{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T02:57:31Z","timestamp":1774061851654,"version":"3.50.1"},"reference-count":76,"publisher":"Wiley","issue":"28","license":[{"start":{"date-parts":[[2014,6,11]],"date-time":"2014-06-11T00:00:00Z","timestamp":1402444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2014,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We found that phenethylcarbamates that bear <jats:italic>ortho<\/jats:italic>\u2010salicylate as an ether group (carbamoyl salicylates) dramatically accelerate O\uf8ffC bond dissociation in strong acid to facilitate generation of isocyanate cation (N\u2010protonated isocyanates), which undergo subsequent intramolecular aromatic electrophilic cyclization to give dihydroisoquinolones. To generate isocyanate cations from carbamates in acidic media as electrophiles for aromatic substitution, protonation at the ether oxygen, the least basic heteroatom, is essential to promote C\uf8ffO bond cleavage. However, the carbonyl oxygen of carbamates, the most basic site, is protonated exclusively in strong acids. We found that the protonation site can be shifted to an alternative basic atom by linking methyl salicylate to the ether oxygen of carbamate. The methyl ester oxygen <jats:italic>ortho<\/jats:italic> to the phenolic (ether) oxygen of salicylate is as basic as the carbamate carbonyl oxygen, and we found that monoprotonation at the methyl ester oxygen in strong acid resulted in the formation of an intramolecular cationic hydrogen bond (&gt;C\uf8feO<jats:sup>+<\/jats:sup>\uf8ffH\u22c5\u22c5\u22c5O&lt;) with the phenolic ether oxygen. This facilitates O\uf8ffC bond dissociation of phenethylcarbamates, thereby promoting isocyanate cation formation. In contrast, superacid\u2010mediated diprotonation at the methyl ester oxygen of the salicylate and the carbonyl oxygen of the carbamate afforded a rather stable dication, which did not readily undergo C\uf8ffO bond dissociation. This is an unprecedented and unknown case in which the monocation has greater reactivity than the dication.<\/jats:p>","DOI":"10.1002\/chem.201402447","type":"journal-article","created":{"date-parts":[[2014,6,11]],"date-time":"2014-06-11T08:40:07Z","timestamp":1402476007000},"page":"8682-8690","source":"Crossref","is-referenced-by-count":30,"title":["Protonation Switching to the Least\u2010Basic Heteroatom of Carbamate through Cationic Hydrogen Bonding Promotes the Formation of Isocyanate Cations"],"prefix":"10.1002","volume":"20","author":[{"given":"Hiroaki","family":"Kurouchi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akinari","family":"Sumita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Otani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiko","family":"Ohwada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,6,11]]},"reference":[{"key":"e_1_2_6_1_2","unstructured":"\u00a0"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00810a029"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0003689"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5457.1493"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio703"},{"key":"e_1_2_6_6_2","unstructured":"\u00a0"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200460916"},{"key":"e_1_2_6_7_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200460916"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja994280y"},{"key":"e_1_2_6_9_2","unstructured":"For urea:"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00091a007"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja036972z"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200503132"},{"key":"e_1_2_6_12_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200503132"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200500227"},{"key":"e_1_2_6_13_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200500227"},{"key":"e_1_2_6_14_2","unstructured":"\u00a0"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/cr068374j"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0029-1218801"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja067417a"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja057444l"},{"key":"e_1_2_6_19_2","unstructured":"\u00a0"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja037705w"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol060939a"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja408641g"},{"key":"e_1_2_6_23_2","unstructured":"\u00a0"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1039\/c39940000707"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar960056r"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/recl.19760950102"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00753a047"},{"key":"e_1_2_6_28_2","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1139\/v99-080","volume":"77","author":"Barber S. 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For the present reactions of the substrates in which 4\u2010substituted phenol derivatives are used as the leaving group the\u03c1value of the Hammett plot between\u03c3values of 4\u2010substituents and the reaction rates was found to be positive (\u03c1=+0.65) thus indicating that electron\u2010withdrawing substituents can accelerate the reactions. For more information see the Supporting Information."},{"key":"e_1_2_6_53_2","first-page":"1699","volume":"11","author":"Ko\u017eelj M.","year":"2007","journal-title":"Synlett"},{"key":"e_1_2_6_54_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo301848g"},{"key":"e_1_2_6_55_2","unstructured":"\u00a0"},{"key":"e_1_2_6_56_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00085a010"},{"key":"e_1_2_6_57_2","doi-asserted-by":"publisher","DOI":"10.1039\/c0ob01276a"},{"key":"e_1_2_6_58_2","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.39.2718"},{"key":"e_1_2_6_59_2","unstructured":"A large excess amount of acids was employed to minimize the decrease in acidity of the media which is caused by protonation of the substrate. We have already checked the effect of addition of the base on lowering the acidity of the media. Lowering the acidity occurred upon addition of a base substrate such as water but the magnitude of the change was constant. Therefore the relationship between the relative acidity strength and the rate of reactions does not change significantly. See"},{"key":"e_1_2_6_60_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja980090w"},{"key":"e_1_2_6_61_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo982019e"},{"key":"e_1_2_6_62_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja01511a053"},{"key":"e_1_2_6_63_2","unstructured":"\u00a0"},{"key":"e_1_2_6_64_2","doi-asserted-by":"publisher","DOI":"10.1039\/c29710001470"},{"key":"e_1_2_6_65_2","doi-asserted-by":"publisher","DOI":"10.1039\/p29720002057"},{"key":"e_1_2_6_66_2","unstructured":"For example Anderson et\u2005al. proposed a mechanism of base\u2010catalyzed hydrolysis of benzaldehyde disalicyl acetal shown below (see Ref.\u2005[24\u2009a])."},{"key":"e_1_2_6_67_2","unstructured":"\u00a0"},{"key":"e_1_2_6_68_2","doi-asserted-by":"publisher","DOI":"10.1039\/j29680000275"},{"key":"e_1_2_6_69_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja01025a038"},{"key":"e_1_2_6_70_2","doi-asserted-by":"publisher","DOI":"10.1139\/v05-142"},{"key":"e_1_2_6_71_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo00923a031"},{"key":"e_1_2_6_72_2","unstructured":"Gaussian\u200509 Revision\u2005A.02 M.\u2005J. 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