How does an OH or NH group approach an aromatic ring to hydrogen bond with its π-face?

I previously used data mining of crystal structures to explore the directing influence of substituents on aromatic and heteroaromatic rings. Here I explore, quite literally, a different angle to the hydrogen bonding interactions between a benzene ring and OH or NH groups.

aromatic-pi-query

I start by defining a benzene ring with a centroid. The distance is from that centroid to the H atom of an OH or NH group and the angle is C-centroid-H. To limit the search to approach of the OH or NH group more or less orthogonal to the ring, the absolute value of the torsion between the centroid-H vector and the ring C-C vector is constrained to lie between 70-100° (the other constraints being no disorder, no errors, T < 140K and R < 0.05).[cite]10.14469/hpc/673[/cite]

aromatic-pi-HN-140

The above shows the results for NH groups interacting with the aromatic ring. The maximum distance 2.8Å is more or less the van der Waals contact distance between a hydrogen and a carbon and as you can see the contacts "funnel down" to the centroid at < 2.1Å. The shortest distance[cite]10.1107/S0108768199012318[/cite] is for ammonium tetraphenylborate, which you can view in e.g. spacefill mode here[cite]10.5517/CC4V6TZ[/cite]

390

The other interesting close contact derives from a protonated pyridine[cite]10.1021/cg100831c[/cite], which can in turn be viewed here.[cite]10.5517/CCWHC5W[/cite] The main message from the distribution shown above is that as the distances between the HN and the centroid get shorter, the "trajectory" of approach remains orthogonal to the ring (the angle defined above remains ~90°) and heads towards the centroid of the π-cloud. The hotspot itself (red, ~2.6Å) also lies along this trajectory.

Recollect that when I used such hydrogen bonding to see if crystal structures discriminate between the ortho or meta positions of a ring carrying an electron donating substituent, it was the distance from a HO to the carbon that was measured as the discriminator. So it's a faint surprise to find that with HN, and without the necessary perturbation of an electron donating substituent, the intrinsic preference seems to be for the ring centroid and not any specific carbon atom of the ring.

So how about the OH group? There are in fact rather fewer examples, and so the statistics are a bit less clear-cut. But there is a tantalising suggestion that this time, the trajectory is not ~90° but rather less, implying that the destination is no longer the centroid of the π-cloud but one of the carbon atoms of the ring itself. For those who like to "read between the lines" and spot things that are absent rather than present, you may have asked yourself why I did not use NH probes in my earlier post. Well, it appears that the NH group is less effective at e.g. o/p discrimination than is an OH group.

aromatic-pi-OH-140

I can only speculate as to the origins (real or not) of the difference in behaviour between OH and NH groups towards a phenyl π-face. Perhaps it is simply bias in the CSD database? Or might there be electronic origins? Time to end with that phrase "watch this space".

 

Tags: , , , , , , , , , , , , ,

3 Responses to “How does an OH or NH group approach an aromatic ring to hydrogen bond with its π-face?”

  1. Henry Rzepa says:

    How does a CH group approach an aromatic ring to hydrogen bond with its π-face? could be a follow up to the post above. Here are some crystal searches in which the ring-H-C interaction is split into H-C(sp), H-C(sp2), H-C(sp3). The shortest interactions to the ring centroid are again ~2.2Å  and the trajectories for the last two types of H-C are both perpendicular to the plane of the aromatic ring, just like the HN in the post.

        

        

        

  2. Prof. Rzepa,
    Can you provide a recent literature reference for N-H..pi interactions? I see some theoretical and data-mining articles from 1998 to 2002, or so, but wondered if you know of something more recent. I and a colleague are working on a transition metal complex that shows this interaction, and we are seeking relevant recent comparisons.

    Thanks

  3. Henry Rzepa says:

    I have not tried to track down any reviews, but the CSD itself can provide some breakdowns. Here, I have searched for close contacts between the centroid of either a C=C or a C≡C bond and the H of an HN. The table shows the closest such contacts up to 2.3Å.

    Identifier CC centroid…HN distance, Å Publication Year NAME (RefCode)
    search2_1|AJARIM|0 2.339 2003 AJARIM
    search2_1|AJISOC|1 2.384 2009 AJISOC
    search2_1|ATAXAW|2 2.286 2016 ATAXAW
    search2_1|CUVQIT|3 2.351 2000 CUVQIT
    search2_1|DACPUU|4 2.302 2011 DACPUU
    search2_1|DACPUU|5 2.384 2011 DACPUU
    search2_1|DOWQAJ|6 2.335 2014 DOWQAJ
    search2_1|DUNPUY|7 2.359 2010 DUNPUY
    search2_1|DUNPUY|8 2.373 2010 DUNPUY
    search2_1|DUNPUY|9 2.284 2010 DUNPUY
    search2_1|ERERUP|10 2.365 2011 ERERUP
    search2_1|GOLSAB01|11 2.339 2004 GOLSAB01
    search2_1|GOQSAI|12 2.396 2014 GOQSAI
    search2_1|GOQSAI|13 2.361 2014 GOQSAI
    search2_1|HOGFAM|14 2.241 2014 HOGFAM
    search2_1|JADHOM|15 2.365 2003 JADHOM
    search2_1|JIZLAF|16 2.347 1991 JIZLAF
    search2_1|KESDAO|17 2.208 2006 KESDAO
    search2_1|KESDAO|18 2.108 2006 KESDAO
    search2_1|LAFYIA|19 2.369 1999 LAFYIA
    search2_1|MINGEX01|20 2.358 2015 MINGEX01
    search2_1|MINGEX01|21 2.367 2015 MINGEX01
    search2_1|MIYFUV|22 2.389 2002 MIYFUV
    search2_1|OCOYUC|23 2.239 2011 OCOYUC
    search2_1|OCOYUC|24 2.326 2011 OCOYUC
    search2_1|OCOYUC|25 2.388 2011 OCOYUC
    search2_1|OCOYUC|26 2.298 2011 OCOYUC
    search2_1|ORALEZ|27 2.3 2010 ORALEZ
    search2_1|ORUVII|28 2.276 2016 ORUVII
    search2_1|PEJGIW|29 2.392 2012 PEJGIW
    search2_1|PUYVIO|30 2.337 2002 PUYVIO
    search2_1|QEZCED|31 2.369 2000 QEZCED
    search2_1|SASBET|32 2.382 1998 SASBET
    search2_1|SEBRIC|33 2.344 2012 SEBRIC
    search2_1|SETBAV|34 2.348 2006 SETBAV
    search2_1|SPBTZB|35 2.34 1978 SPBTZB
    search2_1|TIQXOH|36 2.27 2007 TIQXOH
    search2_1|TIXYUV|37 2.361 2008 TIXYUV
    search2_1|VUKZIL|38 2.162 2009 VUKZIL
    search2_1|VUKZIL|39 2.206 2009 VUKZIL
    search2_1|WUJCAF|40 2.25 2002 WUJCAF
    search2_1|XORBOX|41 2.305 2015 XORBOX
    search2_1|XOSZAI|42 2.325 2015 XOSZAI
    search2_1|YUXJAC|43 2.28 1993 YUXJAC
    search2_1|YUXJAC|44 2.282 1993 YUXJAC
    search2_1|YUXJAC|45 2.126 1993 YUXJAC
    search2_1|YUXJAC|46 2.278 1993 YUXJAC
    search2_1|ZASROA|47 2.381 1995 ZASROA
    search2_1|ZASRUG|48 2.396 1995 ZASRUG

    Using the Name (RefCode), you can then do individual searches for each entry, ie https://www.ccdc.cam.ac.uk/structures/Search?Ccdcid=KESDAO for one interesting example. This should then give the original literature reference for the entry.

    Hope this helps.

Leave a Reply