CN110015999B - Synthesis method of 1,2, 3-triazole compound - Google Patents
Synthesis method of 1,2, 3-triazole compound Download PDFInfo
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- CN110015999B CN110015999B CN201910341758.4A CN201910341758A CN110015999B CN 110015999 B CN110015999 B CN 110015999B CN 201910341758 A CN201910341758 A CN 201910341758A CN 110015999 B CN110015999 B CN 110015999B
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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 invention discloses a synthesis method of a 1,2, 3-triazole compound, which comprises the following steps: under the condition that acid is used as an additive, p-toluenesulfonyl azide, an amine compound and a dicarbonyl compound react in an organic solvent to obtain the 1,2, 3-triazole compound. According to the synthesis method of the 1,2, 3-triazole compound, all the steps are carried out in one reactor, no separation step is needed in the middle, the method belongs to one-pot reaction, metal catalysis and participation are not needed, nitrogen protection or an oxygen-free environment is not needed, and reaction products are easy to purify. The method replaces the organic synthesis reaction with metal catalyst or strong base, simplifies the synthesis reaction conditions and avoids the introduction of metal ions into the product.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing a triazole compound.
Background
Triazole is an important organic compound structural unit, has strong capability of complexing metal ions and forming hydrogen bonds, is popular in the chemical field, widely exists in compounds with biological activity, has properties such as antibiosis, antivirus and antitumor, and is widely applied to the fields of agricultural chemicals and medicines. Therefore, triazole compounds become one of hot fields of drug development, and the market demand is increasing.
At present, the preparation method of the 1,2, 3-triazole compound mainly comprises the following steps: first, a copper (I) -catalyzed 1, 3-dipolar cyclization reaction, known as the Click reaction, was developed by Huisgen, Sharpless, Meldal et al, starting from a terminal alkyne and an organic azide. The method has high yield, but needs a copper catalyst, the obtained 1,2, 3-triazole has a limited structure, and the product is easily polluted by copper ions (Angew. chem., int. Ed. 1963, 2, 633; Angew. chem., int. Ed. 2002, 41, 2596; J. org. chem. 2002, 67, 3057.). (II) terminal alkyne and organic azide are used as raw materials, ruthenium is used as a catalyst to catalyze and cyclize to obtain triazole, a metal catalyst is also used, the structure type of the 1,2, 3-triazole is limited, and the product is easily polluted by metal (J. Am. chem. Soc., 2005, 127, 15998). (III) enamine and organic azide are used as raw materials, and a cyclization reaction is promoted by strong base to synthesize the 1,2, 3-triazole compound, the method avoids the use of a metal catalyst, but the condition of using the strong base is harsh, and side reactions are easy to occur, and the method limits the large-scale application (Angew. chem., int. Ed. 2013, 52, 13265).
In summary, although the prior art has many methods for synthesizing 1,2, 3-triazole compounds, the problems of participation of metal catalysts, harsh reaction conditions, poor applicability, easy pollution of products by metal ions and the like still exist. Therefore, the development of a simple and rapid synthetic method is a problem to be solved urgently.
Disclosure of Invention
In view of the above prior art, the present invention aims to provide a method for synthesizing a 1,2, 3-triazole compound, which has mild reaction conditions, no metal catalyst, and acid as an additive.
In order to achieve the purpose, the invention adopts the following technical scheme:
a method for synthesizing a 1,2, 3-triazole compound comprises the following steps:
in the presence of acid, reacting p-toluenesulfonyl azide, an amine compound and a dicarbonyl compound in an organic solvent to obtain the 1,2, 3-triazole compound;
the structures of the p-toluenesulfonyl azide, the amine compound, the dicarbonyl compound and the 1,2, 3-triazole compound are respectively shown as the following formulas (I), (II), (III) and (IV):
wherein R1 represents Me, OMe, Et, or,t-Bu, F or phenyl; r2 represents Me or Et; r3 represents Me, Et, OMe, OEt or Oi-Pr。
In the above synthesis method, the acid is preferably acetic acid. Compared with other acids (such as pivalic acid and p-toluenesulfonic acid), the acetic acid selected by the invention has better reaction activity.
In the above synthesis method, the organic reagent is preferably dichloromethane. In organic chemistry, most reactions are carried out in solvents, which play a crucial role in chemical reactions. The present invention contemplates a variety of reagents in the assay process, such as: 1, 4-dioxane, DMF, toluene, etc. it was found that when different organic solvents were used for the reaction, the final reaction yields differed greatly, with dichloromethane being the best solvent and the highest reaction yield.
In the synthesis method, the reaction temperature is 40-90 ℃, and the reaction time is 24-48 h; preferably, the reaction temperature is 90 ℃ and the reaction time is 24 h, which are key factors influencing the reaction, and the invention researches and optimizes the reaction temperature and time, and as a result, the invention discovers that when the reaction temperature is 40-90 ℃ and the reaction time is 24-48 h, the yield of the reaction product is higher, the byproducts are fewer, and the purification of the reaction product is convenient.
In the synthesis method, the equivalent ratio of the p-toluenesulfonyl azide to the amine compound to the dicarbonyl compound to the acid is (2-3): (2-3): (2-3): (1-4); the preferable equivalent ratio of the sodium azide to the amine compound to the dicarbonyl compound to the acid is as follows: 15: 12: 10: 15.
in the above synthesis method, the compound represented by the formula (ii) is preferably any one of the following compounds:
aniline, 2-methylaniline, 4-methylaniline, 2, 4-dimethylaniline, 2, 5-dimethylaniline, 2, 3-dimethylaniline, 2-methoxyaniline, 4-methoxyaniline, 3, 4-dimethoxyaniline, 2-ethylaniline, 4-tert-butylaniline, benzidine, alpha-naphthylamine, 2-methyl-4-fluoroaniline.
In the above synthesis method, the compound represented by the formula (iii) is preferably any one of the following compounds:
ethyl acetoacetate, ethyl propionylacetate, isopropyl acetoacetate, 2, 4-pentanedione, 3, 5-diheptanone.
The synthesis method further comprises the step of performing column chromatography separation on the obtained 1,2, 3-triazole compound.
The 1,2, 3-triazole compound obtained by the synthesis method has an important application in the fields of antivirus, antitumor, dye and the like because the compound has a 1,2, 3-triazole structure.
The invention has the following beneficial results:
(1) according to the synthesis method of the 1,2, 3-triazole compound, all the steps are carried out in one reactor, no separation step is needed in the middle, the method belongs to one-pot reaction, the operation is simplified, the reaction efficiency is greatly improved, the yield can reach more than 96%, and the reaction product is easy to purify.
(2) The method has the advantages of mild reaction conditions (reaction at 90 ℃), no need of metal catalyst, no need of nitrogen protection or oxygen-free environment, easily available raw materials required by the reaction and green synthetic reaction.
Drawings
FIG. 1: example 1 hydrogen profile of the prepared product; FIG. 2: example 1 carbon spectrum of the product prepared.
FIG. 3: example 2 hydrogen profile of the prepared product; FIG. 4: example 2 carbon spectrum of the product prepared.
FIG. 5: example 3 hydrogen profile of the prepared product; FIG. 6: example 3 carbon spectrum of the product prepared.
FIG. 7: example 4 hydrogen profile of the product prepared; FIG. 8: example 4 carbon spectrum of the product prepared.
FIG. 9: example 5 hydrogen profile of the prepared product; FIG. 10: example 5 carbon spectrum of the product prepared.
FIG. 11: example 6 hydrogen profile of the prepared product; FIG. 12: example 6 carbon spectrum of the product prepared.
FIG. 13: example 7 hydrogen profile of the product prepared; FIG. 14: example 7 carbon spectrum of the product prepared.
FIG. 15: hydrogen spectrum of the product prepared in example 8; FIG. 16: example 8 carbon spectrum of the product prepared.
FIG. 17: example 9 hydrogen profile of the product prepared; FIG. 18: example 9 carbon spectrum of the product prepared.
FIG. 19: hydrogen spectrum of the product of example 10; FIG. 20: example 10 carbon spectrum of the product prepared.
FIG. 21: hydrogen spectrum of the product of example 11; FIG. 22: example 11 carbon spectrum of the product prepared.
FIG. 23: hydrogen spectrum of the product of example 12; FIG. 24: example 12 carbon spectrum of the product prepared.
FIG. 25: hydrogen spectrum of the product of example 13; FIG. 26: example 13 carbon spectrum of the product prepared.
FIG. 27 is a schematic view showing: example 14 hydrogen profile of the product prepared; FIG. 28: example 14 carbon spectrum of the product prepared.
FIG. 29: example 15 hydrogen profile of the product prepared; FIG. 30: example 15 carbon spectrum of the product prepared.
FIG. 31: hydrogen spectrum of the product of example 16; FIG. 32: example 16 carbon spectrum of the product prepared.
FIG. 33: hydrogen spectrum of the product of example 17; FIG. 34: example 17 carbon spectrum of the product prepared.
FIG. 35: hydrogen spectrum of the product of example 18; FIG. 36: example 18 carbon spectrum of the product prepared.
FIG. 37: hydrogen spectrum of the product of example 19; FIG. 38: example 19 carbon spectrum of the product prepared.
Detailed Description
It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the disclosure herein. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
As introduced in the background art, in the prior art, a transition metal catalyst or strong base is mostly adopted for the synthesis method of the 1,2, 3-triazole compound, the reaction conditions are complex, and the product is easily polluted by metal ions. Based on the above, the invention provides a novel synthesis method of the 1,2, 3-triazole compound, the synthesis method does not need a transition metal catalyst and a strong alkaline environment, the applicability and the economy of the synthesis method are improved, and the preparation method is simple and has high yield.
In one embodiment of the present invention, a method for synthesizing a 1,2, 3-triazole compound is given as follows:
(1) putting 0.3 mmol of p-toluenesulfonyl azide, 0.24 mmol of amine compounds, 0.2 mmol of diketone compounds and 0.3 mmol of acetic acid into a reaction tube, adding dichloromethane serving as a solvent, heating and stirring for reaction at the temperature of 90 ℃ for 24 hours;
(2) after the reaction is finished, the product 1,2, 3-triazole compound is obtained by column chromatography separation.
The reaction formula of the synthesis is as follows:
in order to make the technical solutions of the present application more clearly understood by those skilled in the art, the technical solutions of the present application will be described in detail below with reference to specific embodiments.
The test materials used in the examples of the present invention are all conventional in the art and commercially available.
The p-toluenesulfonyl azide used in the embodiment of the invention is synthesized by taking sodium azide and p-toluenesulfonyl chloride as raw materials, in an ice water bath, 30 mmol of sodium azide dissolved in 10 mL of water is dripped into 20 mmol of p-toluenesulfonyl chloride dissolved in 15 mL of acetone, the mixture is stirred and reacts for 12 hours at room temperature, and then the p-toluenesulfonyl azide is obtained by column chromatography separation. Reactions the above syntheses are conventional in the art.
Example 1:
(1) mu.L of p-toluenesulfonylazide, 22 mu.L of aniline, 22 mu.L of methyl acetoacetate and 17 mu.L of acetic acid are put into a reaction tube, 2 mL of dichloromethane is added as a solvent, the mixture is heated and stirred for reaction, the heating and stirring temperature is 90 ℃, and the reaction time is 24 hours.
(2) After the reaction is finished, the product 5-methyl-1-phenyl-1H- [1,2,3] triazole-4-methyl formate is obtained by column chromatography separation (the column packing is 300-mesh 400-mesh column chromatography silica gel, the eluent is ethyl acetate: petroleum ether = 8: 100 v/v), and the yield is 88%. The structural characterization of the product is shown in fig. 1 and fig. 2, respectively.
Example 2:
(1) mu.L of p-toluenesulfonylazide, 26 mu.L of 2-methylaniline, 22 mu.L of methyl acetoacetate and 17 mu.L of acetic acid are put into a reaction tube, 2 mL of dichloromethane is added as a solvent, the mixture is heated and stirred for reaction, the heating and stirring temperature is 90 ℃, and the reaction time is 24 hours.
(2) After the reaction is finished, the product 1- (2-methylphenyl) -5-methyl-1, 2, 3-triazole-4-methyl formate is obtained by column chromatography separation (the column packing is 300-mesh 400-mesh column chromatography silica gel, and the eluent is ethyl acetate: petroleum ether = 10: 100 v/v), wherein the yield is 82%. The structural characterization of the product is shown in fig. 3 and fig. 4, respectively.
Example 3:
(1) mu.L of p-toluenesulfonylazide, 0.0257 g of 4-methylaniline, 22. mu.L of methyl acetoacetate and 17. mu.L of acetic acid were put in a reaction tube, 2 mL of dichloromethane was added as a solvent, and the mixture was heated and stirred at 90 ℃ for 24 hours.
(2) After the reaction is finished, the product 1- (4-methylphenyl) -5-methyl-1, 2, 3-triazole-4-methyl formate is obtained by column chromatography separation (the column packing is 300-mesh 400-mesh column chromatography silica gel, and the eluent is ethyl acetate: petroleum ether = 15: 100 v/v), wherein the yield is 92%. The structural characterization of the product is shown in fig. 5 and fig. 6, respectively.
Example 4:
(1) mu.L of p-toluenesulfonylazide, 30 mu.L of 2, 4-dimethylaniline, 22 mu.L of methyl acetoacetate and 17 mu.L of acetic acid are put into a reaction tube, 2 mL of dichloromethane is added as a solvent, the mixture is heated and stirred for reaction, the heating and stirring temperature is 90 ℃, and the reaction time is 24 hours.
(2) After the reaction is finished, the product 1- (2, 4-dimethylphenyl) -5-methyl-1, 2, 3-triazole-4-methyl formate is obtained by column chromatography separation (the column packing is 300-mesh 400-mesh column chromatography silica gel, the eluent is ethyl acetate: petroleum ether = 15: 100 v/v), and the yield is 96%. The structural characterization of the product is shown in fig. 7 and fig. 8, respectively.
Example 5:
(1) mu.L of p-toluenesulfonylazide, 30 mu.L of 2, 5-dimethylaniline, 22 mu.L of methyl acetoacetate and 17 mu.L of acetic acid are put into a reaction tube, 2 mL of dichloromethane is added as a solvent, the mixture is heated and stirred for reaction, the heating and stirring temperature is 90 ℃, and the reaction time is 24 hours.
(2) After the reaction is finished, the product 1- (2, 5-dimethylphenyl) -5-methyl-1, 2, 3-triazole-4-methyl formate is obtained by column chromatography separation (the column packing is 300-mesh 400-mesh column chromatography silica gel, the eluent is ethyl acetate: petroleum ether = 13: 100 v/v), and the yield is 93%. The structural characterization of the product is shown in fig. 9 and fig. 10, respectively.
Example 6:
(1) mu.L of p-toluenesulfonylazide, 29 mu.L of 2, 3-dimethylaniline, 22 mu.L of methyl acetoacetate and 17 mu.L of acetic acid were put into a reaction tube, 2 mL of dichloromethane was added as a solvent, and the mixture was heated and stirred for reaction at a temperature of 90 ℃ for 24 hours.
(2) After the reaction is finished, the product 1- (2, 3-dimethylphenyl) -5-methyl-1, 2, 3-triazole-4-methyl formate is obtained by column chromatography separation (the column packing is 300-mesh 400-mesh column chromatography silica gel, the eluent is ethyl acetate: petroleum ether = 10: 100 v/v), and the yield is 81%. The structural characterization of the product is shown in fig. 11 and fig. 12, respectively.
Example 7:
(1) mu.L of p-toluenesulfonylazide, 27 mu.L of 2-methoxyaniline, 22 mu.L of methyl acetoacetate and 17 mu.L of acetic acid are put into a reaction tube, 2 mL of dichloromethane is added as a solvent, the mixture is heated and stirred for reaction, the heating and stirring temperature is 90 ℃, and the reaction time is 24 hours.
(2) After the reaction is finished, the product 1- (2-methoxyphenyl) -5-methyl-1, 2, 3-triazole-4-methyl formate can be obtained by column chromatography separation (the column packing is 300-mesh 400-mesh column chromatography silica gel, the eluant is ethyl acetate: petroleum ether = 10: 100 v/v), and the yield is 82%. The structural characterization of the product is shown in fig. 13 and 14, respectively.
Example 8:
(1) mu.L of p-toluenesulfonylazide, 0.0296 g of 4-methoxyaniline, 22. mu.L of methyl acetoacetate and 17. mu.L of acetic acid were put in a reaction tube, 2 mL of dichloromethane was added as a solvent, and the mixture was heated with stirring at 90 ℃ for 24 hours.
(2) After the reaction is finished, the product 1- (4-methoxyphenyl) -5-methyl-1, 2, 3-triazole-4-methyl formate can be obtained by column chromatography (the column packing is 300-400-mesh column chromatography silica gel, the eluant is ethyl acetate: petroleum ether = 10: 100 v/v), and the yield is 86%. The structural characterization of the product is shown in fig. 15 and fig. 16, respectively.
Example 9:
(1) mu.L of p-toluenesulfonylazide, 0.0368 g of 3, 4-dimethoxyaniline, 22. mu.L of methyl acetoacetate and 17. mu.L of acetic acid were put into a reaction tube, 2 mL of dichloromethane was added as a solvent, and the mixture was heated with stirring at 90 ℃ for 24 hours.
(2) After the reaction is finished, the product 1- (3, 4-dimethoxyphenyl) -5-methyl-1, 2, 3-triazole-4-methyl formate is obtained by column chromatography (the column packing is 300-mesh 400-mesh column chromatography silica gel, the eluant is ethyl acetate: petroleum ether = 10: 100 v/v), and the yield is 94%. The structural characterization of the product is shown in fig. 17 and fig. 18, respectively.
Example 10:
(1) mu.L of p-toluenesulfonylazide, 30 mu.L of 2-ethylaniline, 22 mu.L of methyl acetoacetate and 17 mu.L of acetic acid are put into a reaction tube, 2 mL of dichloromethane is added as a solvent, the mixture is heated and stirred for reaction, the heating and stirring temperature is 90 ℃, and the reaction time is 24 hours.
(2) After the reaction is finished, the product 1- (2-ethylphenyl) -5-methyl-1, 2, 3-triazole-4-methyl formate is obtained by column chromatography separation (the column packing is 300-400 mesh column chromatography silica gel, the eluent is ethyl acetate: petroleum ether = 15: 100 v/v), and the yield is 80%. The structural characterization of the product is shown in fig. 19 and fig. 20, respectively.
Example 11:
(1) mu.L of p-toluenesulfonylazide, 38 mu.L of 4-tert-butylaniline, 22 mu.L of methyl acetoacetate and 17 mu.L of acetic acid are put into a reaction tube, 2 mL of dichloromethane is added as a solvent, the mixture is heated and stirred for reaction, the heating and stirring temperature is 90 ℃, and the reaction time is 24 hours.
(2) After the reaction is finished, the product 1- (4-tert-butylphenyl) -5-methyl-1, 2, 3-triazole-4-carboxylic acid methyl ester can be obtained by column chromatography (the column packing is 300-mesh 400-mesh column chromatography silica gel, the eluent is ethyl acetate: petroleum ether = 10: 100 v/v), and the yield is 85%. The structural characterization of the product is shown in fig. 21 and 22, respectively.
Example 12:
(1) mu.L of p-toluenesulfonylazide, 27 mu.L of 2-methyl-4-fluoroaniline, 22 mu.L of methyl acetoacetate and 17 mu.L of acetic acid were put into a reaction tube, 2 mL of dichloromethane was added as a solvent, and the mixture was heated and stirred for reaction at a temperature of 70 ℃ for 24 hours.
(2) After the reaction is finished, the product 1- (4-chloro-2-methylphenyl) -5-methyl-1, 2, 3-triazole-4-methyl formate is obtained by column chromatography separation (the column packing is 300-mesh 400-mesh column chromatography silica gel, the eluant is ethyl acetate: petroleum ether = 10: 100 v/v), and the yield is 75%. The structural characterization of the product is shown in fig. 23 and fig. 24, respectively.
Example 13:
(1) mu.L of p-toluenesulfonylazide, 0.0406 g of benzidine, 22. mu.L of methyl acetoacetate and 17. mu.L of acetic acid were put in a reaction tube, 2 mL of dichloromethane was added as a solvent, and the mixture was heated with stirring at 90 ℃ for 24 hours.
(2) After the reaction is finished, the product 1- (biphenyl-2-yl) -5-methyl-1, 2, 3-triazole-4-methyl formate is obtained by column chromatography separation (the column packing is 300-mesh 400-mesh column chromatography silica gel, the eluent is ethyl acetate: petroleum ether = 7: 100 v/v), and the yield is 92%. The structural characterization of the product is shown in fig. 25 and 26, respectively.
Example 14:
(1) mu.L of p-toluenesulfonylazide, 0.0344 g of alpha-naphthylamine, 22 mu.L of methyl acetoacetate and 17 mu.L of acetic acid are put into a reaction tube, 2 mL of dichloromethane is added as a solvent, the mixture is heated and stirred for reaction, the heating and stirring temperature is 90 ℃, and the reaction time is 24 hours.
(2) After the reaction is finished, the product 5-methyl-1- (naphthalene-1-yl) -1H- [1,2,3] triazole-4-methyl formate is obtained by column chromatography (the column packing is 300-mesh 400-mesh column chromatography silica gel, the eluant is ethyl acetate: petroleum ether = 8: 100 v/v), and the yield is 93%. The structural characterization of the product is shown in fig. 27 and 28, respectively.
Example 15:
(1) mu.L of p-toluenesulfonylazide, 22 mu.L of aniline, 25 mu.L of ethyl acetoacetate and 17 mu.L of acetic acid are put into a reaction tube, 2 mL of dichloromethane is added as a solvent, the mixture is heated and stirred for reaction, the heating and stirring temperature is 90 ℃, and the reaction time is 24 hours.
(2) After the reaction is finished, the product 5-methyl-1-phenyl-1H- [1,2,3] triazole-4-ethyl formate is obtained by column chromatography separation (the column packing is 300-mesh 400-mesh column chromatography silica gel, the eluant is ethyl acetate: petroleum ether = 10: 100 v/v), and the yield is 81%. The structural characterization of the product is shown in fig. 29 and fig. 30, respectively.
Example 16:
(1) the reaction was carried out by adding 62. mu.L of p-toluenesulfonylazide, 22. mu.L of aniline, 25. mu.L of methyl propionylacetate and 17. mu.L of acetic acid to a reaction tube, adding 2 mL of dichloromethane as a solvent, and heating and stirring at 70 ℃ for 24 hours.
(2) After the reaction is finished, the product 5-ethyl-1-phenyl-1H- [1,2,3] triazole-4-methyl formate is obtained by column chromatography separation (the column packing is 300-mesh 400-mesh column chromatography silica gel, the eluant is ethyl acetate: petroleum ether = 10: 100 v/v), and the yield is 72%. The structural characterization of the product is shown in fig. 31 and fig. 32, respectively.
Example 17:
(1) mu.L of p-toluenesulfonyl azide, 22 mu.L of aniline, 29 mu.L of isopropyl acetoacetate and 17 mu.L of acetic acid are put into a reaction tube, 2 mL of dichloromethane is added as a solvent, the mixture is heated and stirred for reaction, the heating and stirring temperature is 90 ℃, and the reaction time is 24 h.
(2) After the reaction is finished, the product 5-methyl-1-phenyl-1H- [1,2,3] triazole-4-isopropyl formate is obtained by column chromatography separation (the column packing is 300-mesh 400-mesh column chromatography silica gel, the eluant is ethyl acetate: petroleum ether = 8: 100 v/v), and the yield is 70%. The structural characterization of the product is shown in fig. 33 and fig. 34, respectively.
Example 18:
(1) mu.L of p-toluenesulfonylazide, 21. mu.L of aniline, 21. mu.L of 2, 4-pentanedione and 17. mu.L of acetic acid were put into a reaction tube, and 2 mL of dichloromethane as a solvent was added to conduct a reaction under heating and stirring at 60 ℃ for 24 hours.
(2) After the reaction is finished, the product 1- (5-methyl-1-phenyl-1H-1, 2, 3-triazole-3-yl) ethanone can be obtained by column chromatography separation (the column packing of the column is 300-mesh 400-mesh column chromatography silica gel, the eluent is ethyl acetate: petroleum ether = 10: 100 v/v), and the yield is 70%. The structural characterization of the product is shown in fig. 35 and fig. 36, respectively.
Example 19:
(1) mu.L of p-toluenesulfonylazide, 21 mu.L of aniline, 27 mu.L of 3, 5-diheptanone and 17 mu.L of acetic acid were added to a reaction tube, 2 mL of dichloromethane was added as a solvent, and the mixture was heated and stirred at 60 ℃ for 24 hours.
(2) After the reaction is finished, the product 1- (5-methyl-1-phenyl-1H-1, 2, 3-triazole-3-yl) -1-acetone can be obtained by column chromatography separation (the column packing of the column is 300-mesh 400-mesh column chromatography silica gel, the eluent is ethyl acetate: petroleum ether = 2: 100 v/v), and the yield is 85%. The structural characterization of the product is shown in fig. 37 and fig. 38, respectively.
Comparative example 1:
the acid "acetic acid" in example 1 was adjusted to "TsOH. H2O ", the rest of the same procedure as in example 1, gave the product in a calculated yield of 17%.
Comparative example 2:
the acid "acetic acid" in example 1 was adjusted to " t- BuCOOH ", otherwise prepared as in example 1, gave a product in a calculated yield of 84%.
Comparative example 3:
the product was prepared in the same manner as in example 1 except that the organic solvent "dichloromethane" in example 1 was changed to "N, N-dimethylformamide", and the yield of the product was calculated to be 23%.
Comparative example 4:
the product was prepared in the same manner as in example 1 except that the organic solvent "dichloromethane" in example 1 was changed to "toluene", and the yield of the product was calculated to be 51%.
Comparative example 5:
the product was prepared in the same manner as in example 1 by adjusting the heating and stirring temperature to 60 c in example 1, and the yield of the product was calculated to be 65%.
The above description is only a preferred embodiment of the present application and is not intended to limit the present application, and those skilled in the art can make any modification and variation. Any modification, equivalent replacement, improvement and the like made within the spirit and principle of the present application shall be included in the protection scope of the present application.
Claims (9)
1. A method for synthesizing a 1,2, 3-triazole compound is characterized by comprising the following steps:
under the condition that acid is used as an additive, p-toluenesulfonyl azide, an amine compound and a dicarbonyl compound react in an organic solvent to obtain the 1,2, 3-triazole compound;
the structures of the p-toluenesulfonyl azide, the amine compound, the dicarbonyl compound and the 1,2, 3-triazole compound are respectively shown as the following formulas (I), (II), (III) and (IV):
r1 represents Me, OMe, Et, t-Bu, F or phenyl; r2 represents Me or Et; r3 represents Me, Et, OMe, OEt or Oi-Pr.
2. The method of synthesis of claim 1, wherein the acid additive is acetic acid.
3. The method of synthesis according to claim 1, wherein the organic solvent is dichloromethane.
4. The synthesis method according to claim 1, wherein the reaction temperature is 60-90 ℃ and the reaction time is 24-48 h.
5. The synthesis method according to claim 4, characterized in that the reaction temperature is 90 ℃ and the reaction time is 24 h.
6. The synthesis method according to claim 1, wherein the equivalent ratio of p-toluenesulfonyl azide to amine compound to dicarbonyl compound to acid is (2-3): (2-3): (2-3): (1-4).
7. The method of claim 1, wherein the compound of formula (ii) is any one of the following compounds:
aniline, 2-methylaniline, 4-methylaniline, 2, 4-dimethylaniline, 2, 5-dimethylaniline, 2, 3-dimethylaniline, 2-methoxyaniline, 4-methoxyaniline, 3, 4-dimethoxyaniline, 2-ethylaniline, 4-tert-butylaniline, benzidine, alpha-naphthylamine, 2-methyl-4-fluoroaniline.
8. The method of synthesis according to claim 1, wherein the compound of formula (iii) is any one of the following compounds:
ethyl acetoacetate, ethyl propionylacetate, isopropyl acetoacetate, acetylacetone, 3, 5-diheptanone.
9. The synthesis method according to claim 1, further comprising the step of subjecting the obtained 1,2, 3-triazole compound to column chromatography.
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