FeCl₃-Mediated Synthesis of 2-(Trifluoromethyl)quinazolin-4(3H)-ones from Isatins and Trifluoroacetimidoyl Chlorides

Abstract

General comments, general procedure, optimization details, analytic data, and NMR spectra PDF)Accession Codes CCDC 2010044 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_

Palladium‐Catalyzed Carbonylative Synthesis of 2‐(Trifluoromethyl)quinazolin‐4(3H)‐ones from Trifluoroacetimidoyl Chlorides and Nitro Compounds

“…3‐(4‐ethylphenyl)‐2‐(trifluoromethyl)quinazolin‐4(3 H )‐one (4 d) : [12c] Yield: 89%; 56.6 mg, white solid; m.p=137.8–139.1 °C; 1 H NMR (400 MHz, CDCl 3 ) δ 8.33 (d, J =7.9 Hz, 1H), 7.92–7.84 (m, 2H), 7.64 ( t , J =7.2 Hz, 1H), 7.36 (d, J =7.9 Hz, 2H), 7.21 (d, J =7.9 Hz, 2H), 2.76 (q, J =7.6 Hz, 2H), 1.31 (t, J =7.6 Hz, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 162.0, 146.3, 145.3, 142.5 (q, J (C‐F) =35.2 Hz), 135.3, 132.3, 129.6, 128.8, 128.8, 127.5, 122.3, 118.0 (q, J (C‐F) =277.6 Hz), 28.7, 15.2.…”

“…3‐(4‐fluorophenyl)‐2‐(trifluoromethyl)quinazolin‐4(3 H )‐one (4 h) : [12c] Yield: 94%; 57.9 mg, white solid; m.p=132.6–134.6 °C; 1 H NMR (CDCl 3 , 400 MHz) δ (ppm) 8.31 (d, J =7.8 Hz, 1H), 7.92 ‐ 7.85 (m, 2H), 7.67–7.63 (m, 1H), 7.31–7.28 (m, 2H), 7.26–7.18 (m, 2H). 13 C NMR (CDCl 3 , 101 MHz) δ (ppm) 163.3 (d, J (C‐F) =250.4 Hz), 161.9, 145.2, 142.2 (q, J (C‐F) =35.4 Hz), 135.5, 131.1 (d, J (C‐F) =9.0 Hz), 130.6, 129.8, 128.9, 127.5, 122.1, 117.9 (q, J (C‐F) =277.9 Hz), 116.6 (d, J (C‐F) =23.2 Hz).…”

Copper‐Catalyzed Aerobic Oxidative Ring Expansion of Isatins: A Facile Entry to Isoquinolino‐Fused Quinazolinones

“…Over the past decade, the development of the synthesis of nitrogen-containing heterocycles through the decarbonylative cyclization of isatins has been extensively studied. [8][9][10][11] For instance, in 2013, Wang's group developed a concise method for the synthesis of tryptanthrins from commercially available indoles and isatins (Scheme 1, a). [8] In 2016, Huang's group found an appealing strategy for the synthesis of pyrido-fused quinazolinone derivatives by Cu-catalyzed decarbonylative cyclization of substituted isatins and 2-bromopyridine derivatives (Scheme 1, b).…”

Pd‐Catalyzed Decarboxylative Ortho‐Aroylation of 2‐Aryl‐quinazolinone Comprising Intrinsic Directing Group with α‐Oxocarboxylic Acids

“…Quinazolinone is one of the most intriguing and essential core found in bio-active and medicinally vital natural products (Figure 1). [14] Moreover, numerous marketed drugs are having quinazolinone as active core unit which tempting synthetic modification of quinazolinones. To our knowledge, decarboxylative acylation of quinazolinone is not known till date.…”

“…Interestingly, motivating yield (48%) was observed after carrying the reaction in trifluorotoluene solvent (entry 12). Replacement of oxidant with Na 2 S 2 O 8 and (NH 4 ) 2 S 2 O 8 produced slightly lower yield (45 and 42%, entry [13][14] whereas use of O 2 , oxone and PhI(OAC) 2 failed to produce desired product (entry [15][16][17]. Gratifyingly, when trifluoroacetic acid (TFA) was used as additive (0.1 mL) the desired product 6 a was formed in 79% (entry 18).…”