Repository logo
 
Publication

Unanticipated reactivity toward nucleophilic attack in the synthesis of saccharyl-1,3,4-thiadiazolyl conjugates: structure and mechanistic insights

2025-11-11Journal article Restricted access
Simple item page
dc.contributor.authorGuerreiro, Bruno
dc.contributor.authorCarvalho, Daniel F.
dc.contributor.authorCoelho, Jaime A. S.
dc.contributor.authorFrija, Luís M. T.
dc.contributor.authorPaixão, José A.
dc.contributor.authorCristiano, Maria de Lurdes
dc.date.accessioned2025-12-19T11:12:19Z
dc.date.available2025-12-19T11:12:19Z
dc.date.issued2025-11-11
dc.description.abstractAlong with the synthetic process optimization of 3- [(5-methyl-1,3,4-thiadiazole-2-yl)sulfanyl]-1,2-benzothiazole 1,1- dioxide (MTSB), a selective copper chelator with potential interest in cancer chemotherapy, the unprecedented isolation of a novel compound, 3-(1,1-dioxidobenzo[d]isothiazol-3-yl)-5-methyl-1,3,4- thiadiazole-2(3H)-thione (BMTT), evidenced an unexpected reactivity of the starting 5-methyl-1,3,4-thiadiazole-2-thiol. To shed light into the reaction mechanisms, quantum chemical calculations were conducted at the M06-2X/def2-TZVPP/PCM- (THF)//M06-2X/6-31++G(d,p) level of theory. The results conjecture the formation of BMTT from nucleophilic attack of the nitrogen at position 3 of the thiadiazole ring, involved in an Sto-N delocalized thiadiazole-2-thiolate structure, which is thermodynamically more favorable in the presence of Na+ . Experimental assays refute a plausible concerted 1,3-sigmatropic S- to Nrearrangement of MTSB that would lead to BMTT. Hence, contradicting the nucleophilicity indices of sulfur (from thiol) and nitrogen atoms of 5-methyl-1,3,4-thiadiazole-2-thiol, it is believed that an exotic nucleophilic attack by the nitrogen at 3-position of this reagent to the sp2 carbon in position 3 of pseudo-saccharyl chloride should take place. Besides, the crystal structures of the MTSB and BMTT hybrids were investigated in detail by X-ray crystallography.eng
dc.description.sponsorship2023.07905.CEECIND/CP2830/CT0012
dc.identifier.doi10.1021/acs.joc.5c01116
dc.identifier.issn0022-3263
dc.identifier.issn1520-6904
dc.identifier.urihttp://hdl.handle.net/10400.1/27992
dc.language.isoeng
dc.peerreviewedyes
dc.publisherAmerican Chemical Society (ACS)
dc.relationAlgarve Centre for Marine Sciences
dc.relationAlgarve Centre for Marine Sciences
dc.relationCentre for Marine and Environmental Research
dc.relationCentro de Química Estrutural
dc.relationCentro de Química Estrutural
dc.relationInstitute of Molecular Sciences
dc.relationCenter for Physics of the University of Coimbra
dc.relationCenter for Physics of the University of Coimbra
dc.relation.ispartofThe Journal of Organic Chemistry
dc.rights.uriN/A
dc.titleUnanticipated reactivity toward nucleophilic attack in the synthesis of saccharyl-1,3,4-thiadiazolyl conjugates: structure and mechanistic insightseng
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAlgarve Centre for Marine Sciences
oaire.awardTitleAlgarve Centre for Marine Sciences
oaire.awardTitleCentre for Marine and Environmental Research
oaire.awardTitleCentro de Química Estrutural
oaire.awardTitleCentro de Química Estrutural
oaire.awardTitleInstitute of Molecular Sciences
oaire.awardTitleCenter for Physics of the University of Coimbra
oaire.awardTitleCenter for Physics of the University of Coimbra
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04326%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04326%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0101%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F00100%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00100%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/LA%2FP%2F0056%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F04564%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDP%2F04564%2F2020/PT
oaire.citation.endPage16309
oaire.citation.issue46
oaire.citation.startPage16301
oaire.citation.titleThe Journal of Organic Chemistry
oaire.citation.volume90
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream6817 - DCRRNI ID
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85
person.familyNameGuerreiro
person.familyNameCristiano
person.givenNameBruno
person.givenNameMaria de Lurdes
person.identifier.ciencia-id1116-64F6-3D01
person.identifier.ciencia-idE411-6006-5A01
person.identifier.orcid0000-0001-7219-7939
person.identifier.orcid0000-0002-9447-2855
person.identifier.ridG-2345-2012
person.identifier.scopus-author-id9238724800
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
relation.isAuthorOfPublicationb29af8f2-6553-4fd0-a50f-4a51489f3d83
relation.isAuthorOfPublicationb16751a6-748e-44b0-9c59-058cbd5b2cc3
relation.isAuthorOfPublication.latestForDiscoveryb29af8f2-6553-4fd0-a50f-4a51489f3d83
relation.isProjectOfPublicationfafa76a6-2cd2-4a6d-a3c9-772f34d3b91f
relation.isProjectOfPublication15f91d45-e070-47d8-b6b8-efd4de31d9a8
relation.isProjectOfPublication794d4c77-c731-471e-bc96-5a41dcd3d872
relation.isProjectOfPublication36364d2a-b4fe-4b0f-a8c8-ca575b121cf4
relation.isProjectOfPublicationdf39fd72-bd68-4aaf-8b89-25d17b8c5ebd
relation.isProjectOfPublicationd53ccdb3-ac58-4a26-8444-4b0ccd9621bc
relation.isProjectOfPublication1a46f916-3c4d-48b1-809e-313ff9369cae
relation.isProjectOfPublication7bfa0524-1e1b-4f66-a031-9996cbb6ae96
relation.isProjectOfPublication.latestForDiscoveryfafa76a6-2cd2-4a6d-a3c9-772f34d3b91f

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
unanticipated-reactivity-toward-nucleophilic-attack-in-the-synthesis-of-saccharyl-1-3-4-thiadiazolyl-conjugates.pdf
Size:
3.08 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
3.46 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

CCM2-Artigos (em revistas ou actas indexadas)