KR101080519B1 - Efficient synthetic method of benzopyranobenzopyrans using domino aldol―type reaction／hetero Diels―Alder reaction - Google Patents
Efficient synthetic method of benzopyranobenzopyrans using domino aldol―type reaction／hetero Diels―Alder reaction Download PDFInfo
- Publication number
- KR101080519B1 KR101080519B1 KR1020090031460A KR20090031460A KR101080519B1 KR 101080519 B1 KR101080519 B1 KR 101080519B1 KR 1020090031460 A KR1020090031460 A KR 1020090031460A KR 20090031460 A KR20090031460 A KR 20090031460A KR 101080519 B1 KR101080519 B1 KR 101080519B1
- Authority
- KR
- South Korea
- Prior art keywords
- formula
- reaction
- domino
- benzaldehyde
- mmol
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
본 발명은 벤조피란 화합물의 새로운 합성방법에 관한 것으로, 보다 상세하게는 레조시놀 또는 나프톨 중 어느 하나의 화합물과 O-알릴 에테르를 지닌 벤즈알데히드를 출발물질로 이용하며, 도미노 알돌형 반응 및 헤테로 디엘스-알더 반응(domino aldol-type reaction/hetero Diels-Alder reaction)에 의해 벤조피라노벤조피란 고리화합물을 신속하고 효율 좋게 합성할 수 있다.The present invention relates to a novel method for synthesizing a benzopyran compound, and more particularly, using a benzaldehyde having O -allyl ether and any one of resorcinol or naphthol as a starting material, and a domino aldol type reaction and hetero di The benzopyranobenzopyran ring compound can be synthesized quickly and efficiently by the Els-Alder reaction (domino aldol-type reaction / hetero Diels-Alder reaction).
벤조피란, 레조시놀, 나프톨, 도미노 알돌형 반응/헤테로 디엘스-알더 반응 Benzopyrans, resorcinol, naphthol, domino aldol type reaction / hetero diels-alder reaction
Description
본 발명은 도미노 알돌형 반응 및 헤테로 디엘스-알더 반응을 이용한 벤조피라노벤조피란 고리화합물의 새로운 합성방법에 관한 것이다. The present invention relates to a new method for synthesizing benzopyranobenzopyran ring compounds using a domino aldol type reaction and a hetero diels-alder reaction.
헤테로 디엘스-알더 반응(hetero Diels-Alder reaction)은 헤테로고리 화합물 및 천연물을 합성하는 데에 유용한 합성 방법으로서, 헤테로 디엘스-알더 반응과 다른 반응의 도미노 조합은 다양한 탄소-탄소 결합 형성에 널리 이용되어 오고 있다. The hetero Diels-Alder reaction is a synthetic method useful for synthesizing heterocyclic compounds and natural products. The domino combination of the hetero dies-Alder reaction and other reactions is widely used to form various carbon-carbon bonds. It has been used.
벤조피란기 및 나프토피란기를 지닌 분자는 천연에서 널리 발견되고 있다. 이러한 화합물들은 항산화, 항암, 항염증, 항바이러스, 항박테리아 및 항-HIV 활성 등을 포함한 다양한 생리활성 및 약리활성 특성을 나타낸다. 또, 이러한 화합물들은 광변색성 선글라스, 미소전자공학, 광학메모리, 생물학적 광스위치와 같이 다양한 분야에 응용되고 있다. Molecules having benzopyran and naphthopyran groups are widely found in nature. These compounds exhibit various physiological and pharmacological properties, including antioxidant, anticancer, anti-inflammatory, antiviral, antibacterial and anti-HIV activities. In addition, these compounds have been applied to various fields such as photochromic sunglasses, microelectronics, optical memory, and biological optical switches.
따라서, 다양한 활성 및 특성을 지닌 벤조피란기 및 나프토피란기를 지닌 폴리헤테로 고리를 합성하는 데에 간편하고 효과적인 방법의 개발이 시급한 실정이다. Therefore, it is urgent to develop a simple and effective method for synthesizing a polyhetero ring having a benzopyran group and a naphthopyran group having various activities and properties.
상기 종래기술의 문제점을 해결하기 위하여, 본 발명은 간편하고 신속하면서 효율 좋게 벤조피라노벤조피란 고리화합물을 합성할 수 있는 새로운 방법을 개발하고자 하는 데에 그 목적이 있다.In order to solve the problems of the prior art, an object of the present invention is to develop a new method for synthesizing a benzopyranobenzopyran ring compound simply, quickly and efficiently.
상기 목적을 달성하기 위하여, 본 발명은 레조시놀 또는 나프톨 중 어느 하나의 화합물과 O-알릴 에테르를 지닌 벤즈알데히드를 출발물질로 이용하며, 도미노 알돌형 반응 및 헤테로 디엘스-알더 반응(domino aldol-type reaction/hetero Diels-Alder reaction)에 의해 합성되는 것을 특징으로 하는 벤조피라노벤조피란 고리화합물의 합성방법을 제공한다.In order to achieve the above object, the present invention uses benzaldehyde having O -allyl ether and a compound of either resorcinol or naphthol as a starting material, a domino aldol type reaction and a hetero diels-alder reaction (domino aldol- It provides a method for synthesizing a benzopyranobenzopyran ring compound, characterized in that synthesized by a type reaction / hetero Diels-Alder reaction.
보다 상세하게는, 본 발명의 합성방법은 O-알릴 에테르를 지닌 벤즈알데히드를 준비하는 단계(제1단계) 및 상기 벤즈알데히드와 레조시놀 또는 나프톨을 도미노 알돌형 반응 및 헤테로 디엘스-알더 반응 시키는 단계(제2단계)를 포함하여 이루어진다.More specifically, the synthetic method of the present invention comprises the steps of preparing benzaldehyde with O -allyl ether (first step) and the step of domino aldol-type reaction and hetero diels-aldehyde reaction of the benzaldehyde and resorcinol or naphthol (Second step).
상기 제2단계의 도미노 알돌형 반응 및 헤테로 디엘스-알더 반응은 반응촉매로서 트리에틸아민 또는 에틸렌디아민 다이아세테이트 중에서 선택된 어느 하나의 촉매 또는 이들의 혼합 촉매를 사용하는 것이 바람직하다. The domino aldol type reaction and the hetero diels-alder reaction of the second step preferably use any one catalyst selected from triethylamine or ethylenediamine diacetate or a mixed catalyst thereof as the reaction catalyst.
이때, 상기 도미노 알돌형 반응 및 헤테로 디엘스-알더 반응은 크실렌, 클로로포름 및 벤젠으로 이루어진 군에서 선택된 어느 하나의 유기용매 환류 하에서 24 시간 동안 수행되는 것이 바람직하다.In this case, the domino aldol type reaction and the hetero diels-alder reaction is preferably carried out for 24 hours under reflux of any one organic solvent selected from the group consisting of xylene, chloroform and benzene.
또한, 본 발명에서 사용된 상기 O-알릴 에테르를 지닌 벤즈알데히드는 하기 화학식 I로 표시되는 화합물이다.In addition, benzaldehyde having the O -allyl ether used in the present invention is a compound represented by the following formula (I).
[화학식 I][Formula I]
상기 화학식 I에서, 상기 R은 수소, 프레닐(prenyl) 및 제라닐(geranyl)로 이루어진 군에서 선택됨.In formula (I), R is selected from the group consisting of hydrogen, prenyl and geranyl.
또한, 본 발명에서 사용된 상기 레조시놀은 하기 화학식 II로 표시된 화합물이다.In addition, the resorcinol used in the present invention is a compound represented by the following formula (II).
[화학식 II]≪ RTI ID = 0.0 &
상기 화학식 II에서, 상기 R1 및 R2는 각각 수소, C1-C10의 알킬, C1-C10의 알킬카르보닐, C1-C10의 알콕시카르보닐 및 페논으로 이루어진 군에서 선택됨.In Formula II, R 1 and R 2 are each selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 alkylcarbonyl, C1-C10 alkoxycarbonyl and phenone.
또한, 본 발명에서 사용된 상기 나프톨은 하기 화학식 III로 표시된 화합물이다.In addition, the naphthol used in the present invention is a compound represented by the following general formula (III).
[화학식 III][Formula III]
상기 화학식 III에서, 상기 R3은 수소, C1-C10의 알킬, C1-C10의 알콕시 및 할로겐으로 이루어진 군에서 선택됨.In Formula III, R 3 is selected from the group consisting of hydrogen, alkyl of C1-C10, alkoxy and halogen of C1-C10.
또한, 본 발명에서 합성된 상기 벤조피란은 화학식 IV 또는 화학식 V로 표시되는 벤조피라노벤조피란, 또는 화학식 VI 또는 화학식 VII로 표시되는 나프톨피라노벤조피란 중에서 선택된 어느 하나이다.In addition, the benzopyran synthesized in the present invention is any one selected from benzopyranobenzopyran represented by the formula (IV) or (V), or naphtholpyranobenzopyran represented by the formula (VI) or (VII).
[화학식 IV][Formula IV]
[화학식 V][Formula V]
[화학식 VI][Formula VI]
[화학식 VII][Formula VII]
상기 화학식 IV 내지 화학식 VII에서, In Chemical Formulas IV to VII,
상기 R1 및 R2는 각각 수소, C1-C10의 알킬, C1-C10의 알킬카르보닐, C1-C10의 알콕시카르보닐 및 페논으로 이루어진 군에서 선택되고, 상기 R3은 수소, C1-C10의 알킬, C1-C10의 알콕시 및 할로겐으로 이루어진 군에서 선택되며, n은 1 내지 10의 정수임.R 1 and R 2 are each selected from the group consisting of hydrogen, C1-C10 alkyl, C1-C10 alkylcarbonyl, C1-C10 alkoxycarbonyl and phenone, wherein R 3 is hydrogen, C1-C10 Alkyl, C 1 -C 10 alkoxy and halogen, n is an integer from 1 to 10.
본 발명에 따른 벤조피란 화합물의 합성방법은 도미노 알돌형 반응 및 헤테로 디엘스-알더 반응을 이용함으로써 종래 방법보다 신속하고도 간편하면서 효율좋게 벤조피라노벤조피란 고리화합물을 합성할 수 있다.The method for synthesizing the benzopyran compound according to the present invention can synthesize the benzopyranobenzopyran ring compound more quickly and simply and efficiently than the conventional method by using a domino aldol type reaction and a hetero diels-alder reaction.
본 발명에 따른 벤조피란 화합물의 합성방법은 크게 O-알릴 에테르를 지닌 벤즈알데히드를 준비하는 단계(제1단계) 및 상기 벤즈알데히드와 레조시놀 또는 나프톨을 도미노 알돌형 반응 및 헤테로 디엘스-알더 반응 시키는 단계(제2단계)를 포함하여 이루어지며, 이하 실시예를 들어 본 발명을 보다 상세하게 설명한다.The method for synthesizing the benzopyran compound according to the present invention comprises the steps of preparing benzaldehyde having O -allyl ether (first step) and reacting benzaldehyde and resorcinol or naphthol with a domino aldol type reaction and a hetero diels-aldehyde reaction. It comprises a step (second step), and the present invention will be described in more detail with reference to the following examples.
상기 제1단계에서 O-알릴 에테르를 지닌 벤즈알데히드는 하기 반응식 1과 같이, 살리실알데히드(1)에 DMF 용매하에서 K2CO3를 사용하여 실온에서 12시간 동안 프레닐 브로마이드, 제라닐 브로마이드 또는 트랜스,트랜스-파네실 브로마이드로 처리함으로써 제조된다.Benzaldehyde with O -allyl ether in the first step is prenyl bromide, geranyl bromide or trans for 12 hours at room temperature using K 2 CO 3 in salicyaldehyde (1) in a DMF solvent It is prepared by treatment with trans-panesyl bromide.
[반응식 1]Scheme 1
반응식 2와 같이, 앞서 합성된 벤즈알데히드(2)의 2.0 당량과 2,4-디히드록시아세토페논(5)을 하기 표 1에 나타난 바와 같이 다양한 조건 하에서 반응시켜 벤조피라노벤조피란(6)을 합성하였고, EDDA 및 TEA를 함께 촉매로 사용하여 2시간 동안 환류 시켰을 때 크실렌에서 가장 좋은 수율을 나타내었다.As shown in Scheme 2, benzopyranobenzopyran (6) was reacted under a variety of conditions as shown in Table 1 by reacting 2.0 equivalents of benzaldehyde (2) and 2,4-dihydroxyacetophenone (5). It was synthesized and showed the best yield in xylene when refluxed for 2 hours using EDDA and TEA together as a catalyst.
[반응식 2]Scheme 2
이렇게 합성된 벤조피란 화합물(6)은 하기 반응식 3과 같이 엔도-전이상태(endo-transition structure)에 의해 설명될 수 있다. 즉, EDDA/TEA 존재 하에서 벤즈알데히드(2)와 2,4-디히드록시아세토페논(5)의 반응에 의해 알돌형 산물의 중간체(7)를 얻는다. TEA가 상기 중간체(7)의 탈수를 증가시켜 퀴논 메타이드(8a, 8b)를 형성시키며, 엔도-전이상태가 엑소-전이상태보다 더 안정하여 벤조피란 화합물(6)을 얻게 된다.The benzopyran compound (6) thus synthesized may be described by an endo-transition structure as in Scheme 3 below. That is, the intermediate (7) of the aldol-type product is obtained by reacting benzaldehyde (2) with 2,4-dihydroxyacetophenone (5) in the presence of EDDA / TEA. TEA increases the dehydration of the intermediate (7) to form quinone metades (8a, 8b), the endo-transition state is more stable than the exo-transition state to obtain the benzopyran compound (6).
[반응식 3]Scheme 3
또한, 하기 표 2와 같이, 상기 벤즈알데히드(2-4)와 다양한 레조시놀 간의 반응에 의해 벤조피라노벤조피란 화합물을 합성하였다.In addition, as shown in Table 2, the benzopyranobenzopyran compound was synthesized by the reaction between the benzaldehyde (2-4) and various resorcinol.
또한, 하기 표 3과 같이, 상기 벤즈알데히드(2-4)와 다양한 나프톨 간의 반응에 의해 나프톨피라노벤조피란 화합물을 합성하였다. In addition, as shown in Table 3, a naphtholpyranobenzopyran compound was synthesized by the reaction between the benzaldehyde (2-4) and various naphthols.
또한, 본 발명은 상기 합성된 벤조피라노벤조피란 고리화합물을 유효성분으로 하는 약학조성물을 제공한다. 이러한 약학조성물은 천연에서 폭넓게 발견된 벤조피란기 및 나프토피란기를 지닌 화합물들과 유사하게 항산화제, 항암제, 항염증제, 항바이러스제, 항박테리아제 또는 항-HIV제 등을 포함한 다양한 용도로 사용될 수 있다. The present invention also provides a pharmaceutical composition comprising the benzopyranobenzopyran ring compound synthesized as an active ingredient. Such pharmaceutical compositions can be used in various applications, including antioxidants, anticancer agents, anti-inflammatory agents, antiviral agents, antibacterial agents or anti-HIV agents, similarly to compounds having benzopyran and naphthopyran groups widely found in nature. .
본 발명에 따른 약학조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다.The pharmaceutical composition according to the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to a conventional method .
제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 화합물은 적어도 하나 이상의 부형제, 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제한다. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid form preparations include at least one excipient such as starch, calcium carbonate, sucrose ( Prepare by mixing sucrose or lactose, gelatin, etc.
또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. .
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
또한, 본 발명에 따른 벤조피란의 투여량은 투여경로, 질병의 정도, 성별, 체중, 나이 등에 따라서 증감될 수 있다. 따라서, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.In addition, the dose of benzopyran according to the present invention may be increased or decreased depending on the route of administration, the degree of disease, sex, weight, age, and the like. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.
상기 약학조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내(intracerebroventricular)주사에 의해 투여될 수 있다.The pharmaceutical composition may be administered to various mammals such as mice, mice, livestock, humans, and the like. All modes of administration can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
이하, 하기 실시예를 통해 본 발명을 보다 상세하게 설명한다. 다만, 이러한 실시예에 의해 본 발명이 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to the following examples. However, the present invention is not limited by these examples.
I. I. OO -알킬 에테르를 포함한 벤즈알데히드 제조Benzaldehyde production including alkyl ethers
<실시예 1> 2-(3-메틸부트-2-에닐옥시)벤즈알데히드(2)의 제조Example 1 Preparation of 2- (3-methylbut-2-enyloxy) benzaldehyde (2)
DMF(20mL)에 용해된 화학식 1의 화합물 용액(1.807g, 14.8mmol)에 소듐 하이드라이드(1.776g, 60%, 44.4mmol)를 4℃에서 첨가하였다. 20분 후, DMF(3mL)에 용해된 프레닐 브로마이드(2.426g, 16.3mmol)를 서서히 가하였다. 이러한 반응혼합물을 실온에서 12시간 동안 교반하였고, 물(30mL)을 0℃에서 천천히 가하였다. To a solution of the compound of formula 1 (1.807 g, 14.8 mmol) dissolved in DMF (20 mL) was added sodium hydride (1.776 g, 60%, 44.4 mmol) at 4 ° C. After 20 minutes, prenyl bromide (2.426 g, 16.3 mmol) dissolved in DMF (3 mL) was added slowly. This reaction mixture was stirred at rt for 12 h and water (30 mL) was added slowly at 0 ° C.
상기 반응혼합물을 에틸아세테이트(30mLx3)로 추출하고, 물(30mL) 및 포화 NH4Cl 용액(30mL)으로 세정하며, MgSO4로 건조하고, 증발시켰다. 얻어진 잔유물을 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 20:1)에 의해 정제하여 화학식 2의 화합물(2.787g, 99%)을 오일로 얻었다.The reaction mixture was extracted with ethyl acetate (30 mL × 3), washed with water (30 mL) and saturated NH 4 Cl solution (30 mL), dried over MgSO 4 and evaporated. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate, 20: 1) to obtain a compound of formula 2 (2.787 g, 99%) as an oil.
1H NMR (300 MHz, CDCl3) δ 10.54(1H, s), 7.80 (1H, dd, J=7.6, 1.7 Hz), 7.70 (1H, ddd, J=8.0, 7.6, 1.7 Hz), 7.00-6.95 (2H, m), 5.50-5.45 (1H, m), 4.64 (2H, d, J=6.6 Hz), 1.78 (3H, s), 1.73 (3H, s); 13C NMR (75 MHz, CDCl3) δ 189.9, 161.3, 138.6, 135.7, 128.2, 125.1, 120.5, 118.9, 112.9, 65.4, 25.7, 18.2; IR (neat) 2976, 2861, 1688, 1599, 1481, 1458, 1383, 1287, 1236, 1190, 1161, 1101, 1044, 993, 758 cm-1 m/z (EI) 190 (M+, 4), 148 (6), 147 (6), 123 (8), 122 (100), 121 (46), 120 (7), 69 (97), 68 (13), 65 (13), 53 (6); HRMS m/z (M+) calcd for C12H14O2: 190.0994. Found: 190.0992. 1 H NMR (300 MHz, CDCl 3 ) δ 10.54 (1H, s), 7.80 (1H, dd, J = 7.6, 1.7 Hz), 7.70 (1H, ddd, J = 8.0, 7.6, 1.7 Hz), 7.00- 6.95 (2H, m), 5.50-5.45 (1H, m), 4.64 (2H, d, J = 6.6 Hz), 1.78 (3H, s), 1.73 (3H, s); 13 C NMR (75 MHz, CDCl 3 ) δ 189.9, 161.3, 138.6, 135.7, 128.2, 125.1, 120.5, 118.9, 112.9, 65.4, 25.7, 18.2; IR (neat) 2976, 2861, 1688, 1599, 1481, 1458, 1383, 1287, 1236, 1190, 1161, 1101, 1044, 993, 758 cm -1 m / z (EI) 190 (M + , 4), 148 (6), 147 (6), 123 (8), 122 (100), 121 (46), 120 (7), 69 (97), 68 (13), 65 (13), 53 (6); HRMS m / z (M + ) calcd for C 12 H 14 O 2 : 190.0994. Found: 190.0992.
<실시예 2> (<Example 2> ( EE )-2-(3,7-디메틸옥타-2,6-디에닐옥시)벤즈알데히드(3)의 제조 Preparation of) -2- (3,7-dimethylocta-2,6-dienyloxy) benzaldehyde (3)
DMF(20mL)에 용해된 화학식 1의 화합물 용액(0.904g, 7.4mmol)에 소듐 하이드라이드(0.888g, 60%, 22.2mmol)를 0℃에서 첨가하였다. 20분 후, DMF(3mL)에 용해된 제라닐 브로마이드(1.770g, 8.2mmol)를 서서히 가하였다. 이러한 반응혼합물을 실온에서 12시간 동안 교반하였고, 물(30mL)을 0℃에서 천천히 가하였다. To a solution of the compound of formula 1 (0.904 g, 7.4 mmol) dissolved in DMF (20 mL) was added sodium hydride (0.888 g, 60%, 22.2 mmol) at 0 ° C. After 20 minutes, geranyl bromide (1.770 g, 8.2 mmol) dissolved in DMF (3 mL) was added slowly. This reaction mixture was stirred at rt for 12 h and water (30 mL) was added slowly at 0 ° C.
상기 반응혼합물을 에틸아세테이트(30mLx3)로 추출하고, 물(30mL) 및 포화 NH4Cl 용액(30mL)으로 세정하며, MgSO4로 건조하고, 증발시켰다. 얻어진 잔유물을 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 20:1)에 의해 정제하여 화학식 3의 화합물(1.893g, 99%)을 오일로 얻었다.The reaction mixture was extracted with ethyl acetate (30 mL × 3), washed with water (30 mL) and saturated NH 4 Cl solution (30 mL), dried over MgSO 4 and evaporated. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate, 20: 1) to obtain a compound of formula 3 (1.893 g, 99%) as an oil.
1H NMR (300 MHz, CDCl3) δ 10.48 (1H, s), 7.80 (1H, dd, J=7.5, 1.7 Hz), 7.49 (1H, ddd, J=8.0, 7.5, 1.7 Hz), 7.00-6.94 (2H, m), 5.49-5.44 (1H, m), 5.14-5.11 (1H, m), 4.63 (2H, d, J=6.4 Hz), 1.72 (3H, s), 2.16-2.00 (4H, m), 1.64 (3H, s), 1.57 (3H, s); 13C NMR (75 MHz, CDCl3) δ 189.9, 161.3, 141.8, 135.8, 135.7, 131.9, 128.2, 123.6, 120.5, 118.8, 113.0, 65.5, 39.4, 26.2, 25.6, 17.6, 16.7; IR (neat) 2969, 2920, 2859, 1690, 1599, 1481, 1456, 1383, 1287, 1236, 1190, 1161, 1103, 992, 833, 758 cm1 m/z (EI) 258 (M+, 2), 137 (26), 136 (15), 122 (31), 121 (21), 95 (13), 93 (18), 81 (49), 69 (100), 68 (13), 67 (13); HRMS m/z (M+) calcd for C17H22O2: 258.1620. Found: 258.1623. 1 H NMR (300 MHz, CDCl 3 ) δ 10.48 (1H, s), 7.80 (1H, dd, J = 7.5, 1.7 Hz), 7.49 (1H, ddd, J = 8.0, 7.5, 1.7 Hz), 7.00- 6.94 (2H, m), 5.49-5.44 (1H, m), 5.14-5.11 (1H, m), 4.63 (2H, d, J = 6.4 Hz), 1.72 (3H, s), 2.16-2.00 (4H, m), 1.64 (3H, s), 1.57 (3H, s); 13 C NMR (75 MHz, CDCl 3 ) δ 189.9, 161.3, 141.8, 135.8, 135.7, 131.9, 128.2, 123.6, 120.5, 118.8, 113.0, 65.5, 39.4, 26.2, 25.6, 17.6, 16.7; IR (neat) 2969, 2920, 2859, 1690, 1599, 1481, 1456, 1383, 1287, 1236, 1190, 1161, 1103, 992, 833, 758 cm 1 m / z (EI) 258 (M + , 2), 137 (26), 136 (15), 122 (31), 121 (21), 95 (13), 93 (18), 81 (49), 69 (100), 68 (13), 67 (13); HRMS m / z (M + ) calcd for C 17 H 22 O 2 : 258.1620. Found: 258.1623.
<실시예 3> (<Example 3> ( EE ),(), ( EE )-2-(3,7,11-트리메틸도데카-2,6,10-트리에닐옥시)벤즈알데히드(4)의 제조Preparation of) -2- (3,7,11-trimethyldodeca-2,6,10-trienyloxy) benzaldehyde (4)
DMF(20mL)에 용해된 화학식 1의 화합물 용액(0.904g, 7.4mmol)에 소듐 하이드라이드(0.888g, 60%, 22.2mmol)를 0℃에서 첨가하였다. 20분 후, DMF(3mL)에 용해된 트랜스,트랜스-파네실 브로마이드(2.325g, 8.2mmol)를 서서히 가하였다. 이러한 반응혼합물을 실온에서 12시간 동안 교반하였고, 물(30mL)을 0℃에서 천천히 가하였다. To a solution of the compound of formula 1 (0.904 g, 7.4 mmol) dissolved in DMF (20 mL) was added sodium hydride (0.888 g, 60%, 22.2 mmol) at 0 ° C. After 20 minutes, trans, trans-panesyl bromide (2.325 g, 8.2 mmol) dissolved in DMF (3 mL) was added slowly. This reaction mixture was stirred at rt for 12 h and water (30 mL) was added slowly at 0 ° C.
상기 반응혼합물을 에틸아세테이트(30mLx3)로 추출하고, 물(30mL) 및 포화 NH4Cl 용액(30mL)으로 세정하며, MgSO4로 건조하고, 증발시켰다. 얻어진 잔유물을 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 20:1)에 의해 정제하여 화학식 4의 화합물(2.368g, 98%)을 오일로 얻었다.The reaction mixture was extracted with ethyl acetate (30 mL × 3), washed with water (30 mL) and saturated NH 4 Cl solution (30 mL), dried over MgSO 4 and evaporated. The obtained residue was purified by silica gel column chromatography (hexane / ethyl acetate, 20: 1) to obtain a compound of formula 4 (2.368 g, 98%) as an oil.
1H NMR (300 MHz, CDCl3) δ 10.48 (1H, s), 7.80 (1H, dd, J=7.5, 1.7 Hz), 7.49 (1H, ddd, J=8.0, 7.5, 1.7 Hz), 7.01-6.94 (2H, m), 5.50.5.46 (1H, m), 5.11-5.04 (1H, m), 4.64 (2H, d, J=6.4 Hz), 2.18-1.91 (8H, m), 1.73 (3H, s), 1.65 (3H, s), 1.58 (3H, s); 13C NMR (75 MHz, CDCl3) δ 189.9, 161.3, 141.8, 135.7, 135.5, 131.2, 128.2, 125.1, 124.2, 123.5, 120.5, 118.8, 112.9, 65.5, 39.6, 39.4, 26.6, 26.1, 25.6, 17.6, 16.7, 16.0; IR (neat) 2967, 2922, 2857, 1690, 1599, 1481, 1456, 1383, 1287, 1236, 1190, 1161, 1103, 992, 833, 758 cm-1, m/z (EI) 326 (M1, 2), 207 (7), 189 (6), 161 (9), 149 (10), 137 (34), 122 (30), 121 (24), 93 (33), 81 (95), 69 (100), 55 (20); HRMS m/z (M+) calcd for C22H30O2: 326.2246. Found: 326.2244. 1 H NMR (300 MHz, CDCl 3 ) δ 10.48 (1H, s), 7.80 (1H, dd, J = 7.5, 1.7 Hz), 7.49 (1H, ddd, J = 8.0, 7.5, 1.7 Hz), 7.01- 6.94 (2H, m), 5.50.5.46 (1H, m), 5.11-5.04 (1H, m), 4.64 (2H, d, J = 6.4 Hz), 2.18-1.91 (8H, m), 1.73 (3H, s), 1.65 (3H, s), 1.58 (3H, s); 13 C NMR (75 MHz, CDCl 3 ) δ 189.9, 161.3, 141.8, 135.7, 135.5, 131.2, 128.2, 125.1, 124.2, 123.5, 120.5, 118.8, 112.9, 65.5, 39.6, 39.4, 26.6, 26.1, 25.6, 17.6 , 16.7, 16.0; IR (neat) 2967, 2922, 2857, 1690, 1599, 1481, 1456, 1383, 1287, 1236, 1190, 1161, 1103, 992, 833, 758 cm -1 , m / z (EI) 326 (M 1 , 2), 207 (7), 189 (6), 161 (9), 149 (10), 137 (34), 122 (30), 121 (24), 93 (33), 81 (95), 69 ( 100), 55 (20); HRMS m / z (M + ) calcd for C 22 H 30 O 2 : 326.2246. Found: 326.2244.
II. 벤조피라노벤조피란 및 나프톨피라노벤조피란 제조II. Preparation of benzopyranobenzopyran and naphtholpyranobenzopyran
에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL)를 실온에서 크실렌(10mL)에 용해된 레조시놀 또는 나프톨(1.0mmol)에 벤즈알데히드(2.0mmol)를 가하였다. 상기 반응혼합물을 12-24 시간 동안 크실렌에서 환류 교반하였다. Ethylenediamine diacetate (36 mg, 0.2 mmol) and TEA (2 mL) were added benzaldehyde (2.0 mmol) to resorcinol or naphthol (1.0 mmol) dissolved in xylene (10 mL) at room temperature. The reaction mixture was stirred at reflux in xylene for 12-24 hours.
감압 하에서 용매를 제거하여 오일상의 잔유물을 얻은 후, 실리카겔 컬럼 크로마토그래피로 정제하여 생성물을 얻었다.The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography to obtain a product.
<실시예 4> 1-(1-히드록시-6,6-디메틸-6a,12b-디하이드로-6H,7H-5,8-디옥사벤조[c]페난트렌-2-일)에타논(6)의 제조Example 4 1- (1-hydroxy-6,6-dimethyl-6a, 12b-dihydro-6H, 7H-5,8-dioxabenzo [c] phenanthren-2-yl) ethanone ( 6) Manufacture
실온에서 크실렌 용매에 2,4-디히드록시아세토페논(5)(0.152g, 1.0mmol)과 벤즈알데히드(2) (0.380g, 2.0mmol)를 가한 후 에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL) 넣고 그 혼합물을 24 시간 동안 환류 교반하였다. 감압 하에서 용매를 제거하여 오일상의 잔유물을 얻은 후, 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 10:1)로 정제하여 화학식 6의 화합물(0.208g, 64%)을 고체로 얻었다.2,4-dihydroxyacetophenone (5) (0.152 g, 1.0 mmol) and benzaldehyde (2) (0.380 g, 2.0 mmol) were added to a xylene solvent at room temperature, followed by ethylenediamine diacetate (36 mg, 0.2 mmol) and TEA (2 mL) was added and the mixture was stirred at reflux for 24 hours. The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography (hexane / ethyl acetate, 10: 1) to obtain a compound of formula 6 (0.208 g, 64%) as a solid.
mp 152-153℃; 1H NMR (300 MHz, CDCl3) δ 13.47 (1H, s), 7.59 (1H, d, J=8.9 Hz), 7.23 (1H, d, J=8.0 Hz), 7.06 (1H, dd, J=8.0, 7.5 Hz), 6.80 (1H, dd, J=7.8, 7.5 Hz), 6.70 (1H, d, J=7.8 Hz), 6.37 (1H, d, J=8.9 Hz), 4.50 (2H, dd, J=12.0, 4.2 Hz), 4.47 (1H, d, J=4.3 Hz), 2.58 (3H, s), 2.24-2.18 (1H, m), 1.53 (3H, s), 1.08 (3H, s); 13C NMR (75 MHz, CDCl3) δ 202.6, 163.5, 160.0, 153.9, 130.9, 129.2, 127.6, 122.3, 120.7, 115.8, 112.9, 110.7, 109.3, 78.6, 65.5, 38.5, 29.0, 28.8, 26.1, 23.8; IR (KBr) 2969, 1618, 1487, 1449, 1412, 1373, 1323, 1267, 1127, 1084, 1059, 893, 828, 804, 758 cm-1; m/z (EI) 324 (M+, 100), 325 (21), 324 (100), 309 (16), 282 (11), 281 (50), 268 (9), 255 (13), 240 (11), 239 (67), 159 (13), 69 (8); HRMS m/z (M+) calcd for C20H20O4: 324.1362. Found: 324.1363.mp 152-153 ° C; 1 H NMR (300 MHz, CDCl 3 ) δ 13.47 (1H, s), 7.59 (1H, d, J = 8.9 Hz), 7.23 (1H, d, J = 8.0 Hz), 7.06 (1H, dd, J = 8.0, 7.5 Hz), 6.80 (1H, dd, J = 7.8, 7.5 Hz), 6.70 (1H, d, J = 7.8 Hz), 6.37 (1H, d, J = 8.9 Hz), 4.50 (2H, dd, J = 12.0, 4.2 Hz), 4.47 (1H, d, J = 4.3 Hz), 2.58 (3H, s), 2.24-2.18 (1H, m), 1.53 (3H, s), 1.08 (3H, s); 13 C NMR (75 MHz, CDCl 3 ) δ 202.6, 163.5, 160.0, 153.9, 130.9, 129.2, 127.6, 122.3, 120.7, 115.8, 112.9, 110.7, 109.3, 78.6, 65.5, 38.5, 29.0, 28.8, 26.1, 23.8 ; IR (KBr) 2969, 1618, 1487, 1449, 1412, 1373, 1323, 1267, 1127, 1084, 1059, 893, 828, 804, 758 cm −1 ; m / z (EI) 324 (M + , 100), 325 (21), 324 (100), 309 (16), 282 (11), 281 (50), 268 (9), 255 (13), 240 (11), 239 (67), 159 (13), 69 (8); HRMS m / z (M + ) calcd for C 20 H 20 O 4 : 324.1362. Found: 324.1363.
<실시예 5> 3,6,6-트리메틸-6a,12b-디히드로-6H,7H-5,8-디옥사벤조[c]페난트렌-1-올(16)의 제조Example 5 Preparation of 3,6,6-trimethyl-6a, 12b-dihydro-6H, 7H-5,8-dioxabenzo [c] phenanthren-1-ol (16)
실온에서 크실렌(10mL) 용매에 오시놀(9)(0.124g, 1.0mmol)과 벤즈알데히드(2)0.380g, 2.0mmol)을 가한 후 에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL) 넣고 그 반응혼합물을 18 시간 동안 환류 교반하였다. 감압 하에서 용매를 제거하여 오일상의 잔유물을 얻은 후, 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 10:1)로 정제하여 화학식 16의 화합물(0.166g, 56%)을 고체로 얻었다.Ossin (9) (0.124 g, 1.0 mmol) and benzaldehyde (2) 0.380 g, 2.0 mmol) were added to a xylene (10 mL) solvent at room temperature, followed by ethylenediamine diacetate (36 mg, 0.2 mmol) and TEA (2 mL). The reaction mixture was stirred at reflux for 18 hours. The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography (hexane / ethyl acetate, 10: 1) to obtain a compound of formula 16 (0.166 g, 56%) as a solid.
mp 140-141℃; 1H NMR (300 MHz, CDCl3) δ 12.01 (1H, s), 7.30 (1H, d, J=7.8 Hz), 7.11 (1H, d, J=7.8, 7.4 Hz), 6.84 (1H, dd, J=8.0, 7.4 Hz), 6.76 (1H, d, J=8.0 Hz), 6.29 (1H, s), 6.24 (1H, s), 4.47 (1H, dd, J=11.8, 4.6 Hz), 4.35 (1H, dd, J=11.8, 4.6 Hz), 4.33 (1H, d, J=4.6 Hz), 2.27-2.20 (1H, m), 2.22 (3H, s), 1.46 (3H, s), 1.09 (3H, s); 13C NMR (75 MHz, CDCl3) δ 154.9, 154.4, 153.9, 139.0, 129.3, 128.1, 123.3, 120.9, 116.4, 110.6, 108.3, 106.8, 76.2, 65.8, 39.2, 30.2, 28.5, 24.0, 21.1; IR (KBr) 3428, 3036, 2982, 2942, 1618, 1584, 1489, 1450, 1240, 1175, 1132, 1080, 1049, 995, 885, 853, 816, 748 cm-1; m/z (EI) 296 (M+, 60), 281 (7), 253 (17), 227 (20), 212 (15), 211 (100), 159 (13); HRMS m/z (M+) calcd for C19H20O3: 296.1412. Found: 296.1411.mp 140-141 ° C .; 1 H NMR (300 MHz, CDCl 3 ) δ 12.01 (1H, s), 7.30 (1H, d, J = 7.8 Hz), 7.11 (1H, d, J = 7.8, 7.4 Hz), 6.84 (1H, dd, J = 8.0, 7.4 Hz), 6.76 (1H, d, J = 8.0 Hz), 6.29 (1H, s), 6.24 (1H, s), 4.47 (1H, dd, J = 11.8, 4.6 Hz), 4.35 ( 1H, dd, J = 11.8, 4.6 Hz), 4.33 (1H, d, J = 4.6 Hz), 2.27-2.20 (1H, m), 2.22 (3H, s), 1.46 (3H, s), 1.09 (3H , s); 13 C NMR (75 MHz, CDCl 3 ) δ 154.9, 154.4, 153.9, 139.0, 129.3, 128.1, 123.3, 120.9, 116.4, 110.6, 108.3, 106.8, 76.2, 65.8, 39.2, 30.2, 28.5, 24.0, 21.1; IR (KBr) 3428, 3036, 2982, 2942, 1618, 1584, 1489, 1450, 1240, 1175, 1132, 1080, 1049, 995, 885, 853, 816, 748 cm −1 ; m / z (EI) 296 (M + , 60), 281 (7), 253 (17), 227 (20), 212 (15), 211 (100), 159 (13); HRMS m / z (M + ) calcd for C 19 H 20 O 3 : 296.1412. Found: 296.1411.
<실시예 6> 6,6-디메틸-3-펜틸-6a,12b-디히드로-6H,7H-5,8-디옥사벤조[c]페난트렌-1-올(17)의 제조Example 6 Preparation of 6,6-dimethyl-3-pentyl-6a, 12b-dihydro-6H, 7H-5,8-dioxabenzo [c] phenanthren-1-ol (17)
실온에서 크실렌(10mL) 용매에 올리베톨(10)(0.180g, 1.0mmol)과 벤즈알데히드(2)(0.380g, 2.0mmol)을 가한 후 에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL)를 넣고 그 반응혼합물을 18 시간 동안 환류 교반하였다. 감압 하에서 용매를 제거하여 오일상의 잔유물을 얻은 후, 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 20:1)로 정제하여 화학식 17의 화합물(0.183g, 52%)을 고체로 얻었다.Olibetol (10) (0.180 g, 1.0 mmol) and benzaldehyde (2) (0.380 g, 2.0 mmol) were added to a xylene (10 mL) solvent at room temperature, followed by ethylenediamine diacetate (36 mg, 0.2 mmol) and TEA (2 mL). The reaction mixture was stirred at reflux for 18 hours. The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography (hexane / ethyl acetate, 20: 1) to obtain a compound of formula 17 (0.183 g, 52%) as a solid.
mp 113.114 C; 1H NMR (300 MHz, CDCl3) δ 12.51 (1H, s), 7.31 (1H, d, J=7.8 Hz), 7.10 (1H, d, J=7.8, 7.4 Hz), 6.84 (1H, dd, J=8.0, 7.4 Hz), 6.75 (1H, d, J=8.0), 6.29 (1H, s), 6.25 (1H, s), 4.48 (1H, dd, J=11.8, 4.6 Hz), 4.35 (1H, dd, J=11.8, 4.6 Hz), 4.33 (1H, d, J=4.6 Hz), 2.46 (2H, t, J=7.5 Hz), 2.26-2.21 (1H, m), 1.62-1.52 (3H, m), 1.46 (3H, s), 1.37-1.29 (3H, m), 1.09 (3H, s), 0.87 (3H, t, J=6.6 Hz); 13C NMR (75 MHz, CDCl3) δ 154.8, 154.4, 153.8, 144.0, 129.1, 128.0, 123.3, 120.8, 116.3, 109.8, 107.6, 107.0, 76.2, 65.8, 39.2, 35.6, 31.5, 30.6, 30.2, 28.5, 24.0, 22.5, 14.0; IR (KBr) 3368, 2930, 1624, 1487, 1452, 1429, 1348, 1246, 1171, 1136, 1078, 1043, 889, 790, 754 cm-1 HRMS m/z (M+) calcd for C23H28O3: 352.2038. Found: 352.2034.mp 113.114 C; 1 H NMR (300 MHz, CDCl 3) δ 12.51 (1H, s), 7.31 (1H, d, J = 7.8 Hz), 7.10 (1H, d, J = 7.8, 7.4 Hz), 6.84 (1H, dd, J = 8.0, 7.4 Hz), 6.75 (1H, d, J = 8.0), 6.29 (1H, s), 6.25 (1H, s), 4.48 (1H, dd, J = 11.8, 4.6 Hz), 4.35 (1H, dd, J = 11.8, 4.6 Hz), 4.33 (1H, d, J = 4.6 Hz), 2.46 (2H, t, J = 7.5 Hz), 2.26-2.21 (1H, m), 1.62-1.52 (3H, m ), 1.46 (3H, s), 1.37-1.29 (3H, m), 1.09 (3H, s), 0.87 (3H, t, J = 6.6 Hz); 13 C NMR (75 MHz, CDCl 3 ) δ 154.8, 154.4, 153.8, 144.0, 129.1, 128.0, 123.3, 120.8, 116.3, 109.8, 107.6, 107.0, 76.2, 65.8, 39.2, 35.6, 31.5, 30.6, 30.2, 28.5 , 24.0, 22.5, 14.0; IR (KBr) 3368, 2930, 1624, 1487, 1452, 1429, 1348, 1246, 1171, 1136, 1078, 1043, 889, 790, 754 cm -1 HRMS m / z (M + ) calcd for C 23 H 28 0 3 : 352.2038. Found: 352.2034.
<실시예 7> 1-히드록시-6,6-디메틸-6a,12b-디히드로-6H,7H-5,8-디옥사벤조[c]페난트렌-2-카르복실산 메틸 에스테르(18)의 제조Example 7 1-hydroxy-6,6-dimethyl-6a, 12b-dihydro-6H, 7H-5,8-dioxabenzo [c] phenanthrene-2-carboxylic acid methyl ester (18) Manufacture
실온에서 크실렌(10mL) 용매에 메틸 2,4-디히드록시벤조에이트(11)(0.168g, 1.0mmol)과 벤즈알데히드(2)(0.380g, 2.0mmol)를 가한 후 에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL)를 넣고 그 반응혼합물을 18 시간 동안 환류 교반하였다. 감압 하에서 용매를 제거하여 오일상의 잔사를 얻은 후, 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 20:1)로 정제하여 화학식 18의 화합물(0.194g, 57%)을 고체로 얻었다.Methyl 2,4-dihydroxybenzoate (11) (0.168 g, 1.0 mmol) and benzaldehyde (2) (0.380 g, 2.0 mmol) were added to a xylene (10 mL) solvent at room temperature, followed by ethylenediamine diacetate (36 mg, 0.2 mmol) and TEA (2 mL) were added and the reaction mixture was stirred at reflux for 18 hours. The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography (hexane / ethyl acetate, 20: 1) to obtain a compound of formula 18 (0.194 g, 57%) as a solid.
mp 123-124 ℃; 1H NMR (300 MHz, CDCl3) δ 11.62 (1H, s), 7.70 (1H, d, J=8.9 Hz), 7.25 (1H, d, J=7.7 Hz), 7.07 (1H, d, J=7.7, 7.4 Hz), 6.80 (1H, dd, J=8.0, 7.4 Hz), 6.72 (1H, d, J=8.0 Hz), 6.38 (1H, d, J=8.9 Hz), 4.53-4.46 (3H, m), 3.92 (3H, s), 2.24-2.18 (1H, m), 1.53 (3H, s), 1.07 (3H, s); 13C NMR (75 MHz, CDCl3) δ 170.9-161.9, 159.4, 154.0, 129.7, 129.2, 127.6, 122.5, 120.7, 115.9, 110.5-109.5, 104.3, 78.2, 65.7, 52.0, 38.6, 29.3, 28.9, 23.8; IR (KBr) 2980, 1664, 1622, 1584, 1489, 1439, 1345, 1267, 1217, 1134, 1061, 997, 889, 791, 752 cm-1; m/z (EI) 340 (M+, 92), 309 (26), 308 (100), 293 (11), 281 (11), 280 (48), 239 (17), 224 (10), 223 (59), 159 (20); HRMS m/z (M+) calcd for C20H20O5: 340.1311. Found: 340.1313.mp 123-124 ° C; 1 H NMR (300 MHz, CDCl 3 ) δ 11.62 (1H, s), 7.70 (1H, d, J = 8.9 Hz), 7.25 (1H, d, J = 7.7 Hz), 7.07 (1H, d, J = 7.7, 7.4 Hz), 6.80 (1H, dd, J = 8.0, 7.4 Hz), 6.72 (1H, d, J = 8.0 Hz), 6.38 (1H, d, J = 8.9 Hz), 4.53-4.46 (3H, m), 3.92 (3H, s), 2.24-2.18 (1H, m), 1.53 (3H, s), 1.07 (3H, s); 13 C NMR (75 MHz, CDCl 3 ) δ 170.9-161.9, 159.4, 154.0, 129.7, 129.2, 127.6, 122.5, 120.7, 115.9, 110.5-109.5, 104.3, 78.2, 65.7, 52.0, 38.6, 29.3, 28.9, 23.8 ; IR (KBr) 2980, 1664, 1622, 1584, 1489, 1439, 1345, 1267, 1217, 1134, 1061, 997, 889, 791, 752 cm −1 ; m / z (EI) 340 (M + , 92), 309 (26), 308 (100), 293 (11), 281 (11), 280 (48), 239 (17), 224 (10), 223 59, 159 (20); HRMS m / z (M + ) calcd for C 20 H 20 O 5 : 340.1311. Found: 340.1313.
<실시예 8> 1-히드록시-6,6-디메틸-6a,12b-디히드로-6H,7H-5,8-디옥사벤조[c]페난트렌-2-카르복실산 에틸 에스테르(19)의 제조Example 8 1-hydroxy-6,6-dimethyl-6a, 12b-dihydro-6H, 7H-5,8-dioxabenzo [c] phenanthrene-2-carboxylic acid ethyl ester (19) Manufacture
실온에서 크실렌(10mL) 용매에 에틸 2,4-디히드록시벤조에이트(12)(0.182g, 1.0mmol)과 벤즈알데히드(2)0.380g, 2.0mmol)를 가한 후 에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL)를 넣고 그 반응혼합물을 18 시간 동안 환류 교반하였다. 감압 하에서 용매를 제거하여 오일상의 잔유물을 얻은 후, 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 20:1)로 정제하여 화학식 19의 화합물(0.220g, 62%)을 고체로 얻었다.Ethyl 2,4-dihydroxybenzoate (12) (0.182 g, 1.0 mmol) and benzaldehyde (2) 0.380 g, 2.0 mmol) were added to a xylene (10 mL) solvent at room temperature, followed by ethylenediamine diacetate (36 mg, 0.2 mmol) and TEA (2 mL) were added and the reaction mixture was stirred at reflux for 18 hours. The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography (hexane / ethyl acetate, 20: 1) to obtain a compound of formula 19 (0.220 g, 62%) as a solid.
mp 134-135℃; 1H NMR (300 MHz, CDCl3) δ 11.60 (1H, s), 7.64 (1H, d, J=8.9 Hz), 7.17 (1H, d, J=7.8 Hz), 6.99 (1H, d, J=7.8, 7.4 Hz), 6.72 (1H, dd, J=8.0, 7.4 Hz), 6.63 (1H, d, J=8.0 Hz), 6.29 (1H, d, J=8.9 Hz), 4.46-4.28 (5H, m), 2.32-2.20 (1H, m), 1.44 (3H, s), 1.33 (3H, t, J=7.2 Hz), 0.99 (3H, s); 13C NMR (75 MHz, CDCl3) δ 170.6, 162.0, 159.3, 154.0, 129.7, 129.2, 127.6, 122.5, 120.7, 115.9, 110.4, 109.3, 104.6, 78.2, 65.7, 61.0, 38.7, 29.3, 28.9, 23.8, 14.3; IR (KBr) 2980, 1661, 1584, 1489, 1373, 1265, 1136, 1061, 1020, 910, 793, 752 cm-1; HRMS m/z (M+) calcd for C21H22O5: 354.1467. Found: 354.1469.mp 134-135 ° C .; 1 H NMR (300 MHz, CDCl 3 ) δ 11.60 (1H, s), 7.64 (1H, d, J = 8.9 Hz), 7.17 (1H, d, J = 7.8 Hz), 6.99 (1H, d, J = 7.8, 7.4 Hz), 6.72 (1H, dd, J = 8.0, 7.4 Hz), 6.63 (1H, d, J = 8.0 Hz), 6.29 (1H, d, J = 8.9 Hz), 4.46-4.28 (5H, m), 2.32-2.20 (1H, m), 1.44 (3H, s), 1.33 (3H, t, J = 7.2 Hz), 0.99 (3H, s); 13 C NMR (75 MHz, CDCl 3 ) δ 170.6, 162.0, 159.3, 154.0, 129.7, 129.2, 127.6, 122.5, 120.7, 115.9, 110.4, 109.3, 104.6, 78.2, 65.7, 61.0, 38.7, 29.3, 28.9, 23.8 , 14.3; IR (KBr) 2980, 1661, 1584, 1489, 1373, 1265, 1136, 1061, 1020, 910, 793, 752 cm −1 ; HRMS m / z (M + ) calcd for C 21 H 22 O 5 : 354.1467. Found: 354.1469.
<실시예 9> 1-히드록시-3,6,6-트리메틸-6a,12b-디히드로-6H,7H-5,8-디옥사벤조[c]페난트렌-2-카르복실산 에틸 에스테르(20)의 제조Example 9 1-hydroxy-3,6,6-trimethyl-6a, 12b-dihydro-6H, 7H-5,8-dioxabenzo [c] phenanthrene-2-carboxylic acid ethyl ester ( Manufacture of 20)
실온에서 크실렌(10mL) 용매에 에틸 2,4-디히드록시-6-메틸벤조에이트(13) (0.196g, 1.0mmol)과 벤즈알데히드(2)(0.380g, 2.0mmol)를 가한 후 에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL)를 넣고 그 반응혼합물을 18 시간 동안 환류 교반하였다. 감압 하에서 용매를 제거하여 오일상의 잔유물을 얻은 후, 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 20:1)로 정제하여 화학식 20의 화합물(0.221g, 60%)을 고체로 얻었다.Ethyl 2,4-dihydroxy-6-methylbenzoate (13) (0.196 g, 1.0 mmol) and benzaldehyde (2) (0.380 g, 2.0 mmol) were added to a xylene (10 mL) solvent at room temperature, followed by ethylenediamine di Acetate (36 mg, 0.2 mmol) and TEA (2 mL) were added and the reaction mixture was stirred under reflux for 18 hours. The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography (hexane / ethyl acetate, 20: 1) to obtain a compound of formula 20 (0.221 g, 60%) as a solid.
mp 126-127℃; 1H NMR (300 MHz, CDCl3) δ 12.55 (1H, s), 7.27 (1H, d, J=7.7 Hz), 7.06 (1H, d, J=7.7, 7.4 Hz), 6.80 (1H, dd, J=8.0, 7.4 Hz), 6.71 (1H, d, J=8.0 Hz), 6.24 (1H, s), 4.53-4.39 (5H, m), 2.51 (3H, s), 2.23-2.16 (1H, m), 1.52 (3H, s), 1.43 (3H, t, J=7.1 Hz), 1.06 (3H, s); 13C NMR (75 MHz, CDCl3) δ 172.3, 163.7, 157.7, 154.0, 141.6, 129.3, 127.5, 122.8, 120.7, 115.8, 112.5, 108.5, 104.4, 78.1, 65.7, 61.2, 38.9, 29.3, 28.9, 24.2, 23.8, 14.3; IR (KBr) 3038, 2980, 2936, 1644, 1397, 1489, 1453, 1397, 1368, 1323, 1269, 1246, 1136, 1090, 1009, 806, 752 cm-1 m/z (EI) 368 (M1, 55), 323 (27), 322 (100), 295 (14), 294 (66), 293 (10), 279 (15), 253 (12), 237 (34); HRMS m/z (M+) calcd for C22H24O5: 368.1624. Found: 368.1621.mp 126-127 ° C; 1 H NMR (300 MHz, CDCl 3 ) δ 12.55 (1H, s), 7.27 (1H, d, J = 7.7 Hz), 7.06 (1H, d, J = 7.7, 7.4 Hz), 6.80 (1H, dd, J = 8.0, 7.4 Hz), 6.71 (1H, d, J = 8.0 Hz), 6.24 (1H, s), 4.53-4.39 (5H, m), 2.51 (3H, s), 2.23-2.16 (1H, m ), 1.52 (3H, s), 1.43 (3H, t, J = 7.1 Hz), 1.06 (3H, s); 13 C NMR (75 MHz, CDCl 3 ) δ 172.3, 163.7, 157.7, 154.0, 141.6, 129.3, 127.5, 122.8, 120.7, 115.8, 112.5, 108.5, 104.4, 78.1, 65.7, 61.2, 38.9, 29.3, 28.9, 24.2 , 23.8, 14.3; IR (KBr) 3038, 2980, 2936, 1644, 1397, 1489, 1453, 1397, 1368, 1323, 1269, 1246, 1136, 1090, 1009, 806, 752 cm -1 m / z (EI) 368 (M 1 , 55), 323 (27), 322 (100), 295 (14), 294 (66), 293 (10), 279 (15), 253 (12), 237 (34); HRMS m / z (M + ) calcd for C 22 H 24 O 5 : 368.1624. Found: 368.1621.
<실시예 10> 1-(1-히드록시-6,6-디메틸-6a,12b-디히드로-6H,7H-5,8-디옥사벤조[c]페난트렌-2-일)프로판-1-온(21)의 제조Example 10 1- (1-hydroxy-6,6-dimethyl-6a, 12b-dihydro-6H, 7H-5,8-dioxabenzo [c] phenanthren-2-yl) propane-1 Preparation of On-21
실온에서 크실렌(10mL) 용매에 2,4-디히드록시프로피오페논(14)(0.166g, 1.0mmol)과 벤즈알데히드(2)(0.380g, 2.0mmol)를 가한 후 에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL)를 넣고 그 반응혼합물을 12 시간 동안 환류 교반하였다. 감압 하에서 용매를 제거하여 오일상의 잔유물을 얻은 후, 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 20:1)로 정제하여 화학식 21의 화합물(0.213g, 63%)을 고체로 얻었다.2,4-Dihydroxypropiophenone (14) (0.166 g, 1.0 mmol) and benzaldehyde (2) (0.380 g, 2.0 mmol) were added to a xylene (10 mL) solvent at room temperature, followed by ethylenediamine diacetate (36 mg, 0.2 mmol) and TEA (2 mL) were added and the reaction mixture was stirred at reflux for 12 hours. The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography (hexane / ethyl acetate, 20: 1) to obtain a compound of formula 21 (0.213 g, 63%) as a solid.
mp 124-125℃; 1H NMR (300 MHz, CDCl3) δ 13.59 (1H, s), 7.64 (1H, d, J=8.9 Hz), 7.25 (1H, d, J=7.8 Hz), 7.07 (1H, d, J=7.8, 7.4 Hz), 6.80 (1H, dd, J=8.0, 7.4 Hz), 6.71 (1H, d, J=8.0 Hz), 6.38 (1H, d, J=8.9 Hz), 4.54-4.48(3H, m), 2.99 (2H, q, 7.2 Hz), 2.25.2.20 (1H, m), 1.54 (3H, s), 1.27 (3H, t, J=7.5 Hz), 1.09 (3H, s); 13C NMR (75 MHz, CDCl3) δ 205.5, 163.6, 159.8, 154.0, 130.1, 129.2, 127.7, 122.4, 120.8, 115.9, 112.4, 110.8, 109.2, 78.6, 65.6, 38.6, 31.1, 29.1, 28.9, 23.8, 8.7; IR (KBr) 2980, 1620, 1489, 1416, 1323, 1258, 1123, 1071, 910, 891, 797, 754 cm-1 m/z (EI) 338 (M+, 100), 310 (13), 309 (64), 295 (33), 253 (45), 241 (25), 159 (9), 69 (10); HRMS m/z (M+) calcd for C21H22O4: 338.1518. Found: 338.1520.mp 124-125 ° C .; 1 H NMR (300 MHz, CDCl 3 ) δ 13.59 (1H, s), 7.64 (1H, d, J = 8.9 Hz), 7.25 (1H, d, J = 7.8 Hz), 7.07 (1H, d, J = 7.8, 7.4 Hz), 6.80 (1H, dd, J = 8.0, 7.4 Hz), 6.71 (1H, d, J = 8.0 Hz), 6.38 (1H, d, J = 8.9 Hz), 4.54-4.48 (3H, m), 2.99 (2H, q, 7.2 Hz), 2.25.2.20 (1H, m), 1.54 (3H, s), 1.27 (3H, t, J = 7.5 Hz), 1.09 (3H, s); 13 C NMR (75 MHz, CDCl 3 ) δ 205.5, 163.6, 159.8, 154.0, 130.1, 129.2, 127.7, 122.4, 120.8, 115.9, 112.4, 110.8, 109.2, 78.6, 65.6, 38.6, 31.1, 29.1, 28.9, 23.8 , 8.7; IR (KBr) 2980, 1620, 1489, 1416, 1323, 1258, 1123, 1071, 910, 891, 797, 754 cm -1 m / z (EI) 338 (M + , 100), 310 (13), 309 64, 295 (33), 253 (45), 241 (25), 159 (9), 69 (10); HRMS m / z (M + ) calcd for C 21 H 22 O 4 : 338.1518. Found: 338.1520.
<실시예 11> 1-(1-히드록시-6,6-디메틸-6a,12b-디히드로-6H,7H-5,8-디옥사벤조[c]페난트렌-2-일)페닐메타논(22)의 제조Example 11 1- (1-hydroxy-6,6-dimethyl-6a, 12b-dihydro-6H, 7H-5,8-dioxabenzo [c] phenanthren-2-yl) phenylmethanone Manufacture of 22
실온에서 크실렌(10mL) 용매에 2,4-디히드록시벤조페논(15)(0.214g, 1.0mmol)과 벤즈알데히드(2)(0.380g, 2.0mmol)를 가한 후 에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL)를 넣고 그 반응혼합물을 12 시간 동안 환류 교반하였다. 감압 하에서 용매를 제거하여 오일상의 잔유물을 얻은 후, 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 15:1)로 정제하여 화학식 22의 화합물(0.274g, 71%)을 고체로 얻었다.2,4-Dihydroxybenzophenone (15) (0.214 g, 1.0 mmol) and benzaldehyde (2) (0.380 g, 2.0 mmol) were added to a xylene (10 mL) solvent at room temperature, followed by ethylenediamine diacetate (36 mg, 0.2 mmol) and TEA (2 mL) were added and the reaction mixture was stirred at reflux for 12 hours. The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography (hexane / ethyl acetate, 15: 1) to obtain a compound of formula 22 (0.274 g, 71%) as a solid.
mp 65-66℃; 1H NMR (300 MHz, CDCl3) δ 13.46 (1H, s), 7.65 (2H, d, J=8.9 Hz), 7.55-7.44 (4H, m), 7.33 (1H, d, J=7.8 Hz), 7.08 (1H, d, J=7.8, 7.4 Hz), 6.83 (1H, dd, J=8.0, 7.4 Hz), 6.72 (1H, d, J=8.0 Hz), 6.33 (1H, d, J=8.9 Hz), 4.63-4.49 (3H, m), 2.28-2.20 (1H, m), 1.54 (3H, s), 1.10 (3H, s); 13C NMR (75 MHz, CDCl3) δ 200.2, 164.8, 160.3, 154.0, 138.3, 133.9, 131.4, 129.3, 128.9, 128.3, 127.8, 122.3, 120.8, 115.9, 112.2, 111.0, 109.2, 78.8, 65.6, 38.6, 29.2, 28.9, 23.9; IR (KBr) 2980, 1615, 1487, 1348, 1269, 1138, 1071, 885, 756 cm-1; HRMS m/z (M+) calcd for C25H22O4: 386.1518. Found: 386.1522.mp 65-66 ° C .; 1 H NMR (300 MHz, CDCl 3 ) δ 13.46 (1H, s), 7.65 (2H, d, J = 8.9 Hz), 7.55-7.44 (4H, m), 7.33 (1H, d, J = 7.8 Hz) , 7.08 (1H, d, J = 7.8, 7.4 Hz), 6.83 (1H, dd, J = 8.0, 7.4 Hz), 6.72 (1H, d, J = 8.0 Hz), 6.33 (1H, d, J = 8.9 Hz), 4.63-4.49 (3H, m), 2.28-2.20 (1H, m), 1.54 (3H, s), 1.10 (3H, s); 13 C NMR (75 MHz, CDCl 3 ) δ 200.2, 164.8, 160.3, 154.0, 138.3, 133.9, 131.4, 129.3, 128.9, 128.3, 127.8, 122.3, 120.8, 115.9, 112.2, 111.0, 109.2, 78.8, 65.6, 38.6 , 29.2, 28.9, 23.9; IR (KBr) 2980, 1615, 1487, 1348, 1269, 1138, 1071, 885, 756 cm −1 ; HRMS m / z (M + ) calcd for C 25 H 22 O 4: 386.1518. Found: 386.1522.
<실시예 12> [1-히드록시-6-메틸-6-(4-메틸펜트-3-에닐)-6a,12b-디히드로-6H,7H-5,8-디옥사벤조[c]페난트렌-2-일]페닐메타논(23)의 제조Example 12 [1-hydroxy-6-methyl-6- (4-methylpent-3-enyl) -6a, 12b-dihydro-6H, 7H-5,8-dioxabenzo [c] phenan Preparation of Tren-2-yl] phenylmethanone (23)
실온에서 크실렌(10mL) 용매에 2,4-디히드록시벤조페논(15)(0.214g, 1.0mmol)과 벤즈알데히드(3)(0.517g, 2.0mmol)를 가한 후 에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL)를 넣고 그 반응혼합물을 24 시간 동안 환류 교반하였다. 감압 하에서 용매를 제거하여 오일상의 잔유물을 얻은 후, 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 15:1)로 정제하여 화학식 23의 화합물(0.291g, 64%)을 고체로 얻었다.2,4-Dihydroxybenzophenone (15) (0.214 g, 1.0 mmol) and benzaldehyde (3) (0.517 g, 2.0 mmol) were added to a xylene (10 mL) solvent at room temperature, followed by ethylenediamine diacetate (36 mg, 0.2 mmol) and TEA (2 mL) were added and the reaction mixture was stirred at reflux for 24 hours. The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography (hexane / ethyl acetate, 15: 1) to obtain a compound of formula 23 (0.291 g, 64%) as a solid.
1H NMR (300 MHz, CDCl3) δ 13.47 (1H, s), 7.66 (2H, d, J=8.9 Hz), 7.56-7.45 (4H, m), 7.35 (1H, d, J=7.8 Hz), 7.09 (1H, d, J=7.8, 7.4 Hz), 6.85 (1H, dd, J=8.0, 7.4 Hz), 6.74 (1H, d, J=8.0 Hz), 6.36 (1H, d, J=8.9 Hz), 5.16-5.12 (1H, m), 4.60 (1H, d, J=5.4 Hz), 4.52 (1H, dd, J=12.0, 3.9 Hz), 4.44 (1H, d, J=12.0 Hz), 2.40-2.32 (1H, m), 2.20-2.08 (2H, m), 1.86-1.80 (2H, m), 1.69 (3H, s), 1.61 (3H, s), 1.11 (3H, s); 13C NMR (75 MHz, CDCl3) δ 200.1, 164.8, 160.5, 154.1, 138.4, 133.9, 132.2, 131.4, 129.3, 129.9, 129.8, 128.3, 128.2, 127.7, 123.6, 122.7, 120.8, 115.9, 112.1, 110.9, 109.2, 80.2, 65.4, 40.6, 35.7, 29.1, 25.7, 22.7, 21.6,17.7; IR (neat) 2924, 1613, 1487, 1449, 1412, 1381, 1346, 1269, 1155, 1111, 1069, 999, 909, 816, 733 cm-1; m/z (EI) 454 (M+, 7), 371 (11), 370 (26), 369 (100), 301 (21), 105 (22), 77 (9), 69 (14); HRMS m/z (M+) calcd for C30H30O4: 454.2144. Found: 454.2145. 1 H NMR (300 MHz, CDCl 3 ) δ 13.47 (1H, s), 7.66 (2H, d, J = 8.9 Hz), 7.56-7.45 (4H, m), 7.35 (1H, d, J = 7.8 Hz) , 7.09 (1H, d, J = 7.8, 7.4 Hz), 6.85 (1H, dd, J = 8.0, 7.4 Hz), 6.74 (1H, d, J = 8.0 Hz), 6.36 (1H, d, J = 8.9 Hz), 5.16-5.12 (1H, m), 4.60 (1H, d, J = 5.4 Hz), 4.52 (1H, dd, J = 12.0, 3.9 Hz), 4.44 (1H, d, J = 12.0 Hz), 2.40-2.32 (1H, m), 2.20-2.08 (2H, m), 1.86-1.80 (2H, m), 1.69 (3H, s), 1.61 (3H, s), 1.11 (3H, s); 13 C NMR (75 MHz, CDCl 3 ) δ 200.1, 164.8, 160.5, 154.1, 138.4, 133.9, 132.2, 131.4, 129.3, 129.9, 129.8, 128.3, 128.2, 127.7, 123.6, 122.7, 120.8, 115.9, 112.1, 110.9 , 109.2, 80.2, 65.4, 40.6, 35.7, 29.1, 25.7, 22.7, 21.6, 17.7; IR (neat) 2924, 1613, 1487, 1449, 1412, 1381, 1346, 1269, 1155, 1111, 1069, 999, 909, 816, 733 cm −1 ; m / z (EI) 454 (M + , 7), 371 (11), 370 (26), 369 (100), 301 (21), 105 (22), 77 (9), 69 (14); HRMS m / z (M + ) calcd for C 30 H 30 O 4 : 454.2144. Found: 454.2145.
<실시예 13> (E)-[6-(4,8-디메틸노나-3,7-디에닐)-1-히드록시-6-메틸-6a,12b-디히드로-6H,7H-5,8-디옥사벤조[c]페난트렌-2-일]페닐메타논(24)의 제조Example 13 (E)-[6- (4,8-Dimethylnona-3,7-dienyl) -1-hydroxy-6-methyl-6a, 12b-dihydro-6H, 7H-5, Preparation of 8-dioxabenzo [c] phenanthren-2-yl] phenylmethanone (24)
실온에서 크실렌(10mL)에 용매에 2,4-디히드록시벤조페논(15)(0.214g, 1.0mmol)과 벤즈알데히드(4)(0.653g, 2.0mmol)를 가한 후 에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL)를 넣고 그 반응혼합물을 24 시간 동안 환류 교반하였다. 감압 하에서 용매를 제거하여 오일상의 잔유물을 얻은 후, 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 15:1)로 정제하여 화학식 24의 화합물(0.314g, 60%)을 고체로 얻었다.2,4-dihydroxybenzophenone (15) (0.214 g, 1.0 mmol) and benzaldehyde (4) (0.653 g, 2.0 mmol) were added to a solvent in xylene (10 mL) at room temperature, followed by ethylenediamine diacetate (36 mg, 0.2 mmol) and TEA (2 mL) were added and the reaction mixture was stirred at reflux for 24 hours. The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography (hexane / ethyl acetate, 15: 1) to obtain a compound of formula 24 (0.314 g, 60%) as a solid.
1H NMR (300 MHz, CDCl3) δ 13.51 (1H, s), 7.69 (2H, d, J=8.9 Hz), 7.59-7.47 (4H, m), 7.38 (1H, d, J=7.8 Hz), 7.11 (1H, d, J=7.8, 7.4 Hz), 6.86 (1H, dd, J=8.0, 7.4 Hz), 6.76 (1H, d, J=8.0 Hz), 6.40 (1H, d, J=8.9 Hz), 5.21-5.16 (1H, m), 5.14-5.09 (1H, m), 4.63 (1H, d, J=5.0 Hz), 4.53 (1H, dd, J=12.0, 4.0 Hz), 4.45 (1H, dd, J=12.0, 3.6 Hz), 2.42-2.34 (1H, m), 2.24-1.96 (6H, m), 1.90-1.84 (2H, m), 1.70 (3H, s), 1.64 (3H, s), 1.62 (3H, s), 1.14 (3H, s); 13C NMR (75 MHz, CDCl3) δ 200.1, 164.8, 160.5, 154.1, 138.3, 135.8, 133.8, 131.4, 131.3, 129.2, 128.8, 128.7, 128.2, 128.1, 127.7, 124.2, 123.4, 122.6, 120.7, 115.9, 112.1, 110.9, 109.2, 80.2, 65.4, 40.5, 39.6, 35.6, 29.1, 26.6, 25.7, 22.6, 21.5, 17.7, 16.0; IR (neat) 2922, 1613, 1487, 1449, 1412, 1381, 1346, 1269, 1154, 1109, 1067, 999, 903, 754 cm-1; m/z (EI) 522 (M+, 7), 371 (12), 370 (26), 369 (100), 301 (18), 105 (19), 81 (16), 69 (41); HRMS m/z (M+) calcd for C35H38O4: 522.2770. Found: 522.2774. 1 H NMR (300 MHz, CDCl 3 ) δ 13.51 (1H, s), 7.69 (2H, d, J = 8.9 Hz), 7.59-7.47 (4H, m), 7.38 (1H, d, J = 7.8 Hz) , 7.11 (1H, d, J = 7.8, 7.4 Hz), 6.86 (1H, dd, J = 8.0, 7.4 Hz), 6.76 (1H, d, J = 8.0 Hz), 6.40 (1H, d, J = 8.9 Hz), 5.21-5.16 (1H, m), 5.14-5.09 (1H, m), 4.63 (1H, d, J = 5.0 Hz), 4.53 (1H, dd, J = 12.0, 4.0 Hz), 4.45 (1H , dd, J = 12.0, 3.6 Hz), 2.42-2.34 (1H, m), 2.24-1.96 (6H, m), 1.90-1.84 (2H, m), 1.70 (3H, s), 1.64 (3H, s ), 1.62 (3H, s), 1.14 (3H, s); 13 C NMR (75 MHz, CDCl 3 ) δ 200.1, 164.8, 160.5, 154.1, 138.3, 135.8, 133.8, 131.4, 131.3, 129.2, 128.8, 128.7, 128.2, 128.1, 127.7, 124.2, 123.4, 122.6, 120.7, 115.9 , 112.1, 110.9, 109.2, 80.2, 65.4, 40.5, 39.6, 35.6, 29.1, 26.6, 25.7, 22.6, 21.5, 17.7, 16.0; IR (neat) 2922, 1613, 1487, 1449, 1412, 1381, 1346, 1269, 1154, 1109, 1067, 999, 903, 754 cm −1 ; m / z (EI) 522 (M + , 7), 371 (12), 370 (26), 369 (100), 301 (18), 105 (19), 81 (16), 69 (41); HRMS m / z (M + ) calcd for C 35 H 38 O 4 : 522.2770. Found: 522.2774.
<실시예 14> 6,6-디메틸-6a,7-디히드로-6H,12bH-5,8-디옥사벤조[c]-크리센(30)의 제조Example 14 Preparation of 6,6-dimethyl-6a, 7-dihydro-6H, 12bH-5,8-dioxabenzo [c] -crysen (30)
실온에서 크실렌(10mL)에 용매에 1-나프톨(27)(0.144g, 1.0mmol)과 벤즈알데히드(2)(0.380g, 2.0mmol)를 가한 후 에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL)를 넣고 그 반응혼합물을 12 시간 동안 환류 교반하였다. 감압 하에서 용매를 제거하여 오일상의 잔유물을 얻은 후, 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 30:1)로 정제하여 화학식 30의 화합물(0.297g, 94%)을 고체로 얻었다.1-naphthol (27) (0.144 g, 1.0 mmol) and benzaldehyde (2) (0.380 g, 2.0 mmol) were added to a solvent in xylene (10 mL) at room temperature, followed by ethylenediamine diacetate (36 mg, 0.2 mmol) and TEA ( 2 mL) and the reaction mixture was stirred under reflux for 12 hours. The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography (hexane / ethyl acetate, 30: 1) to obtain a compound of formula 30 (0.297 g, 94%) as a solid.
mp 108-109℃; 1H NMR (300 MHz, CDCl3) δ 8.30-8.28 (1H, m), 7.78-7.73 (1H, m), 7.54-7.45 (4H, m), 7.35 (1H, d, J=8.6 Hz), 7.26 (1H, dd, J=8.0, 7.4 Hz), 7.07 (1H, dd, J=7.6, 7.4 Hz), 6.90 (1H, d, J=8.0 Hz), 4.53 (1H, d, J=11.8 Hz), 4.33 (1H, d, J=4.6 Hz), 3.96 (1H, dd, J=11.8, 11.1 Hz), 2.37-2.30 (1H, m), 1.69 (3H, s), 1.52 (3H, s); 13C NMR (75 MHz, CDCl3) δ 154.0, 146.4, 133.4,132.4, 128.4, 127.3, 126.3, 126.0, 125.4, 125.1, 122.4, 122.0, 119.7, 119.6, 116.8, 114.8, 74.7, 63.5, 37.1, 33.5, 26.4, 26.2; IR (KBr) 3057, 2980, 2926, 1583, 1491, 1454, 1387, 1329, 1302, 1238, 1148, 1093, 1057, 1042, 1026, 965, 939, 909, 870, 814, 791, 758 cm-1; HRMS m/z (M+) calcd for C22H20O2: 316.1463. Found: 316.1465.mp 108-109 ° C .; 1 H NMR (300 MHz, CDCl 3 ) δ 8.30-8.28 (1H, m), 7.78-7.73 (1H, m), 7.54-7.45 (4H, m), 7.35 (1H, d, J = 8.6 Hz), 7.26 (1H, dd, J = 8.0, 7.4 Hz), 7.07 (1H, dd, J = 7.6, 7.4 Hz), 6.90 (1H, d, J = 8.0 Hz), 4.53 (1H, d, J = 11.8 Hz ), 4.33 (1H, d, J = 4.6 Hz), 3.96 (1H, dd, J = 11.8, 11.1 Hz), 2.37-2.30 (1H, m), 1.69 (3H, s), 1.52 (3H, s) ; 13 C NMR (75 MHz, CDCl 3 ) δ 154.0, 146.4, 133.4,132.4, 128.4, 127.3, 126.3, 126.0, 125.4, 125.1, 122.4, 122.0, 119.7, 119.6, 116.8, 114.8, 74.7, 63.5, 37.1, 33.5 , 26.4, 26.2; IR (KBr) 3057, 2980, 2926, 1583, 1491, 1454, 1387, 1329, 1302, 1238, 1148, 1093, 1057, 1042, 1026, 965, 939, 909, 870, 814, 791, 758 cm -1 ; HRMS m / z (M + ) calcd for C 22 H 20 O 2 : 316.1463. Found: 316.1465.
<실시예 15> 6-메틸-6-(4-메틸펜트-3-에닐)-6a,7-디히드로-6H,12bH-5,8-디옥사벤조[c]-크리센(31)의 제조Example 15 of 6-methyl-6- (4-methylpent-3-enyl) -6a, 7-dihydro-6H, 12bH-5,8-dioxabenzo [c] -chrysene (31) Produce
실온에서 크실렌(10mL) 용매에 1-나프톨(27)(0.144g, 1.0mmol)과 벤즈알데히드(3)(0.517g, 2.0mmol)를 가한 후 에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL)를 넣고 그 반응혼합물을 24 시간 동안 환류 교반하였다. 감압 하에서 용매를 제거하여 오일상의 잔유물을 얻은 후, 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 30:1)로 정제하여 화학식 31의 화합물(0.319g, 83%)을 고체로 얻었다.1-naphthol (27) (0.144 g, 1.0 mmol) and benzaldehyde (3) (0.517 g, 2.0 mmol) were added to a xylene (10 mL) solvent at room temperature, followed by ethylenediamine diacetate (36 mg, 0.2 mmol) and TEA (2 mL). ) Was added and the reaction mixture was stirred under reflux for 24 hours. The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography (hexane / ethyl acetate, 30: 1) to obtain a compound of formula 31 (0.319 g, 83%) as a solid.
1H NMR (300 MHz, CDCl3) δ 8.59-8.47 (1H, m), 7.99-7.97 (1H, m), 7.76-7.69 (4H, m), 7.57 (1H, d, J=9.0 Hz), 7.48 (1H, dd, J=8.0, 7.4 Hz), 7.29 (1H, dd, J=7.6, 7.4 Hz), 7.13 (1H, d, J=8.0 Hz), 5.34-5.30 (1H, m), 4.53 (1H, dd, J=11.8, 1.8 Hz), 4.55 (1H, d, J=4.0 Hz), 4.23 (1H, dd, J=11.8, 11.4 Hz), 2.72-2.63 (1H, m), 2.48-2.36 (2H, m), 2.13-2.02 (2H, m), 1.88 (6H, s), 1.80 (3H, s); 13C NMR (75 MHz, CDCl3) δ 154.1, 146.3, 133.4, 132.4, 132.0, 128.4, 127.3, 126.2, 126.0, 125.4, 125.1, 123.5, 122.4, 122.0, 119.7, 119.6, 116.8, 115.1, 76.9, 63.7, 38.2, 35.4, 33.3, 25.6, 22.8, 22.7, 22.1, 17.5; IR (neat) 2918, 1584, 1491, 1454, 1386, 1327, 1262, 1240, 1099, 1057, 964, 812, 758 cm-1; m/z (EI) 384 (M+, 23), 300 (22), 299 (94), 248 (18), 247 (15), 232 (19), 231 (100), 69 (22); HRMS m/z (M+) calcd for C27H28O2: 384.2089. Found: 384.2086. 1 H NMR (300 MHz, CDCl 3 ) δ 8.59-8.47 (1H, m), 7.99-7.97 (1H, m), 7.76-7.69 (4H, m), 7.57 (1H, d, J = 9.0 Hz), 7.48 (1H, dd, J = 8.0, 7.4 Hz), 7.29 (1H, dd, J = 7.6, 7.4 Hz), 7.13 (1H, d, J = 8.0 Hz), 5.34-5.30 (1H, m), 4.53 (1H, dd, J = 11.8, 1.8 Hz), 4.55 (1H, d, J = 4.0 Hz), 4.23 (1H, dd, J = 11.8, 11.4 Hz), 2.72-2.63 (1H, m), 2.48- 2.36 (2H, m), 2.13-2.02 (2H, m), 1.88 (6H, s), 1.80 (3H, s); 13 C NMR (75 MHz, CDCl 3 ) δ 154.1, 146.3, 133.4, 132.4, 132.0, 128.4, 127.3, 126.2, 126.0, 125.4, 125.1, 123.5, 122.4, 122.0, 119.7, 119.6, 116.8, 115.1, 76.9, 63.7 , 38.2, 35.4, 33.3, 25.6, 22.8, 22.7, 22.1, 17.5; IR (neat) 2918, 1584, 1491, 1454, 1386, 1327, 1262, 1240, 1099, 1057, 964, 812, 758 cm −1 ; m / z (EI) 384 (M + , 23), 300 (22), 299 (94), 248 (18), 247 (15), 232 (19), 231 (100), 69 (22); HRMS m / z (M + ) calcd for C 27 H 28 O 2 : 384.2089. Found: 384.2086.
<실시예 16> (E)-6-(4,8-디메틸노나-3,7-디에닐)-6-메틸-6a,7-디히드로-6H,12bH-5,8-디옥사벤조[c]-크리센(32)의 제조Example 16 (E) -6- (4,8-dimethylnona-3,7-dienyl) -6-methyl-6a, 7-dihydro-6H, 12bH-5,8-dioxabenzo [ c] -making of chrysene 32
실온에서 환류 크실렌(10mL)에 용해된 1-나프톨(27) 용액(0.144g, 1.0mmol)과 벤즈알데히드(4) 용액(0.653g, 2.0mmol)을 에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL) 하에서 혼합한 반응혼합물을 24 시간 동안 교반하였다. 감압 하에서 용매를 제거하여 오일상의 잔사를 얻은 후, 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 30:1)로 정제하여 고상의 화학식 32의 화합물(0.317g, 70%)을 얻었다.1-naphthol (27) solution (0.144 g, 1.0 mmol) and benzaldehyde (4) solution (0.653 g, 2.0 mmol) dissolved in reflux xylene (10 mL) at room temperature were treated with ethylenediamine diacetate (36 mg, 0.2 mmol) and TEA. The reaction mixture mixed under (2 mL) was stirred for 24 hours. The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography (hexane / ethyl acetate, 30: 1) to obtain a solid compound of formula 32 (0.317 g, 70%).
1H NMR (300 MHz, CDCl3) δ 8.23-8.19 (1H, m), 7.72-7.68 (1H, m), 7.49-7.39 (4H, m), 7.28 (1H, d, J=8.9 Hz), 7.20 (1H, dd, J=8.0, 7.4 Hz), 7.00 (1H, dd, J=7.6, 7.4 Hz), 6.83 (1H, d, J=8.0 Hz), 5.06-5.00 (2H, m), 4.53-4.48 (1H, m), 4.27 (1H, d, J=4.0 Hz), 3.95 (1H, dd, J=11.8, 11.1 Hz), 2.45-2.39 (1H, m), 2.22-2.09 (2H, m), 2.00-195 (2H, m), 1.91-1.77 (4H, m), 1.63 (3H, s), 1.61 (3H, s), 1.53 (3H, s), 1.51 (3H, s); 13C NMR (75 MHz, CDCl3) δ 154.1, 146.3, 135.7, 133.4, 132.3, 131.3, 128.4, 127.2, 126.2, 126.0, 125.4, 125.1, 124.2, 123.3, 122.4, 122.0, 119.7, 119.6, 116.8, 115.0, 76.9, 63.6, 39.6, 38.2, 35.4, 33.3, 26.6, 25.6, 22.8, 22.0, 17.6, 15.9; IR (neat) 2922, 1584, 1491, 1454, 1385, 1240, 1101, 1055, 965, 812, 758 cm-1; HRMS m/z (M+) calcd for C32H36O2: 452.2715. Found: 452.2713. 1 H NMR (300 MHz, CDCl 3 ) δ 8.23-8.19 (1H, m), 7.72-7.68 (1H, m), 7.49-7.39 (4H, m), 7.28 (1H, d, J = 8.9 Hz), 7.20 (1H, dd, J = 8.0, 7.4 Hz), 7.00 (1H, dd, J = 7.6, 7.4 Hz), 6.83 (1H, d, J = 8.0 Hz), 5.06-5.00 (2H, m), 4.53 -4.48 (1H, m), 4.27 (1H, d, J = 4.0 Hz), 3.95 (1H, dd, J = 11.8, 11.1 Hz), 2.45-2.39 (1H, m), 2.22-2.09 (2H, m ), 2.00-195 (2H, m), 1.91-1.77 (4H, m), 1.63 (3H, s), 1.61 (3H, s), 1.53 (3H, s), 1.51 (3H, s); 13 C NMR (75 MHz, CDCl 3 ) δ 154.1, 146.3, 135.7, 133.4, 132.3, 131.3, 128.4, 127.2, 126.2, 126.0, 125.4, 125.1, 124.2, 123.3, 122.4, 122.0, 119.7, 119.6, 116.8, 115.0 , 76.9, 63.6, 39.6, 38.2, 35.4, 33.3, 26.6, 25.6, 22.8, 22.0, 17.6, 15.9; IR (neat) 2922, 1584, 1491, 1454, 1385, 1240, 1101, 1055, 965, 812, 758 cm −1 ; HRMS m / z (M + ) calcd for C 32 H 36 O 2 : 452.2715. Found: 452.2713.
<실시예 17> 14-메톡시-6,6-디메틸-6a,7-디히드로-6H,12bH-5,8-디옥사벤조[c]-크리센(33)의 제조Example 17 Preparation of 14-methoxy-6,6-dimethyl-6a, 7-dihydro-6H, 12bH-5,8-dioxabenzo [c] -criscene (33)
실온에서 크실렌(10mL) 용매에 4-메톡시-1-나프톨(28)(0.174g, 1.0mmol)과 벤즈알데히드(2)(0.380g, 2.0mmol)를 가한 후 에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL)를 넣고 그 반응혼합물을 18 시간 동안 환류 교반하였다. 감압 하에서 용매를 제거하여 오일상의 잔유물을 얻은 후, 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 10:1)로 정제하여 화학식 33의 화합물(0.236g, 68%)을 고체로 얻었다.4-methoxy-1-naphthol (28) (0.174 g, 1.0 mmol) and benzaldehyde (2) (0.380 g, 2.0 mmol) were added to a xylene (10 mL) solvent at room temperature, followed by ethylenediamine diacetate (36 mg, 0.2 mmol). ) And TEA (2 mL) were added and the reaction mixture was stirred under reflux for 18 hours. The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography (hexane / ethyl acetate, 10: 1) to obtain a compound of formula 33 (0.236 g, 68%) as a solid.
mp 154-155℃; 1H NMR (300 MHz, CDCl3) δ 8.22-8.12 (2H, m), 7.55-7.43 (3H, m), 7.22 (1H, dd, J=8.0, 7.6 Hz), 7.03 (1H, dd, J=7.6, 7.4 Hz), 6.87 (1H, d, J=8.0 Hz), 6.83 (1H, s), 4.54-4.48 (1H, m), 4.26 (1H, d, J=3.8 Hz), 3.95 (1H, dd, J=11.2, 8.2 Hz), 3.84 (3H, s), 2.33-2.26 (1H, m), 1.62 (3H, s), 1.47 (3H, s); 13C NMR (75 MHz, CDCl3) δ 170.9, 154.1, 148.9, 140.0, 131.9, 128.3, 126.2, 125.7, 125.4, 122.5, 121.7, 121.5, 119.6, 116.8, 113.9, 103.8, 74.2, 63.7, 55.3, 37.2, 33.8, 26.2, 26.0; IR (KBr) 3067, 2976, 1632, 1586, 1491, 1460, 1383, 1329, 1308, 1267, 1236, 1152, 1126, 1099, 1042, 1026, 962, 932, 756 cm-1 HRMS m/z (M+) calcd for C23H22O3: 346.1569. Found: 346.1568.mp 154-155 ° C; 1 H NMR (300 MHz, CDCl 3 ) δ 8.22-8.12 (2H, m), 7.55-7.43 (3H, m), 7.22 (1H, dd, J = 8.0, 7.6 Hz), 7.03 (1H, dd, J = 7.6, 7.4 Hz), 6.87 (1H, d, J = 8.0 Hz), 6.83 (1H, s), 4.54-4.48 (1H, m), 4.26 (1H, d, J = 3.8 Hz), 3.95 (1H , dd, J = 11.2, 8.2 Hz), 3.84 (3H, s), 2.33-2.26 (1H, m), 1.62 (3H, s), 1.47 (3H, s); 13 C NMR (75 MHz, CDCl 3 ) δ 170.9, 154.1, 148.9, 140.0, 131.9, 128.3, 126.2, 125.7, 125.4, 122.5, 121.7, 121.5, 119.6, 116.8, 113.9, 103.8, 74.2, 63.7, 55.3, 37.2 , 33.8, 26.2, 26.0; IR (KBr) 3067, 2976, 1632, 1586, 1491, 1460, 1383, 1329, 1308, 1267, 1236, 1152, 1126, 1099, 1042, 1026, 962, 932, 756 cm -1 HRMS m / z (M + ) calcd for C 23 H 22 O 3 : 346.1569. Found: 346.1568.
<실시예 18> 14-클로로-6,6-디메틸-6a,7-디히드로-6H,12bH-5,8-디옥사벤조[c]-크리센(34)의 제조Example 18 Preparation of 14-Chloro-6,6-dimethyl-6a, 7-dihydro-6H, 12bH-5,8-dioxabenzo [c] -crysen (34)
실온에서 크실렌(10mL) 용매에 4-클로로-1-나프톨(29)(0.179g, 1.0mmol)과 벤즈알데히드(2)(0.380g, 2.0mmol)를 가한 후 에틸렌디아민 디아세테이트(36mg, 0.2mmol) 및 TEA(2mL)를 넣고 그 반응혼합물을 18 시간 동안 환류 교반하였다. 감압 하에서 용매를 제거하여 오일상의 잔유물을 얻은 후, 실리카겔 컬럼 크로마토그래피(헥산/에틸아세테이트, 40:1)로 정제하여 화학식 34의 화합물(0.256g, 73%)을 고체로 얻었다.4-chloro-1-naphthol (29) (0.179 g, 1.0 mmol) and benzaldehyde (2) (0.380 g, 2.0 mmol) were added to a xylene (10 mL) solvent at room temperature, followed by ethylenediamine diacetate (36 mg, 0.2 mmol). And TEA (2 mL) were added and the reaction mixture was stirred at reflux for 18 hours. The solvent was removed under reduced pressure to obtain an oily residue, which was then purified by silica gel column chromatography (hexane / ethyl acetate, 40: 1) to obtain a compound of formula 34 (0.256 g, 73%) as a solid.
mp 155-156℃; 1H NMR (300 MHz, CDCl3) δ 8.25 (1H, d, J=8.0 Hz), 8.11 (1H, d, J=7.6 Hz), 7.60-7.44 (4H, m), 7.23 (1H, dd, J=8.0, 7.6 Hz), 7.04 (1H, dd, J=7.6, 7.4 Hz), 6.85 (1H, d, J=8.0 Hz), 4.52-4.46 (1H, m), 4.25 (1H, d, J=4.5 Hz), 3.87 (1H, dd, J=11.4, 11.3 Hz), 2.34-2.25 (1H, m), 1.68 (3H, s), 1.47 (3H, s); 13C NMR (75 MHz, CDCl3) δ 153.9, 145.6, 132.1, 130.3, 128.6, 127.1, 126.5, 126.1, 125.8, 124.0, 122.8, 122.4, 121.7, 120.0, 116.9, 115.4, 77.2, 75.1, 63.3, 36.8, 33.3, 26.2, 26.0; IR (KBr) 3073, 2982, 1586, 1493, 1454, 1375, 1327, 1300, 1263, 1229, 1146, 1107, 1042, 914, 760, 737 cm-1 HRMSmp 155-156 ° C; 1 H NMR (300 MHz, CDCl 3 ) δ 8.25 (1H, d, J = 8.0 Hz), 8.11 (1H, d, J = 7.6 Hz), 7.60-7.44 (4H, m), 7.23 (1H, dd, J = 8.0, 7.6 Hz), 7.04 (1H, dd, J = 7.6, 7.4 Hz), 6.85 (1H, d, J = 8.0 Hz), 4.52-4.46 (1H, m), 4.25 (1H, d, J = 4.5 Hz), 3.87 (1H, doublet of doublets, J = 11.4, 11.3 Hz), 2.34-2.25 (1H, m), 1.68 (3H, s), 1.47 (3H, s); 13 C NMR (75 MHz, CDCl 3 ) δ 153.9, 145.6, 132.1, 130.3, 128.6, 127.1, 126.5, 126.1, 125.8, 124.0, 122.8, 122.4, 121.7, 120.0, 116.9, 115.4, 77.2, 75.1, 63.3, 36.8 , 33.3, 26.2, 26.0; IR (KBr) 3073, 2982, 1586, 1493, 1454, 1375, 1327, 1300, 1263, 1229, 1146, 1107, 1042, 914, 760, 737 cm -1 HRMS
m/z (M+) calcd for C22H19ClO2: 350.1074. Found: 350.1073. m / z (M + ) calcd for C 22 H 19 ClO 2 : 350.1074. Found: 350.1073.
Claims (8)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020090031460A KR101080519B1 (en) | 2009-04-10 | 2009-04-10 | Efficient synthetic method of benzopyranobenzopyrans using domino aldol―type reaction／hetero Diels―Alder reaction |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020090031460A KR101080519B1 (en) | 2009-04-10 | 2009-04-10 | Efficient synthetic method of benzopyranobenzopyrans using domino aldol―type reaction／hetero Diels―Alder reaction |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20100112923A KR20100112923A (en) | 2010-10-20 |
| KR101080519B1 true KR101080519B1 (en) | 2011-11-04 |
Family
ID=43132692
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020090031460A KR101080519B1 (en) | 2009-04-10 | 2009-04-10 | Efficient synthetic method of benzopyranobenzopyrans using domino aldol―type reaction／hetero Diels―Alder reaction |
Country Status (1)
| Country | Link |
|---|---|
| KR (1) | KR101080519B1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115433200B (en) * | 2022-08-17 | 2023-07-21 | 广州大学 | Tetracyclic compound containing chroman-4-one structure, synthesis method and application |
-
2009
- 2009-04-10 KR KR1020090031460A patent/KR101080519B1/en not_active IP Right Cessation
Non-Patent Citations (1)
| Title |
|---|
| J. Org. Chem. 61: 6768-6769 (1996) |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20100112923A (en) | 2010-10-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2006297300B2 (en) | Process for production of delta-9-tetrahydrocannabinol | |
| Zhang et al. | Regioselective synthesis of 6-aryl-benzo [h][1, 2, 4]-triazolo [5, 1-b] quinazoline-7, 8-diones as potent antitumoral agents | |
| EP2436669A2 (en) | Novel preparation of anticancer-active tricyclic compounds via alkyne coupling reaction | |
| JPH02178278A (en) | Heart protecting tocopherol analog | |
| Lee et al. | Efficient one-pot synthesis of benzopyranobenzopyrans and naphthopyranobenzopyrans by domino aldol-type reaction/hetero Diels–Alder reaction of resorcinols and naphthols | |
| WO2008062830A1 (en) | Spiroquinone compound and pharmaceutical composition | |
| WO1999050258A1 (en) | Polyethoxylated ascorbic acid derivatives as a novel antioxidant and process for preparing thereof | |
| WO2014020101A1 (en) | Griseofulvin derivatives | |
| CN104974123A (en) | Coumarin compound with antioxidant activity, and preparation method and application thereof | |
| FI95250C (en) | A process for the preparation of new therapeutically useful chromium derivatives | |
| KR101080519B1 (en) | Efficient synthetic method of benzopyranobenzopyrans using domino aldol―type reaction／hetero Diels―Alder reaction | |
| US8501803B2 (en) | Garcinia derivative, its preparing method and medicinal use | |
| Nagaraju et al. | Microwave-assisted One-pot Synthesis of 7-Dimethylamino-4-Aryl-2-methylamino-3-nitro-4H-chromenes | |
| EP0409163B1 (en) | Novel cyclic vinylogous N-hydroxy-N-methylureas useful as 5-lipoxygenase inhibitors | |
| CN109053798B (en) | Rhein ester derivative and preparation method and application thereof | |
| WO2009049493A1 (en) | Preparation of seselin and its derivatives | |
| KR20110029576A (en) | Derivatives of novel bicyclic compound and the use thereof | |
| CN106673967B (en) | Preparation method of 4- (2-methallyl) -1, 2-benzenediol | |
| WO2010034512A1 (en) | Compounds with antimalarial activity | |
| KR101056878B1 (en) | Novel Jasmonate Derivatives and Their Pharmaceutical Uses | |
| US6191279B1 (en) | Dipyrano-quinolinones useful as anti viral agents and a process for preparing the same | |
| HRP20040489A2 (en) | PREPARATION OF CIS-FUSED 3,3a,8,12b-TETRAHYDRO-2H-DIBENZO[3,4:6,7] YKLOHEPTA[1,2-b]FURAN | |
| KR101554562B1 (en) | Novel macrosphelide derivatives, preparation method thereof and pharmaceutical composition for the prevention or treatment of cancer disease containing the same as an active ingredient | |
| JP7320593B2 (en) | Method for producing demethyl nobiletin | |
| KR101146826B1 (en) | Efficient synthetic method for sumadain A and its derivatives |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant | ||
| FPAY | Annual fee payment |
Payment date: 20141014 Year of fee payment: 4 |
|
| FPAY | Annual fee payment |
Payment date: 20151001 Year of fee payment: 5 |
|
| FPAY | Annual fee payment |
Payment date: 20161017 Year of fee payment: 6 |
|
| LAPS | Lapse due to unpaid annual fee |