10 - MED-108 NMR Spectroscopy PPT 2024 90 min.pdf

MED-108 Organic Chemistry NMR Spectroscopy LOBs covered Interpret NMR spectra to determine molecular structure Nuclear Magnetic Resonance Spectroscopy Some atomic nuclei have a finite spin, as if they were spinning about an axis Atomic nuclei are positively charged (protons), hence when they spin, t...

MED-108 Organic Chemistry NMR Spectroscopy LOBs covered Interpret NMR spectra to determine molecular structure Nuclear Magnetic Resonance Spectroscopy Some atomic nuclei have a finite spin, as if they were spinning about an axis Atomic nuclei are positively charged (protons), hence when they spin, they create a finite electric field, and a finite magnetic field This magnetic field can interact with an external magnetic field Nuclei with Nuclear Spin NMR spectroscopy can be achieved with 13C or with 1H nuclei, as they have a finite nuclear spin. Organic compounds contain both of these elements. Carbon-13 NMR is possible but signals are weak due to the lower abundance of 13C. In this course, we will concentrate on 1H (proton) NMR. Hydrogen (Proton) NMR Since the nuclear spin of carbon-12 nuclei is 0, we cannot do carbon-12 NMR Carbon-13 NMR is possible, but due to the low natural abundance of carbon-13 this is faced with practical problems (C-13 NMR is an established method) Hydrogen-1 has a nuclear spin of ½ thus we can do proton NMR (Remember: the nucleus of hydrogen-1 is a mere proton) External Magnetic Field In the presence of an external magnetic field, spins align Parallel and anti-parallel spinning nuclei Anti-parallel spins have higher energy than parallel spins Two Quantum States When we have two different quantum states having different energies, the possibility of a transition emerges The energy separation is tiny – radio waves Spin Energy and H0 As the strength of the external magnetic field increases, the energy separation between the parallel and anti-parallel states increases too NMR Spectrometer We can have different magnet strength BUT the radiowave radio frequency (RF) is constant NMR Spectrometer Higher radio frequency means better resolution Proton (1H) NMR spectrum of ethanol Nature of NMR Absorptions If all H nuclei absorbed energy at the same radio frequency, NMR would be totally useless You would see only one signal for all H atoms in all molecules Luckily electrons exist! Shielding Effect Electrons shield (surround) nuclei As thickness of electron cloud increases, the strength of the external magnet has to increase to penetrate more electron density in order to get to the nucleus and cause an NMR transition Shielding Effect Highly shielded nuclei (thick electron cloud) require a stronger magnetic field to get through to the nucleus and achieve resonance Relatively bare nuclei (thin electron cloud) require a weaker magnetic field to get through to the nucleus and achieve resonance Which atomic property is involved in affecting the thickness of the electron cloud around an atomic nucleus? An Example 5-Minute Break Another Example Methyl acetate The blue H’s are more deshielded (bare) than the red H’s since they are closer to the electronegative oxygen Another Example Methyl acetate NMR Spectrum Figure Explanation for Revision The NMR spectrum x-axis is called chemical shift and it is measured in parts-per-million (ppm) of the spectrometer operating frequency. The TMS signal is the zero-point of chemical shift. The more shielded the H atoms, the further to the right they appear. In the spectrum above, the blue H atoms are closer to the highly electronegative O atom and they are therefore deshielded (thinner electron cloud). They require a lower external magnetic field to reach the nucleus. The red H atoms are more shielded (thicker electron cloud) and therefore need a stronger external magnetic field to penetrate through to the nucleus. Chemical Shift The x-axis of the NMR spectrum This is inversely proportional to the field strength = Actual chemical shift in Hz away from TMS Spectrometer operating frequency in MHz Units = parts per million (ppm) of the spectrometer frequency High field = low  Low field = high  Chemical Shift What is TMS? It stands for tetramethylsilane, Si(CH4)4 Si electronegativity = 1.8 C electronegativity = 2.5 Methyl groups are highly shielded as electron density flows toward the more electronegative C atoms Chemical Shift TMS is likely to have H’s that are more highly shielded than any conceivable organic compound Thus, it is set to the 0.0 ppm point, and typical organic compounds absorb downfield of TMS 1H NMR Spectroscopy Proton Equivalence Sets of hydrogen atoms can be equivalent to each other due to similarities in the chemical environment All 6 protons are equivalent One NMR signal only for all 6 Proton Equivalence Propane The edge methyl H atoms are equivalent The middle H atoms are equivalent to each other but different from the methyl H atoms Two unique NMR signals will be observed Proton Equivalence Dimethyl ether Due to the symmetry in the molecule, the methyl group H atoms are equivalent One NMR signal will be observed Proton Equivalence Ethanal (acetaldehyde) The 3 methyl group H atoms are equivalent The aldehyde H atom is different Two NMR signals will be observed Proton Equivalence 1-propene The methyl group H atoms are equivalent The other 3 H atoms are different because no rotation is possible around the C=C bond Four NMR signals will be observed Further Explanations for Revision The 3 methyl (-CH3) H atoms are identical to each other, and different from all other H atoms. They will give rise to one unique signal. The H atom labelled ‘2’ has a methyl group above it and a H (labelled ‘3’) to its left. This H will give its own unique signal. The H labelled ‘3’ has a H atom (‘2’) to its right, and another H (‘4’) above it. Therefore, it is different than H ‘2’ and will give its own unique signal. Finally, H ‘4’ has a methyl group to its right and another H atom ‘3’ below it. Since the alkene distances up-down and left-right are not the same, H ‘4’ will give rise to its own unique signal. Proton Equivalence 1-butanol Due to different distances from the –OH group, all sets of protons are different – this is because the degree of deshielding depends on how far from the O atom the H atoms are. Five NMR signals will be observed Exercise How many unique NMR signals will be observed? Toluene 5-Minute Break 1H NMR – Chemical Shifts Depend on shielding-deshielding effects More deshielded H – higher chemical shift Integration of 1H NMR Signals Counting Protons Area under the curve (the integral in mathematics) is related to the number of protons (H atoms) Proton Counting Figure Explanations for Revision The 9 H atoms from the three leftmost methyl groups are identical. The 3 rightmost methyl group H atoms are identical to each other but different from the 9 H atoms on the left. Finally, the benzene ring has 4 H atoms on it, which are highly deshielded. So, we expect 4:3:9 ratio of areas under the peaks, from left to right. In the diagram above, we have distances 3.8:2.9:8.8, or roughly 4:3:9, which corresponds to the expected ratios. Proton Counting Figure Explanations for Revision The 9 H atoms from the three methyl groups on the left are identical, giving one unique signal. The 3 methyl group H atoms are identical to each other but different from the 9 H on the left. The 3 H atoms on the right are more deshielded because they have O right next to them. The left methyl group H atoms are two positions away from the O atom, hence less deshielded. The expected ratio is 3:9 or 1:3. We see 2 spaces: 6 spaces above, which is the expected 1:3 ratio. Proton Counting 5 H atoms on the benzene ring. 2 in the CH2 group and 3 in the CH3 group Expected ratio is 5:2:3 Divide all numbers by 9 Proton Counting Sometimes, relative numbers of H atoms are given CH3-O-CH2CH2-O-CH3 Due to the symmetry of the molecule, we have 6 H (two CH3) and 4 H (CH2CH2) Expected ratio 3:2 Summary for Revision Some nuclei has a finite nonzero nuclear spin. When they are exposed to an external magnetic field, their nuclear spins orient themselves either parallel or anti-parallel to the external magnetic field. Anti-parallel spins have slightly higher energy, creating two energy states. A transition in the radiowave frequency domain is possible between the two energy states. This allows for nuclear magnetic resonance spectroscopy. Proton (1H) NMR involves the H atoms in an organic molecule. In an NMR spectrometer, the radiofrequency signal is held constant, while the strength of the external magnetic field is varied. Atoms with thicker electron clouds (shielded) require stronger magnetic fields to penetrate to the nucleus. Atoms with thinner electrons clouds (deshielded) require weaker magnetic fields to cause a spin state transition. Close proximity to a highly electronegative atom causes the electron cloud to become thinner. Deshielded nuclei appear on the left side on the NMR spectrum. Shielded nuclei appear on the right side. The zero mark is set by using the silicon compound TMS. Proton equivalence is important in determining how many unique signals there will be in the NMR spectrum. The area under individual peaks is directly proportional to the number of H atoms of a unique signal. This area is calculated automatically if the NMR spectrometer has a digital integration ship in it. Frequently, the relative number of H atoms will be provided above the peaks.