{"id":22649,"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":"2020-08-14T11:21:15","modified_gmt":"2020-08-14T10:21:15","slug":"the-willgerodt-kindler-reaction-mechanistic-reality-check-2","status":"publish","type":"post","link":"https:\/\/www.rzepa.net\/blog\/?p=22649","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,"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":[1085],"tags":[],"class_list":["post-22649","post","type-post","status-publish","format-standard","hentry","category-reaction-mechanism-2"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p1gPyz-5Tj","jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/22649","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=22649"}],"version-history":[{"count":0,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/22649\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=22649"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=22649"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=22649"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}