Nucleophile vs. Base Strength

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Organic Chemistry | Predicting the Mechanism as SN1 or SN2.

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Key Questions

  • This is a tricky one, but to sum it up, nucleophiles tend to be less basic.

    Nucleophilicity refers to "how much" a reactant wants to "find" a positive charge. In other words, it measures the instability of the reactant's negative charge.
    Basicity refers to "how much" a reactant wants to "find" a Hydrogen ion.

    In both of these, the underlying drive is the same--both the base and the nucleophile want to stabilize their negative charge with a positive one.

    So, the more unstable the negative charge of a reactant is, the higher its nucleophilicity AND its basicity.

    The defining difference, then, is how a reactant behaves in the presence of a substrate that contains an electrophile or an abstractable hydrogen

    A strong base will have such a great thermodynamic instability (great energy--such as #H^-# or hydride) that it will attack a protic hydrogen to form #H_2#
    A good nucleophile, then, is not as basic and is more likely to be sterically unhindered. Consider #CN#. It will tend to act as a nucleophile and attack an electrophile

    A reactant can be a good nucleophile and a good base and act as either.
    Consider # HO^- # or hydroxide. Depending on the conditions, it can act as a base and turn into water, or it can attack an electrophile in an #SN_2# fashion
    Consider #Br^- # which is a base and a good nucleophile, It will tend to act in an SN2 fashion

    As you can see it is very nuanced, and you have to consider the whole reaction when determining nucleophilicity and basicity.

    I have to sign off now, but feel free to ask more questions or add more detail.

    Hope it helps!

  • With a few exceptions, a strong nucleophile is also a strong base.

    All nucleophiles are Brønsted bases — they donate a pair of electrons to form a bond to another atom.

    If they bond to a hydrogen atom, we call them bases. If they bond to any other atom (especially carbon), we call them nucleophiles.

    Strong Bases/Strong Nucleophiles

    A good base is usually a good nucleophile. So, strong bases — substances with negatively charged O, N, and C atoms — are strong nucleophiles.

    Examples are: RO⁻, OH⁻, RLi, RC≡C:⁻, and NH₂⁻.

    Strong Bases/Poor Nucleophiles

    Some strong bases are poor nucleophiles because of steric hindrance.

    Examples are t-BuO⁻, t-BuLi, and LiN[CH(CH₃)₂]

    Weak Bases/Good Nucleophiles

    I⁻ is a weak base, but it is a good nucleophile because the large electron cloud is highly polarizable.

  • The key factors that determine the nucleophile's strength are charge, electronegativity, steric hindrance, and nature of the solvent.

    Charge

    Nucleophilicity increases as the density of negative charge increases.

    An anion is always a better nucleophile than a neutral molecule, so the conjugate base is always a better nucleophile.

    Thus, #"HO"^(-) > "H"_2"O"#; #"H"_2"N"^(-) > "H"_3"N"#; #"HS"^(-) > "H"_2"S"#

    Electronegativity

    A highly electronegative atom is a poor nucleophile because it is unwilling to share its electrons.

    As electronegativity increases, nucleophilicity decreases.

    The order of electronegativity is

    #"C"# <# "N"# < #"O"# < #"F"#

    So the order of nucleophilicity is

    #"CH"_3^(-) > "NH"_2^(-) > "HO"^(-) > "F"^(-)#

    Steric hindrance

    The bulkier a nucleophile is, the more difficult it is to attack the substrate, and the weaker the nucleophile becomes.

    So the order of nucleophilicity is

    #("CH"_3)_3"CO"^(-) < ("CH"_3)_2"CHO"^(-) < "CH"_3"CH"_2"O"^(-) > "CH"_3"O"^(-)#

    Effect of Solvent

    A polar protic solvent such as water or methanol can hydrogen bond with a nucleophile.

    This creates a shell of solvent molecules around the nucleophile that hinders its access to the substrate and decreases its nucleophilicity.

    A polar aprotic solvent like acetone or dimethylformamide preferentially solvates cations, leaving an almost "bare" nucleophile. This increases its nucleophilicity .

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