In a blatant plug for the Reagent Guide and the Reagents App for iPhone, each Friday I profile a different reagent that is commonly encountered in Org 1/ Org 2.
Sometime back in general chemistry you (hopefully) learned that hydroxide ion (HO-) is a strong base. It’s the conjugate base of water – that is to say, that’s what’s left behind once we’ve ripped a proton (H+) off of it. Likewise, alcohols (ROH) are strong bases too – once you remove the proton to get the conjugate base (RO-). Similar in strength to the hydroxide ion, these are called alkoxides.
Today’s reagent, potassium t-butoxide, is a strong base just like all alkoxides, but there’s something about it that makes it special. If you’ve come across the tert-butyl group before, you should be able to remember one main thing: it’s really darn fat (although in these more sensitive times, “bulky” is the preferred nomenclature). And as the conjugate base of t-butanol, that makes t-butoxide a bulky base just like our old friend LDA. (Note that the “potassium” isn’t so crucial here and we can leave it out or replace it with sodium or lithium- it’s really the “t-butoxide” part we really care about.)
Potassium t-butoxide is like a really angry Sumo wrestler. It attacks things that are out in the open with fierce and sturdy determination. However, anything that requires the least bit of navigation through a narrow opening (like a doorway) is going to be difficult. In the chemical sense, this means that t-butoxide is very sensitive to steric interactions. (What are “steric interactions” ? Think about 4 hungry Sumos trying to fit themselves around your tiny dinner table). More specifically, steric interactions are the repulsive interactions between electron clouds that happens when atoms “bump” into each other.
So what does this mean for the chemical reactions of t-butoxide? Two things.
- t-butoxide is a poorer nucleophile than smaller alkoxides (like ethoxide, methoxide and so on) in nucleophilic substitution reactions (like the SN2). Why? Because the SN2 is very sensitive to steric interactions, and t-butoxide is bulky.
- t-butoxide can be used to form the “less substituted” alkenes in elimination reactions (the E2, specifically). Most of the time, elimination reactions favor the “more substituted” alkene – that is, the Zaitsev product. However, when t-butoxide is used, it will preferentially remove the proton from the smaller group. This produces the so-called “Hoffmann” product. Let’s have a look.
P.S. You can read about the chemistry of Grignard reagents and more than 80 other reagents in undergraduate organic chemistry in the “Organic Chemistry Reagent Guide”, available here as a downloadable PDF. The Reagents App is also available for iPhone, click on the icon below!
Synthesis (7): Reaction Map of Benzene and Related Aromatic Compounds
The Strecker Synthesis of Amino Acids
Regioselectivity In The Diels-Alder Reaction
The Ruff Degradation and Kiliani-Fischer Synthesis
Aromatic Synthesis (2) - Polarity Reversal
What Makes A Good Nucleophile?
3 Trends That Affect Boiling Points
Five Key Factors That Influence Acidity
Polar Protic? Polar Aprotic? Nonpolar? All About Solvents
Table of Functional Group Priorities for Nomenclature
{ 10 comments… read them below or add one }
I’m curious to know: if the leaving group and the hydrogen are not antiperiplanar, can the molecule be rotated so that they are in order to do an E2 reaction.
Yes, so long as they’re not in a ring that would forbid rotation (like a cycloalkane for example)
Can t-butanol, not t-butoxide, engage in an E1 reaction?
Yes, if the reaction is heated.
When you say ”it will preferentially remove the proton from the smaller group”, do you mean the least substituted group?? Also the Zaitsev rule state that ”the poorer get poorer” (in Hydrogen), is that why it favours the ”more substituted alkene”? (less hydrogens= more functional groups= more substituted)?
Yes, the hydrogen should be removed from the least substituted group (e.g. CH3 vs. CH2CH3) in the case of KOtBu.
Zaitsev favors the “most substituted alkene” because these tend to be more thermodynamically stable. The reason takes a while to explain – it involves hyper conjugation. I don’t go into that here.
Even if tert-butoxide is sterically large, can it engage in Sn2 reactions if the leaving group is primary? If so, would that mean tert-butoxide was in fact a strong nucleophile, just that it cannot be a nucleophile if the substrate is secondary.
Yes, it can engage in SN2 reactions if the leaving group is primary. It’s not as good a nucleophile as less bulky alkoxides, but still OK
Can we use tert-Butoxide for the removal of hydrogen from -OH group.
Yes, absolutely.