{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:34:45Z","timestamp":1787240085760,"version":"build-2736575974"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T00:00:00Z","timestamp":1590105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003549","name":"Hungarian Scientific Research Fund","doi-asserted-by":"publisher","award":["FK124331"],"award-info":[{"award-number":["FK124331"]}],"id":[{"id":"10.13039\/501100003549","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Higher Education Excellence Programme of the Ministry for Innovation and Technology in Hungary","award":["TUDFO\/47138\/2019-ITM"],"award-info":[{"award-number":["TUDFO\/47138\/2019-ITM"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Organophosphorus compounds occupy a significant position among the plethora of organic compounds, but a limited number of paramagnetic phosphorus compounds have been reported, including paramagnetic phosphonates. This paper describes the syntheses and further transformations of pyrroline and piperidine nitroxide phosphonates by well-established methods, such as the Pudovik, Arbuzov and Horner-Wadsworth-Emmons (HWE) reactions. The reaction of paramagnetic \u03b1-bromoketone produced a vinylphosphonate in the Perkow reaction. Paramagnetic \u03b1-hydroxyphosphonates could be subjected to oxidation, elimination and substitution reactions to produce various paramagnetic phosphonates. The synthesized paramagnetic phosphonates proved to be useful synthetic building blocks for carbon-carbon bond-forming reactions in the Horner-Wadsworth-Emmons olefination reactions. The unsaturated compounds achieved could be transformed into various substituted pyrroline nitroxides, proxyl nitroxides and paramagnetic polyaromatics. The Trolox\u00ae equivalent antioxidant capacity (TEAC) of new phosphonates was also screened, and tertiary \u03b1-hydroxyphosphonatate nitroxides exhibited remarkable antioxidant activity.<\/jats:p>","DOI":"10.3390\/molecules25102430","type":"journal-article","created":{"date-parts":[[2020,5,22]],"date-time":"2020-05-22T10:18:18Z","timestamp":1590142698000},"page":"2430","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Syntheses and Reactions of Pyrroline, Piperidine Nitroxide Phosphonates"],"prefix":"10.3390","volume":"25","author":[{"given":"Mostafa","family":"Isbera","sequence":"first","affiliation":[{"name":"Institute of Organic and Medicinal Chemistry, Medical School, University of P\u00e9cs, Szigeti st. 12, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6695-6839","authenticated-orcid":false,"given":"Bal\u00e1zs","family":"Bogn\u00e1r","sequence":"additional","affiliation":[{"name":"Institute of Organic and Medicinal Chemistry, Medical School, University of P\u00e9cs, Szigeti st. 12, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f3zsef","family":"Jek\u0151","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Ny\u00edregyh\u00e1za, S\u00f3st\u00f3i st. 31\/B, 4440 Ny\u00edregyh\u00e1za, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"S\u00e1r","sequence":"additional","affiliation":[{"name":"Institute of Organic and Medicinal Chemistry, Medical School, University of P\u00e9cs, Szigeti st. 12, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00e1lm\u00e1n","family":"Hideg","sequence":"additional","affiliation":[{"name":"Institute of Organic and Medicinal Chemistry, Medical School, University of P\u00e9cs, Szigeti st. 12, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"K\u00e1lai","sequence":"additional","affiliation":[{"name":"Institute of Organic and Medicinal Chemistry, Medical School, University of P\u00e9cs, Szigeti st. 12, 7624 P\u00e9cs, Hungary"},{"name":"Szent\u00e1gothai Research Centre, Ifj\u00fas\u00e1g st. 20, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Savignac, P., and Iorga, B. (2003). Modern Phosphonate Chemistry, CRC Press.","DOI":"10.1201\/9780203503676"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Keglevich, G. (2018). Phosphorus Chemistry 2018, MDPI.","DOI":"10.1515\/9783110535839"},{"key":"ref_3","unstructured":"Timperley, M.C. (2015). Best Synthetic Methods: Organophosphorus (V) Chemistry, Academic Press."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wadsworth, W.S. (1977). Synthetic Applications of Phosphoryl-stabilized Anions in Organic Reactions, Wiley.","DOI":"10.1002\/0471264180.or025.02"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1351\/pac196409020307","article-title":"Michaelis-Arbusow- und Perkow-Reaktionen","volume":"9","author":"Arbusow","year":"1964","journal-title":"Pure Appl. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1055\/s-1979-28566","article-title":"Addition reactions of Esters of Phosphorus (III) acids with Unsaturated Systems","volume":"11","author":"Pudovik","year":"1979","journal-title":"Synthesis"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1021\/cr60214a004","article-title":"The chemistry and properties of enol phosphates","volume":"61","author":"Lichtenthaler","year":"1961","journal-title":"Chem. Rev."},{"key":"ref_8","first-page":"1902","article-title":"The syntheses of Novel Isoindoline Nitroxides Bearing Water-Solubilizing Functionality","volume":"12","author":"Brackmann","year":"2009","journal-title":"Eur. J. Org. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1007\/s00723-015-0716-x","article-title":"The structure and EPR Behaviour of Nitroxide Biradical Containing Phosphorus Atom in the Bridge","volume":"46","author":"Kokorin","year":"2015","journal-title":"Appl. Magn. Reson."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1246\/bcsj.80.1791","article-title":"Synthesis and redox Properties of Crowded Triarylphosphines Carrying a Nitroxide Radical and Related Compounds","volume":"80","author":"Shigeru","year":"2007","journal-title":"Bull. Chem. Soc. Jpn."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"5903","DOI":"10.1021\/jp049730+","article-title":"Spin Transfer and Magnetic Interaction via Phosphorus in Nitronyl Nitroxide Radical-Substituted Triphenylphosphine Derivatives","volume":"108","author":"Rancurel","year":"2004","journal-title":"J. Phys. Chem. A."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1139\/v80-031","article-title":"Long-range phosphorus hyperfine coupling in a persistent nitroxide nitroxide radical","volume":"58","author":"Livant","year":"1980","journal-title":"Can. J. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"5484","DOI":"10.1021\/jp048652n","article-title":"ESR Investigation of chemical Exchange in Geminally Diphosphorilated Linear Nitroxide Radicals","volume":"108","author":"Rockenbauer","year":"2004","journal-title":"J. Phys. Chem. A."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3729","DOI":"10.1039\/C6OB00359A","article-title":"The beta-phosphorus hyperfine coupling constant in nitroxides: 6. Solvent effects in non-cyclic nitroxides","volume":"14","author":"Audran","year":"2016","journal-title":"Org. Biomol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13379","DOI":"10.1002\/anie.201506267","article-title":"Enzymatically Shifting Nitroxides for EPR Spectroscopy and Overhauser-Enchanced Magnetic Resonance Imaging","volume":"54","author":"Audran","year":"2015","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4465","DOI":"10.1021\/jo00068a049","article-title":"\u03b2-Phosphorylated Five-Membered Ring Nitroxides: Synthesis and ESR Study of 2-Phosphonyl-(4-hydroxymethyl)pyrrolidine Aminoxyl Radicals","volume":"58","author":"Stipa","year":"1993","journal-title":"J. Org. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1139\/v86-244","article-title":"Further syntheses with-Nitroxide \u03b1,\u03b2-unsaturated aldehydes and allylic bromides","volume":"64","author":"Hideg","year":"1986","journal-title":"Can. J. Chem."},{"key":"ref_18","unstructured":"K\u00fcrti, L., and Czak\u00f3, B. (2005). Strategic Applications of Named Reactions in Organic Synthesis, Elsevier Academic Press."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1055\/s-1980-29269","article-title":"Nitroxyls. VII: Synthesis and Reactions of Highly Reactive 1-Oxyl-2,2,5,5-tetramethyl-2,5-dihydropyrrole-3-ylmethyl Sulfonates","volume":"12","author":"Hankovszky","year":"1980","journal-title":"Synthesis"},{"key":"ref_20","first-page":"1476","article-title":"4-Bromo-3-Substituted-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-1-yloxyl Radicals as Versatile Synthons for Synthesis of New Paramagnetic Heterocycles","volume":"30","author":"Balog","year":"1998","journal-title":"Synthesis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1139\/v85-156","article-title":"Synthesis of novel, highly reactive 1-oxyl-2,2,6,6-tetramethyl-1,2,5,6-tetrahydropyridine derivatives","volume":"63","author":"Hankovszky","year":"1985","journal-title":"Can. J. Chem."},{"key":"ref_22","first-page":"973","article-title":"Synthesis and Reactions of Symmetric Paramagnetic Pyrrolidine Diene","volume":"31","author":"Balog","year":"1999","journal-title":"Synthesis"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Rozantsev, E.G. (1970). Free Nitroxyl Radicals, Plenum Press.","DOI":"10.1007\/978-1-4757-0710-6"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1139\/v74-499","article-title":"New Synthesis of Nitroxyl Radicals of the Piperidine and Tetrahydropyridine Series","volume":"52","author":"Wong","year":"1974","journal-title":"Can. J. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3414","DOI":"10.1021\/jo00116a029","article-title":"A Study of the Favorskii Rearrangement with 3-Bromo-4-oxo-2,2,6,6-tetramethylpiperidine-1-oxyl","volume":"60","author":"Sosnovsky","year":"1995","journal-title":"J. Org. Chem."},{"key":"ref_26","unstructured":"Quin, L.D., and Williams, A.J. (2004). Practical Interpretation of P-31 NMR spectra and Computer assisted Structure Verifications, Advanced Chemistry Development Inc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1016\/j.ejmech.2009.12.013","article-title":"Synthesis, in vitro antibacterial and antifungal evaluations of new \u03b1-hydroxyphosphonate and new \u03b1-acetoxyphosphonate derivativesof tetrazolo [1, 5-a] quinolone","volume":"45","author":"Kategaonkar","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1080\/10426507.2018.1544132","article-title":"\u03b1-Hydroxyphosphonates as versatile starting materials","volume":"194","year":"2019","journal-title":"Phosp. Sulfur Sil. Rel. Elem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"206","DOI":"10.2174\/1573406410666140706154046","article-title":"Green Synthesis and Antioxidant Activity of Novel gamma-Cyano-alpha-hydroxyphosphonate Derivatives","volume":"11","author":"Aouani","year":"2015","journal-title":"Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1080\/10426507.2019.1630407","article-title":"Green Synthesis of potentially bioactive \u03b1-hydroxyphosphonates and related derivatives","volume":"194","author":"Kiss","year":"2019","journal-title":"Phosp. Sulfur Sil. Rel. Elem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"R\u00e1dai, Z., and Keglevich, G. (2018). Synthesis and Reactions of alpha-Hidroxyphosphonates. Molecules, 23.","DOI":"10.3390\/molecules23061493"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.crci.2012.10.009","article-title":"Mechanistic approach for expeditious and solvent-free synthesis of alpha-hydroxy phosphonates using potassium phosphate as catalyst","volume":"16","author":"Kulkarni","year":"2013","journal-title":"C. R. Chim."},{"key":"ref_33","first-page":"339","article-title":"Nitroxides. II: 1-Oxyl-2,2,5,5-tetramethylpyrroline-3-carboxylic Acid Derivatives","volume":"98","author":"Hankovszky","year":"1978","journal-title":"Acta Chim. Acad. Sci. Hung."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1055\/s-1980-29268","article-title":"Nitroxyls. VI: Synthesis and Reactions of 3-Hydroxymethyl-2,2,5,5-tetramethyl-2,5-dihydropyrrole-1-oxyl and 3-Formyl Derivatives","volume":"12","author":"Hideg","year":"1980","journal-title":"Synthesis"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1002\/poc.3247","article-title":"Effect of the structure of nitroxyl radicals on the kinetics of their acid-catalyzed disproportionation","volume":"27","author":"Tikhonov","year":"2014","journal-title":"J. Phys. Org. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3601","DOI":"10.1016\/j.tetasy.2004.10.001","article-title":"Microwave assisted synthesis of chiral pyrrolines with biological activity","volume":"15","author":"Collina","year":"2004","journal-title":"Tetrahedron Assym."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4155","DOI":"10.1021\/jo00170a070","article-title":"Readily accessible 12-I-5 oxidant for the conversion of primary and secondary alcohols to aldehydes and ketones","volume":"48","author":"Dess","year":"1983","journal-title":"J. Org. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1055\/s-1992-26111","article-title":"An expedient synthesis of diethyl 1-azidoalkylphosphonates via the Mitsunobu reaction","volume":"24","author":"Gajda","year":"1992","journal-title":"Synthesis"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1055\/s-1981-29317","article-title":"The use of diethyl azodicarboxylate and triphenylphosphine in synthesis and transformation of natural products","volume":"13","author":"Mitsunobu","year":"1981","journal-title":"Synthesis"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhdanov, R.I. (1992). Nitroxyl Radicals and Non-Radical Reactions of Free Radicals in Bioactive Spin Labels, Springer.","DOI":"10.1007\/978-3-642-48724-8"},{"key":"ref_41","first-page":"1768","article-title":"Silicon- and phosphorus containing ethylene derivatives","volume":"45","author":"Chernyshev","year":"1975","journal-title":"Zh. Obschch. Khim."},{"key":"ref_42","first-page":"15","article-title":"Microwave-assisted Hirao reaction: Recent developments","volume":"1","author":"Brahmarchari","year":"2015","journal-title":"Chem. Texts"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1016\/j.tetlet.2016.01.012","article-title":"Facile syntheses of 3,4-disubstituted pyrroline nitroxides and their further synthetic applications","volume":"57","author":"Hideg","year":"2016","journal-title":"Tetrahedron Lett."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2593","DOI":"10.1039\/b504354a","article-title":"Synthesis of profluorescent isoindoline nitroxides via palladium-catalysed Heck alkenylation","volume":"3","author":"Keddie","year":"2005","journal-title":"Org. Biomol. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10382","DOI":"10.1039\/C3CC46146G","article-title":"A novel protecting group methodology for syntheses using nitroxides","volume":"49","author":"Chalmers","year":"2013","journal-title":"Chem. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2122","DOI":"10.1080\/00397911.2015.1066391","article-title":"Synthesis of New Pyrroline Nitroxides with Ethynyl Functional Group","volume":"45","author":"Balog","year":"2015","journal-title":"Synthetic Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/S0891-5849(98)00315-3","article-title":"Antioxidant activity applying an improved ABTS radical cation decolorization assay","volume":"26","author":"Re","year":"1999","journal-title":"Free Rad. Biol. Med."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1016\/j.freeradbiomed.2007.02.030","article-title":"The chemistry and biology of nitroxide compounds","volume":"42","author":"Soule","year":"2007","journal-title":"Free Rad. Biol. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1055\/s-1993-25870","article-title":"Synthesis of New 3,4-Disubstituted 2,5-Dihydro-1H-pyrrol-1-yloxyl Spin-label Reagents via Allylic Rearrangements","volume":"25","author":"Hideg","year":"1993","journal-title":"Synthesis"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/10\/2430\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:31:36Z","timestamp":1760175096000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/10\/2430"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,22]]},"references-count":49,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,5]]}},"alternative-id":["molecules25102430"],"URL":"https:\/\/doi.org\/10.3390\/molecules25102430","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,22]]}}}