Chem 215-216 HH W11 Notes - Dr. Masato Koreeda Date: January 5, 2011 Topic: _NMR-II___ page 1 of 10. IV. Chemical Shifts - δ unit Each H nucleus in a molecule has a different degree of electron surrounding it. Higher the electron density is found surrounding the 1H nucleus, more the external magnetic energy is needed for the excitation of that 1H nucleus as the electron shields the nucleus. Where each 1H peak appears in the 1H NMR spectrum is the reflection of what kind of a chemical environment each 1H nucleus is in,* thus the name “chemical shift.” *This is manifested in the electron density surrounding each 1H nucleus. NMR spectra are obtained usually in CDCl3 (99.8% D and 0.2% 1H) with (CH3)4Si [tetramethylsilane or TMS] as internal reference in a certain operating magnetic field such as 200 MHz, 400 MHz, etc.

H3C CH3

O (acetone)in CDCl3 on a 200 MHz magnet NMR spectrometer:

TMS

acetoneresidualCHCl3 in CDCl3

lower fieldor down-field

higher fieldor up-field440

Hz"The peak of acetone 1H's appears as one peak at 440 Hz down-filed from TMS on a 200 MHz NMR spectrometer"

H3C CH3

O (acetone)in CDCl3 on a 400 MHz magnet NMR spectrometer:

TMS

acetone

residualCHCl3 in CDCl3

lower fieldor down-field

higher fieldor up-field880 Hz

"The peak of acetone 1H's appears as one peak at 880 Hz down-filed from TMS on a 200 MHz NMR spectrometer"

note: MHz = 106 Hz MHz (mega Hertz); Hz = cps

Since these are too lengthy descriptions of 1H NMR data and the acetone peak appears at a down field position from TMS proportionally to the strength of an operating magnetic field, the following dimension less ppm unit has been introduced. (H3C)2C=O on a 200 MHz NMR spectrometer: 440 Hz / 200 x 106 Hz = 2.2 x 10-6 ≡ 2.2 ppm

(H3C)2C=O on a 400 MHz NMR spectrometer: 880 Hz / 400 x 106 Hz = 2.2 x 10-6 ≡ 2.2 ppm

Now, these are independent of the strength of an operating magnetic field.

Chem 215-216 HH W11 Notes - Dr. Masato Koreeda Date: January 5, 2011 Topic: _NMR-II___ page 2 of 10. Conversely, 1 ppm on a 200 MHz NMR spectrometer corresponds to: 1 x 10-6 x 200 x 106 Hz = 200 Hz and 1 ppm on a 400 MHz NMR spectrometer corresponds to: 1 x 10-6 x 400 x 106 Hz = 400 Hz This ppm scale relative to TMS and the increasing value to the lower magnetic field (i.e., to the left from TMS) is called “the δ-scale.” The 1H peaks of most of the organic compounds fall in between δ = 0 ~ 10 ppm (see Table 10.3 on p. 361 of Ege’s book). The Factors That Affect Chemical Shifts (1) Hybridization

C Hsp3

typically δ = 0.5 ~ 1.5 ppm

CHsp2

alkenes

typically δ = 5 ~ 6 ppm

However, -C ≡ C - Hsp

δ = ~ 2.2 ppm!

note:H typically δ = 7 ~ 8 ppm

aromatic H's

(2) Electron Density on each 1H Heffective = H0 (1 – σ) H0 : applied magnetic field σ = shielding constant, 10-2 ~ 10-5 (reflects chemical environments of a specific 1H) • increasing electron density on a 1H → more shielding (larger σ) → more external Ho to reach Heffective → 1H peak at a higher field → a smaller δ value for the peak. Examples: (i) tetramethylsilane (TMS):

H3CCH3

CH3CHH

H

electronegativity: 2.1

e.n.: 2.5e.n.: 1.8

SiConsequently, the electron density of the 1H's of the CH3 increases--> 1H's of the CH become highly shielded --> requires more external magnetic field energy.

Therefore, (H3C)4Si H’s appear at a significantly higher field than H’s in most of the organic compounds; one of the reasons why TMS is used as the internal reference compound.

(ii) Halomethanes [H3C-X]

HH

H

electronegativity: 4.0

e.n.: 2.5

C F

δ 4.30

HH

H

e.n.: 3.0

e.n.: 2.5

C Cl

δ 3.05

HH

He.n.: 2.5

C Br

δ 2.70e.n.: 2.8

HH

He.n.: 2.5

C I

δ 2.10e.n.: 2.5

least shielded;most deshielded

Chem 215-216 HH W11 Notes - Dr. Masato Koreeda Date: January 5, 2011 Topic: _NMR-II___ page 3 of 10. (iii) H3C---OR H3C---NR2 H3C---SR δ 3.5 e.n.: 3.5 δ 2.5-3.0 e.n.: 3.0 δ 2.2-2.5 e.n.: 2.5 (iv) alkenes vs α,β-unsaturated ketones

H

H

H

HO

δ 5.22

5.5

6.5 H

HO

H

HO

+ HO

+

--

Hdeshielded

α

β

(3) Magnetic Anisotropy ----- A through-space effect (i) Aromatic Ring-Current Effect

See: Günther, H. NMR Spectroscopy; Wiley: New York, 1998; p. 85. For a recent dispute on the origin of the aromatic ring-current effect, see: Wannere, C. S.; von Ragué Schleyer, P. Org. Lett. 2003, 5, 605.

H

aromatic H'sH

Hδ 5.22

H

HH

HH

7.22|Δδ| = ca. 2 ppm

H

H

HH

H

H

Induced magnetic field

Induced magnetic fieldHo

These aromatic delocalized 6 π electrons start circulatinginto one direction in an external magnetic field (Ho). Thiscirculation of the 6 π-electrons results in the induction of a secondary magnetic field following the Fleming's rule.

flow of the 6 π-electrons in the ring

induced magneticfield opposed tothe applied magneticfield

induced magnetic fieldreinforcing the appliedmagnetic field

Ho

This type of differenct effect in magnetic properties at a different point in space is referred to as "magnetic anisotropy."

H

circulatingπ-electrons

Chem 215-216 HH W11 Notes - Dr. Masato Koreeda Date: January 5, 2011 Topic: _NMR-II___ page 4 of 10. (3) (i) Aromatic Ring-Current Effect (continued)

H

ca. 55 °H's located inside this imaginarycone requires more external magnetic field power for their excitation --> high- field shifted; smaller δ values

H's located outside the cone, including the H's on the benzene ring, requires less externalmagnetic field power (i.e., energy) for their excitation --> down-field shift; larger δ values

CH2

CH2

CH2

H2C

H2CH2C

H2C

H2C

CH2H2C

shieldingzone

deshielding zone

δ 2.63

1.55

1.08

0.70

0.51

Example:

Strongly deshielded

Strongly shielded by the ringcurrent effect of the benzene6π-electrons

The closer the H is to the center of the benzene ring, the stronger the extent of the ring current effect is.

(ii) Acetylene groups.

C C HR

R

H

In a magnetic field, theseπ-electrons induce a secondarymagnetic field

C C HR

shielding zonedeshielding zone

As this H is quite close to the center of the C ≡ C bond,an extremely strong shielding effect is observed for this H.

δ 2.2

V. Integration The peak intensity is proportional to the number of H’s belonging to each peak in the case of 1H NMR.

H3COCH2OCH3

TMS

3.55.0 0 ppm

12 36

These integrated areas are expressed in arbitrary numbers. Only their numerical ratio is important.

chemical shifts

integration of each of the peaks

These 12 and 36 represent the integrated areas of each peak and their ratios correspond to the ratios of the number of H’s belonging to each peak, i.e., 12 : 36 = 1 : 3. This could mean 1 H and 3 H’s, 2H’s and 6 H’s, or 3 H’s and 9 H’s, etc.

Chem 215-216 HH W11 Notes - Dr. Masato Koreeda Date: January 5, 2011 Topic: _NMR-II___ page 5 of 10. Integration (continued). • If there is a 1 : 1 mixture (on a molar basis) of acetone and chlorform [CHCl3], the integrated ratio of each of the two peaks should be 1 : 6.

TMS

2.27.26 0 ppm

2 12

chemical shiftsintegration of each of the peaks

acetone [C3H6O]chloroform[CHCl3]

Conversely, if the 1H NMR spectrum of a mixture of acetone and chloroform shows a 1 : 1 intensity by integration, what is the molar ratio of these two solvents in the solution?

TMS

2.27.26 0 ppm

3.5 3.5

chemical shiftsintegration value of each of the peaks

acetone [C3H6O]chloroform[CHCl3] integration

trace

VI. Spin-Spin Couplings [Nuclear Spin-Nuclear Spin Interactions]-Through-Bond Interactions Acyclic Systems

Cl C C BrCl Br

H H δ 4.5δ 5.8

3-bond interaction

This 3-bond interaction is often referredto as a "vicinal coupling" and is expressedas

3J1,2 = 7.0 Hzbetween H-1 and H-2

1 2

through 3 bonds(i.e., H1-C1, C1-C2, and C2-H2)

The two spin states of H1 interact, through bonds, with the two spin states of H2, called "coupling," resulting in the formation of the spectral pattern consisting of a pair of doublets.

These H's are called a 3-bond neighbor to each other..

4.55.8 δ (ppm)

3J1,2

Chem 215-216 HH W11 Notes - Dr. Masato Koreeda Date: January 5, 2011 Topic: _NMR-II___ page 6 of 10. V. Spin-Spin Coupling (continued)

3-Bond Neighbor Analysis:

Cl H

H H

ClH

has 2 3-bond neighbors (i.e., neighboring H's)

have 4 3-bond neighbors

have 2 3-bond neighborsH

H

============================================================ ethyl acetate [H3C-CH2-O-C(=O)-CH3 ]

HC

CO CH3

HH

H H O

δ (ppm)

2 chemicallyequiv. H's;have 3 3-bond neighbors

3 chemically equivalent H's;have 2 3-bond neighbors

01.02.04.17.2

CHCl3TMS

triplet

quartet-CH2-

-CH3

4.0 6.1 6.02 : 3 : 3

integration values

1H NMR spectrum of ethyl acetate

integration orintensity ratio

singlet O CH3

O

For the CH3 H's: there are two 3-bond neighbors.

After the interaction with thefirst 3-bond neighbor(assuming J = 6 Hz)

After the interation with thesecond 3-bond neighbor -each of the above doublet peaks splits to a doublet

6 Hz

These middle two peaks overlap.

6 Hz6 Hz 6 Hz6 Hz

Overall,

peak intensity ratio1 : 2 : 1

Chem 215-216 HH W11 Notes - Dr. Masato Koreeda Date: January 5, 2011 Topic: _NMR-II___ page 7 of 10. V. Spin-Spin Coupling (continued)

6 Hz 6 Hz6 Hz

6 Hz 6 Hz6 Hz

Now, the interation with thethird 3-bond neighbor - each of the 1 : 2 : 1 triplet peaks splits to a doublet

Overall, the CH2 peaksshow up as a 1 : 3 : 3 : 1quartet.

For the CH2 H's: there are three 3-bond neighbors.

After the interaction with thefirst 3-bond neighbor(assuming J = 6 Hz)

After the interation with thesecond 3-bond neighbor -each of the above doublet peaks splits to a doublet

6 Hz

These middle two peaks overlap.

6 Hz6 Hz 6 Hz6 Hz

Thus, becoming a tripletwith a 1 : 2 : 1 intensity ratio.

These two peaks overlap.

These two peaks overlap.

++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ In general, in an sp3 acyclic system:

If an H has an n-number of 3-bond neighbor H’s, the NMR signal of the former splits into an (n + 1)-number of peaks. This is due to the fact that all of the vicinal couplings (i.e., 3J) are virtually identical in a freely rotating acyclic system.

++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ For example,

CCH

H C

H H

H H

HO C

HH

Hhas 6 3-bond neighbors

have no 3-bond neighbors

have 1 3-bond neighbor

(6 + 1) = 7 peaks: septet

(0 + 1) = 1 peak: singlet

(1 + 1) = 2 peaks: doublet

Chem 215-216 HH W11 Notes - Dr. Masato Koreeda Date: January 5, 2011 Topic: _NMR-II___ page 8 of 10.

V. Spin-Spin Coupling (continued)

“A 1H-1H spin-spin coupling exists between any 2- and 3-bond neighboring H’s. However, the only couplings that can be observed in the spectrum are those between chemically non-equivalent H’s.”

Chem 215-216 HH W11 Notes - Dr. Masato Koreeda Date: January 5, 2011 Topic: _NMR-II___ page 9 of 10. V. Spin-Spin Coupling (continued) (6) vinyl acetate

HB HX

O

OHA

CH3δ 2.15 (singlet)

4.88 (doublet of doublets)

4.57 (doublet of doublets) 7.27 (doublet of doublets)

H H

O

OH

CH3

H H

O

OH

CH3

These are high-field shifted due to the following resonance contribution:

The coupling constants among these three H's are:3JAX = 14.2 Hz (trans-vicinal); 3JBX = 6.5 Hz (cis-vicinal); 2JAB = 1.2 Hz (geminal)

down-field shifted due to the strong inductive effect by the oxygen atom

For HX:

Upon interaction with HA

Then, upon interactionwith HB, each of the doubletsplits into a doublet

3JAX

14.2 Hz

6.5 Hz

6.5 Hz

3JBX3JBX

"a doublet of doublets"

Unlike those in an acyclic system, these middle two peaks do not overlap, thus not producing a 1 : 2 : 1 triplet pattern.

3JAX3JBX≠

The situation is the same for both HA and HB. Therefore, HA and HB each shows a doublet of doublets.

Chem 215-216 HH W11 Notes - Dr. Masato Koreeda Date: January 5, 2011 Topic: _NMR-II___ page 10 of 10.

V. Spin-Spin Coupling (continued) (7) Aromatic Hydrogens: typically 3J ~ 8Hz (ortho); 4J ~ <1 Hz (meta); 5J ~ 0 Hz (para)

HB HA

HAHB

Cl H

O

H H

HH

Two groups of chemically equivalent aromatic H's: each shows up as a doublet as a result of 3JAB ~ 8 Hzwith a 2 H-intensity.

(a) para-Disubstituted Benzene

quartet (3 3-bond neighbors) at 2.8 ppm

triplet (2 3-bond neighbors) at 1.2 ppm

(c) Long-range couplings

HA

Br

HB

CH3HC

NO2

singlet at 2.5 ppm

HA

Br

HB

CH3HC

NO2

~ 0 Hz

8.6 Hz

2.2 Hz

3J (ortho coupling)

4J (meta coupling)

5J (para coupling)

doublet at7.40 ppm

a doublet of doublets at 8.04 ppm

doublet at 8.38 ppm

(b) Three isomers of nitroaniline

NO2

HA

HC

NH2HD

HB

7.48 (s)6.95 (d)

7.55 (d)

HA

NO2

HC

NH2HD

HB 7.36 (t)HB

HA

NH2HA

HBNO28.08 (d)

ortho meta para

6.67 (t)

7.34 (t)

6.82 ppm (d)

6.61 (d)

7.93 (d)

Chemical shifts of each of these aromatic H's are explainable in terms of resonance contributions of the NH2 and NO2 groups.

NH H NH H

HNH H

H

N HH

H

H

HH

H most e-density increase

highest field-shift (smaller δ ppm)

some e-density increase

high-field shift