KR20050035692A - One-step synthetic methods for cinnamaldehyde derivatives - Google Patents
One-step synthetic methods for cinnamaldehyde derivatives Download PDFInfo
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- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
- C07C45/72—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms by reaction of compounds containing >C = O groups with the same or other compounds containing >C = O groups
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- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
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- C07C47/26—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms containing hydroxy groups
- C07C47/27—Unsaturated compounds having —CHO groups bound to acyclic carbon atoms containing hydroxy groups containing six-membered aromatic rings
Abstract
본 발명은 하기 화학식 1의 신남알데하이드 유도체의 새로운 합성 방법에 관한 것으로, 본 발명에서는 종래의 방법에 비해 보다 안전하고 취급이 용이한 반응물질인 탄산칼륨을 사용하여 제조공정을 용이하게 하고 공정을 개선한 새로운 합성방법에 관한 것이다. 또한, 본 발명에 따른 신남알데하이드 유도체의 합성은 전체적인 공정의 개선으로 합성시간, 합성에 소요되는 비용 등에서 많이 감소되었다는 장점이 있다.The present invention relates to a new synthesis method of the cinnamic aldehyde derivative of the formula (1), in the present invention to facilitate the manufacturing process and improve the process using potassium carbonate, which is a safer and easier to handle than the conventional method One new synthesis method is concerned. In addition, the synthesis of cinnamic aldehyde derivatives according to the present invention has the advantage that the synthesis time, the synthesis time, the cost required for the synthesis is greatly reduced.
[화학식 1][Formula 1]
상기 화학식 1에서, In Chemical Formula 1,
R1, R2, R3은 같거나 다르며, 수소, 하이드록시, 할로겐으로부터 선택된다.R 1 , R 2 , R 3 are the same or different and are selected from hydrogen, hydroxy, halogen.
Description
본 발명은 신남알데하이드 유도체를 합성하는 새로운 방법에 관한 것으로, 보다 안전하고 취급이 용이한 반응물질을 사용하여 제조공정을 개선한 새로운 합성방법에 관한 것이다. 하기 화학식 1의 신남알데하이드 유도체 (cinnamaldehyde derivatives)는 파네실단백질전달효소(farnesyl protein transferase)억제 작용, 신생혈관형성억제 작용, 세포분열억제 작용, 면역기능조절 작용 등의 효과를 나타낸다.The present invention relates to a new method for synthesizing cinnamic aldehyde derivatives, and to a new synthetic method for improving the manufacturing process using a safer and easier to handle reactant. The cinnamaldehyde derivatives of Formula 1 show effects such as farnesyl protein transferase inhibitory activity, angiogenesis inhibitory activity, cell division inhibitory action, and immune function regulation.
[화학식 1][Formula 1]
상기 화학식 1에서, In Chemical Formula 1,
R1, R2, R3은 같거나 다르며, 수소, 하이드록시, 할로겐으로부터 선택된다.R 1 , R 2 , R 3 are the same or different and are selected from hydrogen, hydroxy, halogen.
신남알데하이드 유도체의 종래의 합성방법으로는 국내특허 제176415호 및 제213897호 등이 알려져 있으며 일반적으로, As a conventional method for synthesizing cinnamic aldehyde derivatives, Korean Patent Nos. 176415 and 213897 and the like are known.
1. 신남산(Cinnamic acid)를 이용하여 신남산 메틸에스텔(cinnamic methylester)를 합성하는 단계;1. Synthesis of cinnamic acid methyl ester (cinnamic methylester) using Cinnamic acid (Cinnamic acid);
2. 신남산 메틸에스텔(Cinnamic methylester)를 환원하여 신남산 알콜 (cinnamic alcohol)을 합성하는 단계;2. synthesizing cinnamic alcohol by reducing Cinnamic methylester;
3. 신남산 알콜(Cinnamic alcohol)을 산화시켜 신남알데하이드 (cinnamaldehyde)를 합성하는 단계로 이루어진다. 이를 반응식으로 나타내면 다음과 같다. 3. It consists of oxidizing Cinnamic alcohol to synthesize cinnamaldehyde. This is represented by the following scheme.
[반응식 1]Scheme 1
2'-하이드록시신남알데하이드(2'-Hydroxycinnamaldehyde(R : 2'-OH)를 예로하는 각 단계의 구체적인 합성방법은 다음과 같다.2'-Hydroxycinnamaldehyde (R: 2'-OH) as an example of the specific synthesis method of each step is as follows.
단계 1 : 2'-하이드록시신남산 메틸에스텔(2'-Hydroxycinnamic methylester)을 합성하는 단계.Step 1: Synthesis of 2'-Hydroxycinnamic methylester.
2'-하이드록시신남산(2'-hydroxycinnamic acid) 2 g (98 %)을 250 ml 둥근 플라스크에 넣고 메탄올로 완전히 녹인 후 1 ㎖의 진한황산 (H2SO4)를 천천히 적가하고 12 시간 동안 가열ㆍ환류한다. TLC를 이용하여 반응의 종료를 확인 한 후 감압농축한다. 흰색의 고체를 에틸아세테이트를 이용하여 완전히 녹인 후 소듐바이카보네이트 용액을 이용하여 반응에 사용된 진한황산을 씻어낸 다음 증류수를 이용하여 소듐바이카보네이트를 씻어낸 후 감압 건조하여 2'-하이드록시신남산 메틸에스텔(2'-hydroxycinnamic methylester)를 얻는다.(수득량 : 2.1 g, 수율 96 %)2 g (98%) of 2'-hydroxycinnamic acid is placed in a 250 ml round flask, completely dissolved in methanol, and slowly added dropwise with 1 ml of concentrated sulfuric acid (H 2 SO 4 ) for 12 hours. Heat and reflux. After confirming the completion of the reaction using TLC, the mixture was concentrated under reduced pressure. The white solid was completely dissolved with ethyl acetate, washed with sodium bicarbonate solution using concentrated sodium sulfate, then washed with sodium bicarbonate with distilled water and dried under reduced pressure to remove 2'-hydroxycinnamic acid. Obtain 2'-hydroxycinnamic methylester. (Yield: 2.1 g, Yield 96%)
단계 2 : 2'-하이드록시신남산 알콜(2'-hydroxycinnamic alcohol)을 합성하는 단계.Step 2: synthesizing 2'-hydroxycinnamic alcohol.
250 ㎖ 둥근바닥플라스크에 2'-하이드록시신남산 메틸에스텔(2'-hydroxycinnamic methylester) (2.1 g)을 넣은 다음 질소가스를 둥근바닥 플라스크에 채운다. 그리고 무수 테트라하이드로퓨란 (THF) 50 ㎖를 이용하여 완전히 녹인 후 아세톤과 드라이아이스를 이용하여 플라스크 온도를 -75 ℃까지 냉각시킨다. 온도가 냉각된 후 다이아이소뷰틸알루미늄하이드라이드 (DIBAL-H)을 3 당량 첨가한다. TLC를 이용하여 반응의 종료를 확인한 다음 반응용액을 시트릭산 용액으로 씻고, 증류수로 씻어준다. 그리고 마그네슘설페이트 (MgSO4)를 이용하여 물을 제거한 후 감압농축 하여 0.8 g의 2'-하이드록시신남산 알콜(2'-hydroxycinnamic alcohol)을 얻는다. (수득량 : 0.8 g, 수율 : 45 %)2'-hydroxycinnamic methylester (2.1 g) is added to a 250 ml round bottom flask and nitrogen gas is charged into a round bottom flask. After complete dissolution with 50 ml of anhydrous tetrahydrofuran (THF), the flask was cooled to -75 ° C using acetone and dry ice. After the temperature has cooled down, 3 equivalents of diisobutylaluminum hydride (DIBAL-H) is added. After confirming the completion of the reaction using TLC, the reaction solution is washed with citric acid solution and washed with distilled water. Magnesium sulfate (MgSO 4 ) to remove the water and then concentrated under reduced pressure to obtain 0.8 g of 2'-hydroxycinnamic alcohol (2'-hydroxycinnamic alcohol). (Yield: 0.8 g, Yield: 45%)
단계 3 : 2'-하이드록시신남알데하이드(2'-hydroxycinnamaldehyde)를 합성하는 단계.Step 3: synthesizing 2'-hydroxycinnamaldehyde.
2'-하이드록시신남산 알콜(2'-hydroxycinnamic alcohol) 0.8 g을 250 ㎖ 둥근바닥플라스크에 넣고 아세톤-다이클로로메탄 (1 : 1)을 이용하여 완전히 녹인다. 그리고 MnO2를 첨가한 후 2 시간 동안 교반한다. 반응물을 여과하여 감압농축 후 실리카겔컬럼크로마토그래피를 실시하여 0.2 g의 2'-하이드록시신남알데하이드(2'- hydroxycinnamaldehyde)를 얻는다. (수득량 : 0.2 g, 수율 : 25 %)0.8 g of 2'-hydroxycinnamic alcohol is added to a 250 ml round bottom flask and completely dissolved in acetone-dichloromethane (1: 1). And MnO 2 is added, followed by stirring for 2 hours. The reaction product was filtered, concentrated under reduced pressure, and subjected to silica gel column chromatography to obtain 0.2 g of 2'-hydroxycinnamaldehyde. (Yield: 0.2 g, Yield: 25%)
상기의 합성방법에서 단계 1에서의 수율은 우수하다. 하지만 단계 2에서 다이아이소부틸알루미늄하이드라이드 (DIBAL-H)는 매우 독성이 강하고 불안정한 물질이며, 이 물질을 사용하기 위해 플라스크 외부온도를 -75 ℃까지 냉각시키는 것이 어렵고 공정상의 주의를 요하게 된다. 또한 3 단계의 합성과정이 필요하기 때문에 합성에 많은 시간이 소요되었고, 수율 또한 저조하였다.The yield in step 1 in the above synthesis method is excellent. However, in step 2, diisobutylaluminum hydride (DIBAL-H) is a highly toxic and unstable material, and in order to use it, it is difficult to cool the flask's external temperature to -75 ° C and requires process caution. In addition, since the three-step synthesis process is required, the synthesis takes a lot of time, and the yield is also low.
따라서, 보다 안전하고 취급이 용이한 반응물질을 사용하면서도 제조공정의 효율을 높일 수 있는 방법과 시간을 단축하는 합성방법이 계속 요구되었으나, 전체적인 반응속도와 수율 등을 만족시킬 수 있는 대체시약과 반응조건에 관한 연구결과가 발표된 바는 없다.Therefore, there has been a continuous need for a method that can increase the efficiency of the manufacturing process and a method of shortening the synthesis process while using a safer and easier to handle reactant, but alternative reagents and reactions can satisfy the overall reaction rate and yield No research on conditions has been published.
본 발명의 목적은, 종래의 보고 되어있는 방법에 사용한 반응물질인 독성이 강하고, 고가인 다이아이소부틸알루미늄하이드라이드 대신 보다 안전하고 취급이 용이한 탄산칼륨을 사용하여 저비용으로 대량생산이 가능한 합성법을 제공하고자 하는 것이다. 본 발명을 통하여 한번의 반응(One-step synthetic method)으로 대량생산이 가능한 합성법을 제공할 뿐만 아니라 수율과 생산에 소요되는 비용절감 측면에 있어서 종전의 방법보다 우수한 합성방법을 제공하고자 하는 것이다. An object of the present invention is to provide a synthetic method that can be mass-produced at low cost using potassium carbonate, which is safer and easier to handle, instead of the highly toxic and expensive diisobutylaluminum hydride used in the conventionally reported methods. It is to provide. Through the present invention, not only to provide a synthesis method that can be mass-produced in one reaction (one-step synthetic method), but also to provide a synthesis method superior to the conventional method in terms of yield and cost required for production.
또한, 본 발명의 목적은, 전체적인 공정의 개선으로 반응조건, 수율 등에서 공정효율이 향상되고 제조가 용이해진 새로운 신남알데하이드 유도체 (cinnamaldehyde derivatives)의 합성방법을 제공하는 것이다. It is also an object of the present invention to provide a method for synthesizing new cinnamaldehyde derivatives (cinnamaldehyde derivatives), which is easy to manufacture and improves process efficiency under reaction conditions, yields, etc. due to the improvement of the overall process.
상기와 같은 목적을 달성하기 위하여, 본 발명에서는 독성이 강하고 불안정한 다이아이소부틸알루미늄하이드라이드보다 비교적 독성이 약하고 안정한 탄산칼륨을 사용하였다. 또한, 3 단계의 과정을 통해 합성하는 과정을 1 단계로 줄임으로써 전체적인 수율에서 큰 차이가 없고 순도가 우수한 제품을 얻을 수 있는 신남알데하이드 유도체(cinnamaldehyde derivatives)의 새로운 합성방법을 제공한다.In order to achieve the above object, in the present invention, a relatively toxic and stable potassium carbonate is used, which is more toxic and unstable than diisobutyl aluminum hydride. In addition, by reducing the synthesis process through a three-step process to provide a new synthesis method of the cinnamaldehyde derivatives (cinnamaldehyde derivatives) that can obtain a product with excellent purity without significant difference in overall yield.
즉, 본 발명의 신남알데하이드 유도체의 제조방법은, 벤즈알데하이드 유도체(2)와 바이닐아세테이트(3)을 탄산칼륨과 물 존재하 아세토니트릴 또는 메탄올 용매중에서 가열, 환류시켜 신남알데하이드 유도체(1)을 제조하는 방법이다. That is, in the method for producing cinnamic aldehyde derivative of the present invention, benzaldehyde derivative (2) and vinyl acetate (3) are heated and refluxed in acetonitrile or methanol solvent in the presence of potassium carbonate and water to prepare cinnamic aldehyde derivative (1). That's how.
보다 상세하게는, 2-하이드록시 벤즈알데하이드, 바이닐아세테이트, 탄산칼륨 그리고 소량의 물을 첨가하고 아세토니트릴을 가한 후 40 시간 가열ㆍ환류 한다. 반응물을 냉각시킨 다음, 헥산-에틸아세테이트 (1 : 2)용액이 있는 분획 깔대기에 섞어준다. 다음 수산화나트륨 수용액을 이용하여 2 회 추출 후 염산 수용액을 이용하여 pH를 2 ∼ 3 정도로 조정한다. 산성으로 조정된 물 층을 메칠렌클로라이드를 이용하여 3 회 추출하고, pH 조정에 사용된 염산을 제거하기 위해 증류수로 3 회 씻는다. 유기용매 층을 분리하여 건조한 후 감압 농축하고 정제하여 고순도의 활성물질을 얻는다. 본 발명에서 탄산칼륨의 사용량은 출발물질에 대하여 1 ~ 2 당량이 바람직하며, 그 이하와 이상시는 수율에 영양을 끼쳐 바람직하지 못하다.More specifically, 2-hydroxy benzaldehyde, vinyl acetate, potassium carbonate and a small amount of water are added, and acetonitrile is added, followed by heating and reflux for 40 hours. The reaction is cooled and then mixed in a fraction funnel with hexane-ethyl acetate (1: 2) solution. Next, after extraction twice using aqueous sodium hydroxide solution, the pH is adjusted to 2-3 using aqueous hydrochloric acid solution. The acidified water layer is extracted three times with methylene chloride and washed three times with distilled water to remove hydrochloric acid used for pH adjustment. The organic solvent layer is separated, dried, concentrated under reduced pressure and purified to obtain a high purity active material. In the present invention, the amount of potassium carbonate used is preferably 1 to 2 equivalents based on the starting material, and less than or equal to nutrition yields yields, which is not preferable.
이를 반응식으로 나타내면 다음과 같다.This is represented by the following scheme.
[반응식 2]Scheme 2
상기식에서, R1, R2, R3은 같거나 다르며, 수소, 하이드록시, 할로겐으로부터 선택된다.Wherein R 1 , R 2 , R 3 are the same or different and are selected from hydrogen, hydroxy, halogen.
이하, 본 발명의 실시예를 기재한다.Hereinafter, the Example of this invention is described.
실시예 1. 신남알데하이드 유도체(1, R1=OH, R2=H, R3=H)의 제조방법.Example 1 Preparation of cinnamic aldehyde derivative (1, R 1 = OH, R 2 = H, R 3 = H).
출발물질인 2-하이드록시 벤즈알데하이드 1.22 g(1 당량, 10 mmol), 바이닐아세테이트 1.03 g(1.2 당량, 12 mmol), 탄산칼륨 1.65 g(1.2 당량, 12 mmol) 그리고 소량의 물을 첨가하고 아세토니트릴을 가한 후 40 시간 가열ㆍ환류 한다. 반응물을 냉각시킨 다음, 헥산-에틸아세테이트 (1 : 2)용액이 있는 분획 깔대기에 섞어준다. 다음 수산화나트륨 수용액을 이용하여 2 회 추출 후 염산 수용액을 이용하여 pH를 2 ~ 3 정도로 조정한다. 산성으로 조정된 물 층을 메칠렌클로라이드를 이용하여 3 회 추출하고, pH 조정에 사용된 염산을 제거하기 위해 증류수로 3 회 씻는다. 유기용매 층을 분리하여 건조한 후 감압 농축하고 정제하여 고순도의 표제화합물 2-하이드록시신남알데하이드 0.5 g을 얻는다.(수율 34 %)1.22 g (1 equivalent, 10 mmol) of 2-hydroxy benzaldehyde as starting material, 1.03 g (1.2 equivalents, 12 mmol) of vinyl acetate, 1.65 g (1.2 equivalents, 12 mmol) of potassium carbonate and a small amount of water were added and the aceto After adding nitrile, it is heated and refluxed for 40 hours. The reaction is cooled and then mixed in a fraction funnel with hexane-ethyl acetate (1: 2) solution. Next, after extraction twice with aqueous sodium hydroxide solution, the pH is adjusted to 2 to 3 using aqueous hydrochloric acid solution. The acidified water layer is extracted three times with methylene chloride and washed three times with distilled water to remove hydrochloric acid used for pH adjustment. The organic solvent layer was separated, dried, concentrated under reduced pressure and purified to give 0.5 g of the title compound 2-hydroxycinnaaldehyde with high purity (yield 34%).
실시예 2. 신남알데하이드 유도체(1, R1=Cl, R2=H, R3=H)의 제조방법.Example 2. Preparation of cinnamic aldehyde derivative (1, R 1 = Cl, R 2 = H, R 3 = H).
출발물질인 2-클로로 벤즈알데하이드 1.4 g(1 당량, 10 mmol), 바이닐아세테이트 1.03 g(1.2 당량, 12 mmol), 탄산칼륨 1.65 g(1.2 당량, 12 mmol) 그리고 소량의 물을 첨가하고 아세토니트릴을 가한 후 40 시간 가열ㆍ환류 한다. 반응물을 냉각시킨 다음, 헥산-에틸아세테이트 (1 : 2)용액이 있는 분획 깔대기에 섞어준다. 다음 수산화나트륨 수용액을 이용하여 2 회 추출 후 염산 수용액을 이용하여 pH를 2 ~ 3 정도로 조정한다. 산성으로 조정된 물 층을 메칠렌클로라이드를 이용하여 3 회 추출하고, pH 조정에 사용된 염산을 제거하기 위해 증류수로 3 회 씻는다. 유기용매 층을 분리하여 건조한 후 감압 농축하고 정제하여 고순도의 표제화합물 2-클로로신남알데하이드 0.66 g을 얻는다.(수율 40 %)1.4 g (1 equiv, 10 mmol) of 2-chloro benzaldehyde, 1.03 g (1.2 equiv, 12 mmol) of vinyl acetate, 1.65 g (1.2 equiv, 12 mmol) of potassium carbonate and a small amount of water were added and acetonitrile was added. After adding, heat and reflux for 40 hours. The reaction is cooled and then mixed in a fraction funnel with hexane-ethyl acetate (1: 2) solution. Next, after extraction twice with aqueous sodium hydroxide solution, the pH is adjusted to 2 to 3 using aqueous hydrochloric acid solution. The acidified water layer is extracted three times with methylene chloride and washed three times with distilled water to remove hydrochloric acid used for pH adjustment. The organic solvent layer was separated, dried, concentrated under reduced pressure, and purified to give 0.66 g of the title compound 2-chlorocinnaaldehyde with high purity (yield 40%).
실시예 3. 신남알데하이드 유도체(1, R1=Br, R2=H, R3=H)의 제조방법.Example 3 Preparation of cinnamic aldehyde derivative (1, R 1 = Br, R 2 = H, R 3 = H).
출발물질인 2-브로모 벤즈알데하이드 1.85 g(1 당량, 10 mmol), 바이닐아세테이트 1.03 g(1.2 당량, 12 mmol), 탄산칼륨 1.65 g(1.2 당량, 12 mmol) 그리고 소량의 물을 첨가하고 아세토니트릴을 가한 후 40 시간 가열ㆍ환류 한다. 반응물을 냉각시킨 다음, 헥산-에틸아세테이트 (1 : 2)용액이 있는 분획 깔대기에 섞어준다. 다음 수산화나트륨 수용액을 이용하여 2 회 추출 후 염산 수용액을 이용하여 pH를 2 ~ 3 정도로 조정한다. 산성으로 조정된 물 층을 메칠렌클로라이드를 이용하여 3 회 추출하고, pH 조정에 사용된 염산을 제거하기 위해 증류수로 3 회 씻는다. 유기용매 층을 분리하여 건조한 후 감압 농축하고 정제하여 고순도의 표제화합물 2-브로모신남알데하이드 0.84 g을 얻는다.(수율 40 %)1.85 g (1 equivalent, 10 mmol) of 2-bromo benzaldehyde, 1.03 g (1.2 equivalents, 12 mmol) of vinyl acetate, 1.65 g (1.2 equivalents, 12 mmol) of potassium carbonate and a small amount of water After adding nitrile, it is heated and refluxed for 40 hours. The reaction is cooled and then mixed in a fraction funnel with hexane-ethyl acetate (1: 2) solution. Next, after extraction twice with aqueous sodium hydroxide solution, the pH is adjusted to 2 to 3 using aqueous hydrochloric acid solution. The acidified water layer is extracted three times with methylene chloride and washed three times with distilled water to remove hydrochloric acid used for pH adjustment. The organic solvent layer was separated, dried, concentrated under reduced pressure and purified to give 0.84 g of the title compound 2-bromosinnamaldehyde with high purity (yield 40%).
실시예 4. 신남알데하이드 유도체(1, R1=H, R2=OH, R3=H)의 제조방법.Example 4 Preparation of cinnamic aldehyde derivative (1, R 1 = H, R 2 = OH, R 3 = H).
출발물질인 3-하이드록시 벤즈알데하이드 1.22 g(1 당량, 10 mmol), 바이닐아세테이트 1.03 g(1.2 당량, 12 mmol), 탄산칼륨 1.65 g(1.2 당량, 12 mmol) 그리고 소량의 물을 첨가하고 아세토니트릴을 가한 후 40 시간 가열ㆍ환류 한다. 반응물을 냉각시킨 다음, 헥산-에틸아세테이트 (1 : 2)용액이 있는 분획 깔대기에 섞어준다. 다음 수산화나트륨 수용액을 이용하여 2 회 추출 후 염산 수용액을 이용하여 pH를 2 ~ 3 정도로 조정한다. 산성으로 조정된 물 층을 메칠렌클로라이드를 이용하여 3 회 추출하고, pH 조정에 사용된 염산을 제거하기 위해 증류수로 3 회 씻는다. 유기용매 층을 분리하여 건조한 후 감압 농축하고 정제하여 고순도의 표제화합물 3-하이드록시신남알데하이드 0.63 g을 얻는다.(수율 43 %)1.22 g (1 equivalent, 10 mmol) of 3-hydroxy benzaldehyde, 1.03 g (1.2 equivalents, 12 mmol) of vinyl acetate, 1.65 g (1.2 equivalents, 12 mmol) of potassium carbonate and a small amount of water After adding nitrile, it is heated and refluxed for 40 hours. The reaction is cooled and then mixed in a fraction funnel with hexane-ethyl acetate (1: 2) solution. Next, after extraction twice with aqueous sodium hydroxide solution, the pH is adjusted to 2 to 3 using aqueous hydrochloric acid solution. The acidified water layer is extracted three times with methylene chloride and washed three times with distilled water to remove hydrochloric acid used for pH adjustment. The organic solvent layer was separated, dried, concentrated under reduced pressure and purified to give 0.63 g of the title compound 3-hydroxycinnaaldehyde of high purity (yield 43%).
상기 실시예 1 내지 4에 따라 제조된 화합물을 표 1에 요약하였다.The compounds prepared according to Examples 1-4 above are summarized in Table 1.
[표 1] TABLE 1
본 발명은 상기와 같이, 독성이 강하고 불안정한 다이아이소부틸알루미늄하이드라이드 대신 안전하고 취급이 용이한 탄산칼륨을 반응물질로 사용하고, 3 단계의 합성공정을 1 단계로 줄임으로써 제조공정시간을 단축한 안전하면서도 고수율, 고순도의 효율적인 방법으로 신남알데하이드 유도체(cinnamaldehyde derivatives)를 얻을 수 있다는 특장점이 있다.The present invention uses a safe and easy to handle potassium carbonate as a reactant instead of a highly toxic and unstable diisobutyl aluminum hydride as a reaction material, and reduces the manufacturing process time by reducing the three-step synthesis process to one step Cinnamic aldehyde derivatives can be obtained in a safe, high-yield, high-purity and efficient way.
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