Versatile, tunable method for NaNO2/HX (Cl or Br)–mediated radical dihalogenation or nitration of olefins

Versatile, tunable method for NaNO2/HX (Cl or Br)–mediated radical dihalogenation or nitration of olefins | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Versatile, tunable method for NaNO2/HX (Cl or Br)–mediated radical dihalogenation or nitration of olefins Yaxin Wang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5535688/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract We have developed a versatile, tunable method for NaNO2/HX (Cl or Br)–mediated radical nitration or vicinal dihalogenation of olefins. The method allowed us to synthesize high-added-value vicinal dihalides by using inexpensive, low-molecular-weight HCl or HBr as a chloride or bromide source and commercially available NaNO2 under irradiation with blue LEDs without the need for a photocatalyst or metal catalyst. In the absence of light, reactions of the olefins with NaNO2 and HCl gave nitration products in a controllable fashion. This regio- and chemoselective method was compatible with a diverse array of olefin substrates, showed good functional group tolerance, and was successfully used for late-stage dihalogenation and nitration of dozens of derivatives of natural products and active pharmaceutical ingredients. Mechanistic studies showed that in the dihalogenation reactions, a nitrosyl halide (X–N=O) generated in situ by reaction of NaNO2 and aqueous HX not only delivered a halogen radical upon photoirradiation to initiate olefin dihalogenation but also underwent halogen-atom transfer (XAT) process with a carbon radical intermediate to form the vicinal dihalogenation product. In the nitration reactions, a nitric oxide (NO or NO2) that was formed in situ from NaNO2 and the same equivalent of HCl selectively triggered olefin nitration. Physical sciences/Chemistry/Photochemistry/Photocatalysis Physical sciences/Chemistry/Chemical synthesis/Flow chemistry Full Text Additional Declarations There is NO Competing Interest. Supplementary Files WangYXdichlorinationandnitrationofolefinsSI1127final.pdf Versatile, tunable method for NaNO2/HX (Cl or Br)–mediated radical dihalogenation or nitration of olefins Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5535688","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":385930259,"identity":"3a2767a8-9efa-4924-b94d-b01c986cd936","order_by":0,"name":"Yaxin Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYBACeWbG9g8JBjYMjA1gPjNhLYbtzccYPlSkkaCF4cyxNMYZZw7DuERoYZyRY/aYt+18HvOM5KcbGCqsExvYzx7Aq4VdIsfcmLftdjHjjDSzGwxn0hMbePISCNliIA3Uktg4I4ftBmPb4cQGCR4D/C67AdZyDqrlHzFagN6XnHHmAFRLAxFagIF82OBDRXJiY88zsxsJx9KN23hy8GsBRmXjgwQDu8SN7cnPbnyosZbtZz9DwGFw6xqARAIQsxGnHmQd0SpHwSgYBaNgxAEAHF5L2hI5i+8AAAAASUVORK5CYII=","orcid":"","institution":"Nanjing University of Chinese Medicine","correspondingAuthor":true,"prefix":"","firstName":"Yaxin","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2024-11-27 13:15:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5535688/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5535688/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":74311785,"identity":"eed65d65-7d18-4aad-b46f-9d20c92aa75a","added_by":"auto","created_at":"2025-01-21 02:18:31","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3182168,"visible":true,"origin":"","legend":"Article File","description":"","filename":"WangYXdihalogenationornitrationofolefinsmanuscript20241127final.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5535688/v1_covered_457de87c-297a-4ecb-ad84-6c17897f20fa.pdf"},{"id":70630298,"identity":"86c7d938-6bdf-45f8-b70b-f583dfbc18fc","added_by":"auto","created_at":"2024-12-05 05:29:39","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":20081996,"visible":true,"origin":"","legend":"Versatile, tunable method for NaNO2/HX (Cl or Br)\u0026#x2013;mediated radical dihalogenation or nitration of olefins","description":"","filename":"WangYXdichlorinationandnitrationofolefinsSI1127final.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5535688/v1/5649102968e9e2e884a2f41f.pdf"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e Competing Interest.","formattedTitle":"Versatile, tunable method for NaNO2/HX (Cl or Br)–mediated radical dihalogenation or nitration of olefins","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-5535688/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5535688/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"We have developed a versatile, tunable method for NaNO2/HX (Cl or Br)–mediated radical nitration or vicinal dihalogenation of olefins. 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Mechanistic studies showed that in the dihalogenation reactions, a nitrosyl halide (X–N=O) generated in situ by reaction of NaNO2 and aqueous HX not only delivered a halogen radical upon photoirradiation to initiate olefin dihalogenation but also underwent halogen-atom transfer (XAT) process with a carbon radical intermediate to form the vicinal dihalogenation product. 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