Yale Freshman Organic Chemistry with J. Michael McBride

Yale Freshman Organic Chemistry with J. Michael McBride

Freshman Organic Chemistry (CHEM 125)
Professor McBride outlines the course with its goals and requirements, including the required laboratory course. To the course’s prime question “How do you know” he proposes two unacceptable answers (divine and human authority), and two acceptable answers (experiment and logic). He illustrates the fruitfulness of experiment and logic using the rise of science in the seventeenth century. London’s Royal Society and the “crucial” experiment on light by Isaac Newton provide examples. In his correspondence with Newton Samuel Pepys, diarist and naval purchasing officer, illustrates the attitudes and habits which are most vital for budding scientists – especially those who would like to succeed in this course. The lecture closes by introducing the underlying goal for the first half of the semester: understanding the Force Law that describes chemical bonds.
00:00 – Chapter 1. Introduction: Logistics
05:37 – Chapter 2. The Goals of Freshman Organic Chemistry: How Do You Know?
15:17 – Chapter 3. Bacon’s Instauration: Experimentation over Philosophy
30:17 – Chapter 4. How to Succeed in Chem 125: Following Samuel Pepys
41:56 – Chapter 5. Atoms, Molecules, and Hooke’s Law
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Professor McBride begins by following Newton’s admonition to search for the force law that describes chemical bonding. Neither direct (Hooke’s Law) nor inverse (Coulomb, Gravity) dependence on distance will do – a composite like the Morse potential is needed. G. N. Lewis devised a “cubic-octet” theory based on the newly discovered electron, and developed it into a shared pair model to explain bonding. After discussing Lewis-dot notation and formal charge, Professor McBride shows that in some “single-minimum” cases the Lewis formalism is inadequate and salvaging it required introducing the confusing concept of “resonance.”
00:00 – Chapter 1. Newton’s “Additions”: An Inquiry into Small Forces
09:15 – Chapter 2. Is there a Chemical Force Law?
18:26 – Chapter 3. The Morse Potential
21:42 – Chapter 4. What are Bonds? Early Understandings of Valence
32:52 – Chapter 5. Deriving Structure and Reactivity from Valence Electrons
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Continuing the discussion of Lewis structures and chemical forces from the previous lecture, Professor McBride introduces the double-well potential of the ozone molecule and its structural equilibrium. The inability for inverse-square force laws to account for stable arrangements of charged particles is prescribed by Earnshaw’s Theorem, which may be visualized by means of lines of force. J.J. Thomson circumvented Earnshaw’s prohibition on structure by postulating a “plum-pudding” atom. When Rutherford showed that the nucleus was a point, Thomson had to conclude that Coulomb’s law was invalid at small distances.
00:00 – Chapter 1. Distinguishing Equilibrium and Resonance
06:37 – Chapter 2. The Structure and Surface Potential of Ozone
20:57 – Chapter 3. Visualizing Electrostatic Force: Earnshaw’s Theorem
35:07 – Chapter 4. J. J. Thomson’s Plum Pudding Model
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
This lecture asks whether it is possible to confirm the reality of bonds by seeing or feeling them. It first describes the work of “clairvoyant” charlatans from the beginning of the twentieth century, who claimed to “see” details of atomic and molecular structure, in order to discuss proper bases for scientific belief. It then shows that the molecular scale is not inconceivably small, and that Newton and Franklin performed simple experiments that measure such small distances. In the last 25 years various realizations of Scanning Probe Microscopy have enabled chemists to “feel” individual molecules and atoms, but not bonds.
00:00 – Chapter 1. Early Attempts to Visualize Atoms: Clairvoyance
15:39 – Chapter 2. Measuring Small Distances: Newton’s Rings and Franklin’s Oil-Water Experiment
29:51 – Chapter 3. Scanning Probe Microscopy: Feeling out Electron Pairs
41:23 – Chapter 4. Resonance Structures for H, C, N, O Isomers
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Professor McBride introduces the theory behind light diffraction by charged particles and its application to the study of the electron distribution in molecules by x-ray diffraction. The roles of molecular pattern and crystal lattice repetition are illustrated by shining laser light through diffraction masks to generate patterns reminiscent of those encountered in X-ray studies of ordered solids.
00:00 – Chapter 1. Introduction: Focusing Lux
07:11 – Chapter 2. Defining and Scattering Light to See: X-Ray Crystallography and Diffraction
25:06 – Chapter 3. Wave Machines
39:42 – Chapter 4. Structural Information in Wave Machines: The Case of Benzene
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Professor McBride uses a hexagonal “benzene” pattern and Franklin’s X-ray pattern of DNA, to continue his discussion of X-ray crystallography by explaining how a diffraction pattern in “reciprocal space” relates to the distribution of electrons in molecules and to the repetition of molecules in a crystal lattice. He then uses electron difference density mapping to reveal bonds, and unshared electron pairs, and their shape, and to show that they are only one-twentieth as dense as would be expected for Lewis shared pairs. Anomalous difference density in the carbon-fluorine bond raises the course’s second great question, “Compared to what?”
00:00 – Chapter 1. Understanding Diffraction Patterns: Continuing the Case of the Hexagonal “Benzene”
15:10 – Chapter 2. Double Helices and DNA: Even and Offset Planes
29:04 – Chapter 3. Revealing Bonds and Unshared Electron Pairs via Electron Difference Density Maps
43:23 – Chapter 4. The Second Great Question: “Compared with What?”
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
After pointing out several discrepancies between electron difference density results and Lewis bonding theory, the course proceeds to quantum mechanics in search of a fundamental understanding of chemical bonding. The wave function ψ, which beginning students find confusing, was equally confusing to the physicists who created quantum mechanics. The Schrödinger equation reckons kinetic energy through the shape of ψ. When ψ curves toward zero, kinetic energy is positive; but when it curves away, kinetic energy is negative!
00:00 – Chapter 1. Limits of the Lewis Bonding Theory
08:35 – Chapter 2. Introduction to Quantum Mechanics
16:36 – Chapter 3. Understanding Psi as a Function of Position
33:24 – Chapter 4. Understanding Negative Kinetic Energy and Finding Potential Energy
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Professor McBride expands on the recently introduced concept of the wave function by illustrating the relationship of the magnitude of the curvature of the wave function to the kinetic energy of the system, as well as the relationship of the square of the wave function to the electron probability density. The requirement that the wave function not diverge in areas of negative kinetic energy leads to only certain energies being allowed, a property which is explored for the harmonic oscillator, Morse potential, and the Columbic potential. Consideration of the influence of mass reveals an “isotope effect” on dynamics, on the energy, vibration frequency, and length of bonds.
00:00 – Chapter 1. Review: The Curvature of the Wave Function and Kinetic Energy
06:44 – Chapter 2. Relationships between Nodes and Curvature of the Wave Function
23:49 – Chapter 3. The Square of Psi as the Probability Density
31:46 – Chapter 4. Constraints of Energy in the Harmonic Oscillator, the Morse Potential and the Coulombic Potential
42:12 – Chapter 5. The Influence of Mass on Bond Dynamics, Strength, and Distance
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
After showing how a double-minimum potential generates one-dimensional bonding, Professor McBride moves on to multi-dimensional wave functions. Solving Schrödinger’s three-dimensional differential equation might have been daunting, but it was not, because the necessary formulas had been worked out more than a century earlier in connection with acoustics. Acoustical “Chladni” figures show how nodal patterns relate to frequencies. The analogy is pursued by studying the form of wave functions for “hydrogen-like” one-electron atoms. Removing normalizing constants from the formulas for familiar orbitals reveals the underlying simplicity of their shapes.
00:00 – Chapter 1. 1-D Bonding from Double-Minimum Potentials
09:03 – Chapter 2. Addressing Multi-Dimensional Problems: Chladni’s Acoustics
22:52 – Chapter 3. Applying Chladni’s Nodal Patterns to the Form of One-Electron Atoms
32:05 – Chapter 4. Removing Normalizing Constants to Understand Orbital Shapes
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
In discussions of the Schrödinger equation thus far, the systems described were either one-dimensional or involved a single electron. After discussing how increased nuclear charge affects the energies of one-electron atoms and then discussing hybridization, this lecture finally addresses the simple fact that multi-electron systems cannot be properly described in terms of one-electron orbitals.
00:00 – Chapter 1. Atom-in-a-Box Plots: Assessing Probability Density
14:07 – Chapter 2. Scaling the Wave Function for Changing Nuclear Charge
21:20 – Chapter 3. Scaling Energy with Respect to Nuclear Charge
27:34 – Chapter 4. Superposition, and the Orientation and Shape of Hybrid Orbitals
40:43 – Chapter 5. An Inconvenient Truth: Troubles Describing Multi-Electron Systems
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
The lecture opens with tricks (“Z-effective” and “Self Consistent Field”) that allow one to correct approximately for the error in using orbitals that is due to electron repulsion. This error is hidden by naming it “correlation energy.” Professor McBride introduces molecules by modifying J.J. Thomson’s Plum-Pudding model of the atom to rationalize the form of molecular orbitals. There is a close analogy in form between the molecular orbitals of CH4 and NH3 and the atomic orbitals of neon, which has the same number of protons and neutrons. The underlying form due to kinetic energy is distorted by pulling protons out of the Ne nucleus to play the role of H atoms.
00:00 – Chapter 1. Introduction
01:53 – Chapter 2. Correcting for Electron Repulsion when Using Orbitals
15:26 – Chapter 3. Correlation Energy and the Limits of Orbital Theory
30:52 – Chapter 4. Kinetic Energy’s Effects on the Shapes of Atomic Orbitals
40:32 – Chapter 5. Moving Nuclei to Distort “Electric Puddings”: Case Studies with Methane and Ammonia
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
This lecture begins by applying the united-atom “plum-pudding” view of molecular orbitals, introduced in the previous lecture, to more complex molecules. It then introduces the more utilitarian concept of localized pairwise bonding between atoms. Formulating an atom-pair molecular orbital as the sum of atomic orbitals creates an electron difference density through the cross product that enters upon squaring a sum. This “overlap” term is the key to bonding. The hydrogen molecule is used to illustrate how close a simple sum of atomic orbitals comes to matching reality, especially when the atomic orbitals are allowed to hybridize.
00:00 – Chapter 1. The United-Atom “Plum-Pudding” View for Ethane and Methanol
13:24 – Chapter 2. The Orbital Shape of 1-Flouroethanol
19:37 – Chapter 3. Localized Pairwise Bonding Between Atoms and the Idea of Overlap
36:36 – Chapter 4. Hydrogen at Bonding Distance: A Case for Overlap
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Professor McBride uses this lecture to show that covalent bonding depends primarily on two factors: orbital overlap and energy-match. First he discusses how overlap depends on hybridization; then how bond strength depends on the number of shared electrons. In this way quantum mechanics shows that Coulomb’s law answers Newton’s query about what “makes the Particles of Bodies stick together by very strong Attractions.” Energy mismatch between the constituent orbitals is shown to weaken the influence of their overlap. The predictions of this theory are confirmed experimentally by measuring the bond strengths of H-H and H-F during heterolysis and homolysis.
00:00 – Chapter 1. Distance and Hybridization in the Overlap Integral
18:49 – Chapter 2. Influence of Overlap on Molecular Orbital Energy
29:45 – Chapter 3. “Inferior” Orbitals and Energy-Matching
46:59 – Chapter 4. Experimental Evidence and Conclusion
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
This lecture brings experiment to bear on the previous theoretical discussion of bonding by focusing on hybridization of the central atom in three XH_3 molecules. Because independent electron pairs must not overlap, hybridization can be related to molecular structure by a simple equation. The “Umbrella Vibration” and the associated rehybridization of the central atom is used to illustrate how a competition between strong bonds and stable atoms works to create differences in molecular structure that discriminate between bonding models. Infrared and electron spin resonance experiments confirm our understanding of the determinants of molecular structure.
00:00 – Chapter 1. A Relationship between Hybridization and Molecular Structure
08:30 – Chapter 2. Optimizing Hybridization in XH3 Molecules
19:17 – Chapter 3. Infrared Spectroscopy on the Structures of the XH3 Molecules
29:43 – Chapter 4. Electron Spin Resonance on Hybridization and Electron Density
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Professor McBride begins by using previous examples of “pathological” bonding and the BH_3 molecule to illustrate how a chemist’s use of localized bonds, vacant atomic orbitals, and unshared pairs to understand molecules compares with views based on the molecule’s own total electron density or on computational molecular orbitals. This lecture then focuses on understanding reactivity in terms of the overlap of singly-occupied molecular orbitals (SOMOs) and, more commonly, of an unusually high-energy highest occupied molecular orbital (HOMO) with an unusually low-energy lowest unoccupied molecular orbital (LUMO). This is shown to be a generalization of the traditional concepts of acid and base. Criteria for assessing reactivity are outlined and illustrated.
00:00 – Chapter 1. Introduction: “Pathological” Bonding in the BH3
10:45 – Chapter 2. Viewing BH3 via Electron Density and Molecular Orbitals
20:25 – Chapter 3. Assessing Reactivity through HOMO-LUMO Interactions
40:15 – Chapter 4. Criteria for Assessing Reactivity
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
This lecture continues the discussion of the HOMO/LUMO view of chemical reactivity by focusing on ways of recognizing whether a particular HOMO should be unusually high in energy (basic), or a particular LUMO should be unusually low (acidic). The approach is illustrated with BH_3, which is both acidic and basic and thus dimerizes by forming unusual “Y” bonds. The low LUMOs that make both HF and CH_3F acidic are analyzed and compared underlining the distinction between MO nodes that derive from atomic orbitals nodes (AON) and those that are antibonding (ABN). Reaction of HF as an acid with OH- is shown to involve simultaneous bond-making and bond-breaking.
00:00 – Chapter 1. Why So High, Why So Low? The HOMO/LUMO View of Chemical Reactivity
15:19 – Chapter 2. Is BH3 an Acid or a Base?
25:38 – Chapter 3. HOMO-LUMO Mixing for Reactivity and Resonance: The Cases of HF
34:49 – Chapter 4. Comparing HF and CH3F to Distinguish Molecular Orbital Nodes
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Continuing the examination of molecular orbital theory as a predictor of chemical reactivity, this lecture focuses on the close analogy among seemingly disparate organic chemistry reactions: acid-base, SN2 substitution, and E2 elimination. All these reactions involve breaking existing bonds where LUMOs have antibonding nodes while new bonds are being formed. The three-stage oxidation of ammonia by elemental chlorine is analyzed in the same terms. The analysis is extended to the reactivity of the carbonyl group and predicts the trajectory for attack by a high HOMO. This predicted trajectory was validated experimentally by Bürgi and Dunitz, who compared numerous crystal structures determined by X-ray diffraction.
00:00 – Chapter 1. Similarities Among Acid-Base, SN2 Substitution, and E2 Elimination Reactions
15:23 – Chapter 2. The Oxidation of Ammonia by Chlorine in Molecular Orbital Terms
26:05 – Chapter 3. Reactivity of the Carbonyl Group
36:11 – Chapter 4. Dunitz and Burgi’s Experimental Results on Carbonyl Attack Trajectory
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
This lecture completes the first half of the semester by analyzing three functional groups in terms of the interaction of localized atomic or pairwise orbitals. Many key properties of biological polypeptides derive from the mixing of such localized orbitals that we associate with “resonance” of the amide group. The acidity of carboxylic acids and the aggregation of methyl lithium into solvated tetramers can be understood in analogous terms. More amazing than the panoply of modern experimental and theoretical tools is that their results would not have surprised traditional organic chemists who already had developed an understanding of organic structure with much cruder tools. The next quarter of the semester is aimed at understanding how our scientific predecessors developed the structural model and nomenclature of organic chemistry that we still use.
00:00 – Chapter 1. Resonance of the Amide Group
14:16 – Chapter 2. Acidity of Carboxylic Acids
20:46 – Chapter 3. The Aggregation of Alkyl Lithium
41:21 – Chapter 4. Why Wouldn’t Past Organic Chemists Be Surprised?
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
This lecture begins a series describing the development of organic chemistry in chronological order, beginning with the father of modern chemistry, Lavoisier. The focus is to understand the logic of the development of modern theory, technique and nomenclature so as to use them more effectively. Chemistry begins before Lavoisier’s “Chemical Revolution,” with the practice of ancient technology and alchemy, and with discoveries like those of Scheele, the Swedish apothecary who discovered oxygen and prepared the first pure samples of organic acids. Lavoisier’s Traité Élémentaire de Chimie launched modern chemistry with its focus on facts, ideas, and words. Lavoisier weighed gases and measured heat with a calorimeter, as well as clarifying language and chemical thinking. His key concepts were conservation of mass for the elements and oxidation, a process in which reaction with oxygen could make a “radical” or “base” into an acid.
00:00 – Chapter 1. The Predecessors of Chemists: Alchemists
08:50 – Chapter 2. Scheele’s Acids and Elements
19:58 – Chapter 3. On Radicals, Lavoisier, and the Chemical Revolution
29:54 – Chapter 4. The Elementary Treatise of Chemistry: Facts, Ideas, and Words
36:51 – Chapter 5. New Nomenclature: Elements, Calories, and Radicals
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
This lecture traces the development of elemental analysis as a technique for the determination of the composition of organic compounds beginning with Lavoisier’s early combustion and fermentation experiments, which showed a new, if naïve, attitude toward handling experimental data. Dalton’s atomic theory was consistent with the empirical laws of definite, equivalent, and multiple proportions. The basis of our current notation and of precise analysis was established by Berzelius, but confusion about atomic weight multiples, which could have been clarified early by the law of Avogadro and Gay-Lussac, would persist for more than half a century.
00:00 – Chapter 1. The Development of Elemental Analysis: Lavoisier’s Early Combustion and Fermentation Experiments
12:24 – Chapter 2. The Correct Experiment: Early Dealings with Experimental Data
28:05 – Chapter 3. John Dalton’s Proportions and Atomic Theory
37:28 – Chapter 4. Berzelius’s Contributions to Modern Precise Analysis and the Atomic Weight Confusion
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
The most prominent chemist in the generation following Lavoisier was Berzelius in Sweden. Together with Gay-Lussac in Paris and Davy in London, he discovered new elements, and improved atomic weights and combustion analysis for organic compounds. Invention of electrolysis led not only to new elements but also to the theory of dualism, with elements being held together by electrostatic attraction. Wöhler’s report on the synthesis of urea revealed isomerism but also persistent naiveté about treating quantitative data. In their collaborative investigation of oil of bitter almonds Wöhler and Liebig extended dualism to organic chemistry via the radical theory.
00:00 – Chapter 1. Confusion over Silicon Chloride: Discussion on Atomic Weights and Equivalents
06:06 – Chapter 2. Combustion Analysis and the Beginnings of Electrolysis
15:56 – Chapter 3. Dualism: An Organizing Principle
23:07 – Chapter 4. The Honest Experimenter and the Persistent Naivety on Quantitative Data
29:18 – Chapter 5. Ammonium Cyanate, Urea, and the Idea of Isomerism
38:31 – Chapter 6. Wohler, Liebig, and Transmission of Dualism via the Radical Theory
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Work by Wöhler and Liebig on benzaldehyde inspired a general theory of organic chemistry focusing on so-called radicals, collections of atoms which appeared to behave as elements and persist unchanged through organic reactions. Liebig’s French rival, Dumas, temporarily advocated radicals, but converted to the competing theory of types which could accommodate substitution reactions. These decades teach more about the psychology, sociology, and short-sightedness of leading chemists than about fundamental chemistry, but both theories survive in competing schemes of modern organic nomenclature. The HOMO-LUMO mechanism of addition to alkenes and the SOMO mechanism of free-radical chain reactions are introduced.
00:00 – Chapter 1. Benzaldehyde and the Focus on Radicals
12:52 – Chapter 2. Dumas’s “Note on the Present State of Organic Chemistry”
21:39 – Chapter 3. The Mystery of the Chlorinated Candle
34:59 – Chapter 4. Further Development of the Law of Substitution and the Theory of Types
47:35 – Chapter 5. Kolbe and the First Free Methyl Radical
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Youthful chemists Couper and Kekulé replaced radical and type theories with a new approach involving atomic valence and molecular structure, and based on the tetravalence and self-linking of carbon. Valence structures offered the first explanation for isomerism, and led to the invention of nomenclature, notation, and molecular models closely related to those in use today.
00:00 – Chapter 1. Archibald Couper: “Look to the Elements”
10:25 – Chapter 2. Tetravalence and Self-Linking of Carbon
19:39 – Chapter 3. Kekule’s Advancements in Chemical and Molecular Notation
38:32 – Chapter 4. 3-D Molecular Models: From Brass Strips to Croquet-Balls
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Half a century before direct experimental observation became possible, most structures of organic molecules were assigned by inspired guessing based on plausibility. But Wilhelm Körner developed a strictly logical system for proving the structure of benzene and its derivatives based on isomer counting and chemical transformation. His proof that the six hydrogen positions in benzene are equivalent is the outstanding example of this chemical logic but was widely ignored because, in Palermo, he was far from the seats of chemical authority.
00:00 – Chapter 1. How Did Kekule Know Benzene is Hexagonal?
20:10 – Chapter 2. Koerner’s System of Isomer Counting and Chemical Transformation
29:53 – Chapter 3. Koerner’s Assumptions on Replacement and Experimental Distinguishability
34:22 – Chapter 4. The Koerner Equivalence Proof
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Despite cautions from their conservative elders, young chemists like Paternó and van’t Hoff began interpreting molecular graphs in terms of the arrangement of a molecule’s atoms in 3-dimensional space. Benzene was one such case, but still more significant was the prediction, based on puzzling isomerism involving “optical activity,” that molecules could be “chiral,” that is, right- or left-handed. Louis Pasteur effected the first artificial separation of racemic acid into tartaric acid and its mirror-image.
00:00 – Chapter 1. Venturing into 3-D Arrangements of a Molecule’s Atoms
11:41 – Chapter 2. Exchanges between van’t Hoff and Ladenburg on Aromaticity and Chirality
22:58 – Chapter 3. In-Class Observations and Experiments on Chirality
39:14 – Chapter 4. Louis Pasteur’s Artificial Separation of Racemic Acid
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
With his tetrahedral carbon models van’t Hoff explained the mysteries of known optical isomers possessing stereogenic centers and predicted the existence of chiral allenes, a class of molecules that would not be observed for another sixty-one years. Symmetry operations that involve inverting an odd number of coordinate axes interconvert mirror-images. Like printed words, only a small fraction of molecules are achiral. Verbal and pictorial notation for stereochemistry are discussed.
00:00 – Chapter 1. Interpreting the Rotations of Light for Optically Active Compounds
09:25 – Chapter 2. Van’t Hoff’s Proof of the Existence of Chiral Allenes
19:57 – Chapter 3. Superimposition, Mirror Images and Handedness: Chirality in Alice’s Looking Glass
36:24 – Chapter 4. How Special is Chirality?
41:04 – Chapter 5. Conclusion: Exploring Stereochemistry
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
It is important that chemists agree on notation and nomenclature in order to communicate molecular constitution and configuration. It is best when a diagram is as faithful as possible to the 3-dimensional shape of a molecule, but the conventional Fischer projection, which has been indispensable in understanding sugar configurations for over a century, involves highly distorted bonds. Ambiguity in diagrams or words has led to multibillion-dollar patent disputes involving popular drugs. International agreements provide descriptive, unambiguous, unique, systematic “IUPAC” names that are reasonably convenient for most organic molecules of modest molecular weight.
00:00 – Chapter 1. The Development of the Fischer Projections
16:27 – Chapter 2. Diastereomers and Enantiomers in van’t Hoff’s Brochure
23:14 – Chapter 3. Notation Ambiguities and Multibillion Dollar Pharmaceutical Disputes
39:26 – Chapter 4. The IUPAC and the Standardization of Molecular Nomenclature
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Determination of the actual atomic arrangement in tartaric acid in 1949 motivated a change in stereochemical nomenclature from Fischer’s 1891 genealogical convention (D, L) to the CIP scheme (R, S) based on conventional group priorities. Configurational isomers can be interconverted by racemization and epimerization. Pure enantiomers can be separated from racemic mixtures by resolution schemes based on selective crystallization of conglomerates or temporary formation of diastereomers.
00:00 – Chapter 1. Ambiguity in the D/L Genealogical Designations
10:15 – Chapter 2. The Discovery of Tartaric Acid’s Atomic Arrangement and Notation by Priority
24:49 – Chapter 3. The Cahn-Ingold-Prelog Priority Scheme
34:12 – Chapter 4. Racemization and Epimerization
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Within a lecture on biological resolution, the synthesis of single enantiomers, and the naming and 3D visualization of omeprazole, Professor Laurence Barron of the University of Glasgow delivers a guest lecture on the subject of how chiral molecules rotate polarized light. Mixing wave functions by coordinated application of light’s perpendicular electric and magnetic fields shifts electrons along a helix that can be right- or left-handed, but so many mixings are involved, and their magnitudes are so subtle, that predicting net optical rotation in practical cases is rarely simple.
00:00 – Chapter 1. Introduction: Challenges in Isolating Enantiomers Despite Optical Activity
06:09 – Chapter 2. Barron: A Sketch of Lord Kelvin and Chirality
12:35 – Chapter 3. Natural and Magnetic Optical Rotation
20:49 – Chapter 4. Understanding Optical Activity via the Carbonyl Chromophore
37:22 – Chapter 5. Who Cares? Chiral Switches in Life and Drugs
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
The chemical mode of action of omeprazole is expected to be insensitive to its stereochemistry, making clinical trials of the proposed virtues of a chiral switch crucial. Design of the clinical trials is discussed in the context of marketing. Otolaryngologist Dr. Dianne Duffey provides a clinician’s perspective on the testing and marketing of pharmaceuticals, on the FDA approval process, on clinical trial system, on off-label uses, and on individual and institutional responsibility for evaluating pharmaceuticals.
00:00 – Chapter 1. Introduction: The Chemical Properties and Reactivity of Prilosec
06:58 – Chapter 2. The Economics of Clinical Trials
19:57 – Chapter 3. Duffey: How Do I Know that the Drug is Effective?
30:26 – Chapter 4. The Phases of Clinical Trials, Results for Esomeprazole and Omeprazole, and Off-Label Use
42:01 – Chapter 5. Pharmaceutical Marketing Mentality and Q&A
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
After mentioning some legal implications of chirality, the discussion of configuration concludes using esomeprazole as an example of three general methods for producing single enantiomers. Conformational isomerism is more subtle because isomers differ only by rotation about single bonds, which requires careful physico-chemical consideration of energies and their relation to equilibrium and rate constants. Conformations have their own notation and nomenclature. Curiously, the barrier to rotation about the C-C bond of ethane was established by measuring its heat capacity.
00:00 – Chapter 1. Introduction: Legal Implications of Chirality
03:36 – Chapter 2. Methods for Isolating Esomeprazole into a Single Enantiomer
15:14 – Chapter 3. Conformational Isomerism: An Introduction
31:36 – Chapter 4. Newman Projections and Nomenclature for Conformations
37:30 – Chapter 5. Understanding the Barrier to Rotate about the C-C Bond of Ethane
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Why ethane has a rotational barrier is still debatable. Analyzing conformational and configurational stereotopicity relationships among constitutionally equivalent groups reveals a subtle discrimination in enzyme reactions. When Baeyer suggested strain-induced reactivity due to distorting bond angles away from those in an ideal tetrahedron, he assumed that the cyclohexane ring is flat. He was soon corrected by clever Sachse, but Sachse’s weakness in rhetoric led to a quarter-century of confusion.
00:00 – Chapter 1. What is the Source of the Rotational Barrier in Ethane?
06:34 – Chapter 2. Topicity, Reactivity Difference, and Enzyme Specificity
27:49 – Chapter 3. Baeyer’s Strain-Induced Reactivity Theory: Assumptions and Weaknesses
36:42 – Chapter 4. Sachse’s Muddled Insights on Cyclohexane
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Understanding conformational relationships makes it easy to draw idealized chair structures for cyclohexane and to visualize axial-equatorial interconversion. After quantitative consideration of the conformational energies of ethane, propane, and butane, cyclohexane is used to illustrate the utility of molecular mechanics as an alternative to quantum mechanics for estimating such energies. To give useful accuracy this empirical scheme requires thousands of arbitrary parameters. Unlike quantum mechanics, it assigns strain to specific sources such as bond stretching, bending, and twisting, and van der Waals repulsion or attraction.
00:00 – Chapter 1. The 1918 Ernst Mohr Illustrations of Cyclohexane
09:40 – Chapter 2. The Invention of Conformational Analysis
22:24 – Chapter 3. Conformational Animations of Ethane, Propane, and Butane
32:05 – Chapter 4. Molecular Mechanics as an Alternative to Quantum Mechanics
40:13 – Chapter 5. Assigning Strain to Estimate Energy in Bonds
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Professor Barry Sharpless of Scripps describes the Nobel prize-winning development of titanium-based catalysts for stereoselective oxidation, the mechanism of their reactions, and their use in preparing esomeprazole. Conformational energy of cyclic alkanes illustrates the use of molecular mechanics.
00:00 – Chapter 1. Introduction for Professor Barry Sharpless
02:52 – Chapter 2. The Reactivity of Allyic Alcohols and Vanadium-Catalyzed Epoxidations
11:44 – Chapter 3. Research with Katsuki and the Discovery of Combining Titanium with Tartaric Acid
21:10 – Chapter 4. The Mechanism for Asymmetric Epoxidation of Olefins and the Story of Nexium
41:05 – Chapter 5. The Conformation of Rings: Carvone and Cyclohexane
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
Although molecular mechanics is imperfect, it is useful for discussing molecular structure and energy in terms of standard covalent bonds. Analysis of the Cambridge Structural Database shows that predicting bond distances to within 1% required detailed categorization of bond types. Early attempts to predict heats of combustion in terms of composition proved adequate for physiology, but not for chemistry. Group- or bond-additivity schemes are useful for understanding heats of formation, especially when corrected for strain. Heat of atomization is the natural target for bond energy schemes, but experimental measurement requires spectroscopic determination of the heat of atomization of elements in their standard states.
00:00 – Chapter 1. The Limits of Molecular Mechanics Programs
07:32 – Chapter 2. The Cambridge Structural Database and the Demands of Predicting Bond Characteristics
21:36 – Chapter 3. Calculating Chemically Useful Heats of Formation
42:17 – Chapter 4. Measuring Heats of Atomization with Bond Energies
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
After discussing the classic determination of the heat of atomization of graphite by Chupka and Inghram, the values of bond dissociation energies, and the utility of average bond energies, the lecture focuses on understanding equilibrium and rate processes through statistical mechanics. The Boltzmann factor favors minimal energy in order to provide the largest number of different arrangements of “bits” of energy. The slippery concept of disorder is illustrated using Couette flow. Entropy favors “disordered arrangements” because there are more of them than there are of recognizable ordered arrangements.
00:00 – Chapter 1. Chupka and Inghram’s Determination of Graphite’s Heat of Atomization
14:19 – Chapter 2. Calculating Equilibrium Constants from Bond Dissociation Energies
27:55 – Chapter 3. The Boltzmann Factor: How is Temperature Related to Energy?
36:24 – Chapter 4. Entropy and the Tendency toward “Disordered Arrangements”
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.

Freshman Organic Chemistry (CHEM 125)
After discussing the statistical basis of the law of mass action, the lecture turns to developing a framework for understanding reaction rates. A potential energy surface that associates energy with polyatomic geometry can be realized physically for a linear, triatomic system, but it is more practical to use collective energies for starting material, transition state, and product, together with Eyring theory, to predict rates. Free-radical chain halogenation provides examples of predicting reaction equilibria and rates from bond dissociation energies. The lecture concludes with a summary of the semester’s topics from the perspective of physical-organic chemistry.
00:00 – Chapter 1. The Boltzmann Factor and Entropy Against Traditional Views on Society
07:40 – Chapter 2. The Statistical Basis of the Law of Mass Action
13:13 – Chapter 3. Understanding Reaction Rates: The Potential Energy Surface and Collective Energies
29:40 – Chapter 4. Free Radical Halogenations: Predicting Reaction Equilibria and Rates
43:01 – Chapter 5. A Summary of the First Semester
Complete course materials are available at the Open Yale Courses website: http://open.yale.edu/courses
This course was recorded in Fall 2008.