CHM136H Spectroscopy: Determining Molecular Structures PDF

Infrared Spectroscopy (IR) and Nuclear Magnetic Resonance (NMR) Spectroscopy: Determining Molecular Structures Chapter 13 and 14 of Ogilvie “Organic Chemistry: Mechanistic Patterns” 2nd Edition CHM136HS University of Toronto...

Infrared Spectroscopy (IR) and Nuclear Magnetic Resonance (NMR) Spectroscopy: Determining Molecular Structures Chapter 13 and 14 of Ogilvie “Organic Chemistry: Mechanistic Patterns” 2nd Edition CHM136HS University of Toronto 1  How Do Chemists Know What The Structure Is? Organic compounds vary tremendously in their structure! Small structural changes can cause dramatic changes in their properties, including their physiological effects. OH OH OH H H HN H H N H H HN H2N HO O Dimethyltryptamine Serotonin Estradiol Testosterone (hallucinogen) (neurotransmitter) (female sex hormone) (male sex hormone) Structural elucidation (methods for solving molecular structures) is very important! CHM136HS University of Toronto 2  Chemistry Connections Spectroscopy for Food Safety The Canadian Food Inspection Agency (CFIA) uses spectroscopic techniques to investigate the safety and quality of food. Greater Toronto Area (GTA) laboratory uses infrared spectroscopy (a technique you will learn about!) to collect a “fingerprint” spectrum from food products. This fingerprint is unique to each product and any unusual patterns can indicate contamination or a false product. Fruit juice fraud: Infrared spectroscopy can even be used to indicate whether fruit juices are filled with cheap additives or substitutes. CHM136HS University of Toronto 3  Degree of Unsaturation If you know a molecule’s molecular formula, you can calculate the degree of unsaturation (DOU)! The degree of unsaturation is the number of π bonds and/or rings in a molecule. Molecules with π bonds and/or rings have fewer hydrogens per carbon than do saturated alkanes. Each double bond or ring in a molecule results in a loss of 2 H from the formula CnH2n+2. Examples of C6H10 (DOU = 2) CHM136HS University of Toronto 4  Degree of Unsaturation The degree of unsaturation is the number of π bonds and/or rings in a molecule: DOU = (2C + 2) – (# of H) + Group V – Group VII 2 Considerations with Group V, VI and VII atoms (in singly-bonded molecules): H H N H H H H O H Group V (N, P, etc.): Group VI (O, S, etc.): Add 1 hydrogen No change H Cl Group VII (F, Cl, Br, etc.): lose 1 hydrogen When given spectroscopic information and the formula of an unknown compound, work out the DOU first! CHM136HS University of Toronto 5  Degree of Unsaturation: Practice Calculate the degree of unsaturation for the following four compounds: CHM136HS University of Toronto 6  Chemistry Challenge: Research & Development Scientist You are working as a Research & Development (R&D) scientist at a large pharmaceutical company and your team wants to make a large batch of amphetamine as a starting material to synthesize a novel drug. Amphetamine (recognized as Adderall) is a medication that can be prescribed to treat attention deficit hyperactivity disorder (ADHD). However, your product is unexpectedly contaminated with an unknown impurity! NH2 How can you determine the + ? structure of this impurity? amphetamine unknown impurity We will come back to this problem! CHM136HS University of Toronto 7  Mass Spectrometry (MS) MS gives information about the mass of a compound and the fragments from which it is formed. A typical mass spectrometer: Molecules are ionized (made into charged species) and fragmented Ions are separated based on mass depending on their mass- to-charge ratio (m/z). CHM136HS University of Toronto 8  Mass Spectrometry (MS): A Typical Spectrum A mass spectrum shows the detected ion masses (m/z) and their relative abundance (%). The most important peak is the molecular ion peak (usually the heaviest ion in large abundance, M+) as it represents the molecular mass of the compound. CHM136HS University of Toronto 9  Chemistry Challenge: Mass Spectrometry The first thing you do is obtain a mass spectrum of your unknown impurity and you get a mass ion (m/z) of 135… the same as amphetamine! What does this result suggest? NH2 + ? amphetamine unknown impurity C9H13N m/z 135 m/z 135 CHM136HS University of Toronto 10  The Electromagnetic Spectrum Spectroscopy is the measurement of the interaction between a molecule and electromagnetic radiation 1 E = hν = hc    λ www.abc.net.au CHM136HS University of Toronto 11  Infrared Spectroscopy (IR): Bond Vibrations Infrared radiation causes excited stretching and bending vibrations (oscillations) of bonds that contain a dipole (no dipole = no vibration): symmetrical asymmetrical in-plane out-of-plane stretching stretching bending bending where K = force constant μ = reduced mass = c = 3 x 1010 cm/s Stronger bonds and lighter atoms vibrate at higher frequencies (higher energies) CHM136HS University of Toronto 12  An IR Spectrometer An infrared spectrometer consists of a high-quality infrared light source, a slit to create a parallel beam, a sample carrier, and a detector. CHM136HS University of Toronto 13  A Typical IR Spectrum Different bonds vibrate at different energies which give rise to unique absorption bands with characteristic intensity, shape and frequency: stated as wavenumber (cm-1): Remember: bonds that do not have a dipole do not give 4 main regions bands in the IR! hydrogen triple double N O H region bonds bonds N O H fingerprint region (less useful) Increasing energy and frequency CHM136HS University of Toronto 14  IR Spectroscopy: Correlation Table *this information will be provided in all assessments* Functional Group Wavenumber (cm-1) Functional Group Wavenumber (cm-1) O – H (alcohols) 3200 – 3600 (s, b) C–N 1180 – 1360 (w) O – H (acids) 2700 – 3200 (s, b) CΞN 2110 – 2260 (m) N–H 3300 – 3500 (w, b) C – H (sp3) 2800 – 3000 (s) C–O 1080 – 1300 (s) (sp2) 3000 – 3100 (s) C=O (carboxylic acid) 1710 – 1800 (s) (sp) 3300 – 3325 (s) (aldehyde) 1720 – 1740 (s) (ketone) 1708 – 1720 (s) C = C (alkene) 1640 – 1680 (m) (ester) 1735 – 1750 (s) C Ξ C (alkyne) 2100 – 2260 (w) (acid chloride) 1785 – 1815 (s) C=C (aromatic) 1500 – 1600 (m) (acid anhydride) 1740 – 1870 (s, 2 peaks) (amide) 1626 – 1786 (m) s = strong, m = medium, w = weak, b = broad CHM136HS University of Toronto 15  Chemistry Connections IR Spectroscopy and Global Warming Potential Chlorofluorocarbons (CFCs), used previously as refrigerants and aerosol propellants, were a threat to the ozone layer and also potent greenhouse gases, which warm the Earth by absorbing IR radiation emitted by Earth’s surface. Scientists can calculation a chemical’s global warming potential (GWP) by comparing its IR spectra to the Earth’s emission spectrum. Freon, one of the most common CFCs, had a GWP that was 10,000 times that of CO2, whereas HFO-1225, a current-use refrigerant, has a GWP below that of CO2. CHM136HS University of Toronto 16  Sample IR Spectra: Alkanes Alkanes primarily give C-H stretches (sp3) at 2800-3000 cm-1: sp3 C-H: 2800-3000 CHM136HS University of Toronto 17  Sample IR Spectra: Alkenes and Alkynes Alkenes: C-H stretches (sp2) at 3000-3100 cm-1 and C=C stretches at 1640-1680 cm-1 C=C: 1650 sp2 C-H: 3000-3100 Alkynes: C-H stretches (sp) at 3300-3325 cm-1 and CΞC stretches at 2100-2260 cm-1 CΞC: 2100 sp C-H: C=C: 1625-1450 3300 CHM136HS University of Toronto 18  Sample IR Spectra: Aromatic Rings Aromatics: C-H stretches (sp2) at 3090-3000 cm-1 C=C stretches at 1625-1450 cm-1 sp2 C-H: 3090-3000 C=C: 1625-1450 CHM136HS University of Toronto 19  Sample IR Spectra: OH and NH O-H bands (alcohols, carboxylic acids) and N-H bands Note: (amines, amides) are broad at 2700 - 3600 cm-1 O-H bands are broader and stronger than N-H bands NH = 1 band NH2 = 2 bands O-H: 3300 N-H: 3300 and 3400 CHM136HS University of Toronto 20  Sample IR Spectra: Carbonyls Carbonyl groups produce strong and sharp C=O bands between 1670 - 1780 cm-1 (unique to carbonyl type): C=O: 1715 C=O: 1735 CHM136HS University of Toronto 21  IR Practice Which characteristic IR peak(s) can be used to differentiate between the following pairs of compounds? CHM136HS University of Toronto 22  What Compound Is It? What compound does this spectrum represent? 1730 cm-1 CHM136HS University of Toronto 23  Chemistry Challenge: Infrared Spectroscopy Recall: You are an R&D scientist trying to identify an impurity while making amphetamine in the lab. You decide to collect an IR spectrum: NH2 + ? amphetamine unknown impurity *Based on the MS, both share the same mass (could be constitutional isomers?) Identify the functional groups that correspond to each of the labeled peaks. What does the IR tell us? CHM136HS University of Toronto 24  Nuclear Magnetic Resonance (NMR) Spectroscopy NMR spectroscopy has become one of the most powerful tools in organic chemistry for structural elucidation of compounds. 1950s: “…no single tool has had a more dramatic effect upon organic chemistry than infrared measurements … Nuclear magnetic resonance is even now on the horizon, and we shall be surprised if it does not permit another great step forward.” R. B. Woodward Nobel Prize 1965 CHM136HS University of Toronto 25  How Does Nuclear Magnetic Resonance (NMR) Work? Some atomic nuclei, like protons (1H), behave like spinning spheres. Since the nuclei (positively charged) have electrons (negatively charged) surrounding them, a small local magnetic field is created when they spin (magnetic moment): In the absence of an external When an external magnetic field (B0) is magnetic field, the magnetic applied, the magnetic moments align, with moments are randomly oriented. some opposed to and some parallel to B0. CHM136HS University of Toronto 26  How Does Nuclear Magnetic Resonance (NMR) Work? 3. As the nuclei relax back, they 1. The population of nuclei emit a signal that provides in the lower (more stable information about their unique state) is slightly greater chemical environment. 2. Electromagnetic radiation causes some nuclei to become excited from a lower to higher E state (spin-flip). The frequency at which this spin flip occurs is called the resonance frequency. CHM136HS University of Toronto 27  What Does an NMR Spectrometer Look Like? Small organic molecules: 300-700 MHz magnetic field strength Large biomolecules (proteins, DNA, RNA, oligosaccharides): 700+ MHz http://lucas.lakeheadu.ca/luil/nuclear-magnetic-resonance-nmr-facility/ CHM136HS University of Toronto 28  Chemistry Connections NMR vs. Magnetic Resonance Imaging (MRI) MRI is a non-invasive imaging technique used to study tissue anatomy and physiology and is used widely for medical diagnosis. MRI scanners use strong magnetic fields and radio wave pulses to excite the protons in the tissues (mainly in water), creating a 3D image based on slight variations in tissue density. Images: www.magnet.fsu.edu CHM136HS University of Toronto 29  Chemistry Connections Diversity in Organic Chemistry Mildren Cohn (1913-2009) was a trailblazer in the fields of biochemistry and biophysics. After graduate school, she applied for industrial positions but as a Jewish woman, she couldn’t get interviews for positions that were advertised for male, Christian applicants. Instead, she remained in academia. “My career has been affected at every stage by the fact that I am a woman, beginning with my undergraduate education”. Her work: Pioneered the use of NMR to investigate how enzymes and proteins behave during chemical reactions in the body. Source: Mildren Cohn (1913–2009) (American Chemical Society). https://www.acs.org/content/acs/en/education/whatischemistry/women-scientists/mildren-cohn.html. CHM136HS University of Toronto 30  Why is NMR such a Powerful Tool? Every chemically distinct 1H nucleus in an organic molecule has a unique electronic environment: each requires a slightly different radiofrequency to undergo resonance. This causes each unique 1H atom to produce a distinct peak in the NMR spectrum: 1H NMR spectrum: CH3 CH3 CH2 CH2 CHM136HS University of Toronto 31  What Information Does a 1H NMR Spectrum Provide? 1. Hydrogen Types The # of signals shows the ____________________________ 2. Integration The peak area for each hydrogen type gives _____________________________ associated with each hydrogen type 3. Chemical Shift The position on x axis of each signal gives the ___________________________ of each proton type. This includes hybridization of attached carbon, presence of adjacent functional groups, etc. Note: other information, such as coupling & multiplicity (signals splitting into multiple line clusters) is also very useful in providing structural information. However, this is reserved for 2nd year organic chemistry (CHM247H and CHM249H). CHM136HS University of Toronto 32  Number of Hydrogen Types Each signal (or resonance) in a spectrum is produced by a hydrogen or group of hydrogens in a different chemical environment. CHM136HS University of Toronto 33  Number of Hydrogen Types Chemically equivalent hydrogens have: identical environments (interchangeable by bond rotation or a plane of symmetry) identical chemical shifts (share the same signal) # hydrogen types = # signals CHM136HS University of Toronto 34  Number of Hydrogen Types: Aromatic Rings What are the chemical equivalent protons on each aromatic ring? What does each integrate to? Mono-substituted: 5H 3H Note: Peaks from aromatic protons commonly overlap with each other within 7-8 ppm as they can have very Di-substituted: similar chemical shifts! CHM136HS University of Toronto 35  Integration The area under each NMR signal is represented as a ratio and is proportional to the number of hydrogen atoms it represents: 3H 3H 2H 2H CHM136HS University of Toronto 36  Practice Determine the number of signals you would expect for the following compounds and predict the integration for each signal: CHM136HS University of Toronto 37  Practice Determine the number of signals you would expect for the following compounds and predict the integration for each signal: CHM136HS University of Toronto 38  Chemical Shift The chemical shift (δ) of a proton depends upon its chemical “environment” Chemical shifts are reported as a value in ppm (parts per million) relative to a standard compound (TMS: tetramethylsilane, (CH3)4Si). Since different NMR spectrometers are used with different magnetic field strengths (e.g., 400 MHz, 600 MHz), the chemical shift is normalized to give a value independent of the field strength: 1H chemical shift (δ) = νsample (Hz from TMS) = ppm νspectrometer (MHz) CHM136HS University of Toronto 39  Chemical Shift Chemical shift provides information about the chemical environment of an atom. Neighboring electrons influence the magnetic environment. Shielding: the electrons around a nucleus create a magnetic field opposing the applied field. This reduces the apparent field, thereby shielding it from the applied magnetic field. CHM136HS University of Toronto 40  Chemical Shift Nuclei are said to be shielded by electron magnetic fields as they oppose the applied magnetic field. Electron rich nuclei are considered shielded and have signals upfield (lower chemical shift). Electron-withdrawing groups decrease electron density and deshield nuclei which shift signals downfield (higher chemical shift). 41  Chemical Shift Influences: Electronegative Groups Electronegativity Effects Electronegative atoms “deshield” and shift protons towards the left: higher radiofrequency (more energy) needed for proton resonance: increasing electronegativity, less electron density around H CHM136HS University of Toronto 42  Chemical Shift Influences: Electronegative Groups Electronegativity Effects The effect is roughly additive and depends on proximity (inductive effect diminishes with distance): CHM136HS University of Toronto 43  Chemical Shift: Magnetic Anisotropy Magnetic Anisotropy Effects Pi-electrons generate a local diamagnetic current that opposes the applied magnetic field (B0). This causes a shielding cone where nuclei inside the cone are shielded (smaller ppm) and nuclei outside the cone are deshielded (larger ppm): CHM136HS University of Toronto 44  Chemical Shift Influences: Attached π-Systems Magnetic anisotropy causes hydrogen atoms attached to π-systems to have a dramatic deshielding effect compared to alkane H’s: CHM136HS University of Toronto 45  Chemical Shift Influences: Adjacent π-Systems Adjacent π-systems also have a small deshielding effect: Compare to: CHM136HS University of Toronto 46  Chemical Shift Influences: H-Bonding Hydrogen atoms on heteroatoms (O-H and N-H) are usually broad signals that have variable chemical shifts due to H-bonding: CH3CH2OH CHM136HS University of Toronto 47  Chemical Shift: Regions to Consider CHM136HS University of Toronto 48  1H NMR Spectroscopy: Correlation Table *this information will be provided in all assessments* 1 H NMR Chemical Shifts Type of Proton Chemical Shift (ppm) RC–H alkane 0.9 – 1.7 C=C–C–H allylic 1.7 – 3.0 O=C–C–H α-proton 1.8 – 2.2 Ar–C–H benzylic 2.2 – 2.5 C≡C–C–H propargylic 1.7 – 2.8 C≡C–H alkynyl 2.0 – 3.0 X–C–H X = O, N, halide 2.5 – 4.8 C=C–H vinylic 4.0 – 7.0 Ar–H aromatic 6.5 – 8.5 RCHO aldehyde 9.0 – 10.0 O–H, N–H alcohol, amine 1 – 5 (broad) phenol, aniline 8-10 (broad) COOH carboxylic acid 10 – 13 (broad) CHM136HS University of Toronto 49  The problems on the following slides should be done after class once you are comfortable with the material. Print off the IR and NMR correlation tables to use while working through the problems. Answers will be posted on Quercus. CHM136HS University of Toronto 50  NMR Practice Based on predicted chemical shifts, assign each peak in the 1H NMR spectrum to the protons in the compound, and indicate the appropriate integration: 5 4 3 2 1 0 PPM CHM136HS University of Toronto 51  NMR Practice 1. Based on predicted chemical shifts, assign each peak in the 1H NMR spectrum to the protons in the compound, and indicate the appropriate integration. 2. What absorption bands would you expect to see in the IR spectrum for this compound? CHM136HS University of Toronto 52  Spectroscopy Practice You are working in a research laboratory for the summer and you find a bottle of colourless liquid that has a damaged label and all you can see is “C9H10O”. You obtain the following IR and 1H NMR data. Suggest a structure for this mystery compound. IR data: 1682 cm-1 (strong, sharp) 1H NMR 3H Degree of unsaturation: _______ 3H 2H 2H CHM136HS University of Toronto 53  Spectroscopy Practice Note: Peaks from aromatic protons Identify the structure: C8H10O commonly overlap with each other as IR data: 3300 cm-1 (strong, broad) they can have very similar chemical Degree of unsaturation: _______ shifts: R H H 1H NMR 5H All aromatic H’s look like 1 signal integrating to 5H H H H 2H 1H 2H CHM136HS University of Toronto 54  Spectroscopy Practice Consider the molecule 4-nitro-3-(trifluoromethyl)aniline shown below: a very important compound in the synthesis of Flutamide, a drug used to treat prostate cancer. Flutamide (Proscar, Eulexin) Determine the number of 1H NMR signals you would expect for Flutamide and predict the integration for each signal. What major bands in the IR spectrum would you expect? CHM136HS University of Toronto 55  Spectroscopy Practice Always having wondered why Identify the structure: C6H12O2 eating an apple a day apparently IR data: 1750 cm-1 (strong, sharp) keeps the doctor away, you attempt to isolate this miracle Degree of unsaturation: _______ drug found in apples. Disappointingly, you instead only isolate the compound responsible 3H for their delicious smell. Given the following chemical 2H 3H formula, as well as IR/NMR data, 2H 2H propose a structure. CHM136HS University of Toronto 56  Spectroscopy Practice Salicylic acid can be used to make acetylsalicylic acid, also known as the drug Aspirin, that you will be purifying and analyzing in the CHM136H lab! Salicylic acid can also be used to make methyl salicylate through a Fischer esterification (which you’ll also be doing in another CHM136H lab)! Despite their similarities, describe how you could distinguish acetylsalicylic acid from methyl salicylate using IR and NMR spectroscopy. CHM136HS University of Toronto 57  Chemistry Challenge: 1H-NMR spectroscopy Recall: You are an R&D scientist trying to identify an impurity while making amphetamine in the lab. You decide to try collecting a 1H-NMR spectrum of your unknown impurity. a b c 5H 2H 2H NH2 + ? d 2H e amphetamine unknown impurity 2H *Based on the MS and IR, they are very likely constitutional isomers What does the NMR spectrum tell us? What is the structure of the impurity? Assign each signal (a-e) to the proton(s) to your proposed structure. CHM136HS University of Toronto 58  Chemistry Challenge: 1H-NMR spectroscopy CHM136HS University of Toronto 59