{"id":10408,"date":"2013-05-11T16:07:41","date_gmt":"2013-05-11T15:07:41","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=10408"},"modified":"2013-05-11T16:07:41","modified_gmt":"2013-05-11T15:07:41","slug":"concerted-14-addition-of-thioacetic-acid-a-requested-reality-check","status":"publish","type":"post","link":"https:\/\/www.rzepa.net\/blog\/?p=10408","title":{"rendered":"Concerted 1,4-addition of thioacetic acid: a (requested) reality check."},"content":{"rendered":"
\n

Lukas, who occasionally comments on this blog, sent me the following challenge. In a recent article[1]<\/a><\/span> he had proposed that the stereochemical outcome (Z<\/strong>) of reaction between a butenal and thioacetic acid as shown below arose by an unusual concerted cycloaddtion involving an S-H bond. He wrote in the article “…this scheme … recommends itself for evaluation by in silico methods<\/em>“. I asked if the answer could be posted here, and he agreed. So here it is.<\/p>\n

\"Click

Click for 3D<\/p><\/div>\n

My initial instinct was that it might prove to be a reaction with “hidden intermediates<\/em>” (for example transfer of the S-H proton onto the oxygen to form a zwitterionic “hidden intermediate”). Well, this is what the computed transition state[2]<\/a><\/span> and the IRC[3]<\/a><\/span> look like.<\/p>\n

\"Lukas\"<\/p>\n

\u00a0\"Lukas\"<\/p>\n

\"LukasG\"<\/p>\n

    \n
  1. For acrolein itself, the forward free-energy barrier \u0394G\u2020<\/sup>298<\/sub> is 25.8 kcal\/mol (\u03c9B97XD\/6-311G(d,p)\/SCRF=acetone) and the reverse barrier 27.7 kcal\/mol, which makes the overall free energy for the reaction -1.8 kcal\/mol. These values are not inconsistent with an equilibrium thermal reaction at room temperatures or above.<\/span><\/li>\n
  2. The gradients show no sign of any “hidden intermediates”. The reaction indeed is nicely concerted, albeit with O-H bond formation asynchronously preceding that of C-S. This reaction should indeed be added to the pantheon of facile pericyclic (or pseudopericyclic) reaction types.<\/li>\n
  3. For the methyl substituted system (R=Me) the forward barrier is a little lower than before (23.8 kcal\/mol)[4]<\/a><\/span> and the reverse likewise (25.5).\u2021<\/sup> The (Z) product far dominates the (E) (61:1).\u00a0The IRC[5]<\/a><\/span> is similar to the unsubstituted reaction, but with the faintest of hints of a hidden intermediate (at IRC ~0.8).<\/li>\n<\/ol>\n

    \"Lukas_mea\"<\/p>\n

    \"Lukas_me\"\"Lukas_meG\"<\/p>\n

    The reaction itself is a smaller-ring thia-homologue of one reported by Birney[6]<\/a><\/span> and classified there as a pseudopericyclic reaction, the point of interest being the difference in behaviour between the O-H acid and the S-H acid.\"birney\"<\/p>\n

    Well, that is the in silico<\/em> counterpart to the in silica<\/em> experiment. It took a few hours (about the same as a few NMR measurements?).<\/p>\n

    \n

    \u2021<\/sup>Slightly lower values are obtained for the s-cis<\/i> conformation[7]<\/a><\/span> of the thio-acid:\u00a0\u0394G\u2020<\/sup>298<\/sub>\u00a0is 21.0 kcal\/mol for the forward and 22.0 for the reverse reactions.<\/p>\n

    \n

    References<\/h2>\n
    1. L. Hintermann, and A. Turo\u010dkin, \"Reversible Generation of Metastable Enols in the 1,4-Addition of Thioacetic Acid to \u03b1,\u03b2-Unsaturated Carbonyl Compounds\", The Journal of Organic Chemistry<\/i>, vol. 77, pp. 11345-11348, 2012. https:\/\/doi.org\/10.1021\/jo3021709<\/a>\n\n<\/li>\n
    2. H.S. Rzepa, \"Gaussian Job Archive for C5H8O2S\", 2013. https:\/\/doi.org\/10.6084\/m9.figshare.701466<\/a>\n\n<\/li>\n
    3. H.S. Rzepa, \"Gaussian Job Archive for C5H8O2S\", 2013. https:\/\/doi.org\/10.6084\/m9.figshare.701174<\/a>\n\n<\/li>\n
    4. H.S. Rzepa, \"Gaussian Job Archive for C6H10O2S\", 2013. https:\/\/doi.org\/10.6084\/m9.figshare.701467<\/a>\n\n<\/li>\n
    5. H.S. Rzepa, \"Gaussian Job Archive for C6H10O2S\", 2013. https:\/\/doi.org\/10.6084\/m9.figshare.701468<\/a>\n\n<\/li>\n
    6. H. Ji, L. Li, X. Xu, S. Ham, L.A. Hammad, and D.M. Birney*, \"Multiphoton Infrared Initiated Thermal Reactions of Esters: Pseudopericyclic Eight-Centered<i>cis<\/i>-Elimination\", Journal of the American Chemical Society<\/i>, vol. 131, pp. 528-537, 2008. https:\/\/doi.org\/10.1021\/ja804812c<\/a>\n\n<\/li>\n
    7. H.S. Rzepa, \"Gaussian Job Archive for C6H10O2S\", 2013. https:\/\/doi.org\/10.6084\/m9.figshare.701501<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

      Lukas, who occasionally comments on this blog, sent me the following challenge. In a recent article he had proposed that the stereochemical outcome (Z) of reaction between a butenal and thioacetic acid as shown below arose by an unusual concerted cycloaddtion involving an S-H bond. He wrote in the article “…this scheme … recommends itself […]<\/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":[6],"tags":[1530],"class_list":["post-10408","post","type-post","status-publish","format-standard","hentry","category-interesting-chemistry","tag-reaction-mechanism"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p1gPyz-2HS","jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/10408","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=10408"}],"version-history":[{"count":0,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/10408\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=10408"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=10408"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=10408"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}