{"id":12678,"date":"2014-06-26T14:44:02","date_gmt":"2014-06-26T13:44:02","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=12678"},"modified":"2016-06-18T07:54:27","modified_gmt":"2016-06-18T06:54:27","slug":"amides-and-inverting-the-electronics-of-the-burgi-dunitz-trajectory","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12678","title":{"rendered":"Amides and inverting the electronics of the B\u00fcrgi\u2013Dunitz trajectory."},"content":{"rendered":"
\n

\n\tThe Bürgi–Dunitz angle<\/a> describes the trajectory of an approaching nucleophile towards the carbon atom of a carbonyl group. A colleague recently came to my office to ask about the inverse, that is what angle would an electrophile approach (an amide)? Thus it might approach either syn <\/em>or anti<\/em> with respect to the nitrogen, which is a feature not found with nucleophilic attack. \"amide\"<\/a> My first thought was to calculate the wavefunction and identify the location and energy (= electrophilicity) of the lone pairs (the presumed attractor of an electrophile). But a better more direct approach soon dawned. A search of the crystal structure database. Here is the search definition, with the C=O-E angle, the O-E distance and the N-C=O-E torsion defined (also specified for R factor < 5%, no errors and no disorder). \"search\"<\/a>   The first plot is of the torsion vs<\/em> the distance, for E = H-X (X=O,F, Cl) \"amides\"<\/a>\n<\/p>\n

    \n
  1. \n\t\tThe first observation is to note the prominent "hotspot" at a torsion of 180° and a (hydrogen bonding) distance of ~1.60-1.65Å. Amides, so it seems, prefer the electrophile (a proton) to approach anti<\/em> to the nitrogen\n\t<\/li>\n
  2. \n\t\tThere is a smaller hotspot at a torsion of 0° and a rather longer distance of ~1.8Å corresponding to syn<\/em> approach.\n\t<\/li>\n
  3. \n\t\tAnd finally a barely discernible (but real) one at ~90°, corresponding to the proton attaching itself to the carbonyl π-bond.\n\t<\/li>\n
  4. \n\t\tA plot of the angles involved reveals that the anti<\/em> hotspot occurs at ~100° whilst the syn<\/em> hotspot is about 120°.\"amides-angles\"<\/a>\n\t<\/li>\n
  5. \n\t\twhilst replacing the proton as electrophile by any metal results in a distinct change.\"amides-angles1\"<\/a>\"amides-angles2\"<\/a>\n\t<\/li>\n
  6. \n\t\tSyn<\/em> approach now holds the (red) hotspot, and the angle opens up to ~135°, whilst the anti<\/em> approach covers a wider angle range of 130-150°\n\t<\/li>\n
  7. \n\t\tA third hotspot region occurs for the 90° torsion, again metal-π-bond interactions.\n\t<\/li>\n<\/ol>\n

    \n\tThe above is a very general statistical survey. As with most bonding effects, one really should investigate every example to discover any perturbing circumstances or structural motifs that might distort the outcome. But for a ten minute exercise in response to a fascinating question from a colleague, it's not bad! And it certainly nicely inverts the usual Bürgi–Dunitz view of carbonyl groups.<\/p>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    The Bürgi–Dunitz angle describes the trajectory of an approaching nucleophile towards the carbon atom of a carbonyl group. A colleague recently came to my office to ask about the inverse, that is what angle would an electrophile approach (an amide)? Thus it might approach either syn or anti with respect to the nitrogen, which is a feature […]<\/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":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2},"jetpack_post_was_ever_published":false},"categories":[1745,1,4],"tags":[1080,24,1239,1240,1001],"ppma_author":[2661],"class_list":["post-12678","post","type-post","status-publish","format-standard","hentry","category-crystal_structure_mining","category-general","category-interesting-chemistry","tag-electronics","tag-energy","tag-metal-results","tag-metal--bond-interactions","tag-search-definition"],"yoast_head":"\nAmides and inverting the electronics of the B\u00fcrgi\u2013Dunitz trajectory. - 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=12678\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Amides and inverting the electronics of the B\u00fcrgi\u2013Dunitz trajectory. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"The Bürgi–Dunitz angle describes the trajectory of an approaching nucleophile towards the carbon atom of a carbonyl group. 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Thus it might approach either syn or anti with respect to the nitrogen, which is a feature […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12678\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2014-06-26T13:44:02+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2016-06-18T06:54:27+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2014\/06\/amide.svg\" \/>\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":"Amides and inverting the electronics of the B\u00fcrgi\u2013Dunitz trajectory. - 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=12678","og_locale":"en_GB","og_type":"article","og_title":"Amides and inverting the electronics of the B\u00fcrgi\u2013Dunitz trajectory. - Henry Rzepa's Blog","og_description":"The Bürgi–Dunitz angle describes the trajectory of an approaching nucleophile towards the carbon atom of a carbonyl group. 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Some special types of nucleophile such as hydrazines (R2N-NR2) are supposed to have enhanced reactivity due to what might be described as\u00a0buttressing of adjacent lone\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":[]},{"id":14016,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=14016","url_meta":{"origin":12678,"position":1},"title":"The B\u00fcrgi\u2013Dunitz angle revisited: a mystery?","author":"Henry Rzepa","date":"May 12, 2015","format":false,"excerpt":"The B\u00fcrgi\u2013Dunitz angle is one of those memes that most students of organic chemistry remember.\u00a0It hypothesizes the geometry of attack of a\u00a0nucleophile\u00a0on a\u00a0trigonal\u00a0unsaturated (sp2) carbon in a\u00a0molecule\u00a0such as\u00a0ketone, aldehyde,\u00a0ester, and\u00a0amide\u00a0carbonyl. Its value obviously depends on the exact system, but is generally taken to be in the range 105-107\u00b0. A very\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":[]},{"id":13688,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=13688","url_meta":{"origin":12678,"position":2},"title":"Mechanism of the Lithal (LAH) reduction of cinnamaldehyde.","author":"Henry Rzepa","date":"April 1, 2015","format":false,"excerpt":"The reduction of cinnamaldehyde by lithium aluminium hydride (LAH) was reported in a classic series of experiments,, dating from 1947-8. The reaction was first introduced into the organic chemistry laboratories here at Imperial College decades ago, vanished for a short period, and has recently been reintroduced again.\u2021 The experiment is\u2026","rel":"","context":"In "reaction mechanism"","block_context":{"text":"reaction mechanism","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1086"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":6874,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6874","url_meta":{"origin":12678,"position":3},"title":"Transition state models for Baldwin’s rules of ring closure.","author":"Henry Rzepa","date":"June 2, 2012","format":false,"excerpt":"The Baldwin rules for ring closure follow the earlier ones by B\u00fcrgi and Dunitz\u00a0in stating the preferred angles of nucleophilic (and electrophilic) attack in bond forming reactions, and are as famous for the interest in their exceptions as for their adherence. Both sets of rules fundamentally explore the geometry of\u2026","rel":"","context":"In "General"","block_context":{"text":"General","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1"},"img":{"alt_text":"","src":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/06\/baldwin.svg","width":350,"height":200},"classes":[]},{"id":14423,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=14423","url_meta":{"origin":12678,"position":4},"title":"Intermolecular atom-atom bonds in crystals? The O…O case.","author":"Henry Rzepa","date":"July 25, 2015","format":false,"excerpt":"I recently followed this bloggers trail; link1 \u2192 link2 to arrive at this delightful short commentary on atom-atom bonds in crystals by Jack Dunitz. Here he discusses that age-old question (to chemists), what is a bond? Even almost 100 years after Gilbert Lewis' famous analysis, we continue to ponder this\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":"OO-query","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2015\/07\/OO-query.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":10656,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=10656","url_meta":{"origin":12678,"position":5},"title":"Mechanism of the Van Leusen reaction.","author":"Henry Rzepa","date":"May 29, 2013","format":false,"excerpt":"This is a follow-up to comment posted by Ryan, who asked about isocyanide\u2019s role (in the form of the anion of tosyl isocyanide, or TosMIC): \"In Van Leusen, it (the isocyanide) acts as an electrophile\". The Wikipedia article (recently updated by myself) shows nucleophilic attack by an oxy-anion on the\u2026","rel":"","context":"In \"low energy\"","block_context":{"text":"low energy","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?tag=low-energy"},"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\/12678","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=12678"}],"version-history":[{"count":8,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/12678\/revisions"}],"predecessor-version":[{"id":16549,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/12678\/revisions\/16549"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=12678"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=12678"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=12678"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=12678"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}