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

Ramamohan Mekala; Raghunadh Akula; Raghavendra Rao Kamaraju; Chandrasekhar Kothapalli Bannoth; Sridhar Regati; Jayaprakash Sarva

doi:10.1055/s-0033-1340786

Synlett, Table of Contents

Synlett 2014; 25(6): 821-826
DOI: 10.1055/s-0033-1340786

letter

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

Ramamohan Mekala

^aTechnology Development Centre, Custom Pharmaceutical Services, Dr. Reddy's Laboratories Ltd, Bollaram Road, Miyapur, Hyderabad, 500049, India Fax: +91(40)44658699 Email: sarvaj@drreddys.com

^bDepartment of Chemistry, Jawaharlal Nehru Technological University, Anantapur, Andhra Pradesh 515002, India

,

Raghunadh Akula

^aTechnology 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

^aTechnology 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

^bDepartment of Chemistry, Jawaharlal Nehru Technological University, Anantapur, Andhra Pradesh 515002, India

,

Sridhar Regati

^aTechnology 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*

^aTechnology 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

Abstract

All articles of this category

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.

Key words

heterocycles - polycycles - ketones - catalysis - iron - quinazolinones

Full Text

References

References and Notes

1a Mhaske SB, Argade NP. Tetrahedron 2006; 62: 9787
1b Sharma PC, Kaur G, Pahza R, Sharma A, Rajak H. Curr. Med. Chem. 2011; 18: 4786
1c Arora R, Kapoor A, Gill NS, Rana AC. Int. Res. J. Pharm. 2011; 2: 22
1d Reisch J, Kamal GM, Gunaherath G. J. Nat. Prod. 1989; 52: 404
1e Liu J.-F, Wilson CJ, Ye P, Sprague K, Sargent K, Si Y, Beletsky G, Yohannes D, Ng S.-C. Bioorg. Med. Chem. Lett. 2006; 16: 686
1f Liu J.-F, Kaselj M, Isome Y, Ye P, Sargent K, Sprague K, Cherrak D, Wilson CJ, Si Y, Yohannes D, Ng S.-C. J. Comb. Chem. 2006; 8: 7
1g Ma C, Li Y, Niu S, Zhang H, Liu X, Che Y. J. Nat. Prod. 2011; 74: 32
1h Nett M, Hertweck C. J. Nat. Prod. 2011; 74: 2265

2 Liu J.-F, Ye P, Sprague K, Sargent K, Yohannes D, Baldino CM, Wilson CJ. Org. Lett. 2005; 7: 3363

3a Chenard BL, Menniti FS, Pagnozzi MJ, Shenk KD, Ewing FE, Welch WM. Bioorg. Med. Chem. Lett. 2000; 10: 1203
3b Bhogal N, Balls M. Curr. Drug Discovery Technol. 2008; 5: 250

4a Ma ZZ, Hano Y, Nomura T, Chen YJ. Heterocycles 1997; 46: 541
4b Cagir A, Jones SH, Gao R, Eisenhauer BM, Hecht SM. J. Am. Chem. Soc. 2003; 125: 13628

5 Sun HH, Barrow CJ, Sedlock DM, Gillum AM, Copper R. J. Antibiot. 1994; 47: 515

6a Chen AL, Chen KK. J. Am. Pharm. Assoc. 1933; 22: 716
6b Hibino S, Choshi T. Nat. Prod. Rep. 2001; 18: 66
6c Deng P.-Y, Ye F, Cai W.-J, Tan G.-S, Hu C.-P, Deng H.-W, Li Y.-J. J. Hypertens. 2004; 22: 1819

7a Hisano T, Ichikawa M, Nakagawa A, Tsuji M. Chem. Pharm. Bull. 1975; 23: 1910
7b Mitobe Y, Ito S, Mizutani T, Nagase T, Sato N, Tokita S. Bioorg. Med. Chem. Lett. 2009; 19: 4075
7c Balakumar C, Lamba P, Kishore DP, Narayana BL, Rao KV, Rajwinder K, Rao AR, Shireesha B, Narsaiah B. Eur. J. Med. Chem. 2010; 45: 4904
7d Abdel-Jalil RJ, Aldoqum HM, Ayoub MT, Voelter W. Heterocycles 2005; 65: 2061

8 Zhou J, Fang J. J. Org. Chem. 2011; 76: 7730

9a Lingaiah BV, Ezikiela G, Yakaiaha T, Reddy GV, Rao PS. Synlett 2006; 2507
9b Chen J, Wu D, He F, Liu M, Wu H, Ding J, Su W. Tetrahedron Lett. 2008; 49: 3814
9c Zeng L.-Y, Cai C. J. Heterocycl. Chem. 2010; 47: 1035
9d Wang X.-S, Yang K, Zhang M.-M, Yao C.-S. Synth. Commun. 2010; 40: 2633
9e Salehi P, Dabiri M, Zolfigolc MA, Baghbanzadeh M. Tetrahedron Lett. 2005; 46: 7051

10 Draghici B, El-Gendy BEl-D. M, Katritzky AR. Synthesis 2012; 44: 547

11a Agirbas H, Sumengen D, Durust Y, Durust N. Synth. Commun. 1992; 22: 209
11b Durust Y, Akcan M, Martiskainen O, Siirola E, Pihlaja K. Polyhedron 2008; 27: 999
11c Hussein AQ. Heterocycles 1987; 26: 163
11d Rai NP, Narayanaswamy VK, Govender T, Manuprasad BK, Shashikanth S, Arunachalam PN. Eur. J. Med. Chem. 2010; 45: 2677

12 2-Substituted Quinazolin-4(3H)-ones 8a–m; 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 C₁₄H₁₂N₃O: 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 C₁₂H₁₃N₂O: 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 C₁₅H₁₂N₃O₃: 282.0879; found: 282.0877.

Supplementary Material

Supporting Information