A method for preparing anthracycline derivatives

Abstract

The present invention discloses a method for preparing anthracycline derivatives. Using o-dihalobenzene and benzoylacetonitrile or diphenylethanone substrate as raw materials, in the presence of an alkaline metal hydride, a 9,10-disubstituted anthracycline derivative of the anthracycline skeleton is obtained. The method for constructing the anthracycline skeleton disclosed by the present invention does not use a transition metal catalyst, does not involve harsh conditions such as high temperature and high pressure, and the raw materials are cheap and easily available, providing a more convenient, effective and economical synthesis method for the application field of anthracyclines.

Description

Technical Field

[0001] The present invention belongs to the field of organic synthesis, and particularly relates to a method for preparing anthracene ring derivatives using simple raw materials. Background Art

[0002] Anthracene (C 14 H 10 ) and its derivatives are a class of common polycyclic aromatic hydrocarbons (PAHs), and have unique photophysical, photochemical properties and gelation ability due to their aromatic conjugated π system. Anthracene rings and their derivatives have been widely used in fluorescent probes, organic light-emitting diodes (OLEDs), organic field-effect transistors (OFETs), polymer materials, supramolecular assemblies, and photopolymerization reactions. For example, 9,10-diphenylanthracene (DPA) is a promising hole-transporting (p-type) semiconductor material for OFETs and a key skeleton of important fluorescent material 9,10-disubstituted anthracene derivatives, which has important research significance and value. The extensive practical value has made the preparation research of anthracene rings highly concerned. However, traditional anthracene ring synthesis methods such as Friedel-Crafts reaction, Elbs reaction, and aromatic ring dehydration generally have deficiencies such as high catalyst prices, difficult-to-obtain raw materials, and harsh reaction conditions. Therefore, finding new synthesis methods with milder reaction conditions and cheaper and more easily available raw materials is still a research hotspot. Summary of the Invention

[0003] The prior art for preparing anthracene ring derivatives has problems such as high cost and harsh reaction conditions. The present invention discloses a method for preparing anthracene ring derivatives using simple raw materials, without using transition metal catalysts, without involving harsh conditions such as high temperature and high pressure, and with cheap and easily available raw materials, providing a more convenient, effective, and economical synthesis method for the application field of anthracene rings.

[0004] The technical solution adopted by the present invention is as follows:

[0005] A method for preparing anthracene ring derivatives, comprising the following steps: using o-dihalobenzene and benzophenone compounds as raw materials, and reacting in the presence of an alkaline metal hydride to obtain anthracene ring derivatives.

[0006] In the present invention, the alkaline metal hydride is one or more of NaH, KH, CaH2, and LiH, preferably NaH and KH, and more preferably NaH.

[0007] In the present invention, the reaction is carried out in a solvent, and the solvent is one or more of THF, DMA, 1,4-dioxane, and DME, preferably THF and DME, and more preferably THF.

[0008] In the present invention, the reaction temperature is 30 °C to 70 °C, preferably 40 °C to 60 °C, and most preferably 50 °C.

[0009] In the present invention, the molar ratio of the benzophenone compound, o-dihalobenzene, and alkali metal hydride is 1: (1-5): (2-8), preferably 1: (2-3): (5-7), such as 1: 2.5: 7.

[0010] In the present invention, the benzophenone compound is a benzoylacetonitrile compound or a benzil compound. The chemical structural formulas of the benzoylacetonitrile compounds are as follows:

[0011]

[0012] The chemical structural formula of the benzil compound is as follows:

[0013]

[0014] The chemical structural formula of o-dihalobenzene is as follows:

[0015]

[0016] The chemical structural formula of the product anthracycline derivative is as follows:

[0017]

[0018] In the above chemical structural formulas, Ar is a substituted or unsubstituted aryl group, such as a substituted or unsubstituted phenyl group or naphthyl group; R1, R`, and R`` independently selected from one of alkyl, halogen, alkoxy, and aryl; preferably, the alkyl is a straight-chain or branched-chain alkyl group with 1 to 10 carbon atoms, such as methyl, ethyl, tert-butyl, etc.; the halogen is fluorine, chlorine, bromine, etc.; the alkoxy is an alkoxy group with 1 to 10 carbon atoms, such as methoxy, ethoxy, etc.; the aryl is a phenyl group, etc.; R2 is selected from one of alkyl and alkoxy; preferably, the alkyl has 1 to 10 carbon atoms, and the alkoxy has 1 to 10 carbon atoms; X is selected from one of chlorine, bromine, iodine, and OTf; preferably, X is iodine.

[0019] As an embodiment thereof, the reaction of the present invention can be represented as follows:

[0020]

[0021] Preferably, the alkali metal compound is NaH, the solvent is THF, the reaction temperature is 50 °C, and the reaction time is 8-24 h.

[0022] The present invention uses o-dihalobenzene and benzoylacetonitrile or benzophenone as raw materials, and reacts in the presence of an alkaline metal hydride to obtain 9,10-disubstituted anthracycline derivatives with an anthracycline skeleton. This is an effective method for preparing complex polycyclic aromatic hydrocarbon compounds (PAHs) - anthracycline derivatives from simple and readily available raw materials. This method for constructing the anthracycline skeleton does not use transition metal catalysts, does not involve harsh conditions such as high temperature and high pressure, and the raw materials are cheap and easy to obtain, providing a more convenient, effective and economical synthesis method for the application field of anthracyclines, and having important application value.

[0023] The beneficial effects of the preparation method of the anthracycline derivatives provided by the present invention are as follows:

[0024] 1) Without transition metal catalysis, low cost, simple operation, less pollution, and environmentally friendly;

[0025] 2) The reaction conditions are mild, do not involve high temperature and high pressure, and have a high safety factor. Specific Embodiments

[0026] In order to more clearly understand the technical content of the present invention, the following specific examples are given for detailed description.

[0027] The present invention uses o-dihalobenzene and benzoylacetonitrile or benzophenone as raw materials, and reacts in the presence of an alkaline metal hydride to obtain 9,10-disubstituted anthracycline derivatives with an anthracycline skeleton. Specifically, under an N2 atmosphere, a solvent is added to a two-necked reaction flask containing an alkaline hydride, and then benzoylacetonitrile or benzophenone is added. After conventional stirring, o-dihalobenzene is added dropwise. After the addition is completed, stirring is continued for 8-24 h to obtain 9,10-disubstituted anthracycline derivatives.

[0028] All raw materials are commercially available products or prepared according to the literature methods, and the specific operation and testing methods are conventional techniques.

[0029] Nuclear Magnetic Resonance Spectra 1 1H NMR and 13 13C NMR were measured using Agilent 400 MHz and Bruker 400 MHz instruments, and the sample solvent was CDCl3 (7.26 ppm). The nuclear magnetic data report includes: chemical shift, peak area integration, coupling constant, peak shape, etc. The TLC thin layer chromatography plate was produced by Yantai Huanghai Chemical Factory and was visually monitored at wavelengths of 254 nm and 365 nm. The silica gel mesh number used for flash column chromatography was 200-300 mesh. All reagents used were commercially available analytical pure or chemical pure, and were directly used without special instructions. All anhydrous solvents were redistilled solvents or commercially available dry solvents (J&K).

[0030] Example 1

[0031] Under N2 protection, after stirring the alkali metal hydride, benzoylacetonitrile 1a, and the solvent in a two-necked reaction flask for 15 min, o-diiodobenzene 2a was added dropwise. The addition was completed in 1 minute, and then the mixture was reacted at the specified temperature. After the reaction was completed, ice water was added for quenching. The aqueous phase was extracted three times with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous Na2SO4, filtered, the solvent was evaporated, and purified by silica gel column chromatography to obtain the crude product 3a of 9-cyano-10-phenylanthracene. The reaction results under different operating conditions are shown in Table 1.

[0032]

[0033] In the table, a Reaction conditions: N2 atmosphere, NaH and 1a were dispersed in THF, 2a was added dropwise, and the reaction was stirred at a certain temperature for 12 hours. b Isolated yield, c Air.

[0034] Example 2

[0035] Under N2 protection, THF (2 mL) was added to a two-necked reaction flask containing weighed NaH (3.5 mmol, 7.0 equiv, 60% suspended in kerosene) to suspend NaH. A solution of benzoylacetonitrile 1 (0.5 mmol, 1.0 equiv) in THF (3 mL) was added with stirring. After stirring at 50 °C for 15 min, o-diiodobenzene 2 (2.5 equiv) was added dropwise. The addition was completed in 1 minute, and the reaction was continued by stirring at 50 °C. After the reaction was completed, ice water was added for quenching. The aqueous phase was extracted three times with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous Na2SO4, filtered, the solvent was evaporated, and purified by silica gel column chromatography to obtain the crude product 3 of 9-cyano-10-phenylanthracene. High-purity product was obtained by conventional trituration. Different reaction substrates (benzoylacetonitrile 1 and o-diiodobenzene 2) and the obtained 9-cyano-10-phenylanthracene ring derivative 3 are shown in Table 2, where the time is the reaction time.

[0036]

[0037] The above product data are characterized as follows:

[0038] 10-phenylanthracene-9-carbonitrile(3a)

[0039] Pale yellow solid, yield 48%. Mp. 183-188 °C. 1 H NMR (400 MHz, CDCl3) δ8.47 (d, J= 8.7 Hz, 2H), 7.71 (t, J = 7.8 Hz, 3H), 7.67 (dd, J =6.0, 4.0 Hz, 1H),7.59 - 7.61 (m, 3H), 7.44 (ddd, J = 8.4, 6.6, 1.2 Hz, 2H), 7.36 (dd, J = 6.4, 3.2Hz, 2H). 13 C NMR (101 MHz, CDCl3) δ 143.81, 137.27, 133.09, 130.67, 129.62, 128.66, 128.60, 128.33, 127.87, 126.27, 125.45, 117.54, 105.60. LR-MS (ESI): m / z 280.1 [M + H] + 。

[0040] 10-(p-tolyl)anthracene-9-carbonitrile (3b)

[0041] Pale yellow solid, yield 70%. Mp. 228 - 232 ℃. 1 H NMR (400 MHz, CDCl3) δ8.47 (d, J = 8.7 Hz, 2H), 7.76 (d, J = 8.8 Hz, 2H), 7.68 (t, J = 7.6 Hz, 2H), 7.40 - 7.45 (m, 4H), 7.25 (d, J = 7.6 Hz, 2H), 2.54 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ144.10, 138.11, 134.18, 133.12, 130.58, 129.75, 129.29, 128.64, 128.00, 126.16, 125.43, 117.64, 105.36, 21.48. LR-MS (ESI): m / z 294.1 [M + H] + 。

[0042] 10-(4-methoxyphenyl)anthracene-9-carbonitrile (3c)

[0043] Yellow solid, yield 41%. Mp. 217 - 220 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.48(d, J = 8.6 Hz, 2H), 7.82–7.75 (m, 2H), 7.69 (ddd, J = 8.7, 6.6, 1.2 Hz, 2H),7.45 (ddd, J = 8.8, 6.6, 1.2 Hz, 2H), 7.31 (d, J = 8.6 Hz, 2H), 7.14 (d, J = 8.7Hz, 2H), 3.96 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 159.74, 143.92, 133.26,131.97, 130.08, 129.34, 128.71, 128.07,126.24, 125.56, 117.72, 114.14,105.46, 55.55. LR-MS (ESI): m / z 310.1 [M + H] + 。

[0044] 10-(4-fluorophenyl)anthracene-9-carbonitrile (3d)

[0045] Yellow solid, yield 47%. Mp. 201 - 207 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.48(d, J = 8.4 Hz, 2H), 7.68 - 7.72 (m, 4H), 7.47 (q, J = 2.3 Hz, 2H), 7.29 - 7.38 (m,4H). 13 C NMR (101 MHz, CDCl3) δ 162.96 (d, J = 248.46 Hz), 142.60, 133.16 (d, J =2.02 Hz), 133.12, 132.50, 132.42, 129.85, 127.62 (t, J= 116.15 Hz), 125.62, 117.48, 115.95, 115.74, 105.99. 19 19F NMR (377 MHz, CDCl3) δ -113.28. LR-MS(ESI): m / z 298.1 [M+H] + 。

[0046] 10-(4-bromophenyl)anthracene-9-carbonitrile(3e)

[0047] Yellow-green solid, yield 16%. Mp. 281-282 ℃. 1 1H NMR (400 MHz, CDCl3)δ 8.49 (d, J = 8.7 Hz, 2H), 7.79–7.66 (m, 6H), 7.52–7.44 (m, 2H), 7.28 (d, J =8.3 Hz, 2H). 13 13C NMR (101 MHz, CDCl3) δ 142.28, 136.34, 133.16, 132.46, 132.02, 129.62, 128.85, 127.56, 126.67, 125.72, 122.82, 117.47, 106.23. LR-MS (ESI):m / z 358.0 [M+H] + 。

[0048] 10-(4-chlorophenyl)anthracene-9-carbonitrile (3f)

[0049] Yellow solid, yield 31%. Mp. 178-205 ℃. 1 1H NMR (400 MHz, CDCl3) δ 8.49(d, J = 8.6 Hz, 2H), 7.75–7.66 (m, 4H), 7.60 (d, J = 8.2 Hz, 2H), 7.52–7.44 (m,2H), 7.34 (d, J = 8.2 Hz, 2H). 1313C NMR (101 MHz, CDCl3) δ 142.31, 135.82, 134.66, 133.14, 132.15, 129.68, 129.06, 128.83, 127.56, 126.65, 125.70, 117.48, 106.17. LR-MS (ESI): m / z 314.0 [M+H] + 。

[0050] 10-(4-(trifluoromethyl)phenyl)anthracene-9-carbonitrile (3g)

[0051] Yellow solid, yield 57%. Mp. 300 - 307 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J J = 8.7 Hz, 2H), 7.90 (d, J J = 7.9 Hz, 2H), 7.77–7.69 (m, 2H), 7.62 (d, J J = 8.8 Hz, 2H), 7.55 (d, J J = 7.9 Hz, 2H), 7.54–7.45 (m, 2H). 13 13C NMR (101 MHz, CDCl3) δ 141.82, 141.40 (d, J J = 5.05 Hz), 133.11, 131.27, 130.96, 130.64, 129.50, 128.93, 127.36, 126.88, 125.80 (q, J J = 4.04 Hz), 122.89, 117.42, 106.54. 19 19F NMR (377 MHz, CDCl3) δ -62.50. LR-MS (ESI): m / z 348.0 [M+H] + 。

[0052] 10-(4-(trifluoromethoxy)phenyl)anthracene-9-carbonitrile (3h)

[0053] Yellow solid, yield 46%. Mp. 257 - 259 °C. 11H NMR (400 MHz, CDCl3) δ 8.49 (d, J J = 8.6 Hz, 2H), 7.76–7.64 (m, 4H), 7.54–7.39 (m, 6H). 13 13C NMR (101 MHz, CDCl3) δ 149.44, 142.05, 136.04, 133.15, 132.33, 129.74, 128.87, 127.51, 126.74, 125.74, 122.01, 121.21, 117.45, 106.33. 19 19F NMR (377 MHz, CDCl3) δ -57.63. LR-MS (ESI): m / z 364.0 [M+H] + 。

[0054] 10-(4-cyanophenyl)anthracene-9-carbonitrile (3i)

[0055] Yellow solid, yield 23%. Mp. 260 - 266 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J J = 8.7 Hz, 2H), 7.97–7.90 (m, 2H), 7.74 (ddd, J J = 8.7, 6.5, 1.3 Hz, 2H), 7.61–7.54 (m, 4H), 7.50 (ddd, J J = 8.9, 6.5, 1.2 Hz, 2H). 13 13C NMR (101 MHz, CDCl3) δ 142.64, 141.01, 133.06, 132.59, 131.75, 129.27, 128.98, 127.10, 127.01, 125.88, 118.61, 117.24, 112.71, 106.92. LR-MS (ESI): m / z 305.1 [M+H] + 。

[0056] 10-(4-(benzyloxy)phenyl)anthracene-9-carbonitrile (3j)

[0057] Yellow solid, yield 43%. Mp. 198 - 205 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.49(d, J = 8.7 Hz, 2H), 7.80 (d, J = 8.8 Hz, 2H), 7.74–7.66 (m, 2H), 7.55 (d, J = 6.8Hz, 2H), 7.47 (td, J = 7.7, 7.2, 1.8 Hz, 4H), 7.41 (d, J = 7.3 Hz, 1H), 7.32 (d, J = 8.6 Hz, 2H), 7.22 (d, J = 8.7 Hz, 2H), 5.22 (s, 2H). 13 C NMR (101 MHz, CDCl3) δ158.98, 143.83, 136.89, 133.23, 132.01, 130.04, 129.61, 128.83, 128.70,128.29, 128.05, 127.72, 126.24, 125.54, 117.69, 115.00, 105.48, 70.34. LR-MS(ESI): m / z 386.1 [M+H] + 。

[0058] 10-(4-(tert-butyl)phenyl)anthracene-9-carbonitrile(3k)

[0059] Yellow solid, yield 40%. Mp. 305 - 310 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.49(d, J = 8.7 Hz, 2H), 7.77 (d, J = 8.9 Hz, 2H), 7.70 (t, J = 7.9 Hz, 2H), 7.61 (d, J =7.9 Hz, 2H), 7.46 (t, J = 8.0 Hz, 2H), 7.32 (d, J= 7.9 Hz, 2H), 1.47 (s, 9H). 13 C NMR (101 MHz, CDCl3) δ 151.42, 144.34, 134.27, 133.30, 130.50, 129.95, 128.74, 128.22, 126.21, 125.56, 117.76, 105.49, 34.97, 31.61. LR-MS (ESI): m / z 336.1 [M+H] + 。

[0060] 10-(o-tolyl)anthracene-9-carbonitrile (3l)

[0061] Yellow solid, yield 34%. Mp. 160 - 162 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.52(d, J = 8.8 Hz, 2H), 7.71 (ddd, J = 8.8, 6.5, 1.3 Hz, 2H), 7.60 (d, J = 8.8 Hz, 2H), 7.52–7.39 (m, 5H), 7.21 (d, J = 7.4 Hz, 1H), 1.85 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 143.56, 137.31, 136.82, 133.26, 130.61, 130.41, 129.52, 128.82, 128.73, 127.55, 126.54, 126.13, 125.72, 117.63, 105.62, 19.79. LR-MS (ESI): m / z 294.1 [M+H] + 。

[0062] 10-(m-tolyl)anthracene-9-carbonitrile (3m)

[0063] Yellow solid, yield 68%. Mp. 153 - 154 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.49(d, J= 8.7 Hz, 2H), 7.75 (d, J = 8.8 Hz, 2H), 7.69 (ddd, J = 8.3, 6.7, 1.2 Hz,2H), 7.52–7.43 (m, 3H), 7.39 (d, J = 7.7 Hz, 1H), 7.23–7.16 (m, 2H), 2.48 (s,3H). 13 C NMR (101 MHz, CDCl3) δ 144.19, 138.33, 137.28, 133.18, 131.31, 129.71,129.09, 128.70, 128.51, 128.06, 127.81, 126.23, 125.49, 117.66, 105.49,21.61. LR-MS (ESI): m / z 294.1 [M+H] + 。

[0064] 10-(2-methoxyphenyl)anthracene-9-carbonitrile (3n)

[0065] Yellow solid, yield 40%. Mp. 236-240 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.51(d, J = 8.4 Hz, 2H), 7.73–7.66 (m, 4H), 7.59 (ddd, J = 8.9, 7.1, 2.2 Hz, 1H),7.49–7.43 (m, 2H), 7.25–7.15 (m, 3H), 3.62 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ157.61, 141.18, 133.23, 132.17, 130.26, 129.90, 128.63, 127.82, 126.19,125.82, 125.54, 120.87, 117.76, 111.36, 105.54, 55.65. LR-MS (ESI): m / z 310.1[M+H] + 。

[0066] 10-(3-methoxyphenyl)anthracene-9-carbonitrile (30)

[0067] Yellow solid, yield 45%. Mp. 182-183 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.47(d, J = 8.7 Hz, 2H), 7.77 (d, J = 8.8 Hz, 2H), 7.72–7.66 (m, 2H), 7.51 (t, J = 7.9Hz, 1H), 7.48–7.42 (m, 2H), 7.13 (dd, J = 8.3, 2.6 Hz, 1H), 7.01–6.92 (m, 2H),3.87 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 159.75, 143.65, 138.68, 133.12,129.71, 129.57, 128.70, 127.94, 126.31, 125.45, 123.13, 117.54, 116.33,113.88, 105.64, 55.43. LR-MS (ESI): m / z 310.1 [M+H] + 。

[0068] 10-(3-bromophenyl)anthracene-9-carbonitrile (3p)

[0069] Yellow solid, yield 34%. Mp. 169-170 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.46(d, J = 8.6 Hz, 2H), 7.76–7.64 (m, 5H), 7.55 (s, 1H), 7.52–7.43 (m, 3H), 7.31(d, J = 7.6 Hz, 1H). 1313C NMR (101 MHz, CDCl3) δ 141.70, 139.48, 133.52, 133.01, 131.57, 130.25, 129.50, 129.44, 128.79, 127.46, 126.71, 125.61, 122.91, 117.34, 106.28. LR-MS (ESI): m / z 358.0 [M+H] + 。

[0070] 10-(3-(trifluoromethyl)phenyl)anthracene-9-carbonitrile (3q)

[0071] Yellow solid, yield 44%. Mp. 175 - 176 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.50 (d, J J = 8.7 Hz, 2H), 7.88 (d, J J = 7.9 Hz, 1H), 7.77 (t, J J = 7.7 Hz, 1H), 7.75–7.69 (m, 3H), 7.65–7.59 (m, 3H), 7.50 (ddd, J J = 8.6, 6.6, 1.2 Hz, 2H). 13 13C NMR (101 MHz, CDCl3) δ 141.61, 138.36, 134.21, 133.10, 131.42 (q, J J = 32.32 Hz), 129.64, 129.39, 128.89, 127.49 (q, J J = 4.04 Hz), 127.29, 126.92, 125.77, 125.41 (q, J J = 4.04 Hz), 122.76, 117.35, 106.58. 19 19F NMR (377 MHz, CDCl3) δ -62.44. LR-MS (ESI): m / z 348.1 [M+H] + 。

[0072] 10-(3-fluorophenyl)anthracene-9-carbonitrile (3r)

[0073] Yellow solid, yield 78%. Mp. 179-180 ℃. 1 1H NMR (400 MHz, CDCl3) δ 8.48(d, J J = 8.8 Hz, 2H), 7.72-7.68 (m, 4H), 7.58 (td, J J = 8.0, 5.8 Hz, 1H), 7.51–7.45(m, 2H), 7.30 (td, J J = 8.6, 2.6 Hz, 1H), 7.17 (d, J J = 7.5 Hz, 1H), 7.12 (dd, J J=9.0, 1.8 Hz, 1H). 13 13C NMR (101 MHz, CDCl3) δ 164.13, 161.66, 142.01 (d, J J = 2.02Hz), 139.54 (d, J J = 7.07 Hz), 133.07, 130.39 (d, J J = 9.09 Hz), 129.48, 128.81,127.50, 126.65,126.59 (d, J J = 3.03 Hz), 125.61, 117.40,116.70 (dd, J J = 247.45,22.22 Hz), 106.21. 19 19F NMR (376 MHz, CDCl3) δ -112.36. LR-MS (ESI): m / z 298.1[M+H] + 。

[0074] 10-(2-fluorophenyl)anthracene-9-carbonitrile(3s)

[0075] Yellow solid, yield 51%. Mp. 175-179 ℃. 1 1H NMR (400 MHz, CDCl3) δ8.53–8.48 (m, 2H), 7.74–7.67 (m, 4H), 7.65–7.58 (m, 1H), 7.52–7.47 (m, 2H),7.42–7.33 (m, 3H). 1313C NMR (101 MHz, CDCl3) δ 161.59, 159.13, 137.24, 133.06, 132.79 (d, J J = 3.03 Hz), 130.88 (d, J J = 8.08 Hz), 128.78, 127.22 (t, J J = 265.63Hz), 126.79, 125.66, 124.67, 124.53, 117.40, 116.20 (d, J J = 21.21 Hz), 106.57. 19 19F NMR (377 MHz, CDCl3) δ -112.89. LR-MS (ESI): m / z 298.1 [M+H] + 。

[0076] 10-(3,4-difluorophenyl)anthracene-9-carbonitrile(3t)

[0077] Yellow solid, yield 31%. Mp. 117-119 ℃. 1 1H NMR (400 MHz, CDCl3) δ 8.49(d, J J = 8.7 Hz, 2H), 7.76–7.64 (m, 4H), 7.51 (ddd, J J = 8.9, 6.6, 1.2 Hz, 2H),7.43 (dt, J J = 10.2, 8.2 Hz, 1H), 7.28 – 7.19 (m, 1H), 7.14 (ddt, J J = 8.1, 3.8,1.7 Hz, 1H). 13 13C NMR (101 MHz, CDCl3) δ 151.80 (d, J J = 12.12 Hz), 149.30 (d, J J =13.13 Hz), 141.00, 134.17 (dd, J J = 6.06, 4.04 Hz), 133.08, 129.67, 128.89, 127.28, 127.13 (dd, J J = 6.06, 4.04 Hz), 126.90, 125.76, 120.03 (d, J= 17.17Hz), 117.89 (d, J = 17.17 Hz), 117.34, 106.56. 19 19F NMR (377 MHz, CDCl3) δ -136.75 (dt, J = 19.9, 9.5 Hz), -137.69 (m). LR-MS (ESI): m / z 316.0 [M+H] + 。

[0078] 10-(3,5-dimethylphenyl)anthracene-9-carbonitrile(3u)

[0079] Yellow solid, yield 59%. Mp. 197-198 ℃. 1 1H NMR (400 MHz, CDCl3) δ 8.49(d, J = 8.7 Hz, 2H), 7.79 (d, J = 8.9 Hz, 2H), 7.73–7.64 (m, 2H), 7.49–7.41 (m,2H), 7.22 (s, 1H), 7.02 (s, 2H), 2.45 (s, 6H). 13 13C NMR (101 MHz, CDCl3) δ144.45, 138.13, 137.20, 133.16, 129.90, 129.68, 128.65, 128.44, 128.17,126.11, 125.42, 117.66, 105.32, 21.46. LR-MS (ESI): m / z 308.1 [M+H] + 。

[0080] 10-(3,4-dimethoxyphenyl)anthracene-9-carbonitrile(3v)

[0081] Yellow solid, yield 50%. Mp. 259-272 ℃. 1 1H NMR (400 MHz, CDCl3) δ 8.46(d, J = 8.7 Hz, 2H), 7.81 (d, J= 8.9 Hz, 2H), 7.73–7.64 (m, 2H), 7.46 (t, J = 7.7Hz, 2H), 7.10 (d, J = 8.1 Hz, 1H), 6.99 – 6.89 (m, 2H), 4.03 (s, 3H), 3.87 (s,3H). 13 C NMR (101 MHz, CDCl3) δ 149.02, 143.84, 133.16, 129.96, 129.61(2×C),128.70, 128.02, 126.29, 125.47, 123.18, 117.63, 113.78, 111.18, 105.43,56.12, 56.10. LR-MS (ESI): m / z 340.1 [M+H] + 。

[0082] 10-(3,4,5-trimethoxyphenyl)anthracene-9-carbonitrile(3w)

[0083] Yellow solid, yield 38%. Mp. 224-247 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.47(d, J = 8.6 Hz, 2H), 7.82 (d, J = 8.8 Hz, 2H), 7.71 (ddd, J = 8.6, 6.6, 1.2 Hz,2H), 7.50 (ddd, J = 8.9, 6.6, 1.2 Hz, 2H), 6.63 (s, 2H), 4.03 (s, 3H), 3.85 (s,6H). 13 C NMR (101 MHz, CDCl3) δ 153.46, 143.83, 137.87, 133.15, 132.86, 129.73,128.80, 127.99, 126.45, 125.53, 117.56, 107.88, 105.67, 61.21, 56.36. LR-MS(ESI): m / z 370.1 [M+H] + 。

[0084] 10-(benzo[d][1,3]dioxol-5-yl)anthracene-9-carbonitrile(3x)

[0085] Yellow solid, yield 30%. Mp. 261-289 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.48(d, J = 8.7 Hz, 2H), 7.82 (d, J = 8.8 Hz, 2H), 7.70 (td, J = 8.0, 1.3 Hz, 2H), 7.47(td, J = 8.0, 4.0 Hz 2H),7.04 (d, J = 7.8 Hz, 1H), 6.88–6.81 (m, 2H), 6.13 (s,2H). 13 C NMR (101 MHz, CDCl3) δ 148.05, 147.82, 143.47, 133.24, 130.80, 130.03,128.76, 127.95, 126.39, 125.61, 124.36, 117.63, 111.35, 108.67, 105.74,101.58. LR-MS (ESI): m / z 324.1 [M+H] + 。

[0086] 10-(naphthalen-1-yl)anthracene-9-carbonitrile (3y)

[0087] Yellow solid, yield 76%. Mp. 187-188 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.59(d, J = 8.7 Hz, 2H), 8.12 (d, J = 8.3 Hz, 1H), 8.04 (d, J = 8.3 Hz, 1H), 7.75–7.66(m, 3H), 7.56– 7.46 (m, 4H), 7.39–7.30 (m, 2H), 7.23 (t, J = 7.5 Hz, 1H), 7.01(d, J= 8.5 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ 142.20, 134.90, 133.66, 133.14,132.97, 130.43, 128.95, 128.83, 128.79, 128.48, 127.93, 126.78, 126.50,126.39, 126.11, 125.59, 125.50, 117.59, 106.05. LR-MS (ESI): m / z 330.1 [M+H] + .

[0088] 10-(naphthalen-2-yl)anthracene-9-carbonitrile (3z)

[0089] Yellow solid, yield 57%. Mp. 270 - 272 °C. 1 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J = 8.7 Hz, 2H), 7.84 (dd, J = 8.5, 3.8 Hz, 4H), 7.78–7.74 (m, 2H), 7.71 (d, J = 7.7 Hz, 1H), 7.54 (t, J = 7.5 Hz, 2H), 7.50–7.44 (m, 4H). 13 C NMR (101 MHz,CDCl3) δ 143.60, 141.21, 140.51, 136.25, 133.19, 131.23, 129.74, 129.10,128.77, 127.95, 127.84, 127.31, 127.27, 126.39, 125.57, 117.65, 105.71. LR-MS(ESI): m / z 330.1 [M+H] + 。

[0090] 2,3,6,7-tetramethyl-10-phenylanthracene-9-carbonitrile (3aa)

[0091] Yellow solid, yield 65%. Mp. > 310 °C. 11H NMR (400 MHz, CDCl3) δ 8.18 (s, 2H), 7.66–7.53 (m, 3H), 7.36 (s, 4H), 2.51 (s, 6H), 2.33 (s, 6H). 13 13C NMR (101MHz, CDCl3) δ 141.26, 139.16, 138.03, 136.23, 132.28, 130.78, 128.61, 128.64, 128.07, 126.51, 124.49, 118.44, 102.59, 20.62, 20.59. LR-MS (ESI): m / z 336.1 [M+H] + 。

[0092] 13-phenyl-2,3,9,10-tetrahydroanthra[2,3-b:6,7-b']bis([1,4]dioxine)-6-carbonitrile (3ab)

[0093] Yellow solid, yield 46%. Mp. 305 - 310 ℃. 1 1H NMR (400 MHz, CDCl3) δ 7.76(s, 2H), 7.50 - 7.56 (m, 3H), 7.30 (dd, J =8.0, 1.6 Hz, 2H), 6.99 (s, 2H), 4.40–4.36 (m, 4H), 4.31 (t, J = 3.3 Hz, 4H). 13 13C NMR (101 MHz, CDCl3) δ 146.75, 144.18, 139.89, 137.96, 130.50, 130.17, 128.79, 128.17, 125.87, 118.38, 111.54, 109.03, 100.73, 64.78, 64.51. LR-MS (ESI): m / z 396.1 [M+H] + 。

[0094] 11-phenylanthra[2,3-d:6,7-d']bis([1,3]dioxole)-5-carbonitrile (3ac)

[0095] Yellow solid, yield 87%. Mp. > 310 °C. 1 1H NMR (400 MHz, CDCl3) δ 7.62 (s, 2H), 7.53 - 7.59 (m, 3H), 7.29 (dd, J J = 6.0, 2.0 Hz, 2H), 6.77 (s, 2H), 6.06 (s, 4H). 13 13C NMR (101 MHz, CDCl3) δ 150.04, 148.04, 140.67, 138.25, 131.03, 130.40, 128.98, 128.31, 126.93, 118.36, 103.25, 102.55, 101.84, 100.56. LR-MS (ESI): m / z 368.0 [M+H] + 。

[0096] 2,3,6,7 - tetramethoxy - 10 - phenylanthracene - 9 - carbonitrile (3ad)

[0097] Yellow solid, yield 48%. Mp. 249 - 250 °C. 1 1H NMR (400 MHz, CDCl3) δ 7.59–7.52 (m, 3H), 7.49 (s, 2H), 7.33 (dd, J J = 8.0, 1.6 Hz, 2H), 6.72 (s, 2H), 4.09 (s, 6H), 3.71 (s, 6H). 13 13C NMR (101 MHz, CDCl3) δ 151.81, 149.46, 139.06, 138.10, 130.34, 129.61, 128.83, 128.23, 125.15, 118.68, 104.62, 102.54, 100.70, 56.23, 55.65. LR-MS (ESI): m / z 340.1 [M+H] + 。

[0098] 2,3,6,7 - tetramethoxy - 10 - (4 - (trifluoromethoxy)phenyl)anthracene - 9 - carbonitrile (3ae)

[0099] Yellow solid, yield 41%. Mp. 240 - 242 °C. 1 H NMR (400 MHz, CDCl3) δ 7.54(s, 2H), 7.47 (d, J J = 8.3 Hz, 2H), 7.42 (dd, J J = 8.7 Hz, 2H), 6.67 (s, 2H), 4.11(s, 6H), 3.74 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 152.05, 149.92, 149.23,137.23, 136.97, 132.05, 129.69, 125.31, 121.97, 121.37, 119.40, 118.53,104.25, 102.76, 101.38, 56.33, 55.76. 19 F NMR (377 MHz, CDCl3) δ -57.72. LR-MS(ESI): m / z 484.1 [M+H] + 。

[0100] 2,3,6,7-tetramethyl-10-(p-tolyl)anthracene-9-carbonitrile (3af)

[0101] Yellow solid, yield 57%. Mp. 291 - 292 °C. 1 H NMR (400 MHz, CDCl3) δ 8.15(s, 2H), 7.41 (s, 2H), 7.40 (s, 2H), 7.24 (d, J J = 7.6 Hz, 2H), 2.56 (s, 3H),2.50 (s, 6H), 2.33 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 141.45, 139.04, 137.70,136.05, 134.82, 132.22, 130.62, 129.27, 128.66, 126.57, 124.40, 118.46,102.29, 21.56, 20.58, 20.53. LR-MS (ESI): m / z 350.1 [M+H] + 。

[0102] Example 3

[0103] Referring to the above method, benzoylacetonitrile was replaced with benzophenone. Different reaction substrates (benzophenone and o-diiodobenzene) and the corresponding 9,10-diphenyl-substituted anthracene derivatives 5 are shown in Table 3, where the time is the reaction time.

[0104]

[0105] In the table, a Reaction conditions: Under N2 atmosphere, NaH (3.5 mmol, 7.0 equiv), 2 (1.25 mmol, 2.5 equiv) were dispersed in THF (3.0 mL), and a solution of 4 (0.5 mmol, 1.0 equiv) in THF (2.0 mL) was added dropwise, and the reaction was stirred at 50 °C.

[0106] The above product data is characterized as follows:

[0107] 9,10-diphenylanthracene (5a)

[0108] Yellow solid, yield 41%. Mp. 250-256 °C. 1 1H NMR (400 MHz, CDCl3) δ 7.74 (dt, J J = 6.8, 4.0 Hz, 4H), 7.58-7.66 (m, 6H), 7.55–7.49 (m, 4H), 7.36 (dt, J J = 6.3, 3.0 Hz, 4H). 13 13C NMR (101 MHz, CDCl3) δ 139.23, 137.26, 131.47, 130.02, 128.56, 127.61, 127.11, 125.14. LR-MS (ESI): m / z 331.1 [M+H] + .

[0109] 9-phenyl-10-(p-tolyl)anthracene (5b)

[0110] Yellow solid, yield 38%. Mp. 195-199 °C. 1 1H NMR (400 MHz, CDCl3) δ 7.76 (dd, J= 6.9, 3.2 Hz, 2H), 7.72 (dd, J = 6.8, 3.2 Hz, 2H), 7.65–7.59 (m, 2H), 7.58 (d, J = 7.2 Hz, 1H), 7.53–7.48 (m, 2H), 7.42 (q, J = 7.9 Hz, 4H), 7.34 (dd, J = 6.8, 3.3 Hz, 4H), 2.57 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 139.29, 137.38, 137.22, 137.08, 136.11, 131.49, 131.35, 130.14, 130.04, 129.27, 128.54, 127.58, 127.21, 127.09, 125.11, 125.03, 21.55. LR-MS (ESI): m / z 345.1 [M+H] + 。

[0111] 9-phenyl-10-(4-(trifluoromethoxy)phenyl)anthracene(5c)

[0112] White solid, yield 90%. Mp. 206-208 ℃. 1 1H NMR (400 MHz, CDCl3) δ 7.74–7.70 (m, 2H), 7.67–7.60 (m, 4H), 7.59–7.55 (m, 1H), 7.54–7.46 (m, 6H), 7.40–7.33 (m, 4H). 13 13C NMR (101 MHz, CDCl3) δ 148.93, 139.05, 137.92, 137.83, 135.47, 132.92, 131.41, 130.02, 128.60, 127.72, 127.26, 126.65, 125.52, 125.25, 122.09, 121.11, 119.53. 19 19F NMR (377 MHz, CDCl3) δ -57.59. LR-MS (ESI): m / z 415.1 [M+H] + 。

[0113] 9-(4-methoxyphenyl)-10-phenylanthracene(5d)

[0114] White solid, yield 34%. Mp. 227-229 ℃. 1 H NMR (400 MHz, CDCl3) δ 7.80–7.75 (m, 2H), 7.73–7.69 (m, 2H), 7.62 (t, J = 7.0 Hz, 2H), 7.56 (t, J = 7.3 Hz,1H), 7.52–7.48 (m, 2H), 7.42 (d, J = 8.6 Hz, 2H), 7.37–7.32 (m, 4H), 7.16 (d, J =8.6 Hz, 2H), 3.98 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 159.18, 139.28, 137.09,137.06, 132.53, 131.48, 131.24, 130.36, 130.06, 128.55, 127.58, 127.19,127.10, 125.11, 125.05, 114.02, 55.52. LR-MS (ESI): m / z 361.1 [M+H] + 。

[0115] 9-(4-fluorophenyl)-10-phenylanthracene(5e)

[0116] White solid, yield 35%. Mp. 249-251 ℃. 1 H NMR (400 MHz, CDCl3) δ 7.75–7.67 (m, 4H), 7.62 (dd, J = 7.9, 6.2 Hz, 2H), 7.59–7.55 (m, 1H), 7.52–7.44 (m,4H), 7.39–7.29 (m, 6H). 1313C NMR (101 MHz, CDCl3) δ 163.77, 161.32, 139.12, 137.57, 136.00, 135.03, 133.08, 133.00, 131.43, 130.10 (d, J J = 17.17 Hz), 128.58, 127.67, 127.21, 126.81, 125.27 (d, J J = 16.16 Hz), 115.62 (d, J J = 21.21 Hz). 19 19F NMR (377 MHz, CDCl3) δ -114.94. LR-MS (ESI): m / z 349.1 [M+H] + .

[0117] 9-(4-chlorophenyl)-10-phenylanthracene(5f)

[0118] White solid, yield 40%. Mp. 245-247 ℃. 1 1H NMR (400 MHz, CDCl3) δ 7.90 (d, J J = 7.9 Hz, 2H), 7.75–7.71 (m, 2H), 7.66–7.57 (m, 7H), 7.51–7.48 (m, 2H), 7.39–7.34 (m, 4H). 13 13C NMR (101 MHz, CDCl3) δ 143.32, 138.96, 138.05, 135.34, 131.93, 131.38, 129.98, 129.77, 128.62, 127.76, 127.31, 126.50, 125.64, 125.59, 125.56, 125.29. LR-MS (ESI): m / z 365.1 [M+H] + .

[0119] 9-(4-bromophenyl)-10-phenylanthracene(5g)

[0120] Yellow solid, yield 66%. Mp. 193-206 ℃. 1 1H NMR (400 MHz, CDCl3) δ 7.76 (d, J= 8.3 Hz, 2H), 7.74–7.67 (m, 4H), 7.59–7.66 (m, 3H), 7.51 (dd, J = 8.3, 0.3Hz, 2H), 7.41–7.34 (m, 6H). 13 C NMR (101 MHz, CDCl3) δ 139.06, 138.20, 137.73, 135.66, 133.21, 131.84, 131.41, 130.00, 129.89, 128.59, 127.70, 127.24, 126.70, 125.45, 125.23, 121.90. LR-MS (ESI): m / z 409.0 [M+H] + 。

[0121] 9-(3-bromophenyl)-10-phenylanthracene(5h)

[0122] White solid, yield 42%. Mp. 183-185 ℃. 1 1H NMR (400 MHz, CDCl3) δ 7.79(d, J = 3.1 Hz, 1H), 7.78–7.71 (m, 5H), 7.65 (q, J = 8 Hz, 2H), 7.60 (dd, J = 8, 4Hz, 1H), 7.56–7.53 (m, 2H), 7.52 (s, 2H), 7.40 (dtd, J = 12.0, 6.4, 3.2 Hz,4H). 13 C NMR (101 MHz, CDCl3) δ 141.48, 139.01, 137.86, 135.29, 134.34, 131.41, 131.35, 130.79, 130.18, 130.13, 129.95, 129.87, 128.58, 128.55, 127.68, 127.21, 126.65, 125.54, 125.23, 122.80. LR-MS (ESI): m / z 409.0 [M+H] + 。

[0123] 9-(4-ethoxyphenyl)-10-phenylanthracene(5i)

[0124] Yellow solid, yield 32%. Mp. 210-214 ℃. 1 H NMR (400 MHz, CDCl3) δ7.80–7.74 (m, 2H), 7.73–7.68 (m, 2H), 7.64–7.58 (m, 2H), 7.58–7.53 (m, 1H),7.51–7.47 (m, 2H), 7.42–7.38 (m, 2H), 7.37–7.31 (m, 4H), 7.17–7.12 (m, 2H),4.20 (q, J = 7.0 Hz, 2H), 1.54 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ158.56, 139.29, 137.16, 137.03, 132.51, 131.48, 131.07, 130.36, 130.06,128.54, 127.57, 127.22, 127.08, 125.10, 125.02, 114.52, 63.68, 15.13. LR-MS(ESI): m / z 375.1 [M+H] + 。

[0125] 9-(4-ethylphenyl)-10-phenylanthracene(5 j )

[0126] White solid, yield 46%. Mp. 210-213 ℃. 1 H NMR (400 MHz, CDCl3) δ 7.79–7.75 (m, 2H), 7.72 (dd, J = 7.1, 3.0 Hz, 2H), 7.65–7.54 (m, 3H), 7.53–7.49 (m,2H), 7.44 (q, J = 8.1 Hz, 4H), 7.37–7.32 (m, 4H), 2.87 (q, J = 7.6 Hz, 2H), 1.43(t, J= 7.6 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 143.51, 139.32, 137.47, 137.06, 136.33, 131.50, 131.39, 130.17, 130.06, 128.55, 128.01, 127.58, 127.26, 127.08, 125.12, 125.02, 28.90, 15.71. LR-MS (ESI): m / z 359.1 [M+H] + 。

[0127] 9-(4-isopropylphenyl)-10-phenylanthracene(5k)

[0128] Yellow solid, yield 55%. Mp. 241 - 248 ℃. 1 1H NMR (400 MHz, CDCl3) δ 7.80–7.76 (m, 2H), 7.72 (dd, J J = 7.0, 2.7 Hz, 2H), 7.66–7.57 (m, 3H), 7.53–7.46 (m, 4H), 7.43 (d, J J = 8.1 Hz, 2H), 7.37–7.32 (m, 4H), 3.12 (p, J J = 7.0 Hz, 1H), 1.44 (d, J J = 6.9 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 148.13, 139.32, 137.53, 137.03, 136.39, 131.50, 131.35, 130.17, 130.05, 128.55, 127.57, 127.30, 127.06, 126.57, 125.11, 125.01, 34.15, 24.30. LR-MS (ESI): m / z 373.1 [M+H] + 。

[0129] 9-(4-(tert-butyl)phenyl)-10-phenylanthracene(5l)

[0130] White solid, yield 56%. Mp. 264 - 266 ℃.1 1H NMR (400 MHz, CDCl3) δ 7.78–7.74 (m, 2H), 7.72–7.68 (m, 2H), 7.61 (dd, J J = 7.9, 6.1 Hz, 4H), 7.58–7.54 (m,1H), 7.51–7.47 (m, 2H), 7.42 (d, J J = 8.3 Hz, 2H), 7.36–7.31 (m, 4H), 1.49 (s,9H). 13 13C NMR (101 MHz, CDCl3) δ 150.42, 139.32, 137.50, 137.02, 136.00, 131.50,131.08, 130.17, 130.04, 128.55, 127.57, 127.32, 127.06, 125.41, 125.12,125.00, 34.90, 31.70. LR-MS (ESI): m / z 387.1 [M+H] + 。

[0131] 9-(4-(benzyloxy)phenyl)-10-phenylanthracene(5m)

[0132] Yellow solid, yield 37%. Mp. 193-195 ℃. 1 1H NMR (400 MHz, CDCl3)δ 7.83–7.77 (m, 2H), 7.76–7.71 (m, 2H), 7.65–7.56 (m, 5H), 7.49 (dd, J J = 15.5, 7.0 Hz,4H), 7.43 (dd, J J = 7.6, 5.3 Hz, 3H), 7.39–7.33 (m, 4H), 7.25 (d, J J = 8.5 Hz, 2H),5.23 (s, 2H). 1313C NMR (101 MHz, CDCl3) δ 158.47, 139.27, 137.20, 137.10, 137.01, 132.57, 131.54, 131.47, 130.34, 130.06, 128.82, 128.54, 128.22, 127.78, 127.58, 127.19, 127.10, 125.12, 125.07, 114.90, 70.33. LR-MS (ESI): m / z 437.1 [M+H] + 。

[0133] 9-(4-phenoxyphenyl)-10-phenylanthracene(5n)

[0134] White solid, yield 33%. Mp. 227-228 ℃. 1 1H NMR (400 MHz, CDCl3) δ 7.78(dd, J J = 7.6, 2.4 Hz, 2H), 7.72 (dd, J J = 7.1, 2.3 Hz, 2H), 7.64–7.54 (m, 3H), 7.51–7.48 (m, 2H), 7.47–7.41 (m, 4H), 7.39–7.32 (m, 4H), 7.23 - 7.27 (m, 4H), 7.19 (t, J J = 7.4 Hz, 1H). 13 13C NMR (101 MHz, CDCl3) δ 157.12, 157.10, 139.20, 137.32, 136.61, 133.78, 132.81, 131.45, 130.23, 130.04, 128.56, 127.62, 127.16, 127.03, 125.21, 125.17, 123.76, 119.54, 118.60. LR-MS (ESI): m / z 423.1 [M+H] + 。

[0135] 5-(10-phenylanthracen-9-yl)benzo [1,3]dioxole(5o)

[0136] Yellow solid, yield 42%. Mp. 176 - 177 °C. 1 1H NMR (400 MHz, CDCl3) δ 7.82 (dd, J J = 7.0, 2.1 Hz, 2H), 7.72 (dd, J J = 7.4, 2.6 Hz, 2H), 7.65–7.56 (m, 3H), 7.52–7.48 (m, 2H), 7.40 – 7.33 (m, 4H), 7.08 (d, J J = 7.8 Hz, 1H), 7.01–6.94 (m, 2H), 6.14 (s, 2H). 13 13C NMR (101 MHz, CDCl3) δ 147.89, 147.16, 139.19, 137.29, 136.72, 132.71, 131.45, 130.27, 130.02, 128.55, 127.61, 127.12, 127.05, 125.18, 125.14, 124.78, 112.00, 108.55, 101.33. LR-MS (ESI): m / z 375.1 [M+H] + 。

[0137] 6-(10-phenylanthracen-9-yl)-2,3-dihydrobenzo[1,4]dioxine(5p)

[0138] Yellow solid, yield 42%. Mp. 260 - 265 °C. 1 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J J = 8.2 Hz, 2H), 7.71 (d, J J = 8.2 Hz, 2H), 7.62 - 7.56 (m, 3H), 7.50 (d, J J = 7.2 Hz, 2H), 7.35 (t, J J = 6.4 Hz, 4H), 7.11 (d, J J = 8.1 Hz, 1H), 7.04 (s, 1H), 6.97 (d, J J = 8.0 Hz, 1H), 4.41 (s, 4H). 1313C NMR (101 MHz, CDCl3) δ 143.62, 143.20, 139.26, 137.12, 136.74, 132.27, 131.47, 130.19, 130.01, 128.53, 127.57, 127.21, 127.05, 125.12, 125.07, 124.67, 120.31, 117.34, 64.64. LR-MS (ESI): m / z 389.1 [M+H] + 。

[0139] 9-(3,5-dimethoxyphenyl)-10-phenylanthracene (5q)

[0140] Pale yellow solid. Mp. 242 - 245 °C. 1 1H NMR (400 MHz, CDCl3) δ 7.85 (dd, J J = 7.4, 2.8 Hz, 2H), 7.74 (dd, J J = 7.3, 2.8 Hz, 2H), 7.66–7.57 (m, 3H), 7.55–7.51 (m, 2H), 7.42–7.35 (m, 4H), 6.72 (s, 3H), 3.89 (s, 6H). 13 13C NMR (101 MHz, CDCl3) δ 160.93, 141.31, 139.17, 137.27, 137.13, 131.44, 129.95, 129.74, 128.55, 127.61, 127.14, 127.05, 125.19, 109.48, 99.95, 55.57. LR-MS (ESI): m / z 391.1 [M+H] + 。

[0141] 9-(3,5-dimethylphenyl)-10-phenylanthracene (5r)

[0142] White solid, yield 30%. Mp. 172 - 174 °C. 11H NMR (400 MHz, CDCl3) δ 7.79–7.74 (m, 2H), 7.72–7.68 (m, 2H), 7.65–7.55 (m, 3H), 7.51–7.48 (m, 2H), 7.37–7.31 (m, 4H), 7.20 (s, 1H), 7.12 (s, 2H), 2.46 (s, 6H). 13 13C NMR (101 MHz,CDCl3) δ 139.32, 139.04, 137.95, 137.72, 136.96, 131.50, 130.02, 129.99,129.23, 129.15, 128.54, 127.57, 127.32, 127.05, 125.09, 124.98, 21.57. LR-MS(ESI): m / z 359.1 [M+H] + 。

[0143] 9-([1,1'-biphenyl]-4-yl)-10-phenylanthracene(5s)

[0144] Yellow solid, yield 57%. Mp. 270-277 ℃. 1 1H NMR (400 MHz, CDCl3) δ 7.86(d, J = 8.1 Hz, 2H), 7.84 –7.78 (m, 4H), 7.76–7.72 (m, 2H), 7.66–7.57 (m, 5H),7.53 (dd, J = 8.0, 6.3 Hz, 4H), 7.44 (t, J = 7.4 Hz, 1H), 7.40 – 7.34 (m, 4H). 13 13C NMR (101 MHz, CDCl3) δ 141.02, 140.42, 139.23, 138.22, 137.35, 136.91,131.95, 131.48, 130.07, 130.06,129.06, 128.57, 127.63, 127.59, 127.33,127.25, 127.16, 127.12, 125.22, 125.19. LR-MS (ESI): m / z 407.1 [M+H] + 。

[0145] 9-(naphthalen-2-yl)-10-phenylanthracene(5t)

[0146] White solid, yield 47%. Mp. 251-253 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.10(d, J = 8.3 Hz, 1H), 8.07 – 8.03 (m, 1H), 8.01 (d, J = 1.6 Hz, 1H), 7.96–7.92 (m,1H), 7.76 (dd, J = 8.8, 1.4 Hz, 4H), 7.68–7.58 (m, 6H), 7.54 (dd, J = 7.0, 1.6Hz, 2H), 7.34 (td, J = 7.8, 1.6 Hz, 4H). 13 C NMR (101 MHz, CDCl3) δ 139.23,137.42, 137.05, 136.75, 133.57, 132.91, 131.49, 130.39, 130.19, 130.06,129.72, 128.58, 128.24, 128.11, 128.05, 127.64, 127.17, 127.05,126.58,126.37, 125.25, 125.19. LR-MS (ESI): m / z 381.1 [M+H] + .

[0147] 9-(naphthalen-1-yl)-10-phenylanthracene(5u)

[0148] White solid, yield 51%. Mp. 226-228 ℃. 1 H NMR (400 MHz, CDCl3) δ 8.09(d, J = 8.3 Hz, 1H), 8.04 (d, J = 8.2 Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.73 (t, J= 7.6 Hz, 1H), 7.69–7.52 (m, 7H), 7.48 (d, J = 8.6 Hz, 3H), 7.36–7.31 (m, 2H), 7.24 (d, J = 9.4 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 139.22, 137.62, 136.94, 135.16, 133.85, 133.76, 131.53, 131.54, 130.78, 130.08, 129.36, 128.58, 128.37, 128.24, 127.66, 127.19, 126.82, 126.42, 126.15, 125.75, 125.31, 125.22. LR-MS (ESI): m / z 381.1 [M+H] + 。

[0149] 9,10 - di - p - tolylanthracene(5v)

[0150] Yellow solid, yield 40%. Mp. 266 - 274 ℃. 1 H NMR (400 MHz, CDCl3) δ 7.75(dd, J = 6.8, 3.3 Hz, 4H), 7.44 - 7.37 (m, 8H), 7.33 (dd, J = 6.8, 3.3 Hz, 4H), 2.56 (s, 6H). 13 C NMR (101 MHz, CDCl3) δ 137.19, 136.16, 131.36, 130.16, 129.25, 127.19, 125.00, 123.61, 21.54. LR-MS (ESI): m / z 359.1 [M+H] + 。

[0151] 9 - (4 - fluorophenyl) - 10 - (p - tolyl)anthracene(5w)

[0152] White solid, yield 48%. Mp. 200 - 202 ℃. 11H NMR (400 MHz, CDCl3) δ 7.78–7.73 (m, 2H), 7.69–7.65 (m, 2H), 7.47–7.41 (m, 4H), 7.38–7.29 (m, 8H), 2.55(s, 3H). 13 13C NMR (101 MHz, CDCl3) δ 163.75, 161.30, 137.70, 137.29, 135.99,135.80, 135.06 (d, J J = 3.03 Hz), 133.05 (d, J J = 8.08 Hz), 131.30, 130.17 (d, J J =7.07 Hz), 129.28, 127.31, 126.79, 125.31, 125.07, 115.60(d, J J = 21.21 Hz),21.55. 19 19F NMR (377 MHz, CDCl3) δ -115.33. LR-MS (ESI): m / z 363.1 [M+H] + 。

[0153] 2,3,6,7-tetramethyl-9,10-diphenylanthracene(5aa)

[0154] Yellow solid, yield 30%. Mp. 245-288 ℃. 1 1H NMR (400 MHz, CDCl3) δ7.67–7.58 (m, 6H), 7.52–7.49 (m, 4H), 7.42 (s, 4H), 2.33 (s, 12H). 13 13C NMR (101MHz, CDCl3) δ 139.80, 134.82, 134.75, 131.52, 128.97, 128.49, 127.29, 125.75,20.60. LR-MS (ESI): m / z 387.1 [M+H] + 。

[0155] 2,3,6,7-tetramethoxy-9,10-diphenylanthracene(5ab)

[0156] Yellow solid, yield 30%. Mp.>310 ℃. 1 H NMR (400 MHz, CDCl3) δ 7.64–7.59 (m, 4H), 7.56–7.51 (m, 2H), 7.51–7.48 (m, 4H), 6.83 (s, 4H), 3.74 (s,12H). 13 C NMR (101 MHz, CDCl3) δ 148.89, 139.89, 133.21, 131.14, 128.81,127.53, 125.92, 103.98, 55.58. LR-MS (ESI): m / z 451.1 [M+H] + 。

[0157] 5-(2,3,6,7-tetramethyl-10-phenylanthracen-9-yl)benzo [3] [1,3]dioxole(5ac)

[0158] Yellow solid, yield 28%. Mp. 295-304 ℃. 1 H NMR (400 MHz, CDCl3) δ7.64–7.55 (m, 3H), 7.48–7.44 (m, 4H), 7.37 (s, 2H), 7.07 (d, J = 7.8 Hz, 1H),6.96–6.90 (m, 2H), 6.15 (s, 2H), 2.34 (s, 6H), 2.31 (s, 6H). 13 C NMR (101 MHz,CDCl3) δ 147.80, 146.90, 139.79, 134.86, 134.82, 134.78,134.20, 133.39,131.51, 129.25, 128.99, 128.48, 127.30, 125.77, 125.72, 124.75, 112.02,108.51, 101.26, 20.60, 20.57. LR-MS (ESI): m / z 431.1 [M+H] + 。

[0159] 9-(4-(tert-butyl)phenyl)-2,3,6,7-tetramethoxy-10-phenylanthracene(5ad)

[0160] White solid, yield 38%. Mp. 274-288 ℃. 1 H NMR (400 MHz, CDCl3) δ 7.63–7.58 (m, 4H), 7.53 (d, J = 7.4 Hz, 1H), 7.50–7.47 (m, 2H), 7.41 (d, J = 8.3 Hz,2H), 6.85 (d, J = 21.8 Hz, 4H), 3.74 (d, J = 6.9 Hz, 12H), 1.47 (s, 9H). 13 C NMR(101 MHz, CDCl3) δ 150.32, 148.95, 148.86, 140.02, 136.68, 133.41, 133.04,131.20, 130.80, 128.81, 127.51, 126.10, 126.01, 125.58, 104.34, 104.02,55.65, 55.59, 34.87, 31.62. LR-MS (ESI): m / z 507.1 [M+H] + 。

[0161] 9-(4-fluorophenyl)-2,3,6,7-tetramethoxy-10-phenylanthracene(5ae)

[0162] Yellow solid, yield 32%. Mp. 287-289 ℃. 1 H NMR (400 MHz, CDCl3) δ 7.61(t, J = 7.3 Hz, 2H), 7.54 (d, J = 7.4 Hz, 1H), 7.46 (dd, J = 11.0, 6.3 Hz, 4H),7.32 (t, J = 8.7 Hz, 2H), 6.80 (d, J= 20.8 Hz, 4H), 3.74 (d, J = 8.8 Hz, 12H). 13 13C NMR (101 MHz, CDCl3) δ 163.60, 161.15, 149.08 (d, J = 3.03 Hz), 139.85, 135.86(d, J = 4.04 Hz), 133.53, 132.82 (d, J = 8.08 Hz), 131.90, 131.14, 128.86,127.62, 126.17, 125.97, 115.93 (d, J = 21.21 Hz), 104.16, 103.75, 55.65,55.63. 19 19F NMR (377 MHz, CDCl3) δ -114.89. LR-MS (ESI): m / z 469.1 [M+H] + 。

[0163] The present invention discloses that o-diiodobenzene can react with active methylene compounds benzoylacetonitrile or benzophenone under the action of NaH to form 9,10-disubstituted anthracene derivatives. This method is an effective method for preparing complex polycyclic aromatic hydrocarbon compounds (PAHs) - anthracene derivatives from simple and readily available substrate raw materials. This method for constructing the anthracene skeleton does not use transition metal catalysts, does not involve harsh conditions such as high temperature and high pressure, and the raw materials are cheap and easily available, providing a more convenient, effective and economical synthesis method for the application field of anthracene, and having important significance and value for the future development of drug synthesis.

[0164] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments, and what is described in the above embodiments and the specification only illustrates the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention will have various changes and improvements, and these changes and improvements all fall within the scope of the present invention claimed. The scope of protection claimed by the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing an anthracycline derivative, characterized in that, The following steps are included. Using o-dihalobenzene and benzophenone compound as raw materials, reacting in the presence of an alkaline metal hydride to obtain an anthracycline derivative; the benzophenone compound is a benzoylacetonitrile compound or a benzil compound; the alkaline metal hydride is one or more of NaH and KH; the reaction temperature is 30 °C to 70 °C; The chemical structural formulas of the benzoylacetonitrile compounds are as follows: ； The chemical structural formula of the benzil compound is as follows: ； The chemical structural formula of o-dihalobenzene is as follows: ； The chemical structural formula of the product anthracycline derivative is as follows: ； In the above chemical structural formulas, Ar is a substituted or unsubstituted phenyl or naphthyl; R1, R`, R`` are independently selected from one of alkyl, halogen, alkoxy, and aryl, wherein the alkyl is a straight-chain or branched-chain alkyl with 1 to 10 carbon atoms, the alkoxy is an alkoxy with 1 to 10 carbon atoms, and the aryl is a phenyl; R2 is selected from one of alkyl and alkoxy, wherein the alkyl has 1 to 10 carbon atoms and the alkoxy has 1 to 10 carbon atoms.

2. The method for preparing an anthracycline derivative according to claim 1, wherein The reaction is carried out in a solvent.

3. The method for preparing an anthracycline derivative according to claim 2, wherein, The solvent is one or more of THF, DMA, 1,4-dioxane, and DME.

4. The method for preparing an anthracycline derivative according to claim 1, wherein The molar ratio of the benzophenone compound, o-dihalobenzene, and alkali metal hydride is 1: (1 to 5): (2 to 8).

5. The method for preparing an anthracycline derivative according to claim 1, wherein The halogen is fluorine, chlorine, bromine, etc.; X is selected from one of chlorine, bromine, iodine, and OTf.

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