{"id":8961,"date":"2013-01-06T17:35:28","date_gmt":"2013-01-06T17:35:28","guid":{"rendered":"http:\/\/www.ch.imperial.ac.uk\/rzepa\/blog\/?p=8961"},"modified":"2013-01-06T17:35:28","modified_gmt":"2013-01-06T17:35:28","slug":"the-mechanism-of-the-benzidine-rearrangement","status":"publish","type":"post","link":"https:\/\/www.rzepa.net\/blog\/?p=8961","title":{"rendered":"The mechanism of the Benzidine rearrangement."},"content":{"rendered":"
\n

The benzidine rearrangement is claimed to be an example of the quite rare\u00a0[5,5] sigmatropic migration[1]<\/a><\/span>, which is a ten-electron homologation<\/a> of the very common [3,3] sigmatropic reaction (e.g.<\/em> the Cope or Claisen). Some benzidine rearrangements are indeed thought to go through the [3,3] route[2]<\/a><\/span>. The topic has been reviewed here[3]<\/a><\/span>.<\/p>\n

\"benzidine\"<\/p>\n

In this post, I offer a calculated transition state<\/a> and IRC<\/a> for this reaction, to see what insights might accrue. How was this obtained?<\/p>\n

    \n
  1. At the \u03c9B97XD\/6-311G(d,p)\/SCRF=water level. This procedure would allow for any dispersion-like effects to be allowed for in the \u03c0-\u03c0-stacking.\u00a0<\/li>\n
  2. The rearrangement is normally promoted by acid, and the active species is thought to be diprotonated[4]<\/a><\/span>\u2021<\/sup> (although monoprotonated catalysis<\/a> is also observed[1]<\/a><\/span>. Here I report just the diprotonated route, together with chloride anions to balance the charges, and have added a continuum water field to allow this double ion-pair to be at least partially stabilised.<\/li>\n
  3. The rate determining step is the N-N cleavage\/C-C bond formation. This is followed by presumed rapid proton transfers, which are not modelled here.<\/li>\n<\/ol>\n\n\n\n\n
    \n
    \"The

    The [5,5] transition state for the benzidine rearrangement. Click for 3D.<\/p><\/div>\n<\/td>\n

    		\"benzidine-55\"<\/td>\n<\/tr>\n
    \"benzidine-55E\"<\/td>\n\"benzidine-55G\"<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

    This [5,5] transition state is 2.9 kcal\/mol lower in \u0394G\u2021<\/sup>298<\/sub> than the transition state<\/a> for the isomeric [3,3] rearrangement. The NCI (non-covalent-interactions) shows the forming C-C bond to be on the border of covalent, and non-covalent (blue), but that the\u00a0\u03c0-\u03c0-stacking region is all weakly attractive (green). You can also observe the strong hydrogen bonds between the chloride anion and an N-H group (blue), and the weak attractive zones between the two nitrogen centres, between the chloride and the ortho-C-H hydrogens, and even between the two chloride anions (blue-green or green). I should point out that the initial position for these anions was over the aryl ring, but they migrated to the NH region during optimisation of the transition state.<\/p>\n

    \"NCI

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

    The molecular electrostatic potential (isosurface = 0.11 au) shows both aryl rings as a single unit attracted by a positive potential (blue)<\/p>\n

    \"Calculated

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

    The highest-occupied molecular orbital shows the two bonds involved in the [5,5] shift (N-N and C-C) are both bonding, but more significantly, the central region of the two stacked aryl rings is also bonding. This is a clear manifestation of a \u03c0-complex, which the benzidine rearrangement has often (and it has to be said controversially) described as, and which elevates this particular reaction from that of a simple bond forming\/bond cleaving sigmatropic. Another way of looking at it is that secondary orbital interactions (such as often invoked in Diels-Alder cycloadditions) are exceptionally important here.<\/p>\n

    \"HOMO

    HOMO for 5,5 benzidine rearrangement. Click for 3D.<\/p><\/div>\n

    The LUMO is strongly antibonding in that region; indeed adding two electrons to form a 12-electron process would be strongly destabilising. In this regard, this unusual sigmatropic reaction follows the same 4n+2 electron rule as more conventional ones.<\/p>\n

    \"LUMO.

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

    The next two diagrams illustrate the competing (higher energy) [3,3] shift, which also has some \u03c0-complex character.<\/p>\n

    \"A

    A [3,3] alternative to the benzidine rearrangement. Click for 3D.<\/p><\/div>\n

     <\/p>\n

    \"NCI

    NCI surface for 3,3 rearrangement. Click for 3D.<\/p><\/div>\n

    I will end with three autobiographical notes.<\/p>\n

      \n
    1. The benzidine rearrangement was one of the earliest reactions I did in my home laboratory, at the age of about \u00a013. As I recollect, I prepared about 1.5 grams (blissfully ignorant of how carcinogenic it is), and used it via<\/em> diazotization to couple to phenol. My fascination with chemistry most certainly started with colour (and how to express the bonding in nitric oxide).<\/li>\n
    2. About eight years later, I was about to commence my Ph.D. studies. The objective was to use kinetic isotope effects to infer the structure of transition states. In my case (proton transfers to indoles) I never did achieve this objective. But it is noteworthy that the mechanism of the benzidine rearrangement was largely unravelled using such isotopic studies.<\/li>\n
    3. By 1974 as a post-doctoral researcher, I had moved on to studying mechanisms using \u00a0quantum theory and had decided that it was easier to invert the use of isotope effects by predicting a transition structure using this method, and then seeing if the computed isotope effects matched the experiment. We did this for the Diels-Alder reaction[5]<\/a><\/span> and more generally[6]<\/a><\/span>, and then for some gas-phase eliminations[7]<\/a><\/span>, this latter being my first entirely independent publication.<\/li>\n
    4. So, putting all this together, one might infer that armed with a computed transition state structure for the benzidine rearrangement, it is trivial to compute the kinetic isotope effects and hence to see if they correspond to those measured. You might expect a report on this in a future post here<\/a>.<\/li>\n<\/ol>\n
      \n

      \u2021<\/sup> Crystal structures of diprotonated dimethyl hydrazines[4]<\/a><\/span> show a N-N bond length of ~1.45\u00c5 (typical counter-anions being nitrate, perchlorate or sulfate). That calculated for the diprotonated diphenyl hydrazine is ~2.5\u00c5, which suggests that with the phenyl group, electrons from the N-N region may be borrowed to contribute to the\u00a0\u03c0-\u03c0-complex.<\/p>\n

      References<\/h2>\n
      1. H.J. Shine, K.H. Park, M.L. Brownawell, and J. San Filippo, \"Benzidine rearrangements. 19. The concerted nature of the one-proton rearrangement of 2,2'-dimethoxyhydrazobenzene\", Journal of the American Chemical Society<\/i>, vol. 106, pp. 7077-7082, 1984. https:\/\/doi.org\/10.1021\/ja00335a035<\/a>\n\n<\/li>\n
      2. H.J. Shine, L. Kupczyk-Subotkowska, and W. Subotkowski, \"Heavy-atom kinetic isotope effects in the acid-catalyzed rearrangement of N-2-naphthyl-N'-phenylhydrazine. Rearrangement is shown to be a concerted process\", Journal of the American Chemical Society<\/i>, vol. 107, pp. 6674-6678, 1985. https:\/\/doi.org\/10.1021\/ja00309a041<\/a>\n\n<\/li>\n
      3. H.J. Shine, \"Reflections on the \u03c0\u2010complex theory of benzidine rearrangements\", Journal of Physical Organic Chemistry<\/i>, vol. 2, pp. 491-506, 1989. https:\/\/doi.org\/10.1002\/poc.610020702<\/a>\n\n<\/li>\n
      4. C.M. Sabat\u00e9, and H. Delalu, \"Energetic Salts of Symmetrical Dimethylhydrazine (SDMH)\", European Journal of Inorganic Chemistry<\/i>, vol. 2012, pp. 866-877, 2011. https:\/\/doi.org\/10.1002\/ejic.201101115<\/a>\n\n<\/li>\n
      5. M.J.S. Dewar, S. Olivella, and H.S. Rzepa, \"Ground states of molecules. 49. MINDO\/3 study of the retro-Diels-Alder reaction of cyclohexene\", Journal of the American Chemical Society<\/i>, vol. 100, pp. 5650-5659, 1978. https:\/\/doi.org\/10.1021\/ja00486a013<\/a>\n\n<\/li>\n
      6. S.B. Brown, M.J.S. Dewar, G.P. Ford, D.J. Nelson, and H.S. Rzepa, \"Ground states of molecules. 51. MNDO (modified neglect of diatomic overlap) calculations of kinetic isotope effects\", Journal of the American Chemical Society<\/i>, vol. 100, pp. 7832-7836, 1978. https:\/\/doi.org\/10.1021\/ja00493a008<\/a>\n\n<\/li>\n
      7. H.S. Rzepa, \"MNDO SCF-MO calculations of kinetic isotope effects for dehydrochlorination reactions of chloroalkanes\", Journal of the Chemical Society, Chemical Communications<\/i>, pp. 939, 1981. https:\/\/doi.org\/10.1039\/c39810000939<\/a>\n\n<\/li>\n<\/ol>\n\n<\/div> ","protected":false},"excerpt":{"rendered":"

        The benzidine rearrangement is claimed to be an example of the quite rare\u00a0[5,5] sigmatropic migration, which is a ten-electron homologation of the very common [3,3] sigmatropic reaction (e.g. the Cope or Claisen). Some benzidine rearrangements are indeed thought to go through the [3,3] route. The topic has been reviewed here. In this post, I offer […]<\/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,"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":[6],"tags":[185,1528,1529,1530,967],"class_list":["post-8961","post","type-post","status-publish","format-standard","hentry","category-interesting-chemistry","tag-higher-energy","tag-historical","tag-pericyclic","tag-reaction-mechanism","tag--complex"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"","jetpack_sharing_enabled":true,"jetpack_shortlink":"https:\/\/wp.me\/p1gPyz-2kx","jetpack_likes_enabled":true,"_links":{"self":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/8961","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=8961"}],"version-history":[{"count":0,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=\/wp\/v2\/posts\/8961\/revisions"}],"wp:attachment":[{"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=8961"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=8961"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.rzepa.net\/blog\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=8961"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}