{"id":5483,"date":"2011-11-13T18:24:23","date_gmt":"2011-11-13T18:24:23","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=5483"},"modified":"2018-03-11T07:33:42","modified_gmt":"2018-03-11T07:33:42","slug":"the-dawn-of-organic-reaction-mechanism-the-prequel","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=5483","title":{"rendered":"The dawn of organic reaction mechanism: the prequel."},"content":{"rendered":"
\n

Following on from Armstrong’s almost electronic theory of chemistry<\/a>\u00a0in 1887-1890,\u00a0and Beckmann’s radical idea around the same time that molecules undergoing transformations\u00a0might do so via a reaction\u00a0mechanism<\/em><\/strong> involving unseen intermediates (in his case, a transient enol of a ketone<\/a>) I here describe how these concepts underwent further evolution in the early 1920s. My focus is on Edith Hilda Usherwood, who was then a PhD student at Imperial College working under the supervision of Martha Whitely.1<\/sup><\/p>\n

The doctoral degree itself had only been introduced into British universities in 1919,1<\/sup> and so Usherwood was very much a forerunner of the modern system of training.The academic staff and students at Imperial totalled 30, making it one of the largest research schools in UK chemistry at the time. Usherwood’s project was on tautomers, or isomers of molecules which differ only in the position of a labile hydrogen atom. The then quite novel electron-pair symbolism introduced by\u00a0G. N. Lewis’\u00a0<\/a>in\u00a01916\u00a0was adopted to represent two\u00a0tautomeric equilibria<\/a>\u00a0(the supposed mobile or tautomeric hydrogens being enclosed in […])2<\/sup><\/p>\n

    \n
  1. [H]C:::N \u21d4 C::N[H]<\/li>\n
  2. [H]C:::CH\u00a0\u21d4\u00a0C::CH[H]<\/li>\n<\/ol>\n

    or in our more modern representation (in which lines replace colons, and charges are used to ensure the octet rule is adhered to when possible):<\/p>\n

      \n
    1. H-C\u2261N \u21d4 –<\/sup>C\u2261N+<\/sup>-H<\/li>\n
    2. HC\u2261CH\u00a0\u21d4 :C=CH2<\/sub><\/li>\n<\/ol>\n

      Modern structural techniques such as electron diffraction or microwave spectroscopies not yet existing, the problem was tackled using specific heat measurements as a function of temperature. This method suggested to Usherwood that for e.g.<\/strong> equilibrium 2<\/strong>, the concentration of iso-acetylene (we now call this vinylidene) was insignificant at ordinary temperatures, but it became appreciable between 200-300\u00b0C. Further evidence was claimed for the formation of the “unseen” vinylidene by observing ketene as a by-product of the oxidation of acetylene. This article very much set the trend of (an almost mandatory) speculation on the outcome of (nowadays much more complex) reactions by the need to formulate a reaction mechanism in which various (otherwise undetected but) plausible intermediates are involved.<\/p>\n

      Moving on some 90 years, and how might one approach such a problem nowadays? Well, I have oft argued on this blog that a good place to obtain an immediate reality check on a proposed mechanism<\/a> is a calculation. It will come as no surprise that a very accurate calculation can be done on the systems shown above. For example, CCSD(T)\/cc-pVTZ will yield a free energy for the equilibria with a pretty small error (< 1 kcal\/mol). We use \u0394G = -RT Ln K to inter-convert free energies and equilibrium constants. If we are generous and state that in order to observe an appreciable concentration of a minor species, the equilibrium constant can be no smaller than 10-3<\/sup>, its energy cannot be greater than 4 kcal\/mol above the more abundant isomer. Our reality check will be to see if the free energy of vinylidene is indeed no more than 4 kcal\/mol greater than acetylene. Well, CCSD(T)\/cc-pVTZ predicts vinylidene is 41.3 kcal\/mol higher @298K, reduced to 33.8 @2000K (and before you ask, these results took a total of perhaps 30 minutes to obtain).<\/p>\n

      In 1924, the concept of calculating the relative energies of two species using first principles was not even a glimmer on the horizon. The nature of mechanisms was slowly and often painfully established by recourse to experiments alone. And many of the unseen intermediates often remained just such, their existence only inferred indirectly from the models one constructed (of specify heats in\u00a0Usherwood’s case). It is perhaps no great surprise that these models do not always stand the test of time. In this case, within a year of Usherwood’s publication, Partington<\/a> was suggesting that the model for the specific heats of acetylene should have included allowance for polymer formation.3<\/sup>\u00a0The modern take, armed with the calculation I note above, might in fact side with Partington after all. As for the formation of ketene by oxidation, it is indeed known that (peracid) oxidation of an alkyne will produce ketene, but the modern mechanism (an interesting exercise in arrow pushing for a student) does not involve vinylidene intermediates.<\/p>\n

      I will add at this point that Hilda Usherwood was married to Christopher Ingold, and the pair of them subsequently published many of the seminal articles in what became known as physical organic chemistry. That legacy continues to this day with (as I noted above) the almost mandatory speculation about the mechanism of any new reaction. But it is only in the last five years or so that these speculations have started to be increasingly tested against reliably accurate computation. A new era is underway.<\/p>\n

      \n

      1<\/sup> My post was inspired by reading W. H. Brock, \u201cThe case of the Poisonous Socks\u201d, chapter 28, RSC Publishing, 2011, 978-1-84973-324-3.<\/p>\n

      2<\/sup> These representations are taken from ref 1, p 225 (and include a correction of replacing C:C as drawn there by C::C. The original article apparently appeared in the proceedings of the British Association of 1924, which is not yet available online.<\/p>\n

      3<\/sup> Brock, in ref 1, p226, suggests that\u00a0Usherwood stood her ground on this one, and won her case by showing that Partington’s evidence for polymerization was valid for only a small part of the temperature range she had investigated. I have not managed to track down the original sources for this exchange.<\/p>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

      Following on from Armstrong’s almost electronic theory of chemistry\u00a0in 1887-1890,\u00a0and Beckmann’s radical idea around the same time that molecules undergoing transformations\u00a0might do so via a reaction\u00a0mechanism involving unseen intermediates (in his case, a transient enol of a ketone) I here describe how these concepts underwent further evolution in the early 1920s. My focus is on […]<\/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":[4],"tags":[908,676,767,24,40,766,2651,37,768,769,126,747,635],"ppma_author":[2661],"class_list":["post-5483","post","type-post","status-publish","format-standard","hentry","category-interesting-chemistry","tag-200-300","tag-by-product","tag-christopher-ingold","tag-energy","tag-free-energy","tag-hilda-usherwood","tag-historical","tag-imperial-college","tag-martha-whitely","tag-microwave","tag-polymerization","tag-rsc-publishing","tag-united-kingdom"],"yoast_head":"\nThe dawn of organic reaction mechanism: the prequel. - 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=5483\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The dawn of organic reaction mechanism: the prequel. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"Following on from Armstrong’s almost electronic theory of chemistry\u00a0in 1887-1890,\u00a0and Beckmann’s radical idea around the same time that molecules undergoing transformations\u00a0might do so via a reaction\u00a0mechanism involving unseen intermediates (in his case, a transient enol of a ketone) I here describe how these concepts underwent further evolution in the early 1920s. 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Nick Greeves, purveyor of the excellent ChemTube3D site, contacted me about the\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":"cis-diazo","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2014\/03\/cis-diazo.gif?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":19828,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=19828","url_meta":{"origin":5483,"position":1},"title":"The “White City Trio” – The formation of an amide from an acid and an amine in non-polar solution (updated).","author":"Henry Rzepa","date":"August 8, 2018","format":false,"excerpt":"White City is a small area in west london created as an exhibition site in 1908, morphing over the years into an Olympic games venue, a greyhound track, the home nearby of the BBC (British Broadcasting Corporation) and most recently the new western campus for Imperial College London.\u2663 The first\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\/2018\/08\/reactants-1024x719.jpg?resize=350%2C200&ssl=1","width":350,"height":200},"classes":[]},{"id":25391,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25391","url_meta":{"origin":5483,"position":2},"title":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 catalyst design.","author":"Henry Rzepa","date":"August 13, 2022","format":false,"excerpt":"Previously, a mechanism with a reasonable predicted energy was modelled for the isomerisation of an oxetane carboxylic acid to a lactone by using two further molecules of acid to transfer the proton and in the process encouraging an Sn2 reaction with inversion to open the oxetane ring. We are now\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":17771,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=17771","url_meta":{"origin":5483,"position":3},"title":"Reaction coordinates vs Dynamic trajectories as illustrated by an example reaction mechanism.","author":"Henry Rzepa","date":"March 20, 2017","format":false,"excerpt":"The example a few posts back of how methane might invert its configuration by transposing two hydrogen atoms illustrated the reaction mechanism by locating a transition state and following it down in energy using an intrinsic reaction coordinate\u00a0(IRC). Here I explore an alternative method based instead on computing a molecular\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":20440,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=20440","url_meta":{"origin":5483,"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":20354,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=20354","url_meta":{"origin":5483,"position":5},"title":"Epoxidation of ethene: a new substituent twist.","author":"Henry Rzepa","date":"December 21, 2018","format":false,"excerpt":"Five years back,\u00a0I speculated about the mechanism of the epoxidation of ethene by a peracid, concluding that kinetic isotope effects provided interesting evidence that this mechanism is highly asynchronous and involves a so-called \"hidden intermediate\". Here I revisit this reaction in which a small change is applied to the atoms\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\/2018\/12\/imine2.gif?resize=350%2C200&ssl=1","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\/5483","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=5483"}],"version-history":[{"count":1,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/5483\/revisions"}],"predecessor-version":[{"id":19497,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/5483\/revisions\/19497"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=5483"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=5483"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=5483"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=5483"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}