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
In the Kinetically Controlled Reactions activity we just explored how analyses
Example C. 3. on p. 4
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
a
²G b
reactions were completed in a single step, we could predict the structures
²G a
b
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
b
G
(lengths of vertical arrows in Fig. 1) and therefore the relative rates of the
b
a
reactions being compared (shorter vertical arrow -> lower G -> greater
products
reactants
rate). In Figure 1 the G of reaction b is larger than that of reaction a. So we
a
can predict that the reaction with the lower G , reaction a, should occur at a
Rxn Coordinate
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
Figure 2 above.
(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.
C, because it is at a lower point on the graph than D, representing lower e
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.
Y because it is the highest point on the graph
(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 between C and D there is the highest (G )
(4.) The G for the overall reaction is the energy increase from the initial
reactants to the highest energy in the reaction.
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, the step between C and D because it is the highest energy state.
Substitution at Saturated Carbon-1
2
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.
They should start at the same point on the graph because the HEE’s in both reactants are on the same molecule and the changes are similar.
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.
C should be lower energy because there is less steric energy, due to less amount of large molecule groups.
3. Locate and mark the positions of the ’s for reactions C & D on the graph. Explain how you identified each .
We identified each transition state because both reactions start with the HEE’s on OCH3 and end with the HEE’s on I. Therefore the only energy
difference should occur between the transition states of the reactions.
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 difference between the transition states are greater than that between the reactants because the HEE’s for both reactions start on OCH3 and
end on I, also based on the relative rates of reaction we know that C occurs at a faster rate than D, therefore C should have a lower energy transition
state than D in order for it to occur at a faster rate.
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.
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Substitution at Saturated Carbon-1
The highest energy electrons in the transition states are on different molecules because the energies of the transition states differ. Whereas the HEE’s
were the same for both C and D in the reactants and products and so they both had the same energy. So to explain the energy difference the HEE’s
must be on different molecules. The relative rate of reaction also tells us that the energy of C and D are different because they take place at different
rates. Must be affected by the extra methyl group.
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 rates of reaction of the two mechanisms are different, because the reaction for D needs more energy to occur based on its relative rate of reaction. D
requires more energy than C in order to complete the reaction, which leads D to have a slower rate of reaction than C.
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
CH3CH2-Br + OH
H
(3.)
Br + OH
CH3
+
Br
103
CH3CH2-OH +
H
Br
30
+ OH
(2.)
Group b.
Relative
Rate
Reaction
CH3-OH
OH + Br
CH3
CH3
1
(1.) CH3-I +
(2.) CH3-I
C
(3.) CH3-I +
CH3 O
CH3
O
+
O
CH3
C
CF3
CH3
O
S
CH3
+ 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
O
Reaction
O
+ CH3
C
O
Group c.
(1.) HO
Relative
Rate
Reaction
O
O
CH3
4
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. All are substitution.
(2.) What are the similarities in the overall reactions among all of the groups?
As the number of large groups increases on the reactants, the relative rate of reaction slows down.
(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.
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b.
Substitution at Saturated Carbon-1
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.
Each has a nucleophile, a central carbon, and a leaving group. The nucleophile starts off negative and the leaving group ends up negative in the
products.
(2.) WITHIN each group (a. -> c.), what structural aspects of your simple model are CHANGING from reaction to reaction?
The number of carbons, the type of substituants, and steric forces.
(3.) How many structural aspects of your model are varied in each group? Explain.
The nucleophile and the leaving group vary.
(4.) What effects do the structural changes identified in (2.) have on the reaction rate? (Increase, decrease or no change)
The number of carbons: in general the more carbons that are on the nucleophile, the slower the reaction rate.
The type of substituants: The bigger the electron cloud on the substituent, the higher the energy and the slower the reaction rate. Ex: F has a bigger
electron cloud than H does.
The steric forces: The larger the molecule, the bigger its electron cloud and the higher its energy, which leads to a slower reaction rate.
Substitution at Saturated Carbon-1
6
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?
Look at the subsituants coming off of the central carbon. The greater the number of large molecules and the larger the electron clouds on the molecules,
the higher the energy and the slower the reaction rate.
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.
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Substitution at Saturated Carbon-1
e. Now consider the reactions illustrated in group d. What new aspect of the reaction do these reactions explore?
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.
Substitution at Saturated Carbon-1
8
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
O
+
O
CH3
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.
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Substitution at Saturated Carbon-1
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
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.
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