Ch. 13: NMR Spectroscopy Sections 13.1-13.4 Chem 30B, Lecture 3 Molecular Spectroscopy • Nuclear magnetic resonance (NMR) spectroscopy: A spectroscopic technique that gives us information about the number and types of atoms in a molecule, for example, about the number and types of – hydrogen atoms using 1H-NMR spectroscopy. – carbon atoms using 13C-NMR spectroscopy. – phosphorus atoms using 31P-NMR spectroscopy. Nuclear Spin States • An electron has a spin quantum number of 1/2 with allowed values of +1/2 and -1/2. – This spinning charge has an associated magnetic field. – In effect, an electron behaves as if it is a tiny bar magnet and has what is called a magnetic moment. • The same effect holds for certain atomic nuclei. – Any atomic nucleus that has an odd mass number, an odd atomic number, or both, also has a spin and a resulting nuclear magnetic moment. – The allowed nuclear spin states are determined by the spin quantum number, I, of the nucleus. Nuclear Spin States – A nucleus with spin quantum number I has 2I + 1 spin states; if I = 1/2, there are two allowed spin states. – Spin quantum numbers and allowed nuclear spin states for atoms common to organic compounds. 1 2 12 13 14 15 16 19 31 32 Element H H C C N N O F P S Nuclear spin quantum 1/2 1 0 1/2 1 1/2 0 1/2 1/2 0 number ( I ) Number of 2 3 1 2 3 2 1 2 2 1 spin states Nuclear Spins in B0 – Within a collection of 1H and 13C atoms, nuclear spins are completely random in orientation. – When placed in a strong external magnetic field of strength B0, however, interaction between nuclear spins and the applied magnetic field is quantized. The result is that only certain orientations of nuclear magnetic moments are allowed. Nuclear Spins in B0 – for 1H and 13C, only two orientations are allowed. Nuclear Spins in B0 • In an applied field strength of 7.05T the difference in energy between nuclear spin states for – 1H is approximately 0.120 J (0.0286 cal)/mol, which corresponds to a frequency of 300 MHz (300,000,000 Hz). – 13C is approximately 0.030 J (0.00715 cal)/mol, which corresponds to a frequency of 75MHz (75,000,000 Hz). Nuclear Spin in B0 – The energy difference between allowed spin states increases linearly with applied field strength. – Values shown here are for 1H nuclei. Nuclear Magnetic Resonance – When nuclei with a spin quantum number of 1/2 are placed in an applied field, a small majority of nuclear spins are aligned with the applied field in the lower energy state. – The nucleus begins to precess and traces out a cone-shaped surface, in much the same way a spinning top or gyroscope traces out a cone- shaped surface as it precesses in the earth’s gravitational field. Nuclear Magnetic Resonance • If the precessing nucleus is irradiated with electromagnetic radiation of the same frequency as the rate of precession, – the two frequencies couple – energy is absorbed – the nuclear spin is flipped from spin state +1/2 (with the applied field) to -1/2 (against the applied field). Nuclear Magnetic Resonance – (a) Precession and (b) after absorption of electromagnetic radiation. Nuclear Magnetic Resonance • Resonance: In NMR spectroscopy, resonance is the absorption of energy by a precessing nucleus and the resulting “flip” of its nuclear spin from a lower energy state to a higher energy state. • The precessing spins induce an oscillating magnetic field that is recorded as a signal by the instrument. – Signal: A recording in an NMR spectrum of a nuclear magnetic resonance. Nuclear Magnetic Resonance – If we were dealing with 1H nuclei isolated from all other atoms and electrons, any combination of applied field and radiation that produces a signal for one 1H would produce a signal for all 1H. The same is true of 13C nuclei. – Hydrogens in organic molecules, however, are not isolated from all other atoms. They are surrounded by electrons, which are caused to circulate by the presence of the applied field. – The circulation of electrons around a nucleus in an applied field is called diamagnetic current and the nuclear shielding resulting from it is called diamagnetic shielding. Nuclear Magnetic Resonance – The difference in resonance frequencies among the various hydrogen nuclei within a molecule due to shielding/deshielding is generally very small. – The difference in resonance frequencies for hydrogens in CH3Cl compared to CH3F under an applied field of 7.05T is only 360 Hz, which is 1.2 parts per million (ppm) compared with the irradiating frequency. 360 Hz 1.2 6 = 6 = 1.2 ppm 300 x 10 Hz 10 Nuclear Magnetic Resonance – Signals are measured relative to the signal of the reference compound tetramethylsilane (TMS). CH3 CH3 Si CH3 CH3 Tetrameth yls ilane (TMS) – For a 1H-NMR spectrum, signals are reported by their shift from the 12 H signal in TMS. – For a 13C-NMR spectrum, signals are reported by their shift from the 4 C signal in TMS. – Chemical shift (): The shift in ppm of an NMR signal from the signal of TMS. NMR Spectrometer • Schematic diagram of a nuclear magnetic resonance spectrometer. NMR Spectrometer • Essentials of an NMR spectrometer are a powerful magnet, a radio-frequency generator, and a radio-frequency detector. • The sample is dissolved in a solvent, most commonly CDCl3 or D2O, and placed in a sample tube which is then suspended in the magnetic field and set spinning. • Using a Fourier transform NMR (FT-NMR) spectrometer, a spectrum can be recorded in about 2 seconds. NMR Spectrum • 1H-NMR spectrum of methyl acetate. – High frequency: The shift of an NMR signal to the left on the chart paper. – Low frequency: The shift of an NMR signal to the right on the chart paper. Ch. 13: NMR Spectroscopy Sections 13.5-13.7 Chem 30B, Lecture 4 Equivalent Hydrogens • Equivalent hydrogens: Hydrogens that have the same chemical environment. – A molecule with 1 set of equivalent hydrogens gives 1 NMR signal. O H3 C CH3 CH3 CCH3 ClCH 2 CH2 Cl C C H3 C CH3 Propanone 1,2-Dichloro- Cyclope ntane 2,3-Dime thyl- (Aceton e) ethane 2-bute ne Equivalent Hydrogens – A molecule with 2 or more sets of equivalent hydrogens gives a different NMR signal for each set. Cl Cl CH3 CH3 CHCl O C C H H 1,1-D ich loro- Cyclop ent- (Z)-1-Ch loro- Cyclohexen e eth ane an on e prop ene (3 signals) (2 signals ) (2 s ign als) (3 signals) Signal Areas – Relative areas of signals are proportional to the number of H giving rise to each signal, Modern NMR spectrometers electronically integrate and record the relative area of each signal. Chemical Shift - 1H-NMR • Average values of chemical shifts of representative types of hydrogens. Type of Chemical Type of Chemical Hydrogen Shift () Hydrogen Shift () Chemical ( CH3 ) 4 Si 0 (by defin ition) O Shifts RCH3 0.8-1.0 RCOCH3 3.7-3.9 1H-NMR RCH2 R 1.2-1.4 O R3 CH 1.4-1.7 RCOCH2 R 4.1-4.7 R2 C= CRCH R2 1.6-2.6 RCH 2 I 3.1-3.3 RC CH 2.0-3.0 RCH 2 Br 3.4-3.6 A rCH3 2.2-2.5 RCH 2 Cl 3.6-3.8 A rCH2 R 2.3-2.8 RCH 2 F 4.4-4.5 ROH 0.5-6.0 A rOH 4.5-4.7 RCH2 OH 3.4-4.0 R2 C= CH 2 4.6-5.0 RCH2 OR 3.3-4.0 R2 C= CHR 5.0-5.7 R2 NH 0.5-5.0 A rH 6.5-8.5 O O RCCH 3 2.1-2.3 RCH 9.5-10.1 O O RCCH 2 R 2.2-2.6 RCOH 10-13 Chemical Shift • Chemical shift depends on the (1) electronegativity of nearby atoms, (2) hybridization of adjacent atoms, and (3) diamagnetic effects from adjacent pi bonds. • Electronegativity Electron eg- Chemical CH3 -X ativity of X Shift () CH3 F 4.0 4.26 CH3 OH 3.5 3.47 CH3 Cl 3.1 3.05 CH3 Br 2.8 2.68 CH3 I 2.5 2.16 (CH3 ) 4 C 2.1 0.86 (CH3 ) 4 Si 1.8 0.00 Chemical Shift • Hybridization of adjacent atoms. Type of Hydrogen N ame of Chemical (R = alkyl) Hydrogen Sh ift () RCH3 , R2 CH2 , R3 CH Alk yl 0.8 - 1.7 R2 C=C(R)CHR2 Allylic 1.6 - 2.6 RC CH Acetylen ic 2.0 - 3.0 R2 C=CHR, R2 C=CH2 Vin ylic 4.6 - 5.7 RCHO Ald ehydic 9.5-10.1 Chemical Shift • Diamagnetic effects of pi bonds – A carbon-carbon triple bond shields an acetylenic hydrogen and shifts its signal to lower frequency (to the right) to a smaller value. – A carbon-carbon double bond deshields vinylic hydrogens and shifts their signal to higher frequency (to the left) to a larger value. Chemical Type of H N ame Shift () RCH3 Alk yl 0.8- 1.0 RC CH Acetylenic 2.0 - 3.0 R2 C=CH2 Vin ylic 4.6 - 5.7 Chemical Shift – Magnetic induction in the p bonds of a carbon- carbon triple bond shields an acetylenic hydrogen and shifts its signal lower frequency. Chemical Shift – Magnetic induction in the p bond of a carbon- carbon double bond deshields vinylic hydrogens and shifts their signal higher frequency. Chemical Shift – The magnetic field induced by circulation of p electrons in an aromatic ring deshields the hydrogens on the ring and shifts their signal to higher frequency. Ch. 13: NMR Spectroscopy Sections 13.8-13.9 Lecture 5 Signal Splitting; the (n + 1) Rule • Peak: The units into which an NMR signal is split; doublet, triplet, quartet, multiplet, etc. • Signal splitting: Splitting of an NMR signal into a set of peaks by the influence of neighboring nonequivalent hydrogens. • (n + 1) rule: If a hydrogen has n hydrogens nonequivalent to it but equivalent among themselves on the same or adjacent atom(s), its 1H-NMR signal is split into (n + 1) peaks. Signal Splitting (n + 1) – 1H-NMR spectrum of 1,1-dichloroethane. For these hydrogens, n = 1; For this hydrogen, n = 3; their signal is split into CH3 - CH- Cl its signal is split into (1 + 1) = 2 peaks; a doublet Cl (3 + 1) = 4 peaks; a quartet Signal Splitting (n + 1) Problem: Predict the number of 1H-NMR signals and the splitting pattern of each. O (a) CH3 CCH2 CH 3 O (b) CH3 CH2 CCH2 CH3 O (c) CH3 CCH( CH3 ) 2 Origins of Signal Splitting • Signal coupling: An interaction in which the nuclear spins of adjacent atoms influence each other and lead to the splitting of NMR signals. • Coupling constant (J): The separation on an NMR spectrum (in hertz) between adjacent peaks in a multiplet. – A quantitative measure of the spin-spin coupling with adjacent nuclei. Origins of Signal Splitting • Illustration of spin-spin coupling that gives rise to signal splitting in 1H-NMR spectra. Origins of Signal Splitting – The quartet-triplet 1H-NMR signals of 3- pentanone with the original trace and an expansion to show the signal splitting clearly. Coupling Constants • Coupling constant (J): The distance between peaks in a split signal, expressed in hertz. – The value is a quantitative measure of the magnetic interaction of nuclei with coupled spins. Ha Ha Ha Hb H C C Hb Hb a Hb 6-8 Hz 8-14 Hz 0-5 Hz 0-5 Hz Ha Ha Hb Ha Ha C C C C C C Hb Hb Hb 11-18 Hz 5-10 Hz 0-5 Hz 8-11 Hz Origins of Signal Splitting • The origins of signal splitting patterns. Each arrow represents an Hb nuclear spin orientation. Signal Splitting • Pascal’s triangle. – As illustrated by the highlighted entries, each entry is the sum of the values immediately above it to the left and the right. Physical Basis for (n + 1) Rule • Coupling of nuclear spins is mediated through intervening bonds. – H atoms with more than three bonds between them generally do not exhibit coupling. – For H atoms three bonds apart, the coupling is called vicinal coupling. Physical Basis for (n + 1) Rule • Coupling that arises when Hb is split by two different nonequivalent H atoms, Ha and Hc. Coupling Constants – An important factor in vicinal coupling is the angle a between the C-H sigma bonds and whether or not it is fixed. – Coupling is a maximum when a is 0° and 180°; it is a minimum when a is 90°. More Complex Splitting Patterns – Complex coupling that arises when Hb is split by Ha and two equivalent atoms Hc. More Complex Splitting Patterns – Since the angle between C-H bond determines the extent of coupling, bond rotation is a key parameter. – In molecules with free rotation about C-C sigma bonds, H atoms bonded to the same carbon in CH3 and CH2 groups are equivalent. – If there is restricted rotation, as in alkenes and cyclic structures, H atoms bonded to the same carbon may not be equivalent. – Nonequivalent H on the same carbon will couple and cause signal splitting. – This type of coupling is called geminal coupling. More Complex Splitting Patterns – In ethyl propenoate, an unsymmetrical terminal alkene, the three vinylic hydrogens are nonequivalent. More Complex Splitting Patterns – Tree diagram for the complex coupling seen for the three alkenyl H atoms in ethyl propenoate. More Complex Splitting Patterns – Cyclic structures often have restricted rotation about their C-C bonds and have constrained conformations. – As a result, two H atoms on a CH2 group can be nonequivalent, leading to complex splitting. More Complex Splitting Patterns – A tree diagram for the complex coupling seen for the vinyl group and the oxirane ring H atoms of 2-methyl-2-vinyloxirane. More Complex Splitting Patterns • Complex coupling in flexible molecules. – Coupling in molecules with unrestricted bond rotation often gives only m + n + I peaks. – That is, the number of peaks for a signal is the number of adjacent hydrogens + 1, no matter how many different sets of equivalent H atoms that represents. – The explanation is that bond rotation averages the coupling constants throughout molecules with freely rotation bonds and tends to make them similar; for example in the 6- to 8-Hz range for H atoms on freely rotating sp3 hybridized C atoms. More Complex Splitting Patterns – Simplification of signal splitting occurs when coupling constants are the same. More Complex Splitting Patterns – Peak overlap occurs in the spectrum of 1-chloro- 3-iodopropane. – Hc should show 9 peaks, but because Jab and Jbc are so similar, only 4 + 1 = 5 peaks are distinguishable. Ch. 13: NMR Spectroscopy Sections 13.10-13.11 Chem 30B, Lecture 6 Stereochemistry & Topicity • Homotopic atoms or groups H Subs titute H Cl Cl Subs titution doe s not C one H by D C produce a ste reocente r; Cl Cl th erefore hydrogens H D are homotopic. Dichloro- Achiral methane (achiral) – Homotopic atoms or groups have identical chemical shifts under all conditions. Stereochemistry & Topicity • Enantiotopic groups H Subs titute Subs titution produce s a Cl H C one H by D Cl stereocenter; C th erefore, h ydrogens are F H F enan tiotopic. Both D hydrogen s are prochiral; Chlorofluoro- Chiral one is pro-R-chiral, the methane other is pro-S-chiral. (achiral) – Enantiotopic atoms or groups have identical chemical shifts in achiral environments. – They have different chemical shifts in chiral environments. Stereochemistry & Topicity • Diastereotopic groups – H atoms on C-3 of 2-butanol are diastereotopic. – Substitution by deuterium creates a chiral center. – Because there is already a chiral center in the molecule, diastereomers are now possible. H OH Subs titute one H OH H on CH 2 by D H H D H 2-Butanol Chiral (chiral) – Diastereotopic hydrogens have different chemical shifts under all conditions. Stereochemistry & Topicity • The methyl groups on carbon 3 of 3-methyl-2- butanol are diastereotopic. – If a methyl hydrogen of carbon 4 is substituted by deuterium, a new chiral center is created. – Because there is already one chiral center, diastereomers are now possible. OH 3-Methyl-2-butanol – Protons of the methyl groups on carbon 3 have different chemical shifts. Stereochemistry and Topicity • 1H-NMR spectrum of 3-methyl-2-butanol. – The methyl groups on carbon 3 are diastereotopic and appear as two doublets. 13C-NMR Spectroscopy • Each nonequivalent 13C gives a different signal – A 13C signal is split by the 1H bonded to it according to the (n + 1) rule. – Coupling constants of 100-250 Hz are common, which means that there is often significant overlap between signals, and splitting patterns can be very difficult to determine. • The most common mode of operation of a 13C-NMR spectrometer is a proton-decoupled mode. 13C-NMR Spectroscopy • In a proton-decoupled mode, a sample is irradiated with two different radiofrequencies, – one to excite all 13C nuclei. – a second broad spectrum of frequencies to cause all protons in the molecule to undergo rapid transitions between their nuclear spin states. • On the time scale of a 13C-NMR spectrum, each proton is in an average or effectively constant nuclear spin state, with the result that 1H-13C spin-spin interactions are not observed; they are decoupled. 13C-NMR Spectroscopy – Proton-decoupled 13C-NMR spectrum of 1- bromobutane. Chemical Shift - 13C-NMR 13C-NMR chemical shifts of representative groups Chemical Shift - 13C-NMR Typ e of Chemical Type of Chemical Carbon S hift () Carb on Sh ift () RCH3 10-40 RCH2 R 15-55 C R 110-160 R3 CH 20-60 O RCH2 I 0-40 RCOR 160 - 180 RCH2 Br 25-65 O RCH2 Cl 35-80 RCNR2 165 - 180 R3 COH 40-80 O R3 COR 40-80 RCCOH 165 - 185 RC CR 65-85 O O R2 C=CR2 100-150 RCH, RCR 180 - 215 Ch. 13: NMR Spectroscopy Section 13.12 Chem 30B, Lecture 7 Interpreting NMR Spectra • Alkanes – 1H-NMR signals appear in the range of 0.8-1.7. – 13C-NMR signals appear in the considerably wider range of 10-60. • Alkenes – 1H-NMR signals appear in the range 4.6-5.7. – 1H-NMR coupling constants are generally larger for trans-vinylic hydrogens (J= 11-18 Hz) compared with cis-vinylic hydrogens (J= 5-10 Hz). – 13C-NMR signals for sp2 hybridized carbons appear in the range 100-160, which is to higher frequency from the signals of sp3 hybridized carbons. Interpreting NMR Spectra – 1H-NMR spectrum of vinyl acetate. Interpreting NMR Spectra • Alcohols • 1H-NMR O-H chemical shift often appears in the range 3.0-4.0, but may be as low as 0.5. – 1H-NMR chemical shifts of hydrogens on the carbon bearing the -OH group are deshielded by the electron-withdrawing inductive effect of the oxygen and appear in the range 3.0-4.0. • Ethers – A distinctive feature in the 1H-NMR spectra of ethers is the chemical shift, 3.3-4.0, of hydrogens on the carbons bonded to the ether oxygen. Interpreting NMR Spectra – 1H-NMR spectrum of 1-propanol. Interpreting NMR Spectra • Aldehydes and ketones – 1H-NMR: aldehyde hydrogens appear at 9.5-10.1. – 1H-NMR: a-hydrogens of aldehydes and ketones appear at 2.2-2.6. – 13C-NMR: carbonyl carbons appear at 180-215. • Amines – 1H-NMR: amine hydrogens appear at 0.5- 5.0 depending on conditions. Interpreting NMR Spectra • Carboxylic acids – 1H-NMR: carboxyl hydrogens appear at 10-13, higher than most other types of hydrogens. – 13C-NMR: carboxyl carbons in acids and esters appear at 160-180. Interpreting NMR Spectra • Spectral Problem 1; molecular formula C5H10O. Interpreting NMR Spectra • Spectral Problem 2; molecular formula C7H14O.