{"id":29121,"date":"2025-07-22T07:42:35","date_gmt":"2025-07-22T06:42:35","guid":{"rendered":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=29121"},"modified":"2025-08-21T13:56:59","modified_gmt":"2025-08-21T12:56:59","slug":"why-an-electron-withdrawing-group-is-an-o-m-director-rather-than-m-director-in-electrophilic-aromatic-substitution-the-example-of-cn-vs-nc","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=29121","title":{"rendered":"Why an Electron-Withdrawing Group is an o, m-Director rather than m-Director in Electrophilic Aromatic Substitution: The example of CN vs NC."},"content":{"rendered":"
\n

In the previous post[1]<\/a><\/span> I followed up on an article published on the theme “Physical Organic Chemistry: Never Out of Style<\/em>“.[2]<\/a><\/span> Paul Rablen presented the case that the amount of o<\/em> (ortho) product in electrophilic substitution of a phenyl ring bearing an EWG (electron withdrawing group) is often large enough to merit changing the long held rule-of-thumb for EWGs from being just meta directors into being ortho and<\/b> meta-directors, with a preference for meta.<\/em> I showed how Paul’s elegant insight could be complemented by an NBO7 analysis of the donor-acceptor interactions in the σ-complex formed by protonating the phenyl ring bearing the EWG. Both the o<\/em>– and m<\/em>– isomers showed similar NBO orbital patterns and associated E(2) donor\/acceptor interaction energies and also matched the observation that the proportion of meta is modestly greater than ortho substitution (steric effects not modelled). These interactions were both very different from those calculated for the para isomer. <\/p>\n

Here using the same NBO7 analysis, I look at what happens when you transpose the atoms of CN to form the isocyanide NC.<\/p>\n

\"\"<\/p>\n

The orbital overlaps for NC as substituent can be seen as 3D rotatable models below (click on image to open model).<\/p>\n\n\n\n\n
\"\"<\/td>\n\"\"<\/td>\n<\/tr>\n
\"\"<\/td>\n\"\"<\/td>\n<\/tr>\n
\n\"\"<\/td>\n<\/tr>\n<\/table>\n

<\/p>\n

These effects (ωB97XD\/Def2-QZVPP\/SCRF=DCM) can be summarised in the table below.<\/p>\n\n\n\n\n\n\n\n\n\n
ΔΔG, kcal\/mol<\/th>\n o<\/i><\/th>\nm<\/i><\/th>\np<\/i><\/th>\n<\/tr>\n
CN<\/td>\n0.51<\/td>\n0.0<\/td>\n1.23<\/td>\n<\/tr>\n
NC<\/td>\n0.36<\/td>\n2.86<\/td>\n0.0<\/td>\n<\/tr>\n
NBO7 E(2) Terms:<\/th>\no<\/i><\/th>\nm<\/i><\/th>\np<\/i><\/th>\n<\/tr>\n
CN as donor<\/td>\n14.3<\/td>\n9.4<\/td>\n0.2<\/td>\n<\/tr>\n
CN as acceptor<\/td>\n18.8<\/td>\n23.9<\/td>\n0.2<\/td>\n<\/tr>\n
NC as donor<\/td>\n28.8<\/td>\n17.9<\/td>\n0.4<\/td>\n<\/tr>\n
NC as acceptor<\/td>\n12.4<\/td>\n15.7<\/td>\n–<\/td>\n<\/tr>\n<\/table>\n

What emerges is that the two groups cyanide (CN) and isocyanide (NC) can act as both<\/b> π-electron acceptors and<\/b> π-electron donors. For the former, the o<\/i>– and m<\/i>– electron acceptor interactions are larger, whilst for the latter the o<\/i>– and m<\/i>– electron donor effects dominate. However, the interactions for both o<\/i>– and m<\/i>– are qualitatively very similar and it is therefore correct to group them together, as was implied in the title of the recently published article.[2]<\/a><\/span> In contrast it seems appropriate to treat p<\/i>– direction as a qualitatively different effect.<\/p>\n

\n

This post has DOI: [3]<\/a><\/span><\/p>\n

References<\/h2>\n
  1. H. Rzepa, \""Typical Electron-Withdrawing Groups Are o, m-Directors Rather than m-Directors in Electrophilic Aromatic Substitution"\", 2025. https:\/\/doi.org\/10.59350\/rzepa.28993<\/a>\n\n<\/li>\n
  2. P.R. Rablen, \"Typical Electron-Withdrawing Groups Are <i>ortho<\/i>, <i>meta<\/i>-Directors Rather than <i>meta<\/i>-Directors in Electrophilic Aromatic Substitution\", The Journal of Organic Chemistry<\/i>, vol. 90, pp. 6090-6093, 2025. https:\/\/doi.org\/10.1021\/acs.joc.5c00426<\/a>\n\n<\/li>\n
  3. H. Rzepa, \"Why an Electron-Withdrawing Group is an o, m-Director rather than m-Director in Electrophilic Aromatic Substitution: The example of CN vs NC.\", 2025. https:\/\/doi.org\/10.59350\/rzepa.29121<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    In the previous post I followed up on an article published on the theme “Physical Organic Chemistry: Never Out of Style“. Paul Rablen presented the case that the amount of o (ortho) product in electrophilic substitution of a phenyl ring bearing an EWG (electron withdrawing group) is often large enough to merit changing the long […]<\/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":"federated","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":[1086],"tags":[],"ppma_author":[2661],"class_list":["post-29121","post","type-post","status-publish","format-standard","hentry","category-reaction-mechanism-2"],"yoast_head":"\nWhy an Electron-Withdrawing Group is an o, m-Director rather than m-Director in Electrophilic Aromatic Substitution: The example of CN vs NC. - 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=29121\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Why an Electron-Withdrawing Group is an o, m-Director rather than m-Director in Electrophilic Aromatic Substitution: The example of CN vs NC. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"In the previous post I followed up on an article published on the theme “Physical Organic Chemistry: Never Out of Style“. 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Introductory organic chemistry tells us that electron donating substituents promote the ortho and para positions over the meta. Here I try 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":14492,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=14492","url_meta":{"origin":29121,"position":2},"title":"Mesomeric resonance in substituted benzenes: a crystallographic reality check.","author":"Henry Rzepa","date":"August 26, 2015","format":false,"excerpt":"Previously, I showed how conjugation in dienes and diaryls can be visualised by inspecting bond lengths as a function of torsions. Here is another illustration, this time of the mesomeric resonance on a benzene ring induced by an electron donating substituent (an amino group) or an electron withdrawing substituent (cyano).\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":2423,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=2423","url_meta":{"origin":29121,"position":3},"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":12115,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12115","url_meta":{"origin":29121,"position":4},"title":"Aromatic electrophilic substitution. A different light on the bromination of benzene.","author":"Henry Rzepa","date":"March 12, 2014","format":false,"excerpt":"My previous post related to the aromatic electrophilic substitution of benzene using as electrophile phenyl diazonium chloride. Another prototypical reaction, and again one where benzene is too inactive for the reaction to occur easily, is the catalyst-free bromination of benzene to give bromobenzene and HBr.\u00a0 The \"text-book\" mechanism involves nucleophilic\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":"br2+benzene","src":"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2014\/03\/br2+benzene.svg","width":350,"height":200},"classes":[]},{"id":16563,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16563","url_meta":{"origin":29121,"position":5},"title":"Exploring the electrophilic directing influence of heteroaromatic rings using crystal structure data mining.","author":"Henry Rzepa","date":"June 21, 2016","format":false,"excerpt":"This is a follow-up to the post on\u00a0exploring the directing influence of (electron donating) substituents on benzene with the focus on heteroaromatic rings such indoles, pyrroles and group 16 analogues (furans, thiophenes etc). 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":[]}],"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\/29121","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=29121"}],"version-history":[{"count":102,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/29121\/revisions"}],"predecessor-version":[{"id":29600,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/29121\/revisions\/29600"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=29121"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=29121"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=29121"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=29121"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}