DOCSLIB.ORG

Determination of Molecular Stereochemistry Using Chiroptical Spectroscopic Methods Vanderbilt Chemistry

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Determination of Molecular Stereochemistry Using Chiroptical Spectroscopic Methods Vanderbilt Chemistry Determination of Molecular Stereochemistry Using Chiroptical Spectroscopic Methods Vanderbilt Chemistry Prasad L. Polavarapu Department of Chemistry Vanderbilt University Nashville TN 37235 USA Presented to Synthetic community/ Chemical-Biology training program February 15, 2011 Food for thought Vanderbilt Chemistry How would you determine: (A). the absolute configuration of: (1). Bromochlorofluoromethane, CHFClBr (2). Molecules that are chiral solely due to isotopic substitution (3). Diastereomers of Natural Products (B). The secondary structures of peptides/proteins Vanderbilt Chemistry ORD ECD Optical Electronic Circular Rotatory Dichroism dispersion Chiroptical Spectroscopic Vibrational methods Circular Vibrational Raman Dichroism Optical Activity VCD VROA Enantiomers of chiral molecules give oppositely signed chiroptical spectra and thus enable distinguishing enantiomers Optical Rotation: Experimental Measurement Vanderbilt Chemistry Chiral sample monochromator detector Analyzer Linear polarizer Specific Rotation: []= /c l is observed rotation c is concentration in g / mL l is path length in dm Specific Rotation & Molecular structure Vanderbilt Chemistry “Experimental determination of the absolute configuration of bromochlorofluoromethane is a challenge”. Wilen SH, Bunding KA, Kascheres CM, Weider MJ. J Am Chem Soc 1985; 107:6997-6998 Lack of a reliable method to correlate observed Specific rotation with molecular structure prevented optical rotation from becoming a structural tool for the most part of twentieth century. This status has changed now due to advances in quantum chemical theories and ever changing computer technology Vanderbilt Chemistry -1 2 2 Static method of Amos G’=-(4/h){[1/( ns- )]Im{,snm,ns}} Chem. Phys. Lett. 1982; 87: 23-26 -1 = -(1/3) [G’xx+ G’yy+ G’zz] -1 lim G’=-(h/) Im (s/F)|(s/B) 0 [] = 13.43 x10-5 2/M CPHF method implemented (in deg.cc.dm-1.g-1) in CADPAC program Molecule Pred Expt (R)-methyloxirane 2 14 (S)-methylthiirane -50 -51 (R,R)-dimethyloxirane 70 59 (S,S)-dimethylthiirane -248 -129 Using specific rotation at 589nm and Raman optical activity, absolute configuration of bromochlorofluoromethane was assigned as (S)-(+)/(R)-(-). Hecht L, Costante J, Polavarapu PL, Collet A, Barron LD. Angew. Chem. 1997; 36: 885-887; Calculations were done at Hartree-Fock level of Chem. Eng. News, 1997 theory using 6-31G*/DZP basis sets for 11 molecules Advanced theoretical methods Time dependent density functional theory for specific rotation Vanderbilt Chemistry (1). K. Yabana, G. F. Bertsch, Application of time-dependent density functional theory to optical activity, Phys. Rev. A 60 (1999) 1271-1279; (2). J. R. Cheeseman, M. J. Frisch, F. J. Devlin, P. J. Stephens, Hartree-Fock and Density functional theory ab initio calculation of optical rotation using GIAOs: Basis set dependence, J. Phys. Chem. A.104 (2000) 1039-1046; (3). S. Grimme, Calculation of frequency dependent optical rotation using density functional response theory, Chem. Phys. Lett. 339 (2001) 380-388 (4).K. Ruud, T. Helgaker, Optical rotation studied by density functional and coupled-cluster methods, Chem Phys Lett. 352 (2002) 533-539. (5). J. Autschbach, S. Patchkovskii, T. Ziegler, S. J. A. van Gisbergen, E. J. Baerends, Chiroptical properties from time- dependent density functional theory. II. Optical rotations of small to medium size organic molecules, J. Chem. Phys.117 (2002) 581-592. Advanced theoretical methods Coupled cluster theory for specific rotation Vanderbilt Chemistry (1). K. Ruud, T. Helgaker, Optical rotation studied by density-functional and coupled-cluster methods, Chem Phys Lett. 352 (2002) 533-539. (2). Ruud K, Stephens PJ, Devlin FJ, Taylor PR, Cheeseman JR, Frisch MJ. Coupled cluster calculations of optical rotation, Chem. Phys. Lett. 2003; 373:606-614. (3). Tam MC, Russ NJ, Crawford TD, Coupled cluster calculation of optical rotatory dispersion of (S)-methyloxirane, J. Chem. Phys. 2004; 121:3550-3557. (4). Pedersen TB, Sanchez de Meras AMJ, Koch H. Polarizability and optical rotation calculated from the approximate coupled cluster singles and doubles CC2 linear response theory using Cholesky decomposition. J. Chem. Phys. 2004; 120: 8887-8897. (5). Kongsted J, Pedersen TB, Strange M, Osted A, Hansen AE, Mikkelsen KV, Pawlowski F, Jorgensen P, Hattig C. “Coupled cluster calculations of optical rotation of S-propylene oxide in gas phase and solution”, Chem. Phys. Lett. 2005; 401:385-392 Absolute configuration of Bromochlorofluoromethane Vanderbilt Chemistry Optical rotatory dispersion in bromochlorofluoromethane (S)-(+)-CHFClBr Predicted with 4 in C H 6 12 B3LYP/aug-cc-pVTZ 3 neat liquid For (S)-CHFClBr 2 H 1 Specicic Rotation B3LYP/aug-cc-pVTZ 0 C 350 450 550 650 F Br nm) Cl Experimental data from: Canceill J, Lacombe L, Collet A., J Am Chem Soc 1985; 107: 6993-6996. Hecht L, Costante J, Polavarapu PL, Collet A, Barron LD. Angewandte Chemie 1997; 36: 885-887 P. L.Polavarapu, Angewandte Chemie Int. Ed 41(23),4544-4546 (2002). Summary for Optical rotatory dispersion Vanderbilt Chemistry Remarkable advances in calculation of specific rotations. ORD can now be calculated through resonant regions using sophisticated levels of theory Optical rotation at a single wavelength should never be used for establishing Molecular structure “Protocols for the analysis of theoretical optical rotations”, P. L. Polavarapu, Chirality 2006; 18: 348-356 However need a significant culture change in reporting Experimental solution phase optical rotations Vanderbilt Chemistry Errors are not usually reported for optical rotation measurements in liquid solutions Significant errors can arise from (a). Preparing solutions with smaller amount (~mg) of samples (b). Preparing smaller volume (~ mL) solutions (c). Measuring small (<0.01) optical rotation values Optical rotation measurements of organometallic compounds: Caveats and recommended procedures. Dewey MA, Gladysz JA. Organometallics 1993, 12, 2390-2392. Electronic Circular Dichroism (ECD) Vanderbilt Chemistry Excited electronic state AL-AR First Vibrational excited state 1 Ground electronic state Vibrational ground state 0 ECD technique is more than 100 yrs old Gained a new life, in the last decade, with the advent of reliable quantum chemical theories Measurement of Electronic Circular Dichroism Vanderbilt Chemistry Circularly Polarized light sample Detector Visible light source Experimental Theoretical Dipole Strength Absorbance 2 D01=|<0||1>| A= - log(I/I0) Circular Dichroism Rotational Strength R01=Im[<0||1>•<1|m|0>] A=AL-AR A typical ECD spectrum Vanderbilt Chemistry (aS)- 3,3'-diphenyl-[2,2'-binaphthalene]-1,1'-diol ECD and Molecular Structures… the Old Way Vanderbilt Chemistry Empirical rules: Octant rule etc [Lightner, D. A.; Gurst, J. E. Organic Conformational Analysis and Stereochemistry from Circular Dichroism Spectroscopy, John Wiley & Sons: New York, 2000.] Exciton coupling model [Harada, N.; Nakanishi, K. Circular Dichroism Spectroscopy: Exciton coupling in Organic Stereochemistry; University Science Books: Mill Valley, CA, 1983.; ] Semi-classical models: Devoe’s Polarizability model [Superchi, S.; Giorgio, E.; Rosini, A. Structural determinations by circular dichroism spectra analysis using coupled oscillator methods: An update of the applications of the DeVoe polarizability model, Chirality, 2004, 16, 422-451] ECD and Molecular Structures… the Modern Way Vanderbilt Chemistry th For i electronic transition, calculate rotational strength, Ri. o o o Ri Im s i i m s 2 Corresponding absorption intensity as dipole strength, Di=|<s||i>| 8 2 m D or dimensionless oscillator strength, f . f e i i i i 3e 2 h 3298.8 i Ri 40 Peak intensity of Lorentzian band: i,0 10 22.94 i 2 () i Lorentzian band intensity distribution: i i,0 2 2 ( i ) i Early Quantum chemical calculations with Random phase approximation: Hansen AE, Bouman TD, Natural chiroptical spectroscopy: Theory and computations, Adv Chem Phys 1980;44:545–644. Hansen AE, Voigt B, Rettrup S, Large-scale RPA calculations of chiroptical properties of organic molecules: Program RPAC, Int J Quantum Chem 1983;23: 595–611. Modern Quantum chemical calculations: Density functional theoretical method for ECD Vanderbilt Chemistry Autschbach, J.; Ziegler T.; van Gisbergen SJA.; Baerends EJ. Chiroptical properties from time-dependent density functional theory. I. Circular dichroism spectra of organic molecules, J. Chem. Phys. 2002; 116: 6930-6940. Diedrich C.; Grimme S. Systematic Investigation of Modern Quantum Chemical Methods to Predict Electronic Circular Dichroism Spectra, J. Phys. Chem. A. 2003, 107, 2524-2539; Pecul M.; Ruud K.; Helgaker T. Density functional theory calculation of electronic circular dichroism using London orbitals, Chem. Phys. Lett. 2004; 388: 110-119; Stephens PJ, McCann DM, Devlin FJ, Cheeseman JR, Frisch MJ. Determination of the absolute configuration of [3(2)](1,4) barrelenophanedicarbonitrile using concerted time-dependent density functional theory calculations of optical rotation and electronic circular dichroism. J Am Chem Soc 126 (2004) 7514-7521. Modern Quantum chemical calculations: Coupled Cluster theoretical method for ECD Vanderbilt Chemistry Pedersen TB.; Koch H.; Ruud K. Coupled cluster response calculation of natural chiroptical spectra, J. Chem. Phys. 1999; 110: 2883-2892; Crawford TD.; Tam MC.; Abrams ML. The current state of ab initio calculations of optical rotation and electronic circular dichroism spectra. J. Phys. Chem. 2007, 111, 12057-12068 Molecular stereochemistry:
Load more

Recommended publications
  • Prebiological Evolution and the Metabolic Origins of Life
    Prebiological Evolution and the Andrew J. Pratt* Metabolic Origins of Life University of Canterbury Keywords Abiogenesis, origin of life, metabolism, hydrothermal, iron Abstract The chemoton model of cells posits three subsystems: metabolism, compartmentalization, and information. A specific model for the prebiological evolution of a reproducing system with rudimentary versions of these three interdependent subsystems is presented. This is based on the initial emergence and reproduction of autocatalytic networks in hydrothermal microcompartments containing iron sulfide. The driving force for life was catalysis of the dissipation of the intrinsic redox gradient of the planet. The codependence of life on iron and phosphate provides chemical constraints on the ordering of prebiological evolution. The initial protometabolism was based on positive feedback loops associated with in situ carbon fixation in which the initial protometabolites modified the catalytic capacity and mobility of metal-based catalysts, especially iron-sulfur centers. A number of selection mechanisms, including catalytic efficiency and specificity, hydrolytic stability, and selective solubilization, are proposed as key determinants for autocatalytic reproduction exploited in protometabolic evolution. This evolutionary process led from autocatalytic networks within preexisting compartments to discrete, reproducing, mobile vesicular protocells with the capacity to use soluble sugar phosphates and hence the opportunity to develop nucleic acids. Fidelity of information transfer in the reproduction of these increasingly complex autocatalytic networks is a key selection pressure in prebiological evolution that eventually leads to the selection of nucleic acids as a digital information subsystem and hence the emergence of fully functional chemotons capable of Darwinian evolution. 1 Introduction: Chemoton Subsystems and Evolutionary Pathways Living cells are autocatalytic entities that harness redox energy via the selective catalysis of biochemical transformations.
    [Show full text]
  • Density Functional Theory
    Density Functional Approach Francesco Sottile Ecole Polytechnique, Palaiseau - France European Theoretical Spectroscopy Facility (ETSF) 22 October 2010 Density Functional Theory 1. Any observable of a quantum system can be obtained from the density of the system alone. < O >= O[n] Hohenberg, P. and W. Kohn, 1964, Phys. Rev. 136, B864 Density Functional Theory 1. Any observable of a quantum system can be obtained from the density of the system alone. < O >= O[n] 2. The density of an interacting-particles system can be calculated as the density of an auxiliary system of non-interacting particles. Hohenberg, P. and W. Kohn, 1964, Phys. Rev. 136, B864 Kohn, W. and L. Sham, 1965, Phys. Rev. 140, A1133 Density Functional ... Why ? Basic ideas of DFT Importance of the density Example: atom of Nitrogen (7 electron) 1. Any observable of a quantum Ψ(r1; ::; r7) 21 coordinates system can be obtained from 10 entries/coordinate ) 1021 entries the density of the system alone. 8 bytes/entry ) 8 · 1021 bytes 4:7 × 109 bytes/DVD ) 2 × 1012 DVDs 2. The density of an interacting-particles system can be calculated as the density of an auxiliary system of non-interacting particles. Density Functional ... Why ? Density Functional ... Why ? Density Functional ... Why ? Basic ideas of DFT Importance of the density Example: atom of Oxygen (8 electron) 1. Any (ground-state) observable Ψ(r1; ::; r8) 24 coordinates of a quantum system can be 24 obtained from the density of the 10 entries/coordinate ) 10 entries 8 bytes/entry ) 8 · 1024 bytes system alone. 5 · 109 bytes/DVD ) 1015 DVDs 2.
    [Show full text]
  • Chapter 3 • Ratio: Cnh2n+2
    Organic Chemistry, 5th Edition Alkane Formulas L. G. Wade, Jr. • All C-C single bonds • Saturated with hydrogens Chapter 3 • Ratio: CnH2n+2 Structure and Stereochemistry • Alkane homologs: CH3(CH2)nCH3 of Alkanes • Same ratio for branched alkanes H H H H H H CH H C C C C H H H H C CCH Jo Blackburn H H H H H H Richland College, Dallas, TX H => Butane, C4H10 Dallas County Community College District Chapter 3Isobutane, C H 2 © 2003, Prentice Hall 4 10 Common Names Pentanes H H H H H H H CH • Isobutane, “isomer of butane” H C C C C C H H H • Isopentane, isohexane, etc., methyl H H H H H H H C CCC H branch on next-to-last carbon in chain. H H H H • Neopentane, most highly branched n-pentane, C5H12 isopentane, C5H12 • Five possible isomers of hexane, CH3 18 isomers of octane and 75 for H3C C CH3 decane! CH3 => => neopentane, C5H12 Chapter 3 3 Chapter 3 4 Longest Chain IUPAC Names • The number of carbons in the longest • Find the longest continuous carbon chain determines the base name: chain. ethane, hexane. (Listed in Table 3.2, • Number the carbons, starting closest to page 81.) the first branch. • If there are two possible chains with the • Name the groups attached to the chain, same number of carbons, use the chain using the carbon number as the locator. with the most substituents. • Alphabetize substituents. H3C CH CH CH • Use di-, tri-, etc., for multiples of same 2 3 CH3 substituent.
    [Show full text]
  • Stereochemistry of Alkanes and Cycloalkanes
    STEREOCHEMISTRY OF ALKANES AND CYCLOALKANES CONFORMATIONAL ISOMERS 1 CONFORMATIONAL ISOMERS • Stereochemistry concerned with the 3-D aspects of molecules • Rotation is possible around C-C bonds in open- chain molecules • A conformation is one of the many possible arrangements of atoms caused by rotation about a single bond, and a specific conformation is called a conformer (conformational isomer). 2 SOME VOCABULARY • A staggered conformation is the conformation in which all groups on two adjacent carbons are as far from each other as possible. • An eclipsed conformation is the conformation in which all groups on two adjacent carbons are as close to each other as possible. • Dihedral angle is angle between the substituents on two adjacent carbons; changes with rotation around the C-C bond 3 MORE VOCABULARY • Angle strain is the strain caused by the deformation of a bond angle from its normal value. • Steric strain is the repulsive interaction caused by atoms attempting to occupy the same space. • Torsional strain is the repulsive interaction between two bonds as they rotate past each other. Torsional strain is responsible for the barrier to rotation around the C-C bond. The eclipsed from higher in energy than the staggered form. 4 CONFORMATION OF ETHANE • Conformation- Different arrangement of atoms resulting from bond rotation • Conformations can be represented in 2 ways: 5 TORSIONAL STRAIN • We do not observe perfectly free rotation • There is a barrier to rotation, and some conformers are more stable than others • Staggered- most stable:
    [Show full text]
  • Camcasp 5.9 Alston J. Misquitta† and Anthony J
    CamCASP 5.9 Alston J. Misquittay and Anthony J. Stoneyy yDepartment of Physics and Astronomy, Queen Mary, University of London, 327 Mile End Road, London E1 4NS yy University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW September 1, 2015 Abstract CamCASP is a suite of programs designed to calculate molecular properties (multipoles and frequency- dependent polarizabilities) in single-site and distributed form, and interaction energies between pairs of molecules, and thence to construct atom–atom potentials. The CamCASP distribution also includes the programs Pfit, Casimir,Gdma 2.2, Cluster, and Process. Copyright c 2007–2014 Alston J. Misquitta and Anthony J. Stone Contents 1 Introduction 1 1.1 Authors . .1 1.2 Citations . .1 2 What’s new? 2 3 Outline of the capabilities of CamCASP and other programs 5 3.1 CamCASP limits . .7 4 Installation 7 4.1 Building CamCASP from source . .9 5 Using CamCASP 10 5.1 Workflows . 10 5.2 High-level scripts . 10 5.3 The runcamcasp.py script . 11 5.4 Low-level scripts . 13 6 Data conventions 13 7 CLUSTER: Detailed specification 14 7.1 Prologue . 15 7.2 Molecule definitions . 15 7.3 Geometry manipulations and other transformations . 16 7.4 Job specification . 18 7.5 Energy . 23 7.6 Crystal . 25 7.7 ORIENT ............................................... 26 7.8 Finally, . 29 8 Examples 29 8.1 A SAPT(DFT) calculation . 29 8.2 An example properties calculation . 30 8.3 Dispersion coefficients . 34 8.4 Using CLUSTER to obtain the dimer geometry . 36 9 CamCASP program specification 39 9.1 Global data .
    [Show full text]
  • Chapter 4: Stereochemistry Introduction to Stereochemistry
    Chapter 4: Stereochemistry Introduction To Stereochemistry Consider two of the compounds we produced while finding all the isomers of C7H16: CH3 CH3 2-methylhexane 3-methylhexane Me Me Me C Me H Bu Bu Me Me 2-methylhexane H H mirror Me rotate Bu Me H 2-methylhexame is superimposable with its mirror image Introduction To Stereochemistry Consider two of the compounds we produced while finding all the isomers of C7H16: CH3 CH3 2-methylhexane 3-methylhexane H C Et Et Me Pr Pr 3-methylhexane Me Me H H mirror Et rotate H Me Pr 2-methylhexame is superimposable with its mirror image Introduction To Stereochemistry Consider two of the compounds we produced while finding all the isomers of C7H16: CH3 CH3 2-methylhexane 3-methylhexane .Compounds that are not superimposable with their mirror image are called chiral (in Greek, chiral means "handed") 3-methylhexane is a chiral molecule. .Compounds that are superimposable with their mirror image are called achiral. 2-methylhexane is an achiral molecule. .An atom (usually carbon) with 4 different substituents is called a stereogenic center or stereocenter. Enantiomers Et Et Pr Pr Me CH3 Me H H 3-methylhexane mirror enantiomers Et Et Pr Pr Me Me Me H H Me H H Two compounds that are non-superimposable mirror images (the two "hands") are called enantiomers. Introduction To Stereochemistry Structural (constitutional) Isomers - Compounds of the same molecular formula with different connectivity (structure, constitution) 2-methylpentane 3-methylpentane Conformational Isomers - Compounds of the same structure that differ in rotation around one or more single bonds Me Me H H H Me H H H H Me H Configurational Isomers or Stereoisomers - Compounds of the same structure that differ in one or more aspects of stereochemistry (how groups are oriented in space - enantiomers or diastereomers) We need a a way to describe the stereochemistry! Me H H Me 3-methylhexane 3-methylhexane The CIP System Revisited 1.
    [Show full text]
  • Jaguar 5.5 User Manual Copyright © 2003 Schrödinger, L.L.C
    Jaguar 5.5 User Manual Copyright © 2003 Schrödinger, L.L.C. All rights reserved. Schrödinger, FirstDiscovery, Glide, Impact, Jaguar, Liaison, LigPrep, Maestro, Prime, QSite, and QikProp are trademarks of Schrödinger, L.L.C. MacroModel is a registered trademark of Schrödinger, L.L.C. To the maximum extent permitted by applicable law, this publication is provided “as is” without warranty of any kind. This publication may contain trademarks of other companies. October 2003 Contents Chapter 1: Introduction.......................................................................................1 1.1 Conventions Used in This Manual.......................................................................2 1.2 Citing Jaguar in Publications ...............................................................................3 Chapter 2: The Maestro Graphical User Interface...........................................5 2.1 Starting Maestro...................................................................................................5 2.2 The Maestro Main Window .................................................................................7 2.3 Maestro Projects ..................................................................................................7 2.4 Building a Structure.............................................................................................9 2.5 Atom Selection ..................................................................................................10 2.6 Toolbar Controls ................................................................................................11
    [Show full text]
  • Thomas–Fermi–Dirac–Von Weizsäcker Models in Finite Systems Garnet Kin-Lic Chan, Aron J
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Caltech Authors - Main Thomas–Fermi–Dirac–von Weizsäcker models in finite systems Garnet Kin-Lic Chan, Aron J. Cohen, and Nicholas C. Handy Citation: 114, (2001); doi: 10.1063/1.1321308 View online: http://dx.doi.org/10.1063/1.1321308 View Table of Contents: http://aip.scitation.org/toc/jcp/114/2 Published by the American Institute of Physics JOURNAL OF CHEMICAL PHYSICS VOLUME 114, NUMBER 2 8 JANUARY 2001 Thomas–Fermi–Dirac–von Weizsa¨cker models in finite systems Garnet Kin-Lic Chan,a) Aron J. Cohen, and Nicholas C. Handy Department of Chemistry, Lensfield Road, Cambridge CB2 1EW, United Kingdom ͑Received 7 June 2000; accepted 8 September 2000͒ To gain an understanding of the variational behavior of kinetic energy functionals, we perform a numerical study of the Thomas–Fermi–Dirac–von Weizsa¨cker theory in finite systems. A general purpose Gaussian-based code is constructed to perform energy and geometry optimizations on polyatomic systems to high accuracy. We carry out benchmark studies on atomic and diatomic systems. Our results indicate that the Thomas–Fermi–Dirac–von Weizsa¨cker theory can give an approximate description of matter, with atomic energies, binding energies, and bond lengths of the correct order of magnitude, though not to the accuracy required of a qualitative chemical theory. We discuss the implications for the development of new kinetic functionals. © 2001 American Institute of Physics. ͓DOI: 10.1063/1.1321308͔ I. INTRODUCTION
    [Show full text]
  • Organic Chemistry by Robert C
    (2/94)(6,7,9/95)(8,9/97)(12/99)(1/00) Neuman Chapter 4 Chapter 4 Stereochemistry from Organic Chemistry by Robert C. Neuman, Jr. Professor of Chemistry, emeritus University of California, Riverside [email protected] <http://web.chem.ucsb.edu/~neuman/orgchembyneuman/> Chapter Outline of the Book ************************************************************************************** I. Foundations 1. Organic Molecules and Chemical Bonding 2. Alkanes and Cycloalkanes 3. Haloalkanes, Alcohols, Ethers, and Amines 4. Stereochemistry 5. Organic Spectrometry II. Reactions, Mechanisms, Multiple Bonds 6. Organic Reactions *(Not yet Posted) 7. Reactions of Haloalkanes, Alcohols, and Amines. Nucleophilic Substitution 8. Alkenes and Alkynes 9. Formation of Alkenes and Alkynes. Elimination Reactions 10. Alkenes and Alkynes. Addition Reactions 11. Free Radical Addition and Substitution Reactions III. Conjugation, Electronic Effects, Carbonyl Groups 12. Conjugated and Aromatic Molecules 13. Carbonyl Compounds. Ketones, Aldehydes, and Carboxylic Acids 14. Substituent Effects 15. Carbonyl Compounds. Esters, Amides, and Related Molecules IV. Carbonyl and Pericyclic Reactions and Mechanisms 16. Carbonyl Compounds. Addition and Substitution Reactions 17. Oxidation and Reduction Reactions 18. Reactions of Enolate Ions and Enols 19. Cyclization and Pericyclic Reactions *(Not yet Posted) V. Bioorganic Compounds 20. Carbohydrates 21. Lipids 22. Peptides, Proteins, and α−Amino Acids 23. Nucleic Acids **************************************************************************************
    [Show full text]
  • Quantum Chemical Calculations of NMR Parameters
    Quantum Chemical Calculations of NMR Parameters Tatyana Polenova University of Delaware Newark, DE Winter School on Biomolecular NMR January 20-25, 2008 Stowe, Vermont OUTLINE INTRODUCTION Relating NMR parameters to geometric and electronic structure Classical calculations of EFG tensors Molecular properties from quantum chemical calculations Quantum chemistry methods DENSITY FUNCTIONAL THEORY FOR CALCULATIONS OF NMR PARAMETERS Introduction to DFT Software Practical examples Tutorial RELATING NMR OBSERVABLES TO MOLECULAR STRUCTURE NMR Spectrum NMR Parameters Local geometry Chemical structure (reactivity) I. Calculation of experimental NMR parameters Find unique solution to CQ, Q, , , , , II. Theoretical prediction of fine structure constants from molecular geometry Classical electrostatic model (EFG)- only in simple ionic compounds Quantum mechanical calculations (Density Functional Theory) (EFG, CSA) ELECTRIC FIELD GRADIENT (EFG) TENSOR: POINT CHARGE MODEL EFG TENSOR IS DETERMINED BY THE COMBINED ELECTRONIC AND NUCLEAR WAVEFUNCTION, NO ANALYTICAL EXPRESSION IN THE GENERAL CASE THE SIMPLEST APPROXIMATION: CLASSICAL POINT CHARGE MODEL n Zie 4 V2,k = 3 Y2,k ()i,i i=1 di 5 ATOMS CONTRIBUTING TO THE EFG TENSOR ARE TREATED AS POINT CHARGES, THE RESULTING EFG TENSOR IS THE SUM WITH RESPECT TO ALL ATOMS VERY CRUDE MODEL, WORKS QUANTITATIVELY ONLY IN SIMPLEST IONIC SYSTEMS, BUT YIELDS QUALITATIVE TRENDS AND GENERAL UNDERSTANDING OF THE SYMMETRY AND MAGNITUDE OF THE EXPECTED TENSOR ELECTRIC FIELD GRADIENT (EFG) TENSOR: POINT CHARGE MODEL n Zie 4 V2,k = 3 Y2,k ()i,i i=1 di 5 Ze V = ; V = 0; V = 0 2,0 d 3 2,±1 2,±2 2Ze V = ; V = 0; V = 0 2,0 d 3 2,±1 2,±2 3 Ze V = ; V = 0; V = 0 2,0 2 d 3 2,±1 2,±2 V2,0 = 0; V2,±1 = 0; V2,±2 = 0 MOLECULAR PROPERTIES FROM QUANTUM CHEMICAL CALCULATIONS H = E See for example M.
    [Show full text]
  • Stereochemistry of Bruice's Organic Chemistry Before Embarking on Comprehending This Summary
    Enantioselective synthesis It helps if you review the concepts in Chapter 5: Stereochemistry of Bruice's Organic Chemistry before embarking on comprehending this summary Most of the molecules on earth are chiral, such as amino acids and carbohydrates. Enantioselective synthesis is an important means by which enantiopure chiral molecules may be obtained for study and medicine. The study of enantioselective synthesis has evolved from issues of diastereoselectivity, through auxiliary-based methods for the synthesis of enantiomerically pure compounds (diastereoselectivity followed by separation and auxiliary cleavage), to asymmetric catalysis. In the latter technology, enantiomers are the products, and highly selective reactions allow preparation - in a single step - of chiral substances in high enantiomeric excess (ee) for many reaction types. Enantioselective synthesis, also known as asymmetric synthesis, is organic synthesis that introduces one or more new and desired elements of chirality. This methodology is important in the field of pharmaceuticals because the different enantiomers or diastereomers of a molecule often have different biological activity. See examples from Chapter 5 of Bruice's Organic Chemistry. Methodologies of Asymmetric Synthesis Chiral pool synthesis Chiral pool synthesis is the easiest approach: A chiral starting material is manipulated through successive reactions using achiral reagents that retain its chirality to obtain the desired target molecule. This is especially attractive for target molecules having the similar chirality to a relatively inexpensive naturally occurring building-block such as a sugar or amino acid. However, the number of possible reactions the molecule can undergo is restricted, and lengthy synthetic routes may be required. Also, this approach requires a stoichiometric amount of the enantiopure starting material, which may be rather expensive if not occurring in nature, whereas chiral catalysis requires only a catalytic amount of chiral material.
    [Show full text]
  • NMR and Stereochemistry Chem 4010/5326: Organic Spectroscopic Analysis
    NMR and Stereochemistry Chem 4010/5326: Organic Spectroscopic Analysis © 2015 Andrew Harned General flow for solving structures C10H20O Molecular weight/formula (MS) Exact Mass: 156.1514 Molecular Weight: 156.2652 Functional groups (IR, NMR) Carbon connectivities (substructures) (NMR) Positions of functional groups within framework (gross structure) (2D NMR, coupling constants) How can this Stereochemical issues be solved??? Relative Stereochemistry (Diastereomers) Can be determined with many of the tools we have already discussed, along with some new ones Bifulco, G.; Dambruoso, P.; Gomex-Paloma, L.; Riccio, R. Chem. Rev. 2007, 107, 3744. NMR Spectroscopy Strategies for determining relative stereochemistry Chemical Shifts – Diastereotopic protons will have different chemical shifts, this will only tell you that diastereomers are present, cannot necessarily tell which is which by inspection only by comparison to known structures – Spatial orientation may place certain protons in shielding/deshielding portions of functional groups Coupling Constants – In acyclic systems, usually cannot tell which is which by inspection – Often must convert to rigid/cyclic structure Both require some knowledge of 3D structure –> Make model(s) NMR Spectroscopy Proximity of Protons Nuclear Overhauser Effect (nOe) – Through space interactions between nuclei, whether or not they are directly coupled – Magnitude decreases as inverse of sixth power of distance – Strongly irradiate one, get larger # in excited state – The others then shift to lower state to compensate
    [Show full text]