Synthesis of Triarylpyrylium Salts Using a Mild, Eco-friendly Route

Abstract

Pyrylium salts based on a cationic oxygen heterocycle are a key class of chromophores. However, synthesis of these salts generally requires use of harsh acids, copious organic solvents, and in many cases, hazardous conditions. This work provides a two-pot synthesis for substituted triphenyl pyrylium salts wherein chalcone intermediates are first prepared and then mild methanesulfonic acid is used in combination with a dehydrating agent to drive pyrylium cyclization. Purification is achieved through a simple, aqueous workup involving counterion metathesis which avoids the need for environmentally unfriendly organic solvents. This mild, green approach has been applied to synthesize a collection of known pyryliums as well as a new family of red-shifted pyrylium chromophores bearing p-pyrrolidinylphenyl substituents. The synthesis of the latter group demonstrates that unlike other current methods, our approach offers enhanced functional group tolerance as well as finer control over substituent placement.

Key words

photochemistry - green chemistry - condensation - chromophores - cyclization

Publikationsverlauf

Eingereicht: 20. Oktober 2023

Angenommen nach Revision: 28. Dezember 2023

Accepted Manuscript online:
28. Dezember 2023

Artikel online veröffentlicht:
29. Januar 2024

• References and Notes

• 1 New address: C. T. Owen, Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
• 2 New address: N. C. Starvaggi, Department of Chemistry, Texas A&M University, College Station, TX, USA.
• 3 Li Y, Wang H, Li X. Chem. Sci. 2020; 11: 12249
• 4 Basch CH, Liao J, Xu J, Piane JJ, Watson MP. J. Am. Chem. Soc. 2017; 139: 5313
• 5 Cheng XH, Höger S, Fenske D. Org. Lett. 2003; 5: 2587
• 6 Kargapolova IYu, Shmuilovich KS, Beregovaya IV, Orlova NA. Russ. Chem. Bull. 2010; 59: 1414
• 7 Wu J, He L, Noble A, Aggarwal VK. J. Am. Chem. Soc. 2018; 140: 10700
• 8 Breit B, Winde R, Mackewitz T, Paciello R, Harms K. Chem. Eur. J. 2001; 7: 3106
• 9 Saettel NJ, Wiest O, Singleton DA, Meyer MP. J. Am. Chem. Soc. 2002; 124: 11552
• 10 Hola E, Ortyl J. Eur. Polym. J. 2021; 150: 110365
• 11 Alfonzo E, Alfonso FS, Beeler AB. Org. Lett. 2017; 19: 2989
• 12 Chandu P, Ghosh KG, Sureshkumar D. J. Org. Chem. 2019; 84: 8771
• 13 Bao L, Cheng J.-T, Wang Z.-X, Chen X.-Y. Org. Chem. Front. 2022; 9: 973
• 14 Kar S, Akhir A, Chopra S, Ohki S, Karanam B, Golakoti NR. Med. Chem. Res. 2021; 30: 877
• 15 Zhang Y, Li Q, Chao W, Qin Y, Chen J, Wang Y, Liu R, Lv Q, Wang J. Molecules 2022; 27: 4450
• 16 Romero NA, Nicewicz DA. Chem. Rev. 2016; 116: 10075
• 17 Haucke G, Czerney P, Cebulla F. Ber. Bunsenges. Phys. Chem. 1992; 96: 880
• 18 VanAllan JA, Reynolds GA. J. Org. Chem. 1968; 33: 1102
• 19 Cruz CL, Holmberg-Douglas N, Onuska NP. R, McManus JB, MacKenzie IA, Hutson BL, Eskew NA, Nicewicz DA. J. Chem. Educ. 2020; 97: 1572
• 20 Schroth W, Spitzner R, Kleinpeter E. Tetrahedron Lett. 1988; 29: 4695
• 21 Wizinger R, Grüne A, Jacobi E. Helv. Chim. Acta 1956; 39: 1-4
• 22 Koh JJ, Lee CI, Ciulei MA, Han H, Bhowmik PK, Kartazaev V, Gayen SK. J. Mol. Struct. 2018; 1171: 458
• 23 Kohler EP, Chadwell HM. Org. Synth. 1922; 2: 1
• 24 Synthetic Protocol and Data for New Pyrrolidine-Bearing Pyryliums To a 40 mL EPA vial were added 10.0 mmol of appropriate acetophenone derivative and 10.0 mmol of appropriate chalcone derivative. 4 mL of acetic anhydride and 3 mL of methanesulfonic acid (approx. 23 mmol) were then added, a stir bar was added, and the vial was then sealed. The reaction mixture was heated to between 100–120 °C overnight with stirring. The reaction mixture was then added to approximately 200 mL of 90–100 °C water and stirred briefly. The aqueous mixture was then hot-filtered through a Celite pad and precipitated using 5–10 mL of a saturated solution of KPF₆ in water. The resulting precipitate was then collected via vacuum filtration and washed with water. The analytically pure compound may be used as-is or further purified via a plug on basic alumina using an ethyl acetate to acetonitrile gradient. Characterization Data for Product 10 Mp 239–243 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.72–8.63 (m, 2 H), 8.59 (d, J = 9.04 Hz, 2 H), 8.50–8.39 (m, 4 H), 7.82–7.69 (m, 6 H), 6.88 (d, J = 8.92 Hz, 2 H), 3.61 (br s, 4 H), 2.04 (br s, 4 H). ¹³C NMR (100.6 MHz, DMSO-d ₆): δ = 165.04, 164.68, 158.55, 153.39, 133.71, 133.39, 129.87, 129.51, 127.61, 127.53, 118.21, 113.84, 109.18, 48.35, 24.72. MS (ESI, MeOH): m/z = 378.2 (100%, M – PF₆) Characterization Data for Product 11 Mp 210–221 °C.¹H NMR (400 MHz, DMSO-d ₆): δ = 8.73 (d, J = 1.29 Hz, 1 H), 8.58 (d, J=1.14 Hz, 1 H), 8.49–8.40 (m, 6 H), 7.83–7.69 (m, 6 H), 6.88 (d, J = 9.26 Hz, 2 H), 3.55 (t, J = 6.58 Hz, 4 H), 2.07–2.01 (m, 4 H). ¹³C NMR (100.6 MHz, DMSO-d ₆): δ = 170.05, 164.99, 159.54, 152.67, 133.63, 133.43, 133.24, 131.76, 129.70, 129.59, 129.51, 129.00, 127.56, 114.37, 113.32, 110.53, 48.06, 24.77. MS (ESI, MeOH): m/z = 378.3 (100%, M – PF₆). Characterization Data for Product 12 Mp 263–266 °C. ¹H NMR (400 MHz, DMSO-d ₆): δ = 8.34–8.29 (m, 2 H), 8.27 (s, 2 H), 8.21 (d, J = 9.1 Hz, 4 H), 7.76–7.64 (m, 3 H), 6.74 (d, J = 9.2 Hz, 4 H), 3.43 (t, J = 6.28 Hz, 8 H), 2.04–1.98 (m, 8 H). ¹³C NMR (100.6 MHz, DMSO-d ₆): δ = 167.13, 158.42, 151.52, 133.69, 133.09, 130.12, 129.37, 128.62, 114.79, 112.62, 108.38, 47.70, 24.85. MS (ESI, MeOH): m/z = 447.3 (100%, M – PF₆).
• 25 Gayton J, Autry S, Fortenberry R, Hammer N, Delcamp J. Molecules 2018; 23: 3051
• 26 Franconetti A, Contreras-Bernal L, Prado-Gotor R, Cabrera-Escribano F. RSC Adv. 2015; 5: 74274
• 27 Koh JJ. Master’s Thesis. University of Nevada; USA: 2015
• 28 Sambiagio C, Ferrari M, van Beurden K, della Ca’ N, van Schijndel J, Noël T. Org. Lett. 2021; 23: 2042
• 29 Núñez-Franco R, Jiménez-Osés G, Jiménez-Barbero J, Cabrera-Escribano F, Franconetti A. Phys. Chem. Chem. Phys. 2022; 24: 1965
• 30 Bhowmik PK, Lee CI, Koh JJ, Han H, Jubair A, Kartazaev V, Gayen SK. J. Mol. Struct. 2020; 1202: 127325