Strong Nucleophiles [with Study Guide & Chart] - Organic Chemistry

What are strong nucleophiles?

Strong nucleophiles:

Strong nucleophiles…this is why molecules react. The nucleophilic site of the nucleophile is the region of a molecule that is reactive and has the electron density.

Strong nucleophiles are VERY important throughout organic chemistry, but will be especially important when trying to determine the products of elimination and substitution (SN1 vs SN2) reactions. In fact, there is not a more important part of an organic chemistry reaction than the nucleophile and the electrophile. So, let’s look at what makes strong nucleophiles:

There are generally three factors to remember when discussing how nucleophilic a reactant is:

1) Size – Generally (but not always) the more linear and/or smaller the nucleophile, the more nucleophilic it will be. This is because it can react at more sites and will not be sterically hindered if it is smaller or linear. Remember, smaller nucleophiles can fit into more places, therefore will be able to react at more places and will necessarily be more nucleophilic. This has a lot to do with sterics. You will hear a lot about bulky bases, which are nucleophilic but too darn big to be a nucleophile and can only be a base.

2) Electronegativity– The more electronegative an atom is, the less nucleophilic it will be. This is because more electronegative atoms will hold electron density closer, and therefore will be less likely to let that electron density participate in a reaction. We see this in calculations and experiments that show nucleophilicity decreases as you get closer to fluorine on the periodic table (C > N > O > F).

3) Polarizability– The more polarizable an atom is, the more nucleophilic it will be. Polarizability is defined as the ability to distort the electron cloud of an atom, which allows it interact with a reaction site more easily. Generally, polarizability increases as you travel down a column of the periodic table (I > Br > Cl > F)

Below is a table of relative nucleophilic strength. This is relative because nucleophilic strength is also dependent on other factors in the reaction, such as solvent. I am not a huge fam of memorizing charts, but this might be a good one to know pretty well.

VERY Good nucleophiles	HS–, I–, RS–
Good nucleophiles	Br–, HO–, RO–, CN–, N3–
Fair nucleophiles	NH3, Cl–, F–, RCO2–
Weak nucleophiles	H2O, ROH
VERY weak nucleophiles	RCO2H

As shown above, as a general rule, the anion of a reactant will be a better nucleophile than the neutral form. (i.e. RCO2– is a better nucleophile than RCO2H)

But nucleophiles are also bases?

Think about it for a second….good nucleophiles (as shown above) can have a negative charge and will almost always have a lone pair. Bases accept protons, with a negative charge or lone pair. [gasp] So it makes sense there will be at least some overlap between bases and nucleophiles. This is a major consideration when looking at SN vs E reactions.

Here are a couple of good rules to remember:

1. Bases will not be good nucleophiles if they are really bulky or hindered. A variety of amine bases can be bulky and non-nucleophilic.

2. Nucleophiles will not be good bases if they are highly polarizable. I- is the best example of this. Great nucleophile, really poor base.

Why do we care about strong nucleophiles?

Organic chemistry is all about reactions. We really need to know what is nucleophilic and what is not so that we can determine what is going to react at the electrophilic site. If you know this, you can predict the products of organic chemistry reactions, even ones that you have not seen before.

The next step is to learn about electrophiles.

Please visit our recent post on this topic –> Electrophilic addition. Not to humble brag, but it is pretty good.

For more information on this and other topics of organic chemistry interest, please visit organic chemistry

Reference: Nucleophilic strength

Dr. Michael Pa

Dr. Michael Pa got a bachelors degree in chemistry from Binghamton University, a masters degree in organic chemistry from the University of Arizona and a Ph.D. in organic chemistry from the University of Arizona. His research focus was on novel pain killers which were more potent than morphine but designed to have fewer side effects. There may even be a patent or two that came out of it. Prior to all of this, he was a chemist at Procter and Gamble. After all of that, he (briefly) worked as a post-doctoral assistant at Syracuse University, working on novel organic light-emitting diodes (OLEDs). In between, he did NOT compete at the 1996 Olympics, make the Atlanta Braves opening day roster, or become the head coach of the Indiana Pacers, as he had intended. #fail During this entire time, he always loved helping students, especially if they were struggling with organic chemistry. In 2006, Dr. Pa founded AceOrganicChem.com in order to make learning organic chemistry fast and easy. 14 years and about 60,000 students later we are still helping students to learn organic chemistry one reaction at a time at https://www.aceorganicchem.com