12 hours under room temperature, and reaction process is used
TLC is monitored.It is extracted with ethyl acetate, is cleaned after organic phase through the pure of the isolated target product of silica gel column chromatography after reaction
Product, yield 79%, product are viscous fluid.1H NMR(400MHz,CDCl3) δ 7.24-6.95 (m, 4H), 5.32 (t, J=
7.9Hz,1H),3.82–3.67(m,4H),0.40-0.20(m,6H).13C NMR(101MHz,CDCl3)δ167.4,135.2,
128.9,128.8,128.7,127.4,121.0,64.9,53.4,37.1,29.5.HRMS(ESI)m/z calculate for
(M+H+)C15H21IN3O2Si+:430.0442,Found:430.0446。
Embodiment 5
In 10ml round-bottomed flasks, 1mmol 1- benzyls -4-TMS-5-I-1,2,3- triazoles, 1.2mmol are sequentially added
Phenol, 0.1mmol cuprous iodides, 0.2mmol 2- oxocyclohex alkane Ethyl formates and 2mmol cesium carbonates are in 70 DEG C of mixings
24 hours, reaction process was monitored with TLC.It is extracted with ethyl acetate, is cleaned after organic phase through silica gel column chromatography point after reaction
From the sterling of target product, yield 85% is obtained, product is white solid, 38-40 DEG C of fusing point.1H NMR(CDCl3,
400MHz) δ 7.39-7.30 (m, 7H), 7.21 (t, J=7.4Hz, 1H), 7.14 (s, 1H), 7.05-6.99 (m, 2H), 5.46
(s,2H).13C NMR(CDCl3,101MHz):δ155.6,149.6,134.6,130.10,128.9,128.4,128.0,
125.3,118.3,117.7,77.3,77.0,76.7,50.5.HRMS(ESI)m/z calculate for(M+H+)C15H14N3O+:252.1131,Found:252.1139。
Embodiment 6
In 10ml round-bottomed flasks, 1mmol 1- benzyls -4-TMS-5-I-1,2,3- triazoles, 1.2mmol are sequentially added
Benzenethiol, 0.1mmol cuprous iodides, 0.2mmol 2- oxocyclohex alkane Ethyl formates and 2mmol cesium carbonates are stirred in 70 DEG C of mixing
It mixes 24 hours, reaction process is monitored with TLC.After waiting for consumption of raw materials, 2mmol Anhydrous potassium carbonates are added, 40 DEG C of stirrings 6 are small
When.It is extracted with ethyl acetate after stopping reaction, cleans the sterling through the isolated target product of silica gel column chromatography after organic phase, production
Rate is 90%, and product is thick liquid.1H NMR(400MHz,CDCl3)δ7.83(s,1H),7.25-7.14(m,7H),7.05-
6.97(m,2H),5.53(s,2H).13C NMR(101MHz,CDCl3)δ134.4,133.0,129.4,128.7,128.3,
127.9,127.3,52.0.HRMS(ESI)m/z calculate for(M+H+)C15H14N3S+:268.0903,Found:
268.0911。
Embodiment 7
In 10ml round-bottomed flasks, 1mmol 1- benzyls -4-TMS-5-I-1,2,3- triazoles, 1.2mmol are sequentially added
Phenyl boric acid, the bi triphenyl phosphine composition of 0.05mmol palladium bichlorides and 2mmol cesium carbonates are mixed 24 hours in 50 DEG C, reaction
Process is monitored with TLC.After waiting for consumption of raw materials, tetrabutyl ammonium fluoride is added, is stirred at room temperature 6 hours.Second is used after reaction
Acetoacetic ester extracts, and cleans the sterling through the isolated target product of silica gel column chromatography after organic phase, yield 91%, product is viscous
Thick liquid.1H NMR(400MHz,CDCl3) δ 7.75 (s, 1H), 7.42 (d, J=6.9Hz, 3H), 7.31-7.21 (m, 5H),
7.12-7.00(m,2H),5.55(s,2H).13C NMR(101MHz,CDCl3)δ7.8,7.4,7.4,7.3,7.3,7.3,7.3,
7.3,7.3,7.2,7.1,7.1,7.1,5.6.HRMS(ESI)m/z calculate for(M+H+)C15H13N3 +:235.1125,
Found:235.1119。
Embodiment 8
In 10ml round-bottomed flasks, 1mmol 1- benzyls -4-TMS-5-I-1,2,3- triazoles, 1.2mmol are sequentially added
Benzyne, the bi triphenyl phosphine composition of 0.05mmol palladium bichlorides and 2mmol cesium carbonates are mixed 24 hours in 50 DEG C, react
Journey is monitored with TLC.After waiting for consumption of raw materials, tetrabutyl ammonium fluoride is added, is stirred at room temperature 6 hours.Acetic acid is used after reaction
Ethyl ester extracts, and cleans the sterling through the isolated target product of silica gel column chromatography after organic phase, yield 89%, and product is sticky
Liquid.1H NMR(400MHz,CDCl3)δ7.85(s,1H),7.50-7.33(m,10H),5.65(s,2H).13C NMR
(101MHz,CDCl3)δ137.0,136.8,131.6,129.7,128.9,128.6,128.1,121.3,100.4,100.0,
52.8.HRMS(ESI)m/z calculate for(M+H+)C17H14N3 +:260.1182,Found:260.1190。
Embodiment 9
In 10ml round-bottomed flasks, 1mmol 1- benzyls -4-TMS-5-I-1,2,3- triazoles, 1.2mmol are sequentially added
Positive hexin, the bi triphenyl phosphine composition of 0.05mmol palladium bichlorides and 2mmol cesium carbonates are mixed 24 hours in 50 DEG C, reaction
Process is monitored with TLC.After waiting for consumption of raw materials, tetrabutyl ammonium fluoride is added, is stirred at room temperature 6 hours.Second is used after reaction
Acetoacetic ester extracts, and cleans the sterling through the isolated target product of silica gel column chromatography after organic phase, yield 87%, product is viscous
Thick liquid.1H NMR(400MHz,CDCl3)δ7.85(s,1H),7.50-7.33(m,10H),5.65(s,2H).13C NMR
(101MHz,CDCl3)δ137.0,136.8,131.6,129.7,128.9,128.6,128.1,121.3,100.4,100.0,
52.8.HRMS(ESI)m/z calculate for(M+H+)C17H14N3 +:260.1182,Found:260.1190。
Embodiment 10
In 10ml round-bottomed flasks, 1mmol 1- benzyls -5-I-1 are sequentially added, 2,3- triazoles, 1.2mmol are to methyl
Phenol, the cuprous iodide of 0.1mmol, 0.2mmol 2- oxocyclohex alkane Ethyl formates and 2mmol cesium carbonates are stirred in 70 DEG C of mixing
It mixes 24 hours, reaction process is monitored with TLC.It is extracted with ethyl acetate, is cleaned after organic phase through silica gel column chromatography after reaction
The sterling of isolated target product, yield 82%, product are white solid.53-55 DEG C of of fusing point1H NMR(CDCl3,
400MHz) δ 7.34 (s, 5H), 7.15 (d, J=8.3Hz, 2H), 7.07 (s, 1H), 6.92 (d, J=8.4Hz, 2H), 5.45
(s,2H),2.35(s,3H).13C NMR(CDCl3,101MHz)δ153.5,149.9,135.1,130.5,128.8,128.3,
128.0,117.7,77.3,77.0,76.7,50.4,20.7.HRMS(ESI)m/z calculate for(M+H+)C16H16N3O+:266.1288,Found:266.1293。
Embodiment 11
In 10ml round-bottomed flasks, 1mmol 1- benzyls -5-I-1 are sequentially added, 2,3- triazoles, 1.2mmol are to methyl
Benzenethiol, 0.1mmol cuprous iodides, 0.2mmol 2- oxocyclohex alkane Ethyl formates and 2mmol cesium carbonates are stirred in 70 DEG C of mixing
It mixes 24 hours, reaction process is monitored with TLC.It is extracted with ethyl acetate, is cleaned after organic phase through silica gel column chromatography after reaction
The sterling of isolated target product, yield 91%.Product is thick liquid.1H NMR(400MHz,CDCl3)δ7.76(s,
1H),7.26-6.93(m,8H),5.51(s,2H),2.29(s,3H).13C NMR(101MHz,CDCl3)δ139.3,137.8,
134.6,130.2,129.2,128.7,128.2,127.9,51.9,29.5 20.99.HRMS(ESI)m/z calculate
for(M+H+)C16H16N3S+:282.1059,Found:282.1058。
Embodiment 12
In 10ml round-bottomed flasks, 1mmol 1- benzyls -5-I-1 are sequentially added, 2,3- triazoles, 1.2mmol are to methyl
Phenyl boric acid, the bi triphenyl phosphine composition of 0.05mmol palladium bichlorides and 2mmol cesium carbonates are mixed 24 hours in 50 DEG C, reaction
Process is monitored with TLC.It is extracted with ethyl acetate, is produced through the isolated target of silica gel column chromatography after cleaning organic phase after reaction
The sterling of object, yield 88%.Product is thick liquid.1H NMR(400MHz,CDCl3)δ7.73(s,1H),7.37-6.99
(m,9H),5.55(s,2H),2.41(s,3H).13C NMR(101MHz,CDCl3)δ139.7,138.2,135.7,133.2,
129.7,128.8,128.1,127.1,123.9,77.4,77.1,76.7,51.7,21.3.HRMS(ESI)m/z calculate
for(M+H+)C16H16N3 +:250.1339,Found:250.1342。
Embodiment 13
In 10ml round-bottomed flasks, 1mmol 1- benzyls -5-I-1 are sequentially added, 2,3- triazoles, 1.2mmol are to fluorobenzene
Alkynes, the bi triphenyl phosphine composition of 0.05mmol palladium bichlorides and 2mmol cesium carbonates are mixed 24 hours in 50 DEG C, reaction process
It is monitored with TLC.It is extracted with ethyl acetate, is cleaned after organic phase through the isolated target product of silica gel column chromatography after reaction
Sterling, yield 87%, product are thick liquid.1H NMR(400MHz,CDCl3)δ7.84(s,1H),7.47-7.41(m,
2H), 7.34 (s, 5H), 7.08 (t, J=8.4Hz, 2H), 5.64 (s, 2H)13C NMR(101MHz,CDCl3)δ136.9,
135.2,134.6,133.7,133.6,128.9,128.6,128.0,121.1,116.2,116.0,99.4,52.8.HRMS
(ESI)m/z calculate for(M+H+)C17H12FN3 +:278.1088,Found:278.1078。
Embodiment 14
In 10ml round-bottomed flasks, sequentially add the positive hexin of 1mmol 1- benzyls -5-I-1,2,3- triazoles, 1.2mmol,
The bi triphenyl phosphine composition and 2mmol cesium carbonates of 0.05mmol palladium bichlorides are mixed 24 hours in 50 DEG C, and reaction process is used
TLC is monitored.It is extracted with ethyl acetate, is cleaned after organic phase through the pure of the isolated target product of silica gel column chromatography after reaction
Product, yield 91%, product are thick liquid.1H NMR(400MHz,CDCl3)δ7.85(s,1H),7.50-7.33(m,10H),
5.65(s,2H).13C NMR(101MHz,CDCl3)δ137.0,136.8,131.6,129.7,128.9,128.6,128.1,
121.3,100.4,100.0,52.8.HRMS(ESI)m/z calculate for(M+H+)C17H14N3 +:260.1182,
Found:260.1190。
It is the specific implementation mode by applying example forms below, the above of the present invention is further described,
But the range that this should not be interpreted as to the above-mentioned theme of the present invention is only limitted to the above embodiments, all to be based on the above of the present invention
The technology of realization all belongs to the scope of the present invention.
Claims (6)
1.1- alkyl -5- arylthios -1,2, the synthetic method of 3- triazole compounds, it is characterised in that building-up process is：With
1- benzyl -4-TMS-5-I-1,2,3- 3-triazole compounds and benzenethiol are raw material, acetonitrile is solvent, cuprous iodide or protobromide
Copper is catalyst, 2- oxocyclohex alkane Ethyl formates are ligand and cesium carbonate is accelerating agent, and 1- benzyls -5- is made in 70 DEG C of reactions
Thiophenyl -1,2,3- 3-triazole compounds；
The building-up process of the 1- benzyls -4-TMS-5-I-1,2,3- 3-triazole compounds is：It sequentially adds in the reaction vessel
Solvent acetonitrile, raw material benzyl azide and trimethyl silicane ethyl-acetylene, alkali N- diisopropyl ethyl amines, catalyst cuprous iodide and oxidation
Agent N- chloro butyryl diimines, reaction vessel is placed under room temperature and is stirred to react, and entire reaction process is examined with thin-layer chromatography TLC
It surveys, is extracted with ethyl acetate after reaction, pillar layer separation obtains sterling 1- benzyls -4-TMS-5-I- after organic phase is cleaned
1,2,3- 3-triazole compounds, the 1- benzyls -4-TMS-5-I-1, the structural formula of 2,3- 3-triazole compounds are
Wherein R is benzyl.
2. 1- alkyl -5- arylthios -1,2 according to claim 1, the synthetic method of 3- triazole compounds is special
Sign is：1- benzyl -4TMS-5-I-1,2 in the building-up process of the 1- benzyls -5- thiophenyl -1,2,3- 3-triazole compounds,
3- 3-triazole compounds, benzenethiol, catalyst, 2- oxocyclohex alkane Ethyl formates and cesium carbonate molar ratio be 1:1.2:
0.1:0.2:2。
3. 1- alkyl -5- arylthios -1,2 according to claim 1, the synthetic method of 3- triazole compounds is special
Sign is：Benzyl azide and trimethyl silicane in the building-up process of the 1- benzyls -4-TMS-5-I-1,2,3- 3-triazole compounds
The molar ratio of ethyl-acetylene is 1:1.2, catalyst cuprous iodide, oxidant N- chloro butyryl diimines and alkali N- diisopropyls
The dosage of ethylamine is respectively 1.2 times of benzyl azide mole.
4.1- alkyl -5- arylthios -1,2, the synthetic method of 3- triazole compounds, it is characterised in that building-up process is：With
1- benzyl -5-I-1,2,3- 3-triazole compounds and be raw material to methylbenzene phenyl-sulfhydrate, acetonitrile is solvent, cuprous iodide or protobromide
Copper is catalyst, 2- oxocyclohex alkane Ethyl formates are ligand and cesium carbonate is accelerating agent, and 1- benzyls -5- is made in 70 DEG C of reactions
To methylphenyl-sulfanyl -1,2,3- 3-triazole compounds；
The building-up process of the 1- benzyls -5-I-1,2,3- 3-triazole compounds is：With 1- benzyls -4-TMS-5-I-1,2,3- three
Nitrogen azole compounds are raw material, methanol is solvent and potassium carbonate is deprotection agent, in 40 DEG C of selectivity deprotection 1- benzyls-obtained
5-I-1,2,3- 3-triazole compounds, the 1- benzyls -5-I-1, the structural formula of 2,3- 3-triazole compounds areWherein
R is benzyl；
The building-up process of the 1- benzyls -4-TMS-5-I-1,2,3- 3-triazole compounds is：It sequentially adds in the reaction vessel
Solvent acetonitrile, raw material benzyl azide and trimethyl silicane ethyl-acetylene, alkali N- diisopropyl ethyl amines, catalyst cuprous iodide and oxidation
Agent N- chloro butyryl diimines, reaction vessel is placed under room temperature and is stirred to react, and entire reaction process is examined with thin-layer chromatography TLC
It surveys, is extracted with ethyl acetate after reaction, pillar layer separation obtains sterling 1- benzyls -4-TMS-5-I- after organic phase is cleaned
1,2,3- 3-triazole compounds, the 1- benzyls -4-TMS-5-I-1, the structural formula of 2,3- 3-triazole compounds are
Wherein R is benzyl.
5. 1- alkyl -5- arylthios -1,2 according to claim 4, the synthetic method of 3- triazole compounds is special
Sign is：1- benzyl-the 5- to 1- benzyl -5-I-1 in the building-up process of methylphenyl-sulfanyl -1,2,3- 3-triazole compounds,
2,3- 3-triazole compounds, to the molar ratio of methylbenzene phenyl-sulfhydrate, catalyst, 2- oxocyclohex alkane Ethyl formate and cesium carbonate
It is 1:1.2:0.1:0.2:2.
6. 1- alkyl -5- arylthios -1,2 according to claim 4, the synthetic method of 3- triazole compounds is special
Sign is：Benzyl azide and trimethyl silicane in the building-up process of the 1- benzyls -4-TMS-5-I-1,2,3- 3-triazole compounds
The molar ratio of ethyl-acetylene is 1:1.2, catalyst cuprous iodide, oxidant N- chloro butyryl diimines and alkali N- diisopropyls
The dosage of ethylamine is respectively 1.2 times of benzyl azide mole.
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| CN106966994A (en) * | 2017-03-15 | 2017-07-21 | 大连理工大学 | A kind of triazole of N sulfonyls 1,2,3 of new 4 allyl acetic acid ester group substitution and preparation method thereof |
| CN109053603A (en) * | 2018-05-29 | 2018-12-21 | 河南师范大学 | A method of multicomponent synthesizes 5-I-1,2,3- triazole compound in aqueous solution |
| CN109134881B (en) * | 2018-09-18 | 2021-01-26 | 中原工学院 | Preparation method and application of copper complex-based heterogeneous catalytic material |
| CN109503502B (en) * | 2018-12-29 | 2020-05-05 | 山东师范大学 | Preparation method of N-vinyl-1, 2, 3-triazole compound |
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