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A Primer On Organic Reactions

By James Ashenhurst

The Three Classes of Nucleophiles

Last updated: July 7th, 2023 |

I know I’ve said this before, but a whole lot of organic chemistry can be boiled down to “nucleophile attacks electrophile“.

A nucleophile is a compound that can donate a pair of electrons to (you guessed it) an electrophile, which results in the formation of a chemical bond.

If you look closely at nucleophiles, you’ll see that they fall into three broad categories. That’s what today’s post is about: seeing these patterns.

1) Lone Pairs

This is probably the easiest class of nucleophiles to understand, because of the parallels to basicity. After all, what is an acid-base reaction but the combination of a lone pair on an atom with a proton?

lone-pairs-are-nucleophiles-with-examples-of-nucleophility-trends-charge-basicity-and-polarizability

There are several key trends to keep track of when assessing the strength of lone pairs as nucleophiles.

  1. The nucleophilicity increases as the charge of the atom it is attached to decreases. A simpler way to put this is, “the conjugate base is always a stronger nucleophile”.
  2. The nucleophilicity increases as you increase the basicity. So as you go across the periodic table from right to left, nucleophilicity also increases. [H3C(-) > H2N(-) > HO(-) > F(-) ).
  3. Nucleophilicity increases as you go down the periodic table. So comparing halides, I(-) > Br (-) > Cl (-) > F(-)

Of course you might be able to spot a contradiction here: iodine is more polarizable than fluorine, but it is also less basic. So when these two trends collide, what wins? The wishy washy  answer is that “it depends”. Solvent is a key variable here.  In polar protic solvents, nucleophilicity increases with polarizability, because hydrogen bonds form a shell around the less polarizable atoms and decrease their nucleophilicity. In polar aprotic solvents, this is not an issue, so basicity is the most important variable. [Ultimately, when trends collide, however, the final arbiter is experiment].

EDIT: Alert reader Prasanna reminds me that these trends hold for SN2 reactions, but trend #3 is less important for reactions where the nucleophile is adding to unsaturated carbon (carbonyls and aromatics). One of the challenges of understanding nucleophilicity is that it is highly dependent on the electrophile.

2) π bonds.

π bonds can also be thought of as nucleophiles: they donate a pair of electrons as well, but in this case the pair is shared between two atoms. This not only covers double bonds, but also triple bonds (alkynes) as well as aromatics and even enols and enolates (in Org 2).

pi-bonds-can-be-nucleophiles-examples-in-addition-of-acids-to-alkenes-aromatic-substitution-enols-and-enolates

The key trend that determines nucleophilicity of π bonds is the presence of donor groups. By donor groups I mean an atom that can share electrons with the double bond to help stabilize it after it has donated its pair of electrons to the electrophile. This should hopefully make sense: after all, when a double bond reacts with an electrophile, the result is a carbocation (a high-energy species). Electron-donor groups help to stabilize the carbocation through donation of electrons. Anything which makes the carbocation more stable is going to lower the activation energy for the reaction and make it faster.

3) Sigma bonds.

Finally,  the pair of electrons in a sigma bond can, on occasion, also act as nucleophiles.  This third important class of nucleophiles is probably more subtle and less commonly encountered than the previous two, but you might recognize it when you see it. Here are some examples:

sigma-bonds-can-be-nucleophiles-for-example-nabh4-and-hydride-shifts-and-rearrangements

Note that in order for a sigma bond to act as a nucleophile, we have to break that sigma bond. Therefore, the #1 most important factor governing the nucleophilicity of sigma bonds is the leaving group. In two of those cases, the sigma bond is attached to a negatively charged atom that will become neutral once the bond is broken. In the third case (the hydride shift) we’re changing from a very unstable secondary carbocation to a more stable tertiary carbocation.

***

Did this post miss anything? Anything I should have covered? Leave a comment!

00 General Chemistry Review
01 Bonding, Structure, and Resonance
02 Acid Base Reactions
03 Alkanes and Nomenclature
04 Conformations and Cycloalkanes
05 A Primer On Organic Reactions
06 Free Radical Reactions
07 Stereochemistry and Chirality
08 Substitution Reactions
09 Elimination Reactions
10 Rearrangements
11 SN1/SN2/E1/E2 Decision
12 Alkene Reactions
13 Alkyne Reactions
14 Alcohols, Epoxides and Ethers
15 Organometallics
16 Spectroscopy
17 Dienes and MO Theory
18 Aromaticity
19 Reactions of Aromatic Molecules
20 Aldehydes and Ketones
21 Carboxylic Acid Derivatives
22 Enols and Enolates
23 Amines
24 Carbohydrates
25 Fun and Miscellaneous
26 Organic Chemistry Tips and Tricks
27 Case Studies of Successful O-Chem Students

Comments

Comment section

19 thoughts on “The Three Classes of Nucleophiles”

  1. Ok, after further research let me see if I have my thought processes in order.
    1.) when moving across a row nucleophilicity follows basicity. The less electronegative an atom is the more basic it is.

    2.)When going down a group it is not so simple. Nucleophilicity does not necessarily mirror basicity. This idea stems from the fact that when we consider an negatively charged ion as a nucleophile we must take into consideration the type of solvent used.If a polar protic solvent is used, the nucleophile will be hindered from being able to share its electrons in attacking an electrophile because the protic solvent will hydrogen bond and form a solvation shell around the nucleophile. Basically, this means that larger anions, which are more polarizable, will be more nucleophilic because their electrons will be less hindered when compared to smaller anions in their group.Thus, in this case nucleophilicity increases as you go down a group, not up a group.

    3.)However, if you use a polar apriotic solvent on a negatively charged ion no hydrogen bonding occurs.Thus, no solvation shell. In consequence, you will have nucleophilicty following basicity up or down the column(Note: I have read that even then this is not always the case.Could you elaborate?)

    4.)When it concerns nucleophiles that are uncharged size dicatates nucleophilicity.The larger the atom the greater a nucleophile it is.
    5.) Sterically hindered nucleophiles react more slowly.

    Reply

  2. The third trend of nucleophilicity of lone pairs states-nucleophilicity increases as you go down the periodic table .Do we always assume nucleophilicity always increases as we go down any group in the periodic table or must we always consider the solvent along with this trend?Please explain.

    Reply

  3. (I know this post is really old but trying does no harm)
    In a previous post you mentioned that electronegativity increases the stability of negative charge (therefore basicity as well)
    But as you said in this post, F(-) is the worst nucleophile despite havint the most basicity (if I’m not mistaken)
    So does it mean that nucleophility DEcreases with basicity? (Sorry if I’m asking nonsense, I’m just a high school student interested in org chem ><)

    Reply

    1. Nucleophilicity is solvent-dependent. Polar protic solvents can hydrogen bond with halides. F- is most basic, but also forms strongest hydrogen bonds, and will carry around with it a shell of solvent molecules which hinder nucleophilicity. That is why F- is the worst nucleophile among halides in polar protic solvents.

      In polar aprotic solvents trend is reversed; F- is best nucleophile, I- worst. See this post on solvents:
      https://www.masterorganicchemistry.com/2012/04/27/polar-protic-polar-aprotic-nonpolar-all-about-solvents/

      Reply

    1. It certainly can! For example, carbonate ion can react with an electrophile (e.g. dimethyl sulfate) to give CH3-O-CO2(-) in a nucleophilic substitution reaction. The problem with the resulting product is that it is unstable towards loss of CO2 (it’s a carbonic acid) and will form an alkoxide (alcohol after protonation). If multiple equivalents of the electrophile are used, the R-O-CO2(-) will react further to give another substitution product, e.g. CH3-O-CO-O-CH3. This product, “dimethyl carbonate” is stable.

      Reply

  5. Why is Iodine less basic than Fluorine? Iodine outer electrons would be held less tightly than Fluorine as it is a much larger atom and its inner electron shells would shield the valence electrons from the nuclear pull where the protons lie.

    Reply

    1. Iodine is less basic in reactions than fluorine is because it is less electronegative. Fluorine has the highest electronegativity of any chemical element.

      Reply

  7. I don’t understand how the sigma bond is broken in hydroboration reaction. Which is the electrophile on this case

    Reply

    1. The electrophile is the weak O-O bond, specifically the sigma* orbital of the O-O bond. The nucleophile is the C-B bond. It’s a strange reaction the first time you see it, but there are more examples in org 2.

      Reply

  9. Hi, I’m having trouble understanding why CH3 is more basic than OH. Isn’t OH considered to be a very strong base, or am I getting mixed up here?

    Anyways, thank you for your helpful website!

    Reply

    1. (-)OH is a very strong base. However as we go to the left of O on the periodic table, electronegativity goes down, which means the electrons are held less tightly. So a negative charge on nitrogen such as in (-)NH2 will be considerably more unstable , which translates as “more basic”. A full negative charge on carbon, which is even less electronegative than nitrogen, will be even less tightly held (and more unstable). (-)CH3 is thus even more basic than (-)NH2 which in turn is more basic than (-)OH.

      Reply

  10. What would be the order of increasing nucleophilicity between these 3 factors? Is it lone pairs > pi bond > sigma bond, which produce greater nucleophile strength, or what other factors would it depend upon?

    Reply

  12. It is really difficult to think pi bond or Sigma bond as nucleophiles. Can’t i consider Cl(-ve) or Br(-ve) as nucleophiles when reacting with double bond or triple bond, i mean wherever u are considering pi bond as nucleophile i am considering the negative ion” as nucleophile and it becomes really easy yet I have faced no objection in explaining the reaction. My question is would I be hampered in future if I continue to do this??

    Reply

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