Chemical Reactions & Mechanisms & Structures of Organic Molecules Questionnaire

Description

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Learning Goals and Skills for Chemistry 307/308
Introduction
Comments
Chapter 1
Chapter 2 (see also Localized MO Supplement, pg 69)
Chapter 3
Chapter 4
Chapter 5
Chapter 6
Chapter 7
Chapter 8
Chapter 9
Chapter 10 (see also Localized MO Supplement, pg 69)
Chapter 11
Chapter 12
Chapter 13
Chapter 14
Chapter 15
Chapter 17 (see also Localized MO Supplement, pg 69)
Chapter 18
Chapter 19
Chapter 20
Chapter 21
Chapter 22
Chapter 23
Chapter 24
… Chemistry Emoji’s
Supplement: Localized Molecular Orbital Theory
Supplement: Drawing Mechanism Arrows
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Introduction: The Learning Goals of Organic Chemistry focus on knowledge and skills that build
on the principles introduced in General Chemistry. The hallmark of mastery of organic chemistry
is the knowledge of and ability to use multiple models of structure and reactivity to analyze
experimental data, to design organic molecules according to various criteria, and to offer
compelling justification for one’s reasoning. These Goals prepare students for courses in
Molecular Structure and Bonding, Physical Chemistry, Biochemistry, Biophysics, other courses
that include molecular species, as well as graduate studies in organic chemistry.
There are four major questions that the study of Organic Chemistry aims to answer:
What structures do organic molecules adopt?
To answer this we focus on electronic structure.
How do we know what structures molecules adopt?
To answer this we focus on methods of structure determination.
How do chemical transformations occur?
To answer this we focus on key concepts of thermodynamics and
transition state theory.
What are the major classes of reactions and how are they used
to build molecules?
To answer this we focus on major reaction classes and synthesis.
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Comments:
1. The language I have used to communicate learning goals is verb-based. Our students are
expected to be able to recall terms, definitions, concepts, and representative data, to apply
these separately or together to analyze specific data and problems, to predict approximate
expected outcomes/data, to justify their reasoning, and to design molecules and experiments.
These are the terms used below to enumerate the undergraduate organic chemistry learning
goals. We call the successful integration and realization of the learning goals understanding
organic chemistry.
2. There is some overlap among the learning goals assigned to the chapters. The concepts listed
as learning goals for each chapter are introduced and discussed or are prerequisite concepts
that were introduced in an earlier chapter or course (general chemistry) and are further
developed in the chapter.
3. The end of each chapter lists the Honors Organic learning goals that are related to the
content of Sorrell but are not included in the 307/8 learning goals list. This ‘related content’
may be of interest to the instructional team – and to students who wish to better understand
the differences between the courses. They are included since they may be of interest or
deemed appropriate for inclusion as 307/8 learning goals. The learning goals for Honors
Organic (315/6) will move to include any Sorrell learning goals not already included in the
Honors learning goal list.
4. Italicized learning goals are those learning goals that have been introduced previously in
General Chemistry.
5. Other chapter-specific notes appear at the end of each learning goals section.
The sections that follow provide a framework for the course organized by chapter. The learning
goals are assigned by chapter and, not surprisingly, they overlap. Italicized learning goals have
been introduced previously in General Chemistry. Under each chapter, where applicable, there is
an “honors-specific learning goals” section that have been included in an attempt to give a
sense of the concepts covered in 315/316 that are relevant to each chapter but aren’t directly
discussed in that chapter. The honors learning goals are listed in an order relevant to the
organization of that course a separate document.
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Organic Chemistry
Second Edition
Thomas N. Sorrell
Chapter 1: The Structures of Organic Molecules
Students are expected to be able to:
1. Define, draw/write/depict, and/or recognize common features of molecular structure using
conventional representations (skeletal, line-angle, wedge-dash), specifically:
a.
b.
c.
d.
e.
Hydrocarbon frameworks
Hydrocarbon fragments (methyl, ethyl, etc.), multipliers, and branching prefixes (iso-,
tert-, etc.)
Major functional groups [Heteroatom functional groups (hydroxy, ether, amino, nitro,
thiol, sulfonate, aldehyde, ketone, ester, carboxylic acid, acid halide, etc.) and Carbon
functional group and common cyclic hydrocarbons (benzene, etc.)]
IUPAC and common names and abbreviations of relatively simple organic compounds
Constitutional isomers
2. Apply knowledge of molecular structure to analyze, rationalize, and predict structural
features, to design molecular variants with alternative structures, to identify impossible or
errant structures, and to be able to justify their reasoning in order to:
Draw and identify organic compounds, functional groups, fragments and hydrocarbon
frameworks
b. Name and identify molecular features
i.
Functional groups (e.g. alcohols, amines, halides and other heteroatom
substituted alkanes, alkenes, alkynes, as well as carbonyl groups, carboxylic acids
and acid derivatives, cyclic groups, heterocycles)
ii.
Longest hydrocarbon chain frameworks
iii.
Prefix for hydrocarbon or functional group appendages (e.g. methyl, ethyl,
hydroxyl, etc.) and multipliers (e.g. di, tri, etc. – as well)
iv.
Apply naming rules of order of priority
c. Name and draw compounds based on IUPAC nomenclature and common names
a.
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Honors-specific learning goals
Students are expected to be able to:
Define, draw/write/depict, and/or recognize common features of molecular structure,
specifically:
• Complex group multipliers (bis-, tris-, tetrakis-, etc.)
• Other major functional groups and moieties [Heteroatom functional groups (enol,
peroxy, epoxide, imine, iminium, enamine, cyano, nitroso, halo, thio, sulfoxide, sulfone,
phosphino, phosphonate, phosphite, borane, acid anhydride, enone) and Carbon
functional group and common cyclic hydrocarbons (benzyl, phenyl, naphthalene,
anthracene, phenanthrene, norbornene)
Chapter 2: Bonding in Organic Molecules
*Learning goals for localized molecular orbital theory (especially sigma and pi bonds from 1s,
2s, 2p, and hybridized orbitals) are listed at the end of this document.*
Students are expected to be able to:
3. Describe and explain the Periodic Table trends – especially for atoms in the first two rows of
the Periodic Table – specifically:
Number of protons, neutrons, electrons, and valence electrons for neutral and charged
species
b. Stable oxidation states
c. Electronegativity
a.
4. Apply knowledge of periodic trends to analyze, rationalize, and predict experimental data,
to design molecular variants with attenuated or enhanced properties, and to be able to
justify their reasoning in order to:
a.
b.
c.
d.
e.
f.
g.
h.
i.
Explain how periodic trends correlate with the number, energetics, and reactivity of
valence electrons
Describe how nuclear charge impacts atomic radii
Describe how electronegativity impacts bond dipole
Describe how cumulative bond dipoles can be used to approximate molecular dipole
Determine formal charge
Assign oxidation states to atoms in neutral and charged species
Estimate and compare relative bond strengths
Compare formal charge, oxidation state, and bond dipole
Describe covalent bond, polar covalent bond, ionic bond, hydrogen bond, van der Waals
interaction (attractive and repulsive)
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j.
Explain the effect of intermolecular hydrogen bonding on boiling point and melting
point
5. Define/explain what is meant by and/or describe energy in terms of elementary electronic
structural features, specifically:
Principle quantum number
Electron probability density/the lobe depiction of probability densities
Node
Orbital phase
Atomic orbital
s-orbital, especially the geometry and the differences between 1s vs 2s orbitals
p-orbital, especially the geometry and the differences between 2p vs 3p orbital
Aufbau principle
Pauli exclusion principle
Hund’s rule
Electronic configuration
Valence electrons
Core electrons
Valence electron hybridization
i.
Hybridization of n-atomic orbitals generates n-hybrid orbitals (n = 2, 3, 4)
ii.
sp1: Hybrid orbitals derived from one 2s and one 2p orbital
§ Including the relative energies, shapes, and geometries of sp1 orbitals
relative to other hybridized and unhybridized orbitals
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iii.
sp : Hybrid orbitals derived from one 2s and two 2p orbitals
§ Including the relative energies, shapes, and geometries of sp2 orbitals
relative to other hybridized and unhybridized orbitals
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iv.
sp : Hybrid orbitals derived from one 2s and three 2p orbitals
§ Including the relative energies, shapes, and geometries of sp3 orbitals
relative to other hybridized and unhybridized orbitals
o. Covalent (shared electron) bonds
i.
Lewis dot and Valence Bond structure
ii.
Optimal orbital overlap
§ Proximity (distance)
§ Orientation (geometry)
§ Phasing (orbital symmetry)
iii.
Relative orbital geometry
§ Sigma symmetry & sigma bond
§ Pi symmetry & pi bond
iv.
How matched and mismatched phasing generates bonding and antibonding
MOs, respectively
v.
Unpaired and spin-paired electrons
p. Delocalization/conjugation
i.
Valence bond resonance structures
a.
b.
c.
d.
e.
f.
g.
h.
i.
j.
k.
l.
m.
n.
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6. Apply knowledge of electronic structure to analyze, rationalize, and predict experimental
data, to design molecular variants with attenuated or enhanced properties, and to be able
to justify their reasoning in order to:
a.
b.
c.
d.
e.
f.
g.
h.
Illustrate molecular bonding using Lewis structures based on preferred numbers of
bonds and formal charges
Apply Aufbau principle, Pauli exclusion principle, and Hund’s rule to fill atomic orbitals
Predict hybridization of an atom and its corresponding geometry
Draw atomic orbital shapes and nodes according to principle and angular momentum
quantum number
Construct hybrid atomic orbital diagrams from atomic orbitals
Draw and rationalize hybrid atomic orbital shapes and energies based on the mixed
atomic orbitals
Draw resonance structures and rank relative contributions of resonance structures to
overall ground state electronic structure
Identify the limitations of an abstract model (e.g. simple hybridization models are not
applicable to row 3 atoms, simple valence bond theory models assume only valence
electrons contribute to bonding, simple molecular orbital theory models assume only
pairwise interactions) and the molecular reality.
7. Apply knowledge of molecular structure to analyze, rationalize, and predict experimental
data, to design molecular variants with attenuated or enhanced properties, and to be able
to justify their reasoning in order to:
a.
Identify and justify geometries of bonded atoms as linear, planar, tetrahedral, and
distorted variants
8. Apply knowledge of electronic structure to determine, explain, and justify (as appropriate):
How changes in coulombic, dipolar, electrostatic, and van der Waals interactions
contribute to the energetics of ground state and transition state energies
b. The impact of electronegativity and polarizability on reactivity and bonding
c. How resonance effects influence reactivity and bonding
a.
9. Represent canonical bond lengths and angles, stereochemistry, and resonance structures:
a.
b.
c.
Dashed and wedged bonds to represent stereochemistry
Double-headed arrows between contributing resonance structures
Dashed bonds to represent resonance hybrids
Notes:
1. A portion of the General Chemistry prerequisite learning goals included in this chapter
are not directly discussed in the chapter.
2. Localized molecular orbitals of pi – systems are discussed in chapter 10.
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Chapter 3: The Conformations of Organic Molecules
Students are expected to be able to:
10. Define, draw/write/depict, and/or recognize common features of molecular structure,
specifically:
Hydrocarbon frameworks (cyclic, bicyclic-fused and bridged, spirocyclic, polycyclic
frameworks)
b. IUPAC names for fused bicyclic, and bridged bicyclic compounds
c. Cis/trans
d. Conformation
i.
Newman projections
ii.
Dihedral angle
iii.
Strain (Angle strain and Torsional Strain)
iv.
Bond rotation energetics and common destabilizing interactions (eclipsed
hydrogens, eclipsed methyls, eclipsed methyl-hydrogen, gauche hydrogens,
gauche methyls, gauche methyl-hydrogen)
v.
Monocyclic rings of size 3, 4, 5, 6
vi.
Angle and torsional strain in 3 and 4 compared to 5 and 6
vii.
Envelope conformations of 5 membered rings
viii.
Cyclohexane
ix.
Axial vs equatorial
x.
Chair and boat conformations of 6 membered rings
xi.
1,3-diaxial relationship and destabilization of 1,3-diaxial groups
xii.
A-values of axial vs equatorial substituents
xiii.
Gauche interactions in cyclohexyl systems
a.
11. Apply knowledge of molecular structure to analyze, rationalize, and predict experimental
data, to design molecular variants with attenuated or enhanced properties, and to be able
to justify their reasoning in order to:
a.
b.
c.
d.
e.
f.
g.
Identify and draw structures with canonical bond angles and (relative) lengths in 2D and
3D depictions, including converting 2D to 3D and 3D to 2D
Recognize staggered, anti-periplanar, syn-periplanar, eclipsed, and gauche
conformations and compare their corresponding relative approximate energies
Convert standard drawings in 2D or 3D to Newman projections for linear alkanes and
cyclohexane given a partial Newman projection template
Evaluate bond rotation energetics for simple alkanes
Draw both chair conformations for six membered ring structures
Compare energetics of cyclohexane conformers
Draw conformational isomer interconversions
Honors-specific learning goals
Students are expected to be able to:
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Define, draw/write/depict, and/or recognize common features of molecular structure,
specifically:
• Conformation
o Common destabilizing interactions (syn-pentane, relative relationship of methyl
destabilization to other groups, including common heteroatoms, relative
relationship of hydrogen destabilization to other groups, including lone pairs)
o Bow-tie conformations of cyclohexenes
o Half chair and twist boat conformations of 6 membered rings
o Syn-pentane interactions in cyclohexyl systems
Apply knowledge of molecular structure to analyze, rationalize, and predict experimental data,
to design molecular variants with attenuated or enhanced properties, and to be able to justify
their reasoning in order to:
• Identify alpha and beta stereochemistry
• Recognize syn-pentane conformations and compare its corresponding relative
approximate energy
• Draw conformational interconversions for cis-decalin
Apply knowledge of molecular structure to analyze and justify the:
• Influence of steric strain, torsional strain, and angle (ring) strain on ground state
structures as a means to approximate differences in transition state structures
• Compare diastereomeric transition structure energy differences
• Use energy differences of transition structures to approximate differences in reaction
rates of reactants that give rise to diastereomeric products
• Use energy differences of transition structures to approximate diastereomeric product
ratios
Chapter 4: The Stereochemistry of Organic Molecules
Students are expected to be able to:
12. Define, draw/write/depict, and/or recognize common features of molecular structure,
specifically:
Configuration (relative and absolute, R and S)
Constitutional isomers
Stereoisomers
Chirality/enantiomers
i.
Optical activity
§ Dextrorotatory (d) vs levorotatory (l)
e. Diastereomers
f. Geometric isomers
i.
E vs Z isomers (as needed)
ii.
cis vs trans isomers
g. Meso
a.
b.
c.
d.
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h.
Conformation
i.
Fischer projections
ii.
The majority of conformations are chiral objects
13. Apply knowledge of molecular structure to analyze, rationalize, and predict experimental
data, to design molecular variants with attenuated or enhanced properties, and to be able
to justify their reasoning in order to:
a.
b.
c.
d.
e.
f.
g.
Determine whether a molecule is chiral or achiral and identify the total number of
stereoisomers of molecules if chiral, for simple cases
Determine whether two molecules are identical/superimposable, enantiomers,
diastereomers, or not stereoisomers
Assign E/Z isomers of alkenes using the Cahn-Ingold-Prelog convention
Assign R/S configuration for molecules with stereogenic centers using the Cahn-IngoldPrelog convention
Determine whether a structure contains stereogenic carbon but are achiral (a meso
compound)
Depict molecules as 2D and/or 3D
Recognize that enantiomers have identical physical properties with the exception of the
rotation of plane-polarized light
14. Apply knowledge of molecular structure to analyze and justify:
a.
Outcomes of reactions that give racemic or non-racemic mixtures
Honors-specific learning goals
Students are expected to be able to:
Define, draw/write/depict, and/or recognize common features of molecular structure,
specifically:
• Epimers
• Elements of molecular symmetry
o Mirror relationship between chiral molecules and their enantiomeric forms
o Types of molecular symmetry
§ Rotational
§ Inversion
§ Mirror
§ Improper rotation
Apply knowledge of molecular structure to depict, classify, analyze, determine, and/or justify:
• The relationships between starting material, transition structure, intermediate, and
product stereochemistry
• The stereochemical relationships between products of reactions that generate
stereogenic sites
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•
Stereochemical stability of stereogenic nitrogen, sulfur, and phosphorous derivatives
Chapter 5: Chemical Reactions and Mechanisms
Students are expected to be able to:
15. Define, draw/write/depict, and/or recognize common features of reactions, specifically:
a.
b.
c.
d.
e.
f.
g.
h.
i.
j.
Reactants
Products
Reaction arrows
Double (equilibrium) arrows
Catalysts
Reagents
Sequential reactions through numbering reagents
Percent yield
Reaction conditions (including solvent and temperature)
Equilibrium constants (including pKa and pKaH)
16. Define, draw/write/depict, and/or recognize common features of molecular structure,
specifically:
Common solvents, reagents, structures, abbreviations, terms, and symbols (e.g. THF,
DMF, DMSO, DCM, TEA, reflux, SM, P)
b. Bronsted-Lowry acid/base
c. Lewis acid/base
a.
17. Apply knowledge of molecular structure to analyze, rationalize, and predict experimental
data, to design molecular variants with attenuated or enhanced properties, and to be able
to justify their reasoning in order to:
a.
Identify alpha, beta, and gamma positions
18. Apply knowledge of electronic structure to determine, explain, and justify (as appropriate):
a.
The factors that influence acid strength (i.e. stabilization of conjugate base by
substituent effects due to number, size, electronegativity, distance (number of
intervening bonds), and/or electron delocalization effects)
19. Discuss, analyze, and apply the determinants of reactivity and reaction rates, including:
Standard enthalpy, entropy, and Gibbs free energy of reactants, products, and transition
states
b. Activation free energy/free energy of activation (ΔG‡)
c. Le Chatelier’s Principle
a.
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20. Interpret and create reaction coordinate diagrams, including:
Single-step and multi-step reactions
Exergonic vs endergonic; exothermic vs endothermic
Components:
i.
Starting material(s)
ii.
Transition state(s)
iii.
Intermediate(s)
iv.
Product(s)
v.
Activation energy
vi.
Rate-determining step
vii.
Axes
§ x-axis: reaction progress
§ y-axis: free energy, enthalpy
d. Practical limits of reversibility (in principle any transformation is reversible, but in
practice many reactions are irreversible)
a.
b.
c.
21. Identify, compare, rank, and provide approximate values for (as appropriate):
a.
b.
c.
d.
e.
f.
g.
h.
Nucleophiles and electrophiles in reactions
Acids and bases in reactions, including predicting whether starting material or product
are favored under equilibrium conditions
pKa’s of acids and pKaH’s (as appropriate) of:
i.
Mineral strong acids: hydrofluoric acid, hydrobromic acid, hydrochloric acid,
hydroiodic acid, sulfuric acid, sulfonic acids, hydronium ion and related species,
phosphoric acid
ii.
Major hydrocarbon functional groups: sp3 carbon/alkanes, sp2 carbon/alkenes,
including aromatic systems, and sp carbon/alkynes
iii.
Common functional groups and their protonated forms (as appropriate): alkyl
amines, amides, esters, ketones, aldehydes, carboxylic acids, nitriles, alcohols,
and water
iv.
Common functional group arrays and their substituted variants: substituted
carboxylic acids, phenol, pyridine, and aniline
Strong vs weak acids
Strong vs weak bases
Conjugate acids and conjugate bases
The most acidic hydrogens in moderately complex molecules
The most basic lone pairs in moderately complex molecules
22. Depict reaction mechanisms using the curved arrow notation (as appropriate) to indicate:
a.
b.
Electron flow toward electron deficient sites
Electron flow toward an electrophilic atom
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Electron flow from lone pairs, sigma bonds, and pi bonds (in charged or uncharged
species)
d. Realize, recognize and understand that curved arrows can originate from the center of a
sigma or pi bond or from a lone pair at a specific atom (NOT from a grouping of atoms)
e. Realize, recognize and understand that curved arrows end at a specific atom NEVER at a
group)
f. Realize, recognize and understand that making a bond requires AT LEAST two orbitals
(donors and acceptors)
g. Realize, recognize and understand that breaking a bond heterolytically requires TWO
orbitals (with corresponding changes in formal charge)
c.
23. *TBD* Draw curved mechanism arrow notation to represent:
Non-bonded lone pair electrons adding (formally) to sigma*, pi*, or empty p orbital to
form a new sigma or pi bonded species
b. Bonded pair of electrons breaking via
i.
Heterolytic cleavage to give an anion and a cation
ii.
Heterolytic cleavage coupled to addition to a sigma*, pi*, or empty p orbital to
form new bonded species
a.
24. Identify and classify major reaction classes by mechanism and/or reaction type:
Mechanism:
i.
Heterolytic reactions
§ With charged intermediates (ionic/polar reactions)
§ Without intermediates
§ With uncharged intermediates
ii.
Homolytic reactions (radical reactions)
b. Major Reaction type:
i.
Proton-transfer, substitution, addition, elimination, rearrangement, oxidation
and reduction
a.
Honors-specific learning goals
Students are expected to be able to:
Apply knowledge of molecular structure to analyze, rationalize, and predict experimental data,
to design molecular variants with attenuated or enhanced properties, and to be able to justify
their reasoning in order to:
• Analyze by pairwise comparison the relative energetics of molecular species (starting
materials, intermediates, transition structures, and products) based on ground state
differences in electronic effects (intramolecular dipole, electrostatic, inductive, and
resonance), steric effects (van der Waals repulsions), stereoelectronic effects (orbital
interaction), conformation, and/or configuration
• Describe how relative energy differences of starting materials, intermediates, transition
states, and products impact relative reactivity
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Identify, discuss, analyze, and/or apply the determinants of reactivity/relative reaction rates,
including:
• Overall kinetic factors
o Rate equations
o Elementary mechanistic steps
o Catalysis
• Overall thermodynamic factors
o temperature effects of on equilibria and reaction rate
o enthalpy
o entropy
• Sterics effects
• Conformational effects
• Electronic effects
o Inductive effects (through bond)
o Resonance effects (relative contributions of resonance contributors to ground
state energy)
• Stereoelectronics
o Orbital interaction dependence on conformation
Discuss and/or apply:
• Hammond Postulate (introduced in chapter 6 of Sorrell)
• Curtin-Hammett principle to:
o Identify the thermodynamic and kinetic product(s)
o Determine if the major product is a thermodynamic or kinetic product given
reaction conditions and reversibility
o Determine product ratios given reactants with multiple conformational isomers
• Principle of microscopic reversibility to:
o Rationalize and give the reaction mechanism for the reverse reaction
Interpret and create reaction coordinate diagrams, including:
• Dependence on molecular species/components
• Relative effects of solvent on equilibria processes and reaction rate
• Practical limits of reversibility (in principle any transformation is reversible, but in
practice many reactions are irreversible)
Identify, compare, rank, and provide approximate values for (as appropriate):
• pKa’s of acids and pKaH’s (as appropriate) of:
o Mineral strong acids: perchloric acid, nitric acid
o Major hydrocarbon functional groups, as well as hybridization variants and
substituted variants
o Common functional groups and their protonated forms (as appropriate): acid
chlorides, azide, cyanide, amines, alcohols, etc.
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Common functional group arrays and their substituted variants: nitroalkenes,
carbonyls, dicarbonyls, etc.
The most and least acidic hydrogens in complex molecules
The most and least basic lone pairs in complex molecules
o
•
•
Apply knowledge of electronic structure to determine, explain, and justify (as appropriate):
• How changes in coulombic, dipole, electrostatic, and van der Waals interactions
contribute to reactivity of ground state and transition state energies
• The close association of nucleophilicity with the HOMO and electrophilicity with the
LUMO
• The impact of orbital overlap on cyclic and acyclic transition states
• The effects of neighboring groups on rate/acceleration of reactions
Draw curved mechanism arrow notation to represent changes in bonding for:
c. Non-bonded lone pair electrons adding to sigma*, pi*, or empty p orbital to form a new
sigma or pi bonded species
d. Non-bonded single electron adding to sigma* or pi* to form a new sigma or pi bonded
species
e. Bonded pair of electrons breaking via
i.
Heterolytic cleavage to give an anion and a cation
ii.
Heterolytic cleavage coupled to addition to a sigma*, pi*, or empty p orbital to
form new bonded species
iii.
Homolytic cleavage to give two radical species
iv.
Homolytic cleavage coupled to addition to a sigma* or pi* orbitals to form new
bonded and radical species
Note: The Hammond postulate is discussed in chapter 6.
Chapter 6: Substitution Reactions of Alkyl Halides
Students are expected to be able to:
25. Define, draw/write/depict, and/or recognize common features of reactions, specifically:
a.
Molecularity of reactions
i.
Unimolecular vs bimolecular
26. Identify, compare, rank, and provide approximate values for (as appropriate):
a.
Nucleophiles and leaving groups
i.
Nucleophilicity depending on several factors: basicity, atomic size (polarizability
of the electrons), steric effects
ii.
Weak bases as good leaving groups
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27. Discuss, apply, and/or justify the use of the Hammond postulate to:
Describe a transition state as closer in energy to the reactants than the products in an
exothermic reaction
b. Describe a transition state as closer in energy to the products than the reactants in an
endothermic reaction
c. Approximate relative transition state energy by comparing its structure to the reactants,
intermediates, or products, depending on which is closer in energy
a.
28. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of substitution at saturated carbon, specifically for:
Reaction subtypes
i.
SN1 substitution
ii.
SN2 substitution
b. Factors that govern substitution at saturated carbon
i.
Rate-determining step
ii.
Nucleophiles that can substitute in SN1 versus SN2
§ Solvolysis reaction
iii.
Influence of SN1 on stereochemistry
§ Racemization
§ Ion pairing leading to inversion of configuration for SN1
iv.
Influence of SN2 on stereochemistry
§ Inversion of stereochemistry
v.
Leaving groups that can be substituted for in SN1
vi.
Leaving groups that can be substituted for in SN2
vii.
Nature of the transition states
viii.
Nature of the intermediates
§ SN1: carbocation
§ Occurs only for stabilized cations (e.g. cations stabilized by
delocalization/resonance or hyperconjugation)
§ Methyl cations do not appear to form
§ Primary cations do not appear to form without stabilization
§ SN2: none
c. Relative rate of SN2 reactions for ammonia, primary amines, secondary amines and
tertiary amines
d. Discriminating between competing substitution mechanisms in SN1 and SN2 reactions
according to:
i.
Nucleophile strength
ii.
Base strength
iii.
Methyl, primary, secondary, or tertiary carbon
iv.
Polar protic or polar aprotic solvent
v.
Vinyl and aryl halides and phenols do not undergo either substitution mechanism
a.
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29. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of cationic and related rearrangements:
Factors that govern rearrangements
i.
Stability of electrophilic center (methyl, primary, secondary and tertiary
carbocations)
ii.
Stability of migrating group (priority of shifting groups in carbocation
rearrangements)
b. Reaction subtypes
i.
Migration to electrophilic carbon
ii.
1,2 hydride and alkyl shifts including ring-expansion and ring-contraction
a.
Honors-specific learning goals
Students are expected to be able to:
Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of substitution at saturated carbon:
• Factors that govern substitution at saturated carbon
o Leaving groups that can be substituted for in SN2
§ Exception of neopentyl and tertiary butyl centers
o Nature of the transition states
§ SN2: via backside attack
Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of cationic and related rearrangements:
• Factors that govern rearrangements
o Stability of electrophilic center (methyl, primary, secondary and tertiary
carbocations)
§ Cyclopropylcarbinyl system
o Stereoelectronic constraints
Note: Chapter 6 discusses the principles of substitution reactions and focuses on substitution
reactions of alkyl halides. Chapter 7 also covers substitution reactions but is specific to alcohols
and related compounds.
Chapter 7: Substitution Reactions of Alcohols and Related Compounds
Students are expected to be able to:
30. Recognize common features of molecular structure, specifically:
a.
b.
IUPAC and common names and abbreviations of thiols and thioethers/sulfides
Draw thiols and thioethers/sulfides
18
31. Identify and compare acidity/basicity of thiols and thioesters versus their oxygen analogues
a.
b.
Thiols are less likely to become protonated than alcohols
Thioethers are less likely to become protonated than ethers
32. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of substitution at saturated carbon:
Intermolecular and intramolecular substitution reactions
Methods to convert functional groups into better leaving groups for substitution
reactions and the associated mechanisms, nucleophiles, leaving groups, substrates, and
stereochemical outcomes:
i.
Hydroxyl group:
§ Using a hydrohalic acid (HX) to protonate the OH group
§ Using sulfonyl chloride and a base to make the alkyl sulfonate ester
derivative
§ Common sulfonates (methanesulfonate/mesylate/-OMs,
trifluoromethanesulfonate/triflate/-OTf, and ptoluenesulfonate/tosylate/-OTs) and their leaving group ability
§ Using phosphorus tribromide or thionyl chloride to make alkyl bromides
or chlorides, respectively
ii.
Ether group:
§ Using HBr or HI
c. Methods to generate:
i.
Ethers
§ Using an alcohol or alkoxide ion and an alkyl halide or alkyl sulfonate
(Williamson ether synthesis)
ii.
Alkoxide ions
§ Using sodium or potassium hydride
§ Using Li, Na, or K metal
a.
b.
Chapter 8: Elimination Reactions of Alkyl Halides, Alcohols, and Related Compounds
Students are expected to be able to:
33. Define, draw and/or recognize:
a. Exocyclic versus endocyclic alkene functionality
34. Apply knowledge of molecular structure to depict, classify, analyze, determine, and/or
justify:
a.
Thermodynamic and kinetic control:
i.
If sufficient energy is available to the system so that the forward and reverse
steps of the reaction mechanism can and will occur the reaction is considered to
be under equilibrium/thermodynamic conditions
19
ii.
iii.
iv.
v.
vi.
If the energy of the system is such that the forward and reverse steps of the
reaction mechanism cannot and do not occur the reaction is considered to be
under kinetic conditions
Product that corresponds to the lowest energy species is designated as the
thermodynamic product
Product that corresponds to the lowest energy pathway is designated as the
kinetic product
Under thermodynamic conditions the extent to which products are formed
depends on the product energies (the product corresponding to the lowest
energy product forms to the greatest extent, the product corresponding to the
highest energy product forms to the least extent)
Under kinetic conditions the extent to which products are formed depends on
the activation barriers that lead to those products (the product corresponding to
the lowest energy barrier forms to the greatest extent, the product
corresponding to the highest energy barrier forms to the least extent)
35. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of elimination at saturated carbon:
Reaction subtypes
i.
E1 elimination
ii.
E2 elimination
iii.
Acid-catalyzed elimination of alcohols
b. Factors that govern elimination at saturated carbon
i.
Rate-determining step
ii.
Role of the leaving group in E1 and E2 reactions
iii.
Nature of the transition states
§ E2:
§ Antiperiplanar arrangement of leaving group and proton
§ Trans and diaxial for cyclohexyl halides
§ Conformationally destabilizing effects may slow reaction
iv.
Nature of the intermediates
§ E1: carbocation
§ E2: none
v.
Regioselectivity of E2 eliminations
§ Kinetic process (relative energy of the transition state determines favored
pathway)
§ Antiperiplanar arrangement of leaving group and proton must be
achievable for E2 to occur
§ Access to the proton by the base must be achievable for E2 to
occur
§ Planarity of the alkene must be achievable for E2 to occur
§ Use of bulky bases (e.g. LDA, t-butoxide) favors less substituted
alkene product
a.
20
To avoid two large groups cis to one another the pathway that
leads to the less substituted alkene will be favorable
§ For viable E2 processes the thermodynamic product (i.e. more highly
substituted and stable alkene) forms fastest
§ Stability of alkenes
§ Tetrasubstituted > trisubstituted > disubstituted (trans > cis) >
monosubstituted
§ Endocyclic > exocyclic (for simple cyclohexyl systems)
§ Relative stability of alkenes assessed by measuring the change of
enthalpy for hydrogenation
§ Saytzeff elimination rule
vi.
Alkyne production via successive E2 reactions of geminal and vicinal dihalides
§ Stepwise mechanism from alkane to alkene to alkyne
c. Discriminating between competing substitution and elimination mechanisms according
to conditions and the effect of changing:
i.
Nucleophile strength
ii.
Base strength
iii.
Methyl, primary, secondary, or tertiary carbon character
iv.
Polar protic or polar aprotic solvent
v.
Temperature
§
36. Depict and/or recognize
a. Newman projections of possible reactive conformers (depict stereochemistry and
conformation) given partial templates
b. Most/least reactive conformer for a set of related Newman projections (most reactive
conformer/least reactive conformer)
Honors-specific learning goals
Students are expected to be able to:
Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of elimination at saturated carbon –
• Reaction subtypes
o E1cB elimination
• Factors that govern elimination at saturated carbon
o Role of the leaving group in E1cB reactions
o Nature of the intermediates
§ E1cB: carbanion
• Regioselectivity of E2 eliminations
o Kinetic process (relative energy of the transition state determines favored
pathway)
§ Hofmann elimination favors less substituted alkene product
21
Note: The E1cb mechanism is not discussed until chapter 23 but is included here under the
honors-specific learning goals for chapter 8.
22
Chapter 9: Addition Reactions of Alkenes and Alkynes
Students are expected to be able to:
37. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of electrophilic addition to alkenes and alkynes:
Factors that govern electrophilic addition to alkenes and alkynes
i.
Two-step mechanism of electrophilic addition to alkenes
§ Carbocation intermediate
ii.
Stereochemical and regiochemical outcomes
§ Linked with the specific mechanism by which each transformation occurs
§ Regioselectivity of electrophilic addition to unsymmetrical alkenes
§ Regioselectivity of unsymmetrical bromonium ion opening
iii.
Alkyne π bond is less nucleophilic than an alkene π bond
§ Sometimes requires additional electrophilic activation, especially for
terminal alkynes
iv.
Free energy of activation is higher for addition to alkyne than to an alkene
b. Reaction subtypes for alkenes
i.
Halogenation (addition of chlorine or bromine)
§ Product: dihaloalkane
§ Halonium ion formation and its outcomes
§ Stereochemistry: stereospecific (trans- or anti-addition)
§ Enantiospecificity/enantioselectivity: neither
§ Basis for testing for presence of a π bond
§ Br2/CH2Cl2 red-orange solution is added to an unknown
compound in CH2Cl2 and look for color discharge
ii.
Halohydrin formation (addition of halogens in the presence of water)
§ Product: vicinal halohydrin
§ Stereochemistry: trans
§ Regiochemistry: nucleophile reacts preferentially at the carbon atom that
better supports a positive charge (broader corollary)
§ Enantioselectivity: none
iii.
Hydroboration
§ Product: organoborane
§ Occurs via a four-membered ring transition state
§ Stereochemistry: stereospecific (syn- or cis-addition)
§ Regioselectivity: “anti-”
iv.
Hydration
§ Addition of water
§ Product: alcohol
§ Regiochemistry:
§ Oxymercuration-reduction (or more generally, solvomercuration)
§ Product: alcohol
a.
23
Mercurinium ion reacts in the same way as halonium ions
Stereochemistry: stereospecific (anti)
Regiochemistry:
Demercuration disrupts the chirality
§ Hydroboration-oxidation hydrolysis
§ Product: alcohol
§ Using hydroperoxide ion and hydroxide ion
§ R group migrations
§ Migration of alkyl group from boron to oxygen of
hydroperoxide occurs with retention of configuration
§ Regiochemistry
v.
Addition of carbocations
§ Product: polymer
§ Polymer: in acid
§ Elimination ends the polymerization process
§ Regiochemistry:
vi.
Cyclopropanation
§ Product: cyclopropane
§ Concerted process
§ Stereochemistry is retained
§ Simmons-Smith reaction
c. Reaction subtypes for alkynes
i.
Hydration
§ Product: methyl ketone
§ Use of a metal ion
§ Vinyl alcohol undergoes tautomerism (mechanism)
§ Regiochemistry:
ii.
Addition of hydrogen bromide
§ Product: geminal dibromide
§ Regiochemistry:
iii.
Hydroboration-oxidation hydrolysis
§ Product: aldehyde
§ Same considerations as that for organoboranes formed via hydroboration
of alkenes
§
§
§
§
Honors-specific learning goals
Students are expected to be able to:
Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of electrophilic addition to alkenes:
• Factors that govern electrophilic addition to alkenes
o Regioselectivity of unsymmetrical bromonium ion opening
§ Compare to epoxide opening in acidic conditions
24
•
Reaction subtypes
o Hydroxylation
Note: Electrophilic addition to dienes is discussed in chapter 10. Hydrogenation, oxidative
cleavage, expoxidation, and dihydroxylation are discussed in chapter 11.
Chapter 10: Addition Reactions of Conjugated Dienes
Students are expected to be able to:
38. Define, draw/write/depict, and/or recognize common features of molecular structure,
specifically:
a.
IUPAC and common names and abbreviations of relatively simple organic compounds
i.
Polyenes – number, types, and positions of multiple bonds in a molecule
39. Define/explain what is meant by and/or describe energy in terms of elementary electronic
structural features, specifically:
Double bonds as isolated, conjugated, or cumulated
i.
Isolated double bonds: π bonds separated by at least one sp3-hybridized atom
ii.
Conjugated double bonds: even number of adjacent sp2-hybridized atoms
§ Electrons can be delocalized
iii.
Cumulated bonds: adjacent π bonds with an sp-hybridized carbon atom in
common (e.g. cumulene/allene)
§ Geometry of cumulene/allene can lead to chirality
iv.
Stability: conjugated dienes > isolated and cumulated dienes
§ More s character leading to shorter, stronger bonds → more stable
§ Delocalization of π electrons → more stable
b. Molecular orbital models based on atomic orbitals
i.
LCAO (linear combination of atomic orbitals)
§ The number of atomic orbitals combined is equal to the number of
molecular orbitals created
§ Bonding and antibonding molecular orbitals are created – each pairwise
combination of atomic orbitals generates one bonding and one
antibonding molecular orbital
§ Wave functions of atomic orbitals reinforce each other (addition)
§ Greatest electron density between nuclei
§ Wave functions of atomic orbitals cancel each other (subtraction)
§ Node(s) between nuclei
§ Orbitals combined maintaining sigma-symmetry to generate sigma and
sigma* orbitals
§ Orbitals combined maintaining pi-symmetry to generate pi and pi*
orbitals
§ Orbitals not combined remain atomic orbitals
ii.
Molecular orbitals (MOs) are filled just as atomic orbitals (AOs) are:
a.
25
§
§
§
Start with the MO at the lowest energy level
Only two electrons per MO
Hund’s rule and Pauli exclusion principle apply to MOs
HOMO
LUMO
Bond order
c. Delocalization/conjugation
i.
Huckels’s LCAO of p-orbitals to make pi-MOs
§ Additional node and one less bonding interaction at each level
§ Highest energy level has a node between each pair of atoms and no
bonding interactions
ii.
Delocalization and conjugation
iii.
iv.
v.
40. Apply knowledge of electronic structure to analyze, rationalize, and predict experimental
data, to design molecular variants with attenuated or enhanced properties, and to be able
to justify their reasoning in order to:
a.
b.
c.
d.
e.
Construct molecular orbital diagrams from atomic and hybrid orbitals according to the
linear combination of atomic orbital model
Draw and rationalize molecular orbital shapes for bonding and antibonding orbitals
Illustrate ground and excited energy states of electrons in atomic and molecular orbitals
Recognize that addition of electrons to antibonding orbitals leads to a decrease in bond
order
Draw phasing of p orbitals for conjugated systems as an approximation of the pi MOs
41. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of electrophilic addition to alkenes:
a.
Reaction subtypes
i.
Electrophilic addition to conjugated dienes
§ Two products via 1,2-addition (usually the kinetic pathway/product) and
1,4-addition (usually the thermodynamic pathway/product)
42. Identify and classify major reaction classes by mechanism:
a.
Mechanism:
i. Heterolytic reactions
ii. Without intermediates (Pericyclic reactions)
§ Cycloadditions
§ Sigmatropic rearrangements
§ Electrocyclic reactions
43. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of cycloadditions:
26
Factors that govern cycloadditions
i.
Cyclic transition state
§ Focus on: Symmetries of HOMO and LUMO
ii.
Dienes and dienophiles (in Diels-Alder reaction)
§ Diene needs to be able to adopt s-cis conformation
§ Good dienophiles have at least one electron-withdrawing group (i.e.
electronegative atom or group with unsaturation)
iii.
Stereospecificity in Diels-Alder reaction
§ Stereochemical information of reactants retained in products
iv.
Stereoselectivity in Diels-Alder reaction
§ Endo versus exo (endo pathway is the kinetic pathway and predominates)
v.
Regioselectivity in Diels-Alder reaction
§ Isomers may form when both the diene and dienophile are
unsymmetrical
b. Reaction subtypes
i.
Diels-Alder reaction ([4+2] cycloaddition)
§ Product: cyclohexene derivative
a.
Honors-specific learning goals
Students are expected to be able to:
Define/explain what is meant by and/or describe energy in terms of elementary electronic
structural features, specifically:
•
Localized molecular orbital models based on atomic orbitals
o Total energy is decreased and bonds are stabilizing when bonding orbitals are
occupied by one or two electrons
o Total energy is increased and bonds are destabilized when antibonding orbitals
are occupied by one or two electrons
o Nonbonding electrons are in atomic or hybrid atomic orbitals and may be paired
or unpaired
o Singlet
o Triplet
o Perturbations of orbital energy as a function of rotation, stretching, bending,
changes in electronegativity of atoms involved
o Covalent bond energy dependence on principle quantum number of the atomic
orbitals involved
• Delocalization/conjugation
o pi-MO’s of extended conjugated systems
§ allylic cation, anion, radical
§ butadiene
§ pentadienyl cation, anion, radical
§ extended conjugated systems
27
Students are expected to apply knowledge of electronic structure to analyze, rationalize, and
predict experimental data, to design molecular variants with attenuated or enhanced
properties, and to be able to justify their reasoning in order to:
• Describe probability distribution of ‘locations’ of electrons in atomic and molecular
orbitals
• Identify HOMO/LUMO from molecular orbital diagrams and in molecular structure
• Recognize and justify why occupied antibonding orbitals, nonbonded electrons, and pi
bonds are often the HOMOs of the species that have these electronic structural features
Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of cycloadditions:
• Factors that govern cycloadditions
o Implications of thermal versus photochemical conditions
o Regioselectivity in Diels-Alder reaction
§ Ortho, para, meta
• Reaction subtypes
o Photochemical [2+2] cycloadditions
o Thermal [4+2] cycloadditions
o 1,3-dipolar cycloadditions to make 5-membered rings
o Cycloaddition of alkenes with osmium tetroxide
o Cycloaddition pathways of alkenes with ozone
Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of sigmatropic rearrangements:
• Factors that govern sigmatropic rearrangements
o Cyclic transition state
o Orbital descriptions of sigmatropic rearrangements
o Implications of thermal versus photochemical conditions
o Rate preferences for alkyl shifts
o Suprafacial versus antarafacial shifts in sigmatropic rearrangements
o Why thermal [1,3] sigmatropic rearrangements are geometrically impossible for
hydrogen
• Reaction subtypes
o Photochemical [1,3] sigmatropic shifts
o [2,3] sigmatropic shifts
o [3,3] sigmatropic shifts
§ Claisen rearrangement
§ Cope rearrangement
§ Oxy-cope rearrangement
o [1,5] sigmatropic hydride shifts
o [1,7] sigmatropic shifts
Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of electrocyclic reactions:
28
•
•
Factors that govern electrocyclic reactions
o Cyclic transition state
o Orbital descriptions of electrocyclic reactions
o Implications of thermal versus photochemical conditions
o Stereospecificity of electrocyclic reactions
§ Conrotatory versus disrotatory
Reaction subtypes
o Ring-opening reactions
o Ring-closing reactions
Note: Molecular orbitals will be discussed earlier in the course.
Chapter 11: Oxidation and Reduction Reactions
Students are expected to be able to:
44. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of electrophilic addition to alkenes:
a.
Reaction subtypes for alkenes
i.
Hydrogenation
§ Product: alkane (meso, achiral, or racemic)
§ Kinetically slow without use of a metal catalyst
§ Thermodynamically favorable
§ Stereochemistry: stereospecific (syn-addition)
§ Chemoselectivity: many functional groups are inert to hydrogenation
under these conditions (specifically: benzene react very, very slowly,
carbonyls get reduced very slowly, and alcohols and amines do not get
reduced)
ii.
Oxidative cleavage
§ Ozonolysis
§ Product: carbonyls (type depends on workup reagents and
substitution of alkene)
§ Oxidizing agent → ketones (alkene is disubstituted) or
carboxylic acids (alkene is monosubstituted) or formic acid
(alkene is terminal)
§ Reductive workup → aldehydes (alkene is
monosubstituted) or ketones (alkene is disubstituted) or
formaldehyde (alkene is terminal)
§ Six electron transition state between 5 atoms
§ Periodate cleavage
§ Product: aldehydes or ketones (depending on substitution of
alkene)
§ Periodate ion in conjunction with osmium tetroxide
iii.
Dihydroxylation
29
With osmium tetroxide
§ Product: vicinal cis-diol
§ Five-membered ring osmate ester intermediate
§ Stereochemistry: stereospecific (syn-addition)
§ With epoxides and water in acid
§ Product: vicinal diol
§ Stereochemistry: stereospecific (anti-addition)
iv.
Epoxidation
§ Bromohydrin is treated with base to deprotonate the OH group, followed
by intramolecular substitution
b. Reaction subtypes for alkynes
i.
Hydrogenation
§ Product: alkane (unless stopped at the alkene stage)
§ Lindlar catalyst used as a poisoned catalyst to stop at the cis
alkene
§ Same considerations at that for hydrogenation of alkenes
§
45. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of oxidation and reduction reactions:
Factors that govern oxidation and reduction reactions
i.
Determine oxidation state/level according to number of bonds to heteroatoms
or unsaturation
§ Oxidation: removal of hydrogen atoms or the addition of heteroatoms
§ Reduction: addition of hydrogen atoms or the removal of heteroatoms
§ Change in oxidation level during reaction = oxidation or reduction
b. Reaction subtypes
i.
Reduction of nitrogen-containing groups via hydrogenation
§ Product: primary amine
§ Two-step process of substitution reaction (to get nitrile or azidoalkane)
then hydrogenation (to get primary amine)
§ Use of metal catalyst
ii.
Oxidation of alcohols
§ Product: carbonyl (type depends on alcohol and reagent)
§ Primary alcohol → aldehyde or carboxylic acid (if use chromium
oxide reagent)
§ Secondary alcohol → ketone
§ E2 reaction
§ Stereochemistry: anti-elimination
§ Swern oxidation
§ Using high-valent metal oxides
§ Chromium oxide reagents
§ manganese(IV) oxide
§ Organoiodine compounds
a.
30
Oxidation of carbonyl groups
Oxidation of alkenes to form epoxides
§ Using a peroxycarboxylic acid/peracid
§ Concerted process
§ More highly substituted alkenes react faster with peracids
§ Stereochemistry: stereospecific (syn-addition)
§ Strong oxidant (peracid, hydrogen peroxide)
§ Product: N-oxide (from tertiary amine, more complex products
with primary and secondary amines)
c. Reducing agents and when to use them
i.
Carbonyl reductions with NaBH4 and LiAlH4
ii.
Catalytic hydrogenation using platinum, palladium, or nickel on carbon or
calcium carbonate
iii.
Lindlar catalyst
§ To stop alkyne hydrogenation at the alkene stage
iv.
SnCl2 in hydrochloric acid or Zn in acetic acid, Fe in HBr
§ To form aniline derivatives from nitro compounds
d. Oxidizing agents and when to use them
i.
Chromic acid and sulfuric acid/acetic acid (Jones reagent)
§ To oxidize alcohols to ketones or carboxylic acids
§ To oxidize aldehydes to carboxylic acids
ii.
Chromium oxide-pyridine (Collins’s reagent)
§ To oxidize alcohols to ketones or aldehydes
iii.
Pyridinium chlorochromate (PCC) (Corey’s reagent)
§ To oxidize alcohols to ketones or aldehydes
iv.
Manganese(IV) oxide
§ To oxidize benzylic and allylic alcohols to ketones or aldehydes
v.
Peroxyacids (e.g. mCPBA)
§ To oxidize alkenes to epoxides
vi.
Osmium tetroxide
§ To oxidize alkenes to cis-diols
vii.
Ozone
§ To oxidatively cleave alkenes to ketones and aldehydes/carboxylic acids
viii.
Iodoxybenzoic acid (IBX) and the Dess-Martin Periodinane (DMP)
§ To oxidize alcohols to ketones or aldehydes
iii.
iv.
Honors-specific learning goals
Students are expected to be able to:
46. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of oxidation and reduction reactions:
a.
Reaction subtypes
i.
Reduction of carbonyl groups
31
b.
Reducing agents and when to use them
i.
Lithium aluminum hydride
ii.
Lithium/sodium borohydride
iii.
Zn(Hg) in hydrochloric acid
Note: Chapter 11 focuses predominantly on oxidation reactions and lacks in discussion on
reduction reactions.
Chapter 12: Free Radical Reactions
Students are expected to be able to:
47. Draw curved mechanism arrow notation to represent changes in bonding for:
a.
Bonded pair of electrons breaking via
i.
Homolytic cleavage to give two radical species
ii.
Homolytic cleavage coupled to addition to a sigma* or pi* orbitals to form new
bonded and radical species
48. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of radical reactions:
Factors that govern radical reactions
i.
Bond strength (numerical approximations in kcal/mole for C-H, C-C, C=C, as well
as relative bond strengths, including primary, secondary, tertiary, C-H for sp1,
sp2, and sp3, and the periodic table-based trends of X-H for X = N, O, and
halides, X-Y where X and/or Y are C, N, O, and halides, Sn-X where X is halide vs
H)
ii.
Stability of methyl, primary, secondary, tertiary, allyl, and benzyl radicals
§ Allyl, benzyl > tertiary > secondary > primary > methyl
§ Stabilization by electron donation and hyperconjugation
iii.
Initiation
§ To form at least one species that has unpaired electrons
§ Using heat, UV light, or chemical reagents (e.g. AIBN)
iv.
Propagation
§ To generate product from a radical species, to regenerate the radical
species, and to thereby continue the chain reaction to give the major
product (e.g. polymerization, cyclization)
v.
Termination
§ To combine two radicals and stop propagation
vi.
Bond dissociation energies to approximate enthalpy changes
§ Given bond dissociation energies calculate expected enthalpy
b. Reaction subtypes
i.
Halogenation reactions
§ Chlorination of alkanes
a.
32
Mixture of products due to more than one hydrogen atom able to
be substituted
§ Reactivity ratio for the different types of hydrogen atoms
§ Tertiary hydrogen > secondary hydrogen > primary
hydrogen
§ Transition state resembles the structure of the alkane
starting material
§ Bromination of alkanes
§ More selective than chlorination
§ Transition state resembles the structure of the alkyl radical
§ Degree of substitution is more easily controlled than in
chlorination
§ Allylic and benzylic bromination
§ N-Bromosuccinimide (NBS), benzoyl peroxide, and heat
Reduction via radical intermediates
§ Dissolving metal reduction
§ Alkyne to trans-alkene
§ Minimizes nonbonded steric interactions between R
groups
§ Sodium or lithium metal dissolved in liquid ammonia
§ Conversion of organohalides to hydrocarbons
§ Radical substitution of Br by H
§ Tributyltin hydride
Addition reactions
§ Addition of hydrogen bromide to alkenes
§ Regiochemistry:
§ Hydrogen chloride and hydrogen iodide do not undergo radical
addition to alkenes
§ Addition of an alkyl radical to an alkene
§ Carbon-carbon bond formation with radicals
§ To form polymers or rings
§
ii.
iii.
Honors-specific learning goals
Students are expected to be able to:
Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of radical reactions:
• Factors that govern radical reactions
o Nucleophilic radicals
o Electrophilic radicals
• Reaction subtypes
o Forming allylic radicals from boranes and oxygen
33
Chapter 13: Proton and Carbon NMR Spectroscopy
Students are expected to be able to:
49. Describe the essential features of 1H-NMR experiments and the data obtained therefrom,
specifically, that peaks result from absorption of energy that changes the spin state and
what is meant by magnetic field dependence, ppm, and Hz, including:
a.
b.
c.
d.
e.
f.
g.
h.
i.
1
H-NMR spectra: each signal has three features (chemical shift, splitting pattern,
Integrated intensity values)
Chemical shift and chemical shift range
i.
Chemical shifts of magnetically equivalent protons are identical
ii.
Shielded/deshielded
iii.
Protons absorb at slightly different frequencies due to the influence of electrons
at adjacent atoms or groups
iv.
Protons within a group or groups can be magnetically equivalent
v.
Protons attached to symmetry-equivalent atoms or groups
Symmetry and the number of signals observed
i.
Symmetry reduces the number of observed signals
Chemical equivalence
Magnetic equivalence
ii.
Signal averaging (equivalence) due to conformational dynamics
Proton integration
i.
Integrated intensity values are proportional to the numbers of magnetically
equivalent protons represented
ii.
Note the values are RATIOS, not absolute values
Functional group correlations to chemical shift, especially the major functional classes
i.
Alkanes and heteroatom substituted alkanes
ii.
Alkenes
iii.
Alkynes
iv.
Arenes
v.
Aldehydes
vi.
Heteroatom-bound protons (alcohols, amines, acids, amides)
Effect of partial and full charges
Resonance effects on functional group chemical shift
Hydrogen/deuterium exchange on X-H (heteroatom-H bonds)
i.
Protons attached to heteroatoms are not easily identified from their chemical
shifts and can be identified by adding a drop of D2O and observing the
disappearance of a signal
Spin coupling systems
i.
Proton-proton coupling
ii.
Additional peaks result from the magnetic moments of protons attached to
adjacent carbon atoms, either enhancing or reducing the external field
Also called spin-spin splitting due to the appearance of the spectrum itself, in
which some signals are split into several closed spaced peaks
34
j.
Splitting patterns (n+1 rule)
i.
n = number of equivalent protons on the adjacent carbon atoms
ii.
Multiplicity: observed patterns of peaks (singlets, doublets, triplets, quartets,
quintets, sextets, septets and composite splitting, e.g. doublet of doublet, etc.)
iii.
Chemical shift is at the center of a splitting pattern
iv.
Ratios of peak heights for a given splitting pattern follows Pascal’s Triangle
v.
Multiple splitting patterns
k. Coupling constants (field-independent)
i.
Coupling constant (J): magnitude of the splitting between peaks
ii.
Units = Hertz (not ppm)
iii.
Each J value is associated with a specific coupling system and the number of
neighboring protons
iv.
The coupling between two groups of protons is reciprocal (i.e. JH1H2 = JH2H1)
l. 2-, 3-, and 4-bond coupling (2J, 3J, 4J)
i.
ii.
iii.
iv.
v.
Vicinal coupling (0-15 Hz): coupling between nuclei separated by three bonds (3J)
depends on dihedral angle
Approximate J-values as a function of alkene geometry
Geminal coupling (0-3 Hz for CH2 sp2; typically 12-15 Hz for CH2 sp3): coupling
between nuclei separated by two bonds
Approximate J-values as a function of alkene geometry
Long-range coupling (0-2 Hz): coupling between nuclei separated by more than
three bonds, especially H-C=C-C-H and H-C
C-CH2 structure leads to weak 4bond coupling (4J)
50. Apply knowledge of 1H-NMR to analyze, rationalize, and predict experimental data, to
design molecular variants with specific properties, and to be able to justify their reasoning
in order to:
a. Predict spectral data in graphical and tabular form
b. Interpret spectral data in graphical and tabular form
i.
Three primary characteristics to consider:
Chemical shifts
Integrated intensity values
Multiplicity
a. Use spectral data to solve structural problems of modest complexity – including
stereochemistry- and conformation-specific problems – alone and in combination with
data derived from MS, IR, UV, 13C-NMR, physical and/or chemical property data, degree
of hydrogen deficiency
51. Describe the essential features of 13C-NMR experiments and the data obtained therefrom,
specifically:
a.
13
C-NMR spectra
35
b.
c.
d.
e.
Unlike 1H-NMR, 13C is low abundance, low mag. sensitivity, coupling to protons reduces
signal intensity, causing poor S/N
i.
Peaks result from absorption of energy that changes the spin state
ii.
Lower magnetic sensitivity than 1H-NMR
iii.
Not (normally) integrated
13 13
iv.
C- C splitting is not observed in natural abundance
v.
Broad-band decoupling eliminates coupling to proton (and causes modest
enhancement of signals for carbons with attached protons)
Hertz
i.
Frequency of radiation necessary to cause spin change depends on the energy
difference between the spin states (ΔE = hv)
Parts per million (ppm), chemical shift (δ) and chemical shift range; 13C (typical: 230-0)
has greater resolution than 1H (15-0 for 1H-NMR)
i.
Reference compound = tetramethyl silane (TMS @ 0 ppm)
ii.
Chemical shift: numeric value of a signal relative to the position of the TMS peak
Downfield/deshielded/high chemical shift: a relative terms referring to
the left (higher ppm)
Upfield/shielded/low chemical shift: a relative terms referring to the right
(lower ppm)
Influenced by inductive and resonance (related to presence of electronwithdrawing groups and conjugation of adjacent atoms) effects
Inductive effects are cumulative
iii.
Shielded/deshielded (also apply to 1H-NMR)
Shielding: secondary magnetic field created by electrons at adjacent
atoms or groups that opposes, and thus lowers, the externally applied
magnetic field
Deshielded: experience a slightly stronger magnetic field than those
absorbing upfield and give signals further downfield
Shielded: experience a slightly weaker magnetic field and give signals
further upfield
The number of signals observed including symmetry and dynamics effects
i.
Symmetry determines the number of observed signals, including rotation,
mirror, and inversion
ii.
Signal averaging due to conformational dynamics
Functional group correlations to chemical shift, especially the major functional classes
i.
Alkanes and heteroatom substituted alkanes
ii.
Alkenes
iii.
Alkynes
iv.
Arenes
v.
Carbonyls (ketones, aldehydes, acids, and acid derivatives)
vi.
Nitriles
vii. Resonance effects on functional group chemical shift
36
52. Apply knowledge of 13C-NMR to analyze, rationalize, and predict experimental data, to
design molecular variants with attenuated or enhanced properties, and to be able to justify
their reasoning in order to:
b. Predict spectral data in graphical and tabular form
c. Interpret spectral data in graphical and tabular form
i.
Can be used to identify functional groups containing carbon atoms
d. Use spectral data to solve structural problems of modest complexity alone and in
combination with data derived from MS, IR, UV, 1H-NMR, physical and/or chemical
property data, and degree of hydrogen deficiency (double bond equivalence, DBE)
Honors-specific learning goals
Students are expected to be able to:
Describe the essential features of 13C-NMR experiments and the data obtained therefrom,
specifically:
● Signal intensity
● The impact of field strength (effective and applied) on chemical shift
Describe the essential features of 1H-NMR experiments and the data obtained therefrom,
specifically:
● The impact of field strength (effective and applied) on chemical shift
● Coupling constant dependence on proximity at fixed dihedral angle
● Coupling constant dependence on dihedral angles
● Deviations from ideal splitting as the chemical shift differences (Hz) of coupled protons
approach coupling constant values (Hz) and resultant special splitting patterns (AB
quartet, peak ‘leaning’)
● Diastereotopic protons (and methyl and other groups) in 1H-NMR
● Through-space coupling (NOEs)
● Stereochemistry and conformation-specific NOEs
Chapter 14: Determining the Structures of Organic Molecules
Students are expected to be able to:
53. Define and describe the essential features of degree of hydrogen deficiency, specifically:
a. Sites of unsaturation: π bonds and rings that a compound has
i.
Cannot know specifically whether a p bond or a ring or both are present in a
molecule
b. The expected number of hydrogen atoms of a saturated compound based on molecular
formulae that do not include hydrogen atom counts
c. How atom type impact degree of hydrogen deficiency (O, N, Halide)
d. How to determine the degree of hydrogen deficiency of a particular structure based on
molecular formula or molecular structure
37
54. Apply knowledge of degree of hydrogen deficiency to analyze, rationalize, and predict
experimental data, to design molecular variants with attenuated or enhanced properties,
and to be able to justify their reasoning in order to:
a. Use degree of hydrogen deficiency in combination with spectral data derived from 1HNMR, MS, IR, UV, 13C-NMR, physical and/or chemical property data to solve structural
problems of modest complexity
55. Describe the essential features of positive ion mass spectrometry (MS) experiments and the
data obtained therefrom, specifically:
a. Determination of the molecular weight and formula of a compound
i.
Determine which peak corresponds to molecular/parent ion M+
b. Electron impact ionization
i.
Electron impact (EI) ionization: removes an electron from the molecule to
produce a radical cation (aka molecular ion)
c. Mass-to-charge ratio (m/z)
i.
Charge (z) most often equals +1 so that the m/z value of an ion equals its mass
ii.
Species detected in the mass spectrum must carry a charge
d. Fragmentation patterns and their use in structural determination
i.
Loss of specific fragments from molecules, one neutral and one charged
e. Main and isotope peaks (C, Cl, Br)
i.
Presence of either bromine or chlorine is readily established from the relative
intensities of the (M+2)+ peak
56. Apply knowledge of MS to analyze, rationalize, and predict experimental data, to design
molecular variants with attenuated or enhanced properties, and to be able to justify their
reasoning in order to:
a.
b.
c.
d.
Determine the isotopic composition of elements in a molecule (bromine and chlorine)
Predict MS data in graphical and tabular form
Interpret MS data in graphical and tabular form
Use MS data to solve structural problems of modest complexity alone and in
combination with data derived from 1H-NMR, 13C-NMR, IR, UV, physical and/or chemical
property data, and degree of hydrogen deficiency
57. Describe the essential features of infrared (IR) experiments and the data obtained
therefrom, specifically:
a. Transmission spectra
i.
Generated by measuring the absorption of IR radiation
ii.
Means to identify functional groups
iii.
Plot of percent transmittance versus wavenumber
b. Wavenumbers (cm-1) (proportional to frequency)
38
c.
d.
e.
f.
g.
h.
i.
i.
Inverse of wavelength
Bond vibrations lead to IR activity
i.
Vibration will only give rise to an absorption band when there is a change in the
dipole moment of the bond that is vibrating
ii.
Vibrational modes can be coupled and appear as symmetric and asymmetric
stretching vibrations
Factors that influence frequency, intensity, and width of IR signals
The impact of bond strength on the position of the IR band
i.
Frequency of a vibration will be proportional to the bond strength
The impact of mass on the position of the IR band
i.
Wavenumber of a vibration will be inversely related to square root of the
reduced mass of the interacting atoms
Large changes in dipole moments increase intensity/strength of an IR signal (e.g. OH,
C=O)
The significance of the fingerprint region
i.
Pattern of bands is unique for each compound
ii.
Bending vibrations
Key functional group IR resonances
i.
Function group region
Bond stretching frequencies
ii.
Alcohol, phenol, amine (primary and secondary), amide, alkyne, nitrile, carbonyl
derivatives, alkene, arene, imine, nitro
58. Apply knowledge of IR to analyze, rationalize, and predict experimental data, to design
molecular variants with attenuated or enhanced properties, and to be able to justify their
reasoning in order to:
a. Predict spectral data in graphical and tabular form
b. Interpret spectral data in graphical and tabular form
i.
Three features to consider:
Positions of the bands (wavenumbers)
Intensities of the bands (weak, medium, strong)
Shapes of the bands (broad or sharp)
c. Identify key functional groups of organic compounds based on their spectral signatures
d. Solve structural problems of modest complexity alone and in combination with data
derived from 1H-NMR, 13C-NMR, MS, UV, physical and/or chemical property data, and
degree of hydrogen deficiency
59. Describe the essential features of UV experiments and the data obtained therefrom,
specifically:
a. Absorbance spectroscopy deficiency
b. Lambert-Beer Law, wavelength, and frequency
c. Conjugation effects and the energy transition between HOMO/LUMO
d. The impact of the HOMO/LUMO gap on the energy of light absorbed
39
e. The impact of absorption on visible color
60. Apply knowledge of UV to analyze, rationalize, and predict experimental data, to design
molecular variants with attenuated or enhanced properties, and to be able to justify their
reasoning in order to:
a. Determine and/or compare the extent of conjugation present in organic compounds
effect of alkyl substitution (5 nm/alkyl group on an alkene) deficiency
b. Determine and/or compare differences in color depending on the degree of conjugation
of bonds present in molecules
c. Use UV data to solve structural problems of modest complexity alone and in
combination with data derived from IR, 1H-NMR, 13C-NMR, physical and/or chemical
property data, and degree of hydrogen deficiency
Honors-specific learning goals
Students are expected to be able to:
Describe the essential features of mass spectrometry (MS) experiments and the data obtained
therefrom, specifically:
● Electrospray
Apply knowledge of MS to analyze, rationalize, and predict experimental data, to design
molecular variants with attenuated or enhanced properties, and to be able to justify their
reasoning in order to:
● Explain the isotopic difference between M/z, 2M/2z, M2/2z
● Interpret fragmentation of charged and uncharged species based on differences MS
fragments that result from electrospray
Describe the essential features of infrared (IR) experiments and the data obtained therefrom,
specifically:
Solution, film, KBr pellets, nujol mulls
The impact of mass on the position of the IR band
Hooke’s law, reduced mass
The impact of reduced mass on the position of the IR band
Describe the essential features of x-ray crystallography and the data obtained therefrom,
specifically:
● X-ray scattering/diffracted by electrons in atoms within a crystalline lattice structure
● The scattering/diffraction patterns give atomic positions from which bond lengths and
angles can be deduced
● X-ray crystallography can tell us the shape and symmetry of molecules in a crystal lattice
● Use x-ray data to analyze, rationalize, and predict experimental data, to design
molecular variants with attenuated or enhanced properties, and to be able to justify
their reasoning in order to solve structural problems of modest complexity alone and in
40
combination with data derived from IR, UV, 1H-NMR, 13C-NMR, physical and/or chemical
property data, and DBE
Describe the essential features of UV experiments and the data obtained therefrom,
specifically:
● Absorption spectroscopy (more to the point: electronic spectroscopy)
● Lambert- Beer Law, wavelength, and extinction coefficient
● Conjugation effects and the energy transition between HOMO/LUMO
● The dependence of the energy of light absorbed on the HOMO/LUMO gap
● The impact of absorption on visible color
Apply knowledge of UV to analyze, rationalize, and predict experimental data, to design
molecular variants with attenuated or enhanced properties, and to be able to justify their
reasoning in order to:
● Determine and/or compare the degree of conjugation present in organic compounds
● Determine and/or compare differences in color depending on the degree of conjugation
of bonds present in molecules
● Use UV data to solve structural problems of modest complexity alone and in
combination with data derived from x-ray, IR, 1H-NMR, 13C-NMR, physical and/or
chemical property data, and DBE
Chapter 15: Organometallic Reagents and Chemical Synthesis
Students are expected to be able to:
61. Apply principles of structure and reactivity to make carbon-carbon bonds:
a. Carbon-carbon bond formation involves reaction between electrophilic and nucleophilic
carbon centers
i.
Presence of an electronegative heteroatom usually renders the neighboring
carbon atom electrophilic (e.g. alkyl halides, alcohols, and carbonyl compounds)
b. Grignard reagents are prepared from organohalides
i.
Can reduce an organohalide to a carbanion by reacting it with magnesium metal,
producing a Grignard reagent (general formula: RMgX)
ii.
Starting material: alkyl, aryl, and vinyl chlorides, bromides, and iodides all react
■ Organochlorides are the least reactive
iii.
Solvent: diethyl ether or THF
■ Must be inert to the Grignard reagent but also dissolve it
c. Grignard reagents are potent bases and also react as radicals, both of which suppress a
Grignard reagent’s nucleophilic behavior
i.
As a base
■ Can be used to make compounds that contain deuterium
■ Product: hydrocarbon corresponding to the starting R-X
ii.
As a nucleophile
41
■ With the electrophilic carbon atom of a carbonyl
● Due to the nucleophilicity of the carbonyl oxygen atom and its
attraction toward the electrophilic metal ion
● Adduct formation further enhances the polarity difference
● Reaction subtypes: RMgX with
○ Carbon dioxide
■ Product: carboxylic acid with one carbon atom
more than in the starting R-X
○ Formaldehyde
■ Product: primary alcohol with one carbon atom
more than in the starting R-X
○ Aldehydes
■ Product: secondary alcohol
○ Ketones
■ Aqueous ammonium chloride is used in the
hydrolysis step to prevent elimination
■ Product: tertiary alcohol
■ With epoxides
● Can form an adduct to further activate ring opening
● Reaction subtypes: RMgX with
○ Ethylene oxide
■ Product: primary alcohol with two carbon atoms
more than in the starting R-X
○ Unsymmetrical (substituted) epoxides
■ React at the less hindered carbon atom of the ring
■ Product: secondary or tertiary alcohol
d. Any organohalide that also has an acidic proton or a reactive functional group cannot be
used to prepare a Grignard reagent
i.
Circumvent this limitation by:
■ protecting the reactive center
■ Using a different type of organometallic reagent
■ Employing a functional group that can be converted subsequently to the
desired one; Example: using a protected 1° alcohol and oxidizing to an
aldehyde or carboxylic acid after using the organo metallic reagent
e. Organolithium compounds are prepared from organohalides and lithium metal
i.
React with carbonyl compounds and epoxides in the same way as Grignard
reagents
ii.
Alkynyl organometallic compounds are made by acid-base reactions, including
transmetallation with Mg or Li organic reagents
iii.
C-H bond of a terminal acetylene is much more acidic than that of other kinds of
hydrocarbons
iv.
Terminal alkyne reacts with a strong base to produce the alkynyl anion and the
corresponding metal salt
v.
Alkynyl carbanion is able to react as a nucleophile via the SN2 pathway
42
■ Can make carbon-carbon bonds via reactions with alkyl halides; reaction
is limited to 1° substrates as 2° substrates undergo elimination (E2)
● Monoanion of acetylene reacts with primary alkyl halide to
produce terminal alkynes
vi.
Initial alkyne function can be converted subsequently to a variety of compounds
f. Organocuprates are prepared from organolithium compounds and copper(I) salts
i.
Organolithium compound reacts with copper(I) iodide to form a lithium
diorganocuprate, known as a Gilman reagent
■ Lithium diorganocuprates are weaker bases than Grignard reagents and
more potent nucleophiles with respect to substitution reactions
ii.
Two equivalents of organolithium compound reacts with copper(I) cyanide to
produce higher order cuprates
■ Higher order cuprates behave differently than Gilman reagents
g. Organocuprates react as nucleophiles in substitution reactions
i.
Organocuprates do not react with carbon dioxide or other carbonyl compounds
as Grignard or organolithium reagents do
ii.
Organocuprates react with many organohalides to make carbon-carbon bonds
■ Only primary alkyl bromides and iodides react suitably with Gilman
reagents
● Organoiodides react more readily than the corresponding
organobromides
■ Higher order cuprates react more readily with alkyl halides and tosylates
and with fewer side reactions than the corresponding Gilman reagents
● React as quickly with organobromides as Gilman reagents do with
organoiodides
● Can undergo substitution reactions with secondary alkyl bromides
and iodides
iii.
Both types of organocuprates react with epoxides as Grignard reagents do
h. The reactivity of transition metal organometallic reagents depends on the oxidation
state, coordination number, and geometry of the metal ion
i.
Coordination number: number of groups bonded to the metal ion
ii.
Geometry: how the ligands are arranged around the metal ion
iii.
These three properties dictate the kinds of reactions that a metal complex can
undergo, which include oxidative addition, reductive elimination, and migratory
insertion
■ Oxidative addition: metal ion increases its coordination number as its
oxidation state also increases
● Alkyl halides and H2 are the most common reagents that undergo
this process
■ Reductive elimination: reverse of oxidative addition
● The elimination processes most important in synthesis are those
that create a new C-H or C-C bond
■ Migratory insertion: one group bonded to the metal ion inserts into a π
bond of another ligand that is also bonded to the metal
43
i.
● Occurs most often with an alkene molecule or carbon monoxide
as the acceptor
● Usually no change in oxidation state
● Coordination number can change when another ligand bonds to
the metal ion
iv.
Organocuprates make use of oxidative addition and reductive elimination to
form carbon-carbon bonds
v.
Wilkinson’s catalyst (a homogeneous catalyst) is used to hydrogenate alkenes
■ Utilizes all three mechanism types consecutively
■ More selective than heterogeneous hydrogenation due to the
triphenylphosphine groups providing steric bulk, which slows the reaction
toward more highly substituted alkenes
Palladium complexes catalyze the formation of carbon-carbon bonds
i.
Suzuki reaction: a three step process of palladium-catalyzed coupling of an
organohalide and an organoborane
■ Practical way to couple alkenylboranes with alkenyl or aryl halides
62. Apply principles of reactivity and reaction mechanisms to:
a. Suggest reasonable starting material(s) and reaction condition(s) that lead to certain
product(s)
i.
Retrosynthesis identifies possible intermediate compounds and starting
materials, generating a synthetic tree
ii.
“The disconnection approach” for determining the reactions needed to form the
carbon-carbon bonds
■ Disconnections are most suitable at or adjacent to: a double or triple
bond, a ring junction, a branch point next to a heteroatom, a functional
group
■ Functional group equivalents can reveal more likely disconnection points
■ An alcohol functional group is a logical disconnection site because the
hydrocarbon framework can be readily assembled at that carbon atom by
using an organolithium or Grignard reagent
b. Design reactions that will favor one product over another
c. Represent one or two bond disconnections
d. Introduce or add functional groups via oxidation or reduction
e. Interconvert different functional groups
f. Remove different functional groups
g. Protect different functional groups
i.
Protecting groups are used when incompatible functional groups are present in
the desired product or precursors
ii.
The best protecting groups have the following features:
■ They can be introduced into a molecule under mild conditions
■ They are inert to the reaction conditions that will be used
44
■ They can be removed under conditions that do not affect other
functional groups or the stereochemistry of the product
h. Suggest conditions, draw products, and propose structures for reactions that form
carbon-carbon and heteroatom-carbon bonds (e.g. C-O, C-N, C-S, C-P, C-Cl, C-Br, C-I)
i. Suggest conditions for forming alkenes and alkynes
j. Design experiments to determine regioselectivity, stereoselectivity, and/or
stereospecificity
k. Consider reaction selectivity in planning the synthesis of a compound with more than
one functional group
i.
Chemoselectivity: differentiation between the reactivity patterns of functional
groups
■ Example: oxidation of a primary alcohol in the presence of a tertiary
alcohol
ii.
Regioselectivity: refers to the orientation in addition reactions
■ Example: hydrogen bromide adds to alkenes in Markovnikov fashion
under polar conditions and with anti-Markovnikov orientation under
radical conditions
iii.
Stereoselectivity: has to do with the stereochemistry of the reaction
■ Example: hydroboration occurs by a stereospecific syn addition and the
electrophilic addition of bromine to an alkene is a stereospecific anti
addition
iv.
Enantioselectivity: the selective formation of one enantiomer from an otherwise
achiral molecule at an achiral center
l. Consider the atom economy of a reaction
i.
How much of the reactant(s) actually ends up in the product (Example Gilman
reagent: only ONE of the TWO organic groups is utilized)
Chapter 17: The Chemistry of Benzene and Its Derivatives
Students are expected to be able to:
63. Define/explain what is meant by and/or describe energy in terms of elementary electronic
structural features, specifically:
a. Delocalization/conjugation
i.
Aromaticity
■ Benzene is more stable than other six-membered ring polyenes
● Resonance energy: the energy difference between the enthalpy of
hydrogenation of benzene and that of 1,3,5-cyclohexatriene
(“aromatization energy” is ~30 kcal/mol)
● Unusual stability of benzene is due to the property of aromaticity
ii.
Antiaromaticity
■ Annulenes: cyclic compounds with alternating single and double bonds
that have reactivities that differ from that of benzene
■ Destabilized relative to the analogous cyclic polyene
45
iii.
iv.
■ No orbital degeneracy
■ Electrons allowed to pair
Huckel’s rules for Aromaticity
■ Planar or nearly planar
■ Conjugated
■ Monocyclic
● Huckel’s rule is often used for compounds with multiple rings as
well
■ 4n+2 = Aromatic
● Where n = 0, 1, 2, 3, 4…
● The electrons to be counted in the assessment of aromaticity are:
○ If an atom forms a π bond, then its p electron is included
in the total
○ If an atom forms a π bond and has an unshared electron
pair, only the p electron is included in the total
○ If an atom is not part of a pi bond, but has an unshared
electron pair, contributes the electron pair (C– of
cyclopentadienyl anion)
○ If an atom is not part of a pi bond, but has two unpaired
electron pairs, then only one pair (two electrons) is
included in the total (O of furan, S of thiophen)
pi-MO’s of cyclic Huckel systems
■ Number of cyclic MO’s = number of p-orbitals
■ Pairwise degeneracy of cyclic MO’s
■ Frost circle approximation of cyclic pi-MO energies
● Draw the ring with one atom pointing down and then for every
vertex, draw a horizontal line that corresponds to an energy level
64. Apply knowledge of electronic structure to analyze, rationalize, and predict experimental
data, to design molecular variants with attenuated or enhanced properties, and to be able
to justify their reasoning in order to:
a.
b.
c.
d.
e.
Classify and rationalize compounds as aromatic, antiaromatic, and nonaromatic
Explain and illustrate the differences between aromatic and antiaromatic MO diagrams
Construct Frost circles for cyclic, conjugated neutral and ionic species
Use Frost circles to determine if a neutral or ionic species is aromatic or antiaromatic
Categorize planar (or nearly planar) molecules as aromatic or antiaromatic
65. Define, draw/write/depict, and/or recognize common features of molecular structure using
conventional representations (skeletal, line-angle, wedge-dash) specifically:
a. IUPAC and common names and abbreviations of relatively simple organic compounds
i.
Disubstituted benzene isomers are named using the prefixes ortho (for 1,2disubstitution), meta (for 1,3-disubstitution), and para (for 1,4-disubstitution)
46
66. Describe the essential features of 1H-NMR spectral data for aromatic compounds,
specifically:
a. Ortho coupling: coupling between protons that are ortho to one another
i.
Magnitude of this coupling constant (3J) = ~7-8 Hz
b. Long-range coupling can occur between protons that are meta to each other
i.
Magnitude of this coupling constant (4J) = inductive effects
■ Examples: phenol, ansiole, and acetanilide
iii.
Halogen atoms
■ Deactivating
■ Ortho/para directing
■ Inductive effects > resonance effects
● A withdrawing inductive effect deactivates the ring, but
resonance effects offset this deactivation somewhat at the ortho
and para positions
iv.
Positive or partial charge adjacent to the ring
■ Deactivating
■ Meta directing
■ Resonance effects = inductive effects
● Operate in the same direction and both decrease the electron
density in the ring
■ Examples: nitrobenzene, acetophenone, and benzoic acid
v.
Ammonium ion
■ Deactivating
■ Meta directing
■ Inductive effects only
vi.
Polysubstituted benzene rings
48
■ Effects of each substituent must be evaluated via three factors:
● The positions to which the electrophile will be directed by each
substituent
● The relative strengths of activation or deactivation by each
substituent
● Steric effects
○ Larger substituents produce more para- than orthodisubstituted product
○ An incoming group rarely enters between two groups that
are meta to each other
d. Reaction subtypes
i.
Nitration
■ Nitric acid
■ Sulfuric acid promotes the reaction to generate the electrophilenitronium ion
ii.
Halogenation
■ Chlorine and bromine
■ Lewis acid catalyst
● Iron(III) halides
iii.
Sulfonation
■ HSO3+, the electrophile, is generated either from sulfuric acid with itself
at high temperatures or by dissolving sulfur trioxide in sulfuric acid
(oleum)
iv.
Friedel-Crafts reaction
■ Carbocation as the electrophile
■ Lewis acid catalyst
● Aluminum chloride
■ Friedel-Crafts alkylation and acylation do not occur if the ring has only a
meta-directing substituent
■ Alkylation
● Problems
○ Rearrangement
■ Alkylation is limited to small (methyl, ethyl) and
highly symmetric alkyl substituents such as
isopropyl and tert-butyl groups
○ Polyalkylation
■ An alkyl group makes the ring more reactive than
benzene itself, leading to further alkylation
○ Reversibility
■ An alkyl group can migrate from one molecule to
another, producing a mixture of products
■ Acylation
● An acyl group can be converted to an alkyl group by several
methods
49
v.
● Advantages over alkylation
○ Rearrangement of the incoming group does not occur
○ Polysubstitution does not occur
■ An acyl group deactivates the ring
Diazonium compounds undergo coupling with some arenes
■ If an activated aromatic compound (phenol) is added to the solution of a
diazonium salt, then electrophilic substitution can occur
69. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of oxidation and reduction reactions:
a. Reaction subtypes
i.
Oxidation of methyl and primary and secondary alkyl groups attached to
benzene to form benzoic acid derivatives
■ Radical intermediates (stabilized by resonance) can be formed at the
benzylic carbon atom by transfer of a hydrogen atom to an oxidizing
agent
■ The radical formed initially undergoes single-electron transfer and
oxygen-atom transfer reactions with a reagent (usually potassium
permanganate or a salt of the dichromate ion)
70. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of nucleophilic aromatic substitution:
a. Factors that govern nucleophilic aromatic substitution
i.
Lewis acids as catalysts
ii.
Activating and deactivating groups
iii.
Electron-withdrawing and electron-donating groups
■ Halogens acting as both
iv.
Ortho/para vs. meta directing
v.
Ortho, para, and meta products and when and why they occur
vi.
Fluoride ion is a good leaving group in nucleophilic aromatic substitution
vii. Benzyne is highly reactive
b. Reaction subtypes
i.
SN1 mechanism with diazonium compounds
■ Aniline derivatives are converted to diazonium compounds
● Sodium nitrate is treated with a mineral acid to form nitrous acid,
which reacts with the mineral acid to generate NO+
● The nucleophilic amine group from the aniline derivative reacts
with the electrophilic NO+
● A series of acid-base reactions occur to produce the diazonium ion
■ An aryl diazonium compound is converted to an arene derivative
● Nitrogen dissociates from a diazonium ion to form a phenyl cation
50
ii.
iii.
iv.
● If a nucleophile is present, it could react and form a benzene
derivative via substitution (though radical intermediates are
involved)
○ Phenol- diazonium salt (via sodium nitrate and sulfuric
acid) and water
○ Iodobenzene derivatives- diazonium salt and iodide ion
● If HBF4 is added to the diazonium reaction mixture, then the BF4salt often precipitates from solution
● Hypophosphorous acid reduces the carbon-nitrogen bond,
replacing the diazonium ion with a hydrogen atom
■ Strong basic conditions
Addition-elimination mechanism
■ A resonance-stabilized intermediate is formed that has two heteroatoms
attached to the same carbon atom
■ The halide is then displaced to regenerate the aromatic system
Sandmeyer reaction
■ Chloride, bromide, and cyanide can replace the nitrogen leaving group of
a diazonium compound
■ Copper(I) salt must be supplied
Benzyne mechanism (moved from ii to iv)
Honors-specific learning goals
Students are expected to be able to:
Define/explain what is meant by and/or describe energy in terms of elementary electronic
structural features, specifically:
Delocalization/conjugation
Non-aromaticity
Huckel’s rules for Aromaticity
■ 4n = Antiaromatic
Apply knowledge of electronic structure to analyze, rationalize, and predict experimental data,
to design molecular variants with attenuated or enhanced properties, and to be able to justify
their reasoning in order to:
● Explain how aromaticity affects the color of organic compounds
● Use Frost circles to determine if a neutral or ionic species is non-aromatic
● Categorize planar molecules as non-aromatic
● Predict whether molecules will be planar based on expected aromatic vs antiaromatic
character
Chapter 18: Nucleophilic Addition Reactions of Aldehydes and Ketones
Students are expected to be able to:
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71. Define/explain what is meant by and/or describe:
a. Cyanohydrin
b. Carbonyl hydrate
c. Clemmensen reduction
d. Baeyer-Villiger oxidation
72. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of nucleophilic addition to carbonyls and their analogues:
a. Factors that govern nucleophilic addition to carbonyls and their analogues
i.
Polarity of carbonyl group
■ Electrophilic carbon atom is susceptible to reactions with nucleophiles
ii.
Stability of carbonyl
iii.
Acid/base catalysis
■ If the nucleophile used is the conjugate base of a moderately strong acid,
the conjugate acid of the nucleophile protonates the carbonyl oxygen
■ Activates the carbonyl group by making the carbonyl carbon more
electrophilic
b. Reaction subtypes
i.
Mechanism of cyanohydrin formation from reaction of hydrogen cyanide (HCN)
with aldehydes or ketones
■ All steps are in equilibria
■ Product formation optimal near pH = 9
■ General for aldehydes and limited to ketones with small groups due to
steric effects
ii.
Alcohol formation from attack by “hydride” on aldehydes and ketones
■ NaBH4 or LiAlH4 are hydride ion transfer reagents
● NaBH4 is less reactive and is often used with ethanol as the
solvent
● LiAlH4 is extremely reactive with water and alcohols and is used
with THF or ether as the solvents
● Up to 4 equivalents of the ketone or aldehyde can be reduced
with only 1 mole equivalent of hydride transfer reagents
iii.
Hydrate (geminal diol) formation from addition of water to aldehydes and
ketones
■ Under basic conditions
● Alkoxide ion intermediate removes a proton from water, forming
the hydrate
● Hydroxide ion acts as a catalyst
■ Under acidic conditions
● Carbonyl oxygen atom is protonated, increasing the
electrophilicity of the carbonyl carbon
● Acid catalyzed
■ Equilibrium normally lies to side with ketone or aldehyde
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■ Some hydrates are reasonably stable
● More often for aldehydes than ketones due to steric effects
● Electron-withdrawing R groups promote hydrate formation and
stability
73. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of oxidation and reduction reactions:
Reaction subtypes
a. Reduction of carbonyl groups
i.
Hydrogen gas and a metal catalyst can reduce the carbonyl group
ii.
Clemmensen reduction (zinc, mercury, and HCl) converts the carbonyl
group to a methylene group
b. Oxidation of carbonyl groups
i.
Ketones to esters
● Baeyer-Villiger reaction (mechanism)
○ Addition of a peracid to the carbonyl group
○ R group migration to an oxygen of the peracid
○ Carboxylic acid as a leaving group
○ Driving force of reaction: breaking of a weak O-O bond
with formation of an additional C-O bonds
Honors-specific learning goals
Students are expected to be able to:
Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of nucleophilic addition to carbonyls and their analogues:
Reaction subtypes
New carbon-carbon bond formation from reaction of organometallic reagents
(carbanions) with aldehydes and ketones
■ Making organometallics from halogenated compounds or deprotonation
of carbon atoms
Bisulfite addition compounds
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Chapter 19: Addition-Substitution Reactions of Aldehydes and Ketones: Carbohydrate
Chemistry
Students are expected to be able to:
74. Apply principles of structure and reactivity to rationalize outcomes or predict and justify
expected outcomes of nucleophilic addition to carbonyls and their analogues:
a. Acetals form readily under conditions that remove water
b. Reaction subtypes
i.
Hemiacetal formation from reaction of alcohols with aldehydes and ketones
(acid-catalyzed mechanism)
■ Hemiacetal: OH and OR group on what was the carbonyl carbon atom
■ Hemiacetals are normally unstable
● Equilibrium lies toward carbonyl and alcohol reactants
■ Cyclic hemiacetals may be stable and are generated from hydroxy
aldehydes or ketones
● Equilibrium favorable for five- and six-membered ring systems
ii.
Acetal formation from reaction of alcohols with aldehydes and ketones (acid
catalyzed mechanism)
■ Acetal: geminal dialkoxy compound
■ Each step is reversible so an acetal can be hydrolyzed to regenerate the
aldehyde or ketone
75. Apply principles of …
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