NMR Spectroscopy CHEM 430.

NMR Spectroscopy CHEM 430

FACTORS THAT INFLUENCE PROTON SHIFTS
NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Local Fields Shielding by e- that surround the resonating nuclei arise from local fields They are a simple function of e- density affected by induction, resonance and hybridization effects The magnetic field at the nucleus is altered from B0 to a quantity B0(1-s) where s is called the shielding CHEM 430 – NMR Spectroscopy

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Local Fields Electronegativity effects A nearby e- withdrawing atom or group with decrease e- density moving the observed resonance downfield to higher n Conversely, a nearby e- donating atom or group will increase e- density moving the observed resonance upfield to lower n OH B0 CH3 B0(1 – s) sOH < sCH3 DE = hn CHEM 430 – NMR Spectroscopy 3

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Local Fields B0 B0(1 – s) sO < sC DE = hn CHEM 430 – NMR Spectroscopy 4

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Local Fields Electronegativity effects The trend follows Pauling electronegativity (EN) scale: CH3F CH3O- CH3Cl CH3Br CH3I CH4 (CH3)4Si CH3Li EN 4.0 3.5 3.1 2.8 2.5 2.1 1.8 1.0 d of H 4.26 3.40 3.05 2.68 2.16 0.23 0.0 -0.4 CHEM 430 – NMR Spectroscopy 5

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Local Fields Electronegativity effects The effect is cumulative: The effect drops sharply with distance: CH3Cl CH2Cl2 CHCl3 d of H 3.05 5.30 7.27 -CH2Br -CH2CH2Br -CH2CH2CH2Br d of H 3.30 1.69 1.25 CHEM 430 – NMR Spectroscopy 6

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Local Fields Electronegativity effects The effect is a useful tool in quickly deducing simple aliphatic chains: CHEM 430 – NMR Spectroscopy 7

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Local Fields Resonance effects Donation or withdrawal of e- through resonance will have shielding or deshielding effects, respectively: resonance donation shielding effect resonance withdrawal deshielding effect CHEM 430 – NMR Spectroscopy 8

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Local Fields Hybridization effects Hybridization of the carbon atom influences e- density As proportion of s-character increases (sp3  sp2  sp) bonding electrons move toward C and away from hydrogen - deshielding This effect however is secondary to the influence of the p-cloud of electrons from the unhybridized p-orbitals as we will see CHEM 430 – NMR Spectroscopy 9

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields Purely magnetic effects from a neighboring group can influence nuclear shielding As we saw earlier the combined effects of local and nonlocal fields: Nonlocal fields have a major influence on chemical shift only if the group has a non-spherical shape CHEM 430 – NMR Spectroscopy 10

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields The electrons in a spherical substituent also precess in the applied field, creating a non-local field As the molecule tumbles the lines of magnetic force will remain lined up with the applied field, but the position of the attached nuclei will change The effect cancels itself out leaving only the effect on the local field by the substituent CHEM 430 – NMR Spectroscopy 11

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields The electrons in a non-spherical substituent also precess in the applied field, creating a non-local field In benzene, the 6-p-orbitals overlap to allow full circulation of electrons; as these electrons circulate in the applied magnetic field they oppose the applied magnetic field at the center: B0 CHEM 430 – NMR Spectroscopy 12

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields At the ring periphery, the effect is opposite and the protons are deshielded : CHEM 430 – NMR Spectroscopy 13

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields The benzene system is not spherical, but an oblate ellipsoid As the molecule tumbles in in solution there is either the effect of shielding inside the ring or deshielding outside the ring if the ring is perpendicular to the applied field OR No effect if the ring is parallel to the applied field CHEM 430 – NMR Spectroscopy 14

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields Groups that have appreciably different currents induced by B0 resulting from different orientations in space are said to have diamagnetic anisotropy Just as the local effect can result in shielding (electron donation) or deshielding (electron withdrawal) the nonlocal effect can result in either permutation Regions of shielding are indicated by (+) and deshielding (-) CHEM 430 – NMR Spectroscopy 15

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields The effect was modeled quantitatively by McConnell The following equation relates shielding to the influence of a magnetic dipole on the point in space where a proton(nuclei) resides: At q = 54o 44’ the expression (3cos2q – 1) goes to zero On either side of this ‘magic angle’ sA changes sign sA – shielding for a proton at (r, q) cL and cT are the diamagnetic susceptibilities of the group longitudinal and transverse to B0 CHEM 430 – NMR Spectroscopy 16

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields The protons of benzene reside on the periphery of the ring within the deshielding cone Molecules have been constructed for the purpose of confirming the shielding effect predicted by the model: 9.3 -3.0 -0.5 -1.0 d 2.0 d CHEM 430 – NMR Spectroscopy 17

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields 4n + 2 p-electrons (aromatic) result in the diamagnetic circulation of e-s Pople demonstrated that 4n p-systems have the opposite or paramagnetic circulation: 5.2 10.3 CHEM 430 – NMR Spectroscopy 18

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields For a prolate ellipsoid it is sometimes not as clear as to which arrangement has the stronger induced current The acetylene system provides a simple example CHEM 430 – NMR Spectroscopy 19

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields We say the shift for the terminal acetylene proton experiences magnetic anisotropy. Usual shifts for this H are d For reference sp3 ethane is at 0.86 and sp2 ethene at 5.28 CHEM 430 – NMR Spectroscopy 20

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields Alkanes do not possess the same degree of electron circulation as alkynes but do exert nonlocal fields on adjacent nuclei The C—C s-bond shields a proton on its side more than its end CHEM 430 – NMR Spectroscopy 21

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields The result of which is a deshielding of equatorial protons in conformationally locked systems: Even simple alkane systems show anisotropy: CHEM 430 – NMR Spectroscopy 22

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields The result of which is a deshielding of equatorial protons in conformationally locked systems: Even simple alkane systems show anisotropy: CHEM 430 – NMR Spectroscopy 23

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields The highly shielded position of cyclopropane resonances may be attributed either to an aromatic-like ring current or to the anisotropy of the bond that is opposite to a group in the three- membered ring: The effect is much larger than the indicated 1.2 ppm , because the cyclopropane carbon orbital to hydrogen ( compared with the orbital in cyclohexane) deshields the proton. A cyclopropane ring also can shield more distant hydrogens: Heq 1.2 less than Hax CHEM 430 – NMR Spectroscopy 24

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields Most common single bonds (C-N, C-O) have shielding properties that parallel those of the bond, although the geometry is more complex than that for the C-C bond. Lone electron pairs can have a special effect: In N-methylpiperidine the axial lone pair shields the vicinal Hax by an n  s* interaction without any effect on Heq. As a result, Hax increases to about 1.0 ppm or more in similar systems. CHEM 430 – NMR Spectroscopy 25

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields The anisotropy of double bonds is more difficult to assess, because they have three nonequivalent axes (the McConnell equation, with only two axes, does not apply). Protons situated over double bonds are, in general, more shielded than those in the plane both for alkenes and for carbonyl groups The position of the methylene protons in norbornene may be explained in this fashion since the syn and endo protons, respectively, are shielded with respect to the anti and exo protons. CHEM 430 – NMR Spectroscopy 26

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields The highly deshielded position of aldehydes ( ca. 9.8) is attributed to a combination of a strong polar effect and the diamagnetic anisotropy of the carbonyl group. CHEM 430 – NMR Spectroscopy 27

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields The nonspherical array of lone pairs of e- may exhibit diamagnetic anisotropy, although, alternatively, the effect may be considered a perturbation of local currents. A proton that is H-bonded to a lone pair is invariably deshielded. For example: the -OH proton in ethanol CCl4 resonates at 0.7 (dilute no H-bonding) CD3CD2OH resonates at 5.3 (H-bonding) Carboxylic protons resonate at extremely high frequency (11– 14), because every proton is H-bonded within a dimer or higher aggregate. CHEM 430 – NMR Spectroscopy 28

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Nonlocal Fields Lone- pair anisotropy also has been invoked to explain trends in ethyl groups : For XCH2CH3: The resonance position of –CH2- attached to X is explained by the polar effect The trend for the more distant –CH3 group is opposite; as X increases size, the lone pair moves closer to the –CH3 group and deshields it. X d -CH2- d –CH3 F 4.36 1.24 Cl 3.47 1.33 Br 3.37 1.65 I 3.16 1.86 CHEM 430 – NMR Spectroscopy 29

NMR - The Chemical Shift 3-1 FACTORS THAT INFLUENCE PROTON SHIFTS Summary Functional group effects on proton chemical shifts are explained largely by two general effects.: Local Effects: Electron withdrawal or donation by induction (including hybridization) or by resonance alters the electron density and hence the local field around the resonating proton. Higher electron density shields the proton (lower n, upfield) Low electron density deshields the proton (higher n, downfield) Nonlocal Effects: Diamagnetic anisotropy of nonspherical substituents is largely responsible for the proton resonance positions of aromatics, acetylenes, aldehydes, cyclopropanes, cyclohexanes, alkenes, and hydrogen- bonded species. CHEM 430 – NMR Spectroscopy 30

PROTON CHEMICAL SHIFTS AND STRUCTURE
NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2a Saturated Aliphatics Alkanes. CHEM 430 – NMR Spectroscopy 31

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2a Saturated Aliphatics Functionalized Alkanes. Oxygen: Nitrogen: Sulfur and the Halides: CHEM 430 – NMR Spectroscopy 32

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2a Saturated Aliphatics Functionalized Alkanes. CHEM 430 – NMR Spectroscopy 33

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2a Saturated Aliphatics Functionalized Alkanes. After years of collective observation of 1H (and 13C) NMR it is possible to predict chemical shift to a fair precision using Shoolery Tables These tables use a base value for 1H (and 13C) chemical shift to which are added adjustment increments for each group on the carbon atom d = DX + DY + DZ The tables work well for methyl and methylene but diverge greatly with methine due to the increased interaction between effects CHEM 430 – NMR Spectroscopy 34

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2a Saturated Aliphatics Functionalized Alkanes. Example Shoolery Table - Methylene X or Y Increment -H 0.34 -OC(=O)OR 3.01 -CH3 0.68 -OC(=O)Ph 3.27 -C—C 1.32 -C(=O)R 1.50 -CC- 1.44 -C(=O)Ph 1.90 -Ph 1.83 -C(=O)OR 1.46 -CF2- 1.12 -C(=O)NR2 or H2 1.47 -CF3 1.14 -CN 1.59 -F 3.30 -NR2 or H2 1.57 -Cl 2.53 -NHPh 2.04 -Br 2.33 -NHC(=O)R 2.27 -I 2.19 -N3 1.97 -OH 2.56 -NO2 3.36 -OR 2.36 -SR or H 1.64 -OPh 2.94 -OSO2R 3.13 CHEM 430 – NMR Spectroscopy 35

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2a Saturated Aliphatics Functionalized Alkanes. Example Shoolery Table - Methine X ,Y or Z Increment X, Y or Z -F 1.59 -OC(=O)OR 0.47 -Cl 1.56 -C(=O)R -Br 1.53 -C(=O)Ph 1.22 -NO2 1.84 -CN 0.66 -NR2 or H2 0.64 -C(=O)NH2 0.60 -NH3+ 1.34 -SR or H 0.61 -NHC(=O)R 1.80 -OSO2R 0.94 -OH 1.14 -CC- 0.79 -OR -C=C 0.46 -C(=O)OR 2.07 -Ph 0.99 -OPh 1.79 CHEM 430 – NMR Spectroscopy 36

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2a Saturated Aliphatics Functionalized Alkanes. After years of collective observation of 1H (and 13C) NMR it is possible to predict chemical shift to a fair precision using Shoolery Tables These tables use a base value for 1H (and 13C) chemical shift to which are added adjustment increments for each group on the carbon atom d = DX + DY + DZ The tables work well for methyl and methylene but diverge greatly with methine due to the increased interaction between effects CHEM 430 – NMR Spectroscopy 37

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2b Unsaturated Aliphatics Alkynes. Anisotropy of C≡C results in a low frequency for terminal-H (1.8 – 3.0) Alkenes. Anisotropy of C=C results in a higher frequency for alkenylic (vinyl)-H Range is very large (4.5 – 7.7) and highly subject to other groups on C=C Reference value used for ethene is 5.28 CHEM 430 – NMR Spectroscopy 38

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2b Unsaturated Aliphatics Alkenes. Conjugation usually increases the observed frequency Angle strain increases s-character and therefore moves the resonance to higher frequency The presence of a C=O group w/d electrons by both resonance and induction: CHEM 430 – NMR Spectroscopy 39

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2b Unsaturated Aliphatics Alkenes. CHEM 430 – NMR Spectroscopy 40

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2b Unsaturated Aliphatics Alkenes. These effects were quantified by Tobey and of Pascual, Meier, and Simon, Using an empirical approach they tabulated a series of geminal, cis and trans substituents relative to the proton being observed: d = Zgem + Zcis + Ztrans Although the parameters incorporate inductive and resonance effects, steric effects can cause deviations from observed positions. CHEM 430 – NMR Spectroscopy 41

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2b Unsaturated Aliphatics Alkenes. CHEM 430 – NMR Spectroscopy 42

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2c Aromatics Diamagnetic anisotropy from aromatic ring current shifts the protons to high frequency – benzene is used as a reference (7.27) Rings with only aliphatic substituents tend to bunch the resonances about this frequency (toluene, ~ 7.2) Conjugating substituents tend to spread the aromatic resonances based on contributing resonance structures and inductive effects: CHEM 430 – NMR Spectroscopy 43

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2c Aromatics The a-protons in aromatic heterocycles are shifted due to the polar effect of the heteroatom: As with the alkane and alkene systems a systematic observation has been made of aromatic H-resonances. They can be predicted from the following: d = SSi CHEM 430 – NMR Spectroscopy 44

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2c Aromatics CHEM 430 – NMR Spectroscopy 45

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2c Aromatics Aromatics: CHEM 430 – NMR Spectroscopy 46

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2c Aromatics Heteroaromatics: CHEM 430 – NMR Spectroscopy 47

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2d Protons on Oxygen and Nitrogen Chemical shifts of protons attached to highly electronegative atoms such as O or N are influenced strongly by acidity, basicity, and hydrogen-bonding Protons on Oxygen For –OH, minute amounts of acidic or basic impurities can bring about rapid exchange They are averaged with other exchangeable protons, either in the same molecule or in other molecules, including the solvent. Only a single resonance is observed for all the exchangeable pro-tons at a weighted-average position and no coupling is observed. The resonance varies from sharp to slightly broadened, depending on the exchange rate. CHEM 430 – NMR Spectroscopy 48

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2d Protons on Oxygen and Nitrogen -OH may be determined by exchange experiments described earlier (shaking the NMR sample with D2O) At infinite dilution in (no H-bonding), the OH resonance of alcohols may be found at about 0.5. Under more normal conditions of 5% to 20% solutions, hydrogen bonding results in resonances in the 2– 4 range. More acidic phenols (ArOH) have resonances downfield at 4– 8. Interaction with an ortho group shifts this to 10 or higher. CHEM 430 – NMR Spectroscopy 49

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2d Protons on Oxygen and Nitrogen Most carboxylic acids exist as H-bonded dimers or oligomers, even in dilute solution. Hydrogen bonding coupled with the strong deshielding of the carboxlate group places the acid protons resonate far downfield (11– 14) Likewise, other highly H-bonded acidic protons also may be found in this range, such as sulfonic, phosphonic and enolic protons CHEM 430 – NMR Spectroscopy 50

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2d Protons on Oxygen and Nitrogen Protons on nitrogen Similar properties to -OH Lower electronegativity of N results upfield shifts than those OH protons: 0.5– 3.5 for aliphatic amines, - NH2 3– 5 for aromatic amines ( anilines), Ar-NH2 4– 8 for amides, pyrroles, and indoles 6– 8.5 for ammonium salts, -NH3+ (amino acid protons can exchange rapidly with solvent or other exchangeable protons to achieve an averaged position) The most common nuclide 14N is quadrupolar and possesses unity spin – (could split the resonance of attached protons into a 1: 1: 1 triplet) - rapid relaxation of quadrupolar 14N averages the spin states usually appearing as a broadened resonance Broadening may render NH resonances almost invisible. CHEM 430 – NMR Spectroscopy 51

NMR - The Chemical Shift 3-2 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-2d Protons on Oxygen and Nitrogen CHEM 430 – NMR Spectroscopy 52

NMR - The Chemical Shift 3-4 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-4 Factors That Influence Carbon Shifts Carbon is the defining element in organic compounds, but its major nuclide 12C has a spin of zero. Advent of pulsed FT-methods allowed practical examination of the low- abundance nuclide 13C ( 1.11%) The low probability of having two adjacent nuclei (0.01%) in a single molecule removes complications from carbon–carbon couplings. When C-H couplings are removed by decoupling techniques, the spectrum is essentially free of all spin–spin coupling, and one singlet arises for each distinct type of carbon. Integration is rarely done as 13C has a much larger range of relaxation times than 1H and because the decoupling field perturbs intensities CHEM 430 – NMR Spectroscopy 53

NMR - The Chemical Shift 3-4 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-4 Factors That Influence Carbon Shifts Analysis therefore is simpler for 13C than for 1H spectra – but… Diamagnetic shielding (sd) which is responsible for 1H chemical shifts, is caused by circulation of the electron cloud about the nucleus – 1Hs are surrounded solely by s electrons ( lacking angular momentum) and consequently exhibit only diamagnetic shielding In carbon 2p electrons have angular momentum that can hinder free circulation - hindrance to free electron circulation creates an additional mechanism called paramagnetic shielding (sp) Because sp serves to reduce sd the two mechanisms have opposite signs 13C nuclei (and almost all other nuclides as well) additionally are surrounded by p electrons and exhibit both forms of shielding. CHEM 430 – NMR Spectroscopy 54

NMR - The Chemical Shift 3-4 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-4 Factors That Influence Carbon Shifts The paramagnetic component can be quite large! Chemical-shift range for 1H is only a few ppm, while paramagnetic shifts for other nuclei can extend over a range of hundreds or even thousands of ppm. Qualitatively, angular momentum can arise from excited electronic states and from bonding. The effects are larger when electron density about the nucleus increases. These three considerations were gathered by Ramsay, Karplus, and Pople into the simple empirical relationship… CHEM 430 – NMR Spectroscopy 55

NMR - The Chemical Shift 3-4 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-4 Factors That Influence Carbon Shifts s𝑃 ∝ − 𝑄 𝑖𝑗 ∆𝐸∙ 𝑟 3 DE = average energy of excitation of certain electronic transitions, such as the n  p* transition for many 13C and 15N nuclei. The radial term includes the average distance r from the nucleus of the 2p electrons - this term serves as a measure of electron density. SQij represents the degree of p-bonding to carbon. The negative sign in the equation indicates that paramagnetic shielding is in the opposite direction from sd. More shielding  downfield shift. CHEM 430 – NMR Spectroscopy 56

NMR - The Chemical Shift 3-4 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-4 Factors That Influence Carbon Shifts s𝑃 ∝ − 𝑄 𝑖𝑗 ∆𝐸∙ 𝑟 3 The quantity DE represents the weighted-average energy difference between the ground and certain excited states. Because of symmetry considerations, the p  p* transition is excluded Low-lying excited states (with small DE) make the largest contribution, since DE appears in the denominator. s p n s* p* s* p s p* n DE CHEM 430 – NMR Spectroscopy 57

NMR - The Chemical Shift 3-4 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-4 Factors That Influence Carbon Shifts s𝑃 ∝ − 𝑄 𝑖𝑗 ∆𝐸∙ 𝑟 3 Saturated molecules, such as alkanes, typically have no low-lying excited states ( and hence possess a large DE), so that sp is small and alkane carbon resonances are found upfield *Note that paramagnetic shielding causes shifts to high frequency, whereas diamagnetic shielding causes shifts to low frequency On the other hand carbonyl carbons have a low-lying excited state involving the movement of electrons from the oxygen lone pair to the antibonding p orbital that generates a paramagnetic current. This n  p* transition causes the large shift to high frequency that characterizes carbonyl groups— up to 220 ppm CHEM 430 – NMR Spectroscopy 58

NMR - The Chemical Shift 3-4 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-4 Factors That Influence Carbon Shifts s𝑃 ∝ − 𝑄 𝑖𝑗 ∆𝐸∙ 𝑟 3 The radial term is responsible for effects related to electron density that parallel polar effects on proton chemical shifts. sP is larger when the p-electrons are closer to the nucleus. Thus, substituents that donate or withdraw electrons influence the paramagnetic shift. CHEM 430 – NMR Spectroscopy 59

NMR - The Chemical Shift 3-4 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-4 Factors That Influence Carbon Shifts s𝑃 ∝ − 𝑄 𝑖𝑗 ∆𝐸∙ 𝑟 3 e- donation increases repulsion between electrons, which can be relieved by an increase in r, sP decreases, causing a shift upfield e- withdrawal permits electrons to move closer to the nucleus, increasing sP, causing a shift downfield CHEM 430 – NMR Spectroscopy 60

NMR - The Chemical Shift 3-4 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-4 Factors That Influence Carbon Shifts SQij is related to charge densities and bond orders and can be considered a measure of multiple bonding. The greater the degree of multiple bond-ing, the greater the downfield shift This term provides a rationale for the series: CH3CH3 ( 6) < H2C=CH2 (123) < H2C=C=CH2 ( 214) Arene shifts are similar to those of alkenes (benzene, 129) - The effects of diamagnetic anisotropy on carbon chemical shifts are similar in magnitude to the effects on protons, but are small in relation to the range of carbon shifts. CHEM 430 – NMR Spectroscopy 61

NMR - The Chemical Shift 3-4 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-4 Factors That Influence Carbon Shifts Alkynes do not follow this pattern, but are at an intermediate position (72 for acetylene), because their linear structure has zero angular momentum about the axis. There are exceptions, the most prominent being the effect of heavy atoms. The series ( CH3Br (10), CH2Br2 (22), CHBr3 (12), and CBr4 (-29) defies any explanation based on electronegativity, unlike the analogous series given before for chlorine. This so-called heavy-atom effect has been attributed to a new source of angular momentum from spin–orbit coupling. CHEM 430 – NMR Spectroscopy 62

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5 Carbon Chemical Shifts and Structure You should know the most basic of shift tables: CHEM 430 – NMR Spectroscopy 63

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5 Carbon Chemical Shifts and Structure CHEM 430 – NMR Spectroscopy 64

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5 Carbon Chemical Shifts and Structure CHEM 430 – NMR Spectroscopy 65

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Saturated Aliphatics The observed resonance for an aliphatic 13C will shift depending on the number of C atoms a, b, g and d to it. For straight chain aliphatics, the base value for CH4 (d -2.5) is adjusted 9.1 for a, 9.4 for b, -2.5 for g and 0.3 for d carbons present. CHEM 430 – NMR Spectroscopy 66

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Saturated Aliphatics For this reason 13C shifts lend themselves readily to empirical analysis: Each Ai or substituent parameter is added to -2.5 ppm (shift for CH4) for a maximum set of five carbons: CHEM 430 – NMR Spectroscopy 67

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Saturated Aliphatics Some complications: Corrections must be applied if branching is present The 13C methyl is corrected for the presence of an adjacent 3o carbon by adding -1.1 and for an adjacent 4o carbon by adding -3.4. The 13C methylene has corrections of and -2.5 and -7.2, respectively, for adjacent 3o and 4o carbons. CHEM 430 – NMR Spectroscopy 68

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Saturated Aliphatics Some complications: Corrections must be applied if branching is present The 13C methine has respective corrections of -3.7, -9.5 and -1.5 for adjacent 2o, 3o, and 4o carbons. 4o carbons have corrections of -1.5 and -8.4 for adjacent 1o and 2o carbons. Corrections for adjacent tertiary and quaternary carbons undoubtedly are significant, but are not known accurately. CHEM 430 – NMR Spectroscopy 69

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Saturated Aliphatics In general –CH3 resonances appear at 5-20, -CH2- at and –CH- at 25-45 CHEM 430 – NMR Spectroscopy 70

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Cyclic Alkanes. For small cycloalkanes: -3.8 , cyclopropane has the most upfield resonance of hydrocarbons. Cyclobutane and cyclopentane are higher. Larger cycloalkanes generally resonate within 2 ppm of cyclohexane, at 27.7. The fixed stereochemistry of cyclohexane requires a set of empirical parameters that depend on the axial or equatorial nature of the substituents, as well as on the distance from the resonating carbon. CHEM 430 – NMR Spectroscopy 71

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Cyclic Alkanes. The following table lists parameters for methyl substitution are added to the value for cyclohexane ( 27.7). The substituent parameter for g -axial methyl is large and negative , reflecting the pure gauche stereochemistry between the perturbing and resonating carbons. A g -equatorial group represents g -anti effect and has little perturbation CHEM 430 – NMR Spectroscopy 72

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Cyclic Alkanes. Corrections again are needed for branching. Geminal methyls: a = -3.4, b = -1.2 Example: the calculated resonance for C2 of 1,1,3- trimethylcyclohexane : (8.9 * 2) = 49.5 ( observed 49.9) Other examples: CHEM 430 – NMR Spectroscopy 73

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Functionalized Alkanes. The replacement of a hydrogen atom on carbon with a heteroatom or an unsaturated group usually results in downfield shifts due to polar effects on the radial term. The effect parallels the same structural change on 1H chemical shifts but arises from a different mechanism. CHEM 430 – NMR Spectroscopy 74

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Functionalized Alkanes. Alkyl Halides. Strongly EWGs have large positive effects. In the halogen series: CH3F 75.4 CH3Cl CH3Br 10.2 CH3I Multiple substitution results in larger effects— 77.7 for CHCl3 Recall that the effect of heavy atoms such as iodine or bromine is influenced by a spin– orbit mechanism and hence may not follow the simple order of electronegativity. The general range for the halogen effect in hydrocarbons extends from the values given above for the simple systems to about a 25 ppm downfield shift for CH2X and CHX systems, since the a and b effects of the unspecified hydrocarbon pieces contribute to the downfield shift CHEM 430 – NMR Spectroscopy 75

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Functionalized Alkanes. Alcohols and Ethers: The range for HO- substituted carbons is 49–75. (MeOH at 49.2) The range for RO-substituted carbons is 59–80. (CH3OCH3 at 59.5) The ether range is translated a few ppm downfield from alcohols, because each ether must have one additional b-effect with respect to the analogous alcohol. CHEM 430 – NMR Spectroscopy 76

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Functionalized Alkanes. Amines: The lower EN of nitrogen moves the amine range somewhat upfield (CH3NH2 at 28.3), the range for amines extending some 30 ppm higher The amine range is larger than the alcohol range because nitrogen can carry up to three substituents, with more a and b effects possible Other EN groups: CH3SCH3 at 19.5, CH3CN at 1.8, and CH3NO2 at 62.6, with the respective ranges for thioalkoxy, cyano, and nitro substitution extending some 25 ppm downfield The anomalous low- frequency position for -CN substitution is related to the cylindrical shape of the group and its reduced angular momentum. CHEM 430 – NMR Spectroscopy 77

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Functionalized Alkanes. Attached C=C or C=O An attached double bond has only a small effect on a methyl group. For example, the position for the methyls of trans-2-butene is 17.3, and that for the methyl of toluene is 21.3. The range for carbons on double bonds is about 15– 40. Methyls on carbonyl groups are at a slightly downfield: 30.8 for acetone and 31.2 for acetaldehyde, with a range of about 30– 45. CHEM 430 – NMR Spectroscopy 78

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Functionalized Alkanes. Introducing heteroatoms or unsaturation into alkane chains requires completely new sets of empirical parameters that depend on the substituent, on its distance from the resonating carbon ( a, b, g), and on whether the substituent is terminal or internal: These parameters on the next slide represent the effect on a resonating carbon of replacing a hydrogen atom with X: CHEM 430 – NMR Spectroscopy 79

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Functionalized Alkanes. CHEM 430 – NMR Spectroscopy 80

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Functionalized Alkanes. With the exception of cyano-, acetyleno-, and the heavy atom iodine, the a-effects are determined largely by the ENof the substituent. The b-effects are all positive and generally of similar magnitude ( 6 to 11 ppm) and that the g-effects are all negative and generally of similar magnitude (-2 to -5 ppm). Although the details are not entirely understood, it is clear that simple polar considerations do not dominate the b- and g-effects. CHEM 430 – NMR Spectroscopy 81

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5a Functionalized Alkanes. Examples: To use the substituent parameters given in the table, one adds the appropriate values to the chemical shift of the 13C in the unsubstituted hydrocarbon analogue (already having the C-effects): In the first example 16 is the base value for the 1-carbon in propane and 27 is the base value for the carbons in cyclopentane CHEM 430 – NMR Spectroscopy 82

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5b Unsaturated Compounds. The effects of diamagnetic anisotropy on a carbon and a proton have similar magnitudes, but the much larger paramagnetic shielding renders the phenomenon relatively unimportant for carbon. Thus, benzene (128.4) and the alkenic carbon of cyclohexene (127.3) have almost identical carbon resonance positions, in contrast to the situation with their protons. The full range of alkene and aromatic resonances is about 100– 170. CHEM 430 – NMR Spectroscopy 83

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5b Unsaturated Compounds. Alkenes Alkenic carbons that bear no substituents resonate at 104– 115 for hydrocarbons (isobutylene [ (CH3)2C=CH2] at 107.7) Alkenic carbons that have one substituent resonate in the range 120– 140 (trans-2-butene at 123.3) Finally, disubstituted alkenic carbons resonate the most downfield at 140– 165 (isobutylene [ (CH3)2C=CH2] at 146.4) CHEM 430 – NMR Spectroscopy 84

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5b Unsaturated Compounds. Alkenes Polar substituents on double bonds, especially those in conjugation, can alter the resonance position appreciably; e- donation or w/d alters the radial term through resonance. Unsaturated ketones have more upfield a resonances and more downfield b resonances. The effect is reduced in acyclic molecules Electron donation in enol ethers reverses the trend: CH2=CHOCH3 (a = 153.2, b = 84.2) CHEM 430 – NMR Spectroscopy 85

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5b Unsaturated Compounds. Alkenes Alkene chemical shifts may be estimated from substituent parameters added to the shift for ethene ( 123.3). For a, b and g carbons on the same end of the double bond as the resonating carbon, respective increments of 10.6, 7.2, and -1.5 are added. For a, b and g carbons on the opposite end of the double bond from the resonating carbon, respective increments of -7.9, -1.8 and -1.5 are added. An increment of -1.1 is added if any two substituents are cis to each other. CHEM 430 – NMR Spectroscopy 86

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5b Unsaturated Compounds. Alkenes CHEM 430 – NMR Spectroscopy 87

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5b Unsaturated Compounds. Alkynes and Nitriles Terminal alkyne carbon generally resonates in the narrow range 67– 70. An alkyne carbon that carries a carbon substituent resonates at a slightly higher frequency ( 74– 85), because of a and b effects from the R group. Effects of conjugating, polar substituents expand the range to 20– 90. Nitriles resonate in the range 117– 130 (CH3C≡N at 116.9). The n p * transition pushes the range downfield. CHEM 430 – NMR Spectroscopy 88

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5b Unsaturated Compounds. Aromatics Alkyl substitution has its major effect on the ipso carbon. Because this carbon has no attached proton, its relaxation time is much longer than those of the other carbons, and its intensity is usually lower. Conjugating substituents like –NO2 have strong perturbations on the aromatic resonance positions, as the result of a combination of traditional a, b and g effects and changes in e- density through delocalization CHEM 430 – NMR Spectroscopy 89

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5b Unsaturated Compounds. Aromatics Heteroaromatics display a similar interplay of effects: Aromatic resonances may be calculated empirically by adding increments to the benzene chemical shift (128.4) for each substituent that is ipso, ortho, meta, or para to the resonating carbon as seen on the following table: CHEM 430 – NMR Spectroscopy 90

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5b Unsaturated Compounds. Aromatics CHEM 430 – NMR Spectroscopy 91

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5c Carbonyl Groups General Carbonyl groups have no direct representation in 1H NMR spectra, so 13C NMR provides unique information for their analysis. The entire carbonyl chemical shift range, 160– 220, is well removed to high frequency from that of almost all other functional groups, on account of the effect of the n  p* transition on the magnitude of the paramagnetic shift. Like aromatic ipso carbons and nitriles, carbonyl carbons other than those in aldehydes carry no attached protons and hence relax more slowly and tend to have low intensities. CHEM 430 – NMR Spectroscopy 94

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5c Carbonyl Groups Aldehydes and Ketones Aldehydes resonate toward the middle of the carbonyl range, at about 190– 205 (acetaldehyde at 199.6) Unsaturated aldehydes, in which the carbonyl group is conjugated with a double bond or phenyl ring, are shifted upfield (benzaldehyde at 192.4) The a, b and g effects of substituents on ketones add to the carbonyl chem-ical shift and hence are found on the downfield end of the carbonyl range from195– 220 (acetone at and cyclohexanone at 208.8) Again, adjacent unsaturation shifts the resonances to lower frequency. CHEM 430 – NMR Spectroscopy 95

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5c Carbonyl Groups Carboxylic Acid Derivatives Carboxylic derivatives fall into the range 155– 185. The resonances for the series carboxylate , carboxyl , and ester often are well defined: NaOAc (181.5), HOAc (177.3), and CH3OAc (170.7) The range for esters is about 165– 175, and that for acids is d 170– 185. Acid chlorides are at slightly upfield at 160– 170, (168.6 for AcCl) . Anhydrides have a similar range: 165– 175 (167.7 for Ac2O). CHEM 430 – NMR Spectroscopy 96

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5c Carbonyl Groups Carboxylic Acid Derivatives Lactones overlap the ester range, with the six- membered lactone at Amides have a similar range: 160– 175 (172.7 for AcNH2) . Oximes have a larger range, from 145– 165. CHEM 430 – NMR Spectroscopy 97

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5c Carbonyl Groups CHEM 430 – NMR Spectroscopy 98

NMR - The Chemical Shift 3-5 PROTON CHEMICAL SHIFTS AND STRUCTURE 3-5c Carbonyl Groups CHEM 430 – NMR Spectroscopy 99

NMR Spectroscopy CHEM 430.

Similar presentations

Presentation on theme: "NMR Spectroscopy CHEM 430."— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

NMR Spectroscopy CHEM 430.

Similar presentations

Presentation on theme: "NMR Spectroscopy CHEM 430."— Presentation transcript:

Similar presentations

About project

Feedback