Exception #1: “Is This Too Basic For You?” A Cautionary Note About Amide Bases There are three big exceptions to this rule of thumb: 1) strong bases, 2) bulky amines, and 3) a few highly nucleophilic but weakly basic nitrogens. So if basicity mostly correlates with nucleophilicity, you might ask: what are the exceptions? Think of this sketch, which shows basicity increasing with nucleophilicity (note: this is not drawn to any reasonable scale) In general, the stronger the base, the stronger the nucleophile (you can think of this as the “fairy tale” scenario I mentioned above). A Good First Approximation: “The Stronger The Base, The Stronger The Nucleophile…” In real life, the course of love does not always run smooth. In fairy tales, the answer is, “of course”. To put this in perspective, let’s tie it back to human relationships.ĭoes the fact that two people fall in love with each other make for a stable long-term marriage? To be sure, there’s a lot of correlation, but it’s just as important to know the situations where the correlations DON’T hold. The position of an equilibrium (“how stable are two reactants, relative to their products”) and the reaction rate ( “how rapidly do two reactants combine to give a product?” ) are two very different measurements.
Some Rules Of Thumb For Comparing Basicity and Nucleophilicity So what we call “strong” nucleophile is one that reacts quickly with a given electrophile, whereas a “weak” nucleophile reacts slowly with the same electrophile.ģ. The only option available is to measure the rate.
The (negative) log of the acidity constant, pK a, measures the strength of acids, and it goes from about –10 for strong acids (–10 for HI ) to over 50 for weak acids (>50 for alkanes). Acid-base reactions are generally reversible and therefore the equilibrium constant (“acidity constant”) K a can be measured.Here, we’re going to confine ourselves largely to the reactions of amine bases with carbon-based electrophiles, since it’s the most relevant for our purposes. Since the electrophile can potentially be any atom on the periodic table (except for H, which would make nitrogen a “base”), there’s inherently a lot more variability possible for nucleophilicity than there is for basicity. When an amine reacts to form a bond with any atom other than H, we say it is acting as a nucleophile. The reaction partner is called an electrophile.The reactive partner of a base is called an “acid”, “Brønsted acid”, or simply a “proton”. (A Brønsted base, specifically, if you want to tie it back to a familiar concept from general chemistry). When an amine reacts to form a bond with a proton (H+) we say it is acting as a base.Here, we’ll look at it from the perspective of amines, but a lot of the principles are general. Always a good question, because sometimes it takes approaching the subject from a few different angles to really make it sink in. “ Um, how are basicity and nucleophilicity different again“? you might ask. (Advanced) References and Further Readingġ.Bonus Section: Quantifying The Nucleophilicity Trends of Amines With The Mayr Scale.Exception #3: Poorly Basic Amines That Are Great Nucleophiles.Why Is Nucleophilicity Much More Sensitive To Steric Effects Than Basicity?.Exception #1: “Is This Too Basic For You?” A Cautionary Note About Amide Bases.A Good First Approximation: “The Stronger The Base, The Stronger The Nucleophile”.Some Rules Of Thumb For Comparing Basicity and Nucleophilicity.There are, however, a few interesting wrinkles which might help to put some of these concepts into a broader focus. Most of what follows shouldn’t come as a great surprise, as it will echo a lot of concepts and themes that have made previous appearances in the course (Org 1 in particular). The relative nucleophilicity of amines doesn’t get a lot of coverage (translation: doesn’t get tested) in many organic chemistry courses, but if we’re going to cover amines, it seems worthwhile to at least devote one post to their nucleophilicity trends.