{"id":13899,"date":"2015-04-12T21:41:26","date_gmt":"2015-04-12T20:41:26","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=13899"},"modified":"2025-10-15T13:23:21","modified_gmt":"2025-10-15T12:23:21","slug":"the-mechanism-of-borohydride-reductions-part-1-ethanal","status":"publish","type":"post","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=13899","title":{"rendered":"The mechanism of borohydride reductions. Part 1: ethanal."},"content":{"rendered":"
\n

Sodium borohydride<\/a> is the tamer cousin of lithium aluminium hydride<\/a> (LAH). It is used in aqueous solution to e.g.<\/em> reduce aldehydes and ketones, but it leaves acids, amides and esters alone. Here I start an exploration of why it is such a different reducing agent.
\n\"BH4\"<\/a><\/p>\n

Initially, I am using Li, not Na (X=Li), to enable a more or less equal comparison with LAH, with water molecules to solvate rather than ether (n=2,3,5) and R set to Me. First, n=2, for which the IRC is shown below. In this model, we will assume that the carbonyl has not first reacted with water to form a gem<\/em>-diol. The free energy barrier is 9.6 kcal\/mol (\u03c9B97XD\/6-311+G(d,p)\/SCRF=water) which corresponds to a very fast reaction at room temperatures.<\/p>\n

\"BH4a\"
\nThe immediate product is, if anything, more interesting than the transition state[1]<\/a><\/span> with quite a stretched length for the newly formed C-H bond and predicted stretching wavenumber for this bond of 2137 cm-1<\/sup>. This effect is similar to that seen for the LAH reduction of cinnamaldehyde<\/a>, and is due to stereoelectronic antiperiplanar alignment of the oxyanionic oxygen lone pair with the C-H bond. This species is also some 6.5 kcal\/mol higher in energy than the reactant, and is clearly not the final product of the reaction (which must contain e.g. B-O bonds), the mechanism for which will not be investigated here immediately.
\n\"BH4-2p\"<\/a>
\nFor n=3, we see new solvation patterns, including a dihydrogen<\/em> bond formed between water and the borohydride at the transition state; \u0394G\u2020<\/sup> is 10.0 kcal.mol.<\/p>\n

\"Click

Click for 3D.<\/p><\/div>\n

Finally, n=5, where the TS is showing a cage-like structure of complex weak interactions, \u0394G\u2020 is 11.3 kcal.mol. We see a model where inclusion of explicit solvent molecules can have a significant influence on the size of the barrier obtained.<\/p>\n

\"Click

BH4-5-TS<\/p><\/div>\n

\"BH4-5\"<\/a><\/p>\n

\"NCI

NCI surface. Click for 3D. Blue=strong attractions, green=weak.<\/p><\/div>\n\n\n\n\n\n\n
n<\/th>\n\u0394G298<\/sub>\u2021<\/sup><\/th>\nFAIR Data citation<\/th>\n<\/tr>\n
2<\/td>\n9.6<\/td>\n[2]<\/a><\/span><\/td>\n<\/tr>\n
3<\/td>\n10.0<\/td>\n[3]<\/a><\/span><\/td>\n<\/tr>\n
5<\/td>\n11.3<\/td>\n[4]<\/a><\/span><\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

With a mechanistic prototype now identified, it is time to start varying some of the parameters, such as X and R. This will enable us to assess the models built here to see if they reflect reality.<\/p>\n

References<\/h2>\n
  1. H.S. Rzepa, and H.S. Rzepa, \"C 2 H 12 B 1 Li 1 O 3\", 2015. https:\/\/doi.org\/10.14469\/ch\/191186<\/a>\n\n<\/li>\n
  2. H.S. Rzepa, and H.S. Rzepa, \"C 2 H 12 B 1 Li 1 O 3\", 2015. https:\/\/doi.org\/10.14469\/ch\/191188<\/a>\n\n<\/li>\n
  3. H.S. Rzepa, and H.S. Rzepa, \"C 2 H 14 B 1 Li 1 O 4\", 2015. https:\/\/doi.org\/10.14469\/ch\/191189<\/a>\n\n<\/li>\n
  4. H.S. Rzepa, and H.S. Rzepa, \"C 2 H 18 B 1 Li 1 O 6\", 2015. https:\/\/doi.org\/10.14469\/ch\/191192<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

    Sodium borohydride is the tamer cousin of lithium aluminium hydride (LAH). It is used in aqueous solution to e.g. reduce aldehydes and ketones, but it leaves acids, amides and esters alone. Here I start an exploration of why it is such a different reducing agent. Initially, I am using Li, not Na (X=Li), to enable […]<\/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":"federated","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":[1362,1402,557,1395,1451,24,835,206,1450,1449,851,1448,691],"ppma_author":[2661],"class_list":["post-13899","post","type-post","status-publish","format-standard","hentry","category-reaction-mechanism-2","tag-aqueous-solution","tag-chemical-bond","tag-chemical-bonding","tag-chemistry","tag-electronic-effect","tag-energy","tag-final-product","tag-free-energy-barrier","tag-hydride","tag-hydrogen-bond","tag-immediate-product","tag-lithium-aluminium-hydride","tag-reduction"],"yoast_head":"\nThe mechanism of borohydride reductions. Part 1: ethanal. - 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=13899\" \/>\n<meta property=\"og:locale\" content=\"en_GB\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The mechanism of borohydride reductions. Part 1: ethanal. - Henry Rzepa's Blog\" \/>\n<meta property=\"og:description\" content=\"Sodium borohydride is the tamer cousin of lithium aluminium hydride (LAH). It is used in aqueous solution to e.g. reduce aldehydes and ketones, but it leaves acids, amides and esters alone. Here I start an exploration of why it is such a different reducing agent. Initially, I am using Li, not Na (X=Li), to enable […]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=13899\" \/>\n<meta property=\"og:site_name\" content=\"Henry Rzepa's Blog\" \/>\n<meta property=\"article:published_time\" content=\"2015-04-12T20:41:26+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2025-10-15T12:23:21+00:00\" \/>\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=\"4 minutes\" \/>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"The mechanism of borohydride reductions. 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Part 2: 4-t-butyl-cyclohexanone – Dispersion induced stereochemistry.","author":"Henry Rzepa","date":"October 21, 2025","format":false,"excerpt":"Part one of this topic was posted more than ten years ago. I clearly forgot about it, so belatedly, here is part 2 - dealing with the stereochemistry of the reduction of tert-butyl-cyclohexanone by borohydride in water. The known stereochemistry is nicely summarised in this article, along with an extensive\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":13688,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=13688","url_meta":{"origin":13899,"position":1},"title":"Mechanism of the Lithal (LAH) reduction of cinnamaldehyde.","author":"Henry Rzepa","date":"April 1, 2015","format":false,"excerpt":"The reduction of cinnamaldehyde by lithium aluminium hydride (LAH) was reported in a classic series of experiments,, dating from 1947-8. The reaction was first introduced into the organic chemistry laboratories here at Imperial College decades ago, vanished for a short period, and has recently been reintroduced again.\u2021 The experiment is\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":13802,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=13802","url_meta":{"origin":13899,"position":2},"title":"A better model for the mechanism of Lithal (LAH) reduction of cinnamaldehyde?","author":"Henry Rzepa","date":"April 10, 2015","format":false,"excerpt":"Previously on this blog: modelling the reduction of cinnamaldehyde using one molecule of lithal shows easy reduction of the carbonyl but a high barrier at the next stage, the reduction of the double bond. Here is a quantum energetic exploration of what might happen when a second LAH is added\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":4719,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=4719","url_meta":{"origin":13899,"position":3},"title":"A stable borylene. An exercise in lateral thinking.","author":"Henry Rzepa","date":"August 7, 2011","format":false,"excerpt":"I have often heard the question posed \"how much of chemistry has been discovered?\" Another might be \"has most of chemistry, like low-hanging fruit, already been picked?\". Well, time and time again, one comes across examples which are only a simple diagram or so away from what might be found\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\/2011\/08\/borylene.jpg?resize=350%2C200","width":350,"height":200},"classes":[]},{"id":19383,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=19383","url_meta":{"origin":13899,"position":4},"title":"Hypervalent Helium – not!","author":"Henry Rzepa","date":"February 16, 2018","format":false,"excerpt":"Last year, this article attracted a lot of attention as the first example of molecular helium in the form of Na2He. In fact, the helium in this species has a calculated\u2021 bond index of only 0.15 and it is better classified as a sodium electride with the ionisation induced by\u2026","rel":"","context":"In "Hypervalency"","block_context":{"text":"Hypervalency","link":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?cat=7"},"img":{"alt_text":"","src":"","width":0,"height":0},"classes":[]},{"id":19807,"url":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/?p=19807","url_meta":{"origin":13899,"position":5},"title":"A Theoretical Method for Distinguishing X\u2010H Bond Activation Mechanisms.","author":"Henry Rzepa","date":"July 25, 2018","format":false,"excerpt":"Consider the four reactions. The first two are taught in introductory organic chemistry as (a) a proton transfer,\u00a0often abbreviated PT,\u00a0from X to B (a base) and (b) a hydride transfer from X to A (an acid). The third example is taught as a hydrogen atom transfer or HAT from X\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\/07\/024-1024x350.jpg?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","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\/13899","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=13899"}],"version-history":[{"count":49,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/13899\/revisions"}],"predecessor-version":[{"id":29723,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=\/wp\/v2\/posts\/13899\/revisions\/29723"}],"wp:attachment":[{"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=13899"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=13899"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=13899"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.ch.ic.ac.uk\/rzepa\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fppma_author&post=13899"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}