{"id":12056,"date":"2014-03-08T21:46:30","date_gmt":"2014-03-08T21:46:30","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=12056"},"modified":"2014-03-08T21:46:30","modified_gmt":"2014-03-08T21:46:30","slug":"the-mechanism-of-diazo-coupling-more-hidden-mechanistic-intermediates","status":"publish","type":"post","link":"https:\/\/rzepa.net\/blog\/2014\/03\/08\/the-mechanism-of-diazo-coupling-more-hidden-mechanistic-intermediates\/","title":{"rendered":"The mechanism of diazo coupling: more hidden mechanistic intermediates."},"content":{"rendered":"

The diazo-coupling reaction dates back to the 1850s (and a close association with Imperial College via<\/em> the first professor of chemistry there, August von Hofmann<\/a>) and its mechanism was much studied in the heyday of physical organic chemistry.[cite]10.1021\/ja00830a009[\/cite] Nick Greeves, purveyor of the excellent ChemTube3D<\/a> site, contacted me about the transition state (I have commented previously<\/a> on this aspect of aromatic electrophilic substitution). ChemTube3D recruits undergraduates to add new entries; Blue Jenkins is one such adding a section on dyes.<\/p>\n

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

The mechanism can be rate limiting either in the initial electrophilic attack (black arrows) or in the subsequent proton removal (red arrows using an intermolecular base such as chloride anion).[cite]10.1039\/P29750001209[\/cite].\u2021<\/sup> The product is normally assumed to be the trans<\/em>-diazo compound rather than cis<\/em>. This distribution is certainly true in the crystal structure database (below, although some examples of cis<\/em> are known, including azobenzene itself). Would this distribution be reflected in the transition states? Initial attempts by the ChemTube3D team had resulted only in a cis<\/em>-transition state being located, and they asked me to check this out.<\/p>\n

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

\u03c9B97XD\/6-311G(d,p)\/SCRF=water calculations using phenyl diazonium chloride (I do like my counter-ions) coupling to benzene resulted in location of both cis<\/em>[cite]10.6084\/m9.figshare.956138[\/cite] and trans<\/em>[cite]10.6084\/m9.figshare.956139[\/cite] transition states, the former being the lower<\/strong> by 1.0 kcal\/mol in free energy (this might well be due to the dispersion stabilisation from \u03c0-\u03c0 stacking).\u2020<\/sup> The IRC for the cis<\/em> is shown below.[cite]10.6084\/m9.figshare.956209[\/cite]<\/p>\n

\"cis-diazo\"<\/a>\"cis-diazoE\"<\/a>\"cis-diazoG\"<\/a><\/p>\n

You can see that the entire process is concerted. The Wheland intermediate normally invoked as part of the mechanism of aromatic electrophilic substitution is not a proper intermediate but a hidden one for the reaction with X=Y=H. The reaction coordinate has a flat top, and that passage along this part represents the hidden Wheland. The reaction barrier is high however, and it is certainly observed that only activated arenes (phenols, anilines, X,Y=OH, NH2<\/sub>) actually couple with diazonium cations. For these, the hidden intermediate is stabilized by the substituent, and no doubt emerges as a real intermediate.<\/p>\n

For my thesis work, I studied[cite]10.1039\/P29750001209[\/cite] diazo-coupling of indoles<\/a>. I might have a go at returning to that work, to see if calculations can replicate my finding, that for unhindered indoles proton removal from the Wheland intermediate is fast, but add a few t-butyl hindering groups and it becomes slow.<\/p>\n

\n

PS<\/b>. Here is the IRC for the formation of trans<\/em>-diazobenzene.[cite]10.6084\/m9.figshare.956213[\/cite]<\/p>\n

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

\n

\u2021<\/sup>Such diazo compounds make up a significant proportion of the 50 or so real molecules I have personally added to the collection of 84 million or so thus far identified.<\/p>\n

\u2020<\/sup>Working with ions has one statistical problem that covalent systems do not have; where to geometrically place the counter-ion. One should really stochastically explore reasonable locations before concluding the likely location of the globally lowest energy pose.<\/p>\n","protected":false},"excerpt":{"rendered":"

The diazo-coupling reaction dates back to the 1850s (and a close association with Imperial College via the first professor of chemistry there, August von Hofmann) and its mechanism was much studied in the heyday of physical organic chemistry.[cite]10.1021\/ja00830a009[\/cite] Nick Greeves, purveyor of the excellent ChemTube3D site, contacted me about the transition state (I have commented […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[13],"tags":[681,1010,1038,1251,1508,1730,1985],"class_list":["post-12056","post","type-post","status-publish","format-standard","hentry","category-reaction-mechanism-2","tag-covalent-systems","tag-first-professor","tag-free-energy","tag-imperial-college","tag-lowest-energy-pose","tag-nick-greeves","tag-professor-of-chemistry"],"_links":{"self":[{"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/posts\/12056","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/comments?post=12056"}],"version-history":[{"count":0,"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/posts\/12056\/revisions"}],"wp:attachment":[{"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/media?parent=12056"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/categories?post=12056"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/rzepa.net\/blog\/wp-json\/wp\/v2\/tags?post=12056"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}