Organic Spectroscopy - NDSUcook.chem.ndsu.nodak.edu/wordpress/wp-content/uploads/2015/08/01... · Organic Spectroscopy ... ‣ Structure elucidation by modern NMR: A workbook,

©2015 Gregory R. Cook, NDSU

Organic Spectroscopy

Chem 744 / 754Fall 2015

Gregory R. Cook

Tuesday, August 25, 15

©2015 Gregory R. Cook, NDSU 2

Web Page

‣ cook.chem.ndsu.nodak.edu



Resources

‣ Books on reserve in the Library

‣ Introduction to Spectroscopy 3rd Ed., Pavia, Lampman, Kriz; Saunders Publishing, 2001.

‣ Spectrometric Identification of Organic Compounds 5th Ed., Silverstein, Bassler, Morrill; Wiley, 1991.

‣ Basic one- and two-dimensional NMR Spectroscopy, Horst, Weinheim, 2005.

‣ NMR - from spectra to structures: an experimental approach, Mitchell and Costisella, Springer, 2004.

‣ Structure elucidation by modern NMR: A workbook, Duddeck, Dietrich, Toth, Springer, 1998.

‣ Other References and Texts

‣ Organic Structure Analysis, Crews, Rodríguez, Jaspars; Oxford Press, 1998

‣ Spectrometric Identification of Organic Compounds 6th Ed., Silverstein, Bassler, Morrill; Wiley, 1998.

‣ ABCs of FT-NMR, Roberts, University Science Books, 2000.



744 Course Information

‣ Introduction

‣ This course is designed to provide a theoretical and practical working knowledge of modern spectroscopic techniques as applied to the elucidation of the structure of organic compounds.

‣ Mass spectroscopy, infrared spectroscopy, and NMR spectroscopy will be covered. If time permits, we will discuss Raman and UV spectroscopy.

‣ You are expected to have a solid understanding of physical organic chemistry and organic structure.




‣ Introduction

‣ Grading

‣ Midterm exam (Sep 17) (25%)Final exam (TBA) (50%)Homework (25%)

‣ Grades will be assigned as follows (subject to change): A - 85-100%B - 70-84%C - 57-69%D - 45-56%F - <45%




‣ Introduction

‣ The lab course is designed to train users on the various instruments for spectroscopic determination of organic compounds and to interpret data.

‣ Users will run known and unknown samples on the GC-Mass Spec, Infrared spectrometer, and NMR instruments.




‣ Grading

‣ Grades will be assigned as follows:

‣ A - 90-100%B - 80-89%C - 70-79%D - 60-69%F - <60%.

‣ Grades are based upon two laboratory reports;report on a known sample (40%)report on an an unknown sample (60%)

‣ In analyzing the data obtained, the following approximate percentages will be applied to the various spectroscopic techniques.Mass Spec - 20%, IR - 15%, NMR (1H, 13C, etc) - 65%.




‣ Plan

‣ Training on the instruments ASAP - Contact Dan Wanner and Angel Ugrinov to schedule training.

‣ You will be provided with a known sample. You must obtain all the data and analyze it. The first report is due on October 19.

‣ When you turn in your report, you will be provided with an unkown sample.

‣ The final report will be due on Nov 30.




‣ Reports

‣ Reports should be typewritten in manuscript style.

‣ A good model to follow would be a paper on the structure determination of a natural product found in J. Nat. Prod. or J. Am. Chem. Soc.

‣ MS - Determine the m/e peak and m+1 and m+2 if present. Explain the fragmentation patterns observed for as many peaks as possible. You should include the structure of the fragments as well as the fragmentation pathway from which it arose.

‣ IR - Identify all functional groups in your molecule.

‣ 1H NMR - Assign all resonances to the protons on the structure. All coupling constants should be calculated and splitting patterns explained.

‣ 13C NMR - Assign all resonances to the carbons on the structure. Advanced NMR experiments may be necessary to correlate the peaks.

‣ 2D NMR - Explain your analysis of the data as it pertains to your structure.



Tentative Course ScheduleDate Topic

Aug 25/27 Introduction and Basics of NMR Spectroscopy

Sep 1/3 NMR Spin Coupling and Multiplet Analysis

Sep 8/10 Multiplet Analysis and Multipulse NMR

Sep 15 NMR Stereochemistry

Sep 17 MIDTERM EXAM

Sep 22/24 NMR Practical Considerations and 2D NMR

Sep 29/Oct 1 Mass Spectrometry

Oct 6/8 Infrared Spectroscopy

Oct 13 UV Spectroscopy

TBA* FINAL EXAM

*we will schedule the final for the week of Oct 19.



StructureDetermination



How to determine the structure of molecules?

‣ Probe physical properties

‣ Elemental Analysis

‣ atomic composition (relative ratios)

‣ empirical formula

‣ Mass Spectrometry

‣ molecular formula

‣ element identification (isotopes)

‣ connectivity



Mass Spectrometer



Electromagnetic Spectrum



Ultraviolet - Visible Spectroscopy

‣ Electronic (UV-VIS) Spectroscopy

‣ energy to excite an electron to a higher excited state

‣ More conjugation, lower energy

220 nm 258 nm

455 nm



Infrared Spectroscopy

‣ Vibrational (Infrared) Spectroscopy

‣ functional groups



Nuclear Magnetic Resonance Spectroscopy

‣ NMR probes the spin transitions of nuclei

‣ energy in the radio frequency range

‣ NMR provides a wealth of information about structure

‣ Functional Groups

‣ Atom Connectivity

‣ Stereochemistry

‣ Higher Order Structure



Magnetic Resonance Imaging

‣ NMR is the basis for MRI



X-Ray Crystallography

‣ X-Ray Crystallography

‣ 3D positions of atoms



Empirical Formula from Elemental Analysis

C - 63.31%H - 6.28%Cl - 16.99%N - 13.42%

Assume 100 g of analyte

% composition proportional to grams

Moles of C = 63.31 g / 12.011 g/mol = 5.27 / 0.48 = 11

Moles of H = 6.28 g / 1.008 g/mol = 6.23 / 0.48 = 13

Moles of Cl = 16.99 g / 35.453 g/mol = 0.48 / 0.48 = 1

Moles of N = 13.42 g / 14.007 g/mol = 0.96 / 0.48 = 2

Empirical Formula: C11H13ClN2



Units of Unsaturation

Empirical Formula: C11H13ClN2

‣ Degrees of unsaturation is the number of pi-bonds and/or rings

‣ For saturated hydrocarbons: CnH2n+2

every halogen replaces one Hevery nitrogen adds one H

(2n+2) - #H - #X + #N

2UN =

(2*11+2) - 13 - 1 + 2

2= 6UN = N

N

H Cl



Molecular Formula from Mass

‣ Rule of 13

‣ M / 13 = n+r/13 where CnHn+r

for example - take a molecule with a M=164

164 / 13 = 12 + 8/13 therefore a MF would be C12H12+8 or C12H20

(2*12+2) - 20 - 0 + 0

2= 3UN =



Molecular Formula from Mass

‣ What if there are other atoms besides C and H?

‣ Subtract their mass equivalents of C and H from the formula

for example - take a molecule with a M=164

164 / 13 = 12 + 8/13 C12H20

O = 16 equivalent to CH4 C12H20 C11H16O

Note: Be careful of invalid formulas

e.g. M=32 32/13 = 2 + 6/13 C2H8 impossible UN = -1

must have another atom: CH4O CH6N



Identification of a Natural Product

‣ High Res. Mass Spectrometry

‣ UV Spectroscopy

‣ IR Spectroscopy

EpibatidineJ. Am. Chem. Soc. 1992, 112, 3475

Isolated from the Ecuadorian tree frog - Epibatis Tricolor

Analgesic activity 500 times greater than morphine.

210.0764 4.4% C11H13N237Cl

208.0769 15.5% C11H13N235Cl

217 nm and 250-280 nm indicates pyridine ring

1428 and 1112 cm-1 suggests a pyridine ring

NN

H Cl



Proton NMR


NN

H Cl



Carbon NMR


NN

H Cl



Steps in Structure Elucidation

27

Pure Compound

Molecular Formula

Functional Groups

Sub-structures

3D structure

EA, MS, NMR

NMR, IR, UV

NMR

X-RAY

Working 2D

structures

UN

examineall isomers

determine bestpossibilities

NMR, MS, IR, UV

Best 2D structures

Reasonable3D

structure

NMRmodel

TotalSynthesis


Documents

Organic Spectroscopy - NDSUcook.chem.ndsu.nodak.edu/wordpress/wp-content/uploads/2015/08/01... · Organic Spectroscopy ... ‣ Structure elucidation by modern NMR: A workbook,