Chemistry 31

Summer 2017

Organic Chemistry I

Class Packet Problems

Keys

Dr. Brian McNelis

Chemistry Department
Santa Clara University
Orbital Picture Drawing Practice - Answers
For the following compounds, draw an orbital picture showing the s-bonds and lines and
the p-bonds as overlapping p-orbitals. Are the H’s in allene and cumulene coplanar? Are
the H’s and the nonbonding electrons on oxygen in ketene coplanar?
Hybridization Practice Problems

1. The molecule shown below is Biotin, a necessary vitamin for cell growth.

a. Draw in all lone pairs in this molecule consistent with the bonding rules. All
atoms are uncharged.
See above

b. Give the bond angles for angle a and b. Assume no distortions from lone pairs
or other effect.

a: 120o; b: 109o

c. Give the hybridization of carbon 1, 2 and 3. Also give the hybridization of

sulfur, either nitrogen and oxygen 1.

C1: __sp2______ C2: __sp3______ C3: __sp3______

S: ___sp3_______, N: ___sp3_______, O1: __sp2_______

d. What is the total number of sp2 oxygen atoms? __2______

e. What is the total number of sp3 carbons?_____8_____

2. The molecule shown below is Tetracycline, a common antibacterial drug.

a. Draw in all lone pairs in this molecule consistent with the bonding rules. All
atoms are uncharged.

b. Give the hybridization of Carbons 1, 2, 3 and Oxygen 4

C1: ___sp2_____ C2: __sp3______ C3 ___sp2______ O4 __sp2_______

c. What is the geometry at each of these atoms? (ignoring distortions)

C1:trigonal planar C2: tetrahedral C3: trigonal planar O4: trigonal planar

d. What is the geometry of 6-membered ring on the left of the structure above?

All the carbon atoms in the ring are trigonal planar, so all the carbons are
coplanar, or in simple terms the ring is flat.

e. What is the total number of sp2 oxygen atoms? __3______

f. What is the total number of sp2 carbons?____13______

3. Determine the hybridization of all atoms in the following structural formulas.
Add to the structures any lone pair electrons before assigning hybridizaiton.

Just for fun, give the name of these amino acids. You don’t have to know these
for my course, I just thought it would be fun since you are doing this in Bio 24

4. Two possible orbital pictures for BCl3 are shown below.

A. B.

a. What hybridization for Boron is depicted in A and B?

A: sp3 B: sp2

b. Which picture is the best orbital representation of BCl3?

Why is A or B a better structure?

B, maximum distance, 120o, between bonding pairs and Cl atoms when in the
sp2 hybridization and trigonal planar geometry

c. What type of orbital is the empty orbital in A and B?

A: sp3 B: p
- -
d. BCl3 reacts with Cl to form BCl4 as the product. Predict the hybridization of
this compound and draw an orbital picture.

sp3 hybridization for boron, note the hybridization

changes when the number of bonds to boron changes.

5. Draw a complete orbital picture for formaldehyde, CH2O and label hybridized
orbitals (sp3, sp2 or sp), sigma and pi bonds and p-orbitals that overlap to form
any pi bonds.

Top View

Side View
6. Two possible charged states for carbon are +1 and -1, which we call a
carbocation and a carbanion, respectively. Example structures for each of these
charged species are given below. Determine the hybridization for both structures
and draw an orbital picture. Note: you can do this problem now, even though we
have not discussed formal charge-we will cover that topic next week. Also, all
the electrons are shown, the carbon in the carbocation has only three bonds and
no lone pair.
Bonding Rules and Lewis Structures Practice Problems-Key

1. Given what you know about the bonding rules for nonmetals, use the molecule
formula to complete the following structures. Also draw in any lone pair electrons
to complete the structures.

2. Complete the molecular formulas below and draw a Lewis structure for the
compound.

CF4 CH2Cl2 CH3SH

CH3NH2
NH2OH CH2O

3. Draw the Lewis structure for the following molecular and condensed formulas.

N2 H4 CH3CO2H

BF3 CH3OCH3

4. Given the molecular formulas and the templates given, complete the following
Lewis structures.
 Skeletal drawings in organic chemistry
Rules
1. Carbon atoms are represented by the ends of lines or the junctions between lines
without using the chemical symbol, C. The lines represent the bonds between carbon
atoms.
2. Hydrogen atoms attached to carbon atoms are not shown explicitly. Sufficient
hydrogen atoms are assumed to be attached to the carbons so that each carbon has four
bonds. Be sure to count the correct number of bonds - double bonds count as two bonds
and triple bonds count as three bonds.
3. All other types of atoms (e.g. O, S, N, Cl) are shown explicitly.
4. Hydrogens attached to atoms other than carbon are always shown explicitly.
5. Nonbonding electron pairs on atoms are not typically shown. Sufficient nonbonding
pairs are assumed so that each atom has a full outer shell of 8 electrons.

Note- at times carbon atoms, assumed hydrogens and nonbonding electron pairs will be
shown for emphasis.

Example and Practice – Convert the following Lewis structures to skeletal drawings and
convert the following skeletal drawings to a complete Lewis structures.
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Key:

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Formal Charge Practice: Key
1. For the following compounds, determine the formal charge for all the heteroatoms (O, N and S).
All nonbonding electrons are shown. For carbon atoms, assume zero charge and fill in the correct
number of assumed hydrogens. Note: there are no assumed electrons on carbon, they have to be
explicitly shown with nonbonding electrons and/or with a charge notation.

2. For the following compounds, determine the charge for all the atoms. All assumed hydrogens and
nonbonding electrons are shown.

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3. For the following compounds, all charges are shown as they might typically be in texts or the
chemical literature. Add to these structures the correct number of assumed nonbonding electrons
and hydrogens consistent with the formal charges as shown. Recall from the drawing conventions,
hydrogens are always shown on heteroatoms (O, N and S) so only hydrogens on carbons are
assumed and need to be added to the structure below. As always, assume zero charge unless a
charge is shown.

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IR Spectra In-Class Problems Answer Key
Interpret each spectrum to determine the functional group(s)
1. carboxylic acid

2. alcohol and the usual C-H aliphatic peaks (just below 3000 cm-1)

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3. carbonyl: ketone, not aldehyde, ester or amide and the usual C-H aliphatic peaks (just below 3000
cm-1)

4. carbonyl: aldehyde, conjugation (carbonyl peak is at 1693 cm-1)

some small peaks at the C-H aliphatic peaks (just below 3000 cm-1) and the C-H Aromatic/Vinyl range
(just above 3000 cm-1)

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5. carbonyl: ester and the usual C-H aliphatic peaks (just below 3000 cm-1)

6. amine with NH, also there is Aromatic or Vinyl C-H just above 3000 cm-1 and the usual C-H
aliphatic peaks (just below 3000 cm-1)

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IR Spectra In-Class Problems: Actual compounds

Note that you can not determine the actual structure, but comparing the compounds below to the
functional groups assigned above confirms the spectral interpretation. You don’t need this
information, and the complete, correct answers are next to the spectra, but I thought you might be
interested.

1. 3-Phenylpropanoic acid

2. 1-Pentanol

3. 2-Pentanone

4. trans-2-Butenal

5. Methyl butanoate

6. N-butylbenzylamine

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IR Practice Problems:
Interpret each spectrum to determine the functional group(s). Then after you have analyzed the spectra, use the
Compound List to determine which compound best correlates to the spectra data. There will be one best match
for each spectrum.
1. only major peak is the usual C-H aliphatic peaks (just below 3000 cm-1)

2. both the Aromatic or Vinyl C-H (just above 3000 cm-1) and the usual C-H aliphatic peaks (just
below 3000 cm-1)

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3. carbonyl peak at 1718 cm-1, ketone most likely, not aldehyde, amide or ester
Recall that aldehyde (no C-H peaks 2750 and 2850 cm-1), ester (should be 1735 cm-1) or amide (should
be at 1690 cm-1 or lower) usually have a peaks at different frequencies.

4. alcohol peak at 3335 cm-1 with peaks in the C-H aliphatic peaks (just below 3000 cm-1) and the C-H
Aromatic/Vinyl range (just above 3000 cm-1)

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5. carbonyl, most likely ester because carbonyl peak at 1741 cm-1; the usual C-H aliphatic peaks (just
below 3000 cm-1)

6. carboxylic acid due to huge peak starting at about 3200 cm-1; note that you can not really see C-H
aliphatic or aromatic vinyl with carboxylic acids

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7. carbonyl peak at 1703 cm-1: aldehyde, because of two C-H peaks at 2737 and 2820 cm-1; some
small peaks at the C-H Aromatic/Vinyl range (just above 3000 cm-1) but it looks like no peaks at the
C-H aliphatic peaks (just below 3000 cm-1)

8. peaks at the C-H Aromatic/Vinyl range (just above 3000 cm-1) and again it looks like no peaks at
the C-H aliphatic peaks (just below 3000 cm-1). Big peak at 2229 cm-1,

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IR Problem Set - List of Compounds

Match the compounds below to the appropriate spectrum, 1-8 above.

Answers to Matching Spectra to Compound List

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13
C NMR Problem Set: Key

1. Determine the numbers of peaks observed in the 13C NMR spectrum for the following
compounds.
They are annotated to let you know the types. Total # of peaks is the highest number
for each compound.

2. You have been given a sample that contains one of the two following compounds. How
would determine which compound you have?
Take a 13C NMR spectrum and count the peaks. If it is the first compound, all the
carbons are of different types, so you'll have 9 peaks. Because of the symmetry of the second
compound, that isomer will only show 3 peaks.

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Conformational Analysis Practice Problems:

1. For the following molecule, perform a complete conformational analysis using the data provided in
Table 4.3 and 4.4. Follow the following steps to complete the analysis. (Assume no distortion of the
ring due to the oxygen, and assume no steric strain due to electron pairs on oxygen.)

a. Draw the two chair conformations possible for the compound.

b. Calculate the energy difference between the two chair conformations drawn above.

c. Estimate the ratio of most stable to least stable conformation that could be found in a sample of this
compound at 25oC.

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2. Identify the more stable conformation in each of the following pairs and explain your answer.

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R and S Designation Assignment
Practice Problems: Assign R and S to all Chiral Centers
Br O

OH
CH3 OH NH2

CH3 OH HO OH

CH3

HO O Cl Cl CH3
Cl
CH3

HO

Br Br Br
Br

OH

Answers:

No chiral center

HO O Cl Cl CH3 CH 3
R

Cl S CH3
CH3 Redraw from top view using
wedges, dash notation then assign R and S

R S S R S

HO

Br Br Br
Br

OH
S R R S S S

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Resonance Practice Problems --Key
Draw additional resonance structures for each of the following molecules. Because most of the
molecules are drawn using skeletal structures, be particularly aware of the valence electrons and where
the implicit hydrogens are. Make sure to assign formal charges where appropriate and use curved
arrows to indicate the movement of electrons to reach the next resonance structure. As a hint, I have
indicated the number of additional resonance structures you should find in each case.

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Draw all valid resonance structures for the following molecules. Note that in some cases there may not
be any.

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 STABILITY RULES IN THE EVALUATION OF ORGANIC COMPOUNDS--KEY

We will evaluate whether reactions occur based on the stability of the products as compared to
reactants. In addition, we will decide on the product’s structure based on the energetics of reaction
pathways, which will require us to determine the stability of charged species (anions and cations),
often referred to as intermediates.

We have a number of tools to evaluate a compound’s stability:

1. Resonance
2. Electronegativity
3. Inductive effect
4. Hybridization
5. Bond strengths
6. Size of atoms – bond strength and anion stability
7. Steric interactions between substituents
8. pKa – ranking of acidity and conjugate base (anion) stability

The evaluation of stability using these tools is extremely valuable in organic chemistry, because
reaction results can be rationalized and as we master these skills, we can predict reaction outcomes
rather than simply memorize them. Importantly, we will use these tools all year so it will be a good
investment to learn these concepts.

Below are example compounds exhibiting the use of these tools. This document is a template to
facilitate lecture and allow for you to think about the questions presented rather than just writing
content down to be learned later. The goal is to present examples that elucidate how the tools we
have learned are applied to stability evaluations.

Stability of Uncharged Compounds

1. Alkene Stability – Cis or Trans

Which is more stable, products or reactants?

a.

more stable – trans, steric hindrance

or

more stable – trans, steric hindrance

b.

more stable – largest groups trans, steric hindrance

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2. Alkene Stability – Degree of Substitution

most stable trans cis least stable

or

most stable trans cis least stable

Why?
Hyperconjugation: stabilizing effect due to partial “bonding” interactions (sharing of electron density)
between a filled ⌠-bonding orbital and an empty adjacent orbital. Increasing the substitution of an
alkene, increases the number of possible hyperconjugation interactions between the adjacent
σ -bonding orbitals and the π* molecular orbital of the alkene.
WHAT????!! We will discuss later…

3. Alkene Stability – Conjugation

more stable, pi bonds in conjugation - Resonance

more stable, pi bonds in conjugation - Resonance

Special Case:

more stable, more pi bonds in conjugation, but even more

important is the formation of benzene or aromatic ring, which is
super stable

Two more examples: These elimination reactions are very favorable, products are aromatic rings

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4. Cis or Trans Substituents in Cyclics

trans substituents, less steric interactions

trans substituents, less steric interactions but…

When looking at cyclohexanes, make sure you do a chair conformational analysis

5. Bond Strengths and Product vs. Reactant Stability

Recall our approximate numbers for σ-bonds vs. π-bonds:

~ 100 kcal/mol for σ-bonds
~ 50 kcal/mol for -bond

As we go down a column on the periodic table, atomic size increases, bond length increases and
bond strength decreases. Halogens are a good example, H-F is a weak acid and HI is a very strong
acid. Bond strengths with carbon: C-F > C-Cl > C-Br > C-I. Note, C-Br and C-I ⌠-bonds are not much
stronger than π-bond.

This same analysis works for other periodic table column comparisons:

H2S vs. H2O which is more acidic?

The H-S bond should be a _longer, weaker_ bond therefore H2S is _more__ acidic.
Could check pKa of each, but you do not need pKa to answer these questions.

Do the following reactions occur as written? Why?

more stable, C-F bond is stronger than C-Cl

can also do anion analysis, Cl- is more stable than F-

more stable, C-OH bond is stronger than C-Br

can also do anion analysis, Br- is more stable than HO-
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5. Bond Strengths, continued
Do the following reactions occur as written? Why?

more stable, C-C bond is stronger than C-Br

Anion analysis: Br- is much more stable than HC=C- (see pka table in CP)

cation stability- we will see later

how cation stability affects addition rxn

made two sigma bonds

broke one sigma (H-Br) and one pi bond, products more stable

But one has to be careful with bond strengths: Elmination reaction shown below favors products

make pi bond and one sigma bond, broke two sigma bonds.
Products seem less stable, yet this reaction proceeds to products.
Why, energy is close, products about 3 kcal/mol more stable due to
Water stability and HO- reactivity, products are favored.

6. Acidity
We can determine if an acid-base reaction occurs, since the product acid must be more stable and
therefore have a higher pKa. This gives us information about the strength of a Y-H bond (Y = any
atom) using pKa’s. Anion analysis works here as well (just like in our acidity comparisons where we
considered the conjugate bases or anions in most cases), which is especially effective if you do not
have pKa values.

Examples: We did many of these in class, this is just a refresher

Acid-base reactions below all favor products, product acids have higher pKa’s

pKa=5 pKa=50

pKa=16 pKa=36

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But sometimes need pKa’s for less obvious examples, especially for compounds that you have not
seen comparable pKa values. Can use pKa, but anion analysis works well without pKa,s

pKa=20 less stable resonance stabilized pKa=50

Stability of Charged Compounds

1. Anions
Which is more stable and why?
Applications of resonance, inductive effects, electronegativity, size of the atom. Could use pKa table,
but you will not have a pKa table most of the time.

Recall that the Inductive effect is a shift of electron density in a molecule due to the polarization of a
bond by a nearby electronegative atom.

more stable more stable

O more electronegative than C S is bigger than O

more stable more stable

inductive effects O more electronegative than N

more stable more stable

inductive effects, F more electroneg. both have resonance
O more electroneg. than C

more stable more stable

Inductive effects, F closer resonance

more stable Tough one! More stable,

resonance pKa=20 pKa=16
But left one has resonance! Some charge
localized on carbon destabilizes the anion.
Which is most stable and why?
Hybridization is changing, electrons are in different hybridized orbitals

sp sp2 sp3

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Orbital Pictures:

more stable least stable

pKa=25 pKa=40 pKa=50

electrons in sp orbital, more s-character,closer to the nucleus, anion more stable

2. Carbocations

3o 2o 1o methyl
more stable very unstable, almost never formed

or

3o 2o 1o methyl
more stable very unstable, almost never formed

Orbital Picture of a Carbocation: 3o carbocation

Hyperconjugation involves partial sharing of electron density between a σ-bonding orbital and an
adjacent empty orbital. In carbocations, the empty p-orbital receives electron density from neighboring
σ-bonds by partial sharing of σ-bonding electrons. This process explains why alkyl groups are weak
electron donating groups (EDG).

Below are two orbital pictures of a 2o carbocation and the partial donation of σ-bonding electrons via
hyperconjugation. Note that any alkyl group attached to the carbocation (including the –CH3 group on
the left side of the molecule) can do this same partial donation of σ-bonding electrons
(hyperconjugation) to help stabilize the positive charge, which is why more alkyl groups attached to
the C+ makes the carbocation more stable.

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Which carbocation is more stable and why?

more stable, resonance 3o cation more stable resonance

more stable more stable, resonance

Inductive effects
Pulling electron density from cation destabilizes it

more stable, both have resonance, the cation more stable, nitrogen a better donor via on the
right puts 6e- around O, not a good or resonance than oxygen, less electronegative
reasonable resonance form

Bonus Topic:
Alkene Stabilization via Hyperconjugation

Hyperconjugation: stabilizing effect due to partial “bonding” interactions (sharing of electron density)
between a filled ⌠-bonding orbital and an empty adjacent orbital. Increasing the substitution of an
alkene, increases the number of possible hyperconjugation interactions between the adjacent ⌠ -
bonding orbitals and the π* molecular orbital of the alkene.

In common language, we know that more highly substituted alkenes are more stable and we are not
really sure why. Best theoretical explanation is the partial donation of the ⌠-bonding electrons to the
π* antibonding orbital, when one considers the molecular orbital description of a compound with a π-
bond. Below are two pictures that might help you visualize this:

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Why does donation of electron density to the π∗-antibonding orbital yield stabilization for the alkene
compound? And what is the π*-antibonding orbital? We will cover molecular orbital theory in more
detail later in the course, so be happy for now that you can talk about complicated chemistry terms
you know nothing about. What we do need to know is more highly substituted alkenes are more
stable and the theoretical explanation is less critcal, we care more about the experimental results and
the trends that we can use to predict reaction outcomes.

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EXAMPLE REACTIONS-MECHANISM TEMPLATES

Substitution Reaction

Stereochemistry of Substitution Reaction

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Elimination Reaction

Predict Products Using Stability Rules

select the H anti to the Br more high substituted, trans alkene

more highly substituted alkene

alkene in resonance with

benzene ring
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Addition Reaction

Summary: On the addition of HX (HCl, HBr, HI) the Cl, Br or I goes where the cation was formed, so
the most stable carbocation controls the location of addition of H+ and therefore, X-

Predict Products Using Stability Rules – Use Intermediate Cation Stability and Not Product Stability

3o Cation more stable than 2o

more stablecation not resonance

stabilized
Both 2o cations, first cation more stable, resonance
Reaction Coordinate for Substitution Reaction
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Mechanism:

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Reaction Coordinate for Elimination Reaction

Mechanism:

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Reaction Coordinate for Addition Reaction

Mechanism:

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Draw a stepwise mechanism for the following reaction: HBr Addition

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SN2 vs. E2 Reactions -- Focusing on the most important, competing reactions KEY

The basicity of the base/nucleophile and the structure of the alkyl halide are the most important factors
to consider when deciding whether a reaction proceeds by a SN2 or E2 mechanism. See the simplified
rules for SN2 vs. E2 below.

Primary Alkyl Halides:

SN2 reaction is favored, E2 can only occur in one special case but we will learn that on Friday.

Secondary Alkyl Halides:

a. With Bases/Nucleophiles that are strongly basic, such as NaOH (pKa of H2O=15) and RONa (pKa
of alcohols=16-18) elimination will predominate. Bases that lead to E2, reaction with secondary alkyl
halides are the conjugate bases of acids with a pKa>15.
b. With weakly basic but good nucleophiles (NaCN, NaO2CCH3, NaN3) SN2 will predominate (pKa
range 5-15 for the above bases/nucleophiles).

3. Tertiary Alkyl Halides:

Bases/Nucleophiles that are strongly basic, such as NaOH and RONa will yield E2 reaciton outcomes.
SN2 can not occur with 3o alkyl halides.

Practice Problems-SN2 or E2 KEY

Give the major product of the reaction and the mechanism by which it is produced (SN2 and E2 only
for this set of reactions; we will add in SN1 /E1 later). Be sure to include the stereochemical outcome.
Be sure to follow the guidelines we discussed in class for 1o, 2o and 3o alkyl halides and the pKa ranges
for 2o systems. The pKa table from the class packet on the last page of this problem set could also be
useful in deciding if the product is an SN2 or E2 product.
a.

b.

c.

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d.

e.

f.

h.

i.

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j.

k.

l.

m.

n.

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o.

p.

q.

r.

s.

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t.

u.

v.

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Substitution vs Elimination Practice Problems: KEY
For the following reactions give the major product of the reaction and the mechanism (SN1, SN2, E1,
E2). Be sure to include the stereochemical outcome.
a.

b.

d.

e.

f.

g.

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h.

i.

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Substitution vs Elimination Practice Problems: In Class Problems 2 KEY
For the following reactions give the major product of the reaction and the mechanism (SN1, SN2, E1,
E2). Be sure to include the stereochemical outcome.

a.

b.

d.

e.

f.

g.

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Alkene Reaction Drill Problems

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Alkyne Addition Reactions-Predict HBr Addition to Alkynes
-Addition of 1 equivalent of HBr or Addition of 2 equivalents of HBr
HBr
Br H

Mechanism:
Br
HBr H Br H

H H
H

HBr
Br

Mechanism:
Br
HBr Br

H H
H

HBr
Br H
Br H
2 equiv. H

Mechanism:
Br
HBr Br H Br H Br H
H Br H
H 2nd addition H H
H HBr Resonance
Stabilized Br H
Cation
H
HBr
Br H
Br H
2 equiv. H

Mechanism:
Br
HBr Br Br Br
H Br H
H H H
2nd addition
H Resonance
HBr Stabilized Br
Cation H
H

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Bromine Addition (Br2) - Addition of 1 equivalent of Br2 or Addition of 2 equivalents of Br2
-Bromonium Ion Intermediate?
Br 2 Br H H
+
Br Br Br

Mechanism:
Br
Br 2 H Br H H
top or bottom +
Br face attack of Br- Br Br Br
Br Br Br Get mixture of products, sterics are
not significant with Br and -CH3

Br 2 Br
+
Br Br Br

Mechanism:
Br
Br 2 top face attack Br
+
Br of Br- preferred
Br Br Br
Br Br Major
Product - biggest groups trans

Br 2 Br Br
Br H
Br
2 equiv.
Mechanism:
1st Additon Br
Product
Br 2 Br H Br 2
Br H Br Br
Br Br H
Br Br
2nd addition
Br

Bromonium Ion

Br 2
Br
Br Br
2 equiv. Br
Br- can attach either
Mechanism: carbon
1st Additon Br
Product
Br 2 Br Br 2 Br Br
Br Br Br
Br Br
2nd addition Br

Br Br Bromonium Ion

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Hydration Reactions
-Overview of Hydration and Tautomerization of Enols to Carbonyl – Mechanism
-Oxymercuration and Hydroboration: Differences in Regiochemistry to form Enols

Acid Catalyzed Hydration:

H 2SO 4 O H
HO H
H
H 2O H H

Mechanism:

H H H 2O H O H -H O H Resonance O H H

H H H H

Oxymercuration:

HgSO 4, H 2SO 4 H O H O H
H
H 2O
H H

Mechanism:

Add -H and -OH

H O H -H O H Resonance O H H O H
Recall H
-H to less highly substituted side H H H H
-OH to more highlysubstituted side
From alkene hydration
via oxymercuration

Hydroboration:

1. BH 3,, THF H O H H O
H
2. H 2O2, NaOH
H H

Mechanism:

Add -H and -OH H O H -H H O Resonance H H O H O

H
Recall
H H H H
-H to more highly substituted side
-OH to less highlysubstituted side
From alkene hydration
via hydroboration

Hydroboration or Oxymercuration (or Acid Catalyzed Hydration):

1. BH 3,, THF
HgSO 4, H 2SO 4 or O H
H or H
H 2O 2. H 2O2, NaOH
H O

Mechanism:

Add -H and -OH H O -H O Resonance O H O

H
Recall

No regiochemistry H H H H
to consider

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Hydrogenation – Addition of H2 to an Alkyne
-Alkyne vs. Alkene Stability
H2 H2

catalyst catalyst
Reaction 1 Reaction 2
Alkyne to Alkene is faster than
Reaction 2, Alkene to Alkane

-Addition of H2 and Pd/C catalyst – Can not stop at 1 H2 addition

H 2, Pd/C H 2 in excess

AND Alkenes
react with Pd/C H 2
Surface catalyst
yields Syn Addition

Addition of 1 equivalent of H2

-Lindlar’s Catalyst and H2 -- A catalyst that is “deactivated” to stop the reaction at the Alkene stage.
So Reaction 2 (shown above) is so slow it effectively does not occur. Reaction 1 is faster and can
occur even with the deactivated Lindlar’s Catalyst:

H 2, Lindlars Catalyst H 2 in excess as always

But alkenes do not react
H 2, Pd/CaCO 3 with Lindlars H 2
Pb(OAc) 2, quinoline
Surface catalyst
quinoline: yields Syn Addition
N

-Reduction using Na or Li and NH3, Mechanism of Na or Li and NH3 reduction

-Na or Li metal is a one electron donor, mechanism is a complex, stepwise process that yields Anti
addition predominantly. Not all Anti or Trans products are formed, but major product is trans alkene

Na, NH 3 Na, NH 3 could be in excess or not, it

would not affect the results because
alkenes do not react with Na, NH 3
Stepwise mechanism
yields Anti or Trans Addition
-Mechanism is complicated but interesting and explains the stereochemical outcome (you don’t need
to know this mechanism). Why does it explain the stereochemical outcome?

H
+H from H H +H from
Na, NH 3 H N H
H

Add electron NH 3 or Add electron NH 3 or

from Na H
Na from Na
OH OH
Na
H N H

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Oxidative Cleavage of Alkynes
-Ozonolysis (1. O3; 2. Zn AcOH)
1) O3 O O Alkynes are cleaved to form
+ carboxylic acids.
2) Zn, HOAc OH OH

O O Oxid. O
1) O3
+ CO 2 + H 2O
OH H OH HO OH
2) Zn, HOAc

For alkynes at the end of a chain, CO 2 is formed,

The formic acid that is formed gets oxidized to carbonate
and the carbonate breaks down to CO 2 and water

Synthesis Problems – Two Step Process

1. Prepare the carbon skeleton using alkyne anions and alkylation
O

Lets Consider Two Possible Targets: 1 2

-Deprotonation of Alkynes Using Butyl Lithium (BuLi) or NaNH2, either can be used
Example 1:
1. NaNH 2

Mechanism of Acid-Base Reaction:

H NH 2

Example 2: Acetylene Anion Formation:

1. BuLi
H C C H H C C or
Mechanism:

H C C H
H C C or

-Carbon-Carbon Formation via SN2 reaction

Example 1 Alkylation:
2. Br

SN2
Mechanism:

Br

made new C-C sigma bond

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Example 2 Acetylene Anion Alkylation:
2. Br
or C
H C C or C
SN2 H

Mechanism:

H C C or C
or C
Br H

made new C-C sigma bond made new C-C sigma bond
2. Transform the Alkyne to the Desired Functional Group
-Functional Group Interconversion (FGI) – change or transform the triple bond to another functional
group

We have our compounds with the correct chain length with the triple bond in the proper location:
So now we just need to transform the triple bond to the functional group we need in the target
compound. Could take one or more reactions.
FGI: What reaction(s)
need to be used to convert
triple bond to trans alkene?

Answer: Na, NH 3 or Li, NH 3 1

FGI: What reaction(s)

need to be used to convert O
triple bond to trans alkene?
or C
C H
H Answer: 1. BH 3, THF
2. NaOH, H 2O 2
2
Synthesis Planning – Retrosynthetic Analysis
-Thinking Backwards in Synthetic Planning from Final Product: How do we plan a synthesis when
presented with a target compound?
Step 1: Find the two carbons that “come from” the triple bond
"think backwards
arrow"

or Retrosynthetic
1 Arrow
1

O O

H H H
2 2
Step 2: Determine how to make the carbon backbone by specifically deciding on what R-Br
compound(s) will be needed to make the chain the correct length.
Compound 1: Compound 2:

Br
H
Br

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