One-Pot Regioselective Synthesis of Imidazole and 2,3-Dihydroquinazolinone Derivatives – An Easy Access to ‘Nature-Like Molecules’; Part XIII in the 
Series: ‘Studies on Novel Synthetic Methodologies’

Koneni V. Sashidhara; Gopala Reddy Palnati; Ranga Prasad Dodda; Srinivasa Rao Avula; Priyanka Swami

doi:10.1055/s-0033-1339466

Synlett, Table of Contents

Synlett 2013; 24(14): 1795-1800
DOI: 10.1055/s-0033-1339466

letter

One-Pot Regioselective Synthesis of Imidazole and 2,3-Dihydroquinazolinone Derivatives – An Easy Access to ‘Nature-Like Molecules’; Part XIII in the Series: ‘Studies on Novel Synthetic Methodologies’

Authors

Koneni V. Sashidhara*

^aMedicinal and Process Chemistry Division, Central Drug Research Institute, CSIR-CDRI, Lucknow, 226 001, India Fax: +91(522)2623405 Email: sashidhar123@gmail.com Email: kv_sashidhara@cdri.res.in
Gopala Reddy Palnati

^aMedicinal and Process Chemistry Division, Central Drug Research Institute, CSIR-CDRI, Lucknow, 226 001, India Fax: +91(522)2623405 Email: sashidhar123@gmail.com Email: kv_sashidhara@cdri.res.in
Ranga Prasad Dodda

^aMedicinal and Process Chemistry Division, Central Drug Research Institute, CSIR-CDRI, Lucknow, 226 001, India Fax: +91(522)2623405 Email: sashidhar123@gmail.com Email: kv_sashidhara@cdri.res.in
Srinivasa Rao Avula

^aMedicinal and Process Chemistry Division, Central Drug Research Institute, CSIR-CDRI, Lucknow, 226 001, India Fax: +91(522)2623405 Email: sashidhar123@gmail.com Email: kv_sashidhara@cdri.res.in
Priyanka Swami

^bMedicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Raebareli 229 010, India

Abstract

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Abstract

A mild and highly practical regioselective synthesis of imidazole and 2,3-dihydroquinazolinone derivatives from 5-alkyl-4-hydroxyisophthalaldehydes with suitable substrates in acetic acid is reported. Further exploration of the molecular diversity of 2,3-dihydroquinazolinone is demonstrated by the synthesis of diverse pharmacologically relevant natural-product-like scaffolds.

Key words

one-pot synthesis - regioselective synthesis - imidazole - 2,3-dihydroquinazolinone - 5-alkyl-4-hydroxyisophthalaldehydes - nature-like molecules

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References

References and Notes

1a Grimmett MR In Comprehensive Heterocyclic Chemistry II . Katritzky AR, Ress CW, Schriven EF. Pergamon Press; Oxford: 1996
1b Tsukamoto S, Kato H, Hirota H, Fusetani N. J. Nat. Prod. 1996; 108: 2288
1c Hassan W, Edrada R, Ebel R, Wray V, Berg A, Van Soest R, Wiryowidagdo S, Proksch P. J. Nat. Prod. 2004; 67: 817
1d Kobayashi Y, Nakano Y, Kizaki M, Hoshikuma K, Yokoo Y, Kamiya T. Planta Med. 2001; 67: 628
1e Christina F, Foy JM, Pratt CN. F. W, Purvis JR. J. Pharm. Pharmacol. 1981; 33: 219
1f Atwell GA, Fan JY, Tan K, Denny WA. J. Med. Chem. 1998; 41: 4744
1g Lopez SE, Rosales ME, Urdaneta N, Gody MV, Charris JE. J. Chem. Res. 2000; 6: 258
1h Hamel E, Lin CM, Plowman J, Wang H, Lee K, Paull KD. Biochem. Pharmacol. 1996; 51: 53

2a Michael JP. Nat. Prod. Rep. 2004; 21: 650
2b Mhaske SB, Argade NP. Tetrahedron 2006; 62: 9787

3a Zhu YP, Fei Z, Liu MC, Jia FC, Wu AX. Org. Lett. 2013; 15: 378
3b Wood KW, Bergnes G. Annu. Rep. Med. Chem. 2004; 39: 173
3c Bergnes G, Brejc K, Belmont L. Curr. Top. Med. Chem. 2005; 5: 127

4a Morteza S. Chem. Rev. 2012; 112: 3508
4b Gu Y. Green Chem. 2012; 14: 2091
4c Balme G, Bossharth E, Monteiro N. Eur. J. Org. Chem. 2003; 4101
4d Brase S, Gil C, Knepper K. Bioorg. Med. Chem. 2002; 10: 2415
4e Dömling A, Ugi I. Angew. Chem. Int. Ed. 2000; 39: 3168
4f Qian W, Amegadzie A, Winterheimer D, Allen J. Org. Lett. 2013; 15: 2986

5a Ohno H, Ohta Y, Oishi S, Fujii N. Angew. Chem. Int. Ed. 2007; 46: 2295
5b Bonne D, Dekhane M, Zhu J. Angew. Chem. Int. Ed. 2007; 46: 2485
5c Pinto A, Neuville L, Zhu J. Angew. Chem. Int. Ed. 2007; 46: 3291
5d Komagawa S, Saito S. Angew. Chem. Int. Ed. 2006; 45: 2446
5e Yoshida H, Fukushima H, Ohshita J, Kunai A. J. Am. Chem. Soc. 2006; 128: 11040
5f Pache S, Lautens M. Org. Lett. 2003; 5: 4827
5g Duan XH, Liu XY, Guo LN, Liao MC, Liu WM, Liang YM. J. Org. Chem. 2005; 70: 6980

6a Porco JA. Jr. Beilstein J. Org. Chem. 2012; 8: 827
6b Schreiber SL. Nature 2009; 457: 153
6c O’Connor CJ, Beckmannw HS. G, Spring DR. Chem. Soc. Rev. 2012; 41: 4444
6d Burke MD, Schreiber SL. Angew. Chem. Int. Ed. 2004; 43: 46
6e Spandl RJ, Bender A, Spring DR. Org. Biomol. Chem. 2008; 6: 1149

7a Kantevari S, Patpi SR, Addla D, Putapatri SR, Sridhar B, Yogeeswari P, Sriram D. ACS Comb. Sci. 2011; 13: 427
7b Markina NA, Mancuso R, Neuenswander B, Lushington GH, Larock RC. ACS Comb. Sci. 2011; 13: 265
7c Zhu MY, Lim BJ, Koh M, Park SB. ACS Comb. Sci. 2012; 14: 124
7d Wang ZY, Wang B, Wu J. J. Comb. Chem. 2007; 9: 811

8a Multicomponent Reactions . Zhu J, Bienayme H. Wiley-VCH; Weinheim: 2005
8b Dömling A, Ugi I. Angew. Chem. Int. Ed. 2000; 39: 3168
8c Simon C, Constantieux T, Rodriguez J. Eur. J. Org. Chem. 2004; 4957
8d Sadek KU, Mekheimer RA, Mohamed TM, Moustafa MS, Elnagdi MH. Beilstein J. Org. Chem. 2012; 8: 18
8e Laschat S, Becheanu A, Bell T, Baro A. Synlett 2005; 2547
8f Nowrouzi F, Batey RA. Angew. Chem. Int. Ed. 2013; 52: 892

9a Sha F, Wu L, Huang X. J. Org. Chem. 2012; 77: 3754
9b Jiang B, Li QY, Tu SJ, Li G. Org. Lett. 2012; 14: 5210

10 Ruijter E, Scheffelaar R, Orru RV. A. Angew. Chem. Int. Ed. 2011; 50: 6234

11a Hao WJ, Xu XP, Bai HW, Wang SY, Ji SJ. Org. Lett. 2012; 14: 4894
11b Sparks RB, Combs AP. Org. Lett. 2004; 6: 2473
11c Martorana A, Pace A, Buscemi S, Piccionello AP. Org. Lett. 2012; 14: 3240
11d Kaim LE, Grimaud L, Vieu E. Org. Lett. 2007; 9: 4171
11e Wang C, Han ZY, Luo HW, Gong LZ. Org. Lett. 2010; 12: 2266

12a Sashidhara KV, Palnati GR, Dodda RP, Avula SR, Swami P. Synlett 2013; 24: 105
12b Sashidhara KV, Palnati GR, Avula SR, Kumar A. Synlett 2012; 23: 611
12c Sashidhara KV, Avula SR, Singh LR, Palnati GR. Tetrahedron Lett. 2012; 53: 4880
12d Sashidhara KV, Kumar A, Dodda RP, Kumar B. Tetrahedron Lett. 2012; 53: 3281
12e Sashidhara KV, Kumar M, Kumar A. Tetrahedron Lett. 2012; 53: 2355
12f Sashidhara KV, Kumar A, Agarwal S, Kumar M, Kumar M, Sridhar B. Adv. Synth. Catal. 2012; 354: 1129
12g Sashidhara KV, Kumar A, Rao KB. Tetrahedron Lett. 2011; 52: 5659
12h Sashidhara KV, Kumar A, Chatterjee M, Rao KB, Singh S, Verma AK, Palit G. Bioorg. Med. Chem. Lett. 2011; 21: 1937

13 Ganem B. Acc. Chem. Res. 2009; 42: 463
14 Sashidhara KV, Rosaiah JN. Tetrahedron Lett. 2007; 48: 3285
15 Typical Method for the Preparation of Compound 4b via MCR A mixture of 5-ethyl-4-hydroxyisophthalaldehyde (1b, 1.0 mmol), NH₄OAc (2, 1.5 mmol), and 4,4′-dimethoxybenzil (3, 1.0 mmol) in AcOH (5 mL) was heated at 110 °C with stirring for 4.0 h (progress of the reaction was monitored by TLC). After completion of the reaction, the reaction mixture was diluted with H₂O (25 mL), followed by extraction with CHCl₃ (2 × 25 mL). The combined extracts were dried over Na₂SO₄ and dried under high vacuum to afford the crude product. It was subjected to further purification by column chromatography (silica 100–200) using 20% EtOAc–hexane as eluent. The desired product 4b was obtained as a yellow solid; yield 85%; mp 135–137 °C. IR (KBr): 3527, 3010, 2964, 1660, 1239, 1032 cm^–1. ¹H NMR (300 MHz, DMSO-d ₆): δ = 12.51 (s, 1 H), 11.09 (s, 1 H), 10.12 (s, 1 H), 8.30 (d, J = 2.1 Hz, 1 H), 8.18 (d, J = 2.0 Hz, 1 H), 7.45 (d, J = 8.6 Hz, 4 H), 7.00–6.89 (m, 4 H), 3.78 (s, 3 H), 3.77 (s, 3 H), 2.70 (q, J = 7.4 Hz, 2 H), 1.23 (t, J = 7.4 Hz, 3 H). ¹³C NMR (75 MHz, DMSO-d ₆): δ = 197.7, 159.0, 144.9, 133.4, 133.2, 129.8, 128.2, 123.6, 121.7, 115.0, 114.7, 56.0, 22.8, 14.6. ESI-MS: m/z = 429 [M + H]⁺.
16 Sashidhara KV, Kumar A, Kumar M, Sarkar J, Sinha S. Bioorg. Med. Chem. Lett. 2010; 20: 7205

17a Hosseini-Zare MS, Mahdavi M, Saeedi M, Asadi M, Javanshir S, Shafiee A, Foroumadi A. Tetrahedron Lett. 2012; 53: 3448
17b Kumar KS, Kumar PM, Rao VS, Jafar AA, Meda CL. T, Kapavarapu R, Parsa KV. L, Pal M. Org. Biomol. Chem. 2012; 10: 3098
17c Siddiqui SA, Narkhede UC, Palimkar SS, Daniel T, Lahoti RJ, Srinivasa KV. Tetrahedron 2005; 61: 3539

18 General Procedure for the Preparation of 9c via MCR A mixture of 4-hydroxy-5-propylisophthalaldehyde (1c, 1.0 mmol), methylamine (7, 1.5 mmol), and isatoicanhydride (8, 1.0 mmol) in AcOH (5.0 mL) was stirred in a round-bottom flask for 2.0 h at 110 °C (initially effervescence was observed due to the generation of CO₂ gas). Upon completion of the reaction, the reaction mixture was diluted with H₂O (25 mL), followed by extraction with CHCl₃ (2 × 25 mL). The combined organic phases were dried over anhyd Na₂SO₄ and concentrated in vacuo. The crude product was purified by column chromatography on silica gel (100–200) in 40% CH₂Cl₂–hexane solvent system. The required compound was obtained as a white solid; yield 78%; mp 173–175 °C. IR (KBr): 3516, 3412, 3015, 2934, 1650, 1190, 1042 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 11.39 (s, 1 H), 9.84 (s, 1 H), 7.96 (d, J = 7.7 Hz, 1 H), 7.48 (s, 1 H), 7.42 (s, 1 H), 7.31–7.28 (m, 1 H), 6.90–6.85 (m, 1 H), 6.59 (d, J = 7.8 Hz, 1 H), 5.72 (s, 1 H), 4.59 (s, 1 H), 2.88 (s, 3 H), 2.64 (t, J = 7.4 Hz, 2 H), 1.66–1.59 (m, 2 H), 0.94 (t, J = 7.2 Hz, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 196.5, 163.8, 160.7, 145.4, 135.3, 133.7, 132.7, 130.6, 129.6, 128.5, 119.8, 115.6, 114.3, 73.5, 31.8, 31.2, 22.4, 13.9. ESI-MS: m/z = 325 [M + H]⁺.

19a Siva Kumar K, Mahesh Kumar P, Anil Kumar K, Sreenivasulu M, Ahamed AJ, Rambabu D, Rama Krishna G, Malla Reddy C, Ravikumar K, Shivakumar K, Krishna Priya K, Kishore VL. P, Pal M. Chem. Commun. 2011; 47: 5010
19b Panja SK, Dwivedi N, Saha S. Tetrahedron Lett. 2012; 53: 6167

20 Boehm TL, Showalter HD. H. J. Org. Chem. 1996; 61: 6498
21 Sashidhara KV, Kumar M, Modukuri RK, Srivastava RK, Soni A, Srivastava K, Singh SV, Saxena JK, Gauniyal HM, Puri SK. Bioorg. Med. Chem. 2012; 20: 2971

Supplementary Material

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