Section 7.5: Carbon acids and enolate ions
Table of contents
So far, we have limited our discussion of acidity and basicity to heteroatom acids, where the acidic proton is bound to an oxygen, nitrogen, sulfur, or halogen. Another very important application of acid-base theory is to the study of carbon acids, in which the acidic proton is bound to a carbon.
A hydrogen on an alkane is not at all acidic – its pKa is somewhere on the order of 50, about as non-acidic as it gets in the organic chemistry world. The reason for this is that if the hydrogen were to be abstracted, the electrons from that carbon-hydrogen bond would have nowhere to go, and would have no choice but to sit uncomfortably on a single carbon.
Because carbon is not electronegative and is terrible at holding a negative charge, such carbanion species are extremely high in energy, and their formation is highly unlikely.
How, then, can we cause a carbon-hydrogen bond to be acidic? The answer is simple – we need to find a way to stabilize the negative charge on the carbanion conjugate base. How do we stabilize a negative charge? By spreading it out – in other words, by resonance delocalization, preferably to an electronegative atom like oxygen. This is possible when the carbon in question is located adjacent to a carbonyl group. Consider, for example, the conjugate base of acetone.
One resonance contributor puts the negative charge on the C1 carbon . Due to the presence of the carbonyl group at C2, however, a second resonance contributor can be drawn in which the negative charge is located on the carbonyl oxygen – where it is much happier! This type of anion species is specifically referred to as an enolate. The negative charge on the conjugate base is stabilized because it is delocalized, by resonance, onto an oxygen atom. Consequently, acetone is acidic –weakly so, but acidic nonetheless, with a pKa of about 19. The importance of the position of the carbonyl group is evident when we consider 2-butanone: here, the protons on C1 and C3 are somewhat acidic (in the neighborhood of pKa = 19), but the protons on C4 are not acidic at all, because C4 is not adjacent to the carbonyl.
A carbon that is located next to a carbonyl group is referred to as an alpha-carbon, (α-carbon) and any proton bound to it is an α-proton. In 2-butanone, C1 and C3 are alpha-carbons, and their five protons are alpha-protons. The C4 carbon is called a β-carbon (beta-carbon), and its three protons are beta-protons.
If a carbon is in the a position relative to two carbonyl groups rather than just one, the acidity is increased even more because of the more extensive charge delocalization that is possible for the conjugate base. This keto-ester compound, for example, has a pKa of approximately 11, close to that of ammonium and phenol groups.
The negative charge on the conjugate base can be spread to two oxygens.
The acidity of alpha-protons is an extremely important concept in organic chemistry, biological organic chemistry in particular. Look through a biochemistry textbook, and you will see reaction after reaction in which the first mechanistic step is the abstraction of an alpha-proton to form an enolate intermediate. Three examples are shown here. Reaction A below is from fatty acid oxidation, while reactions B and C are both part of carbohydrate metabolism.
Protons that are positioned alpha to imine (Schiff base) groups are also acidic, due to charge delocalization onto the imine nitrogen. The conjugate base in this case is called an enamine.
Two entire chapters in this book (13 and 14) are devoted to reactions in which a key step is the abstraction of an alpha-proton next to a carbonyl or imine group.
Exercise 7.12: For each molecule shown below:
a) Show the location of all alpha-protons.
b) Draw the structure(s) of all possible enolate conjugate bases.
Terminal alkynes are another kind of carbon acid which are relevant more to laboratory organic chemistry than to biological chemistry.
Terminal alkynes are more acidic than alkenes or alkanes for the same reason that protonated imines are more acidic than protonated amines (section 7.4B): the alkyne carbon is sp-hybridized, meaning that it has 50% s-orbital character and is therefore more electronegative. With a pKa of approximately 26, alkynes are only weakly acidic, but nonetheless can be fully deprotonated through the use of a strong base such as sodium amide (NaNH2). As we will see in section 13.6A, this property of terminal alkynes can be useful in the organic laboratory when trying to form new carbon-carbon bonds.