Chapter 1--Title

Nuclear Magnetic Resonance and Mass Spectrometry:

Tools for Structure DeterminationSPECTROSCOPY OF CARBON COMPOUNDSOBJECTIVESChapter 92Describe the concept of spectroscopy for structural identificationElucidate the structure of organic compounds from Infrared spectrumElucidate the structure of organic compounds from the Proton and Carbon-13 Nuclear Magnetic Resonance spectrum

Chapter 931. Describe the concept of spectroscopy for structural identification

IntroductionSpectroscopy: the study of the interaction of energy with matterEnergy applied to matter can be absorbed, emitted, cause a chemical change, or be transmittedSpectroscopy can be used to elucidate the structure of a moleculeExamples of SpectroscopyInfrared (IR) Spectroscopy (Chapter 2)Infrared energy causes bonds to stretch and bendIR is useful for identifying functional groups in a moleculeNuclear Magnetic Resonance (NMR)Energy applied in the presence of a strong magnetic field causes absorption by the nuclei of some elements (most importantly, hydrogen and carbon nuclei)NMR is used to identify connectivity of atoms in a moleculeMass Spectrometry (MS)Molecules are converted to ions by one of several methods (including bombardment by a beam of electrons)The ions formed may remain intact (as molecular ions, M+), or they may fragment The resulting mixture of ions is sorted by mass/charge (m/z) ratio, and detected Molecular weight and chemical formula may be derived from the M+ and M+1 ionsMolecular structure may be deduced from the distribution of fragment ions Chapter 942. Elucidate the structure of organic compounds from Infrared spectrum

Chapter 95F.T.I.RChapter 96

Chapter 2 7Infrared Spectroscopy: An Instrumental Method for Detecting Functional GroupsElectromagnetic radiation in the infrared (IR) frequency range is absorbed by a molecule at certain characteristic frequenciesEnergy is absorbed by the bonds in the molecule and they vibrate fasterThe bonds behave like tiny springs connecting the atoms The bonds can absorb energy and vibrate faster only when the added energy is of a particular resonant frequencyThe frequencies of absorption are very characteristic of the type of bonds contained in the sample moleculeThe type of bonds present are directly related to the functional groups presentA plot of these absorbed frequencies is called an IR spectrum

Chapter 2 8Infrared SpectrometerAn infrared spectrometer detects the frequencies absorbed by the sample moleculeLight of all the various IR frequencies is transmitted to the molecule and the frequencies absorbed are recordedThe absorption frequencies are specified as wavenumbers in units of reciprocal centimeters (cm-1)Alternatively the wavelength (l) in units of microns (mm) can be specified

The spectrum is a plot of frequency on the horizontal axis versus strength of absorption on the vertical axis

Chapter 2 9There are different types of stretching and bending vibrations induced by the absorption of infrared energy

The actual relative frequency of vibration can be predicted Bonds with lighter atoms vibrate faster than those with heavier atoms

Chapter 2 10Triple bonds (which are stiffer and stronger) vibrate at higher frequencies than double bondsDouble bonds in turn vibrate at higher frequencies than single bonds

The IR spectrum of a molecule usually contains many peaksThese peaks are due to the various types of vibrations available to each of the different bondsAdditional peaks result from overtone (harmonic) peaks which are weaker and of lower frequencyThe IR is a fingerprint of the molecule because of the unique and large number of peaks seen for a particular molecule

Chapter 2 11

Chapter 2 12Interpreting IR SpectraGenerally only certain peaks are interpreted in the IRThose peaks that are large and above 1400 cm-1 are most valuable

HydrocarbonsThe C-H stretching regions from 2800-3300 cm-1 is characteristic of the type of carbon the hydrogen is attached toC-H bonds where the carbon has more s character are shorter, stronger and stiffer and thus vibrate at higher frequencyC-H bonds at sp centers appear at 3000-3100 cm-1C-H bonds at sp2 centers appear at about 3080 cm-1C-H bonds at sp3 centers appear at about 2800-3000 cm-1C-C bond stretching frequencies are only useful for multiple bondsC-C double bonds give peaks at 1620-1680 cm-1C-C triple bonds give peaks at 2100-2260 cm-1These peaks are absent in symmetrical double and triple bondsChapter 2 13Example: octane

Example: 1- hexyne

Chapter 2 14AlkenesThe C-H bending vibration peaks located at 600-1000 cm-1 can be used to determine the substitution pattern of the double bond

Chapter 2 15Example: 1-hexene

Chapter 2 16Aromatic CompoundsThe C-C bond stretching gives a set of characteristic sharp peaks between 1450-1600 cm -1Example: Methyl benzene

Chapter 2 17Other Functional GroupsCarbonyl Functional GroupsGenerally the carbonyl group gives a strong peak which occurs at 1630-1780 cm-1 The exact location depends on the actual functional group present

Chapter 2 18Alcohols and Phenols The O-H stretching absorption is very characteristicIn very dilute solutions, hydrogen bonding is absent and there is a very sharp peak at 3590-3650 cm-1In more concentrated solutions, the hydroxyl groups hydrogen bond to each other and a very broad and large peak occurs at 3200-3550 cm-1A phenol has a hydroxyl group directly bonded to an aromatic ring

Chapter 2 19Carboxylic AcidsThe carbonyl peak at 1710-1780 cm-1 is very characteristicThe presence of both carbonyl and O-H stretching peaks is a good proof of the presence of a carboxylic acidExample: propanic acid

Chapter 2 20AminesVery dilute solution of 1o and 2o amines give sharp peaks at 3300-3500 cm-1 for the N-H stretching1o amines give two peaks and 2o amines give one peak3o have no N-H bonds and do not absorb in this regionMore concentrated solutions of amines have broader peaksAmides have amine N-H stretching peaks and a carbonyl peakChapter 9213. Elucidate the structure of organic compounds from the Proton and Carbon-13 Nuclear Magnetic Resonance spectrum

N.M.RChapter 922

The Electromagnetic SpectrumElectromagnetic radiation has the characteristics of both waves and particlesThe wave nature of electromagnetic radiation is described by wavelength (l) or frequency (n)The relationship between wavelength (or frequency) and energy (E) is well defined

Wavelength and frequency are inversely proportional (n= c/l) The higher the frequency, the greater the energy of the waveThe shorter the wavelength, the greater the energy of the wave

Chapter 923

NMR involves absorption of energy in the radiofrequency range

Chapter 924

Nuclear Magnetic Resonance (NMR) SpectroscopyThe nuclei of protons (1H) and carbon-13 (13C), and certain other elements and isotopes, behave as if they were tiny bar magnetsWhen placed in a magnetic field and irradiated with radio frequency energy, these nuclei absorb energy at frequencies based on their chemical environmentsNMR spectrometers are used to measure these absorptions

Continuous-Wave (CW) NMR SpectrometersThe oldest type of NMR spectrometer The magnetic field is varied as the electromagnetic radiation is kept at a constant frequencyDifferent nuclei absorb the electromagnetic energy based on their chemical environment and produce peaks in different regions of the spectrum

Chapter 925Fourier Transform (FT) NMR SpectrometersThe sample is placed in a constant (and usually very strong) magnetic fieldThe sample is irradiated with a short pulse of radio frequency energy that excites nuclei in different environments all at onceThe resulting signal contains information about all of the absorbing nuclei at onceThis signal is converted to a spectrum by a Fourier transformationFT NMR allows signal-averaging, which leads to enhancement of real spectral signals versus noise The strong, superconducting magnets used in FTNMR spectrometers lead to greater sensitivity and much higher resolution than continuous wave instrumentsChapter 926Chemical Shift: Peak Position in an NMR SpectrumNuclei in different chemical environments in a molecule will absorb at slightly different frequenciesThe position of the signals in the spectrum is called the chemical shiftThere are two reasons for differences in the magnetic environment for a protonThe magnetic field generated by electrons circulating around the nucleus giving the signalLocal magnetic fields generated by electrons elsewhere in the molecule

Chapter 927Example: 1,4-dimethylbenzene

The spectrum is measured on a delta (d) scale in units of parts per million (ppm)Lower frequency is to the left in the spectrum; these absorptions are said to be downfieldHigher frequency is to the right in the spectrum: these absorptions are said to be upfieldThe small signal at d 0 corresponds to an internal standard called tetramethylsilane (TMS) used to calibrate the chemical shift scaleThe number of signals in the spectrum corresponds to the number of unique sets of protons1,4-dimethylbenzene has protons in two unique environments and so shows two signalsChapter 928

Integration of Peak Areas. The Integral CurveThe area under each signal corresponds to the relative number of hydrogen atoms in each unique environment within a moleculeThe height of each step in the integral curve is proportional to the area of the signal underneath the stepSignal SplittingThe signal from a given proton will be split by the effect of magnetic fields associated with protons on adjacent carbonsCharacteristic peak patterns result from signal splitting that are related to the number of protons on adjacent carbonsExample: 1,1,2-trichloroethaneChapter 929

Nuclear Spin: The Origin of the SignalThe nuclei of certain elements and isotopes have spin states that are quantized1H has a spin quantum number I = 1/2 and has allowed spin states of +1/2 or -1/2Other nuclei with I = 1/2 are 13C, 19F and 31P and these also respond to an external magnetic fieldNuclei with I = 0 do not have spin (12C and 16O) and do not respond to an external magnetic fieldThe nuclei of NMR-active nuclei behave like tiny bar magnetsIn the absence of an external magnetic field these bar magnets are randomly orientatedIn an external magnetic field they orient either with (a spin state) or against (b spin state) the magnetic fieldChapter 930

Nuclei aligned with the magnetic field are lower in energy than those aligned against the fieldThe nuclei aligned with the magnetic field can be flipped to align against it if the right amount of energy is added (DE)The amount of energy required depends on the strength of the external magnetic fieldThe stronger the external magnetic field, the higher the radio frequency energy required to flip the nuclear spin

At (a) there is no external magnetic field and therefore no energy difference between the two statesAt (b) the external magnetic field is 1.41 Tesla and energy corresponding to a frequency of about 60MHz is needed to flip between the spin statesAt (c) the external magnetic field is 7.04 Tesla energy corresponding to a frequency of about 300MHz is needed to flip between the spin statesChapter 931

Shielding and Deshielding of ProtonsProtons in an external magnetic field absorb at different frequencies depending on the electron density around that protonHigh electron density around a nucleus shields the nucleus from the external magnetic fieldShielding causes absorption of energy at higher frequencies (more energy is required for this nucleus to flip between spin states) - the signals are upfield in the NMR spectrumLower electron density around a nucleus deshields the nucleus from the external magnetic fieldDeshielding causes absorption of energy at lower frequencies (less energy is required for this nucleus to flip between spin states) - the signals are downfield in the NMR spectrumChapter 932

Electronegative atoms draw electron density away from nearby protons and therefore deshield themCirculation of p electrons leads to a local induced magnetic fieldThe induced field can reinforce or diminish the external field sensed by a proton (depending on the location of the proton), causing deshielding or shielding, respectivelyAlkene and aromatic ring hydrogens are deshielded by the circulation of p electrons. A terminal alkyne hydrogen is shielded by the circulation of p electrons. Chapter 933

Chemical ShiftChemical shifts are measured in relation to the internal reference tetramethylsilane (TMS)The protons of TMS are highly shielded because of the strong electron donating capability of siliconThe signal for TMS is well away from most other proton absorptions

The d scale for chemical shifts is independent of the magnetic field strength of the instrument (whereas the absolute frequency depends on field strength)

Thus, the chemical shift in d units for protons on benzene is the same whether a 60 MHz or 300 MHz instrument is usedChapter 934

Chapter 935

Chemical Shift Equivalent and Nonequivalent ProtonsTo predict the number of signals to expect in an NMR spectrum it is necessary to determine how many sets of protons are in unique environmentsChemically equivalent protons are in the same environment and will produce only one signalHomotopic HydrogensHydrogens are chemically equivalent or homotopic if replacing each one in turn by the same group would lead to an identical compoundChapter 936

Enantiotopic and Diastereotopic Hydrogen AtomsIf replacement of each of two hydrogens by some group leads to enantiomers, those hydrogens are enantiotopicIn the absence of a chiral influence, enantiotopic hydrogens have the same chemical shift and appear in the same signal

If replacement of each of two hydrogens by some group leads to diastereomers, the hydrogens are diastereotopicDiastereotopic hydrogens have different chemical shifts and will give different signalsChapter 937

Signal Splitting: Spin-Spin CouplingThe signal from a given proton will be split by the effect of magnetic fields associated with protons on adjacent carbonsCharacteristic peak patterns result from signal splitting that are related to the number of protons on adjacent carbonsThe effect of signal splitting is greatest between atoms separated by 3 or fewer s bonds

Signal splitting is not observed between homotopic or enantiotopic protons

Signal splitting occurs only when two sets of protons have different chemical shifts (i.e., are not chemical shift equivalent) Chapter 938

The magnetic field sensed by a proton (Ha) being observed is affected by the magnetic moment of an adjacent proton (Hb)A proton (Hb) can be aligned with the magnetic field or against the magnetic field, resulting in two energy states for HbThe observed proton (Ha) senses the two different magnetic moments of Hb as a slight change in the magnetic field; one magnetic moment reinforces the external field and one substracts from itThe signal for Ha is split into a doublet with a 1:1 ratio of peak areasThe magnitude of the splitting is called the coupling constant Jab and is measured in Hertz (Hz)Chapter 939Chapter 940

When two adjacent protons Hb are coupled to Ha, there are four possible combinations of the magnetic moments for the two HbsTwo of these combinations involve pairings of magnetic moments that cancel each other, causing no net displacement of signalOne combination of magnetic moments reinforces and another subtracts from the applied magnetic fieldHa is split into a triplet having a 1:2:1 ratio of signal areasChapter 941

When three adjacent protons are coupled to Ha, there are 10 possible combinations of the magnetic moments for the HbsFour unique orientations exist and so Ha is split into a quartet with intensities 1:4:4:1Chapter 942

The general rule for splitting is that if there are n equivalent protons on adjacent atoms, these will split a signal into n + 1 peaksCoupled peaks have the same coupling constants JComparison of coupling constants can help with the analysis of complex spectraSeveral factors complicate analysis of NMR spectraPeaks may overlapSpin-spin coupling can be long-range (i.e., more than 3 bonds)Splitting patterns in aromatic groups can be confusingA monosubstituted aromatic ring can appear as an apparent singlet or a complex pattern of peaksChapter 943

Much more complex splitting can occur when two sets of adjacent protons split a particular set of protonsIn the system below, Hb is split by two different sets of hydrogens : Ha and HcTheortically Hb could be split into a triplet of quartets (12 peaks) but this complexity is rarely seenThe spectrum of 1-nitropropane shows splitting of Hb into only 6 peaksChapter 944

Chapter 945

Proton NMR Spectra and Rate ProcessesAn NMR spectrometer is like a camera with a slow shutter speedThe NMR spectrometer will observe rapid processes as if they were a blur, i.e., only an average of the changes will be seenWhen a 1H NMR spectrum of very pure ethanol is taken, the hydroxyl proton is split into a triplet by the two adjacent hydrogensWhen an 1H NMR of regular ethanol is taken the hydroxyl proton is a singletImpure ethanol contains acid and base impurities which catalyze the exchange of hydroxyl protonsThis rapid exchange is so fast that coupling to the adjacent CH2 is not observedThis process is called spin decouplingChapter 946Spin decoupling is typical in the 1H NMR spectra of alcohols, amines and carboxylic acidsThe proton attached to the oxygen or nitrogen normally appears as a singlet because of rapid exchange processesChapter 947

Carbon-13 NMR Spectroscopy13C accounts for only 1.1% of naturally occurring carbon12C has no magnetic spin and produces no NMR signalOne Peak for Each Unique Carbon AtomSince the 13C isotope of carbon is present in only 1.1% natural abundance, there is only a 1 in 10,000 chance that two 13C atoms will occur next to each other in a moleculeThe low probability of adjacent 13C atoms leads to no detectable carbon-carbon splitting 1H and 13C do split each other, but this splitting is usually eliminated by adjusting the NMR spectrophotometer accordinglyThe process of removing the coupling of 1H to an attached carbon is called broadband (BB) proton decouplingMost 13C NMR, therefore, consist of a single peak for each unique carbon

Chapter 94813C Chemical ShiftsJust as in 1H NMR spectroscopy, chemical shifts in 13C NMR depend on the electron density around the carbon nucleusDecreased electron density causes the signal to move downfield (desheilding)Increased electron density causes the signal to move upfield (sheilding)

Because of the wide range of chemical shifts, it is rare to have two 13C peaks coincidentally overlapA group of 3 peaks at d 77 comes from the common NMR solvent deuteriochloroform and can be ignoredChapter 949

Off-Resonance Decoupled SpectraBroad-band decoupling removes all information about the number of hydrogens attached to each carbonOff-resonance decoupling removes some of the coupling of carbons to hydrogens so that the coupled peaks will not overlapUse of off-resonance decoupled spectra has been replaced by use of DEPT 13C NMR

DEPT 13C NMRDEPT (distortionless enhanced polarization transfer) spectra are created by mathematically combining several individual spectra taken under special conditionsThe final DEPT spectra explicitly show C, CH, CH2 , and CH3 carbons To simplify the presentation of DEPT data, the broadband decoupled spectrum is annotated with the results of the DEPT experiments using the labels C, CH, CH2 and CH3 above the appropriate peaks

Chapter 950Example: 1-chloro-2-propanol(a) The broadband decoupled spectrum and (b) a set of DEPT spectra showing the separate CH, CH2, and CH3 signalsChapter 951