MadSci Network: Chemistry

Re: Leaving Groups in Organic Chemistry

Date: Mon Feb 18 10:46:50 2002
Posted By: Dan Berger, Faculty Chemistry/Science, Bluffton College
Area of science: Chemistry
ID: 1013158286.Ch

What are factors that determine how good a leaving group (in organic chemistry) is? I have heard that the stability of the leaving group and its [strength as a Brønsted base] affect how good a leaving group (e.g. Cl-) is. Could you tell me whether there are other factors, or could you provide me more information as to how these factors affect the leaving group?
While it may not seem to make sense, in fact the best correlation with how good a leaving group is, is with the group's weakness as a Brønsted base. Or, to put it another way, how strong is the conjugate acid? The lower the pKa of the conjugate acid, the better the leaving group.
"Conjugate acid" and "conjugate base" are terms used to describe what you get when you protonate or deprotonate something. For example, consider the Brønsted acid-base reaction shown below:

HCN + H2O ® CN- + H3O+

HCN is the conjugate acid of CN-, and CN- is the conjugate base of HCN. H2O is the conjugate base of H3O+; and what is the conjugate acid of H2O?

Usually we talk about stability of the conjugate base as being the biggest factor in how acidic something is, and this is possibly true--but the other factor is the question, "How strong is the H-A bond in the acid compared with the H-O bond in H3O+?" This becomes quite important in the case of acidity within families on the periodic table. For example, HF is a much weaker acid than HCl, even though F- is not really any less stable than Cl- (they have similar electron affinities). The reason HF is so much weaker an acid is that the H-F bond is so much stronger.

Now, what makes a good leaving group? To some extent, it's stability of the group as an "anion"--I use quotes because sometimes you can have neutral leaving groups, for example in

CH3OH2+ + CH3S- ® CH3SCH3 + H2O

But the other factor is the strength of the group's bond to carbon--and it is an experimental fact that the strength of an atom's bond to carbon correlates well with the strength of its bond to hydrogen.

So again, the ability of something to act as a leaving group in a nucleophilic substitution or elimination reaction depends on its standalone stability as an anion, and on the strength of its bond to carbon--and both correlate well with its Brønsted basicity. This is often given as the pKa of the conjugate acid--the lower the pKa, the better the leaving group as a general rule.

pKa is the negative logarithm of the acid dissociation constant (Ka). As pKa gets larger, the acidity gets weaker.
My rule of thumb is that anything with a (conjugate acid) pKa of 6 or more is a poor leaving group. It should be remembered that these rules are only for leaving groups from electrically neutral molecules. Anything with a pKa of less than about 25 is a good leaving group if the molecule bears a negative charge and can form a carbonyl group when the leaving group leaves.

Dan Berger
Bluffton College

Current Queue | Current Queue for Chemistry | Chemistry archives

Try the links in the MadSci Library for more information on Chemistry.

MadSci Home | Information | Search | Random Knowledge Generator | MadSci Archives | Mad Library | MAD Labs | MAD FAQs | Ask a ? | Join Us! | Help Support MadSci

MadSci Network,
© 1995-2002. All rights reserved.