{"id":4030,"date":"2011-05-13T14:27:40","date_gmt":"2011-05-13T14:27:40","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=4030"},"modified":"2011-11-29T15:09:04","modified_gmt":"2011-11-29T15:09:04","slug":"updating-a-worked-problem-in-conformational-analysis-part-1-the-question","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030","title":{"rendered":"Updating a worked problem in conformational analysis. Part 1: the question."},"content":{"rendered":"
\n

Conformational analysis comes from the classical renaissance of physical organic chemistry in the 1950s and 60s. The following problem is taken from\u00a0E. D. Hughes and J. Wilby J. Chem. Soc.<\/em><\/strong>, 1960, 4094-4101, DOI: 10.1039\/JR9600004094<\/a>, the essence of which is that Hofmann<\/a> elimination of a neomenthyl derivative (C below) was observed as anomalously<\/strong><\/em> faster than its menthyl analogue. Of course, what is anomalous in one decade is a standard student problem (and one Nobel prize) five decades later.<\/p>\n

\"\"<\/a>

Hofmann elimination from a family of cyclic systems.<\/p><\/div>\n

One can pose two questions about these systems:<\/p>\n

    \n
  1. What is the expected product formed by reaction of A-D; E or F or both?<\/li>\n
  2. Can the four reactions be ranked in the order fastest to slowest (the hint that C is anomalously fast may or may not be given the students!)<\/li>\n<\/ol>\n

    Its a problem that simply requires a model to be built for its solution. And probably some hints. I give the students two:<\/p>\n

      \n
    1. Each of the reactants can have two alternative chair conformations; let us call them A1 and A2 etc (although a really adventurous student might ask if any twist-boats are also possible). In general, only one of these two can react to eliminate the trimethylammonium group to form an alkene. The task is to determine which, and whether that also reveals whether E or F or both might be formed.<\/li>\n
    2. The rate of reaction (all other things being equal, which they might not be) will be related to the concentration of the active conformation compared to the inactive one. So one has to decide which of the two conformations is likely to be lower in energy, and by how much. Here one can bring as many rules as you might find in the texts books (or lecture courses<\/a>) to bear whilst you decide. If you are really keen, you can try building a model using suitable molecular modelling software.<\/li>\n<\/ol>\n

      So that I do not spoil your fun, I will not reveal (my) answers here, but in the next post<\/a>. Try writing down answers to these two questions, and see if they agree with mine!<\/p>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

      Conformational analysis comes from the classical renaissance of physical organic chemistry in the 1950s and 60s. The following problem is taken from\u00a0E. D. Hughes and J. Wilby J. Chem. Soc., 1960, 4094-4101, DOI: 10.1039\/JR9600004094, the essence of which is that Hofmann elimination of a neomenthyl derivative (C below) was observed as anomalously faster than its […]<\/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":[48,17,528,24,529,373],"ppma_author":[2661],"class_list":["post-4030","post","type-post","status-publish","format-standard","hentry","tag-chair","tag-conformational-analysis","tag-cyclic-systems","tag-energy","tag-suitable-molecular-modelling-software","tag-tutorial-material"],"yoast_head":"\nUpdating a worked problem in conformational analysis. Part 1: the question. - 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=4030\" \/>\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 1: the question. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"Conformational analysis comes from the classical renaissance of physical organic chemistry in the 1950s and 60s. The following problem is taken from\u00a0E. D. Hughes and J. Wilby J. Chem. Soc., 1960, 4094-4101, DOI: 10.1039\/JR9600004094, the essence of which is that Hofmann elimination of a neomenthyl derivative (C below) was observed as anomalously faster than its […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2011-05-13T14:27:40+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2011-11-29T15:09:04+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/05\/menthyl.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=\"2 minutes\" \/>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Updating a worked problem in conformational analysis. Part 1: the question. - 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=4030","og_locale":"en_GB","og_type":"article","og_title":"Updating a worked problem in conformational analysis. Part 1: the question. - Henry Rzepa's Blog","og_description":"Conformational analysis comes from the classical renaissance of physical organic chemistry in the 1950s and 60s. The following problem is taken from\u00a0E. D. Hughes and J. Wilby J. Chem. Soc., 1960, 4094-4101, DOI: 10.1039\/JR9600004094, the essence of which is that Hofmann elimination of a neomenthyl derivative (C below) was observed as anomalously faster than its […]","og_url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030","og_site_name":"Henry Rzepa's Blog","article_published_time":"2011-05-13T14:27:40+00:00","article_modified_time":"2011-11-29T15:09:04+00:00","og_image":[{"url":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/05\/menthyl.jpg","type":"","width":"","height":""}],"author":"Henry Rzepa","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Henry Rzepa","Estimated reading time":"2 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030#article","isPartOf":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030"},"author":{"name":"Henry Rzepa","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281"},"headline":"Updating a worked problem in conformational analysis. Part 1: the question.","datePublished":"2011-05-13T14:27:40+00:00","dateModified":"2011-11-29T15:09:04+00:00","mainEntityOfPage":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030"},"wordCount":369,"commentCount":1,"image":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030#primaryimage"},"thumbnailUrl":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/05\/menthyl.jpg","keywords":["chair","conformational analysis","cyclic systems","energy","suitable molecular modelling software","Tutorial material"],"inLanguage":"en-GB","potentialAction":[{"@type":"CommentAction","name":"Comment","target":["https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030#respond"]}]},{"@type":"WebPage","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030","url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030","name":"Updating a worked problem in conformational analysis. Part 1: the question. - Henry Rzepa's Blog","isPartOf":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#website"},"primaryImageOfPage":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030#primaryimage"},"image":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030#primaryimage"},"thumbnailUrl":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/05\/menthyl.jpg","datePublished":"2011-05-13T14:27:40+00:00","dateModified":"2011-11-29T15:09:04+00:00","author":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281"},"breadcrumb":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030#breadcrumb"},"inLanguage":"en-GB","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030"]}]},{"@type":"ImageObject","inLanguage":"en-GB","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030#primaryimage","url":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/05\/menthyl.jpg","contentUrl":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/05\/menthyl.jpg"},{"@type":"BreadcrumbList","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4030#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog"},{"@type":"ListItem","position":2,"name":"Updating a worked problem in conformational analysis. Part 1: the question."}]},{"@type":"WebSite","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#website","url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/","name":"Henry Rzepa's Blog","description":"Chemistry with a twist","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-GB"},{"@type":"Person","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281","name":"Henry Rzepa","image":{"@type":"ImageObject","inLanguage":"en-GB","@id":"https:\/\/secure.gravatar.com\/avatar\/897b6740f7f599bca7942cdf7d7914af5988937ae0e3869ab09aebb87f26a731?s=96&d=blank&r=g370be3a7397865e4fd161aefeb0a5a85","url":"https:\/\/secure.gravatar.com\/avatar\/897b6740f7f599bca7942cdf7d7914af5988937ae0e3869ab09aebb87f26a731?s=96&d=blank&r=g","contentUrl":"https:\/\/secure.gravatar.com\/avatar\/897b6740f7f599bca7942cdf7d7914af5988937ae0e3869ab09aebb87f26a731?s=96&d=blank&r=g","caption":"Henry Rzepa"},"description":"Henry Rzepa is Emeritus Professor of Computational Chemistry at Imperial College London.","sameAs":["https:\/\/orcid.org\/0000-0002-8635-8390"],"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?author=1"}]}},"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/pDef7-130","jetpack-related-posts":[{"id":4038,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4038","url_meta":{"origin":4030,"position":0},"title":"Updating a worked problem in conformational analysis. Part 2: an answer.","author":"Henry Rzepa","date":"May 17, 2011","format":false,"excerpt":"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\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":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2011\/05\/problem_sheet_answer42.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":4030,"position":1},"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":4030,"position":2},"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":6205,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6205","url_meta":{"origin":4030,"position":3},"title":"An orbital analysis of the stereochemistry of the E2 elimination reaction","author":"Henry Rzepa","date":"February 4, 2012","format":false,"excerpt":"The so-called E2 elimination mechanism is another one of those mainstays of organic chemistry. It is important because it introduces the principle that anti-periplanarity of the reacting atoms is favoured over other orientations such as the syn-periplanar form; Barton used this principle to great effect in developing the theory of\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":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/02\/E2.svg","width":350,"height":200},"classes":[]},{"id":9090,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=9090","url_meta":{"origin":4030,"position":4},"title":"A conflation of concepts: Conformation and pericyclic.","author":"Henry Rzepa","date":"January 10, 2013","format":false,"excerpt":"This is an interesting result I got when studying the [1,4] sigmatropic rearrangement of\u00a0heptamethylbicyclo-[3.1.0]hexenyl cations. It fits into the last lecture of a series on pericyclic mechanisms, and just before the first lecture on conformational analysis. This is how they join. The experiment it relates to may well be a\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":"Click for 3D.","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2013\/01\/14me.gif?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":6262,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6262","url_meta":{"origin":4030,"position":5},"title":"An exothermic E2 elimination: an unusual intrinsic reaction coordinate.","author":"Henry Rzepa","date":"February 6, 2012","format":false,"excerpt":"The previous post explored why E2 elimination reactions occur with an antiperiplanar geometry for the transition state. Here I have tweaked the initial reactant to make the overall reaction exothermic rather than endothermic as it was before. The change is startling. The exothermicity is of course due to the aromatisation\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\/E2-benzo.svg","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\/4030","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=4030"}],"version-history":[{"count":1,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/4030\/revisions"}],"predecessor-version":[{"id":5751,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/4030\/revisions\/5751"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=4030"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=4030"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=4030"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=4030"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}