{"id":13962,"date":"2015-04-17T15:30:23","date_gmt":"2015-04-17T14:30:23","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=13962"},"modified":"2023-09-16T18:26:23","modified_gmt":"2023-09-16T17:26:23","slug":"a-new-way-of-exploring-the-directing-influence-of-electron-donating-substituents-on-benzene","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=13962","title":{"rendered":"A new way of exploring the directing influence of (electron donating) substituents on benzene."},"content":{"rendered":"
\n

\n\tThe knowledge that substituents on a benzene ring direct an electrophile engaged in a ring substitution reaction according to whether they withdraw or donate electrons is very old<\/a>.[1]<\/a><\/span> Introductory organic chemistry tells us that electron donating substituents promote the ortho<\/em> and para<\/em> positions over the meta<\/em>. Here I try to recover some of this information by searching crystal structures.\n<\/p>\n

\n\tI conducted the following search:
\n\t\"xray\"<\/a>\n<\/p>\n

    \n
  1. \n\t\tAny electron donating group as a ring substituent, defined by any of the elements N, O, F, S, Cl, Br.\n\t<\/li>\n
  2. \n\t\tA distance from the H of an OH fragment (as a hydrogen bonder to the aryl ring) to the ortho<\/em> position relative to the electron donating group.\n\t<\/li>\n
  3. \n\t\tA similar distance to the meta<\/em> position.\n\t<\/li>\n
  4. \n\t\tThe |torsion angle| between the aryl plane and the C…H axis to be constrained to 90° ± 20.\n\t<\/li>\n
  5. \n\t\tRestricting the H…C contact distance to the van der Waals sum of the radii -0.3Å (to capture only the stronger interactions)\n\t<\/li>\n
  6. \n\t\tThe usual crystallographic requirements of R < 0.1, no disorder, no errors and normalised H positions.\n\t<\/li>\n<\/ol>\n

    \n\tThe result of such a search is seen below. The red line indicates those hits where the distance from the H to the ortho<\/em> and meta<\/em> positions is equal. In the top left triangle, the distance to ortho<\/em> is shorter than to meta <\/em>(and the converse in the bottom right triangle). You can see that both the red hot-spot and indeed the majority of the structures conform to ortho<\/em> direction (of π-facial ) hydrogen bonding.\n<\/p>\n

    \n\t\"benzene-xray\"<\/a>Here is a little calculation, optimising the position that HBr adopts with respect to bromobenzene. You can see that the distance discrimination towards ortho<\/em> is ~ 0.17Å, a very similar value to the "hot-spot" in the diagram above.\n<\/p>\n

    \n\t\"benzene-HBr\"<\/a>\n<\/p>\n

    \n\tThis little search of course has hardly scratched the surface of what could be done. Changing eg<\/em> the OH acceptor to other electronegative groups. Restricting the wide span of N, O, F, S, Cl, Br. Probing rings bearing two substituents. What of the minority of points in the bottom right triangle; are they true exceptions or does each have extenuating circumstances? Why do many points actually lie on the diagonal? Can one correlate the distances with the substituent? Is there a difference between intra<\/em> and inter<\/em>molecular H-bonds? What of electron withdrawing groups?\n<\/p>\n

    \n\tThe above search took perhaps 20 minutes to define and optimise, and it gives a good statistical overview of this age-old effect. It is something every new student of organic chemistry can try for themselves! If you run an introductory course in organic aromatic chemistry, or indeed a laboratory, try to see what your students come up with![2]<\/a><\/span>\n<\/p>\n

    \n

    Acknowledgments<\/h4>\n

    This post has been cross-posted in PDF format at Authorea<\/a>.<\/p>\n

    References<\/h2>\n
    1. H.E. Armstrong, \"XXVIII.\u2014An explanation of the laws which govern substitution in the case of benzenoid compounds\", J. Chem. Soc., Trans.<\/i>, vol. 51, pp. 258-268, 1887. https:\/\/doi.org\/10.1039\/ct8875100258<\/a>\n\n<\/li>\n
    2. H.S. Rzepa, \"Discovering More Chemical Concepts from 3D Chemical Information Searches of Crystal Structure Databases\", Journal of Chemical Education<\/i>, vol. 93, pp. 550-554, 2015. https:\/\/doi.org\/10.1021\/acs.jchemed.5b00346<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

      The knowledge that substituents on a benzene ring direct an electrophile engaged in a ring substitution reaction according to whether they withdraw or donate electrons is very old. Introductory organic chemistry tells us that electron donating substituents promote the ortho and para positions over the meta. Here I try to recover some of this information […]<\/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":[2,1745],"tags":[992,1446,16,951,1395,1383,1444,1447,1445,1412,1384,1410,1442,1443],"ppma_author":[2661],"class_list":["post-13962","post","type-post","status-publish","format-standard","hentry","category-chemical-it","category-crystal_structure_mining","tag-above-search","tag-aromatic-compounds","tag-aromaticity","tag-birch-reduction","tag-chemistry","tag-electron-donating","tag-electrophile","tag-electrophilic-aromatic-substitution","tag-ether","tag-functional-groups","tag-little-search","tag-organic-chemistry","tag-physical-organic-chemistry","tag-substitution-reactions"],"yoast_head":"\nA new way of exploring the directing influence of (electron donating) substituents on benzene. - 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=13962\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"A new way of exploring the directing influence of (electron donating) substituents on benzene. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"The knowledge that substituents on a benzene ring direct an electrophile engaged in a ring substitution reaction according to whether they withdraw or donate electrons is very old. Introductory organic chemistry tells us that electron donating substituents promote the ortho and para positions over the meta. Here I try to recover some of this information […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=13962\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2015-04-17T14:30:23+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2023-09-16T17:26:23+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2015\/04\/xray1.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":"A new way of exploring the directing influence of (electron donating) substituents on benzene. - 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=13962","og_locale":"en_GB","og_type":"article","og_title":"A new way of exploring the directing influence of (electron donating) substituents on benzene. - Henry Rzepa's Blog","og_description":"The knowledge that substituents on a benzene ring direct an electrophile engaged in a ring substitution reaction according to whether they withdraw or donate electrons is very old. Introductory organic chemistry tells us that electron donating substituents promote the ortho and para positions over the meta. 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The search query is shown above\u00a0(and is available here). As before, the distance is compared\u00a0from an electrophile,\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":"","src":"","width":0,"height":0},"classes":[]},{"id":16573,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16573","url_meta":{"origin":13962,"position":1},"title":"How does an OH or NH group approach an aromatic ring to hydrogen bond with its \u03c0-face?","author":"Henry Rzepa","date":"June 22, 2016","format":false,"excerpt":"I previously used data mining of crystal structures to explore the directing influence of substituents on aromatic and heteroaromatic rings. Here\u00a0I explore, quite literally, a different angle to the hydrogen bonding interactions between a benzene ring and\u00a0OH or NH groups. I start by defining a benzene ring with a centroid.\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":"aromatic-pi-query","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2016\/06\/aromatic-pi-query-1-e1466580253270.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":2423,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=2423","url_meta":{"origin":13962,"position":2},"title":"The oldest reaction mechanism: updated!","author":"Henry Rzepa","date":"September 14, 2010","format":false,"excerpt":"Unravelling reaction mechanisms is thought to be a 20th century phenomenon, coincident more or less with the development of electronic theories of chemistry. Hence electronic\u00a0arrow pushing as a term. But here I argue that the true origin of this immensely powerful technique in chemistry goes back to the 19th century.\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\/09\/wheland.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":9917,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=9917","url_meta":{"origin":13962,"position":3},"title":"Concerted vs stepwise (Meisenheimer) mechanisms for aromatic nucleophilic substitution.","author":"Henry Rzepa","date":"March 25, 2013","format":false,"excerpt":"My two previous explorations of aromatic substitutions have involved an electrophile (NO+ or Li+). Time now to look at a nucleophile, representing nucleophilic aromatic substitution. The mechanism of this is thought to pass through an intermediate analogous to the Wheland for an electrophile, this time known as the Meisenheimer complex.\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":"Click for 3D.","src":"https:\/\/i0.wp.com\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2013\/03\/trinitro.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":20440,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=20440","url_meta":{"origin":13962,"position":4},"title":"Free energy relationships and their linearity: a test example.","author":"Henry Rzepa","date":"January 13, 2019","format":false,"excerpt":"Linear free energy relationships (LFER) are associated with the dawn of physical organic chemistry in the late 1930s and its objectives in understanding chemical reactivity as measured by reaction rates and equilibria. The Hammett equation is the best known of the LFERs, albeit derived \"intuitively\". It is normally applied to\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":111,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=111","url_meta":{"origin":13962,"position":5},"title":"Aromatic electrophilic substitution: a different way of predicting regiospecificity","author":"Henry Rzepa","date":"April 4, 2009","format":false,"excerpt":"Every introductory course or text on aromatic electrophilic substitution contains an explanation along the lines of the resonance diagram shown below. With an o\/p directing group such as NH2, it is argued that negative charge accumulates in those positions as a result of the resonance structures shown. The opposite occurs\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":"groups1","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2009\/04\/groups1.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\/13962","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=13962"}],"version-history":[{"count":8,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/13962\/revisions"}],"predecessor-version":[{"id":26470,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/13962\/revisions\/26470"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=13962"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=13962"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=13962"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=13962"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}