Experimental and Hirshfeld Surface Investigations for Unexpected Aminophenazone Cocrystal Formation under Thiourea Reaction Conditions via Possible Enamine Assisted Rearrangement
Considering the astounding biomedicine properties of pharmaceutically active drug, 4-aminophenazone, also known as 4-aminoantipyrine, the work reported in this manuscript details the formation of novel cocrystals of rearranged 4-aminophenazone and 4-nitro-<i>N</i>-(4-nitrobenzoyl) benzam...
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MDPI AG
2022-04-01
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| Online Access: | https://www.mdpi.com/2073-4352/12/5/608 |
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| author | Asma Khurshid Aamer Saeed Tuncer Hökelek Umama Taslim Madiha Irfan Saba Urooge Khan Aneela Iqbal Hesham R. El-Seedi |
| author_facet | Asma Khurshid Aamer Saeed Tuncer Hökelek Umama Taslim Madiha Irfan Saba Urooge Khan Aneela Iqbal Hesham R. El-Seedi |
| author_sort | Asma Khurshid |
| collection | DOAJ |
| description | Considering the astounding biomedicine properties of pharmaceutically active drug, 4-aminophenazone, also known as 4-aminoantipyrine, the work reported in this manuscript details the formation of novel cocrystals of rearranged 4-aminophenazone and 4-nitro-<i>N</i>-(4-nitrobenzoyl) benzamide in 1:1 stoichiometry under employed conditions for thiourea synthesis by exploiting the use of its active amino component. However, detailed analysis via various characterization techniques such as FT-IR, nuclear magnetic resonance spectroscopy and single crystal XRD, for this unforeseen, but useful cocrystalline synthetic adduct (<b>4</b> and <b>5</b>) prompted us to delve into its mechanistic pathway under provided reaction conditions. The coformer 4-nitro-<i>N</i>-(4-nitrobenzoyl) benzamide originates via nucleophilic addition reaction following tetrahedral mechanism between para-nitro substituted benzoyl amide and its acid halide (<b>1</b>). While the enamine nucleophilic addition reaction by 4-aminophenazone on 4-nitrosubstituted aroyl isothiocyanates under reflux temperature suggests the emergence of rearranged counterpart of cocrystal named <i>N</i>-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1<i>H</i>-pyrazole-4-carbonothioyl)-4-nitrobenzamide. Crystallographic studies reveal triclinic system <i>P</i>-1 space group for cocrystal (<b>4</b> and <b>5</b>) and depicts two different crystallographically independent molecules with prominent C–H···O and N–H···O hydrogen bonding effective for structure stabilization. Hirshfeld surface analysis also displays hydrogen bonding and van der Waals interactions as dominant interactions in crystal packing. Further insight into the cocrystal synthetic methodologies supported the occurrence of solution-based evaporation/cocrystallization methodology in our case during purification step, promoting the synthesis of this first-ever reported novel cocrystal of 4-aminophenazone with promising future application in medicinal industry. |
| first_indexed | 2024-03-10T03:05:50Z |
| format | Article |
| id | doaj.art-7fec31c68f654ba28902ffe93966a0d5 |
| institution | Directory Open Access Journal |
| issn | 2073-4352 |
| language | English |
| last_indexed | 2024-03-10T03:05:50Z |
| publishDate | 2022-04-01 |
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| record_format | Article |
| series | Crystals |
| spelling | doaj.art-7fec31c68f654ba28902ffe93966a0d52023-11-23T10:34:22ZengMDPI AGCrystals2073-43522022-04-0112560810.3390/cryst12050608Experimental and Hirshfeld Surface Investigations for Unexpected Aminophenazone Cocrystal Formation under Thiourea Reaction Conditions via Possible Enamine Assisted RearrangementAsma Khurshid0Aamer Saeed1Tuncer Hökelek2Umama Taslim3Madiha Irfan4Saba Urooge Khan5Aneela Iqbal6Hesham R. El-Seedi7Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, PakistanDepartment of Chemistry, Quaid-I-Azam University, Islamabad 45320, PakistanDepartment of Physics, Hacettepe University, Ankara 06800, TurkeyDepartment of Chemistry, Quaid-I-Azam University, Islamabad 45320, PakistanDepartment of Chemistry, Khawaja Farid University of Engineering and Information Technology, Rahim Yar Khan 64200, PakistanInstitute of Polymer and Textile Engineering, University of Punjab, Lahore 54590, PakistanNational Centre for Physics, Shahdara Valley Road, Islamabad 44000, PakistanPharmacognosy Group, Department of Pharmaceutical Biosciences, BMC, Uppsala University, P.O. Box 591, SE 751 24 Uppsala, SwedenConsidering the astounding biomedicine properties of pharmaceutically active drug, 4-aminophenazone, also known as 4-aminoantipyrine, the work reported in this manuscript details the formation of novel cocrystals of rearranged 4-aminophenazone and 4-nitro-<i>N</i>-(4-nitrobenzoyl) benzamide in 1:1 stoichiometry under employed conditions for thiourea synthesis by exploiting the use of its active amino component. However, detailed analysis via various characterization techniques such as FT-IR, nuclear magnetic resonance spectroscopy and single crystal XRD, for this unforeseen, but useful cocrystalline synthetic adduct (<b>4</b> and <b>5</b>) prompted us to delve into its mechanistic pathway under provided reaction conditions. The coformer 4-nitro-<i>N</i>-(4-nitrobenzoyl) benzamide originates via nucleophilic addition reaction following tetrahedral mechanism between para-nitro substituted benzoyl amide and its acid halide (<b>1</b>). While the enamine nucleophilic addition reaction by 4-aminophenazone on 4-nitrosubstituted aroyl isothiocyanates under reflux temperature suggests the emergence of rearranged counterpart of cocrystal named <i>N</i>-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1<i>H</i>-pyrazole-4-carbonothioyl)-4-nitrobenzamide. Crystallographic studies reveal triclinic system <i>P</i>-1 space group for cocrystal (<b>4</b> and <b>5</b>) and depicts two different crystallographically independent molecules with prominent C–H···O and N–H···O hydrogen bonding effective for structure stabilization. Hirshfeld surface analysis also displays hydrogen bonding and van der Waals interactions as dominant interactions in crystal packing. Further insight into the cocrystal synthetic methodologies supported the occurrence of solution-based evaporation/cocrystallization methodology in our case during purification step, promoting the synthesis of this first-ever reported novel cocrystal of 4-aminophenazone with promising future application in medicinal industry.https://www.mdpi.com/2073-4352/12/5/608cocrystalaminophenazonethiourea reaction conditionssingle crystalHirshfeld surface analysisplausible mechanism |
| spellingShingle | Asma Khurshid Aamer Saeed Tuncer Hökelek Umama Taslim Madiha Irfan Saba Urooge Khan Aneela Iqbal Hesham R. El-Seedi Experimental and Hirshfeld Surface Investigations for Unexpected Aminophenazone Cocrystal Formation under Thiourea Reaction Conditions via Possible Enamine Assisted Rearrangement Crystals cocrystal aminophenazone thiourea reaction conditions single crystal Hirshfeld surface analysis plausible mechanism |
| title | Experimental and Hirshfeld Surface Investigations for Unexpected Aminophenazone Cocrystal Formation under Thiourea Reaction Conditions via Possible Enamine Assisted Rearrangement |
| title_full | Experimental and Hirshfeld Surface Investigations for Unexpected Aminophenazone Cocrystal Formation under Thiourea Reaction Conditions via Possible Enamine Assisted Rearrangement |
| title_fullStr | Experimental and Hirshfeld Surface Investigations for Unexpected Aminophenazone Cocrystal Formation under Thiourea Reaction Conditions via Possible Enamine Assisted Rearrangement |
| title_full_unstemmed | Experimental and Hirshfeld Surface Investigations for Unexpected Aminophenazone Cocrystal Formation under Thiourea Reaction Conditions via Possible Enamine Assisted Rearrangement |
| title_short | Experimental and Hirshfeld Surface Investigations for Unexpected Aminophenazone Cocrystal Formation under Thiourea Reaction Conditions via Possible Enamine Assisted Rearrangement |
| title_sort | experimental and hirshfeld surface investigations for unexpected aminophenazone cocrystal formation under thiourea reaction conditions via possible enamine assisted rearrangement |
| topic | cocrystal aminophenazone thiourea reaction conditions single crystal Hirshfeld surface analysis plausible mechanism |
| url | https://www.mdpi.com/2073-4352/12/5/608 |
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