Alcohols (3) – Acidity and Basicity

by James

in Alcohols, Organic Chemistry 1

In the last post we said that one of the keys to the reactions of alcohols as we go forward is that the conjugate acid is a better leaving group and the conjugate base is a better nucleophile.

We might have gotten a little ahead of ourselves broaching that topic, because we haven’t yet really revisited some of the fundamentals about alcohol acidity and basicity.

That’s the purpose of today’s post! In this post we’re going to:

  1. Review 4 key points about acid base reactions
  2. Give 2 examples of alcohol acid-base reactions
  3. Review the key factors which determine the acidity
  4. Show examples of how this applies to alcohols.
  5. Give a practice question at the end.

Let’s go!

Four Key Points To Review About Acid Base Reactions

  1. Every acid-base reaction has 4 components: an acid, a base, a conjugate acid, and a conjugate base.When an acid loses a proton, it becomes its conjugate base. When a base gains a proton, it becomes its conjugate acid. As mentioned in the previous post, the conjugate bas of an alcohol is called an alkoxide. The conjugate acid of an alcohol is called an oxonium ion.
  2. We usually describe acid-base reactions as an equilibrium. In acid-base reactions, the equilibrium will favor the direction where a stronger acid and stronger base produces a weaker acid and a weaker base.When you add HCl to NaOH, a violent acid-base reaction occurs, which leads to the formation of H2O (a weaker acid than HCl) and NaCl (a weaker base than NaOH). As you’ve no doubt discovered when adding table salt (NaCl) to water, this reaction doesn’t proceed to any significant extent in the reverse direction.
  3. We measure acidity using a term called pKa. This is a measure of the equilibrium constant for a species giving up a proton to form its conjugate base.pKa is on a scale of about -10 to 50. Sixty orders of magnitude! The higher the pKa the less acidic it is.  Lower pKa (more negative ) = more acidic.
    Water (pKa of 15.7) is a weaker acid than HCl (pKa of -8).
  4.  The stronger the acid, the weaker the conjugate base. The weaker the acid, the stronger the conjugate base. The conjugate base of the strong acid HCl (pKa -8) is the innocuous chloride ion (Cl-), a very weak baseThe conjugate base of the weak acid H2O (pKa 15.7) is the strongly basic hydroxide ion (HO-).

Examples of Acid-Base Reactions Of Alcohols

Here’s an example of a favorable acid-base reaction of alcohols. Note how we’re going from a stronger acid and stronger base to a weaker acid and weaker base [pKa values tell us for sure] Here, deprotonation is very favourable. Note that the conjugate base of an alcohol is called an alkoxide.

1-acidbase

Here’s an example of a (very) unfavorable acid-base reaction of alcohols: protonation of an alcohol by NH3. The most important reason why this is unfavourable is because we’re going from a weaker acid (pKa 38) and weaker base to a stronger acid (pKa -2) and stronger base. The equilibrium constant is about 40 orders of magnitude in the wrong direction!

2-acidbase

The Key Factors Which Determine Acidity

What determines how acidic a molecule is, anyway?

The key factor in determining acidity is the stability of the conjugate base. Any factor which makes the conjugate base more stable will increase the acidity of the acid.

What does that mean, exactly? Usually, it means stabilizing negative charge since the conjugate base will always be one unit of charge more “negative” than the acid.

How is negative charge stabilized? Two ways.

  • First, by bringing the charge closer to the positively charged nucleus [“opposite charges attract”, remember]. Across a row of the periodic table, for example, basicity decreases as we go from H3C to H2N to HO to F  because the electronegativity of the atom is increasing. That negative charge is being held closer to the nucleus, and therefore is more stable. A good rule of thumb is, “the more stable a lone pair, the less basic it is. This is also why certain species are made acidic by adjacent electron-withdrawing groups.
  • Second, by spreading charge out over a larger volume. Diffuse charge is more stable than concentrated charge. Down a row of the periodic table, for example, basicity decreases as we go from F to Cl to Br to I– because that negative charge is being spread out over a larger volume (larger atoms). The larger atoms are said to be more “polarizable”. [Note that this effect dominates rather than electronegativity in this case.] This is also why resonance serves to stabilize charges; the charge is being spread across multiple atoms, therefore reducing individual charge density.

Applying These Principles To The Acidity Of Alcohols

How do these principles relate to alcohols? It’s quite simple, actually. Since we’ll always be comparing the same atom (oxygen) we don’t need to worry about periodic trends, and we just need to focus on resonance and adjacent electron-withdrawing groups.

Alcohols where the conjugate base is resonance stabilized will be more acidic. The classic example is cyclohexanol and phenol.

Cyclohexanol has the pKa of a typical alcohol (about 16). The pKa of phenol, however, is about 10. Let’s look:

3-phenol-cyclohexanol

See how that negative charge on the oxygen of phenol can be “delocalized” back into the ring? That means the charge can be spread out throughout the molecule, which is stabilizing. Any factor which stabilizes the conjugate base will increase acidity. 

4-phenolate resonance

Here’s another example. Compare ethanol (pKa 16) to 2,2,2-trifluoroethanol (pKa about 12). Why do you think trifluoroethanol is more acidic?

5-ethanol tfe

Compare their conjugate bases. What is fluorine doing here to make the conjugate base more stable?

This is an example of an inductive effect. Fluorine, being highly electronegative, pulls electron density away from the neighbouring carbon. That carbon, now being electron poor, pulls electron density away from the carbon next door. And that carbon, being slightly electron poor, can pull some electron density away from the oxygen.

The net result is that the oxygen has lower electron density, which is stabilizing. Again, stabilize the conjugate base –>  increase acidity. 

This also works if we compare alcohol variations where we change the distance between the OH and the fluorine atom.

6-EWG-distance

That’s because the inductive effect decreases in magnitude the farther away we go from the electronegative atom.

We can also use electronegativity trends to determine the order of acidity in these molecules. Since fluorine is more electronegative than chlorine which is more electronegative than bromine which is more electronegative than iodine, the inductive effect will be highest for CF3 and lowest for CI3.

7-ewg halides

Finally, one last example. We can even think of examples where these two effects are combined:

8-acidity

Which do you think might be most acidic here?

Conclusion

Now that we’ve covered the key factors governing the acidity of alcohols, we’re more prepared to get into the nitty gritty of their different reactions. In the next post we’ll start discussing how acidity and basicity affects the reaction conditions we can use.

For alcohols, since we’re always dealing with oxygen, the only relevant factors here are resonance and electron withdrawing groups.

Questions? Post ’em in the comments!

Next Post – The Williamson Ether Synthesis 

Related Posts:

{ 7 comments… read them below or add one }

mamid

I apologize if I’m wrong, but isn’t the pKa of ethanol closer to 16 (15.9 is the most cited value)?
Also, “the electronegativity of the nucleus is increasing” and “the negatively charged oxygen on trifluoroethanol will have some of its charge redistributed to fluorine” might be somewhat difficult to understand to undergraduate students. Maybe a little bit of elaboration and/or rephrasing might be in order.

Reply

James

Thank you once more. Fixed. I am in your debt for your excellent suggestions.

Reply

George Dionne

Thank you for sharing the article. It’s very interesting. I’d love to hear more from you.

Reply

Aditya

Just one word for this-awesome! really helpful! u saved me man :-)

Reply

Rida

thanku so much! it is really helping me get through my MCAT :)

Reply

Idan

Regarding the phenol vs cyclohexanol example, since most resonance forms break the aromaticity of the ring, is the charge delocalization still significant enough as to make it a more stable conjugate base?

Reply

Jingbo

Amazing. Reopen my mind of organic chem.
I have a question. Do you think the acidity/basicity is correlated to its 1H NMR chemical shift? Specifically for protonated amino acids.
Thanks.

Reply

Leave a Comment