Transcript Chemical Shift

核磁共振光譜與影像導論
Introduction to NMR Spectroscopy and
Imaging
Lecture 02 Chemical Shift and JCoupling
(Spring Term, 2011)
Department of Chemistry
National Sun Yat-sen University
Chemical Shift and J-Coupling
In the beginning….
All spins were of no difference…same, identical, equal, I/You/He/We/You/They were
all the same…or believed to be so….then...the apple of discern came in…
(Proctor says: "until it is clearly understood, the accuracy of magnetic
moments determined under certain chemical conditions remains
somewhat in doubt").
Proctor
1922-2006
Valuable reading: http://www.ebyte.it/library/hist/ProctorWG_Reminiscences.html
?
Dickinson?
Who can find his photo?
Yu
1913-2003
W.G.Proctor, F.C.Yu(虞福春), Phys Rev 1950,77,717. W.C.Dickinson, Phys Rev 1950 77, 736.
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".
Ramsey
Chemical Shift (Shielding)
B0
Induced shielding
field
Bloc  B0  Binduced
Binduced    B0
chemical shift tensor
Chemical Shift:
a molecule becomes a dipole
B0
m
The induced dipole
moment shifts the
resonance frequency
of the nuclear spin.
 loc  0  Binduced
Binduced    B0
chemical shift tensor
Shielding Depends on Chemical Environment
Different environments cause different shieldings
B(r )  B0  Bs  B0 (1   (r ))
 
B  B0
B0

 0
0
(Representing different local chemical
environments, Proctor and Yu, 1951)
   
 0
0
Hence chemical shift (of resonance frequency relative
to Zeeman frequency ω0.)
Anti-shielding Is Possible
B(r)  B0  Bs  B0 (1   (r))
Anybody cares to find some interesting literature?
Some proton chemical shifts
The more localized AO/MO, the more shielding
Stronger/more bonds mean smaller CS.
Less shielded.(downfield)
You can tell a lot from this diagram
Increasing δ
(these trends for σ,δ,B, |ν| are
same for γ>0 or γ<0 nuclei.
However, for γ<0, ν is negative.)
Larger shift/small shielding
Small shift/large shielding
Downfield (high freq)
 relative 
( ref )
0

[( 0 ) (ref 0 )]
0
 ( ref   absolute )
=( ref   absolute ) 106 ppm
Reference shift
Upfield (low freq)
These words were from CW NMR. ‘Downfield’ means for a
given resonance frequency, the magnetic field used is lower.
‘High frequency’ means at a fixed magnetic field, the spins in
this region have higher resonance frequencies.
The OH bonding in vaporized water clearly differs from that in liquid water!
(hydrogen bonding has significant effect on chemical shift)
Why CHn have smaller CS than H atom?
B0
C
H
H atom
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.
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 correspond
to large shielding (small CS).
The CS is smallest when the magnetic
field 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
Most internal NMR referencing standards are pH and temperature sensitive.
Proton and Carbon Standards for Organic Solents
Chemical Shift
Chemical Formula
Chemical Structure
Boiling Point
H1
C13
Tetramethylsilane (TMS)
C4H12Si
27
0.000
0.000
Dioxane
C4H8O
--
3.75
--
2
Proton Standards for Aqueous Solents
3-(Trimethylsilyl)- Propionic
acid-D4, sodium salt (TSP)
C6H9D4NaO2SI
302
0.000
0.000
2,2-Dimethyl-2-silapentane5-sulfonate sodium salt (DSS)
C6H15NaO3SSi
120
0.000
(labelled as DSS)
--
More info http://www.bmrb.wisc.edu/home/iupac.pdf.
P31 Standards
B. P. (oC)
Chemical Shift
H3PO4
--
0.00
(CH3O)3PO
--
0.00
Chemical Name
Chemical Formula
85% Phosphoric Acid (external)
10% trimethylphosphate (internal)
Chemical Structure
OTHER NMR RESOURCES
N15 Standards
Chemical Name
Chemical Formula
liquid NH3> (external)
NH3
Chemical Structure
B. P. (oC)
Chemical Shift
--
0.00
NMR Internal Referencing Standard Samples
Chemical Name
(oC)
Solvent
1H
Chemical Shift (multiplicity)
JHD (Hz)
HOD in solvent
(approx.)
13C
Chemical Shift (multiplicity)
JCD
(Hz)
B.P. (oC)
M.P. (oC)
11.65
2.04
1
5
-2.2
11.5
178.99
20.0
1
7
-20
118
17
Acetone-d6
2.05
5
2.2
2.8
206.68
29.92
13
7
0.9
19.4
57
-94
Acetonitrile-d3
1.94
5
2.5
2.1
118.69
1.39
1
7
-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-Dimethylformamide
8.03
2.92
2.75
1
5
5
-1.9
1.9
3.5
163.15
34.89
29.76
3
7
7
29.4
21.0
21.1
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
5.29
3.56
1.11
1
1
m
--
5.3
-56.96
17.31
-5
7
-22
19
79
<-130
Methanol-d4
4.87
3.31
1
5
-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-d5
8.74
7.58
7.22
1
1
1
--
5.0
150.35
135.91
123.87
3
3
5
27.5
24.5
25
116
-42
Tetrahydrofurand8
3.58
1.73
1
1
--
2.4 - 2.5
67.57
25.37
5
5
22.2
20.2
66
-109
Toluene-d8
-7.09
7.00
6.98
2.09
-m
1
m
5
----2.3
0.4
137.86
129.24
128.33
125.49
20.4
1
3
3
3
7
-23
24
24
19
111
-95
Trifluoroacetic
Acid-d
11.50
1
--
11.5
164.2
116.6
4
4
72
-15
Trifluoroethanold3
5.02
3.88
1
4x3
-2 (9)
5
126.3
61.5
4
4x5
75
-44
1
and C
13
Chemical Shifts of NMR Solvents
-22
H
Acetic Acid-d4
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
CHARACTERISTIC PROTON CHEMICAL SHIFTS
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 Shift
Range (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
Be aware of “abnormal” chemical shifts …...
1H
1H
13C
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.
Harald Hilbig and Frank H. Koehler, New J Chem, 2001.
•
•
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.
Phosphorous-31 Chemical Shifts
Phosphorous-31
Environment
Chemical Shift
Range (ppm)
PBr3
-228
(C2H5O)3 P
-137
PF3
-97
85% phosphoric acid
0
PCl5
80
PH3
238
P4
450
Compoun
d
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)
Compound
Chemical 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
Phosphorous
(V) Chemical
Shift Table
(from Bruker
Almanac 1991)
Fluorine-19 Chemical Shifts
Fluorine-19
Environment
Chemical Shift
Range (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 Shift
Range (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 meter
or a barometer.
(Only very smart guys would like
to buy an NMR spectrometer
for those purposes though)
Solvent
H2O
D2O
DMSO
acetone
CD Cl3
C6D6
* Relative to TMS.
Shift *(H2O)
4.83
4.79
3.3
2.5
1.4
0.3
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
B  B0  Bs  B0 (1   )
Shielding Anisotropy (CSA)
Electron clouds are seldom
spherically symmetrical. They
are anisotropic in almost
all molecules.
B0
B0
B  B 0  (1   )
Chemical shift anisotropy
(CSA) tensor
In liquids, CSA is averaged out by rapid molecular tumbling; in solids, CSA is kept.
Oriented Molecules
B0
Oriented Single Crystals
B0
Powder (Polycrystalline Solid)
B0
Chemical Shift Tensor
E  B0   (r )  
Applications of Chemical Shift
Applications of Chemical Shift
Applications of Chemical Shift
Applications of Chemical Shift
Relaxation, dynamics
Solid state NMR
CS Imaging
……
Story Goes On
Indirect Dipolar Interaction
(J-Coupling)
Interaction between spins mediated by electrons around them.
J-coupling is usually much smaller than direct dipolar coupling.
J-Coupling
NMR/I
Homonuclear system
A Heteronuclear System AX System
X
X
J AX
J AX
A
X
General Cases of Two-Site Homonuclear Systems
1=“up”
0=“down”
Spin A:
1 : Cn1 : Cn2 : Cn3  Cnn 1 : 1
Spin B:
m 1
m
1 : C : C :  : C
1
m
2
m
00000…000
000…00
10000…000
100…00
01000…000
010…00
00100…000
001…00
…
…
11000…000
110…00
01100…000
011…00
00110…000
0011..00
…
…
:1
11111…101
111…01
11111…110
111…10
11111…111
111…11
Spin A
Spin B
Exercise: Who are They?
ABC System
ABCD system
200 MHz 1H-NMR spectrum of dibromo benzonorbornene derivative in CDCl3 and
expansions of the signals.
Equivalent Spins
Coupled with Quadrupolar Spins
Strong Coupling and Quantum
Mechanical Treatment
Example
Ｅ ｉｓ ｂｒｏａｄ
ｂｅｃａｕｅ ｏｆ
ｅｘｃｈａｎｇｅ．
Ha
Hb
Ｈｃ
Ha（Ｈｏｙｅ）
Ａｎａｌｙｓｉｓ
Ａｎａｌｙｓｉｓ
Ｈｃ
Ｈｄ
Ｈｄ
Ｒｅｓｕｌｔ
Ｒｅｓｕｌｔ
Karplus Equation
Φ
Karplus Equation showing the relationship between the observed coupling
constant and the φ(=θ-135o) angle. Note that unique solutions are obtained
only for J > 8 Hz and J <5 Hz .
Karplus Equations
Karplus Equations
3J
2
0
H-C-C-H = 10 cos q for 0 £<q <90 , and
3J
2
0
H-C-C-H = 12 cos q for 90 £<q £< 180
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) 448457
A. de Marco et al. Biochemistry 18 (1979) 38473JPOCH 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) 741V.F. Bystrov，Prog. NMR Spectrosc. 10 (1976) 413JCNCH L.-F. Kao et al. J. Am. Chem. Soc. 107 (1985) 23233JCNCC L.-F. Kao et al. J. Am. Chem. Soc. 107 (1985) 23233JHCOH 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,I
CH3CH2-
Leucine, leu,L
(CH3)2CHCH2-
Lysine, lys,K
+H3N(CH2)4-
Methionine, met,M
CH3SCH2CH2-
Phenylalanine,phe,F
Ph-CH2-
CH(CH3)-
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