Acid–base reactions are the most common reactions in this course, by a wide margin. Protons move on and off oxygen and nitrogen in nearly every mechanism you will draw: to make one partner more reactive, to free up a lone pair, or to tidy up a charge at the end. Curved arrows already drew this step, a proton transfer, with two arrows. This page names the two partners in it, shows how to find them in a molecule you have not seen before, and uses pKa, the number you met in Resonance, to tell which way a proton transfer goes.
The Brønsted–Lowry definition
Hydrogen chloride and ammonia react the moment they meet. The hydrogen of HCl moves onto ammonia's nitrogen, and the products are the ammonium ion, NH₄⁺, and the chloride ion, Cl⁻.
That hydrogen travels without its electron. A hydrogen atom that has lost its only electron is a bare nucleus, a single proton, so chemists call H⁺ a proton. The reaction moves one proton from chlorine to nitrogen.
This is the Brønsted–Lowry picture of acids and bases. A Brønsted–Lowry acid is a proton donor, as HCl is here. A Brønsted–Lowry base is a proton acceptor, as ammonia is. Every Brønsted acid–base reaction is a proton transfer from the acid to the base.
A proton never floats free in solution. It is always bonded to something, so an acid can give up its proton only when a base is there to take it.
Each product has a name, and this chapter uses both from here on. What is left of the acid after it loses the proton is its conjugate base, so chloride is the conjugate base of HCl. What the base becomes after it gains the proton is its conjugate acid, so ammonium is the conjugate acid of ammonia. In the same way, acetate is the conjugate base of acetic acid. Conjugate acids/bases works out what the pairing is good for.
You may have met the older Arrhenius definition in general chemistry: an acid produces H⁺ in water, and a base produces OH⁻ in water. It works only in water. The Brønsted–Lowry definition works in any solvent, or with no solvent at all. That matters here, because most organic reactions run in solvents such as ether, dichloromethane, THF (tetrahydrofuran) or DMSO (dimethyl sulfoxide) rather than in water.
Ammonia's nitrogen has a lone pair. In HCl, chlorine pulls the bonding pair toward itself, which leaves the hydrogen δ+ (slightly positive).
Arrow 1 starts on nitrogen's lone pair and ends on the hydrogen. It makes the new N–H bond.
Arrow 2 starts on the H–Cl bond and ends on chlorine, which leaves with both electrons as chloride. This arrow is not optional. Without it, the hydrogen would end up with two bonds.
Now check the charges. Both molecules go in neutral. Coming out, nitrogen carries +1 and chlorine −1, so the total is still 0.
In the terms that Curved arrows introduced, the base is the nucleophile, the proton is the electrophile, and the conjugate base is the leaving group. Every proton transfer has these three roles.
Here are the same two arrows on a reaction you could run in the lab. Sodium methoxide, NaOMe, is dissolved in methanol, and acetic acid is added. The sodium ion, Na⁺, takes no part, so the base is methoxide, CH₃O⁻.
Step 1: find the acid. Acetic acid has four hydrogens. Three sit on the methyl carbon, and one sits on oxygen. The O–H hydrogen is the one that leaves. Losing it gives acetate, a carboxylate ion whose negative charge is shared over two oxygens by resonance. Losing a methyl hydrogen would instead give a carbanion, a carbon carrying the negative charge, which is far less stable. Factors affecting acidity explains why the more stable anion decides which hydrogen leaves.
Step 2: find the base. Methoxide's oxygen carries a negative charge and three lone pairs. Any one of those pairs can take the proton.
Step 3: draw both arrows. Arrow 1 starts on a methoxide lone pair and ends on the acidic hydrogen. Arrow 2 starts on the O–H bond and ends on acetic acid's oxygen.
Step 4: check the charges. Going in, methoxide is −1 and acetic acid is neutral. Coming out, methanol is neutral and acetate is −1.
Arrow 2 is what makes the conjugate base negative: the old O–H bonding pair stays on oxygen when the proton leaves. Drawn alone, though, arrow 2 would say that acetic acid falls apart by itself, with no base involved, and it does not.
Which side does the equilibrium favor?
Go back to methoxide and acetic acid. The reaction can also run backward, with acetate taking a proton from methanol. Both directions run at once, so the mixture settles into an equilibrium. Every proton transfer is an equilibrium for this reason. Chemists often draw a plain → when one side wins overwhelmingly, as in the examples above, but ⇌ is always correct. The question is which side the mixture ends up on.
To answer it, compare the acids by their pKa, the number you met in Resonance. The lower the pKa, the stronger the acid, which means the more readily it gives up its proton, and each unit is a factor of ten. pKa explains where the number comes from.
Acetic acid, the acid on the left, has a pKa of 4.76. Methanol, the acid on the right, has a pKa of 15.5. Methanol is by far the weaker acid, so it keeps its proton, and the equilibrium lies on the right. Methoxide therefore removes the proton from acetic acid essentially completely. That is why carboxylate salts are so easy to make, and why a carboxylic acid cannot survive in a flask that contains an alkoxide.
The general rule follows from that example. A proton transfer favors the side with the weaker acid and the weaker base, which is the more stable, lower-energy side. Put another way, the proton ends up where it is held most tightly.
The gap between the two pKa values tells you how strongly one side is favored. Take acetic acid and ammonia, which give acetate and ammonium, pKa 9.2. The gap is about 4.5 units, so the right side wins by about 104.5, roughly 30,000 to one. As a rough guide, a gap of about 4 units, 104 to one, is already complete for practical purposes. The methoxide reaction, with its gap of 10.7 units, favors the right side by about 5 × 1010 to one.
Chemists say a reaction "goes" when the acid on the right is much weaker than the acid on the left, and many steps in synthesis use a base chosen to make that gap large.
Proton transfers are fast
Proton transfers between electronegative atoms, such as oxygen to oxygen or oxygen to nitrogen, are among the fastest reactions in chemistry. Many are diffusion-limited: the proton moves as soon as the two molecules touch, so the only limit on the rate is how fast they find each other in solution. Such a transfer is effectively never the step that holds up a mechanism.
You will rely on this often. In a mechanism with several steps, you can move protons between oxygen and nitrogen atoms freely, and a mechanism is not wrong for including a step that only shuffles a proton. Removing a proton from carbon is different: it is much slower, and Enolate Chemistry gives it a chapter of its own.
Recognizing the acid and the base
In a mechanism, the acid is often not a bottle of HCl. It may be the solvent, a protonated intermediate made two steps earlier, or the starting material itself. Likewise, the base may be a carboxylate, an amine, a halide ion or just water.
"Find the most acidic proton" and "find the most basic site" are the two questions this topic asks most. A short scan answers both. Run it in this order, because checking O–H and N–H first settles most molecules in one pass.
- O–H and N–H first. A carboxylic acid O–H has a pKa around 5, a phenol O–H around 10, and an alcohol or water around 16. An amine N–H is around 38. If a molecule has an O–H anywhere, that is almost certainly the answer.
- Then C–H, but only two kinds. A hydrogen on the carbon next to a C=O has a pKa near 20 in a ketone, and higher in an ester or a carboxylic acid. A terminal alkyne C–H sits at 25. Every other C–H has a pKa of about 40 to 50 and is not acidic in any useful sense. An alkane C–H, at about 50, is beyond the reach of every base in the first half of the course.
- For the basic site, find the most available lone pair. A negative charge beats a neutral atom. Among neutral atoms, nitrogen beats oxygen: nitrogen is less electronegative, so it holds its lone pair more loosely and shares it more readily.
4-Aminobutan-1-ol, H₂N–CH₂CH₂CH₂CH₂–OH, has an NH₂ at one end of the chain and an OH at the other. Run the scan on it.
Most acidic proton: the O–H, with a pKa of about 16. It beats the N–H, at 38, by 22 units, a factor of 1022, and the C–H bonds, at roughly 50, are not in the running. So one equivalent (one mole per mole of the compound) of a strong base such as sodium hydride, NaH, removes the O–H proton and nothing else. The base in NaH is the hydride ion, H⁻, which takes the proton and leaves as hydrogen gas, H₂.
Most basic site: the nitrogen lone pair, not one on oxygen. Both atoms have lone pairs, but nitrogen holds its pair less tightly. So one equivalent of HCl puts its proton on nitrogen every time, giving the ammonium salt and leaving the alcohol untouched.
The two answers sit on different atoms. The molecule is neither "an acid" nor "a base" in the abstract: which role it plays depends on what else is in the flask. A species that can act as either an acid or a base is amphoteric, and Conjugate acids/bases takes that idea further.
The acid is often a cation
Add HCl to water, and the proton does not stay on chlorine. It moves to a water molecule and gives hydronium, H₃O⁺, which is what "aqueous acid" really means. Hydronium is the acid that then acts in the flask, and its pKa is −1.7.
Hydronium shows a general pattern. Protonating a neutral oxygen or nitrogen gives a species with a full positive charge, and the charge makes it a far stronger acid. When the proton leaves, the charge does not have to go anywhere: it disappears, and a neutral molecule is left. A neutral acid, by contrast, has to leave a negative charge behind.
So when a mechanism has an acidic step but no acid from a bottle, look for a cation made earlier in the mechanism. Each one hands its proton to almost any base it meets.
A protonated alcohol, R–OH₂⁺, is another cationic acid you will meet constantly. Compare each cation with its neutral parent: hydronium is −1.7 and water 15.7, a protonated alcohol is about −2 and the alcohol 16. In both pairs, the positive charge lowers the pKa by about 17 to 18 units.
A protonated ketone, R₂C=OH⁺, has a pKa of about −7. The ketone has no O–H to compare it with, and that is the point: protonation creates an acidic hydrogen where there was none.
Preview. Two uses of these cations come in later chapters, and nothing on this page depends on them. A protonated alcohol can lose water as a neutral molecule, which starts the substitution and elimination reactions of Substitution & Elimination. A protonated carbonyl is how an acid catalyst makes the carbonyl carbon more electrophilic in Carbonyl Chemistry.
What carries forward
The pKa scale is built on the Brønsted framework, and it is the most quantitative tool in the course. In later chapters it predicts how good a leaving group is, how strong a nucleophile is, and whether a given base can remove a given proton. Conjugate acids/bases and pKa come next and build that scale. Lewis acids/bases, at the end of this chapter, widens the idea to reactions that move an electron pair but no proton. And from Carbonyl Chemistry through Enolate Chemistry, acid and base catalysts are what make half the reactions run at a useful rate.