Relaxation, Multi pulse Experiments and 2D NMR

Relaxation, Multi pulse Experiments and 2D NMR

To Do s Read Chapter 6 Complete the end of chapter problems; 6 1, 6 2, 6 3, 6 5, 6 9 and 6 10. Read Chapter 15 and do as many problems as you can.

Relaxation in NMR In NMR, the term relaxation describes several processes by which nuclear magnetization prepared in a non equilibrium state to the equilibrium distribution. e -t/t T: relaxation time constant Short T Fast relaxation Broad peak Long T Slow relaxation Sharp peak

T1 and T2 Relaxation Net magnetization M 0 at thermal equilibrium, Followed by a 90 RF excitation pulse M xy = zero M z = M 0 M xy = M 0 M z = zero T1 >= T2 Decay of M xy (time constant T2), and recovery of M z (time constant T1) T2: spin-spin relaxation T1: spin-lattice relaxation

Relaxation Mechanisms T1 (Spin Lattice relaxation or longitudinal relaxation) Magnetic field fluctuation by nearby magnetically active nuclei Most effective when they occur at the Larmor precession frequency T2 (Spin spin relaxation or transverse relaxation) Energy transfer within the spin system or spin diffusion

Inversion Recovery Experiment τ = 0

T1 and Structural Information r CH, r HH T1 τ c : time required for molecule to rotate one radian Rotation τ c T1

Chlorobenzene Quaternary carbon r CH T1 Slower relaxation

Other Examples Slower relaxation C1(3) Quaternary carbon C5 C2 C4(6) Relaxed by H5 and CH3

T1 and Anisotropic Motion Rotation τ c T1

T1 and Segment Motion H-bonding with each other Rotation τ c T1

Solvent Suppression Selective saturation Selective relaxation Selective excitation and detection

Solvent Suppression by Selective Relaxation Solvent molecules are generally smaller in size than the molecules of interest. Thus, solvent protons and carbons relax more slowly. Use π t D π/2 Acquire where t D is set such that the solvent is nulled.

Summary of Common 2D NMR Techniques?

COSY (Correlation Spectroscopy) Proton proton correlation through J coupling Use two 90 degree pulses, (π/2)x t1 (π/2)x Acquire FID Fourier Transform 2 dimensional NMR

Magnetization Changes in COSY Experiment FID FID

COSY of CHCl 3 t 1 FT FT t 2 A collection of FIDs

COSY of Methyl Acetate 1D 1 H-NMR COSY

J coupled Spin System J AX f 2 Diagonal axis f 1

COSY of β Chloroacrylic acid Stacked plot Contour plot

Typical COSYs are Recorded in Lower Digital Resolution

Predicted COSY for 1 Nitropropane a Cross peaks c b a b c Diagonal peaks

Ethyl Benzene

Annulene Start with a proton with only one cross peak, and trace the connectivity.

Citronellol Virtual coupling Diastereotopic H4s Diastereotopic H2s Allylic coupling

HMQC (Hetronuclear Multiple-Quantum Correlation): A modern equivalent of HETCOR The HMQC (Heteronuclear Multiple-Quantum Correlation) experiment is a heteronuclear correlation technique that offers a means of identifying 1-bond H-C connectivities within a molecule.

HMQC Example

Unknown (IHD = 4) -CH 3 5H X-CH 2 2H 4H 2H

Unknown CH DEPT135 CH 2 DEPT90 C CH 3 Normal 13 C-NMR

Unknown Two CH 2 overlapping

Chapter 6 Problems 6.1(a) -CH 2 -CH 2 -CH 2 -CH 2 -CH 3

Unknown 2 (C 6 H 10 O) (IHD = 2) 1642

Unknown 2 3 alkene protons 1H 1H 2H 1H 2H 2H 1H

Unknown 2 DEPT135 DEPT90 CH CH2 CH2 CH CH2 CH2

Unknown 2 1H 1H Diastereotopic CH2 Allylic coupling to CH2

Unknown 2 CH CH 2 2 CH

Unknown 2

HMBC (Heteronuclear Multiple Bond Correlation) HMBC is closely related to HMQC and operates in essentially the same manner. In this case, however, the sequence timings are optimized for much smaller coupling constants and therefore seeks the correlations across more than one bond that arise from so-called long-range couplings. In HMBC, direct one-bond correlations are suppressed. This gives connectivity information much like a proton-proton COSY. H H H C C - C H H H C C - C

Easy Unknown 3-Methyl-2-Pentanone

3-Methyl-2-Pentanone, Predicted HMBC 3-H 5-H 6-H 2-H 4-H 4-H 4 2 6 5 3 1

HMBC example

Unknown, C 11 H 12 O, IR & MS A ketone? M-15 IHD = 6

Unknown, C 11 H 12 O, 1 H- and 13 C-NMR CH2 CH3 CH3, CH2, C and C=O C=O 4CH + 2C C Ortho splitting pattern! 6H 4H 2H

Unknown, C 11 H 12 O, HMQC CH3 CH2 C

Unknown, C 11 H 12 O, HMBC CH2 is adjacent to CH3 and C=O CH3 CH2 C=O C=O is close to aromatic proton CH2 is NOT correlated with aromatic CH

MS, IR and UV/Vis Data 1 H, 13 C NMR, DEPT C H correlation from HSQC H H correlation from COSY Check assignment of diastereotopic protons using COSY and HSQC Assemble substructures using COSY data Combine substructures using long range H C data from HMBC Check all working structures for consistency with 2D NMR data

Use NOE and NOESY data to determine stereochemistry