{"id":9572,"date":"2013-02-21T10:51:22","date_gmt":"2013-02-21T10:51:22","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=9572"},"modified":"2014-01-17T07:34:22","modified_gmt":"2014-01-17T07:34:22","slug":"a-to-and-fro-of-electrons-operating-in-s-cis-esters","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=9572","title":{"rendered":"A to-and-fro of electrons operating in s-cis esters."},"content":{"rendered":"
\n

I conclude my exploration of conformational preferences by taking a look at esters. As before<\/a>, I start with a search definition, the ester being restricted to one bearing only sp3<\/sup> carbon centers.<\/p>\n

\"s-cis-ester-torsion-search\"<\/p>\n

The result of such a search is pretty clear-cut; they all exist in just one conformation, the s-cis<\/em><\/a>, in which a lone pair of electrons on the alkyl-oxygen is aligned quite precisely anti-periplanar with the axis of the C=O bond. This very narrow distribution suggests a relatively large energy preference for this orientation, and we need to seek its origins.<\/p>\n

\"s-cis-ester-torsion\"<\/p>\n

This arises from two electronic alignments. The first orients the in-plane alkyl oxygen lone pair (orange-purple below) anti-periplanar with the C=O \u03c3* empty orbital (red-blue; orange=red, blue=purple), an interaction mapping to 7.7 kcal\/mol in the NBO E(2) energy. The second reinforcement (not shown) aligns the (O=)C-Me donor bond with the antiperiplanar O-Me acceptor (5.3 kcal\/mol). These two interactions are weaker in the s-trans<\/em> ester<\/a>, which is 8.1 kcal\/mol higher in \u0394G298<\/sub> and for which the E(2) terms are respectively 3.0 and 0.6 kcal\/mol.\u00a0<\/p>\n

\"Click

Lp(alkyl-O)\/C=O \u03c3* Click for 3D.<\/p><\/div>\n

But wait, this interaction has electrons moving from the alkyl oxygen to the acyl oxygen (red arrows below) and apparently weakening the C=O bond in the process. But in an entirely different context, we learn that the C=O vibrational stretching wavenumber for an ester (1750 cm-1<\/sup>) is higher than that of a ketone (~1715 cm-1<\/sup>); the C=O is stronger rather than weaker in the ester. So now we have to move the \u03c3-electrons back again (green arrows below).\"s-cis-ester\"<\/p>\n

This strengthening of the C=O bond arises from the following overlap of the \u03c3-lone pair on the carbonyl oxygen with the alkyl-O-C\u00a0\u03c3* empty orbital, for which E(2) is 41.5 kcal\/mol, much larger than the previous effect. It however does NOT discriminate between the s-cis<\/em> and s-trans<\/em>\u00a0 conformations, since this interaction is almost the same in the latter (41.8). So we have a to-of-(red)-electrons<\/em> which promote the s-cis conformation, and rather stronger fro-of-(green)-electrons<\/em> which strengthen the C=O bond. But they do not cancel each-other; each has its own job to do!<\/p>\n

\"Click

Lp(acyl-O)\/C-O \u03c3* Click for 3D.<\/p><\/div>\n

There is one other overlap which may differentiate between s-cis<\/em> and s-trans<\/em>, but a rather less obvious one. That is the alkyl-O\u03c0<\/sub> donating to the acyl C=O\u03c0*<\/sub> which has E(2) 64.7 for the former and 59.4 kcal\/mol for the latter. It is not immediately apparent why this overlap should favour s-cis<\/em>. It is however the effect that induces a significant rotational barrier about the C-O bond (~12 kcal\/mol).<\/p>\n

\"Click

Lp (alkyl-O \u03c0)\/C=O \u03c0* Click for 3D.<\/p><\/div>\n

Here is the result of another search of the crystal database; \u00a0namely the C=O distance (DIST1) vs the \u00a0C-O distance (DIST2). You can see that the red hot spot (~1400 examples) is very isolated (the blue squares represent < 200 hits), and there seems to be no significant correlation between the two lengths and the structure.<\/p>\n<\/p>\n

\"s-cis-ester-distance\"
I will conclude with a brief discussion of the carbonyl lone pairs. There are two, and one of them has been shown above in the\u00a0Lp(acyl-O)\/C-O \u03c3* interaction. There is another, but it plays no role in the conformation, and is of quite a different character. Although a low-lying orbital, it is clearly non bonding; indeed might be slightly anti-bonding along the C=O axis. These two carbonyl lone pairs are quite different in character, since each performs a different role in the molecule.<\/p>\n

\"Click

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

So the conformational analysis of this simple little molecule reveals some interesting toos-and-fros in the electrons. I will deal with the issue of the carbonyl stretching frequencies in another post.<\/p>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

I conclude my exploration of conformational preferences by taking a look at esters. As before, I start with a search definition, the ester being restricted to one bearing only sp3 carbon centers. The result of such a search is pretty clear-cut; they all exist in just one conformation, the s-cis, in which a lone pair […]<\/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,"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":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[4],"tags":[17,24,1000,1001,373],"ppma_author":[2661],"class_list":["post-9572","post","type-post","status-publish","format-standard","hentry","category-interesting-chemistry","tag-conformational-analysis","tag-energy","tag-large-energy-preference","tag-search-definition","tag-tutorial-material"],"yoast_head":"\nA to-and-fro of electrons operating in s-cis esters. - 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=9572\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"A to-and-fro of electrons operating in s-cis esters. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"I conclude my exploration of conformational preferences by taking a look at esters. As before, I start with a search definition, the ester being restricted to one bearing only sp3 carbon centers. The result of such a search is pretty clear-cut; they all exist in just one conformation, the s-cis, in which a lone pair […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=9572\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2013-02-21T10:51:22+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2014-01-17T07:34:22+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2013\/02\/s-cis-ester-torsion-search.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":"A to-and-fro of electrons operating in s-cis esters. - 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=9572","og_locale":"en_GB","og_type":"article","og_title":"A to-and-fro of electrons operating in s-cis esters. - Henry Rzepa's Blog","og_description":"I conclude my exploration of conformational preferences by taking a look at esters. 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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":17333,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=17333","url_meta":{"origin":9572,"position":1},"title":"Ritonavir: a look at a famous example of conformational polymorphism.","author":"Henry Rzepa","date":"January 2, 2017","format":false,"excerpt":"Here is an inside peek at another one of Derek Lowe's 250 milestones in chemistry, the polymorphism of Ritonavir.\u00a0The story in a nutshell concerns one of a pharma company's worst nightmares; a drug which has been successfully brought to market unexpectedly\u00a0\"changes\" after a few years on market to a less\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":8850,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=8850","url_meta":{"origin":9572,"position":2},"title":"Sharpless epoxidation, enantioselectivity and conformational analysis.","author":"Henry Rzepa","date":"January 3, 2013","format":false,"excerpt":"I return to this reaction one more time. 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":9360,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=9360","url_meta":{"origin":9572,"position":3},"title":"\u03c3-\u03c0-Conjugation: seeking evidence by a survey of crystal structures.","author":"Henry Rzepa","date":"February 3, 2013","format":false,"excerpt":"The electronic interaction between a single bond and an adjacent double bond is often called \u03c3-\u03c0-conjugation (an older term for this is hyperconjugation), and the effect is often used to e.g. explain why more highly substituted carbocations are more stable than less substituted ones. This conjugation is more subtle in\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":"C-H\/alkene interaction. Click for 3D.","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2013\/02\/cis-butene-orbitals.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":9500,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=9500","url_meta":{"origin":9572,"position":4},"title":"The conformational preference of s-cis amides. Ramachandran plots.","author":"Henry Rzepa","date":"February 11, 2013","format":false,"excerpt":"This is really just a postscript to the previous post. There I showed how a search of the (small molecule) crystal database revealed the s-cis conformation about the N-C amide bond (the one with partial double bond character that prevents rotation) and how this conformation means that a C-H approaches\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":16557,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16557","url_meta":{"origin":9572,"position":5},"title":"Why is the carbonyl IR stretch in an ester higher than in a ketone: crystal structure data mining.","author":"Henry Rzepa","date":"June 18, 2016","format":false,"excerpt":"In this post, I pondered upon the C=O infra-red spectroscopic\u00a0properties of esters, and showed three possible electronic influences: The red (and blue) arrows imply the C-O bond might shorten and the C=O bond would lengthen; the green the reverse. So time for a search of the crystal structure database as\u2026","rel":"","context":"In "Chemical IT"","block_context":{"text":"Chemical IT","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=2"},"img":{"alt_text":"","src":"","width":0,"height":0},"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\/9572","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=9572"}],"version-history":[{"count":19,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/9572\/revisions"}],"predecessor-version":[{"id":11921,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/9572\/revisions\/11921"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=9572"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=9572"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=9572"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=9572"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}