Nuclear Magnetic Resonance Spectroscopy Organic Chemistry Second Edition David Klein Chapter 16 Nuclear Magnetic Resonance Spectroscopy Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.1 Intro to NMR Spectroscopy What is spectroscopy? Nuclear Magnetic Resonance (NMR) spectroscopy may be the most powerful method of gaining structural information about organic compounds NMR involves an interaction between electromagnetic radiation (light) and the nucleus of an atom We will focus on C and H nuclei. WHY? The structure (connectivity) of a molecule affects how the radiation interacts with each nucleus in the molecule Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.1 Intro to NMR Spectroscopy Protons and neutrons in a nucleus behave as if they are spinning If the total number of neutrons and protons is an ODD number, the atoms will have net nuclear spin Examples: The spinning charge in the nucleus creates a magnetic moment Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.1 Intro to NMR Spectroscopy Like a bar magnet, a magnetic moment exists perpendicular to the axis of nuclear spin Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.1 Intro to NMR Spectroscopy If the normally disordered magnetic moments of atoms are exposed to an external magnetic field, their magnetic moments will align WHAT if the total number of neutrons and protons is an EVEN number? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.1 Intro to NMR Spectroscopy The aligned magnetic moments can be either with or against the external magnetic field The α and β spin states are not equal in energy. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.1 Intro to NMR Spectroscopy When an atom with an α spin state is exposed to radio waves of just the right energy, it can be promoted to a β spin state The stronger the magnetic field, the greater the energy gap Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.2 Acquiring a 1H NMR Spectrum NMR requires a strong magnetic field and radio wave energy The strength of the magnetic field affects the energy gap Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.2 Acquiring a 1H NMR Spectrum Solvents are used such as chloroform-d. WHY? The magnet is super-cooled, but the sample is generally at room temp Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.3 Characteristics of a 1H NMR Spectrum NMR spectra contain a lot of structural information Number of signals Signal location – shift Signal area – integration Signal shape – splitting pattern Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.4 Number of Signals Protons with different electronic environments will give different signals Protons that are homotopic will have perfectly overlapping signals Protons are homotopic if the molecule has an axis of rotational symmetry that allows one proton to be rotated onto the other without changing the molecule Find the rotational axis of symmetry in each molecule below Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.4 Number of Signals Another test for homotopic protons is to replace the protons one at a time with another atom If the resulting compounds are identical, then the protons that you replaced are homotopic Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.4 Number of Signals Protons that are enantiotopic will also have perfectly overlapping signals Protons are enantiotopic if the molecule has a plane of symmetry that makes one proton the mirror image of the other Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.4 Number of Signals The replacement test is universal These equivalents protons are enantiotopic If the resulting compounds are enantiomers, then the protons that you replaced are enantiotopic Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.4 Number of Signals If the protons are neither homotopic nor enantiotopic, then the are NOT chemically equivalent Perform the replacement test on the protons shown in the molecule below Practice with SkillBuilder 16.1 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.4 Number of Signals If the protons are neither homotopic nor enantiotopic, then the are NOT chemically equivalent Perform the replacement test on the protons shown in the molecule below Diastereotopic Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.4 Number of Signals There are some shortcuts you can take to identify how many signals you should see in the 1H NMR The 2 protons on a CH2 group will be equivalent if there are NO chirality centers in the molecule: Homotopic Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.4 Number of Signals There are some shortcuts you can take to identify how many signals you should see in the 1H NMR The 2 protons on a CH2 group will NOT be equivalent if there is a chirality center in the molecule: Diastereotopic Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.4 Number of Signals There are some shortcuts you can take to identify how many signals you should see in the 1H NMR The 3 protons on any methyl group will always be equivalent to each other Multiple protons are equivalent if they can be interchanged through either a rotation or mirror plane Practice with SkillBuilder 16.2 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.4 Number of Signals Identify all the groups of equivalent protons in the molecules below and describe their relationships Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.5 Chemical Shifts Tetramethylsilane (TMS) is used as the standard for NMR chemical shift In many NMR solvents, 1% TMS is added as an internal standard The shift for a proton signal is calculated as a comparison to TMS Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.5 Chemical Shifts Early NMRs analyzed samples at a constant energy over a range of magnetic field strengths from low field strength = downfield to high field strength = upfield Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.5 Chemical Shifts Current NMRs analyze samples at a constant field strength over a range of energies Shielded protons have a smaller magnetic force acting on them, so they have smaller energy gaps and absorb lower energy radio waves Higher Energy Lower Energy Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.5 Chemical Shifts Alkane protons generally give signals around 1-2 ppm Protons can be shifted downfield when nearby electronegative atoms cause deshielding. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.5 Chemical Shifts To predict chemical shifts, start with the standard ppm for the type of proton (methyl, methylene, or methine) Use table 16.1 to adjust the ppm depending on proximity to certain function groups Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.5 Chemical Shifts Klein, Organic Chemistry 2e Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.5 Chemical Shifts Predict chemical shifts for all of the protons in the molecule below Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.5 Chemical Shifts When the electrons in a pi system are subjected to an external magnetic field, they circulate a great deal causing diamagnetic anisotropy Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.5 Chemical Shifts The result of the diamagnetic anisotropy effect is similar to deshielding for aromatic protons. What about the other protons? Why does it appear that only one signal is given for all of the aromatic protons? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.5 Chemical Shifts Explain all of the shifts in table 16.2 Practice conceptual checkpoints 16.10 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.6 Integration The integration or area under the peak quantifies the relative number of protons giving rise to a signal A computer will calculate the area of each peak representing that area with a step-curve The curve height represents the integration Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.6 Integration Integrations represent numbers of protons, so you must adjust the values to whole numbers If the integration of the first peak is doubled, the computer will adjust the others according to the ratio 2.96 3.12 2.00 2.10 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.6 Integration The integrations are relative quantities rather than an absolute count of the number of protons Predict the 1H shifts and integrations for tert-butyl methyl ether Symmetry can also affect integrations Predict the 1H shifts and integrations for 3-pentanone Practice with SkillBuilder 16.4 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.7 Multiplicity When a signal is observed in the 1H NMR, often it is split into multiple peaks Multiplicity or a splitting patterns results Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.7 Multiplicity Multiplicity results from magnetic affects that protons have on each other Consider protons Ha and Hb We already saw that protons align with or against the external magnetic field Hb will be aligned with the magnetic field in some molecules. Other molecules in the sample will have Hb aligned against the magnetic field Some Hb atoms have a slight shielding affect on Ha and others have a slight deshielding affect Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.7 Multiplicity The resulting multiplicity or splitting pattern for Ha is a doublet A doublet generally results when a proton is split by only one other proton on an adjacent carbon Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.7 Multiplicity Consider an example where there are two protons on the adjacent carbon There are three possible affects the Hb protons have on Ha Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.2 Acquiring a 1H NMR Spectrum NMR requires a strong magnetic field and radio wave energy The strength of the magnetic field affects the energy gap Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.7 Multiplicity Ha appears as a triplet WHY? The three peaks in the triplet have an integration ratio of 1:2:1 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.7 Multiplicity Consider a scenario where Ha has three equivalent Hb atoms splitting it Explain how the magnetic fields cause shielding or deshielding Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.7 Multiplicity Ha appears as a quartet What should the integration ratios be for the 4 peaks of the quartet? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.7 Multiplicity Table 16.3 shows how the multiplicity trend continues By analyzing the splitting pattern of a signal in the 1H NMR, you can determine the number of equivalent protons on adjacent carbons Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.7 Multiplicity Remember three key rules Equivalent protons can not split one another Predict the splitting patterns observed for 1,2-dichloroethane To split each other, protons must be within a 2 or 3 bond distance Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.7 Multiplicity Remember three key rules To split each other, protons must be within a 2 or 3 bond distance Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.7 Multiplicity The degree to which a neighboring proton will shield or deshield its neighbor is called a coupling constant The coupling constant or J value is the distance between peaks of a splitting pattern measured in units of Hz When protons split each other, their coupling constants will be equal Jab = Jba Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.7 Multiplicity A peak with an integration equal to 9 suggests the presence of a tert-butyl group An isolated isopropyl group gives a doublet and a septet Note the integrations Practice with conceptual checkpoint 16.17 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.7 Multiplicity Splitting is not observed for some protons. Consider ethanol The protons bonded to carbon split each other, but the hydroxyl proton is not split Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.7 Multiplicity of OH The hydroxyl proton and other labile or exchangeable protons undergo rapid exchange with trace amounts of acid. Such exchange blurs the shielding/deshielding affect of the neighboring protons giving a singlet that is often broadened Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.9 Using 1H Spectra to Distinguish Between Compounds The three molecules below might be difficult to distinguish by IR of MS. 1H NMR could distinguish between them Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.9 Using 1H Spectra to Distinguish Between Compounds Explain how 1H NMR could be used to distinguish between the two molecules below Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.10 Analyzing a 1H NMR Spectrum With a given formula and 1H NMR spectrum, you can determine a molecule’s structure by a 4-step process Calculate the degree or unsaturation or hydrogen deficiency index (HDI). What does the HDI tell you? Consider the number of NMR signals and integration to look for symmetry in the molecule Analyze each signal, and draw molecular fragments that match the shift, integration, and multiplicity Assemble the fragments into a complete structure like puzzle pieces Practice with SkillBuilder 16.8 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.11 Acquiring a 13C NMR Spectrum Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.11 Acquiring a 13C NMR Spectrum In 13C NMR, the 1H-13C splitting is often so complex that the spectrum is unreadable To elucidate the 13C spectrum and make it easier to determine the total number of 13C signals, 13C NMR are generally decoupled In the vast majority of 13C spectra, all of the signals are singlets Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.12 Chemical Shifts in 13C NMR Spectra Compared to 1H, 13C atoms require a different frequency of energy to excite (resonate) Compared to the standard TMS, 13C NMR signals generally appear between 220 and 0 ppm Each signal on the 13C spectra represents a carbon with a unique electronic environment Planes and axes of symmetry can cause carbon signals to overlap if their electronic surroundings are equivalent Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.12 Chemical Shifts in 13C NMR Spectra Note how symmetry affect the number of signals for the molecules above How many 13C signals should be observed for the molecule below Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.12 Chemical Shifts in 13C NMR Spectra Like 1H signals, chemical shifts for 13C signals are affected by shielding or deshielding Practice with SkillBuilder 16.9 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.12 Chemical Shifts in 13C NMR Spectra Predict the number of signals and chemical shifts in the 13C NMR spectrum for the molecule below Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.13 DEPT 13C NMR Spectra Distortionless Enhancement by Polarization Transfer (DEPT) 13C NMR provides information the number of hydrogen atoms attached to each carbon Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.13 DEPT 13C NMR Spectra Full decoupled 13C spectrum: shows all carbon peaks DEPT-90: Only CH signals appear DEPT-135: CH3 and CH = (+) signals, CH2 = (-) signals Practice with SkillBuilder 16.10 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

16.13 DEPT 13C NMR Spectra Explain how DEPT 13C spectra could be used to distinguish between the two molecules below Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Additional Practice Problems Predict the number of signals and chemical shifts in the 13C NMR spectrum and DEPT spectrum for the molecule below Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e