Chemistry 211-212
Preparative Experiments
Name:_____________________________ TA Name: ________________________
Experiment # 17 ____________________ Lab Day:________________________
Pre-lab exercises
(20 points)
Pre-lab write-up (Sections I-VI)
(92 points)
Completed report (Sections VII-IX)
( 6 points)
Answers to Assigned Problems (Section X)
(20 points)
Product (yield, purity, appearance)
__________ (20 points)
TOTAL:
__________
(218 points)
SCORE
___________ (percent)
This is your report cover. Please fill this form out and attach it to your write-up form.
PLEASE NOTE: THIS IS A FORM WRITE-UP. Form is at the end of
experiment.
17-1
General Safety Considerations
Experiment 17
The Haloform Reaction of Acetophenone
and
The Aldol Reaction
1.
All the organic chemicals used in these reactions should be considered to be
flammable, toxic irritants.
2.
Bleach is an irritant and is harmful if swallowed. Bleach can give off chlorine gas
which is a respiratory and eye irritant.
3.
Concentrated HCI is corrosive.
4. As always, constantly wear gloves, goggles and work in the hood. In the event that
you come in contact with any of the chemicals being used, flush the exposed area
with cold water for fifteen minutes. Alert your instructor when chemical exposure
occurs and when large spills occur.
A flow chart for the Aldol reaction is not included because the procedure is so simple.
Experiment 17
The Haloform Reaction of Acetophenone
The Aldol Reaction
By now you should be acquainted with the fact that hydrogens in the alpha
position to a carbonyl are relatively acidic. For example, the hydrogens in
acetone have a pK a of approximately 20, whereas the hydrogens of ethane have
a pK a of approximately 50. If treated with a suitable base, these “acidic"
hydrogens can be abstracted forming an enolate anion which can be used as a
nucleophile in a variety of reactions, e.g., aldol reaction, Claisen condensation,
alpha-alkylation, haloform, etc. The following equations outline the abstraction of
an alpha hydrogen by a base (B:) and the subsequent reaction of the resulting
nucleophile with an electrophile (E+).
If the electrophile used is a halogen, the resulting product will have substitution of
halogen for hydrogen as shown in the following equation.
If a molecule has multiple alpha hydrogens, all can be substituted with halogen if
excess base and halogen are used. In fact, methyl ketones go one step further. When
treated with excess base and halide, all three hydrogens are replaced with halogen and the
carbon-carbon bond between the carbonyl and the alpha carbon will cleave due to the final
nucleophilic attack of the base on the carbonyl. This process is outlined below using NaOH
as the base.
The products of this reaction are haloform (H-CX3 - hence the name of the reaction!) and
the salt of a carboxylic acid.
The haloform reaction was used more typically in the years when spectroscopy was less
available as a test for methyl ketones where an unknown compound is treated with I 2 and
NaOH (Iodoform test). The formation of iodoform (a yellow, crystalline solid) is taken as
evidence for the presence of a methyl ketone grouping. Methyl secondary alcohols,
methyl primary alcohols and methyl aldehydes also give positive iodoforms.
In this week's experiment you will convert acetophenone into benzoic acid and
chloroform using bleach (NaOCl(sodium hypochlorite - active ingredient) as the base and
chlorine source as outlined in the following equation:
acetophenone
benzoic acid
chloroform
In addtion to the haloform reaction, this week's experiment will include the
microscale synthesis of tetraphenylcyclopentadienone via double aldols followed by
double hydrolyses. The overall reaction is as follows.
17-6
In preparation for this week's lab, you should read about the haloform and aldol reactions in
your textbook and answer the following questions.
1.
In terms of resonance theory, explain the markedly increased acidity of acetone relative to
ethane.
2.
Explain the following reaction results in terms of electrophilicity and leaving group ability.
3.
Which of the following compounds should give a positive iodoform test. Explain, a.
2-pentanone b. 3-hexanol c. acetone
17-7
Haloform
Reaction
Procedure
1.
Add 40 mL of bleach, 1.0 mL of acetophenone and a boiling stone to a 100 ml
round-bottom flask.
2.
Vigorously swirl the flask and then equip it with a reflex condenser. Heat the flask over a hot
water bath (at or near boiling) for 15 minutes.
3.
Remove the flask from the heat source and add 8-10 drops of acetone.
4.
Equip the round-bottomed flask for simple distillation. Use a 10 ml graduated cylinder as a
receiver. During the distillation, cool the receiver in an ice bath. Distill the mixture until the
still head reaches 7 0 ° C . Remove the heat source. Identify any chloroform (CHCl 3) obtained
using its density vs. H2 O. You may not isolate any CHCI3 depending on lab temperatures and
yield.
5.
When the still pot is sufficiently cool, remove the round-bottom and add a small amount of
decolorizing carbon. While intermittently swirling the mixture, heat it to the boiling point
and gravity filter.
6.
Add concentrated hydrochloric acid (HCl)dropwise to the hot solution to achieve a pH = 2.
Use care when using HCl. Wear gloves goggles and aprons and clean up your area. If
you have a bad spill, notify your instructor or TA. Use your pH paper to measure the pH.
Allow the mixture to cool to room temperature.
7. Further cool the mixture in an ice bath and collect the resulting crystals by vacuum filtration.
Rinse the crystals with a small amount of ice cold water.
8. Allow the crystals to dry for several days and then weigh them and measure the dried crystal
melting point range .
Aldol Reaction
Procedure no. A – microscale using a microwave
Procedure
1. Add 0.11 gram of benzil and 0.11 gram of 1.3-diphenylacetone to a standard test tube.
2. Using a Pasteur pipette, wash down the sides of the test tube with 1 mL of
triethylene glycol.
3. Mix the contents of the tube and irradiate the tube in the microwave (see your instructor for
guidance before you begin) for 1 minute at fifty percent power. We will be doing the
irradiations in groups of one to five in a large beaker.
4. Add approximately 1 pellet of crushed KOH to the hot tube. Do not handle KOH with your
hands or your gloved hands. Close the lid on the KOH bottle as it is hygroscopic.
5. Using a Pasteur pipette wash down the sides of the tube with 5 drops of methanol.
6. Irradiate the tube in the microwave for one minute at fifty percent power.
7. When the tube becomes cool enough to handle, add 1 mL of methanol and cool it in ice.
8. The solid, deep purple tetraphenylcyclopentadienone can be isolated by vacuum filtering
out the crystals (be sure to use your micro vacuum apparatus). Rinse the test tube out with 1 mL
of cold methanol several times. Pour these rinsings through the Buchner (Hirsch) funnel.
9. The sample can be weighed and the melting point can be measured after drying the
tetraphenylcyclopentadienone for several days. Unrecrystallized
tetraphenylcyclopentadienone typically has a melting point range of 218-220°.
10. The UV/visible spectrum ( llambda max) of your product may also be measured (ask your
instructor). To measure llambda max for your compound, take several crystals of
tetraphenylcyclopentadienone and dissolve them in approximately 5 mL of cyclohexane in a vial.
The solution should look like very dilute grape juice. This solution must be transferred into a cuvette
(the special test tubes used with the Spec 20). You will make a series of measurements from 480-520
nm. You will be looking for the wavelength at which the maximum amount of light is absorbed
(minimum transmittance). It is up to you to determine how many measurements to make. The
Spec 20 must be 'blanked" prior to each measurement at a new wavelength using a cuvette
containing pure cyclohexane.
Blanking instructions are given on the instrument. CLEAN OUT THE CUVETTES
AFTER USING THEM.
The following "color wheel" will be useful to you in interpreting your UV/vis results.
Review color using your textbook. It is often a subtractive phenomeonon. The color
on the wheel corresponding to the llambda max you measure is the color absorbed.
The color directly opposite is that corresponding to the combination of "leftover"
wavelengths that you observe.
Larger Scale Aldol Procedure for Synthesis of Tetraphenylcyclopentanone (normally gives
larger yield)
Procedure:
1. Obtain a large test tube from your TA or instructor. To this test tube, add 0.82 gram of
1,3-diphenylpropanone (1,3-diphenylacetone), 0.82 g of benzil and 6 mL of absolute ethanol. To a
smaller test tube (from your locker) add 1 crushed pellet of potassium hydroxide and 1.2 rnL of
absolute ethanol. Do not handle potassium hydroxide with your gloved or ungloved hand. Make
sure you place the lid back on the bottle as it is hygroscopic. Make sure each test tube has a
boiling stoned contained within. Gently heat both test tubes on a hot water bath until all solids
dissolve. This dissolution can be a little challenging and occasionally a little extra anhydrous
ethanol has to be added (by little I mean a few drops).
2. When dissolution has been achieved, raise the temperature of the large test tube ( the one
containing the benz.il and 1,3-diphenylpropanone) so that it is hovering between boiling and just
below boiling. This may require taking the tube out of the bath occasionally. Maintaining the
elevated temperature, very cautiously (slowly) add the potassium hydroxide solution to the large test
tube. If the reaction is working properly, the reaction mixture will turn dark purple (it will look black).
After the base addition is complete, allow the contents of the test tube to reflux very gently for 15
minutes with some mild agitation_ The reflux must be monitored very closely because you do not have
a condenser. The problem is, that it can bump over, so if it appears to be boiling too vigorously raise
it out of the hot water bath for a minute or two.
3. The solid, deep purple tetraphenylcyclopentadienone can be isolated by cooling the test tube in an
ice bath for ten minutes and then vacuum filtering out the crystals (be sure to use your smaller
vacuum apparatus – one larger than the micro set up – it will be a substantial amount of material. ).
Rinse the crystals with three small portions of cold, 95 % ethanol. The melting point can be measured
after drying the tetraphenylcyclopentadienone for several days. Unrecsystallized,
tetraphenylcyclopentadienone typically has a melting point range of 218-220°. Without
recrystallization, it is normally extremely pure. The reaction is also very high yielding. Why
Lab Report
In addition to the normal components of a preparative lab report, be sure to include the
following.
1.
An analysis of the IR and 1 H NMR spectra of benzoic acid (spectra on reserve in the
Collier Science Library).
2.
The answers to the following questions.
b. Why is the acetone added to the reaction mixture?
c. Predict the major product for the following reaction. (Hint: Bronsted Acid/Base
reaction only ).
d. Why is tetraphenylcyclopentadienone colored? Explain in terms of pi to pi*
transitons.
Experiment 17 Worksheet
Name:
TA:
Prelab Questions
1. (6 points)
2. a. ( 4 points)
b. (4 points)
3.a. 2-pentanone (2 points)
b.3-pentanol (2 points)
c.acetone (2 points)
Postlab
questions
a. (4 points)
b. (4 points)
c. (4 points)
d. ( 8 points)
Introduction
The purpose of this i nvesti gation is to carr y out a mi croscale aldol reaction
and a microscal e haloform reaction. The products will be characterized b y
melting point det erm ination. Additionall y, a visible spectrum of the highly
colored aldol adduct will be measured. (+ 6 points) Through these experiences
an appreciation of enolate chemistry and a better understanding of how the
absorption of visible light relat es to color and how color rel ates to the
structure of organic compounds will be obtained. (+ 1 poi nt)
The procedures for t hese experim ents are as found in the Br yn Mawr Coll ege
Organic Chemistr y L a b o r a t o r y Manual, pages ####. (+ 1 point)
Main R e a c t i o n s
1. haloform (2 point s)
2. aldol ( 2 points)
Mechanisms (20 points)
l.haloform
2. Aldol
17-17
Side Reactions
Self-aldols are possible
Haloform
(+ 6 points for reaction)
Minimization
Excess hypochlorite drives the equilibrium to the right, lowering the
concentration of the unreacted acetophenone. As soon as one hydrogen is
deprotonated and replaced with chlorine the pK a of the other hydrogens goes
done increasing the concentration of deprotonated species, decreasing the
likelihood of self-aldol.(+ 2 points)
Aldo1
(+ 6 points for reaction)
Minimization
The extra resonance stabilization of the enolate means that the pKa is lower than
twenty for the conjugate acid. This means that there will be more
1,3-diphenylacetone ionized than a typical aldol and it makes it even more
probable that the attack will occur on benzil
which can't ionize in this way. The insolubility and high stability of
tetraphenylcyclopentadienone drives the reaction almost exclusively in the
desired direction. This is the most important issue. (+ 2 points)
Purification
Haloform
1.
Addition of acetone:
(+ 2 points)
2.
Addition of carbon
(+ 2 points)
3.
Vacuum filtration
(+ 2 points)
4.
Rinsing the crystals with cold water
(+ 2 points)
Aldol
1. Vacuum filtration:
(+ 4 points)
2. Rinsing with 95% ethanol:
(+ 4 points)
Table of Reagents
Haloform
Reactant
grams (mL)
MW
moles density
m.p. b.p.
MW
moles density
m.p. b.p.
acetophenone
(+ 5 points )
bleach
5.25% NaOCl
(+3 points)
Aldol
Reactant
grams (mL)
1,3-diphenyl-2-p
ropanone
(+4 points )
benzil
(+4 points)
Table of Products (theoretical)
Haloform
Product
grams (mL)
benzoic acid
(+ 6 points)
Aldol
tetraphenylcyclopentadienone
(+6 points)
MW
moles density
m.p. b,p.
Observations and Data
(8 points)
Haloform Reaction (4 points)
Aldol Reaction (4 points)
Results
Yield benzoic acid in grams:
(1 point)
Yield benzoic acid in moles:
(2 points)
Percent yield benzoic acid:
(2 points)
Melting point benzoic acid:
(2 points)
Interpretation of literature IR benzoic acid
( 4 points)
Interpretation of literature NMR benzoic acid ( 6 points)
Yield aldol product grams:
(1 point)
Yield aldol product moles:
(2 points)
Percent yield aldol product:
(2 points)
Melting points aldol product:
( 2 points)
lambda max for aldol product:
( 4 points)
Discussion/Conclusion
Haloform (15 points)
c
Aldol Reaction (15 points)