{"id":4038,"date":"2011-05-17T14:09:04","date_gmt":"2011-05-17T14:09:04","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=4038"},"modified":"2011-11-29T15:08:43","modified_gmt":"2011-11-29T15:08:43","slug":"updating-a-worked-problem-in-conformational-analysis-part-2-an-answer","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4038","title":{"rendered":"Updating a worked problem in conformational analysis. Part 2: an answer."},"content":{"rendered":"
\n

The previous post<\/a> set out a problem in conformational analysis. Here is my take, which includes an NCI (non-covalent interaction) display as discussed in another post<\/a>.<\/p>\n

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

The lowest energies of the four diastereomers A-D<\/strong>, each in two conformations (1\/2<\/strong>) were calculated at the \u03c9B97D\/6-311G(d,p)\/SCRF=ethanol level, and are shown here relative to A1<\/strong> (kcal\/mol) as free energies. The values of \u0394\u0394G of each pair (relative to the lower energy conformation) are converted to relative concentrations using \u0394\u0394G = -RT Ln<\/em> K and these are shown in blue. Those conformations where a C-H bond is aligned anti-periplanar (app<\/em>) with the C-NMe3<\/sub> bond are highlighted in red. Various aspects of the questions posed include:<\/p>\n

    \n
  1. Those conformations with two app<\/em> combinations are likely to result in a mixture of two alkenes E<\/strong> and F<\/strong> (shown in the previous post<\/a>), and likewise those with only one app<\/em> alignment will give a single alkene.<\/li>\n
  2. The concentration of the neomenthyl system (C) favours the conformer C1<\/strong>, which is also the one with app<\/em> allignments. This will react readily. The menthyl system A<\/strong> has only a low relative concentration of A2<\/strong>, and so will react slowly. The experiments show the rate is about 10 times less than C<\/strong>, whereas the ratio of relative concentrations is larger. This may be due to difference in the transition state for the elimination, or possibly effects due to the presence of a counterion.<\/li>\n
  3. The concentration of D1<\/strong> is the lowest of the four pairs of conformational isomers. This might be due to buttressing, in which the relative proximity of the NMe3<\/sub> and iPr groups forces the former into closer proximity with the axial methyl than is found in A2<\/strong>, the other conformer with an unfavourable 1,3-diaxial interaction.<\/li>\n
  4. The relative energies of most of the pairs of combinations of conformers\/diasteromers are interesting, and I leave it to you to play with them and draw conclusions (or detect mysteries).<\/li>\n<\/ol>\n

    I thought I would finish by adding an NCI analysis<\/a> using a wavefunction computed for \u03c9B97D\/6-31G(d,p)\/SCRF=ethanol. The green surfaces are indicative of regions where non-covalent interactions<\/em><\/strong> are occurring (which include electrostatic and van der Waals effects). The colour scheme is set to blue(ish) to indicate more attractive NCIs (such as strong hydrogen bonds),\u00a0green to indicate weak(ish) NCIs, with a red or orange tinge indicating a repulsive \u00a0NCI.<\/p>\n\n\n\n\n\n\n
    \"\"

    A2 diaxial. Click for 3D.<\/p><\/div><\/td>\n

    \"\"

    B2 Axial-equatorial. click for 3D.<\/p><\/div><\/td>\n<\/tr>\n

    \"\"

    A1. Di-equatorial. Click for 3D.<\/p><\/div><\/td>\n

    \"\"

    B1.Di-equatorial. click for 3D.<\/p><\/div><\/td>\n<\/tr>\n

    \"\"

    C2. Equatorial-axial. Click for 3D.<\/p><\/div><\/td>\n

    \"\"

    D2. Equatorial-axial. Click for 3D.<\/p><\/div><\/td>\n<\/tr>\n

    \"\"

    C1 SRR. Axial-equatorial. Click for 3D.<\/p><\/div><\/td>\n

    \"\"

    D1 SSS. Axial-equatorial. Click for 3D.<\/p><\/div><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

    Amongst the many features visible in these plots is the strong 1,3-diaxial NCIs seen for A2<\/strong> and particularly\u00a0D1<\/strong> and the conformational variability in the NCI between the iPr and NMe3<\/sub> groups.<\/p>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    The previous post set out a problem in conformational analysis. Here is my take, which includes an NCI (non-covalent interaction) display as discussed in another post. The lowest energies of the four diastereomers A-D, each in two conformations (1\/2) were calculated at the \u03c9B97D\/6-311G(d,p)\/SCRF=ethanol level, and are shown here relative to A1 (kcal\/mol) as free […]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_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":false,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2},"jetpack_post_was_ever_published":false},"categories":[],"tags":[17,530,249,532,531,527,373],"ppma_author":[2661],"class_list":["post-4038","post","type-post","status-publish","format-standard","hentry","tag-conformational-analysis","tag-ipr","tag-julia-contreras-garcia","tag-lower-energy-conformation","tag-nme","tag-non-covalent-interactions","tag-tutorial-material"],"yoast_head":"\nUpdating a worked problem in conformational analysis. Part 2: an answer. - 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=4038\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Updating a worked problem in conformational analysis. Part 2: an answer. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"The previous post set out a problem in conformational analysis. Here is my take, which includes an NCI (non-covalent interaction) display as discussed in another post. The lowest energies of the four diastereomers A-D, each in two conformations (1\/2) were calculated at the \u03c9B97D\/6-311G(d,p)\/SCRF=ethanol level, and are shown here relative to A1 (kcal\/mol) as free […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4038\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2011-05-17T14:09:04+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2011-11-29T15:08:43+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/05\/problem_sheet_answer42.jpg\" \/>\n<meta name=\"author\" content=\"Henry Rzepa\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Henry Rzepa\" \/>\n\t<meta name=\"twitter:label2\" content=\"Estimated reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 minutes\" \/>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Updating a worked problem in conformational analysis. Part 2: an answer. - Henry Rzepa's Blog","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4038","og_locale":"en_GB","og_type":"article","og_title":"Updating a worked problem in conformational analysis. Part 2: an answer. - Henry Rzepa's Blog","og_description":"The previous post set out a problem in conformational analysis. Here is my take, which includes an NCI (non-covalent interaction) display as discussed in another post. The lowest energies of the four diastereomers A-D, each in two conformations (1\/2) were calculated at the \u03c9B97D\/6-311G(d,p)\/SCRF=ethanol level, and are shown here relative to A1 (kcal\/mol) as free […]","og_url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4038","og_site_name":"Henry Rzepa's Blog","article_published_time":"2011-05-17T14:09:04+00:00","article_modified_time":"2011-11-29T15:08:43+00:00","og_image":[{"url":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/05\/problem_sheet_answer42.jpg","type":"","width":"","height":""}],"author":"Henry Rzepa","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Henry Rzepa","Estimated reading time":"3 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4038#article","isPartOf":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4038"},"author":{"name":"Henry Rzepa","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281"},"headline":"Updating a worked problem in conformational analysis. 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Trying to explain why it is enantioselective for the epoxide product poses peculiar difficulties. Most of the substituents can adopt one of several conformations, and some exploration of this conformational space is needed. Amongst the conformational possibilities are the two rotations shown\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":"","width":0,"height":0},"classes":[]},{"id":1887,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=1887","url_meta":{"origin":4038,"position":1},"title":"The conformation of 1,2-difluoroethane","author":"Henry Rzepa","date":"April 6, 2010","format":false,"excerpt":"Here I offer another spin-off from writing a lecture course on conformational analysis. This is the famous example of why 1,2-difluoroethane adopts a gauche rather than antiperiplanar conformation. One major contribution to the greater stability of the gauche is the stereoelectronic interactions, and this is best probed using the NBO\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\/04\/difluoroethane.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":6279,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6279","url_meta":{"origin":4038,"position":2},"title":"E2 elimination vs ring contraction: anti-periplanarity in action.","author":"Henry Rzepa","date":"February 20, 2012","format":false,"excerpt":"The anti-periplanar principle permeates organic reactivity. Here I pick up on an example of the antiperiplanar E2 elimination (below, blue) by comparing it to a competing reaction involving a [1,2] antiperiplanar migration (red). The relative rates of these two processes will depend on several factors such as the ability of\u2026","rel":"","context":"In \"conformational analysis\"","block_context":{"text":"conformational analysis","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?tag=conformational-analysis"},"img":{"alt_text":"","src":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/02\/Ring.svg","width":350,"height":200},"classes":[]},{"id":248,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=248","url_meta":{"origin":4038,"position":3},"title":"Conformational analysis and enzyme activity: models for amide hydrolysis.","author":"Henry Rzepa","date":"April 12, 2009","format":false,"excerpt":"The diagram below summarizes an interesting result recently reported by Hanson and co-workers (DOI: 10.1021\/jo800706y. At ~neutral pH, compound 13 hydrolyses with a half life of 21 minutes, whereas 14 takes 840 minutes. Understanding this difference in reactivity may allow us to understand why some enzymes can catalyze the hydrolysis\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":"Models for peptide cleavage.","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2009\/04\/amide-cleavage.png?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":9459,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=9459","url_meta":{"origin":4038,"position":4},"title":"The conformational preference of s-cis amides.","author":"Henry Rzepa","date":"February 10, 2013","format":false,"excerpt":"Amides with an H-N group are a component of the peptide linkage\u00a0(O=C-NH). Here I ask what the conformation (it could also be called a configuration) about the C-N bond is. A search of the following type can be defined: The dihedral shown is for H-N-C=O (but this is equivalent to\u2026","rel":"","context":"In "crystal_structure_mining"","block_context":{"text":"crystal_structure_mining","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1745"},"img":{"alt_text":"cis-amide","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2013\/02\/cis-amide.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":9320,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=9320","url_meta":{"origin":4038,"position":5},"title":"Secrets of a university tutor: conformational analysis and NMR spectroscopy.","author":"Henry Rzepa","date":"February 3, 2013","format":false,"excerpt":"In a previous post, I set out how to show how one can reduce a\u00a01H NMR spectrum to the structure [A] below. I speculated how a further test could be applied to this structure; back predicting its spectrum using just quantum mechanics. Overkill I know, but how well might the\u2026","rel":"","context":"In \"1H NMR\"","block_context":{"text":"1H NMR","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?tag=1h-nmr"},"img":{"alt_text":"C=C-C-S","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2013\/02\/CC-C-S.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\/4038","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=4038"}],"version-history":[{"count":1,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/4038\/revisions"}],"predecessor-version":[{"id":5750,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/4038\/revisions\/5750"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=4038"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=4038"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=4038"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=4038"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}