{"id":7822,"date":"2012-09-25T15:34:13","date_gmt":"2012-09-25T14:34:13","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=7822"},"modified":"2012-09-25T15:34:13","modified_gmt":"2012-09-25T14:34:13","slug":"oxime-formation-from-hydroxylamine-and-ketone-part-2-elimination","status":"publish","type":"post","link":"https:\/\/www.rzepa.net\/blog\/?p=7822","title":{"rendered":"Oxime formation from hydroxylamine and ketone. Part 2: Elimination."},"content":{"rendered":"
\n

This is the follow-up to the previous post<\/a> exploring a typical nucleophilic addition-elimination reaction. Here is the elimination step, which as before requires proton transfers. We again adopt a cyclic mechanism to try to avoid the build up of charge separation during those proton movements.<\/p>\n

\"\"<\/p>\n

\"\"

Elimination step to form an oxime. Click for animation of reaction mode.<\/p><\/div>\n

    \n
  1. Overall, the transition state<\/a> for this second stage is 12.1 kcal\/mol higher in free energy than the addition step described previously, and some 30 kcal\/mol starting from the tetrahedral intermediate. Unlike the first step, where neutral water could participate in a reaction with a low barrier, here neutral water does not do the trick. To reduce the barrier, one probably needs to add e.g.<\/em> an acid, say HCl to the components. Knowing precisely where to place such an acid is non trivial – I will not reveal an answer now, but will reserve it for a future post.\"\"<\/li>\n
  2. It is worth observing the features (best seen in the gradient norm plot below) in the \u00a0IRC. The small feature at \u00a0IRC -9 \u00a0corresponds to rotation of the \u00a0C-OH group away from an anomeric conformation to prepare it for accepting a proton.<\/li>\n
  3. By IRC -2 (i.e.<\/em> before the actual transition state is reached), the first proton transfer is well under way from the C-OH group to the first water molecule. The cleavage of the C-OH bond is also starting.<\/li>\n
  4. At the transition state (IRC =0.0), this first transfer is almost complete and the second between the two water molecules is starting. The cleavage of the \u00a0C-OH bond is largely complete.<\/li>\n
  5. By IRC +3, \u00a0this second transfer is largely complete and a third from the N-H to the second water is underway.<\/li>\n
  6. By IRC +5, the proton transfers are all finished, and the C=N double bond of the oxime is also largely formed.
    \"\"<\/li>\n<\/ol>\n

    Well, this particular sequence of events is clearly not the full (or even a partial) answer to the mechanism of the second elimination step for this reaction. We know this because it predicts far too large a barrier. Something is missing from this model, and that something is probably a polarizing group such as HCl. Watch this space.<\/p>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    This is the follow-up to the previous post exploring a typical nucleophilic addition-elimination reaction. Here is the elimination step, which as before requires proton transfers. We again adopt a cyclic mechanism to try to avoid the build up of charge separation during those proton movements. Overall, the transition state for this second stage is 12.1 […]<\/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":[1],"tags":[1530,1527],"class_list":["post-7822","post","type-post","status-publish","format-standard","hentry","category-uncategorized","tag-reaction-mechanism","tag-tutorial-material"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p1gPyz-22a","jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/7822","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=7822"}],"version-history":[{"count":0,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/7822\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=7822"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=7822"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=7822"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}