Applications of sublimation in the synthesis and crystal growth of Organosulfones Lamis Alaa Eldin Refat 1,2 , Saidulu Konda 1 , Paul Murphy 1,2 , Patrick McArdle 1 , Andrea Erxleben 1,2 1 School of Biological and Chemical Sciences, University of Galway, Ireland, 2 Synthesis and Solid State Pharmaceutical Centre (SSPC), Ireland Sublimation has been established as a successful method of producing solvent-free high-quality single crystals of several APIs 1–3 . Further applications of sublimation in combined organic synthesis through thermal transformation and crystal growth of organosulfones are currently investigated in this work. Aromatic sulfones are valuable intermediates in industrial applications and organic synthesis. Diaryl sulfones are of particular importance in pharmaceuticals. Diphenyl sulfone is an intermediate in the synthesis of Dapsone (4,4’-diamino diphenyl sulfone) which is used in the treatment of leprosy 4 . Substituted diaryl sulfones were also found to suppress replication of human immunodeficiency virus type-1 (HIV-1) in vitro 5 . The preparation of 4-phenylsulfonyl biphenyl typically involves multistep reactions that require the use of catalysts and solvents 4 . An in-house low thermal gradient sublimation apparatus 1–3 has shown success in eliminating phenylsulfinic acid from trienes ( 1a – 1f ) to produce biphenyls ( 2 ). 1 was synthesized by reacting [(E)-3-(benzenesulfonyl)allyl]sulfonylbenzene with an equivalent amount of a substituted trans-cinnamaldehyde and 33 equivalents of aluminium oxide to produce a family of substituted derivatives of 2 . In the case of 1a yellow crystalline needles of the starting compound were transformed into colourless crystalline blocks of the phenyl derivative of 4-phenylsulfonyl biphenyl in quantitative yield . Controlled thermal transformation and crystal growth through sublimation has proved to be a green method that provides a single-step process for the efficient production of a quantitative yield of organosulfones without the need for solvents, catalysts or further purification. References 1. Karpinska, J.; Erxleben, A.; McArdle, P. 17β-Hydroxy-17α-Methylandrostano[3,2-c]Pyrazole, Stanozolol: The Crystal Structures of Polymorphs 1 and 2 and 10 Solvates. Cryst. Growth Des. 2011 , 11 (7), 2829–2838. 2. Karpinska, J.; Erxleben, A.; Mcardle, P. Applications of Low Temperature Gradient Sublimation In Vacuo: Rapid Production of High Quality Crystals. The First Solvent-Free Crystals of Ethinyl Estradiol. Cryst. Growth Des. 2013 , 13 (3), 1122–1130. 3. Kamali, N.; O’Malley, C.; Mahon, M. F.; Erxleben, A.; McArdle, P. Use of Sublimation Catalysis and Polycrystalline Powder Templates for Polymorph Control of Gas Phase Crystallization. Cryst. Growth Des. 2018 , 18 (6), 3510–3516. 4. Jin, T.; Yang, M.; Feng, G.; Li, T. An Efficient and Convenient Method for the Synthesis of Aromatic Sulfones Catalysed by ZrO2/S2O82- Solid Superacid. J. Chem. Res. - Part S 2003 , 1 (11), 721–723. 5. McMahon, J. B.; Gulakowski, R. J.; Weislow, O. S.; Schultz, R. J.; Narayanan, V. L.; Clanton, D. J.; Pedemonte, R.; Wassmundt, F. W.; Buckheit, R. W.; Decker, W. D.; White, E. L.; Bader, J. P.; Boyd, M. R. Diarylsulfones, A New Chemical Class of Nonnucleoside Antiviral Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase. Antimicrob. Agents Chemother. 1993 , 37 (4), 754–760.
P10
© The Author(s), 2023
Made with FlippingBook Learn more on our blog