Leaving Groups

Key Questions

  • Answer:

    Good leaving groups are weak bases.


    Consider a general nucleophilic substitution reaction.


    The second arrow always shows a pair of electrons going toward the leaving group.

    The best leaving groups "want" those electrons. They don't want to share them with other atoms.

    Good leaving groups are weak bases.

    Weak bases have strong conjugate acids. So we can identify weak bases by looking at a #"p"K_"a"# table.

    Caution: The #"p"K_"a"# value measures the position of an equilibrium. But leaving group ability is based on reaction rates. So although the correlation is good, it's not perfect.


    In general, the weaker the base, the better the leaving group.

    Exception: Fluorine is a poor leaving group.

    F⁻ is a small ion. Its high charge density makes it relatively unpolarizable. The leaving group needs to be polarizable to lower the energy of the transition state. You should never see F⁻ leave in an #"S"_"N"2# reaction.

    Question: Why is water a good leaving group?
    Answer#color(white)(ll)#: It isn't! Hydronium ion is the leaving group.


    Consider the equilibrium

    #"R-OH ⇌ R"^"+" + underbrace("OH"^"-")_color(red)("conj. base of H"_2"O")#

    Water is a weak acid, so the hydroxide ion is a strong base. It "wants" to use its lone pair electrons to form a covalent bond.

    Thus, the position of equilibrium lies far to the left.

    If we protonate the alcohol, we get

    #"R-"stackrelcolor(blue)(+)("O")"H"_2 ⇌ "R"^"+" + underbrace("OH"_2)_color(red)("conj. base of H"_3"O"^"+")#

    Water is the conjugate base of hydronium ion, the strongest acid that can exist in water.Thus water is a weak base.

    It has little tendency to share its electron pairs with another species.

    Water in the form of hydronium ion is an excellent leaving group.

    Here's a video on what makes a good leaving group.

  • The general idea is that "poor" leaving groups have a strong nucleophilicity, or a strong "desire" to not bring its electrons with it and allow the bond to break.

    For example, #I^-# is quite a good leaving group because it is pretty large (#196# pm, compared to #F^-#, which is #133# pm), meaning its internuclear distance is far and the bonding interactions are weak. That's why #HI# (pKa #~~ -9#) is a stronger acid than #HF# (pKa #~~ 3.14#). As an example on the other extreme, a methyl cation (#CH_3^+#) is one of the worst leaving groups there is.

    You can determine how "poor" of a leaving group it is by knowing the pKa of the acid related to the leaving group. The pKa of #CH_4# is somewhere around 50~60, which makes it a very strong base. That alone tells you that it's almost always going to want to stay attached to the rest of the compound.

    Also, as a general rule, weaker acids tend to be more stable than stronger ones (weaker acid, stronger basicity in the bonds, tends more to maintain the interaction, doesn't dissociate as easily), so since the conjugate acid of a strong base is a strong acid, the #CH_3^+# leaving group must then be really unstable and reactive.

  • The leaving group is the part of the substrate that is missing at the end of the reaction.

    The equation for a typical nucleophilic substitution reaction is

    Nu⁻ + R-L → Nu-R + L⁻

    Nu⁻ is the nucleophile, and R-L is the substrate.

    The L group is missing from the substrate, so L is the leaving group.

    Suppose the reaction had been

    N≡C⁻ + CH₃CH₃CH₂-Br → CH₃CH₂CH₂-C≡N + Br⁻

    The product no longer has the Br atom that was in the CH₃CH₃CH₂-Br.

    The leaving group was the Br atom.

    Here's a video on leaving groups.