First x-ray crystal structure characterization, computational studies, and improved synthetic route to the bioactive 5-arylimino-1,3,4-thiadiazole derivatives
N-arylcyanothioformamides are useful coupling components for building key chemical intermediates and biologically active molecules in an expedited and efficient manner. Similarly, substituted (Z)-2-oxo-N-phenylpropanehydrazonoyl chlorides have been utilized in numerous one-step heteroannulation reac...
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sg-ntu-dr.10356-1695712023-07-28T15:31:42Z First x-ray crystal structure characterization, computational studies, and improved synthetic route to the bioactive 5-arylimino-1,3,4-thiadiazole derivatives Moussa, Ziad Paz, Alejandro Perez Judeh, Zaher M. A. Alzamly, Ahmed Saadeh, Haythem A. Asghar, Basim H. Alsaedi, Sara Masoud, Bayan Almeqbaali, Salama Estwani, Saeda Aljaberi, Amna Al-Rooqi, Munirah M. Ahmed, Saleh A. School of Chemistry, Chemical Engineering and Biotechnology Science::Chemistry Isothiocyanate Hydrazonoyl Chloride N-arylcyanothioformamides are useful coupling components for building key chemical intermediates and biologically active molecules in an expedited and efficient manner. Similarly, substituted (Z)-2-oxo-N-phenylpropanehydrazonoyl chlorides have been utilized in numerous one-step heteroannulation reactions to assemble the structural core of several different types of heterocyclic compounds. Herein, we demonstrate the effectiveness of the reaction of N-arylcyanothioformamides with various substituted (Z)-2-oxo-N-phenylpropanehydrazonoyl chlorides to produce, stereoselectively and regioselectively, a range of 5-arylimino-1,3,4-thiadiazole derivatives decorated with a multitude of functional groups on both aromatic rings. The synthetic methodology features mild room-temperature conditions, large substrate scope, wide array of functional groups on both reactants, and good to high reaction yields. The products were isolated by gravity filtration in all cases and structures were confirmed by multinuclear NMR spectroscopy and high accuracy mass spectral analysis. Proof of molecular structure of the isolated 5-arylimino-1,3,4-thiadiazole regioisomer was obtained for the first time by single-crystal X-ray diffraction analysis. Crystal-structure determination was carried out on (Z)-1-(5-((3-fluorophenyl)imino)-4-(4-iodophenyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)ethan-1-one and (Z)-1-(4-phenyl-5-(p-tolylimino)-4,5-dihydro-1,3,4-thiadiazol-2-yl)ethan-1-one. Similarly, the tautomeric structures of the N-arylcyanothioformamides and (Z)-geometries of the 2-oxo-N-phenylpropanehydrazonoyl chloride coupling partners were proven by X-ray diffraction studies. As representative examples, crystal-structure determination was carried out on (4-ethoxyphenyl)carbamothioyl cyanide and (Z)-N-(2,3-difluorophenyl)-2-oxopropanehydrazonoyl chloride. Density functional theory calculations at the B3LYP-D4/def2-TZVP level were carried out to rationalize the observed experimental findings. Published version Ziad Moussa is grateful to the United Arab Emirates University (UAEU) and to the Research Office for supporting the research developed in his laboratory and reported herein (SUREPLUS Grant code G00003918). The authors would like to acknowledge the Deanship of Scientific Research at Umm Al-Qura University for supporting this work by Grant code: 22UQU4220005DSR01. Alejandro Perez Paz thanks the UAEU for an internal start-up grant (No. 31S410). 2023-07-25T01:11:26Z 2023-07-25T01:11:26Z 2023 Journal Article Moussa, Z., Paz, A. P., Judeh, Z. M. A., Alzamly, A., Saadeh, H. A., Asghar, B. H., Alsaedi, S., Masoud, B., Almeqbaali, S., Estwani, S., Aljaberi, A., Al-Rooqi, M. M. & Ahmed, S. A. (2023). First x-ray crystal structure characterization, computational studies, and improved synthetic route to the bioactive 5-arylimino-1,3,4-thiadiazole derivatives. International Journal of Molecular Sciences, 24(4), 3759-. https://dx.doi.org/10.3390/ijms24043759 1661-6596 https://hdl.handle.net/10356/169571 10.3390/ijms24043759 36835167 2-s2.0-85149009431 4 24 3759 en International Journal of Molecular Sciences © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). application/pdf |
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Science::Chemistry Isothiocyanate Hydrazonoyl Chloride Moussa, Ziad Paz, Alejandro Perez Judeh, Zaher M. A. Alzamly, Ahmed Saadeh, Haythem A. Asghar, Basim H. Alsaedi, Sara Masoud, Bayan Almeqbaali, Salama Estwani, Saeda Aljaberi, Amna Al-Rooqi, Munirah M. Ahmed, Saleh A. First x-ray crystal structure characterization, computational studies, and improved synthetic route to the bioactive 5-arylimino-1,3,4-thiadiazole derivatives |
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N-arylcyanothioformamides are useful coupling components for building key chemical intermediates and biologically active molecules in an expedited and efficient manner. Similarly, substituted (Z)-2-oxo-N-phenylpropanehydrazonoyl chlorides have been utilized in numerous one-step heteroannulation reactions to assemble the structural core of several different types of heterocyclic compounds. Herein, we demonstrate the effectiveness of the reaction of N-arylcyanothioformamides with various substituted (Z)-2-oxo-N-phenylpropanehydrazonoyl chlorides to produce, stereoselectively and regioselectively, a range of 5-arylimino-1,3,4-thiadiazole derivatives decorated with a multitude of functional groups on both aromatic rings. The synthetic methodology features mild room-temperature conditions, large substrate scope, wide array of functional groups on both reactants, and good to high reaction yields. The products were isolated by gravity filtration in all cases and structures were confirmed by multinuclear NMR spectroscopy and high accuracy mass spectral analysis. Proof of molecular structure of the isolated 5-arylimino-1,3,4-thiadiazole regioisomer was obtained for the first time by single-crystal X-ray diffraction analysis. Crystal-structure determination was carried out on (Z)-1-(5-((3-fluorophenyl)imino)-4-(4-iodophenyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)ethan-1-one and (Z)-1-(4-phenyl-5-(p-tolylimino)-4,5-dihydro-1,3,4-thiadiazol-2-yl)ethan-1-one. Similarly, the tautomeric structures of the N-arylcyanothioformamides and (Z)-geometries of the 2-oxo-N-phenylpropanehydrazonoyl chloride coupling partners were proven by X-ray diffraction studies. As representative examples, crystal-structure determination was carried out on (4-ethoxyphenyl)carbamothioyl cyanide and (Z)-N-(2,3-difluorophenyl)-2-oxopropanehydrazonoyl chloride. Density functional theory calculations at the B3LYP-D4/def2-TZVP level were carried out to rationalize the observed experimental findings. |
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School of Chemistry, Chemical Engineering and Biotechnology |
author_facet |
School of Chemistry, Chemical Engineering and Biotechnology Moussa, Ziad Paz, Alejandro Perez Judeh, Zaher M. A. Alzamly, Ahmed Saadeh, Haythem A. Asghar, Basim H. Alsaedi, Sara Masoud, Bayan Almeqbaali, Salama Estwani, Saeda Aljaberi, Amna Al-Rooqi, Munirah M. Ahmed, Saleh A. |
format |
Article |
author |
Moussa, Ziad Paz, Alejandro Perez Judeh, Zaher M. A. Alzamly, Ahmed Saadeh, Haythem A. Asghar, Basim H. Alsaedi, Sara Masoud, Bayan Almeqbaali, Salama Estwani, Saeda Aljaberi, Amna Al-Rooqi, Munirah M. Ahmed, Saleh A. |
author_sort |
Moussa, Ziad |
title |
First x-ray crystal structure characterization, computational studies, and improved synthetic route to the bioactive 5-arylimino-1,3,4-thiadiazole derivatives |
title_short |
First x-ray crystal structure characterization, computational studies, and improved synthetic route to the bioactive 5-arylimino-1,3,4-thiadiazole derivatives |
title_full |
First x-ray crystal structure characterization, computational studies, and improved synthetic route to the bioactive 5-arylimino-1,3,4-thiadiazole derivatives |
title_fullStr |
First x-ray crystal structure characterization, computational studies, and improved synthetic route to the bioactive 5-arylimino-1,3,4-thiadiazole derivatives |
title_full_unstemmed |
First x-ray crystal structure characterization, computational studies, and improved synthetic route to the bioactive 5-arylimino-1,3,4-thiadiazole derivatives |
title_sort |
first x-ray crystal structure characterization, computational studies, and improved synthetic route to the bioactive 5-arylimino-1,3,4-thiadiazole derivatives |
publishDate |
2023 |
url |
https://hdl.handle.net/10356/169571 |
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1773551206663192576 |