Bài giảng Organic Chemistry - Chapter 10: Nuclear Magnetic Resonance (NMR) Spectroscopy

Chapter 10: Nuclear Magnetic Resonance (NMR) SpectroscopyWhat is spectroscopy? Molecular response to radiative stimulus is quantized (“geared”). (Molecule = nuclei + electrons). Excitation: 1. Electronic (UV-visible spectra)2. Vibrational (IR) 3. Rotation (microwave) 4. Nuclear spin orientation in magnet (NMR)Spectrometer scans ν to find ΔE : The spectrumΔE = hν ν = c/λ Excitation causes an “absorption”, apeak in a graphA General Spectrometerkcal mol-1What is ∆E in NMR? Nuclei behave as tiny magnets (random orientation). In a magnetic field H0, they organize with (α, lower energy) or against (β, higher energy) the field. ∆E = hν0 resonance frequency: The frequency that matches exactly the energy difference. Protons as Tiny Magnets Line Up With and Against an External Magnetic FiledRatio α:β ~ 1:1Absorption of Light, Spin Flip, and Resonance  Spectral Lineν0 is proportional to H0. (ν0 is specific for element/isotope)For 1H: at H0 = 21,150 gauss, ν0 = 90 MHz. ∆E (300 MHz) ~ 10-5 kcal mol-1. Nα/Nβ = 1.000004NMR “active” nuclei: 1H and 13C (not 12C)At H0 = 70500 gauss, ν0 = 300 MHz. H0 (earth): 0.7 gauss!A Hypothetical NMR Spectrum: Active Elements Absorb at Differing FrequenciesThe NMR SpectrometerSolvents: CDCl3, CD2Cl2, THF-d8, etc.High Resolution NMR!Why are there two peaks? The Chemical ShiftCauses shielding, i.e.,Peak moves to the rightElectrons in Vicinity of Nucleus Affect νConsider H+: No e, no shielding, peak furthest to the left. But:When we add an e-withdrawing group: e.g., CH3 Cl, causes deshielding (to left). Chemical shift provides a finely tuned picture of electronic environment around each H.CHHHH+-Electrons cause shielding: Peak moves upfield (to right).If we substitute with e-negative groups, shielding of observed nucleus is diminished; or nucleus is “deshielded” (relatively).One e-poor neighborTwo e-poor neighborsThe Chemical Shift δThe position of peak relative to an internal standard. Most common isTetramethylsilane: (CH3)4Si or “TMS”, the “zero” point in the spectrum.=ν (from TMS) HzRF (e.g., 300 MHz)ppm,is independent of machine (90, 300 MHz, etc.)δDistance from TMS in Hz/300 MHz in ppm266 Hz0.89 ppm541 Hz1.80 ppm978 Hz3.26 ppmApplication of δCH3 CH3 CH3CH2BrBr2hυ+ CH3CHBr2 + BrCH2CH2BrEPM of 1-bromopropane2 signals2 signals1 signalMost deshielded of all1-22+3-4VariableChemically equivalent Hs: same δs. Use symmetry operations: rotation, mirror planes. “Fast” processes, such as methyl rotation, equilibrate Hs:For calibration: A BEakEa ~ 20 kcal mol-1, k ~ 10-2 sec-1, t1/2 = 1 minEa ~ 25 kcal mol-1, k ~ 10-6 sec-1, t1/2 = 66 hNMR time scale > J : first order patterns. Otherwise complex signals: non-first order multiplets. δ (Heq) > δ (Hax)11423Multiplets are typical of alkyl chains: all δs similar. e.g.,One solution: stronger magnet higher field spectra For example, what might be non-first-order at 90 MHz, may resolve into a first-order pattern at 300 or 500 MHz.(Recall ν ~ H0 ), “spreads out” spectrum, but Js stay same (field independent).90 MHz500 MHzRibonuclease A, 40 MHz Ribonuclease A“Sequential” [N+1] Rule1st Order patterns can be analyzed for neighbors with differing Js.Js should differ for non-equivalent neighbors.CH3CCClClClHbHacJab = 3.6 HzJbc = 6.8 HzApply split sequentiallyCH3CCClClClHbHacJab = 3.6 HzJbc = 6.8 HzCH3—CH2—CH2—Br (J2)t?(J1)tJ1 > J2 :J1 < J2 :J1J2J2J1qt or tq Quartet of triplets or triplet of quartets or.. ?Jab = Jbc  N + 1 RuleIf Js accidentally the same: [N+1] ruleSextetSextetStereocenters and Methylene GroupsH Bonded/Acidic Protons:OH, SH, N HRecall CH2 O HWhy? Fast H+ exchange (Hα and Hβ trade places) “decouples” hydrogens.Variable s !Variable  (concentration and moisture-dependent) and no coupling ! Coupling is restored on cooling, because proton exchange is “frozen” (on the NMR time scale).CH3OHOH peak often broad; disappears on addition of D2O to the sample (H/D exchange).13C NMR SpectroscopyOnly 1% 13C in nature: No 13C—13C splitting, since chances of finding two 13C adjacent are small (~0.01%).(For the same reason: No 13C—H seen in 1H NMR. 99% of sample is 12C).Large Js 13C H J ~ 100-150 Hz13C C H J ~ 5-10 Hz But: 13C—H visible in 13C NMR.Triplet of quartetsQuartet of tripletsCoupling to H can be removed by “broad band” irradiation of all HsHence: all lines are singlets !averages Hα/βSymmetryC7H14 isomersNumber of Cs:5544317Chemical shift range : 200 ppm (1H: 10 ppm)Rules for deshielding same as in 1H NMR (multiply by a factor of 10-20)Chemical Shift RangeAdvanced TechniquesDistortionless polarization transfer (“DEPT”) 13C NMR spectrum. Tells us whether the carbon is attached to 3, 2, 1 or no hydrogen, i.e. CH3, CH2, CH, or C. Requires running the spectrum in three different ways (using specific laser pulse sequences).Example : Limonene.Normal spectrumDEPT-90 spectrum: only CHDEPT-135 spectrum: CH and CH3 positiveCH2 negative peaksTwo Dimensional NMRCorrelated spectroscopy (COSY). H/H or H/C1H NMR1H NMR10 ppm010Coupled Hs1H13C010200C—H connectivityMRI : Magnetic Resonance ImagingBased on “relaxation” times β α, “T1”T1 values differ with tissue (environment)Whole body NMRMRI of Human AbdomenspleenkidneysliverMRI, median sagittal section: cervicodorsal syringomyelia. This condition is characterized by the presence of fluid-filled cavities in the spinal cord substance. Brain Tumor About to be ZappedA French BrainMy BrainThis spiral represents the 23 stages occurring in the first trimester of pregnancy and every two weeks of the second and third trimesters.Stage 1Fertilization 1 Oocyte, 300 Million Sperm, 24 hours 0.1 - 0.15 mm 1 day post-ovulation Fertilization begins when a sperm penetrates an oocyte (an egg) and it ends with the creation of the zygote. The fertilization process takes about 24 hours.Stage 5Implantation Complete, Placental Circulation System Begins0.1 – 0.2 mm7-12 days post-ovulationStage 2Stage 10CleavageFirst Cell Division, Blastomeres, Mitotic division0.1-0.2 mm1.5-3 days post-ovulationNeural Folds Begin to Fuse, Heart Tube Fuses1.5-3.0 mm21-23 days post-ovulationCross Sections of 3-D Image of a human embryo, 44 days after conception. Roughly thesize of a navy bean, it still has webbed fingers and toes, but is already developing a brain with two hemispheres, the precursors of vertebrae (dashlike structures in right slice) and internal organs.Stage 15Stage 23(6 to 8 weeks post fertilization)Lens vesicle, nasal pit, hand plate; trunk widens; future cerebral hemispheres distinctHead and neck(approximately 56-57 postovular days)Essential external and internal structures complete