{"id":25227,"date":"2022-06-11T07:24:19","date_gmt":"2022-06-11T06:24:19","guid":{"rendered":"https:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=25227"},"modified":"2022-06-11T07:24:19","modified_gmt":"2022-06-11T06:24:19","slug":"checking-a-conclusion-we-made-in-1987-tetrahedral-intermediates-formed-by-nitrogen-and-oxygen-attack-of-aromatic-hydroxylamines-on-acetyl-cyanide","status":"publish","type":"post","link":"https:\/\/www.rzepa.net\/blog\/?p=25227","title":{"rendered":"Checking a conclusion we made in 1987: Tetrahedral intermediates formed by nitrogen and oxygen attack of aromatic hydroxylamines on acetyl cyanide"},"content":{"rendered":"
\n

Minds (and memories) can work in wonderful ways. In 1987[1]<\/a><\/span> we were looking at the properties of “stable” tetrahedral intermediates formed in carbonyl group reactions. The reaction involved adding phenylhydroxylamine to acetyl cyanide. NMR signals for two new species were detected, and we surmised one was due to N-attack on the carbonyl and one was due to O-attack, in each case to form a stable tetrahedral intermediate<\/a>. To try to identify which was which, 15<\/sup>N labelled hydroxylamine was used and then the 15<\/sup>N-13<\/sup>C coupling constants were measured, which could either be 1-bond<\/sup>J (for N-attack) or 2-bond<\/sup>J (for O-attack).<\/p>\n

Well, 35 years later, literally in a dream on the morning of 7th June, 2022, these results came back to me and the dream involved wondering whether we had gotten the assignments of the N- and O-species the correct way around. You see we had assigned the larger of the 15<\/sup>N-13<\/sup>C\u00a0couplings to the two bond (O-attack, species 3<\/strong> below) rather than one-bond (N-attack, species 4<\/strong> below) coupling. In 1987, the art of accurately computing such couplings was still in its infancy, but now in 2022 it is quick and easy to do. So here I report the results, which 35 years on allows a check of those assignments.<\/p>\n

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

The necessary calculations are assembled at FAIR DOI: 10.14469\/hpc\/10593<\/a> conducted at the \u03c9B97XD\/aug-cc-pvdz\/scrf=acetonitrile level. Firstly, it is important that the conformational space of these molecules is explored, since they contain a plethora of interesting anomeric effects.\u00a0I will not discuss this process, simply quoting what\u00a0I believe to be the lowest energy conformation for both isomers.<\/p>\n

\"\"<\/a>\"\"<\/a><\/p>\n\n\n\n\n\n\n\n\n\n\n
#<\/th>\nProperty<\/th>\nSpecies 3<\/th>\nSpecies 4<\/th>\n<\/tr>\n
1<\/td>\n\u0394G298<\/sub><\/td>\n-608.600542<\/td>\n-608.598472<\/td>\n<\/tr>\n
2<\/td>\n\u0394G215<\/sub><\/td>\n-608.586956<\/td>\n-608.585163<\/td>\n<\/tr>\n
3<\/td>\nNBO E(2)<\/td>\n14.3,19.4,10.9,8.1<\/td>\n10.0,11.2,9.9<\/td>\n<\/tr>\n
4<\/td>\n\u03b4C<\/sub> obs<\/td>\n94.3 ppm<\/td>\n85.0 ppm<\/td>\n<\/tr>\n
5<\/td>\n\u03b4C<\/sub> calc<\/td>\n97.2 (\u0394\u03b4 2.9)<\/td>\n88.1 (\u0394\u03b4 3.1)<\/td>\n<\/tr>\n
6<\/td>\nJN-C<\/sub> obs<\/td>\n2<\/sup>J \u00b12.5 Hz<\/td>\n1<\/sup>J \u00b11.3 Hz<\/td>\n<\/tr>\n
7<\/td>\nJN-C<\/sub> calc<\/td>\n2<\/sup>J +1.7<\/td>\n1<\/sup>J +0.8<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
    \n
  1. The relative free energies \u0394\u0394G298<\/sub>\u00a0favour 3<\/strong> over 4<\/strong> by\u00a01.3 kcal\/mol at 298K (9:1). The article notes that 3<\/strong> is significantly<\/em> favoured over 4<\/strong> at higher temperatures (i.e. ~298K) but that the concentration of 4<\/strong> increases at lower temperatures.\u00a0<\/li>\n
  2. At 215K, \u0394\u0394G215<\/sub>\u00a0reduces to 1.1 kcal\/mol, but this equates to 13:1 at this temperature.\u00a0\u0394\u0394G215<\/sub> would need to be about 0.8 kcal\/mol for 4<\/strong> to increase (6.5:1), but these are small errors in energy and a more accurate calculation would have to be done to get this aspect correct.<\/li>\n
  3. The NBO E(2) terms indicating overlap between a lone pair and an acceptor orbital (the anomeric effect), show a dazzling variety of interactions<\/a> for such a small molecule. Species 3<\/strong> shows four significant interactions, species 4<\/strong>\u00a0one less.<\/li>\n
  4. The chemical shifts measured for 3<\/strong> and 4<\/strong> –<\/li>\n
  5. – are matched by the calculation, the error being similar for both species.<\/li>\n
  6. The 15<\/sup>N-13<\/sup>C coupling constants –<\/li>\n
  7. – are again matched, with the 1<\/sup>J coupling being about half the value of the 2<\/sup>J coupling for both obs and calculated values.<\/li>\n<\/ol>\n

    The nature of modern scientific research, and the funding available for it, means that old work is rarely re-investigated using more recent techniques. In this case, the reinvestigation does not require the molecules to be re-synthesized again, merely that a retrospective computational layer be applied. As a result of my dream of four days ago, this process has produced an interesting new layer which thankfully confirms the original conclusions.<\/p>\n

    References<\/h2>\n
    1. A.M. Lobo, M.M. Marques, S. Prabhakar, and H.S. Rzepa, \"Tetrahedral intermediates formed by nitrogen and oxygen attack of aromatic hydroxylamines on acetyl cyanide\", The Journal of Organic Chemistry<\/i>, vol. 52, pp. 2925-2927, 1987. https:\/\/doi.org\/10.1021\/jo00389a050<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

      Minds (and memories) can work in wonderful ways. In 1987 we were looking at the properties of “stable” tetrahedral intermediates formed in carbonyl group reactions. The reaction involved adding phenylhydroxylamine to acetyl cyanide. NMR signals for two new species were detected, and we surmised one was due to N-attack on the carbonyl and one was […]<\/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":[1526],"class_list":["post-25227","post","type-post","status-publish","format-standard","hentry","category-reaction-mechanism-2","tag-interesting-chemistry"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p1gPyz-6yT","jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/25227","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=25227"}],"version-history":[{"count":0,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/25227\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=25227"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=25227"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=25227"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}