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Química Orgânica I

Ciências Farmacêuticas

Bioquímica

Química

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Nuclear Magnetic Resonance Spectroscopy (II)

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� Adaptado de Organic Chemistry, 6th Edition; L.G. Wade, Jr.

� Leitura complementar recomendada:

� Espectroscopia de RessonânciaMagnética Nuclear; A.M.d’A.R. Gonsalves, T.M.V.D. Pinho e Melo, 2007

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(rev)

� Desvio químico (ambiente electrónico)

� Nº de sinais (grupos de protões equivalentes)

� Intensidade (nº de protões equivalentes)

� Multiplicidade de sinal (protões adjacentes)

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Chemical shift

2.70 ppm2.70 ppmδδδδ value:

270 Hz162 HzShift From TMS:

100 MHz60 MHzOperating Frequency:

B0 = 2.35 TeslaB0 = 1.41 TeslaStrength of Field:

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Me-H; Me-F

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4.263.052.682.160.23Chemical Shift δδδδ

4.03.12.82.52.1Electronegativity of X

FClBrIHElement X

CH3FCH3ClCH3BrCH3ICH3HCompound CH3X

Electronegativity effects on proton chemical shifts

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δ

=>

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Number of Signals

� Equivalent hydrogens have the same chemical shift.

=>

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Intensity of Signals

� The area under each peak is proportional to the number of protons.

� Shown by integral trace.

=>

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1,1,2-Tribromoethane

Nonequivalent protons on adjacent carbons.

=>

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Doublet: 1 Adjacent Proton

=>

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Triplet: 2 Adjacent Protons

=>

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Explain observed signals

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distance between split peaks = 1.26 ppm - 1.14 ppm = 0.12 ppm J = 0.12 ppm * (60 Hz / 1 ppm) = 7.2 Hz

J

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Values for Coupling Constants

=>

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The N + 1 Rule

If a signal is split by N equivalent protons,

it is split into N + 1 peaks.

=>

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Range of Magnetic Coupling

� Equivalent protons do not split each other.

� Protons bonded to the same carbon will split each other only if they are not equivalent.

� Protons on adjacent carbons normally will couple.

� Protons separated by four or more bonds will not couple.

=>

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Splitting for Ethyl Groups

=>

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Splitting for Isopropyl Groups

=>

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Coupling Constants (rev.)

� Distance between the peaks of multiplet

� Measured in Hz

� Not dependent on strength of the external field

� Multiplets with the same coupling constants may come from adjacent groups of protons that split each other.

=>

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Complex Splitting

� Signals may be split by adjacent protons, different from each other, with different coupling constants.

� Example: Ha of styrene which is split by an adjacent H trans to it (J = 17 Hz) and an adjacent H cis to it (J = 11 Hz).

=>

C C

H

H

Ha

b

c

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Splitting Tree C C

H

H

Ha

b

c

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Spectrum for Styrene

=>

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Stereochemical Nonequivalence

� Usually, two protons on the same C are equivalent and do not split each other.

� If the replacement of each of the protons of a -CH2 group with an imaginary “Z” gives stereoisomers, then the protons are non-equivalent and will split each other.

=>

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Some Nonequivalent Protons

C C

H

H

Ha

b

c

OH

H

H

H

a

b

c

d

CH3

H Cl

H H

Cl

a b

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(S)-1,2-dichloropropane

H Cl

H H

Cl

3.96

1.59

3.74 3.49

=>

01234PPM

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2 conformers

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Time Dependence

� Molecules are tumbling relative to the magnetic field, so NMR is an averaged spectrum of all the orientations.

� Axial and equatorial protons on cyclohexaneinterconvert so rapidly that they give a single signal.

� Proton transfers for OH and NH may occur so quickly that the proton is not split by adjacent protons in the molecule.

=>

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Hydroxyl Proton

� Ultrapure samples of ethanol show splitting.

� Ethanol with a small amount of acidic or basic impurities will not show splitting.

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N-H Proton

� Moderate rate of exchange.

� Peak may be broad.

=>

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Identifying the O-H or N-H Peak

� Chemical shift will depend on concentration and solvent.

� To verify that a particular peak is due to O-H or N-H, shake the sample with D2O.

� Deuterium will exchange with the O-H or N-H protons.

� On a second NMR spectrum the peak will be absent, or much less intense.

=>

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Modern NMR

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Carbon-13

� 12C has no magnetic spin.

� 13C has a magnetic spin, but is only 1% of the carbon in a sample.

� The gyromagnetic ratio of 13C is one-fourth of that of 1H.

� Signals are weak, getting lost in noise.

� Hundreds of FT-NMR spectra are taken, averaged.=>

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Fourier Transform NMR

� Radio-frequency pulse given.

� Nuclei absorb energy and precess (spin) like little tops.

� A complex signal is produced, then decays as the nuclei lose energy.

� Free induction decay is converted to spectrum. =>

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Hydrogen and Carbon Chemical Shifts

=>

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Combined 13C and 1H Spectra

=>

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Differences in 13C Technique

� Resonance frequency is ~ one-fourth, 15.1 MHz instead of 60 MHz.

� Peak areas are not proportional to number of carbons.

� Carbon atoms with more hydrogens absorb more strongly.

=>

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Spin-Spin Splitting

� It is unlikely that a 13C would be adjacent to another 13C, so splitting by carbon is negligible.

� 13C will magnetically couple with attached protons and adjacent protons.

� These complex splitting patterns are difficult to interpret.

=>

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O

O

7.14

7.07

7.14

7.06

7.06 3.51

4.12

1.30

O

O

129.2

127.6

129.2

129.8

134.8

129.8 46.0

171.361.3

14.1

calculated

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Proton Spin Decoupling

� To simplify the spectrum, protons are continuously irradiated with “noise,”so they are rapidly flipping.

� The carbon nuclei see an average of all the possible proton spin states.

� Thus, each different kind of carbon gives a single, unsplit peak.

=>

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Two 13C NMR Spectra

=>

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Proton-decoupled 13C spectra for ethyl phenylacetate

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Off-Resonance Decoupling

� 13C nuclei are split only by the protons attached directly to them.

� The N + 1 rule applies: a carbon with N number of protons gives a signal with N + 1 peaks.

=>

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Off-resonance proton-coupled 13C spectra for ethyl phenylacetate

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DEPT

� Distortionless Enhancement by Polarization Transfer

� 1H magnetization is generated first, then transferred to 13C.

� This "polarization transfer" enhances sensitivity.

� Also, the experiment repetition rate is dependent on relaxation of 1H, rather than 13C, so a shorter delay is needed.

http://www.acornnmr.com/codeine/dept.htm

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DEPT - codeine

DEPT-135 CH and CH3 peaks up, CH2 peaks invertedDEPT-90 CH peaks onlyDEPT-45 all protonated carbonsnormal 13C spectrum

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solvents

4.82 (singlet)water - d2

5.32 (singlet)methylene chloride - d2

3.31 (singlet), 4.78 (singlet)methanol - d4

1.11, 3.56, 5.19ethanol - d6

2.49 (singlet)dimethylsulfoxide - d6

7.25 (singlet)chloroform - d

nonecarbon tetrachloride

7.15 (singlet)benzene - d6

1.93 (singlet)acetonitrile - d3

2.09 (singlet)acetone - d6

2.0 (singlet), 11.7(singlet)acetic acid - d4

δδδδ (ppm)Solvent

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Solvents for 13C-NMR

49.0methanol

66.5dioxane

39.5dimethylsulfoxide

77.0chloroform

128.0benzene

206.0, 24.8acetone

δδδδ (ppm)Solvent

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MRI

� Magnetic resonance imaging, noninvasive

� “Nuclear” is omitted because of public’s fear that it would be radioactive.

� Only protons in one plane can be in resonance at one time.

� Computer puts together “slices” to get 3D.

� Tumors readily detected.

=>

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� http://www.cem.msu.edu/~reusch/VirtualText/Spectrpy/nmr/nmr1.htm#nmr1

� http://www.chemistry.ccsu.edu/glagovich/teaching/316/index.html

� http://orgchem.colorado.edu/hndbksupport/nmrtheory/main.html

� http://www.chemie.uni-erlangen.de/oc/research/NMR/music.html