Spektroskopi Molekul Organik (SMO): Nuclear Magnetic Resonance

(NMR) Spectroscopy

All is adopted from McMurry’s Organic Chemistry

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The Use of NMR Spectroscopy

Used to determine relative location of atoms within a moleculeMost helpful spectroscopic technique in organic chemistryMaps carbon-hydrogen framework of moleculesDepends on very strong magnetic fields(imagine the strongest electromagnet you can and the imagine it on steroids)

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Why This Chapter?

NMR is the most valuable spectroscopic technique used for structure determination

More advanced NMR techniques are used in biological chemistry to study protein structure and folding

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Nuclear Magnetic Resonance Spectroscopy

1H or 13C nucleus spins and the internal magnetic field aligns parallel to or against an aligned external magnetic fieldParallel orientation is lower in energy making this spin state more populatedRadio energy of exactly correct frequency (resonance) causes nuclei to flip into anti-parallel state Energy needed is related to molecular

environment (proportional to field strength, B)

The spin state of a nucleus is affected by an appliedmagnetic field

The energy difference between the two spin statesdepends on the strength of the magnetic field (that the atom “feels”)

absorb ΔE

α-spin states β-spin states

release ΔE

Signals detected by NMR

FID

The electrons surrounding a nucleus affect the effectivemagnetic field sensed by the nucleus

Electron poor environment

Electron rich environment

Shielded nuclei do not ‘sense’ as large a magnetic field as deshieldednuclei do. As a result, the energy difference between the α- and β-spin states is much lower in energy for shielded nuclei and resonate at a lower frequency.

Deshielded nuclei have a much higher energy difference between the α- and β-spin states and these resonate at a much higher frequency.

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The Nature of NMR AbsorptionsElectrons in bonds shield nuclei from magnetic fieldDifferent signals appear for nuclei in different environments

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The NMR Measurement

The sample is dissolved in a solvent that does not have a signal itself* and placed in a long thin tubeThe tube is placed within the gap of a magnet and spunRadio frequency (Rf) energy is transmitted and absorption is detectedSpecies that interconvert give an averaged signal that can be analyzed to find the rate of conversionCan be used to measure rates and activation energies of very fast processes

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Chemical Shifts

The relative energy of resonance of a particular nucleus resulting from its local environment is called chemical shift NMR spectra show applied field strength increasing from left to rightLeft part is downfield the right is upfieldNuclei that absorb on upfield side are strongly shieldedChart calibrated versus a reference point, set as 0, tetramethylsilane [TMS]

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Measuring Chemical ShiftNumeric value of chemical shift: difference between strength of magnetic field at which the observed nucleus resonates and field strength for resonance of a reference

Difference is very small but can be accurately measuredTaken as a ratio to the total field and multiplied by 106 so the shift is in parts per million (ppm)

Absorptions normally occur downfield of TMS, to the left on the chartCalibrated on relative scale in delta (δ) scale

Independent of instrument’s field strength

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13C NMR Spectroscopy: Signal Averaging and FT-NMR

Carbon-13: only carbon isotope with a nuclear spinNatural abundance 1.1% of C’s in moleculesSample is thus very dilute in this isotope

Sample is measured using repeated accumulation of data and averaging of signals, incorporating pulse and the operation of Fourier transform (FT-NMR)All signals are obtained simultaneously using a broad pulse of energy and resonance recordedFrequent repeated pulses give many sets of data that are averaged to eliminate noise Fourier-transform of averaged pulsed data gives spectrum (see Figure 13-6)

1 scan of conc. sample

200 scans of same sample

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Characteristics of 13C NMR Spectroscopy

Provides a count of the different types of environments of carbon atoms in a molecule13C resonances are 0 to 220 ppm downfield from TMSChemical shift affected by electronegativity of nearby atoms

O, N, halogen decrease electron density and shielding (“deshield”), moving signal downfield.

sp3 C signal is at δ 0 to 9; sp2 C: δ 110 to 220C(=O) at low field, δ 160 to 220

13C NMR

1H NMR

Low Field High Field

Deshielding ShieldingDown field Up field

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Spectrum of 2-butanone is illustrative- signal for C=O carbons on left edge

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DEPT 13C NMR Spectroscopy

Improved pulsing and computational methods give additional informationDEPT-NMR (distortionless enhancement by polarization transfer)Normal spectrum shows all C’s then:

Obtain spectrum of all C’s except quaternary (broad band decoupled)Change pulses to obtain separate information for CH2, CHSubtraction reveals each type (See Figure 13-10)

DEPT 13C NMR distinguish among CH3, CH2, and CHGroups (Distortionless Enhancement by Polarization Transfer

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Uses of 13C NMR Spectroscopy

Provides details of structureExample: product orientation in elimination from 1-chloro-methyl cyclohexaneDifference in symmetry of products is directly observed in the spectrum1-chloro-methylcyclohexane has five sp3 resonances (δ 20-50) and two sp2 resonances δ 100-150

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1H NMR Spectroscopy and Proton EquivalenceProton NMR is much more sensitive than 13C and the active nucleus (1H) is nearly 100 % of the natural abundanceShows how many kinds of nonequivalent hydrogens are in a compoundTheoretical equivalence can be predicted by seeing if replacing each H with “X” gives the same or different outcomeEquivalent H’s have the same signal while nonequivalent are “different” and as such may cause additional splitting (diastereotopic effect)

There are degrees of nonequivalence

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Nonequivalent H’sReplacement of each H with “X” gives a different constitutional isomerThen the H’s are in constitutionally heterotopic environments and will have different chemical shifts – they are nonequivalent under all circumstances

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Equivalent H’sTwo H’s that are in identical environments (homotopic) have the same NMR signalTest by replacing each with X

if they give the identical result, they are equivalentProtons are considered homotopic

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Enantiotopic DistinctionsIf H’s are in environments that are mirror images of each other, theyare enantiotopicReplacement of each H with X produces a set of enantiomersThe H’s have the same NMR signal (in the absence of chiralmaterials)

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Diastereotopic DistinctionsIn a chiral molecule, paired hydrogens can have different environ-ments and different shiftsReplacement of a pro-R hydrogen with X gives a different diastereomer than replacement of the pro-S hydrogen Diastereotopic hydrogens are distinct chemically and spectrocopically

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Chemical Shifts in 1H NMR Spectroscopy

Proton signals range from δ 0 to δ 10Lower field signals are H’s attached to sp3 CHigher field signals are H’s attached to sp2 CElectronegative atoms attached to adjacent C cause downfield shift

Chemical Shifts in 1H NMR Spectroscopy

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Integration of 1H NMR Absorptions: Proton Counting

The relative intensity of a signal (integrated area) is proportional to the number of protons causing the signalThis information is used to deduce the structureFor example in ethanol (CH3CH2OH), the signals have the integrated ratio 3:2:1For narrow peaks, the heights are the same as the areas and can be measured with a ruler

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Spin-Spin Splitting in 1H NMR Spectra

Peaks are often split into multiple peaks due to interactions between nonequivalent protons on adjacent carbons, called spin-spin splitting

The splitting is into one more peak than the number of H’s on the adjacent carbon (“n+1 rule”)

The relative intensities are in proportion of a binomial distribution and are due to interactions between nuclear spins that can have two possible alignments with respect to the magnetic field

The set of peaks is a multiplet (2 = doublet, 3 = triplet, 4 = quartet)

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Simple Spin-Spin Splitting

An adjacent CH3 group can have four different spin alignments as 1:3:3:1This gives peaks in ratio of the adjacent H signalAn adjacent CH2 gives a ratio of 1:2:1The separation of peaks in a multiplet is measured is a constant, in Hz

J (coupling constant)

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Rules for Spin-Spin Splitting

Equivalent protons do not split each otherThe signal of a proton with n equivalent neighboring H’s is split into n + 1 peaksProtons that are farther than two carbon atoms apart do not split each other

01.02.03.04.05.06.07.08.09.010.0

Chemical shift (δ, ppm)

BrCH2CH3

4 lines;

quartet

3 lines;

triplet

CH3

CH2

01.02.03.04.05.06.07.08.09.010.0

Chemical shift (Chemical shift (δδ, , ppmppm))

BrCH(CH3)2

7 lines;7 lines;

septetseptet

2 lines;

doublet

CH3

CH

Protons Bonded to Oxygen and Nitrogen

These protons can undergo proton exchange

They always appear as broad signals

The greater the extent of the hydrogen bond, the greaterthe chemical shift

dry ethanol

ethanol with acid

To observe well-defined splitting patterns, the difference in the chemical shifts (in Hz) must be 10 times the coupling constant values

1H NMR Spectra of 2-sec-butylphenol at Different Field Strengths

60 MHz

300 MHz

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More Complex Spin-Spin Splitting Patterns

Spectra can be more complex due to overlapping signals, multiple nonequivalenceExample: trans-cinnamaldehyde

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Uses of 1H NMR Spectroscopy

The technique is used to identify likely products in the laboratory quickly and easilyExample: regiochemistry of hydroboration/oxidation of methylenecyclohexaneOnly that for cyclohexylmethanol is observed

Peaks in a 13C NMR spectrum are typicallysinglets

13C—13C splitting is not seen because the probability of two 13C nuclei being in the same molecule is very small.

13C—1H splitting is not normally seen because spectrum is measured under conditions that suppress this splitting (broadband decoupling).

1H Decoupled and Coupled 13C Spectra of 2-butanol

coupled

decoupled