阅读说明：本技术 一种2-烷氧基-2-环戊烯-1-酮的制备方法 (Preparation method of 2-alkoxy-2-cyclopentene-1-ketone ) 是由 闫溢哲 贺远 李林 徐改改 彭百祥 薛欣欢 安虹 于 2020-06-04 设计创作，主要内容包括：本发明公开了一种制备2-烷氧基-2-环戊烯-1-酮的方法,具体为以环戊酮和脂肪醇为反应底物,在当量碘和铜盐存在下,经由碘化、取代、氧化及加成消除的串联反应得到2-烷氧基-2-环戊烯-1-酮。环戊酮的化学结构通式为,醇的化学结构通式为R～2OH,铜盐选自乙酸铜、碘化亚铜、单质铜和氧化铜中的一种。本发明公开的制备方法具有原料易得、底物范围广、操作简单方便和绿色安全等优点。(The invention discloses a method for preparing 2-alkoxy-2-cyclopentene-1-ketone, which specifically comprises the steps of taking cyclopentanone and fatty alcohol as reaction substrates, and obtaining the 2-alkoxy-2-cyclopentene-1-ketone through a series reaction of iodination, substitution, oxidation and addition elimination in the presence of equivalent iodine and copper salt. The chemical structural general formula of cyclopentanone is The chemical structural general formula of the alcohol is R 2 And OH, wherein the copper salt is selected from one of copper acetate, cuprous iodide, elementary copper and copper oxide. The preparation method disclosed by the invention has the advantages of easily available raw materials, wide substrate range, simplicity and convenience in operation, greenness, safety and the like.)

1. a preparation method of 2-alkoxy-2-cyclopentene-1-ketone is characterized in that: firstly, cyclopentanone, iodine and ketone salt are added into a reaction container, then 20-60 mL of aliphatic alcohol is added, then the reaction is carried out for 12 hours at the temperature of 100 ℃, and after the reaction is finished, the 2-alkoxy-2-cyclopentene-1-ketone is obtained by filtering, reduced pressure distillation and column chromatography.

2. The process for producing 2-alkoxy-2-cyclopenten-1-one according to claim 1, characterized in that: the chemical structural general formula of the cyclopentanone isWherein R is¹Is one of hydrogen, methyl and ethyl.

3. The process for producing 2-alkoxy-2-cyclopenten-1-one according to claim 1The method is characterized in that: the chemical structural general formula of the fatty alcohol is R²OH, wherein R²Is one of methyl, ethyl, n-propyl, n-butyl, isobutyl and isopropyl.

4. The process for producing 2-alkoxy-2-cyclopenten-1-one according to claim 1, characterized in that: the copper salt is selected from one of copper acetate, cuprous iodide, elementary copper and copper oxide.

5. The process for producing 2-alkoxy-2-cyclopenten-1-one according to claim 1, characterized in that: the ratio of cyclopentanone, iodine and ketone salt is 1:1: 0.5-1.5.

Technical Field

The invention relates to a preparation method of 2-alkoxy-2-cyclopentene-1-ketone.

Background

2-alkoxy-2-cyclopenten-1-ones are a very important class of cyclic compounds which can be used as precursors for drug synthesis. The conventional method is generally obtained by reacting 1, 2-cyclopentanedione with an alkoxy reagent in the presence of an acid (Oncogene 2016, 35, 2518; j.med.chem.2009, 52, 5152; eur.j.org.chem.2010, 6354). However, the further application is limited by the defects of narrow substrate range, generally low yield, difficult raw material acquisition, complex operation and the like.

Disclosure of Invention

Aiming at the technical problems, the invention aims to provide the preparation method of the 2-alkoxy-2-cyclopentene-1-ketone, which has the advantages of wider substrate range, higher yield, simpler and more convenient operation, greenness and safety.

The technical scheme adopted by the invention is as follows: cyclopentanone, iodine and ketone salt (in a ratio of 1: 0.5-1.5) are added to a reaction vessel, and then 20-60 mL of aliphatic alcohol is added, followed by reaction at 100 ℃ for 12 hours. After the reaction is finished, filtering, distilling under reduced pressure and carrying out column chromatography to obtain the 2-alkoxy-2-cyclopentene-1-ketone.

The chemical structural general formula of the cyclopentanone isWherein R is¹Is one of hydrogen, methyl and ethyl.

The chemical structural general formula of the fatty alcohol is R²OH, wherein R²Is one of methyl, ethyl, n-propyl, n-butyl, isobutyl and isopropyl.

The copper salt is selected from one of copper acetate, cuprous iodide, elementary copper and copper oxide.

Due to the application of the technical scheme, compared with the prior art, the invention has the following advantages:

1. the raw materials are cheap and easy to obtain, and the economic cost is low;

2. the method does not need anhydrous and anaerobic operation, is simple and practical to operate, and is easy to realize large-scale production;

3. the method has higher yield, is applicable to different fatty alcohols and cyclopentanone, and has wider substrate range;

4. the reaction byproducts in the invention are inorganic salt and water, thus being more green and safe.

Detailed Description

The present invention will be described in further detail with reference to specific examples. Reagents, equipment and methods employed in the present invention are reagents, equipment and methods conventionally commercially available in the art and conventionally used unless otherwise specified.

The first embodiment is as follows:

cyclopentanone (1a, 5mmol), iodine (5mmol), copper oxide (7.5mmol) and ethanol (2a, 60mL) were charged into a reaction flask, followed by heating at 100 ℃ for 12 hours. After the reaction is finished, filtering, distilling under reduced pressure and carrying out column chromatography to obtain a product 3aa, wherein the yield is 76%. A light yellow oily liquid;¹H NMR(600MHz，CDCl₃)：δ6.39(t，J＝3.1Hz，1H)，3.93(q，J＝7.1Hz，2H)，2.54-2.51(m，2H)，2.44-2.42(m，2H)，1.40(t，J＝7.1Hz，3H)；¹³C NMR(150MHz，CDCl₃)：δ202.6，156.5，127.2，65.4，32.9，21.8，14.2。

example two:

cyclopentanone (1a, 5mmol), iodine (5mmol), copper oxide (7.5mmol) and methanol (2b, 60mL) were charged into a reaction flask, followed by heating at 100 ℃ for 12 hours. After the reaction is finished, filtering, distilling under reduced pressure and carrying out column chromatography to obtain a product 3ab, wherein the yield is 40%. A colorless oily liquid;¹H NMR(400MHz，CDCl₃)：δ6.41-6.38(m，1H)，3.75-3.73(m，3H)，2.54-2.51(m，2H)，2.47-2.43(m，2H)；¹³C NMR(100MHz，CDCl₃)：δ202.4，157.5，126.9，57.0，33.1，21.8。

example three:

cyclopentanone (1a, 5mmol), iodine (5mmol), copper oxide (7.5mmol) and n-propanol (2c, 60mL) were added to a reaction flask, followed by heating at 100 ℃ for 12 hours. After the reaction is finished, filtering, distilling under reduced pressure and carrying out column chromatography to obtain a product 3ac, wherein the yield is 67%. A light yellow oily liquid;¹H NMR(400MHz，CDCl₃)：δ6.37(t，J＝3.0Hz，1H)，3.81(t，J＝6.7Hz，2H)，2.54-2.50(m，2H)，2.45-2.42(m，2H)，1.83-1.77(m，2H)，1.00(t，J＝7.4Hz，3H)；¹³C NMR(100MHz，CDCl₃)：δ202.6，156.7，127.2，71.4，33.1，22.0，21.8，10.3；HRMS(ESI)：calcd for C₈H₁₂NaO₂[M+Na]⁺163.0730，found 163.0726。

example four:

cyclopentanone (1a, 5mmol), iodine (5mmol), copper oxide (7.5mmol) and n-butanol (2d, 60mL) were charged into a reaction flask, followed by heating at 100 ℃ for 12 hours. After the reaction is finished, filtering, distilling under reduced pressure and carrying out column chromatography to obtain the product 3ad with the yield of 72 percent. A light yellow oily liquid;¹H NMR(400MHz，CDCl₃)：δ6.37(t，J＝3.0Hz，1H)，3.85(t，J＝6.6Hz，2H)，2.54-2.50(m，2H)，2.45-2.42(m，2H)，1.79-1.71(m，2H)，1.48-1.41(m，2H)，0.94(t，J＝7.4Hz，3H)；¹³C NMR(100MHz，CDCl₃)：δ202.7，156.7，127.3，69.7，33.1，30.7，21.8，19.1，13.7；HRMS(ESI)：calcd for C₉H₁₄NaO₂[M+Na]⁺177.0886，found 177.0883。

example five:

cyclopentanone (1a, 5mmol), iodine (5mmol), copper oxide (7.5mmol) and isobutanol (2e, 60mL) were added to a reaction flask, followed by heating at 100 ℃ for 12 hours. After the reaction is finished, the product 3ae can be obtained by filtering, reduced pressure distillation and column chromatography, and the yield is 44%. A light yellow oily liquid;¹H NMR(400MHz，CDCl₃)：δ6.36(t，J＝3.0Hz，1H)，3.60(d，J＝6.7Hz，2H)，2.53-2.49(m，2H)，2.45-2.42(m，2H)，2.10(hept，J＝6.7Hz，1H)，0.98(d，J＝6.7Hz，6H)；¹³C NMR(100MHz，CDCl₃)：δ202.5，156.9，127.3，76.3，33.1，27.8，21.8，19.2。

example six:

cyclopentanone (1a, 5mmol), iodine (5mmol), copper oxide (7.5mmol) and isopropanol (2f, 60mL) were added to a reaction flask, followed by heating at 100 ℃ for 12 hours. After the reaction is finished, filtering, distilling under reduced pressure and carrying out column chromatography to obtain a product 3af with the yield of 83%. A light yellow oily liquid;¹H NMR(400MHz，CDCl₃)：δ6.36(t，J＝3.0Hz，1H)，4.31(hept，J＝6.1Hz，1H)，2.55-2.51(m，2H)，2.45-2.41(m，2H)，1.32(d，J＝6.1Hz，6H)；¹³CNMR(100MHz，CDCl₃)：δ203.4，155.3，127.6，72.1，32.9，21.9，21.3；HRMS(ESI)：calcd for C₈H₁₂NaO₂[M+Na]⁺163.0730，found 163.0727。

example seven:

3-methylcyclopentanone (1b, 5mmol), iodine (5mmol), copper oxide (7.5mmol) and ethanol (2a, 60mL) were added to a reaction flask, followed by heating at 100 ℃ for 12 hours. After the reaction is finished, the product 3ba can be obtained by filtering, reduced pressure distillation and column chromatography, and the yield is 46%. Light yellow oily liquidA body;¹H NMR(600MHz，CDCl₃)：δ6.28(d，J＝2.9Hz，1H)，3.94-3.88(m，2H)，2.90-2.84(m，1H)，2.66(dd，J₁＝19.1Hz，J₂＝6.2Hz，1H)，1.98(dd，J₁＝19.1Hz，J₂＝1.8Hz，1H)，1.39(t，J＝7.0Hz，3H)，1.18(d，J＝7.0Hz，3H)；¹³C NMR(150MHz，CDCl₃)：δ202.5，155.8，132.8，65.4，41.8，29.1，21.5，14.3；HRMS(ESI)：calcd for C₈H₁₂NaO₂[M+Na]⁺163.0730，found 163.0725。

example eight:

3-Ethylcyclopentanone (1c, 5mmol), iodine (5mmol), copper oxide (7.5mmol) and ethanol (2a, 60mL) were added to a reaction flask, followed by heating at 100 ℃ for 12 hours. After the reaction is finished, filtering, distilling under reduced pressure and carrying out column chromatography to obtain a product 3ca with the yield of 59%. A light yellow oily liquid;¹H NMR(600MHz，CDCl₃)：δ6.33(d，J＝2.8Hz，1H)，3.92(qd，J₁＝7.0Hz，J₂＝0.8Hz，2H)，2.74-2.68(m，1H)，2.62-2.57(m，1H)，2.06-2.02(m，1H)，1.60-1.51(m，1H)，1.49-1.41(m，1H)，1.39(tt，J₁＝7.0Hz，J₂＝1.0Hz，3H)，0.97(tt，J₁＝7.4Hz，J₂＝1.0Hz，3H)；¹³C NMR(150MHz，CDCl₃)：δ202.3，156.0，131.2，65.4，39.7，35.9，28.8，14.2，11.5；HRMS(ESI)：calcd for C₉H₁₄NaO₂[M+Na]⁺177.0886，found 177.0878。

example nine:

cyclopentanone (1a, 5mmol), iodine (5mmol), copper oxide (7.5mmol) and ethanol (2a, 40mL) were added to a reaction flask, which was then heated at 100 deg.C for reactionShould be 12 hours. After the reaction is finished, the product 3aa can be obtained by filtering, reduced pressure distillation and column chromatography, and the yield is 73%. A light yellow oily liquid;¹H NMR(600MHz，CDCl₃)：δ6.39(t，J＝3.1Hz，1H)，3.93(q，J＝7.1Hz，2H)，2.54-2.51(m，2H)，2.44-2.42(m，2H)，1.40(t，J＝7.1Hz，3H)；¹³C NMR(150MHz，CDCl₃)：δ202.6，156.5，127.2，65.4，32.9，21.8，14.2。

example ten:

cyclopentanone (1a, 5mmol), iodine (5mmol), copper oxide (7.5mmol) and ethanol (2a, 20mL) were charged into a reaction flask, followed by heating at 100 ℃ for 12 hours. After the reaction is finished, filtering, distilling under reduced pressure and carrying out column chromatography to obtain a product 3aa, wherein the yield is 69%. A light yellow oily liquid;¹H NMR(600MHz，CDCl₃)：δ6.39(t，J＝3.1Hz，1H)，3.93(q，J＝7.1Hz，2H)，2.54-2.51(m，2H)，2.44-2.42(m，2H)，1.40(t，J＝7.1Hz，3H)；¹³C NMR(150MHz，CDCl₃)：δ202.6，156.5，127.2，65.4，32.9，21.8，14.2。

example eleven:

cyclopentanone (1a, 5mmol), iodine (5mmol), copper oxide (2.5mmol) and ethanol (2a, 20mL) were charged into a reaction flask, followed by heating at 100 ℃ for 12 hours. After the reaction is finished, filtering, distilling under reduced pressure and carrying out column chromatography to obtain a product 3aa, wherein the yield is 48%. A light yellow oily liquid;¹H NMR(600MHz，CDCl₃)：δ6.39(t，J＝3.1Hz，1H)，3.93(q，J＝7.1Hz，2H)，2.54-2.51(m，2H)，2.44-2.42(m，2H)，1.40(t，J＝7.1Hz，3H)；¹³C NMR(150MHz，CDCl₃)：δ202.6，156.5，127.2，65.4，32.9，21.8，14.2。

example twelve:

cyclopentanone (1a, 5mmol), iodine (5mmol), copper oxide (5mmol) and ethanol (2a, 20mL) were charged into a reaction flask, followed by heating at 100 ℃ for 12 hours. After the reaction is finished, filtering, distilling under reduced pressure and carrying out column chromatography to obtain a product 3aa, wherein the yield is 47%. A light yellow oily liquid;¹H NMR(600MHz，CDCl₃)：δ6.39(t，J＝3.1Hz，1H)，3.93(q，J＝7.1Hz，2H)，2.54-2.51(m，2H)，2.44-2.42(m，2H)，1.40(t，J＝7.1Hz，3H)；¹³C NMR(150MHz，CDCl₃)：δ202.6，156.5，127.2，65.4，32.9，21.8，14.2。

example thirteen:

cyclopentanone (1a, 5mmol), iodine (5mmol), copper powder (5mmol) and ethanol (2a, 20mL) were charged into a reaction flask, followed by heating at 100 ℃ for 12 hours. After the reaction is finished, filtering, distilling under reduced pressure and carrying out column chromatography to obtain a product 3aa, wherein the yield is 13%. A light yellow oily liquid;¹H NMR(600MHz，CDCl₃)：δ6.39(t，J＝3.1Hz，1H)，3.93(q，J＝7.1Hz，2H)，2.54-2.51(m，2H)，2.44-2.42(m，2H)，1.40(t，J＝7.1Hz，3H)；¹³C NMR(150MHz，CDCl₃)：δ202.6，156.5，127.2，65.4，32.9，21.8，14.2。

example fourteen:

cyclopentanone (1a, 5mmol), iodine (5mmol), cuprous iodide (5mmol) and ethanol (2a, 20mL) were added to a reaction flask, followed by heating at 100 ℃ for 12 hours. After the reaction is finished, filtering, distilling under reduced pressure and carrying out column chromatography to obtain a product 3aa, wherein the yield is 24%. Light yellowA colored oily liquid;¹H NMR(600MHz，CDCl₃)：δ6.39(t，J＝3.1Hz，1H)，3.93(q，J＝7.1Hz，2H)，2.54-2.51(m，2H)，2.44-2.42(m，2H)，1.40(t，J＝7.1Hz，3H)；¹³C NMR(150MHz，CDCl₃)：δ202.6，156.5，127.2，65.4，32.9，21.8，14.2。

example fifteen:

cyclopentanone (1a, 5mmol), iodine (5mmol), copper acetate (5mmol) and ethanol (2a, 20mL) were added to a reaction flask, followed by heating at 100 ℃ for 12 hours. After the reaction is finished, filtering, distilling under reduced pressure and carrying out column chromatography to obtain a product 3aa, wherein the yield is 25%. A light yellow oily liquid;¹H NMR(600MHz，CDCl₃)：δ6.39(t，J＝3.1Hz，1H)，3.93(q，J＝7.1Hz，2H)，2.54-2.51(m，2H)，2.44-2.42(m，2H)，1.40(t，J＝7.1Hz，3H)；¹³C NMR(150MHz，CDCl₃)：δ202.6，156.5，127.2，65.4，32.9，21.8，14.2。