NMR 1 & 2 PDF

Introduction More important than infrared spectroscopy. Most powerful tool for organic structure determination. Used to determine relative location of atoms within a molec...

Introduction More important than infrared spectroscopy. Most powerful tool for organic structure determination. Used to determine relative location of atoms within a molecule. It 13 is 15 used 19 31 to study a wide variety of nuclei: 1H, C, N, F, P Depends on very strong magnetic field. 2 The NMR Spectrometer NUCLEAR SPIN STATES Many atomic nuclei have a property called “SPIN” and all nuclei are electrically charged. These nuclei behave as if they were spinning. ….. we don’t know if they actually do spin! This is like the spin property of an electron, which can have two spins: +1/2 and -1/2. Each spin-active nucleus has a number of spins defined by its spin quantum number, I.  Spin Quantum Numbers of Some Common Nuclei The principle behind NMR is The most abundant isotopes of C and O do not have spin. that many nuclei have spin The principle of NMR and all nuclei are electrically charged. Element 1H 2H 12C 13C 14N 16O 17O 19F If an external magnetic field is applied, an energy transfer is possible between the base Nuclear Spin energy to a higher energy level (generally a single Quantum No 1/2 1 0 1/2 1 0 5/2 1/2 energy gap). (I) The energy transfer takes No. of Spin 2 3 0 2 3 0 6 2 place at a wavelength that States corresponds to radio frequencies and when the spin returns to its base level, energy is emitted at the same Elements with either odd mass or odd atomic number frequency. have the property of nuclear “spin”. The signal that matches this transfer is measured in many ways and processed in order The number of spin states is 2I + 1, to yield an NMR spectrum for where I is the spin quantum number. the nucleus concerned. Nuclear Spin External Magnetic Field The spinning charged nucleus generates a When placed in an external field, spinning magnetic field. protons act like bar magnets. 7 8  Protons in a Molecule Two Energy States Depending on their chemical environment, protons in a molecule are shielded by different amounts. The magnetic fields of the spinning nuclei will align either with the external field, or against the field. A photon with the right amount of energy can be absorbed and cause the spinning proton to flip. 9 The NMR Spectrum NMR Signals The number of signals shows how many different kinds of protons are present. The location of the signals shows how shielded or deshielded the proton is. The intensity of the signal shows the number of protons of that type. Signal splitting shows the number of protons on adjacent atoms. => 11 12  Tetramethylsilane Chemical Shift TMS is added to the sample. Measured in parts per million. Since silicon is less electronegative than carbon, TMS protons are highly shielded. Signal defined Ratio of shift downfield from TMS (Hz) to as zero. total spectrometer frequency (Hz). Organic protons absorb downfield (to the left) of Same value for 60, 100, or 300 MHz machine. the TMS signal. Called the delta scale. CH3 H3C Si CH3 CH3 13 14 Delta Scale Location of Signals More electronegative atoms deshield more and give larger shift values. Effect decreases with distance. Additional electronegative atoms cause increase in chemical shift. 16 15 =>  Typical Values NMR Correlation Chart -OH -NH DOWNFIELD UPFIELD DESHIELDED SHIELDED CHCl3 , H TMS 12 11 10 9 8 7 6 5 4 3 2 1 0 d (ppm) H CH2F CH2Ar C-CH-C RCOOH RCHO C=C CH2Cl CH2NR2 CH2S C CH2Br CH2I C C-H C-CH2-C CH2O C=C-CH2 C-CH3 CH2NO2 CH2-C- O Ranges can be defined for different general types of protons. 17 => This chart is general, the next slide is more definite. 18 Number of Signals YOU DO NOT NEED TO MEMORIZE THE PREVIOUS CHART Equivalent hydrogens have the same chemical shift. IT IS USUALLY SUFFICIENT TO KNOW WHAT TYPES OF HYDROGENS COME IN SELECTED AREAS OF THE NMR CHART C-H where C is CH on C acid aldehyde benzene alkene attached to an next to aliphatic COOH CHO CH =C-H electronega- pi bonds C-H tive atom X=C-C-H X-C-H 12 10 9 7 6 4 3 2 0 MOST SPECTRA CAN BE INTERPRETED WITH A KNOWLEDGE OF WHAT IS SHOWN HERE => 19 20  Intensity of Signals How Many Hydrogens? The area under each peak is proportional When the molecular formula is known, each integral rise can be to the number of protons. assigned to a particular number of hydrogens. Shown by integral trace. Benzyl Acetate The integral line rises an amount proportional to the number of H in each peak Actually : 5 2 3 58.117 / 11.3 21.215 / 11.3 33.929 / 11.3 = 5.14 = 1.90 = 3.00 O METHOD 1 CH2 O C CH3 integral line METHOD 2 digital assume CH3 integral 33.929 / 3 = 11.3 line integration Integrals are good to about 10% accuracy. simplest ratio 55 : 22 : 33 = 5:2:3 of the heights Modern instruments report the integral as a number.  SPIN-SPIN SPLITTING Often a group of hydrogens will appear as a multiplet rather than as a single peak. Multiplets are named as follows: SPIN-SPIN SPLITTING Singlet Quintet Doublet Sextet Triplet Septet Quartet Octet This happens because of interaction with neighboring hydrogens and is called SPIN-SPIN SPLITTING. 1,1,2-Trichloroethane The two kinds of hydrogens do not appear as single peaks, rather there is a “triplet” and a “doublet”. integral = 2 Cl H integral = 1 H C C Cl Cl H n + 1 RULE doublet The subpeaks are due to triplet spin-spin splitting and are predicted by the n+1 rule. 1,1,2-Trichloroethane this hydrogen’s peak these hydrogens are MULTIPLETS is split by its two neighbors split by their single neighbor integral = 2 singlet doublet Cl H H H H H triplet H C C Cl C C C C quartet integral = 1 Cl H H H quintet sextet two neighbors n+1 = 3 one neighbor septet triplet n+1 = 2 doublet Where do these multiplets come from ? ….. interaction with neighbors SOME COMMON SPLITTING PATTERNS X CH CH Y CH3 CH (x=y) CH2 CH CH3 CH2 SOME COMMON PATTERNS CH3 X CH2 CH2 Y CH (x=y) CH3 NMR Spectrum of Bromoethane Br CH2CH3 OVERVIEW TYPES OF INFORMATION FROM THE SPECTROSCOPY IS A POWERFUL TOOL NMR SPECTRUM Generally, with only three pieces of data 1. Each different type of hydrogen gives a peak or group of peaks (multiplet). 1) empirical formula (or % composition) 2. The chemical shift (d, in ppm) gives a clue as to the type of hydrogen generating the peak (alkane, alkene, 2) infrared spectrum benzene, aldehyde, etc.) 3) NMR spectrum 3. The integral gives the relative numbers of each type of hydrogen. a chemist can often figure out the complete structure of 4. Spin-spin splitting gives the number of hydrogens an unknown molecule. on adjacent carbons. EACH TECHNIQUE YIELDS VALUABLE DATA MICRO ELEMENTAL ANALYSIS Gives the relative numbers of C and H and other atoms THANK YOU INFRARED SPECTRUM Organic Chemistry, 5th Edition, L.G. Wade, Jr. Reveals the types of bonds that are present. NMR SPECTRUM Reveals the enviroment of each hydrogen and the relative numbers of each type. SALIENT FACTS ABOUT 13C NMR 12C is not NMR-active I= 0 NMR II however…. 13C does have spin, I = 1/2 (odd mass) 13C signals are 6000 times weaker than 1H because: CARBON-13 NMR 1. Natural abundance of 13C is small (1.08% of all C) 2. Magnetic moment of 13C is small PULSED FT-NMR IS REQUIRED The chemical shift range is larger than for protons 0 - 200 ppm  SALIENT FACTS ABOUT 13C NMR SALIENT FACTS ABOUT 13C NMR (cont) Because of its low natural abundance (0.0108) there For a given field strength 13C has its resonance at a is a low probability of finding two 13C atoms next to different (lower) frequency than 1H. each other in a single molecule. Divide the hydrogen 13C not probable - 13C coupling NO! 1H frequency by 4 (approximately) for carbon-13 Spectra are determined by many molecules contributing 1.41 T 60 MHz to the spectrum, each having only one 13C atom. 2.35 T 100 MHz 7.05 T 300 MHz 13C However, 13C does couple to hydrogen atoms (I = 1/2) 1.41 T 15.1 MHz 13C very common 2.35 T 25.0 MHz - 1H coupling YES! 7.05 T 75.0 MHz COUPLING TO ATTACHED PROTONS 3 protons 2 protons 1 proton 0 protons H H 13 13 13 13 C H C H C H C H n+1 = 4 n+1 = 3 n+1 = 2 n+1 = 1 COUPLING TO ATTACHED PROTONS Methyl Methylene Methine Quaternary carbon carbon carbon carbon The effect of attached protons on 13C resonances ( n+1 rule applies ) (J’s are large ~ 100 - 200 Hz)  ETHYL PHENYLACETATE 13C coupled to the hydrogens DECOUPLED SPECTRA DECOUPLING THE PROTON SPINS PROTON-DECOUPLED SPECTRA In this method the hydrogen nuclei are “saturated”, a situation where there are as many downward as A common method used in determining a carbon-13 there are upward transitions, all occuring rapidly. NMR spectrum is to irradiate all of the hydrogen nuclei in the molecule at the same time the carbon During the time the carbon-13 spectrum is being resonances are being measured. determined, the hydrogen nuclei cycle rapidly between This requires a second radiofrequency (RF) source their two spin states (+1/2 and -1/2) and the carbon nuclei (the decoupler) tuned to the frequency of the hydrogen see an average coupling (i.e., zero) to the hydrogens. nuclei, while the primary RF source is tuned to the 13C frequency. The hydrogens are said to be decoupled from the RF source 1 carbon-13 nuclei. RF source 2 1H-13C “the decoupler” pulse tuned to carbon-13 You no longer see multiplets for the 13C resonances. continuously saturates Each carbon gives a singlet, and the spectrum is hydrogens easier to interpret. 13C signal (FID) measured  ETHYL PHENYLACETATE SOME INSTRUMENTS SHOW THE MULTIPLICITIES in some cases the peaks of the OF THE PEAKS ON THE DECOUPLED SPECTRA multiplets will overlap s = singlet t = triplet 13C coupled CODE : d = doublet q = quartet to the hydrogens d d q this is an s s t 13C easier spectrum t decoupled to interpret from the hydrogens d This method gives the best of both worlds. APPROXIMATE 13C CHEMICAL SHIFT RANGES FOR SELECTED TYPES OF CARBON (ppm) R-CH3 8 - 30 C C 65 - 90 R2CH2 15 - 55 C=C 100 - 150 R3CH 20 - 60 C N 110 - 140 CHEMICAL SHIFTS 110 - 175 OF 13C ATOMS C-I 0 - 40 C-Br 25 - 65 O O C-Cl 35 - 80 R-C-OR R-C-OH 155 - 185 O C-N 30 - 65 R-C-NH2 155 - 185 O O C-O 40 - 80 R-C-H R-C-R 185 - 220  200 150 100 50 0 RANGE R-CH3 8 - 30 Saturated carbon - sp3 R-CH2-R 15 - 55 nitriles no electronegativity effects 20 - 60 acid anhydrides R3CH / R4C acid chlorides C-O 40 - 80 Saturated carbon - sp3 amides electronegativity effects C-Cl 35 - 80 esters C-Br 25 - 65 carboxylic acids C C Alkyne 65 - 90 aldehydes Unsaturated carbons - sp carbon - sp2 C=C 100 - 150 a,b-unsaturated ketones Aromatic ring 110 - 175 ketones carbons Acids Amides 155 - 185 220 200 180 160 140 120 100 ppm C=O Esters Anhydrides C=O Aldehydes 185 - 220 Ketones 13C Correlation Chart for Carbonyl and Nitrile Functional Groups 200 150 100 50 0 Correlation chart for 13C Chemical Shifts (ppm) 1-PROPANOL HO-CH2-CH2-CH3 c b a PROTON DECOUPLED SPECTRA 200 150 100 50 0 Proton-decoupled 13C spectrum of 1-propanol (22.5 MHz) 2,2-DIMETHYLBUTANE BROMOCYCLOHEXANE CYCLOHEXANOL TOLUENE  CYCLOHEXENE CYCLOHEXANONE 1,2-DICHLOROBENZENE 1,3-DICHLOROBENZENE solvent Cl b d b c Cl a a a Cl c Cl c d b a  Mass spectrometer an apparatus for measuring the masses of isotopes, molecules, and molecular fragments by ionizing them and determining their trajectories in electric and magnetic fields. MASS SPECTROMETRY It measures mass better than any other technique. It can give information about chemical structures. Acquiring a mass spectrum How does a it work? Ionization Mass Sorting (filtering) Detection Sample Ion Ion Source Mass Analyzer Detector Form ions Sort Ions by Mass (m/z) Detect ions (charged molecules) Mass Ion source: analyzer: Mass spectrum: makes ions separates presents 100 ions information 75 Inlet Solid 50 Liquid 25 Vapor 0 1330 1340 1350 Mass Spectrum To identify, verify, and measure: Applications Pharmaceutical analysis Metabolites Bioavailability studies recombinant proteins Drug metabolism studies, pharmacokinetics proteins isolated from natural sources Characterization of potential drugs oligonucleotides Drug degradation product analysis Screening of drug candidates drug candidates Identifying drug targets peptides Biomolecule characterization Proteins and peptides synthetic organic chemicals Oligonucleotides Polymers Environmental analysis Pesticides on foods etc. Soil and groundwater contamination Forensic analysis/clinical THANK YOU Organic Chemistry, 5th Edition, L.G. Wade, Jr.