Synlett 2020; 31(18): 1795-1799
DOI: 10.1055/s-0040-1707248
letter
© Georg Thieme Verlag Stuttgart · New York

Electrochemical Synthesis of Quinazolinones by the Metal-Free and Acceptor-Free Dehydrogenation of 2-Aminobenzamides

Yan Yao
a   State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, P. R. of China   Email: qinghuteng@163.com
,
Xiu-Jin Meng
a   State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, P. R. of China   Email: qinghuteng@163.com
,
Qing-Hu Teng
a   State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, P. R. of China   Email: qinghuteng@163.com
b   Guangxi Key Laboratory of Electrochemical and Magnetochemical Function Materials, College of Chemistry and Bioengineering, Guilin University of Technology, Guilin 541004, P. R. of China
,
Yan-Yan Chen
c   Pharmacy School, Guilin Medical University, Guilin 541004, P. R. of China   Email: chenyy269614@163.com
› Author Affiliations
We thank the National Natural Science Foundation of China (21861006), Ministry of Education of the People’s Republic of China (IRT_16R15), Natural Science Foundation of Guangxi Province (2016GXNSFEA380001, 2016GXNSFGA380005, 2018GXNSFBA281151), Guangxi Key R&D Program (No. AB18221005), Science and Technology Major Project of Guangxi (AA17204058-21), Guangxi Science and Technology Base and Special Talents (guike AD19110027), Guangxi Funds for Distinguished Experts and State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (CMEMR2019-A03), and Guangxi Science and Technology Base and Talents Program (AD18281035, AD18281028) for financial support.
Further Information

Publication History

Received: 02 June 2020

Accepted after revision: 26 July 2020

Publication Date:
19 August 2020 (online)


Abstract

An efficient approach has been developed for the construction of quinazolin-4(3H)-ones by the selective anodic dehydrogenative oxidation/cyclization of benzylic chlorides and 2-aminobenzamides. The method features acceptor-free and metal-free dehydrogenation of amines to imines; a subsequent intermolecular addition provides the products in moderate to good yields.

Supporting Information

 
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  • 19 Quinazolinones 3aq; General Procedure A mixture of the appropriate 2-aminobenzamide 1 (0.5 mmol), benzylic chloride 2 (0.6 mmol), and Bu4NBF4 (10 mol%) was placed in a 25 mL three-necked round-bottomed flask equipped with a condenser, an RVC (100 PPI) anode, and a Pt plate (1 × 1 cm) cathode. The flask was opened to air and MeCN (6 mL) was added. Electrolysis was carried out at 80 °C (oil-bath temperature) at a constant current of 10 mA until the substrate was completely consumed (TLC). The mixture was then cooled to rt, and the solvent was removed under reduced pressure. The residue was purified by chromatography (silica gel, EtOAc–PE). 2-Phenylquinazolin-4(3H)-one (3a) White solid; yield: 88.8 mg (80%); mp 233–235 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 12.52 (s, 1 H), 8.22–8.12 (m, 3 H), 7.84–7.77 (m, 1 H), 7.73 (d, J = 8.0 Hz, 1 H), 7.53 (qt, J = 11.0, 5.2 Hz, 4 H). 13C NMR (101 MHz, DMSO): δ = 162.80, 152.84, 149.28, 135.09, 133.26, 131.90, 129.12, 128.30, 128.03, 127.09, 126.39, 121.51. 2-(4-Fluorophenyl)quinazolin-4(3H)-one (3b) White solid; yield: 72.0 mg (60%); mp 240–242 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 12.57 (s, 1 H), 8.25 (dd, J = 8.8, 5.6 Hz, 2 H), 8.15 (d, J = 6.4 Hz, 1 H), 7.84 (t, J = 6.8 Hz, 1 H), 7.73 (d, J = 8.1 Hz, 1 H), 7.55–7.50 (m, 1 H), 7.39 (t, J = 8.8 Hz, 2 H). 13C NMR (100 MHz, DMSO): δ = 162.69, 151.86, 149.11, 135.15, 130.85 (d, J = 9.3 Hz), 130.10, 129.66 (d, J = 3.2 Hz), 127.92, 127.11, 126.32, 121.32, 116.11 (d, J = 22.0 Hz). 2-(4-Chlorophenyl)quinazolin-4(3H)-one (3c) White solid; yield: 81.9 mg (64%); mp 295.5–298 °C. 1H NMR (400 MHz, DMSO-d 6): δ = 12.61 (s, 1 H), 8.21 (d, J = 8.7 Hz, 2 H), 8.16 (d, J = 7.9 Hz, 1 H), 7.85 (t, J = 6.9 Hz, 1 H), 7.75 (d, J = 8.0 Hz, 1 H), 7.64 (d, J = 8.6 Hz, 2 H), 7.54 (t, J = 7.5 Hz, 1 H). 13C NMR (100 MHz, DMSO): δ = 163.04, 152.10, 149.31, 137.04, 135.45, 132.29, 130.37, 129.44, 128.27, 127.55, 126.62, 121.72.