Synlett 2014; 25(6): 821-826
DOI: 10.1055/s-0033-1340786
letter
© Georg Thieme Verlag Stuttgart · New York

An Efficient Synthesis of 2-Substituted Quinazolin-4(3H)-ones Catalyzed by Iron(III) Chloride

Ramamohan Mekala
a   Technology Development Centre, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd, Bollaram Road, Miyapur, Hyderabad, 500049, India   Fax: +91(40)44658699   Email: sarvaj@drreddys.com
b   Department of Chemistry, Jawaharlal Nehru Technological University, Anantapur, Andhra Pradesh 515002, India
,
Raghunadh Akula
a   Technology Development Centre, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd, Bollaram Road, Miyapur, Hyderabad, 500049, India   Fax: +91(40)44658699   Email: sarvaj@drreddys.com
,
Raghavendra Rao Kamaraju
a   Technology Development Centre, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd, Bollaram Road, Miyapur, Hyderabad, 500049, India   Fax: +91(40)44658699   Email: sarvaj@drreddys.com
,
Chandrasekhar Kothapalli Bannoth
b   Department of Chemistry, Jawaharlal Nehru Technological University, Anantapur, Andhra Pradesh 515002, India
,
Sridhar Regati
a   Technology Development Centre, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd, Bollaram Road, Miyapur, Hyderabad, 500049, India   Fax: +91(40)44658699   Email: sarvaj@drreddys.com
,
Jayaprakash Sarva*
a   Technology Development Centre, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd, Bollaram Road, Miyapur, Hyderabad, 500049, India   Fax: +91(40)44658699   Email: sarvaj@drreddys.com
› Author Affiliations
Further Information

Publication History

Received: 22 October 2013

Accepted after revision: 15 January 2014

Publication Date:
10 February 2014 (online)


Abstract

A simple and highly efficient synthesis of 2-substituted quinazolin-4(3H)-ones by the iron(III) chloride catalyzed reaction of isatoic anhydride with various amidoxime derivatives was developed. Several aryl and alkyl amidoximes were screened to demonstrate the scope of the methodology.

Supporting Information

 
  • References and Notes

  • 2 Liu J.-F, Ye P, Sprague K, Sargent K, Yohannes D, Baldino CM, Wilson CJ. Org. Lett. 2005; 7: 3363
  • 5 Sun HH, Barrow CJ, Sedlock DM, Gillum AM, Copper R. J. Antibiot. 1994; 47: 515
  • 8 Zhou J, Fang J. J. Org. Chem. 2011; 76: 7730
  • 10 Draghici B, El-Gendy BEl-D. M, Katritzky AR. Synthesis 2012; 44: 547
  • 12 2-Substituted Quinazolin-4(3H)-ones 8am; General Procedure The appropriate amidoxime 7 (1.1 mmol) and FeCl3 (10 mol%) were added sequentially to a solution of isatoic anhydride (6; 1 mmol.) in 1,4-dioxane (10 mL), and the mixture was stirred at 80 °C for 2–9 h until the reaction was complete (TLC). The mixture was then diluted with EtOAc (10 mL) and washed with H2O (2 × 5 mL). The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure to give a crude product that was purified by column chromatography (silica gel, 30% EtOAc–hexanes). All new compounds gave satisfactory analytical and spectroscopic results. 2-(4-Aminophenyl)quinazolin-4(3H)-one (8e) Yellow solid; yield: 284 mg (78%); mp 250–254 °C; 1H NMR (400 MHz, DMSO-d 6): δ = 5.83 (s, 2 H, NH2), 6.62 (d, J = 8.8 Hz, 2 H, ArH), 7.40 (t, J = 6.9 Hz, 1 H, ArH), 7.61 (d, J = 8.3 Hz, 1 H, ArH), 7.76 (t, J = 6.8 Hz, 1 H, ArH), 7.95 (d, J = 8.8 Hz, 2 H, ArH), 8.08 (dd, J = 6.9, 1 Hz, 1 H, ArH), 12.06 (br s, 1 H, NH); 13C NMR (100 MHz, DMSO-d 6): δ = 113.0, 121.5, 125.3, 125.8, 126.9, 128.7, 129.1, 134.4, 149.6, 152.2, 152.4, 162.4; MS: m/z = 238.1 [M + H]; HRMS (ESI): m/z [M + H] calcd for C14H12 N3O: 238.0980; found: 238.0969. 2-[4-(Methylsulfanyl)phenyl]quinazolin-4(3H)-one (8g) White solid; yield: 383 mg (93%); mp 237–239 °C; 1H NMR (400 MHz, DMSO-d 6): δ = 2.55 (s, 3 H, SCH3), 7.40 (d, J = 8.4 Hz, 2 H, ArH), 7.50 (t, J = 7.2 Hz, 1 H, ArH), 7.72 (d, J = 7.6 Hz, 1 H, ArH), 7.83 (t, J = 7.6 Hz, 1 H, ArH), 8.13–8.16 (m, 3 H, ArH), 12.48 (br s, 1 H, NH); 13C NMR (400 MHz, DMSO-d 6): δ = 14.1, 120.8, 125.1, 125.8, 126.4, 127.4, 128.0, 128.6, 134.6, 143.0, 148.7, 151.78, 162.2; MS: m/z = 269.0 [M + H]; HRMS (ESI): m/z [M + H] calcd for C15H13N2OS: 269.07486; found: 269.07446. 2-(5-Fluoropyridin-2-yl)quinazolin-4(3H)-one (8j) Brown solid; yield: 296 mg (80%); mp 180–183 °C; 1H NMR (400 MHz, CDCl3): δ = 7.51–7.56 (m, 1 H, ArH), 7.61–7.65 (m, 1 H, ArH), 7.77–7.80 (m, 2 H, ArH), 8.35 (d, J = 7.4 Hz, 1 H, ArH), 8.51 (d, J = 2.9 Hz, 1 H, ArH), 8.63 (dd, J = 8.8, 4.8 Hz, 1 H, ArH), 10.76 (br s, 1 H, NH); 13C NMR (100 MHz, CDCl3): δ = 122.2, 123.7 (d, J = 5.4 Hz), 124.4 (d, J = 18.4 Hz), 126.7, 127.4, 127.9, 134.6, 137.2 (d, J = 25.2 Hz), 144.7, 147.9, 148.9, 161.1 (d, J = 260.0 Hz), 161.3; MS: m/z = 242.1 [M + H]; HRMS (ESI): m/z [M + H] calcd for C13H9N3OF: 242.0730; found: 242.0722. 2-(Cyclopropylmethyl)quinazolin-4(3H)-one (8k) White solid; yield: 279 mg (91%); mp 210–213 °C; 1H NMR (400 MHz,, CDCl3): δ = 0.38–0.42 (m, 2 H, CH2), 0.70–0.73 (m, 2 H, CH2), 1.14–1.21 (m, 1 H, CH), 2.70 (d, J = 7.6 Hz, 2 H, CH2), 7.26–7.49 (m, 1 H, ArH), 7.68 (d, J = 7.6 Hz, 1 H, ArH), 7.74–7.79 (m, 1 H, ArH), 8.28 (dd, J = 6.8, 1.2 Hz, 1 H, ArH), 10.20 (br s, 1 H, NH); 13C NMR (100 MHz, DMSO-d 6): δ = 4.2, 9.2, 39.2, 120.8, 125.7, 126.0, 126.8, 134.3, 149.0, 157.2, 161.8; MS: m/z = 201.1 [M + H]; HRMS (ESI): m/z [M + H] calcd for C12H13 N2O: 201.1028; found: 201.1037. 2-(4-Nitrobenzyl)quinazolin-4(3H)-one (8m) Light-brown solid; yield: 383 mg (89%); mp >300 °C; 1H NMR (400 MHz, DMSO-d 6): δ = 4.11 (s, 2 H, PhCH2), 7.48 (t, J = 7.4 Hz, 1 H, ArH), 7.58 (d, J = 8.4 Hz, 1 H, ArH), 7.65 (d, J = 8.4 Hz, 2 H, ArH), 7.75–7.79 (m, 1 H, ArH), 8.08 (d, J = 6.9 Hz, 1 H, ArH), 8.20 (d, J = 8.8 Hz, 2 H, ArH), 12.49 (br s, 1 H, NH); 13C NMR (100 MHz, DMSO-d 6): δ = 40.7, 121.3, 123.6, 125.7, 126.4, 126.9, 128.3, 128.6, 130.4, 134.4, 144.4, 154.9, 161.7; MS: m/z = 282.0 [M + H]; HRMS (ESI): m/z [M + H] calcd for C15H12 N3O3: 282.0879; found: 282.0877.