{"id":22578,"date":"2020-08-14T11:21:15","date_gmt":"2020-08-14T10:21:15","guid":{"rendered":"https:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=22578"},"modified":"2020-08-14T11:27:09","modified_gmt":"2020-08-14T10:27:09","slug":"the-willgerodt-kindler-reaction-mechanistic-reality-check-2","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=22578","title":{"rendered":"The Willgerodt-Kindler Reaction: mechanistic reality check 2."},"content":{"rendered":"
\n

Continuing an exploration of the mechanism of this reaction, an alternative new mechanism was suggested in 1989 (having been first submitted to the journal ten years earlier!).[1]<\/a><\/span> Here the key intermediate proposed is a thiirenium cation (labelled 8<\/strong> in the article) and labelled\u00a0Int3<\/strong> below.<\/p>\n

\"\"<\/a><\/p>\n

The model chosen is the same as before (B3LYP+GD3+BJ\/Def2-TZVPP\/Solvent=water) but now includes a specific base (ammonia) to help remove and add protons. Species 8<\/strong> (Int3<\/strong>) sits in the middle of the rearrangement mechanism and can account for isomerisation in which (above) the Ph and H substituents of the starting ketone end up transposed. It also has the apparent merit that cations such as 8<\/strong> are known as crystal structures[2]<\/a><\/span>,[3]<\/a><\/span>+ DOI: 10.5517\/cc112bct<\/a>,[3]<\/a><\/span>+DOI: 10.5517\/cc112bfw<\/a>. As you can see from the relative free energies (FAIR data at DOI:\u00a010.14469\/hpc\/7336<\/a>)\u00a0that of Int3<\/strong> is 50 kcal\/mol higher than the reactant, and the \u00a0transition state leading to it is even higher. So whereas species such as 8<\/strong> (Int3<\/strong>) can exist (albeit substituted with sterically hindering groups), they probably play no actual role in the mechanism of this reaction.<\/p>\n

The hunt continues for a mechanism for which the computed energies along the reaction path are \u2264 31 kcal\/mol at 403K, which would correspond approximately to a half life of ~60 minutes.\u00a0\u00a0<\/p>\n

References<\/h2>\n
  1. M. Carmack, \"The willgerodt\u2010kindler reactions. 7. The mechanisms\", Journal of Heterocyclic Chemistry<\/i>, vol. 26, pp. 1319-1323, 1989. https:\/\/doi.org\/10.1002\/jhet.5570260518<\/a>\n\n<\/li>\n
  2. R. Destro, V. Lucchini, G. Modena, and L. Pasquato, \"X-ray Structures and Anionotropic Rearrangements of Di-<i>tert<\/i>-butyl-Substituted Thiiranium and Thiirenium Ions. A Structure\u2212Reactivity Relationship\", The Journal of Organic Chemistry<\/i>, vol. 65, pp. 3367-3370, 2000. https:\/\/doi.org\/10.1021\/jo991731o<\/a>\n\n<\/li>\n
  3. H. Poleschner, and K. Seppelt, \"XeF<sub>2<\/sub>\/Fluoride Acceptors as Versatile One\u2010Electron Oxidants\", Angewandte Chemie International Edition<\/i>, vol. 52, pp. 12838-12842, 2013. https:\/\/doi.org\/10.1002\/anie.201307161<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    Continuing an exploration of the mechanism of this reaction, an alternative new mechanism was suggested in 1989 (having been first submitted to the journal ten years earlier!). Here the key intermediate proposed is a thiirenium cation (labelled 8 in the article) and labelled\u00a0Int3 below. The model chosen is the same as before (B3LYP+GD3+BJ\/Def2-TZVPP\/Solvent=water) but now […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"activitypub_content_warning":"","activitypub_content_visibility":"","activitypub_max_image_attachments":5,"activitypub_interaction_policy_quote":"anyone","activitypub_status":"","footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[1086],"tags":[],"ppma_author":[2661],"class_list":["post-22578","post","type-post","status-publish","format-standard","hentry","category-reaction-mechanism-2"],"yoast_head":"\nThe Willgerodt-Kindler Reaction: mechanistic reality check 2. - Henry Rzepa's Blog<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=22578\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The Willgerodt-Kindler Reaction: mechanistic reality check 2. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"Continuing an exploration of the mechanism of this reaction, an alternative new mechanism was suggested in 1989 (having been first submitted to the journal ten years earlier!). 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There is a much rarer alternative: alkyl-oxygen cleavage (green bond) which I now place under the microscope. Here, guanidine is used as a general acid\/base, which results in a reasonable activation barrier for\u2026","rel":"","context":"In \"acetic acid\"","block_context":{"text":"acetic acid","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?tag=acetic-acid"},"img":{"alt_text":"alkylg","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2013\/03\/alkylg.gif?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":18822,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=18822","url_meta":{"origin":22578,"position":4},"title":"Hydrogen capture by boron: a crazy reaction path!","author":"Henry Rzepa","date":"September 21, 2017","format":false,"excerpt":"A recent article reports, amongst other topics, a computationally modelled reaction involving the capture of molecular hydrogen using a substituted borane (X=N, Y=C). The mechanism involves an initial equilibrium between React and Int1, followed by capture of the hydrogen by Int1 to form a 5-coordinate borane intermediate (Int2 below, as\u2026","rel":"","context":"In "reaction mechanism"","block_context":{"text":"reaction mechanism","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1086"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":3003,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=3003","url_meta":{"origin":22578,"position":5},"title":"Janus mechanisms (the past and the future): Reactions of the diazonium cation.","author":"Henry Rzepa","date":"December 11, 2010","format":false,"excerpt":"Janus was the mythological Roman god depicted as having two heads facing opposite directions, looking simultaneously into the past and the future. Some of the most ancient (i.e. 19th century) known reactions can be considered part of a chemical mythology; perhaps it is time for\u00a0a Janus-like look into their future.\u2026","rel":"","context":"In "Interesting chemistry"","block_context":{"text":"Interesting chemistry","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=4"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2010\/12\/diazonium.jpg?resize=350%2C200","width":350,"height":200},"classes":[]}],"jetpack_likes_enabled":false,"authors":[{"term_id":2661,"user_id":1,"is_guest":0,"slug":"admin","display_name":"Henry Rzepa","avatar_url":"https:\/\/secure.gravatar.com\/avatar\/897b6740f7f599bca7942cdf7d7914af5988937ae0e3869ab09aebb87f26a731?s=96&d=blank&r=g","0":null,"1":"","2":"","3":"","4":"","5":"","6":"","7":"","8":""}],"_links":{"self":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/22578","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=22578"}],"version-history":[{"count":12,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/22578\/revisions"}],"predecessor-version":[{"id":22594,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/22578\/revisions\/22594"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=22578"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=22578"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=22578"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=22578"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}