Ph₃P/I₂-Mediated Synthesis of 3-Aryl-Substituted and 3,4-Disubstituted Coumarins

Abstract

Ph₃P/I₂–Et₃N-mediated one-pot two-step esterification–cyclization toward 3-aryl coumarins and 3-aryl-4-methylcoumarins is reported. The reaction of a variety of aryl acetic acids containing steric or reactive group with 2-hydroxybenzaldehydes or 2′-hydroxyacetophenone proceeded smoothly at room temperature to afford the corresponding products in good to excellent yields using inexpensive and readily available reactants and reagents.

Key words

carboxylic acids - chemoselectivity - phosphorous - cyclization

• References and Notes

• 1a Peng X.-M, Damu GL. V, Zhou C.-H. Curr. Pharm. Des. 2013; 19: 3884
• 1b Medina FG, Marrero JG, Macias-Alonso M, Gonzalez MC, Cordova-Guerrero I, Teissier Garcia AG, Osegueda-Robles S. Nat. Prod. Rep. 2015; 32: 1472
• 1c Borges F, Roleira F, Milhazes N, Santana L, Uriarte E. Curr. Med. Chem. 2005; 12: 887
• 2 Sashidhara KV, Kumar A, Chatterjee M, Rao KB, Singh S, Verma AK, Palit G. Bioorg. Med. Chem. Lett. 2011; 21: 1937
• 3a Yang J, Liu G.-Y, Dai F, Cao X.-Y, Kang Y.-F, Hu L.-M, Tang J.-J, Li X.-Z, Li Y, Jin X.-L, Zhou B. Bioorg. Med. Chem. Lett. 2011; 21: 6420
• 3b Zhao H, Yan B, Peterson LB, Blagg BS. J. ACS Med. Chem. Lett. 2012; 3: 327
• 4a Matos MJ, Vazquez-Rodriguez S, Uriarte E, Santana L, Vina D. Bioorg. Med. Chem. Lett. 2011; 21: 4224
• 4b Matos MJ, Teran C, Perez-Castillo Y, Uriarte E, Santana L, Vina D. J. Med. Chem. 2011; 54: 7127
• 4c Jameel E, Umar T, Kumar J, Hoda N. Chem. Biol. Drug Des. 2016; 87: 21
• 5a Frullano L, Zhu J, Wang C, Wu C, Miller RH, Wang Y. J. Med. Chem. 2012; 55: 94
• 5b Frullano L, Wang C, Miller RH, Wang Y. J. Am. Chem. Soc. 2011; 133: 1611
• 6 Vekariya RH, Patel HD. Synth. Commun. 2014; 44: 2756
• 7a Yavari I, Adib M, Hojabri L. Tetrahedron 2002; 58: 6895
• 7b Upadhyay PK, Kumar P. Tetrahedron Lett. 2009; 50: 236
• 8 Heravi MM, Khaghaninejad S, Mostofi M. Adv. Heterocycl. Chem. 2014; 112: 1
• 9a Crawford IM, Shaw JA. M. J. Chem. Soc. 1953; 3435
• 9b Augustine JK, Bombrun A, Ramappa B, Boodappa C. Tetrahedron Lett. 2012; 53: 4422
• 9c Matos MJ, Delogu G, Podda G, Santana L, Uriarte E. Synthesis 2010; 2763
• 10 Rahmani-Nezhad S, Khosravani L, Saeedi M, Divsalar K, Firoozpour L, Pourshojaei Y, Sarrafi Y, Nadri H, Moradi A, Mahdavi M, Shafiee A, Foroumadi A. Synth. Commun. 2015; 45: 741
• 11 Sashidhara KV, Palnati GR, Avula SR, Kumar A. Synlett 2012; 23: 611
• 12a Hans N, Singhi M, Sharma V, Grover SK. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1996; 35: 1159
• 12b Vina D, Matos MJ, Yanez M, Santana L, Uriarte E. Med. Chem. Commun 2012; 3: 213
• 13 Sripathi SK, Logeeswari K. Int. J. Org. Chem. 2013; 3: 42
• 14 Awasthi AK, Tewari RS. Synthesis 1986; 1061
• 15 Taksande K, Borse DS, Lokhande P. Synth. Commun. 2010; 40: 2284
• 16 Gallastegui J, Lago JM, Palomo C. J. Chem. Res., Synop. 1984; 170
• 17 Mashraqui SH, Vashi D, Mistry HD. Synth. Commun. 2004; 34: 3129
• 18a Sharma RK, Katiyar D. Synthesis 2016; 48: 2303
• 18b Zeng H, Li C.-J. Angew. Chem. Int. Ed. 2014; 53: 13862
• 18c Zhao Y, Han F, Yang L, Xia C. Org. Lett. 2015; 17: 1477
• 18d Wu X.-F, Wu L, Jackstell R, Neumann H, Beller M. Chem. Eur. J. 2013; 19: 12245
• 18e Yang Y, Han J, Wu X, Xu S, Wang L. Tetrahedron Lett. 2015; 56: 3809
• 18f Zhang X.-S, Li Z.-W, Shi Z.-J. Org. Chem. Front. 2014; 1: 44
• 18g She Z, Shi Y, Huang Y, Cheng Y, Song F, You J. Chem. Commun. 2014; 50: 13914
• 18h Sasano K, Takaya J, Iwasawa N. J. Am. Chem. Soc. 2013; 135: 10954
• 18i Sharma U, Naveen T, Maji A, Manna S, Maiti D. Angew. Chem. Int. Ed. 2013; 52: 12669
• 19a Allen DW. Organophosphorus Chem. 2012; 41: 1
• 19b Pedrosa LF. Synlett 2008; 1581
• 20a Froyen P. Tetrahedron Lett. 1997; 38: 5359
• 20b Kumar A, Akula HK, Lakshman MK. Eur. J. Org. Chem. 2010; 2709
• 20c Caputo R, Cassano E, Longobardo L, Mastroianni D, Palumbo G. Synthesis 1995; 141
• 20d Kawagoe Y, Moriyama K, Togo H. Tetrahedron 2013; 69: 3971
• 20e Sardarian AR, Zandi M, Motevally S. Acta Chim. Slov. 2009; 56: 729
• 20f Morcillo SP, Alvarez de Cienfuegos L, Mota AJ, Justicia J, Robles R. J. Org. Chem. 2011; 76: 2277
• 20g Mamidi N, Manna D. J. Org. Chem. 2013; 78: 2386
• 20h Gopinath P, Vidyarini RS, Chandrasekaran S. J. Org. Chem. 2009; 74: 6291
• 21a Phakhodee W, Duangkamol C, Wangngae S, Pattarawarapan M. Tetrahedron Lett. 2016; 57: 325
• 21b Wangngae S, Duangkamol C, Pattarawarapan M, Phakhodee W. RSC Adv. 2015; 5: 25789
• 21c Duangkamol C, Wangngae S, Pattarawarapan M, Phakhodee W. Eur. J. Org. Chem. 2014; 7109
• 21d Phakhodee W, Duangkamol C, Pattarawarapan M. Tetrahedron Lett. 2016; 57: 2087
• 22 General Procedure To a solution of Ph₃P (0.62 mmol) in CH₂Cl₂ (4 mL) was added I₂ (0.62 mmol) at 0 °C. The resulting solution was sequentially added with aryl acetic acid (0.41 mmol) and hydroxybenzaldehyde (0.45 mmol) at 0 °C, followed by Et₃N (2.05 mmol). After that, the solution was allowed to warm up to r.t. and stirred until the completion of reaction. The crude material was purified by column chromatography using EtOAc–hexanes as the eluent to afford pure product. 3-(4-Methoxyphenyl)-2H-chromen-2-one (Table 2, Entry 4) White solid (0.1013 g, 98% yield); mp 140–141 °C (lit.² mp 140 °C); R_f = 0.38 (30% EtOAc–hexanes). ¹H NMR (400 MHz, CDCl₃): δ = 7.75 (s, 1 H), 7.68 (d, J = 8.8 Hz, 2 H), 7.53–7.48 (m, 2 H), 7.34 (d, J = 7.6 Hz, 1 H), 7.28 (t, J = 7.6 Hz, 1 H), 6.97 (d, J = 8.8 Hz, 2 H), 3.85 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 160.8, 160.2, 153.3, 138.5, 131.0, 129.9, 127.8, 127.1, 124.5, 119.9, 116.3, 113.9, 55.4. 6-Nitro-3-(2-nitrophenyl)-2H-chromen-2-one (Table 2, Entry 6) Yellow solid (0.0912 g, 71% yield); mp 217–218 °C; R_f = 0.41 (40% EtOAc–hexanes). ¹H NMR (400 MHz, CDCl₃ + TFA): δ = 8.55 (d, J = 2.4 Hz, 1 H), 8.47 (dd, J = 9.2, 2.4 Hz, 1 H), 8.22 (d, J = 7.6 Hz, 1 H), 7.94 (s, 1 H), 7.80 (t, J = 7.6 Hz, 1 H), 7.70 (t, J = 7.6 Hz, 1 H), 7.58 (d, J = 9.2 Hz, 1 H), 7.51 (d, J = 7.6 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃+TFA): δ = 160.4, 156.8, 148.2, 144.8, 139.3, 134.6, 132.1, 131.2, 130.1, 129.0, 127.1, 125.5, 124.2, 119.5, 118.5. HRMS (ESI-TOF): m/z calcd for C₁₅H₉N₂O₆ [M + H]⁺: 313.0461; found. 313.0467. 6-Chloro-3-(2-nitrophenyl)-2H-chromen-2-one (Table 2, Entry 8) White solid (0.0832 g, 67% yield); mp 214–215 °C; R_f = 0.46 (30% EtOAc–hexanes). ¹H NMR (400 MHz, CDCl₃ + TFA): δ = 8.20 (d, J = 8.0 Hz, 1 H), 7.85 (s, 1 H), 7.77 (td, J = 8.0, 1.2 Hz, 2 H), 7.67 (td, J = 8.0, 1.2 Hz, 1 H), 7.62 (s, 1 H), 7.60 (dd, J = 8.8, 2.4 Hz, 1 H), 7.49 (dd, J = 8.0, 1.2 Hz, 1 H), 7.41 (d, J = 8.8 Hz, 1 H). ¹³C NMR (100 MHz, CDCl₃ + TFA): δ = 162.6, 151.6, 148.2, 140.6, 134.5, 132.9, 132.2, 131.4, 130.9, 129.3, 127.7, 125.4, 118.6, 110.3. HRMS (ESI-TOF): m/z calcd for C₁₅H₉ClNO₄ [M + H]⁺: 302.0220; found: 302.0226. 3-(4-Fluorophenyl)-4-methyl-2H-chromen-2-one (Table 2, Entry 18) White solid (0.0921 g, 88% yield); mp 183–184 °C; R_f = 0.30 (20% EtOAc–hexanes). ¹H NMR (400 MHz, CDCl₃): δ = 7.68 (dd, J = 8.0, 1.2 Hz, 1 H), 7.55 (td, J = 8.0, 1.2 Hz, 1 H), 7.36 (t, J = 8.8 Hz, 2 H), 7.31–7.26 (m, 2 H), 7.14 (td, J = 8.8, 2.0 Hz, 2 H), 2.32 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 163.9, 161.4, 161.0, 152.7, 148.1, 132.07, 131.99, 131.6, 130.4 (d, J = 14.4 Hz), 126.4, 125.3, 124.5, 120.5, 117.0, 115.70, 115.5, 16.7. HRMS (ESI-TOF): m/z calcd for C₁₆H₁₂FO₂ [M + H]⁺: 255.0821; found: 255.0824. 3-(3,4-Dichlorophenyl)-4-methyl-2H-chromen-2-one (Table 2, Entry 19) White solid (0.0901 g, 72% yield); mp 209–210 °C; R_f = 0.31 (20% EtOAc–hexanes). ¹H NMR (400 MHz, CDCl₃ + TFA): δ = 7.76 (dd, J = 8.4, 1.6 Hz, 1 H), 7.64 (td, J = 8.4, 1.6 Hz, 1 H), 7.55 (d, J = 8.4 Hz, 1 H), 7.45–7.41 (m, 2 H), 7.41 (d, J = 2.0 Hz, 1 H), 7.15 (dd, J = 8.4, 2.0 Hz, 1 H), 2.39 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃ + TFA): δ = 163.2, 152.3, 151.4, 133.7, 133.2, 133.0, 132.7, 132.1, 130.9, 129.6, 125.6, 125.5, 124.6, 120.3, 117.3, 113.3, 16.9. HRMS (ESI-TOF): m/z calcd for C₁₆H₁₁ClO₂ [M + H]⁺: 305.0136; found: 305.0129. 4-Methyl-3-(2-nitrophenyl)-2H-chromen-2-one (Table 2, Entry 20) White solid (0.0957 g, 83% yield); mp 167–168 °C; R_f = 0.37 (30% EtOAc–hexanes). ¹H NMR (400 MHz, CDCl₃): δ = 8.21 (d, J = 8.0 Hz, 1 H), 7.72 (td, J = 7.6, 1.2 Hz, 1 H), 7.67 (dd, J = 8.0, 1.6 Hz, 1 H), 7.62–7.55 (m, 2 H), 7.40–7.32 (m, 3 H), 2.27 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 159.9, 152.8, 148.8, 147.2, 133.8, 132.7, 131.9, 130.2, 129.8, 125.19, 125.17, 125.0, 124.6, 120.2, 117.2, 16.6. HRMS (ESI-TOF): m/z calcd for C₁₆H₁₂NO₄ [M + H]⁺: 282.0766; found: 282.0767.
• 23a Shen W, Mao J, Sun J, Sun M, Zhang C. Med. Chem. Res. 2013; 22: 1630
• 23b Ye D, Wang L, Li H, Zhou J, Cao D. Sens. Actuators, B 2013; 181: 234
• 23c Wang L, Zou H, Ye D, Cao D. J. Heterocycl. Chem. 2013; 50: 551
• 23d Ranjith C, Paul N, Vijayan KK. Asian J.Chem. 2011; 23: 235
• 23e Pu W, Lin Y, Zhang J, Wang F, Wang C, Zhang G. Bioorg. Med. Chem. Lett. 2014; 24: 5432
• 24a Camp D, Jenkins ID. J. Org. Chem. 1989; 54: 3045
• 24b Camp D, Jenkins ID. J. Org. Chem. 1989; 54: 3049
• 24c Schenk S, Weston J, Anders E. J. Am. Chem. Soc. 2005; 127: 12566
• 25 Mali RS, Joshi PP. Synth. Commun. 2001; 31: 2753