Organic Chemistry Laboratory
Spring 2005
David Schedler and Regina Arnold-Stanton
Birmingham-Southern College
Chemistry 212L
Organic Laboratory
INSTRUCTOR
Dr. David JA Schedler
338 Stephens Science Center
ph 226-4876
Dr. Regina Arnold-Stanton
TEXT
1) BSC Lab Manual
2) Laboratory Notebook
3) “Techniques in Organic Chemistry”, Mohrig, et. al.
By the BSC Honor Code: You may not look at old lab reports.
LAB NOTEBOOK
A laboratory notebook will be kept for all labs. The notebook must be bound (stitched,
not spiral) and its pages should be numbered. All writing should be in ink with any errors
corrected by lining-out the entry then writing the correct entry above or to one side of the
error.
SAFETY
Because many of the reagents and solvents used in organic chemistry are flammable or
corrosive, students MUST wear safety glasses at all times in the laboratory. DO NOT
WEAR CONTACTS IN THE LAB. All work with chemicals MUST be done in the
hoods. Many organic compounds stain or dissolve clothing, therefore do not wear
expensive clothing or any sentimental items in the lab. Proper footwear is also necessary,
no sandals or open-toed shoes. Be conscious of what is going on around you. Most
injuries are caused by someone else's experiment going wrong. Please take time when
you first enter the laboratory to locate the nearest exit, the eyewash, the safety shower,
and a fire extinguisher. Failure to follow safe practices may be cause for disciplinary
action and could be reflected in your grade.
GRADING
The grade in the laboratory section of this class is part of the overall grade for the course
(see syllabus for lecture). A formal written report will be turned in for each lab project.
Each report will be worth 35 points (140 pts.). In addition, each week an attitude and
participation point can be earned (11 pts.). The lab final is worth 100 points. You are
expected to come to lab each week with an understanding of the exercise to be
completed.
SCHEDULE
Labs will meet in SSC 317.
i
Week
Laboratory Exercises
February 7
Infrared Spectroscopy
Project 1 – Molecular Modeling Predictions of Organic Reactions
February 14
Part 1 - Which Nitrogen?
February 21
Part 1 – Cont’d.
February 28
Part 2 – Reduction of (R)-(+)-3-methylcyclohexanone
Project 2 – Kinetic Versus Thermodynamic Control
March 7
Completion of Part 2, Project 1 and Part 1, Project 2 – Predictions
and Synthesis
March 14
Part 2 - Analysis of data
Project 3 – Prediction and Determination of the Product of A DielsAlder Reaction
March 21
Part 1 – Predictions and Synthesis
March 28
SPRING BREAK!!!
April 4
Part 2 – Analysis of data
April 11
Part 2 – Cont’d.
April 18
HONORS WEEK – no lab
Project 4 – Electrophilic Aromatic Substitution: Nitration of
Unknown Organic Compounds
April 25
May 2
Nitration of Unknown Organic Compounds
Esterification: Design your own Synthesis
The Lab final will be during the scheduled lab period on May 10th, 11th, or 12th .
ii
Formal Reports
After the completion of each lab project, an individual formal write-up should be
written and turned in the following week. The report should follow the guidelines
outlined below. They should be word processed and stapled. Honor Code should be
followed. In addition, you MAY NOT LOOK AT OLD LAB REPORTS.
I. Title Sheet
This cover page should include a title, lab section, date, and names of the
investigators involved.
II. Abstract
Give a concise summary of the project in one single-spaced paragraph
(all other sections should be double-spaced). What were you trying to accomplish
in this laboratory project? What was the result?
III. Introduction
Give an overview of the background information necessary for the reader’s
understanding of the significance of the experiment (i.e. techniques and
instrumentation). Describe the theory behind any method used in the experiment.
You should cite the primary references used.
IV. Experimental Procedure
Describe in detail the investigations you did with your lab partner(s). This should
be double-spaced and in paragraph form. Give the procedure you used, but not
the results at this time. Give all materials and reagents used. If you perform a
reaction, give a balanced equation. An investigator should be able to duplicate
your procedure from this description. This section should be a narrative of what
you did in the lab. It should be written in the past tense and in passive voice.
V. Results and Observations
This should give the results of your experiments and not be a discussion of why
they occurred. For the investigations you did, you should detail your results and
any observations or problems you encountered. You should include a table for all
of the data collected (i.e. melting points and percent yields).
VI. Discussion
In this section you will discuss your results. In addition, describe how you used
the results from each week to design your protocols. Why was this procedure
chosen and what advantages does it have over other procedures? Be as specific as
possible about any assumptions you have made in your analysis of results.
VII. Conclusion
How did all of the information presented above led you to meeting the
outcome desired for the lab project.
A well-written report should be around 8-12 pages.
iii
Notes:
-Students should review the definition of plagiarism in the BSC Honor Code. If you are
uncertain, ask for help at the writing center. Ignorance is not an excuse.
-Structures can be hand drawn neatly and inserted in the text.
-Any tables or graphs should have a meaningful title or caption and be clearly labeled.
The reader should be able to independently read the table or graph and get all the
information needed without having to read the laboratory report.
-References should be presented in American Chemical Society format. You may use
either endnotes or footnotes but indicate where the reference goes using a superscript in
the text1. DO NOT USE WEBSITES AS REFERENCES. The internet can be used
as a search engine to locate primary sources, but that is all. Also, your BSC lab
manual is NOT a reference.
Books should use the format:
Author (Last name, Intials; separate with semicolon if more than 1). Title (in italics);
Publisher: City, year.
Example:
1
Anthony, S; Brauch, T. W.; Longley, E. J. What Should We Do About Global
Warming?; Wiley: New York, 1998.
Journal:
Author (same as above). Journal name(abbreviated and in italics). Year (bold), volume,
page.
Example:
Porter, D. J.; Stewart, A. T.; Wigal, C. T. J. Chem. Educ. 1995, 72, 1039.
Project Write-up Due by 10:40 am on:
Project 1: March 11th (35 pts.)
Project 2: March 25th (35 pts.)
Project 3: April 22nd (35 pts.)
Project 4: May 61h (35 pts.)
Each week will have a 1pt. participation/attitude grade for a total of 11 pts.
iv
Infrared Spectroscopy
Objectives:
In this lab, you will be using infrared spectroscopy (IR) to analyze the functional
groups present in various compounds. You will also be determining the relationship
between the bond energy present in the functional group (Hooke’s law) and the frequency
where its absorption occurs.
Outcomes:
At the end of this lab, you should have:
1) determined the absorption of the characteristic bonds for each functional group
2) made a comparison between bond energy and frequency.
Introduction:
Infrared spectroscopy is used to identify the presence of functional groups in a
compound. In this method, the sample is irradiated with infrared radiation, which is
absorbed by the bonds in the molecule, increasing the amplitude of the bond vibrations.
The spectrophotometer records the frequency at which the molecules absorb the infrared
radiation. IR spectra are measured in units called wavenumbers (cm-1 = υ / c, where c
equals the speed of light and υ equals frequency.)
The vibrations that occur in the chemical bonds are best described by Hooke’s
law, which states that the frequency of a stretching vibration is directly proportional to
the strength of the spring (in our case, the bond) and inversely proportional to the masses
(the atoms) connected by the spring (bond). This leads to the conclusion that a bond that
joins together a heavy atom (C, N, O) to a lighter atom (H) has stretching vibrations that
are higher in frequency than a bond that joins together two heavy atoms (C, N, O).
Shorter, stiffer bonds also have stretching vibrations of a higher frequency than the
stretching vibrations of long, flexible bonds. Therefore, triple bonds vibrate at higher
frequency than double bonds, higher than single bonds (if the atoms are the same).
When the frequency of the IR radiation is equal to the frequency of vibration of
the chemical bond, the molecule will absorb the radiation and its molecular vibrations
will increase in amplitude. The chemical bonds that absorb IR radiation at a frequency
below 1500 cm-1 have absorption peaks that occur in the fingerprint region, a region of
the IR spectra that is unique for each molecule and offers little discernable information.
In this lab, you will use IR to analyze the functional groups in the following
molecules:
1
CH3
CHO
COOH
OH
Benzoic acid
C
Benzaldehyde
N
Benzonitrile
Benzyl alcohol
O
Toluene
O
Cyclohexanone
Cyclohexene
2-cyclohexenone
O
OH
CNH2
Benzamide
Cyclohexanol
1-pentyne
Experiments:
Week1:
Infrared Spectroscopy:
Procedures:
Students should work in groups of two. Each group will predict the spectra for
each compound above. Then, each group will perform an IR on one of the previously
shown compounds with the assistance of the T.A. Students will then discuss, as a group,
the characteristics of each IR spectra and compare individual spectra in order to
determine what absorptions are characteristic of each functional group. Students should
2
then discuss the relationship between the bond energy and the frequency where the
absorption occurs.
Draw Your Predictions and Experimental Data in you lab notebook.
3
Which Nitrogen?
Adapted from: Hull, Leslie A. “Which Nitrogen? Combining Computer Modeling with
Laboratory Work in Organic Chemistry” J. Chem. Educ. 2001, 78, 420.
Objectives:
In this lab, you will be using molecular modeling to determine which nitrogen in
the compound 4-(dimethylamino)pyridine, DMAP, is more nucleophilic. 1H-NMR will
be used to determine the structure of the product formed. You will then compare your
predicted product structure to the structure of the experimentally obtained product.
Outcomes:
At the end of this lab, you should have done the following:
1) modeled the structure of DMAP
2) determined the electron density around each nitrogen.
3) made a prediction about which nitrogen is more nucleophilic.
4) carried out the reaction and determined which product formed using NMR.
Introduction:
Molecular Modeling is a very useful method to predict the reactivity of a
molecule. In this exercise, it will be used to predict which nitrogen in DMAP is more
nucleophilic. NMR is also an extremely powerful tool for the determination of structure.
As such it can be used to answer many types of questions that arise in chemistry. One of
the simplest questions it can answer is “What is the product of this reaction?” In this
experiment, you are going to do an SN2 reaction between an amine and an alkyl halide. A
generic picture of the type of reaction is given below, with the amine nitrogen acting as
the nucleophile because of its nonbonding electrons and the alkyl halide acting as the
electrophile because of the bond polarity in its carbon to halide bond.
N
+
N+
C X
C
X-
The product is a salt, the nitrogen has four bonds and is positive (cation) and the
displaced halide exists as the anion and is the counterion. The combination of the cation
and the anion is a salt, making it easy to isolate when produced in a nonpolar solvent like
the one used in this experiment. WHY?
4
This relatively simple idea becomes more complex if the starting material has two
different nitrogen atoms, either of which can act as a nucleophile. In the reaction that
will be investigating in this experiment (shown below), the starting material, 4(dimethylamino)pyridine (DMAP; MW 122.17) has two nitrogen atoms. It will be
reacted with the alkyl halide, methyl iodide (MW 141.94).
N (CH3)3
I
Path A
N(CH3)2
+
N
CH3I
N(CH3)2
I
N
DMAP
methyl
iodide
Path B
N
CH3
In order to understand further why one of the nitrogen atoms is more nucleophilic,
you will also construct a molecular model of DMAP and perform molecular orbital
calculations to determine and map the electron density about each of the nitrogens. The
data obtained is called an electrostatic potential plot. Each of the nitrogen atoms in
DMAP has a pair of nonbonding electrons and can potentially be the nucleophilic
nitrogen. Whichever nitrogen is predicted to have a higher electron density farthest from
the nucleus should be more nucleophilic. Using this data, predict which nitrogen will act
as the nucleophile and determine which path the reaction will proceed through and what
the NMR of the product will look like. Once the reaction has been completed, using 1HNMR, you will determine the structure of the product and decide which of the paths (A or
B) the reaction followed. You can then determine if the predictions you made with the
aid of molecular modeling corresponded to the experimental result..
Experiments:
Week 2:
SN2 Reaction Using DMAP:
Procedures:
Students should work in groups of two to complete the experiment.
5
You should use the molecular modeling software PC Spartan Plus to determine
which nitrogen in the starting material DMAP is more nucleophilic.
Modeling Instructions:
1.
2.
3.
4.
Enter the PC Spartan (Plus) program and build the starting material DMAP.
Click the Setup menu at the top of the screen, and then choose Surfaces.
A window should appear and for the Surface and Property slots choose Elpot.
Click Add (then “Elpot pending” should appear in the blank space) and then
click OK.
5. Go back to the Setup menu, and click on Submit.
6. When the save window appears, save your file under your name in a folder on the
network.
7. Then a start window will appear and you should click OK.
8. After about 30 seconds, a task-completed window should appear at which time
you should click OK.
9. After the task-completed window has closed, you should go to the Display menu
at the top of the screen and then go to Surfaces.
10. Highlight the name of your image (which should be listed at the top of the
window) and for Display choose Surface and for Style choose Solid.
Then click OK and an image should appear.
Determine the correct amount of each material to use in the reaction. In a hood, set up a
reflux apparatus (see TOC p. 49). Be sure to wear gloves throughout the experiment.
Weigh directly into the tared round-bottomed flask 1.5 mmol of 4-(dimethylamino)
pyridine (DMAP); 2.0 mL of CH2Cl2 (methylene chloride). Swirl the mixture until all of
the DMAP dissolves. Add the volume equivalent of 1.5 mmol of methyl iodide (CH3I).
Add several boiling chips (3) to the round bottom flask, and start refluxing on a low
temperature. Reflux the mixture for 30 minutes being careful not to evaporate all the
solvent or distilling any liquid. The mixture will distill over if the reaction is not kept at a
relatively low temperature.
After the 30 minutes of refluxing, remove the flask from the heat and then cool
the flask briefly in an ice bath. Use a Hirsch funnel to filter out the solid that formed.
Cold methylene chloride can be used to transfer any remaining crystals from the flask to
the funnel. Continue pulling air through the crystals for two minutes to dry them. Scrape
the crystals onto a piece of tared filter paper and weigh them.
Week 3:
Product Analysis:
Procedures:
The product you obtained last week should be analyzed using 1H-NMR and 13CNMR. While you are waiting on the spectra, you should make a prediction about which
product will be formed based on your modeling data. Compare your prediction from the
modeling with the experimental results from the NMR spectra.
6
Be Sure Your Report Answers The Following Questions:
1) Which nitrogen was more nucleophilic? Why?
2) Which of the paths (A or B) did the reaction follow?
3) Is this consistent with which nitrogen was more nucleophilic in the starting
material?
4) What is the mechanism of the reaction?
7
Reduction of (R)-(+)-3-Methylcyclohexanone
Objectives:
In this lab, you will be examining the reduction of (R)-(+)-3-methylcyclohexanone. Using molecular modeling, you will be predicting which of two possible
products will form. Using 1H-NMR, you will determine the structure and
stereochemistry of the product and whether it agrees with your prediction.
NOTE: YOU SHOULD BRING YOUR MOLECULAR MODELING CD TO LAB!
Outcomes:
At the end of this lab, you should have done the following:
1) predicted the product(s) of the reaction using Molecular Modeling.
2) carried out the reduction reaction
3) predicted the NMR specta for each possible product and how you would
differentiate the two.
4) analyzed the product(s) using NMR
5) determined the structure and stereochemistry of the product(s).
6) Compared experimental results to predictions.
Introduction:
The reaction you will carry out this week is a nucleophilic addition of a hydride,
sodium borohydride (NaBH4), to a ketone, (R)-(+)-3-methylcyclohexanone. The resulting
product is an alcohol. In this specific case, a secondary alcohol is formed that can have
the hydroxyl group either cis- or trans- to the methyl group. In this ketone reduction
reaction, the reducing agent, NaBH4, donates a hydride ion (H-) to the ketone. The
hydride can attack the sp2-hybridized carbon from either side resulting in a tetrahedral
intermediate. The tetrahedral intermediate can then react with water or an aqueous acid
to form the secondary alcohol as shown below:
8
H
O-
O
H2O+
OH
-
H
H
H
The specific reaction and possible products are shown below:
OH
O
NaBH4
NaOH, H2O
H3C
OH
H3C
H3C
cis-3-methylcyclohexan-1-ol
trans-3-methylcyclohexan-1-ol
Proton Coupling Relationship
J Value (Hz)
Equatorial-Equatorial
Axial-Axial
Axial-Equatorial
2-3
6-12
2-3
Experiments:
Week 4:
Reduction of a Ketone:
Procedures:
Students should work in groups of two. Place 0.25 mL of 3-methylcyclohexanone
and 5.5 mL of water in a short-necked round- bottomed flask. Add 1 pellet of sodium
hydroxide (NaOH) while swirling the flask. After the NaOH pellet dissolves, slowly add
0.04 g of sodium borohydride (NaBH4) to the flask. Continue to swirl the flask for five
minutes, add several boiling chips, and then attach the flask to a reflux column. Heat the
solution so that the vapors are near 100ºC for 30 minutes (attempt to keep the reflux ring
9
about half-way up the column). Cool the flask in an ice bath and then transfer the
contents to a centrifuge tube. Add 3.5 mL of ether, extract the organic layer. Repeat the
ether extraction and combine the organic layers in a clean Erlenmeyer flask. Dry the
combined layers with anhydrous magnesium sulfate. Tare a filter flask and remove the
drying agent by vacuum filtration. Evaporate off the ether using the vacuum, and then
analyze the product remaining in the flask.
Week 5:
Use molecular modeling to determine the theoretical structure and
stereochemistry of the product and compare that with your predictions and experimental
data using 1H-NMR and/or 13C-NMR.
Be Sure Your Report Answers The Following Questions:
1) What product was predicted by molecular modeling analysis?
2) Is this what you expected?
3) How did you determine the structure of the product and differentiate it from other
possible products?
When you have finished analyzing your product, you should begin
the first section of the Kinetic/Thermodynamic experiment.
10
Kinetic Versus Thermodynamic Control, Product Identification, and Molecular
Modeling
Adapted from: Cook, Gilbert A., Kreeger, Pamela K. “Reaction of Morpholine with tButyl Acetoacetate: A study in Kinetic vs Thermodynamic Control, Product
Identification, and Molecular Modeling” J. Chem. Educ. 2000, 77, 90.
Objectives:
In this lab, you will be determining how kinetic and thermodynamic control
affects the product(s) formed in a reaction.
Outcomes:
At the end of this lab, you should have done the following:
1) used molecular modeling and mechanistic analysis to predict which product is
characteristic of thermodynamic or kinetic control and why.
2) predicted the NMR spectra for each possible product.
3) carried out the two reactions.
4) obtained and analyzed the products.
5) identified any major/minor products.
6) determined if your predictions matched the experimental results.
Introduction:
In some reactions two different products can form from the same reaction done
under different conditions. For example, consider the general reaction shown below:
A
B+ C
Assume product B goes through the more stable intermediate; therefore its activation
energy is lower than product C, causing it to form faster. Also assume that product C is
the more stable product because it is lower in energy. If the reaction is carried out at
higher temperatures, there is enough energy for the process to be reversible. In this case,
the product formed is determined by thermodynamics and, therefore, C is the major
because it is more stable. Under these conditions, the reaction is said to be under
thermodynamic control and the major product depends only on product stability.
If the same reaction is carried out at lower temperatures then there is not enough
energy present for the process to be reversible. Under these conditions, the reaction is
irreversible and the product with the lowest activation energy (lowest reaction barrier)
will be the major product. In this example it will be B. This reaction is said to be under
kinetic control because the major product depends only on the rate of the processes.
11
The diagram below illustrates thermodynamic and kinetic control.
In this lab, you will be carrying out the following reaction under different
conditions. Each arrow indicates a different reaction pathway, leading to different
products. One pathway is favored at low temperature, one at higher temperature.
O
C(CH3)3
O
N
O
O
O
C(CH3)3 +
O
NH
O
O
O
N
O
Experiments:
Week 5:
Kinetic and Thermodynamic Reactions:
Procedures:
At the beginning of lab, start your sand bath heating and clamp a thermometer in
the sand. The target temperature is 165 °C. The thermometer should be roughly at the
same depth that the flask will be during the experiment. Students should work in groups
of two and use Spartan Build (WFKIT) to predict the expected product for each set of
12
conditions. Then the students should predict the 1H- NMR spectra for each possible
product.
Each group should place a mixture consisting of a 1:1 molar ratio of morpholine
(MW 87.12) and t-butyl acetoacetate (158.2) into a beaker cooled with ice water. Be sure
to use a small amount of both reactants. The TA should check your calculations. Add a
few molecular sieves to the beaker, mix well, cover it with a watch glass, and store it in a
safe place until next week’s lab period.
Once students are convinced that the temperature of the sand is holding at around
165ºC, an appropriate amount of t-butyl acetoacetate should be placed in a 5 mL longnecked round-bottomed flask with a boiling chip. A simple distillation apparatus should
be set up with a column with a septumed sidearm inserted below the distilling head .
Then an equimolar amount of morpholine should be added in small amounts through the
septum using a syringe. While the morpholine is being added, some liquid (t-butanol)
distills over. After the morpholine addition is complete, the liquid continues to distill.
When the distillation of the lower boiling point liquid is complete, the long-necked flask
may be removed from the sand. The remaining liquid should be placed in a small beaker,
covered with a watch glass, and placed in a drawer until next week’s lab period.
Week 6:
Product Analysis:
Procedures:
The crystals from the room temperature reaction should be extracted from the
beaker and dried using the vacuum. The crystals or oil from the higher temperature
reaction should be isolated. Deuterated chloroform should be used as the solvent for the
NMR analyses of both products.
Students should then analyze the 1H-NMR spectra and determine which addition
is characteristic of thermodynamic control and which is characteristic of kinetic control.
Be Sure Your Report Answers The Following Questions:
1) Why are molecular sieves used in the unheated reaction but not in the heated one?
2) What is the kinetic product? What is the thermodynamic product? Why?
3) What are the mechanisms of the two separate reactions?
4) What structural and energetic aspects of each product contribute to its formation?
13
Diels-Alder Reaction
Adapted from: McDaniel, Keith F.; Weekley, R. Matthew “The Diels-Alder Reaction
of 2,4-Hexadien-1-ol with Maleic Anhydride: A Novel Preparation for the Undergraduate
Organic Chemistry Laboratory Course” J. Chem. Educ. 1997, 74, 1465.
Objectives:
In this lab, you will be performing a Diels-Alder reaction with 2,4-hexadien-1-ol
and maleic anhydride, predicting the product, and analyzing the product using 1H-NMR.
Outcomes:
At the end of this lab, you should have:
1) predicted the product and its 1H-NMR spectrum.
2) completed the Diels-Alder reaction.
3) analyzed the product and compared it to your prediction.
Introduction:
The Diels-Alder reaction consists of a dienophile and a diene reacting in a
concerted mechanism, which is shown below.
COOH
COOH
+
Diene
Dienophile
Since the Diels-Alder reaction is concerted there is no reaction intermediate. The two
reactants are the diene and the dienophile. A diene can be acyclic or cyclic as long as it
has two conjugated double bonds. The two double bonds must be in the s-cis
conformation shown above. The dienophile is the alkene that reacts with the diene. The
dienophile is more reactive if it has electron-withdrawing groups attached to it. The
Diels-Alder reaction is stereospecific. The stereochemistry of the dienophile is always
maintained in the product. In the case of bicyclic products, two possible isomeric
configurations can be envisioned. The electron-withdrawing group can either be in either
the endo or exo position. In the endo conformation, the electron-withdrawing group is
syn to the larger of the bridge. In the exo conformation, the electron-withdrawing group
is anti to the larger bridge. The electron-withdrawing group is usually in the endo
position. If there is not a larger bridge, there is no endo or exo conformation.
14
Experiments:
Week 7:
Diels-Alder Reaction:
Procedures:
Students should work in groups of two. A mixture of 0.08 g of maleic anhydride
and 0.08 g of E, E-2, 4-hexadien-1-ol in 0.5 mL of toluene in a reaction tube is refluxed
in the proper apparatus. The mixture should be heated for five minutes so that the reflux
ring (height of the boiling liquid) is most of the way up the reaction tube. After five
minutes of refluxing, allow the solution to slowly cool to room temperature. The reaction
tube is then cooled in an ice-water bath for 10 minutes. A brown oil should settle to the
bottom of the reaction tube as the product. Isolate the oil by removing it with a pipette,
and verify its purity. If the product is pure, then prepare it for structural analysis and save
it for use in weeks 8 and 9. Predict the structure of the product obtained from the
reaction and its NMR spectrum.
Week 8/9:
Analysis of Product:
Procedures:
As a section, determine the structure of your product. The NMR spectra should
be done in groups of two, but then the entire section may collaborate on the analysis.
Compare your results to the predictions you have made and explain any inconsistencies.
If needed, any other methods may be used to determine the structure of your product. As
a section, you should also determine the proper structure for the product and mechanism
of the reaction.
Be Sure Your Report Answers The Following Questions:
1) What is the relationship between an electrophile and a dienophile?
2) What were methods were used to determine the structure of the product?
3) Were there any inconsistencies between your predictions and the experimental
data, if so what were they and how did you try to explain them?
4) What is the mechanism of the reaction?
5) How did you arrive at your determination of the proper structure for the product?
15
Nitration of Unknown Organic Compounds
Adapted from: McElveen, Sonia R.; Gavardinas, Kostas; Stamberger, Jean A.; Mohan,
Ram S. “The Discovery-Oriented Approach to Organic Chemistry. 1. Nitration of
Unknown Organic Compounds. An Exercise in 1H NMR and 13C NMR Spectrosopy for
Sophomore Organic Laboratories” J. Chem. Educ. 1999, 76, 535.
Objectives:
In this lab, you will be carrying out a nitration reaction and identifying the starting
material and product based on NMR analysis of the product.
Outcomes:
At the end of this lab, you should have done the following:
1) completed a nitration reaction on an unknown aromatic starting material
2) analyzed the product using 13C and 1H-NMR
3) determined whether the isomer obtained was ortho, meta, or para
4) identified the product and starting material based on the spectra
Introduction:
Nitration reactions are classified as electrophilic aromatic substitution reactions.
The electrophile in the reaction is a nitronium ion (NO2+) that is produced when nitric
acid (HNO3) and sulfuric acid (H2SO4) are combined. The NO2+ reacts with the
nucleophile, a benzenoid ring, and produces a carbocation intermediate. The loss of a
proton from the carbocation during rearomatization results in the formation of the neutral
product. An example of a nitration reaction is shown below.
NO2
HNO3
H2SO4
If there are other substituents already present on the benzene ring, they will affect
the regiochemistry and relative reactivity of the aromatic substitution. These substituents
can be either ortho- and para- directing or meta- directing. Ortho- and para-directing
groups are considered activators because they increase the electron density in the
aromatic ring through resonance or inductive effects. Some groups that are ortho- and
para-directing are –OH, -NH2, -CH3, -OCH3, and -NHCOCH3.
Meta- directing groups are deactivators because they withdraw electron density in
the ring through inductive and/or resonance effects, making the ring less nucleophilic and
16
less reactive. Some meta- directing deactivator groups are –NO2, -NR3+, -SO3H, -CN, and
carbonyls. Halides are the exception to these trends. They are deactivators but are orthoand para-directing groups. This is because their resonance effect influences the
regiochemistry, leading to ortho and para products, while their inductive effect
determines the reactivity.
Experiments:
Week 10:
Nitration of Unknown Compound:
Procedures:
Students should work in groups of two. Each group should obtain an unknown
from the T. A.
Add 0.500 g of the unknown to a flask containing 3 mL of sulfuric acid that has
been cooled to 5ºC in an ice bath. Then add 1.1 mL of ice-cold nitric acid dropwise to
the solution while making sure that the temperature of the solution is less than 8ºC.
Swirl the flask after each addition and pace the addition so it takes around 20 minutes to
complete. The flask should then be placed in an ice bath for 10 minutes. After cooling,
the resulting yellow solution should be poured onto 10 g of crushed ice in a 50 mL beaker
and stirred vigorously with a glass-stirring rod. Collect the solid using a Hirsch funnel
(add the mixture in small increments) and wash with cold water until the filtrate tests
neutral. The crystals should be left under suction for 5 minutes, and then analyzed using
NMR. The NMR spectra should be integrated using the Delta software.
Be Sure Your Report Answers The Following Questions:
1)
2)
3)
4)
5)
6)
7)
Which isomer (ortho, meta, or para) was formed in the reaction?
What is the structure of the starting material?
What is the structure of the product?
How did you determine the structure?
What were the other groups’ data (unknown, product, regiochemistry, etc.)?
What was the mechanism for your reaction?
What were the mechanisms for the other groups’ reactions?
17
The Production of Fragrances Using Fischer Esterification
Objectives:
In this lab, you will be synthesizing an ester from a protocol you design.
Outcomes:
At the end of this lab, you should have a product that smells like the ester you
chose to synthesize.
Introduction:
Esters are derivatives of carboxylic acids that are found frequently in nature.
Volatile esters, unlike carboxylic acids, generally have a pleasant odor and are
responsible for the essences of many fruits, vegetables, and flowers. Commercially,
esters are used extensively as perfumes and as flavoring agents. For instance, the cyclic
ester (or lactone) known as coumarin has an aroma similar to vanilla and is used by
pharmaceutical companies as a flavoring agent.
One way to prepare esters is via a process known as Fischer esterification. It
involves a proton catalyzed reversible reaction between a carboxylic acid or acid
anhydride and an alcohol yielding an ester and water (a carboxylic acid if the anhydride
is used). This process normally gives 60% to 70% of the maximum ester yield if equal
quantities of both reactants are used. The reaction progresses via the mechanism shown
on the following page.
Shown below is an example of an esterification reaction.
CH3CH2OH + CH3C
Ethanol
O
O
O
O
O
CH3C
CCH3
Acetic Anhydride
OCH2CH3
Ethyl acetate
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+
CH3C
OH
Acetic Acid
First step:
CH3C OH + H+
CH3
C
O H
Second step:
O H
CH3
C O H
OH
C2H5OH
CH3
C OH
O H
C2H5
Third step:
OH
OH
CH3
C OH
CH3
C O H
O H
O H
C2H5
C2H 5
Fourth step:
O H
OH
CH3
C O H
H2O + CH3
C OC2H5
O H
C2H5
Fifth step:
O H
CH3
O H
O H
O
C OC2H5
O
H+ + CH3
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C OC2H5
CH3
C O H
Pre-lab Excersise-Week 11:
You should have picked the ester you want to synthesize and determined what starting
materials and amounts you will use in lab. (Try to avoid using Butyric Acid due to its
terrible odor.)
Week 11:
Procedure:
Design a protocol in which you prepare one of the esters shown below by use of
the Fischer esterification process. There should be an excess of one reagent. Then, carry
out the preparation and purify the ester. The aroma of the purified product should be
indicative of the correct ester. If there is an acidic smell to your product, you should run
it through an alumina column.
O
O
HCOCH2CHCH3
CH3COCH2
(Raspberry)
O
COCH3
O
CH3
CH3CH2CH2COCH3
(Apple)
(Banana)
O
CH3COCH2CH2CH3
O
O
CH3
CH3COCH2CH2CHCH3
(Pear)
OH
(Wintergreen)
(Peach)
O
CH3
CH 3CH2COCH2CHCH3
CH3CH2CH2COCH2CH3
(Pineapple)
O
CH3COCH2(CH2)6CH3
(Orange)
(Rum)
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