TWI777478B - The method of making 4-azapyrene compounds - Google Patents

Abstract

The invention is a method of making 4-azapyrene compounds. This method constitutes a palladium-catalyzed dehydrogenative annulation of N-acyl-2-aminobiaryls with in situ 1,3-diynes as a key step, giving substituted phenanthrenes via a rollover C-H bond activation, followed by Bischler–Napieralski cyclization to produce the 4-azapyrene compounds.

Description

製備4-氮雜芘化合物之方法Method for preparing 4-azapyrene compound

本發明係有關於一種製備4-氮雜芘化合物之方法。The present invention relates to a method for preparing 4-azapyrene compounds.

含有單陽離子和雙陽離子的氮雜芘（Azapyrenes）及其異構體類似物（isomeric analogues）表現出令人感興趣的藥理特性和生物學活性，例如抗病毒、抗菌和抗癌活性。然而，先前的1-氮雜、2-氮雜和4-氮雜芘的合成依賴常規的多步驟有機合成，並且這些氮雜芘通常在370和390nm處顯示出兩種不同的螢光發射。Azapyrenes and their isomeric analogues containing mono- and di-cations exhibit interesting pharmacological properties and biological activities, such as antiviral, antibacterial and anticancer activities. However, previous syntheses of 1-aza, 2-aza, and 4-azapyrene have relied on conventional multi-step organic synthesis, and these azapyrenes typically show two distinct fluorescence emissions at 370 and 390 nm.

此外，菲（phenanthrenes）是合成複雜分子或天然產物的重要合成基石，研發菲合成方法一直依賴於光化學合成、鈀催化芳基鹵化物（aryl halides）的偶聯以及鈀催化2-苯基苯甲酸（2-phenylbenzoic acids）與炔烴（alkynes）的脫羧偶聯，如下方化學反應1所示：

化學反應1：先前合成菲係藉由內部炔烴透過C-H和C-C鍵活化的環化反應 In addition, phenanthrenes are important synthetic building blocks for the synthesis of complex molecules or natural products. The development of phenanthrene synthesis methods has always relied on photochemical synthesis, palladium-catalyzed coupling of aryl halides and palladium-catalyzed 2-phenylbenzene. Decarboxylation coupling of formic acid (2-phenylbenzoic acids) with alkynes, as shown in chemical reaction 1 below:

Chemical Reaction 1: Previously synthesized phenanthrene cyclization via internal alkyne activation through CH and CC bonds

N-（9, 10-二苯菲基-4-基）乙酰胺（N-(9,10-diphenylphenanthren-4-yl)acetamide）曾被報導為N-醯基2-氨基聯苯（N-acyl 2-aminobiphenyl）與二苯乙炔（diphenylacetylene）在鈀催化下通過雙C-H鍵活化反應的副產物（＜6％）。此外，由Glaser-Hay反應製備的1,3-二炔（1,3-diynes）係廣泛用於製備各種芳烴和雜芳烴。 Glorius et al. （D.-G. Yu, F. de Azambuja, T. Gensch, C. G. Daniliuc, F. Glorius, Angew . Chem. Int. Ed.2014, 53, 9650-9654.）首次揭示透過C-H鍵活化，以1,3-二炔及銠催化苯甲酰胺（benzamides）的區域選擇性環化反應，可用於合成多種多取代的雙環雜環（bisheterocycles），如下方化學反應2所示：

化學反應2：1,3-二炔高度選擇性環化生成雙環雜環 N-(9,10-diphenylphenanthren-4-yl)acetamide (N-(9,10-diphenylphenanthren-4-yl)acetamide) has been reported as acyl 2-aminobiphenyl) and diphenylacetylene by palladium catalyzed by double-CH bond activation by-product (<6%). In addition, 1,3-diynes (1,3-diynes) prepared by the Glaser-Hay reaction are widely used in the preparation of various aromatic and heteroaromatic hydrocarbons. Glorius et al. (D.-G. Yu, F. de Azambuja, T. Gensch, CG Daniliuc, F. Glorius, Angew . Chem. Int. Ed. 2014, 53, 9650-9654.) revealed for the first time that through the CH bond Activated, 1,3-diyne and rhodium catalyzed regioselective cyclization of benzamides, which can be used to synthesize a variety of polysubstituted bicyclic heterocycles (bisheterocycles), as shown in chemical reaction 2 below:

Chemical Reaction 2: Highly Selective Cyclization of 1,3-Diynes to Bicyclic Heterocycles

然而，若使用習知常規的多步驟有機合成將是耗費時間及成本的，本發明係為提供一種更有效且更便宜的合成方法。However, if conventional multi-step organic synthesis would be time-consuming and cost-intensive, the present invention aims to provide a more efficient and less expensive synthesis method.

發明人發現取代性4-氮雜芘（substituted 4-azapyrenes）的光物理性質，促使發明人開始研究透過將2-氨基聯芳基（2-aminobiaryls）與炔（alkynes）環合產生菲，然後進行Bischler-Napieralski環化反應來合成4-氮雜芘的可行性。這種方法需要有效的C-H鍵翻轉激活，由於在鈀環（palladacycle）中存在固有強Pd（II）-N鍵，因此之前被認為在2-氨基聯芳基作為基質的情況下是無法實現的，如下方化學反應3所示：。

化學反應3：烯基-鈀翻轉金屬化進行環化 The inventors discovered the photophysical properties of substituted 4-azapyrenes, which prompted the inventors to study the generation of phenanthrenes by cyclization of 2-aminobiaryls with alkynes, and then Feasibility of performing Bischler-Napieralski cyclization to synthesize 4-azapyrene. This approach requires efficient C-H bond inversion activation, which was previously thought to be unachievable with 2-aminobiaryl as a substrate due to the inherently strong Pd(II)-N bond in the palladium cycle. , as shown in chemical reaction 3 below: .

Reaction 3: Alkenyl-palladium flip metallation for cyclization

然而，經過發明人長期努力研究下，發現1,3-二炔可以成為進行π-擴展環化（π-extended annulation）的合適偶聯化合物，即能在可靠且直接的催化體系下生產菲。接著再以三氯氧磷（POCl ₃）處理菲進行Bischler–Napieralski反應，透過分子內親電芳族取代反應生成雙發射和深藍/綠色螢光取代性4-氮雜芘。 However, after long-term efforts of the inventors, it was found that 1,3-diynes can be suitable coupling compounds for π-extended annulation, that is, phenanthrene can be produced under a reliable and direct catalytic system. The phenanthrene was then treated with phosphorus oxychloride (POCl ₃ ) to carry out the Bischler–Napieralski reaction, and the substituted 4-azapyrene with double emission and dark blue/green fluorescence was generated through the intramolecular electrophilic aromatic substitution reaction.

因此，本發明之主要目的在於提供一種方法，以能更加有效率地合成4-氮雜芘，透過以鈀催化的N-醯基-2-氨基聯芳基的脫氫與原位1,3-二炔進行環化反應，再透過側翻碳氫鍵活化生成取代菲，然後進行Bischler-Napieralski環化以產生4-氮雜芘。Therefore, the main object of the present invention is to provide a method to more efficiently synthesize 4-azapyrene through palladium-catalyzed dehydrogenation of N-acyl-2-aminobiaryl and in situ 1,3 -Diynes undergo cyclization, which is then activated by rollover carbon-hydrogen bonds to generate substituted phenanthrenes, followed by Bischler-Napieralski cyclization to generate 4-azapyrene.

因此，本發明揭露一種製備4-氮雜芘化合物之方法，包括a）將N-醯基-2-氨基聯芳基（N-acyl 2-aminobiaryls）及1,3-二炔（1,3-diynes）化合物置於包含鈀金屬催化劑之反應環境中，並於一特定溫度下進行反應產生取代菲（substituted phenanthrene）；以及b）將該取代菲與三氯氧磷（POCl ₃）反應，以獲得該4-氮雜芘（4-azapyrene）。藉此，本發明僅需簡單的反應步驟，即可得到4-氮雜芘化合物。其中該4-氮雜芘化合物之化學結構如下：

R ¹包括：H、烷基、環烷基、鹵素或烷氧基； R ²包括：H、烷基、環烷基、鹵素、烷氧基或硝基；R包括：具取代的芳香基、雜環芳香基、鹵素、烷基或環烷基。於一實施例中，R之結構式包括：

其中，R ³係選自下列之一者：H、F 、CH ₃、OMe、 ^t Bu及 ⁿ Bu；R ⁴係選自下列之一者：H、F； R ⁵為選自下列之一者：C(CH ₃) ₂OH、環丙基（cyclopropyl）、環戊基（cyclopentyl）、環己基（cyclohexyl）、正戊基（ n-pentyl）、正己基（ n-hexyl）、正辛基（ n-octyl）及正癸基（ n-decyl）。 Therefore, the present invention discloses a method for preparing 4-azapyrene compounds, comprising a) combining N-acyl 2-aminobiaryls and 1,3-diynes (1,3 -diynes) compound is placed in a reaction environment comprising a palladium metal catalyst and reacted at a specific temperature to produce substituted phenanthrene; and b) the substituted phenanthrene is reacted with phosphorus oxychloride (POCl ₃ ) to obtain This 4-azapyrene was obtained. Thereby, the present invention only needs a simple reaction step to obtain the 4-azapyrene compound. The chemical structure of the 4-azapyrene compound is as follows:

R ¹ includes: H, alkyl, cycloalkyl, halogen or alkoxy; R ² includes: H, alkyl, cycloalkyl, halogen, alkoxy or nitro; R includes: substituted aryl, Heterocyclic aryl, halogen, alkyl or cycloalkyl. In one embodiment, the structural formula of R includes:

Wherein, R ³ is selected from one of the following: H, F, CH ₃ , OMe, ^t Bu and ⁿ Bu; R ⁴ is selected from one of the following: H, F; R ⁵ is selected from one of the following : C(CH ₃ ) ₂ OH, cyclopropyl (cyclopropyl), cyclopentyl (cyclopentyl), cyclohexyl (cyclohexyl), n-pentyl ( n -pentyl), n-hexyl ( n -hexyl), n-octyl ( n -octyl) and n-decyl ( n -decyl).

在一實施例中，其中該鈀金屬催化劑為乙酸鈀（Pd(OAc) ₂），該特定溫度為120℃。 In one embodiment, wherein the palladium metal catalyst is palladium acetate (Pd(OAc) ₂ ), and the specific temperature is 120°C.

在一實施例中，其中該1,3-二炔化合物係由下列化合物之一者所形成：末端芳基炔烴（terminal arylalkynes）化合物、脂族炔烴（aliphatic alkynes）化合物及5-苯基-2,4-戊二炔酸甲酯(Methyl 5-phenyl-2,4-pentadiynoate)，其中該5-苯基-2,4-戊二炔酸甲酯之結構式如下

。 In one embodiment, wherein the 1,3-diyne compound is formed from one of the following compounds: terminal arylalkynes, aliphatic alkynes, and 5-phenyl -Methyl 5-phenyl-2,4-pentadiynoate (Methyl 5-phenyl-2,4-pentadiynoate), wherein the structural formula of the methyl 5-phenyl-2,4-pentadiynoate is as follows

.

在一實施例中，其中該N-醯基-2-氨基聯芳基之結構包括：

。 In one embodiment, wherein the structure of the N-acyl-2-aminobiaryl group includes:

.

在一實施例中，其中該N-醯基-2-氨基聯芳基之結構包括：

其中，R ¹為選自下列之一者：H、F、Me；R ²為選自下列之一者：H、OMe、Me、NO ₂。 In one embodiment, wherein the structure of the N-acyl-2-aminobiaryl group includes:

Wherein, R ¹ is one selected from the following: H, F, Me; R ² is one selected from the following: H, OMe, Me, NO ₂ .

在一實施例中，其中該末端芳基炔烴化合物之結構式如下：

其中，R ³為選自下列之一者：H、F、Me、 ^tBu、OCH ₃及 ⁿBu；R ⁴為選自下列之一者：H及F。 In one embodiment, the structural formula of the terminal aryl alkyne compound is as follows:

Wherein, R ³ is one selected from the following: H, F, Me, ^t Bu, OCH ₃ and ⁿ Bu; R ⁴ is one selected from the following: H and F.

在一實施例中，其中該脂族炔烴化合物之結構式如下：

其中，R ⁵為選自下列之一者：C(CH ₃) ₂OH、環丙基（cyclopropyl）、環戊基（cyclopentyl）、環己基（cyclohexyl）、正戊基（ n-pentyl）、正己基（ n-hexyl）、正辛基（ n-octyl）及正癸基（ n-decyl）。 In one embodiment, the structural formula of the aliphatic alkyne compound is as follows:

Wherein, R ⁵ is one selected from the following: C(CH ₃ ) ₂ OH, cyclopropyl (cyclopropyl), cyclopentyl (cyclopentyl), cyclohexyl (cyclohexyl), n-pentyl ( n -pentyl), n-hexyl base ( n -hexyl), n-octyl ( n -octyl) and n-decyl ( n -decyl).

在一實施例中，其中該反應環境中包括含有氧化劑、溶劑及添加劑，該氧化劑為乙酸銅（Cu(OAc) ₂），該溶劑為二甲基甲醯胺（DMF），該添加劑為丙酸（propionic acid）。 In one embodiment, the reaction environment includes an oxidant, a solvent and an additive, the oxidant is copper acetate (Cu(OAc) ₂ ), the solvent is dimethylformamide (DMF), and the additive is propionic acid (propionic acid).

在一實施例中，其中該反應環境中包括含有氧化劑、溶劑及添加劑，該氧化劑為乙酸銅（Cu(OAc) ₂），該溶劑為二甲基甲醯胺（DMF），該添加劑為乙酸鋰（LiOAc）。 In one embodiment, the reaction environment includes an oxidant, a solvent and an additive, the oxidant is copper acetate (Cu(OAc) ₂ ), the solvent is dimethylformamide (DMF), and the additive is lithium acetate (LiOAc).

在一實施例中，更包括加入一強酸與該取代菲或該4-氮雜芘反應，以產生π延伸4-氮雜芘（π-extended 4-azapyrene）。In one embodiment, the method further comprises adding a strong acid to react with the substituted phenanthrene or the 4-azapyrene to generate a π-extended 4-azapyrene (π-extended 4-azapyrene).

在一實施例中，其中該強酸包括三氟甲磺酸（triflic acid）。In one embodiment, wherein the strong acid comprises triflic acid.

綜上所述，本發明將以特定實施例詳述於下。以下實施例僅為舉例之用，而非限定本發明之保護範圍。熟諳此技藝者，將可輕易理解各種非關鍵參數，其可改變或調整而產生實質相同的結果。In summary, the present invention will be described in detail below with specific embodiments. The following examples are for illustrative purposes only, and are not intended to limit the protection scope of the present invention. Those skilled in the art will readily understand that various non-critical parameters can be varied or adjusted to produce substantially the same results.

本發明係提供一種製備4-氮雜芘之方法，包括a）將N-醯基-2-氨基聯芳基（N-acyl 2-aminobiaryls）及1,3-二炔（1,3-diynes）化合物置於包含鈀金屬催化劑之反應環境中，並於一特定溫度下進行反應產生取代菲（substituted phenanthrene）；以及b）將該取代菲與三氯氧磷（POCl ₃）反應，以獲得該4-氮雜芘（4-azapyrene）。藉此，本發明僅需簡單的反應步驟，即可得到4-氮雜芘。藉此，本發明能透過簡易反應而更加有效率地合成4-氮雜芘。以下將對本發明進行詳細的說明。 The present invention provides a method for preparing 4-azapyrene, comprising a) combining N-acyl-2-aminobiaryls (N-acyl 2-aminobiaryls) and 1,3-diynes (1,3-diynes). ) the compound is placed in a reaction environment comprising a palladium metal catalyst and reacted at a specific temperature to produce substituted phenanthrene; and b) the substituted phenanthrene is reacted with phosphorus oxychloride (POCl ₃ ) to obtain the substituted phenanthrene 4-Azapyrene (4-azapyrene). Thereby, the present invention only needs a simple reaction step to obtain 4-azapyrene. Thereby, the present invention can more efficiently synthesize 4-azapyrene through a simple reaction. The present invention will be described in detail below.

合成取代菲（substituted phenanthrenes）化合物：Synthesis of substituted phenanthrenes:

將0.1 mmol 的N-醯基2-氨基聯苯（N-acyl-2-aminobiphenyls）1a、0.01 mmol, 2.24 mg 的乙酸鈀（Pd(OAc) ₂）、0.2 mmol 的乙酸銅（Cu(OAc) ₂）、1.0 mmol的丙酸（propionic acid）或0.1 mmol的乙酸鋰（LiOAc）、0.6 mmol的苯乙炔（phenylacetylene）2a和攪拌子放入乾燥的反應管中，然後，加入新鮮蒸餾的4 mL二甲基甲醯胺（DMF）。 添加完成後，將反應混合物用氧氣（O ₂）吹洗5分鐘，並用螺帽密封，在劇烈攪拌下將其置於120℃的油浴中24小時。 反應完成後，將反應混合物冷卻至室溫，並用乙酸乙酯（ethyl acetate）稀釋，然後通過矽藻土（Celite）薄墊過濾。該過濾物以真空濃縮並通過矽膠柱色譜法（己烷/乙酸乙酯）純化，得到N-(9-苯基-10-(苯基乙炔基)菲基-4-基)乙酰胺（N-(9-phenyl-10-(phenylethynyl)phenanthren-4-yl)acetamide）3a，此條件下的產率為86%，請見下段的表1的項目14。

0.1 mmol of N-acyl-2-aminobiphenyls (N-acyl-2-aminobiphenyls) 1a, 0.01 mmol, 2.24 mg of palladium acetate (Pd(OAc) ₂ ), 0.2 mmol of copper acetate (Cu(OAc) ₂ ), 1.0 mmol of propionic acid (propionic acid) or 0.1 mmol of lithium acetate (LiOAc), 0.6 mmol of phenylacetylene 2a, and a stirrer were placed in a dry reaction tube, and then, 4 mL of freshly distilled Dimethylformamide (DMF). After the addition was complete, the reaction mixture was purged with oxygen ( _O2 ) for 5 minutes, sealed with a screw cap, and placed in an oil bath at 120 °C for 24 hours with vigorous stirring. After the reaction was complete, the reaction mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a thin pad of Celite. The filtrate was concentrated in vacuo and purified by silica gel column chromatography (hexane/ethyl acetate) to give N-(9-phenyl-10-(phenylethynyl)phenanthryl-4-yl)acetamide (N -(9-phenyl-10-(phenylethynyl)phenanthren-4-yl)acetamide) 3a in 86% yield under these conditions, see entry 14 of Table 1 in the next paragraph.

此外，為了研究合成菲的最適條件，另進行各種反應條件測試，並將各反應條件產生的產物使用 ¹H和 ¹³C NMR光譜對進行系統分析，並通過單晶X射線衍射（XRD）技術進一步分析，呈現如下表1： 表1：取代菲合成的條件優化研究 ^a)

In addition, in order to study the optimal conditions for synthesizing phenanthrene, various reaction conditions were also tested, and the products produced by each reaction condition were systematically analyzed using ¹ H and ¹³ C NMR spectra, and further analyzed by single crystal X-ray diffraction (XRD) technology. Analysis, presented in Table 1 below: Table 1: Study on the optimization of conditions for the synthesis of substituted phenanthrene ^a)

上述表1中，a）除非另有說明，否則所有反應均在所列溶劑中於120℃的O ₂（1 atm）下以N-醯基2-氨基聯苯（N-acyl-2-aminobiphenyls）1a（0.1 mmol）、苯乙炔（phenylacetylene）2a（0.2 mmol）、10 mol%的乙酸鈀（Pd(OAc) ₂）和氧化劑進行反應24小時 ； b）80℃； c）100℃； d）以馬來酸二甲酯（dimethyl maleate）為內部標準，通過 ¹H NMR光譜測定產率； e）苯乙炔2a為4當量； f）苯乙炔2a為6當量。 In Table 1 above, a) Unless otherwise stated, all reactions were carried out with N-acyl-2-aminobiphenyls in the listed solvents under O ₂ (1 atm) at 120 °C. ) 1a (0.1 mmol), phenylacetylene 2a (0.2 mmol), 10 mol% palladium acetate (Pd(OAc) ₂ ) and oxidizing agent were reacted for 24 hours; b) 80 °C; c) 100 °C; d) Yields were determined by ¹ H NMR spectroscopy using dimethyl maleate as internal standard; e) phenylacetylene 2a was 4 equiv; f) phenylacetylene 2a was 6 equiv.

有關表1的內容說明如下： (1)調整反應溫度為80℃、100℃，產率分別為9%及28%，如表1的項目2及3；(2)改變氧化劑為氯化銅（CuCl）（1.0當量），其效果不佳，如表1的項目4；(3)比較添加劑乙酸鋰（LiOAc）、乙酸鉀（KOAc），使用乙酸鋰（LiOAc）的產率優於使用乙酸鉀（KOAc），如表1的項目5及6；(4) 改變溶劑為二甲基亞碸（DMSO），其效果不佳，如表1的項目7；(5)調整乙酸銅（Cu(OAc) ₂）的當量由1改為1.5及2，其產率增加為38%及45%，如表1的項目8及9。因此，確認乙酸銅（Cu(OAc) ₂）/氧氣（O ₂）及二甲基甲醯胺（DMF）的組合有重要的作用，可能是與苯乙炔（phenylacetylene）原位（in situ）氧化偶聯有關。另外，增加苯乙炔（phenylacetylene）的當量為4及6，使用乙酸鋰（LiOAc）為添加劑及稀釋該溶液，產量分別增加至51%及57%，如表1的項目10及11。 The contents of Table 1 are explained as follows: (1) Adjust the reaction temperature to 80°C and 100°C, and the yields are 9% and 28%, respectively, as shown in items 2 and 3 in Table 1; (2) change the oxidant to copper chloride ( CuCl) (1.0 equiv), its effect is not good, as shown in item 4 of Table 1; (3) Comparing additives lithium acetate (LiOAc) and potassium acetate (KOAc), the yield using lithium acetate (LiOAc) is better than using potassium acetate (KOAc), such as items 5 and 6 in Table 1; (4) change the solvent to dimethyl sulfoxide (DMSO), and its effect is not good, such as item 7 in Table 1; (5) adjust copper acetate (Cu(OAc) ) ₂ ) was changed from 1 to 1.5 and 2, and the yields were increased to 38% and 45%, as shown in items 8 and 9 in Table 1. Therefore, it is confirmed that the combination of copper acetate (Cu(OAc) ₂ )/oxygen (O ₂ ) and dimethylformamide (DMF) plays an important role, possibly in situ oxidation with phenylacetylene related to coupling. In addition, increasing the equivalents of phenylacetylene to 4 and 6, using lithium acetate (LiOAc) as an additive and diluting the solution increased the yields to 51% and 57%, respectively, as shown in Table 1, items 10 and 11.

在利用鹼性添加劑的產率達到57%後，改為測試各種不同的酸性添加劑，以破壞惰性鈀環（palladacycle）中間體中的Pd(II)-N鍵，從而進一步增強協同金屬化及去質子化反應（concerted metalation-deprotonation, CMD）途徑的翻轉環金屬化（rollover cyclometalation）。在測試過的添加劑中，與其他酸添加劑例如乙酸（acetic acid）、新戊酸（pivalic acid）、異丁酸（isobutyric acid）和丁酸（butyric acid）相比，丙酸（propionic acid）具有較高產率86%，如表1的項目12至16。 基於前述的篩選和各種反應參數，總結了兩種不同的催化條件：對於鹼性條件，項目11是最佳的；在酸性條件下，項目14是最佳的。After reaching 57% yield with basic additives, various acidic additives were tested instead to disrupt the Pd(II)-N bonds in the inert palladacycle intermediate, thereby further enhancing synergistic metallation and desorption Rollover cyclometalation of the concerted metalation-deprotonation (CMD) pathway. Among the additives tested, propionic acid has Higher yield of 86%, as in Table 1 items 12 to 16. Based on the aforementioned screening and various reaction parameters, two different catalytic conditions were summarized: for basic conditions, item 11 was optimal; under acidic conditions, item 14 was optimal.

下表2顯示已研究的[4 + 2]環化策略的基質範圍。各種帶有推電子基團（electron-donating groups, EDG）或拉電子基團（electron-withdrawing groups, EWG）的芳基乙炔（arylacetylenes）與N-醯基2-氨基聯苯（N-acyl-2-aminobiphenyls）1順利進行環化反應，從而獲得一系列中等至良好產率的取代菲（substituted phenanthrenes）。 表2：基質範圍研究 ^a)

Table 2 below shows the range of substrates for the [4+2] cyclization strategies that have been investigated. Various arylacetylenes with electron-donating groups (EDG) or electron-withdrawing groups (EWG) and N-acyl-2-aminobiphenyls (N-acyl- 2-aminobiphenyls)1 undergoes a smooth cyclization reaction, resulting in a series of substituted phenanthrenes in moderate to good yields. Table 2: Matrix range studies ^a)

上述表2中，a）反應條件：10 mol %的乙酸鈀（Pd(OAc) ₂）、2當量的乙酸銅（Cu(OAc) ₂）、10當量的丙酸（propionic acid）、氧氣1大氣壓、4 mL DMF，於120 ℃反應24小時。 In the above table 2, a) reaction conditions: 10 mol % palladium acetate (Pd(OAc) ₂ ), 2 equivalents of copper acetate (Cu(OAc) ₂ ), 10 equivalents of propionic acid, 1 atmosphere of oxygen , 4 mL DMF, and react at 120 °C for 24 hours.

有關表2的內容說明如下：初步篩選芳基乙炔上存在的EDG，如Me、 ^tBu、OCH ₃和 ⁿBu，其轉化率為中等至良好，生產出所需產物的產率為61%~92%（表2、3a~3e）；這歸因於EDG對芳基乙炔的電子作用。芳基乙炔的EWGs也顯示出對環化反應的積極作用，並產生了相應的產物，具有良好的產率為80%~82%（表2、3f~3g）。另外，3-乙炔基噻吩（3-ethynyl thiophene）以中等產率58%（表2、3h）產生了所需產物。此外，這項研究還研究了使用2-萘基苯胺（2-naphthyl aniline）作為基質的空間效應，從而獲得了所需的環狀結構，並顯示了酰胺型旋轉異構體（amide rotamers），其產率為57%（表2、3i）。兩個芳基環上電子效應的相互作用（R ¹和R ²= EDGs）提供相似的產率： 含有4'-OMe或4'-Me的下環R ²和帶有4-Me的上環R ¹具有相似的電子效應，產生的產率高達71%（表2、3j~3l）。在R ¹和R ²環上均帶有EDGs的基質也具有良好的耐受性，從而產生良好的轉化率及產率84%（表2、3m）。此外，強力EWGs之間的電子相互作用以及推電子和拉電子部分的組合均顯示出輕微的負面影響，從而導致[4 + 2]環化產物（3n~3p）具有中等產率（45%~62%）。 儘管效率較低，但在兩個環上均具有強EWGs的基質也導致形成3q，產率為44%。值得注意的是，當下環配備了能增加首次C-H鍵活化速率的EDG時，環化效率相對較高。 The contents of Table 2 are explained as follows: preliminary screening of EDG existing _on arylacetylene, such as Me, ^tBu , OCH and ^nBu , its conversion rate is moderate to good, and the yield of producing the desired product is 61%~ 92% (Table 2, 3a~3e); this is attributed to the electronic effect of EDG on arylacetylenes. The EWGs of arylacetylenes also showed a positive effect on the cyclization reaction and produced the corresponding products in good yields of 80%~82% (Table 2, 3f~3g). Additionally, 3-ethynyl thiophene gave the desired product in moderate yields of 58% (Tables 2, 3h). In addition, this study investigated the steric effects of using 2-naphthyl aniline as a substrate to obtain the desired cyclic structure and showed amide rotamers, The yield was 57% (Tables 2, 3i). Interaction of electronic effects on the ^two aryl rings (R1 and R2 ⁼ EDGs) provides similar yields: lower ring R2 with 4'-OMe or 4'-Me and upper ring R2 with ⁴ -Me ¹ has a similar electronic effect and produces yields as high as 71% (Table 2, 3j~3l). Substrates with ^EDGs on both the R1 and R2 rings ^were also well tolerated, resulting in good conversions and yields of 84% (Tables 2, 3m). In addition, the electronic interactions between the strong EWGs and the combination of the electron-pushing and electron-pulling moieties all showed slightly negative effects, resulting in the [4 + 2] cyclization product (3n~3p) in moderate yield (45%~3p). 62%). Although less efficient, the substrate with strong EWGs on both rings also led to the formation of 3q in 44% yield. It is worth noting that the cyclization efficiency is relatively high when the lower ring is equipped with EDG that can increase the rate of activation of the first C-H bond.

進一步的，將該方法的適用性擴展到其他脂族炔烴（aliphatic alkynes）。但是，最佳的條件（表1，項目14）不適合脂族炔烴，於是在鹼性條件下調整了最佳條件（項目11），所有無環和環狀烷基炔烴均以完全選擇性和合成有用的產率成功地形成了相應的產物，如下表3。 表3：脂族炔烴的基質範圍 ^a)

Further, the applicability of this method was extended to other aliphatic alkynes. However, the optimal conditions (Table 1, entry 14) were not suitable for aliphatic alkynes, so the optimal conditions (entry 11) were adjusted under basic conditions, all acyclic and cyclic alkyl alkynes with full selectivity and the corresponding products were successfully formed in useful yields, as shown in Table 3 below. Table 3: Matrix range for aliphatic alkynes ^a)

上述表3中，a）反應條件：10 mol %的乙酸鈀（Pd(OAc) ₂）、2當量的乙酸銅（Cu(OAc) ₂）、1當量的乙酸鋰（LiOAc）、4 mL DMF，於120 ℃反應24小時。 In the above table 3, a) reaction conditions: 10 mol% palladium acetate (Pd(OAc) ₂ ), 2 equivalents of copper acetate (Cu(OAc) ₂ ), 1 equivalent of lithium acetate (LiOAc), 4 mL DMF, The reaction was carried out at 120°C for 24 hours.

有關表3的內容說明如下：觀察到3r~3y適中的產率是由於原料的不完全轉化所致。特別的是，1a與2-甲基丁-3-炔-2-醇（2-methylbut-3-yn-2-ol）（2i）的反應產生了氧化產物內酯（lactone）3r，產率41%， 其形成機理尚不清楚。環狀脂族炔烴（Cyclic aliphatic alkynes），例如環丙基（cyclopropyl）（2j）、環戊基（cyclopentyl）（2k）和環己基（cyclohexyl）（2l），也導致氧化[4 + 2] 環化產率40~47%（3s~3u）的中等產率。無環脂族炔烴（Acyclic aliphatic alkynes），例如正戊基（n-pentyl）（2m）、正己基（n-hexyl）（2n）、正辛基（n-octyl）（2o）和正癸基（n-decyl）（2p），也能產生中等產率（3v~3y）。這種[4 + 2]環化反應中脂族炔烴的總產率中等，這可能是由於它們形成原位1,3-二炔的效率較低。The contents of Table 3 are explained as follows: Moderate yields of 3r-3y were observed due to incomplete conversion of the starting materials. In particular, the reaction of 1a with 2-methylbut-3-yn-2-ol (2i) gave the oxidation product lactone 3r in yields 41%, and its formation mechanism is still unclear. Cyclic aliphatic alkynes, such as cyclopropyl (2j), cyclopentyl (2k) and cyclohexyl (2l), also lead to oxidation [4+2] The cyclization yields were moderate yields of 40~47% (3s~3u). Acyclic aliphatic alkynes such as n-pentyl (2m), n-hexyl (2n), n-octyl (2o) and n-decyl (n-decyl) (2p), which also gave moderate yields (3v~3y). The overall yield of aliphatic alkynes in this [4+2] cyclization reaction is moderate, probably due to their low efficiency in forming 1,3-diynes in situ.

在對照實驗中，首先驗證了使用芳基乙炔在標準反應條件下分別使用和不使用乙酸鈀時，會形成中間產物1,3-二炔，分別產生87%和89%的1,3-二炔（如下圖的a、b反應式）。這是對當前催化系統的改良式Glaser-Hay反應。

In a control experiment, it was first verified that the use of arylacetylenes with and without palladium acetate under standard reaction conditions resulted in the formation of the intermediate 1,3-diyne, yielding 87% and 89% of 1,3-diyne, respectively. Alkynes (reaction formulas a and b in the following figure). This is a modified Glaser-Hay reaction of current catalytic systems.

此外，在標準條件下透過使用1a和製備的1,3-二炔2a'進行反應產生46%的3a，伴隨著40%的未反應的1a（如下圖的反應式）。使用1,3-二炔作為基質的產物3a產量降低，表明所需的反應可能需要在反應過程中以較低的1,3-二炔濃度進行，並可能形成螯合複合物，從而阻礙了在較高濃度的2a'下反應。

In addition, 46% of 3a was obtained by reacting 1a with the prepared 1,3-diyne 2a' under standard conditions, accompanied by 40% of unreacted 1a (reaction scheme below). The reduced yield of product 3a using 1,3-diyne as a substrate suggests that the desired reaction may require lower 1,3-diyne concentrations during the reaction and may form chelate complexes that hinder the React at higher concentrations of 2a'.

動力學同位素效應研究顯示，在10分鐘的反應中形成3a/3a-d ₄的k _H/ k _D值為3.01，這表明主要的同位素效應，而C–H鍵的活化可能是速率限制步驟（如下圖的反應式）。

Kinetic isotope effect studies revealed a kH/kD value of 3.01 for the formation of 3a/3a- _{d 4} in the 10-min reaction, suggesting a predominant isotope effect, whereas activation of the C– _H bond may be the rate-limiting step ( The reaction formula in the figure below).

不對稱的diynoate　2q'經過***和環化反應以形成3z，產率52％（如下圖的反應式）。

The asymmetric diynoate 2q' was inserted and cyclized to form 3z in 52% yield (reaction scheme below).

上述產生3z的方式為：於配有磁力攪拌棒的乾燥試管中裝入0.1 mmol 的N-醯基2-氨基聯苯（N-acyl-2-aminobiphenyls）1a、0.01 mmol, 2.24 mg 的乙酸鈀（Pd(OAc) ₂）、0.2 mmol 的乙酸銅（Cu(OAc) ₂）、0.1 mmol的乙酸鋰（LiOAc）、0.3 mmol 的5-苯基-2,4-戊二炔酸甲酯（Methyl 5-phenyl-2,4-pentadiynoate）2q'和新鮮蒸餾的4 mL二甲基甲醯胺（DMF）。 將反應混合物在氧氣下於120 ℃攪拌24小時。 反應完成後，將混合物冷卻至室溫，然後通過矽藻土薄墊過濾。 真空蒸發殘餘物，並通過柱色譜（己烷/乙酸乙酯）純化，得到相應的產物4-乙酰氨基-10-（苯基乙炔基）菲-9-羧酸甲酯（methyl 4-acetamido-10-(phenylethynyl)phenanthrene-9-carboxylate）3z。 The above method for generating 3z was as follows: a dry test tube equipped with a magnetic stir bar was charged with 0.1 mmol of N-acyl-2-aminobiphenyls 1a, 0.01 mmol, 2.24 mg of palladium acetate (Pd(OAc) ₂ ), 0.2 mmol of copper acetate (Cu(OAc) ₂ ), 0.1 mmol of lithium acetate (LiOAc), 0.3 mmol of methyl 5-phenyl-2,4-pentadiynoate (Methyl 5-phenyl-2,4-pentadiynoate) 2q' and freshly distilled 4 mL of dimethylformamide (DMF). The reaction mixture was stirred under oxygen at 120°C for 24 hours. After the reaction was complete, the mixture was cooled to room temperature and filtered through a thin pad of celite. The residue was evaporated in vacuo and purified by column chromatography (hexane/ethyl acetate) to give the corresponding product methyl 4-acetamido-10-(phenylethynyl)phenanthrene-9-carboxylate (methyl 4-acetamido- 10-(phenylethynyl)phenanthrene-9-carboxylate)3z.

下圖提出了一種機制，透過改良式Glaser-Hay偶聯及翻轉C-H活化/環化形成取代菲化合物。起初，在基質1與鈀（II）配位後，鄰位C–H鍵在2-芳基部分上被活化，生成中間產物Ia。原位1,3-二炔2'與中間產物Ia的配位和選擇性遷移可產生八元的Palladacycle Ib。酸性添加劑可能在產生中間產物Ic時的Pd（II）-N鍵解離中具有關鍵作用。此外，烯基-鈀翻轉金屬化透過CMD途徑將C ₃-H活化導致七元的Palladacycle Ie。 Pd（II）–N鍵解離後，可能由於NHAc和烯基鈀部分會產生空間排斥，因此發生翻轉。隨後，還原消除得到菲3和Pd（0）。透過用Cu（II）將Pd（0）氧化為Pd（II）來提供催化循環。使用鹼性添加劑LiOAc，Ib的Pd（II）-N鍵可能會被乙酸解離並置換。

The figure below proposes a mechanism for the formation of substituted phenanthrene compounds via modified Glaser-Hay coupling and inversion CH activation/cyclization. Initially, after the coordination of substrate 1 with palladium(II), the ortho C–H bond was activated on the 2-aryl moiety to generate intermediate Ia. Coordination and selective migration of the in situ 1,3-diyne 2' to the intermediate Ia yields the octa-membered Palladacycle Ib. The acidic additive may have a key role in the dissociation of the Pd(II)-N bond in the production of the intermediate Ic. In addition, alkenyl-palladium flip metallation activates C3 _- H through the CMD pathway leading to the seven-membered Palladacycle Ie. After the dissociation of the Pd(II)–N bond, the inversion may occur due to the steric repulsion of the NHAc and alkenyl palladium moieties. Subsequently, reduction and elimination gave phenanthrene 3 and Pd(0). The catalytic cycle is provided by the oxidation of Pd(0) to Pd(II) with Cu(II). With the basic additive LiOAc, the Pd(II)-N bond of Ib may be dissociated and displaced by acetic acid.

此外，透過使用三氯氧磷（POCl ₃）經過Bischler-Napieralski親電環化反應，將指定的菲3轉化為4-氮雜芘（如下表4、4a-4f），其產率為中等至良好。 形成氟-取代4-氮雜芘4f的化學產率為中等，可能是由於其電子不足的電子效應。 除4c外，這些取代4-氮雜芘在一般環境溫度下相對穩定，並顯示深藍色或綠色螢光。 表4：合成4-氮雜芘 ^a)

In addition, the indicated phenanthrene 3 was converted to 4-azapyrene (Tables 4, 4a-4f below) in moderate to moderate yields by Bischler-Napieralski electrophilic cyclization using phosphorus oxychloride (POCl ₃ ). good. The chemical yield to form fluoro-substituted 4-azapyrene 4f is moderate, probably due to its electron-deficient electron effect. With the exception of 4c, these substituted 4-azapyrenes are relatively stable at typical ambient temperatures and exhibit deep blue or green fluorescence. Table 4: Synthesis of 4-azapyrene ^a)

上述表4中，a）反應條件：0.05 mmol的3a、3當量的三氯氧磷（POCl ₃）、6 mL DCE，於110℃反應14小時。 In the above Table 4, a) reaction conditions: 0.05 mmol of 3a, 3 equivalents of phosphorus oxychloride (POCl ₃ ), and 6 mL of DCE, react at 110° C. for 14 hours.

以下說明合成4-氮雜芘4a的方式為：將化合物3a（0.05 mmol）、POCl ₃（3當量）、攪拌子和新鮮蒸餾的DCE（6 mL）在氮氣下加入乾燥的反應管中， 然後用螺帽將反應管密封，在劇烈攪拌下置於110 ℃的油浴中14小時。 反應完成後，將反應混合物用冰淬滅，然後用飽和碳酸氫鈉溶液處理，並用乙酸乙酯萃取。 真空濃縮有機層，並通過矽膠柱色譜法純化（己烷/乙酸乙酯/甲醇）得到4a，如下圖所示。

The following describes the synthesis of 4-azapyrene 4a by adding compound 3a (0.05 mmol), _POCl3 (3 equiv.), a stirring bar and freshly distilled DCE (6 mL) to a dry reaction tube under nitrogen, followed by The reaction tube was sealed with a screw cap and placed in an oil bath at 110 °C for 14 hours with vigorous stirring. After completion of the reaction, the reaction mixture was quenched with ice, then treated with saturated sodium bicarbonate solution, and extracted with ethyl acetate. The organic layer was concentrated in vacuo and purified by silica gel column chromatography (hexane/ethyl acetate/methanol) to give 4a as shown below.

用三氟甲磺酸（triflic acid）處理菲3a和4-氮雜芘4a，分別形成61%和78%產率的環狀化合物5a′和6。這兩個不同的部分對超酸質子化的傑出化學反應性歸因於菲上醯胺部分帶來的不同電子特性。 由於醯胺基團產生的共振效應，在菲遠端的sp混成碳相對較富電子，而更靠近4-氮雜芘的碳更富電子。 因此，它們的質子化發生在不同的 sp 碳上，從而導致不同的環化（如下圖）。 值得注意的是，在Bischler–Napieralski條件下無法形成化合物5b'，取而代之的是，獲得化合物5係由環外的C＝C鍵被裂解形成酮。

Treatment of phenanthrene 3a and 4-azapyrene 4a with triflic acid gave cyclic compounds 5a' and 6 in 61% and 78% yields, respectively. The outstanding chemical reactivity of these two distinct moieties towards superacid protonation is attributed to the different electronic properties brought about by the phenanthroid moiety. Due to the resonance effect produced by the amide group, the sp-mixed carbon at the far end of the phenanthrene is relatively electron-rich, while the carbon closer to 4-azapyrene is more electron-rich. Therefore, their protonations occur at different sp carbons, leading to different cyclizations (Fig. Notably, compound 5b' could not be formed under Bischler–Napieralski conditions, and instead, compound 5 was obtained by cleavage of the exocyclic C=C bond to form a ketone.

合成π延伸4-氮雜芘5a′和6的方式：在含有化合物3a或4a的乾燥反應管中分別添加含有二氯甲烷（1 mL）的三氟甲磺酸（triflic acid）（15.1 mg，0.1 mmol）和三氟甲磺酸（75 mg，0.5 mmol）。 將反應混合物在室溫攪拌12小時。 所得反應混合物用碳酸氫鈉溶液淬滅。分離有機層，水層用二氯甲烷萃取。 隨後，合併的有機層經無水硫酸鈉（Na ₂SO ₄）乾燥並在減壓下濃縮。 粗產物在矽膠上色譜分離，得到所需化合物5a'或6。 Synthesis of π-extended 4-azapyrenes 5a′ and 6: To a dry reaction tube containing compound 3a or 4a, respectively, triflic acid (15.1 mg, 0.1 mmol) and triflic acid (75 mg, 0.5 mmol). The reaction mixture was stirred at room temperature for 12 hours. The resulting reaction mixture was quenched with sodium bicarbonate solution. The organic layer was separated and the aqueous layer was extracted with dichloromethane. Subsequently, the combined organic layers were dried over anhydrous sodium sulfate (Na ₂ SO ₄ ) and concentrated under reduced pressure. The crude product was chromatographed on silica gel to give the desired compound 5a' or 6.

在5、9、10位點上具有甲基、苯基和炔基取代基的取代4-氮雜芘具有良好的光物理性質，並具有355至394 nm的典型吸收帶（見第1圖）。 在4b和4c的情況下，觀察到一個與電荷轉移相關的另外一個可見帶，範圍為400至475 nm，這可能是由於取代基的性質所致。螢光研究顯示在375~500 nm的可見光區域有很強的雙重發射（表5）。 根據Franck–Condon原理，4-氮雜芘發色團的異常雙發射行為涉及兩種不同激發電子態的非輻射振動弛豫（nonradiative vibrational relaxation）和發射。 與UV-vis研究相比，取代基的性質在發射波長（λ _em）中起著至關重要的作用，發射波長從紫藍色到藍色都有變化。此外，4b顯示較大的斯托克斯位移（Stokes shift）（54 nm），表明π-共軛體系相對於其他化合物（4a-4f）具有較高的極化率，這很可能是炔基部分上的EDGs引起的。在CHCl ₃中獲得的氮雜芘的量子產率Φ _F（0.29–0.60）取決於取代基的性質和位置。除具有氟取代基的4c和4f外，4-氮雜芘4a-b和4d-4e的Φ _F大於0.42，並且螢光壽命相對較長（10.7-18.1 ns）。值得注意的是，π延伸的萘4-氮雜芘6在410 nm處顯示深藍色發射，具有窄的半峰全寬為52 nm，並且螢光壽命為7.0 ns。 表5：化合物4a-4f 及6的光物理性質 化合物 λ _abs(nm) ^[a] λ _f(nm) ^[b] Φ _f ^[c] 生命週期(ns) ^[d] 4a 355, 373, 384 397, 414 0.42 10.7 4b 318, 353, 416 409, 499 0.60 18.1 4c 353, 365, 420 391, 409 0.29 7.6 4d 356, 369, 388 397, 416 0.56 14.1 4e 355, 368, 384 396, 415 0.50 13.2 4f 357, 367, 386 401, 414 0.33 4.3 6 355, 369, 394 408, 418 0.45 7.0 Substituted 4-azapyrenes with methyl, phenyl, and alkynyl substituents at positions 5, 9, and 10 exhibit favorable photophysical properties and exhibit typical absorption bands from 355 to 394 nm (see Figure 1) . In the case of 4b and 4c, an additional visible band related to charge transfer was observed, ranging from 400 to 475 nm, possibly due to the nature of the substituents. Fluorescence studies showed strong double emission in the visible region from 375 to 500 nm (Table 5). According to the Franck–Condon principle, the anomalous double-emission behavior of the 4-azapyrene chromophore involves nonradiative vibrational relaxation and emission of two different excited electronic states. In contrast to UV-vis studies, the nature of the substituents plays a crucial role in the emission wavelength (λ _em ), which varies from violet-blue to blue. In addition, 4b shows a large Stokes shift (54 nm), indicating that the π-conjugated system has a higher polarizability relative to the other compounds (4a-4f), which are most likely alkynyl groups Partially caused by EDGs. The quantum yields ΦF ( _0.29–0.60 ) of the azapyrenes obtained in _CHCl3 depend on the nature and position of the substituents. Except for 4c and 4f with fluorine substituents, 4- _azapyrenes 4a-b and 4d-4e have ΦF greater than 0.42 and relatively long fluorescence lifetimes (10.7–18.1 ns). Notably, the π-extended naphthalene 4-azapyrene 6 displays deep blue emission at 410 nm with a narrow full width at half maximum of 52 nm and a fluorescence lifetime of 7.0 ns. Table 5: Photophysical properties of compounds 4a-4f and 6 compound λ _abs (nm) ^[a] λ _f (nm) ^[b] Φ _f ^[c] Lifetime (ns) ^[d] 4a 355, 373, 384 397, 414 0.42 10.7 4b 318, 353, 416 409, 499 0.60 18.1 4c 353, 365, 420 391, 409 0.29 7.6 4d 356, 369, 388 397, 416 0.56 14.1 4e 355, 368, 384 396, 415 0.50 13.2 4f 357, 367, 386 401, 414 0.33 4.3 6 355, 369, 394 408, 418 0.45 7.0

上述表5中，[a]表示在室溫下在氯仿（chloroform）溶液（10 ^-5M）中測量吸收光譜；[b]表示在室溫下於氯仿溶液（10 ^-5M）中測量螢光光譜；[c]表示使用積分球（integrating sphere）在300K（於340 nm激發）下，在二氯甲烷（dichloromethane）溶液中測量絕對量子產率；[d]表示在300K的二氯甲烷脫氣溶液中測量的螢光生命週期。 In Table 5 above, [a] represents the measurement of the absorption spectrum in a chloroform solution (10 ^-5 M) at room temperature; [b] represents the measurement of the fluorescence spectrum in a chloroform solution (10 ^-5 M) at room temperature. Optical spectrum; [c] represents absolute quantum yield measured in dichloromethane solution at 300K (excitation at 340 nm) using integrating sphere; [d] represents desorption of dichloromethane at 300K Fluorescence lifetime measured in gas solution.

綜上，本發明揭露一種製備4-氮雜芘之方法，該方法以鈀催化的N-醯基-2-氨基聯芳基的脫氫與原位1,3-二炔進行環化反應為關鍵步驟，通過側翻碳氫鍵活化生成取代菲，然後進行Bischler-Napieralski環化以產生4-氮雜芘，係為一種有效率地合成4-氮雜芘之方法。此外，藉由超強酸介導的環化進一步進行π-延伸產生藍色螢光萘4-氮雜芘。這些4-氮雜芘顯示出雙發射和深藍色/綠色螢光，具有窄的帶隙和高達0.6的高量子產率，這可能在生物成像和溶液處理的有機發光二極體中具有潛在的應用前景。To sum up, the present invention discloses a method for preparing 4-azapyrene. The method uses palladium-catalyzed dehydrogenation of N-acyl-2-aminobiaryl group and in-situ 1,3-diyne to carry out a cyclization reaction as The key step is to generate substituted phenanthrenes through rollover carbon-hydrogen bond activation, followed by Bischler-Napieralski cyclization to generate 4-azapyrene, which is an efficient method for synthesizing 4-azapyrene. In addition, further π-extension via superacid-mediated cyclization yields blue fluorescent naphthalene 4-azapyrene. These 4-azapyrenes display dual emission and deep blue/green fluorescence with narrow band gaps and high quantum yields up to 0.6, which may have potential in bioimaging and solution-processed organic light-emitting diodes application prospects.

本發明在上文中以較佳實施例揭露，然熟習本項技術者應理解的是，該實施例僅用於描述本發明，而不應解讀為限制本發明之範圍。舉凡與該實施例均等或等效之變化與置換，皆應認為涵蓋於本發明之範疇內。因此，本發明之保護範圍應當以申請專利範圍所界定者為準。The present invention is disclosed above with preferred embodiments, but those skilled in the art should understand that the embodiments are only used to describe the present invention, and should not be construed as limiting the scope of the present invention. All the equivalent or equivalent changes and substitutions to this embodiment should be considered to be covered within the scope of the present invention. Therefore, the protection scope of the present invention should be defined by the scope of the patent application.

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第1圖係為本發明化合物4a~4f及化合物6在298K的氯仿中的UV-vis吸收光譜（虛線）和發射光譜（實線）。Figure 1 shows the UV-vis absorption spectra (dotted lines) and emission spectra (solid lines) of compounds 4a to 4f of the present invention and compound 6 in chloroform at 298K.

Claims (9)

一種製備4-氮雜芘化合物之方法，該方法包括：a)將N-醯基-2-氨基聯芳基(N-acyl 2-aminobiaryls)及1,3-二炔(1,3-diynes)化合物置於包含鈀金屬催化劑之反應環境中，並於一特定溫度下進行反應產生取代菲(substituted phenanthrene)化合物，其中，該鈀金屬催化劑為乙酸鈀(Pd(OAc)₂)，該特定溫度為120℃；以及b)將該取代菲化合物與三氯氧磷(POCl₃)反應，以獲得該4-氮雜芘(4-azapyrene)化合物；其中該4-氮雜芘化合物之化學結構如下：

其中，R¹包括：H、烷基、環烷基、鹵素或烷氧基；R²包括：H、烷基、環烷基、鹵素、烷氧基或硝基；R包括：具取代的芳香基、雜環芳香基、鹵素、烷基或環烷基。 A method for preparing a 4-azapyrene compound, the method comprising: a) combining N-acyl 2-aminobiaryls and 1,3-diynes (1,3-diynes) ) compound is placed in a reaction environment containing a palladium metal catalyst, and reacts at a specific temperature to produce a substituted phenanthrene compound, wherein the palladium metal catalyst is palladium acetate (Pd(OAc) ₂ ), and the specific temperature and b) react the substituted phenanthrene compound with phosphorus oxychloride (POCl ₃ ) to obtain the 4-azapyrene (4-azapyrene) compound; wherein the chemical structure of the 4-azapyrene compound is as follows :

Wherein, R ¹ includes: H, alkyl, cycloalkyl, halogen or alkoxy; R ² includes: H, alkyl, cycloalkyl, halogen, alkoxy or nitro; R includes: substituted aromatic radical, heterocyclic aryl, halogen, alkyl or cycloalkyl. 如請求項1所述之方法，其中該1,3-二炔化合物係由下列化合物之一者所形成：末端芳基炔烴(terminal arylalkynes)化合物、脂族炔烴(aliphatic alkynes)化合物及5-苯基-2,4-戊二炔酸甲酯(Methyl 5-phenyl-2,4-pentadiynoate)。 The method of claim 1, wherein the 1,3-diyne compound is formed from one of the following compounds: a terminal arylalkynes compound, aliphatic alkynes compound and 5 -Methyl 5-phenyl-2,4-pentadiynoate. 如請求項1所述之方法，其中該N-醯基-2-氨基聯芳基之結構包括：

The method of claim 1, wherein the structure of the N-acyl-2-aminobiaryl group comprises:

如請求項1所述之方法，其中該N-醯基-2-氨基聯芳基之結構包括：

其中，R¹為選自下列之一者：H、F、Me；R²為選自下列之一者：H、OMe、Me、NO₂。 The method of claim 1, wherein the structure of the N-acyl-2-aminobiaryl group comprises:

Wherein, R ¹ is one selected from the following: H, F, Me; R ² is one selected from the following: H, OMe, Me, NO ₂ . 如請求項2所述之方法，其中該末端芳基炔烴化合物之結構式如下：

其中，R³為選自下列之一者：H、F、Me、^tBu、OCH₃及ⁿBu；R⁴為選自下列之一者：H及F。 The method as claimed in claim 2, wherein the structural formula of the terminal aryl alkyne compound is as follows:

Wherein, R ³ is one selected from the following: H, F, Me, ^t Bu, OCH ₃ and ⁿ Bu; R ⁴ is one selected from the following: H and F. 如請求項2所述之方法，其中該脂族炔烴化合物之結構式如下：

其中，R⁵為選自下列之一者：C(CH₃)₂OH、環丙基(cyclopropyl)、環戊基(cyclopentyl)、環己基(cyclohexyl)、正戊基(n-pentyl)、正己基(n-hexyl)、正辛基(n-octyl)及正癸基(n-decyl)。 The method of claim 2, wherein the structural formula of the aliphatic alkyne compound is as follows:

Wherein, R ⁵ is one selected from the following: C(CH ₃ ) ₂ OH, cyclopropyl (cyclopropyl), cyclopentyl (cyclopentyl), cyclohexyl (cyclohexyl), n-pentyl ( n -pentyl), n-hexyl base ( n -hexyl), n-octyl ( n -octyl) and n-decyl ( n -decyl). 如請求項5所述之方法，其中該反應環境中包括含有氧化劑、溶劑及添加劑，該氧化劑為乙酸銅(Cu(OAc)₂)，該溶劑為二甲基甲醯胺(DMF)，該添加劑為丙酸(propionic acid)。 The method of claim 5, wherein the reaction environment includes an oxidant, a solvent and an additive, the oxidant is copper acetate (Cu(OAc) ₂ ), the solvent is dimethylformamide (DMF), the additive For propionic acid (propionic acid). 如請求項6所述之方法，其中該反應環境中包括含有氧化劑、溶劑及添加劑，該氧化劑為乙酸銅(Cu(OAc)₂)，該溶劑為二甲基甲醯胺(DMF)，該添加劑為乙酸鋰(LiOAc)。 The method of claim 6, wherein the reaction environment includes an oxidant, a solvent and an additive, the oxidant is copper acetate (Cu(OAc) ₂ ), the solvent is dimethylformamide (DMF), the additive For lithium acetate (LiOAc). 如請求項1所述之方法，更包括加入一強酸與該取代菲化合物或該4-氮雜芘化合物反應，以產生π延伸4-氮雜芘(π-extended 4-azapyrene)化合物，其中，該強酸包括三氟甲磺酸(triflic acid)。 The method of claim 1, further comprising adding a strong acid to react with the substituted phenanthrene compound or the 4-azapyrene compound to produce a π-extended 4-azapyrene (π-extended 4-azapyrene) compound, wherein, The strong acid includes triflic acid.

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