TWI814416B - Five-membered ring fused naphthoquinone compound and method of preparing the same - Google Patents

Five-membered ring fused naphthoquinone compound and method of preparing the same Download PDF

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TWI814416B
TWI814416B TW111120522A TW111120522A TWI814416B TW I814416 B TWI814416 B TW I814416B TW 111120522 A TW111120522 A TW 111120522A TW 111120522 A TW111120522 A TW 111120522A TW I814416 B TWI814416 B TW I814416B
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naphthoquinone
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fused ring
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TW202348223A (en
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莊士卿
拉煦 蘇
曾閩風
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國立陽明交通大學
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Abstract

A five-membered ring fused naphthoquinone compound has a structure of the following formula (1): formula (1). R 1is selected from the group consisting of hydrogen, 4-chloro, and 5-chloro. n is 1 or 2. R 2is selected from the group consisting of phenyl, 4-methylphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitrophenyl, and 2-naphthyl. X is selected from the group consisting of and , in which * represents a connecting bond. R 3is selected from the group consisting of phenyl, 4-tert-butylphenyl, and 4-methylphenyl. Y is selected from the group consisting of , , and , in which * represents a connecting bond. R 4is selected from the group consisting of methyl, methoxy, and ethoxy. PAr 3is selected from the group consisting of tricyclohexylphosphino, triphenylphosphino, tri-m-tolylphosphino, tri-p-tolylphosphino, tri-p-fluorophenyl phosphino, tri-p-chlorophenyl phosphino, and diphenyl tolyl phosphino.

Description

萘醌五元稠環化合物及其製備方法Naphthoquinone five-membered fused ring compound and preparation method thereof

本揭示內容是關於一種萘醌五元稠環化合物及其製備方法。 The present disclosure relates to a naphthoquinone five-membered fused ring compound and its preparation method.

萘醌(Naphthoquinone)藉由將萘上雙鍵轉化為接上氧的羰基而形成具共軛體系的二酮結構，例如如下所示的1,4-萘醌(Naphthalene-1,4-dione)：

Figure 111120522-A0305-02-0004-2
Naphthoquinone forms a diketone structure with a conjugated system by converting the double bond on naphthalene into a carbonyl group connected to oxygen, such as 1,4-naphthoquinone (Naphthalene-1,4-dione) as shown below :
Figure 111120522-A0305-02-0004-2

具有上述萘醌結構的化合物及其衍生物具多種特性，包括可抗癌、抗菌、抗真菌、抗病毒、抗瘧疾、殺真菌和抗炎等。因此亟需開發多種製備方法以形成具有不同取代基的萘醌化合物及其衍生物，其中藉由環擴張(Ring Expansion)的方法可製備具較大分子量和/或較難得到的藥物分子，藉此提升發掘不同碳環結構並應用於藥物領 域的速度。 Compounds with the above naphthoquinone structure and their derivatives have various properties, including anticancer, antibacterial, antifungal, antiviral, antimalarial, fungicidal and anti-inflammatory properties. Therefore, there is an urgent need to develop a variety of preparation methods to form naphthoquinone compounds and their derivatives with different substituents. Among them, drug molecules with larger molecular weights and/or that are difficult to obtain can be prepared through ring expansion. This improvement explores different carbon ring structures and applies them to the pharmaceutical field domain speed.

然而受到活化位置的限制，製備具良好官能基耐受性(Functional Group Tolerance)的萘醌結構化合物及其衍生物並不容易，使所得萘醌結構化合物及其衍生物在後續應用上亦受到限制。此外以往製備萘醌結構化合物及其衍生物的方法使用重金屬催化，例如銀或銅催化，不僅造成環境汙染、經濟成本高，亦可能在生物體內殘留，因此不適合做為藥物的製備方法。 However, due to the limitation of the activation site, it is not easy to prepare naphthoquinone structural compounds and their derivatives with good functional group tolerance, which limits the subsequent applications of the obtained naphthoquinone structural compounds and their derivatives. . In addition, previous methods for preparing naphthoquinone structural compounds and their derivatives use heavy metal catalysis, such as silver or copper catalysis, which not only causes environmental pollution and high economic costs, but may also remain in the body, so it is not suitable as a drug preparation method.

因此開發具良好官能基耐受性的萘醌結構化合物及其衍生物，且反應條件溫和並具高產率的製備方法就顯得至關重要，其中製備方法亦必須簡單安全，原料取得容易，以符合高的原子經濟性(Atom Economy)。 Therefore, it is crucial to develop naphthoquinone structural compounds and their derivatives with good functional group tolerance, as well as preparation methods with mild reaction conditions and high yields. The preparation method must also be simple and safe, and the raw materials must be easily available to meet the requirements. High atomic economy (Atom Economy).

本揭示內容是關於一種萘醌五元稠環化合物，具有以下式(1)的結構：

Figure 111120522-A0305-02-0005-3
R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2。R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組。X選自由*-R3及
Figure 111120522-A0305-02-0005-4
所 組成的群組，其中*表示連接鍵，以及R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組。Y選自由*-CH3、
Figure 111120522-A0305-02-0006-5
及
Figure 111120522-A0305-02-0006-6
所組成的群組，其中*表示連接鍵，R4選自由甲基、甲氧基及乙氧基所組成的群組，以及PAr3選自由三環己基膦基、三苯基膦基、三間甲苯基膦基、三對甲苯基膦基、三對氟苯基膦基、三對氯苯基膦基及二苯基甲苯基膦基所組成的群組。 The present disclosure relates to a naphthoquinone five-membered fused ring compound, which has the structure of the following formula (1):
Figure 111120522-A0305-02-0005-3
 R 1 is selected from the group consisting of hydrogen, 4-chloro and 5-chloro, and n is 1 or 2. R 2 is selected from phenyl, 4-methylphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitro The group consisting of phenyl and 2-naphthyl. X Select Free * -R 3 &
Figure 111120522-A0305-02-0005-4
The group consisting of, where * represents a connecting bond, and R 3 is selected from the group consisting of phenyl, 4-tert-butylphenyl and 4-methylphenyl. Y is free to choose * -CH 3 ,
Figure 111120522-A0305-02-0006-5
and
Figure 111120522-A0305-02-0006-6
The group consisting of, where * represents a linking bond, R 4 is selected from the group consisting of methyl, methoxy and ethoxy, and PAr 3 is selected from the group consisting of tricyclohexylphosphine, triphenylphosphine, tri- The group consisting of tolylphosphine group, tri-p-tolylphosphine group, tri-p-fluorophenylphosphine group, tri-p-chlorophenylphosphine group and diphenyltolylphosphine group.

在一些實施方式中，萘醌五元稠環化合物具有以下式(2)的結構：

Figure 111120522-A0305-02-0006-7
R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2。R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組。R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組。R4選自由甲氧基及乙氧基所組成的群組。PAr3為三環己基膦基。 In some embodiments, the naphthoquinone five-membered fused ring compound has the structure of the following formula (2):
Figure 111120522-A0305-02-0006-7
 R 1 is selected from the group consisting of hydrogen, 4-chloro and 5-chloro, and n is 1 or 2. R 2 is selected from phenyl, 4-methylphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitro The group consisting of phenyl and 2-naphthyl. R 3 is selected from the group consisting of phenyl, 4-tert-butylphenyl and 4-methylphenyl. R 4 is selected from the group consisting of methoxy and ethoxy. PAr 3 is tricyclohexylphosphine group.

在一些實施方式中，萘醌五元稠環化合物具有以下式(3)的結構：

Figure 111120522-A0305-02-0007-8
R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2。R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組。R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組。PAr3選自由三苯基膦基、三間甲苯基膦基、三對甲苯基膦基、三對氟苯基膦基、三對氯苯基膦基及二苯基甲苯基膦基所組成的群組。 In some embodiments, the naphthoquinone five-membered fused ring compound has the structure of the following formula (3):
Figure 111120522-A0305-02-0007-8
 R 1 is selected from the group consisting of hydrogen, 4-chloro and 5-chloro, and n is 1 or 2. R 2 is selected from phenyl, 4-methylphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitro The group consisting of phenyl and 2-naphthyl. R 3 is selected from the group consisting of phenyl, 4-tert-butylphenyl and 4-methylphenyl. PAr 3 is selected from the group consisting of triphenylphosphine, tri-m-tolylphosphine, tri-p-tolylphosphine, tri-p-fluorophenylphosphine, tri-p-chlorophenylphosphine and diphenyltolylphosphine. group.

在一些實施方式中，萘醌五元稠環化合物具有以下式(4)的結構：

Figure 111120522-A0305-02-0007-9
R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2。R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組。R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組。 In some embodiments, the naphthoquinone five-membered fused ring compound has the structure of the following formula (4):
Figure 111120522-A0305-02-0007-9
 R 1 is selected from the group consisting of hydrogen, 4-chloro and 5-chloro, and n is 1 or 2. R 2 is selected from phenyl, 4-methylphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitro The group consisting of phenyl and 2-naphthyl. R 3 is selected from the group consisting of phenyl, 4-tert-butylphenyl and 4-methylphenyl.

在一些實施方式中，萘醌五元稠環化合物具有以下式(5)的結構：

Figure 111120522-A0305-02-0008-10
R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2。R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組。R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組。R4選自由甲基、甲氧基及乙氧基所組成的群組。 In some embodiments, the naphthoquinone five-membered fused ring compound has the structure of the following formula (5):
Figure 111120522-A0305-02-0008-10
 R 1 is selected from the group consisting of hydrogen, 4-chloro and 5-chloro, and n is 1 or 2. R 2 is selected from phenyl, 4-methylphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitro The group consisting of phenyl and 2-naphthyl. R 3 is selected from the group consisting of phenyl, 4-tert-butylphenyl and 4-methylphenyl. R 4 is selected from the group consisting of methyl, methoxy and ethoxy.

本揭示內容是關於一種製備萘醌五元稠環化合物之方法，在一些實施方式中方法包括以下操作。混合具有以下式(A)的結構的1,3-茚滿二酮化合物；具有以下式(B)的結構的二炔化合物；三芳香基膦或三環己基膦；及第一有機溶劑，以形成混合物：

Figure 111120522-A0305-02-0008-11
其中R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2。R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯 基及2-萘基所組成的群組。R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組。R4選自由甲基、甲氧基及乙氧基所組成的群組。以及在0℃至30℃下反應混合物6小時至24小時。 The present disclosure relates to a method for preparing a naphthoquinone five-membered fused ring compound. In some embodiments, the method includes the following operations. Mix a 1,3-indandione compound having a structure of the following formula (A); a diyne compound having a structure of the following formula (B); triarylphosphine or tricyclohexylphosphine; and a first organic solvent, to Form the mixture:
Figure 111120522-A0305-02-0008-11
 Wherein R 1 is selected from the group consisting of hydrogen group, 4-chloro group and 5-chloro group, and n is 1 or 2. R 2 is selected from phenyl, 4-methylphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitro The group consisting of phenyl and 2-naphthyl. R 3 is selected from the group consisting of phenyl, 4-tert-butylphenyl and 4-methylphenyl. R 4 is selected from the group consisting of methyl, methoxy and ethoxy. and the reaction mixture at 0°C to 30°C for 6 hours to 24 hours.

在一些實施方式中，R4選自由甲氧基及乙氧基所組成的群組，並在0℃至27℃下反應混合物6小時至24小時。 In some embodiments, R 4 is selected from the group consisting of methoxy and ethoxy, and the reaction mixture is reacted at 0°C to 27°C for 6 hours to 24 hours.

在一些實施方式中，當混合具有式(A)的結構的1,3-茚滿二酮化合物、具有式(B)的結構的二炔化合物、三環己基膦及第一有機溶劑時，以及第一有機溶劑為甲苯、四氫呋喃或其組合時，形成具有式(2)的萘醌五元稠環化合物。 In some embodiments, when the 1,3-indandione compound having the structure of Formula (A), the diyne compound having the structure of Formula (B), tricyclohexylphosphine and the first organic solvent are mixed, and When the first organic solvent is toluene, tetrahydrofuran or a combination thereof, a naphthoquinone five-membered fused ring compound having formula (2) is formed.

在一些實施方式中，方法更包括將具有式(2)的萘醌五元稠環化合物與間氯過氧苯甲酸及第二有機溶劑混合，並在20℃至30℃下反應30分鐘至1小時，以形成具有式(5)的萘醌五元稠環化合物。 In some embodiments, the method further includes mixing the naphthoquinone five-membered fused ring compound of formula (2) with m-chloroperoxybenzoic acid and a second organic solvent, and reacting at 20°C to 30°C for 30 minutes to 1 hours to form a naphthoquinone five-membered fused ring compound of formula (5).

在一些實施方式中，R4為甲基，並在20℃至30℃下反應混合物12小時至24小時。 In some embodiments, R 4 is methyl, and the reaction mixture is stirred at 20°C to 30°C for 12 hours to 24 hours.

在一些實施方式中，三芳香基膦為三苯基膦、三間甲苯基膦、三對甲苯基膦、三對氟苯基膦、三對氯苯基膦、二苯基甲苯基膦或其組合，以及第一有機溶劑為甲苯、四氫呋喃、1,4-二氧陸圜、二氯甲烷、乙腈、苯或其組合，以形成具有式(3)的萘醌五元稠環化合物及具有式(4)的萘醌五元稠環化合物。 In some embodiments, the triarylphosphine is triphenylphosphine, tri-m-tolylphosphine, tri-p-tolylphosphine, tri-p-fluorophenylphosphine, tri-p-chlorophenylphosphine, diphenyltolylphosphine, or combinations thereof , and the first organic solvent is toluene, tetrahydrofuran, 1,4-dioxanone, methylene chloride, acetonitrile, benzene or a combination thereof to form a naphthoquinone five-membered fused ring compound with formula (3) and a naphthoquinone five-membered fused ring compound with formula (3) 4) Naphthoquinone five-membered fused ring compound.

在一些實施方式中，方法更包括將具有式(3)的萘醌五元稠環化合物與間氯過氧苯甲酸及第二有機溶劑混合，並在20℃至30℃下反應30分鐘至1小時，以形成具有式(5)的萘醌五元稠環化合物。 In some embodiments, the method further includes mixing the naphthoquinone five-membered fused ring compound of formula (3) with m-chloroperoxybenzoic acid and a second organic solvent, and reacting at 20°C to 30°C for 30 minutes to 1 hours to form a naphthoquinone five-membered fused ring compound of formula (5).

為了使本揭示內容的敘述更加詳盡與完備，下文針對本揭露的實施態樣與具體實施例做出說明性的描述，這並非限制實施本揭露的具體實施例為唯一形式。本揭露的實施例在有益的情形下可相互組合或取代，也可對本揭露的實施例附加其他的實施例，無須進一步記載或說明。 In order to make the description of the present disclosure more detailed and complete, the following is an illustrative description of the implementation aspects and specific embodiments of the present disclosure. This does not limit the implementation of the specific embodiments of the present disclosure to the only form. The embodiments of the present disclosure can be combined or replaced with each other under beneficial circumstances, and other embodiments can be added to the embodiments of the present disclosure without further description or explanation.

本揭示內容提供一種萘醌五元稠環化合物，具有以下式(1)的結構：

Figure 111120522-A0305-02-0010-12
。在式(1)中，R1選自由氫基、4-氯基及5-氯基所組成的群組，而n為1或2，表示R1為1個或2個。當R1為2個時，表示其各自獨立鍵結於如上所示的苯環上。下文的(R1)n的表示方式同理，不再贅述。R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基 及2-萘基所組成的群組。X選自由*-R3及
Figure 111120522-A0305-02-0011-13
所組成的群組，其中*表示連接鍵，以及R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組。Y選自由*-CH3、
Figure 111120522-A0305-02-0011-15
及
Figure 111120522-A0305-02-0011-16
所組成的群組，其中*表示連接鍵，R4選自由甲基、甲氧基及乙氧基所組成的群組，以及PAr3選自由三環己基膦基(PCy3)、三苯基膦基(PPh3)、三間甲苯基膦基(P(m-tolyl)3)、三對甲苯基膦基(P(p-tolyl)3)、三對氟苯基膦基(P(p-F-Ph)3)、三對氯苯基膦基(P(p-Cl-Ph)3)及二苯基甲苯基膦基(PPh2(p-tolyl))所組成的群組。本揭示內容提供的新穎的萘醌五元稠環化合物，具有良好的官能基耐受性，因此具諸多應用。下文詳細說明本揭示內容的萘醌五元稠環化合物。 The present disclosure provides a naphthoquinone five-membered fused ring compound having the structure of the following formula (1):
Figure 111120522-A0305-02-0010-12
. In formula (1), R 1 is selected from the group consisting of a hydrogen group, a 4-chloro group and a 5-chloro group, and n is 1 or 2, indicating that R 1 is 1 or 2. When R 1 is 2, it means that each of them is independently bonded to the benzene ring shown above. The expression of (R 1 ) n below is the same and will not be described again. R 2 is selected from phenyl, 4-methylphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitro The group consisting of phenyl and 2-naphthyl. X Select Free * -R 3 &
Figure 111120522-A0305-02-0011-13
The group consisting of, where * represents a connecting bond, and R 3 is selected from the group consisting of phenyl, 4-tert-butylphenyl and 4-methylphenyl. Y is free to choose * -CH 3 ,
Figure 111120522-A0305-02-0011-15
and
Figure 111120522-A0305-02-0011-16
The group consisting of, where * represents a connecting bond, R 4 is selected from the group consisting of methyl, methoxy and ethoxy, and PAr 3 is selected from the group consisting of tricyclohexylphosphine (PCy 3 ), triphenyl Phosphine group (PPh 3 ), tri-m-tolylphosphine group (P(m-tolyl) 3 ), tri-p-tolylphosphine group (P(p-tolyl) 3 ), tri-p-fluorophenylphosphine group (P(pF- Ph) 3 ), tri-p-chlorophenylphosphine (P(p-Cl-Ph) 3 ) and diphenyltolylphosphine (PPh 2 (p-tolyl)). The novel naphthoquinone five-membered fused ring compound provided by this disclosure has good functional group tolerance and therefore has many applications. The naphthoquinone five-membered fused ring compound of the present disclosure is described in detail below.

在一些實施例中，萘醌五元稠環化合物具有以下式(2)的結構：

Figure 111120522-A0305-02-0011-17
。在式(2)中，R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2。R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、 4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組。R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組。R4選自由甲氧基及乙氧基所組成的群組。PAr3為三環己基膦基。 In some embodiments, the naphthoquinone five-membered fused ring compound has the structure of the following formula (2):
Figure 111120522-A0305-02-0011-17
. In formula (2), R 1 is selected from the group consisting of hydrogen group, 4-chloro group and 5-chloro group, and n is 1 or 2. R 2 is selected from phenyl, 4-methylphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitro The group consisting of phenyl and 2-naphthyl. R 3 is selected from the group consisting of phenyl, 4-tert-butylphenyl and 4-methylphenyl. R 4 is selected from the group consisting of methoxy and ethoxy. PAr 3 is tricyclohexylphosphine group.

更詳細地說，在一些實施例中，具有式(2)的萘醌五元稠環化合物如下，其中Me為甲基、Et為乙基、Ph為苯基、PCy3為三環己基膦基以及tBu為叔丁基：

Figure 111120522-A0305-02-0012-18
In more detail, in some embodiments, the naphthoquinone five-membered fused ring compound of formula (2) is as follows, wherein Me is methyl, Et is ethyl, Ph is phenyl, and PCy3 is tricyclohexylphosphine group and tBu is tert-butyl:
Figure 111120522-A0305-02-0012-18

上述實施例中，

Figure 111120522-A0305-02-0013-19
的名稱為2-(4,9-二氧代-3,3a-二苯基-3a,9-二氫-4H-環戊二烯[b]萘-1-基)-2-(三環己基-λ5-膦烯)乙酸甲酯(Methyl 2-(4,9-dioxo-3,3a-diphenyl-3a,9-dihydro-4H-cyclopenta[b]naphthalen-1-yl)-2-(tricyclohexyl-λ5-phosphaneylidene)acetate)，下文將其結構稱為式(2’)。具有式(2’)的萘醌五元稠環化合物的分子式為C46H51O4P，質譜測得分子帶一氫正離子時的質荷比(m/z)為699.3603。紅色固體。熔點為147℃至150℃。層析測得Rf值為0.28，使用體積比7：3的己烷：乙酸乙酯作為沖提液。氫譜測得以ppm為單位表示的峰位置包括7.98(d，J=6.8Hz，1H)、7.84(d，J=7.6Hz，1H)、7.55-7.48(m，2H)、7.38-7.35(m，2H)、7.24(d，J=6Hz，2H)、7.18(d，J=6.8Hz，2H)、7.07-7.01(m，3H)、6.69(s，1H)、3.64(s，3H)、2.80-2.66(m，3H)、2.34-2.20(m，3H)、1.92-1.86(m，3H)、1.78-1.70(m，9H)、1.61-1.45(m，6H)、1.35-1.23(m，4H)以及1.20-1.14(m，5H)。碳譜測得以ppm為單位表示的峰位置包括196.5、176.6、171.4(d，JP-C=16.3Hz)、156.1、155.9(d，JP-C=7.6Hz)、138.3、137.9、136.5、135.5、135.4、135.4、133.1、131.5、128.5(d，JP-C=12.1Hz)、128.0、 127.9、127.8、127.1、127.1、127.0、126.1、77.9、50.1、44.8(d，JP-C=107Hz)、32.9(d，JP-C=47.8Hz)、27.9、27.9(d，JP-C=33.3Hz)、27.4、27.3以及26.0。紅外光譜測得以cm-1為單位表示的峰位置包括2931、1693、1637以及1128。具有式(2’)的萘醌五元稠環化合物的製備方法將於下文的實施例1中闡述。 In the above embodiment,
Figure 111120522-A0305-02-0013-19
The name is 2-(4,9-dioxo-3,3a-diphenyl-3a,9-dihydro-4H-cyclopentadien[b]naphthyl-1-yl)-2-(tricyclo Methyl 2-(4,9-dioxo-3,3a-diphenyl-3a,9-dihydro-4H-cyclopenta[b]naphthalen-1-yl)-2-(tricyclohexyl)acetate -λ5-phosphaneylidene)acetate), its structure will be referred to as formula (2') below. The molecular formula of the naphthoquinone five-membered fused ring compound with formula (2') is C 46 H 51 O 4 P. The mass-to-charge ratio (m/z) of the molecule with a hydrogen cation measured by mass spectrometry is 699.3603. Red solid. The melting point is 147°C to 150°C. The R f value measured by chromatography was 0.28, and hexane:ethyl acetate with a volume ratio of 7:3 was used as the eluent. The peak positions measured in ppm in the hydrogen spectrum include 7.98 (d, J=6.8Hz, 1H), 7.84 (d, J=7.6Hz, 1H), 7.55-7.48 (m, 2H), 7.38-7.35 (m , 2H), 7.24(d, J=6Hz, 2H), 7.18(d, J=6.8Hz, 2H), 7.07-7.01(m, 3H), 6.69(s, 1H), 3.64(s, 3H), 2.80-2.66(m, 3H), 2.34-2.20(m, 3H), 1.92-1.86(m, 3H), 1.78-1.70(m, 9H), 1.61-1.45(m, 6H), 1.35-1.23(m , 4H) and 1.20-1.14 (m, 5H). The peak positions measured in ppm in the carbon spectrum include 196.5, 176.6, 171.4 (d, J PC =16.3Hz), 156.1, 155.9 (d, J PC =7.6Hz), 138.3, 137.9, 136.5, 135.5, 135.4, 135.4, 133.1, 131.5, 128.5(d, J PC =12.1Hz), 128.0, 127.9, 127.8, 127.1, 127.1, 127.0, 126.1, 77.9, 50.1, 44.8(d, JP-C=107Hz), 32.9(d, J PC =47.8Hz), 27.9, 27.9 (d, J PC =33.3Hz), 27.4, 27.3 and 26.0. The peak positions measured in the infrared spectrum and expressed in cm -1 units include 2931, 1693, 1637 and 1128. The preparation method of the naphthoquinone five-membered fused ring compound having the formula (2') will be described in Example 1 below.

在一些實施例中，萘醌五元稠環化合物具有以下式(3)的結構：

Figure 111120522-A0305-02-0014-20
。在式(3)中，R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2。R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組。R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組。PAr3選自由三苯基膦基、三間甲苯基膦基、三對甲苯基膦基、三對氟苯基膦基、三對氯苯基膦基及二苯基甲苯基膦基所組成的群組。 In some embodiments, the naphthoquinone five-membered fused ring compound has the structure of the following formula (3):
Figure 111120522-A0305-02-0014-20
. In formula (3), R 1 is selected from the group consisting of hydrogen group, 4-chloro group and 5-chloro group, and n is 1 or 2. R 2 is selected from phenyl, 4-methylphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitro The group consisting of phenyl and 2-naphthyl. R 3 is selected from the group consisting of phenyl, 4-tert-butylphenyl and 4-methylphenyl. PAr 3 is selected from the group consisting of triphenylphosphine, tri-m-tolylphosphine, tri-p-tolylphosphine, tri-p-fluorophenylphosphine, tri-p-chlorophenylphosphine and diphenyltolylphosphine. group.

更詳細地說，在一些實施例中，具有式(3)的萘醌五元稠環化合物如下，其中Me為甲基、Ph為苯基、tBu為叔丁基以及PAr3選自由三苯基膦基、三間甲苯基膦基、三對甲苯基膦基、三對氟苯基膦基、三對氯苯基膦基及二 苯基甲苯基膦基所組成的群組：

Figure 111120522-A0305-02-0015-21
In more detail, in some embodiments, the naphthoquinone five-membered fused ring compound of formula (3) is as follows, wherein Me is methyl, Ph is phenyl, tBu is tert-butyl, and PAr is selected from triphenyl The group consisting of phosphinoyl, tri-m-tolylphosphine, tri-p-tolylphosphine, tri-p-fluorophenylphosphine, tri-p-chlorophenylphosphine and diphenyltolylphosphine:
Figure 111120522-A0305-02-0015-21

上述實施例中，

Figure 111120522-A0305-02-0015-22
的名稱為1-(2-氧代-1-(三苯基膦烯)丙基)-3,3a-二苯基-3a氫-環戊二烯[b]萘-4,9-二酮(1-(2-oxo-1-(triphenylphosphoranylidene)propyl)-3,3a-diphenyl-3aH-cyclopenta[b]naphthalene-4,9-dione)，下文將其結構稱為式(3’)。具有式(3’)的萘醌五元稠環化合物的分子式為C46H34O3P，質譜測得分子帶一氫正離子時的質荷比 (m/z)為665.2243。橘色固體。熔點為114℃至116℃。層析測得Rf值為0.44，使用乙酸乙酯作為沖提液。氫譜測得以ppm為單位表示的峰位置包括8.06-8.00(m，1H)、7.93-7.87(m，1H)、7.66(dd，J=12.7，7.6Hz，6H)、7.62-7.57(m，2H)、7.47(t，J=7.3Hz，3H)、7.41(dt，J=9.5，4.6Hz，6H)、7.10(dd，J=14.4，6.2Hz，6H)、6.99(d，J=7.0Hz，2H)、6.91(d，J=7.3Hz，2H)、6.03(s，1H)以及2.31(s，3H)。碳譜測得以ppm為單位表示的峰位置包括196.0、192.3、178.5、154.7、154.5(d，3JPC=12.4Hz)、139.0(d，1JPC=119.0Hz)、137.5、136.6、136.5(d，4JPC=2.9Hz)、134.8、133.7(d，2JPC=9.9Hz)、133.4、132.3、132.1(d，2JPC=9.7Hz)、131.8(d，4JPC=3.0Hz)、128.8(d，3JPC=12.2Hz)、128.7、127.9、127.7、127.6、127.3、127.2、126.7、126.5、126.2、125.6、70.7(d，1JPC=112.0Hz)以及26.3(d，3JPC=7.5Hz)。磷譜測得以ppm為單位表示的峰位置包括15.7。紅外光譜測得以cm-1為單位表示的峰位置包括2955、1734、1590以及1250。具有式(3’)的萘醌五元稠環化合物的製備方法將於下文的實施例2中闡述。 In the above embodiment,
Figure 111120522-A0305-02-0015-22
The name is 1-(2-oxo-1-(triphenylphosphine)propyl)-3,3a-diphenyl-3ahydro-cyclopentadiene[b]naphthalene-4,9-dione (1-(2-oxo-1-(triphenylphosphoranylidene)propyl)-3,3a-diphenyl-3aH-cyclopenta[b]naphthalene-4,9-dione), whose structure is hereinafter referred to as formula (3'). The molecular formula of the naphthoquinone five-membered fused ring compound with formula (3') is C 46 H 34 O 3 P. The mass-to-charge ratio (m/z) of the molecule with a hydrogen cation measured by mass spectrometry is 665.2243. Orange solid. The melting point is 114°C to 116°C. The R f value measured by chromatography was 0.44, and ethyl acetate was used as the eluent. The peak positions measured in ppm in the hydrogen spectrum include 8.06-8.00 (m, 1H), 7.93-7.87 (m, 1H), 7.66 (dd, J=12.7, 7.6Hz, 6H), 7.62-7.57 (m, 2H), 7.47 (t, J=7.3Hz, 3H), 7.41 (dt, J=9.5, 4.6Hz, 6H), 7.10 (dd, J=14.4, 6.2Hz, 6H), 6.99 (d, J=7.0 Hz, 2H), 6.91 (d, J=7.3Hz, 2H), 6.03 (s, 1H) and 2.31 (s, 3H). The peak positions measured in ppm in the carbon spectrum include 196.0, 192.3, 178.5, 154.7, 154.5 (d, 3 J PC =12.4Hz), 139.0 (d, 1 J PC =119.0Hz), 137.5, 136.6, 136.5 ( d, 4 J PC =2.9Hz), 134.8, 133.7 (d, 2 J PC =9.9Hz), 133.4, 132.3, 132.1 (d, 2 J PC =9.7Hz), 131.8 (d, 4 J PC =3.0Hz ), 128.8 (d, 3 J PC =12.2Hz), 128.7, 127.9, 127.7, 127.6, 127.3, 127.2, 126.7, 126.5, 126.2, 125.6, 70.7 (d, 1 J PC =112.0Hz) and 26.3 (d, 3 J PC =7.5Hz). The phosphorus spectrum measured peak positions expressed in ppm including 15.7. The peak positions measured in the infrared spectrum and expressed in cm -1 units include 2955, 1734, 1590 and 1250. The preparation method of the naphthoquinone five-membered fused ring compound having the formula (3') will be described in Example 2 below.

在一些實施例中，萘醌五元稠環化合物具有以下式(4)的結構：

Figure 111120522-A0305-02-0017-23
。在式(4)中，R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2。R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組。R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組。 In some embodiments, the naphthoquinone five-membered fused ring compound has the structure of the following formula (4):
Figure 111120522-A0305-02-0017-23
. In formula (4), R 1 is selected from the group consisting of hydrogen group, 4-chloro group and 5-chloro group, and n is 1 or 2. R 2 is selected from phenyl, 4-methylphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitro The group consisting of phenyl and 2-naphthyl. R 3 is selected from the group consisting of phenyl, 4-tert-butylphenyl and 4-methylphenyl.

更詳細地說，在一些實施例中，具有式(4)的萘醌五元稠環化合物如下，其中Me為甲基、Ph為苯基、以及tBu為叔丁基：

Figure 111120522-A0305-02-0017-24
Figure 111120522-A0305-02-0018-25
 In more detail, in some embodiments, the naphthoquinone five-membered fused ring compound having formula (4) is as follows, wherein Me is methyl, Ph is phenyl, and tBu is tert-butyl:
Figure 111120522-A0305-02-0017-24
Figure 111120522-A0305-02-0018-25

上述實施例中，

Figure 111120522-A0305-02-0018-26
的名稱為1-甲基-3a-苯基-3-(苯乙炔基)-3a氫-環戊二烯[b]萘-4,9-二酮(1-methyl-3a-phenyl-3-(phenylethynyl)-3aH-cyclopenta[b]naphthalene-4,9-dione)，下文將其結構稱為式(4’)。具有式(4’)的萘醌五元稠環化合物的分子式為C28H18O2，質譜測得分子帶一正電時的質荷比(m/z)為386.1315。黃色固體。熔點為74℃至76℃。層析測得Rf值為0.40，使用體積比為9：1的己烷：乙酸乙酯作為沖提液。氫譜測得以ppm為單位表示的峰位置包括8.08(d，J=7.7Hz，1H)、7.88(d，J=7.0Hz，1H)、7.59-7.53(m，2H)、7.44-7.43(m，2H)、7.34-7.32(m，2H)、7.30-7.29(m，3H)、7.19(t，J=7.7，6.3Hz，2H)、7.16-7.13(m，1H)、6.66(s，1H)以及2.49(s，3H)。碳譜測得以ppm為單位表示的峰位置包括191.7、182.4、155.1、140.2、139.2、138.5、136.7、135.9、135.4、133.6、133.2、131.6、129.0、128.8、128.3、128.2、127.4、126.9、126.1、122.8、101.6、85.4、78.7以及14.8。紅外 光譜測得以cm-1為單位表示的峰位置包括2918、1736、1466以及1181。具有式(4’)的萘醌五元稠環化合物的製備方法將於下文的實施例2中闡述。值得注意的是，實施例2的製備方法不僅可得到具有式(3’)的萘醌五元稠環化合物亦可得到具有式(4’)的萘醌五元稠環化合物。 In the above embodiment,
Figure 111120522-A0305-02-0018-26
The name is 1-methyl-3a-phenyl-3-(phenylethynyl)-3ahydro-cyclopentadiene[b]naphthalene-4,9-dione (1-methyl-3a-phenyl-3- (phenylethynyl)-3aH-cyclopenta[b]naphthalene-4,9-dione), its structure will be referred to as formula (4') below. The molecular formula of the naphthoquinone five-membered fused ring compound with formula (4') is C 28 H 18 O 2 , and the mass-to-charge ratio (m/z) of the molecule when it is positively charged is 386.1315, as measured by mass spectrometry. Yellow solid. The melting point is 74°C to 76°C. The R f value measured by chromatography was 0.40, and hexane:ethyl acetate with a volume ratio of 9:1 was used as the eluent. The peak positions measured in ppm in the hydrogen spectrum include 8.08 (d, J=7.7Hz, 1H), 7.88 (d, J=7.0Hz, 1H), 7.59-7.53 (m, 2H), 7.44-7.43 (m , 2H), 7.34-7.32(m, 2H), 7.30-7.29(m, 3H), 7.19(t, J=7.7, 6.3Hz, 2H), 7.16-7.13(m, 1H), 6.66(s, 1H ) and 2.49(s, 3H). The peak positions measured in ppm in the carbon spectrum include 191.7, 182.4, 155.1, 140.2, 139.2, 138.5, 136.7, 135.9, 135.4, 133.6, 133.2, 131.6, 129.0, 128.8, 128.3, 128.2, 127.4, 126.9, 126.1, 122.8, 101.6, 85.4, 78.7 and 14.8. The peak positions measured in the infrared spectrum and expressed in cm -1 units include 2918, 1736, 1466 and 1181. The preparation method of the naphthoquinone five-membered fused ring compound having the formula (4') will be described in Example 2 below. It is worth noting that the preparation method of Example 2 can not only obtain a naphthoquinone five-membered fused ring compound with formula (3') but also a naphthoquinone five-membered fused ring compound with formula (4').

在一些實施例中，萘醌五元稠環化合物具有以下式(5)的結構：

Figure 111120522-A0305-02-0019-27
。在式(5)中，R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2。R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組。R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組。R4選自由甲基、甲氧基及乙氧基所組成的群組。 In some embodiments, the naphthoquinone five-membered fused ring compound has the structure of the following formula (5):
Figure 111120522-A0305-02-0019-27
. In formula (5), R 1 is selected from the group consisting of hydrogen group, 4-chloro group and 5-chloro group, and n is 1 or 2. R 2 is selected from phenyl, 4-methylphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitro The group consisting of phenyl and 2-naphthyl. R 3 is selected from the group consisting of phenyl, 4-tert-butylphenyl and 4-methylphenyl. R 4 is selected from the group consisting of methyl, methoxy and ethoxy.

更詳細地說，在一些實施例中，具有式(5)的萘醌五元稠環化合物如下，其中Me為甲基、Et為乙基、Ph為苯基以及tBu為叔丁基：

Figure 111120522-A0305-02-0019-28
Figure 111120522-A0305-02-0020-29
Figure 111120522-A0305-02-0021-30
 In more detail, in some embodiments, the naphthoquinone five-membered fused ring compound of formula (5) is as follows, wherein Me is methyl, Et is ethyl, Ph is phenyl, and tBu is tert-butyl:
Figure 111120522-A0305-02-0019-28
Figure 111120522-A0305-02-0020-29
Figure 111120522-A0305-02-0021-30

上述實施例中，

Figure 111120522-A0305-02-0021-31
的名稱為2-(3a-(4-氰基苯基)-4,9-二氧代-3-苯基-3a,9-二氫-4H-環戊二烯[b]萘-1-基)-2-氧代乙酸乙酯(ethyl 2-(3a-(4-cyanophenyl)-4,9-dioxo-3-phenyl-3a,9-dihydro-4H-cyclopenta[b]naphthalen-1-yl)-2-oxoacetate)，下文將其結構稱為式(5’)。具有式(5’)的萘醌五元稠環化合物的分子式為C30H20NO5，質譜測得分子帶一氫正離子時的質荷比(m/z)為474.1336。黃色固體。熔點為214℃至217℃。層析測得Rf值為0.40，使用體積比為9：1的己烷：乙酸乙酯作為沖提液。氫譜測得以ppm為單位表示的峰位置包括7.84(s，1H)、7.99-7.98(m，2H)、7.86-7.83(m，2H)、7.27(dd，J=2，6.8Hz，2H)、7.31-7.27(m，3H)、7.25-7.22(m，2H)、4.24(q，J=7.2Hz 2H)以及1.36(t，J=7.2Hz，3H)。碳譜測得以ppm為單位表示的峰位置包括194.4、176.9、160.4、155.6、148.8、146.6、143.4、143.2、138.0、136.1、132.3、132.2、129.3、129.0、128.7、128.4、124.2、118.0、112.4、 79.3、62.6以及13.9。紅外光譜測得以cm-1為單位表示的峰位置包括2982、1732、1708、1651以及1127。具有式(5’)的萘醌五元稠環化合物的製備方法將於下文的實施例3中闡述。 In the above embodiment,
Figure 111120522-A0305-02-0021-31
The name is 2-(3a-(4-cyanophenyl)-4,9-dioxo-3-phenyl-3a,9-dihydro-4H-cyclopentadiene[b]naphthalene-1- ethyl)-2-oxoacetate (ethyl 2-(3a-(4-cyanophenyl)-4,9-dioxo-3-phenyl-3a,9-dihydro-4H-cyclopenta[b]naphthalen-1-yl )-2-oxoacetate), its structure will be referred to as formula (5') below. The molecular formula of the naphthoquinone five-membered fused ring compound with formula (5') is C 30 H 20 NO 5 , and the mass-to-charge ratio (m/z) of the molecule with a hydrogen cation measured by mass spectrometry is 474.1336. Yellow solid. The melting point is 214°C to 217°C. The R f value measured by chromatography was 0.40, and hexane:ethyl acetate with a volume ratio of 9:1 was used as the eluent. The peak positions measured in ppm in the hydrogen spectrum include 7.84 (s, 1H), 7.99-7.98 (m, 2H), 7.86-7.83 (m, 2H), 7.27 (dd, J=2, 6.8Hz, 2H) , 7.31-7.27(m, 3H), 7.25-7.22(m, 2H), 4.24(q, J=7.2Hz 2H) and 1.36(t, J=7.2Hz, 3H). The peak positions measured in ppm in the carbon spectrum include 194.4, 176.9, 160.4, 155.6, 148.8, 146.6, 143.4, 143.2, 138.0, 136.1, 132.3, 132.2, 129.3, 129.0, 128.7, 128.4, 124.2, 118.0, 112.4、 79.3, 62.6 and 13.9. The peak positions measured in the infrared spectrum and expressed in cm -1 units include 2982, 1732, 1708, 1651 and 1127. The preparation method of the naphthoquinone five-membered fused ring compound having the formula (5') will be described in Example 3 below.

本揭示內容亦提供一種製備上述萘醌五元稠環化合物之方法，方法包括以下操作。混合具有式(A)的結構的1,3-茚滿二酮化合物；具有式(B)的結構的二炔化合物；三芳香基膦或三環己基膦；及第一有機溶劑，以形成混合物。以及在0℃至30℃下反應混合物6小時至24小時。式(A)及式(B)分別如下：

Figure 111120522-A0305-02-0022-32
，
Figure 111120522-A0305-02-0022-33
。在式(A)及式(B)中，R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2。R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組。R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組。R4選自由甲基、甲氧基及乙氧基所組成的群組。本揭示內容提供的新穎的方法使用三芳香基膦或三環己基膦介導二炔化合物與1,3-茚滿二酮化合物進行反麥可加成(Anti-Michael Addition)，得到罕見的[2+3]環化反應，反應條件溫和，產物具高產率，且原料容易取得，符合高的原子經濟性。需注意的是，不同於傳統麥可加成(Michael Addition) 反應在β位置進行加成反應，本揭示內容的反麥可加成反應在α位置進行加成反應。下文詳細說明本揭示內容提供的方法。 The present disclosure also provides a method for preparing the above-mentioned naphthoquinone five-membered fused ring compound, which method includes the following operations. Mixing a 1,3-indanedione compound having a structure of formula (A); a diyne compound having a structure of formula (B); triarylphosphine or tricyclohexylphosphine; and a first organic solvent to form a mixture . and the reaction mixture at 0°C to 30°C for 6 hours to 24 hours. Formula (A) and formula (B) are as follows respectively:
Figure 111120522-A0305-02-0022-32
,
Figure 111120522-A0305-02-0022-33
. In formula (A) and formula (B), R 1 is selected from the group consisting of hydrogen group, 4-chloro group and 5-chloro group, and n is 1 or 2. R 2 is selected from phenyl, 4-methylphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitro The group consisting of phenyl and 2-naphthyl. R 3 is selected from the group consisting of phenyl, 4-tert-butylphenyl and 4-methylphenyl. R 4 is selected from the group consisting of methyl, methoxy and ethoxy. The novel method provided by this disclosure uses triarylphosphine or tricyclohexylphosphine to mediate the Anti-Michael Addition of diyne compounds and 1,3-indanedione compounds to obtain rare [ 2+3] cyclization reaction, the reaction conditions are mild, the product has high yield, and the raw materials are easy to obtain, which is consistent with high atom economy. It should be noted that unlike the traditional Michael Addition reaction, which performs the addition reaction at the β position, the anti-Michael Addition reaction of the present disclosure performs the addition reaction at the α position. The methods provided by this disclosure are described in detail below.

在一些實施例中，為了形成上述具有式(2)的萘醌五元稠環化合物，R4選自由甲氧基及乙氧基所組成的群組，並在0℃至27℃下反應混合物6小時至24小時，混合具有式(A)的結構的1,3-茚滿二酮化合物、具有式(B)的結構的二炔化合物、三環己基膦及第一有機溶劑，以及第一有機溶劑為甲苯、四氫呋喃或其組合。需注意的是，反應溫度高於27℃可能使反應物分解，無法形成產物；反應溫度低於0℃可能使反應活化能過低，亦無法形成產物。 In some embodiments, in order to form the above-mentioned naphthoquinone five-membered fused ring compound having formula (2), R 4 is selected from the group consisting of methoxy and ethoxy, and the reaction mixture is heated at 0°C to 27°C From 6 hours to 24 hours, mix the 1,3-indandione compound having the structure of formula (A), the diyne compound having the structure of formula (B), tricyclohexylphosphine and the first organic solvent, and the first The organic solvent is toluene, tetrahydrofuran or a combination thereof. It should be noted that if the reaction temperature is higher than 27°C, the reactants may decompose and the product cannot be formed; if the reaction temperature is lower than 0°C, the reaction activation energy may be too low and the product cannot be formed.

在一些實施例中，方法更包括將具有式(2)的萘醌五元稠環化合物與間氯過氧苯甲酸及第二有機溶劑混合，並在20℃至30℃下反應30分鐘至1小時，以形成具有上述式(5)的萘醌五元稠環化合物。在一些實施例中，第二有機溶劑為二氯甲烷、四氫呋喃、三氯甲烷、苯或其組合。 In some embodiments, the method further includes mixing the naphthoquinone five-membered fused ring compound of formula (2) with m-chloroperoxybenzoic acid and a second organic solvent, and reacting at 20°C to 30°C for 30 minutes to 1 hours to form a naphthoquinone five-membered fused ring compound having the above formula (5). In some embodiments, the second organic solvent is dichloromethane, tetrahydrofuran, chloroform, benzene, or combinations thereof.

在一些實施例中，為了形成上述具有式(3)的萘醌五元稠環化合物以及上述具有式(4)的萘醌五元稠環化合物，R4為甲基，並在20℃至30℃下反應混合物12小時至24小時，其中三芳香基膦為三苯基膦、三間甲苯基膦、三對甲苯基膦、三對氟苯基膦、三對氯苯基膦、二苯基甲苯基膦或其組合，以及第一有機溶劑為甲苯、四氫呋喃、 1,4-二氧陸圜、二氯甲烷、乙腈、苯或其組合。需注意的是，反應溫度高於30℃可能使反應物分解，無法形成產物；反應溫度低於20℃可能使反應活化能過低，亦無法形成產物。另需注意的是，三芳香基膦進攻上述具有式(B)的二炔化合物的α位置，使形成的碳負離子共振至β位置和/或δ位置，其中位於β位置的共振結構形成具有式(4)的萘醌五元稠環化合物，而位於δ位置的共振結構形成具有式(3)的萘醌五元稠環化合物。 In some embodiments, in order to form the above-mentioned naphthoquinone five-membered fused ring compound with formula (3) and the above-mentioned naphthoquinone five-membered fused ring compound with formula (4), R 4 is methyl, and at 20°C to 30 The reaction mixture is 12 hours to 24 hours at ℃, wherein the triarylphosphine is triphenylphosphine, tri-m-tolylphosphine, tri-p-tolylphosphine, tri-p-fluorophenylphosphine, tri-p-chlorophenylphosphine, diphenyltoluene base phosphine or a combination thereof, and the first organic solvent is toluene, tetrahydrofuran, 1,4-dioxanone, dichloromethane, acetonitrile, benzene or a combination thereof. It should be noted that if the reaction temperature is higher than 30°C, the reactants may decompose and the product cannot be formed; if the reaction temperature is lower than 20°C, the reaction activation energy may be too low and the product cannot be formed. It should also be noted that the triarylphosphine attacks the α position of the above-mentioned diyne compound of formula (B), causing the formed carbanion to resonate to the β position and/or the δ position, wherein the resonance structure at the β position forms a structure with the formula (4) is a naphthoquinone five-membered fused ring compound, and the resonance structure located at the δ position forms a naphthoquinone five-membered fused ring compound having formula (3).

在一些實施例中，方法更包括將具有式(3)的萘醌五元稠環化合物與間氯過氧苯甲酸及第二有機溶劑混合，並在20℃至30℃下反應30分鐘至1小時，以形成具有式(5)的萘醌五元稠環化合物。在一些實施例中，第二有機溶劑為二氯甲烷、四氫呋喃、三氯甲烷、苯或其組合。 In some embodiments, the method further includes mixing the naphthoquinone five-membered fused ring compound of formula (3) with m-chloroperoxybenzoic acid and a second organic solvent, and reacting at 20°C to 30°C for 30 minutes to 1 hours to form a naphthoquinone five-membered fused ring compound of formula (5). In some embodiments, the second organic solvent is dichloromethane, tetrahydrofuran, chloroform, benzene, or combinations thereof.

接下來以實施例1至實施例3詳細說明本揭示內容提供的方法。 Next, Examples 1 to 3 will be used to describe the method provided by this disclosure in detail.

在實施例1中，製備上文所述具有式(2’)的萘醌五元稠環化合物。首先，在氮氣保護的反應試管中加入0.20mmol的2-芳香亞甲基-1,3-茚滿二酮(2-benzylidene-indane-1,3-diones)、0.24mmol的5-苯基戊烷-2,4-二炔甲酸甲酯(methyl 5-phenylpenta-2,4-diynoate)以及10mL的四氫呋喃(Tetrahydrofuran，THF)或是10mL的甲苯(Toluene)。接著，加入0.24mmol的三環己基膦(PCy3)至反應試管中，以形成混合物。然後，將混合物 保持在0℃至27℃之間反應6小時至24小時。反應結束後甲苯以矽膠管柱層析去除，四氫呋喃以減壓旋轉濃縮儀器去除。殘餘物真空濃縮後藉由己烷和乙酸乙酯進行管柱層析以分離混合物，得到87mg具有式(2’)的萘醌五元稠環化合物，產率為62%。具有式(2’)的萘醌五元稠環化合物的詳細物性和化性請參上文。實施例1反應式如下：

Figure 111120522-A0305-02-0025-34
In Example 1, the naphthoquinone five-membered fused ring compound of formula (2') described above was prepared. First, add 0.20 mmol of 2-aromatic methylene-1,3-indanedione (2-benzylidene-indane-1,3-diones) and 0.24 mmol of 5-phenylpentane into a nitrogen-protected reaction tube. Alkane-2,4-diyncarboxylic acid methyl ester (methyl 5-phenylpenta-2,4-diynoate) and 10 mL of tetrahydrofuran (THF) or 10 mL of toluene (Toluene). Next, 0.24 mmol of tricyclohexylphosphine (PCy 3 ) was added to the reaction tube to form a mixture. Then, the mixture was kept between 0°C and 27°C for 6 hours to 24 hours. After the reaction, toluene was removed by silica gel column chromatography, and tetrahydrofuran was removed by a reduced-pressure rotary concentrator. The residue was concentrated in vacuo and then subjected to column chromatography with hexane and ethyl acetate to separate the mixture to obtain 87 mg of a naphthoquinone five-membered fused ring compound of formula (2') with a yield of 62%. Please refer to the above for detailed physical properties and chemical properties of the naphthoquinone five-membered fused ring compound having formula (2'). The reaction formula of Example 1 is as follows:
Figure 111120522-A0305-02-0025-34

在實施例2中，製備上文所述具有式(3’)的萘醌五元稠環化合物以及具有式(4’)的萘醌五元稠環化合物。首先，在氮氣保護的反應試管中加入0.15mmol的2-芳香亞甲基-1,3-茚滿二酮(2-benzylidene-indane-1,3-diones)、0.18mmol的6-苯基己烷-3,5-二炔酮(6-phenylhexa-3,5-diyn-2-one)以及3mL的甲苯(Toluene)。接著，加入0.15mmol的三苯基膦(PPh3)至反應試管中，以形成混合物。然後，將混合物保持在20℃至30℃之間反應12小時至24小時。反應結束後甲苯以矽膠管柱層析去除。殘餘物真空濃縮後藉由己烷和乙酸乙酯進行管柱層析以分離混合物，得到9mg具有式(3’)的萘醌五元稠環化合物以及17mg具有式(4’)的萘醌五元稠環化合物。具有式(3’)的萘醌五元稠環化合物的產率為10%。具有式(4’)的萘醌五元稠環化合物的產率為30%。 具有式(3’)的萘醌五元稠環化合物以及具有式(4’)的萘醌五元稠環化合物的詳細物性和化性請參上文。實施例2反應式如下：

Figure 111120522-A0305-02-0026-35
In Example 2, the naphthoquinone five-membered fused ring compound having the formula (3') and the naphthoquinone five-membered fused ring compound having the formula (4') described above were prepared. First, add 0.15 mmol of 2-aromatic methylene-1,3-indanedione (2-benzylidene-indane-1,3-diones) and 0.18 mmol of 6-phenylhexane into a nitrogen-protected reaction tube. Alkane-3,5-diynone (6-phenylhexa-3,5-diyn-2-one) and 3 mL of toluene. Next, 0.15 mmol of triphenylphosphine (PPh 3 ) was added to the reaction tube to form a mixture. Then, the mixture was kept at 20°C to 30°C for 12 hours to 24 hours. After the reaction, toluene was removed by silica gel column chromatography. The residue was concentrated in vacuo and subjected to column chromatography with hexane and ethyl acetate to separate the mixture to obtain 9 mg of a five-membered naphthoquinone fused ring compound of formula (3') and 17 mg of a five-membered naphthoquinone of formula (4'). Fused ring compounds. The yield of naphthoquinone five-membered fused ring compound having formula (3') is 10%. The yield of naphthoquinone five-membered fused ring compound having formula (4') is 30%. Please refer to the above for detailed physical and chemical properties of the naphthoquinone five-membered fused ring compound having the formula (3') and the naphthoquinone five-membered fused ring compound having the formula (4'). The reaction formula of Example 2 is as follows:
Figure 111120522-A0305-02-0026-35

在實施例3中，製備上文所述具有式(5’)的萘醌五元稠環化合物。首先，溫度保持在20℃至30℃之間，在氮氣保護的反應試管中加入20mL的二氯甲烷(Dichloromethane，DCM)以及0.014mmol的式(2”)，式(2”)結構如下，為具有式(2)的結構的萘醌五元稠環化合物。接著，通過注射器緩慢滴加0.034mmol間氯過氧苯甲酸(meta-Chloroperoxybenzoic acid，m-CPBA)與10mL的二氯甲烷的混合液於反應試管中，並攪拌30分鐘到1小時以進行反應。反應完成之後，將混合物用飽和碳酸氫鈉(NaHCO3)淬滅反應並攪拌30分鐘使反應完全終止。然後，使用3mL的二氯甲烷進行萃取三次，以及用硫酸鈉進行乾燥。二氯甲烷以減壓旋轉濃縮儀器去除之後，將所得固體重新溶解在2mL的氯仿中，並用6mL的正己烷沉澱，然後透過離心機進行沉降，重覆3次，得到6mg具有式(5’)的萘醌五元稠環化合物，產率為89%。具有式(5’)的萘醌五元稠環化合物的詳細物性和化性請參上文。實施例3反應式如下：

Figure 111120522-A0305-02-0027-36
In Example 3, the naphthoquinone five-membered fused ring compound of formula (5') described above was prepared. First, the temperature is maintained between 20°C and 30°C, and 20 mL of dichloromethane (DCM) and 0.014 mmol of formula (2”) are added to a nitrogen-protected reaction tube. The structure of formula (2”) is as follows: A naphthoquinone five-membered fused ring compound having a structure of formula (2). Then, a mixture of 0.034 mmol meta-Chloroperoxybenzoic acid (m-CPBA) and 10 mL of dichloromethane was slowly added dropwise through a syringe into the reaction tube, and stirred for 30 minutes to 1 hour to proceed with the reaction. After the reaction was completed, the mixture was quenched with saturated sodium bicarbonate (NaHCO 3 ) and stirred for 30 minutes to completely terminate the reaction. Then, extraction was performed three times with 3 mL of methylene chloride, and dried with sodium sulfate. After the methylene chloride was removed by a reduced-pressure rotary concentrator, the solid obtained was redissolved in 2 mL of chloroform, precipitated with 6 mL of n-hexane, and then sedimented through a centrifuge. Repeated three times to obtain 6 mg of formula (5') Naphthoquinone five-membered fused ring compound, the yield was 89%. Please refer to the above for detailed physical properties and chemical properties of the naphthoquinone five-membered fused ring compound having the formula (5'). The reaction formula of Example 3 is as follows:
Figure 111120522-A0305-02-0027-36

本揭示內容提供的新穎的萘醌五元稠環化合物，具良好的官能基耐受性，可在多個官能基位置上做後續應用，因此不論在工業或醫藥上都極具潛力，例如作為原料應用於醫藥(如抗腫瘤藥物)、農藥、染料或顏料、殺菌劑、橡膠或樹酯(如聚合調節劑)、感光材料或熱敏紀錄材料等。而本揭示內容提供的新穎的製備萘醌五元稠環化合物的方法，使用三芳香基膦或三環己基膦介導二炔化合物與1,3-茚滿二酮化合物進行反麥可加成以得到罕見的[2+3]環化反應，作為產物的萘醌五元稠環化合物的產率高達78%。多種三芳香基膦的使用亦提升合成的多樣性，而且過程無需使用重金屬，成本降低亦避免可能的重金屬殘留。此外，由於反應物的容易取得以及反應方式具備高的原子經濟性，使成本降低的同時亦減少對環境造成的污染。 The novel naphthoquinone five-membered fused ring compound provided by this disclosure has good functional group tolerance and can be used for subsequent applications at multiple functional group positions. Therefore, it has great potential in industry and medicine, such as as a Raw materials are used in medicines (such as anti-tumor drugs), pesticides, dyes or pigments, fungicides, rubber or resins (such as polymerization regulators), photosensitive materials or heat-sensitive recording materials, etc. The novel method for preparing naphthoquinone five-membered fused ring compounds provided by this disclosure uses triarylphosphine or tricyclohexylphosphine to mediate the trans-Micable addition of diyne compounds and 1,3-indandione compounds. To obtain a rare [2+3] cyclization reaction, the yield of naphthoquinone five-membered fused ring compound as the product is as high as 78%. The use of a variety of triarylphosphines also enhances the diversity of synthesis, and the process does not require the use of heavy metals, reducing costs and avoiding possible heavy metal residues. In addition, due to the easy availability of reactants and the high atom economy of the reaction method, the cost is reduced and the pollution to the environment is reduced.

本文概述一些實施例的特徵，使領域中的通常知識者可更好地了解當前揭露的方面。領域中的通常知識者應認知到他們可隨時利用本揭示內容作為設計或修改其他流程和結構的基礎，以實現相同的目的和/或實現此處介紹的實施例的相同優勢。領域中的通常知識者還應認知到這種等價建構不會偏離本揭示內容的精神和範圍，他們可在不偏離本揭示內容的精神和範圍下在此進行各種改變、替換 和修改。 This article summarizes features of some embodiments to enable those of ordinary skill in the art to better understand the aspects currently disclosed. Those of ordinary skill in the art should recognize that they may readily utilize the present disclosure as a basis for designing or modifying other processes and structures for carrying out the same purposes and/or achieving the same advantages of the embodiments introduced herein. Those with ordinary knowledge in the field should also realize that such equivalent constructions will not deviate from the spirit and scope of the disclosure, and they can make various changes and substitutions here without departing from the spirit and scope of the disclosure. and modifications.

Claims (12)

一種萘醌五元稠環化合物，具有以下式(1)的結構：
Figure 111120522-A0305-02-0029-37
 其中R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2；R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組；X選自由*-R3及
Figure 111120522-A0305-02-0029-38
所組成的群組，其中*表示連接鍵，以及R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組；以及Y選自由*-CH3、
Figure 111120522-A0305-02-0029-40
及
Figure 111120522-A0305-02-0029-41
所組成的群組，其中*表示連接鍵，R4選自由甲基、甲氧基及乙氧基所組成的群組，以及PAr3選自由三環己基膦基、三苯基膦基、三間甲苯基膦基、三對甲苯基膦基、三對氟苯基膦基、三對氯苯基膦基及二苯基甲苯基膦基所組成的群組。 A naphthoquinone five-membered fused ring compound has the structure of the following formula (1):
Figure 111120522-A0305-02-0029-37
 Wherein R 1 is selected from the group consisting of hydrogen group, 4-chloro group and 5-chloro group, n is 1 or 2; R 2 is selected from the group consisting of phenyl, 4-methylphenyl and 3-methoxyphenyl , the group consisting of 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitrophenyl and 2-naphthyl; X is selected from * -R 3 and
Figure 111120522-A0305-02-0029-38
The group consisting of, where * represents a connecting bond, and R 3 is selected from the group consisting of phenyl, 4-tert-butylphenyl and 4-methylphenyl; and Y is selected from the group consisting of * -CH 3 ,
Figure 111120522-A0305-02-0029-40
and
Figure 111120522-A0305-02-0029-41
The group consisting of, where * represents a linking bond, R 4 is selected from the group consisting of methyl, methoxy and ethoxy, and PAr 3 is selected from the group consisting of tricyclohexylphosphine, triphenylphosphine, tri- The group consisting of tolylphosphine group, tri-p-tolylphosphine group, tri-p-fluorophenylphosphine group, tri-p-chlorophenylphosphine group and diphenyltolylphosphine group. 如請求項1所述之萘醌五元稠環化合物，具 有以下式(2)的結構：
Figure 111120522-A0305-02-0030-42
 其中R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2；R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組；R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組；R4選自由甲氧基及乙氧基所組成的群組；以及PAr3為三環己基膦基。 The naphthoquinone five-membered fused ring compound described in claim 1 has the structure of the following formula (2):
Figure 111120522-A0305-02-0030-42
 Wherein R 1 is selected from the group consisting of hydrogen group, 4-chloro group and 5-chloro group, n is 1 or 2; R 2 is selected from the group consisting of phenyl, 4-methylphenyl and 3-methoxyphenyl , the group consisting of 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitrophenyl and 2-naphthyl; R 3 is selected from phenyl, R 4 is selected from the group consisting of 4-tert-butylphenyl and 4-methylphenyl; R 4 is selected from the group consisting of methoxy and ethoxy; and PAr 3 is tricyclohexylphosphine. 如請求項1所述之萘醌五元稠環化合物，具有以下式(3)的結構：
Figure 111120522-A0305-02-0030-43
 其中R1選自由氫基、4-氯基及5-氯基所組成的群組，n 為1或2；R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組；R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組；以及PAr3選自由三苯基膦基、三間甲苯基膦基、三對甲苯基膦基、三對氟苯基膦基、三對氯苯基膦基及二苯基甲苯基膦基所組成的群組。 The naphthoquinone five-membered fused ring compound described in claim 1 has the structure of the following formula (3):
Figure 111120522-A0305-02-0030-43
 Wherein R 1 is selected from the group consisting of hydrogen, 4-chloro and 5-chloro, n is 1 or 2; R 2 is selected from phenyl, 4-methylphenyl and 3-methoxyphenyl , the group consisting of 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitrophenyl and 2-naphthyl; R 3 is selected from phenyl, the group consisting of 4-tert-butylphenyl and 4-methylphenyl; and PAr 3 is selected from the group consisting of triphenylphosphine, tri-m-tolylphosphine, tri-p-tolylphosphine, and tri-p-fluorophenylphosphine A group consisting of tri-p-chlorophenylphosphine group and diphenyltolylphosphine group. 如請求項1所述之萘醌五元稠環化合物，具有以下式(4)的結構：
Figure 111120522-A0305-02-0031-44
 其中R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2；R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組；以及R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組。 The naphthoquinone five-membered fused ring compound described in claim 1 has the structure of the following formula (4):
Figure 111120522-A0305-02-0031-44
 Wherein R 1 is selected from the group consisting of hydrogen group, 4-chloro group and 5-chloro group, n is 1 or 2; R 2 is selected from the group consisting of phenyl, 4-methylphenyl and 3-methoxyphenyl , the group consisting of 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitrophenyl and 2-naphthyl; and R 3 is selected from phenyl , the group consisting of 4-tert-butylphenyl and 4-methylphenyl. 如請求項1所述之萘醌五元稠環化合物，具有以下式(5)的結構：
Figure 111120522-A0305-02-0032-45
 其中R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2；R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組；R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組；以及R4選自由甲基、甲氧基及乙氧基所組成的群組。 The naphthoquinone five-membered fused ring compound described in claim 1 has the structure of the following formula (5):
Figure 111120522-A0305-02-0032-45
 Wherein R 1 is selected from the group consisting of hydrogen group, 4-chloro group and 5-chloro group, n is 1 or 2; R 2 is selected from the group consisting of phenyl, 4-methylphenyl and 3-methoxyphenyl , the group consisting of 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitrophenyl and 2-naphthyl; R 3 is selected from phenyl, 4-tert-butylphenyl and 4-methylphenyl; and R 4 is selected from the group consisting of methyl, methoxy and ethoxy. 一種製備萘醌五元稠環化合物之方法，包括：混合具有以下式(A)的結構的1,3-茚滿二酮化合物；具有以下式(B)的結構的二炔化合物；三芳香基膦或三環己基膦；及一第一有機溶劑，以形成一混合物：
Figure 111120522-A0305-02-0032-46
 其中R1選自由氫基、4-氯基及5-氯基所組成的群組，n為1或2；R2選自由苯基、4-甲基苯基、3-甲氧基苯基、4-氟苯基、4-氯苯基、4-溴苯基、4-氰基苯基、4-硝基苯基及2-萘基所組成的群組；R3選自由苯基、4-叔丁基苯基及4-甲基苯基所組成的群組；R4選自由甲基、甲氧基及乙氧基所組成的群組；以及在0℃至30℃下反應該混合物6小時至24小時。 A method for preparing a naphthoquinone five-membered fused ring compound, including: mixing a 1,3-indanedione compound with a structure of the following formula (A); a diyne compound with a structure of the following formula (B); triaryl phosphine or tricyclohexylphosphine; and a first organic solvent to form a mixture:
Figure 111120522-A0305-02-0032-46
 Wherein R 1 is selected from the group consisting of hydrogen group, 4-chloro group and 5-chloro group, n is 1 or 2; R 2 is selected from the group consisting of phenyl, 4-methylphenyl and 3-methoxyphenyl , the group consisting of 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-cyanophenyl, 4-nitrophenyl and 2-naphthyl; R 3 is selected from phenyl, The group consisting of 4-tert-butylphenyl and 4-methylphenyl; R 4 is selected from the group consisting of methyl, methoxy and ethoxy; and the reaction is performed at 0°C to 30°C Mix for 6 hours to 24 hours. 如請求項6所述之方法，其中R4選自由該甲氧基及該乙氧基所組成的群組，並在0℃至27℃下反應該混合物6小時至24小時。 The method of claim 6, wherein R 4 is selected from the group consisting of the methoxy group and the ethoxy group, and the mixture is reacted at 0°C to 27°C for 6 hours to 24 hours. 如請求項7所述之方法，其中當混合具有該式(A)的結構的1,3-茚滿二酮化合物、具有該式(B)的結構的二炔化合物、該三環己基膦及該第一有機溶劑時，以及該第一有機溶劑為甲苯、四氫呋喃或其組合時，形成如請求項2所述之具有式(2)的萘醌五元稠環化合物。 The method of claim 7, wherein when mixing the 1,3-indanedione compound having the structure of formula (A), the diyne compound having the structure of formula (B), the tricyclohexylphosphine and When the first organic solvent is used, and when the first organic solvent is toluene, tetrahydrofuran or a combination thereof, a naphthoquinone five-membered fused ring compound having formula (2) as described in claim 2 is formed. 如請求項8所述之方法，更包括將具有式(2)的萘醌五元稠環化合物與間氯過氧苯甲酸及一第二有機溶劑混合，並在20℃至30℃下反應30分鐘至1小時，以形成如請求項5所述之具有式(5)的萘醌五元稠環化合物。 The method as described in claim 8, further comprising mixing the naphthoquinone five-membered fused ring compound of formula (2) with m-chloroperoxybenzoic acid and a second organic solvent, and reacting at 20°C to 30°C for 30 minutes to 1 hour to form the naphthoquinone five-membered fused ring compound of formula (5) as described in claim 5. 如請求項6所述之方法，其中R4為該甲基，並在20℃至30℃下反應該混合物12小時至24小時。 The method of claim 6, wherein R 4 is methyl, and the mixture is reacted at 20°C to 30°C for 12 hours to 24 hours. 如請求項10所述之方法，其中該三芳香基膦為三苯基膦、三間甲苯基膦、三對甲苯基膦、三對氟苯基膦、三對氯苯基膦、二苯基甲苯基膦或其組合，以及該第一有機溶劑為甲苯、四氫呋喃、1,4-二氧陸圜、二氯甲烷、乙腈、苯或其組合，以形成如請求項3及請求項4所述之具有式(3)的萘醌五元稠環化合物及具有式(4)的萘醌五元稠環化合物。 The method according to claim 10, wherein the triarylphosphine is triphenylphosphine, tri-m-tolylphosphine, tri-p-tolylphosphine, tri-p-fluorophenylphosphine, tri-p-chlorophenylphosphine, diphenyltoluene base phosphine or a combination thereof, and the first organic solvent is toluene, tetrahydrofuran, 1,4-dioxanone, methylene chloride, acetonitrile, benzene or a combination thereof, to form a solution as described in claim 3 and claim 4 A naphthoquinone five-membered fused ring compound having the formula (3) and a naphthoquinone five-membered fused ring compound having the formula (4). 如請求項11所述之方法，更包括將具有式(3)的萘醌五元稠環化合物與間氯過氧苯甲酸及一第二有機溶劑混合，並在20℃至30℃下反應30分鐘至1小時，以形成如請求項5所述之具有式(5)的萘醌五元稠環化合物。The method as described in claim 11, further comprising mixing the naphthoquinone five-membered fused ring compound of formula (3) with m-chloroperoxybenzoic acid and a second organic solvent, and reacting at 20°C to 30°C for 30 minutes to 1 hour to form the naphthoquinone five-membered fused ring compound of formula (5) as described in claim 5.
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