{"id":25439,"date":"2022-08-17T18:13:30","date_gmt":"2022-08-17T17:13:30","guid":{"rendered":"https:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=25439"},"modified":"2022-09-11T06:15:42","modified_gmt":"2022-09-11T05:15:42","slug":"unexpected-isomerization-of-oxetane-carboxylic-acids-an-alternative-autocatalytic-mechanism-evaluated","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439","title":{"rendered":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 an alternative autocatalytic mechanism evaluated."},"content":{"rendered":"
\n

Previously, I looked at autocatalytic mechanisms where the carboxyl group of an oxetane-carboxylic acid could catalyse its transformation to a lactone, finding that a chain of two such groups were required to achieve the result. Here I look at an alternative mode where the oxetane-carboxylate itself acts as the transfer chain, via a H-bonded dimer shown below.<\/p>\n

\"\"<\/a><\/p>\n

The IRC energy profile is shown below for a C2<\/sub>-symmetric stationary point in which each molecule catalyses the opening of the other in a concerted manner. The apparent free energy barrier is 72.6 kcal\/mol\u00a0(\u03c9B97XD\/Def2-SVPP).<\/p>\n

\"\"<\/p>\n

\"\"<\/a> <\/sub><\/p>\n

In fact this is what is called a second order saddle point, having two negative force constants in its calculated diagonalised force constant matrix. To remove the unwanted one, it is necessary to find transition states that accomplish the transfer consecutively rather than concurrently. There are two and their IRC energy profiles are stitched together below. This shows also that the proton transfers (IRC -1, +2) also happen asynchronously.<\/p>\n

\"\"<\/a><\/sub><\/p>\n

This results in a lower barrier (49.0 kcal\/mol), but still far higher than the one obtained using a chain of two carboxylic acids. So this particular version of an autocatalytic transform is not in the event viable.<\/p>\n

 <\/p>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

Previously, I looked at autocatalytic mechanisms where the carboxyl group of an oxetane-carboxylic acid could catalyse its transformation to a lactone, finding that a chain of two such groups were required to achieve the result. Here I look at an alternative mode where the oxetane-carboxylate itself acts as the transfer chain, via a H-bonded dimer […]<\/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_feature_clip_id":0,"_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":[1086],"tags":[],"ppma_author":[2661],"class_list":["post-25439","post","type-post","status-publish","format-standard","hentry","category-reaction-mechanism-2"],"yoast_head":"\nUnexpected Isomerization of Oxetane-Carboxylic Acids \u2013 an alternative autocatalytic mechanism evaluated. - 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=25439\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 an alternative autocatalytic mechanism evaluated. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"Previously, I looked at autocatalytic mechanisms where the carboxyl group of an oxetane-carboxylic acid could catalyse its transformation to a lactone, finding that a chain of two such groups were required to achieve the result. Here I look at an alternative mode where the oxetane-carboxylate itself acts as the transfer chain, via a H-bonded dimer […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2022-08-17T17:13:30+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2022-09-11T05:15:42+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/oxetane-dimer.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=\"1 minute\" \/>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 an alternative autocatalytic mechanism evaluated. - 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=25439","og_locale":"en_GB","og_type":"article","og_title":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 an alternative autocatalytic mechanism evaluated. - Henry Rzepa's Blog","og_description":"Previously, I looked at autocatalytic mechanisms where the carboxyl group of an oxetane-carboxylic acid could catalyse its transformation to a lactone, finding that a chain of two such groups were required to achieve the result. Here I look at an alternative mode where the oxetane-carboxylate itself acts as the transfer chain, via a H-bonded dimer […]","og_url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439","og_site_name":"Henry Rzepa's Blog","article_published_time":"2022-08-17T17:13:30+00:00","article_modified_time":"2022-09-11T05:15:42+00:00","og_image":[{"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/oxetane-dimer.svg","type":"","width":"","height":""}],"author":"Henry Rzepa","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Henry Rzepa","Estimated reading time":"1 minute"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439#article","isPartOf":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439"},"author":{"name":"Henry Rzepa","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281"},"headline":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 an alternative autocatalytic mechanism evaluated.","datePublished":"2022-08-17T17:13:30+00:00","dateModified":"2022-09-11T05:15:42+00:00","mainEntityOfPage":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439"},"wordCount":212,"commentCount":0,"image":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439#primaryimage"},"thumbnailUrl":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/oxetane-dimer.svg","articleSection":["reaction mechanism"],"inLanguage":"en-GB","potentialAction":[{"@type":"CommentAction","name":"Comment","target":["https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439#respond"]}]},{"@type":"WebPage","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439","url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439","name":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 an alternative autocatalytic mechanism evaluated. - Henry Rzepa's Blog","isPartOf":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#website"},"primaryImageOfPage":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439#primaryimage"},"image":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439#primaryimage"},"thumbnailUrl":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/oxetane-dimer.svg","datePublished":"2022-08-17T17:13:30+00:00","dateModified":"2022-09-11T05:15:42+00:00","author":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281"},"breadcrumb":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439#breadcrumb"},"inLanguage":"en-GB","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439"]}]},{"@type":"ImageObject","inLanguage":"en-GB","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439#primaryimage","url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/oxetane-dimer.svg","contentUrl":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/oxetane-dimer.svg"},{"@type":"BreadcrumbList","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25439#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog"},{"@type":"ListItem","position":2,"name":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 an alternative autocatalytic mechanism evaluated."}]},{"@type":"WebSite","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#website","url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/","name":"Henry Rzepa's Blog","description":"Chemistry with a twist","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"en-GB"},{"@type":"Person","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281","name":"Henry Rzepa","image":{"@type":"ImageObject","inLanguage":"en-GB","@id":"https:\/\/secure.gravatar.com\/avatar\/897b6740f7f599bca7942cdf7d7914af5988937ae0e3869ab09aebb87f26a731?s=96&d=blank&r=g370be3a7397865e4fd161aefeb0a5a85","url":"https:\/\/secure.gravatar.com\/avatar\/897b6740f7f599bca7942cdf7d7914af5988937ae0e3869ab09aebb87f26a731?s=96&d=blank&r=g","contentUrl":"https:\/\/secure.gravatar.com\/avatar\/897b6740f7f599bca7942cdf7d7914af5988937ae0e3869ab09aebb87f26a731?s=96&d=blank&r=g","caption":"Henry Rzepa"},"description":"Henry Rzepa is Emeritus Professor of Computational Chemistry at Imperial College London.","sameAs":["https:\/\/orcid.org\/0000-0002-8635-8390"],"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?author=1"}]}},"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/pDef7-6Cj","jetpack-related-posts":[{"id":25391,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25391","url_meta":{"origin":25439,"position":0},"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":25313,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25313","url_meta":{"origin":25439,"position":1},"title":"Unexpected Isomerization of Oxetane-Carboxylic Acids – a first look at the mechanism","author":"Henry Rzepa","date":"August 7, 2022","format":false,"excerpt":"Derek Lowe's blog has a recent post entitled A Downside to Oxetane Acids which picks up on a recent article describing how these acids are unexpectedly unstable, isomerising to a lactone at a significant rate without the apparent need for any catalyst. This is important because these types of compound\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":25338,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25338","url_meta":{"origin":25439,"position":2},"title":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 a viable mechanism","author":"Henry Rzepa","date":"August 12, 2022","format":false,"excerpt":"In the previous post, I looked at the intramolecular rearrangement of the oxetane carboxylic acid to a lactone, finding the barrier to the Sn2 reaction with retention was unfeasibly high. Here I explore alternatives. This first attempt uses a second molecule of a carboxylic acid (modelled as formic acid for\u2026","rel":"","context":"Similar post","block_context":{"text":"Similar post","link":""},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/Rtn.gif?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/Rtn.gif?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2022\/08\/Rtn.gif?resize=525%2C300&ssl=1 1.5x"},"classes":[]},{"id":25415,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=25415","url_meta":{"origin":25439,"position":3},"title":"Unexpected Isomerization of Oxetane-Carboxylic Acids \u2013 substrate design.","author":"Henry Rzepa","date":"August 14, 2022","format":false,"excerpt":"Having established a viable model for the unexpected isomerism of oxetane carboxylic acids to lactones, and taken a look at a variation in the proton transfer catalyst needed to accomplish the transformation, I now investigate the substrate itself. R' is set to have three values, R'=H (the original substituent), R'=\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":5114,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=5114","url_meta":{"origin":25439,"position":4},"title":"Mechanism of the reduction of a carboxylic acid by borane: revisited and revised.","author":"Henry Rzepa","date":"October 16, 2011","format":false,"excerpt":"I asked a while back\u00a0whether blogs could be considered a serious form of scholarly scientific communication (and so has Peter Murray-Rust more recently). A case for doing so might be my post of about a year ago, addressing why borane reduces a carboxylic acid, but not its ester, where I\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\/2011\/10\/acyloxy1-page001.svg","width":350,"height":200},"classes":[]},{"id":6816,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=6816","url_meta":{"origin":25439,"position":5},"title":"The mechanism (in 4D) of the reaction between thionyl chloride and a carboxylic acid.","author":"Henry Rzepa","date":"May 25, 2012","format":false,"excerpt":"If you have not previously visited, take a look at Nick Greeves' ChemTube3D\u00a0, an\u00a0ever-expanding gallery of reactions and their mechanisms. The 3D is because all molecules are offered with X, Y and z coordinates. You also get arrow pushing\u2021\u00a0in 3D. Here, I argue that we should adopt Einstein, and go\u2026","rel":"","context":"In \"acetic acid\"","block_context":{"text":"acetic acid","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?tag=acetic-acid"},"img":{"alt_text":"","src":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2012\/05\/thionyl.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","author_category":"1","first_name":"Henry","last_name":"Rzepa","user_url":"https:\/\/orcid.org\/0000-0002-8635-8390","job_title":"","description":"Henry Rzepa is Emeritus Professor of Computational Chemistry at Imperial College London."}],"_links":{"self":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/25439","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=25439"}],"version-history":[{"count":4,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/25439\/revisions"}],"predecessor-version":[{"id":25447,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/25439\/revisions\/25447"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=25439"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=25439"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=25439"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=25439"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}