Chemistry 212
Spring 2009
Substitution at Saturated Carbon-1
A. Determining reaction mechanisms from kinetic and stereochemical data:
1. One-Step Reactions:
Figure 1: From Kinetically Controlled Reactions Activity
Example C. 3. on p. 4
a
²G b
²G a
b
G
b
b
a
products
reactants
a
Rxn Coordinate
In the Kinetically Controlled Reactions activity we just explored how
analyses of the relative energies of reactants and transition states can allow
us to predict the relative rates of two or more similar one step reactions.
Since we knew the reactions were completed in a single step, we could
predict the structures of the transition states ( ), and use differences in
structure of the reactants and the ’s to estimate relative magnitudes of
G of the reaction steps (lengths of vertical arrows in Fig. 1) and therefore
the relative rates of the reactions being compared (shorter vertical arrow > lower G -> greater rate). In Figure 1 the G of reaction b is larger
than that of reaction a. So we can predict that the reaction with the lower
G , reaction a, should occur at a higher rate than reaction b.
2. Multistep Reactions:
A + B
1
2
C
D
3
E + F
Reaction Sequence
y
z
n
x
C
G
A&B
o
D
p
m
q
E&F
Rxn Coordinate
Figure 2: Multistep Reaction Coordinate Diagram
(1.) Multi step reactions are simply a series of single step
reactions. Each step has a transition state ( ).
Circle the transition state (x, y or z) for reaction step 3 in
(2.) Intermediate products of a reaction (C & D in Figure 2) occur at
minimum points in the reaction coordinate diagram.
Which intermediate product in Figure 2 has lower energy? Explain
the logic that led to your choice.
Transition state X. Lowest energy change from the products energy.
(3.) The "slow" step in the reaction is the one with the highest energy
. This step is often termed the rate determining step (RDS.).
(a.) What symbol in Figure 2 represents the highest energy ?
Explain the logic that led to your choice.
O because it’s the arrow for the highest energy transition state.
(b.) Which step (1, 2 or 3) in Figure 2 has is the rate determining
step? Explain the logic that led to your choice.
Step 2 because it contains the highest energy transition state.
(4.) The G for the overall reaction is the energy increase from the
initial reactants to the highest energy in the reaction.
Substitution at Saturated Carbon-1
Figure 2 above.
Which arrow in Figure 2 represents the change in energy equal to
the G for the overall reaction? Explain the logic that led to your
choice.
O because it goes from the reactants to the highest energy transition state.
2
3
Substitution at Saturated Carbon-1
3. Determining Reaction Mechanisms of Kinetically Controlled Reactions:
Figure 3
New Activity Example
Rel. Rate
C
CH3-I
+ OCH3
D CH3CH2-I + OCH3
CH3-OCH3
+
I
10
CH3CH2-OCH3
+
I
1
G
Rxn Coordinate
In this and subsequent activities (See Fig. 3) we won't know how many steps might be involved in a new reaction mechanism, so we will not be
able to predict the structures of the ’s from the reactants and products as we did in the Kinetically Controlled Reactions activity. However, we
will have relative rate data for the reactions and can use it to predict the relative G ’s (lengths of vertical arrows in the reaction coordinate
diagram) of the reactions since higher rate -> lower G -> shorter vertical arrow. Fig. 3 provides data on reactions C & D with reaction C having
a higher rate than reaction D.
1. Predict the relative free energies of the reactants and plot their relative positions on the left side of the reaction coordinate graph provided.
Explain the logic that led to your prediction.
The reactions will be the same energy because the HEEs are on identical atoms.
2. Using the relative rate data in Fig. 3, predict the relative G ’s for reactions C & D and illustrate them on the graph using vertical arrows of
appropriate relative lengths. Explain the logic that led to your prediction.
Since C is a faster reaction, its arrow will be shorter.
3. Locate and mark the positions of the ’s for reactions C & D on the graph. Explain how you identified each .
We used the relative rates to determine which transition state would be higher energy. The faster the rate the lower the energy of the transition
state.
4. Is the energy difference between the transition states the same as, greater than or less than that between the reactants? Explain using your
graph.
The energy between the transition states is greater than that between the reactants.
Substitution at Saturated Carbon-1
4
5. What can you say about the location of the highest energy electrons in the two transitions states compared to where they are in the reactants?
Explain on the basis of the differences in energy determined in question 4.
The highest energy electrons in the two transition states are on atoms of different molecules because they have different energies.
6. Assuming that both reactions occur by the same mechanism, what can you conclude about the reaction mechanism from your interpretations
in question 5?
The larger electron cloud from the methyl group in D will increase the energies of the HEEs on the I and OCH3 more than the smaller electron
cloud from the H in C. These electron clouds cause steric effects where D’s steric energy is higher.
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Substitution at Saturated Carbon-1
B. What is the Mechanism of the Following Reactions: See also CGWW CH 17 pp. 407-409, 420-444
1. Reactions:
Group a
(1.)
.
CH3-Br
+
Br
103
CH3CH2-OH +
H
Br
30
+ OH
(2.)
CH3CH2-Br + OH
H
(3.)
CH3
Group b.
Relative
Rate
Reaction
CH3-OH
Br + OH
OH + Br
CH3
CH3
O
(1.) CH3-I +
(2.) CH3-I
1
C
O
CH3
(3.) CH3-I +
CH3 O
CH3
O
+
O
CH3
C
CF3
CH3
+ CH3
O
S
CH3
O
+ O
O
O
(2.)
HO
+ CH3
O
S
HO
+ CH3
O
+ I
105
C
CF3 + I
1
Relative
Rate
S
CH3
104
CF3
106
CF3
1
O
O
CF3
HO-CH3 + O
O
(3.)
102
O
O
HO-CH3
CH3 + I
O CH3
CH3 O
Group c.
(1.) HO
C
O
Reaction
O
Relative
Rate
Reaction
CF3
S
O
HO-CH3 +
O
2. Developing and Testing Potential Reaction Mechanisms.
a. Formation of a Simple Model for the overall reaction to organize our discussions of potential mechanisms:
Consider groups a. -> c. of kinetically controlled reactions above and use similarities in the overall reactions to create a simple model
applicable to all of the reactions .
(1.) Classify the reactions as addition, elimination or substitution.
Substitution
(2.) What are the similarities in the overall reactions among all of the groups?
There is a nucleophile, a central, saturated carbon and a leaving group.
Substitution at Saturated Carbon-1
6
(3.) Using the reaction aspects listed below, devise a simple general model that can represent all of the overall reactions (No mechanism
should be proposed at this point).
Aspects: The overall classification of the reaction, the site (atom) on the central organic molecule at which the reaction occurs and the
nature of the reactants and products other than central organic molecule.
b.
Identification and Isolation of Reaction Variables:
(1.) WITHIN each group (a. -> c.), what structural aspects of your simple model are SIMILAR in all of the reactions? Explain in terms of
the model you devised in a.
In group a, the leaving group and nucleophile stay the same. In group b, the central carbon and leaving group remain the same. In group c,
the central carbon and nucleophile stay the same.
(2.) WITHIN each group (a. -> c.), what structural aspects of your simple model are CHANGING from reaction to reaction?
In group a, the central carbon changes. In group b, the nucleophile changes. In group c, the leaving group changes.
(3.)
How many structural aspects of your model are varied in each group? Explain.
In each group one aspect is changing. See question 2 above for the single structural change in each group.
(4.)
What effects do the structural changes identified in (2.) have on the reaction rate? (Increase, decrease or no change)
Group A: As the central carbon changes as substituents are added, the rate decreases. Group B: As the energy of the HEEs on the
nucleophile decreases, the reaction rate also decreases. Group C:
This was determined by looking at the tables.
c. Assume that all of the reactions occur by the same mechanism and use the approach from part A and the results of your analysis in section
b. to suggest DIFFERENCES BETWEEN the structures of the REACTANTS and those of the RATE DETERMINING (highest energy) ’s
that could account for the effects of structure on reaction rates discovered in b. (4.). (e.g. what do differences in energies determined from
the rates suggest about the bonds that might be partially formed or broken and which atoms are likely to have greater or lesser electron
densities in the vs. the reactants?) HOW DID YOU DETERMINE these differences?
The fastest rate comes from the highest Hee energy nucleophile and the lowest Hee energy leaving group and the lowest Hee energy central
carbon. Since you want to go downhill in energy the nucleophile has the highest hee energy in the reactant b/c you want it to have the highest
energy and you want the leaving group to have the lowest hee energy in the products. The highest energy nucleophile contributes to the lower
energy transition state.
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Substitution at Saturated Carbon-1
d. Using the simple model for these reactions developed part A, propose possible mechanisms (sequences of simple reaction steps) that might be
possible for accomplishing the overall reaction illustrated by your model.
e. Now consider what the ’s for each reaction step in your proposed mechanisms would look like and which
proposed in c. Can one structure account for all of the effects? Explain.
structure best fits the differences
d. Based upon e- energies and the previous reactions that you have studied, use your analyses and hypotheses from sections a. - e. to formulate
the simplest reaction mechanism(s) (using arrows) that can account for all data in groups a -> c.
Substitution at Saturated Carbon-1
e. Now consider the reactions illustrated in group d. What new aspect of the reaction do these reactions explore?
8
Group d.
CH3
Br
(1.)
CH3
+
H
-C
H
N
+ Br -
H
H
Z (cis)
C
E (trans)
only isomer formed
H
(2.)
N
O
O
O
CH3
I
S-2-Iodo-1-phenylpropane
+ CH3
C
O-
C
CH3
CH3
+ I-
H
R-1-phenyl-2-propyl acetate
(only isomer formed)
f. How can your mechanism(s) from section d. account for this additional information on the reactions?
g. Can all reactions be explained by a single mechanism? If not, are there any similarities among the mechanisms you devised? Explain the
logic that led to your conclusions.
h. Review the process that is described in sections a. -> g. above. In one or two sentences, describe how each step contributed to your final
understanding of how these reactions work. Could the steps have been done in a different order? Did you have to add steps that were not
explicitly stated in this activity? Briefly explain each response.
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Substitution at Saturated Carbon-1
3. In Class Application.
Use the mechanism developed in Substitution at Saturated Carbon-1 to predict which reaction, (a.) or (b.), in each of the following pairs of
reactions 1. -> 3. should proceed at a higher rate and explain how your prediction was derived.
CH3
O
CH3
O
CH O CH3 + O S CH3
(a.)
CH
O S CH3
CH3
CH3
O
O
+
O CH3
(b.)
O
CH3 CH2
O
S CH3
O
+
O
CH3 CH2 O CH3
+
O
S CH3
O
O CH3
How was this analytical process used in this application related to that used in devising the reaction mechanism in Part B.2.a-h? Explain
similarities and differences.
Substitution at Saturated Carbon-1
10
Out of Class Applications
A. Reactions:
Use the mechanism developed in Substitution at Saturated Carbon-1 to predict which reaction, (a.) or (b.), in each of the following pairs of
reactions should proceed at a higher rate and explain how your prediction was derived.
1.
O
O
(a.)
CH3 CH2 O
S
CH3
CH3 CH2
+
O
O
+
O
S
O
O
O
(b.) CH3 CH2 O
S
CH3
O
CF3
+
O
CH3 CH2
+
O
O
O
S
CF3
O
2.
(a.)
CH3 CH2
Br
+
O CH2
CH3
CH3 CH2 O
Br
+
O
C
+
Br
O
O
(b.) CH3 CH2
CH2 CH3
CH3 CH2
CH3
O
C
CH3
+
Br
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Substitution at Saturated Carbon-1
3. Predict the configuration of the product(s) of the following reaction. Explain your reasoning.
CH3
5.
O
S
O
CH3
H
O
O
+
C
CH2
CH3
Suggest a reasonable reagent that might best accomplish the following transformation.
CH3
I
N
B. Nomenclature:
See Nomenclature of Chiral compounds- Lab Manual Appendix B (pp. B10 & B11)
Complete Out of Class Applications on p. B11.