Explain the inverse relationship between nucleophilicity and basicity

Ch 8 : Nucleophilicity vs Basicity

Nucleophilicity and basicity are very similar properties in that species that are nucleophiles are usually also bases (e.g. HO-, RO-). This is not too surprising. What's the difference between nucleophicity and basicity? Great, great question. First of all, remember that basicity is a subset of nucleophilicity. (a) Define soft and hard bases (nucleophiles). (b) Which (c) Discuss the relationship of Apparently, the inverse relationship of nucleophilicity and basicity.

Solvation is the process of attraction and association of solvent molecules with ions of a solute. The solute, in this case, is a negatively charged nucleophile.

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The following diagram depicts the interaction that can occur between a protic solvent and a negatively charged nucleophile. The interactions are called hydrogen bonds.

  • Nucleophilicity vs. Basicity

A hydrogen bond results from a from a dipole-dipole force between between an electronegative atom, such as a halogen, and a hydrogen atom bonded to nitrogen, oxygen or fluorine. In the case below, we are using an alcohol ROH as an example of a protic solvent, but be aware that this interaction can occur with other solvents containing a positively polarized hydrogen atom, such as a molecule of water, or amides of the form RNH2 and R2NH.

Why is this important? Solvation weakens the nucleophile; that is, solvation decreases nucleophilicity. This is because the solvent forms a "shell" around the nucleophile, impeding the nucleophile's ability to attack an electrophilic carbon. Furthermore, because the charge on smaller anions is more concentrated, small anions are more tightly solvated than large anions.

The picture below illustrates this concept.

Nucleophilicity vs. Basicity — Master Organic Chemistry

Notice how the smaller fluoride anion is represented as being more heavily solvated than the larger iodide anion. This means that the fluoride anion will be a weaker nucleophile than the iodide anion.

In fact, it is important to note that fluoride will not function as a nucleophile at all in protic solvents. It is so small that solvation creates a situation whereby fluoride's lone pair of electrons are no longer accessible, meaning it is unable to participate in a nucleophilic substitution reaction. Previously we learned how nucleophilicity follows basicity when moving across a row. In our discussion on the effect of protic solvents on nucleophilicity, we learned that solvation weakens the nucleophile, having the greatest effect on smaller anions.

In effect, when using protic solvents, nucleophilicity does not follow basicity when moving up and down a column.

In fact, it's the exact opposite: Aprotic Solvents An aprotic solvent is a solvent that lacks a positively polarized hydrogen. The next diagram illustrates several polar aprotic solvents that you should become familiar with. Aprotic solvents, like protic solvents, are polar but, because they lack a positively polarized hydrogen, they do not form hydrogen bonds with the anionic nucleophile.

The result, with respect to solvation, is a relatively weak interaction between the aprotic solvent and the nucleophile. The consequence of this weakened interaction is two-fold. First, by using an aprotic solvent we can raise the reactivity of the nucleophile. This can sometimes have dramatic effects on the rate at which a nucleophilic substitution reaction can occur. For example, if we consider the reaction between bromoethane and potassium iodide, the reaction occurs times faster in acetone than in methanol.

A second consequence that results from the weak interaction that occurs between aprotic solvents and nucleophiles is that, under some conditions, there can be an inversion of the reactivity order.

Nucleophile

An inversion would result in nucleophilicity following basicity up and down a column, as shown in the following diagram. When we considered the effects of protic solvents, remember that the iodide anion was the strongest nucleophile. Now, in considering aprotic solvents under some conditions, the fluoride anion is the strongest nucelophile. Increasing Atomic Size Increases Nucleophilicity Thus far, our discussion on nucleophilicity and solvent choice has been limited to negatively charged nucleophiles, such as F- Cl- Br- and I.

In general all non nucleophilic base acts by the same mechanism. Reply James Ashenhurst The best guide to basicity is by looking at a pKa table. The pka of water is James This was not a clear cut example where one could point to periodic trends. However with nitrogen being coordinated to C in -CN using that principle, they would draw the wrong conclusion.

Because multiple variables are in play [we are changing the basic atom as well as the substituents connected to that atom] the only recourse is to check a pKa table because the effect of changing two variables at once is not easily predictable. This site is not deficient in describing why certain species are stronger acids and bases according to a set of principles.

I have a whole series of articles where I discuss acidity trends and refer to electronegativity, polarizability, resonance, adjacent electron withdrawing groups, and even aromaticity. The point of the current article is to mention that basicity is measured by pKa — it is an equilibrium — whereas nucleophilicity is measured by rate. So only a brief treatment of basicity was given here, with reference to the series on acid-base reactions.