Subject: pyramidalization of amides

From: Ulrike Salzner <[email-masked]>
Date: Thu, 08 Aug 2002 10:15:52 +0300

Dear Collegues,
thanks for the replies to my question about calculating geometries of 
amides with flat potential energy surfaces. There does not seem to be a 
major problem with applying standard methods, although it seems that 
most people prefer the empirical approach, that is comparing results 
with experiment rather than doing a theoretical analysis. My original 
letter and the anwers are summarized below.
Regards,
Ulrike Salzner

Hello,
I am reviewing a thesis which deals with pyramidalization in amides, S, 
Se anlogues and amids in larger ring systems. Substituent effects are 
analyzed and compared with AIM and NBO. All of these systems have 
inversion barriers smaller than ammonia, some of them are planar. Thus, 
like ammonia, these molecules probably violate the Born-Oppenheimer 
approximation. How reliable are standard calculations (B3LYP/6-31G*, 
MP2/6-31G*) of bond angles, i.e. degree of pyramidalization? Should 
trends be ok? I would appreciate opinions on this.
Sincerely,
Ulrike Salzner

  This is an interesting question.  I am not sure there is a good answer.
It is known that gas phase calculations lead to pyramidalization of 
 nitrogens.  This may or may not be the case in a crystal or in a 
hydrogen bonded network.  One would like to have good crystal data, but 
it is very hard to locate hydrogens with x-ray crystallography. There is 
also a bias towards planarity in comercial programs.  If you enter 
coordinates and do an optimization involving nitrogens, the
molecule comes out planar.
  I have studied this problem in nucleic acids.  I can send you 
references if you like.  As for the amides, the problem would be even 
more difficult.
X-ray structures were probably done in the 60's, so there was no hope
of locating the hydrogens.  One could fine tune the theoretical 
procedures if one knew the answer.  But since the answer is not 
available, I'm not sure what to make of the theoretical claims about  
pyramidalization in the gas phase.

David Close

IMHO, B3LYP and MP2, with 6-31G* basis set, give good geometries for 
anilines:
according to B3LYP/6-31G* aniline is pyramidal N-Me aniline has the Me 
group almost in the plane, but the H notably out NN di methyl aniline is 
planar.

I've never encountered an amide that was not planar in a CHNOX 
[X=halogen]compound.

John McKelvey

(This is a hard question -- I'd be inclined to check geometries with
MP4 or CCSD(T), and also find out how it behaves with increasing the 
basis set size)

-- do you have a reference to molecules with small inversion
barriers and the consequences of violating the Born-Oppenheimer
approximation? I've run into this problem with lactam tautomers
of heterocycles.
 
Yours sincerely,

Jeremy
---------------------------------------------------------------------
Jeremy Greenwood                                  [email-masked]
Department of Medicinal Chemistry                      bh +45 35306117
Royal Danish School of Pharmacy                        fx +45 35306040
Universitetsparken 2, DK-2100 Copenhagen, Denmark      ah +45 32598030
---------------------------------------------------------------------

My opinion: the calculations will be valid, if interpreted properly. 
I tend to think of such systems as "obeying" a modified, three-level 
Born-Oppenheimer approximation.  In the standard two-level 
Born-Oppenheimer approximation, the nuclei are frozen, with the 
electrons treated in quantum mechanical fashion, giving the familiar 
potential energy surface.  However, once we have that potential energy 
surface, we can use it to give the nuclei a quantum treatment: that is 
what we do when calculating zero-point and thermal energies.  

However, hydrogen compounds can be better treated with a three way 
distinction between electrons, hydrogen nuclei (especially if they are 
protons, i.e. 1H), and then the heavier nuclei.  One calculates the 
potential energy surface in the usual fashion (freezing all nuclei and 
allowing quantum mechanical treatment of electrons).  However, once that 
potential energy surface is calculated, the hydrogen atoms would be 
treated quantum mechanically while other nuclei are still frozen.  A new 
heavy atom potential energy surface is thus generated, and wavefunctions 
and probability distributions are calculated for the hydrogen nuclei.  
There was an article in Accounts of Chemical Research a few years ago in 
which this was done for water clusters. 

Back to your question: a planar amide is still distinguished from a 
pyramdialized amide in having a one-minimum or two-minima potential 
energy surface for the amide hydrogen.  These produce one-maximum or 
two-maxima probability distributions (respectively) for the hydrogen 
nuclei. Experimental geometries typically come from diffraction studies, 
which actually measure these probability distributions since the results 
are averaged among the molecules in the sample.  Thus, the experimental 
geometries should correspond to the minima found by B3LYP/6-31G* and the 
like.

--David Shobe
Süd-Chemie Inc.
phone (502) 634-7409
fax     (502) 634-7724
email  [email-masked]

Hello,
        The NIST Computational Chemistry Comparison and Benchmark 
database (http://srdata.nist.gov/cccbdb) has experimental data and a 
bunch of calculations for a few amides: acetamide, urea, and version 7 
(September 2002) will have experimental data as well for formamide and 
alanine. The pyramidalization can be compared at different levels of 
theory by looking a the HNCH dihedral, which is 180 degrees for a planar 
amide.
The comparison can be set up in section IV.D.1

Hope this helps,
Russ Johnson

Dr. Russell D. Johnson III
Research Chemist
National Institute of Standards and Technology
Computational Chemistry Group
100 Bureau Drive, Stop 8380
Gaithersburg, MD 20899-8380
voice 301+975-2513     fax  301+869-4020
email: [email-masked]