KR101305434B1 - Stereoselective 3,4-dimethyleneoxepane compounds substituted and process for preparing them - Google Patents

Stereoselective 3,4-dimethyleneoxepane compounds substituted and process for preparing them Download PDF

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KR101305434B1
KR101305434B1 KR1020110014803A KR20110014803A KR101305434B1 KR 101305434 B1 KR101305434 B1 KR 101305434B1 KR 1020110014803 A KR1020110014803 A KR 1020110014803A KR 20110014803 A KR20110014803 A KR 20110014803A KR 101305434 B1 KR101305434 B1 KR 101305434B1
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dimethylene
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조용서
민선준
이재균
배애님
푼나 레디 울라프
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한국과학기술연구원
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
    • C07D313/02—Seven-membered rings
    • C07D313/04—Seven-membered rings not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
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Abstract

본 발명은 3,4-다이메틸렌옥세페인 화합물과 이의 제조방법에 관한 것으로서, 더욱 상세하게는 알렌닐 알코올 화합물과 알데하이드 화합물을 특정의 루이스산과 특정의 용매 존재하에서 프린스 고리화 반응을 수행하여 제조된, 입체선택성을 가지는 하기 화학식 1로 표시되는 3,4-다이메틸렌옥세페인 화합물과 이 화합물의 제조방법에 관한 것이다.
[화학식 1]

Figure 112011011962926-pat00018

상기 화학식 1에서, R1은 수소원자; C1-6 알킬기; 또는 페닐기를 나타내고, R2는 C1-6 알킬기; 할로, 나이트로, C1-6 알킬, 및 C1-6 알콕시 중에서 선택된 1 내지 3개의 치환기로 치환 또는 비치환된 페닐기; 퓨란일기; 또는 티오펜일기를 나타낸다.The present invention relates to a 3,4-dimethylene oxepine compound and a method for preparing the same, and more particularly, to an allenyl alcohol compound and an aldehyde compound prepared by performing a prince cyclization reaction in the presence of a specific Lewis acid and a specific solvent. And a 3,4-dimethylene oxepine compound represented by the following formula (1) having stereoselectivity and a method for producing the compound.
[Formula 1]
Figure 112011011962926-pat00018

In Formula 1, R 1 is a hydrogen atom; C 1-6 alkyl group; Or a phenyl group, R 2 is a C 1-6 alkyl group; A phenyl group unsubstituted or substituted with 1 to 3 substituents selected from halo, nitro, C 1-6 alkyl, and C 1-6 alkoxy; Furanyl group; Or a thiophenyl group.

Description

입체선택성 3,4―다이메틸렌옥세페인 화합물과 이의 제조방법 {Stereoselective 3,4-dimethyleneoxepane compounds substituted and process for preparing them} Stereoselective 3,4-dimethylene oxepine compound and preparation method thereof {Stereoselective 3,4-dimethyleneoxepane compounds substituted and process for preparing them}

본 발명은 입체선택성을 가지는 3,4-다이메틸렌옥세페인 화합물과 이의 제조방법에 관한 것이다.
The present invention relates to a 3,4-dimethylene oxepine compound having stereoselectivity and a method for preparing the same.

산소원자를 포함하는 7각형의 헤테로고리 즉, 옥세페인 (Oxepane)은 생체활성을 가지는 천연물 또는 의약품을 구성하는 주요한 모핵 구조이다. 옥세페인 (Oxepane)을 기본골격으로 하는 천연물과 의약품은 많이 알려져 있다. [Angew. Chem. Int. Ed. 1996, 35, 589; Nature 1998, 393, 264] 옥세페인 (Oxepane) 구조를 가지는 고리화합물은 그 자체로서도 생활성이 우수한 것으로 알려져 있다. Hexagonal heterocycles containing oxygen atoms, ie, oxephane, are the main nucleus structures that make up natural products or medicines with bioactivity. There are many known natural products and medicines that are based on Oxepane. Angew. Chem. Int. Ed . 1996, 35, 589; Nature 1998, 393, 264] Cyclic compounds having an oxepane structure are known to be excellent in their own life.

그러나, 옥세페인 (Oxepane) 구조의 화합물을 합성하기가 당업자 수준에서 용이하지 않으며, 더욱이 헤테로원자인 산소원자의 양쪽 C2 및 C7 위치에 치환체를 입체선택적으로 도입하기란 더욱 어렵다.However, it is not easy at the level of those skilled in the art to synthesize a compound of Oxepane structure, and moreover it is more difficult to stereoselectively introduce substituents at both C2 and C7 positions of a heteroatom oxygen atom.

본 발명이 특징으로 하는 화합물은 옥세페인 (Oxepane)의 C2 및 C7 위치에 특정의 치환기가 치환체가 도입되어 입체선택성을 가지고 있고, C3 및 C4 위치에는 각각 메틸렌 그룹이 도입된 신규 구조의 3,4-다이메틸렌옥세페인 화합물이다. 이러한 본 발명의 입체선택성을 가지는 3,4-다이메틸렌옥세페인 화합물은 천연물 또는 의약품 합성용 중간체로 유용하게 사용될 수 있고, 특히 두 개의 엑소메틸렌 그룹을 이용하여 디엘스-올더 반응 (Diels-Alder reaction)에 의해 다양한 다중고리 화합물을 합성할 수도 있다.
The compound characterized by the present invention has stereoselectivity by introducing a substituent into the C2 and C7 positions of Oxepane (Oxepane), and 3,4 of the novel structure in which the methylene group is introduced into the C3 and C4 positions, respectively. It is a dimethyl oxepine compound. The 3,4-dimethylene oxepine compound having the stereoselectivity of the present invention can be usefully used as an intermediate for synthesizing natural products or pharmaceuticals, and in particular, the Diels-Alder reaction using two exomethylene groups. Various polycyclic compounds can be synthesized by

본 발명은 C2 및/또는 C7 위치에 치환기가 결합된 입체선택성을 가지는 3,4-다이메틸렌옥세페인 화합물을 제공하는 것을, 발명이 해결하고자 하는 과제로 한다.An object of the present invention is to provide a 3,4-dimethylene oxepine compound having stereoselectivity in which a substituent is bonded to a C2 and / or C7 position.

본 발명은 3,4-다이메틸렌옥세페인 화합물의 제조방법을 제공하는 것을, 발명이 해결하고자 하는 과제로 한다.
The present invention provides a method for producing a 3,4-dimethylene oxephane compound, as an object of the present invention.

본 발명은 하기 화학식 1로 표시되는 입체선택성을 가지는 3,4-다이메틸렌옥세페인 화합물과 이의제조방법을 제공함으로써, 본 발명의 과제를 해결한다.This invention solves the subject of this invention by providing the 3, 4- dimethyl oxepine compound which has the stereoselectivity represented by following General formula (1), and its manufacturing method.

[화학식 1][Formula 1]

Figure 112011011962926-pat00001
Figure 112011011962926-pat00001

R1은 수소원자; C1-6 알킬기; 또는 페닐기를 나타내고, R 1 is a hydrogen atom; C 1-6 alkyl group; Or a phenyl group,

R2는 C1-6 알킬기; 할로, 나이트로, C1-6 알킬, 및 C1-6 알콕시 중에서 선택된 1 내지 3개의 치환기로 치환 또는 비치환된 페닐기; 퓨란일기; 또는 티오펜일기를 나타낸다.
R 2 is a C 1-6 alkyl group; A phenyl group unsubstituted or substituted with 1 to 3 substituents selected from halo, nitro, C 1-6 alkyl, and C 1-6 alkoxy; Furanyl group; Or a thiophenyl group.

본 발명이 특징으로 하는 상기 화학식 1로 표시되는 3,4-다이메틸렌옥세페인 화합물은 두 개의 엑소메틸렌 그룹 (exomethylene group)을 이용하여 다양한 다중고리 화합물을 합성하는 중간체로 유용하다.The 3,4-dimethylene oxepine compound represented by Chemical Formula 1, which is characterized by the present invention, is useful as an intermediate for synthesizing various polycyclic compounds using two exomethylene groups.

본 발명의 제조방법은 시스 배향을 가지는 3,4-다이메틸렌옥세페인 화합물의 제조방법으로 유용하다.
The manufacturing method of this invention is useful as a manufacturing method of the 3, 4- dimethyl oxepine compound which has a cis orientation.

이와 같은 본 발명을 보다 구체적으로 설명하면 다음과 같다.The present invention will be described in more detail as follows.

본 발명에 따른 상기 화학식 1로 표시되는 3,4-다이메틸렌옥세페인 화합물을 정의하기 위해 사용된 치환기를 좀 더 자세히 설명하면 다음과 같다. The substituents used to define the 3,4-dimethylene oxepine compound represented by Formula 1 according to the present invention will be described in more detail as follows.

'알킬기'는 1 내지 6개의 탄소원자를 가진 직쇄상, 분쇄상 및 고리상의 탄소사슬을 모두 포함하며, 선호하는 알킬기는 메틸, 에틸기, 노말프로필기, 아이소프로필기, 노말부틸기, 아이소부틸기, tert-부틸기, 노말펜틸기, 시클로펜틸기, 노말헥실기, 시클로헥실기 등이 있다. '알콕시기'는 산소에 연결된 탄소의 알킬기를 의미하는 것으로, 이때 알킬은 상기에서 정의한 바와 같다. 'Alkyl group' includes all linear, pulverized and cyclic carbon chains having 1 to 6 carbon atoms, and preferred alkyl groups are methyl, ethyl group, normal propyl group, isopropyl group, normal butyl group, isobutyl group, tert -butyl group, normal pentyl group, cyclopentyl group, normal hexyl group, cyclohexyl group, etc. are mentioned. "Alkoxy group" means an alkyl group of carbon connected to oxygen, wherein alkyl is as defined above.

본 발명에 따른 상기 화학식 1로 표시되는 3,4-다이메틸렌옥세페인 화합물에 있어, 바람직하기로는 상기 R1은 수소원자, 메틸기, 에틸기, 노말프로필기, 아이소프로필기, 노말부틸기, 아이소부틸기, tert-부틸기, 또는 페닐기를 나타내고, 상기 R2는 메틸기, 에틸기, 노말프로필기, 아이소프로필기, 노말부틸기, 아이소부틸기, 노말펜틸기, 노말헥실기, 페닐기, o-클로로페닐기, m-클로로페닐기, p-클로로페닐기, 2,3-다이클로로페닐기, 2,4-다이클로로페닐기, 2,3,4-트라이클로로페닐기, o-플루오로페닐기, m-플루오로페닐기, p-플루오로페닐기, o-나이트로페닐기, m-나이트로페닐기, p-나이트로페닐기, o-메틸페닐기, m-메틸페닐기, p-메틸페닐기, 2,3-다이메틸페닐기, 2,4-다이메틸페닐기, 2,3,4-트라이메틸페닐기, o-메톡시페닐기, m-메톡시페닐기, p-메톡시페닐기, 2,3-다이메톡시페닐기, 2,4-다이메톡시페닐기, 2,3,4-트라이메톡시페닐기, 퓨란일기, 또는 티오펜일기인 화합물이다.In the 3,4-dimethylene oxepine compound represented by Formula 1 according to the present invention, preferably, R 1 is a hydrogen atom, a methyl group, an ethyl group, a normal propyl group, an isopropyl group, a normal butyl group, isobutyl Group, tert -butyl group, or a phenyl group, wherein R 2 represents a methyl group, an ethyl group, a normal propyl group, an isopropyl group, a normal butyl group, an isobutyl group, a normal pentyl group, a normal hexyl group, a phenyl group, and an o -chlorophenyl group , m -chlorophenyl group, p -chlorophenyl group, 2,3-dichlorophenyl group, 2,4-dichlorophenyl group, 2,3,4-trichlorophenyl group, o -fluorophenyl group, m -fluorophenyl group, p -fluoro-phenyl, o-nitro phenyl, m-nitro phenyl, p-phenyl group, nitro, o-methylphenyl, m-methylphenyl, p-methylphenyl, 2,3-dimethylphenyl group, a 2,4- dimethylphenyl group, a 2,3,4-trimethylphenyl group, o - methoxyphenyl group, m - methoxyphenyl, p - methoxy Group, a 2,3-dimethoxy-phenyl, 2,4-methoxyphenyl group, a 2,3,4-trimethyl main ethoxy group, a furan group, a thiophene group or compound.

본 발명에 따른 상기 화학식 1로 표시되는 3,4-다이메틸렌옥세페인 화합물을 좀 더 구체적으로 예시하면 하기와 같다.The 3,4-dimethylene oxephane compound represented by Chemical Formula 1 according to the present invention is more specifically illustrated as follows.

시스 3,4-다이메틸렌-2-페닐옥세페인,Cis 3,4-dimethylene-2-phenyloxepine,

시스 3,4-다이메틸렌-2-(2-나이트로페닐)옥세페인 ,Cis 3,4-dimethylene-2- (2-nitrophenyl) oxepine,

시스 2-(4-플루오로페닐)-3,4-다이메틸렌옥세페인,Cis 2- (4-fluorophenyl) -3,4-dimethylene oxepine,

시스 3,4-다이메틸렌-2-p-토일옥세페인,Cis 3,4-dimethylene-2- p -toyloxepine,

시스 2-(4-클로로페닐)-3,4-다이메틸렌옥세페인,Cis 2- (4-chlorophenyl) -3,4-dimethyleneoxepine,

시스 2-(4-메톡시페닐)-3,4-다이메틸렌옥세페인,Cis 2- (4-methoxyphenyl) -3,4-dimethylene oxepine,

시스 3,4-다이메틸렌-2-펜틸옥세페인 ,Cis 3,4-dimethylene-2-pentyloxepine,

시스 3,4-다이메틸렌-2-(티오펜-2-일)옥세페인,Cis 3,4-dimethylene-2- (thiophen-2-yl) oxepine,

시스 2-(퓨란-3-일)-3,4-다이메틸렌옥세페인,Cis 2- (furan-3-yl) -3,4-dimethyleneoxepine,

시스 7-아이소프로필-3,4-다이메틸렌-2-페닐옥세페인,Cis 7-isopropyl-3,4-dimethylene-2-phenyloxepine,

시스 7-아이소프로필-3,4-다이메틸렌-2-펜틸옥세페인, 및Cis 7-isopropyl-3,4-dimethylene-2-pentyloxepine, and

시스 2-(4-플루오로페닐)-3,4-다이메틸렌-7-페닐옥세페인.
Cis 2- (4-fluorophenyl) -3,4-dimethylene-7-phenyloxepine.

또한, 본 발명은 상기 화학식 1로 표시되는 3,4-다이메틸렌옥세페인 화합물의 제조방법을 권리범위로 포함한다.In addition, the present invention includes a method for producing the 3,4-dimethylene oxepine compound represented by the formula (1) as a scope.

본 발명에 따른 제조방법은 하기 반응식 1에 나타낸 바와 같이, 하기 화학식 2로 표시되는 알코올 화합물과 하기 화학식 3으로 표시되는 알데하이드 화합물을 출발물질로 사용하여, 다이에틸이써 및 테트라하이드로퓨란으로부터 선택된 용매와 트라이메틸실릴 트라이플루오로메탄설포네이트(TMSOTf) 및 틴 테트라클로라이드(TiCl4)로부터 선택된 루이스산 존재 하에서 프린스(Prins) 고리화 반응에 의해 하기 화학식 1로 표시되는 입체선택성을 가지는 3,4-다이메틸렌옥세페인 화합물을 제조한다.In the preparation method according to the present invention, a solvent selected from diethyl ether and tetrahydrofuran using an alcohol compound represented by the following formula (2) and an aldehyde compound represented by the following formula (3) as starting materials And 3,4- having stereoselectivity represented by the following formula (1) by Prince cyclization reaction in the presence of a Lewis acid selected from trimethylsilyl trifluoromethanesulfonate (TMSOTf) and tin tetrachloride (TiCl 4 ). A dimethyl oxefein compound is prepared.

[반응식 1][Reaction Scheme 1]

Figure 112011011962926-pat00002
Figure 112011011962926-pat00002

상기 반응식 1에서, R1 및 R2는 각각 상기 화학식 1에서 정의한 바와 같다.In Reaction Scheme 1, R 1 and R 2 are as defined in Formula 1, respectively.

본 발명의 제조방법은 프린스 고리화 반응을 통해 입체선택성을 가지는 3,4-다이메틸렌옥세페인 화합물을 제조하는 것을 목적으로 하나, 일반적인 루이스산 또는 용매 조건에서는 전혀 반응이 진행되지 않거나 낮은 수율로 목적하는 입체선택성 화합물이 제조됨을 실험을 통해 확인하였다. 즉, 트라이메틸실릴 트라이플루오로메탄설포네이트(TMSOTf) 및 틴 테트라클로라이드(TiCl4)로부터 선택된 루이스산 존재 하에서 그리고 다이에틸이써 및 테트라하이드로퓨란으로부터 선택된 용매 존재 하에서 본 발명의 제조방법을 수행하였을 때, 입체선택성을 가지는 상기 화학식 1로 표시되는 3,4-다이메틸렌옥세페인 화합물을 최고의 수율로 합성할 수 있다. 특히 본 발명의 제조방법은 시스(cis) 배향을 가지는 3,4-다이메틸렌옥세페인 화합물의 제조방법으로서 유용하다.The preparation method of the present invention aims to produce a 3,4-dimethylene oxepine compound having stereoselectivity through the Prince cyclization reaction, but the reaction does not proceed at all in a Lewis acid or solvent condition or at a low yield. It was confirmed through experiments that the stereoselective compound to be prepared. That is, the process of the present invention was carried out in the presence of a Lewis acid selected from trimethylsilyl trifluoromethanesulfonate (TMSOTf) and tin tetrachloride (TiCl 4 ) and in the presence of a solvent selected from diethylether and tetrahydrofuran. In this case, the 3,4-dimethylene oxepine compound represented by Formula 1 having stereoselectivity can be synthesized in the best yield. In particular, the production method of the present invention is useful as a method for producing a 3,4-dimethylene oxepine compound having a cis orientation.

상기 프린스 고리화 반응에 사용되는 루이스 산은 상기 화학식 2로 표시되는 알코올 화합물에 대하여 1 내지 2 당량 범위내에서 사용할 수 있다. 반응온도는 -90 ℃ 내지 30℃ 범위, 바람직하기로는 -78℃ 내지 30℃를 유지하도록 하며, 반응시간은 대략 2 내지 5시간이면 충분하다.The Lewis acid used in the Prince cyclization reaction may be used in the range of 1 to 2 equivalents based on the alcohol compound represented by Formula 2. The reaction temperature is maintained in the range of −90 ° C. to 30 ° C., preferably −78 ° C. to 30 ° C., and the reaction time may be approximately 2 to 5 hours.

상기한 바와 같은 본 발명에 따른 분자내 프린스 고리화 반응은 비교적 반응이 간결하고 제조 수율도 높아 산업적 이용 가능성은 매우 높다.As described above, the intramolecular prince cyclization reaction according to the present invention has a relatively simple reaction and a high production yield, and thus has high industrial applicability.

또한, 본 발명에서 합성한 상기 화학식 1로 표시되는 3,4-다이메틸렌옥세페인 화합물은 의약 및 정밀화학 분야에서 유용하게 사용될 수 있는 바, 상기 화학식 1로 표시되는 화합물은 다이엑소메틸렌 구조를 가지는 화합물으로 두 개의 메틸렌기를 이용하여 디엘스-올더 (Diels-Alder) 반응을 수행하게 되면 또 다른 다중고리 화합물을 합성할 수 있다. In addition, the 3,4-dimethylene oxephane compound represented by Chemical Formula 1 synthesized in the present invention may be usefully used in medicine and fine chemistry. The compound represented by Chemical Formula 1 has a diexomethylene structure. By performing the Diels-Alder reaction using two methylene groups as compounds, another polycyclic compound may be synthesized.

이상에서 설명한 바와 같은 본 발명은 하기 실시예에 의거하여 더욱 상세히 설명하겠는 바, 본 발명이 하기 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 : 시스 3,4-다이메틸렌-2-페닐옥세페인Example 1 cis 3,4-dimethylene-2-phenyloxepine

Figure 112011011962926-pat00003
Figure 112011011962926-pat00003

건조된 다이에틸이써 6.0 mL에 4-((트라이메틸실릴)메틸)헥사-4,5-다이엔-1-올 0.587 mmol과 벤즈알데하이드 0.88 mmol을 넣고 -78 ℃로 냉각시킨 후, 루이스 산인 트라이메틸실릴 트라이플루오로메탄설포네이트(TMSOTf) 0.45 mmol을 가하고 2시간 동안 교반한 후 서서히 상온으로 올려주었다. 반응용액에 NaHCO3의 수용액을 넣은 후 다이에틸이써로 묽혀 준 후, 유기층을 물과 소금물로 씻어주고 MgSO4로 건조시키고, 여과 및 농축시켜 관 크로마토그래피를 이용하여 90% 수율로 순수한 표제화합물을 얻었다. 0.587 mmol of 4-((trimethylsilyl) methyl) hexa-4,5-diene-1-ol and 0.88 mmol of benzaldehyde were added to 6.0 mL of dried diethyl ether, and the mixture was cooled to -78 ° C. 0.45 mmol of trimethylsilyl trifluoromethanesulfonate (TMSOTf) was added thereto, stirred for 2 hours, and then slowly raised to room temperature. NaHCO 3 was added to the reaction solution, and the mixture was diluted with diethyl ether. The organic layer was washed with water and brine, dried over MgSO 4 , filtered and concentrated to give 90% yield of the title compound by column chromatography. Got.

무색 오일; 1H NMR (400 MHz, CDCl3) δ 7.34∼7.27 (m, 5H), 5.24 (t, 1H, J = 1.2 Hz), 5.10 (s, 1H), 5.06 (d, 1H, J = 2.0 Hz), 4.90 (s, 1H), 4.46 (t, 1H, J = 1.6 Hz), 4.21∼4.17 (m, 1H), 3.73∼3.66 (m, 1H), 2.64∼58 (m, 1H), 2.46∼2.39 (m, 1H), 1.90∼1.84 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 153.81, 150.14, 141.63, 128.11, 127.38, 127.10, 113.63, 112.46, 84.83, 72.19, 35.00, 32.07.
Colorless oil; 1 H NMR (400 MHz, CDCl 3 ) δ 7.34-7.27 (m, 5H), 5.24 (t, 1H, J = 1.2 Hz), 5.10 (s, 1H), 5.06 (d, 1H, J = 2.0 Hz) , 4.90 (s, 1H), 4.46 (t, 1H, J = 1.6 Hz), 4.21-4.17 (m, 1H), 3.73-3.66 (m, 1H), 2.64-58 (m, 1H), 2.46-2.39 (m, 1H), 1.90-1.84 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 153.81, 150.14, 141.63, 128.11, 127.38, 127.10, 113.63, 112.46, 84.83, 72.19, 35.00, 32.07.

실시예 2 : 시스 3,4-다이메틸렌-2-(2-나이트로페닐)옥세페인 Example 2 cis 3,4-dimethylene-2- (2-nitrophenyl) oxepine

Figure 112011011962926-pat00004
Figure 112011011962926-pat00004

상기 실시예 1과 동일한 방법으로 실시하되, 4-((트라이메틸실릴)메틸)헥사-4,5-다이엔-1-올 0.293 mmol과 2-나이트로벤즈알데하이드 0.322 mmol을 사용하여 55% 수율로 순수한 표제화합물을 얻었다. The same procedure as in Example 1 was carried out, using 5593 yield of 0.293 mmol of 4-((trimethylsilyl) methyl) hexa-4,5-diene-1-ol and 0.322 mmol of 2-nitrobenzaldehyde. Pure title compound was obtained.

무색 오일; 1H NMR(400 MHz, CDCl3) δ 7.97 (dd, 1H, J = 8.0 Hz), 7.90∼7.84 (m, 1H), 7.66 (dt, 1H, J = 8.0Hz), 7.46 (dt, 1H, J = 8.0 Hz), 5.26 (s, 1H), 5.18 (d, 1H, J = 1.6 Hz), 5.02∼4.96 (m, 1H), 4.93 (s, 1H), 4.27 (s, 1H), 4.25∼4.23 (m, 1H), 3.71∼3.62 (m, 1H), 2.67∼2.62 (m, 2H), 1.91∼1.84 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 152.09, 147.34, 139.72, 136.88, 133.18, 129.29, 128.07, 124.17, 112.52, 112.14, 78.36, 73.45, 34.65, 31.98.
Colorless oil; 1 H NMR (400 MHz, CDCl 3 ) δ 7.97 (dd, 1H, J = 8.0 Hz), 7.90-7.84 (m, 1H), 7.66 (dt, 1H, J = 8.0 Hz), 7.46 (dt, 1H, J = 8.0 Hz), 5.26 (s, 1H), 5.18 (d, 1H, J = 1.6 Hz), 5.02-4.96 (m, 1H), 4.93 (s, 1H), 4.27 (s, 1H), 4.25- 4.23 (m, 1 H), 3.71-3.62 (m, 1 H), 2.67-2.62 (m, 2H), 1.91-1.84 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 152.09, 147.34, 139.72, 136.88, 133.18, 129.29, 128.07, 124.17, 112.52, 112.14, 78.36, 73.45, 34.65, 31.98.

실시예 3 : 시스 2-(4-플루오로페닐)-3,4-다이메틸렌옥세페인Example 3: cis 2- (4-fluorophenyl) -3,4-dimethylene oxepine

Figure 112011011962926-pat00005
Figure 112011011962926-pat00005

상기 실시예 1과 동일한 방법으로 실시하되, 4-((트라이메틸실릴)메틸)헥사-4,5-다이엔-1-올 0.146 mmol과 4-플루오로벤즈알데하이드 0.161 mmol을 사용하여 94% 수율로 순수한 표제화합물을 얻었다. In the same manner as in Example 1, except that 0.146 mmol of 4-((trimethylsilyl) methyl) hexa-4,5-diene-1-ol and 0.161 mmol of 4-fluorobenzaldehyde were used to yield 94% yield. Pure title compound was obtained.

무색오일; 1H NMR (400 MHz, CDCl3) δ 7.33∼7.29 (m, 2H), 7.04∼7.00 (m, 2H), 5.23 (s, 1H), 5.08 (s, 1H), 5.02 (d, 1H, J = 2.0 Hz), 4.89 (s, 1H), 4.46 (s, 1H), 4.20∼4.15 (m, 1H), 3.69∼3.65 (m, 1H), 2.63∼2.57 (m, 1H), 2.43∼2.36 (m, 1H), 1.89∼1.83 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 160.89, 153.77, 149.89, 137.49, 128.70, 128.62, 115.02, 114.81, 113.72, 112.62, 84.13, 71.99, 34.98, 31.91.
Colorless oil; 1 H NMR (400 MHz, CDCl 3 ) δ 7.33-7.29 (m, 2H), 7.04-7.00 (m, 2H), 5.23 (s, 1H), 5.08 (s, 1H), 5.02 (d, 1H, J = 2.0 Hz), 4.89 (s, 1H), 4.46 (s, 1H), 4.20-4.15 (m, 1H), 3.69-3.65 (m, 1H), 2.63-2.57 (m, 1H), 2.43-2.36 ( m, 1H), 1.89-1.83 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 160.89, 153.77, 149.89, 137.49, 128.70, 128.62, 115.02, 114.81, 113.72, 112.62, 84.13, 71.99, 34.98, 31.91.

실시예 4 : 시스 3,4-다이메틸렌-2-p-토일옥세페인Example 4 cis 3,4-dimethylene-2- p -toyloxepine

Figure 112011011962926-pat00006
Figure 112011011962926-pat00006

상기 실시예 1과 동일한 방법으로 실시하되, 4-((트라이메틸실릴)메틸)헥사-4,5-다이엔-1-올 0.146 mmol과 4-메틸벤즈알데하이드 0.161 mmol을 사용하여 95% 수율로 순수한 표제화합물을 얻었다. In the same manner as in Example 1, except that 0.146 mmol of 4-((trimethylsilyl) methyl) hexa-4,5-diene-1-ol and 0.161 mmol of 4-methylbenzaldehyde were used in 95% yield. Pure title compound was obtained.

무색오일; 1H NMR (400 MHz, CDCl3) δ 7.24 (d, 2H, J = 8.4 Hz), 7.15 (d, 2H, J = 8.0 Hz), 5.23 (s, 1H), 5.07 (s, 2H), 4.89 (s, 1H), 4.47 (s, 1H), 4.20∼4.15 (m, 1H), 3.72∼3.65 (m, 1H), 2.63∼2.57 (m, 1H), 2.45∼2.38 (m, 1H), 2.34 (s, 3H), 1.91∼1.84 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 153.95, 150.27, 138.71, 136.98, 128.80, 127.04, 113.46, 112.39, 84.77, 72.13, 34.99, 32.10, 21.15.
Colorless oil; 1 H NMR (400 MHz, CDCl 3 ) δ 7.24 (d, 2H, J = 8.4 Hz), 7.15 (d, 2H, J = 8.0 Hz), 5.23 (s, 1H), 5.07 (s, 2H), 4.89 (s, 1H), 4.47 (s, 1H), 4.20-4.15 (m, 1H), 3.72-3.65 (m, 1H), 2.63-2.57 (m, 1H), 2.45-2.38 (m, 1H), 2.34 (s, 3H), 1.91-1.84 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 153.95, 150.27, 138.71, 136.98, 128.80, 127.04, 113.46, 112.39, 84.77, 72.13, 34.99, 32.10, 21.15.

실시예 5 : 시스 2-(4-클로로페닐)-3,4-다이메틸렌옥세페인Example 5 Cis 2- (4-Chlorophenyl) -3,4-dimethyleneoxepine

Figure 112011011962926-pat00007
Figure 112011011962926-pat00007

상기 실시예 1과 동일한 방법으로 실시하되, 4-((트라이메틸실릴)메틸)헥사-4,5-다이엔-1-올 0.234 mmol과 4-클로로벤즈알데하이드 0.258 mmol을 사용하여 98% 수율로 순수한 표제화합물을 얻었다. In the same manner as in Example 1, except that 0.234 mmol of 4-((trimethylsilyl) methyl) hexa-4,5-diene-1-ol and 0.258 mmol of 4-chlorobenzaldehyde were used in 98% yield. Pure title compound was obtained.

무색오일; 1H NMR (400 MHz, CDCl3) δ 7.32∼7.27 (m, 4H), 5.24 (s, 1H), 5.07 (s, 1H), 5.01 (d, 1H, J = 2.0 Hz), 4.89 (s, 1H), 4.48 (s, 1H), 4.20∼4.15 (m, 1H), 3.72∼3.65 (m, 1H), 2.62∼2.57 (m, 1H), 2.43∼2.36 (m, 1H), 1.89∼1.83 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 153.47, 149.72, 140.15, 133.07, 128.42, 128.24, 113.86, 112.68, 84.01, 71.92, 34.97, 31.85.
Colorless oil; 1 H NMR (400 MHz, CDCl 3 ) δ 7.32-7.27 (m, 4H), 5.24 (s, 1H), 5.07 (s, 1H), 5.01 (d, 1H, J = 2.0 Hz), 4.89 (s, 1H), 4.48 (s, 1H), 4.20-4.15 (m, 1H), 3.72-3.65 (m, 1H), 2.62-2.57 (m, 1H), 2.43-2.36 (m, 1H), 1.89-1.83 ( m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 153.47, 149.72, 140.15, 133.07, 128.42, 128.24, 113.86, 112.68, 84.01, 71.92, 34.97, 31.85.

실시예 6 : 시스 2-(4-메톡시페닐)-3,4-다이메틸렌옥세페인 Example 6 cis 2- (4-methoxyphenyl) -3,4-dimethyleneoxepine

Figure 112011011962926-pat00008
Figure 112011011962926-pat00008

상기 실시예 1과 동일한 방법으로 실시하되, 4-((트라이메틸실릴)메틸)헥사-4,5-다이엔-1-올 0.293 mmol과 4-메톡시벤즈알데하이드 0.322 mmol을 사용하여 96% 수율로 순수한 표제화합물을 얻었다. In the same manner as in Example 1, except that 0.293 mmol of 4-((trimethylsilyl) methyl) hexa-4,5-diene-1-ol and 0.322 mmol of 4-methoxybenzaldehyde were used to obtain 96% yield. Pure title compound was obtained.

무색오일; 1H NMR (400 MHz, CDCl3) δ 7.27 (d, 2H, J = 6.8 Hz), 6.89 (d, 2H, J = 6.4 Hz), 5.23 (s, 1H), 5.06 (d, 2H, J = 2.0 Hz), 4.90 (s, 1H), 4.46 (s, 1H), 4.20∼4.15 (m, 1H), 3.80 (s, 3H), 3.71∼3.65 (m, 1H), 2.63∼2.57 (m, 1H), 2.44∼2.39 (m, 1H), 1.89∼1.84 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 158.89, 154.09, 150.28, 134.01, 128.28, 113.53, 112.43, 84.55, 72.09, 55.27, 35.00, 32.10.
Colorless oil; 1 H NMR (400 MHz, CDCl 3 ) δ 7.27 (d, 2H, J = 6.8 Hz), 6.89 (d, 2H, J = 6.4 Hz), 5.23 (s, 1H), 5.06 (d, 2H, J = 2.0 Hz), 4.90 (s, 1H), 4.46 (s, 1H), 4.20-4.15 (m, 1H), 3.80 (s, 3H), 3.71-3.65 (m, 1H), 2.63-2.57 (m, 1H ), 2.44-2.39 (m, 1H), 1.89-1.84 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 158.89, 154.09, 150.28, 134.01, 128.28, 113.53, 112.43, 84.55, 72.09, 55.27, 35.00, 32.10.

실시예 7 : 시스 3,4-다이메틸렌-2-펜틸옥세페인 Example 7 cis 3,4-dimethylene-2-pentyloxepine

Figure 112011011962926-pat00009
Figure 112011011962926-pat00009

상기 실시예 1과 동일한 방법으로 실시하되, 4-((트라이메틸실릴)메틸)헥사-4,5-다이엔-1-올 0.234 mmol과 n-헥산알 0.25 mmol을 사용하여 92% 수율로 순수한 표제화합물을 얻었다. In the same manner as in Example 1, except that 0.234 mmol of 4-((trimethylsilyl) methyl) hexa-4,5-diene-1-ol and 0.25 mmol of n-hexanal were used to obtain pure 92% yield. The title compound was obtained.

무색오일; 1H NMR (400 MHz, CDCl3) δ 5.13 (s, 1H), 4.96 (d, 1H, J = 2.4 Hz), 4.85∼4.82 (m, 3H), 4.05∼4.00 (m, 1H), 3.97∼3.94 (m, 1H), 3.55∼3.49 (m, 1H), 2.55∼2.49 (m, 1H), 2.31∼2.24 (m, 1H), 1.75∼1.57 (m, 6H), 1.44∼1.34 (m, 4H), 0.90∼0.87 (t, 3H, J = 6.4 Hz); 13C NMR (100 MHz, CDCl3) δ 153.98, 150.48, 111.60, 110.84, 81.87, 70.66, 35.01, 34.47, 31.86, 31.14, 25.43, 22.65, 14.09.
Colorless oil; 1 H NMR (400 MHz, CDCl 3 ) δ 5.13 (s, 1H), 4.96 (d, 1H, J = 2.4 Hz), 4.85 to 4.82 (m, 3H), 4.05 to 4.00 (m, 1H), 3.97 to 3.94 (m, 1H), 3.55 to 3.49 (m, 1H), 2.55 to 2.49 (m, 1H), 2.31 to 2.24 (m, 1H), 1.75 to 1.57 (m, 6H), 1.44 to 1.34 (m, 4H ), 0.90 to 0.87 (t, 3H, J = 6.4 Hz); 13 C NMR (100 MHz, CDCl 3 ) δ 153.98, 150.48, 111.60, 110.84, 81.87, 70.66, 35.01, 34.47, 31.86, 31.14, 25.43, 22.65, 14.09.

실시예 8 : 시스 3,4-다이메틸렌-2-(티오펜-2-일)옥세페인 Example 8 Cis 3,4-dimethylene-2- (thiophen-2-yl) oxepine

Figure 112011011962926-pat00010
Figure 112011011962926-pat00010

상기 실시예 1과 동일한 방법으로 실시하되, 4-((트라이메틸실릴)메틸)헥사-4,5-다이엔-1-올 0.176 mmol과 티오펜-2-카바알데하이드 0.193 mmol을 사용하여 90% 수율로 순수한 표제화합물을 얻었다. 무색오일In the same manner as in Example 1, 90% using 0.176 mmol of 4-((trimethylsilyl) methyl) hexa-4,5-diene-1-ol and 0.193 mmol of thiophene-2-carbaaldehyde Yield yielded the pure title compound. Colorless oil

1H NMR(400 MHz, CDCl3) δ 7.26 (m, 1H), 6.97 (d, 2H, J = 3.6 Hz), 5.42 (s, 1H), 5.30 (s, 1H), 5.08 (d, 1H, J = 2.0 Hz), 4.91 (s, 1H), 4.78 (s, 1H), 4.16∼4.12 (m, 1H), 3.74∼3.68 (m, 1H), 2.61∼2.57 (m, 1H), 2.37∼2.34 (m, 1H), 1.87∼1.79 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 153.98, 150.48, 126.25, 124.93, 124.73, 114.15, 112.99, 80.73, 71.11, 34.81, 31.32.
 1 H NMR (400 MHz, CDCl 3 ) δ 7.26 (m, 1H), 6.97 (d, 2H, J = 3.6 Hz), 5.42 (s, 1H), 5.30 (s, 1H), 5.08 (d, 1H, J = 2.0 Hz), 4.91 (s, 1H), 4.78 (s, 1H), 4.16-4.12 (m, 1H), 3.74-3.68 (m, 1H), 2.61-2.57 (m, 1H), 2.37-2.34 (m, 1 H), 1.87-1.79 (m, 2 H); 13 C NMR (100 MHz, CDCl 3 ) δ 153.98, 150.48, 126.25, 124.93, 124.73, 114.15, 112.99, 80.73, 71.11, 34.81, 31.32.

실시예 9 : 시스 2-(퓨란-3-일)-3,4-다이메틸렌옥세페인 Example 9 cis 2- (furan-3-yl) -3,4-dimethyleneoxepine

Figure 112011011962926-pat00011
Figure 112011011962926-pat00011

상기 실시예 1과 동일한 방법으로 실시하되, 4-((트라이메틸실릴)메틸)헥사-4,5-다이엔-1-올 0.176 mmol과 3-퍼퓨알데하이드 0.193 mmol을 사용하여 94% 수율로 순수한 표제화합물을 얻었다. In the same manner as in Example 1, except that 0.176 mmol of 4-((trimethylsilyl) methyl) hexa-4,5-diene-1-ol and 0.193 mmol of 3-perfualdehyde were used in a 94% yield. The title compound was obtained.

무색오일; 1H NMR (400 MHz, CDCl3) δ 7.40 (d, 2H, J = 5.6 Hz), 6.37 (s, 1H), 5.27 (s, 1H), 5.12 (s, 1H), 5.11 (d, 1H, J = 2.0 Hz), 4.89 (s, 1H), 4.75 (s, 1H), 4.13∼4.08 (m, 1H), 3.70∼3.64 (m, 1H), 2.61∼2.55 (m, 1H), 2.42∼2.35 (m, 1H), 1.85∼1.78 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 152.40, 149.72, 143.06, 139.96, 125.76, 113.23, 112.52, 109.54, 77.70, 71.42, 34.83, 31.70.
Colorless oil; 1 H NMR (400 MHz, CDCl 3 ) δ 7.40 (d, 2H, J = 5.6 Hz), 6.37 (s, 1H), 5.27 (s, 1H), 5.12 (s, 1H), 5.11 (d, 1H, J = 2.0 Hz), 4.89 (s, 1H), 4.75 (s, 1H), 4.13-4.08 (m, 1H), 3.70-3.64 (m, 1H), 2.61-2.55 (m, 1H), 2.42-2.35 (m, 1H), 1.85-1.78 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 152.40, 149.72, 143.06, 139.96, 125.76, 113.23, 112.52, 109.54, 77.70, 71.42, 34.83, 31.70.

실시예 10 : 시스 7-아이소프로필-3,4-다이메틸렌-2-페닐옥세페인 Example 10 cis 7-isopropyl-3,4-dimethylene-2-phenyloxepine

Figure 112011011962926-pat00012
Figure 112011011962926-pat00012

상기 실시예 1과 동일한 방법으로 실시하되, 2-메틸-6-((트라이메틸실릴)메틸)옥타-6,7-다이엔-3-올 0.11 mmol과 벤즈알데하이드 0.121 mmol을 사용하여 90% 수율로 순수한 표제화합물을 얻었다. The same procedure as in Example 1 was carried out, except that 90% yield was obtained using 0.11 mmol of 2-methyl-6-((trimethylsilyl) methyl) octa-6,7-dien-3-ol and 0.121 mmol of benzaldehyde. Pure title compound was obtained.

무색오일; 1H NMR (400 MHz, CDCl3) δ 7.37∼7.25 (m, 5H), 5.23 (s, 1H), 5.12 (s, 1H), 5.05 (d, 1H, J = 2.0 Hz), 4.87 (s, 1H), 4.43 (s, 1H), 3.36∼3.31 (m, 1H), 2.64∼2.58 (m, 1H), 2.43∼2.36 (m, 1H), 1.98∼1.91 (m, 1H), 1.72∼1.65 (m, 1H), 1.64∼1.54 (m, 1H), 0.92 (t, 6H, J = 6.4 Hz); 13C NMR (100 MHz, CDCl3) δ 153.30, 149.98, 140.40, 127.87, 127.05, 112.52, 112.06, 101.43, 87.39, 84.28, 34.64, 34.53, 33.97, 19.23, 18.70.
Colorless oil; 1 H NMR (400 MHz, CDCl 3 ) δ 7.37 to 7.25 (m, 5H), 5.23 (s, 1H), 5.12 (s, 1H), 5.05 (d, 1H, J = 2.0 Hz), 4.87 (s, 1H), 4.43 (s, 1H), 3.36 to 3.31 (m, 1H), 2.64 to 2.58 (m, 1H), 2.43 to 2.36 (m, 1H), 1.98 to 1.91 (m, 1H), 1.72 to 1.65 ( m, 1H), 1.64-1.54 (m, 1H), 0.92 (t, 6H, J = 6.4 Hz); 13 C NMR (100 MHz, CDCl 3 ) δ 153.30, 149.98, 140.40, 127.87, 127.05, 112.52, 112.06, 101.43, 87.39, 84.28, 34.64, 34.53, 33.97, 19.23, 18.70.

실시예 11 : 시스 7-아이소프로필-3,4-다이메틸렌-2-펜틸옥세페인 Example 11 Cis 7-Isopropyl-3,4-dimethylene-2-pentyloxepine

Figure 112011011962926-pat00013
Figure 112011011962926-pat00013

상기 실시예 1과 동일한 방법으로 실시하되, 2-메틸-6-((트라이메틸실릴)메틸)옥타-6,7-다이엔-3-올 0.11 mmol과 n-헥산알 0.121 mmol을 사용하여 92% 수율로 순수한 표제화합물을 얻었다. In the same manner as in Example 1, using 92-methyl-6-((trimethylsilyl) methyl) octa-6,7-dien-3-ol and 0.121 mmol of n-hexanal 92 The pure title compound was obtained in% yield.

무색오일; 1H NMR (400 MHz, CDCl3) δ 5.09 (s, 1H), 4.94 (d, 1H, J = 2.4 Hz), 4.84 (s, 1H), 4.22 (s, 1H), 4.77 (s, 1H), 4.00∼3.97 (m, 1H), 3.16∼3.11 (m, 1H), 2.55∼2.50 (m, 1H), 2.25∼2.18 (m, 1H), 1.79∼1.69 (m, 1H), 1.68∼1.63 (m, 4H), 1.54∼1.34 (m, 4H), 0.90 (t, 2H, J = 6.8 Hz); 13C NMR (100 MHz, CDCl3) δ 154.82, 150.54, 111.41, 110.01, 85.32, 81.93, 34.39, 33.77, 31.84, 29.70, 25.50, 23.25, 22.63, 19.38, 18.5, 14.07.
Colorless oil; 1 H NMR (400 MHz, CDCl 3 ) δ 5.09 (s, 1H), 4.94 (d, 1H, J = 2.4 Hz), 4.84 (s, 1H), 4.22 (s, 1H), 4.77 (s, 1H) , 4.00 to 3.97 (m, 1H), 3.16 to 3.11 (m, 1H), 2.55 to 2.50 (m, 1H), 2.25 to 2.18 (m, 1H), 1.79 to 1.69 (m, 1H), 1.68 to 1.63 ( m, 4H), 1.54-1.34 (m, 4H), 0.90 (t, 2H, J = 6.8 Hz); 13 C NMR (100 MHz, CDCl 3 ) δ 154.82, 150.54, 111.41, 110.01, 85.32, 81.93, 34.39, 33.77, 31.84, 29.70, 25.50, 23.25, 22.63, 19.38, 18.5, 14.07.

실시예 12 : 시스 2-(4-플루오로페닐)-3,4-다이메틸렌-7-페닐옥세페인Example 12 cis 2- (4-fluorophenyl) -3,4-dimethylene-7-phenyloxepine

Figure 112011011962926-pat00014
Figure 112011011962926-pat00014

상기 실시예 1과 동일한 방법으로 실시하되, 4-((트라이메틸실릴)메틸)-1-페닐헥사-4,5-다이엔-1-올 0.095 mmol과 4-플루오로벤즈알데하이드 0.105 mmol을 사용하여 88% 수율로 순수한 표제화합물을 얻었다.The same method as in Example 1, except that 0.095 mmol of 4-((trimethylsilyl) methyl) -1-phenylhexa-4,5-dien-1-ol and 0.105 mmol of 4-fluorobenzaldehyde were used. To 88% yield of pure title compound.

무색오일; 1H NMR(400 MHz, CDCl3) δ 7.39∼7.21 (m, 7H), 7.04 (t, 2H, J = 6.8 Hz), 5.32 (s, 1H), 5.29 (s, 1H), 5.10 (d, 1H, J = 1.6 Hz), 4.93 (s, 1H), 4.78 (dd, 1H, J = 10.4, 2.4 Hz), 4.50 (s, 1H), 2.68∼2.65 (m, 1H), 2.61∼2.57 (m, 1H), 2.25∼2.20 (m, 1H), 1.93∼1.88 (m, 1H) ; 13C NMR (100 MHz, CDCl3) δ 153.71, 149.30, 143.67, 137.38, 128.66, 128.59, 128.17, 127.04, 125.64, 114.89, 114.67, 113.34, 112.63, 83.60, 83.40, 39.70, 34.67.
Colorless oil; 1 H NMR (400 MHz, CDCl 3 ) δ 7.39 to 7.21 (m, 7H), 7.04 (t, 2H, J = 6.8 Hz), 5.32 (s, 1H), 5.29 (s, 1H), 5.10 (d, 1H, J = 1.6 Hz), 4.93 (s, 1H), 4.78 (dd, 1H, J = 10.4, 2.4 Hz), 4.50 (s, 1H), 2.68-2.65 (m, 1H), 2.61-2.57 (m , 1H), 2.25 to 2.20 (m, 1H), 1.93 to 1.88 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 153.71, 149.30, 143.67, 137.38, 128.66, 128.59, 128.17, 127.04, 125.64, 114.89, 114.67, 113.34, 112.63, 83.60, 83.40, 39.70, 34.67.

[참고예][Reference Example]

하기 표 1에는 상기 실시예 1의 방법으로 시스 3,4-다이메틸렌-2-페닐옥세페인을 제조하되, 루이스산 또는 용매의 종류를 변화시키면서 목적화합물의 제조수율을 측정한 결과를 나타내었다.In Table 1 below, cis 3,4-dimethylene-2-phenyloxepine was prepared by the method of Example 1, but the production yield of the target compound was measured while changing the type of the Lewis acid or the solvent.

Figure 112011011962926-pat00015
Figure 112011011962926-pat00015
참고예Reference Example 용매menstruum 루이스산Lewis Mountain 수율(%)yield(%) 1One THFTHF TMSOTfTMSOTf 8585 22 Et2OEt 2 O TMSOTfTMSOTf 9090 33 CH2Cl2 CH 2 Cl 2 TMSOTfTMSOTf 00 44 Et2OEt 2 O SnCl4 SnCl 4 4242 55 Et2OEt 2 O TiCl4 TiCl 4 8080 66 Et2OEt 2 O BF3·Et2OBF 3 · Et 2 O 1010 77 Et2OEt 2 O InCl3 InCl 3 00 88 Et2OEt 2 O TfOHTfOH 5656

상기 표 1에 의하면, 프린스 고리화 반응에 의한 시스 3,4-다이메틸렌-2-페닐옥세페인의 제조방법은 루이스산과 용매의 선택에 따라 제조수율이 크게 달라짐을 확인할 수 있다.
According to Table 1, the production method of cis 3,4-dimethylene-2-phenyloxephane by the Prince cyclization reaction can be confirmed that the production yield is greatly changed depending on the choice of the Lewis acid and the solvent.

본 발명에 따른 상기 화학식 1로 표시되는 입체선택성을 가지는 3,4-다이메틸렌옥세페인 화합물은 천연물이나 의약품의 중간체로서 유용하다. The 3,4-dimethylene oxepine compound having the stereoselectivity represented by the formula (1) according to the present invention is useful as an intermediate of natural products or pharmaceuticals.

또한, 상기 화학식 1로 표시되는 3,4-다이메틸렌옥세페인 화합물은 엑소메틸렌 그룹을 이용한 디엘스-올더(Diels-Alder) 반응을 통해 또 다른 고리를 확장시켜, 의약품 또는 정밀화학 분야에서 매우 중요한 7각형 헤테로고리를 포함하는 다중고리 화합물 제조를 위한 중간체로 유용하다.In addition, the 3,4-dimethylene oxepine compound represented by Chemical Formula 1 expands another ring through a Diels-Alder reaction using an exomethylene group, which is very important in pharmaceutical or fine chemical fields. It is useful as an intermediate for the preparation of multicyclic compounds, including hexagonal heterocycles.

Claims (5)

하기 화학식 1로 표시되는 입체선택성을 가지는 3,4-다이메틸렌옥세페인 화합물 :
[화학식 1]
Figure 112011011962926-pat00016

상기 화학식 1에서,
R1은 수소원자; C1-6 알킬기; 또는 페닐기를 나타내고,
R2는 C1-6 알킬기; 할로, 나이트로, C1-6 알킬, 및 C1-6 알콕시 중에서 선택된 1 내지 3개의 치환기로 치환 또는 비치환된 페닐기; 퓨란일기; 또는 티오펜일기를 나타낸다.
3,4-dimethylene oxepine compound having stereoselectivity represented by the following general formula (1):
[Formula 1]
Figure 112011011962926-pat00016

In Chemical Formula 1,
R 1 is a hydrogen atom; C 1-6 alkyl group; Or a phenyl group,
R 2 is a C 1-6 alkyl group; A phenyl group unsubstituted or substituted with 1 to 3 substituents selected from halo, nitro, C 1-6 alkyl, and C 1-6 alkoxy; Furanyl group; Or a thiophenyl group.
제 1 항에 있어서,
시스 3,4-다이메틸렌-2-페닐옥세페인,
시스 3,4-다이메틸렌-2-(2-나이트로페닐)옥세페인 ,
시스 2-(4-플루오로페닐)-3,4-다이메틸렌옥세페인,
시스 3,4-다이메틸렌-2-p-토일옥세페인,
시스 2-(4-클로로페닐)-3,4-다이메틸렌옥세페인,
시스 2-(4-메톡시페닐)-3,4-다이메틸렌옥세페인,
시스 3,4-다이메틸렌-2-펜틸옥세페인 ,
시스 3,4-다이메틸렌-2-(티오펜-2-일)옥세페인,
시스 2-(퓨란-3-일)-3,4-다이메틸렌옥세페인,
시스 7-아이소프로필-3,4-다이메틸렌-2-페닐옥세페인,
시스 7-아이소프로필-3,4-다이메틸렌-2-펜틸옥세페인, 및
시스 2-(4-플루오로페닐)-3,4-다이메틸렌-7-페닐옥세페인
으로 이루어진 군으로부터 선택된 입체선택성을 가지는 3,4-다이메틸렌옥세페인 화합물.
The method of claim 1,
Cis 3,4-dimethylene-2-phenyloxepine,
Cis 3,4-dimethylene-2- (2-nitrophenyl) oxepine,
Cis 2- (4-fluorophenyl) -3,4-dimethylene oxepine,
Cis 3,4-dimethylene-2- p -toyloxepine,
Cis 2- (4-chlorophenyl) -3,4-dimethyleneoxepine,
Cis 2- (4-methoxyphenyl) -3,4-dimethylene oxepine,
Cis 3,4-dimethylene-2-pentyloxepine,
Cis 3,4-dimethylene-2- (thiophen-2-yl) oxepine,
Cis 2- (furan-3-yl) -3,4-dimethyleneoxepine,
Cis 7-isopropyl-3,4-dimethylene-2-phenyloxepine,
Cis 7-isopropyl-3,4-dimethylene-2-pentyloxepine, and
Cis 2- (4-fluorophenyl) -3,4-dimethylene-7-phenyloxepine
3,4-dimethylene oxepine compound having stereoselectivity selected from the group consisting of:
하기 화학식 2로 표시되는 알코올 화합물과 하기 화학식 3으로 표시되는 알데하이드 화합물을 출발물질로 사용하여, 다이에틸이써 및 테트라하이드로퓨란으로부터 선택된 용매와 트라이메틸실릴 트라이플루오로메탄설포네이트(TMSOTf) 및 틴 테트라클로라이드(TiCl4)로부터 선택된 루이스산 존재 하에서, -78 ℃ 내지 30 ℃ 온도로 프린스(Prins) 고리화 반응을 수행하여 제조하는 것을 특징으로 하는 하기 화학식 1로 표시되는 3,4-다이메틸렌옥세페인 화합물의 제조방법 :
Figure 112013026981903-pat00017

상기에서, R1은 수소원자; C1-6 알킬기; 또는 C6-12 아릴기를 나타내고, R2는 C1-6 알킬기; 할로, 나이트로, C1-6 알킬, 및 C1-6 알콕시 중에서 선택된 1 내지 3개의 치환기로 치환 또는 비치환된 C6-12 아릴기; 또는 산소원자(O) 및 황원자(S)로부터 선택된 1 내지 2개의 헤테로원자를 포함하는 5 내지 12 원자의 헤테로아릴기를 나타낸다.
A solvent selected from diethyl ether and tetrahydrofuran, trimethylsilyl trifluoromethanesulfonate (TMSOTf) and tin using an alcohol compound represented by the following formula (2) and an aldehyde compound represented by the following formula (3) as starting materials In the presence of a Lewis acid selected from tetrachloride (TiCl 4 ), 3,4-dimethylene oxe represented by the following formula (1), characterized in that by performing the Prince (Prins) cyclization reaction at a temperature of -78 ℃ to 30 ℃ Method for preparing a payne compound:
Figure 112013026981903-pat00017

In the above, R 1 is a hydrogen atom; C 1-6 alkyl group; Or a C 6-12 aryl group, R 2 is a C 1-6 alkyl group; A C 6-12 aryl group unsubstituted or substituted with 1 to 3 substituents selected from halo, nitro, C 1-6 alkyl, and C 1-6 alkoxy; Or a 5 to 12 membered heteroaryl group including 1 to 2 heteroatoms selected from an oxygen atom (O) and a sulfur atom (S).
제 3 항에 있어서,
상기 화학식 2로 표시되는 알코올 화합물을 기준으로, 상기 루이스산을 1 내지 2 당량 범위로 사용하는 것을 특징으로 하는 제조방법.
The method of claim 3, wherein
Based on the alcohol compound represented by the formula (2), characterized in that the Lewis acid is used in the range of 1 to 2 equivalents.
삭제delete
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