Documente Academic
Documente Profesional
Documente Cultură
Copyright: Kate Graham, T. Nicholas Jones, Edward McIntee, Alicia Peterson and Chris Schaller,
Department of Chemistry, CSB/SJU
TABLE OF CONTENTS
Review
Structural Representations
Nomenclature
91
96
Stereochemistry
128
152
Aromaticity
168
Acid-Base Chemistry
175
Carbonyl Reactions
199
Review
Importantquestionsyoushouldbeabletoanswerbasedonyour
firstyearofchemistry:
i. Whatisabond,andwhydobondsform?
ii. Whatphysicalforcesareresponsiblefortheformationof
bonds?
iii. Aretheredifferenttypesofbonding?Explainthedifferences.
iv. Moleculeshaveshapeandtakeupspace.Why?
v. Givenamolecularformula,canyoupredictamolecule'sshape?
[e.g.ifyoucombineoneN,oneC,oroneOwithenough
hydrogenstomakeneutral,closedshellmolecules,whatwould
betheshapeofeachmolecule?]
vi. Whatisanatomicorbital?Whatisamolecularorbital?
vii. Whatistheaufbauprocess?
viii. Whatismeantbytheterm"valenceshell"?
ix. Whyareorbitalsimportantintermsofbonding?
x. Whatareintermolecularforcesandwhyaretheyimportant?
We have provided some practice problems for you to start getting back on track with.
Enjoy!
1. Arrangethefollowingatomsbyincreasingelectronegativity:Li,Br,Pb,K,Mg,C.
2. DrawLewis(orKekule)structuresforthefollowingcompounds.Includeatleasttwo
resonancestructuresforeachcompoundandALWAYSincludeformalchargesifpresent.
a. carbonmonoxide(CO)
b. potassiumcyanate(KNCO)
3. Indicatepartialpositiveornegativechargesontheatomsinthefollowingmoleculesof
fragments.
a. HF
b. NaH
c. H2
d. C-H
e. C-Cl
f. Si-Li
g.Si-Cl
h. N-Mg
4. IntermolecularForces.Explainwhatismeantbythefollowingtypesofintermolecular
forces.Useillustrations.
a. Hbonding(e.g.water,H2O)
b. dipoledipole(e.g.formaldehyde,CH2O)
c. vanderWaals[alsocalledLondonordispersion](e.g.bromine,Br2)
5. Usepicturestoillustratechangesinintermolecularforces/bondinginthefollowing
cases:
a. methanolisheatedupuntilitboils.
b. sodiumchlorideisdissolvedinwater.
c. ethylacetateismixedwithacetonitrile.
6. Methanol(CH3OH;bp=65C)boilsnearly230higherthanmethane(CH4;bp=164C),
but1decanol(C10H21OH;bp=229C)boilsonly55higherthandecane(C10H22;bp=
174C).Explain.
7. Whichshouldhavethehigherboilingpoint,methanol(CH3OH)orbromomethane
(CH3Br)?Why?
8. Predictthebondanglesinacrylonitrile.
9. Listthefollowingcompoundsinorderfromleastacidictomostacidic.
a. CH4,H2O,NH3
b. HF,HBr,HCl
10. Makearough,qualitativeplotofthechangeinenergythatoccursasthebondinanH2
moleculeisbroken.
DrawLewis/Kekulestructures,includinganyresonancestructuresyoucanthinkof,for
thefollowingmoleculesandions:
a. ethylacetateCH3CO2CH2CH3(noteabbreviatedformulaee.g.CH3means3H
attachedtothatC)
b. acetonitrileCH3CN
c. nitromethane,CH3NO2(Nisconnectedto2oxygensandacarbon)
d. diazomethaneCH2N2(connectedCNN)
e. sodiumazideNaN3
f.
potassiumthiocyanateKSCN
g. sodiumborateNa3BO3
h. calciumcarbonateCaCO3
i.
potassiumphosphateKPO4H2
j.
potassiumphosphiteKPO3H2
k. potassiumhypophosphiteKHPO2H
CH3
CH3OH2
CH4
CH3OCH3
HC
CH2
H 2C
H3C
CH3
H 2C O
HN
CH2
H 2C
H3C
(CH3)3N NH4
NH2
H2C OH
Br
CH2
H 2C
CH3NH2
NH
PH3
H 2C C O
BF4
H2C
CH2
H2C
HS
N
CH2
H2C
O
CH2
H 2C
H3C NH2
H 3C N O
H2N
CH2
H 2C
CH3OH
BF3
HC
CH2
H 2C
CH3O
HC
CH2
H2C
HO
CH2
H 2C
O
OH
CH3
CH3
H3C O CH3
O O
CH2
(CH3)3P
O O O
P
CH2
H2C
CH2 H3C N
PCl3
S
CH2
H 2C
H2B
H3C NH
H2B
H2N NH2
H3C S CH3
H2C N N
H O O H
CH3
H3C
H Cl
N
O
H 3C
H Br
H3C C N H
O
H B
H3C C N
Structural Representations
We will start this semester looking spectroscopy of simple organic compounds.
However, we need a common language and common symbols to discuss the
molecules and some common 2D representations of molecules.
Condensed Formula
Line-Bond
H
CH3CH3
Skeletal
H
C
H
H
CH3CH2CH3
H
H
H
(CH3)2CHCH3
CH3COCH3
CH3CO2H
H
C
C
H
CH3CH2OCH3
H
C
H
Why
Take Home Message: If you draw an atom, then Hydrogen atoms must be
drawn! Hydrogens are implied ONLY in skeletal representations of carbon
atoms.
In most of the representations, the electrons are not shown. How can you
tell if there are any lone pairs on atoms?
Define Isomer
Draw all the isomers of heptane, C7H16 using line bond representation.
Nomenclature
Chapters 5 & 12
Alkanes -- Fill in the Blanks
All alkane names have a prefix telling how many carbons are in the longest chain, and
the suffix "ane", meaning alkane.
Prefixes: meth = 1 carbon; eth = 2; prop = 3; but = 4; pent = 5; hex = 6; hept = 7; oct = 8; non = 9; dec = 10.
Rings have the additional prefix, "cyclo".
branched alkanes
formula
skeletal structure
H
CH4
C2H6
C3H8
H
H
H
H
H
H
H
name
draw 1 isomer
name
(none)
methane
ethane
(none)
1-carbon branch
on 2nd carbon
3-carbon chain
C4H10
(none)
2-methylpropane
2,2-dimethylpropane
C5H12
C6H14
C7H16
C8H18
C9H20
3-ethyl,2-methylheptane
C10H22
cyclopentane
C4H8
H
propene
1-butene
number identifies where
double bond begins (always
the lowest possible number)
C5H10
C5H8
1,4-pentadiene
C6H10
C7H12
benzene
methylbenzene or toluene
1,2-dimethylbenzene or o-dimethylbenzene
1,2-substitution on benzene is sometimes called ortho- or o1,3-substitution on benzene is sometimes called meta- or m1,4-substitution on benzene is sometimes called para- or p-
Br
Cl
name:
Priority Table
O
O
OH
O
CN
Part II. Using IUPAC name, provide structures for the following compounds:
N,N-dimethylpropanamide
3-methoxyhexanoic acid
isopropyl alcohol
4-bromoheptanal
N,N-dimethylheptylamine
Build a 3-D model of ethane (C2H6) using the model kits. Look at the
following 2-D representations of ethane.
HH
HH
HH
HH HH
HH HH
HH
HH HH
HH
Potential Energy
2.8 kcal/mol
H
H
60
120
180
240
300
360
Degrees of Rotation
Some conformations are lower energy and some are higher energy.
Propose some ideas for why these conformations differ in energy.
Conformational Analysis
ImportantTakeHomePoints:
a. Conformationalisomersareinterconvertedbyrotationaroundcarbon
carbonsingle(sigma)bonds.
b. Intramoleculardistancesvarywithconformation.
c. ExaminationofchangesinvanderWaalsrepulsionscanbeusedto
qualitativelypredictrelativeconformationalenergiesand,therefore,
relativeconformationalpopulationsatequilibrium.
d. Constitutionalisomersdonotinterconvertbyrotationsaroundsingle
bonds.
ADDITIONAL PROBLEMS
For this activity consider 1,2-diiodoethane:
0. Here is the data from calculations on 1,2-diiodoethane:
I-C-C-I
Energy
Conformation
dihedral (Kcal/mol) description
angle
0
12
60
0
120
4.5
180
0
Unfavorable
interactions, if
any.
Draw 1,2-diiodoethane.
Draw Newman projections for each of the 4 conformations.
Fill in the remaining column in the table above.
Fill in the graph below showing the energy of the conformations.
Why is there such a BIG energy difference between the conformation with
a dihedral angle of 0 and 120?
What are the bond angles of these molecules? What are the usual bond
angles of a tetrahedral carbon?
Find the conformation of this molecule that has the least torsional, steric
and ring strain.
Draw a 2D chair representation of this molecule including all of the
hydrogens.
Label each hydrogen as axial or equatorial.
Cyclic Alkanes
Conformational Analysis
H
H
H
H
H
H
H
HH
H
H
Additional Problem:
Draw the other ring conformation of t-butylcyclohexane with the tert-butyl equatorial.
Calculate the amount of increased energy due to steric strain in this chair
conformation.
DECALIN SYSTEMS
H
TRANS
H
H
CIS
ADAMANTANE
DRAW Adamantadine
[AKA 1-aminoadamantane]
DRAW Rimantadine
[AKA 1-(1-adamantyl)ethylamine]
DIAMOND LATTICE
Diamond Lattice
e.
f.
g.
h.
i.
Alkane Nomenclature
Constitutional isomers do not interconvert by rotations around
single bonds.
Conformational isomers are interconverted by rotation around
carbon-carbon single (sigma) bonds.
Examination of torsional, steric and angle strain can be used to
qualitatively predict relative conformational energies (acyclic or
cyclic) and, therefore, relative conformational populations at
equilibrium.
5-atom interactions cause no increase in steric strain
6-atom interactions usually increase the energy of conformer
by approx. 1 kcal/mol
7-atom interactions usually increase the energy of conformer
by approx. 3 kcal/mol
There are two chair conformations for each cyclohexane
compound. These are rapidly interconverting.
In general, substituents larger than hydrogen prefer to be
equatorial on a cyclohexane ring.
The presence of two or more substituents on a cyclohexane ring
introduces the possibility of cis/trans isomers.
Wedge-and-Dash indicates tetrahedral geometry but a chair
conformation must be drawn to determine whether a
substituent is axial or equatorial.
Different cis/trans isomers will have different conformations.
The larger substituent will prefer to be equatorial if possible.
All chairs can be drawn on diamond lattice. Substituents should
fall on the extended lattice.
Trans-decalin systems cannot ring flip. Cis-Decalins systems
can.
Additional Problems
1. Now consider cis-1,2-dimethylcyclohexane.
a. Draw the two possible chair conformers.
b. Calculate the relative energy of each and determine which is the most
stable.
2. Now consider trans-1,2-dimethylcyclohexane.
a. Draw the two possible chair conformers.
b. Calculate the relative energy of each and determine which is the most
stable.
3. Now consider cis-1,3-dimethylcyclohexane.
a. Draw the two possible chair conformers.
b. Calculate the relative energy of each and determine which is the most
stable.
4. Now consider trans-1,3-dimethylcyclohexane.
a. Draw the two possible chair conformers.
b. Calculate the relative energy of each and determine which is the most
stable.
5. Now consider cis-1,4-dimethylcyclohexane.
a. Draw the two possible chair conformers.
b. Calculate the relative energy of each and determine which is the most
stable.
6. Now consider trans-1,4-dimethylcyclohexane.
a. Draw the two possible chair conformers.
b. Calculate the relative energy of each and determine which is the most
stable.
8. For the questions on this page please consider the set of molecules found
below.
Using the calculations you made above, Circle the molecule below that
has the lowest energy best chair conformation?
9. For the questions on this page please consider the set of molecules found
below.
Using the calculations you made above, Circle the molecule below that
has the lowest energy best chair conformation?
HO
OH
HO
OH
HO
OH
O
O
OH
OCH3
OH
OCH3
a. What are the two main functional groups involved in this structure?
b. Draw the Newman projections for the different conformations
obtained through 60 bond rotations around the CH2-CH2 bond of
this molecule. Label each conformation with the appropriate term
such as gauche, etc.
c. Draw an energy diagram for the complete rotation around this
bond. Indicate which conformer is the most stable. Which
conformer is the least stable?
d. The two compounds below were synthesized and tested for
cholinomimetic properties - that is tested for the production of a
response resembling that of ACh. Isomer 1 had about the same
activity as ACh; isomer 2 had about 1/500th of the potency of ACh.
Which conformer of ACh must be the active form that binds to the
receptor? Show Newman Projections to support your answer.
Molecule
Explain why the observed number of 13C-NMR peaks can change with a change in
temperature.
Stereochemistry
Chapter 7
Isomers
Constitutional
Isomers
Conformational
Isomers
Enantiomers
Stereoisomers
Diastereomers
Geometric
Isomers
Diastereomers
with multiple
chiral centers
Cl
Cl
CH3
Br
C
Cl
OH
C
CH3
OCH3
O
H
Cl
HOH2C
CH2Ph
CH3
Ph
Cl
Cl
OH
HO
Br
Ph
OH
Cl
OH
O
Ph H
OH
OH
Diastereomers
Before Class, read Chapters SC8 (Biological Building Blocks), SC9
(Carbohydrates and Diastereomers) and SC10 (Diastereomers and
Physical Properties) from Dr. Schallers website:
http://employees.csbsju.edu/cschaller/Principles%20Chem/stereochem/st
ereo_index.htm
Passport to Class:
Additional Problems
Chiral Resolution
Amphetamines are potent central nervous system stimulants capable
of causing addiction. Amphetamines are prescribed as diet pills and
for hyperactivity in children. The basic structure of amphetamine is
shown below.
Concept Mapping
Definition: Concept maps offer a method to represent information visually. There are a
variety of such maps.
Purpose: Concept maps harness the power of our vision to understand complex
information "at-a-glance." The primary function of the brain is to interpret incoming
information to make meaning. It is easier for the brain to make meaning when
information is presented in visual formats..
Making Your Own Concept Maps: Here are some resources for getting started on
making you own concept maps:
Theory of Concept Maps: http://www.msu.edu/~luckie/ctools/
Kinds of Concept Maps: http://classes.aces.uiuc.edu/ACES100/Mind/c-m2.html
Tips on Making Concept Maps: http://classes.aces.uiuc.edu/ACES100/Mind/c-m3.html
IR Unknown
An unknown compound was determined to be one of the three shown below. Use the
data provided to determine which one of the compounds is the actual unknown.
IR (cm-1): 3030, 2915, 2713, 1727, 1456, 1397, 1117, 1016, 985, 828.
Optical rotation = +13.1o
O
O
Cholic Acid
Cholic acid (structure shown below) is a major steroidal constituent of human
bile.
COOH
H
OH
CH3
CH3
H
H
HO
H
OH
H
Calcium Blockers
Calcium channel blockers inhibit the flow of calcium ions into the smooth
muscle cells of blood vessels. This inhibition results in a relaxation of the
muscles in the blood vessels, with the result that there is less resistance to
the flow of blood and a lowering of blood pressure. A critical step in the
synthesis of a pharmaceutically important calcium channel blocker,
diltiazem, is shown below. The single enantiomer of (-)-trans-2phenylcyclohexyl chloroacetate (A) is converted into two compounds (B
and C).
Glucose
CH2OH
CH2OH
HO
HO
O
Ha
HO
OH
OH
!-D-glucose
O
OH
HO
OH
Ha
"-D-glucose
a. Draw the 2 chair conformers for D-glucose. Circle the most stable chair.
b. Draw the 2 chair conformers for D-glucose. Circle the most stable
chair.
diastereomers
conformers
constitutional isomers
iii. How will the coupling change in D-glucose vs Dglucose? (Review rigid systems!)
Hydrogen Bonding:
CO2H
OCH3
CO2H
OCH3
a. Draw the 2 chair conformers for compound A. Circle the most stable chair.
b. Draw the 2 chair conformers for compound B. Circle the most stable
chair.
diastereomers
conformers
constitutional isomers
5.a. Place asterisks at all chiral carbon centers, and then circle the center that relates to
the difference between Testosterone and Epitestosterone.
b. Calculate the max number of stereoisomers.
6. Assign priorities to each group on the circled carbon from question 5a and label the
center as either R or S. What does this tell you about the molecule?
8. Label the axial and equatorial groups on the five-membered rings of each molecule.
10. Below is the mass spectrum for Testosterone. Based on the information in the paper,
predict how the mass spectrum for the synthetic testosterone would differ.
11. Considering what you have read and discussed did Floyd Landis cheat?
Practice Exam
Problem-Solving using spectroscopy, stereochemistry, and conformational analysis
This student wanted to start with 1,3 cyclohexanediol and 2-propanone rather than
the reagents shown above.
Draw the starting material: 1,3 cyclohexanediol.
Draw the product of this reaction with the acetal functional group.
2. The student looked up the structures in CSB stockroom inventory and found more
than one entry for 1,3 cyclohexanediol.
How many possible stereoisomers for 1,3 cyclohexanediol are there?
diastereomers
conformers
constitutional isomers
3. Knowing that water would be produced as a side-product and the reaction was run in
acidic conditions, the student decided to work up the reaction using a liquid-liquid
extraction. Describe the extraction.
What solvents should the student use?
If the student still had some methyl tert-butyl ether left in solution, what peaks
(include shift, integration and multiplicity) would be present in the 1H NMR?
If the reaction did not go to completion and the student had a solution of 25%
starting material (1,3-cyclohexanediol) and 75% of the acetal product, draw
the expected GC trace. Label each peak to indicate which compound would
have a longer retention time.
5. The spectra below were obtained after cis-1,3 cyclohexanediol was reacted with 2propanone in acid. Fully analyze the spectra (on the following page) in the tables
below.
IR
Frequency
Bond Type
13C
Chemical Shift
Type of Carbon
1H
Chemical Shift
Integration
Multiplicity
Interpretation
6. The spectra below were obtained after trans-1,3 cyclohexanediol was reacted with 2propanone in acid. Fully analyze the spectra (on the following page) in the tables
below.
IR
Frequency
Bond Type
13C
Chemical Shift
Type of Carbon
1H
Chemical Shift
Integration
Multiplicity
Interpretation
In order to understand why one of these reactions worked, draw the two
conformers of cis-1,3 cyclohexanediol in chair form.
In order to understand why one of these reactions worked, draw the two
conformers of trans-1,3 cyclohexanediol in chair form.
In order to understand why one of these reactions worked, draw the acetal
product of each diol in chair form.
8. Isotopic experiment
This student noticed that there are 3 oxygens in the starting materials, but there are
two oxygens in the acetal product. The student decided to run the reaction below
with 18O isotope in the aldehyde to determine whether this oxygen is included in the
acetal product. The student used Mass Spectrometry to look at the product.
Explain what the mass spectrum would look like if the 18O isotope was NOT
incorporated into the acetal.
Explain what the mass spectrum would look like if the 18O isotope was incorporated
into the acetal.
Problem 2:
The electron configuration of O2 in MO terms is: ((1s)2, (1s)2, (2s)2, (2s)2,
(2p)2, (2p)2, (2p)2, ( 2p*)1, (2p*)1.
e. Draw the Lewis dot structure of molecular O2. How many unpaired
electrons are in this structure?
f. Liquid molecular oxygen is visibly held in place between the poles
of a strong magnet. Explain this in terms of the electron
configuration.
g. Molecular O2 has a bond length of 0.121 nm while the molecule O2+
has a bond length of 0.112 nm and the oxygen anion, O2-, has a
bond length of 0.126 nm. Explain the trend in bond lengths.
Problem 3:
The electron configuration of NO in MO terms is: (1s)2, (1s)2, (2s)2, (2s)2,
(2p)2, (2p)2, (2p)2, ( 2p*)1.
a. Draw the Lewis dot structure of molecular NO. How many unpaired
electrons are in this structure?
b. Calculate the bond order for NO based on the electron
configuration.
c. The bond length in NO is 0.115 nm while the bond length in NO+ is
0.1062 nm. Calculate the bond order for NO+ and explain the
change in bond length based on this difference.
Problem 4:
a. Propose a reasonable electron configuration in MO terms for BN.
b. Determine the bond order for BN.
c. Is BN diamagnetic or paramagnetic according to the electron
configuration?
Hybrid Orbitals
What is the geometry of the carbon in methane?
In the figure above, an energy plot is shown for the rotation about the C2-C3
bond in 1,3-butadiene.
o Use the MO diagram to explain the rotational barrier observed.
!4
!3
!2
!1
!2C1C2
!2C5C6
!1C1C2
!1C5C6
Allyl systems are the shortest systems to be conjugated the orbitals for a
three atom conjugated system look like this:
o Draw the lewis dot structures of the allyl radical, cation, anion and 1propene.
o Draw the MO diagram for the allyl radical, cation, anion and 1-propene.
Additional Problems
Torsional Strain:
(you may want to read the following reference: Nature, 2001, Vol 411, p 539)
a. Make careful stick or line drawings of staggered and eclipsed ethane.
Problem 2:
a. Draw resonance forms for the following two molecules:
Problem 3:
Unsaturated compounds, such as naphthalene and tetrahydronaphthalene, can
act as Lewis bases to react with Lewis acidic organic molecules. For instance,
addition of an acid chloride such as ethanoyl chloride would result in the following
reactions:
Problem 4:
Use Spartan to generate the molecular orbitals and electron density for
the following molecules:
a.
b.
c.
d.
e.
f.
pyridine
toluene
aniline
1,3-cyclohexadiene
maleic anhydride
phthalic anhydride
Use the electron density maps to predict where these molecules would be
willing to accept electrons (susceptible to nuclephilic attack) or which sites
might be willing to donate electrons (act as nucleophiles).
Aromaticity
Chapter 16
On a separate sheet(s) of paper, draw Hckel MO Diagrams of:
a) cyclobutadiene
b) cyclohexatriene (benzene)
c) cyclooctatetraene
d) cyclodecapentaene
e) cyclododecahexaene
Example:
Cyclobutadiene (orbital pictures are viewed from the top):
1.
2.
c. The following compound reacts with HCl to give a weak acid. What is
the structure of that weak acid?
Heteroaromatic Compounds
Additional Problems:
Problem 1:
Using your concept map,
f. Predict whether each of the following systems is aromatic, antiaromatic or non-aromatic.
Problem 2:
Generate the molecular orbital diagrams for the following molecules:
o Cyclopentadienyl anion (C5H5-)
o Furan
o Cycloheptatrienyl cation (C7H7+)
Problem 3:
Cyclooctatetraene readily reacts with potassium metal to form a dianion.
Draw a Hckel MO diagram for this molecule. Include energy levels, electron
filling, and labels. Label the HOMO and the LUMO.
or
nonaromatic
Planar cyclooctatetraene would have bond angles of 135. This is not stable so
the molecule assumes a nonplanar, tub-shaped geometry. Each double bond is
twisted relative to the adjacent double bonds. Based on this data, what would
you predict for the bond lengths for this compound? Keep in mind:
C-C
1.5
C=C
1.3
Benzene
1.4
Based on the geometry and bond lengths of cyclooctatetrene, would you predict
this compound to be:
aromatic, anti-aromatic
or
nonaromatic
Draw the atomic orbital energy level diagram with electron filling for potassium metal.
Cyclooctatetraene reacts with potassium metal to form the dianion. Draw the Hckel
MO diagram of the dianion.
Acid-Base Chemistry
Chapter 4
We will use pKa tables frequently. Print a copy from one of these sources:
http://www.chem.wisc.edu/areas/reich/pkatable/
http://www2.lsdiv.harvard.edu/labs/evans/pdf/evans_pKa_table.pdf
http://www.cem.msu.edu/~reusch/VirtualText/acidity2.htm
http://research.chem.psu.edu/brpgroup/pKa_compilation.pdf
Part I.
1 H3PO4
1 NaOH
1 H2SO4
1 K2CO3
1 AlCl3
1 PH3
1 NH3
1 HBr
The pKa of water is 16. What does this number say about the equilibrium
constant in the ionization reaction? (K = 10-pka) Is it greater or less than
1? What does this mean?
Which of these compounds is more acidic? Draw the conjugate base for
each. What factor controls the trend in acidity among these three
molecules?
Same question, new molecules (except that we are now looking at Lewis
Acids!)
Same question, new molecules (except that we are now looking at Lewis
Acids!)
Additional Problems
1. In each pair of compounds, choose the stronger acid:
O
a.
OCH3
OH
b.
NH3
H2O
c.
SH
OH
d.
e.
O
OH
Br
OH
Br
a.
Cl
b.
Ph3C
d.
e.
c.
HO
f.
P(CH3)3
H
N
N(CH3)3
Predicted Experimental
pKa
pKa
MeOH
MeOH2+
MeNH2
MeNH3+
Knowing the relationship between basicity and acidity, order the following
ion by increasing basicity (weakest to strongest).
Looking at the pKa table in Hornback (p 129-131), what are the strongest
bases?
ACID-BASE SUMMARY
Explain each of the structural features that effect pKa using an example:
1. Electronegativity
2. Atomic size
3. Delocalization (resonance)
4. Hybridization
5. Inductive
You may move electrons from a double bond to make those two
electrons a lone pair on one of the atoms originally involved in the
double bond (see Arrow 2).
For resonance structures, you may not move any nuclei or break
any single bonds.
You may not change the total number of electrons.
Additional Problems
Explain why the 1,4 disubstituted isomer is more acidic than the 1,3
disubstituted isomer. Draw the conjugate bases and several resonance
structures of each.
OH
OH
CN
CN
Chirality Problem:
Consider the set of ketones shown below:
1. Circle the ketones that would be optically active.
2. Which of the ketones would lose their optical activity under KOH/H2O treatment.
O
H Ph
Ph
Ph
H Ph
tBu
Ph H
tBu
O
tBu
Application Problem
Additional Problems
1.
Butyl Lithium (BuLi) is often used to prepare other important bases used in
organic chemistry. Examine the reaction below and answer the
questions that follow.
c. Can you think of any other factors which make BuLi an attractive base?
2.
b.
3.
4.
Acid-Base Extraction
An organic chemistry student was given a mixture of four compounds for his lab practical. He decided
to use an acid base extraction. Label each compound as neutral, acidic or basic.
OCH3
CO2H
OH
NH2
CH3
CH3
CH3
CH3
This student proposed the following separation outlined in the flow chart below.
1, 2, 3, 4 dissolved in CH2Cl2
Extract with 3M aq HCl
CH2Cl2 layer
aqueous layer
Basify with 10% NaOH and
extract with CH2Cl2
aqueous layer
Acidify with 3M
HCl and extract
with CH2Cl2
Solution C
CH2Cl2 layer
Extract with
5% NaHCO3
CH2Cl2 layer
CH2Cl2 layer
Solution A
aqueous layer
Solution B
aqueous layer
Acidify with 3M
HCl and extract
with CH2Cl2
Solution D
Solution E
There is a problem with the students proposed separation scheme. What is the problem and
how could it be fixed?
pKa
44
Conjugate base
35
22
11
22
3. Draw Huckel MO energy diagrams for the first two acids in the table
above.
4. Draw Huckel MO energy diagrams for the conjugate bases of the first
two acids.
5. What do these Huckel MO energy diagrams illustrate and how does that
help us understand their relative acidities?
pKa
43
PhCH3
41
Ph2CH2
34
Ph3CH
32
Conjugate base
20
18
8. Why are the last two acids on the table so much more acidic than the
others?
9. Draw Huckel MO energy diagrams for the last acid in the table above.
10. Draw Huckel MO energy diagrams for the conjugate base of the last acid.
pKa
44
Conjugate base
27
31
31
17
13. What structural feature do all of the conjugate bases have in common?
14. Explain the relatively large pKa difference between 2-methylpropene and
acetone.
15. Draw the Huckel MO diagram for both acetone and its conjugate base.
More is better!?!?
16. Draw the conjugate bases for each acid below.
17. Using their conjugate bases, compare the pKa values of each acid relative
to the others in the table.
Acid
pKa
20
Conjugate base
11
11
10
18. Draw the Huckel MO energy diagrams for both 2,5-pentadione and its
conjugate base.
Carboxylic acids
19. Draw the conjugate bases for each acid below.
20. Using their conjugate bases, compare the pKa values of each acid relative
to the others in the table.
Acid
pKa
27
Conjugate base
Now lets see what happens to the carboxylic acid pKa as we make systematic
changes to the methyl group.
Acid
pKa
5
Conjugate base
3
2.8
2.8
2.6
1
0.5
21. Draw the Huckel MO energy diagrams for both acetic acid and its
conjugate base.
Additional Problems
Problem 1:
Cis and trans isomers of 3-methoxycyclohexanol are found as components of a
group of antibiotics called macrolides.
Draw both of the chair conformations of cis-3-methoxycyclohexanol.
On your drawings in part a) indicate all 6 and 7 atom interactions.
Indicate the most stable conformation of cis-3-methoxycyclohexanol.
Draw the most stable chair conformation of trans-3-methoxycyclohexanol.
Both isomers are capable of reacting with a strong base. Draw the
reaction of cis-3-methoxycyclohexanol reacting with a strong base.
Is the conjugate base of cis-3-methoxycyclohexanol an electrophile or a
nucleophile?
The conjugate base of cis-3-methoxycyclohexanol can then react with
methyl iodide (CH3I). Is methyl iodide an electrophile or a nucleophile?
Explain (show the dipole moment).
Draw arrows to show the reaction of the conjugate base of cis-3methoxycyclohexanol with methyl iodide.
Both 3-methoxycyclohexanols are chiral. However, one diasteromer
reacts with base and then methyl iodide to give an optically inactive
product. Which one?
Problem 2:
a) Draw a Lewis Dot Structure for formaldehyde (CH2O) including formal charge
and non-bonding pairs.
l) Do the Lewis Dot Structures agree with MO picture of the radical anion of
formaldehyde? How do they differ?
The observation of slow cis-to-trans isomerization (rotation) around the C-N bond in
amides has fascinated chemists for years.
O
R'
N
R1
R2
catalyst
R'
N
R2
R1
Using the resonance structure, explain why there is slow rotation around the C-N
bond.
Label the hybridization of each of the atoms of the amide functional group.
In the figure above, an energy plot is shown for the rotation about the C-N
bond of an amide. Depending upon the substituents, the barrier to rotation
can range from 18 to 22 kcal/mol.
Anti-Aromatic
Non-aromatic
Explain why the barrier to rotation around the amide bond is much
lower in N-acetylpyrrole.
Some of the first evidence of cis-trans isomerisation came from nmr spectra of
amides.
When amides are dissolved in water (or other hydrogen-bonding solvents), the
barrier to rotation increases by up to 3 kcal/mol!
Drakenberg, et.al., Journal of Physical Chemistry, 1969, 73, 3177-3180.
Bronsted Acids can effect the rate of isomerization in amides. For example, the
rate of isomerization of N,N-dimethylacetamide increases 130 fold when the pH
is changed from 7.0 to 1.8.
Gerig, Biopolymers, 1971, 10, 2435-2443.
Draw a Newman Projection looking down the N-CH bond of the ring
for the cis-prolyl analogue.
Draw a Newman Projection looking down the N-CH bond of the ring
for the trans-prolyl analogue.
Binding of biological metal ions such as copper may also play a role in
these systems.
Circle all that pertain to Cu+2:
Bronsted Acid
Base
Bronsted Base
Lewis Acid
Lewis
Show why the copper ion is held in the position shown below.
or
trans
Why did Etzkorn choose to replace the amide bond with an alkene?