Subject: Reactivity and Expert Systems

From: "Phil Hultin" <[email-masked]>
Date: Wed, 5 Dec 2001 17:34:08 -0600

Michael Bartberger and others have suggested CAMEO as a viable way of
predicting reactivity.

I have not seen CAMEO recently, and I certainly do not intend to "diss" it
or its creators.  As I understand it, CAMEO is a sort of "expert system"
based on empirical rules.  This may well be the sort of prediction that
William Laidig was seeking, and there is nothing wrong with that.  Perhaps I
understood the question about "predicting reactivity" in a different context
than was meant.

An "expert system" is only as good as its rules when it comes to addressing
chemical systems outside the range of structures that went into its
parameterization.  Unfortunately, many of the "rules and rationalizations"
that we learned as undergraduates and that are still widely used by research
chemists are simply incorrect at a fundamental level, particularly as they
apply to reactions in solution.  While they are in many cases qualitatively
successful, the fundamental flaws in their logic mean that they will fail
for some (unknown) set of situations.

If you don't agree with this assertion about "rules and rationalizations",
you should consider the usual explanation organic chemists use for the
differing acidities of organic acids.  If it was true that acidities could
be correctly understood in terms of delocalization of charge in the
conjugate base (by inductive withdrawal or by resonance), then a) gas-phase
acidities and solution phase acidities would show parallel trends (they do
not in general) and b)the trend would be reflected in the enthalpies of
ionization in solution (it is not, in general).  The data on this have been
available for decades and can be found in standard (older) physical organic
textbooks as well as compendia of physical data.

So, to return to my argument about reactivity, if we base our analysis of an
unknown reaction on rationalizations that are based on questionable (or
false) premises, are we actually able to predict its behavior?  Or are we
simply lucky?  Speaking as an experimental organic chemist who has turned
recently to computational chemistry to find answers to nagging questions
that conventional wisdom (at least among organic chemists!) has not
adequately addressed, I still maintain that accurate prediction of
reactivity remains a highly challenging problem that is not really dealt
with by off-the-shelf solutions.

Dr. Philip G. Hultin
Associate Department Head and
Associate Professor of Chemistry
University of Manitoba
Winnipeg, MB, Canada R3T 2N2
(vox) 204-474-9814
(fax) 204-474-7608
mailto:[email-masked]
http://www.umanitoba.ca/chemistry/