Impact of Molecular and Crystal Structure on the Melting Points in Halo-Substituted Phenyl-Quinazolinones
Three halo-substituted phenyl-quinazolinone derivatives were prepared and structurally characterized [<b>1</b> = 3-(4-chlorophenyl)-6-iodo-2-methylquinazolin-4(3<i>H</i>)-one, <b>2</b> = 6-iodo-3-(4-methoxyphenyl)-2-methylquinazolin-4(3<i>H</i>)-one, a...
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2024-12-01
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| author | Ivica Đilović Nenad Judaš Mario Komar Maja Molnar Marta Počkaj Tomislav Balić |
| author_facet | Ivica Đilović Nenad Judaš Mario Komar Maja Molnar Marta Počkaj Tomislav Balić |
| author_sort | Ivica Đilović |
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| description | Three halo-substituted phenyl-quinazolinone derivatives were prepared and structurally characterized [<b>1</b> = 3-(4-chlorophenyl)-6-iodo-2-methylquinazolin-4(3<i>H</i>)-one, <b>2</b> = 6-iodo-3-(4-methoxyphenyl)-2-methylquinazolin-4(3<i>H</i>)-one, and <b>3</b> = 7-chloro-2-methyl-3-[4-(trifluoromethoxy)phenyl]quinazolin-4(3<i>H</i>)-one)] in order to explore the relationship between structure and melting point in this group of compounds. Depending on the compound, molecules are interconnected by weak <i>π</i>∙∙∙<i>π</i> interactions, have I···Cl or Cl···Cl halogen bonding, or primarily form C–H∙∙∙N, C–H∙∙∙O, and <i>π</i>∙∙∙<i>π</i> interactions (no halogen bonding). The presence of the OCF<sub>3</sub> group leads to interactions between fluorine atoms that are shorter than the sum of the van der Waals radius for fluorine, suggesting that these interactions contribute to the overall lattice energy. The sequence of melting points cannot be fully explained by intermolecular interactions present in the solid state (enthalpy factor). To address this, a concept related to entropy called the functional group rotation influence, which relates to a decrease in fusion entropy caused by the rotational freedom of polyatomic groups, was introduced. Analysis of previously synthesized 3-phenylquinazolinones showed that the compounds with the highest melting point are the quinazoline-substituted and phenyl-nitro-substituted ones. Among halo-phenyl-substituted compounds, the melting point follows the sequence <i>ortho < meta < para</i>. Regarding the halogen atom type, the order of melting points is Cl ≈ Br > F > I for enantiopure and Br > I ≈ Cl > F for racemic compounds. Also, the melting point order correlates to halogen bond energy (I > Br > Cl > F) only when the geometry and energy of these interactions are favorable. |
| format | Article |
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| institution | Kabale University |
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| publishDate | 2024-12-01 |
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| spelling | doaj-art-8481f62097084e78b7e8e2093e5d7b0d2025-01-24T13:28:05ZengMDPI AGCrystals2073-43522024-12-011513910.3390/cryst15010039Impact of Molecular and Crystal Structure on the Melting Points in Halo-Substituted Phenyl-QuinazolinonesIvica Đilović0Nenad Judaš1Mario Komar2Maja Molnar3Marta Počkaj4Tomislav Balić5Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, CroatiaDepartment of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, CroatiaFaculty of Food Technology Osijek, Josip Juraj Strossmayer University of Osijek, Franje Kuhača 18, 31000 Osijek, CroatiaFaculty of Food Technology Osijek, Josip Juraj Strossmayer University of Osijek, Franje Kuhača 18, 31000 Osijek, CroatiaFaculty of Chemistry and Chemical Technology, University of Ljubljana, Večna Pot 113, 1000 Ljubljana, SloveniaDepartment of Chemistry, Josip Juraj Strossmayer University of Osijek, Cara Hadrijana 8/A, 31000 Osijek, CroatiaThree halo-substituted phenyl-quinazolinone derivatives were prepared and structurally characterized [<b>1</b> = 3-(4-chlorophenyl)-6-iodo-2-methylquinazolin-4(3<i>H</i>)-one, <b>2</b> = 6-iodo-3-(4-methoxyphenyl)-2-methylquinazolin-4(3<i>H</i>)-one, and <b>3</b> = 7-chloro-2-methyl-3-[4-(trifluoromethoxy)phenyl]quinazolin-4(3<i>H</i>)-one)] in order to explore the relationship between structure and melting point in this group of compounds. Depending on the compound, molecules are interconnected by weak <i>π</i>∙∙∙<i>π</i> interactions, have I···Cl or Cl···Cl halogen bonding, or primarily form C–H∙∙∙N, C–H∙∙∙O, and <i>π</i>∙∙∙<i>π</i> interactions (no halogen bonding). The presence of the OCF<sub>3</sub> group leads to interactions between fluorine atoms that are shorter than the sum of the van der Waals radius for fluorine, suggesting that these interactions contribute to the overall lattice energy. The sequence of melting points cannot be fully explained by intermolecular interactions present in the solid state (enthalpy factor). To address this, a concept related to entropy called the functional group rotation influence, which relates to a decrease in fusion entropy caused by the rotational freedom of polyatomic groups, was introduced. Analysis of previously synthesized 3-phenylquinazolinones showed that the compounds with the highest melting point are the quinazoline-substituted and phenyl-nitro-substituted ones. Among halo-phenyl-substituted compounds, the melting point follows the sequence <i>ortho < meta < para</i>. Regarding the halogen atom type, the order of melting points is Cl ≈ Br > F > I for enantiopure and Br > I ≈ Cl > F for racemic compounds. Also, the melting point order correlates to halogen bond energy (I > Br > Cl > F) only when the geometry and energy of these interactions are favorable.https://www.mdpi.com/2073-4352/15/1/39phenyl-quinazolinoneshalogen bond interactionsmelting pointfunctional group rotation influence |
| spellingShingle | Ivica Đilović Nenad Judaš Mario Komar Maja Molnar Marta Počkaj Tomislav Balić Impact of Molecular and Crystal Structure on the Melting Points in Halo-Substituted Phenyl-Quinazolinones Crystals phenyl-quinazolinones halogen bond interactions melting point functional group rotation influence |
| title | Impact of Molecular and Crystal Structure on the Melting Points in Halo-Substituted Phenyl-Quinazolinones |
| title_full | Impact of Molecular and Crystal Structure on the Melting Points in Halo-Substituted Phenyl-Quinazolinones |
| title_fullStr | Impact of Molecular and Crystal Structure on the Melting Points in Halo-Substituted Phenyl-Quinazolinones |
| title_full_unstemmed | Impact of Molecular and Crystal Structure on the Melting Points in Halo-Substituted Phenyl-Quinazolinones |
| title_short | Impact of Molecular and Crystal Structure on the Melting Points in Halo-Substituted Phenyl-Quinazolinones |
| title_sort | impact of molecular and crystal structure on the melting points in halo substituted phenyl quinazolinones |
| topic | phenyl-quinazolinones halogen bond interactions melting point functional group rotation influence |
| url | https://www.mdpi.com/2073-4352/15/1/39 |
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