CN109096211A - A kind of preparation method of polysubstituted triazole derivatives - Google Patents
A kind of preparation method of polysubstituted triazole derivatives Download PDFInfo
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- CN109096211A CN109096211A CN201811002396.8A CN201811002396A CN109096211A CN 109096211 A CN109096211 A CN 109096211A CN 201811002396 A CN201811002396 A CN 201811002396A CN 109096211 A CN109096211 A CN 109096211A
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- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
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- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
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Abstract
The present invention discloses a kind of preparation method of polysubstituted triazole derivatives, the following steps are included: methacrylaldehyde or Propenal derivative, corresponding azido compound or azido derivant, strong acid and solvent are placed in reaction vessel, in 0 DEG C or less 30~120min of reaction, the triethylamine that 2 to 3 times of acid equivalents are added after the reaction was completed terminates reaction；It is extracted after the reaction solution that reaction generates is diluted with the methylene chloride equal to 5~10 times of reaction solution volume, obtains organic phase；By resulting organic phase through washing, drying, concentration and column chromatographic purifying, the polysubstituted triazole derivatives are obtained.A kind of preparation method of polysubstituted triazole derivatives of the present invention, the triazole derivatives with a variety of substituent groups that conventional method is difficult to obtain can be synthesized, the cost of strong acid used is low, has substrate spectrum wide, the advantages of reaction time is short, post-processing simplicity and product yield high.
Description
Technical field
The present invention relates to technical field of organic synthesis, and in particular to be a kind of polysubstituted triazole derivatives preparation
Method.
Background technique
Triazole derivatives are a kind of important nitrogen-containing heterocycle compounds, have extensive pharmaceutical activity, anti-malarial,
Important application value is all had in anti-inflammatory, antitumor and antiepileptic.Therefore, 3-triazole compounds and its derivative
Novel synthesis research have important applying value, the concern by related fields researcher.
The synthetic method of traditional triazole derivatives is usually using terminal alkyne class compound as starting material, with nitrine
Compound or derivatives thereof occurs the reaction of 1,3- ring dipolar addition and carrys out synthesizing triazazole derivative.But traditional synthetic method
There are many limitations, for example reaction temperature height, poor selectivity, processing step are tediously long and yield is more low.
Summary of the invention
The purpose of the present invention is to provide a kind of preparation methods of polysubstituted triazole derivatives, can synthesize tradition side
The triazole derivatives with a variety of substituent groups that method is difficult to obtain, the cost of used catalyst is low, has substrate spectrum wide,
The advantages of reaction time is short, post-processing simplicity and product yield high.
In order to achieve the above objectives, solution of the invention is:
A kind of preparation method of polysubstituted triazole derivatives, comprising the following steps:
Step 1, by methacrylaldehyde or Propenal derivative, corresponding azido compound or azido derivant, strong acid and solvent
It is placed in reaction vessel, in 0 DEG C or less 30~120min of reaction, triethylamine is added after the reaction was completed and terminates reaction；
Step 2 after diluting the reaction solution that step 1 reaction generates with methylene chloride, extracts to obtain organic phase；
Step 3, by the resulting organic phase of step 2 through washing, drying, concentration and column chromatographic purifying, obtain described polysubstituted
Triazole derivatives；
In step 1, methacrylaldehyde or Propenal derivative, corresponding azido compound or azido derivant and strong acid rub
You than being 1:1.2:1~1:2:1.2, the molar ratio of strong acid and triethylamine be 1:2~1:3, methacrylaldehyde or Propenal derivative and
The molal volume ratio of solvent is 1:3~1:5；
In step 2, the volume of the methylene chloride of addition is 5~10 times of the reaction solution volume.
In step 1, the strong acid is trifluoromethanesulfonic acid, double trifluoromethanesulfonimides or boron trifluoride ether.
In step 1, the solvent is methylene chloride, acetonitrile or 1,2- dichloroethanes.
In step 1, the structural formula of the Propenal derivative is as shown in formula I:
Wherein, R1For hydrogen, alkyl, aryl, substituted aryl, amino or alkoxy；
R2For hydrogen, halogen, alkyl, aryl, substituted aryl, amino, nitro or alkoxy；
R4For halogen；
The structural formula of corresponding azido compound or azido derivant is as shown in formula II:
Wherein, R3For hydrogen, halogen, alkyl, aryl, substituted aryl, amino, nitro, ester group or alkoxy.
The structural formula of the polysubstituted triazole derivatives is as shown in formula III:
Wherein, R1For hydrogen, alkyl, aryl, substituted aryl, amino or alkoxy；
R2For hydrogen, halogen, alkyl, aryl, substituted aryl, amino, nitro or alkoxy；
R3For hydrogen, halogen, alkyl, aryl, substituted aryl, amino, nitro, ester group or alkoxy.
Further, R1For hydrogen, methylamino；
R2For hydrogen, ethyl, phenyl, chlorphenyl or methoxyphenyl；
R3For benzyl, phenethyl, different phenethyl, propylene phenyl, aminomethyl phenyl, difluorobenzyl, two trifluoromethylbenzenes
Methyl, nitrobenzene methyl, menaphthyl, butyl, octyl, cyclopenta, cyclohexyl.
The synthetic route of preparation method of the present invention is as follows:
After adopting the above technical scheme, a kind of preparation method of polysubstituted triazole derivatives of the present invention, can synthesize biography
The cost of the triazole derivatives with a variety of substituent groups that system method is difficult to obtain, strong acid (as catalyst) used is low, tool
Have that substrate spectrum is wide, the reaction time is short (most short needs 30min), and post-processing is easy (to be chromatographed through conventional drying, concentration and column
Purifying) and the advantages of product yield high (up to 98%).
Specific embodiment
In order to further explain the technical solution of the present invention, to carry out the present invention below by specific embodiment detailed
It illustrates.
Embodiment 1
The preparation (structural formula is as follows) of 1- (2,6- difluorobenzyl) -1H-1,2,3- triazole -4- formamide:
By 2- bromopropene amide 0.27mmol, 2,6- difluorobenzyl azido compound, 0.32 mmol, trifluoromethanesulfonic acid
0.27mmol, acetonitrile 1mL are added in the reaction tube of 20mL, are placed in -40 DEG C of low temperature bath, react 2h；0.55mmol tri- is added
Ethamine stops reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, organic phase is taken, so
Three times (9mL methylene chloride is added) in extraction every time, and obtained organic phase is washed with water once, then passes through anhydrous Na2SO4It is dry
It is dry, it filters, concentration, column chromatographic purifying obtains 57mg target product, yield 85%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,DMSO)δ8.56(s, 1H),7.88(s,1H),
7.55 (m, 2H), 7.15 (t, 2H, J=8.0Hz), 5.72 (s, 2H)；13C NMR(126MHz,DMSO)δ162.4,161.7,
159.9,143.2,132.2,127.2, 112.4,112.2,111.4,41.5。
Embodiment 2
The preparation (structural formula is as follows) of 1- phenethyl -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromopropene aldehyde 0.27mmol, phenethyl azido compound 0.32mmol, trifluoromethanesulfonic acid 0.27mmol, two
Chloromethanes 1mL is added in the reaction tube of 20mL, is placed in -40 DEG C of low temperature bath, reacts 30min；0.55mmol triethylamine is added
Stop reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, organic phase is taken, is so extracted
(9mL methylene chloride is added every time) three times, obtained organic phase is washed with water once, then passes through anhydrous Na2SO4It is dry,
Filtering, concentration, column chromatographic purifying obtain 53mg target product, yield 97%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.08(s, 1H),7.85(s,1H),
7.35-7.20 (m, 3H), 7.11-7.03 (m, 2H), 4.68 (t, J=7.1Hz, 2H), 3.25 (t, J=7.1Hz, 2H)；13C
NMR(126MHz,CDCl3)δ 185.0,147.4,136.3,129.0,128.6,127.4,125.7,52.1,36.4。
Embodiment 3
The preparation (structural formula is as follows) of 1- butyl -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromopropene aldehyde 0.27mmol, normal-butyl azido compound 0.32mmol, trifluoromethanesulfonic acid 0.27mmol, two
Chloromethanes 1mL is added in the reaction tube of 20mL, is placed in -40 DEG C of low temperature bath, reacts 30min；0.55mmol triethylamine is added
Stop reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, organic phase is taken, is so extracted
(9mL methylene chloride is added every time) three times, obtained organic phase is washed with water once, then passes through anhydrous Na2SO4It is dry,
Filtering, concentration, column chromatographic purifying obtain 38mg target product, yield 90%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.13(s, 1H),8.13(s,1H),
4.44 (t, J=7.2Hz, 2H), 1.97-1.89 (m, 2H), 1.42-1.32 (m, 2H), 0.97 (t, J=7.4Hz, 3H)；13C
NMR(126MHz,CDCl3)δ 185.3,147.8,125.1,50.6,32.1,19.7,13.4。
Embodiment 4
The preparation (structural formula is as follows) of 1- octyl -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromopropene aldehyde 0.27mmol, n-octyl azido compound 0.32mmol, trifluoromethanesulfonic acid 0.27mmol, two
Chloromethanes 1mL is added in the reaction tube of 20mL, is placed in -40 DEG C of low temperature bath, reacts 30min；0.55mmol triethylamine is added
Stop reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, organic phase is taken, is so extracted
(9mL methylene chloride is added every time) three times, obtained organic phase is washed with water once, then passes through anhydrous Na2SO4It is dry,
Filtering, concentration, column chromatographic purifying obtain 48mg target product, yield 85%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.14(s, 1H),8.16(s,1H),
4.45 (t, J=7.2Hz, 2H), 1.96 (t, J=7.3Hz, 2H), 1.38-1.15 (m, 10H), 0.87 (t, J=6.8Hz,
3H)；13C NMR(126MHz,CDCl3)δ 185.2,147.8,125.2,50.9,31.7,30.1,29.0,28.9,26.4,
22.6,14.1。
Embodiment 5
The preparation (structural formula is as follows) of 1- cyclopenta -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromopropene aldehyde 0.27mmol, cyclopenta azido compound 0.32mmol, trifluoromethanesulfonic acid 0.27mmol, two
Chloromethanes 1mL is added in the reaction tube of 20mL, is placed in -40 DEG C of low temperature bath, reacts 30min；0.55mmol triethylamine is added
Stop reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, organic phase is taken, is so extracted
(9mL methylene chloride is added every time) three times, obtained organic phase is washed with water once, then passes through anhydrous Na2SO4It is dry,
Filtering, concentration, column chromatographic purifying obtain 41mg target product, yield 92%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.14(s, 1H),8.16(s,1H),
5.02 (ddd, J=13.7,7.5,6.0Hz, 1H), 2.33 (dtdd, J=14.6,7.5,5.7,1.7Hz, 2H), 2.13-2.03
(m,2H),1.99–1.88(m,2H),1.87 –1.75(m,2H)；13C NMR(126MHz,CDCl3)δ185.3,147.6,
123.9,62.5, 33.5,24.0。
Embodiment 6
The preparation (structural formula is as follows) of 1- cyclohexyl -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromopropene aldehyde 0.27mmol, cyclohexyl azido compound 0.32mmol, trifluoromethanesulfonic acid 0.27mmol, two
Chloromethanes 1mL is added in the reaction tube of 20mL, is placed in -40 DEG C of low temperature bath, reacts 60min；0.55mmol triethylamine is added
Stop reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, organic phase is taken, is so extracted
(9mL methylene chloride is added every time) three times, obtained organic phase is washed with water once, then passes through anhydrous Na2SO4It is dry,
Filtering, concentration, column chromatographic purifying obtain 48mg target product, yield 99%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.14(s, 1H),8.17(s,1H),
4.54 (tt, J=11.7,3.9Hz, 1H), 2.33-2.19 (m, 2H), 1.96 (dt, J=14.3,3.6Hz, 2H), 1.84-
1.73 (m, 3H), 1.50 (dtt, J=13.7,12.7,3.5Hz, 2H), 1.38-1.24 (m, 1H)；13C NMR(126MHz,
CDCl3)δ 185.3,147.5,123.2,60.7,33.4,25.0,25.0。
Embodiment 7
The preparation (structural formula is as follows) of 1- benzyl -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromopropene aldehyde 0.27mmol, benzyl azido compound 0.32mmol, trifluoromethanesulfonic acid 0.27mmol, two
Chloromethanes 1mL is added in the reaction tube of 20mL, is placed in -40 DEG C of low temperature bath, reacts 30min；0.55mmol triethylamine is added
Stop reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, organic phase is taken, is so extracted
(9mL methylene chloride is added every time) three times, obtained organic phase is washed with water once, then passes through anhydrous Na2SO4It is dry,
Filtering, concentration, column chromatographic purifying obtain 43mg target product, yield 85%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.10(s, 1H),8.05(s,1H),
7.44–7.36(m,3H),7.34–7.29(m,2H),5.60(s,2H)；13C NMR(126MHz,CDCl3)δ185.0,148.0,
133.5,129.4,129.3,128.4, 125.3,54.6。
Embodiment 8
The preparation (structural formula is as follows) of the different phenethyl -1H-1,2,3- triazole -4- formaldehyde of 1-:
By 2- bromopropene aldehyde 0.27mmol, different phenethyl azido compound 0.32mmol, trifluoromethanesulfonic acid 0.27mmol,
Methylene chloride 1mL is added in the reaction tube of 20mL, is placed in -40 DEG C of low temperature bath, reacts 30min；Tri- second of 0.55mmol is added
Amine stops reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, organic phase is taken, is so extracted
It takes and (9mL methylene chloride is added every time) three times, obtained organic phase is washed with water once, then pass through anhydrous Na2SO4It is dry
It is dry, it filters, concentration, column chromatographic purifying obtains 44mg target product, yield 81%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.12(s, 1H),8.00(s,1H),
7.43-7.35 (m, 3H), 7.33-7.28 (m, 2H), 5.88 (q, J=7.1Hz, 1H), 2.03 (d, J=7.1Hz, 3H)；13C
NMR(126MHz,CDCl3)δ 185.3,147.7,138.7,129.4,129.2,126.8,124.2,61.1,21.3。
Embodiment 9
The preparation (structural formula is as follows) of 1- propylene phenyl -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromopropene aldehyde 0.27mmol, propylene aziminobenzene compound 0.32mmol, trifluoromethanesulfonic acid 0.27mmol,
Methylene chloride 1mL is added in the reaction tube of 20mL, is placed in -40 DEG C of low temperature bath, reacts 30min；Tri- second of 0.55mmol is added
Amine stops reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, organic phase is taken, is so extracted
It takes and (9mL methylene chloride is added every time) three times, obtained organic phase is washed with water once, then pass through anhydrous Na2SO4It is dry
It is dry, it filters, concentration, column chromatographic purifying obtains 51mg target product, yield 89%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.14(s, 1H),8.20(s,1H),
7.43-7.25 (m, 5H), 6.73 (d, J=15.7,1.3Hz, 1H), 6.34 (dt, J=15.8,6.8Hz, 1H), 5.20 (d, J
=6.8,1.4Hz, 2H)；13C NMR (126MHz,CDCl3)δ185.0,148.0,133.3,133.2,130.8,129.5,
128.0, 128.0,127.9,127.1,127.0,125.4,125.3,54.8。
Embodiment 10
The preparation (structural formula is as follows) of 1- (4- methylbenzyl) -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromopropene aldehyde 0.27mmol, 4- methylbenzyl azido compound 0.32mmol, trifluoromethanesulfonic acid
0.27mmol, methylene chloride 1mL are added in the reaction tube of 20mL, are placed in -40 DEG C of low temperature bath, react 30min；It is added
0.55mmol triethylamine stops reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, take
Three times (9mL methylene chloride is added) in machine phase, so extraction every time, and obtained organic phase is washed with water once, is then passed through
Anhydrous Na2SO4It dries, filters, is concentrated, column chromatographic purifying obtains 53mg target product, yield 98%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.10(s, 1H),8.01(s,1H),
7.20(s,4H),5.55(s,2H),2.36(s,3H)；13C NMR(126 MHz,CDCl3)δ185.1,148.0,139.4,
130.4,130.1,128.5,125.2,54.4, 21.2。
Embodiment 11
The preparation (structural formula is as follows) of 1- (3- methylbenzyl) -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromopropene aldehyde 0.27mmol, 3- methylbenzyl azido compound 0.32mmol, trifluoromethanesulfonic acid
0.27mmol, methylene chloride 1mL are added in the reaction tube of 10mL, are placed in -40 DEG C of low temperature bath, react 30min；It is added
0.55mmol triethylamine stops reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, take
Three times (9mL methylene chloride is added) in machine phase, so extraction every time, and obtained organic phase is washed with water once, is then passed through
Anhydrous Na2SO4It dries, filters, is concentrated, column chromatographic purifying obtains 51mg target product, yield 94%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.10(s, 1H),8.04(s,1H),
7.31-7.28 (m, 1H), 7.20 (d, J=7.7Hz, 1H), 7.11 (d, J=8.0Hz, 2H), 5.55 (s, 2H), 2.35 (s,
3H)；13C NMR(126MHz,CDCl3)δ 185.1,148.0,139.3,133.4,130.1,129.3,129.1,125.5,
125.3,54.6,21.3。
Embodiment 12
The preparation (structural formula is as follows) of 1- (2- methylbenzyl) -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromopropene aldehyde 0.27mmol, 2- methylbenzyl azido compound 0.32mmol, trifluoromethanesulfonic acid
0.27mmol, methylene chloride 1mL are added in the reaction tube of 20mL, are placed in -40 DEG C of low temperature bath, react 30min；It is added
0.55mmol triethylamine stops reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, take
Three times (9mL methylene chloride is added) in machine phase, so extraction every time, and obtained organic phase is washed with water once, is then passed through
Anhydrous Na2SO4It dries, filters, is concentrated, column chromatographic purifying obtains 50mg target product, yield 92%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.10(s, 1H),7.89(s,1H),
7.40–7.12(m,4H),5.60(s,2H),2.28(s,3H)；13C NMR(126MHz,CDCl3)δ185.0,147.8,137.0,
131.3,131.3,129.8, 129.7,126.9,125.0,52.7,18.9。
Embodiment 13
The preparation (structural formula is as follows) of 1- (bis- trifluoromethylbenzel of 3,5-) -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromopropene aldehyde 0.27mmol, 3,5- bis- trifluoromethylbenzel azido compound, 0.32 mmol, trifluoro methylsulphur
Sour 0.27mmol, methylene chloride 1mL are added in the reaction tube of 20mL, are placed in -40 DEG C of low temperature bath, react 30min；It is added
0.55mmol triethylamine stops reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, extraction is taken
Three times (9mL methylene chloride is added) in organic phase, so extraction every time, and obtained organic phase is washed with water once, is then passed through
Anhydrous Na2SO4It dries, filters, is concentrated, column chromatographic purifying obtains 70mg target product, yield 80%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.15(s, 1H),8.24(s,1H),
7.92(s,1H),7.81(s,2H),5.77(s,2H)；13C NMR(126 MHz,CDCl3)δ185.0,148.4,136.2,
133.4,133.1,132.9,132.6,128.5, 128.5,125.6,123.9,123.5,123.5,123.4,123.4,
123.4,121.8,53.5,29.8。
Embodiment 14
The preparation (structural formula is as follows) of 1- (4- nitrobenzene methyl) -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromopropene aldehyde 0.27mmol, 4- nitrobenzene methyl azide 0.32mmol, trifluoromethanesulfonic acid
0.27mmol, methylene chloride 1mL are added in the reaction tube of 20mL, are placed in -40 DEG C of low temperature bath, react 30min；It is added
0.55mmol triethylamine stops reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, take
Three times (9mL methylene chloride is added) in machine phase, so extraction every time, and obtained organic phase is washed with water once, is then passed through
Anhydrous Na2SO4It dries, filters, is concentrated, column chromatographic purifying obtains 50mg target product, yield 80%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3) δ 10.15 (s, 1H), 8.26 (d, J=
8.7Hz, 2H), 8.15 (s, 1H), 7.48 (d, J=8.7Hz, 2H), 5.74 (s, 2H)；13C NMR(126MHz,CDCl3)δ
184.9,148.5,148.4,140.5,129.1, 125.5,124.6,53.6。
Embodiment 15
The preparation (structural formula is as follows) of 1- (2- menaphthyl) -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromopropene aldehyde 0.27mmol, 2- menaphthyl azido compound 0.32mmol, trifluoromethanesulfonic acid 0.27mmol,
Methylene chloride 1mL is added in the reaction tube of 20mL, is placed in -40 DEG C of low temperature bath, reacts 30min；Tri- second of 0.55mmol is added
Amine stops reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, organic phase is taken, is so extracted
It takes and (9mL methylene chloride is added every time) three times, obtained organic phase is washed with water once, then pass through anhydrous Na2SO4It is dry
It is dry, it filters, concentration, column chromatographic purifying obtains 63mg target product, yield 98%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.10(s, 1H),8.05(s,1H),
7.87–7.79(m,3H),7.77(s,1H),7.55–7.49(m,2H), 7.36–7.31(m,1H),5.71(s,2H)；13C NMR
(126MHz,CDCl3)δ185.0, 148.0,133.3,133.2,130.8,129.5,128.0,127.9,127.9,127.1,
127.0, 125.4,125.3,54.8。
Embodiment 16
The preparation (structural formula is as follows) of 1- (1- menaphthyl) -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromopropene aldehyde 0.27mmol, 1- menaphthyl azido compound 0.32mmol, trifluoromethanesulfonic acid 0.27mmol,
Methylene chloride 1mL is added in the reaction tube of 20mL, is placed in -40 DEG C of low temperature bath, reacts 30min；Tri- second of 0.55mmol is added
Amine stops reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, organic phase is taken, is so extracted
It takes and (9mL methylene chloride is added every time) three times, obtained organic phase is washed with water once, then pass through anhydrous Na2SO4It is dry
It is dry, it filters, concentration, column chromatographic purifying obtains 61mg target product, yield 95%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.04(s, 1H),7.96–7.85(m,
3H),7.84(s,1H),7.56–7.45(m,4H),6.01(s,2H)；13C NMR(126MHz,CDCl3)δ185.0,147.9,
134.1,131.0,130.7,129.2, 128.7,128.5,127.7,126.7,125.5,125.3,122.5,52.6。
Embodiment 17
The preparation (structural formula is as follows) of 1- phenethyl -5- ethyl -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromine pentenals 0.27mmol, phenethyl azido compound 0.32mmol, trifluoromethanesulfonic acid 0.27mmol, two
Chloromethanes 1mL is added in the reaction tube of 20mL, is placed in -40 DEG C of low temperature bath, reacts 30min；0.55mmol triethylamine is added
Stop reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, organic phase is taken, is so extracted
(9mL methylene chloride is added every time) three times, obtained organic phase is washed with water once, then passes through anhydrous Na2SO4It is dry,
Filtering, concentration, column chromatographic purifying obtain 59mg target product, yield 95%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.16(s, 1H),7.33–7.17(m,
3H), 7.09-6.97 (m, 2H), 4.49 (t, J=7.1Hz, 2H), 3.27 (t, J=7.1Hz, 2H), 2.66 (q, J=7.6Hz,
2H), 0.99 (t, J=7.6Hz, 3H)；13C NMR(126MHz,CDCl3)δ186.04,143.14,142.78,136.67,
128.93, 128.68,127.31,77.16,48.97,36.52,16.23,12.51。
Embodiment 18
The preparation (structural formula is as follows) of 1- phenethyl -5- phenyl -1H-1,2,3- triazole -4- formaldehyde:
By 2- bromocinnamaldehyde 0.27mmol, phenethyl azido compound 0.32mmol, trifluoromethanesulfonic acid 0.27mmol, two
Chloromethanes 1mL is added in the reaction tube of 20mL, is placed in -40 DEG C of low temperature bath, reacts 30min；0.55mmol triethylamine is added
Stop reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, organic phase is taken, is so extracted
(9mL methylene chloride is added every time) three times, obtained organic phase is washed with water once, then passes through anhydrous Na2SO4It is dry,
Filtering, concentration, column chromatographic purifying obtain 73mg target product, yield 97%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.04(s, 1H),7.52–7.46(m,
1H),7.45–7.39(m,2H),7.23–7.16(m,3H),7.02 –6.96(m,2H),6.91–6.85(m,2H),4.48(t,J
=7.1Hz, 2H), 3.19 (t, J=7.1Hz, 2H)；13C NMR(126MHz,CDCl3)δ184.37,143.27,141.02,
136.51,130.41,129.42,128.89,128.83,128.68,127.18,124.67,77.16, 49.40,36.25。
Embodiment 19
The preparation (structural formula is as follows) of 1- phenethyl -5- (4- chlorphenyl) -1H-1,2,3- triazole -4- formaldehyde:
By the bromo- 3- of 2- (4- chlorphenyl)-methacrylaldehyde 0.27mmol, 0.32 mmol of phenethyl azido compound, trifluoro methylsulphur
Sour 0.27mmol, methylene chloride 1mL are added in the reaction tube of 20mL, are placed in -40 DEG C of low temperature bath, react 30min；It is added
0.55mmol triethylamine stops reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, extraction is taken
Three times (9mL methylene chloride is added) in organic phase, so extraction every time, and obtained organic phase is washed with water once, is then passed through
Anhydrous Na2SO4It dries, filters, is concentrated, column chromatographic purifying obtains 80mg target product, yield 95%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3) δ 10.06 (s, 1H), 7.36 (d, J=
8.4Hz, 1H), 7.26-7.14 (m, 4H), 6.96-6.74 (m, 4H), 4.47 (t, J=6.8Hz, 2H), 3.21 (t, J=
6.8Hz,2H)；13C NMR(126MHz, CDCl3)δ184.6,143.3,139.7,136.8,136.4,130.8,129.2,
128.9,128.7, 127.3,123.1,49.5,36.3。
Embodiment 20
The preparation (structural formula is as follows) of 1- phenethyl -5- (4- methoxyphenyl) -1H-1,2,3- triazole -4- formaldehyde:
By the bromo- 3- of 2- (4- methoxyphenyl)-methacrylaldehyde 0.27mmol, phenethyl azido compound 0.32mmol, trifluoro
Methanesulfonic acid 0.27mmol, methylene chloride 1mL are added in the reaction tube of 20mL, are placed in -40 DEG C of low temperature bath, react 30min；
0.55mmol triethylamine is added and stops reaction, restores to room temperature.After the reaction solution of generation is diluted with 9mL methylene chloride, extraction
Organic phase is taken, three times (9mL methylene chloride is added) in so extraction every time, once, then obtained organic phase is washed with water
By anhydrous Na2SO4It dries, filters, is concentrated, column chromatographic purifying obtains 71mg target product, yield 85%.
The nuclear-magnetism of the compound is characterized as below:1H NMR(500MHz,CDCl3)δ10.06(s, 1H),7.24–7.19(m,
3H), 7.00-6.88 (m, 6H), 4.49 (t, J=7.1Hz, 2H), 3.86 (s, 3H), 3.20 (t, J=7.1Hz, 2H)；13C
NMR(126MHz,CDCl3)δ 184.7,161.2,143.3,141.0,136.7,131.0,128.9,128.8,127.3,
116.5,114.5, 55.5,49.4,36.3。
Above-described embodiment and non-limiting product form and style of the invention, the ordinary skill of any technical field
The appropriate changes or modifications that personnel do it all should be regarded as not departing from patent category of the invention.
Claims (6)
1. a kind of preparation method of polysubstituted triazole derivatives, it is characterised in that: the following steps are included:
Methacrylaldehyde or Propenal derivative, corresponding azido compound or azido derivant, strong acid and solvent are placed in by step 1
In reaction vessel, in 0 DEG C or less 30~120min of reaction, triethylamine is added after the reaction was completed and terminates reaction；
Step 2 after diluting the reaction solution that step 1 reaction generates with methylene chloride, extracts to obtain organic phase；
Step 3, by the resulting organic phase of step 2 through washing, drying, concentration and column chromatographic purifying, obtain polysubstituted three nitrogen
Zole derivatives；
In step 1, the molar ratio of methacrylaldehyde or Propenal derivative, corresponding azido compound or azido derivant and strong acid is
The molar ratio of 1:1.2:1~1:2:1.2, strong acid and triethylamine is 1:2~1:3, methacrylaldehyde or Propenal derivative and solvent
Molal volume ratio is 1:3~1:5；
In step 2, the volume of the methylene chloride of addition is 5~10 times of the reaction solution volume.
2. a kind of preparation method of polysubstituted triazole derivatives according to claim 1, it is characterised in that: in step 1,
The strong acid is trifluoromethanesulfonic acid, double trifluoromethanesulfonimides or boron trifluoride ether.
3. a kind of preparation method of polysubstituted triazole derivatives according to claim 1, it is characterised in that: in step 1,
The solvent is methylene chloride, acetonitrile or 1,2- dichloroethanes.
4. a kind of preparation method of polysubstituted triazole derivatives according to claim 1, it is characterised in that: in step 1,
The structural formula of the Propenal derivative is as shown in formula I:
Wherein, R1For hydrogen, alkyl, aryl, substituted aryl, amino or alkoxy；
R2For hydrogen, halogen, alkyl, aryl, substituted aryl, amino, nitro or alkoxy；
R4For halogen；
The structural formula of the corresponding azido compound or azido derivant is as shown in formula II:
R3-N3
Formula II
Wherein, R3For hydrogen, halogen, alkyl, aryl, substituted aryl, amino, nitro, ester group or alkoxy.
5. a kind of preparation method of polysubstituted triazole derivatives according to claim 1, it is characterised in that: be prepared
The polysubstituted triazole derivatives structural formula as shown in formula III:
Wherein, R1For hydrogen, alkyl, aryl, substituted aryl, amino or alkoxy；
R2For hydrogen, halogen, alkyl, aryl, substituted aryl, amino, nitro or alkoxy；
R3For hydrogen, halogen, alkyl, aryl, substituted aryl, amino, nitro, ester group or alkoxy.
6. a kind of preparation method of polysubstituted triazole derivatives according to claim 5, it is characterised in that: R1For hydrogen, first
Amido；
R2For hydrogen, ethyl, phenyl, chlorphenyl or methoxyphenyl；
R3For benzyl, phenethyl, different phenethyl, propylene phenyl, aminomethyl phenyl, difluorobenzyl, two trifluoromethylbenzels,
Nitrobenzene methyl, menaphthyl, butyl, octyl, cyclopenta, cyclohexyl.
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| CN111807942A (en) * | 2020-08-05 | 2020-10-23 | 厦门华厦学院 | Preparation method of polysubstituted indanone derivative |
| CN113661163A (en) * | 2019-02-28 | 2021-11-16 | 国立大学法人大阪大学 | Molecules for modifying proteins and/or peptides |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN113661163A (en) * | 2019-02-28 | 2021-11-16 | 国立大学法人大阪大学 | Molecules for modifying proteins and/or peptides |
| EP3932912A4 (en) * | 2019-02-28 | 2022-09-07 | Osaka University | Protein and/or peptide modification molecule |
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| CN111807942B (en) * | 2020-08-05 | 2022-11-18 | 厦门华厦学院 | Preparation method of polysubstituted indanone derivative |
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