{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T21:54:53Z","timestamp":1773179693653,"version":"3.50.1"},"reference-count":102,"publisher":"Wiley","issue":"62","license":[{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T00:00:00Z","timestamp":1662076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["CBET-1938838"],"award-info":[{"award-number":["CBET-1938838"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["S10RR028859"],"award-info":[{"award-number":["S10RR028859"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006151","name":"Basic Energy Sciences","doi-asserted-by":"publisher","award":["DE-AC02-05CH11231"],"award-info":[{"award-number":["DE-AC02-05CH11231"]}],"id":[{"id":"10.13039\/100006151","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2022,11,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A synthesis of a \u03b4\u2010ketohydroperoxide is described, addressing potential functional\u2010group compatibilities in these elusive species relevant to combustion and atmospheric chemistries. The hydroperoxide is installed via sulfonylhydrazine substitution, which was found to be more effective than displacement of secondary halides. As part of this protocol, it was observed that 1,2\u2010dimethoxyethane is an advantageous medium for the reaction, avoiding the formation of a tetrahydrofuran hydroperoxide side product. This discovery facilitated the multigram synthesis (6\u2005steps, 41\u2009% yield overall) and discrete characterization of the target \u03b4\u2010ketohydroperoxide.<\/jats:p>","DOI":"10.1002\/chem.202202266","type":"journal-article","created":{"date-parts":[[2022,8,9]],"date-time":"2022-08-09T21:58:26Z","timestamp":1660082306000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multigram Synthesis of a Combustion\u2010Relevant \u03b4\u2010Ketohydroperoxide through Sulfonylhydrazine Substitution"],"prefix":"10.1002","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1404-275X","authenticated-orcid":false,"given":"Yan\u2010Ting","family":"Ke","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Georgia  Athens Georgia 30602 United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley K.","family":"Gall","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Georgia  Athens Georgia 30602 United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9732-3193","authenticated-orcid":false,"given":"Nicholas S.","family":"Dewey","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Georgia  Athens Georgia 30602 United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0533-7131","authenticated-orcid":false,"given":"Brandon","family":"Rotavera","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Georgia  Athens Georgia 30602 United States"},{"name":"College of Engineering University of Georgia  Athens Georgia 30602 United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9412-0713","authenticated-orcid":false,"given":"Eric M.","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Georgia  Athens Georgia 30602 United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,2]]},"reference":[{"key":"e_1_2_8_1_1","unstructured":"\u00a0"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pecs.2010.06.006"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pecs.2021.100925"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pecs.2019.02.003"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja4034439"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.8b00395"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jz4019207"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200906850"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200906850"},{"key":"e_1_2_8_9_1","unstructured":"For select examples see:"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo201910g"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tetlet.2013.03.099"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2020.131874"},{"key":"e_1_2_8_13_1","unstructured":"\u00a0"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pecs.2020.100886"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.proci.2016.07.100"},{"key":"e_1_2_8_16_1","unstructured":"\u00a0"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.proci.2020.06.375"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.proci.2018.06.054"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.proci.2016.07.100"},{"key":"e_1_2_8_20_1","unstructured":"\u00a0"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1039\/C6RA28489B"},{"key":"e_1_2_8_22_2","first-page":"9","volume":"38","author":"Scarso A.","year":"2008","journal-title":"Sci. Synth."},{"key":"e_1_2_8_23_2","first-page":"pp101","volume-title":"Organic Peroxides","author":"Porter N. A.","year":"1992"},{"key":"e_1_2_8_24_1","unstructured":"For select recent reviews see:"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/med.21849"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22111881"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2009.05.008"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2007.04.019"},{"key":"e_1_2_8_29_1","unstructured":"For select reviews addressing ketone\/hydroperoxide processes see:"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1039\/b711647k"},{"key":"e_1_2_8_31_2","unstructured":"Ref.\u2005[7]b."},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c06294"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja01878a048"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpca.8b12510"},{"key":"e_1_2_8_35_1","unstructured":"The \u03b4 descriptor refers to the carbon position of the ketone in relation to the hydroperoxide group."},{"key":"e_1_2_8_36_1","unstructured":"An alternative would be to use a protected hydrogen peroxide nucleophile. The most common cases are monoprotected as acetals which would likely be incompatible with acid-based ketone deprotection or complicate the ketohydroperoxide\/endoperoxide dynamics. These were therefore eliminated from our considerations. For examples see:"},{"key":"e_1_2_8_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00029a043"},{"key":"e_1_2_8_38_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00105a053"},{"key":"e_1_2_8_39_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo4001564"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1039\/c39760001022"},{"key":"e_1_2_8_41_1","unstructured":"\u00a0"},{"key":"e_1_2_8_42_2","doi-asserted-by":"publisher","DOI":"10.1039\/p19840002217"},{"key":"e_1_2_8_43_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00248a035"},{"key":"e_1_2_8_44_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja9814873"},{"key":"e_1_2_8_45_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-9704"},{"key":"e_1_2_8_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja3108966"},{"key":"e_1_2_8_47_1","unstructured":"For other methods of synthesizing secondary hydroperoxides from halide precursors see:"},{"key":"e_1_2_8_48_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-1995-5279"},{"key":"e_1_2_8_49_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx800104c"},{"key":"e_1_2_8_50_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.9b01070"},{"key":"e_1_2_8_51_2","unstructured":"Refs\u2005[14]a b."},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo01103a021"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo00364a035"},{"key":"e_1_2_8_54_1","unstructured":"We were concerned the H2O2concentration would adversely impact this reaction; protocols generally indicated using higher concentrated solutions (85\u201390\u2009%) or anhydrous H2O2. The observed reactivity of iodocyclohexane relative to6and7suggested this concern was not the primary issue."},{"key":"e_1_2_8_55_1","unstructured":"\u00a0"},{"key":"e_1_2_8_56_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)92555-3"},{"key":"e_1_2_8_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/0040-4020(78)88048-X"},{"key":"e_1_2_8_58_1","unstructured":"For alternative hydrazine-based methods see:"},{"key":"e_1_2_8_59_2","doi-asserted-by":"publisher","DOI":"10.1039\/p19910002597"},{"key":"e_1_2_8_60_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00075a003"},{"key":"e_1_2_8_61_1","unstructured":"For examples using Caglioti's tosylhydrazine method for the synthesis of secondary hydroperoxides see:"},{"key":"e_1_2_8_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)90115-2"},{"key":"e_1_2_8_63_2","doi-asserted-by":"publisher","DOI":"10.1039\/P19900002951"},{"key":"e_1_2_8_64_2","doi-asserted-by":"publisher","DOI":"10.1016\/0040-4039(91)80453-D"},{"key":"e_1_2_8_65_2","unstructured":"Ref.\u2005[22]a;"},{"key":"e_1_2_8_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)00557-9"},{"key":"e_1_2_8_67_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm020208q"},{"key":"e_1_2_8_68_2","doi-asserted-by":"publisher","DOI":"10.1021\/tx900433n"},{"key":"e_1_2_8_69_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.5b01996"},{"key":"e_1_2_8_70_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b05161"},{"key":"e_1_2_8_71_1","unstructured":"We cannot speak to the lower yields observed by other investigators. We encountered similar yield discrepancies and were unable to replicate the excellent yields from the original reports."},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1002\/hlca.200590110"},{"key":"e_1_2_8_73_1","unstructured":"In both THF and DME side product cyclooctanol was observed in minor quantities. This side product was not suppressed even under the attempted anhydrous conditions."},{"key":"e_1_2_8_74_1","unstructured":"For discussions comparing THF to Et2O see:"},{"key":"e_1_2_8_75_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00393a018"},{"key":"e_1_2_8_76_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.555887"},{"key":"e_1_2_8_77_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp960982n"},{"key":"e_1_2_8_78_1","unstructured":"Radical intermediates are not invoked in mechanistic proposals but it is conceivable that active radical species are generated through the course of the reaction."},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)89114-5"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)91889-6"},{"key":"e_1_2_8_81_1","unstructured":"Select recent examples:"},{"key":"e_1_2_8_82_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja402058v"},{"key":"e_1_2_8_83_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202104182"},{"key":"e_1_2_8_83_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202104182"},{"key":"e_1_2_8_84_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.1c01489"},{"key":"e_1_2_8_85_1","unstructured":"\u00a0"},{"key":"e_1_2_8_86_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm0512037"},{"key":"e_1_2_8_87_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.7b00632"},{"key":"e_1_2_8_88_1","unstructured":"\u00a0"},{"key":"e_1_2_8_89_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo01304a019"},{"key":"e_1_2_8_90_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol2018533"},{"key":"e_1_2_8_91_1","unstructured":"See the Supporting Information for details and spectra."},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2014.05.009"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.3000004"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.1039\/c001707h"},{"key":"e_1_2_8_95_1","unstructured":"The reaction mechanism forming ketohydroperoxide1is detailed in the Supporting Information."},{"key":"e_1_2_8_96_1","unstructured":"\u00a0"},{"key":"e_1_2_8_97_2","first-page":"341","volume-title":"Organic Peroxides","author":"Shanley E. 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