{"id":7158,"date":"2012-07-19T13:43:14","date_gmt":"2012-07-19T12:43:14","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=7158"},"modified":"2012-07-21T18:01:12","modified_gmt":"2012-07-21T17:01:12","slug":"dynamic-effects-in-nucleophilic-substitution-at-trigonal-carbon-with-na","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=7158","title":{"rendered":"Dynamic effects in nucleophilic substitution at trigonal carbon (with Na+)."},"content":{"rendered":"
\n

In the preceding post<\/a>, I described a fascinating experiment and calculation by Bogle and Singleton<\/a>, in which the trajectory\u00a0distribution of molecules emerging from a single<\/strong> transition state was used to rationalise the formation of two isomeric products 2<\/strong> and 3.\u00a0<\/strong>\u00a0In the present post, I explore possible consequences of including a sodium cation (X=Na+<\/sup> below) in the computational model.<\/p>\n

\"\"<\/p>\n

Sitting down to construct such a model, one is immediately faced with important decisions. Na+<\/sup> comes with baggage, namely groupies in the form of solvent molecules and ionic bonding. The latter means less certainty regarding where to place the ion (covalent bonds have that nice attribute that their orientation and length is pretty predictable most of the time). I decided to construct the model shown below, using not one Na+<\/sup> but two (such structures are known from the Cambridge crystal data base), the second Na+<\/sup> being charge balanced by hydroxide anion.<\/p>\n

\"\"<\/p>\n

The resulting transition state<\/a>\u00a0(B3LYP\/6-31+G(d,p)\/CPCM=ethanol) is shown below, and the free energy activation barrier, \u0394G\u2020<\/sup>\u00a0is 11.7<\/strong> kcal\/mol, well down on the value obtained using X=H+<\/sup>, and entirely reasonable for a reaction occurring at room temperature. This suggests that the model is\u00a0not unreasonable (but of course does not prove it is the best).<\/p>\n

\"\"<\/p>\n

The geometry of this transition state is significant. Of the two C-Cl bond lengths, the shorter (click the image above to inspect the model) is the one cis<\/em> to the carbonyl (subsequent elimination of which would result in formation of the major product 2<\/strong>). But an IRC reveals<\/a> what happens next. Recollect that when\u00a0X=H+<\/sup> a tetrahedral intermediate is formed that then collapses with elimination of H3<\/sub>O+<\/sup>Cl–<\/sup>. This time, no intermediate is seen on the IRC, and the requisite C-Cl bond is broken to form 2<\/strong> in a concerted (but very asynchronous) manner, and in the manner reported by Bogle and Singleton<\/a>\u00a0for a model without counterion and explicit solvent.<\/p>\n

\"\"<\/p>\n\n\n\n
\"\"<\/td>\n\"\"<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Notice how preparation for eviction of the C-Cl bond only starts after<\/strong> the transition state is passed. The forces on the departing chloride start to grow after the dihedral angle of the Ar-S-C-Cl system has become antiperiplanar (IRC -3), resulting in the anion shooting out towards one of the two Na+<\/sup> cations to form solvated NaCl.<\/p>\n

\"\"<\/p>\n

So we now have a rather more complete model. But is it yet complete enough? How would one go about evicting the other chloride, resulting in formation of 3<\/strong>? I think it is fairly clear that the model will have to be enlarged yet again, this time to include at least one more Na+<\/sup> located on the other side of the carbonyl, and ready to receive the anion. Possibly at least another two water molecules and one hydroxide anion would be required to surround this cation. Clearly, such a model would have grown substantially compared to the original one (Occam might not be happy), and that we are gradually edging towards having two quite separate transition state models to account for each of 2<\/strong> and 3<\/strong>. At this stage, it would be interesting to apply Bogle and Singleton<\/a>‘s\u00a0direct dynamics model to try to establish if each transition state leads to only one product, or whether either of these transition states could result in cross-over to the other product.<\/p>\n

I have no feel for whether the\u00a0\u00a0transition state<\/a>\u00a0presented here can be treated using direct dynamics; if it could, that would indeed be an interesting simulation.<\/p>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

In the preceding post, I described a fascinating experiment and calculation by Bogle and Singleton, in which the trajectory\u00a0distribution of molecules emerging from a single transition state was used to rationalise the formation of two isomeric products 2 and 3.\u00a0\u00a0In the present post, I explore possible consequences of including a sodium cation (X=Na+ below) in […]<\/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":false,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[],"tags":[144,866,843,721],"ppma_author":[2661],"class_list":["post-7158","post","type-post","status-publish","format-standard","hentry","tag-cambridge","tag-isomeric-products","tag-reaction-mechanism","tag-simulation"],"yoast_head":"\nDynamic effects in nucleophilic substitution at trigonal carbon (with Na+). - 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=7158\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Dynamic effects in nucleophilic substitution at trigonal carbon (with Na+). - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"In the preceding post, I described a fascinating experiment and calculation by Bogle and Singleton, in which the trajectory\u00a0distribution of molecules emerging from a single transition state was used to rationalise the formation of two isomeric products 2 and 3.\u00a0\u00a0In the present post, I explore possible consequences of including a sodium cation (X=Na+ below) in […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=7158\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2012-07-19T12:43:14+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2012-07-21T17:01:12+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/07\/singleton.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=\"3 minutes\" \/>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Dynamic effects in nucleophilic substitution at trigonal carbon (with Na+). - 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Kinetic isotope effect models for a general acid as a catalyst in the protiodecarboxylation of indoles.","author":"Henry Rzepa","date":"January 10, 2016","format":false,"excerpt":"Earlier I explored models for the heteroaromatic electrophilic protiodecarboxylation of an 3-substituted indole, focusing on the role of water as the proton transfer and delivery agent. Next, came\u00a0models for both water and the general base catalysed\u00a0ionization of indolinones. Here I\u00a0explore\u00a0general acid\u00a0catalysis by evaluating the properties of two possible models for\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":15295,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=15295","url_meta":{"origin":7158,"position":1},"title":"I\u2019ve started so I\u2019ll finish. 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The kinetics are again complex, the mechanism involving protonation\u2021 of the indole carboxylate (by a general acid), followed by the presumption of a zwitterionic Wheland intermediate that then loses carbon dioxide in a second step (blue arrows).\u2026","rel":"","context":"In "Historical"","block_context":{"text":"Historical","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=565"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":7779,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=7779","url_meta":{"origin":7158,"position":2},"title":"Oxime formation from hydroxylamine and ketone: a (computational) reality check on stage one of the mechanism.","author":"Henry Rzepa","date":"September 23, 2012","format":false,"excerpt":"The mechanism of forming an oxime from nucleophilic addition of a hydroxylamine to a ketone is taught early on in most courses of organic chemistry. Here I subject the first step of this reaction to form a tetrahedral intermediate to quantum mechanical scrutiny. The first decision is to decide which\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.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/09\/hydroxylamine%2Bacetone-O-1H2O-6-ring_small.gif?resize=350%2C200&ssl=1","width":350,"height":200},"classes":[]},{"id":13458,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=13458","url_meta":{"origin":7158,"position":3},"title":"How many water molecules does it take to ionise HF and HBr?","author":"Henry Rzepa","date":"February 27, 2015","format":false,"excerpt":"No doubt answers to the question posed in the previous post\u00a0are already being obtained by experiment. Just in case that does not emerge in the next day or so, I offer a prediction here. The methodology is the same as before, and I have not tried to look for new\u2026","rel":"","context":"In "General"","block_context":{"text":"General","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":26997,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=26997","url_meta":{"origin":7158,"position":4},"title":"Exploring Methanetriol – “the Formation of an Impossible Molecule”","author":"Henry Rzepa","date":"May 16, 2024","format":false,"excerpt":"What constitutes an \"impossible molecule\"? Well, here are two, the first being the topic of a recent article. The second is a favourite of organic chemistry tutors, to see if their students recognise it as an unusual (= impossible) form of a much better known molecule. Perhaps we could define\u2026","rel":"","context":"With 2 comments","block_context":{"text":"With 2 comments","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=26997#comments"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2024\/05\/COLRUT.gif?resize=350%2C200&ssl=1","width":350,"height":200},"classes":[]},{"id":6477,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6477","url_meta":{"origin":7158,"position":5},"title":"Stereoselectivities of Proline-Catalyzed Asymmetric Intermolecular Aldol Reactions.","author":"Henry Rzepa","date":"April 22, 2012","format":false,"excerpt":"Astronomers who discover an asteroid get to name it, mathematicians have theorems named after them. Synthetic chemists get to name molecules (Hector's base and Meldrum's acid spring to mind) and reactions between them. What do computational chemists get to name? Transition states! One of the most famous of recent years\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":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/04\/Houk.svg","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\/7158","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=7158"}],"version-history":[{"count":43,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/7158\/revisions"}],"predecessor-version":[{"id":7220,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/7158\/revisions\/7220"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=7158"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=7158"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=7158"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=7158"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}