@ 1974 - Linda M. Sweeting, revised LMS 1978, 1980, 1987, 1989, 1991, 1993, 1995, 1996, 2000, 2001

A. Good Reference Books
 

• Organic Chemistry, Ralph J. Fessenden, Brooks/Cole, Pacific Grove, CA, 1998
• Organic Chemistry, George H. Schmid, Mosby-Year Books, St. Louis, 1996.
• Organic Chemistry, 6th Edition, R. T. Morrison & R. N. Boyd, Allyn and Bacon, Inc., Boston 1992
• Organic Chemistry, 2nd ed, K. P. C. Vollhardt and N. E. Schore, Freeman, San Francisco, 1994

All of the handouts and enrichment materials mentioned in this study guide are now available on line, most as Adobe Acrobat files; link from the lecture schedule or the master list.

C. Basic Study Tips

Organic Chemistry will challenge your study habits and force you to improve them. There are several simple things you can do to ensure success in Organic Chemistry.

1. NEVER get behind. Read ahead using the class schedule provided. Review after every class, comparing text and notes

2. USE the resources you have available to you, such as:

• your textbook and its problems
• solutions manual and study guide
• previous exams available for your use
• Chemistry tutoring center
• your instructor
• this study guide
• your classmates

4. MINIMIZE MEMORIZATION by learning and understanding the mechanisms of the reactions. Chemical reactions are all driven by one thing - electrostatic attraction: positive sites in one molecule attract negative sites in another (and vice versa). Whether a reaction occurs and what the outcome is follows mostly predicatable patterns. The better you understand the simple concept of electrostatic attraction underlying all the mechanisms of chemical reactions, the simpler your learning task will be.

Use of this Study Guide

This study guide is designed to help you identify and understand the important concepts in the course. Since the list of learning goals is designed to be textbook-independent and very complete, not all topics will be presented each semester. You are only responsible for those identified by your instructor by class presentation or text assignment. As you study, you might want to check off the reactions that do appear in your text or classes so that you can tell at a glance what reactions are not included in this semester's course.

Initially the course deals with a lot of structural features of organic (and inorganic) molecules. The best way to study these topics is to make models (the instructor will recommend several) and drawings, using the text problems and old exams as a guide. You must practice both recalling and sketching the structural features. The nature of the course changes about half way through the first semester to emphasize chemical reactions of functional groups while relying on the structural features you learned in the first part.

This guide is organized strictly by functional group, with structural features incorporated as they are needed, and thus is not the same as the lectures or text. This order makes it easy to find things, but does not correspond exactly to the order in any semester. Use the Study Guide as a reference list of things to learn. Use the lectures as a guide for the connections between topics and the importance of individual topics - I will spend more time on something that is more difficult than on something that is less difficult, but equally important, especially during the first semester.

The problems listed as "representative" are chosen from those at the end of the chapter to give you a sampling. If you can do these quickly and easily without reference to the text, you understand and remember the content of the chapter pretty well. If they give you any difficulty, do the other problems in your text and study guide; you can never overdo, but be honest with yourself about your recall and understanding. Other textbooks provide additional problems, esp. McMurry and Fessenden. The text problems progress from simple drills to those requiring thought; you can expect both kinds on exams. If you have difficulty with a problem, attempt those before it before going on to the more complex ones. Don't be shy about asking for help at any stage.

Each person has a different learning style. What seems logical to your instructor or your text may not seem logical to you. Therefore, I have included in this guide references to other texts that are accurate and that many find clear in their presentation. These books and others are available in the TSU library or the Chemistry tutoring center. You need to try a lot of different study techniques to find which ones work best for you - group discussions, making summaries, doing problems, etc. Most students find the following method helpful for learning reactions: using memory, text and notes, identify the reactions of each functional group and the reactions which can be used to synthesize each functional group; summarize these on individual sheets of paper (with specific examples) or on cards (again with specific examples); work problems in the text and on old exams, after you have prepared these summaries, but DO NOT refer to them unless you get stuck (this provides a test of what you remember); use the sheets you have made to review once more for exams. Several of the texts and your instructor provide summaries of reactions for you; use these to check yours, but make the most of the process of summarizing by trying to do it without the text. Note that different texts may have different reagents to accomplish the same transformation: each author chooses a slightly different subset of all the reactions which are used in organic synthesis, but most will correspond to your text.

A note about making your own summaries. There are three basic techniques:

• Simple lists, with generalized reaction and example, synthesis of alcohols (for example) on one page, reactions of alcohols on another page. This is the way most texts summarize.
• Connectivity sketches, with an alcohol (for example) in the center and a spider-web-like sketch with arrows showing all the things they can be converted to (and how) and/or made from (and how. This is a graphic version of 1. and corresponds nicely to the layout of problems.
• Flash cards, with reagents on one side and products on the other. You can design these so that they serve as test and review for both reactions and synthetic techniques.

REFERENCES
Source	Chapters	Dr. Sweeting's Enrichment Handouts
McMurry	1,2	Formal Charge
Schmid	1,3
Fessenden	1,2
Morrison and Boyd	1
Vollhardt	1

REPRESENTATIVE PROBLEMS in McMurry 6
Chapter 1	24,  26, 27, 28, 29 30, 32 36, 39, 41, 44, 45, 46, 47
Chapter 2	27, 28, 29, 30, 31, 35, 36, 37, 40, 43, 44, 45, 55, 56

LEARNING GOALS:

• For many of you, these chapters will be a basic review of your introductory chemistry courses; the review is needed to make sure that everyone has the same conceptual background.

2. Show in a sketch how the sp3, sp2 and sp hybrid orbitals may be constructed from the simple atomic orbitals.

3. Explain the bond angle for the hydrides of all the elements through F using both the VSEPR and hybridization models.

4. Deduce molecular formula from composition and molecular weight.

5. Calculate the formal charge on an atom in a small molecule.

6. Predict the direction and relative magnitudes of the dipole moments of simple molecules.

7. Sketch a reasonable set of molecular orbitals for any 2-carbon molecule, showing the mathematical signs of the lobes and approximate relative energies.

8. Describe the molecular events occurring during melting and boiling for ionic and covalent compounds and molecular crystals like diamond.

9. Predict the relative solubilities, melting points, boiling points and relative acidities and basicities of simple compounds and explain your choice with reference to structure.

10. Explain by words and equations the factors affecting the rate of a chemical reaction.

11. Identify the major functional groups and types of reactions.

12. Calculate the pH of a solution of a weak acid or base from the analytical concentration and Ka.

13. Calculate the concentrations of components in a chemical equilibrium from the equilibrium constant and analytical concentrations.

REFERENCES
McMurry	12, 13, 14
Schmid	5, 10, 18.13-18.16, 19.15
Fessenden	9, 22
Morrison & Boyd	16
Vollhardt & Schore	10, 11, 20
specialized texts listed in laboratory syllabus

REPRESENTATIVE PROBLEMS in McMurry 6
Chapter 12	16, 17, 23, 25, 27, 29, 37, 38, 39, 41, 42, 48, 49
Chapter 13	31, 32, 36, 43, 46, 47, 48, 49, 50, 51, 52, 53, 55, 56,  57, 58, 59
Chapter 14	46, 47

LEARNING GOALS:

ULTRAVIOLET/VISIBLE

1. Explain the effect of conjugation on the absorption wavelength by sketching the relative energies (and occupancies) of several alkenes.

2. Identify and use the terms chromophore, extinction coefficient, wavelength at maximum, forbidden transition, pi - pi *, n - pi*.

3. Use resonance to provide a simple explanation for color differences among similar compounds.

4. Use the UV-VIS spectrum of a compound to assist in determining its structure.

INFRARED

1. Use the characteristic absorption frequencies (list provided) of functional groups to assist in determining the structure of an unknown compound.

2. Use some "fingerprint region" absorptions, such as the CH out-of-plane bending of aromatic rings to assist in determining the structure of an unknown compound.

3. Describe the molecular transitions responsible for the infrared absorption.

4. Briefly explain why some infrared absorptions are much stronger than others and why isotopic substitution affects the absorption frequency.

NUCLEAR MAGNETIC RESONANCE - PROTON

1. Identify the number of different kinds of protons in an unknown compound from its proton NMR spectrum and assign those different kinds of protons to likely chemical environments.

2. Identify the relative numbers of each of the different kind of protons in an unknown, using integration curves (or shrewd guesswork) and/or the formula of the unknown.

3. Identify the presence (and number) or absence of neighboring protons for each different kind of proton (coupling).

4. Distinguish spectral information from solvent and standard reference NMR signals.

5. Predict the appearance of an NMR spectrum from its structure (number, size and multiplicity of absorptions).

5. Use the proton NMR spectrum to assist in determining the structure of an unknown compound.

6. Use and identify the following terms: coupling, chemical shift, integration, intensity, TMS, doublet, triplet, quartet, multiplet, noise.

7. Explain the reason for doublet, triplet and quartet coupling patterns, both multiplicity and intensity.

NUCLEAR MAGNETIC RESONANCE - CARBON-13

1. Identify the number of different kinds of carbons in an unknown compound from its proton noise-decoupled 13C NMR spectrum and assign those different carbons to likely chemical environments.

2. Distinguish solvent and reference NMR signals from that of the sample.

3. Use the proton noise-decoupled 13C NMR spectrum to assist in the determination of the structure of an unknown compound.

4. Predict the appearance of the proton noise-decoupled 13C NMR spectrum from the structure of a compound.

5. Use the relative intensity of the signal to provide structural information about an unknown compound (why do NMR spectra seldom have peaks of equal intensity for equal numbers of carbons?)

6. Use the proton-coupled or off-resonance decoupled spectrum to assist in the determination of the structure of an unknown.

7. Explain some advantages of (pulsed) Fourier transform spectroscopy has over scanning spectroscopy (also applies to IR and proton NMR). Explain why 13C spectra take longer to obtain that 1H spectra.

MASS SPECTROMETRY

1. Using a low resolution mass spectrum, identify the peak most likely to be the molecular ion.

2. Explain and use the difference between the mass of the molecular ion and the molecular weight calculated from the periodic table.

3. Recognize the presence of Cl and Br in a compound from its mass spectrum.

4. Use several characteristic daughter ions, e.g. 77, 91, to determine features of the structure of a compound from its mass spectrum.

5. Use the mass spectrum of an unknown compound to assist in determining its structure.

6. Use and identify the following terms: molecular ion, daughter ion, base peak, fragmentation; describe the fate of a molecule analyzed by mass spectrometry.

REFERENCES
Source	Chapters	Dr. Sweeting's Enrichment Handouts
McMurry	3, 4, 9	IUPAC Nomenclature of Hydrocarbons
Schmid	2, 4, 6	Petroleum
Fessenden	3, 4	Nomenclature of Stereoisomers
Morrison & Boyd	2, 3, 4, 10, 13	Using Your Head and Hands
Vollhardt & Schore	2,3,4,5	Terminology for Isomers

 

REPRESENTATIVE PROBLEMS in McMurry 6
Chapter 3	24, 27, 31, 39, 42, 44, 45, 46, 47, 49, 51, 52
Chapter 4	24, 27, 28, 29, 33, 34, 35, 36, 37, 39, 40, 55
Chapter 9	31, 34, 38, 39, 41, 45, 46, 50, 51, 54, 57, 63, 65, 81, 82

LEARNING GOALS

1. Name by the IUPAC system any saturated hydrocarbon whose parent chain contains 10 or fewer carbon atoms and no more than two simple rings (or sketch the hydrocarbon given its IUPAC name).

2. Sketch the conformations of ethane, propane, butane, cyclobutane, cyclopentane and cyclohexane and simple substituted compounds derived from them.

3. Describe (graphically and verbally) the relation between conformation and potential energy for ethane, propane and butane and closely related compounds (Newman projections).

4. Describe (graphically and verbally) the relation between conformation and potential energy for cyclohexane.

5. Calculate the relative energies of disubstituted (e.g. methyl) cyclohexanes, assuming chair conformations and using the relative energies of monosubstituted cyclohexane or butane.

6. Define and recognize stereoisomer, enantiomer, diastereomer, conformation, configuration, meso, epimer, resolution.

7. Given their structures, state whether 2 compounds are enantiomers or diastereomers or some other kind of isomer.

8. Predict the number of stereoisomers of a compound of known bonding.

9. Sketch a molecule with a chiral center so as to show unambiguously the configuration using both Fisher projection and perspective drawing.

10. Determine the configuration (R or S) of any chiral center from a Fischer projection, perspective drawing, cyclohexane framework or molecular model. NOTE: prerequisite: recognize chirality.

11. Predict from the structure whether a pair of stereoisomers can be interconverted by a conformational change and thus might not be separable.

12. Calculate specific rotation from the experimental rotation and concentration.

13. Define and recognize inversion, retention and racemization.

14. Draw conclusions about the mechanism of a reaction from the stereochemistry.

15. Given a proposed mechanism for a reaction, predict the stereochemistry.

16. Define and recognize regioselective, stereoselective and stereospecific reactions.

17. Describe a common method of resolution of a racemic modification.

19. Outline a synthesis (several steps) of a hydrocarbon using halogenation and metal reductions.

20. Outline syntheses of cyclopropane compounds using carbene-generating compounds.

SEE Unit IV for E / Z.

REFERENCES
Source	Chapters	Dr. Sweeting's Enrichment Handouts
McMurry	5, 6, 7, 8, 14, 30	IUPAC Nomenclature of Hydrocarbons
Schmid	7, 8, 9, 19	Nomenclature of Stereoisomers
Fessenden	10, 16.1 - 16.3	Determination of Mechanisms
Morrison & Boyd	8, 9, 10, 11, 12, 28, 31	Writing Mechanisms
Vollhardt & Schore	11, 12, 13, 14	Polymers and Plastics (Addition)

REPRESENTATIVE PROBLEMS in McMurry 6
Chapter 5	23, 242, 37, 38, 39, 40, 41, 42
Chapter 6	27, 29, 30, 39, 40, 42, 43, 44, 49
Chapter 7	23, 24, 25, 26, 30, 31, 36, 40, 41, 43, 51
Chapter 8	19, 20, 21, 22, 23, 24, 27, 28, 34, 38, 41, 43
Chapter 14 Chapter 30	20, 21, 27, 29, 30, 33, 40, 48,  49 16, 17, 20, 29, 36

 LEARNING GOALS

ALKENES

1. Sketch the molecular orbitals (bonding and antibonding) for ethene and their relative energies.

2. Name by the IUPAC system any alkene whose parent chain contains 10 or fewer carbon atoms and sketch the alkene given its IUPAC name.

3. Define, recognize and name alkene diastereomers (Z/E, cis/trans); predict the direction of the difference in their physical properties and chemical stability.

4. Outline the synthesis of a given alkene from an alkyl (di)halide, alcohol, alkyne or alkane (including stereochemistry).

5. Write chemical equations to describe the currently accepted mechanism(s) of dehydrohalogenation of an alkyl halide (including stereochemistry). Explain how this mechanism is deduced from the experimental data.

6. Write chemical equations to describe the currently accepted mechanism(s) of dehydration of an alcohol (including stereochemistry). Explain how this mechanism is deduced from the experimental data.

7. Describe the evidence for the existence of carbocations and their relative stabilities.

8. Predict and recognize simple carbocation rearrangements (H, CH3, C6H5).

9. Predict the alkenes formed by elimination reactions of given starting materials.

10. Predict the products or use in a synthetic plan the following reactions of alkenes (including stereochemistry): catalytic hydrogenation, addition of halogen and hypohalite, addition of hydrogen halide, addition of water, oxymercuration, addition of carbocations (polymerization and alkylation), hydroxylation, epoxidation, addition of carbenes, hydroboration, ozonolysis.

11. Use the molecular formula, and oxidation and reduction reactions to deduce structural features of an alkene.

12. Write chemical equations to describe the currently accepted mechanism of addition of halogens to alkenes (including stereochemistry). Explain how the mechanism is deduced from the experimental data.

13. Write chemical equations to describe our current understanding of the mechanism of addition of acids (HX, H3O+, H2SO4) to alkenes. Explain how the mechanism is deduced from the experimental data.

14. Using a reasonable mechanism for the reaction, explain why the orientation of addition of HBr is sometimes "anti-Markovnikov" and what experimental evidence exists for the explanation.

15. Write the mechanism for the acid-catalyzed addition of an alkene to itself. Do the same for free radical addition.

16. Describe the structure and uses of several alkene and diene polymers such as PVC and rubber (natural and synthetic).

17. Identify the structural features characteristic of a terpene.

CONJUGATED ALKENES -- DIENES

18. Use allylic halogen substitution as part of a synthetic outline, (distinguish conditions yielding ionic addition and free-radical substitution).

19. Write contributors to the resonance hybrid for simple systems such as allyl radical (cation), carbonate, nitro.

20. Sketch the pi molecular orbitals of butadiene and allyl and indicate their relative energies in a sketch.

21. Predict the products, in order of relative amount, of the addition of halogen or acid to a diene; give an explanation of the effect of temperature on the product distribution.

22. By considering the mechanism and the stabilities of intermediates, explain the differences between the reactions of conjugated double bonds and isolated double bonds.

23. Outline the mechanism and stereochemistry of the Diels-Alder reaction (use lecture as a guide for detail).

ALKYNES

24. Predict the products and use in a synthetic scheme the following reactions of alkynes: addition of hydrogen, halogen, hydrogen halides, water, boron hydrides, and salt formation with very strong base or reducing metals.

25. Outline a synthesis of an alkyne from an alkene, alkyl halide, dihalide or tetrahalide; outline the synthesis of an internal alkyne from a terminal alkyne.

26. Predict products and stereochemistry of a Diels-Alder reaction. Make a sketch of a reasonable transition state for this reaction.

27. Advanced topic: Describe the influence of orbital symmetry on cyclizations (such as the Diels-Alder reaction) and rearrangements of alkenes and polyenes.

28. Explain the origin of the absorption of UV and visible light by alkenes (refer to the molecular orbitals) and use the spectrum to determine structural features.

29. Describe the effect of light as a reagent for unsaturated compounds.

30. Identify a simple alkene from NMR and IR information.

REFERENCES
Source	Chapters	Dr. Sweeting's Enrichment Handouts
McMurry	10, 11	Determination of Mechanisms
Schmid	12,18	Chlorinated Hydrocarbons and Pollution
Fessenden	5,6	Substitution and Elimination Reactions
Morrison & Boyd	5, 7
Vollhardt & Schore	6, 7

REPRESENTATIVE PROBLEMS in McMurry 6
Chapter 10	18, 20,  21, 22, 23, 32, 33, 35, 37, 42
Chapter 11	25, 26, 29, 34, 35, 36, 40, 45, 50, 52, 57, 58, 65

LEARNING GOALS:

1. Name any alkyl halide whose parent chain is 10 carbons or less by the IUPAC system and sketch an alkyl halide given its IUPAC name or alkyl name.

2. Write the mechanism for halogenation of methane. Describe the experiments from which the mechanism was deduced and the reasoning which lead to the mechanism.

3. Calculate bond dissociation energies and heats of reaction given the energies for various steps and draw mechanistic conclusions from this energy data (similarly heats of activation).

4. Given energy data (or relative rate data) and other experimental information about a reaction, sketch a graph of energy vs. reaction progress.

5. Predict the products (including order of abundance) of halogenation of an alkane and explain your choice by reference to the mechanism.

6. Explain the difference between a transition state and an intermediate.

7. BONUS question: Explain the greater selectivity achieved in bromination compared to chlorination.

8. Use the existing experimental evidence to describe the basis of our current understanding of the mechanisms of nucleophilic substitution at sp3 carbon. Write chemical equations to outline the mechanism for a particular halide.

9. Use nucleophilic substitution in a synthetic plan of several steps, taking into consideration elimination, rearrangement and stereochemistry. Note that some of these reactions form carbon-carbon bonds.

10. Predict the products, including stereochemistry, of a nucleophilic substitution of an alkyl halide.

11. Predict (and explain) the effect of alkyl, vinyl and aryl substituents on nucleophilic substitution.

12. Given the identity of nucleophile, leaving group, substrate and solvent, predict whether elimination or substitution will predominate for a particular alkyl halide substrate.

13. Outline in chemical equations the mechanisms of elimination of alkyl halides. Describe the experimental information collected about this reaction and how the mechanisms are deduced from this information.

14. Define and use correctly the terms SN2, SN1, E2, E1.

15. Outline syntheses using organomagnesium and organocopper compounds.

16. Draw conclusions about the mechanism of a reaction from the stereochemistry.

17. Given a proposed mechanism for a reaction, predict the stereochemistry.

18. Given the predominant diastereomer in a stereoselective or stereospecific reaction, provide a mechanistic explanation for the preference.

19. Describe the evidence for the existence of carbocations and their relative stabilities.

20. Predict and recognize simple carbocation rearrangements (H, CH3, C6H5).

21. Identify a simple alkyl halide using NMR and MS data.

REFERENCES
Source	Chapters	Dr. Sweeting's Enrichment Handouts
McMurry	17, 18	Substitution and Elimination Reactions
Schmid	11, 12, 13	Oxidation and Reduction
Fessenden	7, 8	Isoprene, Terpenes, Natural Alkenes
Morrison & Boyd	6	Insect Control
Vollhardt & Schore	8, 9	IUPAC Nomenclature Simple Organics

REPRESENTATIVE PROBLEMS in McMurry 6
Chapter 17	26, 31, 32, 33, 36, 37, 39, 40, 41, 42, 44, 47, 52, 59, 60, 62, 63, 64, 65, 66
Chapter 8	see alkynes, Unit IV

LEARNING GOALS:

ALCOHOLS

1. Name any alcohol whose parent carbon chain consists of 10 or fewer atoms by the IUPAC system and sketch the alcohol given its IUPAC name or carbinol name.

2. Predict the relative acidity of alcohols by referring to the stability of all species in the equilibrium.

3. Using our current understanding of the mechanisms of the two addition reactions, explain why simple acid- catalyzed addition of water can give a different product in both stereochemistry and orientation from the hydroboration-oxidation. Note that the oxymercuration (Hg(OAc)2) / reduction is more regioselective than simple acid-catalyzed addition of water.

4. Show how the mechanism of the hydroboration reaction is deduced from the experimental data about the reaction. Write chemical equations to describe the mechanism, showing transition states if necessary.

5. Write a reasonable mechanism for the Grignard and lithium aluminum hydride synthesis of alcohols from carbonyl compounds.

6. Outline a several-step synthesis involving preparation of an alcohol from an alkene (two ways), a ketone or aldehyde, an alkyl halide, an ester, an epoxide or an ether.

7. Outline the currently accepted mechanisms of the substitution of an alcohol by halogen using HX and describe the experimental evidence for the mechanism.

8. Use HX and thionyl chloride or the phosphorus halides for the conversion of an alcohol to an alkyl halide in a synthetic plan (the differences may be important).

9. Use the oxidation reactions of alcohols to aldehydes, ketones and carboxylic acids in a synthetic plan.

10. Given all the reagents and products in an alcohol oxidation by dichromate or permanganate, determine the number of moles of each ingredient, i.e. balance the equation. Outline the mechanism of the oxidation of an alcohol by chromate.

PHENOLS

Outline a methods for distinguishing alchols and phenols by chemical and spectroscopic means.  See Unit VII.

ETHERS

11. Give the IUPAC name of any ether with 10 carbons or fewer in its parent chain and sketch an ether given its IUPAC name or alkyl name.

12. Outline a several-step synthesis involving preparation of an ether by the Williamson synthesis.

13. Write the currently accepted mechanism for the Williamson synthesis and for the hydrolysis of ethers.

EPOXIDES and DIOLS

14. Outline a synthetic plan using the preparation of an epoxide from an alkene.

15. Outline a synthesis using the conversion of an epoxide to an alcohol, halohydrin or ether-alcohol.

16. Outline a stereospecific synthesis of a cis or trans 1,2-diol from an alkene.

17. Write the currently accepted mechanism of the base-catalyzed and acid-catalyzed cleavage of epoxides; describe the experimental evidence supporting this mechanism.

APPLICATIONS

18. Given sufficient chemical and spectroscopic information (IR, NMR and MS), identify a particular alcohol or ether.

19. Identify uses of alcohols, diols, polyols, epoxides, ethers and polyethers.

20. Evaluate the safety of working with various substances based on their LD50, flash point, etc.

REFERENCES
Source	Chapters	Dr. Sweeting's Enrichment Handouts
McMurry	15, 16, 28	Theories Describing Aromatics
Schmid	19, 20, 21, 23	NMR Evidence for Aromaticity
Fessenden	11, 12, 19, 26
Morrison & Boyd	14, 15, 16, 24, 26, 30
Vollhardt & Schore	15, 16

 

REPRESENTATIVE PROBLEMS in McMurry 6
Chapter 15	18, 19, 22, 23, 24, 29, 32, 33, 36, 38, 40, 44, 45
Chapter 16	29, 30, 31, 32, 34, 35, 36, 42, 43, 45, 47, 48, 53, 54, 55, 64, 73
Chapter 28	24, 25, 30, 34

LEARNING GOALS:

STRUCTURE and NOMENCLATURE

1. Explain the unusual stability of conjugated double bond systems by the valence bond (resonance) and the molecular orbital (Huckel, aromaticity) methods; distinguish the two approaches.

2. Write contributor structures to the resonance hybrid for simple molecules (e.g. allyl radical, butadiene, benzyl cation, vinyl ether, p-nitrophenol) and order the structures in decreasing importance as contributors.

3. Explain the experimental basis for the concept of resonance or aromaticity, i.e. the differences in properties between aromatic and similar non-aromatic compounds.

4. Sketch the molecular orbitals computed by the Huckel method for benzene, butadiene, and allyl; assign relative energies.

5. Predict whether a molecule will be aromatic or antiaromatic (for single and condensed rings, ions, and heterocycles). Prerequisite: determine if the concept of aromaticity is applicable.

6. Use correctly the following terms: resonance, delocalized, resonance energy, hybrid, orbital, bonding, antibonding, non-bonding, aromatic, antiaromatic.

7. Use the concept of resonance and/or aromaticity to account for polarity, basicity, acidity, etc. of benzene derivatives such as phenol, aniline, nitrobenzene, compared to non-conjugated analogs.

8. Name by the IUPAC system compounds with substituted benzene rings (e.g. p-nitroaniline) and sketch substituted benzenes given their IUPAC names.

ELECTROPHILIC AROMATIC SUBSTITUTION

9. Write the mechanism of electrophilic substitution of benzene for nitration, halogenation, alkylation, acylation, protonation, and sulfonation, including production of the electrophile. Sketch contributors to the intermediate resonance-stabilized ion and the electrophiles. Give experimental evidence for the mechanism.

10. Explain, by referring to the mechanism of the reaction, the effect of a previous substituent on the reactivity and orientation of electrophilic aromatic substitution (consider resonance, inductive and steric effects).

11. Outline a several-step synthesis of a substituted benzene which requires careful choice of order of substitution to put the substituents in the correct orientation. This synthesis may involve, in addition to the reactions in 9, oxidation or reduction of a substituent or use of a protecting group (e.g. acyl) and the choice of mild conditions for substitution of aniline and phenol.

12. Explain the ease with which substitution and elimination reactions occur at the carbon to a benzene ring by application of the principles of resonance.

NUCLEOPHILIC AROMATIC SUBSTITUTION

13. Outline the mechanism of nucleophilic aromatic substitution and describe the experimental evidence for our current understanding of the mechanism.

14. Predict and explain the relative reactivity of substituted aryl halides toward nucleophilic substitution by deduction from the mechanism of the reaction.

15. Use nucleophilic aromatic substitution as a step in synthetic sequence.

16. From the experimental evidence, explain why nucleophilic aromatic substitutions in the presence of very strong bases (like NH2-, C6H5-) proceed by elimination followed by addition rather than through an anionic intermediate (benzyne).

MISCELLANEOUS

17. Outline a synthesis using the preparation of a benzenediazonium salt and its substitution by halogen, hydrogen, cyanide, hydroxide with the correct reagents, and the conversion of a diazonium salt into an azo dye. See Unit XI.

18. Outline the synthesis of salicylic acid from phenol.

19. Use the oxidation and reduction of aromatic rings in a synthesis.

20. Given sufficient chemical and spectroscopic (IR, NMR, MS, UV) information, identify a particular aromatic compound, including substitution pattern.

21. Identify likely cumulative toxins among aromatic compounds.

REFERENCES
Source	Chapters	Dr. Sweeting's Enrichment Handouts
McMurry	20, 21, 26, 27	Analgesics, NSAIDS, Lipids
Schmid	15, 16	Reducing Agents, Oxidizing Agents
Fessenden	14, 15, 16, 24, 25	Condensation Polymers
Morrison & Boyd	19,20,33	IUPAC Nomenclature
Vollhardt & Schore	19, 20	Reactivity of Nucleophiles, Reducers

 

REPRESENTATIVE PROBLEMS in McMurry 6
Chapter 20	20, 21, 23, 24, 25, 26, 28, 29, 33, 35, 36, 39, 40, 42, 46, 47, 49, 53, 54, 55, 56
Chapter 21	32, 33, 35, 36, 37, 38, 39, 40, 41, 45, 46, 50, 54, 56, 57, 59, 60, 63, 64, 65, 66
Chapter 27	17, 19, 22, 23, 24, 33

LEARNING GOALS:

1. Name by the IUPAC system any carboxylic acid, ester, amide or anhydride with 10 or fewer carbon atoms in the parent chain and sketch the above given their IUPAC names (and common names up to 4 carbons).

2. Analyze the causes of the relative acidities of carboxylic acids by considering the inductive, resonance and steric effects on the neutral (conjugate acid) form and the anionic (conjugate base) form; use a similar analysis to predict the acidities of others. Similarly analyze phenols, alcohols and compare with carboxylic acids (Unit VI, VII)

3. Outline the synthesis of a given carboxylic acid from the appropriate alcohol, aldehyde, methyl ketone, alkyl benzene, alkyl (aryl) halide, nitrile, amide, ester, anhydride, acyl halide.

4. Outline the synthesis of an acyl halide, amide, substituted amide, ester (lactone) or anhydride from a carboxylic acid directly or from acyl halide or anhydride or ester.

5. Outline the synthesis of compounds with the following functional groups from carboxylic acids or their derivatives: alcohol (p, s, t), -haloacid, -aminoacid, ketone, aldehyde.

6. Describe and recognize lipids, phospholipids, soaps, nylon, proteins, polyesters.

7. Write the currently accepted mechanism for the acid-catalyzed hydrolysis of ester, amide, anhydride or acyl halide to the corresponding carboxylic acid. Similarly base-catalyzed hydrolysis. Explain the experimental basis for each mechanism.

8. Write the currently accepted mechanism for the acid-catalyzed preparation of an ester from an acid and an alcohol and explain the experimental evidence from which it was deduced.

9. Write the currently accepted mechanism for acid or base-catalyzed ester exchange (transesterification) (exactly like hydrolysis and esterification).

10. Outline the mechanism and stereochemistry of the Diels-Alder reaction, e.g. for maleic anhydride. See Unit III.

11. Given sufficient chemical and spectroscopic (IR, UV, NMR, MS) information, identify a particular carboxylic acid, acyl halide, amide, ester or anhydride.

REFERENCES
Source	Chapters	Dr. Sweeting's Enrichment Handouts
McMurry	19	Reducing Agents
Schmid	5, 14	Oxidizing Agents
Fessenden	13, 16	Reactivity of Nucleophiles, Reducers
Morrison & Boyd	18, 27	IUPAC Nomenclature
Vollhardt & Schore	17

 

REPRESENTATIVE PROBLEMS in McMurry 6
Chapter 19	28, 29, 30, 32, 33, 34, 39, 40, 46, 50, 52, 60, 63, 64, 65, 66, 67, 68

LEARNING GOALS

1. Name any aldehyde or ketone which contains ten or fewer carbon atoms in its parent chain by the IUPAC system.

2. Given alkanes, alkenes, alkyl halides, alcohols, ethers, carboxylic acids, ketones (aldehydes) of similar molecular weight, order them in polarity, boiling point, and solubility in water.

3. Outline a synthesis of an aldehyde or ketone from a given alcohol, carboxylic acid, alkene, alkyne, or alkyl benzene (or a precursor of these).

4. Write the currently accepted mechanism of Friedel-Crafts acylation of aromatic compounds and describe the experiments leading to this proposed mechanism.

5. Write the currently accepted mechanisms for the addition of hydride reagents, Grignard reagents, (bisulfite) and cyanide ion to ketones and aldehydes.

6. Write the currently accepted mechanisms for the addition of alcohols (and ammonia and its derivatives) to ketones and aldehydes; describe the experimental basis for these mechanisms, including the effect of pH. Show why some amines give imines and others enamines.

7. Advanced topic: Write the mechanism of the Cannizzaro reaction and describe the experimental basis for the mechanism.

8. Identify starting materials or products for the reactions of aldehydes and ketones with silver ion (in ammonia), permanganate, dichromate, cyanide, (bisulfite), ammonia, amines, hydrazine and its derivatives, alcohols, hydride reagents (at least two), hydrogen, and Grignard and other organometallic reagents.

9. Given sufficient chemical and spectroscopic information, identify a particular aldehyde or ketone (IR, NMR, UV, MS).

10. Predict the site of addition of a nucleophile to an , ß - unsaturated carbonyl compound. Recognize the products of such a reaction and use in a short synthetic scheme.

11. Use organometallic reagents in the synthesis of compounds with new carbon-carbon bonds.

12. Use the reactions of aldehydes and ketones with oxidants, cyanide, ammonia and its derivatives, alcohols, hydride and hydrogen in a short synthetic plan.

13. Give a brief summary of the mechanism of the Wittig reaction and use the reaction in a synthetic plan. Recognize an ylide.

14. Advanced topic: Describe the effect of light as a reagent on carbonyl compounds.

15. Given sufficient chemical and spectroscopic information, deduce the structure of an unknown ketone or aldehyde.

REFERENCES
Source	Chapters	Dr. Sweeting's Enrichment Handouts
McMurry	22, 23	Reactivity of Nucleophiles, Reducers
Schmid	5, 10, 18.13-18.16, 19.15	Condensation Reactions in Synthesis
Fessenden	13, 16, 17	Total Synthesis of Tetracycline
Morrison & Boyd	16
Vollhardt & Schore	10, 11, 20

 

REPRESENTATIVE PROBLEMS in McMurry 6
Chapter 22	21, 22, 23, 24, 25, 26, 28, 29, 30, 37, 44, 46
Chapter 23	25, 26, 37, 38, 39, 42, 44, 45, 46, 52, 54

LEARNING GOALS:

1. Write the currently accepted mechanisms for the acid-catalyzed and base-catalyzed interconversion of keto and enol forms.

2. Write the mechanisms for the base-catalyzed and acid-catalyzed halogenation of aldehydes and ketones and explain how the experimental evidence leads to these mechanisms. Describe the mechanistic basis of the iodoform test.

3. Write the mechanism of the aldol condensation for any simple reactive aldehydes or ketones. Describe the experimental evidence for this reaction mechanism.

4. Recognize aldol condensation products and use the crossed aldol condensation in a practical sythesis.
5. Write the currently accepted mechanism of the Claisen ester condensation.

6. Write the mechanism of formation of enamines and use them as an enol substitute in a synthetic sequence forming new C-C bonds, esp. one in which an enolate reaction mixture would be too basic.

 7. Write the currently accepted mechanisms of the malonic and acetoacetic ester syntheses. Use these reactions in a synthetic plan, including that of a barbiturate.

 8. Write the mechanisms of the decarboxylation of ß-carbonyl acids and the base-catalyzed reverse (Claisen) condensation of ß-dicarbonyl compounds.

 9. Write the mechanism of and explain the reason for nucleophilic addition to the ß-carbon of an , ß-unsaturated carbonyl compound, esp. by carbanions in the Michael reaction.

 10. Recognize products of a Michael reaction and use it in a simple synthetic scheme.

 11. Use the above reactions and the Reformatsky (PBr3 + carboxylic acid) and Hell-Vollhard- Zelinski reactions in a short synthetic sequence.

 12. Recognize reactions similar to the Aldol and Claisen condensations with functional groups similar electronically to carboxyls.

 

REPRESENTATIVE PROBLEMS in McMurry 6
Chapter 24	25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 36, 37, 38, 39, 40, 41, 45, 48, 54, 57, 66, 67, 68
Chapter 26	29, 34, 43, 55
Chapter 28	24, 25, 26, 27, 32

LEARNING GOALS:

 1. Name any primary, secondary or tertiary aliphatic amine with 10 carbons or fewer in the parent chain by the IUPAC system and sketch the amine given its IUPAC name. Name aniline, pyrrole, pyridine and their derivatives.

 2. Given a mixture of up to four organic compounds, outline their separation using a flow chart, by acid-base and solubility properties and by chemical reactions from which they can be recovered.

 3. Analyze the causes of the relative basicities of a series of amines by applying the concepts of resonance, inductive and steric effects to explain the relative stabilities of base and conjugate acid and predict the relative basicity of another amine. Repeat using the acidities of the conjugate acids as your starting point (the way most chemists do it).

 4. Outline the synthesis of an amine using its preparation from a nitrile, nitro compound, alkyl halide, amide or ketone. The synthetic route must be chosen to minimize mixtures of primary, secondary and tertiary. Note that some synthetic methods change the number of carbon atoms in the molecule.

 5. Write the currently accepted mechanism for the preparation of amines from alkyl halides. Explain why this technique is particularly useful for the preparation of -aminoacids. Why is the Gabriel synthesis often preferable?

 6. Give several examples of biologically important amines and amides. Recognize indole, quinoline, isoquinoline alkaloids and 2-arylethylamines.

 7. Advanced topic: Write the mechanism of the Hofmann degradation of amides to amines and comment on the experimental data leading to this complex mechanistic sequence.

 8. Outline the steps in the (Hofmann) elimination of amines to form alkenes for identification. Given the product alkene and other spectroscopic and chemical information, deduce the structure of the original amine.

9. Outline the currently accepted mechanism of the formation of N-substituted amides from amines using experimental observations to support the mechanism. See Unit VIII.

 10. Explain the high reactivity of aniline toward ring substitution.

 11. Explain the chemical basis and practical use of the Hinsburg test.

 12. Propose a mechanism for the reductive amination of a ketone or aldehyde using what you have already learned about reactions of carbonyl compounds and catalytic reduction with hydrogen.

 13. Advanced topic: Write the currently accepted mechanism for the reaction of nitrous acid with amines.

14. Outline the preparation of the corresponding halides, nitrile, phenol, hydrocarbon or azo compound from a primary aromatic amine via the diazonium salt. Use these reactions as part of a short synthetic sequence. See Unit VII.

 15. Describe the primary structure of a protein and give examples of naturally occurring amino acids.

 16. Outline simple syntheses of amino acids using reactions learned for amines and acids.

 17. Identify an unknown amine given sufficient chemical and spectroscopic information.

REPRESENTATIVE PROBLEMS in McMurry 6
Chapter 25	32, 33, 36, 37, 39, 41, 50, 60

LEARNING GOALS:

 1. Describe how Fischer deduced the relative configuration of the glucose chiral centers.

 2. Write a reasonable mechanism for the mutarotation of glucose, based on the chemistry of aldehydes.

 3. Define and use: aldose, ketose, pyranose, furanose, reducing sugar, anomer, disaccharide.

 4. Compare the wet chemical methods for structure determination of saccharides with NMR techniques.

 5. Sketch Haworth and chair structures from each other.

 6. Outline a synthesis of a monosaccharide from one with one fewer carbon atoms.