Home Journals Articles Updates About
CN
image
收藏切换
Visible light induced tandem reactions: An efficient one pot strategy for constructing quinazolinones using in-situ formed aldehydes under photocatalyst-free and room-temperature conditions
收藏切换
PDF
Zongbo Xie, Jin Lan, Haibo Zhu, Gaoyi Lei, Guofang Jiang*, Zhanggao Le*
Chinese Chemical Letters | 2021, 32(4) : 1427 - 1431
Less
收藏切换
Chinese Chemical Letters | 2021, 32(4): 1427-1431
• Communication •
Visible light induced tandem reactions: An efficient one pot strategy for constructing quinazolinones using in-situ formed aldehydes under photocatalyst-free and room-temperature conditions
Full
Zongbo Xie, Jin Lan, Haibo Zhu, Gaoyi Lei, Guofang Jiang*, Zhanggao Le*
Affiliations
  • Jiangxi Province Key Laboratory of Synthetic Chemistry, School of Chemistry, Biology and Material Science, East China University of Technology, Nanchang 330013, China
Published: 2021-04-15 doi: 10.1016/j.cclet.2020.09.059
Outline
收藏切换

A facile tandem route has been developed for constructing quinazolinones from various aminobenzamides and in-situ generated aldehydes. Visible light was found to play a dual role: first oxidizes the alcohol to the aldehyde and then facilitates its cyclization with o-substituted aniline. Furthermore, alcohols are perfect alternatives to aldehydes because they are greener, more available, more economical, more stable, and less toxic than aldehydes. The first reaction step continuously provides material for the second step, which effectively reduces loss through volatilization, oxidation, and polymerization of the aldehyde, while avoiding its toxicity. A variety of quinazolinones can be prepared in the presence of visible light without any additional photocatalyst. The developed synthesis protocol proceeds with the merits of mild conditions, broad substrate scope, operational simplicity, and high atom efficiency, with an eco-energy source under metal-free, photocatalyst-free, and ambient conditions.

Visible light  /  Photocatalyst-free  /  In-situ formed acetaldehyde  /  One pot tandem reaction  /  Quinazolinones  /  Room temperature
Zongbo Xie, Jin Lan, Haibo Zhu, Gaoyi Lei, Guofang Jiang, Zhanggao Le. Visible light induced tandem reactions: An efficient one pot strategy for constructing quinazolinones using in-situ formed aldehydes under photocatalyst-free and room-temperature conditions[J]. Chinese Chemical Letters, 2021 , 32 (4) : 1427 -1431 . DOI: 10.1016/j.cclet.2020.09.059
Full Text
Less
Quinazolinones and their scaffolds are widely used in many fields, especially organic, natural product, medicinal, and agricultural chemistry. For example, the quinazolinone motif and its derivatives are abundant in a number of synthetic compounds and natural alkaloids with diverse biological and pharmacological properties (Fig. 1), including antimalarial [1], antimicrobial [2], anticancer [3], anti-inflammatory [4, 5], anticonvulsant [6], antihypertensive [7], antitumor [8-10], anti-diabetic, dihydrofolate reductase-inhibitory, and kinase-inhibitory activities [11-15]. The substituents at the 2 and 3 positions of the quinazolinone nucleus have been reported to markedly influence pharmacological activity [16]. In view of their importance, several reports have appeared in the literature describing the synthesis of these heterocycles. Among these methods, reacting o-substituted anilines with an aldehyde appears to be the most-employed strategy, with various catalysts used to promote this reaction, including cellulose-SO3H [17], thiamine hydrochloride (VB1) [18], p-TSA [19], β-cyclodextrin-SO3H [20], 2-morpholinoethanesulfonic acid [21], l-proline nitrate [22], SiO2-H3PW12O40 [23], chiral phosphoric acids [24], ascorbic acid [25], ionic liquids [26, 27], zirconium (Ⅳ) chloride [28], scandium triflate(Ⅲ) [29] and metals [30, 31] (Scheme 1A). As a class of compound, alcohols are known to be greener, more economical, more stable, more available, and less toxic than aldehydes. In recent years, the use of alcohols instead of aldehydes has also aroused interest, and various catalysts such as Ru [32], Ir [33, 34], Pd [35], Pt [36-38], Zn [39], Cu [40, 41], Fe [42-44], Ni [45], KOH [46] or high temperatures [47, 48] have been used to prepare these compounds (Scheme 1B). Therefore, the development of more practical, green, and efficient approaches to quinazolinones remains an attractive task for organic chemists [49].
Visible light is clean, easy to handle, and an eco-friendly energy source with excellent prospects for the development of sustainable and eco-friendly protocols. Owing to these advantages, visible-light-promoted chemical reactions have received considerable attention and have emerged as a hot research topic in organic chemistry [50-68], water splitting [69], PCN materials [70], organic photocatalyst [71] or applications in medicine synthesis [72]. As a continuation of our interest in visible-light photochemistry and inspired by the reported results [73], herein we report a novel, green, and mild protocol for the synthesis of quinazolinones by irradiating alcohols and o-substituted anilines with visible light under photocatalyst-free and room-temperature conditions (Scheme 1C). To the best of our knowledge, this is the first example of quinazolinone synthesis involving a tandem reaction promoted by visible light.
To optimize the reaction conditions, we initially chose 2-aminobenzamide (1a) to react with benzyl alcohol (2a) as a model system. To achieve a green reaction outcome, we examined photocatalysts such as eosin Y, rose bengal, Ru(bpy)3Cl2, 9-fluorenone, and benzophenone. The reaction was carried out in DMSO under light from an 18-W blue LED in air for 24h when 9-fluorenone or benzophenone (5.0mol%) was used as the photoredox catalyst; pleasingly the reaction proceeded to afford the desired product 3a in 21% or 24% yield, respectively (Table 1, entries 4 and 5). To our delight, 3a was obtained in 14% yield when the model reaction was conducted in DMSO in the absence of a photocatalyst (entry 6). A further control experiment without the photocatalyst and without irradiation with LED light only recovered the two starting materials (entry 6). Subsequently, a number of solvents, oxidants, times, and molar ratios of substrates were examined with the aim of improving reaction efficiency. It is noteworthy that, among the solvents screened (entries 6–13), the target product was obtained only in DMSO as the solvent (entry 6). Furthermore, when various oxidants were screened (entries 14–18), a slightly improved yield of 3a was achieved when an oxygen balloon was used instead air (entry 14 vs. 6). At the same time, with O2 as the greenest oxidant, we attempted to increase the yield by extending the reaction time, but only obtained 3a in 27% yield (entry 14); however, 3a was only obtained in trace amounts when the reaction was performed in a nitrogen atmosphere (entry 14). It should be noted that tert-butylhydroperoxide (TBHP) was the most effective oxidant for the reaction, affording product 3a in 53% yield (entry 15); therefore, TBHP was selected as the oxidant in subsequent experiments. The amount of oxidant was next investigated, which revealed that that the initial choice of TBHP (1 equiv.) was fortuitous. The 1a: 2a ratio, as well as the reaction time were also optimized, the results of which are summarized in Table 1 (entries 15, 19–26).
With the best reaction conditions in hand (entry 25), we explored the generality of this methodology using various substituted benzyl alcohols, the results of which are summarized in Scheme 2. The good news is that electron-rich benzyl alcohols, including sterically bulky ortho-substituted ones (3d) generally furnished good-to-high yields of products (3b– 3e). To our delight, 4-chlorobenzyl alcohol still afforded a satisfactory yield of the product (3f). The yield obtained using cinnamyl alcohol was also satisfactory (3g), and the reaction of bulky naphthylmethanol successfully gave the desired product (3h). Moreover, 3-pyridinemethanol and 2-thiophenemethanol were chosen to investigate the reaction scope of heterocyclic alcohols, both substrates produced the target products in high yields (3i, 3j). Subsequently, various primary alcohols all gave the corresponding products in satisfactory yields (3k– 3n), however, the yield was observed to decrease with increasing alkyl chain length. Meanwhile, a cycloalkyl containing alcohol (cyclobutanemethanol) also successfully afforded the corresponding product (3o). It is worth mentioning that methanol and secondary alcohols, such as isopropanol can also react well (3p-3r). Methanol is used to replace formaldehyde in one-step synthesis to make the reaction more operable because formaldehyde is a gas. The application of secondary alcohols has greatly expanded the scope of substrates.
To explore the generality of this protocol, we examined a variety of aminobenzamide derivatives. Halogenated aminobenzamides gave the corresponding quinazolinones in good yields (3s, 3t), while an alkyl substituted 2-aminobenzamide was more sluggish and afforded the corresponding product in moderate yield at a prolonged reaction time (3u). Finally, an N-substituted 2-aminobenzamide satisfactorily produced the desired product. The yields obtained for 3v and 3w reveal a very obvious spatial effect.
Several control experiments were conducted with the aim of clarifying the reaction mechanism (Scheme 3). To understand the role of TBHP, we first reacted 1a with 2a in air, which provided 3a in 34% isolated yield, while nitrogen instead of TBHP provided 3a in very low yield (Scheme 3a). We then observed that benzyl alcohol can be converted into benzaldehyde under the standard conditions (Scheme 3b), and that replacing benzyl alcohol with benzaldehyde also led to the successful formation of 3a under the above conditions in a little less time. Moreover, we found that 2, 2, 6, 6-tetramethylpiperidine-N-oxide (TEMPO), a commonly used radical scavenger, completely inhibited the model reaction under the standard conditions, indicating that the reaction may involve a radical pathway (Scheme 3d). Further, the expected intermediate could be successfully prepared from benzaldehyde and 2-aminobenzamide in the presence of visible light and O2 (Scheme 3e); then intermediate could be transformed into product 3a in high yield under visible-light promoted aerobic oxidative conditions (Scheme 3f).
To confirm whether or not the reaction involves a chain process, a "light on/off experiment" was performed. Fig. 2 reveals the product was not generated during the dark period, confirming that light is required throughout the entire reaction period.
Based on the above results, we propose a plausible reaction pathway (Scheme 4). Initially, photoirradiated TBHP produces hydroxyl radicals and tert-butoxyl radicals. Hydrogen atom transfer from benzyl alcohol to the tert-butoxyl radical or the hydroxyl radical gives the α-hydroxybenzyl radical; subsequent the radicals between hydroxyl radicals or tert-butoxy radicals and carbon atom groups undergo a classic alkoxy radical disproportionation reaction [74] driven by polar effects to generate benzaldehyde. Then, 2-aminobenzamide and benzaldehyde are dehydrated and condensed to form imine intermediate. Subsequent intramolecular cyclization gives another intermediate. Finally, visible light irradiation to produce singlet oxygen through energy transfer pathways, lead to the release of H2O2 to form the target product [75].
We developed a novel, simple, efficient, and catalyst-free method for the construction of quinazolinones through the visible-light-promoted in-situ generation of aldehydes from alcohols and subsequent reactions with various 2-aminobenzamides at room temperature. Visible light is necessary in both steps of the tandem reaction. This work solves some of the problems associated with the use of metals, bases, and high temperatures during the synthesis of quinazolinones, as well as avoiding the direct use of aldehydes. Meanwhile, this protocol features mild, tolerant, and operationally simple photocatalyst-free conditions that are easy to implement, and represents a significant green-chemistry enhancement over existing protocols.
Declaration of competing interest
Less
The authors report no declarations of interest.
Acknowledgments
Less
This project was supported by the National Natural Science Foundation of China (No. 21462001) and a Science and Technology Project of Jiangxi Province (No. 20192BBH80012).
Appendix A. Supplementary data
Less
Supplementarymaterial related to this article can befound, in the online version, at doi:https://doi.org/10.1016/j.cclet.2020.09.059.
References
Less
[1]
Z.W. Mei, L. Wang, W.J. Lu, et al., J. Med. Chem. 56(2013) 1431-1442.
[2]
A.A. Al-Amiery, A.A.H. Kadhum, M. Shamel, Med. Chem. Res. 23(2013) 236-242.
[3]
A. Chia, J. Med. Chem. 48(2005) 1359-1366.
[4]
E.A. El-Hashash, M.E. Azab, E.A. Faty, E.G.E. Amr, Chem. Pharm. Bull. 64(2016) 263-271.
[5]
M.B. Patel, S.P. Kumar, N.N. Valand, Y.T. Jasrai, S.K. Menon, J. Mol. Mod. 19(2013) 3201-3217.
[6]
N.M.A. Gawad, H.H. Georgey, R.M. Youssef, N.A.E. Sayed, Med. Chem. Res. 20(2011) 1280-1286.
[7]
J.W. Chern, P.L. Tao, K.C. Wang, et al., J. Med. Chem. 41(1998) 3128-3141.
[8]
A.M. Alafeefy, A.E. Ashour, O. Prasad, et al., Eur. J. Med. Chem. 92(2015) 191-201.
[9]
D. He, M. Wang, S. Zhao, et al., Fitoterapia 119(2017) 136-149.
[10]
M. Mahdavi, K. Pedrood, M. Safavi, et al., Eur. J. Med. Chem. 95(2015) 492-499.
[11]
S. Yin, L. Zhou, J. Lin, L. Xue, C. Zhang, Eur. J. Med. Chem. 101(2015) 462-475.
[12]
S.B. Mhaske, N.P. Argade, Tetrahedron 62(2006) 9787-9826.
[13]
R.S. Rohokale, U.A. Kshirsagar, Synthesis 48(2016) 1253-1268.
[14]
M.A. Ibrahim, S.A.N. Shaikha, Heterocycl. Commun. 21(2015) 115-132.
[15]
V.F. Vavsari, G.M. Ziarani, Chem. Heterocycl. Com. 54(2018) 317-319.
[16]
K.M. Amin, M.M. Kamel, M.M. Anwar, M. Khedr, Y.M. Syam, Eur. J. Med. Chem. 45(2010) 2117-2131.
[17]
B.V. Subba Reddy, A. Venkateswarlu, C. Madan, A. Vinu, Tetrahedron Lett. 52(2011) 1891-1894.
[18]
J. Devi, S.J. Kalita, D.C. Deka, Synth. Commun. 47(2017) 1601-1609.
[19]
M.J. Hour, L.J. Huang, S.C. Kuo, et al., J. Med. Chem. 43(2000) 4479-4487.
[20]
J. Wu, X. Du, J. Ma, et al., Green Chem. 16(2014) 3210-3217.
[21]
V.B. Labade, P.V. Shinde, M.S. Shingare, Tetrahedron Lett. 54(2013) 5778-5780.
[22]
H. Chandak, S. Bahekar, N. Dahake, P. Sarode, Synlett 26(2015) 2575-2577.
[23]
H. Alinezhad, E. Soleymani, M. Zare, Res. Chem. Intermed. 43(2016) 457-466.
[24]
W. Gong, X. Chen, H. Jiang, et al., J. Am. Chem. Soc. 141(2019) 7498-7508.
[25]
G. Chandra Pariyar, B. Mitra, S. Mukherjee, P. Ghosh, ChemistrySelect 5(2020) 104-108.
[26]
J. Chen, W. Su, H. Wu, M. Liu, C. Jin, Green Chem. 9(2007) 972-975.
[27]
S. Das, S. Santra, S. Jana, et al., Eur. J. Org. Chem. 2017(2017) 4955-4962.
[28]
M. Abdollahi-Alibeik, E. Shabani, Chin. Chem. Lett. 22(2011) 1163-1166.
[29]
J.X. Chen, H.Y. Wu, W.K. Su, Chin. Chem. Lett. 18(2007) 536-538.
[30]
S. Guo, Y. Li, L. Tao, W. Zhang, X. Fan, RSC Adv. 4(2014) 59289-59296.
[31]
S. Das, S. Sinha, D. Samanta, et al., J. Org. Chem. 84(2019) 10160-10171.
[32]
A.J.A. Watson, A.C. Maxwell, J.M.J. Williams, Org. Biomol. Chem. 10(2012)240-243.
[33]
J. Zhou, J. Fang, J. Org. Chem. 76(2011) 7730-7736.
[34]
F. Li, L. Lu, P. Liu, Org. Lett. 18(2016) 2580-2583.
[35]
H. Hikawa, Y. Ino, H. Suzuki, Y. Yokoyama, J. Org. Chem. 77(2012) 7046-7051.
[36]
S.M.A. Hakim Siddiki, K. Kon, A.S. Touchy, K.I. Shimizu, Catal. Sci. Technol. 4(2014) 1716-1719.
[37]
J.J. Zhong, W.P. To, Y. Liu, W. Lu, C.M. Che, Chem. Sci. 10(2019) 4883-4889.
[38]
C.Y. Sun, W.P. To, F.F. Hung, et al., Chem. Sci. 9(2018) 2357-2364.
[39]
M. Sharif, J. Opalach, P. Langer, M. Beller, X.F. Wu, RSC Adv. 4(2014) 8-17.
[40]
S. Das, S. Sinha, D. Samanta, et al., J. Org. Chem. 84(2019) 10160-10171.
[41]
M.H. Shinde, U.A. Kshirsagar, RSC Adv. 6(2016) 52884-52887.
[42]
Y. Hu, L. Chen, B. Li, RSC Adv. 6(2016) 65196-65204.
[43]
D. Zhao, Y.R. Zhou, Q. Shen, J.X. Li, RSC Adv. 4(2014) 6486-6489.
[44]
A.R. Oveisi, A. Khorramabadi-zad, S. Daliran, RSC Adv. 6(2016) 1136-1142.
[45]
S. Parua, S. Das, R. Sikari, S. Sinha, N.D. Paul, J. Org. Chem. 82(2017) 7165-7175.
[46]
D. Qiu, Y. Wang, D. Lu, L. Zhou, Q. Zeng, Monatsh. Chem. 146(2015) 1343-1347.
[47]
J. Sun, T. Tao, D. Xu, et al., Tetrahedron Lett. 59(2018) 2099-2102.
[48]
Z.Z. Wang, Y. Tang, Tetrahedron 72(2016) 1330-1336.
[49]
Z.B. Xie, H.X. Li, L.S. Liu, et al., Chin. J. Org. Chem. 39(2019) 2632-2638.
[50]
K. Zeitler, Angew. Chem. Int. Ed. 48(2009) 9785-9789.
[51]
J.M.R. Narayanam, C.R.J. Stephenson, Chem. Soc. Rev. 40(2011) 102-113.
[52]
L. Shi, W. Xia, Chem. Soc. Rev. 41(2012) 7687-7697.
[53]
J.W. Tucker, C.R.J. Stephenson, J. Org. Chem. 77(2012) 1617-1622.
[54]
D.A. Nicewicz, T.M. Nguyen, ACS Catal. 4(2014) 355-360.
[55]
E. Jahn, U. Jahn, Angew. Chem. Int. Ed. 53(2014) 13326-13328.
[56]
G.B. Deng, Z.Q. Wang, J.D. Xia, et al., Angew. Chem. Int. Ed. 52(2013) 1535-1538.
[57]
C. Zhu, H. Yue, L. Chu, M. Rueping, Chem. Sci. 11(2020) 4051-4064.
[58]
A.K. Bagdi, A. Hajra, Org. Biomol. Chem. 18(2020) 2611-2631.
[59]
C.L. Dong, X. Ding, L.Q. Huang, Y.H. He, Z. Guan, Org. Lett. 22(2020) 1076-1080.
[60]
Z. Wei, S. Qi, Y. Xu, et al., Adv. Synth. Catal. 361(2019) 5490-5498.
[61]
N. Spiliopoulou, N.F. Nikitas, C.G. Kokotos, Green Chem. 22(2020) 3539-3545.
[62]
N.F. Nikitas, D.I. Tzaras, I. Triandafillidi, C.G. Kokotos, Green Chem. 22(2020) 471-477.
[63]
X. Mi, Y. Kong, J. Zhang, C. Pi, X. Cui, Chin. Chem. Lett. 30(2019) 2295-2298.
[64]
W.B. He, L.Q. Gao, X.J. Chen, et al., Chin. Chem. Lett. 31(2020) 1895-1898.
[65]
L.Y. Xie, T.G. Fang, J.X. Tan, et al., Green Chem. 21(2019) 3858-3863.
[66]
Z. Cao, Q. Zhu, Y.W. Lin, W.M. He, Chin. Chem. Lett. 30(2019) 2132-2138.
[67]
L. Wang, M. Zhang, Y. Zhang, et al., Chin. Chem. Lett. 31(2020) 67-70.
[68]
L.Y. Xie, Y.L. Chen, L. Qin, et al., Org. Chem. Front. 6(2019) 3950-3955.
[69]
C. Liu, Z. Chen, C. Su, et al., Nat. Commun. 9(2018) 80.
[70]
C. Qiu, Y. Xu, X. Fan, et al., Adv. Sci. 6(2019) 1801403.
[71]
W. Ou, R. Zou, M. Han, L. Yu, C. Su, Chin. Chem. Lett. 31(2020) 1899-1902.
[72]
W. Ou, G. Zhang, J. Wu, C. Su, ACS Catal. 9(2019) 5178-5183.
[73]
W. Schilling, D. Riemer, Y. Zhang, N. Hatami, S. Das, ACS Catal. 8(2018) 5425-5430.
[74]
M.J. Gibian, R.C. Corley, Chem. Rev. 73(1973) 441-464.
[75]
Z. Li, H. Song, R. Guo, et al., Green Chem. 21(2019) 3602-3605.
Appendix
Less
Year 2021 volume 32 Issue 4
PDF
37
20
Cite this Article
BibTeX
Article Info
doi: 10.1016/j.cclet.2020.09.059
  • Receive Date：2020-09-02
  • Online Date：2026-01-04
  • Published：2021-04-15
Article Data
Affiliations
History
  • Received：2020-09-02
  • Revised：2020-09-28
  • Accepted：2020-09-30
Affiliations
    Jiangxi Province Key Laboratory of Synthetic Chemistry, School of Chemistry, Biology and Material Science, East China University of Technology, Nanchang 330013, China
References
Share
https://castjournals.cast.org.cn/joweb/ccl/EN/10.1016/j.cclet.2020.09.059
Share to
QR

Scan QR to access full text

Cite this article
BibTeX
Citations
表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
关闭全屏
  • BibTeX
  • EndNote
  • RefWorks
  • TxT
Links
Articles
Latest Articles
Most Read
Collections
Updates
Events
News
Multimedia
About
About Us
Contact
No. 86 Xueyuan South Road, Haidian District, Beijing
100081
010-62199257
qkjq@cast.org.cn

Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House