Preparation method of amide or ester compound

Abstract

The invention discloses a preparation method of an amide or ester compound, which comprises the steps of under the protection of inert gas, taking substituted carboxylic acid, an amine compound or an alcohol compound as a raw material, and reacting in an organic solvent in the presence of a phosphine oxide compound, an acyl chloride compound and organic alkali to generate the amide or ester compound. According to the preparation method, the phosphine oxide compound and the acyl chloride compound are used as condensing agents, the organic base is used as an acid-binding agent, substituted carboxylic acid and amine or alcohol react in the organic solvent to generate the amide or ester compound, the raw materials are cheap, easy to obtain, green and non-toxic, the green and environment-friendly requirements are met, the reaction rate is high, the yield is high, racemization is not prone to occurring, the atom economic utilization rate is high, the separation and post-treatment processes are simple and easy to operate, and the method is suitable for large-scale industrial production.

Description

technical field

[0001] The invention belongs to the technical field of organic synthesis, in particular to a preparation method of amides or esters. Background technique

[0002] Amides and esters are the two most common functional groups in organic chemistry. Amides or esters play an extremely important role in biochemistry, medicinal chemistry, pesticide chemistry and organic polymer materials [1] , and these two types of compounds are also important intermediates in organic synthesis [2] , so the research on the efficient construction of amide bonds and ester bonds has been receiving much attention.

[0003] The traditional synthesis methods of amides and esters mostly form C-N bonds or C-O bonds through condensation amidation or condensation esterification of carboxylic acids or derivatives with amines or alcohols [3-5] , including acid chloride method, mixed anhydride method, condensing agent as a medium, etc. The acid chloride method usually reacts carboxylic acid w...

Examples

Embodiment 1

[0071]

[0072] In a 25mL round bottom flask, dissolve triphenylphosphine oxide (0.056g, 0.2mmol) in 1.0mL of 1,2-dichloroethane, add thionyl chloride (0.109 mL, 1.5mmol), N-Fmoc-L-alanine (0.311g, 1.0mmol), L-phenylalanine methyl ester (0.269g, 1.5mmol) and triethylamine (0.277mL, 2.0 mmol), The stirring reaction was continued for 10 min at 25°C.

[0073] After the reaction was over, 50 mL of ethyl acetate was added to the reaction solution, and 30 mL of saturated Na 2 CO 3 The solution was washed 2 times and 20mL saturated brine was washed 2 times, and the organic phase was collected after separation, and the organic phase was washed with anhydrous Na 2 SO 4 Drying, filtration, and evaporation of the solvent under reduced pressure gave the crude product; the crude product was purified by column chromatography, and the mixture of ethyl acetate (EA) and petroleum ether (PE) with a volume ratio of 30:70 was used as an eluent for elution, The eluate was collected and dist...

Embodiment 2-4

[0079] All the other are identical with embodiment 1, difference is: the molar mass of triphenylphosphine oxide in embodiment 2,3,4 is respectively 0.1mmol, 0.5mmol and 1.0mmol, the content of condensing agent triphenylphosphine oxide The corresponding relationship with the experimental results is shown in Table 1 below.

[0080] Table 1 Correspondence between the content of the condensing agent triphenylphosphine oxide and the experimental results

[0081]

[0082] Analysis of experimental results: as can be seen from the results of Examples 1-4 and Table 1, the content of the condensing agent triphenylphosphine oxide has a significant impact on the reaction system, and the inventors have found that within a certain range, with the The increase of the condensing agent triphenylphosphine oxide content, the productive rate of product increases thereupon, tends to be stable subsequently; Therefore comprehensively consider the productive rate of the cost of raw material and pr...

Embodiment 5

[0084]

[0085] In a 25mL round bottom flask, dissolve triphenylphosphine oxide (0.056g, 0.2mmol) in 1.0mL 1,2-dichloroethane, and add oxalyl chloride (0.127mL, 1.5 mmol), N-Fmoc-L-leucine (0.353g, 1.0mmol), L-leucine tert-butyl ester (0.281g, 1.5mmol) and triethylamine (0.277mL, 2.0mmol), at 25°C The stirring reaction was continued for 10 min.

[0086] After the reaction was over, 50 mL of ethyl acetate was added to the reaction solution, and 30 mL of saturated Na 2 CO 3 The solution was washed 3 times and 20mL saturated brine twice, and the organic phase was washed with anhydrous Na 2 SO 4 Dry, filter, and evaporate the solvent under reduced pressure to obtain a crude product. The crude product was purified by column chromatography, using a mixture of ethyl acetate (EA) and petroleum ether (PE) with a volume ratio of 30:70 as the eluent for elution, and the eluate was collected and distilled under reduced pressure again to obtain a white solid 0.460g, the dipeptide p...

technical field

[0001] The invention belongs to the technical field of organic synthesis, in particular to a preparation method of amides or esters. Background technique

[0002] Amides and esters are the two most common functional groups in organic chemistry. Amides or esters play an extremely important role in biochemistry, medicinal chemistry, pesticide chemistry and organic polymer materials [1] , and these two types of compounds are also important intermediates in organic synthesis [2] , so the research on the efficient construction of amide bonds and ester bonds has been receiving much attention.

[0003] The traditional synthesis methods of amides and esters mostly form C-N bonds or C-O bonds through condensation amidation or condensation esterification of carboxylic acids or derivatives with amines or alcohols [3-5] , including acid chloride method, mixed anhydride method, condensing agent as a medium, etc. The acid chloride method usually reacts carboxylic acid w...

Examples

Embodiment 1

[0071]

[0072] In a 25mL round bottom flask, dissolve triphenylphosphine oxide (0.056g, 0.2mmol) in 1.0mL of 1,2-dichloroethane, add thionyl chloride (0.109 mL, 1.5mmol), N-Fmoc-L-alanine (0.311g, 1.0mmol), L-phenylalanine methyl ester (0.269g, 1.5mmol) and triethylamine (0.277mL, 2.0 mmol), The stirring reaction was continued for 10 min at 25°C.

[0073] After the reaction was over, 50 mL of ethyl acetate was added to the reaction solution, and 30 mL of saturated Na 2 CO 3 The solution was washed 2 times and 20mL saturated brine was washed 2 times, and the organic phase was collected after separation, and the organic phase was washed with anhydrous Na 2 SO 4 Drying, filtration, and evaporation of the solvent under reduced pressure gave the crude product; the crude product was purified by column chromatography, and the mixture of ethyl acetate (EA) and petroleum ether (PE) with a volume ratio of 30:70 was used as an eluent for elution, The eluate was collected and dist...

Embodiment 2-4

[0079] All the other are identical with embodiment 1, difference is: the molar mass of triphenylphosphine oxide in embodiment 2,3,4 is respectively 0.1mmol, 0.5mmol and 1.0mmol, the content of condensing agent triphenylphosphine oxide The corresponding relationship with the experimental results is shown in Table 1 below.

[0080] Table 1 Correspondence between the content of the condensing agent triphenylphosphine oxide and the experimental results

[0081]

[0082] Analysis of experimental results: as can be seen from the results of Examples 1-4 and Table 1, the content of the condensing agent triphenylphosphine oxide has a significant impact on the reaction system, and the inventors have found that within a certain range, with the The increase of the condensing agent triphenylphosphine oxide content, the productive rate of product increases thereupon, tends to be stable subsequently; Therefore comprehensively consider the productive rate of the cost of raw material and pr...

Embodiment 5

[0084]

[0085] In a 25mL round bottom flask, dissolve triphenylphosphine oxide (0.056g, 0.2mmol) in 1.0mL 1,2-dichloroethane, and add oxalyl chloride (0.127mL, 1.5 mmol), N-Fmoc-L-leucine (0.353g, 1.0mmol), L-leucine tert-butyl ester (0.281g, 1.5mmol) and triethylamine (0.277mL, 2.0mmol), at 25°C The stirring reaction was continued for 10 min.

[0086] After the reaction was over, 50 mL of ethyl acetate was added to the reaction solution, and 30 mL of saturated Na 2 CO 3 The solution was washed 3 times and 20mL saturated brine twice, and the organic phase was washed with anhydrous Na 2 SO 4 Dry, filter, and evaporate the solvent under reduced pressure to obtain a crude product. The crude product was purified by column chromatography, using a mixture of ethyl acetate (EA) and petroleum ether (PE) with a volume ratio of 30:70 as the eluent for elution, and the eluate was collected and distilled under reduced pressure again to obtain a white solid 0.460g, the dipeptide p...

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