Nucleophilicity (Nucleophile Strength)


What I want to do with this
video is talk about nucleophilicity. This is really just how good of
a nucleophile something is. Or I’ll just make up a
definition right now: the ability for an atom slash ion
slash molecule to act as a nucleophile, or to give away
extra electrons and bond with a nucleus or with
something else. I’ll say with a nucleus. I want to say with a nucleus,
because that’s what nucleophilicity is saying. It loves nucleuses, especially
positive ones, that it can give its extra electrons
to it. Now, as a first cut, if you
want to identify a good nucleophile, it should have
extra electrons to give away. The best things that have extra
electrons to give away are negative ions or anions, so
just at a very high level, something like the
fluoride anion. Normally, fluorine has seven
valence electrons: one, two, three, four, five, six, seven,
but it’s so electronegative, it might be able swipe off
another electron from something else and then it
becomes the fluoride anion. Then it becomes the fluoride
anion with a negative charge. You can do that for all
of the halides. You could do that
for chlorine. It can become chloride. Bromine can be bromide. Iodine could be iodide. Let me do iodine, too. Iodine, once again,
it’s a halide. It has seven valence
electrons. It has many, many more electrons
than fluorine, but if you just look at
its valence shell, it has seven electrons. And then it is also reasonably
electronegative, not as electronegative as fluorine. Remember, the trend goes like
this from the bottom left to the top right. So fluorine is extremely
electronegative, but iodine is still pretty electronegative. It is a halogen so it also might
be able to swipe off an electron from someone else
and become iodide. In general, things with extra
electrons, lone pairs of electrons, and especially a
negative charge, are going to be pretty good nucleophiles. Another example that’s
not a halide is the hydroxide anion, so OH. This is an example of something
that is a molecule. Maybe traditionally water
would look like this. Traditionally, this is just
neutral water, and oxygen has two lone pairs like that,
but oxygen is pretty electronegative. It is already kind of taking the
electrons away from one of the hydrogens, and at some
point, it might just take it altogether and then you have
the hydroxide anion. This would look like this. You have your original two lone
pairs, just like that, and then you have this pair
that’s going to be taken. It already had that electron. It takes that electron from the
hydrogen, so now it has two more electrons. Let me color code it so
you see what it took. It took this electron from the
hydrogen and now this also has a negative charge. That’s also a reasonably
good nucleophile. And, of course, you have
your hydrogen now. It lost its one electron. It only has a proton
in its nucleus. Whenever you see H plus, this
is really just a proton. There’s nothing else
to that hydrogen. So that’s hydroxide. These are all reasonably good
nucleophiles in that they have something to give away. They have extra charge. Now, what I want to do is think
about between these, how do you think about what’s going
to be a stronger or weaker nucleophile? And here, it becomes a little
bit more nuanced. What we’re going to do is
differentiate what happens in a protic solvent versus what
happens in an aprotic solvent. Let me write down. Let me start with a
protic solvent. I’ll make two columns here,
protic solvent and then we’ll do aprotic solvent
right over here. Once again, these are fancy
words, but they mean something pretty simple. Protic solvent is something that
has hydrogens that can be taken away or might have free
protons floating around. An example of a protic
solvent is water or really any alcohol. Water is the simplest example
or maybe the most common. The reason why you might have
protons floating around is exactly this reaction
I showed right here. Maybe every now and then a
hydroxide anion forms. Even more likely, maybe a water takes
a hydrogen from one of the other waters. One of the water molecules takes
hydrogen from one of the other water molecules and
becomes a hydronium, where it’s not a proton necessarily,
but it’s an oxygen. Let’s say if you start with
water and one of these electrons were to be given to
some proton floating around, it would look like this. And it has a positive
charge and then this proton is very available. You can almost imagine it’s
almost floating around because that oxygen really wants to
take back that electron. So protic solvent is water. In water, you might see a little
bit of hydroxide, a little bit of proton, a little
bit a hydronium. You see all of it in there, but
the bottom line is that there are protons that can
react with other things. Let me clear this away so that
I have some real estate. Let me just write down water. Water is a protic solvent. Now, wait. Is that always the case? It seems like hydrogens
are everywhere. Well, no, it’s not
always the case. Let me show you an
aprotic solvent. Diethyl ether looks like this. And just so you know the naming,
it’s an ether because it has oxygen, and it’s diethyl
because it has two ethyl groups. That’s one ethyl group right
there and that is the second. So it’s diethyl ether. Now, you might say, hey, this
guy’s got hydrogens lying around as well. Maybe those can get released. But, no, these hydrogens are
bonded to the carbon and carbon is not anywhere near as
electronegative as oxygen. Carbon is unlikely to steal
these hydrogens’ electrons and these hydrogens to be loose. If they were bonded to the
oxygen, that would have been a possibility. With water, you have
obviously H-O-H. In alcohols, you have some maybe
carbon chain bonded to an oxygen, which is then
bonded to a hydrogen. So in either of these cases,
in either water or alcohol, you have these hydrogens where
the electron might be taken by the oxygen because it’s so
electronegative and then the hydrogen floats around. Anyway, that’s a review of
protic versus aprotic. In a protic solvent– and this
is actually a general rule of thumb– if a nucleophile is
likely to react with its solvent, it will be bad at
being a nucleophile. Think about it. If it’s reacting with the
solvent, it’s not going to be able to do this. It’s not going to be able to
give its electrons away to what it needs to give it away,
to maybe what we saw in an Sn2-type reaction. In a protic solvent, what
happens is that the things that are really electronegative
and really small, like a fluoride anion–
let me draw a fluoride anion. In a protic solvent, what’s
going to happen is it’s going to be blocked by
hydrogen bonds. It’s very negative, right? It has a negative charge. And it’s also tightly packed. As you can see right here,
its electrons are very close, tied in. It’s a much smaller atom
or ion, in this case. If we looked at iodide,
iodide has 53 electrons, many orbitals. Actually, iodide
would have 54. It would have the same
as iodine plus one. Fluoride will have 10 electrons,
nine from fluorine plus it gains another one, so
it’s a much smaller atom. So when you have water hanging
around it, let’s say you have something like water. That has a negative charge. Water is polar. Actually, both of these are
polar, so I should write down polar for both of these. This is a polar protic
solvent. This is a polar aprotic
solvent. In this case, water is still
more electronegative than the carbon, so it still has a
partial negative charge. These parts still have
a partial negative. Water still has a partial
negative charge. The hydrogen has a partial
positive charge so it is going to be attracted to
the fluorine. This is going to happen all
around the fluorine. And if these waters are
attracted to the fluorine in kind of forming a tight shell
around it, it makes it hard for fluorine to react. So it’s a worse nucleophile
than, say, iodide or hydroxide in a polar protic solvent. Hydroxide has the same issue. It’s still forming hydrogen
bonds, but if you wanted to compare them, iodide
is much bigger. Maybe I’ll draw it like this. I’ll draw its valence
shell like this. It’s a much bigger ion. It has all these electrons
in here. And so, it still will form
hydrogen bonds with the water. It still will form hydrogen
bonds with the hydrogen end of the water because they’re
partially positive, but it’s going to be less
tightly packed. And on top of that, iodide is
more polarizable, which means that its electron cloud is so
big and the valence electrons are so far away from the nucleus
that they can be influenced by things and then
be more likely to react. So let’s say this iodide is
getting close to a carbon that has a partial positive charge. So let’s say carbon is attached
to a bromine and then it’s attached to three
hydrogens. We’ve seen that this will have
a partial negative charge. It’s more electronegative than
the carbon, which will have a partial positive charge. When this guy, this big guy with
the electrons really far away, gets close to this, more
of the electron cloud is going to be attracted to the partial
positive charge. It’ll get distorted a little bit
and so it is more likely to react in a polar
protic solvent. Fluoride, on the other hand,
is very tightly packed, blocked by the hydrogen bonds. It’s less likely to react. If you were to look at the
Periodic Table, if you look at just the halogens in a polar
protic solvent, the halides– this would be the ion version of
the halogens– the halide’s iodide will be the
best nucleophile. Fluoride will be the worst. So
in a polar protic solvent– let me write this down– we
have a situation where the iodide is the best nucleophile,
followed by bromide, followed by chloride,
and then last of all is the fluoride. The exact opposite is true
in an aprotic solvent. In an aprotic solvent, the
fluoride, which is– fluorine is far more electronegative. Fluoride is more basic. It will be more stable if it
is able to form a bond with something than iodide. Iodide is pretty stable. If you look at a hydrogen
iodide, it’s actually a highly acidic molecule. So iodide itself, the conjugate
base of hydrogen iodide, is going to be
a very bad base. When you’re dealing with an
aprotic solvent, you go in the direction of basicity. We’re going to learn in the
next video that actually basicity and nucleophilicity are
related, but they aren’t the same concept. We’re going to talk about
that in a little bit. If you’re in an aprotic solvent,
you’re not reacting with the solvent as much. And then in this situation,
fluoride is actually the best nucleophile, followed by
chloride, followed by bromide, followed by iodide. So here, you’re going in the
direction of basicity. This is the best. This is the
worse in an aprotic solvent. If it was in a protic solvent,
this is flipped around. This becomes the best and
this becomes the worst.

45 Replies to “Nucleophilicity (Nucleophile Strength)”

  1. I'm a little confused on the suffixes. For instance, what are the differences between fluoride, fluorine, fluorite, and so on?

  2. @junior1984able In a nutshell, SN1 occurs in tertiary carbons (possibly secondary, but it's rare) and it forms an intermediate carbocation. The rate determining step for SN1 is based on the stability of the substrate (Carbocation). In contrast, SN2 occurs mainly in methyl, primary, and secondary (slowly) carbons due to steric hindrance (which Sal explained quite well). SN2 also does not form an intermediate carbocation like SN1 reactions. Bro, watch the other vids for indepth understanding.

  3. so if i were to compare NH3 and H2O in a protic polar solvent then whichever is the weakest base wins? so NH3 is a weaker base and H2O – NH3> H2O? Or do i look at them by their size?

  4. dude!!!! youre so good at explaining this shit!! i pay 30 grand a year here at UCSD and my professors suck when you tutor for free and youre alot better than them!

  5. yo. Basically:
    SN1 Rate=K[Electrophile]
    SN2 Rate=K[Electrophile][Nucleophile]
    Thats from what I remember. Not sure if its 100% correct.

    SN1: tertiary>secondary, primary(no reaction)
    SN2: primary>secondary, tertiary(no reaction)
    Thats probably all you need to know.
    Both SN1 and SN2 are similar to E1 and E2.
    Yeah. Cool story bro! I know. Bye.

  6. It is a true privilege to listen to Sal's lectures. He could give lectures at Harvard, Yale, or any of the highest caliber institutions, but instead he does it in a way for everyone to be able to see it.

  7. Is the I + CH4 reaction in a protic solvent really that plausible? I thought you would need a tertiary or secondary carbon for SN1 reactions.

  8. Thanks I had o chem years ago and was looking for a good refresher. I have tried the online courses and have not had much luck with them.

  9. I have a doubt. If there is more charge on a molecule, wont it have more ability to lose the extra electron since it has more electrons? Also, F- in this video, they said H+ reacts with F-, later quoting "F- does not react much bcz H2O surrounds it". Well, it is reacting with H2O? Nucleophiles are proton loving species. Please correct me where I went wrong.

  10. I was talking to the girl who sits behind me in class about these videos and I said my favorite is the guy who sounds like Markiplier and she knew who I was talking about.

  11. 7:48 – I think "interacting" would be a more appropriate word than reacting here, since reacting sounds like the nucleophile reacts with the protic solvent and grabs its proton, which can lead to confusion. Interacting means that the nucleophile is being inhibited from being a good nucleophile since these interactions with the solvent prevent it from actually REACTING and taking a proton from it.

  12. I paid 1000 dollars for my orgo class, yet I learn way more from your FREE videos. Sir, when my career starts I will actively donate a percentage of my income to Khan Academy. This is a promise.

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