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If you were given a chemical and told to identify it, how would you go about doing that? You could look at different factors like color, boiling point, melting point, or smell, but the answer still might not be clear. Thankfully, today we have a more precise, higher-tech way of identifying chemicals called Nuclear Magnetic Resonance, or NMR. In this episode of Crash Course Organic Chemistry, we’ll look at how NMR allows us to visualize a molecule as a spectrum, and what the peaks on the spectrum tell us about the structure of the molecule.

Episode Sources:
Mahdi, J. G. (2010). Medicinal potential of willow: A chemical perspective of aspirin discovery. Journal of Saudi Chemical Society, 14(3), 317-322.
Dempsey, D.A., Klessig, D.F. How does the multifaceted plant hormone salicylic acid combat disease in plants and are similar mechanisms utilized in humans?. BMC Biol 15, 23 (2017). https://doi.org/10.1186/s12915-017-0364-8
Still, W. C., Kahn, M., & Mitra, A. (1978). Rapid chromatographic technique for preparative separations with moderate resolution. The Journal of Organic Chemistry, 43(14), 2923-2925.
Pastre, J. C., & Duarte Correia, C. R. (2006). Efficient Heck arylations of cyclic and acyclic acrylate derivatives using arenediazonium tetrafluoroborates. A new synthesis of the antidepressant drug (±)-Paroxetine. Organic letters, 8(8), 1657-1660.

Series Sources:
Brown, W. H., Iverson, B. L., Ansyln, E. V., Foote, C., Organic Chemistry; 8th ed.; Cengage Learning, Boston, 2018.
Bruice, P. Y., Organic Chemistry, 7th ed.; Pearson Education, Inc., United States, 2014.
Clayden, J., Greeves, N., Warren., S., Organic Chemistry, 2nd ed.; Oxford University Press, New York, 2012.
Jones Jr., M.; Fleming, S. A., Organic Chemistry, 5th ed.; W. W. Norton & Company, New York, 2014.
Klein., D., Organic Chemistry; 1st ed.; John Wiley & Sons, United States, 2012.
Louden M., Organic Chemistry; 5th ed.; Roberts and Company Publishers, Colorado, 2009.
McMurry, J., Organic Chemistry, 9th ed.; Cengage Learning, Boston, 2016.
Smith, J. G., Organic chemistry; 6th ed.; McGraw-Hill Education, New York, 2020.
Wade., L. G., Organic Chemistry; 8th ed.; Pearson Education, Inc., United States, 2013.

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Hi! I’m Deboki Chakravarti and welcome  to Crash Course Organic Chemistry!

Chemists used to have a real problem  when it came to identifying the crystals,   liquid, or general gloop they found themselves  with at the end of a chemical reaction. Of course, they knew what they were trying  to make, but had they actually made it? They could check boiling points, melting points,  smell, color, or even taste in the bad old days (which is definitely not recommended now).

But all of that took weeks of diligent  effort and was still somewhat inconclusive. Fortunately we’ve moved onto a much  more high-tech analytical technique:. Nuclear Magnetic Resonance, or NMR. [Theme Music].

First off, let’s straighten  one thing out – the “nuclear” part of NMR’s name doesn’t refer to nuclear power. It refers to the nuclei of atoms. All atomic nuclei are made up of protons  and neutrons – except for hydrogen’s, which doesn't have any neutrons.

Adding up the protons and neutrons  give us the atom’s mass number. Nuclei with odd mass numbers  have a property called spin,   and having spin makes them observable using NMR. Obviously, there are quite a lot  of elements with odd mass numbers,   but we're only interested in  a handful of them for NMR.

Nitrogen-15, fluorine-19,  phosphorous-31 all show up occasionally,   but the real stars are carbon-13 and hydrogen. We'll focus on hydrogen today and do proton NMR. Spin is not the nuclei literally spinning; it’s  one of those weird quantum mechanical things.

To avoid getting too into the physics, we’ll  just say that when charged particles (like protons in a nucleus) move, a magnetic  field with a magnetic moment is created. If you've played with iron filings before, you  know they move if you put a magnet near them. Each iron filing has a magnetic moment and, under  normal circumstances, their directions are random.

However, in the presence of a magnet, which  has a magnetic field, they all line up. Similarly, if you stick a nucleus with a  magnetic moment in an external magnetic field,   it either lines up with that  field, or exactly against it. It takes less energy to align with the magnetic  field, and more energy to go against it,   so there's a clear energy difference  between the two different spin states.

Now we've got the "nuclear" and "magnetic" parts  of NMR covered, but what about the "resonance"? It turns out that particular frequencies of radio waves will cause the nuclei to flip from one spin state to the other. When we hit that perfect frequency,  that's what we call "resonance"   and the nuclei absorb the  energy of the radio waves.

This is where a detector measures  the frequency and intensity of the radio wave that got absorbed,   and plots it on a spectrum. In this episode we’re going  to concentrate on proton NMR,   which tells us about the hydrogen nuclei –  and therefore hydrogen atoms – in molecules. In general, we'll get a huge magnet,  and dissolve our chemical sample in a special deuterated solvent, where the hydrogen atoms are replaced by deuterium.

If we used a regular old solvent with  protons, the signals from our organic chemical would be overwhelmed by the  hydrogens on all the solvent molecules! Then, we put our tiny solution of chemical  sample in the middle of the magnet,   blast a pulse of radio waves, and measure  the energy released by the nuclei as the different hydrogen atoms in the chemical go  from resonance back to their ground state. Like IR spectroscopy that we talked about in  Episode 5, we get a spectrum from the sample.

Once we look at some proton NMR spectra,   we'll get the hang of these patterns  – let's start with a simple example! This is the spectrum for chloromethyl methyl  ether, or MOM chloride to its friends. The x-axis is measured in ppm,  which stands for parts per million.

It has to do with the ratio between the radio frequency source and the energy required to cause the nuclei to flip spin. The process of adding deuterium to solvents  isn’t perfect, so a few hydrogens from the NMR solvent show up as a peak, which we can  use to set the scale of our NMR spectrum. Or we can include a standard  chemical called tetramethylsilane,   or TMS in the sample, which  produces a very strong signal.

TMS shows up on the far right of the spectrum and usually doesn’t overlap with the peaks from the hydrogens on our organic chemical. Basically, the standard provides a  comparison point for the other peaks. It’s a bit like measuring times against

GMT:  if you live in New York, your time zone is GMT -5:00    while someone in Paris is on GMT +1:00, and  someone in Canberra, Australia is on GMT +11:00. So, ignoring the peak at 0 from our TMS standard,   there are only two peaks we need  to analyze in this spectrum. Using a computer, we can label each of these  peaks with the integral, the area underneath them,   which corresponds to the ratio of the number  of protons in that part of the molecule. One of our peaks here has an integral  value of three, which means three protons.

So that means there's probably a  methyl group, CH3, in our sample. The other peak has an integral of two, which  suggests our chemical also contains a CH2 group. So if we were a chemist in a lab who didn't know,  but just suspected that we had MOM chloride,   we could check whether the structure of our  suspected molecule fits with our spectrum.

And yep, there sure is a CH3  and a CH2 group in MOM chloride! One of the peaks is upfield,   or further to the right, and the other is  more downfield, or further to the left. That's because the protons making up these peaks  are surrounded by different amounts of electrons,   because of different neighboring atoms.

Nearby electrons from other atoms can shield  the proton nuclei from the magnetic field so they feel it less,    and we need a lower  frequency radio wave to flip the spin. On the other hand, electronegative atoms can draw electrons away from proton  nuclei so they're deshielded,   feel the magnetic field more, and we need a  higher frequency radio wave to flip the spin. Taking a look at MOM chloride,   we can see the CH3 group is attached  to an electronegative element, oxygen.

But the CH2 group is sandwiched  between two electronegative atoms: an oxygen and a chlorine. So the electrons near the CH2 group are more  drawn away, the proton nuclei are more deshielded,   and the peak is downfield of the CH3 group. To keep it really simple: just remember that the presence of electronegative  atoms or groups shifts peaks to the left.

In proton NMR, the peaks on the spectrum actually have pretty consistent shifts based on the electronegativity and hybridization of the atoms near the protons. Tables like this can’t cover  every possibility, though,   which is why we need to understand how to think  about electronegativity and chemical shift! Okay, now that we've talked through the MOM  chloride spectrum, let’s try another example.

This is the proton NMR spectrum of ethanol. There are three peaks in this one, but two  of them are more like… groups of lines. There are lots of protons in organic molecules,   and remember that each nucleus with an odd  mass number has spin and a magnetic moment.

So protons on one carbon can influence protons on  an adjacent carbon in a process called coupling. This leads to the split peaks, or  groups of lines, that we’re seeing here. In fact, this has been observed so regularly that we can predict how many times a peak will be split.

Thanks to the aptly named n+1 rule,  we know that a peak will be split n+1 times, where n is the number  of protons on adjacent carbons. The best way to understand  splitting is by looking at examples,   so let's start with our most shielded peak. It's at about 1 ppm with an integral of  three, so we know it's the CH3 group.

We’re still practicing, so let’s  look at the structure of ethanol. The CH3 group is bonded to a CH2 group. There are two protons on the  neighboring carbon that are coupled.

This means n is 2. Using the n+1 rule, we can do 2+1 = 3. So the CH3 peak should be split into three.

Now, going one peak downfield at about 3  ppm, we see the CH2 group in our spectrum. It's downfield of the CH3 because the CH2 group  is bonded to an electronegative oxygen atom. In the structure of ethanol, we know that  the CH2 group is bonded to the CH3 group,   so there are three protons on the neighboring  carbon that are coupled, and n is 3.

Using the n+1 rule, 3+1 = 4, so  the CH2 peak is split into four. Plus, it has an integral of two,  telling us there are two protons. These split peak patterns or  multiplicities have special names, too.

The CH3 peak split into three is a triplet,  and the CH2 peak split into four is a quartet. The third peak at about 4 ppm is the proton  on the OH group of our ethanol molecule. OH protons are tricky because they can swap  with other protons in the sample solution,   and can turn up as usually unsplit peaks  pretty much anywhere in the spectrum.

In fact, sometimes they don’t show up at all! It’s also important to mention that the  protons on oxygen and nitrogen don’t split the protons on adjacent carbons, so these protons don’t count when figuring out n+1. After you look at more peaks and more spectra,  solving these logic puzzles can be fun!

And because the whole point of proton NMR  is to figure out the structure of molecules,   this next spectrum doesn't come with a named  structure like MOM chloride or ethanol. Fortunately, we have a high resolution mass  spectrum that gives us our chemical formula:  . C5H8O2.

So let’s start with the most  shielded part of the spectrum. We have two single peaks that have  integrals of three protons each. So, it looks like we have two CH3  groups on our mystery molecule.

Next, we can see that the  most deshielded single peak,   has an integral of one proton. Referring back to our handy chart, we can see this  is where the proton on a carboxylic acid shows up. And what do you know, we have  two oxygen atoms in our formula,   which fits perfectly with that thought!

Let’s add this fragment to the  pieces of our molecule puzzle. One more peak to go! And this single peak, corresponding to  one proton, is a bit deshielded too.

In fact, looking at our chart again, it’s  showing up in the range of alkene hydrogen atoms. The trickiest part about putting these four pieces together is figuring out where to place the two methyl groups and the carboxylic acid on our alkene. To start, let's put the two CH3 groups  on different sides of the alkene.

Wait a second though... with this structure,   the methyl group is next to a  carbon atom with a hydrogen. This would split a single peak into a doublet,   and we’d expect the hydrogen atom to be split  by the three hydrogens on the methyl too. Since we don’t see splitting in the spectrum, let’s rearrange our structure so the hydrogen atom and both methyl groups won’t  be split by any adjacent protons.

Even though the two methyl groups are attached  to the same carbon, double bonds are rigid. So one of these groups is stuck on  the same side as the carboxylic acid,   and one is on the same side as the hydrogen. These methyl hydrogens are in  different chemical environments,   and they're not chemically equivalent, so  that's why they show up as two different peaks!

We’ll talk more about chemical equivalence in a later episode when we look at the proton NMR spectra of aromatic compounds. But in this episode we’ve learned:. Nuclear Magnetic Resonance helps us visualize  the atoms in molecules as peaks in a spectrum.

In proton NMR, the integral tells us  how many hydrogens each peak represents. Nuclei close to electronegative  atoms appear downfield on a spectrum. And split peaks, or multiplicity, give clues  about how atoms are joined to other atoms.

In the next episode, we’ll work our way through  reactions of some other often-fragrant compounds: aldehydes and ketones! Until then, thanks for watching this  episode of Crash Course Organic Chemistry. If you want to help keep all Crash  Course free for everybody, forever,   you can join our community on Patreon.