{"id":16889,"date":"2016-09-22T13:07:30","date_gmt":"2016-09-22T12:07:30","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=16889"},"modified":"2016-10-03T09:58:37","modified_gmt":"2016-10-03T08:58:37","slug":"more-stereoelectronics-galore-hexamethylene-triperoxide-diamine","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16889","title":{"rendered":"More stereoelectronics galore: hexamethylene triperoxide diamine."},"content":{"rendered":"
\n

Compounds with O-O bonds often have weird properties. For example, artemisinin, which has some fascinating stereoelectronics<\/a>. Here is another such, recently in the news<\/a>\u00a0and\u00a0known as HMTD (hexamethylene triperoxide diamine).\u00a0The crystal structure was reported some time ago[1]<\/a><\/span> and the article included an inspection of the computed wavefunction. However this did not look at\u00a0the potential stereoelectronics in this species, which I\u00a0now address\u00a0here.<\/p>\n

\"hmtd\"<\/p>\n

A\u00a0\u03c9B97XD\/Def2-TZVPP calculation[2]<\/a><\/span> can be analysed for the NBO-derived interaction terms. This identifies an electron donor (normally a bond or a lone pair) and its E(2) perturbation energy interaction with an acceptor (normally an empty \u03c3*<\/sup> antibond). Here we are interested in the interaction between the nitrogen “lone pair” and the adjacent C-O\u00a0\u03c3*<\/sup>\u00a0antibond, of which there are six in the molecule due to the D3<\/sub> symmetry. E(2) is ~22.4 kcal\/mol, which is a large effect (the equivalent value for the so-called anomeric interaction between an oxygen lone pair and a C-O antibond is ~18 kcal\/mol). The effect of donation into the\u00a0empty C-O \u03c3*<\/sup>\u00a0antibond is to weaken it, unless the effect is balanced by a reciprocal interaction in the opposing direction, which is often the case in sugar-derived anomeric effects. Sugars of course are thermally relatively stable. In the case of HMTD, the reverse effect would be an oxygen Lp donating into the N-C\u00a0\u03c3*<\/sup>\u00a0antibond and this has the value of 14.5 kcal\/mol. Since the two are not balanced, this presumably contributes to the very unstable nature of this molecule.<\/p>\n

An alternative way of looking at what the electrons are up to is ELF,\u00a0a function based on the electron density which identifies the centroids of electron basins. The red arrows point to the four basins associated with the nitrogen “lone pair” (mostly the dumb-bell-shaped p-atomic orbital, hence four basins), and the integration being 3.2e for each nitrogen. This is a rather odd number for a “lone pair”. There is undoubtedly something unusual about this wavefunction which has yet to be identified.<\/p>\n

\"elf\"<\/p>\n

Finally, I ask how common the N(sp3<\/sup>)-C(sp3<\/sup>)-O-O structure motif might be?\u00a0In fact the Cambridge structure database has 81 entries! The scatterplot below includes 51 of them (no disorder, no errors, R<0.05). No clear-cut conclusions emerge from these statistics, except just a hint that as the C-O distance gets longer, the N-C distance might get shorter and that shorter N-C lengths\u00a0are associated with shorter O-O lengths.<\/p>\n

\"elf1\"<\/p>\n

 <\/p>\n

 <\/p>\n

 <\/p>\n

References<\/h2>\n
  1. A. Wierzbicki, E.A. Salter, E.A. Cioffi, and E.D. Stevens, \"Density Functional Theory and X-ray Investigations of P- and M-Hexamethylene Triperoxide Diamine and Its Dialdehyde Derivative\", The Journal of Physical Chemistry A<\/i>, vol. 105, pp. 8763-8768, 2001. https:\/\/doi.org\/10.1021\/jp0123841<\/a>\n\n<\/li>\n
  2. H. Rzepa, \"HMTD Hexamethylenetriperoxidediamine D3 NBO\", 2016. https:\/\/doi.org\/10.14469\/hpc\/1663<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    Compounds with O-O bonds often have weird properties. For example, artemisinin, which has some fascinating stereoelectronics. Here is another such, recently in the news\u00a0and\u00a0known as HMTD (hexamethylene triperoxide diamine).\u00a0The crystal structure was reported some time ago and the article included an inspection of the computed wavefunction. However this did not look at\u00a0the potential stereoelectronics 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":true,"_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":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[4],"tags":[1893,1895,1395,1412,1894,1410,1892,1833,1897,1896],"ppma_author":[2661],"class_list":["post-16889","post","type-post","status-publish","format-standard","hentry","category-interesting-chemistry","tag-amines","tag-artemisinin","tag-chemistry","tag-functional-groups","tag-hexamethylene-triperoxide-diamine","tag-organic-chemistry","tag-organic-peroxides","tag-peroxide","tag-perturbation-energy-interaction","tag-stereoelectronics"],"yoast_head":"\nMore stereoelectronics galore: hexamethylene triperoxide diamine. - 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=16889\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"More stereoelectronics galore: hexamethylene triperoxide diamine. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"Compounds with O-O bonds often have weird properties. For example, artemisinin, which has some fascinating stereoelectronics. Here is another such, recently in the news\u00a0and\u00a0known as HMTD (hexamethylene triperoxide diamine).\u00a0The crystal structure was reported some time ago and the article included an inspection of the computed wavefunction. However this did not look at\u00a0the potential stereoelectronics in […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16889\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2016-09-22T12:07:30+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2016-10-03T08:58:37+00:00\" \/>\n<meta property=\"og:image\" content=\"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2016\/09\/HMTD-1024x986.jpg\" \/>\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=\"2 minutes\" \/>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"More stereoelectronics galore: hexamethylene triperoxide diamine. - 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=16889","og_locale":"en_GB","og_type":"article","og_title":"More stereoelectronics galore: hexamethylene triperoxide diamine. - Henry Rzepa's Blog","og_description":"Compounds with O-O bonds often have weird properties. For example, artemisinin, which has some fascinating stereoelectronics. Here is another such, recently in the news\u00a0and\u00a0known as HMTD (hexamethylene triperoxide diamine).\u00a0The crystal structure was reported some time ago and the article included an inspection of the computed wavefunction. However this did not look at\u00a0the potential stereoelectronics in […]","og_url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16889","og_site_name":"Henry Rzepa's Blog","article_published_time":"2016-09-22T12:07:30+00:00","article_modified_time":"2016-10-03T08:58:37+00:00","og_image":[{"url":"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2016\/09\/HMTD-1024x986.jpg","type":"","width":"","height":""}],"author":"Henry Rzepa","twitter_card":"summary_large_image","twitter_misc":{"Written by":"Henry Rzepa","Estimated reading time":"2 minutes"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"Article","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16889#article","isPartOf":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16889"},"author":{"name":"Henry Rzepa","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/#\/schema\/person\/2b40f7b9c872a4dc1547e040a11b6281"},"headline":"More stereoelectronics galore: hexamethylene triperoxide diamine.","datePublished":"2016-09-22T12:07:30+00:00","dateModified":"2016-10-03T08:58:37+00:00","mainEntityOfPage":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16889"},"wordCount":416,"commentCount":1,"image":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16889#primaryimage"},"thumbnailUrl":"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2016\/09\/HMTD-1024x986.jpg","keywords":["Amines","Artemisinin","Chemistry","Functional groups","Hexamethylene triperoxide diamine","Organic chemistry","Organic peroxides","Peroxide","perturbation energy interaction","Stereoelectronics"],"articleSection":["Interesting chemistry"],"inLanguage":"en-GB","potentialAction":[{"@type":"CommentAction","name":"Comment","target":["https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16889#respond"]}]},{"@type":"WebPage","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16889","url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16889","name":"More stereoelectronics galore: hexamethylene triperoxide diamine. - 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=16889#primaryimage"},"image":{"@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16889#primaryimage"},"thumbnailUrl":"http:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2016\/09\/HMTD-1024x986.jpg","datePublished":"2016-09-22T12:07:30+00:00","dateModified":"2016-10-03T08:58:37+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=16889#breadcrumb"},"inLanguage":"en-GB","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16889"]}]},{"@type":"ImageObject","inLanguage":"en-GB","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16889#primaryimage","url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2016\/09\/HMTD.jpg","contentUrl":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2016\/09\/HMTD.jpg","width":1088,"height":1048},{"@type":"BreadcrumbList","@id":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16889#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"Home","item":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog"},{"@type":"ListItem","position":2,"name":"More stereoelectronics galore: hexamethylene triperoxide diamine."}]},{"@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\/pDef7-4op","jetpack-related-posts":[{"id":16610,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16610","url_meta":{"origin":16889,"position":0},"title":"Anomeric effects at carbon involving lone pairs originating from one or two nitrogens.","author":"Henry Rzepa","date":"July 8, 2016","format":false,"excerpt":"The previous post looked at anomeric effects set up on centres such as B, Si or P, and involving two oxygen groups attached to these atoms. Here I vary the attached groups to include either one or two nitrogen atoms..The\u00a0plot below shows aminols, C(NHR)(OR\"). A torsion along either the C-O\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":"aminol","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2016\/07\/aminol-1-1024x773.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":12276,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=12276","url_meta":{"origin":16889,"position":1},"title":"Artemisinin: are stereo-electronics at the core of its (re)activity?","author":"Henry Rzepa","date":"April 13, 2014","format":false,"excerpt":"Around 100 tons of the potent antimalarial artemisinin is produced annually; a remarkable quantity given its very unusual and fragile looking molecular structure (below). When I looked at this, I was immediately struck by a thought: surely this is a classic molecule for analyzing stereoelectronic effects (anomeric and gauche). Here\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":"artemisinin1","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2014\/04\/artemisinin1.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":14161,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=14161","url_meta":{"origin":16889,"position":2},"title":"The formation of tetrahedral intermediates.","author":"Henry Rzepa","date":"June 12, 2015","format":false,"excerpt":"In the preceding post, I discussed\u00a0the reaction between mCPBA (meta-chloroperbenzoic acid) and cyclohexanone, resulting in Baeyer-Villiger oxidation via a tetrahedral intermediate (TI). Dan Singleton, in whose group the original KIE (kinetic isotope measurements) were made, has kindly\u00a0pointed out\u00a0on this blog that his was a mixed-phase reaction, and that mechanistic comparison\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":16671,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16671","url_meta":{"origin":16889,"position":3},"title":"A periodic table for anomeric centres.","author":"Henry Rzepa","date":"August 6, 2016","format":false,"excerpt":"In the last few posts, I have explored the anomeric effect as it occurs at an atom centre X. Here I try to summarise the atoms for which the effect is manifest in crystal structures. The effect is defined by X bearing two substituents, one of which Z is a\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":[]},{"id":16696,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=16696","url_meta":{"origin":16889,"position":4},"title":"A periodic table for anomeric centres, this time with quantified interactions.","author":"Henry Rzepa","date":"August 8, 2016","format":false,"excerpt":"The previous post contained an exploration of the anomeric effect as it occurs at an atom centre X for which the effect is manifest in crystal structures. Here I\u00a0quantify the effect, by selecting the test molecule MeO-X-OMe, where X is of two types:A two-coordinate atom across the series B-O and\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":3111,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=3111","url_meta":{"origin":16889,"position":5},"title":"Combichem: an introductory example of the complexity of chemistry","author":"Henry Rzepa","date":"December 19, 2010","format":false,"excerpt":"Chemistry gets complex very rapidly. Consider the formula CH3NO as the topic for a tutorial in introductory chemistry. I challenge my group (of about 8 students) to draw as many different molecules as they can using exactly those atoms. I imply that perhaps each of them might find a different\u2026","rel":"","context":"In "General"","block_context":{"text":"General","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=1"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/www.ch.ic.ac.uk\/rzepa\/blog\/wp-content\/uploads\/2010\/12\/ch3noa.jpg?resize=350%2C200","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\/16889","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=16889"}],"version-history":[{"count":7,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/16889\/revisions"}],"predecessor-version":[{"id":16900,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/16889\/revisions\/16900"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=16889"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=16889"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=16889"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=16889"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}