KR102498878B1 - Azulenofuranone compounds and its preparation method - Google Patents

Azulenofuranone compounds and its preparation method Download PDF

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KR102498878B1
KR102498878B1 KR1020210000622A KR20210000622A KR102498878B1 KR 102498878 B1 KR102498878 B1 KR 102498878B1 KR 1020210000622 A KR1020210000622 A KR 1020210000622A KR 20210000622 A KR20210000622 A KR 20210000622A KR 102498878 B1 KR102498878 B1 KR 102498878B1
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이필호
맹찬영
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강원대학교산학협력단
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
    • B01J23/38—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals
    • B01J23/40—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of noble metals of the platinum group metals
    • B01J23/46—Ruthenium, rhodium, osmium or iridium
    • B01J23/468—Iridium
    • 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
    • C07D409/04—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 directly linked by a ring-member-to-ring-member bond

Abstract

본 발명은 생리활성 및 약리활성을 갖는 천연물의 중요 골격 구조로 사용될 수 있는 다중고리 화합물인 아줄레노퓨라논 화합물 및 이의 제조방법에 관한 것이다.The present invention relates to an azulenofuranone compound, which is a multicyclic compound that can be used as an important skeletal structure of natural products having physiological and pharmacological activities, and a method for preparing the same.

Description

아줄레노퓨라논 화합물 및 이의 제조방법{AZULENOFURANONE COMPOUNDS AND ITS PREPARATION METHOD}Azulenofuranone compound and its preparation method {AZULENOFURANONE COMPOUNDS AND ITS PREPARATION METHOD}

본 발명은 생리활성 및 약리활성을 갖는 천연물의 중요 골격 구조로 사용될 수 있는 다중고리 화합물인 아줄레노퓨라논 화합물 및 이의 제조방법에 관한 것이다.The present invention relates to an azulenofuranone compound, which is a multicyclic compound that can be used as an important skeletal structure of natural products having physiological and pharmacological activities, and a method for preparing the same.

융합된 카보사이클은 자연계에서 분자의 핵심 구조적 요소로, 천연물을 합성하는데 기본적인 골격 또는 의약품의 기본골격이 되는 중요한 구조가 되므로 많은 합성법의 개발이 시도되고 있다.The fused carbocycle is a key structural element of molecules in nature, and since it is an important structure that is a basic skeleton for synthesizing natural products or a basic skeleton for pharmaceuticals, many synthesis methods have been attempted.

그 중에서도, 비-벤제노이드 방향족 탄화수소(non-benzenoid aromatic hydrocarbon)의 대표적인 화합물로 널리 알려진 아줄렌 유도체는 천연물, 약학적 활성 물질, 및 기능성 물질에 존재하고 있어 다양한 분야에서 주목받고 있다. 비-벤제노이드 방향족 화합물인 아줄렌은 1.08D의 쌍극자 모멘트[이는 일반적인 벤제노이드 방향족 화합물(예, 나프탈렌 = 0의 쌍극자 모멘트)과는 상이하다]를 가지기 때문에, 벤제노이드 방향족 화합물에 적용되는 다양한 유기 반응은 종종 아줄렌의 작용기화에 적용되지 않는 문제점이 발생된다. 따라서, 아줄렌 유도체에 적용될 수 있는 신규 합성법의 개발은 매우 중요하고 의미있다.Among them, azulene derivatives, which are widely known as representative compounds of non-benzenoid aromatic hydrocarbons, are present in natural products, pharmaceutically active substances, and functional substances, and are attracting attention in various fields. Since azulene, a non-benzenoid aromatic compound, has a dipole moment of 1.08 D [which is different from common benzenoid aromatic compounds (e.g., naphthalene = 0 dipole moment)], it has various organic applications for benzenoid aromatic compounds. The reaction often causes a problem that is not applicable to the functionalization of azulene. Therefore, the development of a novel synthesis method that can be applied to azulene derivatives is very important and meaningful.

최근, 탄소-수소 활성화에 대한 다양한 연구가 보고되고 있으며, 이로부터 종래의 합성법에 의해 전혀 합성될 수 없었던 다양한 작용기가 도입된 화합물의 합성이 가능해지고 있다. 그러나, 기보고된 방법은 주로 방향족 고리 상에 다수의 치환체를 도입하거나 추가적인 고리를 확장시킬 수 있는 벤제노이드 방향족 탄화수소에 대해서만 제한적으로 수행되었다.Recently, various studies on carbon-hydrogen activation have been reported, and from this, it is possible to synthesize compounds into which various functional groups have been introduced, which could not be synthesized at all by conventional synthesis methods. However, previously reported methods have been limited mainly to benzenoid aromatic hydrocarbons capable of introducing a plurality of substituents on an aromatic ring or extending additional rings.

즉, 지향성기(directing group)를 이용한 탄소-수소 활성화 반응은 벤제노이드 방향족 화합물이나 지방족 탄화수소에 국한되어 있으며, 비벤제노이드 방향족 화합물에 지향성기를 도입하여 사용한 예는 없다. 비벤제노이드 방향족 화합물은 벤제노이드 방향족 화합물과 성질이 크게 다르기 때문에 이에 대한 연구 및 이를 이용한 새로운 합성법 개발은 매우 중요하다. 그러나, 지금까지 비벤제노이드 방향족 화합물을 이용한 작용기화 반응들은 많이 보고되어 있지 않다.That is, the carbon-hydrogen activation reaction using a directing group is limited to benzenoid aromatic compounds or aliphatic hydrocarbons, and there is no example of introducing a directing group into a non-benzenoid aromatic compound. Since non-benzenoid aromatic compounds have very different properties from benzenoid aromatic compounds, research on them and development of new synthesis methods using them are very important. However, functionalization reactions using non-benzenoid aromatic compounds have not been reported so far.

기보고된 비벤제노이드 방향족 화합물의 작용기화 반응은 아줄렌카르복실산과 알킨의 Rh-촉매 산화[4+2]고리화 반응을 통한 아줄레노락톤의 합성(a, b), 과량의 TRIPS와 함께 아줄렌-1-카르복실산과 아릴 요오드화물로부터 탈카르복실화 Pd-촉매된 2-아릴화 반응을 통한 2-아릴아줄렌의 합성(c) 등이 있다.The previously reported functionalization reaction of non-benzenoid aromatic compounds is the synthesis of azulenolactone through Rh-catalyzed oxidation [4+2] cyclization of azulenecarboxylic acid and alkyne (a, b), with an excess of TRIPS. and (c) the synthesis of 2-arylazulene from azulene-1-carboxylic acid and aryl iodide through a decarboxylated Pd-catalyzed 2-arylation reaction.

Figure 112021000693139-pat00001
Figure 112021000693139-pat00001

기보고된 상기 합성법의 경우 분자 간 고리화반응이거나, 탈카복실화 반응이 수반된다. 카복실산 기가 흔적이 없는 미량의 지향성기로 사용되는 것도 중요하지만, 원-팟(one-pot) 반응에서 C-H 활성화를 통한 C(2)-아릴화 반응 후 카복실산의 유지, 잇따른 두번째 C-H 활성화를 통한 상기 카복실산의 다른 유용한 작용기로의 변형은 다기능화된 아줄렌의 합성 가능성 때문에 훨씬 어려운 것으로 간주된다.In the case of the previously reported synthesis method, an intermolecular cyclization reaction or a decarboxylation reaction is involved. It is also important that the carboxylic acid group is used as a traceless directing group, but it is important to maintain the carboxylic acid after the C(2)-arylation reaction through C-H activation in a one-pot reaction, followed by the second C-H activation of the carboxylic acid. The transformation of to other useful functional groups is considered to be much more difficult because of the possibility of synthesizing multifunctionalized azulene.

따라서, 탈카복실화 없이 원-팟으로 보다 효율적으로 아줄렌-1-카복실산 화합물로부터 C(2)-아릴화 및 분자내 C-O 결합 형성을 통해 아줄레노퓨라논 화합물을 높은 선택성과 수율로 제조할 수 있는 방법이 요구된다.Therefore, azulenofuranone compounds can be prepared with high selectivity and yield through C(2)-arylation and intramolecular C-O bond formation from azulene-1-carboxylic acid compounds more efficiently in one-pot without decarboxylation. method is required.

KR 10-2081806 B1KR 10-2081806 B1

J. Org. Chem. 2020, 85, 3824-3837. J. Org. Chem. 2020, 85, 3824-3837. Org. Lett. 2020, 22, 5009-5013. Org. Lett. 2020, 22, 5009-5013.

이에 본 발명자들은 비-벤제노이드 방향족 탄화수소 화합물의 탄소-수소 활성화 반응에 대해 연구한 결과, 비-벤제노이드 방향족 탄화수소 화합물인 아줄렌에 대해 5원 고리 상에 카복실산 기를 지향기로 도입시킨 아줄렌-1-카복실산 및 다이아릴아이오도늄염 화합물을 이리듐(Ir) 촉매, 은 산화제 및 아세트산염 첨가제의 하에서 반응시킴으로써 탈카복실화 없이 C(2)-아릴화 및 분자내 C-O 결합 형성을 통해 높은 선택성으로 아줄레노퓨라논 화합물이 원-팟으로 제조됨을 발견하고 본 발명을 완성하였다.Accordingly, the present inventors studied the carbon-hydrogen activation reaction of non-benzenoid aromatic hydrocarbon compounds, and as a result, azulene-1 in which a carboxylic acid group was introduced as a directing group on a 5-membered ring for azulene, a non-benzenoid aromatic hydrocarbon compound -Azuleno with high selectivity through C(2)-arylation and intramolecular C-O bond formation without decarboxylation by reacting carboxylic acid and diaryliodonium salt compound under an iridium (Ir) catalyst, silver oxidizing agent and acetate additive The discovery that furanone compounds are prepared in one-pot completed the present invention.

본 발명은 천연물, 의약품 및 생물학적 활성 화합물에서 핵심 구조로 작용하는 신규한 아줄레노퓨라논 화합물을 제공하는데 목적이 있다.An object of the present invention is to provide a novel azulenofuranone compound that acts as a core structure in natural products, pharmaceuticals and biologically active compounds.

또한 본 발명은 이리듐(Ir) 촉매, 은 산화제 및 아세트산염 첨가제의 존재 하, 아줄렌-1-카복실산 화합물 및 다이아릴아이오도늄염 화합물을 반응시켜 아줄레노퓨라논 화합물을 효율적으로 제조하는 방법을 제공하는데 목적이 있다.In addition, the present invention provides a method for efficiently producing an azulenofuranone compound by reacting an azulene-1-carboxylic acid compound and a diaryliodonium salt compound in the presence of an iridium (Ir) catalyst, a silver oxidizing agent, and an acetate additive has a purpose to

본 발명은 하기 화학식 1로 표시되는 아줄레노퓨라논 화합물을 제공한다.The present invention provides an azulenofuranone compound represented by Formula 1 below.

[화학식 1][Formula 1]

Figure 112021000693139-pat00002
Figure 112021000693139-pat00002

(상기 화학식 1에서,(In Formula 1,

R1는 C1-C20알킬, 할로C1-C20알킬, 할로겐, C1-C20알콕시, 할로C1-C20알콕시, C1-C20알킬카보닐, 할로C1-C20알킬카보닐, C1-C20알콕시카보닐, 할로C1-C20알콕시카보닐, C6-C20아릴C1-C20알킬, C6-C20아릴C1-C20알킬옥시, C6-C20아릴 또는 C3-C20헤테로아릴이고;R 1 is C1-C20 alkyl, haloC1-C20 alkyl, halogen, C1-C20 alkoxy, haloC1-C20 alkoxy, C1-C20 alkylcarbonyl, haloC1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, halo C1-C20 alkoxycarbonyl, C6-C20 arylC1-C20 alkyl, C6-C20 arylC1-C20 alkyloxy, C6-C20 aryl or C3-C20 heteroaryl;

m은 0 내지 5의 정수로, m이 2 이상의 정수인 경우 R1은 서로 동일하거나 상이할 수 있고;m is an integer from 0 to 5, and when m is an integer of 2 or greater, R 1 may be the same as or different from each other;

R2는 수소, C1-C20알킬, 할로겐, C1-C20알콕시, 할로C1-C20알콕시, C1-C20알킬카보닐, 할로C1-C20알킬카보닐, C1-C20알콕시카보닐, 할로C1-C20알콕시카보닐, C6-C20아릴카보닐, C6-C20아릴C1-C20알킬옥시, C6-C20아릴 또는 C3-C20헤테로아릴이고, 상기 R2의 알킬, 아릴 및 헤테로아릴은 C1-C20알킬, 할로C1-C20알킬, C1-C20알콕시, 할로겐, 나이트로, C1-C20알킬카보닐, C1-C20알콕시카보닐, C6-C20아릴, -NHSO2R' 및 C6-C20아릴옥시로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고;R 2 is hydrogen, C1-C20 alkyl, halogen, C1-C20 alkoxy, haloC1-C20 alkoxy, C1-C20 alkylcarbonyl, haloC1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, haloC1-C20 alkoxy carbonyl, C6-C20 arylcarbonyl, C6-C20 arylC1-C20 alkyloxy, C6-C20 aryl or C3-C20 heteroaryl, wherein the alkyl, aryl and heteroaryl of R 2 are C1-C20 alkyl, haloC1 -C20 alkyl, C1-C20 alkoxy, halogen, nitro, C1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, C6-C20 aryl, -NHSO 2 R' and C6-C20 aryloxy selected from the group consisting of may be further substituted with one or more;

R'는 C1-C20알킬, C6-C20아릴, C6-C20아릴C1-C20알킬 또는 C1-C20알킬C6-C20아릴이고;R' is C1-C20 alkyl, C6-C20 aryl, C6-C20 arylC1-C20 alkyl or C1-C20 alkylC6-C20 aryl;

Ar은 C6-C20아릴 또는 C3-C20헤테로아릴이고;Ar is C6-C20 aryl or C3-C20 heteroaryl;

상기 R1 및 Ar의 아릴 및 헤테로아릴은 C1-C20알킬, 할로C1-C20알킬, C1-C20알콕시, 할로겐, C1-C20알킬카보닐, C1-C20알콕시카보닐, C6-C20아릴, C6-C20아릴옥시, C6-C20아릴카보닐 및 C6-C20아릴옥시카보닐로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고;Aryl and heteroaryl of R 1 and Ar are C1-C20 alkyl, haloC1-C20 alkyl, C1-C20 alkoxy, halogen, C1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, C6-C20 aryl, C6- may be further substituted with one or more selected from the group consisting of C20 aryloxy, C6-C20 arylcarbonyl and C6-C20 aryloxycarbonyl;

상기 헤테로아릴은 N, O 및 S로부터 선택되는 1 내지 4개의 헤테로원자를 포함한다.)The heteroaryl contains 1 to 4 heteroatoms selected from N, O and S.)

본 발명은 탈카르복실화 없이 우수한 선택성 및 수율로 상기 화학식 1의 아줄레노퓨라논 화합물을 제조하는 방법을 제공한다.The present invention provides a method for preparing the azulenofuranone compound of Formula 1 with excellent selectivity and yield without decarboxylation.

본 발명의 화학식 1의 아줄레노퓨라논 화합물의 제조방법으로서, 이리듐(Ir) 촉매, 은 산화제 및 아세트산염 첨가제의 존재 하, 하기 화학식 3의 아줄렌-1-카복실산 화합물 및 화학식 4의 다이아릴아이오도늄염 화합물을 반응시켜 상기 화학식 1의 아줄레노퓨라논 화합물을 제조하는 방법을 제공한다:A method for preparing the azulenofuranone compound of formula (1) of the present invention, in the presence of an iridium (Ir) catalyst, a silver oxidizing agent and an acetate additive, an azulene-1-carboxylic acid compound of formula (3) and diarylio of formula (4) Provided is a method for preparing the azulenofuranone compound of Formula 1 by reacting a donium salt compound:

[화학식 3][Formula 3]

Figure 112021000693139-pat00003
Figure 112021000693139-pat00003

[화학식 4][Formula 4]

Figure 112021000693139-pat00004
Figure 112021000693139-pat00004

(상기 화학식 3 및 4에서, R1, R2, Ar 및 m은 상기 화학식 1에서의 정의와 동일하고;(In Chemical Formulas 3 and 4, R 1 , R 2 , Ar and m are the same as defined in Chemical Formula 1;

X-는 1가 음이온이다.)X - is a monovalent anion.)

본 발명의 화학식 1의 아줄레노퓨라논 화합물의 제조방법으로서, 이리듐(Ir) 촉매, 은 산화제 및 아세트산염 첨가제의 존재 하, 하기 화학식 3A의 2-아릴아줄렌-1-카복실산 화합물을 분자내 고리화 반응시켜 상기 화학식 1의 아줄레노퓨라논 화합물을 제조하는 방법을 제공한다:As a method for preparing the azulenofuranone compound of formula 1 of the present invention, in the presence of an iridium (Ir) catalyst, a silver oxidizing agent, and an acetate additive, a 2-arylazulene-1-carboxylic acid compound of formula 3A is formed in an intramolecular ring Provided is a method for preparing the azulenofuranone compound of Formula 1 by reacting with:

[화학식 3A][Formula 3A]

Figure 112021000693139-pat00005
Figure 112021000693139-pat00005

(상기 화학식 3A에서, R1, R2, Ar 및 m은 상기 화학식 1에서의 정의와 동일하다.)(In Formula 3A, R 1 , R 2 , Ar and m are the same as defined in Formula 1 above.)

본 발명에 따른 아줄레노퓨라논 화합물은 생리활성 및 약리활성을 나타내는 천연물의 핵심 골격으로 작용할 수 있는 다중 탄소고리 형태의 신규 화합물로, 다양한 치환체가 도입될 수 있어, 의약화학, 재료화학 등의 분야에서 중요 원료물질 또는 중간체로서 유용하게 이용될 수 있다.The azulenofuranone compound according to the present invention is a novel compound in the form of a multi-carbon ring that can act as a core skeleton of natural products exhibiting physiological and pharmacological activity, and various substituents can be introduced, so that it can be used in fields such as medicinal chemistry and material chemistry. It can be usefully used as an important raw material or intermediate in

또한, 본 발명에 따른 아줄레노퓨라논 화합물은 이리듐(Ir) 촉매, 은 산화제 및 아세트산염 첨가제의 존재 하 아줄렌-1-카복실산 화합물 및 다이아릴아이오도늄염 화합물의 순차적 반응, 즉 C(2)-아릴화 및 분자내 C-O 결합 형성을 통해 원팟(one-pot)으로 제조될 수 있다.In addition, the azulenofuranone compound according to the present invention is a sequential reaction of an azulene-1-carboxylic acid compound and a diaryliodonium salt compound in the presence of an iridium (Ir) catalyst, a silver oxidizing agent and an acetate additive, that is, C(2) -Can be prepared one-pot through arylation and intramolecular C-O bond formation.

본 발명에 따르면, 아줄렌-1-카복실산 화합물 및 다이아릴아이오도늄염 화합물로부터 탈카복실화 없이 이리듐-촉매화된 위치선택적 C(2)-아릴화로부터 유도되는 2-아릴아줄렌-1-카복실산의 생성을 통해 원활하게 순차 반응이 진행되어 다양한 치환체가 도입된 아줄레노퓨라논 화합물을 효율적으로 제조할 수 있다.According to the present invention, 2-arylazulene-1-carboxylic acids derived from iridium-catalyzed regioselective C(2)-arylation without decarboxylation from azulene-1-carboxylic acid compounds and diaryliodonium salt compounds It is possible to efficiently prepare an azulenofuranone compound into which various substituents are introduced by smoothly proceeding sequential reactions through the production of.

또한, 본 발명에 따르면, 대량생산이 가능하며, 반응 후 부산물의 제거를 위한 공정이 필요치 않은 장점이 있다.In addition, according to the present invention, mass production is possible, and there is an advantage that a process for removing by-products after the reaction is not required.

본 발명은 생리활성 및 약리활성을 갖는 천연물의 중요 골격 구조로 사용될 수 있는 다중고리 화합물인 아줄레노퓨라논 화합물 및 이의 제조방법에 관한 것이다.The present invention relates to an azulenofuranone compound, which is a multicyclic compound that can be used as an important skeletal structure of natural products having physiological and pharmacological activities, and a method for preparing the same.

이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.

이때, 사용되는 기술 용어 및 과학 용어에 있어서 다른 정의가 없다면, 이 발명이 속하는 기술 분야에서 통상의 지식을 가진 자가 통상적으로 이해하고 있는 의미를 가진다. 또한, 종래와 동일한 기술적 구성 및 작용에 대한 반복되는 설명은 생략하기로 한다.At this time, unless there is another definition in the technical terms and scientific terms used, they have meanings commonly understood by those of ordinary skill in the art to which this invention belongs. In addition, repeated description of the same technical configuration and operation as in the prior art will be omitted.

본 명세서에서, 용어 "CA-CB"는 "탄소수가 A 이상이고 B 이하"인 것을 의미한다.In this specification, the term “C A -C B ” means “a number of carbon atoms greater than or equal to A and less than or equal to B”.

본 명세서 내 용어 "알킬"은 탄소 및 수소 원자만으로 구성된 1가의 직쇄 또는 분쇄 포화 탄화수소 라디칼을 의미한다. 상기 알킬은 1 내지 10개의 탄소원자를 가질 수 있다. 상기 알킬은 1 내지 7개의 탄소원자를 가질 수 있다. 이러한 알킬 라디칼의 예는 메틸, 에틸, 프로필, 이소프로필, 부틸, 이소부틸, t-부틸, 펜틸, 헥실 등을 포함하지만 이에 한정되지는 않는다.The term “alkyl” in this specification means a monovalent straight-chain or branched saturated hydrocarbon radical composed only of carbon and hydrogen atoms. The alkyl may have 1 to 10 carbon atoms. The alkyl may have 1 to 7 carbon atoms. Examples of such alkyl radicals include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, pentyl, hexyl, and the like.

본 명세서 내 용어 "알콕시"는 -O-알킬 라디칼을 의미하는 것으로, 여기서 ‘알킬’은 상기 정의한 바와 같다. 구체적인 예로는 메톡시, 에톡시, 이소프로폭시, 부톡시, 이소부톡시, t-부톡시 등을 포함되지만 이에 한정되지는 않는다.The term "alkoxy" in this specification refers to an -O-alkyl radical, where 'alkyl' is as defined above. Specific examples include, but are not limited to, methoxy, ethoxy, isopropoxy, butoxy, isobutoxy, t-butoxy, and the like.

본 명세서 내 용어 "아릴"은 하나의 수소 제거에 의해서 방향족 탄화수소로부터 유도된 유기 라디칼로, 각 고리에 적절하게는 4 내지 7개, 바람직하게는 5 또는 6개의 고리원자를 포함하는 단일 또는 융합고리계를 포함하며, 다수개의 아릴이 단일결합으로 연결되어 있는 형태까지 포함한다. 구체적인 예로서는 페닐, 나프틸, 비페닐, 안트릴, 플루오레닐, 인데닐 등을 포함하지만, 이에 한정되지는 않는다.The term "aryl" as used herein refers to an organic radical derived from an aromatic hydrocarbon by the removal of one hydrogen, which is a single or fused ring containing preferably 4 to 7, preferably 5 or 6, ring atoms in each ring. system, including a form in which a plurality of aryls are connected by single bonds. Specific examples include, but are not limited to, phenyl, naphthyl, biphenyl, anthryl, fluorenyl, indenyl, and the like.

본 명세서 내 용어 "아릴옥시"는 -O-아릴 라디칼을 의미하는 것으로, 여기서 '아릴'은 상기 정의한 바와 같다. 이러한 아릴옥시 라디칼의 예는 페녹시, 나프톡시 등을 포함하지만 이에 한정되지는 않는다.The term "aryloxy" in this specification refers to an -O-aryl radical, where 'aryl' is as defined above. Examples of such aryloxy radicals include, but are not limited to, phenoxy, naphthoxy, and the like.

본 명세서 내 용어 "아릴알킬"은 적어도 하나의 아릴로 치환된 알킬 라디칼을 의미하는 것으로, 여기서 '아릴' 및 '알킬'은 상기 정의한 바와 같다. 이러한 아릴알킬 라디칼의 예는 벤질, 트리틸 등을 포함하지만 이에 한정되지는 않는다.The term "arylalkyl" used herein refers to an alkyl radical substituted with at least one aryl, where 'aryl' and 'alkyl' are as defined above. Examples of such arylalkyl radicals include, but are not limited to, benzyl, trityl, and the like.

본 명세서 내 용어 "아릴알킬옥시"는 아릴알킬-O-* 라디칼을 의미하는 것으로, 여기서 '아릴알킬'은 상기 정의한 바와 같다. 이러한 아릴알킬옥시 라디칼의 예는 벤질옥시, 트리틸옥시 등을 포함하지만 이에 한정되지는 않는다.The term "arylalkyloxy" in this specification means an arylalkyl-O-* radical, where 'arylalkyl' is as defined above. Examples of such arylalkyloxy radicals include, but are not limited to, benzyloxy, trityloxy, and the like.

본 명세서 내 용어 "할로" 또는 "할로겐"은 할로겐족 원소를 나타내며, 예컨대, 플루오로, 클로로, 브로모 및 요오도를 포함한다.The term “halo” or “halogen” in this specification refers to a halogen group element and includes, for example, fluoro, chloro, bromo and iodo.

본 명세서 내 용어 "할로알킬"은 적어도 하나의 할로겐으로 치환된 알킬 라디칼을 의미하는 것으로, 여기서 '알킬'은 상기 정의한 바와 같다. 이러한 할로알킬 라디칼의 예는 플루오로메틸, 트리플루오로메틸, 브로모메틸, 퍼플루오로에틸 등을 포함하지만 이에 한정되지는 않는다.The term "haloalkyl" used herein refers to an alkyl radical substituted with at least one halogen, where 'alkyl' is as defined above. Examples of such haloalkyl radicals include, but are not limited to, fluoromethyl, trifluoromethyl, bromomethyl, perfluoroethyl, and the like.

본 명세서 내 용어 "헤테로아릴"은 방향족 고리 골격 원자로서 N, O 및 S로부터 선택되는 1 내지 4개의 헤테로원자를 포함하고, 나머지 방향족 고리 골격 원자가 탄소인 아릴 그룹을 의미하는 것으로, 5 내지 6원 단환 헤테로아릴, 및 하나 이상의 벤젠환과 축합된 다환식 헤테로아릴이다. 또한, 본 발명에서의 헤테로아릴은 하나 이상의 헤테로아릴이 단일결합으로 연결된 형태도 포함한다. 구체적인 예로 퓨릴, 싸이오펜일, 피롤릴, 이미다졸릴, 피라졸릴, 티아졸릴, 이소티아졸릴, 이속사졸릴, 옥사졸릴, 피리딜 등의 단환 헤테로아릴, 벤조퓨란일, 다이벤조퓨란일, 다이벤조티오페일, 벤조티오펜일, 이소벤조퓨란일, 벤조이미다졸릴, 벤조티아졸릴, 벤조이소티아졸릴, 벤조이속사졸릴, 벤조옥사졸릴, 퀴놀릴, 이소퀴놀릴, 카바졸릴 등의 다환식 헤테로아릴 등을 포함하지만, 이에 한정되지 않는다. As used herein, the term "heteroaryl" refers to an aryl group containing 1 to 4 heteroatoms selected from N, O and S as aromatic ring skeletal atoms, and the remaining aromatic ring skeletal atoms being carbon, and is a 5 to 6 membered monocyclic heteroaryl, and polycyclic heteroaryl condensed with one or more benzene rings. In addition, the heteroaryl in the present invention includes a form in which one or more heteroaryls are connected by a single bond. Specific examples include furyl, thiophenyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, isoxazolyl, oxazolyl, monocyclic heteroaryl such as pyridyl, benzofuranyl, dibenzofuranyl, di Polycyclic hetero such as benzothiopyl, benzothiophenyl, isobenzofuranyl, benzoimidazolyl, benzothiazolyl, benzoisothiazolyl, benzoisoxazolyl, benzooxazolyl, quinolyl, isoquinolyl, and carbazolyl aryl; and the like, but are not limited thereto.

본 명세서에 기재된 "알킬카보닐"은 알킬-C(=O)-* 라디칼을 의미하는 것으로, 여기서 '알킬'은 상기 정의한 바와 같다. 이러한 알킬카보닐 라디칼의 예는 메틸카보닐, 에틸카보닐, 이소프로필카보닐, 프로필카보닐, 부틸카보닐, 이소부틸카보닐, t-부틸카보닐 등을 포함하지만 이에 한정되지는 않는다."Alkylcarbonyl" as used herein refers to an alkyl-C(=O)-* radical, where 'alkyl' is as defined above. Examples of such alkylcarbonyl radicals include, but are not limited to, methylcarbonyl, ethylcarbonyl, isopropylcarbonyl, propylcarbonyl, butylcarbonyl, isobutylcarbonyl, t-butylcarbonyl, and the like.

본 명세서에 기재된 "알콕시카보닐"은 알콕시-C(=O)-* 라디칼을 의미하는 것으로, 여기서 '알콕시'는 상기 정의한 바와 같다. 이러한 알콕시카보닐 라디칼의 예는 메톡시카보닐, 에톡시카보닐, 이소프로폭시카보닐, 프로폭시카보닐, 부톡시카보닐, 이소부톡시카보닐, t-부톡시카보닐 등을 포함하지만 이에 한정되지는 않는다.As used herein, "alkoxycarbonyl" means an alkoxy-C(=O)-* radical, where 'alkoxy' is as defined above. Examples of such alkoxycarbonyl radicals include methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, propoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, t-butoxycarbonyl, and the like, but Not limited.

본 명세서에 기재된 "아릴카보닐"은 아릴-C(=O)-* 라디칼을 의미하는 것으로, 여기서 '아릴'은 상기 정의한 바와 같다. 이러한 아릴카보닐 라디칼의 예는 페닐카보닐, 나프틸카보닐, 안트릴카보닐 등을 포함하지만 이에 한정되지는 않는다.As used herein, "arylcarbonyl" means an aryl-C(=O)-* radical, where 'aryl' is as defined above. Examples of such arylcarbonyl radicals include, but are not limited to, phenylcarbonyl, naphthylcarbonyl, anthrylcarbonyl, and the like.

본 명세서에 기재된 "아릴옥시카보닐"은 아릴옥시-C(=O)-* 라디칼을 의미하는 것으로, 여기서 '아릴옥시'는 상기 정의한 바와 같다. 이러한 아릴옥시카보닐 라디칼의 예는 페녹시카보닐, 나프톡시카보닐 등을 포함하지만 이에 한정되지는 않는다.As used herein, "aryloxycarbonyl" means an aryloxy-C(=O)-* radical, where 'aryloxy' is as defined above. Examples of such aryloxycarbonyl radicals include, but are not limited to, phenoxycarbonyl, naphthoxycarbonyl, and the like.

본 발명은 약리활성 및 생리활성을 갖는 천연물의 중요 골격 구조로 사용될 수 있는 신규 구조의 아줄레노퓨라논 화합물 및 이의 제조방법에 관한 것이다.The present invention relates to an azulenofuranone compound having a novel structure that can be used as an important skeletal structure of natural products having pharmacological and physiological activities and a method for preparing the same.

본 발명은 하기 화학식 1로 표시되는 아줄레노퓨라논 화합물을 제공한다:The present invention provides an azulenofuranone compound represented by Formula 1 below:

[화학식 1][Formula 1]

Figure 112021000693139-pat00006
Figure 112021000693139-pat00006

(상기 화학식 1에서,(In Formula 1,

R1는 C1-C20알킬, 할로C1-C20알킬, 할로겐, C1-C20알콕시, 할로C1-C20알콕시, C1-C20알킬카보닐, 할로C1-C20알킬카보닐, C1-C20알콕시카보닐, 할로C1-C20알콕시카보닐, C6-C20아릴C1-C20알킬, C6-C20아릴C1-C20알킬옥시, C6-C20아릴 또는 C3-C20헤테로아릴이고;R 1 is C1-C20 alkyl, haloC1-C20 alkyl, halogen, C1-C20 alkoxy, haloC1-C20 alkoxy, C1-C20 alkylcarbonyl, haloC1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, halo C1-C20 alkoxycarbonyl, C6-C20 arylC1-C20 alkyl, C6-C20 arylC1-C20 alkyloxy, C6-C20 aryl or C3-C20 heteroaryl;

m은 0 내지 5의 정수로, m이 2 이상의 정수인 경우 R1은 서로 동일하거나 상이할 수 있고;m is an integer from 0 to 5, and when m is an integer of 2 or greater, R 1 may be the same as or different from each other;

R2는 수소, C1-C20알킬, 할로겐, C1-C20알콕시, 할로C1-C20알콕시, C1-C20알킬카보닐, 할로C1-C20알킬카보닐, C1-C20알콕시카보닐, 할로C1-C20알콕시카보닐, C6-C20아릴카보닐, C6-C20아릴C1-C20알킬옥시, C6-C20아릴 또는 C3-C20헤테로아릴이고, 상기 R2의 알킬, 아릴 및 헤테로아릴은 C1-C20알킬, 할로C1-C20알킬, C1-C20알콕시, 할로겐, 나이트로, C1-C20알킬카보닐, C1-C20알콕시카보닐, C6-C20아릴, -NHSO2R' 및 C6-C20아릴옥시로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고;R 2 is hydrogen, C1-C20 alkyl, halogen, C1-C20 alkoxy, haloC1-C20 alkoxy, C1-C20 alkylcarbonyl, haloC1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, haloC1-C20 alkoxy carbonyl, C6-C20 arylcarbonyl, C6-C20 arylC1-C20 alkyloxy, C6-C20 aryl or C3-C20 heteroaryl, wherein the alkyl, aryl and heteroaryl of R 2 are C1-C20 alkyl, haloC1 -C20 alkyl, C1-C20 alkoxy, halogen, nitro, C1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, C6-C20 aryl, -NHSO 2 R' and C6-C20 aryloxy selected from the group consisting of may be further substituted with one or more;

R'는 C1-C20알킬, C6-C20아릴, C6-C20아릴C1-C20알킬 또는 C1-C20알킬C6-C20아릴이고;R' is C1-C20 alkyl, C6-C20 aryl, C6-C20 arylC1-C20 alkyl or C1-C20 alkylC6-C20 aryl;

Ar은 C6-C20아릴 또는 C3-C20헤테로아릴이고;Ar is C6-C20 aryl or C3-C20 heteroaryl;

상기 R1 및 Ar의 아릴 및 헤테로아릴은 C1-C20알킬, 할로C1-C20알킬, C1-C20알콕시, 할로겐, C1-C20알킬카보닐, C1-C20알콕시카보닐, C6-C20아릴, C6-C20아릴옥시, C6-C20아릴카보닐 및 C6-C20아릴옥시카보닐로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고;Aryl and heteroaryl of R 1 and Ar are C1-C20 alkyl, haloC1-C20 alkyl, C1-C20 alkoxy, halogen, C1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, C6-C20 aryl, C6- may be further substituted with one or more selected from the group consisting of C20 aryloxy, C6-C20 arylcarbonyl and C6-C20 aryloxycarbonyl;

상기 헤테로아릴은 N, O 및 S로부터 선택되는 1 내지 4개의 헤테로원자를 포함한다.)The heteroaryl contains 1 to 4 heteroatoms selected from N, O and S.)

일 실시예에 있어서, 상기 m은 0 내지 3의 정수일 수 있으며, R1의 위치는 제한되지않으며, m이 2 및 3인 경우 R1은 서로 동일하거나 상이할 수 있다.In one embodiment, m may be an integer from 0 to 3, the location of R 1 is not limited, and when m is 2 and 3, R 1 may be the same as or different from each other.

일 실시예에 있어서, 상기 m은 0 또는 1의 정수일 수 있다.In one embodiment, m may be an integer of 0 or 1.

일 실시예에 있어서, 상기 아줄레노퓨라논 화합물은 하기 화학식 2로 표시될 수 있다:In one embodiment, the azulenofuranone compound may be represented by Formula 2 below:

[화학식 2][Formula 2]

Figure 112021000693139-pat00007
Figure 112021000693139-pat00007

(상기 화학식 2에서, R2 및 Ar은 상기 화학식 1에서의 정의와 동일하고;(In Formula 2, R 2 and Ar are the same as defined in Formula 1;

R11는 수소, C1-C20알킬, 할로C1-C20알킬, 할로겐, C1-C20알콕시, 할로C1-C20알콕시, C1-C20알킬카보닐, 할로C1-C20알킬카보닐, C1-C20알콕시카보닐, 할로C1-C20알콕시카보닐, C6-C20아릴C1-C20알킬, C6-C20아릴C1-C20알킬옥시, C6-C20아릴 또는 C1-C20알킬C6-C20아릴이다.)R 11 is hydrogen, C1-C20 alkyl, haloC1-C20 alkyl, halogen, C1-C20 alkoxy, haloC1-C20 alkoxy, C1-C20 alkylcarbonyl, haloC1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl , haloC1-C20 alkoxycarbonyl, C6-C20 arylC1-C20 alkyl, C6-C20 arylC1-C20 alkyloxy, C6-C20 aryl or C1-C20 alkylC6-C20 aryl.)

일 실시예에 따른 상기 화학식 2에 있어서, 상기 R11는 수소, C1-C20알킬, 할로C1-C20알킬, C6-C20아릴C1-C20알킬, C6-C20아릴 또는 C1-C20알킬C6-C20아릴이고; R2는 수소, C1-C20알킬 또는 C6-C20아릴이고, 상기 R2의 알킬 및 아릴은 C1-C20알킬, 할로C1-C20알킬, 할로겐 및 C6-C20아릴로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고; Ar은 C6-C20아릴 또는 C3-C20헤테로아릴이고, 상기 Ar의 아릴 및 헤테로아릴은 C1-C20알킬, 할로C1-C20알킬, 할로겐, C1-C20알킬카보닐, C1-C20알콕시카보닐, C6-C20아릴, C6-C20아릴카보닐 및 C6-C20아릴옥시카보닐로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있다.In Formula 2 according to an embodiment, R 11 is hydrogen, C1-C20 alkyl, haloC1-C20 alkyl, C6-C20 arylC1-C20 alkyl, C6-C20 aryl or C1-C20 alkylC6-C20 aryl ego; R 2 is hydrogen, C1-C20 alkyl or C6-C20 aryl, and the alkyl and aryl of R 2 are at least one selected from the group consisting of C1-C20 alkyl, haloC1-C20 alkyl, halogen and C6-C20 aryl. may be further substituted; Ar is C6-C20 aryl or C3-C20 heteroaryl, and the aryl and heteroaryl of Ar are C1-C20 alkyl, haloC1-C20 alkyl, halogen, C1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, C6 It may be further substituted with one or more selected from the group consisting of -C20 aryl, C6-C20 arylcarbonyl and C6-C20 aryloxycarbonyl.

일 실시예에 따른 상기 화학식 2에 있어서, 상기 R11는 수소, C1-C10알킬, 할로C1-C10알킬, C6-C12아릴C1-C10알킬, C6-C12아릴 또는 C1-C10알킬C6-C12아릴이고; R2는 수소, C1-C10알킬 또는 C6-C12아릴이고, 상기 R2의 알킬 및 아릴은 C1-C10알킬, 할로C1-C10알킬, 할로겐 및 C6-C12아릴로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고; Ar은 C6-C12아릴 또는 C3-C10헤테로아릴이고, 상기 Ar의 아릴 및 헤테로아릴은 C1-C10알킬, 할로C1-C10알킬, 할로겐, C1-C10알킬카보닐, C1-C10알콕시카보닐, C6-C12아릴, C6-C12아릴카보닐 및 C6-C12아릴옥시카보닐로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있다.In Formula 2 according to an embodiment, R 11 is hydrogen, C1-C10 alkyl, haloC1-C10 alkyl, C6-C12 arylC1-C10 alkyl, C6-C12 aryl or C1-C10 alkylC6-C12 aryl ego; R 2 is hydrogen, C1-C10 alkyl or C6-C12 aryl, and the alkyl and aryl of R 2 are at least one selected from the group consisting of C1-C10 alkyl, haloC1-C10 alkyl, halogen and C6-C12 aryl. may be further substituted; Ar is C6-C12 aryl or C3-C10 heteroaryl, and the aryl and heteroaryl of Ar are C1-C10 alkyl, haloC1-C10 alkyl, halogen, C1-C10 alkylcarbonyl, C1-C10 alkoxycarbonyl, C6 It may be further substituted with one or more selected from the group consisting of -C12 aryl, C6-C12 arylcarbonyl and C6-C12 aryloxycarbonyl.

일 실시예에 따른 상기 화학식 2에 있어서, 상기 R11는 수소, C1-C10알킬 또는 C6-C12아릴이고; R2는 수소 또는 C1-C10알킬이고; Ar은 C6-C12아릴 또는 C3-C10헤테로아릴이고, 상기 Ar의 아릴은 C1-C10알킬, 할로C1-C10알킬, 할로겐 및 C1-C10알콕시카보닐로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있다.In Formula 2 according to an embodiment, R 11 is hydrogen, C1-C10 alkyl or C6-C12 aryl; R 2 is hydrogen or C1-C10 alkyl; Ar is C6-C12 aryl or C3-C10 heteroaryl, and the aryl of Ar may be further substituted with one or more selected from the group consisting of C1-C10 alkyl, haloC1-C10 alkyl, halogen and C1-C10 alkoxycarbonyl. can

일 실시예에 따른 상기 화학식 2에 있어서, 상기 R11는 수소, C1-C5알킬, 페닐 또는 나프틸이고; R2는 수소 또는 C1-C5알킬이고; Ar은

Figure 112021000693139-pat00008
,
Figure 112021000693139-pat00009
,
Figure 112021000693139-pat00010
또는
Figure 112021000693139-pat00011
이고, R' 및 R''는 각각 독립적으로 수소, C1-C5알킬, 할로C1-C5알킬, 할로겐, C1-C5알콕시카보닐이고; Y는 O 또는 S이다.In Formula 2 according to an embodiment, R 11 is hydrogen, C1-C5 alkyl, phenyl or naphthyl; R 2 is hydrogen or C1-C5 alkyl; Ar is
Figure 112021000693139-pat00008
,
Figure 112021000693139-pat00009
,
Figure 112021000693139-pat00010
or
Figure 112021000693139-pat00011
, R' and R'' are each independently hydrogen, C1-C5 alkyl, haloC1-C5 alkyl, halogen, C1-C5 alkoxycarbonyl; Y is O or S;

일 실시예에 따른 아줄레노퓨라논 화합물은 보다 구체적으로 하기의 구조에서 선택될 수 있으나, 이로 한정되는 것은 아니다.The azulenofuranone compound according to one embodiment may be more specifically selected from the following structures, but is not limited thereto.

Figure 112021000693139-pat00012
Figure 112021000693139-pat00012

이하, 본 발명에 따른 아줄레노퓨라논 화합물의 제조방법에 대하여 상세히 설명한다.Hereinafter, a method for preparing the azulenofuranone compound according to the present invention will be described in detail.

본 발명은 탈카르복실화 없이 우수한 선택성 및 수율로 상기 화학식 1의 아줄레노퓨라논 화합물을 제조하는 방법을 제공한다.The present invention provides a method for preparing the azulenofuranone compound of Formula 1 with excellent selectivity and yield without decarboxylation.

본 발명의 화학식 1의 아줄레노퓨라논 화합물의 제조방법으로서, 이리듐(Ir) 촉매, 은 산화제 및 아세트산염 첨가제의 존재 하, 하기 화학식 3의 아줄렌-1-카복실산 화합물 및 화학식 4의 다이아릴아이오도늄염 화합물을 반응시켜 하기 화학식 1의 아줄레노퓨라논 화합물을 제조하는 방법을 제공한다:A method for preparing the azulenofuranone compound of formula (1) of the present invention, in the presence of an iridium (Ir) catalyst, a silver oxidizing agent and an acetate additive, an azulene-1-carboxylic acid compound of formula (3) and diarylio of formula (4) Provided is a method for preparing an azulenofuranone compound of Formula 1 by reacting a donium salt compound:

[화학식 1][Formula 1]

Figure 112021000693139-pat00013
Figure 112021000693139-pat00013

[화학식 3][Formula 3]

Figure 112021000693139-pat00014
Figure 112021000693139-pat00014

[화학식 4][Formula 4]

Figure 112021000693139-pat00015
Figure 112021000693139-pat00015

(상기 화학식 1, 3 및 4에서,(In Chemical Formulas 1, 3 and 4,

R1는 C1-C20알킬, 할로C1-C20알킬, 할로겐, C1-C20알콕시, 할로C1-C20알콕시, C1-C20알킬카보닐, 할로C1-C20알킬카보닐, C1-C20알콕시카보닐, 할로C1-C20알콕시카보닐, C6-C20아릴C1-C20알킬, C6-C20아릴C1-C20알킬옥시, C6-C20아릴 또는 C3-C20헤테로아릴이고;R 1 is C1-C20 alkyl, haloC1-C20 alkyl, halogen, C1-C20 alkoxy, haloC1-C20 alkoxy, C1-C20 alkylcarbonyl, haloC1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, halo C1-C20 alkoxycarbonyl, C6-C20 arylC1-C20 alkyl, C6-C20 arylC1-C20 alkyloxy, C6-C20 aryl or C3-C20 heteroaryl;

m은 0 내지 5의 정수로, m이 2 이상의 정수인 경우 R1은 서로 동일하거나 상이할 수 있고;m is an integer from 0 to 5, and when m is an integer of 2 or greater, R 1 may be the same as or different from each other;

R2는 수소, C1-C20알킬, 할로겐, C1-C20알콕시, 할로C1-C20알콕시, C1-C20알킬카보닐, 할로C1-C20알킬카보닐, C1-C20알콕시카보닐, 할로C1-C20알콕시카보닐, C6-C20아릴카보닐, C6-C20아릴C1-C20알킬옥시, C6-C20아릴 또는 C3-C20헤테로아릴이고, 상기 R2의 알킬, 아릴 및 헤테로아릴은 C1-C20알킬, 할로C1-C20알킬, C1-C20알콕시, 할로겐, 나이트로, C1-C20알킬카보닐, C1-C20알콕시카보닐, C6-C20아릴, -NHSO2R' 및 C6-C20아릴옥시로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고;R 2 is hydrogen, C1-C20 alkyl, halogen, C1-C20 alkoxy, haloC1-C20 alkoxy, C1-C20 alkylcarbonyl, haloC1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, haloC1-C20 alkoxy carbonyl, C6-C20 arylcarbonyl, C6-C20 arylC1-C20 alkyloxy, C6-C20 aryl or C3-C20 heteroaryl, wherein the alkyl, aryl and heteroaryl of R 2 are C1-C20 alkyl, haloC1 -C20 alkyl, C1-C20 alkoxy, halogen, nitro, C1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, C6-C20 aryl, -NHSO 2 R' and C6-C20 aryloxy selected from the group consisting of may be further substituted with one or more;

R'는 C1-C20알킬, C6-C20아릴, C6-C20아릴C1-C20알킬 또는 C1-C20알킬C6-C20아릴이고;R' is C1-C20 alkyl, C6-C20 aryl, C6-C20 arylC1-C20 alkyl or C1-C20 alkylC6-C20 aryl;

Ar은 C6-C20아릴 또는 C3-C20헤테로아릴이고;Ar is C6-C20 aryl or C3-C20 heteroaryl;

상기 R1 및 Ar의 아릴 및 헤테로아릴은 C1-C20알킬, 할로C1-C20알킬, C1-C20알콕시, 할로겐, C1-C20알킬카보닐, C1-C20알콕시카보닐, C6-C20아릴, C6-C20아릴옥시, C6-C20아릴카보닐 및 C6-C20아릴옥시카보닐로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고;Aryl and heteroaryl of R 1 and Ar are C1-C20 alkyl, haloC1-C20 alkyl, C1-C20 alkoxy, halogen, C1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, C6-C20 aryl, C6- may be further substituted with one or more selected from the group consisting of C20 aryloxy, C6-C20 arylcarbonyl and C6-C20 aryloxycarbonyl;

X-는 1가 음이온이다.)X - is a monovalent anion.)

또한, 본 발명은 화학식 1의 아줄레노퓨라논 화합물의 제조방법으로서, 이리듐(Ir) 촉매, 은 산화제 및 아세트산염 첨가제의 존재 하, 하기 화학식 3A의 2-아릴아줄렌-1-카복실산 화합물을 분자내 고리화 반응시켜 상기 화학식 1의 아줄레노퓨라논 화합물을 제조하는 방법을 제공한다:In addition, the present invention is a method for producing an azulenofuranone compound of Formula 1, wherein a 2-arylazulene-1-carboxylic acid compound of Formula 3A below is prepared by molecularly Provided is a method for preparing the azulenofuranone compound of Formula 1 by cyclization reaction within:

[화학식 3A][Formula 3A]

Figure 112021000693139-pat00016
Figure 112021000693139-pat00016

(상기 화학식 3A에서, R1, R2, Ar 및 m은 상기 화학식 1에서의 정의와 동일하다.)(In Formula 3A, R 1 , R 2 , Ar and m are the same as defined in Formula 1 above.)

본 발명의 제조방법에 따르면, 특정 금속 촉매인 이리듐(Ir) 촉매와 특정 산화제와 첨가제인 은 산화제 및 아세트산염 첨가제의 사용으로 인하여 비-벤제노이드 방향족 탄화수소 화합물인 아줄렌-1-카복실산 화합물(화학식 3) 및 다이아릴아이오도늄염 화합물(화학식 4)의 순차 반응, 즉 C(2)-아릴화 및 분자내 C-O 결합 형성을 통해 원팟(one-pot)으로 다양한 치환체가 도입된 아줄레노퓨라논 화합물(화학식 1)을 고선택적으로 효율적으로 제조할 수 있다. According to the production method of the present invention, azulene-1-carboxylic acid compound (chemical formula 3) and a diaryliodonium salt compound (Formula 4), that is, azulenofuranone compound in which various substituents are introduced one-pot through sequential reaction, that is, C(2)-arylation and intramolecular C-O bond formation (Formula 1) can be efficiently prepared with high selectivity.

즉, 이리듐(Ir) 촉매, 은 산화제 및 아세트산염 첨가제의 존재 하, 아줄렌-1-카복실산 화합물(화학식 3) 및 다이아릴아이오도늄염 화합물(화학식 4)로부터 탈카복실화 없이 이리듐-촉매화된 위치선택적 C(2)-아릴화로 유도되는 2-아릴아줄렌-1-카복실산 화합물(화학식 3A)이 생성되고 연이어 분자내 고리화 반응이 진행되어 분자내 C-O 결합을 형성하여 아줄레노퓨라논 화합물(화학식 1)이 원-팟으로 고수율로 제조될 수 있다.That is, in the presence of an iridium (Ir) catalyst, a silver oxidizing agent and an acetate additive, an iridium-catalyzed iridium-catalyzed A 2-arylazulene-1-carboxylic acid compound (Formula 3A) induced by regioselective C(2)-arylation is generated and subsequent intramolecular cyclization proceeds to form intramolecular C-O bonds to form azulenofuranone compounds ( Formula 1) can be prepared in high yield with one-pot.

[반응식 1][Scheme 1]

Figure 112021000693139-pat00017
Figure 112021000693139-pat00017

(상기 반응식 1에서, R1, R2, Ar 및 m은 상기 화학식 1에서의 정의와 동일하고; X-는 상기 화학식 4에서의 정의와 동일하다.)(In Reaction Scheme 1, R 1 , R 2 , Ar and m are the same as defined in Formula 1; X - is the same as defined in Formula 4 above.)

일 실시예에 따른 이리듐(Ir) 촉매는 [Cp*IrCl2]2 (Cp*=pentamethylcyclopentadienyl) (Pentamethylcyclopentadienyliridium(III) chloride dimer), Ir(acac)3 (Iridium(III) acetylacetonate), IrCl3 (Iridium(III) chloride), Ir(ppy)3 (ppy=2-phenylpyridine) (Tris[2-phenylpyridinato-C2,N]iridium(III)), [(ppy)2IrCl]2 (Dichlorotetrakis(2-(2-pyridinyl)phenyl)diiridium(III)), (ppy)2Ir(acac) (Bis[2-(2-pyridinyl-N)phenyl-C](acetylacetonato)iridium(III)), Ir[(ppy)2(dtb-bpy)]PF6 ([4,4'-Bis(1,1-dimethylethyl)-2,2'-bipyridine-N1,N1']bis[2-(2-pyridinyl-N)phenyl-C]iridium(III) hexafluorophosphate), [Ir(cod)Cl]2 (Bis(1,5-cyclooctadiene)diiridium(I) dichloride) 및 IrCp*(OAc)2 (Cp*=pentamethylcyclopentadienyl)로 이루어진 군으로부터 선택되는 하나 또는 둘 이상일 수 있으며, 보다 우수한 반응성 및 수율 측면에서 바람직하게는 [Cp*IrCl2]2를 사용할 수 있다.Iridium (Ir) catalyst according to an embodiment is [Cp*IrCl 2 ] 2 (Cp*=pentamethylcyclopentadienyl) (Pentamethylcyclopentadienyliridium(III) chloride dimer), Ir(acac) 3 (Iridium(III) acetylacetonate), IrCl 3 (Iridium (III) chloride), Ir(ppy) 3 (ppy=2-phenylpyridine) (Tris[2-phenylpyridinato-C 2 ,N]iridium(III)), [(ppy) 2 IrCl] 2 (Dichlorotetrakis(2-( 2-pyridinyl)phenyl)diiridium(III)), (ppy) 2 Ir(acac) (Bis[2-(2-pyridinyl-N)phenyl-C](acetylacetonato)iridium(III)), Ir[(ppy) 2 (dtb-bpy)]PF 6 ([4,4'- Bis (1,1-dimethylethyl)-2,2'-bipyridine- N 1, N 1'] bis [2-(2-pyridinyl- N ) phenyl-C]iridium(III) hexafluorophosphate), [Ir(cod)Cl] 2 (Bis(1,5-cyclooctadiene)diiridium(I) dichloride) and IrCp*(OAc) 2 (Cp*=pentamethylcyclopentadienyl) [Cp*IrCl 2 ] 2 may be preferably used in terms of better reactivity and yield.

상기 이리듐(Ir) 촉매는 상기 화학식 3의 아줄렌-1-카복실산 화합물 또는 화학식 3A의 2-아릴아줄렌-1-카복실산 화합물에 대해 0.5 내지 20 mol%, 바람직하게는 1.0 내지 10.0 mol%, 보다 바람직하게는 1.0 내지 5.0 mol% 범위로 사용할 수 있다.The iridium (Ir) catalyst is present in an amount of 0.5 to 20 mol%, preferably 1.0 to 10.0 mol%, based on the azulene-1-carboxylic acid compound of Formula 3 or the 2-arylazulene-1-carboxylic acid compound of Formula 3A. Preferably it can be used in the range of 1.0 to 5.0 mol%.

일 실시예에 따른 상기 화학식 4에서 상기 X-는 1가 음이온으로, 구체적으로는 할라이드, 테트라플루오로보레이트(tetrafluoroborate, BF4 -), 트리플레이트(triflate, CF3SO3 -, OTf-) 토실레이트(tosylate, CH3C6H4SO3 -, OTs-), 헥사플루오로포스페이트(hexafluorophosphate, PF6 -) 또는 아세테이트(acetate, OAc-)일 수 있다.In Formula 4 according to an embodiment, X - is a monovalent anion, specifically, halide, tetrafluoroborate (BF 4 - ), triflate (CF 3 SO 3 - , OTf - ) tosyl It may be tosylate (CH 3 C 6 H 4 SO 3 - , OTs - ), hexafluorophosphate (PF 6 - ) or acetate (acetate, OAc - ).

일 실시예에 따른 상기 화학식 4의 다이아릴아이오도늄염 화합물은 상기 화학식 3의 아줄렌-1-카복실산 화합물 1 당량에 대해 1 내지 3 당량, 바람직하게는 1 내지 2 당량, 보다 바람직하게는 1 내지 1.5 당량 범위로 사용할 수 있으며, 상기 범위로 사용할 경우 수율 및 경제성 측면에서 가장 바람직할 수 있다.According to an embodiment, the amount of the diaryliodonium salt compound of Formula 4 is 1 to 3 equivalents, preferably 1 to 2 equivalents, more preferably 1 to 2 equivalents, based on 1 equivalent of the azulene-1-carboxylic acid compound of Formula 3. It can be used in the range of 1.5 equivalents, and when used in the above range, it may be most preferable in terms of yield and economy.

일 실시예에 따른 은 산화제는 AgO (silver(II) oxide), Ag2O (silver(I) oxide), Ag2CO3 (silver carbonate), AgOAc (silver acetate), AgSbF6 (silver hexafluoroantimonate(V)), AgNO3 (silver nitrate), AgNTf2 (silver bis(trifluoromethanesulfonyl)imide) 및 AgOTf (silver trifluoromethanesulfonate)로 이루어진 군으로부터 선택되는 하나 또는 둘 이상일 수 있으며, 경제성, 반응성 및 수율 측면에서 바람직하게는 AgOAc을 사용할 수 있다.Silver oxidizing agent according to an embodiment is AgO (silver (II) oxide), Ag 2 O (silver (I) oxide), Ag 2 CO 3 (silver carbonate), AgOAc (silver acetate), AgSbF 6 (silver hexafluoroantimonate (V )), AgNO 3 (silver nitrate), AgNTf 2 (silver bis (trifluoromethanesulfonyl)imide), and AgOTf (silver trifluoromethanesulfonate), and may be one or two or more selected from the group consisting of AgOAc can be used.

상기 은 산화제는 상기 화학식 3의 아줄렌-1-카복실산 화합물 또는 화학식 3A의 2-아릴아줄렌-1-카복실산 화합물 1 당량에 대해 1 내지 5 당량, 바람직하게는 1 내지 3 당량 범위로 사용할 수 있다. 상기 범위 내에서 은 산화제를 사용할 경우 보다 향상된 반응성 및 수율을 나타낼 수 있다.The silver oxidizing agent may be used in the range of 1 to 5 equivalents, preferably 1 to 3 equivalents, based on 1 equivalent of the azulene-1-carboxylic acid compound of Formula 3 or the 2-arylazulene-1-carboxylic acid compound of Formula 3A. . When the silver oxidizing agent is used within the above range, more improved reactivity and yield may be exhibited.

일 실시예에 따른 아세트산염 첨가제는 아세트산 알칼리금속염으로, 구체적으로 KOAc (potassium acetate), LiOAc (lithium acetate), NaOAc (sodium acetate) 및 CsOAc (cesium acetate)로 이루어진 군으로부터 선택되는 하나 또는 둘 이상일 수 있으며, 경제성, 반응성 및 수율 측면에서 바람직하게는 KOAc를 사용할 수 있다.Acetate salt additive according to an embodiment is an alkali metal acetic acid salt, specifically, one or two or more selected from the group consisting of KOAc (potassium acetate), LiOAc (lithium acetate), NaOAc (sodium acetate) and CsOAc (cesium acetate). And, in terms of economy, reactivity and yield, KOAc can be preferably used.

상기 아세트산염 첨가제는 상기 화학식 3의 아줄렌-1-카복실산 화합물 또는 화학식 3A의 2-아릴아줄렌-1-카복실산 화합물 1 당량에 대해 0.5 내지 3 당량, 바람직하게는 1 내지 1.5 당량 범위로 사용할 수 있다. 상기 범위 내에서 아세트산염 첨가제를 사용할 경우 보다 향상된 반응성 및 수율을 나타낼 수 있다.The acetate additive may be used in an amount of 0.5 to 3 equivalents, preferably 1 to 1.5 equivalents, based on 1 equivalent of the azulene-1-carboxylic acid compound of Formula 3 or the 2-arylazulene-1-carboxylic acid compound of Formula 3A. there is. When the acetate additive is used within the above range, more improved reactivity and yield may be exhibited.

일 실시예에 따른 이리듐 촉매, 은 산화제 및 아세트산염 첨가제는 바람직하게는 [Cp*IrCl2]2, AgOAc 및 KOAc의 조합일 수 있다.The iridium catalyst, silver oxidizer and acetate additive according to an embodiment may preferably be a combination of [Cp*IrCl 2 ] 2 , AgOAc and KOAc.

일 실시예에 있어서, 상기 반응은 유기용매 하에서 이루어질 수 있다. 상기 반응에 참여하는 반응물질들을 용해할 수 있는 것이라면 유기용매에 제한을 둘 필요는 없다. 구체적으로 사용가능한 유기용매는 디클로로메탄(DCM), 디클로로에탄(DCE), 1,4-다이옥산, 테트라하이드로퓨란(THF), t-부틸알콜, t-아밀알콜, 트리플루오로에탄올, 자일렌, 헥사플루오로이소프로판올, 아세토나이트릴(MeCN), 톨루엔, 디메틸포름아마이드(DMF), 나이트로메탄, 클로로포름, 아세톤 등으로, 이로 제한되지는 않으나, 반응물의 용해성 등의 용이성을 고려하여 디클로로메탄(DCM), 디클로로에탄(DCE), 아세토나이트릴(MeCN) 및 클로로포름으로 이루어진 군에서 선택되는 하나 또는 둘 이상의 유기용매를 사용할 수 있으며, 보다 향상된 반응성 측면에서 디클로로에탄(DCE), 디메틸포름아마이드(DMF) 또는 이들의 혼합용매를 사용하는 것이 좋다.In one embodiment, the reaction may be performed in an organic solvent. There is no need to limit the organic solvent as long as it can dissolve the reactants participating in the reaction. Specifically usable organic solvents include dichloromethane (DCM), dichloroethane (DCE), 1,4-dioxane, tetrahydrofuran (THF), t-butyl alcohol, t-amyl alcohol, trifluoroethanol, xylene, Dichloromethane (DCM ), dichloroethane (DCE), acetonitrile (MeCN), and one or more organic solvents selected from the group consisting of chloroform may be used, and in terms of more improved reactivity, dichloroethane (DCE) and dimethylformamide (DMF) Alternatively, it is preferable to use a mixed solvent thereof.

일 실시예에 따른 상기 반응은 50 내지 100℃, 바람직하게는 60 내지 80℃에서 수행될 수 있으나, 반응온도가 이로 제한되는 것은 아니며, 필요에 따라 조절될 수 있다. 또한, 반응시간 역시 반응물질, 용매의 종류 및 용매의 양 등에 따라 달라질 수 있으며, TLC 등을 통하여 출발물질이 소모됨과 동시에 생성물을 확인한 후 반응을 완결시킨다. 반응이 완결되면 감암 하에서 용매를 증류시킨 후, 컬럼 크로마토그래피, 재결정 등의 통상의 방법을 통하여 목적물을 분리 정제할 수 있다.The reaction according to an embodiment may be carried out at 50 to 100 ° C, preferably 60 to 80 ° C, but the reaction temperature is not limited thereto and may be adjusted as necessary. In addition, the reaction time may also vary depending on the reactant, the type and amount of the solvent, etc., and the reaction is completed after the starting material is consumed and the product is confirmed through TLC or the like. When the reaction is complete, the solvent can be distilled off under the dark, and then the target substance can be separated and purified through conventional methods such as column chromatography and recrystallization.

일 실시예에 있어, 상기 화학식 3A의 2-아릴아줄렌-1-카복실산 화합물은 이리듐(Ir) 촉매, 은 산화제 및 포스페이트계 첨가제의 존재 하, 상기 화학식 3의 아줄렌-1-카복실산 화합물 및 화학식 4의 다이아릴아이오도늄염 화합물을 반응시켜 제조될 수 있다.In one embodiment, the 2-arylazulene-1-carboxylic acid compound of Chemical Formula 3A is prepared from the azulene-1-carboxylic acid compound of Chemical Formula 3 and Chemical Formula 3 in the presence of an iridium (Ir) catalyst, a silver oxidizing agent, and a phosphate-based additive. It can be prepared by reacting the diaryliodonium salt compound of 4.

상기 이리듐(Ir) 촉매 및 은 산화제의 종류와 함량은 상술한 바와 동일하다.The types and contents of the iridium (Ir) catalyst and the silver oxidizing agent are the same as described above.

상기 포스페이트계 첨가제는 K3PO4, KH2PO4, K2HPO4, NaH2PO4, Na2HPO4, Li3PO4 및 LiH2PO4로 이루어진 군으로부터 하나 또는 둘 이상일 수 있으며, 반응성 및 수율 측면에서 바람직하게는 Na2HPO4을 사용할 수 있으며, 상기 화학식 3의 아줄렌-1-카복실산 화합물 1 당량에 대해 0.5 내지 3 당량, 바람직하게는 1 내지 1.5 당량 범위로 사용할 수 있다. 상기 포스페이트계 첨가제의 사용으로 인하여 아줄렌-1-카복실산 화합물(화학식 3) 및 다이아릴아이오도늄염 화합물(화학식 4)로부터 탈카복실화 없이 이리듐-촉매화된 위치선택적 C(2)-아릴화로 유도되는 2-아릴아줄렌-1-카복실산 화합물(화학식 3A)만을 선택적으로 제조할 수 있다.The phosphate-based additive may be one or two or more from the group consisting of K 3 PO 4 , KH 2 PO 4 , K 2 HPO 4 , NaH 2 PO 4 , Na 2 HPO 4 , Li 3 PO 4 and LiH 2 PO 4 , In terms of reactivity and yield, Na 2 HPO 4 may be preferably used, and may be used in an amount of 0.5 to 3 equivalents, preferably 1 to 1.5 equivalents, based on 1 equivalent of the azulene-1-carboxylic acid compound of Formula 3. The use of the phosphate-based additive leads to iridium-catalyzed regioselective C(2)-arylation without decarboxylation from azulene-1-carboxylic acid compound (Formula 3) and diaryliodonium salt compound (Formula 4) Only the 2-arylazulene-1-carboxylic acid compound (Formula 3A) can be selectively prepared.

상기 화학식 3A의 2-아릴아줄렌-1-카복실산 화합물을 제조하기 위한 반응 온도는 제한되는 것은 아니나, 60 내지 80℃, 바람직하게는 60 내지 70℃일 수 있다.The reaction temperature for preparing the 2-arylazulene-1-carboxylic acid compound of Chemical Formula 3A is not limited, but may be 60 to 80°C, preferably 60 to 70°C.

일 실시예에 따른 상기 화학식 3A에 있어서, 상기 R1는 C1-C10알킬, 할로C1-C10알킬, C6-C12아릴C1-C10알킬, C6-C12아릴 또는 C1-C10알킬C6-C12아릴이고; m은 0 또는 1의 정수이고; R2는 수소, C1-C10알킬 또는 C6-C12아릴이고, 상기 R2의 알킬 및 아릴은 C1-C10알킬, 할로C1-C10알킬, 할로겐 및 C6-C12아릴로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고; Ar은 C6-C12아릴 또는 C3-C10헤테로아릴이고, 상기 Ar의 아릴 및 헤테로아릴은 C1-C10알킬, 할로C1-C10알킬, 할로겐, C1-C10알킬카보닐, C1-C10알콕시카보닐, C6-C12아릴, C6-C12아릴카보닐 및 C6-C12아릴옥시카보닐로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있다.In Formula 3A according to an embodiment, R 1 is C1-C10 alkyl, haloC1-C10 alkyl, C6-C12 arylC1-C10 alkyl, C6-C12 aryl or C1-C10 alkylC6-C12 aryl; m is an integer of 0 or 1; R 2 is hydrogen, C1-C10 alkyl or C6-C12 aryl, and the alkyl and aryl of R 2 are at least one selected from the group consisting of C1-C10 alkyl, haloC1-C10 alkyl, halogen and C6-C12 aryl. may be further substituted; Ar is C6-C12 aryl or C3-C10 heteroaryl, and the aryl and heteroaryl of Ar are C1-C10 alkyl, haloC1-C10 alkyl, halogen, C1-C10 alkylcarbonyl, C1-C10 alkoxycarbonyl, C6 It may be further substituted with one or more selected from the group consisting of -C12 aryl, C6-C12 arylcarbonyl and C6-C12 aryloxycarbonyl.

일 실시예에 따른 상기 화학식 3A에 있어서, 상기 R1는 C1-C5알킬, 페닐 또는 나프틸이고; m은 0 또는 1의 정수이고; R2는 수소 또는 C1-C5알킬이고; Ar은

Figure 112021000693139-pat00018
,
Figure 112021000693139-pat00019
,
Figure 112021000693139-pat00020
또는
Figure 112021000693139-pat00021
이고, R' 및 R''는 각각 독립적으로 수소, C1-C5알킬, 할로C1-C5알킬, 할로겐, C1-C5알콕시카보닐이고; Y는 O 또는 S이다.In Formula 3A according to an embodiment, R 1 is C1-C5 alkyl, phenyl or naphthyl; m is an integer of 0 or 1; R 2 is hydrogen or C1-C5 alkyl; Ar is
Figure 112021000693139-pat00018
,
Figure 112021000693139-pat00019
,
Figure 112021000693139-pat00020
or
Figure 112021000693139-pat00021
, R' and R'' are each independently hydrogen, C1-C5 alkyl, haloC1-C5 alkyl, halogen, C1-C5 alkoxycarbonyl; Y is O or S;

일 실시예에 따른 화학식 3A의 2-아릴아줄렌-1-카복실산 화합물은 하기 구조로 예시될 수 있으나, 이에 한정되는 것은 아니다.The 2-arylazulene-1-carboxylic acid compound of Chemical Formula 3A according to an embodiment may be exemplified by the following structure, but is not limited thereto.

Figure 112021000693139-pat00022
Figure 112021000693139-pat00022

이하, 실시예를 통하여 본 발명의 구성을 보다 구체적으로 설명하지만, 하기의 실시예들은 본 발명에 대한 이해를 돕기 위한 것으로서, 본 발명의 범위가 여기에 국한된 것은 아니다.Hereinafter, the configuration of the present invention will be described in more detail through examples, but the following examples are intended to aid understanding of the present invention, and the scope of the present invention is not limited thereto.

실시예 I : 아줄레노퓨라논(azulenofuranone) 화합물 (1)의 제조Example I: Preparation of azulenofuranone compound (1)

Figure 112021000693139-pat00023
Figure 112021000693139-pat00023

질소 대기 하에서 아줄렌-1-카복실산 화합물 (3) (0.2 mmol, 1.0 equiv), 다이아릴아이오도늄염 화합물 (4) (0.24 mmol, 1.2 equiv, X=OTf (실시예 1-4,6-11), BF4 (실시예 5)), [Cp*IrCl2]2 (4.0 mol%, 6.4 mg), AgOAc (3.0 equiv, 100.2 mg), KOAc (1.0 equiv, 19.7 mg) 및 DMF (1.0 mL)을 혼합하고, 80℃에서 2시간 또는 60℃에서 6시간 동안 교반시켰다. 교반 완료 후 반응 혼합물을 상온으로 냉각시키고, 셀라이트 패드로 여과시킨 다음, 감압 하에서 여액을 농축시켰다. 농축된 잔류물을 실리카 겔 플래쉬 컬럼 크로마토그래피로 정제하여 목적 화합물인 아줄레노퓨라논 화합물 (1)을 수득하였다.Under a nitrogen atmosphere, azulene-1-carboxylic acid compound (3) (0.2 mmol, 1.0 equiv), diaryliodonium salt compound (4) (0.24 mmol, 1.2 equiv, X=OTf (Example 1-4,6-11 ), BF 4 (Example 5)), [Cp*IrCl 2 ] 2 (4.0 mol%, 6.4 mg), AgOAc (3.0 equiv, 100.2 mg), KOAc (1.0 equiv, 19.7 mg) and DMF (1.0 mL) were mixed and stirred at 80°C for 2 hours or at 60°C for 6 hours. After stirring was completed, the reaction mixture was cooled to room temperature, filtered through a celite pad, and the filtrate was concentrated under reduced pressure. The concentrated residue was purified by silica gel flash column chromatography to obtain the target compound, azulenofuranone compound (1).

상기 기재된 방법을 이용하여 다양한 아줄레노퓨라논 화합물 (1)을 제조하였다.Various azulenofuranone compounds (1) were prepared using the methods described above.

[실시예 1] 3-Phenyl-1H-azuleno[1,8-bc]furan-1-one (화합물 1-1)의 제조[Example 1] Preparation of 3-Phenyl- 1H -azuleno[1,8-bc]furan-1-one (Compound 1-1)

Figure 112021000693139-pat00024
Figure 112021000693139-pat00024

반응온도: 80℃; 반응시간 : 2시간Reaction temperature: 80° C.; Reaction time: 2 hours

Yield: 43.3 mg (88%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 106-108℃; 1H NMR (400 MHz, CDCl3) δ 8.37-8.32 (m, 3H), 7.94 (t, J = 10.4 Hz, 1H), 7.63-7.58 (m, 2H), 7.55-7.48 (m, 3H), 7.45-7.41 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.0, 156.8, 148.6, 145.1, 138.3, 137.5, 137.4, 134.1, 129.9, 129.2, 128.6, 128.4, 117.3, 113.9, 110.2; IR (film): 3060, 2360, 1760, 1633, 1495, 1348, 1219, 1104, 756, 668 cm-1; HRMS (EI) m/z:[M]+ Calcd for C17H10O2 246.0681; Found 246.0684.Yield: 43.3 mg (88%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 106-108°C; 1H NMR (400 MHz, CDCl 3 ) δ 8.37-8.32 (m, 3H), 7.94 (t, J = 10.4 Hz, 1H), 7.63-7.58 (m, 2H), 7.55-7.48 (m, 3H), 7.45- 7.41 (m, 1H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 163.0, 156.8, 148.6, 145.1, 138.3, 137.5, 137.4, 134.1, 129.9, 129.2, 128.6, 128.4, 117.3, 110.9, 110.2; IR (film): 3060, 2360, 1760, 1633, 1495, 1348, 1219, 1104, 756, 668 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 17 H 10 O 2 246.0681; Found 246.0684.

[실시예 2] 3-(o-Tolyl)-1H-azuleno[1,8-bc]furan-1-one (화합물 1-2)의 제조[Example 2] Preparation of 3-( o -Tolyl) -1H -azuleno[1,8-bc]furan-1-one (Compound 1-2)

Figure 112021000693139-pat00025
Figure 112021000693139-pat00025

반응온도: 80℃; 반응시간 : 2시간Reaction temperature: 80° C.; Reaction time: 2 hours

Yield: 36.4 mg (70%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 125-127℃; 1H NMR (400 MHz, CDCl3) δ 8.40 (d, J = 9.4 Hz, 1H), 7.98 (t, J = 10.4 Hz, 1H), 7.86-7.84 (m, 1H), 7.63 (t, J = 10.1 Hz, 1H), 7.50 (d, J = 9.9 Hz, 1H), 7.37-7.32 (m, 4H), 2.61 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 162.5, 157.3, 149.1, 144.3, 138.6, 137.8, 137.2, 136.9, 134.3, 131.3, 131.3, 129.1, 128.2, 126.3, 121.7, 113.7, 112.0, 21.2; IR (film): 2359, 2340, 1769, 1634, 1496, 1455, 1337, 1219, 756 cm-1; HRMS (EI) m/z:[M]+ Calcd for C18H12O2 260.0837; Found 260.0834.Yield: 36.4 mg (70%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 125-127°C; 1H NMR (400 MHz, CDCl 3 ) δ 8.40 (d, J = 9.4 Hz, 1H), 7.98 (t, J = 10.4 Hz, 1H), 7.86-7.84 (m, 1H), 7.63 (t, J = 10.1 Hz , 1H), 7.50 (d, J = 9.9 Hz, 1H), 7.37–7.32 (m, 4H), 2.61 (s, 3H); 13 C { 1 H} NMR (100 MHz, CDCL 3 ) Δ 162.5, 157.3, 149.1, 144.3, 138.6, 137.8, 137.2, 136.9, 134.3, 131.3, 131.3, 129.1, 128.2, 126.3, 121.7, 113.7, 112.0, 21.2 ; IR (film): 2359, 2340, 1769, 1634, 1496, 1455, 1337, 1219, 756 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 18 H 12 O 2 260.0837; Found 260.0834.

[실시예 3] 3-(m-Tolyl)-1H-azuleno[1,8-bc]furan-1-one (화합물 1-3)의 제조[Example 3] Preparation of 3-( m -Tolyl) -1H -azuleno[1,8-bc]furan-1-one (Compound 1-3)

Figure 112021000693139-pat00026
Figure 112021000693139-pat00026

반응온도: 80℃; 반응시간 : 2시간Reaction temperature: 80° C.; Reaction time: 2 hours

Yield: 37.5 mg (72%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 181-183℃; 1H NMR (400 MHz, CDCl3) δ 8.31 (d, J = 9.4 Hz, 1H), 8.15-8.12 (m, 2H), 7.90 (t, J = 10.4 Hz, 1H), 7.59-7.54 (m, 2H), 7.45 (d, J = 9.9 Hz, 1H), 7.41 (t, J =7.6 Hz, 1H), 7.24 (d, J = 7.6 Hz, 1H), 2.47 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.1, 156.8, 149.0, 145.2, 138.8, 138.2, 137.6, 137.4, 134.1, 130.9, 129.19, 129.16, 128.3, 126.0, 117.3, 113.9, 110.4, 21.7; IR (film): 2363, 1759, 1634, 1490, 1389, 1218, 741 cm-1; HRMS (EI) m/z:[M]+ Calcd for C18H14O2 260.0837; Found 260.0836.Yield: 37.5 mg (72%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 181-183°C; 1H NMR (400 MHz, CDCl 3 ) δ 8.31 (d, J = 9.4 Hz, 1H), 8.15-8.12 (m, 2H), 7.90 (t, J = 10.4 Hz, 1H), 7.59-7.54 (m, 2H) , 7.45 (d, J = 9.9 Hz, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.24 (d, J = 7.6 Hz, 1H), 2.47 (s, 3H); 13 C { 1 H} NMR (100 MHz, CDCL 3 ) Δ 163.1, 156.8, 149.0, 145.2, 138.8, 138.2, 137.6, 137.4, 134.1, 130.9, 129.19, 129.16, 128.3, 126.0, 117.3, 113.9, 110.4, 21.7 ; IR (film): 2363, 1759, 1634, 1490, 1389, 1218, 741 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 18 H 14 O 2 260.0837; Found 260.0836.

[실시예 4] 3-(p-Tolyl)-1H-azuleno[1,8-bc]furan-1-one (화합물 1-4)의 제조[Example 4] Preparation of 3-( p -Tolyl) -1H -azuleno[1,8-bc]furan-1-one (Compound 1-4)

Figure 112021000693139-pat00027
Figure 112021000693139-pat00027

반응온도: 80℃; 반응시간 : 2시간Reaction temperature: 80° C.; Reaction time: 2 hours

Yield: 37.5 mg (72%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 186-188℃; 1H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 9.4 Hz, 1H), 8.18 (d, J = 8.1 Hz, 2H), 7.84 (t, J = 10.3 Hz, 1H), 7.54-7.49 (m, 2H), 7.39 (d, J = 9.9 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 2.41 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.1, 156.5, 148.9, 145.1, 140.4, 137.8, 137.6, 137.1, 131.5, 129.9, 128.6, 128.3, 116.8, 113.9, 110.2, 21.7; IR (film): 2916, 1758, 1635, 1496, 1455, 1341, 1218, 802, 772, 739 cm-1; HRMS (EI) m/z:[M]+ Calcd for C18H12O2 260.0837; Found 260.0839.Yield: 37.5 mg (72%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 186-188°C; 1H NMR (400 MHz, CDCl 3 ) δ 8.25 (d, J = 9.4 Hz, 1H), 8.18 (d, J = 8.1 Hz, 2H), 7.84 (t, J = 10.3 Hz, 1H), 7.54-7.49 (m , 2H), 7.39 (d, J = 9.9 Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 2.41 (s, 3H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 163.1, 156.5, 148.9, 145.1, 140.4, 137.8, 137.6, 137.1, 131.5, 129.9, 128.6, 128.3, 116.8, 110.72, 113.9, 110.9; IR (film): 2916, 1758, 1635, 1496, 1455, 1341, 1218, 802, 772, 739 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 18 H 12 O 2 260.0837; Found 260.0839.

[실시예 5] 3-(3-Chlorophenyl)-1H-azuleno[1,8-bc]furan-1-one (화합물 1-5)의 제조[Example 5] Preparation of 3-(3-Chlorophenyl) -1H -azuleno[1,8-bc]furan-1-one (Compound 1-5)

Figure 112021000693139-pat00028
Figure 112021000693139-pat00028

반응온도: 60℃; 반응시간 : 6시간Reaction temperature: 60° C.; Response time: 6 hours

Yield: 29.2 mg (52%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 184-186℃; 1H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 9.4 Hz, 1H), 8.30-8.27 (m, 1H), 8.25-8.24 (m, 1H), 7.99 (t, J = 10.4 Hz, 1H), 7.66-7.60 (m, 2H), 7.51 (d, J = 9.9 Hz, 1H), 7.46 (t, J = 7.8 Hz, 1H), 7.40-7.38 (m, 1H); 13C{1H} NMR (100 MHz, DMSO-d 6) δ 166.0, 151.9, 142.0, 140.3, 140.1, 139.7, 138.6, 137.8, 131.8, 130.8, 129.0, 127.9, 127.5, 127.0, 122.5, 119.5, 115.7; IR (film): 2915, 2359, 1768, 1537, 1455, 1106, 741 cm-1; HRMS (EI) m/z:[M]+ Calcd for C17H9 35ClO2 280.0291, C17H9 37ClO2 282.0261; Found 280.0289, 282.0340.Yield: 29.2 mg (52%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 184-186°C; 1H NMR (400 MHz, CDCl 3 ) δ 8.39 (d, J = 9.4 Hz, 1H), 8.30-8.27 (m, 1H), 8.25-8.24 (m, 1H), 7.99 (t, J = 10.4 Hz, 1H) , 7.66–7.60 (m, 2H), 7.51 (d, J = 9.9 Hz, 1H), 7.46 (t, J = 7.8 Hz, 1H), 7.40–7.38 (m, 1H); 13 C{ 1 H} NMR (100 MHz, DMSO- d 6 ) δ 166.0, 151.9, 142.0, 140.3, 140.1, 139.7, 138.6, 137.8, 131.8, 130.8, 129.0, 127.9, 127.5, 129.5, 127.0, 712.5. ; IR (film): 2915, 2359, 1768, 1537, 1455, 1106, 741 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 17 H 9 35 ClO 2 280.0291, C 17 H 9 37 ClO 2 282.0261; Found 280.0289, 282.0340.

[실시예 6] 3-(4-Chlorophenyl)-1H-azuleno[1,8-bc]furan-1-one (화합물 1-6)의 제조[Example 6] Preparation of 3-(4-Chlorophenyl) -1H -azuleno[1,8-bc]furan-1-one (Compound 1-6)

Figure 112021000693139-pat00029
Figure 112021000693139-pat00029

반응온도: 60℃; 반응시간 : 6시간Reaction temperature: 60° C.; Response time: 6 hours

Yield: 42.8 mg (76%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 173-175℃; 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 9.3 Hz, 1H), 8.20 (d, J = 6.8 Hz, 2H), 7.92 (t, J = 10.3 Hz, 1H), 7.58 (t, J = 10.0 Hz, 1H), 7.51 (s, 1H), 7.46-7.42 (m, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 162.9, 157.0, 147.1, 145.1, 138.6, 137.7, 137.5, 135.8, 132.6, 129.8, 129.4, 128.6, 117.3, 114.1, 110.2; IR (film): 2359, 2341, 1780, 1635, 1495, 1113, 1093, 539 cm-1; HRMS (EI) m/z:[M]+ Calcd for C17H9 35ClO2 280.0291, C17H9 37ClO2 282.0261; Found 280.0291, 282.0273.Yield: 42.8 mg (76%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 173-175°C; 1H NMR (400 MHz, CDCl 3 ) δ 8.32 (d, J = 9.3 Hz, 1H), 8.20 (d, J = 6.8 Hz, 2H), 7.92 (t, J = 10.3 Hz, 1H), 7.58 (t, J = 10.0 Hz, 1H), 7.51 (s, 1H), 7.46–7.42 (m, 3H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 162.9, 157.0, 147.1, 145.1, 138.6, 137.7, 137.5, 135.8, 132.6, 129.8, 129.4, 128.6, 117.3, 110.1, 110.2; IR (film): 2359, 2341, 1780, 1635, 1495, 1113, 1093, 539 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 17 H 9 35 ClO 2 280.0291, C 17 H 9 37 ClO 2 282.0261; Found 280.0291, 282.0273.

[실시예 7] 3-(4-Bromophenyl)-1H-azuleno[1,8-bc]furan-1-one (화합물 1-7)의 제조[Example 7] Preparation of 3-(4-Bromophenyl) -1H -azuleno[1,8-bc]furan-1-one (Compound 1-7)

Figure 112021000693139-pat00030
Figure 112021000693139-pat00030

반응온도: 60℃; 반응시간 : 6시간Reaction temperature: 60° C.; Response time: 6 hours

Yield: 50.6 mg (78%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 199-201℃; 1H NMR (400 MHz, CDCl3) δ 8.34 (d, J = 9.4 Hz, 1H), 8.14 (d, J = 8.4 Hz, 2H), 7.94 (t, J = 10.4 Hz, 1H), 7.62-7.57 (m, 3H), 7.53 (s, 1H), 7.46 (d, J = 9.9 Hz, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 162.9, 157.1, 147.2, 145.1, 138.7, 137.8, 137.5, 133.0, 132.4, 130.0, 128.6, 124.3, 117.4, 114.2, 110.2; IR (film): 2926, 2360, 1755, 1635, 1493, 1460, 1336, 1262, 1103, 801 cm-1; HRMS (EI) m/z:[M]+ Calcd for C17H9 79BrO2 323.9786, C17H9 81BrO2 325.9766; Found 323.9788, 325.9782.Yield: 50.6 mg (78%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 199-201°C; 1H NMR (400 MHz, CDCl 3 ) δ 8.34 (d, J = 9.4 Hz, 1H), 8.14 (d, J = 8.4 Hz, 2H), 7.94 (t, J = 10.4 Hz, 1H), 7.62-7.57 (m , 3H), 7.53 (s, 1H), 7.46 (d, J = 9.9 Hz, 1H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 162.9, 157.1, 147.2, 145.1, 138.7, 137.8, 137.5, 133.0, 132.4, 130.0, 128.6, 124.3, 117.4, 114.2, 110.2; IR (film): 2926, 2360, 1755, 1635, 1493, 1460, 1336, 1262, 1103, 801 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 17 H 9 79 BrO 2 323.9786, C 17 H 9 81 BrO 2 325.9766; Found 323.9788, 325.9782.

[실시예 8] 3-(Thiophen-2-yl)-1H-azuleno[1,8-bc]furan-1-one (화합물 1-8)의 제조[Example 8] Preparation of 3-(Thiophen-2-yl) -1H -azuleno[1,8-bc]furan-1-one (Compound 1-8)

Figure 112021000693139-pat00031
Figure 112021000693139-pat00031

반응온도: 60℃; 반응시간 : 6시간Reaction temperature: 60° C.; Response time: 6 hours

Yield: 32.9 mg (65%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 115-117℃; 1H NMR (400 MHz, CDCl3) δ 8.26-8.24 (m, 2H), 7.87 (t, J = 10.4 Hz, 1H), 7.56 (t, J = 10.1 Hz, 1H), 7.46-7.44 (m, 2H), 7.34-7.32 (m, 1H), 7.20-7.18 (m, 1H); 13C{1H} NMR (100 MHz, DMSO-d 6) δ 161.8, 155.7, 144.1, 139.6, 139.5, 138.4, 137.6, 137.4, 130.2, 130.1, 129.9, 129.1, 117.0, 115.1, 107.7; IR (film): 2918, 2360, 1763, 1628, 1498, 1338, 1098, 566 cm-1; HRMS (EI) m/z:[M]+ Calcd for C15H8O2S 252.0245; Found 252.0246.Yield: 32.9 mg (65%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 115-117°C; 1H NMR (400 MHz, CDCl 3 ) δ 8.26-8.24 (m, 2H), 7.87 (t, J = 10.4 Hz, 1H), 7.56 (t, J = 10.1 Hz, 1H), 7.46-7.44 (m, 2H) , 7.34-7.32 (m, 1H), 7.20-7.18 (m, 1H); 13 C{ 1 H} NMR (100 MHz, DMSO- d 6 ) δ 161.8, 155.7, 144.1, 139.6, 139.5, 138.4, 137.6, 137.4, 130.2, 130.1, 129.9, 129.1, 117.0, 107.1, IR (film): 2918, 2360, 1763, 1628, 1498, 1338, 1098, 566 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 15 H 8 O 2 S 252.0245; Found 252.0246.

[실시예 9] 7-Methyl-3-phenyl-1H-azuleno[1,8-bc]furan-1-one (화합물 1-9)의 제조[Example 9] Preparation of 7-Methyl-3-phenyl- 1H -azuleno[1,8-bc]furan-1-one (Compound 1-9)

Figure 112021000693139-pat00032
Figure 112021000693139-pat00032

반응온도: 80℃; 반응시간 : 2시간Reaction temperature: 80° C.; Reaction time: 2 hours

Yield: 37.4 mg (72%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 184-186℃; 1H NMR (400 MHz, CDCl3) δ 8.29 (d, J = 7.6 Hz, 2H), 8.18 (d, J = 9.9 Hz, 1H), 7.53-7.49 (m, 4H), 7.42-7.38 (m, 2H), 2.83 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.2, 156.1, 151.6, 147.5, 144.3, 136.5, 136.1, 134.4, 130.1, 129.7, 129.2, 128.5, 117.3, 115.5, 110.0, 29.9; IR (film): 2928, 2362, 1768, 1644, 1496, 828, 754 cm-1; HRMS (EI) m/z:[M]+ Calcd for C18H12O2 260.0837; Found 260.0836.Yield: 37.4 mg (72%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 184-186°C; 1H NMR (400 MHz, CDCl 3 ) δ 8.29 (d, J = 7.6 Hz, 2H), 8.18 (d, J = 9.9 Hz, 1H), 7.53-7.49 (m, 4H), 7.42-7.38 (m, 2H) , 2.83 (s, 3H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 163.2, 156.1, 151.6, 147.5, 144.3, 136.5, 136.1, 134.4, 130.1, 129.7, 129.2, 128.5, 117.3, 119.5, 115.9, 115.9; IR (film): 2928, 2362, 1768, 1644, 1496, 828, 754 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 18 H 12 O 2 260.0837; Found 260.0836.

[실시예 10] 3,7-Diphenyl-1H-azuleno[1,8-bc]furan-1-one (화합물 1-10)의 제조[Example 10] Preparation of 3,7-Diphenyl- 1H -azuleno[1,8-bc]furan-1-one (Compound 1-10)

Figure 112021000693139-pat00033
Figure 112021000693139-pat00033

반응온도: 80℃; 반응시간 : 2시간Reaction temperature: 80° C.; Reaction time: 2 hours

Yield: 41.2 mg (64%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 195-197℃; 1H NMR (400 MHz, CDCl3) δ 8.35-8.31 (m, 3H), 7.78 (d, J =10.0 Hz, 1H), 7.64-7.62 (m, 3H), 7.58 (s, 1H), 7.55-7.50 (m, 5H), 7.44-7.40 (m, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.2, 155.9, 153.2, 148.5, 144.9, 144.4, 136.6, 136.3, 134.3, 129.9, 129.7, 129.3, 129.2, 129.0, 128.9, 128.6, 117.5, 114.7, 110.5; IR (film): 2915, 2360, 1770, 1638, 1498, 691, 512 cm-1; HRMS (EI) m/z:[M]+ Calcd for C23H14O2 322.0994; Found322.0996.Yield: 41.2 mg (64%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 195-197°C; 1H NMR (400 MHz, CDCl3 ) δ 8.35-8.31 (m, 3H), 7.78 (d, J =10.0 Hz, 1H), 7.64-7.62 (m, 3H), 7.58 (s, 1H), 7.55-7.50 m, 5H), 7.44-7.40 (m, 1H); 13 C { 1 H} NMR (100 MHz, CDCL 3 ) Δ 163.2, 155.9, 153.2, 144.9, 144.4, 136.6, 136.3, 134.3, 129.9, 129.7, 129.3, 129.0, 128.9, 128.6, 117.5, 114.7 , 110.5; IR (film): 2915, 2360, 1770, 1638, 1498, 691, 512 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 23 H 14 O 2 322.0994; Found322.0996.

[실시예 11] 4-Methyl-3-phenyl-1H-azuleno[1,8-bc]furan-1-one (화합물 1-11)의 제조[Example 11] Preparation of 4-Methyl-3-phenyl- 1H -azuleno[1,8-bc]furan-1-one (Compound 1-11)

Figure 112021000693139-pat00034
Figure 112021000693139-pat00034

반응온도: 80℃; 반응시간 : 2시간Reaction temperature: 80° C.; Reaction time: 2 hours

Yield: 40.1 mg (77%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 198-200℃; 1H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 9.4 Hz, 1H), 7.99 (d, J = 7.3 Hz, 2H), 7.93 (t, J = 10.3 Hz, 1H), 7.61-7.53 (m, 3H), 7.45-7.41 (m, 2H), 2.74 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.0, 156.9, 145.2, 143.7, 138.3, 137.6, 135.7, 134.6, 130.0, 128.9, 128.8, 128.2, 127.1, 113.0, 110.7, 12.7; IR (film): 2914, 2359, 1759, 1631, 1501, 748, 606 cm-1; HRMS (EI) m/z:[M]+ Calcd for C18H12O2 260.0837; Found 260.0840.Yield: 40.1 mg (77%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 198-200°C; 1H NMR (400 MHz, CDCl 3 ) δ 8.37 (d, J = 9.4 Hz, 1H), 7.99 (d, J = 7.3 Hz, 2H), 7.93 (t, J = 10.3 Hz, 1H), 7.61-7.53 (m , 3H), 7.45-7.41 (m, 2H), 2.74 (s, 3H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 163.0, 156.9, 145.2, 143.7, 138.3, 137.6, 135.7, 134.6, 130.0, 128.9, 128.8, 128.2, 127.1, 113.7, 110.7, 110.7; IR (film): 2914, 2359, 1759, 1631, 1501, 748, 606 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 18 H 12 O 2 260.0837; Found 260.0840.

실시예 II : 2-아릴아줄렌-1-카복실산 화합물 (3A)의 제조Example II: Preparation of 2-arylazulene-1-carboxylic acid compound (3A)

Figure 112021000693139-pat00035
Figure 112021000693139-pat00035

질소 대기 하에서 아줄렌-1-카복실산 화합물 (3) (0.2 mmol, 1.0 equiv), 다이아릴아이오도늄염 화합물 (4) (0.24 mmol, 1.2 equiv, X=OTf (실시예 12-16,18,20-23), BF4 (실시예 17,19,24-26)), [Cp*IrCl2]2 (4.0 mol%, 6.4 mg), AgOAc (1.0 equiv, 33.4 mg), Na2HPO4 (1.0 equiv, 28.4 mg) 및 DMF (1.0 mL)을 혼합하고, 60℃에서 2시간 또는 12시간 동안 교반시켰다. 교반 완료 후 반응 혼합물을 상온으로 냉각시키고, 셀라이트 패드로 여과시킨 다음, 감압 하에서 여액을 농축시켰다. 농축된 잔류물을 실리카 겔 플래쉬 컬럼 크로마토그래피로 정제하여 목적 화합물인 2-아릴아줄렌-1-카복실산 화합물 (3A)을 수득하였다.Under a nitrogen atmosphere, azulene-1-carboxylic acid compound (3) (0.2 mmol, 1.0 equiv), diaryliodonium salt compound (4) (0.24 mmol, 1.2 equiv, X=OTf (Examples 12-16, 18, 20 -23), BF 4 (Examples 17, 19, 24-26)), [Cp*IrCl 2 ] 2 (4.0 mol%, 6.4 mg), AgOAc (1.0 equiv, 33.4 mg), Na 2 HPO 4 (1.0 equiv, 28.4 mg) and DMF (1.0 mL) were mixed and stirred at 60° C. for 2 or 12 hours. After stirring was completed, the reaction mixture was cooled to room temperature, filtered through a celite pad, and the filtrate was concentrated under reduced pressure. The concentrated residue was purified by silica gel flash column chromatography to obtain the target compound, 2-arylazulene-1-carboxylic acid compound (3A).

상기 기재된 방법을 이용하여 다양한 2-아릴아줄렌-1-카복실산 화합물 (3A)을 제조하였다.Various 2-arylazulene-1-carboxylic acid compounds (3A) were prepared using the methods described above.

[실시예 12] 2-Phenylazulene-1-carboxylic acid (화합물 3A-1)의 제조[Example 12] Preparation of 2-Phenylazulene-1-carboxylic acid (Compound 3A-1)

Figure 112021000693139-pat00036
Figure 112021000693139-pat00036

반응온도: 60℃; 반응시간 : 2시간Reaction temperature: 60° C.; Reaction time: 2 hours

Yield: 43.2 mg (87%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 228-230℃; 1H NMR (400 MHz, CDCl3) δ 9.61 (d, J = 10.0 Hz, 1H), 8.43 (d, J = 9.6 Hz, 1H), 7.79 (t, J = 9.8 Hz, 1H), 7.67-7.45 (m, 2H), 7.59 (t, J = 10.0 Hz, 1H), 7.51-7.38 (m, 4H), 7.34 (s, 1H); 13C{1H} NMR (100 MHz, CDCl3) δ 170.0, 154.9, 143.6, 143.3, 138.7, 138.2, 137.9, 137.8, 130.0, 128.7, 128.1, 127.9, 127.8, 120.5, 113.1; IR (film): 2916, 2360, 1646, 1455, 1416, 1341, 1240, 768, 697 cm-1; HRMS (EI) m/z:[M]+ Calcd for C17H12O2 248.0837; Found 248.0836.Yield: 43.2 mg (87%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 228-230°C; 1H NMR (400 MHz, CDCl 3 ) δ 9.61 (d, J = 10.0 Hz, 1H), 8.43 (d, J = 9.6 Hz, 1H), 7.79 (t, J = 9.8 Hz, 1H), 7.67-7.45 (m , 2H), 7.59 (t, J = 10.0 Hz, 1H), 7.51–7.38 (m, 4H), 7.34 (s, 1H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 170.0, 154.9, 143.6, 143.3, 138.7, 138.2, 137.9, 137.8, 130.0, 128.7, 128.1, 127.9, 127.8, 120.5, 113.1; IR (film): 2916, 2360, 1646, 1455, 1416, 1341, 1240, 768, 697 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 17 H 12 O 2 248.0837; Found 248.0836.

[실시예 13] 2-(o-Tolyl)azulene-1-carboxylic acid (화합물 3A-2)의 제조[Example 13] Preparation of 2-( o -Tolyl)azulene-1-carboxylic acid (Compound 3A-2)

Figure 112021000693139-pat00037
Figure 112021000693139-pat00037

반응온도: 60℃; 반응시간 : 2시간Reaction temperature: 60° C.; Reaction time: 2 hours

Yield: 41.0 mg (78%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 220-222℃; 1H NMR (400 MHz, CDCl3) δ 9.70 (d, J = 10.0 Hz, 1H), 8.44 (d, J = 9.6 Hz, 1H), 7.82 (t, J = 9.8 Hz, 1H), 7.62 (t, J = 10.0 Hz, 1H), 7.51 (t, J = 9.6 Hz, 1H), 7.32-7.27 (m, 4H), 7.21 (s, 1H), 2.20 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d 6) δ 166.4, 153.6, 142.1, 140.7, 139.1, 138.8, 138.0, 137.2, 135.2, 129.3, 129.0, 127.8, 127.4, 127.1, 125.0, 119.6, 115.8, 20.0; IR (film): 1646, 1454, 1433, 1413, 1341, 1239, 768, 605 cm-1; HRMS (EI) m/z:[M]+ Calcd for C18H14O2 262.0994; Found 262.0997.Yield: 41.0 mg (78%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 220-222°C; 1H NMR (400 MHz, CDCl 3 ) δ 9.70 (d, J = 10.0 Hz, 1H), 8.44 (d, J = 9.6 Hz, 1H), 7.82 (t, J = 9.8 Hz, 1H), 7.62 (t, J = 10.0 Hz, 1H), 7.51 (t, J = 9.6 Hz, 1H), 7.32–7.27 (m, 4H), 7.21 (s, 1H), 2.20 (s, 3H); 13 C{ 1 H} NMR (100 MHz, DMSO- d 6 ) δ 166.4, 153.6, 142.1, 140.7, 139.1, 138.8, 138.0, 137.2, 135.2, 129.3, 129.0, 127.8, 127.4, 127.1, 8, 127.1, 8. , 20.0; IR (film): 1646, 1454, 1433, 1413, 1341, 1239, 768, 605 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 18 H 14 O 2 262.0994; Found 262.0997.

[실시예 14] 2-(m-Tolyl)azulene-1-carboxylic acid (화합물 3A-3)의 제조[Example 14] Preparation of 2-( m -Tolyl)azulene-1-carboxylic acid (Compound 3A-3)

Figure 112021000693139-pat00038
Figure 112021000693139-pat00038

반응온도: 60℃; 반응시간 : 2시간Reaction temperature: 60° C.; Reaction time: 2 hours

Yield: 40.4 mg (77%); R f = 0.2 (Acetone:Hexane = 1:4); Blue solid; Melting point: 226-228℃; 1H NMR (400 MHz, DMSO-d 6) δ 9.27 (d, J = 9.9 Hz, 1H), 8.55 (d, J = 9.4 Hz, 1H), 7.87 (t, J = 9.8 Hz, 1H), 7.60 (t, J = 9.9 Hz, 1H), 7.53 (t, J = 9.7 Hz, 1H), 7.45-7.40 (m, 3H), 7.34 (t, J = 7.5 Hz, 1H), 7.20 (d, J = 7.4 Hz, 1H), 2.38 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d 6) δ 167.0, 152.4, 141.7, 140.8, 138.8, 137.9, 137.3, 136.9, 136.8, 130.1, 128.2, 127.8, 127.3, 127.0, 126.8, 118.9, 115.5, 21.1; IR (film): 2915, 2359, 1645, 1454, 1412, 1339, 1239, 767, 733 cm-1; HRMS (EI) m/z:[M]+ Calcd for C18H14O2 262.0994; Found 262.0994.Yield: 40.4 mg (77%); R f = 0.2 (Acetone:Hexane = 1:4); Blue solid; Melting point: 226-228°C; 1H NMR (400 MHz, DMSO- d6 ) δ 9.27 (d, J = 9.9 Hz, 1H), 8.55 (d, J = 9.4 Hz, 1H), 7.87 (t, J = 9.8 Hz , 1H), 7.60 (t, J = 9.9 Hz, 1H), 7.53 (t, J = 9.7 Hz, 1H), 7.45–7.40 (m, 3H), 7.34 (t, J = 7.5 Hz, 1H), 7.20 (d, J = 7.4 Hz, 1H), 2.38 (s, 3H); 13 C{ 1 H} NMR (100 MHz, DMSO- d 6 ) δ 167.0, 152.4, 141.7, 140.8, 138.8, 137.9, 137.3, 136.9, 136.8, 130.1, 128.2, 127.8, 127.3, 121.58, 121.8, 121.9, , 21.1; IR (film): 2915, 2359, 1645, 1454, 1412, 1339, 1239, 767, 733 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 18 H 14 O 2 262.0994; Found 262.0994.

[실시예 15] 2-(p-Tolyl)azulene-1-carboxylic acid (화합물 3A-4)의 제조[Example 15] Preparation of 2-( p -Tolyl)azulene-1-carboxylic acid (Compound 3A-4)

Figure 112021000693139-pat00039
Figure 112021000693139-pat00039

반응온도: 60℃; 반응시간 : 2시간Reaction temperature: 60° C.; Reaction time: 2 hours

Yield: 39.5 mg (75%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 186-188℃; 1H NMR (400 MHz, DMSO-d 6) δ 9.39 (d, J = 9.9 Hz, 1H), 8.62 (d, J = 9.4 Hz, 1H), 8.03 (d, J = 8.5 Hz, 2H), 7.94 (t, J = 9.8 Hz, 1H), 7.74 (d, J = 8.4 Hz, 2H), 7.66 (t, J = 9.9 Hz, 1H), 7.59 (t, J = 9.7 Hz, 1H), 7.51 (s, 1H), 3.90 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d 6) δ 167.1, 152.2, 141.7, 140.8, 138.6, 137.7, 137.0, 136.6, 134.4, 129.6, 128.6, 127.3, 127.0, 118.7, 115.3, 20.8; IR (film): 2361, 2341, 1631, 1451, 1437, 1413, 1345, 806 cm-1; HRMS (EI) m/z:[M]+ Calcd for C18H14O2 262.0994; Found 262.0992.Yield: 39.5 mg (75%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 186-188°C; 1H NMR (400 MHz, DMSO- d6 ) δ 9.39 (d, J = 9.9 Hz, 1H), 8.62 (d, J = 9.4 Hz, 1H), 8.03 (d, J = 8.5 Hz , 2H), 7.94 (t , J = 9.8 Hz, 1H), 7.74 (d, J = 8.4 Hz, 2H), 7.66 (t, J = 9.9 Hz, 1H), 7.59 (t, J = 9.7 Hz, 1H), 7.51 (s, 1H) ), 3.90 (s, 3H); 13 C{ 1 H} NMR (100 MHz, DMSO- d 6 ) δ 167.1, 152.2, 141.7, 140.8, 138.6, 137.7, 137.0, 136.6, 134.4, 129.6, 128.6, 127.3, 127.0, 118.8, 118.7; IR (film): 2361, 2341, 1631, 1451, 1437, 1413, 1345, 806 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 18 H 14 O 2 262.0994; Found 262.0992.

[실시예 16] 2-(4-Fluorophenyl)azulene-1-carboxylic acid (화합물 3A-5)의 제조[Example 16] Preparation of 2-(4-Fluorophenyl)azulene-1-carboxylic acid (Compound 3A-5)

Figure 112021000693139-pat00040
Figure 112021000693139-pat00040

반응온도: 60℃; 반응시간 : 2시간Reaction temperature: 60° C.; Reaction time: 2 hours

Yield: 40.7 mg (76%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 225-227℃; 1H NMR (400 MHz, CDCl3) δ 9.62 (d, J = 10.0 Hz, 1H), 8.42 (d, J = 9.5 Hz, 1H), 7.80 (t, J = 9.8 Hz, 1H), 7.64-7.58 (m, 3H), 7.50 (t, J = 9.6 Hz, 1H), 7.31 (s, 1H), 7.15 (t, J = 8.8 Hz, 2H); 13C{1H} NMR (100 MHz, acetone-d 6) δ 167.0, 164.6, 162.2, 153.3, 143.5, 142.8, 139.7, 138.6 (d, J = 34.0 Hz), 135.3 (d, J = 3.1 Hz), 132.7, 132.6, 128.4 (d, J = 39.1 Hz), 120.3, 115.5, 115.3; 19F NMR (376 MHz, CDCl3) δ -114.48; IR (film): 2359, 2341, 1647, 1417, 1223, 669, 606 cm-1; HRMS (EI) m/z:[M]+ Calcd for C17H11FO2 266.0743; Found 266.0742.Yield: 40.7 mg (76%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 225-227°C; 1H NMR (400 MHz, CDCl 3 ) δ 9.62 (d, J = 10.0 Hz, 1H), 8.42 (d, J = 9.5 Hz, 1H), 7.80 (t, J = 9.8 Hz, 1H), 7.64-7.58 (m , 3H), 7.50 (t, J = 9.6 Hz, 1H), 7.31 (s, 1H), 7.15 (t, J = 8.8 Hz, 2H); 13 C{ 1 H} NMR (100 MHz, acetone- d 6 ) δ 167.0, 164.6, 162.2, 153.3, 143.5, 142.8, 139.7, 138.6 (d, J = 34.0 Hz), 135.3 (d, J = 3.1 Hz) , 132.7, 132.6, 128.4 (d, J = 39.1 Hz), 120.3, 115.5, 115.3; 19 F NMR (376 MHz, CDCl 3 ) δ -114.48; IR (film): 2359, 2341, 1647, 1417, 1223, 669, 606 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 17 H 11 FO 2 266.0743; Found 266.0742.

[실시예 17] 2-(3-Chlorophenyl)azulene-1-carboxylic acid (화합물 3A-6)의 제조[Example 17] Preparation of 2-(3-Chlorophenyl)azulene-1-carboxylic acid (Compound 3A-6)

Figure 112021000693139-pat00041
Figure 112021000693139-pat00041

반응온도: 60℃; 반응시간 : 2시간Reaction temperature: 60° C.; Reaction time: 2 hours

Yield: 41.8 mg (74%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 202-204℃; 1H NMR (400 MHz, DMSO-d 6) δ 12.46 (s, 1H), δ 9.39 (d, J = 10.0 Hz, 1H), 8.60 (d, J = 9.5 Hz, 1H), 7.93 (d, J = 9.8 Hz, 1H), 7.68-7.54 (m, 4H), 7.50-7.43 (m, 3H); 13C{1H} NMR (100 MHz, DMSO-d 6) δ 166.6, 150.5, 141.8, 140.8, 139.7, 139.5, 138.6, 137.6, 132.5, 129.7, 129.2, 128.3, 127.7, 127.4, 127.3, 119.2, 115.2; IR (film): 2922, 2360, 1638, 1455, 1338, 1241, 1093, 887, 782, 691 cm-1; HRMS (EI) m/z:[M]+ Calcd for C17H11 35ClO2 282.0448, C17H11 37ClO2 284.0418; Found 282.0446, 284.0837.Yield: 41.8 mg (74%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 202-204°C; 1H NMR (400 MHz, DMSO- d6 ) δ 12.46 (s, 1H), δ 9.39 ( d, J = 10.0 Hz, 1H), 8.60 (d, J = 9.5 Hz, 1H), 7.93 (d, J = 9.8 Hz, 1H), 7.68-7.54 (m, 4H), 7.50-7.43 (m, 3H); 13 C{ 1 H} NMR (100 MHz, DMSO- d 6 ) δ 166.6, 150.5, 141.8, 140.8, 139.7, 139.5, 138.6, 137.6, 132.5, 129.7, 129.2, 128.3, 127.7, 127.5, 127.4, 127.4. ; IR (film): 2922, 2360, 1638, 1455, 1338, 1241, 1093, 887, 782, 691 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 17 H 11 35 ClO 2 282.0448, C 17 H 11 37 ClO 2 284.0418; Found 282.0446, 284.0837.

[실시예 18] 2-(4-Chlorophenyl)azulene-1-carboxylic acid (화합물 3A-7)의 제조[Example 18] Preparation of 2-(4-Chlorophenyl)azulene-1-carboxylic acid (Compound 3A-7)

Figure 112021000693139-pat00042
Figure 112021000693139-pat00042

반응온도: 60℃; 반응시간 : 2시간Reaction temperature: 60° C.; Reaction time: 2 hours

Yield: 44.0 mg (78%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 216-218℃; 1H NMR (400 MHz, CDCl3) δ 9.63 (d, J = 10.1 Hz, 1H), 8.45 (d, J = 9.6 Hz, 1H), 7.82 (t, J = 9.8 Hz, 1H), 7.65-7.58 (m, 3H), 7.51 (t, J = 9.8 Hz, 1H), 7.44 (d, J = 8.4Hz, 2H), 7.31 (s, 1H); 13C{1H} NMR (100 MHz, DMSO-d 6) δ 166.7, 150.9, 141.8, 140.9, 139.3, 138.4, 137.4, 136.4, 132.5, 131.4, 127.89, 127.88, 127.7, 127.4, 119.0; IR (film): 2360, 2341, 1641, 1439, 1412, 1345, 1240, 1098 cm-1; HRMS (EI) m/z:[M]+ Calcd for C17H11 35ClO2 282.0448, C17H11 37ClO2 284.0418; Found 282.0450, 284.0412.Yield: 44.0 mg (78%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 216-218°C; 1H NMR (400 MHz, CDCl 3 ) δ 9.63 (d, J = 10.1 Hz, 1H), 8.45 (d, J = 9.6 Hz, 1H), 7.82 (t, J = 9.8 Hz, 1H), 7.65-7.58 (m, 3H), 7.51 (t, J = 9.8 Hz, 1H), 7.44 (d, J = 8.4 Hz, 2H), 7.31 (s, 1H); 13 C{ 1 H} NMR (100 MHz, DMSO- d 6 ) δ 166.7, 150.9, 141.8, 140.9, 139.3, 138.4, 137.4, 136.4, 132.5, 131.4, 127.89, 127.88, 127.7, 111.4; IR (film): 2360, 2341, 1641, 1439, 1412, 1345, 1240, 1098 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 17 H 11 35 ClO 2 282.0448, C 17 H 11 37 ClO 2 284.0418; Found 282.0450, 284.0412.

[실시예 19] 2-(2-Bromophenyl)azulene-1-carboxylic acid (화합물 3A-8)의 제조[Example 19] Preparation of 2-(2-Bromophenyl)azulene-1-carboxylic acid (Compound 3A-8)

Figure 112021000693139-pat00043
Figure 112021000693139-pat00043

반응온도: 60℃; 반응시간 : 2시간Reaction temperature: 60° C.; Reaction time: 2 hours

Yield: 47.2 mg (72%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 218-220℃; 1H NMR (400 MHz, DMSO-d 6) δ 9.58 (d, J = 10.0 Hz, 1H), 8.63 (d, J = 9.3 Hz, 1H), 7.97 (t, J = 9.8 Hz, 1H), 7.71-7.66 (m, 2H), 7.61 (t, J = 9.7 Hz, 1H), 7.47-7.38 (m, 2H), 7.34-7.29 (m, 2H); 13C{1H} NMR (100 MHz, DMSO-d 6) δ 166.0, 151.9, 142.0, 140.3, 140.1, 139.7, 138.6, 137.8, 131.8, 130.8, 129.0, 127.9, 127.5, 127.0, 122.5, 119.5, 115.7; IR (film): 2915, 2348, 2360, 1646, 1537, 1118, 668 cm-1; HRMS (EI) m/z:[M]+ Calcd for C17H11 79BrO2 325.9942, C17H11 81BrO2 327.9922; Found 325.9940, 327.9923.Yield: 47.2 mg (72%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 218-220°C; 1H NMR (400 MHz, DMSO- d6 ) δ 9.58 (d, J = 10.0 Hz, 1H), 8.63 (d, J = 9.3 Hz , 1H), 7.97 (t, J = 9.8 Hz, 1H), 7.71-7.66 (m, 2H), 7.61 (t, J = 9.7 Hz, 1H), 7.47–7.38 (m, 2H), 7.34–7.29 (m, 2H); 13 C{ 1 H} NMR (100 MHz, DMSO- d 6 ) δ 166.0, 151.9, 142.0, 140.3, 140.1, 139.7, 138.6, 137.8, 131.8, 130.8, 129.0, 127.9, 127.5, 129.5, 127.0, 712.5. ; IR (film): 2915, 2348, 2360, 1646, 1537, 1118, 668 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 17 H 11 79 BrO 2 325.9942, C 17 H 11 81 BrO 2 327.9922; Found 325.9940, 327.9923.

[실시예 20] 2-(4-Chlorophenyl)azulene-1-carboxylic acid (화합물 3A-9)의 제조[Example 20] Preparation of 2-(4-Chlorophenyl)azulene-1-carboxylic acid (Compound 3A-9)

Figure 112021000693139-pat00044
Figure 112021000693139-pat00044

반응온도: 60℃; 반응시간 : 2시간Reaction temperature: 60° C.; Reaction time: 2 hours

Yield: 51.1 mg (78%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 244-246℃; 1H NMR (400 MHz, DMSO-d 6) δ 12.40 (s, 1H), 9.35 (d, J = 9.8 Hz, 1H), 8.58 (d, J = 9.5 Hz, 1H), 7.90 (t, J = 9.9 Hz, 1H), 7.65-7.63 (m, 3H), 7.60-7.54 (m, 3H), 7.45 (s, 1H); 13C{1H } NMR (100 MHz, DMSO-d 6) δ 166.7, 151.0, 141.9, 140.9, 139.3, 138.4, 137.4, 136.7, 131.7, 130.8, 127.8, 127.4, 121.2, 118.9, 115.0; IR (film): 2360, 2341, 1537, 1451, 1254, 1105, 750, 668 cm-1; HRMS (EI) m/z:[M]+ Calcd for C17H11 79BrO2 325.9942, C17H11 81BrO2 327.9922; Found 325.9943, 327.9931.Yield: 51.1 mg (78%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 244-246°C; 1H NMR (400 MHz, DMSO- d6 ) δ 12.40 (s, 1H) , 9.35 (d, J = 9.8 Hz, 1H), 8.58 (d, J = 9.5 Hz, 1H), 7.90 (t, J = 9.9 Hz, 1H), 7.65-7.63 (m, 3H), 7.60-7.54 (m, 3H), 7.45 (s, 1H); 13 C{ 1 H } NMR (100 MHz, DMSO- d 6 ) δ 166.7, 151.0, 141.9, 140.9, 139.3, 138.4, 137.4, 136.7, 131.7, 130.8, 127.8, 127.4, 121.2, 118.9; IR (film): 2360, 2341, 1537, 1451, 1254, 1105, 750, 668 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 17 H 11 79 BrO 2 325.9942, C 17 H 11 81 BrO 2 327.9922; Found 325.9943, 327.9931.

[실시예 21] 2-(4-(Trifluoromethyl)phenyl)azulene-1-carboxylic acid (화합물 3A-10)의 제조[Example 21] Preparation of 2-(4-(Trifluoromethyl)phenyl)azulene-1-carboxylic acid (Compound 3A-10)

Figure 112021000693139-pat00045
Figure 112021000693139-pat00045

반응온도: 60℃; 반응시간 : 2시간Reaction temperature: 60° C.; Reaction time: 2 hours

Yield: 44.1 mg (69%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 238-240℃; 1H NMR (400 MHz, CDCl3) δ 9.65 (d, J = 9.8 Hz, 1H), 8.46 (d, J = 9.2 Hz, 1H), 7.84 (t, J = 9.4 Hz, 1H), 7.73-7.68 (m, 4H), 7.62 (t, J = 9.6 Hz, 1H), 7.52 (t, J = 9.6 Hz, 1H), 7.32 (s, 1H); 13C{1H} NMR (100 MHz, DMSO-d 6) δ 166.5, 150.6, 141.9, 140.9, 139.8, 138.9, 137.9, 130.33, 130.32, 127.9, 127.7 (q, J = 31.8 Hz), 127.6, 124.6 (q, J = 3.9 Hz), 124.5 (q, J = 272.0 Hz), 119.3, 115.1; 19F NMR (376 MHz, DMSO-d 6) δ -60.84; IR (film): 2928, 2360, 1652, 1455, 1328, 1123, 1067, 808, 668 cm-1; HRMS (EI) m/z:[M]+ Calcd for C18H11F3O2 316.0711; Found 316.0710.Yield: 44.1 mg (69%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 238-240°C; 1H NMR (400 MHz, CDCl 3 ) δ 9.65 (d, J = 9.8 Hz, 1H), 8.46 (d, J = 9.2 Hz, 1H), 7.84 (t, J = 9.4 Hz, 1H), 7.73-7.68 (m , 4H), 7.62 (t, J = 9.6 Hz, 1H), 7.52 (t, J = 9.6 Hz, 1H), 7.32 (s, 1H); 13 C{ 1 H} NMR (100 MHz, DMSO- d 6 ) δ 166.5, 150.6, 141.9, 140.9, 139.8, 138.9, 137.9, 130.33, 130.32, 127.9, 127.7 (q, J = 31.8 Hz), 124.6, 127.6 (q, J = 3.9 Hz), 124.5 (q, J = 272.0 Hz), 119.3, 115.1; 19 F NMR (376 MHz, DMSO- d 6 ) δ -60.84; IR (film): 2928, 2360, 1652, 1455, 1328, 1123, 1067, 808, 668 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 18 H 11 F 3 O 2 316.0711; Found 316.0710.

[실시예 22] 2-(4-(Methoxycarbonyl)phenyl)azulene-1-carboxylic acid (화합물 3A-11)의 제조[Example 22] Preparation of 2-(4-(Methoxycarbonyl)phenyl)azulene-1-carboxylic acid (Compound 3A-11)

Figure 112021000693139-pat00046
Figure 112021000693139-pat00046

반응온도: 60℃; 반응시간 : 2시간Reaction temperature: 60° C.; Reaction time: 2 hours

Yield: 45.9 mg (75%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 240-242℃; 1H NMR (400 MHz, CDCl3) δ 9.65 (d, J = 10.0 Hz, 1H), 8.47 (d, J = 9.6 Hz, 1H), 8.13 (d, J = 8.3 Hz, 2H), 7.84 (t, J = 9.8 Hz, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.63 (t, J = 10.0 Hz, 1H), 7.52 (t, J = 9.6 Hz, 1H), 7.35 (s, 1H), 3.96 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d 6) δ 166.6, 166.2, 150.9, 142.5, 141.9, 140.9, 139.7, 138.9, 137.7, 130.0, 128.7, 128.4, 127.9, 127.6, 119.2, 115.2, 52.2; IR (film): 2923, 2361, 1715, 1649, 1454, 1281, 605 cm-1; HRMS (EI) m/z:[M]+ Calcd for C19H14O4 306.0892; Found 306.0892.Yield: 45.9 mg (75%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 240-242°C; 1H NMR (400 MHz, CDCl 3 ) δ 9.65 (d, J = 10.0 Hz, 1H), 8.47 (d, J = 9.6 Hz, 1H), 8.13 (d, J = 8.3 Hz, 2H), 7.84 (t, J = 9.8 Hz, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.63 (t, J = 10.0 Hz, 1H), 7.52 (t, J = 9.6 Hz, 1H), 7.35 (s, 1H), 3.96 (s, 3H); 13 C{ 1 H} NMR (100 MHz, DMSO- d 6 ) δ 166.6, 166.2, 150.9, 142.5, 141.9, 140.9, 139.7, 138.9, 137.7, 130.0, 128.7, 128.4, 127.9, 127.2, 119.2, 119.6, ; IR (film): 2923, 2361, 1715, 1649, 1454, 1281, 605 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 19 H 14 O 4 306.0892; Found 306.0892.

[실시예 23] 2-(Thiophen-2-yl)azulene-1-carboxylic acid (화합물 3A-12)의 제조[Example 23] Preparation of 2-(Thiophen-2-yl)azulene-1-carboxylic acid (Compound 3A-12)

Figure 112021000693139-pat00047
Figure 112021000693139-pat00047

반응온도: 60℃; 반응시간 : 2시간Reaction temperature: 60° C.; Reaction time: 2 hours

Yield: 34.3 mg (68%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 187-189℃; 1H NMR (400 MHz, CDCl3) δ 9.46 (d, J = 10.1 Hz, 1H), 8.33 (d, J = 9.7 Hz, 1H), 7.74 (d, J = 3.4 Hz, 1H), 7.69 (t, J = 9.7 Hz, 1H), 7.51-7.39 (m, 4H), 7.12 (s, 1H); 13C{1H} NMR (100 MHz, acetone-d 6) δ 167.4, 145.4, 143.1, 142.9, 140.0, 139.2, 138.3, 137.9, 130.4, 128.9, 128.61, 128.60, 128.2, 119.6, 115.3; IR (film): 2919, 2361, 2341, 1647, 1455, 1241, 607 cm-1; HRMS (EI) m/z:[M]+ Calcd for C15H10O2S 254.0402; Found 254.0401.Yield: 34.3 mg (68%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 187-189°C; 1H NMR (400 MHz, CDCl 3 ) δ 9.46 (d, J = 10.1 Hz, 1H), 8.33 (d, J = 9.7 Hz, 1H), 7.74 (d, J = 3.4 Hz, 1H), 7.69 (t , J = 9.7 Hz, 1H), 7.51–7.39 (m, 4H), 7.12 (s, 1H); 13 C{ 1 H} NMR (100 MHz, acetone- d 6 ) δ 167.4, 145.4, 143.1, 142.9, 140.0, 139.2, 138.3, 137.9, 130.4, 128.9, 128.61, 128.60, 128.2, 119.3; IR (film): 2919, 2361, 2341, 1647, 1455, 1241, 607 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 15 H 10 O 2 S 254.0402; Found 254.0401.

[실시예 24] 2-(2-Bromophenyl)-6-methylazulene-1-carboxylic acid (화합물 3A-13)의 제조[Example 24] 2-(2-Bromophenyl)-6-methylazulene-1-carboxylic acid Preparation of (Compound 3A-13)

Figure 112021000693139-pat00048
Figure 112021000693139-pat00048

반응온도: 60℃; 반응시간 : 12시간Reaction temperature: 60° C.; Response time: 12 hours

Yield: 40.8 mg (60%); R f = 0.2 (Acetone:Hexane=1:4); Red solid; Melting point: 233-235℃; 1H NMR (400 MHz, DMSO-d 6) δ 11.96 (s, 1H), 9.41 (d, J =10.5 Hz, 1H), 8.47 (d, J = 10.1 Hz, 1H), 7.67 (dd, J = 8.0 Hz, J = 1.0 Hz, 1H), 7.59 (d, J = 10.5 Hz, 1H), 7.51 (d, J = 10.1 Hz, 1H), 7.45-7.36 (m, 2H), 7.31-7.27 (m, 1H), 7.21 (s, 1H), 2.72 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d 6) δ 166.1, 151.8, 150.6, 140.6, 140.2, 139.0, 137.7, 136.9, 131.8, 130.8, 129.3, 128.9, 128.8, 126.9, 122.6, 119.4, 115.6, 27.5; IR (film): 2739, 1772, 1638, 1454, 1265, 829, 615 cm-1; HRMS (EI) m/z:[M]+ Calcd for C18H13 79BrO2 340.0099, C18H13 81BrO2 342.0079; Found 340.0102, 342.0072.Yield: 40.8 mg (60%); R f = 0.2 (Acetone:Hexane=1:4); Red solid; Melting point: 233-235°C; 1H NMR (400 MHz, DMSO- d6 ) δ 11.96 (s, 1H), 9.41 (d, J =10.5 Hz, 1H), 8.47 (d, J = 10.1 Hz, 1H), 7.67 (dd, J = 8.0 Hz, J = 1.0 Hz, 1H), 7.59 (d, J = 10.5 Hz, 1H), 7.51 (d, J = 10.1 Hz, 1H), 7.45–7.36 (m, 2H), 7.31–7.27 (m, 1H), 7.21 (s, 1H), 2.72 (s, 3H); 13 C{ 1 H} NMR (100 MHz, DMSO- d 6 ) δ 166.1, 151.8, 150.6, 140.6, 140.2, 139.0, 137.7, 136.9, 131.8, 130.8, 129.3, 128.9, 128.8, 121.6, 121.9, 6. , 27.5; IR (film): 2739, 1772, 1638, 1454, 1265, 829, 615 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 18 H 13 79 BrO 2 340.0099, C 18 H 13 81 BrO 2 342.0079; Found 340.0102, 342.0072.

[실시예 25] 2-(2-Bromophenyl)-6-phenylazulene-1-carboxylic acid (화합물 3A-14)의 제조[Example 25] Preparation of 2-(2-Bromophenyl)-6-phenylazulene-1-carboxylic acid (Compound 3A-14)

Figure 112021000693139-pat00049
Figure 112021000693139-pat00049

반응온도: 60℃; 반응시간 : 12시간Reaction temperature: 60° C.; Response time: 12 hours

Yield: 44.3 mg (55%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 238-240℃; 1H NMR (400 MHz, DMSO-d 6) δ 11.85 (s, 1H), 9.61 (d, J = 10.6 Hz, 1H), 8.65 (d, J = 10.2 Hz, 1H), 7.90 (dd, J = 10.6 Hz, J =1.6 Hz, 1H), 7.83-7.79 (m, 3H), 7.70 (d, J = 8.0 Hz, 1H), 7.60-7.56 (m, 2H), 7.54-7.50 (m, 1H), 7.47-7.40 (m, 2H), 7.34-7.30 (m, 2H); 13C{1H} NMR (100 MHz, DMSO-d 6) δ 165.5, 151.6, 151.6, 143.2, 140.4, 139.8, 138.8, 137.4, 136.8, 131.5, 130.5, 128.7, 128.5, 128.3, 128.2, 127.4, 126.9, 126.5, 122.2, 119.4, 116.1; IR (film): 3409, 2341, 2114, 1560, 1234, 669, 588 cm-1; HRMS (EI) m/z:[M]+ Calcd for C23H15 79BrO2 402.0255, C23H15 81BrO2 404.0235; Found 402.0255, 404.0244.Yield: 44.3 mg (55%); R f = 0.2 (Acetone:Hexane=1:4); Blue solid; Melting point: 238-240°C; 1H NMR (400 MHz, DMSO- d6 ) δ 11.85 (s, 1H), 9.61 ( d, J = 10.6 Hz, 1H), 8.65 (d, J = 10.2 Hz, 1H), 7.90 (dd, J = 10.6 Hz , J = 1.6 Hz, 1H), 7.83–7.79 (m, 3H), 7.70 (d, J = 8.0 Hz, 1H), 7.60–7.56 (m, 2H), 7.54–7.50 (m, 1H), 7.47– 7.40 (m, 2H), 7.34-7.30 (m, 2H); 13 C{ 1 H} NMR (100 MHz, DMSO- d 6 ) δ 165.5, 151.6, 151.6, 143.2, 140.4, 139.8, 138.8, 137.4, 136.8, 131.5, 130.5, 128.7, 128.5, 128.2, 128.2, 128.3, 4. , 126.5, 122.2, 119.4, 116.1; IR (film): 3409, 2341, 2114, 1560, 1234, 669, 588 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 23 H 15 79 BrO 2 402.0255, C 23 H 15 81 BrO 2 404.0235; Found 402.0255, 404.0244.

[실시예 26] 2-(2-Bromophenyl)-3-methylazulene-1-carboxylic acid (화합물 3A-15)의 제조[Example 26] Preparation of 2-(2-Bromophenyl)-3-methylazulene-1-carboxylic acid (Compound 3A-15)

Figure 112021000693139-pat00050
Figure 112021000693139-pat00050

반응온도: 60℃; 반응시간 : 12시간Reaction temperature: 60° C.; Response time: 12 hours

Yield: 36.1 mg (53%); R f = 0.3 (Acetone:Hexane=1:4); Blue solid; Melting point: 220-222℃; 1H NMR (400 MHz, DMSO-d 6) δ 11.88 (s, 1H), 9.56 (d, J = 9.9 Hz, 1H), 8.57 (d, J = 9.7 Hz, 1H), 7.91 (t, J = 9.7 Hz, 1H), 7.72 (d, J = 7.8 Hz, 1H), 7.62-7.53 (m, 2H), 7.48-7.45 (m, 1H), 7.35-7.27 (m, 2H), 2.28 (s, 3H); 13C{1H} NMR (100 MHz, DMSO-d 6) δ 165.9, 151.3, 140.0, 139.7, 139.4, 139.4, 137.2, 135.8, 131.7, 130.6, 128.9, 127.2, 127.0, 126.2, 124.2, 122.5, 114.5, 10.6; IR (film): 3351, 2252, 2126, 1663, 1028, 824, 761, 618 cm-1; HRMS (EI) m/z:[M]+ Calcd for C18H13 79BrO2 340.0099, C18H13 81BrO2 342.0079; Found 340.0097, 342.0083.Yield: 36.1 mg (53%); R f = 0.3 (Acetone:Hexane=1:4); Blue solid; Melting point: 220-222°C; 1H NMR (400 MHz, DMSO- d 6 ) δ 11.88 (s, 1H), 9.56 (d, J = 9.9 Hz, 1H), 8.57 (d, J = 9.7 Hz, 1H), 7.91 (t, J = 9.7 Hz, 1H), 7.72 (d, J = 7.8 Hz, 1H), 7.62-7.53 (m, 2H), 7.48-7.45 (m, 1H), 7.35-7.27 (m, 2H), 2.28 (s, 3H) ); 13 C{ 1 H} NMR (100 MHz, DMSO- d 6 ) δ 165.9, 151.3, 140.0, 139.7, 139.4, 139.4, 137.2, 135.8, 131.7, 130.6, 128.9, 127.2, 127.0, 124.2, 126.2, 5. , 10.6; IR (film): 3351, 2252, 2126, 1663, 1028, 824, 761, 618 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 18 H 13 79 BrO 2 340.0099, C 18 H 13 81 BrO 2 342.0079; Found 340.0097, 342.0083.

실시예 III : 아줄레노퓨라논(azulenofuranone) 화합물 (1)의 제조Example III: Preparation of azulenofuranone compound (1)

Figure 112021000693139-pat00051
Figure 112021000693139-pat00051

질소 대기 하에서 2-아릴아줄렌-1-카복실산 화합물 (3A) (0.2 mmol, 1.0 equiv), [Cp*IrCl2]2 (4.0 mol%, 6.4 mg), AgOAc (3.0 equiv, 100.2 mg), KOAc (1.0 equiv, 19.7 mg) 및 DMF (1.0 mL)을 혼합하고, 80℃에서 12시간 동안 교반시켰다. 교반 완료 후 반응 혼합물을 상온으로 냉각시키고, 셀라이트 패드로 여과시킨 다음, 감압 하에서 여액을 농축시켰다. 농축된 잔류물을 실리카 겔 플래쉬 컬럼 크로마토그래피로 정제하여 목적 화합물인 아줄레노퓨라논 화합물 (1)을 수득하였다.2-arylazulene-1-carboxylic acid compound (3A) (0.2 mmol, 1.0 equiv), [Cp*IrCl 2 ] 2 (4.0 mol%, 6.4 mg), AgOAc (3.0 equiv, 100.2 mg), KOAc under nitrogen atmosphere (1.0 equiv, 19.7 mg) and DMF (1.0 mL) were mixed and stirred at 80° C. for 12 hours. After stirring was completed, the reaction mixture was cooled to room temperature, filtered through a celite pad, and the filtrate was concentrated under reduced pressure. The concentrated residue was purified by silica gel flash column chromatography to obtain the target compound, azulenofuranone compound (1).

[실시예 27] 3-Phenyl-1H-azuleno[1,8-bc]furan-1-one (화합물 1-1)의 제조[Example 27] Preparation of 3-Phenyl- 1H -azuleno[1,8-bc]furan-1-one (Compound 1-1)

Figure 112021000693139-pat00052
Figure 112021000693139-pat00052

Yield: 39.4 mg (80%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 198-200℃; 1H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 9.4 Hz, 1H), 7.99 (d, J = 7.3 Hz, 2H), 7.93 (t, J = 10.3 Hz, 1H), 7.61-7.53 (m, 3H), 7.45-7.41 (m, 2H), 2.74 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 163.0, 156.9, 145.2, 143.7, 138.3, 137.6, 135.7, 134.6, 130.0, 128.9, 128.8, 128.2, 127.1, 113.0, 110.7, 12.7; IR (film): 2914, 2359, 1759, 1631, 1501, 748, 606 cm-1; HRMS (EI) m/z:[M]+ Calcd for C18H12O2 260.0837; Found 260.0840.Yield: 39.4 mg (80%); R f = 0.4 (Acetone:Hexane=1:4); Red solid; Melting point: 198-200°C; 1H NMR (400 MHz, CDCl 3 ) δ 8.37 (d, J = 9.4 Hz, 1H), 7.99 (d, J = 7.3 Hz, 2H), 7.93 (t, J = 10.3 Hz, 1H), 7.61-7.53 (m , 3H), 7.45-7.41 (m, 2H), 2.74 (s, 3H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 163.0, 156.9, 145.2, 143.7, 138.3, 137.6, 135.7, 134.6, 130.0, 128.9, 128.8, 128.2, 127.1, 113.7, 110.7, 110.7; IR (film): 2914, 2359, 1759, 1631, 1501, 748, 606 cm -1 ; HRMS (EI) m/z : [M] + Calcd for C 18 H 12 O 2 260.0837; Found 260.0840.

이로부터, 2-아릴아줄렌-1-카복실산 화합물 (3A)는 아줄렌-1-카복실산 화합물 (3)과 다이아릴아이오도늄염 화합물 (4)의 반응으로부터 아줄레노퓨라논 화합물 (1)을 제조하기 위한 중간체임을 알 수 있다.From this, the 2-arylazulene-1-carboxylic acid compound (3A) is prepared from the reaction of the azulene-1-carboxylic acid compound (3) and the diaryliodonium salt compound (4) to obtain the azulenofuranone compound (1). It can be seen that it is an intermediate for

[비교예 1][Comparative Example 1]

상기 실시예 27에서 [Cp*IrCl2]2 를 사용하지 않는 것을 제외하고는 상기 실시예 27과 동일하게 반응시켰다. 그 결과, 목적 화합물인 3-Phenyl-1H-azuleno[1,8-bc]furan-1-one (화합물 1-1)을 얻지 못하였다.The reaction was carried out in the same manner as in Example 27, except that [Cp*IrCl 2 ] 2 was not used in Example 27. As a result, the target compound 3-Phenyl-1 H -azuleno[1,8-bc]furan-1-one (Compound 1-1) was not obtained.

이로부터, 반드시 이리듐 촉매가 존재하는 경우 2-아릴아줄렌-1-카복실산 화합물 (3A)의 분자 내 고리화 반응을 통해 목적하는 아줄레노퓨라논 화합물 (1)이 제조됨을 알 수 있다. 즉, 이리듐 촉매는 2-아릴아줄렌-1-카복실산 화합물 (3A)의 분자 내 C-O 결합 형성에 필수임을 알 수 있다.From this, it can be seen that the desired azulenofuranone compound (1) is prepared through intramolecular cyclization of the 2-arylazulene-1-carboxylic acid compound (3A) when an iridium catalyst is present. That is, it can be seen that the iridium catalyst is essential for forming the intramolecular C-O bond of the 2-arylazulene-1-carboxylic acid compound (3A).

[실시예 28 및 비교예 2-7][Example 28 and Comparative Example 2-7]

반응조건에 따른 아줄레노퓨라논 화합물 (1)의 원-팟 제조 여부를 알아보기 위하여 하기와 같이 실험하였다.In order to determine whether the azulenofuranone compound (1) was prepared in one-pot according to the reaction conditions, an experiment was conducted as follows.

Figure 112021000693139-pat00053
Figure 112021000693139-pat00053

아줄렌-1-카복실산 (3-1) (0.15 mmol, 1.0 equiv), 비스(4-플루오로페닐) 아이오도늄 트리플레이트 (4-1) (1.2 equiv), 촉매 (4.0 mol%), 산화제 (1.0-3.0 equiv), 첨가제 (0.5-1.0 equiv) 및 DMF (0.75 mL)을 사용하여 목적 화합물인 3-Phenyl-1H-azuleno[1,8-bc]furan-1-one (화합물 1-1)을 제조하였다. 반응 조건에 따른 반응 결과를 하기 표 1에 기재하였다.Azulene-1-carboxylic acid (3-1) (0.15 mmol, 1.0 equiv), bis(4-fluorophenyl)iodonium triflate (4-1) (1.2 equiv), catalyst (4.0 mol%), oxidizing agent (1.0-3.0 equiv), additives (0.5-1.0 equiv), and DMF (0.75 mL) to obtain the target compound, 3-Phenyl-1 H -azuleno[1,8-bc]furan-1-one (compound 1- 1) was prepared. The reaction results according to the reaction conditions are shown in Table 1 below.

실시예Example 비교예comparative example 2828 22 33 44 55 66 77 촉매catalyst [Cp*IrCl2]2 [Cp*IrCl 2 ] 2 [Cp*IrCl2]2 [Cp*IrCl 2 ] 2 Pd(OAc)2 Pd(OAc) 2 [Cp*RhCl2]2 [Cp*RhCl 2 ] 2 산화제oxidizer AgOAcAgOAc 3.0 eq3.0 eq. -- 1.0 eq1.0 eq. 1.0 eq1.0 eq. 1.0 eq1.0 eq. 1.0 eq1.0 eq. 1.0 eq1.0 eq. Cu(OAc)2 Cu(OAc) 2 -- 1.0 eq1.0 eq. -- -- -- -- -- 첨가제additive KOAcKOAc 1.0 eq1.0 eq. -- -- -- -- -- -- Li2CO3 Li 2 CO 3 -- 0.5 eq0.5 eq. -- -- -- -- -- LiH2PO4 LiH 2 PO 4 -- -- 1.0 eq1.0 eq. -- -- -- -- NaH2PO4 NaH 2 PO 4 -- -- -- 1.0 eq1.0 eq. -- -- -- Na2HPO4 Na 2 HPO 4 -- -- -- -- 1.0 eq1.0 eq. 1.0 eq1.0 eq. 1.0 eq1.0 eq. 반응 온도reaction temperature 80℃80℃ 60℃60℃ 60℃60℃ 60℃60℃ 60℃60℃ 60℃60℃ 60℃60℃ 반응 시간(h)Response time (h) 22 1212 22 22 22 22 22 화합물 1-1의 NMR 수율 (%)[1] NMR yield (%) of compound 1-1 [1] 91%91% 0%0% 0%0% 0%0% 0%0% 0%0% 0%0% 화합물 3A-1의 NMR 수율 (%)[1] NMR yield (%) of compound 3A-1 [1] 0%0% 14%14% 9%9% 5%5% 90%90% 0%0% 0%0% [1] NMR 수율은 내부 표준으로 디브로모메탄(CH2Br2)을 이용하여 산출됨. [1] NMR yield calculated using dibromomethane (CH 2 Br 2 ) as an internal standard.

상기 표 1의 결과로부터, 본 발명에 따르면 이리듐(Ir) 촉매, 은 산화제 및 아세트산염 첨가제의 존재 하에서 아줄렌-1-카복실산 화합물 (3) 및 다이아릴아이오도늄염 화합물 (4)의 반응을 통해 C(2)-아릴화 및 분자내 C-O 결합 형성이 순차적으로 일어나 원-팟으로 아줄레노퓨라논 화합물 (1)을 고선택적으로 제조함을 알 수 있다.From the results of Table 1, according to the present invention, through the reaction of the azulene-1-carboxylic acid compound (3) and the diaryliodonium salt compound (4) in the presence of an iridium (Ir) catalyst, a silver oxidizing agent and an acetate additive It can be seen that C(2)-arylation and intramolecular C-O bond formation occur sequentially to produce azulenofuranone compound (1) with high selectivity in one-pot.

전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다.The above description of the present invention is for illustrative purposes, and those skilled in the art can understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, the embodiments described above should be understood as illustrative in all respects and not limiting.

Claims (15)

하기 화학식 1로 표시되는 아줄레노퓨라논 화합물:
[화학식 1]
Figure 112022101109022-pat00054

(상기 화학식 1에서,
R1는 C1-C20알킬, 할로C1-C20알킬, 할로겐, C1-C20알콕시, 할로C1-C20알콕시, C1-C20알킬카보닐, 할로C1-C20알킬카보닐, C1-C20알콕시카보닐, 할로C1-C20알콕시카보닐, C6-C20아릴C1-C20알킬, C6-C20아릴C1-C20알킬옥시, C6-C20아릴 또는 C3-C20헤테로아릴이고;
m은 0 내지 3의 정수로, m이 2 이상의 정수인 경우 R1은 서로 동일하거나 상이할 수 있고;
R2는 수소, C1-C20알킬, 할로겐, C1-C20알콕시, 할로C1-C20알콕시, C1-C20알킬카보닐, 할로C1-C20알킬카보닐, C1-C20알콕시카보닐, 할로C1-C20알콕시카보닐, C6-C20아릴카보닐, C6-C20아릴C1-C20알킬옥시, C6-C20아릴 또는 C3-C20헤테로아릴이고, 상기 R2의 알킬, 아릴 및 헤테로아릴은 C1-C20알킬, 할로C1-C20알킬, C1-C20알콕시, 할로겐, 나이트로, C1-C20알킬카보닐, C1-C20알콕시카보닐, C6-C20아릴, -NHSO2R' 및 C6-C20아릴옥시로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고;
R'는 C1-C20알킬, C6-C20아릴, C6-C20아릴C1-C20알킬 또는 C1-C20알킬C6-C20아릴이고;
Ar은 C6-C20아릴 또는 C3-C20헤테로아릴이고;
상기 R1 및 Ar의 아릴 및 헤테로아릴은 C1-C20알킬, 할로C1-C20알킬, C1-C20알콕시, 할로겐, C1-C20알킬카보닐, C1-C20알콕시카보닐, C6-C20아릴, C6-C20아릴옥시, C6-C20아릴카보닐 및 C6-C20아릴옥시카보닐로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고;
상기 헤테로아릴은 N, O 및 S로부터 선택되는 1 내지 4개의 헤테로원자를 포함한다.)Azulenofuranone compound represented by Formula 1 below:
[Formula 1]
Figure 112022101109022-pat00054

(In Formula 1 above,
R 1 is C1-C20 alkyl, haloC1-C20 alkyl, halogen, C1-C20 alkoxy, haloC1-C20 alkoxy, C1-C20 alkylcarbonyl, haloC1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, halo C1-C20 alkoxycarbonyl, C6-C20 arylC1-C20 alkyl, C6-C20 arylC1-C20 alkyloxy, C6-C20 aryl or C3-C20 heteroaryl;
m is an integer from 0 to 3, and when m is an integer of 2 or greater, R 1 may be the same as or different from each other;
R 2 is hydrogen, C1-C20 alkyl, halogen, C1-C20 alkoxy, haloC1-C20 alkoxy, C1-C20 alkylcarbonyl, haloC1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, haloC1-C20 alkoxy carbonyl, C6-C20 arylcarbonyl, C6-C20 arylC1-C20 alkyloxy, C6-C20 aryl or C3-C20 heteroaryl, wherein the alkyl, aryl and heteroaryl of R 2 are C1-C20 alkyl, haloC1 -C20 alkyl, C1-C20 alkoxy, halogen, nitro, C1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, C6-C20 aryl, -NHSO 2 R' and C6-C20 aryloxy selected from the group consisting of may be further substituted with one or more;
R' is C1-C20 alkyl, C6-C20 aryl, C6-C20 arylC1-C20 alkyl or C1-C20 alkylC6-C20 aryl;
Ar is C6-C20 aryl or C3-C20 heteroaryl;
Aryl and heteroaryl of R 1 and Ar are C1-C20 alkyl, haloC1-C20 alkyl, C1-C20 alkoxy, halogen, C1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, C6-C20 aryl, C6- may be further substituted with one or more selected from the group consisting of C20 aryloxy, C6-C20 arylcarbonyl and C6-C20 aryloxycarbonyl;
The heteroaryl contains 1 to 4 heteroatoms selected from N, O and S.) 제 1항에 있어서,
하기 화학식 2로 표시되는 아줄레노퓨라논 화합물:
[화학식 2]
Figure 112021000693139-pat00055

(상기 화학식 2에서, R2 및 Ar은 청구항 제1항의 화학식 1에서의 정의와 동일하고;
R11는 수소, C1-C20알킬, 할로C1-C20알킬, 할로겐, C1-C20알콕시, 할로C1-C20알콕시, C1-C20알킬카보닐, 할로C1-C20알킬카보닐, C1-C20알콕시카보닐, 할로C1-C20알콕시카보닐, C6-C20아릴C1-C20알킬, C6-C20아릴C1-C20알킬옥시, C6-C20아릴 또는 C1-C20알킬C6-C20아릴이다.)According to claim 1,
Azulenofuranone compound represented by Formula 2:
[Formula 2]
Figure 112021000693139-pat00055

(In Formula 2, R 2 and Ar are the same as defined in Formula 1 of claim 1;
R 11 is hydrogen, C1-C20 alkyl, haloC1-C20 alkyl, halogen, C1-C20 alkoxy, haloC1-C20 alkoxy, C1-C20 alkylcarbonyl, haloC1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl , haloC1-C20 alkoxycarbonyl, C6-C20 arylC1-C20 alkyl, C6-C20 arylC1-C20 alkyloxy, C6-C20 aryl or C1-C20 alkylC6-C20 aryl.) 제 2항에 있어서,
R11는 수소, C1-C20알킬, 할로C1-C20알킬, C6-C20아릴C1-C20알킬, C6-C20아릴 또는 C1-C20알킬C6-C20아릴이고;
R2는 수소, C1-C20알킬 또는 C6-C20아릴이고, 상기 R2의 알킬 및 아릴은 C1-C20알킬, 할로C1-C20알킬, 할로겐 및 C6-C20아릴로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고;
Ar은 C6-C20아릴 또는 C3-C20헤테로아릴이고, 상기 Ar의 아릴 및 헤테로아릴은 C1-C20알킬, 할로C1-C20알킬, 할로겐, C1-C20알킬카보닐, C1-C20알콕시카보닐, C6-C20아릴, C6-C20아릴카보닐 및 C6-C20아릴옥시카보닐로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있는 것인, 아줄레노퓨라논 화합물.According to claim 2,
R 11 is hydrogen, C1-C20 alkyl, haloC1-C20 alkyl, C6-C20 arylC1-C20 alkyl, C6-C20 aryl or C1-C20 alkylC6-C20 aryl;
R 2 is hydrogen, C1-C20 alkyl or C6-C20 aryl, and the alkyl and aryl of R 2 are at least one selected from the group consisting of C1-C20 alkyl, haloC1-C20 alkyl, halogen and C6-C20 aryl. may be further substituted;
Ar is C6-C20 aryl or C3-C20 heteroaryl, and the aryl and heteroaryl of Ar are C1-C20 alkyl, haloC1-C20 alkyl, halogen, C1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, C6 -C20 Aryl, C6-C20 Arylcarbonyl and C6-C20 Aryloxycarbonyl that may be further substituted with one or more selected from the group consisting of, azulenofuranone compound. 제 1항에 있어서,
하기 구조에서 선택되는 것인, 아줄레노퓨라논 화합물:
Figure 112021000693139-pat00056
According to claim 1,
An azulenofuranone compound selected from the following structures:
Figure 112021000693139-pat00056
 이리듐(Ir) 촉매, 은 산화제 및 아세트산염 첨가제의 존재 하, 하기 화학식 3의 아줄렌-1-카복실산 화합물 및 화학식 4의 다이아릴아이오도늄염 화합물을 반응시켜 하기 화학식 1의 아줄레노퓨라논 화합물을 제조하는 방법:
[화학식 1]
Figure 112022101109022-pat00057

[화학식 3]
Figure 112022101109022-pat00058

[화학식 4]
Figure 112022101109022-pat00059

(상기 화학식 1, 3 및 4에서,
R1는 C1-C20알킬, 할로C1-C20알킬, 할로겐, C1-C20알콕시, 할로C1-C20알콕시, C1-C20알킬카보닐, 할로C1-C20알킬카보닐, C1-C20알콕시카보닐, 할로C1-C20알콕시카보닐, C6-C20아릴C1-C20알킬, C6-C20아릴C1-C20알킬옥시, C6-C20아릴 또는 C3-C20헤테로아릴이고;
m은 0 내지 3의 정수로, m이 2 이상의 정수인 경우 R1은 서로 동일하거나 상이할 수 있고;
R2는 수소, C1-C20알킬, 할로겐, C1-C20알콕시, 할로C1-C20알콕시, C1-C20알킬카보닐, 할로C1-C20알킬카보닐, C1-C20알콕시카보닐, 할로C1-C20알콕시카보닐, C6-C20아릴카보닐, C6-C20아릴C1-C20알킬옥시, C6-C20아릴 또는 C3-C20헤테로아릴이고, 상기 R2의 알킬, 아릴 및 헤테로아릴은 C1-C20알킬, 할로C1-C20알킬, C1-C20알콕시, 할로겐, 나이트로, C1-C20알킬카보닐, C1-C20알콕시카보닐, C6-C20아릴, -NHSO2R' 및 C6-C20아릴옥시로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고;
R'는 C1-C20알킬, C6-C20아릴, C6-C20아릴C1-C20알킬 또는 C1-C20알킬C6-C20아릴이고;
Ar은 C6-C20아릴 또는 C3-C20헤테로아릴이고;
상기 R1 및 Ar의 아릴 및 헤테로아릴은 C1-C20알킬, 할로C1-C20알킬, C1-C20알콕시, 할로겐, C1-C20알킬카보닐, C1-C20알콕시카보닐, C6-C20아릴, C6-C20아릴옥시, C6-C20아릴카보닐 및 C6-C20아릴옥시카보닐로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고;
X-는 1가 음이온이다.)In the presence of an iridium (Ir) catalyst, a silver oxidizing agent, and an acetate additive, an azulene-1-carboxylic acid compound of Formula 3 and a diaryliodonium salt compound of Formula 4 are reacted to obtain an azulenofuranone compound of Formula 1 below How to make:
[Formula 1]
Figure 112022101109022-pat00057

[Formula 3]
Figure 112022101109022-pat00058

[Formula 4]
Figure 112022101109022-pat00059

(In Chemical Formulas 1, 3 and 4,
R 1 is C1-C20 alkyl, haloC1-C20 alkyl, halogen, C1-C20 alkoxy, haloC1-C20 alkoxy, C1-C20 alkylcarbonyl, haloC1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, halo C1-C20 alkoxycarbonyl, C6-C20 arylC1-C20 alkyl, C6-C20 arylC1-C20 alkyloxy, C6-C20 aryl or C3-C20 heteroaryl;
m is an integer from 0 to 3, and when m is an integer of 2 or greater, R 1 may be the same as or different from each other;
R 2 is hydrogen, C1-C20 alkyl, halogen, C1-C20 alkoxy, haloC1-C20 alkoxy, C1-C20 alkylcarbonyl, haloC1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, haloC1-C20 alkoxy carbonyl, C6-C20 arylcarbonyl, C6-C20 arylC1-C20 alkyloxy, C6-C20 aryl or C3-C20 heteroaryl, wherein the alkyl, aryl and heteroaryl of R 2 are C1-C20 alkyl, haloC1 -C20 alkyl, C1-C20 alkoxy, halogen, nitro, C1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, C6-C20 aryl, -NHSO 2 R' and C6-C20 aryloxy selected from the group consisting of may be further substituted with one or more;
R' is C1-C20 alkyl, C6-C20 aryl, C6-C20 arylC1-C20 alkyl or C1-C20 alkylC6-C20 aryl;
Ar is C6-C20 aryl or C3-C20 heteroaryl;
Aryl and heteroaryl of R 1 and Ar are C1-C20 alkyl, haloC1-C20 alkyl, C1-C20 alkoxy, halogen, C1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, C6-C20 aryl, C6- may be further substituted with one or more selected from the group consisting of C20 aryloxy, C6-C20 arylcarbonyl and C6-C20 aryloxycarbonyl;
X - is a monovalent anion.) 이리듐(Ir) 촉매, 은 산화제 및 아세트산염 첨가제의 존재 하, 하기 화학식 3A의 2-아릴아줄렌-1-카복실산 화합물을 분자내 고리화 반응시켜 하기 화학식 1의 아줄레노퓨라논 화합물을 제조하는 방법:
[화학식 1]
Figure 112022101109022-pat00060

[화학식 3A]
Figure 112022101109022-pat00061

(상기 화학식 1 및 3A에서,
R1는 C1-C20알킬, 할로C1-C20알킬, 할로겐, C1-C20알콕시, 할로C1-C20알콕시, C1-C20알킬카보닐, 할로C1-C20알킬카보닐, C1-C20알콕시카보닐, 할로C1-C20알콕시카보닐, C6-C20아릴C1-C20알킬, C6-C20아릴C1-C20알킬옥시, C6-C20아릴 또는 C3-C20헤테로아릴이고;
m은 0 내지 3의 정수로, m이 2 이상의 정수인 경우 R1은 서로 동일하거나 상이할 수 있고;
R2는 수소, C1-C20알킬, 할로겐, C1-C20알콕시, 할로C1-C20알콕시, C1-C20알킬카보닐, 할로C1-C20알킬카보닐, C1-C20알콕시카보닐, 할로C1-C20알콕시카보닐, C6-C20아릴카보닐, C6-C20아릴C1-C20알킬옥시, C6-C20아릴 또는 C3-C20헤테로아릴이고, 상기 R2의 알킬, 아릴 및 헤테로아릴은 C1-C20알킬, 할로C1-C20알킬, C1-C20알콕시, 할로겐, 나이트로, C1-C20알킬카보닐, C1-C20알콕시카보닐, C6-C20아릴, -NHSO2R' 및 C6-C20아릴옥시로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고;
R'는 C1-C20알킬, C6-C20아릴, C6-C20아릴C1-C20알킬 또는 C1-C20알킬C6-C20아릴이고;
Ar은 C6-C20아릴 또는 C3-C20헤테로아릴이고;
상기 R1 및 Ar의 아릴 및 헤테로아릴은 C1-C20알킬, 할로C1-C20알킬, C1-C20알콕시, 할로겐, C1-C20알킬카보닐, C1-C20알콕시카보닐, C6-C20아릴, C6-C20아릴옥시, C6-C20아릴카보닐 및 C6-C20아릴옥시카보닐로 이루어진 군으로부터 선택되는 하나 이상으로 더 치환될 수 있고;
상기 헤테로아릴은 N, O 및 S로부터 선택되는 1 내지 4개의 헤테로원자를 포함한다.)Method for preparing azulenofuranone compound represented by Chemical Formula 1 by intramolecular cyclization of 2-arylazulene-1-carboxylic acid compound represented by Chemical Formula 3A in the presence of an iridium (Ir) catalyst, a silver oxidizing agent, and an acetate additive :
[Formula 1]
Figure 112022101109022-pat00060

[Formula 3A]
Figure 112022101109022-pat00061

(In Formulas 1 and 3A,
R 1 is C1-C20 alkyl, haloC1-C20 alkyl, halogen, C1-C20 alkoxy, haloC1-C20 alkoxy, C1-C20 alkylcarbonyl, haloC1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, halo C1-C20 alkoxycarbonyl, C6-C20 arylC1-C20 alkyl, C6-C20 arylC1-C20 alkyloxy, C6-C20 aryl or C3-C20 heteroaryl;
m is an integer from 0 to 3, and when m is an integer of 2 or greater, R 1 may be the same as or different from each other;
R 2 is hydrogen, C1-C20 alkyl, halogen, C1-C20 alkoxy, haloC1-C20 alkoxy, C1-C20 alkylcarbonyl, haloC1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, haloC1-C20 alkoxy carbonyl, C6-C20 arylcarbonyl, C6-C20 arylC1-C20 alkyloxy, C6-C20 aryl or C3-C20 heteroaryl, wherein the alkyl, aryl and heteroaryl of R 2 are C1-C20 alkyl, haloC1 -C20 alkyl, C1-C20 alkoxy, halogen, nitro, C1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, C6-C20 aryl, -NHSO 2 R' and C6-C20 aryloxy selected from the group consisting of may be further substituted with one or more;
R' is C1-C20 alkyl, C6-C20 aryl, C6-C20 arylC1-C20 alkyl or C1-C20 alkylC6-C20 aryl;
Ar is C6-C20 aryl or C3-C20 heteroaryl;
Aryl and heteroaryl of R 1 and Ar are C1-C20 alkyl, haloC1-C20 alkyl, C1-C20 alkoxy, halogen, C1-C20 alkylcarbonyl, C1-C20 alkoxycarbonyl, C6-C20 aryl, C6- may be further substituted with one or more selected from the group consisting of C20 aryloxy, C6-C20 arylcarbonyl and C6-C20 aryloxycarbonyl;
The heteroaryl contains 1 to 4 heteroatoms selected from N, O and S.) 제 5항에 있어서,
상기 X-는 할라이드, 테트라플루오로보레이트(tetrafluoroborate, BF4 -), 트리플레이트(triflate, CF3SO3 -, OTf-) 토실레이트(tosylate, CH3C6H4SO3 -, OTs-), 헥사플루오로포스페이트(hexafluorophosphate, PF6 -) 또는 아세테이트(acetate, OAc-)인, 제조방법.According to claim 5,
X - is a halide, tetrafluoroborate (BF 4 - ), triflate (CF 3 SO 3 - , OTf - ) tosylate (CH 3 C 6 H 4 SO 3 - , OTs - ) , Hexafluorophosphate (hexafluorophosphate, PF 6 - ) or acetate (acetate, OAc - ), a manufacturing method. 제 5항 또는 제6항에 있어서,
상기 이리듐(Ir) 촉매는 [Cp*IrCl2]2 (Cp*=pentamethylcyclopentadienyl), Ir(acac)3, IrCl3, Ir(ppy)3 (ppy=2-phenylpyridine), [(ppy)2IrCl]2, (ppy)2Ir(acac), Ir[(ppy)2(dtb-bpy)]PF6, [Ir(cod)Cl]2 및 IrCp*(OAc)2 로 이루어진 군으로부터 선택되는 하나 또는 둘 이상인, 제조방법.According to claim 5 or 6,
The iridium (Ir) catalyst is [Cp*IrCl 2 ] 2 (Cp*=pentamethylcyclopentadienyl), Ir(acac) 3 , IrCl 3 , Ir(ppy) 3 (ppy=2-phenylpyridine), [(ppy) 2 IrCl] one or two selected from the group consisting of 2 , (ppy) 2 Ir(acac), Ir[(ppy) 2 (dtb-bpy)]PF 6 , [Ir(cod)Cl] 2 and IrCp*(OAc) 2 Ideal, manufacturing method. 제 5항 또는 제6항에 있어서,
상기 이리듐(Ir) 촉매는 상기 화학식 3의 아줄렌-1-카복실산 화합물 또는 화학식 3A의 2-아릴아줄렌-1-카복실산 화합물에 대해 0.5 내지 20 mol% 범위로 사용하는 것인, 제조방법.According to claim 5 or 6,
The iridium (Ir) catalyst is used in an amount of 0.5 to 20 mol% relative to the azulene-1-carboxylic acid compound of Formula 3 or the 2-arylazulene-1-carboxylic acid compound of Formula 3A. 제 5항에 있어서,
상기 화학식 4의 다이아릴아이오도늄염 화합물은 상기 화학식 3의 아줄렌-1-카복실산 화합물 1 당량에 대해 1 내지 3 당량 범위로 사용하는 것인, 제조방법.According to claim 5,
The diaryliodonium salt compound of Formula 4 is used in the range of 1 to 3 equivalents with respect to 1 equivalent of the azulene-1-carboxylic acid compound of Formula 3. 제 5항 또는 제6항에 있어서,
상기 은 산화제는 AgO, Ag2O, Ag2CO3, AgOAc, AgSbF6, AgNO3, AgNTf2 및 AgOTf로 이루어진 군으로부터 선택되는 하나 또는 둘 이상인, 제조방법.According to claim 5 or 6,
The silver oxidizing agent is one or two or more selected from the group consisting of AgO, Ag 2 O, Ag 2 CO 3 , AgOAc, AgSbF 6 , AgNO 3 , AgNTf 2 and AgOTf. 제 5항 또는 제6항에 있어서,
상기 은 산화제는 상기 화학식 3의 아줄렌-1-카복실산 화합물 또는 화학식 3A의 2-아릴아줄렌-1-카복실산 화합물 1 당량에 대해 1 내지 5 당량 범위로 사용하는 것인, 제조방법.According to claim 5 or 6,
The silver oxidizing agent is used in the range of 1 to 5 equivalents based on 1 equivalent of the azulene-1-carboxylic acid compound of Formula 3 or the 2-arylazulene-1-carboxylic acid compound of Formula 3A. 제 5항 또는 제6항에 있어서,
상기 아세트산염 첨가제는 KOAc, LiOAc, NaOAc 및 CsOAc로 이루어진 군으로부터 선택되는 하나 또는 둘 이상인, 제조방법.According to claim 5 or 6,
Wherein the acetate additive is one or two or more selected from the group consisting of KOAc, LiOAc, NaOAc and CsOAc. 제 5항 또는 제6항에 있어서,
상기 아세트산염 첨가제는 상기 화학식 3의 아줄렌-1-카복실산 화합물 또는 화학식 3A의 2-아릴아줄렌-1-카복실산 화합물 1 당량에 대해 0.5 내지 3 당량 범위로 사용하는 것인, 제조방법.According to claim 5 or 6,
The acetate additive is used in the range of 0.5 to 3 equivalents based on 1 equivalent of the azulene-1-carboxylic acid compound of Formula 3 or the 2-arylazulene-1-carboxylic acid compound of Formula 3A. 제 5항 또는 제6항에 있어서,
상기 반응은 50 내지 100℃에서 수행되는 것인, 제조방법.According to claim 5 or 6,
The reaction is carried out at 50 to 100 ℃, the manufacturing method.
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