Lab report

CHEM 2315 Fall 2019NUCLEOPHILIC SUBSTITUTION REACTIONS: SN1 VERSUS SN2
Required reading: Smith, J. Organic Chemistry; Chapter 7. Read the chapter on Reflux in Zubrick
or watch this video: https://www.youtube.com/watch?v=fHEk2WFgmXQ
INTRODUCTION
Nucleophilic substitution reactions are extremely important in biology and have been
used to synthesize several important drugs. The biosynthesis of geraniol, an aromatic
molecule found in roses and used in making perfumes, involves an SN1 reaction. Notice,
the SN1 reaction is stepwise and involves the formation of a carboction intermediate. The
reaction is unimolecular, which means that only the substrate (alkyl halide or in this case
the alkyl phosphate, ROPP) is present in the rate-determining step. If a neutral
nucleophile, such as water, is involved an acid/base reaction follows the substitution to
create a neutral final organic product.
(+/-)-2-tert-butylamino-3’-chloropropiophenone or bupropion was originally patented as
an antidepressant by Burroughs-Wellcome (now GlaxoSmithKline). It was later
discovered that the drug was effective at helping people quit smoking and is now
marketed for this purpose as Zyban ®. The synthesis involves the SN2 reaction shown
below. The SN2 reaction is concerted, which means no intermediate carbocation is
formed. Instead, all bonds are formed and broken in a single step. The reaction is
bimolecular, which means two molecules (the nucleophile and the alkylhalide) are both
present in the rate-determining step.
During this week’s laboratory you will:
1) Synthesize n-butylbromide from butanol using a substitution reaction.
1
CHEM 2315 Fall 2019
2) Study the effects of solvent and alkyl halide structure on the relative rates of
nucleophilic substitution reactions.
PART I – REACTION OF n-BUTANOL WITH SODIUM BROMIDE AND SULFURIC ACID
INTRODUCTION:
This reaction will help us to showcase the synthetic utility of the substitution reactions.
While the substitution of alcohols will not be covered until chapter 9, it is important to
realize that this reaction is an extension of the chemistry you are learning in chapter 7.
Use what you have learned to determine if this reaction will proceed via the SN1 or SN2
mechanism. Some ideas to consider when you are attempting to propose a mechanism
for this transformation:
a) What is the nucleophile that will participate in the substitution?
b) Locate the electrophilic carbon atom that will participate in substitution. (Be
sure it is sp3 hybridized!)
c) Sulfuric acid is a strong acid. Because it is an acid it will donate a proton.
Because it is a strong acid it will donate a proton in the first step of the
mechanism.
d) Locate the leaving group. Is it currently a good or bad leaving group? If good,
is it likely it will leave immediately to create a carbocation? Why or why not?
If bad, is there a way to convert it to a better leaving group?
e) Will the substitution most likely be stepwise (SN1) or concerted (SN2)? Why?
EXPERIMENTAL PROCEDURE
Equipment:
Condenser, heating mantle, Variac, ring clamp
Chemicals
Waste Disposal
Butanol and butyl bromide____
Concentrated sulfuric acid
NaBr and other salts
organic waste
inorganic waste
inorganic waste
Safety Notes:
1. Concentrated sulfuric acid is very corrosive! Wear gloves when handling sulfuric acid.
2
CHEM 2315 Fall 2019
2. Concentrated sulfuric acid is a strong oxidizing agent and should NOT be added to
the organic waste.
3. Butanol, ethanol and acetone are flammable.
Procedure:
1) Combine the following in a 25-mL round bottom flask:
a) 2.0 mL 1-butanol (use your 2-mL graduated pipette)
b) 2.66 g NaBr
c) One boiling chip
d) 3.0 mL Distilled Water (measured with a 10mL graduated cylinder)
2) Swirl to mix together and cool the mixture on ice for
10-15 minutes.
3) Add 2.2 mL of concentrated sulfuric acid (measured
with a 10-mL graduated cylinder). Add slowly
dropwise and swirl to mix after each addition.
4) Attach a clamp to the neck of the round bottom flask.
Settle the round bottom into a sand bath/heating
mantle that has been raised up 1-2 inches from the
bottom of the hood using the metal ring clamp.
Raising the source of heat will allow you to lower it
quickly if the reaction mixture begins to heat too
vigorously. Be sure that the bottom 1/3-1/2 of the
round bottom flask is surrounded by sand to ensure
efficient heating.
5) Attach a condenser tube to the round bottom flask
according to the diagram above. Be sure to lightly
grease the ground glass joint. Connect the condenser
to the chilled water loop if it has not already been
done.
6) Be sure the heating mantle/sand bath is plugged into a Variac and NOT directly into
the wall. Set the heat to 80-90%.
7) Reflux for 60 minutes. Observing a reaction at reflux is slightly different than
observing a reaction that is boiling. What is the difference? Start the timer when the
solution begins to reflux. Monitor the position of the condensation line in the
condenser. If it rises higher than 1/3 of the way up the condenser turn down the
heat.
While refluxing, move on to PART II of the lab.
After refluxing for 60 minutes, complete the following:
1) Remove the round-bottomed flask from the heat and allow to cool for 5-10
minutes. Be careful! Hot glassware looks the same as cool glassware.
3
CHEM 2315 Fall 2019
2) Transfer the contents to a pre-weighed, dry centrifuge tube (weigh with cap on).
We will use this tube instead of a separatory funnel to carry out the following
liquid-liquid extractions
3) Fill a 50 mL waste beaker with 25 mL of water.
4) You should observe two layers in the centrifuge tube. Using a Pasteur pipette,
remove the aqueous layer and add to the waste beaker. (The aqueous layer may
be heavier than n-butyl bromide because of salts dissolved in the water.) To
check whether the bottom layer is aqueous or organic, add 2-3 drops of the
bottom layer to 2 mL of water in a test tube. If the 2-3 drops dissolve in the
water, the bottom layer is aqueous. If the 2-3 drops sink to the bottom of the
water in the test tube, the top layer is aqueous, the bottom layer is n-butyl
bromide.)
5) Wash the organic layer with 5 mL of distilled water according to the following:
a. Measure out the distilled water using a 10-mL graduated cylinder and add
the water to the centrifuge tube
b. Cap the centrifuge tube and gently agitate
c. Using a Pasteur pipette, remove the aqueous layer (is it top or bottom?)
How do you know?
d. Discard the aqueous layer into the waste beaker
6) Wash the organic layer with 2 mL 5% NaHCO3 following the procedure described
in part 5). Remove and discard the aqueous layer.
7) Wash the organic layer with 2 mL of saturated sodium chloride (brine) using the
procedure described in 5). Remove and discard the aqueous (remove as much as
possible). You should not be able to see water droplets in your organic layer at
this point. If you do, wash again with brine.
8) Dry the organic layer with Na2SO4. Hopefully a pea-sized amount of drying agent
should suffice. Be careful not to add to much. Allow the solution to dry for 5-10
minutes.
9) Carefully pipet your product into a pre-weighed vial. Record the mass of your
product. Calculate a percent yield.
10) Analyze the product by IR.
4
CHEM 2315 Fall 2019
PART II – SN1/SN2 REACTION RATE AND REACTION MECHANISM
Equipment:
Test tubes
Chemicals
Waste Disposal
butyl bromides____________
ethanol, acetone
NaI__________
organic waste
organic waste
solid waste
Safety Notes:
– Butyl bromides, ethanol and acetone are flammable.
Procedure:
For this section, you will use three alkyl halides under your chosen reaction conditions.
Refer to your prelab (see below) for these conditions. For each, you will determine the
time for reaction completion. Create a table in your prelab to track the reaction times
for all six reactions (three alkyl halides for both SN1 and SN2 conditions). Start with your
SN1 reaction. You might wish to do three reactions in parallel, i.e. all three butyl
bromides under SN1 reaction conditions, and later, all three butyl bromides under SN2
reaction conditions.
1) In a clean, small test tube combine the following:
a. For all SN1 reactions, one drop of bromocresol green to the test tube
i. If the bromocresol green turns yellow immediately, rinse out the
test tube with the following:
1. 5% NaHCO3 Solution
2. Distilled Water
3. Acetone
4. Add another drop of bromocresol green. It should now be
blue. If not, repeat until the blue color remains
b. Your nucleophile (NaI or ethanol), measured using a balance or your 2 mL
graduated pipette according to your prelab volume
c. 1 mL of your chosen solvent (ethanol or acetone) using your 2-mL
graduated pipette. Agitate to dissolve the nucleophile as necessary. Is it
really that important that the nucleophile / alkyl halides are dissolved?
d. 0.25 mL of butyl bromide measured with the syringe provided.
2) Agitate to dissolve and start the timer.
3) Stop the timer when the reaction reaches completion according to the following:
a. SN1: The reaction is complete when the indicator changes from blue to
yellow.
b. SN2: The reaction is complete when cloudiness appears (this is followed by
a precipitation)
c. Note: If the reaction is not completed after 5 minutes, heat on your hot
plate until complete
5
CHEM 2315 Fall 2019
4) Record the times in your table.
5) Repeat with the other two alkyl halides (sec-butyl bromide and tert-butyl
bromide).
6) When you have completed all SN1 reactions, repeat with the SN2 reactions.
6
CHEM 2315 Fall 2019
PRE-LAB INSTRUCTIONS
THE FOLLOWING THINGS NEED TO BE INCLUDED IN YOUR LAB NOTEBOOK AND
COMPLETED BEFORE COMING TO YOUR LAB PERIOD:
A. Title of the experiment.
B. Purpose /Goal of the experiment – this is a brief description of why you are
performing the experiment.
C. Provide a Hypothesis
– Part I: Predict which mechanism (SN2 vs SN1) the reaction will proceed by.
– Part II: Predict which conditions (nucleophile, solvent and alkyl halide) will favor
an SN2 reaction. Predict which conditions will favor an SN1 reaction.
D. Molecular structures and reactions:
1) Draw the structures for n-butyl bromide, sec-butyl bromide and tert-butyl
bromide (note that all three constitutional isomers with the molecular formula
C4H9Br). You should have a primary (1o), secondary (2o) and tertiary alkyl halide
(3o). Label them accordingly.
2) Make a table using the information provided.
Mol Ratio
Butyl Bromide
Ethanol
NaI (source of I-)
1
1
1
Moles
MW
137.02
46.07
149.89
Weight
Density,
g/mL
1.25
0.789
—
Volume,
mL
0.25
—
Start with the volume of butyl bromide. Calculate, using the density, the weight of butyl
bromide. Next, use this weight to find the moles of butyl bromide. As the mol ratio is
1:1:1, all of the mole values will be the same. Complete the table by determining the
volume of ethanol and the weight of NaI using the provided molecular weight and
density. You will use this weight and volume in your lab.
Note: you will add the alkyl halide and nucleophile to 1 mL of your chosen solvent (even
if the solvent is the same as the nucleophile).
7
CHEM 2315 Fall 2019
E. Mechanism.
For Part I:
Suggest a mechanism for the reaction of butanol with sodium bromide and sulfuric
acid. Predict the product of this substitution reaction. Use the list of questions on
page 2 (Introduction to part I) to guide you when attempting to create a mechanism.
For Part II:
1) Classify the following solvents as polar protic or polar
Ethanol:
aprotic:
Acetone:
2) Classify the following nucleophiles as strong or weak:
Ethanol:________________________
Iodide (I-): ________________________
3) For each column below, choose the solvents and nucleophiles above that would
favor either an SN1 or SN2 reaction. (You will use these as the solvents and
nucleophiles in the experiment.)
SN1
SN2
Solvent: __________________________
___________________________
Nucleophile: __________________________
___________________________
4) For each reaction below, write on the arrow the reaction conditions from
question 3. Write the mechanism and predict the products of each (indicate
stereochemistry):
SN1:
SN2:
Br
Br
8
CHEM 2315 Fall 2019
5) Predict the relative rate of reaction for the following alkyl halides according to the
type of reaction. Write numbers 1, 2, and 3 for the reaction rate, ‘1’ being the
slowest and ‘3’ being the fastest.
reaction
SN1
SN2
n-butyl bromide
sec-butyl bromide
tert-butyl bromide
F. Procedure – this should be the experiment written out in your own words. Diagrams
can be helpful to show what exactly you are trying to explain. Someone should be able
to use your procedure to complete the experiment without having the lab manual to
follow.
G. Separation scheme – Only needed for Part I of the experiment.
9
CHEM 2315 Fall 2019
REPORT GUIDELINES
Prepare a 3-4 page typed report that discusses the goals, observations and conclusions.
Note that you will be graded on content and not length. The suggested length is given
as a guideline to let you know how thorough your report should be. Reaction
mechanism, reaction progress diagrams and organic molecules may be written out in
pen. You do not need to include the details of the procedure in your report, unless there
were deviations that caused your experiment to give unusual results.
Students are encouraged to discuss results and conclusions to more fully understand
the experiment, however all written work should be done individually, even when
working in groups. This means that reports may contain similar ideas, but everything
should be presented in your own words and formatting.
The following items should be discussed in your report (feel free to include any additional
points you consider important):
Part I
1) What is the product of the reaction?
2) Draw an arrow pushing mechanism for this reaction. (You will be graded on the
accuracy of your mechanism in your report. Please ask if you have any questions.)
3) Using the IR spectrum of 1-butanol, summarize the observed changes in the IR
spectra between the starting material and the product. What does this change
indicate about the difference between the starting material and the product?
1-Butanol
10
CHEM 2315 Fall 2019
4) Use your IR spectrum to determine how pure the product is and if the reaction
went to completion. Attach a copy of your IR to the last page of your report.
Draw the structure of the molecule and indicate which bond/functional group is
responsible for each of the interesting peaks. Indicate impurities that are present
based on IR.
Part II
1) Draw the alkyl halide that gave the fastest reaction for each mechanism. Write
the mechanism and the products of each reaction:
a. SN1
b. SN2
__________________
__________________
2) a. Draw energy diagrams for each of the SN2 reaction conditions, labeling them as
follows:
a. Starting Material: draw Structure
b. Product: draw Structure
c. Intermediate or Transition State: draw Structure
d. Activation Energy (Ea): clearly indicate using different peak heights the
relative activation energy of each reaction
3) Summarize your trend in reaction rate for the SN2 reaction as a function of the
structure of the alkyl halide. Does the trend match your prediction?
4) Explain this trend using the mechanism of the SN2 reaction, the structure of the
alkyl halide, and the relative activation energy of each reaction.
5) Predict what would happen to the rate of the SN2 reaction if you:
i. Doubled the concentration of the alkyl halide
ii. Doubled the concentration of the nucleophile
6) Draw energy diagrams for each of the SN1 reaction conditions, labeling them as
follows:
a. Starting Material: draw Structure
b. Product: draw Structure
c. Intermediate or Transition State: draw Structure
d. Activation Energy (Ea): clearly indicate using different peak heights the
relative activation energy of each reaction
7) Summarize your trend in reaction rate for the SN1 reaction as a function of the
alkyl halide. Does the trend match your prediction?
8) Explain this trend using the mechanism of the SN1 reaction, the structure of the
alkyl halide, and the relative activation energy of each reaction.
9) Explain your choice of solvent for the SN1 reaction. For example, discuss the
relative rates of the SN1 reaction in acetone versus ethanol.
10) Predict what would happen to the rate of the SN1 reaction if you:
i. Doubled the concentration of the alkyl halide
11
CHEM 2315 Fall 2019
ii. Doubled the concentration of the nucleophile
12