{"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":"2025-07-22T07:42:35","modified_gmt":"2025-07-22T06:42:35","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.rzepa.net\/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":"
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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

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This post has DOI: 10.59350\/rzepa.29121<\/a><\/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<\/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,"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":[1085],"tags":[],"class_list":["post-29121","post","type-post","status-publish","format-standard","hentry","category-reaction-mechanism-2"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p1gPyz-7zH","jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/29121","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=29121"}],"version-history":[{"count":0,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/29121\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=29121"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=29121"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=29121"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}