ORGANIC CHEMISTRY 3351

for Chemistry/Biochemistry Majors

Fall 2006, 9:00-9:50 am, EKLC E1B50

Professor Tad Koch

Office: 159 Cristol Chemistry and Biochemistry

Phone: 303-492-6193; e-mail: tad.koch@colorado.edu

Office Hours: T 1:30-2:30, Th 2:30-3:30, or by appointment

Text:   Introduction to Organic Chemistry by Streitwieser, Heathcock and Kosower       4th Edition, Revised Printing 1998, Macmillan

Solutions Manual and Study Guide, 4th Edition, Revised Printing by Bartlett and Koch

Models: Organic Chemistry Models (Molecular Design, Inc.)

Chem 3351 Recitation and Chem 3361 Laboratory must be taken concurrently

Recitation times and rooms are Tue 8:00-8:50 (EKLC E1B75) or Wed 12:00-12:50 (EKLC M203)

Laboratory times and rooms are MW 1:00-3:50 (EKLC M1B25) or TR 9:00-11:50 (EKLC M1B27)

Prerequisite: Chem 1131 or 1171 with a grade of C or better

Link to Undergraduate Organic Chemistry Web Site

Archive of course syllabus 2003 with examples of exams and quizzes from 2002.

Archive of course syllabus 2004 with examples of exams and quizzes from 2003.

Overarching Learning Goals

Ability to write three dimensional structures of organic molecules showing correct bonding, stereochemistry and most favored conformation.

Ability to predict how functional groups will react with various types of reagents:  nucleophiles, electrophiles, acids, bases, oxidizing agents, reducing agents, free radicals.

Ability to determine a molecular structure of an unknown organic compound from spectral data.

Ability to devise schemes for the synthesis of more complex organic compounds from simple organic compounds.

Ability to predict the role of at least some ingredients in complex commercial formulations from labels:  processed foods, cosmetic formulations, and pharmaceutical preparations.

Schedule of Chapters and Testing

Aug. 28 Chapter 1/2: Introduction/Electronic Structure and Bonding; Problems: in-text+1,2,4,5; Focus Problems for Recitation: 2,4,5

Learning Goals:  (1) What is organic chemistry? 

(2) How is bonding in organic molecules described using valence bond theory, by example, i.e. Lewis Structures?  (3) What is resonance and how are resonance structures used to explain bonding, by example?  Be prepared to draw resonance structures and evaluate their relative contribution to a description of the structure. 

(4) How is bonding described using molecular orbital theory and molecular orbital diagrams, by example? (5) What is an antibonding MO and when is one occupied by an electron?  Approximately how much energy is required to cause an electronic transition? 

(6) What are hybrid atomic orbitals and how are they used to explain bonding and geometry?

(7) How are antibonding molecular orbitals used to explain the color of dyes in fabrics?  Why do you feel warm standing in the sun wearing dark colored clothing?  Why does your car become hot sitting in the summer sun with the windows closed?

Aug. 30 Chapter 3: Organic Structures; Problems:  in-text problems + 1,2,5,8,9,12,15; Focus Problems: 5, 9f,15c

Learning Goals:  (1) What are the functional groups and how are they related in terms of the oxidation state of carbon? 

(2) How is a molecular formula determined from combustion analysis and mass spectral molecular mass? 

(3) What are the various types of isomers? 

(4) How do we systematically name organic compounds?

Sept. 1 Chapter 34, pp1179-1185: Introduction to Mass Spectrometry Chapter 34, problem 1; also see chapter on mass spectrometry in Handbook for Organic Chemistry Lab and MS section of the Organic Chemistry Lab web site.

Power Point Lecture for Chapters 3 and 34 Mass Spectrometry

Learning Goals:  Mass spectrometry gives a precise measure of the molecular mass of an unknown molecule.  A precise molecular mass gives the molecular formula.

(1) How does a mass spectrometer determine molecular mass?  (2) How can a molecular formula be obtained from an exact mass measurement?  (3) What is the difference between an exact mass and an average molecular weight?  (4) How is an exact mass calculated from a molecular formula and atomic weight data, by example?

(5) How might mass spectrometry be used to distinguish between natural and synthetic testosterone in the urine of an athlete?  The technique is isotope ratio MS and an example where it was used is the recent Tour de France.

Sept. 4 Labor Day Holiday

Sept. 6 Chapter 4: Organic Reactions; 2003; Problems:  in-text + 3,4,6,8,10a,13; Focus Problems:  3,10a,13; 2004 Quiz #1; answer key

Learning Goals:  The favorability of a reaction is controlled by its thermodynamics and kinetics.  Thermodynamics controls how far the reaction will proceed to the right in the balanced equation when it reaches equilibrium, and kinetics controls how rapidly it will proceed to that equilibrium.  Favorable reactions release energy and occur quickly.  A reaction can be described as quite favorable if it gives a good yield of product (80 to 90%) in 1 to 3 hrs at temperatures below 100 0C.

(1) For a simple reaction A goes to B that proceeds to 80% B at equilibrium, what is the equilibrium constant K?

(2) How do we define standard states of compounds and elements?  (3) What is the mathematical relationship between free energy change (DG), standard free energy change (DG0), and the equilibrium constant (K) for a reaction?  (4) What is the mathematical relationship between standard free energy change (DG0), enthalpy change (DH0), and entropy change (DS0) and how can these changes be used to predict whether a reaction will be favorable, i.e. give a high yield of product?  (5) What is the entropy of mixing and what role does it play in reaction thermodynamics?

(6) What is the relationship between rate and rate constant (k)?  Write the differential forms of first and second order rate equations.  (7) Integrate the differential form of the first order rate equation.  How can the resulting equation be used to determine the rate constant k?  (8) Under what condition is a second order reaction described as pseudo first order?  Why might the kinetics of a second order reaction be measured under pseudo first order conditions?  (9) What is the free energy of activation (DG‡) for a reaction and what is the relationship between DG‡ and k? 

(10) How are the thermodynamics and kinetics of a reaction described using a reaction co-ordinate diagram?  Explain by example.  Show starting material, transition state, and product.

(11) What is the relationship between acidity, basicity, and pKa?  (12) How is acidity related to electronegativity?

Sept. 8 Free Energy Change: "Delta G"; Power Point Presentation of Free Energy Change; Quiz #1

Sept. 11

Sept. 13 Chapter 5: Alkanes; Problems:  in-text+ 1,2,5,7,9,10,12,14; Focus Problems:  5, 9, 10; 2004 Quiz #2; answer key

Learning Goals:  The energy barrier to rotation about C-C single bonds in a molecule is low, 3 to 10 kcal/mol, and consequently, rotation about C-C bonds is occurring rapidly at room temperature.

(1) What is a conformation, how are conformations represented using Newman Projections, and how is the potential energy of a conformation related to its structure? (2) What is the standard enthalpy of formation (DHf0) for a compound and how is it used to determine the favorability of a reaction and the strain energy of a cyclic compound such as cyclopropane? 

(3) How do we explain the bonding in cyclopropane where bond angles and intra-orbital angles appear to be severely mismatched? 

(4) How can the low energy conformation of cyclohexane be drawn with a chair structure showing axial and equatorial hydrogens?

Sept. 15 Quiz #2

Sept. 18

Sept. 20 Chapter 6: Reactions of Alkanes; Problems: in-text+ 2,4,6,9,12; Focus Problems: 2,6,12; 2004 Quiz #3; answer key

If you haven't made flashcards or if you don't like yours, try these from Ohio State University; however, home made is usually better.

Learning Goals:  (1) Define bond dissociation energy DH0 and average bond energy.  Approximately how strong is a C-C bond?  A C-H bond?  (2) What is a free radical and how is its stability related to bond dissociation energy?  (3) How is DHf0 for a free radical calculated from standard heats of formation and bond dissociation energies? 

(4) Write the mechanism for the free radical halogenation of a hydrocarbon in terms of initiation, propagation, and termination steps.  (5) Define regioselectivity.  How is the favorability and/or regioselectivity of the free radical halogenation reaction controlled by bond dissociation energies? 

(6) Define heat of combustion.  How are heats of combustion used to determine heats of formation, by example?

(7) How are average bond dissociation energies used to predict the favorability of a reaction when heats of formation are not available?

(8) What is oxidative stress?  What is a radical scavenger or anti-oxidant?

Sept. 22 Power Point Lecture for Chapter 6; Quiz #3

Sept. 25

Sept. 27 Review:  Power Point for Review Sheet; 2004 Exam #1:  page 1, page 2, page 3; answers:  page 1, page 2, page 3

Sept. 28 Exam #1, 7-9:00 pm, Location: HLMS 252

Sept. 29 Chapter 7: Stereoisomerism

Learning Goals:  (1) Define stereoisomer, stereo center, chirality (chiral vs. achiral), enantiomer, diastereomer, and racemic mixture (racemate).  (2) What physical property distinguishes enantiomers?  Define dextrorotatary (d, +) and levorotatory (l, -).  (3) What is a polarimeter and how does it work?  (4) Define optical activity and specific rotation. 

(5) For a given molecular connectivity, draw all the possible stereoisomers using wedges and dashes formalism.  (6) How are enantiomers, diastereomers, and meso compounds distinguished by molecular symmetry (C2, s, i or S2, and S4) for both cyclic and acyclic compounds? 

(7) How are stereoisomers named using R and S nomenclature? 

(8) Describe the stereochemistry of the product or products from a reaction of an achiral compound with an achiral reagent that produces a chiral product. 

(9) Why is your nose able to distinguish some enantiomers?  Why do enantiomers of some compounds have different pharmaceutical activity and/or side effects?

(10) Draw Newman projections of chair conformations of monosubstituted cyclohexanes and order their relative energies.

Oct. 2 Problems: in-text+ 1,2,3,4,5,8,9,12,16,17; Focus Problems: 2,3,12

Oct. 4 Some consequences of stereoisomerism; for more about thalidomide and stereochemistry

Oct. 6 Chapter 8: Alkyl Halides and Organometallic Compounds

Learning Goals:  (1) Define van der Waals radius of an atom.  (2) Define dipole moment of a molecule.  (3) How is boiling point of a liquid compound related to molecular size, van der Waals radius of constituent atoms, and dipole moment? 

(4) What is an organometallic compound?  Give important examples with structures and names and describe the bonding.  What is a Grignard reagent?  (5) What is a three center two electron bond and when is it important for describing bonding? 

(6) How are organometallic compounds synthesized?  Explain in terms of electronegativity of the metal.  (7) What is the product of reaction of an organometallic with H2O, with D2O?  Explain exothermicity of the reaction in terms of electronegativity of the metal.

(8) Why dose the FDA (Food and Drug Administration) recommend against high dietary consumption of some seafood such as swordfish and tuna fish, especially by children?

Oct. 9

Oct. 11 Problems: in-text + 1,3,4,6,7,8; Focus Problems: 3,7,8; 2004 Quiz #4; answer key

Oct. 13 Quiz #4; Chapter 9: Nucleophilic Substitution

Learning Goals:  (1) Define nucleophile, nucleophilicity and leaving group.  What is the relationship between nucleophilicity and basicity?  Nucleophilicity and polarizability? What determines how good the leaving group is?  

(2) Using the curved arrow formalism for the migration of electron pairs, write a mechanism for the SN2 reaction that explains second order kinetics and inversion of configuration.  Draw the transition state and the reaction co-ordinate diagram for the reaction.  (3) How and why does substrate structure affect the rate of the SN2 reaction? 

(4) Using the curved arrow formalism, write the mechanism for the E2 reaction.  Draw a reaction co-ordinate diagram.  When will the E2 reaction compete with the SN2 reaction? 

(5) What is a carbocation and what determines its relative stability?  (6) Using the curved arrow formalism, write the mechanism for the SN1 reaction that explains first order kinetics and racemization of configuration.  Draw a reaction co-ordinate diagram for the reaction.

(7) Using the curved arrow formalism, write the mechanism for the E1 reaction.  Draw a reaction co-ordinate diagram.  When will the E1 reaction compete with the SN1 reaction? 

(8) Using your knowledge of the four mechanisms (SN2, E2, SN1, and E1), predict the products and mechanism for a given set of reagents and reaction conditions.

(9) Based upon carbon-halogen bond strengths, substitution of chloride for iodide to form a primary iodoalkane is highly endothermic (Chapter 6); however, reaction of 1-chlorobutane with sodium iodide in acetone solvent gives a good yield of 1-iodobutane.  Explain.

Oct. 16 Problems: in-text+1,2,3,5,6,7,8,13,16; focus 2,8,16

Oct. 18 2004 Quiz #5; answer key

Oct. 20 Quiz #5; Chapter 17, Infrared Spectroscopy; Problems: in-text (minus those involving NMR)+1,8; focus 1,8

Learning Goals:  Infrared Spectroscopy measures the specific frequencies of infrared radiation absorbed by a compound.  Because different functional groups absorb at different frequencies, this information is used to help establish the functional groups present in a molecule of unknown structure. 

(1) What is a vibrational transition and approximately how much energy is required to cause a vibrational transition?  What region of the electromagnetic spectrum causes vibrational transitions?  (2) Illustrate with an NH2 group in a molecular structure allowed stretching and bending modes of vibration.  (3) What properties of a bond or set of connected bonds determine the frequency of a stretching vibrational transition?  The intensity of the transition?  (4) How and why does ring strain affect the stretching frequency of the carbonyl group of a cyclic ketone?

(5) Using your knowledge of infrared spectroscopy, assign the stretching bands that appear in the infrared spectrum for a given compound.  (6) Predict the functional groups that are present in an unknown compound from its infrared spectrum.

Oct. 23 Chapter 11 in Handbook for O-Chem. Laboratory (IR Spectroscopy or web site) ("IR Tutor" software is available through the undergraduate organic lab).

Oct. 25 Review, Stereochemistry (Road Map), SN2, E2, SN1, E1 (Road Map), Alkyl halides; 2004 Exam #2: page 1, page 2, page 3; answer key: page 1, page 2, page 3.

Oct. 26 Exam #2, 7-9:00 pm, Location:  HLMS 252

Oct. 27 Chapter 10: Alcohols and Ethers

Learning Goals:  (1) Give a systematic name for a compound that bears an alcohol functional group or an ether functional group or a common name for a simple alcohol or ether. 

(2) Why does an alcohol have a higher boiling point than an ether with the same molecular formula? 

(3) Using your knowledge of nucleophilic substitution and elimination reactions from Chapter 9, discuss the pros and cons of synthesizing 3-methylbutanol from 1-bromo-3-methylbutane by reaction with sodium hydroxide versus reaction with sodium acetate followed by reaction with sodium hydroxide. 

(4) Why are alcohols more acidic than hydrocarbons?  What is the approximate pKa of a simple alcohol? 

(5) t-Butyl methyl ether can be synthesized by reaction of potassium t-butoxide with iodomethane but not by reaction of sodium methoxide with t-butyl bromide.  Why? 

(6) Bromoethane can be prepared by reaction of ethanol with HBr but not by reaction with NaBr.  Why?  Think about bond strengths. 

(7) Compare the various methods for converting alcohols to alkylhalides in terms of mechanism, control of stereochemistry, rearrangement, and the competition between substitution and elimination.  Reagents:  HBr, HCl/ZnCl2, PBr3, SOCl2, or PhSO2Cl/pyridine followed by halide ion. 

(8) What is a carbocation, and why is the stability of carbocations as follows:  tertiary more stable than secondary more stable than primary?  (9) Illustrate how carbocation rearrangement can affect the reaction of an alcohol with HBr to form an alkylbromide. 

(10) What chromium reagents are used to oxidize alcohols to aldehydes, ketones, and carboxylic acids.  How are aldehydes selectively synthesized by oxidation, preventing further oxidation to carboxylic acids?  Be prepared to balance one of these Cr(VI) redox reactions.

(11) Why is an ether a good solvent for a chemical reaction? 

(12) What are crown ethers and how are they used?

Oct. 30 Problems: in-text+1,2,8,9,10,11,14,17,21; focus: 9,10,21

Nov. 1  Charles Pedersen of the Du Pont Company shared the 1987 Nobel Prize in Chemistry for his discovery of crown ethers. You can view his Nobel address on the web. You may need to open Adobe Acrobat Reader first.

Nov. 3 Chapter 11: Alkenes

Learning Goals:  (1) Give a systematic name to a compound that bears an alkene functional group.  Indicate stereochemistry using E/Z designation. 

(2) Illustrate the synthesis of an alkene using a substrate and conditions that favor the E2 reaction from Chapter 9.  (3) Illustrate the Saytzeff Rule in the synthesis of alkenes from an appropriate alkyl halide.  What is the mechanism? 

(4) Provide an example of catalytic hydrogenation of an alkene that illustrates the preferred stereochemistry. 

(5) Give examples with mechanism that illustrate the regiochemistry and stereochemistry of the following reactions of alkenes:  electrophilic addition of Br2, electrophilic addition of HOCl, oxymercuration/demercuration, and hydroboration/oxidation.  (6) What is the Markovnikov rule?  Illustrate with electrophilic addition of HBr. 

(7) What is a carbene?  A carbenoid?  How are they formed and how do they react with an alkene? 

(8) Illustrate anti-Markovnikov addition of HBr to an alkene showing the mechanism.  Why does this reaction occur with HBr and not with HCl?  Think about bond energies. 

(9) Illustrate reaction of alkenes with the following oxidizing agents showing stereochemistry when appropriate:  cold KMnO4, OsO4, O3 and m-chloroperbenzoic acid.

(10) What is a trans fat?

Nov. 6 Problems: in-text+2,4,5,6,7,9,10,11,12,22; focus: 6,10,12

Nov. 8 2004 Quiz #6; answer key

Nov. 10 Quiz #6; Chapter 13: Nuclear Magnetic Resonance Spectroscopy, NMR tutorial, IR and NMR Spectra on the web, NMR Lectures

Learning Goals:  NMR spectroscopy measures the specific frequencies of nuclear spin transitions.  Important nuclei are 1H for proton NMR and 13C for carbon NMR.  The frequencies are a function of the molecular environment of the hydrogens and carbons in a molecular structure.   Consequently, the spectrum gives information about the number of hydrogens and carbons in a compound and how those hydrogens and carbons are bonded together.  NMR spectroscopy complements IR spectroscopy for determining the structure of an unknown organic compound.

(1) In an NMR experiment, what is the relationship between the applied magnetic field and the frequency of a nuclear magnetic spin transition?  Why is an NMR spectrometer running at 500 MHz more sensitive than one running at 300 MHz?  A more sensitive spectrometer can obtain a spectrum with less compound.

(2) If we know the molecular formula of an unknown compound from mass spectrometry, how do the carbon and proton NMR spectra tell us about molecular symmetry?  What do we mean by the carbon count? 

(3) What does integration of the spectrum mean?  What information do we obtain from integration of the proton spectrum?  The carbon spectrum?

(4) What is meant by the term chemical shift?  What does it tell us about molecular structure?  Explain the terms upfield and downfield.  How do electronegative substituents affect chemical shift?  π-bonds affect chemical shift?

(5) How does proton-proton J coupling affect the appearance of a proton NMR spectrum?  Proton-carbon J coupling affect the appearance of a carbon NMR spectrum?  What do we learn from proton-proton coupling? Proton-carbon coupling?

(6) What is the n+1 rule?  The 2nI+1 rule?  When do protons J couple to each other?  And when don’t they J couple.

(7)  What is the relationship between the magnitude of vicinal J-coupling and dihedral angle?  Geminal J-coupling and bond angle?

(8) Why are chemical shifts reported in parts per million relative to TMS and J coupling constants in Hz?

(9) Be prepared to assign the hydrogens in a molecular structure to signals in its proton NMR spectrum.  Be prepared to draw a molecular structure consistent with a given proton NMR spectrum.

(10) What is the relationship between NMR spectroscopy and MRI?

Nov. 13 Chapter 18 in Handbook for O-Chem. Laboratory (NMR Spectroscopy); Problems: in-text+3,4,6,7,8,9,11,12,17; focus: 3,8,12

Nov. 15 Review, Synthesis Study Sheet, IR Review, Alcohols and Alkenes, NMR page 1, page 2; 2004 Exam #3: page 1, page 2, page 3; answer key: page 1, page 2, page 3

Nov. 16 Exam #3, 7-9:00 pm, Location:  HLMS 252