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Synlett 2018; 29(07): 912-917
DOI: 10.1055/s-0036-1591544
DOI: 10.1055/s-0036-1591544
letter
Metal-Free Oxidative C(sp3)–N Coupling by HBr and DMSO: A Novel Synthesis of 2,3-Dihydroquinazolin-4(1H)-ones
Authors
This research was supported by the Research Council of the University of Tehran.
Further Information
Publication History
Received: 21 November 2017
Accepted after revision: 16 January 2018
Publication Date:
15 February 2018 (online)
Abstract
A metal-free oxidative C(sp3)–N coupling process has been developed for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones. The reaction between primary amines, isatoic anhydride, and benzylic alcohols in the presence of HBr in DMSO at 80 °C affords 2,3-dihydroquinazolin-4(1H)-ones in excellent yields. Under these reaction conditions, benzylic alcohols react with in situ generated bromodimethylsulfonium bromide to form alkoxysulfonium intermediates. These intermediates undergo an oxidative cyclization reaction with primary amines and isatoic anhydride to produce the title products.
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References and Notes
- 1 Bariwal J. Van der Eycken E. Chem. Soc. Rev. 2013; 42: 9283
- 2a Paul F. Patt J. Hartwig JF. J. Am. Chem. Soc. 1994; 116: 5969
- 2b Guram AS. Buchwald SL. J. Am. Chem. Soc. 1994; 116: 7901
- 3 Lam PY. S. Clark CG. Saubern S. Adams J. Winters MP. Chan DM. T. Combs A. Tetrahedron Lett. 1998; 39: 2941
- 4 Batcho AD. Leimgruber W. Org. Synth. 1985; 63: 214
- 5 Bartoli G. Palmieri G. Bosco M. Dalpozzo R. Tetrahedron Lett. 1989; 30: 2129
- 6 Goldberg I. Ber. Dtsch. Chem. Ges. 1906; 39: 1691
- 7 Jeffrey JL. Bartlett ES. Sarpong R. Angew. Chem. Int. Ed. 2013; 52: 2194
- 8 Saravanan G. Alagarsamy V. Prakash CR. Bioorg. Med. Chem. Lett. 2012; 22: 3072
- 9 Levin JI. Chan PS. Bailey T. Katocs AS. Venkatesan AM. Bioorg. Med. Chem. Lett. 1994; 4: 1141
- 10 Wang Z. Wang M. Yao X. Li Y. Tan J. Wang L. Qiao W. Geng Y. Liu Y. Wang Q. Eur. J. Med. Chem. 2012; 53: 275
- 11 Alagarsamy V. Pathak US. Bioorg. Med. Chem. 2007; 15: 3457
- 12a Cao SL. Feng YP. Jiang YY. Liu SY. Ding GY. Li RT. Bioorg. Med. Chem. Lett. 2005; 15: 1915
- 12b Chinigo GM. Paige M. Grindrod S. Hamel E. Dakshanamurthy S. Chruszcz M. Minor W. Brown ML. J. Med. Chem. 2008; 51: 4620
- 13 Bonola G. Da Re P. Magistretti MJ. Massarani E. Setnikar I. J. Med. Chem. 1968; 11: 1136
- 14 Smits RA. de Esch IJ. P. Zuiderveld OP. Broeker J. Sansuk K. Guaita E. Coruzzi G. Adami M. Haaksma E. Leurs R. J. Med. Chem. 2008; 51: 7855
- 15a Abbas SE. Awadallah FM. Ibrahin NA. Said EG. Kamel GM. Eur. J. Med. Chem. 2012; 53: 141
- 15b Kumar A. Sharma S. Bajaj K. Sharma S. Panwar H. Singh T. Srivastava VK. Bioorg. Med. Chem. 2003; 11: 5293
- 16 Tiwari AK. Mishra AK. Bajpai A. Mishra P. Sharma RK. Pandey VK. Singh VK. Bioorg. Med. Chem. Lett. 2006; 16: 4581
- 17 Neil GL. Li LH. Buskirk HH. Moxley TE. Cancer Chemother. 1972; 56: 163
- 18 Okumura K. Oine T. Yamada Y. Hayashi G. Nakama M. J. Med. Chem. 1968; 11: 348
- 19a Bahekar SP. Dahake ND. Sarode PB. Chandak HS. Synlett 2015; 26: 2575
- 19b Wu J. Du X. Ma J. Zhang Y. Shi Q. Luo L. Song B. Yang S. Hu D. Green Chem. 2014; 16: 3210
- 19c Desroses M. Scobie M. Helleday T. New J. Chem. 2013; 37: 3595
- 19d Sharma M. Pandey S. Chauhan K. Sharma D. Kumar B. Chauhan PM. S. J. Org. Chem. 2012; 77: 929
- 19e Ramesh K. Karnakar K. Satish G. Anil Kumar BS. P. Nageswar YV. D. Tetrahedron Lett. 2012; 53: 6936
- 19f Rostamizadeh S. Amani AM. Mahdavinia GH. Sepehrian H. Ebrahimi S. Synthesis 2010; 1356
- 19g Zhang ZH. Lü H.-Y. Yang SH. Gao JW. J. Comb. Chem. 2010; 12: 643
- 19h Chen JX. Wu DZ. He F. Liu MC. Wu HY. Ding JC. Su WK. Tetrahedron Lett. 2008; 49: 3814
- 19i Wang LM. Hu L. Shao JH. Yu JJ. Zhang L. J. Fluorine Chem. 2008; 129: 1139
- 19j Dabiri M. Salehi P. Otokesh S. Baghbanzadeh M. Kozehgary G. Mohammadi AA. Tetrahedron Lett. 2005; 46: 6123
- 20 Adib M. Sheikhi E. Bijanzadeh HR. Synlett 2012; 85
- 21 Azimi SB. Azizian J. Tetrahedron Lett. 2016; 57: 181
- 22 Meerwein H. Zenner KF. Gipp R. Justus Liebigs Ann. Chem. 1965; 688: 67
- 23a Olah GA. Vankar YD. Arvanaghi M. Tetrahedron Lett. 1979; 38: 3653
- 23b Chow YL. Bakker BH. Synthesis 1982; 648
- 23c Chow YL. Bakker BH. Can. J. Chem. 1982; 60: 2268
- 23d Olah GA. Ohannesian L. Arvanaghi M. Synthesis 1986; 868
- 23e Das B. Venkateswarlu K. Krishnaiah M. Holla H. Majhi A. Helv. Chim. Acta 2006; 89: 1417
- 23f Khan AT. Ali MdA. Goswami P. Choudhury LH. J. Org. Chem. 2006; 71: 8961
- 23g Das B. Srinivas Y. Holla H. Laxminarayana K. Narender R. Tetrahedron Lett. 2007; 48: 6681
- 23h Jiang B. Dou Y. Xu X. Xu M. Org. Lett. 2008; 10: 593
- 23i Khan AT. Parvin T. Choudhury LH. J. Org. Chem. 2008; 73: 8398
- 24 Karki M. Magolan J. J. Org. Chem. 2015; 80: 3701
- 25 Olah GA. Vankar YD. Arvanaghi M. Surya Prakash G. Synthesis 1979; 720
- 26 General Procedure for the Preparation of DHQZs 4a-p, Exemplified for 4a A mixture of propylamine (1 mmol) and isatoic anhydride (1 mmol) in DMSO (3 mL) was stirred for 20 min at 80 °C. Then, 4-chlorobenzyl alcohol (1 mmol) and HBr (48% aq., 1 mmol) were added to the reaction mixture and stirring was continued at 80 °C for 10 min. The progress of reaction was followed by TLC. After the reaction was complete, the reaction mixture was cooled to ambient temperature, quenched by addition of water (2 mL), and stirring was continued for 10 min at ambient temperature. The resulting precipitate was filtered, washed with water, dried, and recrystallized from ethanol to afford the pure product 4a. 2-(4-Chlorophenyl)-3-propyl-2,3-dihydroquinazolin-4(1H)-one (4a) White solid, yield: 0.291 g (97%); mp = 160–162 °C. 1H NMR (500.1 MHz, DMSO-d6 ): δ = 0.84 (3 H, t, J = 7.4 Hz, CH3), 1.42–1.52 (1 H, m, ABCDX3 system, CHC H DCH3), 1.53–1.63 (1 H, m, ABCDX3 system, CH CHDCH3), 2.73 (1 H, ddd, ABCDX3 system, 2 J = 13.8 Hz, 3 J = 8.6 Hz, 3 J = 5.7 Hz, NCHA H B), 3.85 (1 H, ddd, ABCDX3 system, 2 J =13.8 Hz, 3 J = 8.6 Hz, 3 J = 5.7 Hz, NCH AHB), 5.88 (1 H, d, J = 2.4 Hz, NHCH), 6.65 (1 H, d, J = 8.4 Hz, CH), 6.66 (1 H, t, J = 7.4 Hz, CH), 7.20 (1 H, dt, 3 J = 8.4, 4 J = 1.5 Hz, CH), 7.34 (2 H, d, J = 8.5 Hz, 2 CH), 7.39 (1 H, d, J = 2.4 Hz, NH), 7.42 (2 H, d, J = 8.5 Hz, 2 CH), 7.65 (1 H, dd,3 J = 7.4, 4 J = 1.1 Hz, CH). 13C NMR (125.8 MHz, DMSO-d6 ): δ = 11.61 (CH3), 21.26 (CH2CH3), 46.65 (NCH2), 69.83 (NCHN), 114.79 (CH), 115.54 (C), 117.73 (CH), 127.90, 128.43, 128.94 (3CH), 133.35 (C), 133.63 (CH), 140.77, 146.45 (2C), 162.59 (C=O). 2,3-Dihydro-2-(3-hydroxyphenyl)-3-propylquinazolin-4(1H)-one (4c) White solid, yield: 0.262 g (93%); mp = 198–200 °C. 1H NMR (500.1 MHz, DMSO-d6 ): δ = 0.85 (3 H, t, J = 7.4 Hz, CH3), 1.49 (1 H, m, ABCDX3 system, CHC H DCH3), 1.60 (1 H, m, ABCDX3 system, CH CHDCH3), 2.73 (1 H, ddd, ABCDX3 system, 2 J = 13.7 Hz, 3 J = 8.6 Hz, 3 J = 6.5 Hz, NCHA H B), 3.86 (1H, ddd, ABCDX3 system, 2 J =13.7 Hz, 3 J = 8.6 Hz, 3 J = 6.5 Hz, NCH AHB), 5.76 (1 H, d, J = 2.2 Hz, NHCH), 6.65 (1 H, d, J = 7.9 Hz, CH), 6.66 (1 H, t, J = 8.0 Hz, CH), 6.72 (1 H, dd, 3 J = 8.0 Hz, 4 J = 1.6 Hz, CH), 6.78 (1 H, s, CH), 6.79 (1 H, d, J = 7.9 Hz, CH), 7.14 (1 H, t, J = 7.9 Hz, CH), 7.20 (1 H, dt, 3 J = 8.0, 4 J = 1.4 Hz, CH), 7.29 (1 H, d, J = 2.2 Hz, NH), 7.68 (1 H, dd, 3 J = 8.0 Hz, 4 J = 1.2 Hz, CH), 9.49 (1 H, s, OH). 13C NMR (125.8 MHz, DMSO-d6 ): δ = 11.67 (CH3), 21.20 (CH2CH3), 46.61 (NCH2), 70.72 (NCHN), 113.47, 114.66 (2CH), 115.45, 115.78 (2C), 117.37, 117.43 (2CH), 127.89, 129.95, 133.51 (3CH), 143.26, 146.76 (2C), 157.96 (CH), 162.71 (C=O). 3-Butyl-2-phenyl-2,3-dihydroquinazolin-4(1H)-one (4d)19i White solid, yield: 0.255 g (91%); mp = 121 °C. 1H NMR (500.1 MHz, DMSO-d6 ): δ = 0.84 (3 H, t, J = 7.3 Hz, CH3), 1.23–1.30 (2 H, m, CH2), 1.41–1.49 (1 H, m, ABCDM2X3 system, CHC H DCH2CH3), 1.50–1.59 (1 H, m, ABCDM2X3 system, CH CHDCH2CH3), 2.74 (1 H, ddd, ABCDM2X3 system, 2 J = 13.7 Hz, 3 J = 8.3 Hz, 3 J = 5.8 Hz, NCHA H B), 3.88–3.94 (1 H, m, ABCDM2X3 system, NCH AHB), 5.85 (1 H, s, NHCH), 6.65 (1 H, d, J = 7.8 Hz, CH), 6.66 (1 H, t, J = 7.1 Hz, CH), 7.19 (1 H, t, J = 7.1 Hz, CH), 7.30–7.36 (6 H, m, 5CH and NH), 7.67 (1 H, d, J = 7.8 Hz, CH). 13C NMR (125.8 MHz, DMSO-d6 ): δ = 14.12 (CH3), 20.02 (CH2CH3), 30 (CH2CH2), 44.41 (NCH2), 70.56 (NCHN), 114.69 (CH), 115.51 (C), 117.52, 127.86, 126.6, 128.78, 128.94 (5CH), 133.53, 141.68 (2C), 146.71 (CH), 162.67 (C=O). 2,3-Dihydro-2-(4-methoxyphenyl)-3-phenylquinazolin-4(1H)-one (4h)27c White solid, yield: 0.300 g (91%); mp = 204 °C. 1H NMR (300 MHz, DMSO-d6 ): δ = 3.67 (3 H, s, OCH3), 6.22 (1 H, br s, CH), 6.71 (1 H, t, J = 7.7 Hz, CH), 6.76 (1 H, d, J = 7.7 Hz, CH), 6.84 (2 H, d, J = 8.6 Hz, 2 CH), 7.17 (1 H, t, J = 7.0 Hz, 1 CH), 7.22–7.35 (7 H, m, 7 CH), 7.55 (1 H, br s, NH), 7.73 (1 H, d, J = 7.7 Hz, CH). 13C NMR (75 MHz, DMSO-d6 ): δ = 55.00 (OCH3), 72.32 (NCHN), 113.65 (CH), 114.78 (C), 115.34 (CH), 117.43 (C), 125.95, 126.30, 127.91, 128.56 (4CH), 128.58 (C), 132.61 (CH), 133.68 (C), 140.83 (CH), 146.66 (C), 159.11 (CH), 162.33 (C=O). 2,3-Bis(4-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one (4m)27c Pale yellow solid, yield: 0.339 g (92%); mp = 249–251 °C. 1H NMR (500.1 MHz, DMSO-d6 ): δ = 6.35 (1H, s, NHCH), 6.74 (1 H, t, J = 7.4 Hz, CH), 6.79 (1 H, d, J = 8.1 Hz, CH), 7.28–7.31 (3 H, m, 3CH), 7.37–7.41 (6 H, m, 6CH), 7.68 (1 H, br s, NH), 7.74 (1 H, d, J = 7.7 Hz, CH). 13C NMR (125.8 MHz, DMSO-d6 ): δ = 72.35 (NCHN), 115.35 (CH), 115.45 (C), 118.28 (CH), 128.52 (C), 128.57, 128.93, 129.07, 129.10 (4CH), 130.82 (C), 133.55 (C), 134.51 (C), 139.66 (CH), 139.77 (CH), 146.98 (C), 162.76 (C=O).
- 27a Wang M. Zhang TT. Gao JJ. Liang Y. Chem. Heterocycl. Comp. 2012; 48: 897
- 27b Darvatkar NB. Bhilare SV. Deorukhkar AR. Raut DG. Salunkhe MM. Green. Chem. Lett. Rev. 2010; 3: 301
- 27c Safari J. Gandomi-Ravandi S. J. Mol. Struct. 2014; 1072, 173
- 27d Safari J. Gandomi-Ravandi S. J. Mol. Catal. A: Chem. 2013; 371: 135