IV. Chemical Shifts - Δ Unit

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.

1 NMR spectra are obtained usually in CDCl3 (99.8% D and 0.2% H) with (CH3)4Si [tetramethylsilane or TMS] as internal reference in a certain operating magnetic field such as 200 MHz, 400 MHz, etc.

H3C CH3 in CDCl3 on a 200 MHz magnet NMR spectrometer: O (acetone) acetone residual TMS CHCl3 in CDCl3

lower field 440 higher field or down-field Hz or up-field "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 in CDCl3 on a 400 MHz magnet NMR spectrometer: (acetone) O acetone

residual TMS CHCl3 in CDCl3

lower field higher field or down-field 880 Hz or up-field

"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.

6 -6 (H3C)2C=O on a 200 MHz NMR spectrometer: 440 Hz / 200 x 10 Hz = 2.2 x 10 ≡ 2.2 ppm

6 -6 (H3C)2C=O on a 400 MHz NMR spectrometer: 880 Hz / 400 x 10 Hz = 2.2 x 10 ≡ 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 sp3 C H typically δ = 0.5 ~ 1.5 ppm

sp2 H typically δ = 5 ~ 6 ppm note: C H typically δ = 7 ~ 8 ppm alkenes = ~ 2.2 ppm! However, -C ≡ C - H δ aromatic H's sp

(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) 1 → more external Ho to reach Heffective → H peak at a higher field → a smaller δ value for the peak.

Examples: (i) tetramethylsilane (TMS):

CH3 H electronegativity: 2.1 H3C Si C H 1 CH3 H Consequently, the electron density of the H's of the CH3 increases e.n.: 1.8 e.n.: 2.5 --> 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] electronegativity: δ 3.05 δ 2.70 δ 2.10 δ 4.30 H 4.0 H e.n.: 3.0 H e.n.: 2.8 H e.n.: 2.5 H C F H C Cl H C Br H C I H H H H e.n.: 2.5 e.n.: 2.5 e.n.: 2.5 e.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 - - O O O 5.5 O H H α H + H H δ 5.22 deshielded + H β H 6.5 H H H

(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 H H H 7.22 δ 5.22 |Δδ| = ca. 2 ppm H H H aromatic H's H

Induced magnetic field H H

H H These aromatic delocalized 6 π electrons start circulating into one direction in an external magnetic field (Ho). This circulation of the 6 π-electrons results in the induction of a H H secondary magnetic field following the Fleming's rule. circulating π-electrons Induced magnetic field Ho

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

H induced magnetic field reinforcing the applied magnetic field flow of the 6 π- electrons in the ring

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) Strongly shielded by the ring H's located inside this imaginary Example: current effect of the benzene ca. 55 ° cone requires more external magnetic 6π-electrons field power for their excitation --> high- field shifted; smaller δ values 0.70 shielding H zone 2 H2 C 1.08 C H2C H2C CH2 CH2 deshielding zone 1.55 0.51 H2C CH2 H H's located outside the cone, including the H's on the benzene ring, requires less external H2C CH2 magnetic field power (i.e., energy) for their δ 2.63 excitation --> down-field shift; larger δ values Strongly deshielded

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. δ 2.2 R C C H

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

R shielding zone deshielding zone In a magnetic field, these π-electrons induce a secondary magnetic field

V. Integration

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

O O H3C C CH3 H2

TMS

chemical shifts 5.0 3.5 0 ppm

integration of each of the peaks 12 36

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

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.

chloroform acetone [C3H6O] [CHCl3]

TMS

chemical shifts 7.26 2.2 0 ppm integration of each of the peaks 2 12

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?

chloroform acetone [C3H6O] [CHCl3] integration trace

TMS

chemical shifts 7.26 2.2 0 ppm integration value of each of the peaks 3.5 3.5

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

Acyclic Systems

3-bond The two spin states of H1 interact, through bonds, with the two spin states interaction of H2, called "coupling," resulting in the formation of the spectral pattern δ 5.8 consisting of a pair of doublets. H H δ 4.5 1 C C 2 Cl Br These H's are called a 3-bond neighbor to each other.. Cl Br This 3-bond interaction is often referred to as a "vicinal coupling" and is expressed 3 as J1,2 3 J1,2 = 7.0 Hz through 3 bonds between H-1 and H-2 (i.e., H1-C1, C1-C2, and C2-H2)

5.8 4.5 δ (ppm) 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:

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

Cl H have 2 3-bond neighbors H H

Cl H

H H

have 4 3-bond neighbors

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ethyl acetate [H3C-CH2-O-C(=O)-CH3 ] singlet O CH3 3 chemically equivalent H's; have 2 3-bond neighbors 1H NMR spectrum of ethyl acetate O H -CH3 H triplet C O CH3 H C -CH2- H H O quartet TMS 2 chemically CHCl3 equiv. H's; have 3 3-bond neighbors 7.2 4.1 2.0 1.0 0 δ (ppm)

4.0 6.1 6.0 integration values 2 : 3 : 3 integration or intensity ratio

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

6 Hz

After the interaction with the first 3-bond neighbor (assuming J = 6 Hz) peak intensity ratio 1 : 2 : 1 These middle two After the interation with the peaks overlap. second 3-bond neighbor - each of the above doublet peaks splits to a doublet Overall,

6 Hz 6 Hz 6 Hz 6 Hz

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)

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

6 Hz After the interaction with the first 3-bond neighbor (assuming J = 6 Hz) Thus, becoming a triplet These middle two with a 1 : 2 : 1 intensity ratio. After the interation with the peaks overlap. second 3-bond neighbor - each of the above doublet peaks splits to a doublet

6 Hz 6 Hz 6 Hz 6 Hz

Now, the interation with the third 3-bond neighbor - each of the 1 : 2 : 1 triplet peaks splits These two to a doublet peaks overlap. These two peaks overlap.

6 Hz 6 Hz 6 Hz

Overall, the CH2 peaks show up as a 1 : 3 : 3 : 1 quartet. 6 Hz 6 Hz 6 Hz

++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++ 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,

have 1 3-bond neighbor (1 + 1) = 2 peaks: doublet

H H has 6 3-bond neighbors (6 + 1) = 7 peaks: septet H C H H C O C H H C H H H have no 3-bond neighbors (0 + 1) = 1 peak: singlet 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 δ 2.15 (singlet) 4.88 (doublet of doublets) CH3

HA O O down-field shifted due to the strong inductive effect by the oxygen atom HB HX 7.27 (doublet of doublets) 4.57 (doublet of doublets)

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

CH3 CH3

H O H O

O O

H H H H

The coupling constants among these three H's are:

3 3 2 JAX = 14.2 Hz (trans-vicinal); JBX = 6.5 Hz (cis-vicinal); JAB = 1.2 Hz (geminal)

3 For HX: JAX 14.2 Hz Upon interaction with HA

3 3 JAX ≠ J Then, upon interaction 3 3 BX JBX JBX with HB, each of the doublet splits into a doublet "a doublet of doublets" 6.5 6.5 Hz Hz Unlike those in an acyclic system, these middle two peaks do not overlap, thus not producing a 1 : 2 : 1 triplet pattern.

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) (a) para-Disubstituted Benzene

HB HA O H triplet (2 3-bond neighbors) at 1.2 ppm Cl H H H H quartet (3 3-bond neighbors) at 2.8 ppm HB HA

Two groups of chemically equivalent aromatic H's: 3 each shows up as a doublet as a result of JAB ~ 8 Hz with a 2 H-intensity. (b) Three isomers of nitroaniline ortho meta para

6.82 ppm NH2 6.95 (d) NH2 7.48 (s) NH2 6.61 (d) (d) HD NO2 HD HA HA HA

H NO HC A HC 2 HB HB 7.34 (t) 8.08 (d) 7.36 (t) HB HB 7.55 (d) NO2 7.93 (d) 6.67 (t) Chemical shifts of each of these aromatic H's are explainable in terms of resonance contributions of the NH2 and NO2 groups. highest field-shift (smaller δ ppm) H H H H H H H H N N N N - H H most e density increase H

H H - H H some e density increase high-field shift

H CH3 5 HB A 3 J (para J (ortho coupling) HC Br a doublet of doublets NO2 coupling) at 8.04 ppm 8.6 Hz doublet HB HA at 8.38 ppm NO2 4 2.2 Hz J (meta coupling)