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One of the most common questions in organic chemistry is ‘which of these two compounds is more acidic?’ Here are the 4 most important factors to consider.
How to determine the stronger acid
In Organic Chemistry, acids and bases is really quite qualitative. We’re often looking at whether a compound is even acidic or basic at all. Or if we compare two compounds, which one is more acidic or more basic or which part of an organic compound is acidic or basic? Watch the video below to find out!
ARIO – Atom, Resonance, Induction & Orbital
When we’re looking at compounds in Organic Chemistry and we’re looking at acidity or basicity, I really want you to remember four general principles.
These are related to the letters A, R, I, and O:
- A stands for Atom
- R stands for Resonance
- I is Induction
- O is Orbital
This is the general order in which I want you to think of in terms of looking at the acidity of a compound. A is more important generally than R, R is more important generally than I, and O is normally the last on the list.
Now, this becomes more clear when we look at examples. Let’s look at a few examples.
A – Atom
If we compare, for example, ethane versus methylamine or ‘methylamine’, then which one of these two is more acidic? And reminder, when we’re looking at acidity, we’re looking at the equilibrium between this compound and its conjugate base. If I draw this in very briefly here, then for ethane, that will be a CH3CH2 minus where we’ve lost a proton of that carbon. I might actually just put that negative charge above that carbon there versus the equilibrium with CH3NH, just one hydrogen, minus. We will lose the proton from that nitrogen. Now, nitrogen is further to the right from carbon and therefore it is more electronegative. There’s more protons in the nucleus that can help to stabilize the extra electron, that negative charge. So overall, as we go to the right in terms of electronegativity, we’re able to stabilize the negative charge more easily. Therefore, those atoms are generally more acidic. And so, we would say that it’s likely that methylamine is going to be more acidic than ethane, and that’s indeed the case.
If we look at the acidity of these compounds, the pKa for ethane is 50 and the pKa for methylamine is around 36. These get difficult to compare because with very non-acidic compounds, the numbers get difficult to measure. Now, what about if we look at the next one along? We’re going towards the right in the periodic table. I’m actually going to look at ethanol. One extra carbon but it’s generally the same principle and was the acidity of ethanol. Ethanol, if I just look it up at my pKa over here, it is 15.9, so around 16. A lot more acidic than an amine. That’s because oxygen is so much more able to stabilize a negative charge. We can pull that proton off ethanol relatively easily compared to off ethylamine. Ethoxide would be the conjugate base for ethanol.
Now, there’s one extra thing to remember in terms of atom and that’s when we go down the periodic table rather than across. As we go down, we actually get to lesser electronegative elements, but we get more protons in the nucleus.
Let’s have a look at ethanol versus ethanethiol.
This is the sulfur analog of ethanol. Now, ethanethiol, imagine if we’re looking at oxygen, we’ve got a nucleus with a certain number of protons and then you can go and look at the atomic number and work out how many protons in the nucleus of oxygen. Compare that to the larger nucleus of sulfur. It has extra protons in the nucleus and so around here, we’ve got electrons. Overall, when we are looking at the conjugate base, we have one extra electron than we should have if we are going to have a neutral species. The ratio for lower row elements is more even so the extra positive charges in the nucleus, the extra protons in the nucleus, means that we’re able to stabilize a negative charge more readily. Therefore, as we go down the periodic table, we tend to get to more acidic compounds because the conjugate base is more stable. The pKa for ethanethiol, if I just look that up over here, we’ve got a 10.6 so quite a bit… It’s about five orders of magnitude, more acidic than ethanol. That’s atom. Atom is really important. Carbon-based molecules are generally very non-acidic. They are not very acidic at all.
Nitrogen. If we’re looking at the nitrogen losing a proton to become an amide anion, then they are also not very acidic and quite strong bases. Ethoxide or other alkoxides are relatively fairly strong bases still. That means that alcohols are not particularly acidic, although they are more acidic than amines. And then thiols are more acidic than alcohols.
R – Resonance
Now, what about resonance?
A common way to look at resonance is to compare an alcohol like ethanol versus a carboxylic acid. If we draw out our equilibrium, we’re going to have the alkoxide again for losing a proton from an alcohol. But for the carboxylic acid, we’re going to have a carboxylate. What we know about carboxylates is that we can draw another resonance form for these. So if you got to curved arrows then, in your course, then we can draw curved arrows to show how one resonance form is related to another and then that will give us a single bond to that oxygen there. I’ll draw in my lone pairs if I like and I get a second resonance form for this carboxylate anion.
We know that the more resonance structures we can draw for a compound or an ion, the more stable it is. And this is really important for ions because in this case, I can share out that negative charge over two different oxygen atoms. And we know that the larger the volume or larger the space we can share out a spread out of charge, the more stable that charge is.
Nature hates to have a charge localized in a small volume. That means that the carboxylate is relatively stabilized relative to the alkoxide, and that means that this equilibrium will be shifted relatively towards the carboxylate compared to the equilibrium for the alcohol in the alkoxide. Therefore, we already know that the pKa for ethanol is 15.9 plus the pKa for the carboxylic acid, which is acidic as in this case is 4.8. A lot more acidic. In fact, about ten orders of magnitude, eleven orders of magnitude more acidic than the alcohol. So carboxylic acids, there’s an appreciable amount of ionization when you put them into water, and that’s important for their biological properties and other properties.
I – Induction
What about induction?
Let’s look at the carboxylic acids again now. If we compare acetic acid here versus a chlorinated version of that compound… This is a 2-chloroacetic acid or alpha chloroacetic acid. We already know that the pKa for acetic acid is 4.8. But when we put in this chlorine, we’re going to put in an electron-withdrawing atom. An electronegative atom near where we can get the negative charge in the conjugate base. So when we draw out this equilibrium, the conjugate base is going to look like this. I won’t draw in both the resonance forms this time but we can see that we have electron-withdrawing chlorine atom near this negative charge and that’s helping to sort of, pull that negative charge, that electron density, towards the chlorine and helps to stabilize the carboxylate. This negatively charged ion. That will help to favor that right-hand side of the equilibrium a little bit compared to the case where we only have hydrogens, which are not particularly electron-withdrawing. And so therefore, they don’t stabilize the negative charge nearly as well as the chlorine does.
Chloroacetic acid has a pKa of 2.9, about two orders of magnitude more acidic than acetic acid. You can use the same reasoning around fluoroacetic acid. Then you can start thinking, “Well, what if I put in a second or a third chlorine atom or a second or a third fluorine atom?” Things like trifluoroacetic acid, it is a really strong acid because it got three electronic-withdrawing fluorine atoms that’s helping it stabilize that negative charge.
O – Orbitals
And finally, what about orbitals?
If we compare this compound, which is acetylene versus ethane, we’ve got an sp hybridized carbon atom here. Whereas here, we’ve got an sp3 hybridized carbon atom. What this means is when this loses a proton, we’re going to get a conjugate base and we put it that there. The conjugate base where we have the negative charge in an orbital like this, which is an sp hybridized orbital. Now, when we think about hybridization of orbitals, we take a certain number of s atomic orbitals and a certain number of p atomic orbitals, and we mix them together. So, if we think about an s orbital, it looks like this. A 2s.
If we then compare that to a 2p orbital…
In the 2p orbital, we have a node here. And the node means that there’s no electron density very close to the nucleus. And so that means that overall, a 2p orbital, the electron sees a little bit less of the nuclear charge than for a 2s orbital, which has no node. If we think about hybridized orbitals, an sp orbital, we have 50% s plus 50% p going into that hybridized orbital. The s character here is able to stabilize the negative charge more effectively because there’s no node near the nucleus. So the electron density sort of sees that nucleus very well, whereas if we think about sp3 hybridize, we’ve got a 25% s plus 75% p because we got three different orthogonal p orbitals being mixed together with the s orbital to get these hybridized atomic orbitals. We say that this has less s character and more p character. And so therefore, a negative charge in an sp3 orbital is less stabilized by seeing that nuclear charge than in an sp orbital. If we look at the pKas for these, the pKa for acetylene is around 25, whereas the pKa for ethane is around 50. A huge difference between these just based on what type of orbital the negative charge is localized in when we generate the conjugate base.
So there’s the four main things I want you to consider when you’re thinking about acidity of organic compounds:
Firstly, A for Atom.
Is it a atom towards the right that’s very electronegative, which will help to stabilize the conjugate base because it has a negative charge? Or is it lower on the periodic table? It has a higher nuclear charge that is able to sort of, counteract that negative charge.
Is there resonance involved that can help to stabilize the conjugate base through delocalization of that negative charge?
Is there an inductive effect? Is there electron-withdrawing element nearby the negative charge and the conjugate base that helps to stabilize it?
Or finally, O, orbital.
What type of atomic orbital or hybridized atomic orbital is that negative charge localized in? The higher the s character, the more stabilized that negative charge is.
Acids and Bases Practice Problems
If you like to get more practice with acids and bases, I’ve got a whole problem sheet devoted to this. Just click on the link and you can download it as a free PDF!