Post on 28-Dec-2015
Introduction to NMR Spectroscopy and Imaging
Lecture 02 Chemical Shift and J-Coupling
(Spring Term, 2011)
Department of ChemistryNational Sun Yat-sen University
核磁共振光譜與影像導論
Chemical Shift and J-Coupling
In the beginning….
Norman Ramsey (Phys.Rev. 1950, 78,699):"Furthermore, with heavier nuclei the ratios of the resonance frequencies for the same nucleus in different molecules have been measured with high precision and discrepancies have been found by various observers that are sometimes called chemical shifts".
(Proctor says: "until it is clearly understood, the accuracy of magnetic moments determined under certain chemical conditions remains somewhat in doubt").
W.G.Proctor, F.C.Yu(虞福春 ), Phys Rev 1950,77,717. W.C.Dickinson, Phys Rev 1950 77, 736.
All spins were of no difference…same, identical, equal, I/You/He/We/You/They wereall the same…or believed to be so….then...the apple of discern came in…
?Dickinson?Who can find his photo?
Ramsey
Yu
Proctor Valuable reading: http://www.ebyte.it/library/hist/ProctorWG_Reminiscences.html
1922-2006
1913-2003
Chemical Shift (Shielding)
0
0
loc induced
induced
B B B
B Bchemical shift tensor
0B
Induced shielding field
Chemical Shift:a molecule becomes a dipole
0
0
loc induced
induced
B
B Bchemical shift tensor
0B
The induced dipole moment shifts the resonance frequency of the nuclear spin.
m
Shielding Depends on Chemical Environment
Different environments cause different shieldings
0 0
0 0
0 0( ) (1 ( ))s
B BB
B r B B B r
(Representing different local chemical environments, Proctor and Yu, 1951)
Hence chemical shift (of resonance frequency relativeto Zeeman frequency ω0.)
0
0
Anti-shielding Is Possible
))(1()( 00 rBBBrB s
Anybody cares to find some interesting literature?
Some proton chemical shifts
0 0
0 0
( ) [( ) ( )]
6
( )
=( ) 10 ppm
ref ref
relative
ref absolute
ref absolute
Reference shift
Less shielded.
Increasing δ
(downfield)
The OH bonding in vaporized water clearly differs from that in liquid water! (hydrogen bonding has significant effect on chemical shift)
The more localized AO/MO, the more shieldingStronger/more bonds mean smaller CS.
You can tell a lot from this diagram
Upfield (low freq)Downfield (high freq)
These words were from CW NMR. ‘Downfield’ means for agiven resonance frequency, the magnetic field used is lower. ‘High frequency’ means at a fixed magnetic field, the spins inthis region have higher resonance frequencies.
(these trends for σ,δ,B, |ν| are same for γ>0 or γ<0 nuclei. However, for γ<0, ν is negative.)
Small shift/large shieldingLarger shift/small shielding
Why CHn have smaller CS than H atom?
B0
Some people said: An H in CHn seems to be less shielded because the C has larger electronegativity so it ‘draws’ electrons to its side. But why an H in CHn has smaller CS than H atom? Answer: The electron density at the C-H bonding area is larger than that of an H atom albeit the electron density at other places is smaller. Overall, the H in CHn is more shielded than in H atom.
H atomHC
This can also explain why H > H2, H>OH>H2 More bonds, more shielded.
Why this CS order: CH>CH2>CH3?
More bonds, more shielded.
The bonding regions correspondto large shielding (small CS).The CS is smallest when the magneticfield is along the bonding direction.
Why this CS order: HF>HCl>HBr>HI?
The fewer number of electrons of the bonding partner, the less the shielding the bonded H. (The more clothes you dress, the more you’re shielded.)
The shielding of s orbitals is smaller than that of p orbitals which is even smaller than that of d orbitals etc. (The more localized the orbitals, the more shielding)
Isotopic Effect• Because CS is generated by electrons, nuclei of isotopic elements
(e.g. H1/D2, N14/N15, Cl35/Cl37) have very similar chemical shift but isotope shift does exist: e.g., 1H CS of HOD is 0.035 ppm upfield (more shielded) of that of HOH (the electrons in HOD is a little ‘heavier’ than in HOH lower vib freq/amp more shielding (you are more shielded by your clothes if you shake yourself less violently.)
• There is a general rule which says that when one substitutes a nuclide in a chemical group with a heavier isotope then all other nuclides in the group become a bit more shielded (this has to do with an overall reduction in vibrational amplitudes).
• Consequently, the chemical shift of protons in standard bulk water should be 4.795 + 0.035 = 4.830 ppm, give or take 0.02 ppm. Of course, heavy water and normal water do not even have the same bulk properties (such as density and magnetic susceptibility) and this introduces a further uncertainty when trying to deduce the chemical shift of normal water from the data on HDO traces in D2O.
You may be able to memorize this table or you may explain it based on your good scientific intuition
Proton and Carbon Standards for Organic Solents
Chemical Name Chemical Formula Chemical Structure Boiling Point (oC)
Chemical Shift
H1 C13
Tetramethylsilane (TMS) C4H12Si 27 0.000 0.000
Dioxane C4H8O 2 -- 3.75 --
Proton Standards for Aqueous Solents
3-(Trimethylsilyl)- Propionic acid-D4, sodium salt (TSP)
C6H9D4NaO2SI 302 0.000 0.000
2,2-Dimethyl-2-silapentane- 5-sulfonate sodium salt (DSS)
C6H15NaO3SSi 120 0.000 (labelled as DSS)
--
P31 Standards
Chemical Name Chemical Formula Chemical Structure B. P. (oC) Chemical Shift
85% Phosphoric Acid (external) H3PO4 -- 0.00
10% trimethylphosphate (internal) (CH3O)3PO -- 0.00
N15 Standards
Chemical Name Chemical Formula Chemical Structure B. P. (oC) Chemical Shift
liquid NH3> (external) NH3 -- 0.00
OTHER NMR RESOURCES
More info http://www.bmrb.wisc.edu/home/iupac.pdf.
Most internal NMR referencing standards are pH and temperature sensitive. N
MR
Intern
al Referen
cing
Stan
dard
S
amp
les
Solvent 1H Chemical Shift (multiplicity) JHD (Hz) HOD in solvent (approx.)
13C Chemical Shift (multiplicity)JCD
(Hz) B.P. (oC) M.P. (oC)
Acetic Acid-d4 11.652.04
15
--2.2
11.5 178.9920.0
17
--20
118 17
Acetone-d6 2.05 5 2.2 2.8 206.6829.92
137
0.919.4
57 -94
Acetonitrile-d3 1.94 5 2.5 2.1 118.691.39
17
--21
82 -45
Benzene-d6 7.16 1 -- 0.4 128.39 3 24.3 80 5
Chloroform-d 7.27 1 -- 1.5 77.23 3 32.0 62 -64
Cyclohexane-d12
1.38 1 -- -- 26.43 5 19 81 6
Deuterium Oxide 4.80 (DSS) 1 -- 4.8 -- -- -- 101.4 3.8
N,N-Dimethyl-formamide
8.032.922.75
155
--1.91.9
3.5 163.1534.8929.76
377
29.421.021.1
153 -61
Dimethyl Sulfoxide-d6
2.50 5 1.9 3.3 39.51 7 21.0 189 18
p-Dioxane-d6 3.53 m -- 2.4 66.66 5 21.9 101 12
Ethanol-d6 5.293.561.11
11
m -- 5.3
--56.9617.31
--57
--2219
79 <-130
Methanol-d4 4.873.31
15
--1.7
4.9--
49.15 --5
--21.4
65 -98
Methylene Chloride-d2
5.32 3 1.1 1.5 54.00 5 24.2 40 -95
Pyridine-d58.747.587.22
111
-- 5.0150.35135.91123.87
335
27.524.525
116 -42
Tetrahydrofuran-d8
3.581.73
11
-- 2.4 - 2.567.5725.37
55
22.220.2
66 -109
Toluene-d8
--7.097.006.982.09
--m1m5
--------
2.3
0.4
137.86129.24128.33125.4920.4
13337
--23242419
111 -95
Trifluoroacetic Acid-d
11.50 1 -- 11.5164.2116.6
44
72 -15
Trifluoroethanol-d3
5.023.88
14x3
--2 (9)
5 126.361.5
44x5
--22
75 -44
H1 an
d C
13 Ch
emical S
hifts o
f NM
R
So
lvents
NOTES: o1H chemical shifts are in PPM, relative to 0.05% TMS (v/v), at 295 K. o13C chemical shifts are in PPM, relative to 1.0% TMS (v/v), at 295 K. o'm' denotes broad peak with some fine structures (at 200 MHz). oHOD peak positions may vary depending upon concentration in solvent, pH and temperature. oM.P. and B.P. values are for the corresponding non-deuterated solvent (except for D2O). o(DSS) denotes chemical shifts relative to 2,2-Dimethyl-2-silapentane- 5-sulfonate sodium salt.o See NMR Referencing for more information
CH
AR
AC
TE
RIS
TIC
PR
OT
ON
CH
EM
ICA
L S
HIF
TS
Type of Proton Structure Chemical Shift, ppm
Cyclopropane C3H6 0.2
Primary R-CH3 0.9
Secondary R2-CH2 1.3
Tertiary R3-C-H 1.5
Vinylic C=C-H 4.6-5.9
Acetylenic triple bond,CC-H 2-3
Aromatic Ar-H 6-8.5
Benzylic Ar-C-H 2.2-3
Allylic C=C-CH3 1.7
Fluorides H-C-F 4-4.5
Chlorides H-C-Cl 3-4
Bromides H-C-Br 2.5-4
Iodides H-C-I 2-4
Alcohols H-C-OH 3.4-4
Ethers H-C-OR 3.3-4
Esters RCOO-C-H 3.7-4.1
Esters H-C-COOR 2-2.2
Acids H-C-COOH 2-2.6
Carbonyl Compounds H-C-C=O 2-2.7
Aldehydic R-(H-)C=O 9-10
Hydroxylic R-C-OH 1-5.5
Phenolic Ar-OH 4-12
Enolic C=C-OH 15-17
Carboxylic RCOOH 10.5-12
Amino RNH2 1-5
Carbon-13 Chemical Shifts
Carbon-13* Environment
Chemical ShiftRange (ppm)
(CH3)2C*O -12
CS2 0
CH3C*OOH 16
C6H6 65
CHCl=CHCl (cis) 71
CH3C*N 73
CCl4 97
dioxane 126
C*H3CN 196
CHI3 332
You may be able to memorize this table or you may explain it based on your good scientific intuition
• For most organic compounds, the 1H chemical shift is in the range of 12 ppm, but the chemical shift range for hydrides (organometallic compounds) is approximately +25 to -60 ppm, the largest range could possibly reach 200 ppm!. The downfield shifts are most common in d0, d10 and early transition metal cases whereas those with other dn counts and late transition metals tend to be upfield of zero.
• Similar phenomenon occurs for other nuclei such as 13C, 31P etc.
Temperature dependence of the 1H NMR spectrum of Ni Ni dissolved in toluene-d8.
The temperature runs from 183 (lowest trace) to 385 K. S = solvent.
Be aware of “abnormal” chemical shifts …...
Harald Hilbig and Frank H. Koehler, New J Chem, 2001.
1H
13C
1H
Phosphorous-31 Chemical Shifts
Phosphorous-31 Environment
Chemical ShiftRange (ppm)
PBr3 -228
(C2H5O)3 P -137
PF3 -97
85% phosphoric acid 0
PCl5 80
PH3 238
P4 450
Compound
Chemical Shift (ppm)Relative to 85% H3PO4
PMe3 -62
PEt3 -20
PPr(n)3 -33
PPr(i)3 +19.4
PBu(n)3 -32.5
PBu(i)3 -45.3
PBu(s)3 +7.9
PBu(t)3 +63
PMeF2 245
PMeH2 -163.5
PMeCl2 +192
PMeBr2 +184
PMe2F +186
PMe2H -99
PMe2Cl -96.5
PMe2Br -90.5
Phosphorous (III) Chemical Shift Table (from Bruker Almanac 1991)
Phosphorous (V) Chemical Shift Table
(from Bruker Almanac
1991)
CompoundChemical Shift (ppm)Relative to 85% H3PO4
Me3PO +36.2
Et3PO +48.3
[Me4P]+1 +24.4
[PO4]-3 +6.0
PF5 -80.3
PCl5 -80
MePF4 -29.9
Me3PF2 -158
Me3PS +59.1
Et3PS +54.5
[Et4p]+1 +40.1
[PS4]-3 +87
[PF6]-1 -145
[PCl4]+1 +86
[PCl6]-1 -295
Me2PF3 +8.0
Fluorine-19 Chemical Shifts
Fluorine-19 Environment
Chemical ShiftRange (ppm)
UF6 -540
FNO -269
F2 -210
bare nucleus 0
C(CF3)4 284
CF3(COOH) 297
fluorobenzene 333
F- 338
BF3 345
HF 415
Nitrogen-14 Chemical Shifts
Nitrogen-14* Environment
Chemical ShiftRange (ppm)
NO2Na -355
NO3- (aqueous) -115
N2 (liquid) -101
pyridine -93
bare nucleus 0
CH3CN 25
CH3CONH2 (aqueous) 152
NH4+ (aqueous) 245
NH3 (liquid) 266
B-11 Chemical Shift
Almost all quadrupolar nuclei have rather small CS range.
Factors Affecting Chemical Shift• Temperature• Solvents (pH,
concentration)• Pressure• Sample shape
(susceptibility)• ……
NMR can be used as a thermometer, a pH meteror a barometer. (Only very smart guys would like to buy an NMR spectrometerfor those purposes though)
Solvent Shift *(H2O)
H2O 4.83
D2O 4.79
DMSO 3.3
acetone 2.5
CD Cl3 1.4
C6D6 0.3* Relative to TMS.
Amide proton chemical shifts of NHA in CDCl2CDCl2 as a function of temperature and concentration.
Derr et al. J. Chem. Soc., Perkin Trans. 1, 2000.
Chemical Shift
The surrounding electrons cause a shielding magnetic field at the nucleus
)1(00 BBBB s
Shielding Anisotropy (CSA)
B0
B0
)1(0 BB
Chemical shift anisotropy (CSA) tensor
In liquids, CSA is averaged out by rapid molecular tumbling; in solids, CSA is kept.
Electron clouds are seldomspherically symmetrical. Theyare anisotropic in almost all molecules.
Oriented Molecules
B0
Oriented Single Crystals
B0
Powder (Polycrystalline Solid)
B0
Chemical Shift Tensor
)(0 rBE
Applications of Chemical Shift
Ap
plicatio
ns o
f Ch
emical S
hift
http://www.bmrb.wisc.edu/data_access/outlier_selection_grid.html
Applications of Chemical Shift
Applications of Chemical Shift
Relaxation, dynamics
Solid state NMR
CS Imaging
……
Story Goes On
Indirect Dipolar Interaction (J-Coupling)
N
SN
S
Interaction between spins mediated by electrons around them.J-coupling is usually much smaller than direct dipolar coupling.
J-CouplingNMR/I
Homonuclear system
A Heteronuclear System AX System
X
X
A X
AXJ AXJ
11 32: :1 1: :nn nnn CC C C
1 2 1: : : : :1 1mmmmC C C
Spin A:
Spin B:
00000…000
10000…000
11111…101
11111…111
11111…110
01000…000
00100…000
…
11000…000
01100…000
00110…000
…
1=“up”0=“down”
General Cases of Two-Site Homonuclear Systems000…00
100…00
111…01
111…11
111…10
010…00
001…00
…
110…00
011…00
0011..00
…
Spin BSpin A
Exercise: Who are They?
ABC System
200 MHz 1H-NMR spectrum of dibromo benzonorbornene derivative in CDCl3 and expansions of the signals.
ABCD system
Equivalent Spins
Coupled with Quadrupolar Spins
Strong Coupling and Quantum Mechanical Treatment
Example
Ｅ ｉｓ ｂｒｏａｄｂｅｃａｕｅ ｏｆ ｅｘｃｈａｎｇｅ．
Ha
Hb
Ｈｃ
Ha（Ｈｏｙｅ）
Ａｎａｌｙｓｉｓ
Ａｎａｌｙｓｉｓ
Ｈｃ
Ｈｄ
Ｈｄ
Ｒｅｓｕｌｔ
Ｒｅｓｕｌｔ
Karplus Equation
Karplus Equation showing the relationship between the observed couplingconstant and the φ(=θ-135o) angle. Note that unique solutions are obtained only for J > 8 Hz and J <5 Hz .
Φ
Karplus Equations
Karplus Equations3JH-C-C-H = 10 cos2 for 0 £ 900, and3JH-C-C-H = 12 cos2 for 90 £ £ 1800
Typical J-coupling constants• 3JCOCH Mulloy et al. Carbohydr. Res. 184 (1988) 39-46 • Tvaroska et al. Carbohydr. Res. 189 (1989) 359-362 • Anderson et al. J. Chem. Soc., Perkin 2 (1994) 1965-1967 • 3JCOCC B. Bose et al. J. Am. Chem. Soc. 120 (1998) 11158-11173 • Q. Xu and A. Bush Carbohydr. Res. 306 (1998) 335-339 • M.J. Milton et al. Glycobiology 8 (1998) 147-153 • 3JCCCH R. Aydin & H. Günther Mag. Reson. Chem. 28 (1990) 448-
457 • A. de Marco et al. Biochemistry 18 (1979) 3847- • 3JPOCH Lankhorst et al. J. Biomol. Struct. Dyn. 1 (1984) 1387-1405 • 3JCCOP Lankhorst et al. J. Biomol. Struct. Dyn. 1 (1984) 1387-1405 • 3JHNCH S. Ludvigsen et al. J. Mol. Biol. 217 (1991) 731- A. Pardi et
al. J. Mol. Biol. 180 (1985) 741- • V.F. Bystrov ， Prog. NMR Spectrosc. 10 (1976) 41- • 3JCNCH L.-F. Kao et al. J. Am. Chem. Soc. 107 (1985) 2323-
3JCNCC L.-F. Kao et al. J. Am. Chem. Soc. 107 (1985) 2323- • 3JHCOH R.R. Fraser et al. Can. J. Chem. 47 (1969) 403-409
Applying the Karplus Equation
Applying the Karplus Equation
Long Range Coupling
The doublet splitting arises from the coupling with the geminal proton Ha. The fact that the Hb, proton does not couple with the bridgehead protons Hc is attributed to the dihedral angle, which is nearly 90°. At the same time, proton Ha couples with the geminal proton Hb and bridgehead protons Hc. Furthermore, proton Ha has long-range coupling to the Hj protons. This can be clearly seen by the further triplet splitting of the signals. This long-range coupling arises from the zigzag orientation of protons Ha and Hd. The zigzag orientation of protons Hb and Hd is impossible because of the rigid geometry. Consequently, there is no long-range coupling between these protons. The fact that proton Ha has long-range coupling to Hd protons clearly indicates the exo configuration of the bromine atoms. In the case of the endo configuration we should not observe any long-range coupling.
Amino Acids
Amino Acid, Name, Abbr. R =
Alanine, ala,A CH3-
Arginine, arg,R H2N-C(=NH2+)-, NH-(CH2)3-
Asparagines,asn,N H2NC(O)CH2-
Aspartic acid, asp,D HOOC-CH2-
Cysteine, cys,C HS-CH2-
Glutamic acid, glu,E HOOC-(CH2)2-
Glutamine, gln,Q H2NC(O)CH2-, CH2-
Glycine, gly,G H-
Histidine, his,H
Isoleucine, ile,ICH3CH2-
CH(CH3)-
Leucine, leu,L (CH3)2CHCH2-
Lysine, lys,K +H3N(CH2)4-
Methionine, met,M CH3SCH2CH2-
Phenylalanine,phe,F Ph-CH2-
Praline, pro,P
Serine, ser,S HOCH2-
Threonine,thr,T CH3CH(OH)-
Tryptophan,trp,W
Tyrosine,tyr,Y HO-Ph-CH2-
Valine,val,V (CH3)2CH-
Summary of one-bond heteronuclear couplings along the polypeptide chain utilized in 3D and 4D NMR experiments
Structure of an A-U ( Ａ ) and a C-G ( Ｂ ) Watson-Crick base pair. Notice that in each case, there is a single N-H ... N hydrogen bond. Scalar coupling across this bond was determined to be approximately 6.3 Hz for the GC bp and 6.7 Hz for the AU bp. Non-Watson Crick bp schemes (such as Hoogsteen) contain different hydrogen bonds that can be distinguished from traditional Watson-Crick.
(CH3)2CH
(CH3)2CH
Coupled
Decoupled
Varian parameters: dn, dm, dmm, dpwr
C-H Coupling and 13C Broadband Decoupling
13C-1H Coupling and 13C Broadband Decoupling
Selective Decoupling of 1H-1H
Selective Decoupling of 1H-1H