阅读说明：本技术 一种2-卤代-2,2-二氟乙酸炔酯的制备方法 (Preparation method of 2-halogenated-2, 2-difluoroacetic acid alkynyl ester ) 是由 章鹏飞 王胜鹏 李万梅 徐伟明 陈八斤 王小君 于 2020-07-28 设计创作，主要内容包括：本发明涉及有机合成技术领域,提供了一种2-卤代-2,2-二氟乙酸炔酯的制备方法。本发明提供的制备方法包括以下步骤：将2-卤代-2,2-二氟乙酸、炔醇和催化剂在溶剂中进行酯化反应,得到2-卤代-2,2-二氟乙酸炔酯；所述催化剂包括硫酸、磷酸和对甲苯磺酸中的一种或多种。本发明提供的方法能够制备得到2-卤代-2,2-二氟乙酸炔酯,且本发明提供的方法操作简单、过程环保、产物收率高。实施例结果表明,本发明提供的2-卤代-2,2-二氟乙酸炔酯制备方法的收率为95.0％～98.8％。(The invention relates to the technical field of organic synthesis, and provides a preparation method of 2-halogenated-2, 2-difluoroacetic acid alkynyl ester. The preparation method provided by the invention comprises the following steps: carrying out esterification reaction on 2-halogenated-2, 2-difluoroacetic acid, alkynol and a catalyst in a solvent to obtain 2-halogenated-2, 2-difluoroacetic acid alkynylester; the catalyst comprises one or more of sulfuric acid, phosphoric acid and p-toluenesulfonic acid. The method provided by the invention can be used for preparing the 2-halogenated-2, 2-difluoroacetic acid alkyne ester, and is simple to operate, environment-friendly in process and high in product yield. The embodiment result shows that the yield of the preparation method of 2-halogenated-2, 2-difluoroacetic acid alkyne ester provided by the invention is 95.0-98.8%.)

1. A preparation method of 2-halogenated-2, 2-difluoroacetic acid alkyne ester is characterized by comprising the following steps:

carrying out esterification reaction on 2-halogenated-2, 2-difluoroacetic acid, alkynol and a catalyst in a solvent to obtain 2-halogenated-2, 2-difluoroacetic acid alkynylester; the catalyst comprises one or more of sulfuric acid, phosphoric acid and p-toluenesulfonic acid.

2. The process according to claim 1, wherein the 2-halo-2, 2-difluoroacetic acid is 2-bromo-2, 2-difluoroacetic acid and/or 2-chloro-2, 2-difluoroacetic acid.

3. The production method according to claim 1, wherein the esterification reaction is carried out under reflux conditions; during the esterification reaction, water produced by the esterification reaction is continuously separated.

4. The method according to claim 1 or 3, wherein the esterification reaction is carried out at a temperature of 60 to 130 ℃ for 5 to 15 hours.

5. The method of claim 1, wherein the alkynol comprises one or more of propargyl alcohol, 3-butyn-1-ol, 4-pentyn-1-ol, and 5-hexyn-1-ol.

6. The method according to claim 1, wherein the molar ratio of the 2-halo-2, 2-difluoroacetic acid to the alkynol is 1:1 to 5.

7. The method according to claim 1, wherein the mass ratio of the 2-halogeno-2, 2-difluoroacetic acid to the catalyst is 1:0.01 to 0.1.

8. The method of claim 1, wherein the solvent comprises one or more of cyclohexane, toluene, and xylene.

9. The method according to claim 1, wherein the mass ratio of the 2-halogeno-2, 2-difluoroacetic acid to the solvent is 1:4 to 10.

Technical Field

The invention relates to the technical field of organic synthesis, in particular to a preparation method of 2-halogenated-2, 2-difluoroacetic acid alkynyl ester.

Background

The polymer auxiliary agent water-based Polyacrylate (PA) generally has the defects of easy water absorption and moisture regain, poor weather resistance and the like. In order to improve the above problems of polyacrylates, the structure of the polyacrylates is generally improved and modified.

The modifying monomer is required not only to be novel in structure but also to be easily copolymerized. The C2 substituent is designed into two fluorine atoms and one bromine atom or chlorine atom, so that the moisture-proof and flame-retardant performance of the auxiliary agent can be further improved while the modified monomer has certain hydrophobicity; in addition, the modified monomer is designed into a structure containing alkynyl, so that the modified monomer can participate in polymerization reaction, and the modification of the material is further realized. Thus, 2-halo-2, 2-difluoroacetyienyl esters are ideal monomers for modifying polyacrylates. However, there is no report in the prior art concerning a process for producing 2-halo-2, 2-difluoroacetic acid alkynyl ester.

Disclosure of Invention

The invention provides a preparation method of 2-halogenated-2, 2-difluoroacetic acid alkyne ester, and the 2-halogenated-2, 2-difluoroacetic acid alkyne ester prepared by the method has the characteristics of high product yield and high purity.

The invention provides a preparation method of 2-halogenated-2, 2-difluoroacetic acid alkyne ester, which comprises the following steps:

carrying out esterification reaction on 2-halogenated-2, 2-difluoroacetic acid, alkynol and a catalyst in a solvent to obtain 2-halogenated-2, 2-difluoroacetic acid alkynylester; the catalyst comprises one or more of sulfuric acid, phosphoric acid and p-toluenesulfonic acid.

Preferably, the 2-halo-2, 2-difluoroacetic acid is 2-bromo-2, 2-difluoroacetic acid and/or 2-chloro-2, 2-difluoroacetic acid.

Preferably, the esterification reaction is carried out under reflux conditions; during the esterification reaction, water produced by the esterification reaction is continuously separated.

Preferably, the esterification reaction is carried out at the temperature of 60-130 ℃ for 5-15 h.

Preferably, the alkynol comprises one or more of propargyl alcohol, 3-butyn-1-ol, 4-pentyn-1-ol and 5-hexyn-1-ol.

Preferably, the molar ratio of the 2-halogenated-2, 2-difluoroacetic acid to the alkynol is 1: 1-5.

Preferably, the mass ratio of the 2-halogenated-2, 2-difluoroacetic acid to the catalyst is 1: 0.01-0.1.

Preferably, the solvent comprises one or more of cyclohexane, toluene and xylene.

Preferably, the mass ratio of the 2-halogenated-2, 2-difluoroacetic acid to the solvent is 1: 4-10.

Has the advantages that:

the invention provides a preparation method of 2-halogenated-2, 2-difluoroacetic acid alkyne ester, which comprises the following steps: carrying out esterification reaction on 2-halogenated-2, 2-difluoroacetic acid, alkynol and a catalyst in a solvent to obtain 2-halogenated-2, 2-difluoroacetic acid alkynylester; the catalyst comprises one or more of sulfuric acid, phosphoric acid and p-toluenesulfonic acid. The method provided by the invention can be used for preparing the 2-halogenated-2, 2-difluoroacetic acid alkyne ester, and is simple to operate, environment-friendly in process and high in product yield. The embodiment result shows that the yield of the preparation method of 2-halogenated-2, 2-difluoroacetic acid alkyne ester provided by the invention is 95.0-98.8%.

Drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of propargyl 2-bromo-2, 2-difluoroacetate prepared in example 1;

FIG. 2 is a nuclear magnetic carbon spectrum of propargyl 2-bromo-2, 2-difluoroacetate prepared in example 1;

FIG. 3 is a nuclear magnetic fluorine spectrum of propargyl 2-bromo-2, 2-difluoroacetate prepared in example 1;

FIG. 4 is a nuclear magnetic hydrogen spectrum of propargyl 2-chloro-2, 2-difluoroacetate prepared in example 5;

FIG. 5 is a nuclear magnetic carbon spectrum of propargyl 2-chloro-2, 2-difluoroacetate prepared in example 5;

FIG. 6 is a nuclear magnetic fluorine spectrum of propargyl 2-chloro-2, 2-difluoroacetate prepared in example 5.

Detailed Description

The invention provides a preparation method of 2-halogenated-2, 2-difluoroacetic acid alkyne ester, which comprises the following steps:

carrying out esterification reaction on 2-halogenated-2, 2-difluoroacetic acid, alkynol and a catalyst in a solvent to obtain 2-halogenated-2, 2-difluoroacetic acid alkynylester; the catalyst comprises one or more of sulfuric acid, phosphoric acid and p-toluenesulfonic acid.

The invention mixes 2-halogenated-2, 2-difluoroacetic acid, alkynol and catalyst in solvent. In the present invention, the 2-halo-2, 2-difluoroacetic acid is preferably 2-bromo-2, 2-difluoroacetic acid and/or 2-chloro-2, 2-difluoroacetic acid. In the present invention, the alkynol preferably includes one or more of propargyl alcohol, 3-butyn-1-ol, 4-pentyn-1-ol and 5-hexyn-1-ol. In the present invention, the solvent preferably includes one or more of cyclohexane, toluene, and xylene.

In the present invention, the molar ratio of the 2-halo-2, 2-difluoroacetic acid to the alkynol is preferably 1:1 to 5, and more preferably 1:1, 1:2, 1:3, 1:4 or 1: 5. In the present invention, the mass ratio of the 2-halo-2, 2-difluoroacetic acid to the catalyst is preferably 1:0.01 to 0.1, and more preferably 1:0.01, 1:0.02, 1:0.03, 1:0.04, 1:0.05, 1:0.06, 1:0.07, 1:0.08, 1:0.09, or 1: 0.1. In the present invention, the mass ratio of the 2-halo-2, 2-difluoroacetic acid to the solvent is preferably 1:4 to 10, and more preferably 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, or 1: 10.

In the present invention, the esterification reaction is preferably performed under a reflux condition, and the reflux temperature is preferably 60 to 130 ℃, and more preferably 60 ℃, 70 ℃, 80 ℃, 90 ℃,100 ℃, 110 ℃, 120 ℃ or 130 ℃. In the esterification reaction process, water generated by the esterification reaction is continuously separated, preferably, a water separator is arranged in a device for carrying out the esterification reaction, and the water in the reaction system is taken out through the reflux of the reaction system, so that the aims of improving the reaction yield and the product purity are fulfilled.

And stopping the esterification reaction when no water is separated out from the reaction system. In the invention, the esterification reaction time is preferably 5-15 h, and more preferably 5h, 6h, 7h, 8h, 9h, 10h, 11h, 12h, 13h, 14h or 15 h.

In the present invention, the formula of the esterification reaction is represented by formula (1) or formula (2):

the invention controls the types of raw materials, the use amount of the raw materials and the reaction conditions of the esterification reaction within the above range, and is beneficial to improving the yield and the product purity of the esterification reaction.

After the esterification reaction is finished, the esterification reaction system is preferably subjected to distillation treatment, the solvent and the excessive alkynol are recovered, then the residual substances after the distillation treatment are subjected to reduced pressure distillation again, and fractions are collected to obtain the 2-halogenated-2, 2-difluoroacetic acid alkynyl ester.

The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention.

Example 1

87.5 g of 2-bromo-2, 2-difluoroacetic acid, 140 g of propargyl alcohol, 8.75 g of phosphoric acid and 350 g of cyclohexane were placed in a reaction vessel equipped with a thermometer, reflux condenser, water separator and stirrer and reacted at 70 ℃ for 15 hours until no water had separated. And after the reaction is finished, distilling to recover the solvent and the excessive propargyl alcohol, and then carrying out reduced pressure distillation to collect the fraction at the temperature of 115-117 ℃/50mmHg to obtain 104.8 g of 2-bromo-2, 2-difluoroacetic acid propargyl ester, wherein the yield is 98.4%, and the purity is 99.4%.

The nuclear magnetic analysis of propargyl 2-bromo-2, 2-difluoroacetate obtained in example 1 showed the results in FIGS. 1 to 3, in which FIG. 1 is a nuclear magnetic hydrogen spectrum, FIG. 2 is a nuclear magnetic carbon spectrum, and FIG. 3 is a nuclear magnetic fluorine spectrum. As can be seen from FIGS. 1 to 3, propargyl 2-bromo-2, 2-difluoroacetate prepared in example 1 of the present invention corresponds to the expected structure.

Nuclear magnetic characterization data¹H NMR(500MHz,CDCl₃)δ4.84(d,J＝2.5Hz,2H),2.56(t,J＝2.2Hz,1H)；

¹³C NMR(126MHz,CDCl₃)δ157.87(t,J＝32.1Hz),107.31(t,J＝313.9Hz),76.32,74.09,54.38；

¹⁹F NMR(471MHz,CDCl₃)δ-61.16。

Example 2

87.5 g of 2-bromo-2, 2-difluoroacetic acid, 35 g of 3-butyn-1-ol, 0.875 g of p-toluenesulfonic acid and 600 g of toluene were charged in a 1L reaction vessel equipped with a thermometer, reflux condenser, water separator and stirrer and reacted at 100 ℃ for 10 hours until no water was removed. And after the reaction is finished, distilling to recover the solvent, and then carrying out reduced pressure distillation to collect a fraction under the condition of 126-127 ℃/50mmHg to obtain 110.2 g of 2-bromo-2, 2-difluoroacetic acid propargyl butyl ester, wherein the yield is 97.1%, and the purity is 99.6%.

Example 3

87.5 g of 2-bromo-2, 2-difluoroacetic acid, 84 g of 4-pentyn-1-ol, 1.5 g of sulfuric acid and 500 g of toluene were charged into a 1L reaction vessel equipped with a thermometer, reflux condenser, water separator and stirrer, and reacted at 110 ℃ for 10 hours until no water was removed. And after the reaction is finished, distilling to recover the solvent and the excessive 4-pentyne-1-ol, and then carrying out reduced pressure distillation to collect a fraction at the temperature of 163-164 ℃/50mmHg to obtain 114.5 g of 2-bromo-2, 2-difluoroacetic acid pentyne ester, wherein the yield is 95.0%, and the purity is 99.6%.

Example 4

87.5 g of 2-bromo-2, 2-difluoroacetic acid, 98 g of 5-hexyn-1-ol, 1.5 g of sulfuric acid, 1.5 g of phosphoric acid and 500 g of xylene were charged into a 1L reaction vessel equipped with a thermometer, reflux condenser, water separator and stirrer, and reacted at 120 ℃ for 5 hours until no water was removed. And after the reaction is finished, distilling to recover the solvent and the excessive 5-hexyne-1-ol, and then carrying out reduced pressure distillation to collect the fraction at the temperature of 165-166 ℃/40mmHg to obtain 123.5 g of 2-bromo-2, 2-difluoroacetic acid propargyl ester, wherein the yield is 96.9%, and the purity is 99.8%.

Example 5

In a 1L reaction vessel equipped with a thermometer, reflux condenser, water separator and stirrer were charged 65.25 g of 2-chloro-2, 2-difluoroacetic acid, 140 g of propargyl alcohol, 1.5 g of sulfuric acid, 1.5 g of p-toluenesulfonic acid and 261 g of cyclohexane, and reacted at 60 ℃ for 15 hours until no water was removed. And after the reaction is finished, distilling to recover the solvent and the excessive propargyl alcohol, and then carrying out reduced pressure distillation to collect the fraction at the temperature of 110-111 ℃/50mmHg to obtain 82.3 g of propargyl 2-chloro-2, 2-difluoroacetate, wherein the yield is 97.6% and the purity is 99.3%.

The nuclear magnetic analysis of propargyl 2-chloro-2, 2-difluoroacetate obtained in example 5 showed the results in FIGS. 4 to 6, in which FIG. 4 is a nuclear magnetic hydrogen spectrum, FIG. 5 is a nuclear magnetic carbon spectrum, and FIG. 6 is a nuclear magnetic fluorine spectrum. As can be seen from FIGS. 4 to 6, propargyl 2-bromo-2, 2-difluoroacetate prepared in example 5 of the present invention corresponds to the expected structure.

Nuclear magnetic characterization data¹H NMR(500MHz,CDCl₃)δ4.93(d,J＝2.5Hz,2H),2.64(t,J＝2.5Hz,1H)；

¹³C NMR(126MHz,CDCl₃)δ157.55(t,J＝35.2Hz),115.60(t,J＝300.5Hz),76.28,74.01,54.39；

¹⁹F NMR(471MHz,CDCl₃)δ-63.98。

Example 6

In a 1L reaction vessel equipped with a thermometer, reflux condenser, water separator and stirrer were charged 65.25 g of 2-chloro-2, 2-difluoroacetic acid, 35 g of 3-butyn-1-ol, 1.5 g of sulfuric acid, 1.5 g of phosphoric acid and 652.5 g of toluene, and reacted at 110 ℃ for 10 hours until no water was removed. And after the reaction is finished, distilling to recover the solvent, and then carrying out reduced pressure distillation to collect the fraction under the condition of 124-125 ℃/50mmHg to obtain 90.2 g of 2-chloro-2, 2-difluoroacetic acid propargyl butyl ester, wherein the yield is 98.8%, and the purity is 99.6%.

Example 7

In a 1L reaction vessel equipped with a thermometer, reflux condenser, water separator and stirrer were charged 65.25 g of 2-chloro-2, 2-difluoroacetic acid, 84 g of 4-pentyn-1-ol, 1.5 g of sulfuric acid and 500 g of toluene, and reacted at 110 ℃ for 10 hours until no water was removed. And after the reaction is finished, distilling to recover the solvent and the excessive 4-pentyne-1-ol, and then carrying out reduced pressure distillation to collect the fraction at 157-158 ℃/50mmHg to obtain 96.6 g of 2-chloro-2, 2-difluoroacetic acid propargyl ester, wherein the yield is 98.3%, and the purity is 99.7%.

Example 8

In a 1L reaction vessel equipped with a thermometer, reflux condenser, water separator and stirrer were charged 65.25 g of 2-chloro-2, 2-difluoroacetic acid, 98 g of 5-hexyn-1-ol, 1.5 g of phosphoric acid and 500 g of xylene, and reacted at 130 ℃ until no water was removed for 5 hours. And after the reaction is finished, distilling to recover the solvent and the excessive 5-hexyne-1-ol, and then carrying out reduced pressure distillation to collect fractions at the temperature of 158-160 ℃/40mmHg to obtain 103.3 g of 2-chloro-2, 2-difluoroacetic acid propargyl ester, wherein the yield is 98.1%, and the purity is 99.4%.

In conclusion, the preparation method of 2-halogenated-2, 2-difluoroacetic acid alkynyl ester provided by the invention has the advantages of higher yield and higher product purity, wherein the yield is 95.0-98.8%, and the purity is 99.3-99.8%.

The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.