KR100531117B1 - New 3,4-diexomethylene tetrahydropyrane derivatives, and process for preparing them - Google Patents

New 3,4-diexomethylene tetrahydropyrane derivatives, and process for preparing them Download PDF

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KR100531117B1
KR100531117B1 KR10-2003-0029741A KR20030029741A KR100531117B1 KR 100531117 B1 KR100531117 B1 KR 100531117B1 KR 20030029741 A KR20030029741 A KR 20030029741A KR 100531117 B1 KR100531117 B1 KR 100531117B1
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diexomethylene
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diethyl ether
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조용서
장문호
고훈영
배애님
차주환
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한국과학기술연구원
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    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/32—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members

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Abstract

본 발명은 신규 3,4-다이엑소메틸렌 테트라하이드로파이란 유도체와 이의 제조방법에 관한 것으로서, 더욱 상세하게는 1-치환된-3-트리메틸실란일메틸-3,4-펜타다이엔-1-올 유도체와 알데히드 유도체를 루이스 산 촉매 하에서 반응시켜 제조된 2,6-위치에 다양한 치환체가 도입된 다음 화학식 1로 표시되는 3,4-다이엑소메틸렌 테트라하이드로파이란 유도체와 이의 제조방법에 관한 것이다.The present invention relates to a novel 3,4-diexomethylene tetrahydropyran derivative and a preparation method thereof, and more particularly to 1-substituted-3-trimethylsilaneylmethyl-3,4-pentadien-1-ol The present invention relates to a 3,4-diexomethylene tetrahydropyrane derivative represented by Chemical Formula 1 followed by introduction of various substituents at the 2,6-position prepared by reacting a derivative with an aldehyde derivative under a Lewis acid catalyst.

상기 화학식 1에서, R1 및 R2는 각각 수소원자, C1∼C10의 포화 또는 불포화된 직쇄, 분쇄 또는 싸이클릭 알킬기, 및 방향족기 중에서 선택된다.In Formula 1, R 1 and R 2 are each selected from a hydrogen atom, a C 1 to C 10 saturated or unsaturated straight chain, crushed or cyclic alkyl group, and an aromatic group.

Description

신규 3,4-다이엑소메틸렌 테트라하이드로파이란 유도체 및 이들의 제조방법{New 3,4-diexomethylene tetrahydropyrane derivatives, and process for preparing them}New 3,4-diexomethylene tetrahydropyrane derivatives and process for preparing them {New 3,4-diexomethylene tetrahydropyrane derivatives, and process for preparing them}

본 발명은 신규 3,4-다이엑소메틸렌 테트라하이드로파이란 유도체와 이의 제조방법에 관한 것으로서, 더욱 상세하게는 1-치환된-3-트리메틸실란일메틸-3,4-펜타다이엔-1-올 유도체와 알데히드 유도체를 루이스 산 촉매 하에서 반응시켜 제조된 2,6-위치에 다양한 치환체가 도입된 다음 화학식 1로 표시되는 3,4-다이엑소메틸렌 테트라하이드로파이란 유도체와 이의 제조방법에 관한 것이다.The present invention relates to a novel 3,4-diexomethylene tetrahydropyran derivative and a preparation method thereof, and more particularly to 1-substituted-3-trimethylsilaneylmethyl-3,4-pentadien-1-ol The present invention relates to a 3,4-diexomethylene tetrahydropyrane derivative represented by Chemical Formula 1 followed by introduction of various substituents at the 2,6-position prepared by reacting a derivative with an aldehyde derivative under a Lewis acid catalyst.

[화학식 1][Formula 1]

상기 화학식 1에서, R1 및 R2는 각각 수소원자, C1∼C10의 포화 또는 불포화된 직쇄, 분쇄 또는 싸이클릭 알킬기, 및 방향족기 중에서 선택된다.In Formula 1, R 1 and R 2 are each selected from a hydrogen atom, a C 1 to C 10 saturated or unsaturated straight chain, crushed or cyclic alkyl group, and an aromatic group.

상기 화학식 1로 표시되는 3,4-다이엑소메틸렌 테트라하이드로파이란 유도체는 신규 화합물이다. 상기 화학식 1로 표시되는 신규 화합물은 헤테로고리의 C-3 및 C-4의 서로 이웃하는 위치에 이중결합기가 치환되어 있으므로, 두개의 이중결합기는 딜스-알더 반응(Diels-Alder 반응)을 통하여 두 개 혹은 세 개의 고리화합물을 손쉽게 제조할 수 있는 아주 중요한 중간체로 사용될 수 있다. 3,4-Diexomethylene tetrahydroparan derivative represented by the formula (1) is a novel compound. Since the new compound represented by Chemical Formula 1 is substituted with a double bond group at adjacent positions of C-3 and C-4 of the heterocycle, the two double bond groups are separated through Diels-Alder reaction (Diels-Alder reaction). It can be used as an important intermediate for the easy production of three or three ring compounds.

따라서, 본 발명은 딜스-알더 반응 등에 이용되어질 수 있는 신규 구조의 3,4-다이엑소메틸렌 테트라하이드로파이란 유도체와 이의 제조방법을 제공하는데 그 목적이 있다. Accordingly, an object of the present invention is to provide a 3,4-diexomethylene tetrahydroparan derivative having a novel structure which can be used in Diels-Alder reaction and the like and a method for preparing the same.

본 발명은 다음 화학식 1로 표시되는 3,4-다이엑소메틸렌 테트라하이드로파이란 유도체와 이의 제조방법을 그 특징으로 한다.The present invention is characterized by a 3,4-diexomethylene tetrahydroparan derivative represented by the following formula (1) and a method for producing the same.

[화학식 1][Formula 1]

상기 화학식 1에서, R1 및 R2는 각각 수소원자, C1∼C10의 포화 또는 불포화된 직쇄, 분쇄 또는 싸이클릭 알킬기, 및 방향족기 중에서 선택된다.In Formula 1, R 1 and R 2 are each selected from a hydrogen atom, a C 1 to C 10 saturated or unsaturated straight chain, crushed or cyclic alkyl group, and an aromatic group.

본 발명에 따른 상기 화학식 1로 표시되는 3,4-다이엑소메틸렌 테트라하이드로파이란 유도체의 제조방법은 다음 반응식 1에 나타낸 바와 같다.The method for preparing the 3,4-diexomethylene tetrahydroparan derivative represented by Chemical Formula 1 according to the present invention is as shown in the following Scheme 1.

상기 반응식 1에서, R1 및 R2는 각각 상기에서 정의한 바와 같다.In Scheme 1, R 1 and R 2 are each as defined above.

상기 반응식 1에 따른 본 발명의 제조방법은, 상기 화학식 2로 표시되는 1-치환된-3-트리메틸실란일메틸-3,4-펜타다이엔-1-올 유도체와 상기 화학식 3으로 표시되는 알데히드 유도체를 루이스 산 촉매 존재 하에서 반응시켜 2,6-위치에 치환체가 도입된 3,4-다이엑소메틸렌 테트라하이드로파이란 유도체를 제조하는 것으로 구성된다.In the preparation method of the present invention according to Scheme 1, the 1-substituted-3-trimethylsilaneylmethyl-3,4-pentadien-1-ol derivative represented by Chemical Formula 2 and the aldehyde represented by Chemical Formula 3 The derivative is reacted in the presence of a Lewis acid catalyst to prepare a 3,4-diexomethylene tetrahydroparan derivative having a substituent introduced at the 2,6-position.

상기 반응은 루이스 산 촉매 존재하에서 수행하는데 루이스 산 촉매는 통상의 촉매로서 예를 들면 트리메틸실릴 트리플루오로메탄술폰네이트(TMSOTf), 알루미늄 할라이드, 인듐(Ⅲ) 할라이드, 보론 할라이드, 티타늄(Ⅳ) 할라이드 등이 사용될 수 있으며, 바람직하기로는 트리메틸실릴 트리플루오로메탄술폰네이트(TMSOTf)을 사용하는 것이다. 루이스 산촉매는 상기 화학식 2로 표시되는 화합물에 대하여 1.0 ∼ 1.5 당량 범위 내에서 사용한다. 그리고, 상기 화학식 3으로 표시되는 알데히드 유도체는 상기 화학식 2로 표시되는 화합물에 대하여 1.0 ∼ 2.0 당량 범위 내에서 사용한다. 상기 반응온도는 -100 ∼ 상온 ℃, 바람직하기로는 -80 ∼ -60 ℃ 범위를 유지하도록 한다. 반응용매로는 통상의 유기용매 예를 들면 디메틸에테르, 디에틸에테르, 테트라하이드로푸란 등을 사용하도록 하며, 바람직하기로는 탈수된 유기용매를 사용하는 것이며, 특히 바람직하기로는 무수 디에틸에테르를 사용하는 것이다.The reaction is carried out in the presence of a Lewis acid catalyst, which is a conventional catalyst, for example trimethylsilyl trifluoromethanesulfonate (TMSOTf), aluminum halides, indium (III) halides, boron halides, titanium (IV) halides Etc. may be used, and preferably, trimethylsilyl trifluoromethanesulfonate (TMSOTf) is used. The Lewis acid catalyst is used in the range of 1.0 to 1.5 equivalents based on the compound represented by Chemical Formula 2. The aldehyde derivative represented by Chemical Formula 3 is used within the range of 1.0 to 2.0 equivalents relative to the compound represented by Chemical Formula 2. The reaction temperature is maintained at -100 to room temperature, preferably -80 to -60 ° C. As a reaction solvent, a conventional organic solvent such as dimethyl ether, diethyl ether, tetrahydrofuran, or the like is used. Preferably, a dehydrated organic solvent is used. Particularly preferably, anhydrous diethyl ether is used. will be.

상기 반응이 완료되면, 유기용매와 물을 사용하여 반응물을 추출한 후 유기층을 분리하여 건조, 감압 증류 및 정제하여 본 발명이 목적하는 상기 화학식 1로 표시되는 화합물을 얻는다. 이때 추출용매로는 디에틸에테르, 메틸렌클로리드, 에틸아세테이트를 사용할 수 있으며, 가장 적합한 추출용매는 디에틸에테르이다. 상기 정제는 유기합성 분야에서 일반적으로 사용되는 것으로, 관 칼럼크로마토그라피, 재결정 등이 포함될 수 있다. When the reaction is complete, the reaction product is extracted using an organic solvent and water, and then the organic layer is separated, dried, reduced pressure distillation and purification to obtain a compound represented by the formula (1). In this case, diethyl ether, methylene chloride, ethyl acetate may be used as the extraction solvent, and the most suitable extraction solvent is diethyl ether. The purification is generally used in the field of organic synthesis, and may include columnar column chromatography, recrystallization, and the like.

상기한 바와 같은 본 발명에 따르면, 출발물질로서 상기 화학식 2로 표시되는 1-치환된-3-트리메틸실란일메틸-3,4-펜타다이엔-1-올을 사용하여 3,4-다이엑소메틸렌 테트라하이드로파이란 유도체의 C-1 및 C-6 위치에 다양한 치환기가 도입된 신규 화합물을 손쉽게 제조할 수 있다. 또한, 본 발명의 제조방법은 한 단계의 반응 공정으로 구성되는 간단한 제조공법으로 이루어져 있고, 그 수율 및 순도가 매우 우수하고, 특히 수득된 상기 화학식 1로 표시되는 화합물은 C-1 및 C-6 위치의 치환기가 같은 방향으로 위치하는 시스형(cis form) 화합물이라는 점에서 특이성이 있다.According to the present invention as described above, 3,4-diexo using 1-substituted-3-trimethylsilaneylmethyl-3,4-pentadien-1-ol represented by the formula (2) as a starting material Novel compounds with various substituents at the C-1 and C-6 positions of the methylene tetrahydroparan derivatives can be readily prepared. In addition, the production method of the present invention consists of a simple manufacturing method consisting of a one-step reaction process, the yield and purity are very excellent, and the compound represented by the formula (1) obtained in particular is C-1 and C-6 There is a specificity in that the substituent at the position is a cis form compound located in the same direction.

이상에서 설명한 바와 같은 본 발명은 다음의 실시예에 의거하여 더욱 상세히 설명하겠는 바, 본 발명이 다음의 실시예에 의해 한정되는 것은 아니다.The present invention as described above will be described in more detail based on the following examples, but the present invention is not limited by the following examples.

실시예 1. 3,4-다이메틸렌-2,6-다이페닐-테트라하이드로파이란 제조Example 1. Preparation of 3,4-dimethylene-2,6-diphenyl-tetrahydroparan

무수 디에틸에테르 1.5 mL에 출발물질인 1-페닐-3-트리메틸실란일메틸-3,4-펜타다이엔-1-올(25 mg, 0.101 mmol)과 벤즈알데히드(21.5 mg, 0.202 mmol)를 녹이고 -78 ℃로 냉각시켰다. 트리메틸실릴 트리플루오로메탄술폰네이트(33.82 mg, 0.152 mmol)을 가하고 반응이 5시간 교반하였다. 디에틸에테르 10 mL와 물을 가하고 유기층을 분리, 건조 및 감압 증류한 후 관 칼럼크로마토그라피하여 순수한 생성물(80%)을 얻었다. In 1.5 mL of anhydrous diethyl ether, 1-phenyl-3-trimethylsilaneylmethyl-3,4-pentadien-1-ol (25 mg, 0.101 mmol) and benzaldehyde (21.5 mg, 0.202 mmol) were dissolved. Cooled to -78 ° C. Trimethylsilyl trifluoromethanesulfonate (33.82 mg, 0.152 mmol) was added and the reaction stirred for 5 hours. 10 mL of diethyl ether and water were added, the organic layer was separated, dried and distilled under reduced pressure, and then purified by column column chromatography to obtain a pure product (80%).

1H NMR(CDCl3) δ 2.55-2.80(m, 2H), 4.83(dd, 3.78, 14.11 Hz, 1H), 4.90(s, 1H), 5.18(s, 1H), 5.21(d, 5,36 Hz, 2H), 7.10-7.50(m, 10H); 13C NMR(CDCl3) δ 43.7, 80.1, 83.0, 110.9, 111.8, 126.3, 128.0, 128.2, 128.4, 128.5, 128.8, 140.2, 142.5, 145.5, 149.0; GC MS(m/z) 262(M+), 141(100%). 1 H NMR (CDCl 3 ) δ 2.55-2.80 (m, 2H), 4.83 (dd, 3.78, 14.11 Hz, 1H), 4.90 (s, 1H), 5.18 (s, 1H), 5.21 (d, 5,36 Hz, 2H), 7.10-7.50 (m, 10H); 13 C NMR (CDCl 3 ) δ 43.7, 80.1, 83.0, 110.9, 111.8, 126.3, 128.0, 128.2, 128.4, 128.5, 128.8, 140.2, 142.5, 145.5, 149.0; GC MS ( m / z ) 262 (M + ), 141 (100%).

실시예 2. 2-벤질-3,4-다이메틸렌-6-페닐-테트라하이드로파이란 제조Example 2. Preparation of 2-benzyl-3,4-dimethylene-6-phenyl-tetrahydroparan

무수 디에틸에테르 2.5 mL에 출발물질인 1-페닐-3-트리메틸실란일메틸-3,4-펜타다이엔-1-올(35 mg, 0.141 mmol)과 페닐아세트알데히드(24.3 mg, 0.202 mmol)를 녹이고 -78 ℃로 냉각시켰다. 트리메틸실릴 트리플루오로메탄술폰네이트(47.00 mg, 0.211 mmol)을 가하고 반응이 7.5시간 교반하였다. 디에틸에테르 15 mL와 물을 가하고 유기층을 분리, 건조 및 감압 증류한 후 관 칼럼크로마토그라피하여 순수한 생성물(91%)을 얻었다. In 2.5 mL of anhydrous diethyl ether, starting materials 1-phenyl-3-trimethylsilaneylmethyl-3,4-pentadien-1-ol (35 mg, 0.141 mmol) and phenylacetaldehyde (24.3 mg, 0.202 mmol) Was dissolved and cooled to -78 ° C. Trimethylsilyl trifluoromethanesulfonate (47.00 mg, 0.211 mmol) was added and the reaction stirred for 7.5 hours. 15 mL of diethyl ether and water were added, the organic layer was separated, dried and distilled under reduced pressure, and then purified by column column chromatography to obtain a pure product (91%).

1H NMR(CDCl3) δ 2.40-2.60(m, 1H), 2.72(dd, 2.79, 14.11 Hz, 1H), 3.08(dd, 3.75, 14.11 Hz, 1H), 3.21(dd, 4.37, 14.19 Hz, 1H), 4.30-4.42(m, 1H), 4.55(dd, 2.81, 11.47 Hz, 1H), 4.86(t, 1.82 Hz, 1H), 4.98(s, 1H), 5.18(t, 2.04 Hz, 1H), 5.28(s, 1H), 7.10-7.43(m, 10H); 13C NMR(CDCl3) δ 39.7, 42.9, 78.81, 79.81, 108.8, 110.8, 125.9, 126.4, 127.6, 128.5, 130.0, 139.3, 142.6, 145.7, 148.0; GC MS(m/z) 276(M+), 185(100%), 91. 1 H NMR (CDCl 3 ) δ 2.40-2.60 (m, 1H), 2.72 (dd, 2.79, 14.11 Hz, 1H), 3.08 (dd, 3.75, 14.11 Hz, 1H), 3.21 (dd, 4.37, 14.19 Hz, 1H), 4.30-4.42 (m, 1H), 4.55 (dd, 2.81, 11.47 Hz, 1H), 4.86 (t, 1.82 Hz, 1H), 4.98 (s, 1H), 5.18 (t, 2.04 Hz, 1H) , 5.28 (s, 1 H), 7.10-7.43 (m, 10 H); 13 C NMR (CDCl 3 ) δ 39.7, 42.9, 78.81, 79.81, 108.8, 110.8, 125.9, 126.4, 127.6, 128.5, 130.0, 139.3, 142.6, 145.7, 148.0; GC MS ( m / z ) 276 (M + ), 185 (100%), 91.

실시예 3. 2-에틸-3,4-다이메틸렌-6-페닐-테트라하이드로파이란 제조Example 3. Preparation of 2-ethyl-3,4-dimethylene-6-phenyl-tetrahydroparan

무수 디에틸에테르 2.5 mL에 출발물질인 1-페닐-3-트리메틸실란일메틸-3,4-펜타다이엔-1-올(35 mg, 0.141 mmol)과 프로피온알데히드(12.3 mg, 0.21 mmol)를 녹이고 -78 ℃로 냉각시켰다. 트리메틸실릴 트리플루오로메탄술폰네이트(47.00 mg, 0.211 mmol)을 가하고 반응이 7시간 교반하였다. 디에틸에테르 15 mL와 물을 가하고 유기층을 분리, 건조 및 감압 증류한 후 관 칼럼크로마토그라피하여 순수한 생성물(98%)을 얻었다.  In 2.5 mL of anhydrous diethyl ether, starting materials 1-phenyl-3-trimethylsilaneylmethyl-3,4-pentadien-1-ol (35 mg, 0.141 mmol) and propionaldehyde (12.3 mg, 0.21 mmol) were added. It was dissolved and cooled to -78 ° C. Trimethylsilyl trifluoromethanesulfonate (47.00 mg, 0.211 mmol) was added and the reaction stirred for 7 hours. 15 mL of diethyl ether and water were added, the organic layer was separated, dried and distilled under reduced pressure, and then purified by column column chromatography to obtain a pure product (98%).

1H NMR(CDCl3) δ 1.06(t, 7.36 Hz, 3H), 1.68-1.83(m, 1H), 1.83-2.00(m, 1H), 2.65(dd, 2.74, 13.99 Hz, 1H), 4.81(s, 1H), 4.86(s, 1H), 5.13(s, 1H), 5.21(s, 1H), 7.17-7.40(m, 5H); 13C NMR(CDCl3) δ 10.5, 26.0, 43.2, 79.2, 80.2, 108.1, 110.4, 126.1, 127.8, 128.7, 142.9, 146.1, 148.1; GC MS(m/z) 214(M+), 185, 93(100%). 1 H NMR (CDCl 3 ) δ 1.06 (t, 7.36 Hz, 3H), 1.68-1.83 (m, 1H), 1.83-2.00 (m, 1H), 2.65 (dd, 2.74, 13.99 Hz, 1H), 4.81 ( s, 1H), 4.86 (s, 1H), 5.13 (s, 1H), 5.21 (s, 1H), 7.17-7.40 (m, 5H); 13 C NMR (CDCl 3 ) δ 10.5, 26.0, 43.2, 79.2, 80.2, 108.1, 110.4, 126.1, 127.8, 128.7, 142.9, 146.1, 148.1; GC MS ( m / z ) 214 (M + ), 185, 93 (100%).

실시예 4. 2,6-다이벤질-3,4-다이메틸렌-테트라하이드로파이란 제조Example 4. Preparation of 2,6-dibenzyl-3,4-dimethylene-tetrahydroparan

무수 디에틸에테르 2.5 mL에 출발물질인 1-벤질-3-트리메틸실란일메틸-3,4-펜타다이엔-1-올(39 mg, 0.150 mmol)과 페닐아세트알데히드(27.1 mg, 0.225 mmol)를 녹이고 -78 ℃로 냉각시켰다. 트리메틸실릴 트리플루오로메탄술폰네이트(50.1 mg, 0.225 mmol)을 가하고 반응이 5시간 교반하였다. 디에틸에테르 15 mL와 물을 가하고 유기층을 분리, 건조 및 감압 증류한 후 관 칼럼크로마토그라피하여 순수한 생성물(91%)을 얻었다.  In 2.5 mL of anhydrous diethyl ether, starting materials 1-benzyl-3-trimethylsilanylmethyl-3,4-pentadien-1-ol (39 mg, 0.150 mmol) and phenylacetaldehyde (27.1 mg, 0.225 mmol) Was dissolved and cooled to -78 ° C. Trimethylsilyl trifluoromethanesulfonate (50.1 mg, 0.225 mmol) was added and the reaction stirred for 5 hours. 15 mL of diethyl ether and water were added, the organic layer was separated, dried and distilled under reduced pressure, and then purified by column column chromatography to obtain a pure product (91%).

1H NMR(CDCl3) δ 2.20-3.30(m, 2H), 2.64(dd, 4.90, 14.05 Hz, 1H), 2.80-2.95(m, 2H), 3.10(dd, 3.57, 13.73 Hz, 1H), 3.54-3.70(m, 1H), 4.00-4.13(m, 1H), 4.72(s, 1H), 4.89(s, 1H), 5.05(s, 1H), 5.18(s, 1H), 7.00-7.28(m, 10H); 13C NMR(CDCl3) δ 39.2, 41.1, 42.7, 78.6, 79.5, 108.2, 110.6, 126.4, 128.5, 129.7, 129.8, 130.0, 139.4, 145.8, 148.5; GC MS(m/z) 290(M+), 199(100%), 91. 1 H NMR (CDCl 3 ) δ 2.20-3.30 (m, 2H), 2.64 (dd, 4.90, 14.05 Hz, 1H), 2.80-2.95 (m, 2H), 3.10 (dd, 3.57, 13.73 Hz, 1H), 3.54-3.70 (m, 1H), 4.00-4.13 (m, 1H), 4.72 (s, 1H), 4.89 (s, 1H), 5.05 (s, 1H), 5.18 (s, 1H), 7.00-7.28 ( m, 10 H); 13 C NMR (CDCl 3 ) δ 39.2, 41.1, 42.7, 78.6, 79.5, 108.2, 110.6, 126.4, 128.5, 129.7, 129.8, 130.0, 139.4, 145.8, 148.5; GC MS ( m / z ) 290 (M + ), 199 (100%), 91.

실시예 5. 6-벤질-3,4-다이메틸렌-2-프로필-테트라하이드로파이란 제조Example 5. Preparation of 6-benzyl-3,4-dimethylene-2-propyl-tetrahydroparan

무수 디에틸에테르 2.5 mL에 출발물질인 1-벤질-3-트리메틸실란일메틸-3,4-펜타다이엔-1-올(39 mg, 0.150 mmol)과 부틸알데히드(16.2 mg, 0.225 mmol)를 녹이고 -78 ℃로 냉각시켰다. 트리메틸실릴 트리플루오로메탄술폰네이트(50.1 mg, 0.225 mmol)을 가하고 반응이 4시간 교반하였다. 디에틸에테르 15 mL와 물을 가하고 유기층을 분리, 건조 및 감압 증류한 후 관 칼럼크로마토그라피하여 순수한 생성물(92%)을 얻었다. In 2.5 mL of anhydrous diethyl ether, starting materials 1-benzyl-3-trimethylsilaneylmethyl-3,4-pentadien-1-ol (39 mg, 0.150 mmol) and butylaldehyde (16.2 mg, 0.225 mmol) were added. It was dissolved and cooled to -78 ° C. Trimethylsilyl trifluoromethanesulfonate (50.1 mg, 0.225 mmol) was added and the reaction stirred for 4 hours. 15 mL of diethyl ether and water were added, and the organic layer was separated, dried and distilled under reduced pressure, and then purified by column column chromatography to obtain a pure product (92%).

1H NMR(CDCl3) δ 0.91(t, 7.32 Hz, 3H), 1.33-1.45(m, 1H), 1.48-1.78(m, 3H), 2.17-2.42(m, 2H), 2.72(dd, 5.77, 13.75 Hz, 1H), 2.98(dd, 7.14, 13.75 Hz, 1H), 3.60-3.75(m, 1H), 3.75-3.85(m, 1H), 4.71(t, 1.95 Hz, 1H), 4.82(s, 1H), 5.05(t, 2.11 Hz, 1H), 5.15(s, 1H), 7.07-7.34(m, 5H); 13C NMR(CDCl3) δ 14.4, 19.2, 34.9, 41.0, 43.0, 78.2, 78.6, 107.6, 110.1, 126.5, 128.5, 129.8, 139.0, 146.1, 148.9; GC MS(m/z) 242(M+), 199, 151, 91(100%). 1 H NMR (CDCl 3 ) δ 0.91 (t, 7.32 Hz, 3H), 1.33-1.45 (m, 1H), 1.48-1.78 (m, 3H), 2.17-2.42 (m, 2H), 2.72 (dd, 5.77 , 13.75 Hz, 1H), 2.98 (dd, 7.14, 13.75 Hz, 1H), 3.60-3.75 (m, 1H), 3.75-3.85 (m, 1H), 4.71 (t, 1.95 Hz, 1H), 4.82 (s , 1H), 5.05 (t, 2.11 Hz, 1H), 5.15 (s, 1H), 7.07-7.34 (m, 5H); 13 C NMR (CDCl 3 ) δ 14.4, 19.2, 34.9, 41.0, 43.0, 78.2, 78.6, 107.6, 110.1, 126.5, 128.5, 129.8, 139.0, 146.1, 148.9; GC MS ( m / z ) 242 (M + ), 199, 151, 91 (100%).

실시예 6. 6-벤질-2-퓨란-3-일-3,4-다이메틸렌-테트라하이드로파이란 제조Example 6 Preparation of 6-benzyl-2-furan-3-yl-3,4-dimethylene-tetrahydropyran

무수 디에틸에테르 2.5 mL에 출발물질인 1-벤질-3-트리메틸실란일메틸-3,4-펜타다이엔-1-올(39 mg, 0.150 mmol)과 퓨란-3-카발데히드(21.6 mg, 0.225 mmol)를 녹이고 -78 ℃로 냉각시켰다. 트리메틸실릴 트리플루오로메탄술폰네이트(50.1 mg, 0.225 mmol)을 가하고 반응이 4시간 교반하였다. 디에틸에테르 15 mL와 물을 가하고 유기층을 분리, 건조 및 감압 증류한 후 관 칼럼크로마토그라피하여 순수한 생성물(95%)을 얻었다. In 2.5 mL of anhydrous diethyl ether, starting materials 1-benzyl-3-trimethylsilanylmethyl-3,4-pentadien-1-ol (39 mg, 0.150 mmol) and furan-3-carbaldehyde (21.6 mg, 0.225 mmol) was dissolved and cooled to -78 ° C. Trimethylsilyl trifluoromethanesulfonate (50.1 mg, 0.225 mmol) was added and the reaction stirred for 4 hours. 15 mL of diethyl ether and water were added, the organic layer was separated, dried and distilled under reduced pressure, and then purified by column column chromatography to obtain a pure product (95%).

1H NMR(CDCl3) δ 2.16-2.40(m, 2H), 2.74(dd, 7.20, 13.52 Hz, 1H), 3.05(dd, 5.57, 13.53 Hz, 1H), 3.68-3.78(m, 1H), 4.53(s, 1H), 4.73(s, 1H), 5.00(s, 1H), 5.07(s, 1H), 5.16(s, 1H), 6.42(s, 1H), 7.03-7.30(m, 5H), 7.43(d, 6.18 Hz, 2H); 13C NMR(CDCl3) δ 40.3, 43.0, 75.3, 78.7, 110.3, 110.7, 110.9, 124.7, 126.7, 128.7, 130.0, 138.4, 141.0, 143.4, 144.9, 147.8; GC MS(m/z) 266(M+), 175, 91(100%). 1 H NMR (CDCl 3 ) δ 2.16-2.40 (m, 2H), 2.74 (dd, 7.20, 13.52 Hz, 1H), 3.05 (dd, 5.57, 13.53 Hz, 1H), 3.68-3.78 (m, 1H), 4.53 (s, 1H), 4.73 (s, 1H), 5.00 (s, 1H), 5.07 (s, 1H), 5.16 (s, 1H), 6.42 (s, 1H), 7.03-7.30 (m, 5H) , 7.43 (d, 6.18 Hz, 2H); 13 C NMR (CDCl 3 ) δ 40.3, 43.0, 75.3, 78.7, 110.3, 110.7, 110.9, 124.7, 126.7, 128.7, 130.0, 138.4, 141.0, 143.4, 144.9, 147.8; GC MS ( m / z ) 266 (M + ), 175, 91 (100%).

실시예 7. 6-(3,4-다이메틸렌-6-페닐-테트라하이드로파이란-2-일)-2,3-다이하이드로-벤조[1,4]다이옥신 제조Example 7. Preparation of 6- (3,4-dimethylene-6-phenyl-tetrahydropharan-2-yl) -2,3-dihydro-benzo [1,4] dioxin

무수 디에틸에테르 2.5 mL에 출발물질인 1-페닐-3-트리메틸실란일메틸-3,4-펜타다이엔-1-올(25 mg, 0.101 mmol)과 2,3-다이하이드로-벤조[1,4]다이옥신-6-카발데히드(24.8 mg, 0.151 mmol)를 녹이고 -78 ℃로 냉각시켰다. 트리메틸실릴 트리플루오로메탄술폰네이트(33.82 mg,0.152 mmol)을 가하고 반응이 4시간 교반하였다. 디에틸에테르 10 mL와 물을 가하고 유기층을 분리, 건조 및 감압 증류한 후 관 칼럼크로마토그라피하여 순수한 생성물(100%)을 얻었다. In 2.5 mL of anhydrous diethyl ether, starting material 1-phenyl-3-trimethylsilanylmethyl-3,4-pentadien-1-ol (25 mg, 0.101 mmol) and 2,3-dihydro-benzo [1 , 4] dioxin-6-carbaldehyde (24.8 mg, 0.151 mmol) was dissolved and cooled to -78 ° C. Trimethylsilyl trifluoromethanesulfonate (33.82 mg, 0.152 mmol) was added and the reaction stirred for 4 hours. 10 mL of diethyl ether and water were added, and the organic layer was separated, dried and distilled under reduced pressure, and then purified by column column chromatography to obtain a pure product (100%).

1H NMR(CDCl3) δ 2.54-2.73(m, 2H), 4.24(s, 4H), 4.31(s, 1H), 4.69(dd, 3.74, 10.34 Hz, 1H), 4.87(s, 1H), 5.02(s, 1H), 5.17(s, 1H), 5.21(s, 1H), 6.78-7.00(m, 3H), 7.20-7.47(m, 5H); 13C NMR(CDCl3) δ 43.7, 64.8, 80.0, 82.6, 110.8, 111.8, 117.2, 117.3, 121.6, 126.3, 128.0, 128.8, 133.7, 142.6, 143.6, 143.7, 145.5, 148.9; GC MS(m/z) 320(M+), 214(100%), 115. 1 H NMR (CDCl 3 ) δ 2.54-2.73 (m, 2H), 4.24 (s, 4H), 4.31 (s, 1H), 4.69 (dd, 3.74, 10.34 Hz, 1H), 4.87 (s, 1H), 5.02 (s, 1H), 5.17 (s, 1H), 5.21 (s, 1H), 6.78-7.00 (m, 3H), 7.20-7.47 (m, 5H); 13 C NMR (CDCl 3 ) δ 43.7, 64.8, 80.0, 82.6, 110.8, 111.8, 117.2, 117.3, 121.6, 126.3, 128.0, 128.8, 133.7, 142.6, 143.6, 143.7, 145.5, 148.9; GC MS ( m / z ) 320 (M + ), 214 (100%), 115.

실시예 8. 6-벤질-3,4-다이메틸렌-2-아세톡시에틸-테트라하이드로파이란Example 8. 6-benzyl-3,4-dimethylene-2-acetoxyethyl-tetrahydroparan

무수 디에틸에테르 2.5 mL에 출발물질인 1-벤질-3-트리메틸실란일메틸-3,4-펜타다이엔-1-올(39 mg, 0.150 mmol)과 3-아세톡시-1-프로판알데히드(26.1 mg, 0.225 mmol)를 녹이고 -78 ℃로 냉각시켰다. 트리메틸실릴 트리플루오로메탄술폰네이트(50.1 mg, 0.225 mmol)을 가하고 반응이 4.5시간 교반하였다. 디에틸에테르 15 mL와 물을 가하고 유기층을 분리, 건조 및 감압 증류한 후 관 칼럼크로마토그라피하여 순수한 생성물(94%)을 얻었다. In 2.5 mL of anhydrous diethyl ether, starting materials 1-benzyl-3-trimethylsilanylmethyl-3,4-pentadien-1-ol (39 mg, 0.150 mmol) and 3-acetoxy-1-propanealdehyde ( 26.1 mg, 0.225 mmol) was dissolved and cooled to -78 ° C. Trimethylsilyl trifluoromethanesulfonate (50.1 mg, 0.225 mmol) was added and the reaction stirred for 4.5 hours. 15 mL of diethyl ether and water were added, the organic layer was separated, dried and distilled under reduced pressure, and then purified by column column chromatography to obtain a pure product (94%).

1H NMR(CDCl3) δ 1.85-2.00(m, 1H), 2.02(s, 3H), 2.08-2.32(m, 2H), 2.34-2.45(m, 1H), 2.71(dd, 5.71, 13.95 Hz, 1H), 2.94(dd, 7.20, 13.65 Hz, 1H), 3.62-3.76(m, 1H), 3.90-3.99(m, 1H), 4.10-4.32(m, 2H), 4.73(s, 1H), 4.80(s, 1H), 5.06(s, 1H), 5.17(s, 1H), 7.12-7.37(m, 5H); 13C NMR(CDCl3) δ 21.21, 31.71, 40.65, 48.68, 61.67, 75.09, 78.45, 107.74, 110.52, 126.48, 128.45, 129.59, 138.62, 145.33, 147.82, 171.28; GC MS(m/z) 286(M+), 226, 195, 91(100%). 1 H NMR (CDCl 3 ) δ 1.85-2.00 (m, 1H), 2.02 (s, 3H), 2.08-2.32 (m, 2H), 2.34-2.45 (m, 1H), 2.71 (dd, 5.71, 13.95 Hz , 1H), 2.94 (dd, 7.20, 13.65 Hz, 1H), 3.62-3.76 (m, 1H), 3.90-3.99 (m, 1H), 4.10-4.32 (m, 2H), 4.73 (s, 1H), 4.80 (s, 1H), 5.06 (s, 1H), 5.17 (s, 1H), 7.12-7.37 (m, 5H); 13 C NMR (CDCl 3 ) δ 21.21, 31.71, 40.65, 48.68, 61.67, 75.09, 78.45, 107.74, 110.52, 126.48, 128.45, 129.59, 138.62, 145.33, 147.82, 171.28; GC MS ( m / z ) 286 (M + ), 226, 195, 91 (100%).

본 발명에 따른 상기 화학식 1로 표시되는 신규 화합물은 헤테로고리의 C-3 및 C-4의 서로 이웃하는 위치에 이중결합기가 치환되어 있으므로, 딜스-알더 반응(Diels-Alder 반응)을 통하여 두 개 혹은 세 개의 고리화합물을 손쉽게 제조할 수 있는 중간체로 유용하게 사용될 수 있다.The novel compound represented by Chemical Formula 1 according to the present invention is a double bond group is substituted at the position adjacent to each other of the C-3 and C-4 of the hetero ring, two through the Diels-Alder reaction (Diels-Alder reaction) Alternatively, it may be usefully used as an intermediate for easily preparing three cyclic compounds.

또한, 본 발명에 따른 제조방법은 1-치환된-3-트리메틸실란일메틸-3,4-펜타다이엔-1-올을 출발물질로 하여 한 단계의 반응 공정에 의해 높은 수율로 목적하는 상기 화학식 1로 표시되는 신규 화합물을 제조할 수 있고, 그리고 수득된 상기 화학식 1로 표시되는 화합물은 C-1 및 C-6 위치의 치환기가 같은 방향으로 위치하는 시스형(cis form) 화합물만을 수득하는데 특히 유용하다.In addition, the production method according to the present invention is a target of the above-mentioned high yield by a one-step reaction process using 1-substituted-3-trimethylsilaneylmethyl-3,4-pentadien-1-ol as a starting material A novel compound represented by the formula (1) can be prepared, and the compound represented by the formula (1) obtained only obtains a cis form compound in which substituents of the C-1 and C-6 positions are located in the same direction. Particularly useful.

Claims (7)

다음 화학식 1로 표시되는 3,4-다이엑소메틸렌 테트라하이드로파이란 유도체:3,4-Diexomethylene tetrahydroparan derivative represented by the following formula (1): [화학식 1][Formula 1] 상기 화학식 1에서, R1은 C1∼C10의 알킬기, 아세톡시에틸기, 페닐기, 벤질기, 퓨란기 및 2,3-디하이드로-벤조[1,4]다이옥신기 중에서 선택되고; R2는 페닐기 및 벤질기 중에서 선택된다.In Formula 1, R 1 is an alkyl group of C 1 ~C 10, an acetoxy group, a phenyl group, a benzyl group, a furan group and a 2,3-dihydroimidazole is selected from benzo [1,4] dioxin group; R 2 is selected from a phenyl group and a benzyl group. 다음 화학식 2로 표시되는 1-치환된-3-트리메틸실란일메틸-3,4-펜타다이엔-1-올 유도체와 다음 화학식 3으로 표시되는 알데히드 유도체를 1-substituted-3-trimethylsilanylmethyl-3,4-pentadien-1-ol derivative represented by the following formula (2) and an aldehyde derivative represented by the following formula (3) 트리메틸실릴 트리플루오로메탄술폰네이트(TMSOTf), 알루미늄 할라이드, 인듐(Ⅲ) 할라이드, 보론 할라이드 및 티타늄(Ⅳ) 할라이드 중에서 선택된 루이스 산 촉매와, 디메틸에테르, 디에틸에테르 및 테트라하이드로푸란 중에서 선택된 용매를 사용하여 -80 ∼ -60 ℃ 온도에서 반응시켜 제조하는 것을 특징으로 하는 다음 화학식 1로 표시되는 3,4-다이엑소메틸렌 테트라하이드로파이란 유도체의 제조방법 :Lewis acid catalyst selected from trimethylsilyl trifluoromethanesulfonate (TMSOTf), aluminum halide, indium (III) halide, boron halide and titanium (IV) halide, and a solvent selected from dimethyl ether, diethyl ether and tetrahydrofuran Method for producing a 3,4-diexomethylene tetrahydropyran derivative represented by the following formula (1), characterized in that the reaction is produced at -80 to -60 ℃ temperature using: 상기 반응식에서, R1 및 R2는 각각 수소원자, C1∼C10의 포화 또는 불포화된 직쇄, 분쇄 또는 싸이클릭 알킬기, 및 방향족기 중에서 선택된다.In the above scheme, R 1 and R 2 are each selected from a hydrogen atom, a C 1 to C 10 saturated or unsaturated straight chain, pulverized or cyclic alkyl group, and an aromatic group. 삭제delete 제 2 항에 있어서, 상기 루이스 산 촉매로는 트리메틸실릴 트리플루오로메탄술폰네이트(TMSOTf)를 사용하는 것을 특징으로 하는 제조방법.The method according to claim 2, wherein the Lewis acid catalyst uses trimethylsilyl trifluoromethanesulfonate (TMSOTf). 삭제delete 제 2 항에 있어서, 상기 반응 용매로는 무수의 디에틸에테르를 사용하는 것을 특징으로 하는 제조방법.The method according to claim 2, wherein anhydrous diethyl ether is used as the reaction solvent. 삭제delete
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