Synthesis method of benzochromene compound

Abstract

The invention discloses a synthesis method of a benzochromene compound, and belongs to the technical field of organic synthesis. According to the method, aryl diazonium salt serving as an aryl source and acetonitrile serving as a C1 synthon react with substituted binaphthol, and the benzochromene compound is synthesized through a three-component one-pot method under a certain temperature condition. The method has the advantages of simple operation, cheap and easily available raw materials, mild reaction conditions, green reaction, no catalyst, no additive, environmental friendliness and the like, and provides a new way for preparation of the benzochromene compound.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, specifically to a method for synthesizing benzo[a]ene compounds by tandem cyclization without catalysts or additives, using aryl diazonium salts as aryl sources, acetonitrile as C1 synthons, and substituted binaphthol as a substrate. Background Technology

[0002] Tinones (also known as benzopyrans) are a class of heterocyclic compounds formed by the fusion of a benzene ring and an oxygen-containing heterocycle. They are widely found in various natural products and microorganisms [Fu Chengyu, Zhang Bo. World Pesticides 2015, 37, 16-28; Hu, QF; Zhou, B.; Gao, XMJ Nat. Prod. 2012, 75, 1909-1914; Lin, LB; Gao, YQ; Han, R.; Xiao, J.; Wang, YM; Zhang, Q.; Zhai, YJ; Han, WB; Li, WL; Gao, JMJ Agric. Food Chem. 2021, 69, 6524-6534; Mazaheri, A.; Bostanian, M. Res. Chem. Intermed. 2020, 46, 2327-2350.], constituting compounds such as tocopherols, polyphenols, alkaloids, and flavonoids [Mandal, TK; Kuznetsov, VV; Soldentkov, A. T. Chem. Heterocycl. Compd. 1994, 30, 867-887; Kulkarni, MV; Kulkarni, GM; Lin, CH; Sun, C. Curr. Med. Chem. 2006, 13, 2795-2818; Bari, A. Heterocyclic Chem. 2016, 53, 461-466; Kong, L.; Thirupathi, N.; Jia, J.; Xu, Z. Sci. China Chem.2019,62,80-86;Dai,C.;Luo,N.;Wang,S.;Wang,C.Org.Lett.2019,21,2828-2832;Ibrahim,MA;El-Gohary,NMJHeterocyclic Chem.2016,53,859-864;Iacobucci,GA;Sweeny,JGTetrahedron.1983,39,3005-3038;Bohm,BA;Choy,JB;Lee,AYMPhytochemistry 1989, 28, 501-503; Gill, M. Aust. J. Chem. 1995, 48, 1-26; Parmar, VS; Jain, SC; Bisht, KS; Jain, R.; Taneja, P.; Jha, A.;Phytochemistry 1997, 46, 597-673.] and the core molecular skeleton of various polyphenols [Ren, Q.; Siau, W.-Y.; Du, Z.; Zhang, K.; Wang, J. Chem.-A Eur. J. 2011, 17, 7781-7785.]. These structures and their derivatives exhibit a rich variety of biological activities [Cassidy, F.; Evans, JM; Hadley, MS, J Med. Chem. 1992, 35, 1623-1627; Shestopalov, AM; Litvinov, YM; Rodinovskaya, LA; Malyshev, OR; Semenova, MN; Semenov, VVACS Comb. Sci. 2012, 14, 484-490; Starks, CM; Williams, RB; Norman, VLP hytochemistry 1997, 46, 597-673.]. 2014,98,216-222;Conti,C.;Desideri,N.Bioorg.Med.Chem.2009,17,3720-3727;Tangmouo,JG;Meli, AL; Komguem, J.; Kuete, V.; Ngounou, FN; Lontsi, D.; Beng, VP; Choudhary, MI; Sondengam, BLTetrahedron Lett.2006,47,30673070;Kjer,J.;Wray,V.;Edrada-Ebel,R.;Ebel,R.;Pretsch,A.;Lin,WH;Proksch,PJNat.Prod.2009,72 ,2053-2057.], covering antiviral [Hu, QF; Zhou, B.; Gao, m.Lett.1997,7,3165-3170;Mori,J.;Iwashima,M.;Takeuchi,M.;Saito,HAChem.Pharm.Bull.2006,54,391-396.], anticancer [Sing h, S.; Tiwari, J.; Jaiswal, D.; Sharma, AK; Singh, J.; Singh, V.; Singh, J. Curr. Organocatal.2018,5,51-57; Subramanyam, M.Sreenivasulu,R.Gundla,R.Rao,MVBRao,KPLett.In DrugDes.&Disc.2018,15,1299-1307.] .HIV[Chiruta,C.,Schubert,D.,Dargusch,R.,Maher,PJMed.Chem.2012,55,378-389 [Larget,R.,Lockhart,B.,Renard,P.,Largeron,M.Biorg.Med.Chem.Lett.2000,10,835-838]. rgusch,R.;Maher,PJMed.Chem.2012,55,378-389;Larget,R.Lockhart,B.,Renard,P.,Largeron,M.Biorg.Med.Chem.Lett.2000,10 ,835-838.]、Revised [Chiruta,C.,Schubert,D.;Dargusch,R.;Maher,PJMed.Chem.2012,55,378-389;Larget,R.;Lockhart,B.;Renard,P .Largeron,M.Biorg.Med.Chem.Lett.2000,10,835-838Milan,M.Mirjana,M.Desanka,B.Sanja,M.Neda,N.Vladimir,M.Int .J.Mol.Sci.2011,12,2822-2841.] [Li,Y.;Luo,BL;Luo,ZF;Ma ,TGFan,LL,Liu,WJFan,JDGuo,B.Xue,W.Tang,L.Molec.Div.2 022,27,589-601;El-Agrody,AM;El-Latif,MSA;El-Hady,NA;Fakery,AH;Bedair,AHMolecules2001,6,519-527;Raj,T.Bhatia,RK:S harma,RK;Gupta,V.Sharma,D.Ishar,MPSEur.J.Med.Chem.2009,44,3209-3216Srinivas,B.Suryachandram,J.Devi,YK;Rao,KPJ Hetrocyclic Chem.2017,54,3730-3734.], antifungal [Chetan, BS; Nimesh, MS; Manish, PP; Ranjan, GPJSerb.Chem.Soc.2012,77,1-8.], anti-inflammatory [Peng, F.; Wang, G.; Li, X.; Cao, D.; Yang, Z.; Ma, L.; Ye, H.; Lian g,X.; Ran, Y.; Chen, J.; Qiu, J.; J. Med. Chem. 2012, 54, 272-280; Moon, DO; Choi, YH; Kim, ND; Park, YM; Kim, GYInt. Immunopha [rmacol. 2007, 7, 506-514.], anti-tumor [Henriette, G.; Lorraine, L.; Bettina, H.; Clemence, D.; Kelly, D.; Irenej, K. Mol. Cancer. Ther. 2004, 3, 1375-1384.] and TNF-α inhibition [Cheng, J.; Ishikawa, A.; Ono, Y.; Arrhenius, T.; Nadzan, A. Bioorg. Med. Chem. Lett. 2003, 13, 3647-3650.] and other pharmacological effects [Dofe, VS; Sarkate, AP; Lokwani, DK; Shinde, DB; Kathwate, SH; Gill, CHJ Heterocyclic Chem. 2017, 54, 2678-2685; Tanaka, N.; Kashiwada, Y.; Nakano, T.; Shibata, H.; Higuchi, T.; Sekiya, M.; Ikeshiro, Y.; Takaishi, Y. Phytochemistry 2009, 70, 141-146. Furthermore, chromone derivatives are also used in the development of drugs for antihypertensive, hypoglycemic, and cardioprotective purposes [Hafez, HN; Hegab, MI; Ahmed-Farag, IS; El-Gazzar, ABABioorg. Med. Chem. Lett. 2008, 18, 4538-4543.], exhibiting central nervous system (CNS) activity [Eiden, F.; Denk, F. Arch. Pharm. 1991, 324, 353-354.].DNA mutagenicity [Al-Sehemi, AG; El-Gogary, SR Chin. J. Chem. 2012, 30, 316-320], influenza virus sialidase inhibitory activity [Smith, PW; Sollis, SL; Howes, PD; Cherry, PC; Starkey, ID; Cobley, KN; Weston, H.; Scicinski, J.; Merritt, A.; Whittington, A.; Wyatt, PJ Med. Chem. 1998, 41, 787-797.], pesticide activity [Sheng, J.; Zhang, M.-M.; Jiang, H.; Wang, X.] [-S.; J. Chin. Chem. Soc. 2012, 59, 650-654.] and its potential as an estrogen receptor modulator [Jain, N.; Xu, J.; Kanojia, RM; Du, F.; Jian-Zhong, G.; Pacia, E.; Lai, MT; Musto, A.; Allan, G.; Reuman, M.; Li, X.; Hahn, D.; Cousineau, M.; Peng, S.; Ritchie, D.; Russell, R.; Lundeen, S.; Sui, ZJ Med. Chem. 2009, 52, 7544-7569.], has thus attracted considerable attention in drug development and pesticide chemistry.

[0003] The lipophilicity of chromene compounds enables them to effectively interfere with cell membrane structure and enhance their biological activity [Nicolaou, KC; Pfefferkorn, JA; Roecker, AJ; Cao, GQ; Barluenga, S.; Mitchell, HJJAm. Chem. Soc. 2000, 122, 9939-9953.]. Besides its wide application in the pharmaceutical and pesticide fields, the benzopyran structure also plays an important role in organic materials chemistry, and is widely used in the development of functional materials such as fluorescent dyes, pigments, synthetic fibers, molecular devices, electrophotographic materials, information storage materials, and decorative and anti-counterfeiting packaging materials [Rao, KP; Kusamoto, T.; Toshimitsu, F.; Inayoshi, K.; Kume, S.; Yamamoto, Y.; Sakamoto, R.; Nishihara, H. J. A. J. M. Chem. Soc. 2010, 132, 12472-12479; Rao, KP; Kondo, M.; Sakamoto, R.; Kusamoto, T.; Kume, S.; Nihei, M.; Oshio, H.; Nishihara, H. Chem. A. Eur. J. 2011, 17, 14010-14019.]. Spirochrome compounds have shown promising application prospects in the field of photochromic materials due to their photochromic properties [Huang Zhennian, Zhao Weili, Fan Meigong. Chemical Bulletin, 1996, 12, 16-21; Liu Yu, Dong Yu, Kang Hongbin, Yang Jin. Journal of Honghe University, 2023, 21, 129-132.].

[0004] From a natural source perspective, chromones and their fused analogues are an important component of many natural products, including alkaloids, flavonoids, tocopherols, anthocyanins, and a variety of antibiotics and anticancer drugs [Iacobucci, GA; Sweeny, J. G. T ... For example, in 1992, Kashman et al. [Kashman, Y.; Gustafson, KR; Fuller, RW; Cardellina, JH; Mahon, JB; Currens, MJ; Buckheit, RW; Hughes, SH; Cragg, GM; Boyd, MRJ Med. Chem. 1992, 35, 2735-2743.] isolated a series of pyranoid coumarin compounds from *Calophyllum lanigerum*, among which (+)-Calanolide As a 2,2-dimethyl-2H-chromene derivative, A exhibits strong biological activity [McKee, TC; Covington, CD; Fuller, RW; Bokesch, HR; Young, S.; Cardellina, JH; Kadushin, MR; Soejarto, DD; Stevens, PF; Cragg, GM; Boyd, MRJ Nat. Prod. 1998, 61, 1252-1256; Galinis, DL; Fuller, RW; McKee, TC; Cardellina, JH; Gulakowski, RJ; McMahon, JB; Boyd, MRJ Med. Chem. 1996, 39, 4507-4510.], such as potent anti-HIV-1 activity, and its EC 50The concentration was 0.1 μM. This compound is effective not only against wild-type HIV-1, but also shows significant inhibitory activity against zidovudine-resistant viral strains and other clinical variants, and belongs to the class of non-nucleoside reverse transcriptase inhibitors (NNRTIs).

[0005] In recent years, chromone compounds have also shown significant potential in research on antiviral activity against plant viruses [Hu, QF; Zhou, B.; Gao, XMJNat.Prod.2012,75,1909-1914.]. In 2015, Yang Guangyu [Yang Guangyu, Chen Yongkuan, Liu Zhihua, Han Yi, Duan Yuanxing, Zhang Xia, Zhang Tao, Miao Mingming.CN 103524472B,2015.] et al. isolated 1-(5-methoxy-2,2-dimethyl-3,4-dihydro-2H-chromene-7-yl)-2-propanone from the rhizomes of Yunyan-85. At a concentration of 50 mg / L, it achieved a relative inhibition rate of 38.5% against tobacco mosaic virus (TMV), which was superior to the control agent ningnanmycin (28.2%).

[0006] In 2023, Dai Jiameng et al. [Dai Jiameng, Li Zhenjie, Wang Kai, Xiao Dong, Yang Guangyu, Yang Fengxian, Wang Jin, Zhang Jianduo, Kong Weisong, Wang Wenyuan, Li Yinke, Zhou Min, Hu Qiufen. CN 115557960A, 2023.] isolated isopentenylated indole alkaloid Isoaspergilline A from the fermentation products of Aspergillus versicolor YATS1111 fungus. At a concentration of 20 μM, it showed an inhibition rate of up to 58.4% against TMV, which was significantly higher than that of ningnanmycin control (33.2%).

[0007] In summary, the broad range of biological activities exhibited further highlights the central role of chromone structures in drug discovery and agricultural chemistry. Therefore, structural modification and functional development of the chromone skeleton have become one of the current hot research directions in pesticide and medicinal chemistry.

[0008] Summary of the Invention

[0009] This invention achieves a green and efficient tandem cyclization reaction of substituted binaphthol without the need for catalysts, additives, or metals, using only two reactants and a solvent.

[0010] This invention uses aryl diazonium salts, which are simple to prepare and widely available, as raw materials and substituted binaphthol as substrates to achieve a tandem cyclization reaction to synthesize benzochrome derivatives.

[0011] A method for synthesizing benzo[a]chromene compounds, characterized in that: using an aryl diazonium salt as an aryl source and acetonitrile as a C1 synthon, a tandem cyclization reaction of naphthol can be achieved under heating conditions to obtain benzo[a]chromene compounds.

[0012] The reaction process is shown in the following reaction formula;

[0013]

[0014] in

[0015] Wherein Ar represents aryl or alkyl, alkoxy, halogen-substituted phenyl or substituted phenyl, aryl represents 1-naphthyl-substituted, 2-naphthyl-substituted, etc., where Ar represents naphthyl substituent or benzene ring substituent, one or more substituents at different positions such as ortho, meta, para, etc. of the phenyl substituent, the substituent on the benzene ring of the substituted phenyl is one or more of C1-C16 alkyl, C1-C16 alkoxy, the number of substituents on the benzene ring is 1-5, preferably 1-2, the halogen is one or more of fluorine, chlorine, bromine, iodine, specifically one or more of 4-methylphenyl, 4-methoxyphenyl, 3,4-dimethylphenyl, 3,5-dimethylphenyl. R represents one or more substituents at different positions (ortho, meta, para, etc.) on the phenyl substituent group. The number of substituents on the benzene ring is 1-5, preferably 1-2, and specifically can be one or more of 2-methyl, 3-chloro, 4-bromo, and 4-iodine. The halogen group is one or more of fluorine, chlorine, bromine, and iodine.

[0016] The reaction includes the following steps:

[0017] Add substituted binaphthol and aryl diazonium salt to a container, then perform nitrogen purging three to five times, add solvent, and stir at 20-120℃ for 0.1-5 hours to obtain various benzochrome compounds (III).

[0018] The reaction temperature is 20-120℃, preferably 60-90℃.

[0019] The solvent in the reaction is acetonitrile, a combination of acetonitrile and n-hexane (volume ratio 4:1), or acetonitrile and cyclohexane (volume ratio 4:1). The preferred solvent is acetonitrile. The concentration of the substituted binaphthol in the solvent is 0.05-0.2M, preferably 0.05M.

[0020] In the reaction, the molar ratio of substituted binaphthol to aryl diazonium salt is 1:0.8-1:5.0, and the preferred molar ratio is 1:2.0-1:4.0.

[0021] The reaction time is 0.1-5 hours, with a preferred reaction time of 1-2 hours.

[0022] The structure of the synthesized benzochromene compound is shown in formula (Ⅲ).

[0023]

[0024] Ar represents a naphthyl substituent or a benzene ring substituent, which is a substituent at one or more different positions such as ortho, meta, and para of the phenyl substituent. The number of substituents on the benzene ring is 1-5, preferably 1-2, and can be one or more of 4-methylphenyl, 4-methoxyphenyl, 3,4-dimethylphenyl, and 3,5-dimethylphenyl.

[0025] R represents one or more substituents at different positions such as ortho, meta, and para of the phenyl substituent. The number of substituents on the benzene ring is 1-5, preferably 1-2, and can be one or more of 2-methyl, 3-chloro, 4-bromo, and 4-iodine.

[0026] As shown in the above reaction formula, under the conditions of no catalyst, no additives, no metals, and only two reactants and solvent, the present invention uses substituted binaphthol (I) and aryl diazonium salt (II) as raw materials, and acetonitrile as both solvent and C1 synthon, to achieve the tandem cyclization reaction of substituted binaphthol under heating conditions, to obtain benzochromene compound (III).

[0027] In this invention, the reaction solvent is acetonitrile, a combination of acetonitrile and n-hexane (volume ratio 4:1), or acetonitrile and cyclohexane (volume ratio 4:1). The preferred solvent is acetonitrile. The concentration of the substituted binaphthol in the solvent is 0.05-0.2M, preferably 0.05M.

[0028] In this invention, the molar ratio of substituted binaphthol to aryl diazonium salt in the reaction is 1:1.0-1:5.0, and preferably the molar ratio is 1:2.0-1:4.0.

[0029] In this invention, the reaction time is 0.1-5 hours, preferably 1-2 hours.

[0030] The advantages of this invention are:

[0031] This invention achieves the green and efficient tandem cyclization of substituted binaphthol to obtain benzo[a]chrome compounds without the need for catalysts or accelerators, under metal-free conditions. The raw materials used in this invention are inexpensive, readily available, and widely sourced; the reaction is green, the operation is simple, and no external catalysts or additives are required. Attached Figure Description

[0032] Figure 1 The image shows the 1H NMR spectrum of the product 1-(5-methyl-5-(o-tolylamino)-5H-dibenzo[c,g]chromen-7-yl)-3-phenylnaphth-2-ol from Example 1.

[0033] Figure 2 This is the carbon NMR spectrum of 1-(5-methyl-5-(o-tolylamino)-5H-dibenzo[c,g]chromen-7-yl)-3-phenylnaphth-2-ol, the product of Example 1.

[0034] Figure 3 The image shows the 1H NMR spectrum of the product 1-(3,5-dimethyl-5-(o-tolylamino)-5H-dibenzo[c,g]chromen-7-yl)-3-(p-tolyl)naphth-2-ol from Example 10.

[0035] Figure 4 This is the carbon NMR spectrum of 1-(3,5-dimethyl-5-(o-tolylamino)-5H-dibenzo[c,g]chromen-7-yl)-3-(p-tolyl)naphth-2-ol, the product of Example 10.

[0036] Figure 5 The image shows the 1H NMR spectrum of the product 1-(3-methoxy-5-methyl-5-(o-tolylamino)-5H-dibenzo[c,g]chromen-7-yl)-3-(4-methoxyphenyl)naphth-2-ol from Example 11.

[0037] Figure 6 This is the carbon NMR spectrum of 1-(3-methoxy-5-methyl-5-(o-tolylamino)-5H-dibenzo[c,g]chromen-7-yl)-3-(4-methoxyphenyl)naphth-2-ol, the product of Example 11.

[0038] Figure 7 This is the 1H NMR spectrum of the product 3-(3,5-dimethylphenyl)-1-(2,4,5-trimethyl-5-(o-tolylamino)-5H-dibenzo[c,g]chromen-7-yl)naphth-2-ol from Example 12.

[0039] Figure 8 This is the carbon NMR spectrum of 3-(3,5-dimethylphenyl)-1-(2,4,5-trimethyl-5-(o-tolylamino)-5H-dibenzo[c,g]chromen-7-yl)naphth-2-ol, the product of Example 12.

[0040] Figure 9 The image shows the 1H NMR spectrum of the product 3-(3,4-dimethylphenyl)-1-(2,3,5-trimethyl-5-(o-tolylamino)-5H-dibenzo[c,g]chromen-7-yl)naphth-2-ol from Example 13.

[0041] Figure 10 This is the carbon NMR spectrum of 3-(3,4-dimethylphenyl)-1-(2,3,5-trimethyl-5-(o-tolylamino)-5H-dibenzo[c,g]chromen-7-yl)naphth-2-ol, the product of Example 13.

[0042] Figure 11 The 1H NMR spectrum of the product 4-(7-methyl-7-(o-tolylamino)-7H-benzo[g]naphtho[2,3-c]chromen-5-yl)-[2,2'-binaphthyl]-3-ol from Example 14 is shown.

[0043] Figure 12 The image shows the carbon NMR spectrum of 4-(7-methyl-7-(o-tolylamino)-7H-benzo[g]naphtho[2,3-c]chromen-5-yl)-[2,2'-binaphthyl]-3-ol, the product of Example 14.

[0044] Figure 13 This is the 1H NMR spectrum of the product 1-(5-methyl-5-(phenylamino)-5H-dibenzo[c,g]chromen-7-yl)-3-phenylnaphth-2-ol from Example 15.

[0045] Figure 14 This is the carbon NMR spectrum of 1-(5-methyl-5-(phenylamino)-5H-dibenzo[c,g]chromen-7-yl)-3-phenylnaphth-2-ol, the product of Example 15. Detailed Implementation

[0046] The present invention will be further described in detail below with reference to specific embodiments. However, the scope of protection of the present invention is not limited to these embodiments. All variations and advantages that can be conceived by those skilled in the art without departing from the spirit and scope of the inventive concept are included in the present invention and are protected by the appended claims. The processes, conditions, reagents, experimental methods, etc., used to implement the present invention, except as specifically mentioned below, are all common knowledge and general knowledge in the art, and the present invention does not have any particular limitations. The data given in the following embodiments include specific operations, reaction conditions, and products. Product purity was determined by NMR.

[0047] Example 1: Synthesis of 1-(5-methyl-5-(o-tolylamino)-5H-dibenzo[c,g]chromen-7-yl)-3-phenylnaphth-2-ol

[0048]

[0049] 3,3'-diphenyl-[1,1'-binaphthyl]-2,2'-diol (1a) (0.1 mmol, 43.8 mg) and o-methylphenyldiazotetrafluoroborate (2a) (0.12 mmol, 24.7 mg) were added to a dry, clean Shrek tube. The mixture was purged with nitrogen three times. Then, 2 mL of CH3CN solvent was added using a syringe. The mixture was stirred at 80 °C for 2 h. After the reaction was complete, the mixture was concentrated under reduced pressure and purified by column chromatography (eluent: petroleum ether / ethyl acetate 100:1-50:1 v / v, 50:1 in this case) to obtain a yellow solid (19.4 mg, 34%) with a melting point of 234.0-235.8 °C. The product parameters were analyzed using nuclear magnetic resonance (NMR) and high-resolution mass spectrometry. 1 H NMR (600MHz, CDCl3) δ8.11(s,1H),8.01(s,1H),7.96(d,J=8.2Hz,1H),7.91(d,J=8.1Hz,1H),7.79(d,J=7.5Hz,2H),7.72(d,J= 7.5Hz,2H),7.49–7.29(m,13H),6.85(d,J=6.5Hz,1H),6.78–6.69(m,2H),6.45(s,1H),5.99(s,1H),1.40(s,3H),1.31(s,3H). 13 C NMR (150MHz, CDCl3) δ149.91,148.28,146.11,138.47,138.31,134.89,133 .48,133.29,132.34,131.18,130.34,130.15,130.01,129.81,129.22,128 .73,128.44,128.36,128.19,128.09,127.78,127.32,127.24,126.67,126 .39,126.10,125.87,123.88,123.52,120.73,17.30,15.83.HRMS(ESI)m / z Calcd for C 41 H 32 NO2, [M+H] + :570.2428,Found:570.2414. This indicates that under the above conditions, the target product with the highest yield can be obtained, and the product can be used as an O,O,N-tridentate ligand in the catalytic reaction of indole with unsaturated keto esters.

[0050] Example 2

[0051] The reaction steps and operating conditions were the same as in Example 1, except that the reaction was carried out at 90°C. The reaction was stopped, and after the same post-treatment as described above, the target product was determined using nuclear magnetic resonance (NMR). Target product 3a (22.0 mg, yield 39%) was obtained, indicating that the target product can be obtained in a better yield under 90°C conditions.

[0052] Example 3

[0053] The reaction steps and operating conditions were the same as in Example 1, except that the reaction was carried out at 100°C. The reaction was stopped, and after the same post-treatment as described above, the target product was determined using nuclear magnetic resonance (NMR), yielding target product 3a (20.8 mg, yield 36%).

[0054] Example 4

[0055] The reaction steps and operating conditions were the same as in Example 2, except that the molar ratio of the reactants was 1:2. The reaction was stopped, and after the same post-treatment as described above, the target product was determined using nuclear magnetic resonance (NMR). Target product 3a (31.6 mg, yield 55%) was obtained, indicating that the target product can be obtained in a high yield under the condition of a 1:2 molar ratio of reactants.

[0056] Example 5

[0057] The reaction steps and operating conditions were the same as in Example 2, except that the molar ratio of the reactants was 1:3. The reaction was stopped, and after the same post-treatment as described above, the target product was determined using nuclear magnetic resonance (NMR). Target product 3a (44.5 mg, yield 78%) was obtained, indicating that the target product can be obtained in a high yield under the condition of a 1:3 molar ratio of reactants.

[0058] Example 6

[0059] The reaction steps and operating conditions were the same as in Example 2, except that the molar ratio of the reactants was 1:4. The reaction was stopped, and after the same post-treatment as described above, the target product was determined using nuclear magnetic resonance (NMR). Target product 3a (42.8 mg, yield 75%) was obtained, indicating that the target product can be obtained in a high yield under the condition of a 1:4 molar ratio of reactants.

[0060] Example 7

[0061] The reaction steps and operating conditions were the same as in Example 5, except that the reaction time was 1 hour. The reaction was stopped, and after the same post-processing as described above, the target product was determined by nuclear magnetic resonance, yielding target product 3a (35.0 mg, yield 61%).

[0062] Example 8

[0063] The reaction steps and operating conditions were the same as in Example 5, except that the reaction time was 3 hours. The reaction was stopped, and after the same post-treatment as described above, the target product was determined using nuclear magnetic resonance (NMR), yielding target product 3a (43.7 mg, yield 77%).

[0064] Example 9

[0065] The reaction steps and operating conditions were the same as in Example 5, except that the reaction was carried out under air conditions. The reaction was stopped, and after the same post-treatment as described above, the target product was determined by nuclear magnetic resonance spectroscopy, yielding target product 3a (34.8 mg, yield 61%).

[0066] Example 10: Synthesis of 1-(3,5-dimethyl-5-(o-tolylamino)-5H-dibenzo[c,g]chromen-7-yl)-3-(p-tolyl)naphth-2-ol

[0067]

[0068] 3,3'-di-p-tolyl-[1,1'-binaphthyl]-2,2'-diol (1b) (0.1 mmol, 46.7 mg) and o-methylphenyldiazotetrafluoroborate (2a) (0.3 mmol, 61.8 mg) were added to a dry, clean Shrek tube. The mixture was purged with nitrogen three times. Then, 2 mL of CH3CN solvent was added using a syringe. The mixture was stirred at 90 °C for 2 h. After the reaction was complete, the mixture was concentrated under reduced pressure and purified by column chromatography (eluent: petroleum ether / ethyl acetate 100:1-50:1 v / v, 50:1 in this case) to obtain a white solid (46.1 mg, 77%) with a melting point of 202.1-203.3 °C. The target product was identified by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HMR). The parameters of the obtained product are as follows: 1H NMR (600MHz, CDCl3) δ8.08(s,1H),7.98(s,1H),7.92(d,J=8.2Hz,1H),7.88(d,J=8.1Hz,1H ),7.67(d,J=8.0Hz,2H),7.61(d,J=7.9Hz,2H),7.43(ddd,J=8.1,6.1,1.9Hz,1H),7.33(t, J=7.2Hz,1H),7.31–7.24(m,6H),7.22(d,J=7.8Hz,2H),6.90–6.82(m,1H),6.75(dd,J=5.0 ,3.6Hz,2H),6.42(s,1H),6.03(s,1H),2.39(s,3H),2.38(s,3H),1.43(s,3H),1.32(s,3H). 13 C NMR (150MHz, CDCl3) δ149.99,148.37,146.18,137.49,136.96,135.52,135. 39,134.84,133.36,133.14,132.36,130.96,130.11,130.08,129.85,129.6 4,129.22,129.11,128.83,128.27,128.10,127.06,126.50,126.29,126.07 ,125.85,123.79,123.47,120.78,21.35,21.34,17.32,15.84.HRMS(ESI)m / z Calcdfor C 43 H 36 NO2, [M+H] + :598.2741,Found:598.2727. This indicates that under the above conditions, the target product with the highest yield can be obtained.

[0069] Example 11: Synthesis of 1-(3-methoxy-5-methyl-5-(o-tolylamino)-5H-dibenzo[c,g]chromen-7-yl)-3-(4-methoxyphenyl)naphth-2-ol

[0070]

[0071] 3,3'-bis(4-methoxyphenyl)-[1,1'-binaphthyl]-2,2'-diol (1c) (0.1 mmol, 49.9 mg) and o-methylphenyldiazotetrafluoroborate (2a) (0.3 mmol, 61.8 mg) were added to a dry, clean Shrek tube. The mixture was purged with nitrogen three times. Then, 2 mL of CH3CN solvent was added using a syringe. The reaction was stirred at 90 °C for 2 h. After the reaction was complete, the mixture was concentrated under reduced pressure and purified by column chromatography (eluent: petroleum ether / ethyl acetate 100:1-50:1 v / v, 50:1 in this case) to obtain 49.1 mg (76%) of a yellow solid with a melting point of 115.4-117.1 °C. The target product was identified by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HMR). The parameters of the obtained product are as follows: 1 H NMR (600MHz, CDCl3) δ8.16(s,1H),8.09(s,1H),8.02(d,J=8.2Hz,1H),7.99(d,J=8.1Hz,1H), 7.82(d,J=8.7Hz,2H),7.77(d,J=8.8Hz,2H),7.53(ddd,J=8.0,6.5,1.4Hz,1H),7.43(t,J=7. 3Hz,1H),7.41–7.34(m,4H),7.11–7.07(m,2H),7.05(d,J=8.7Hz,2H),6.99–6.95(m,1H),6.9 1–6.81(m,2H),6.58(s,1H),6.16(s,1H),3.91(s,3H),3.90(s,3H),1.55(s,3H),1.44(s,3H). 13 C NMR (150MHz, CDCl3) δ159.41,159.02,149.98,148.39,146.12,134.46,133.23 ,133.01,132.36,131.10,130.92,130.84,130.73,130.70,130.13,129.80,12 9.25,128.73,128.19,128.04,126.97,126.40,126.28,126.09,125.81,123.7 9,123.51,120.75,113.85,113.55,55.43,55.37,17.33,15.83.HRMS(ESI)m / z Calcd for C 43 H 36 NO4, [M+H] + :630.2639,Found:630.2626. This indicates that under the above conditions, the target product with the highest yield can be obtained.

[0072] Example 12: Synthesis of 3-(3,5-dimethylphenyl)-1-(2,4,5-trimethyl-5-(o-tolylamino)-5H-dibenzo[c,g]chromen-7-yl)naphth-2-ol

[0073]

[0074] 3,3'-bis(3,5-dimethylphenyl)-[1,1'-binaphthyl]-2,2'-diol (1d) (0.1 mmol, 49.4 mg) and o-methylphenyldiazotetrafluoroborate (2a) (0.3 mmol, 61.8 mg) were added to a dry, clean Shrek tube. The mixture was purged with nitrogen three times. Then, 2 mL of CH3CN solvent was added using a syringe. The reaction was stirred at 90 °C for 2 h. After the reaction was complete, the mixture was concentrated under reduced pressure and purified by column chromatography (eluent: petroleum ether / ethyl acetate 100:1-50:1 v / v, 50:1 in this case) to obtain 44.4 mg (71%) of a white solid with a melting point of 138.6-140.3 °C. The target product was identified by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HMR). The parameters of the obtained product are as follows: 1 H NMR(600MHz, CDCl3)δ8.32(s,1H),8.22(s,1H),8.14–8.09(m,2H),7.65– 7.58(m,5H),7.56–7.52(m,2H),7.52–7.45(m,3H),7.22(d,J=12.9Hz,2H) ,7.11(d,J=7.2Hz,1H),7.04(t,J=6.9Hz,1H),7.00(t,J=7.1Hz,1H),6.72 (s,1H),6.39(s,1H),2.59(s,6H),2.57(s,6H),1.71(s,3H),1.59(s,3H). 13 C NMR (150MHz, CDCl3) δ150.00,148.34,146.21,138.30,138.15,137.78,137.44, 135.00,133.43,133.19,132.30,130.91,130.18,130.14,129.23,129.16,129.0 0,128.84,128.23,128.12,127.78,127.67,127.02,126.52,126.24,126.12,125 .83,123.76,123.51,120.85,117.03,21.52,21.42,17.28,15.82.HRMS(ESI)m / z Calcd for C 45 H 40NO2, [M+H] + :626.3054,Found:626.3041. This indicates that under the above conditions, the target product with the highest yield can be obtained.

[0075] Example 13: Synthesis of 3-(3,4-dimethylphenyl)-1-(2,3,5-trimethyl-5-(o-tolylamino)-5H-dibenzo[c,g]chromen-7-yl)naphthalene-2-ol

[0076]

[0077] 3,3'-bis(3,4-dimethylphenyl)-[1,1'-binaphthyl]-2,2'-diol (1e) (0.1 mmol, 49.4 mg) and o-methylphenyldiazotetrafluoroborate (2a) (0.3 mmol, 61.8 mg) were added to a dry, clean Shrek tube. The mixture was purged with nitrogen three times. Then, 2 mL of CH3CN solvent was added using a syringe. The mixture was stirred at 90 °C for 2 h. After the reaction was complete, the mixture was concentrated under reduced pressure and purified by column chromatography (eluent: petroleum ether / ethyl acetate 100:1-50:1 v / v, 50:1 in this case) to obtain 47.7 mg (76%) of a yellow solid with a melting point of 164.4-166.1 °C. The target product was identified by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HMR). The parameters of the obtained product are as follows: 1 H NMR (600MHz, CDCl3) δ8.31(s,1H),8.22(s,1H),8.12(d,J=8.2Hz,1H),8.10(d,J=8.2Hz,1H ),7.79(s,1H),7.76(s,2H),7.69(d,J=7.8Hz,1H),7.61(t,J=7.4Hz,1H),7.53(dd,J=14.2, 6.8Hz,3H),7.49–7.44(m,2H),7.44–7.39(m,2H),7.10(d,J=7.1Hz,1H),7.05–6.96(m,2H), 6.68(s,1H),6.37(s,1H),2.54(s,3H),2.51(s,3H),2.51(s,6H),1.69(s,3H),1.58(s,3H). 13C NMR (150MHz, CDCl3) δ150.02,148.39,146.22,136.47,136.06,136.00,135.95,135.80,13 5.61,134.89,133.33,133.10,132.34,131.13,130.99,130.83,130.10,130.03,129.61,1 29.47,129.20,128.81,128.21,128.07,127.35,127.14,126.95,126.43,126.21,126.08, 125.82,123.73,123.46,120.84,19.95,19.81,19.62,19.59,17.26,15.82.HRMS(ESI)m / z Calcd for C 45 H 40 NO2, [M+H] + :626.3054,Found:626.3043. This indicates that under the above conditions, the target product with the highest yield can be obtained.

[0078] Example 14: Synthesis of 4-(5-methyl-5-(o-tolylamino)-5H-benzo[g]naphtho[1,2-c]chromen-7-yl)-[2,2'-binaphthyl]-3-ol

[0079]

[0080] [2,2':4',1”:3”,2”'-tetranaphthyl]-2”,3'-diol (1f) (0.1 mmol, 53.9 mg) and o-methylphenyldiazotetrafluoroborate (2a) (0.3 mmol, 61.8 mg) were added to a dry, clean Shrek tube. The mixture was purged with nitrogen three times. Then, CH3CN (2 mL) solvent was added using a syringe. The reaction was stirred at 90 °C for 2 h. After the reaction was complete, the mixture was concentrated under reduced pressure and purified by column chromatography (eluent: petroleum ether / ethyl acetate 100:1-50:1 v / v, 50:1 in this case) to obtain a white solid of 54.1 mg (81%) with a melting point of 145.3-147.1 °C. The target product was identified by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HMR). The parameters of the obtained product are as follows: 1H NMR (600MHz, CDCl3) δ8.40(s,1H),8.37(s,1H),8.37(s,1H),8.29(s,1H),8.13–8. 06(m,3H),8.06–7.94(m,7H),7.65–7.60(m,3H),7.60–7.57(m,2H),7.56(d,J=9.2H z,1H),7.52(t,J=7.3Hz,2H),7.50–7.44(m,2H),6.90(d,J=7.4Hz,1H),6.84–6.80 (m,1H),6.78(s,1H),6.76(t,J=7.3Hz,1H),6.20(s,1H),1.44(s,3H),1.43(s,3H). 13 C NMR (150MHz, CDCl3) δ150.15,148.44,145.89,136.03,135.75,134.79,133.57,133.51,133. 36,132.76,132.70,132.40,131.48,130.68,130.11,129.32,128.84,128.79,128.67,128.39 ,128.36,128.32,128.28,128.16,127.85,127.77,127.70,127.41,127.35,126.80,126.48,1 26.37,126.09,126.04,125.98,125.88,124.00,123.57,120.72,17.24,15.82.HRMS(ESI)m / z Calcd for C 49 H 36 NO2, [M+H] + :670.2740,Found:670.2728. This indicates that under the above conditions, the target product with the highest yield can be obtained.

[0081] Example 15: Synthesis of 1-(5-methyl-5-(phenylamino)-5H-dibenzo[c,g]chromen-7-yl)-3-phenylnaphth-2-ol

[0082]

[0083] 3,3'-diphenyl-[1,1'-binaphthyl]-2,2'-diol (1a) (0.1 mmol, 43.8 mg) and phenyldiazotetrafluoroborate (2b) (0.3 mmol, 57.6 mg) were added to a dry, clean Shrek tube. The mixture was purged with nitrogen three times. Then, 2 mL of CH3CN solvent was added using a syringe. The reaction was stirred at 90 °C for 2 h. After the reaction was complete, the mixture was concentrated under reduced pressure and purified by column chromatography (eluent: petroleum ether / ethyl acetate 100:1-50:1 v / v, 50:1 in this case) to obtain 42.5 mg (76%) of a white solid with a melting point of 210.6-212.4 °C. The target product was identified by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HMR). The parameters of the obtained product are as follows: 1 H NMR (600MHz, DMSO) δ8.43(s,1H),8.15(s,1H),8.10(d,J=8.1Hz,1H),8.00(s,1H),7.95(d,J=8.2Hz, 1H),7.72(dd,J=7.5,1.6Hz,4H),7.52(dd,J=15.3,7.6Hz,3H),7.49(d,J=7.4Hz,2H),7.45(dd,J=14. 3,6.9Hz,2H),7.38(t,J=7.4Hz,1H),7.34(dd,J=11.5,4.4Hz,1H),7.29(t,J=7.5Hz,1H),7.19(d,J=8 .8Hz,1H),7.17(d,J=8.5Hz,2H),7.14–7.10(m,1H),7.01(d,J=8.5Hz,1H),5.69(s,2H),1.23(s,3H). 13 C NMR(150MHz,DMSO)δ150.27,147.91,146.82,138.61,138.43,135.15,133.04,13 3.03,131.68,131.57,131.39,130.04,129.80,129.61,128.99,128.39,128.29, 128.27, 128.09, 128.02, 127.50, 127.14, 126.68, 125.90, 125.77, 125.36, 125.03, 124.94, 123.11, 122.00, 115.61, 115.02, 14.85. This indicates that under the above conditions, the target product with the highest yield can be obtained.

Claims

1. A method for synthesizing benzochrome compounds, characterized in that: Using aryl diazonium salts as aryl sources and acetonitrile as C1 synthons, benzo[a]ene compounds can be generated by tandem cyclization with substituted binaphthols under heating conditions.

2. The synthesis method according to claim 1, characterized in that: The reaction process is shown in the following reaction formula; Where Ar represents an aryl or alkyl, alkoxy, halogen-substituted phenyl or substituted phenyl, aryl represents 1-naphthyl substitution, 2-naphthyl substitution, etc., and substituent represents one or more substituents at different positions such as ortho, meta, para, etc. on the phenyl ring. The number of substituents on the benzene ring is 1-5, preferably 1-2. The substituents on the benzene ring of the substituted phenyl are one or more of C1-C16 alkyl and C1-C16 alkoxy groups. The halogen is one or more of fluorine, chlorine, bromine, and iodine, specifically one or more of 4-methylphenyl, 4-methoxyphenyl, 3,4-dimethylphenyl, and 3,5-dimethylphenyl. R represents one or more substituents at different positions such as ortho, meta, para, etc. on the phenyl ring. The number of substituents on the benzene ring is 1-5, preferably 1-2, and R is C1-C16. 16 The alkyl group, hydrogen group, halogroup, wherein the halogroup is one or more of fluorine, chlorine, bromine, and iodine.

3. The synthesis method as described in claim 2, characterized in that: The reaction includes the following steps: Add substituted binaphthol and aryl diazonium salt to a container, then perform nitrogen purging 3-5 times, add solvent, and stir at 20-120℃ for 0.1-5 hours to obtain benzochrome compound.

4. The synthesis method as described in claim 3, characterized in that: The reaction is carried out at a temperature of 60-90℃ for 1-2 hours.

5. The synthesis method as described in claim 3, characterized in that: The solvent in the reaction is acetonitrile, a combination of acetonitrile and n-hexane (volume ratio 4:1), or acetonitrile and cyclohexane (volume ratio 4:1). The preferred solvent is acetonitrile. The concentration of the substituted binaphthol in the solvent is 0.05-0.2M, preferably 0.05M.

6. The synthesis method according to claim 3, characterized in that: The molar ratio of substituted binaphthol to aryl diazonium salt in the reaction is 1:1.0-1:3.0, and the preferred molar ratio is 1:2.0-1:3.0.

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