{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:49:34Z","timestamp":1790192974676,"version":"4.1.0"},"reference-count":44,"publisher":"American Chemical Society (ACS)","issue":"31","license":[{"start":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T00:00:00Z","timestamp":1595894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["ZIA-MH002793"],"award-info":[{"award-number":["ZIA-MH002793"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Prior studies have shown that trifluoromethylarenes can be labeled in high molar activities (Am &amp;gt; 200 GBq\/\u03bcmol) with positron-emitting carbon-11 (t1\/2 = 20.4 min) by the reaction of the copper(I) derivative of [11C]fluoroform [11C]CuCF3, with several types of precursors, such as aryl iodides, arylboronic acids, and aryldiazonium salts. Nonetheless, these precursors can be challenging to synthesize, and in the case of diazonium salts, are unstable. Methods that reduce challenges in precursor preparation for the synthesis of [11C]trifluoromethylarenes are desirable to enhance possibilities for developing biologically relevant 11C-labeled compounds as radiotracers for biomedical imaging with positron emission tomography (PET). Here, we explored the production of no-carrier-added [11C]trifluoromethylarenes from commercially available primary aromatic amines through reactions of [11C]CuCF3 with diazonium salts that were generated in situ. Moderate to high isolated decay-corrected radiochemical yields (RCY) (32\u201384%) were obtained rapidly (within 2 min) for many para-substituted and meta-substituted primary aromatic amines bearing a halo, methoxy, thiomethyl, hydroxy, nitro, nitrile, carboxyl, ethylcarboxy, or trifluoromethyl substituent. Null to low RCYs (0\u201313%) were observed only for ortho bromo-, nitro-, or nitrile-substituted precursors. This new radiosynthetic method usefully expands options for producing PET radiotracers bearing a [11C]trifluoromethyl group, especially from aryl amine precursors.<\/jats:p>","DOI":"10.1021\/acsomega.0c02027","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T09:54:42Z","timestamp":1595930082000},"page":"19557-19564","source":"Crossref","is-referenced-by-count":14,"title":["Rapid and Efficient Synthesis of [11C]Trifluoromethylarenes\nfrom Primary Aromatic Amines and [11C]CuCF3"],"prefix":"10.1021","volume":"5","author":[{"given":"Nicholas J.","family":"Young","sequence":"first","affiliation":[{"name":"National Institute of Mental Health, National Institutes of Health , , 10 Center Drive, Rm B3 C346 , , ,","place":["Bethesda, Maryland, United States, 20892-1003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9032-2553","authenticated-orcid":true,"given":"Victor W.","family":"Pike","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health, National Institutes of Health , , 10 Center Drive, Rm B3 C346 , , ,","place":["Bethesda, Maryland, United States, 20892-1003"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2271-2127","authenticated-orcid":true,"given":"Carlotta","family":"Taddei","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health, National Institutes of Health , , 10 Center Drive, Rm B3 C346 , , ,","place":["Bethesda, Maryland, United States, 20892-1003"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,7,28]]},"reference":[{"key":"2026090207362844400_cit1","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1177\/009286159703100344","article-title":"The status\nof PET radiochemistry for drug development and evaluation","volume":"31","author":"Pike","year":"1997","journal-title":"Drug Inf. J."},{"key":"2026090207362844400_cit2","doi-asserted-by":"publisher","first-page":"9226","DOI":"10.1073\/pnas.97.16.9226","article-title":"Positron\nemission tomography provides molecular imaging of biological processes","volume":"97","author":"Phelps","year":"2000","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2026090207362844400_cit3","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1007\/s00259-019-04488-0","article-title":"Advances in CNS PET:\nthe state-of-the-art for new imaging targets for pathophysiology and\ndrug development","volume":"47","author":"McCluskey","year":"2019","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"2026090207362844400_cit4","doi-asserted-by":"publisher","first-page":"v","DOI":"10.1016\/j.nucmedbio.2017.09.004","article-title":"Consensus\nnomenclature rules for\nradiopharmaceutical chemistry \u2500 Setting the record straight","volume":"55","author":"Coenen","year":"2017","journal-title":"Nucl. Med. Biol."},{"key":"2026090207362844400_cit5","doi-asserted-by":"publisher","first-page":"1818","DOI":"10.2174\/0929867323666160418114826","article-title":"Considerations\nin the development of reversibly binding PET radioligands for brain\nimaging","volume":"23","author":"Pike","year":"2016","journal-title":"Curr. Med. Chem."},{"key":"2026090207362844400_cit6","doi-asserted-by":"publisher","first-page":"6001","DOI":"10.1002\/anie.200901481","article-title":"Methods\nfor the incorporation of carbon-11 to generate radiopharmaceuticals\nfor PET imaging","volume":"48","author":"Scott","year":"2009","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090207362844400_cit7","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1002\/jlcr.3258","article-title":"Development\nof carbon-11 labelled PET tracers\u2500radiochemical and technological\nchallenges in a historic perspective","volume":"58","author":"Antoni","year":"2015","journal-title":"J. Label.\nCompd. Radiopharm."},{"key":"2026090207362844400_cit8","doi-asserted-by":"publisher","first-page":"8998","DOI":"10.1002\/anie.200800222","article-title":"Synthesis of 11C, 18F, 15O, and 13N radiolabels\nfor positron emission tomography","volume":"47","author":"Miller","year":"2008","journal-title":"Angew. Chem.,\nInt. Ed."},{"key":"2026090207362844400_cit9","doi-asserted-by":"publisher","first-page":"5621","DOI":"10.1039\/c3cc42236d","article-title":"11CO2 Fixation:\na renaissance in PET radiochemistry","volume":"49","author":"Rotstein","year":"2013","journal-title":"Chem. Commun."},{"key":"2026090207362844400_cit10","doi-asserted-by":"publisher","first-page":"4708","DOI":"10.1039\/c6cs00310a","article-title":"11C=O Bonds\nmade easily for positron emission tomography radiopharmaceuticals","volume":"45","author":"Rotstein","year":"2016","journal-title":"Chem. Soc. Rev."},{"key":"2026090207362844400_cit11","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1002\/jlcr.3596","article-title":"Recent progress\nin [11C]carbon dioxide ([11C]CO2)\nand [11C]carbon monoxide ([11C]CO) chemistry","volume":"61","author":"Taddei","year":"2018","journal-title":"J. Label. Compd. Radiopharm."},{"key":"2026090207362844400_cit12","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s41181-019-0073-4","article-title":"[11C]Carbon monoxide: advances in production\nand application to PET radiotracer development over the past 15 years","volume":"4","author":"Taddei","year":"2019","journal-title":"EJNMMI Radiopharm. Chem."},{"key":"2026090207362844400_cit13","first-page":"183","article-title":"Carbon-11\nlabeling\nchemistry based upon [11C]methyl iodide","volume-title":"PET Chemistry\u2500The Driving Force in Molecular Imaging","author":"Wuest","year":"2007"},{"key":"2026090207362844400_cit14","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1021\/op700134j","article-title":"Fluorination\nin medicinal chemistry: methods, strategies, and recent developments","volume":"12","author":"Kirk","year":"2008","journal-title":"Org. Process Res. Dev."},{"key":"2026090207362844400_cit15","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.jfluchem.2014.06.026","article-title":"Recent\nadvances in the trifluoromethylation methodology and new CF3-containing drugs","volume":"167","author":"Zhu","year":"2014","journal-title":"J. Fluorine Chem."},{"key":"2026090207362844400_cit16","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1021\/cr500368h","article-title":"Carbon trifluoromethylation\nreactions of hydrocarbon derivatives and heteroarenes","volume":"115","author":"Alonso","year":"2015","journal-title":"Chem. Rev."},{"key":"2026090207362844400_cit17","doi-asserted-by":"publisher","first-page":"20901","DOI":"10.1021\/ja2081026","article-title":"Direct cupration of fluoroform","volume":"133","author":"Zanardi","year":"2011","journal-title":"J. Am. Chem. Soc."},{"key":"2026090207362844400_cit18","doi-asserted-by":"publisher","first-page":"7767","DOI":"10.1002\/anie.201201613","article-title":"Fluoroform-derived CuCF3 for low-cost, simple,\nefficient, and safe trifluoromethylation of\naryl boronic acids in air","volume":"51","author":"Nova\u0301k","year":"2012","journal-title":"Angew. Chem., Int.\nEd."},{"key":"2026090207362844400_cit19","doi-asserted-by":"publisher","first-page":"11126","DOI":"10.1021\/jo401423h","article-title":"Trifluoromethylation of aryl and\nheteroaryl halides with fluoroform-derived CuCF3: scope,\nlimitations, and mechanistic features","volume":"78","author":"Lishchynskyi","year":"2013","journal-title":"J. Org.\nChem."},{"key":"2026090207362844400_cit20","doi-asserted-by":"publisher","first-page":"10237","DOI":"10.1039\/c4cc04930f","article-title":"Trifluoromethylation\nof arenediazonium\nsalts with fluoroform-derived CuCF3 in aqueous media","volume":"50","author":"Lishchynskyi","year":"2014","journal-title":"Chem. Commun."},{"key":"2026090207362844400_cit21","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1021\/op500109v","article-title":"Continuous process\nfor production\nof CuCF3 via direct cupration of fluoroform","volume":"18","author":"Mazloomi","year":"2014","journal-title":"Org. Process Res. Dev."},{"key":"2026090207362844400_cit22","doi-asserted-by":"publisher","first-page":"155","DOI":"10.3762\/bjoc.14.11","article-title":"Progress in copper-catalyzed\ntrifluoromethylation","volume":"14","author":"Li","year":"2018","journal-title":"Beilstein J. Org. Chem."},{"key":"2026090207362844400_cit23","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1021\/acs.orglett.8b00101","article-title":"Copper-mediated trifluoromethylation\u2013allylation\nof arynes","volume":"20","author":"Yang","year":"2018","journal-title":"Org. Lett."},{"key":"2026090207362844400_cit24","doi-asserted-by":"publisher","first-page":"8156","DOI":"10.1002\/chem.201701701","article-title":"[11C]Fluoroform, a Breakthrough\nfor versatile\nlabeling of PET radiotracer trifluoromethyl groups in high molar activity","volume":"23","author":"Haskali","year":"2017","journal-title":"Chem.\u2500Eur. J."},{"key":"2026090207362844400_cit25","doi-asserted-by":"publisher","first-page":"4018","DOI":"10.1039\/c3cc37833k","article-title":"Efficient\nsynthesis of [18F]trifluoromethane and its application\nin the synthesis of PET tracers","volume":"49","author":"van der Born","year":"2013","journal-title":"Chem. Commun."},{"key":"2026090207362844400_cit26","doi-asserted-by":"publisher","first-page":"14835","DOI":"10.1038\/s41598-019-50747-3","article-title":"A gas phase\nroute to [18F]fluoroform with limited molar activity dilution","volume":"9","author":"Yang","year":"2019","journal-title":"Sci. Rep."},{"key":"2026090207362844400_cit27","doi-asserted-by":"publisher","first-page":"5706","DOI":"10.1039\/c7cc02652h","article-title":"18F-Fluoroform:\na 18F-trifluoromethylating\nagent for the synthesis of SCF218F-aromatic\nderivatives","volume":"53","author":"Carbonnel","year":"2017","journal-title":"Chem. Commun."},{"key":"2026090207362844400_cit28","first-page":"406","article-title":"Mild syntheses\nof [11C\/18F]trifluoromethylarenes from [11C\/18F]fluoroform and aryldiazonium salts","volume":"58","author":"Yang","year":"2017","journal-title":"J. Nucl. Med."},{"key":"2026090207362844400_cit29","first-page":"1060","article-title":"Radiosyntheses\nof [18F]trifluoromethyl\nderivatives of nucleobases and L-phenylalanine from\n[18F]fluoroform produced in gas phase","volume":"59","author":"Yang","year":"2018","journal-title":"J. Nucl. Med."},{"key":"2026090207362844400_cit30","first-page":"619","article-title":"Syntheses\nof [11C]2- and [11C]3-trifluoromethyl-4-aminopyridine:\npotential PET radioligands for imaging demyelinating diseases","volume":"61","author":"Ramos-Torres","year":"2020","journal-title":"J. Nucl. Med."},{"key":"2026090207362844400_cit31","doi-asserted-by":"publisher","first-page":"4574","DOI":"10.1021\/acs.orglett.0c01705","article-title":"Rapid syntheses\nof [11C]arylvinyltrifluoromethanes\nthrough treatment of (E)-arylvinyl(phenyl)iodonium\ntosylates with [11C]trifluoromethylcopper(I)","volume":"22","author":"Jana","year":"2020","journal-title":"Org. Lett."},{"key":"2026090207362844400_cit32","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1021\/ar50070a002","article-title":"Reactivity\nand stability of arenediazonium ions","volume":"6","author":"Zollinger","year":"1973","journal-title":"Acc. Chem.\nRes."},{"key":"2026090207362844400_cit33","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1039\/b200747a","article-title":"Sandmeyer\nreactions. Part 6.1 A mechanistic investigation into the\nreduction and ligand transfer steps of Sandmeyer cyanation","author":"Hanson","year":"2002","journal-title":"J. Chem. Soc., Perkin Trans. 2"},{"key":"2026090207362844400_cit34","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1055\/s-0033-1339118","article-title":"Methanol-promoted\nborylation of arylamines: a simple and green synthetic method to arylboronic\nacids and arylboronates","volume":"25","author":"Xue","year":"2014","journal-title":"Synlett"},{"key":"2026090207362844400_cit35","doi-asserted-by":"publisher","first-page":"6965","DOI":"10.1039\/c4ob01286k","article-title":"Removal of amino groups\nfrom anilines\nthrough diazonium salt-based reactions","volume":"12","author":"He","year":"2014","journal-title":"Org.\nBiomol. Chem."},{"key":"2026090207362844400_cit36","doi-asserted-by":"publisher","first-page":"2518","DOI":"10.1021\/acs.orglett.7b00771","article-title":"One-pot, metal-free\nconversion of anilines to aryl bromides and iodides","volume":"19","author":"Leas","year":"2017","journal-title":"Org. Lett."},{"key":"2026090207362844400_cit37","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1021\/acs.accounts.7b00566","article-title":"Renaissance of Sandmeyer-type reactions:\nconversion of aromatic C\u2013N bonds into C\u2013X bonds (X =\nB, Sn, P, or CF3)","volume":"51","author":"Mo","year":"2018","journal-title":"Acc. Chem. Res."},{"key":"2026090207362844400_cit38","doi-asserted-by":"publisher","first-page":"10330","DOI":"10.1021\/ja4056239","article-title":"Silver-mediated trifluoromethylation\nof aryldiazonium salts: conversion of amino group into trifluoromethyl\ngroup","volume":"135","author":"Wang","year":"2013","journal-title":"J. Am. Chem. Soc."},{"key":"2026090207362844400_cit39","doi-asserted-by":"publisher","first-page":"8436","DOI":"10.1021\/ja404217t","article-title":"Copper-promoted\nSandmeyer trifluoromethylation reaction","volume":"135","author":"Dai","year":"2013","journal-title":"J.\nAm. Chem. Soc."},{"key":"2026090207362844400_cit41","first-page":"457","volume-title":"Mechanism and Structure\nin Organic Chemistry","author":"Gould","year":"1969"},{"key":"2026090207362844400_cit42","doi-asserted-by":"publisher","first-page":"2735","DOI":"10.1039\/a905567c","article-title":"Rates and mechanisms\nof the thermal solvolytic decomposition of arenediazonium ions","author":"Canning","year":"1999","journal-title":"J. Chem. Soc., Perkin Trans. 2"},{"key":"2026090207362844400_cit43","doi-asserted-by":"publisher","first-page":"7972","DOI":"10.1002\/anie.201304276","article-title":"Sandmeyer\ntrifluoromethylation of arenediazonium tetrafluoroborates","volume":"52","author":"Danoun","year":"2013","journal-title":"Angew. Chem., Int. Ed."},{"key":"2026090207362844400_cit44","doi-asserted-by":"publisher","first-page":"2343","DOI":"10.1002\/adsc.201400340","article-title":"One-pot Sandmeyer\ntrifluoromethylation and trifluoromethylthiolation","volume":"356","author":"Bayarmagnai","year":"2014","journal-title":"Adv. Synth. Catal."},{"key":"2026090207362844400_cit45","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1002\/anie.201308997","article-title":"The trifluoromethylating\nSandmeyer reaction: a method for transforming C\u2500N into C\u2500CF3","volume":"53","author":"Browne","year":"2014","journal-title":"Angew. Chem., Int. Ed."}],"container-title":["ACS Omega"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsomega.0c02027","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/31\/19557\/67712113\/acsomega.0c02027.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/acsodf\/article-pdf\/5\/31\/19557\/67712113\/acsomega.0c02027.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T11:36:32Z","timestamp":1788348992000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/acsodf\/article\/5\/31\/19557\/1377234\/Rapid-and-Efficient-Synthesis-of-11C"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,28]]},"references-count":44,"journal-issue":{"issue":"31","published-online":{"date-parts":[[2020,7,28]]},"published-print":{"date-parts":[[2020,8,11]]}},"URL":"https:\/\/doi.org\/10.1021\/acsomega.0c02027","relation":{},"ISSN":["2470-1343"],"issn-type":[{"value":"2470-1343","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,28]]}}}