Multidimensional NMR Experiments

Transcription

1 Multidimensional NMR Experiments Chem 8361/4361: Interpretation of rganic Spectra Andrew arned & Regents of the University of Minnesota

2 General Information More complicated experiments to set up than 1 and 13 C Changes in pulses (#, length, angles, mixing times, etc.) bserve effects based on relationship of nuclei **Can be homonuclear (same nuclei) (e.g. ) or heteronuclear (different nuclei) (e.g. C, P, etc.)** Will only go over the what the experiments tell you and how to interpret, and only for the most common and widely used for solving organic structures DEPT, CSY, MQC (ETCR), MBC, INADEQUATE (C C CSY) There is a whole alphabet soup of other experiments (both 1D and 2D) EXSY, TCSY, AA, INEPT, WATERGATE, and many more

3 Number of Protons on Carbon DEPT (Distortionless Enhancement by Polarisation Transfer Used to be known as APT (Attached Proton Test) DEPT is 1 -detected; APT is 13 C-detected Tells you how many protons are attached to a particular carbon negative peaks = C2 positive peaks = C and C3 (distinguishable with further processing) missing peaks = carbons w/o protons With a little help from IR and chemical shift of 1 and 13 C, can get a rough idea of molecular weight

4 Number of Protons on Carbon DEPT (Distortionless Enhancement by Polarisation Transfer 1 = Carbon spectrum 2 = C2 C, C3 3 = C º pulse 135º pulse 1

5 Who is Talking to Who? 1 1 CSY (Correlation Spectroscopy) Tells you which protons are coupled to one another Very useful when peaks are overlapping in 1 NMR and you are unable to calculate coupling constants, or when there are a lot of similar coupling constants Cross peaks are coupled to each other C C C 1 bond coupling Newer method is DQF (Double Quantum Filtered)-CSY same information, but looks cleaner

6 Who is Talking to Who? 1 1 CSY (Correlation Spectroscopy) verlapping protons and a lot of similar coupling constants Raffinose a trisaccharide

7 Who is Talking to Who? 1 1 CSY (Correlation Spectroscopy) Raffinose a trisaccharide

8 Who is Talking to Who? 1 1 CSY (Correlation Spectroscopy)

9 Who is Talking to Who? 1 1 CSY (Correlation Spectroscopy) DQF-CSY: Double Quantum Filtered CSY cleans up the spectrum by reducing noncoupled systems (e.g. C3 singlets) C 2 C 2 3 C C 3 Ipsenol

10 Who is Talking to Who? 1 1 CSY (Correlation Spectroscopy) DQF-CSY: Double Quantum Filtered CSY cleans up the spectrum by reducing noncoupled systems (e.g. C3 singlets) C 2 C 2 3 C C 3 Ipsenol

11 Who is Talking to Who? 1 1 CSY (Correlation Spectroscopy) C6102

12 Who is Talking to Who? 1 1 CSY (Correlation Spectroscopy)

13 Recall CSY Tells you which protons are coupled to one another Very useful when peaks are overlapping in 1 NMR and you are unable to calculate coupling constants, or when there are a lot of similar coupling constants Cross peaks are coupled to each other C C C 2 & 3 bond coupling

14 Tells you which protons are coupled to one another Very useful when peaks are overlapping in 1 NMR and you are unable to calculate coupling constants, or when there are a lot of similar coupling constants Cross peaks are coupled to each other Recall CSY This can still cause ambiguities! 2 C C C 2 & 3 bond coupling

15 Who is Talking to Who? 1 1 TCSY (Total Correlation Spectroscopy) Tells you which protons are in the same spin system (a continuous chain of spin-spin coupled protons) Magnetization from A is transferred to B, which then transfers to C and on down the line A B C D E C C C C C Can be run as either a 1D or 2D experiment Running as a 1D experiment greatly simplifies spectra with severe signal overlap Related experiment (AA) gives essentially the same information Can also observe one-bond 1 13 C couplings (MQC-TCSY, hetero-tcsy, EAA) - will not discuss

16 1D TCSY Spin System Identification 1 1 TCSY (Total Correlation Spectroscopy) Irradiate at frequency of proton of interest Wait a period of time (typically 20 to 400 ms) and then collect 1D spectrum nly observe protons to which magnetization has been transferred Short periods of time (20 ms) will only give rise to single step transfers; longer periods of time allow magnetization to propagate further α- and β-lactose

17 1D TCSY Spin System Identification 4 β-lactose 5 3 6, 6' ppm

18 1D TCSY N N N A B,C D 2 Claridge, T. D. W. igh-resolution NMR Techniques in rganic Chemistry, 2nd Ed., Elsevier, 2009.

19 1D TCSY D N 2 B,C N N A Claridge, T. D. W. igh-resolution NMR Techniques in rganic Chemistry, 2nd Ed., Elsevier, 2009.

20 2D TCSY Spin System Identification 1 1 TCSY (Total Correlation Spectroscopy) N 3 Cross peaks are in the same spin system CSY TCSY Claridge, T. D. W. igh-resolution NMR Techniques in rganic Chemistry, 2nd Ed., Elsevier, 2009.

21 2D TCSY Cross peaks are in the same spin system N N Intermediate in biomimetic synthesis of manzamine 23 Claridge, T. D. W. igh-resolution NMR Techniques in rganic Chemistry, 2nd Ed., Elsevier, 2009.

22 2D TCSY Cross peaks are in the same spin system N N Intermediate in biomimetic synthesis of manzamine 23 Claridge, T. D. W. igh-resolution NMR Techniques in rganic Chemistry, 2nd Ed., Elsevier, 2009.

23 2D TCSY Cross peaks are in the same spin system N N Intermediate in biomimetic synthesis of manzamine 23 Claridge, T. D. W. igh-resolution NMR Techniques in rganic Chemistry, 2nd Ed., Elsevier, 2009.

24 New Developments Deconvolution via MDEC MDEC (Multi Frequency omonuclear Decoupling) Conceptually the same as the homonuclear decoupling experiment mentioned earlier, but allows multiple frequencies to be decoupled at the same time (dd, J = 3.3, 12.2 z) Me X 3a 3b X 1 X 2 7 Me Me -2 (app dt) (a) 1 NMR (b) -1 (c) -1/-7 (d) -1/-3a/-7-2 (dddd) J. Am. Chem. Soc. 2009, 131,

25 New Developments Deconvolution via MDEC Me Me Me 1D-TCSY-MDEC a X X X (a) 1 NMR (b) 1D-TCSY -3 (c) 1D-TCSY -3 with -1b, -2b, -3 J. Am. Chem. Soc. 2009, 131,

26 1 13 C CSY 2D NMR Spectroscopy Who is Talking to Who? ETCR (eteronuclear Correlation) older experiment; 13 C-detected MQC (eteronuclear Multiple Quantum Correlation) and SQC (eteronuclear Single Quantum Correlation) newer experiments; 1 -detected; largely replaced ETCR Both give same information, experimentally very different Peaks have one-bond coupling (i.e. attached directly) Compliments DEPT Particularly useful for diastereotopic protons C C C 1 bond C coupling

27 Who is Talking to Who? MQC C C C 1 bond C coupling

28 Who is Talking to Who? MQC Diastereotopic Protons C C C 1 bond C coupling

29 Who is Talking to Who? MQC Can see into multiplets 3 C 3 C 2 C C 3 Caryophyllene xide

30 Who is Talking to Who? MQC

31 Cl

32 Cl

33 Cl

34 Who is Talking to Who? 1 13 C CSY (Long Range) CLC (Correlated spectroscopy for Long range Couplings) older experiment; 13 C-detected MBC (eteronuclear Multiple Bond Coherence) newer experiment; 1 -detected; completely replaced CLC Both give same information, experimentally very different Peaks have two- or three-bond coupling Sees through heteroatoms and quaternary carbons Can be very complicated, but is very powerful 1 C C C C C C C C and 3 bond C couplings

35 Who is Talking to Who? MQC C C C 1 bond C coupling

36 Who is Talking to Who? MBC 1 C C C and 3 bond C couplings

37 Who is Talking to Who? or C 3 C 3

38 Who is Talking to Who? or C 3 C 3

39 Who is Talking to Who? or C 3 C 3

40 Who is Talking to Who? or C 3 C 3

41 Who is Talking to Who? or C 3 C 3

42 13 C 13 C CSY 2D NMR Spectroscopy Who is Talking to Who? INADEQUATE (Incredible Natural Abundance Double Quantum Transfer Experiment) tells what carbons are attached to each other if you know what type of carbon it is (C, C=, C, C2, C3, etc.) from DEPT, you can almost write down the entire gross structure by running two NMR experiments BUT it is 13 C 13 C coupling probability of one 13 C is 0.01 two next to each other 0.01x0.01 = (~1 molecule in 10,000) Need lots of sample and instrument time to overcome In our facility: 80% v/v, overnight, 500 Mz = nothing N C C C 1 bond C C coupling

43 INADEQUATE 2D NMR Spectroscopy Who is Talking to Who? C C C 1 bond C C coupling

44 INADEQUATE 2D NMR Spectroscopy Who is Talking to Who? Cross peaks show up as doublets = JCC Diagonal is midway between the two doublets ,7 14

45 C C C C2 C C2 C3,C3,C2,C3

46

47 C C,C

48 C C C C C2 C2 C3 x2 C3 Which Isomer? Br

49 Br

50 Br