Expt 4

The Reaction of Acetophenone with Acrylonitrile in the Presence of KOH:

The Michael Addition
Adapted by R. Minard and J. Emeigh (Penn State Univ.) from an experiment in Integriertes Organisches Praktikum (Verlag Chemie, 1984) as transalted by Scott Denmark at U. of
Illinois, Urbana. Revised 2/20/94.
Introduction:
In the presence of a strong base, in this case, KOH, acetophenone, 1, is converted to an enolate anion
which can then nucleophilically attack the b carbon of acrylonitrile, 2, leading to the formation of carbon-
carbon bond(s). This Michael addition reaction can occur once, twice, or three times, forming product X
in which y can be 2, 1, or 0 and z can be 1, 2, or 3. You will synthesize X and determine its structure
using spectroscopy.
C
O
CH
3
CN
C
O CH
y
( CH
2
CH
2
CN)
z
m.p. = 124-126C
30 - 40 C
KOH
+
1
2
"X"
b.p. = 75C
Prelaboratory Exercise:
There are many examples in your lecture textbook of the formation of carbon-carbon bonds by
condensation chemistry. Give one example reaction along with your text's title and author and the page
referenced. What distinguishes the Michael addition from the other types?
Cautions:
All operations should be carried out in a hood! Acrylonitrile is a known carcinogen in lab animals.
Wear gloves when using it and open the bottle only in a hood, as it is quite volatile. Measure
volumetrically with a pipet (density = .80 g/mL) and rinse the pipet into the reaction tube with the t-butanol
used in the reaction. Acrylonitrile is kept in the refrigerator to minimize its polymerization.
30% methanolic KOH is very corrosive! If you spill it on clothes or skin, wash the affected area with lots of
soap and water.
Synthesis:
Using a clean and dry calibrated 1-mL pipet, add 0.30 g acrylonitrile to a reaction tube. You will have to
calculate the volume of acrylonitrile needed, using its density, 0.80 g/mL. Drain unused acrylonitrile back
into the reagent supply bottle and rinse the inside of the volumetric pipet into the reaction tube by
drawing 1 mL of t-butanol into it from a reaction tube containing a little more than 1 mL of t-butanol. DO
NOT place the volumetric pipet contaminated with acrylonitrile into the t-butanol reagent bottle!
In another reaction tube, place 0.24 g acetophenone and 0.6 mL of t-butanol (t-butyl alcohol). Add 1
drop 30% potassium hydroxide in methanol and tap with your finger to mix. Dropwise, over a period of 2
to 5 min, add the acrylonitrile/t-butanol solution from the other reaction tube. Agitate at regular intervals, and
feel the bottom of the reaction tube to be sure that it is not getting hot. The reaction is exothermic, but heat
dissipation in the microscale reaction tube is very efficient. If the tube does get hot, cool it in a beaker of
water and slow down the addition of the acrylonitrile solution. Allow the reaction to stand for 1 hour at room
temperature with occasional agitation.
Isolation and Purification:
Add 0.4 mL ligroin to the reaction and filter off the resulting precipitate on a Hirsch funnel. Wash with 2 mL
of ligroin, and allow the solid to air dry on the filter. Set aside a few mg for a melting point of the crude
product and recrystallize the remainder from toluene. After suction filtration on a Hirsch funnel, wash with
cold toluene, and allow the solid to dry in an open container in your locker until the next lab period. Weigh,
take the m.p's. of the crude and purified products, and analyze the sample as assigned (normally chemical
ionization MS).
Cleaning Up:
Save both filtrates and allow the solvent to evaporate from them between labs to be sure that you have
not lost a lot of material in each filtrate. If only small amounts of material remain in the filter flasks, these can
be washed out with acetone and flushed down the drain with water.
Final Report:
Draw the correct structure for the isolated product on the mass spectrum. (You may need to refer to your
Organic lecture textbook for some information on the kinds of fragmentation you expect for your product.)
Justify this structural assignment by pointing out the presence or absence of key spectral features that
would be expected for your product and the other possible products. Attach this to your final report.
Use arrow-pushing to show the complete mechanism for the Michael addition of acetophenone to one
acrylonitrile molecule.
Answer the following question at the end of your report: A student neglected to add the acrylonitrile to the
reaction and still got a solid product. What is a possible structure of this product? (Hint: The reaction
involves condensation chemistry. See your organic textbook. )
Synthetic Experiment PreLab Grading Sheet
Name(s):
TA:
Date:
PreLab For Exp't # 4
The Reaction of Acetophenone with Acrylonitrile in the Presence of KOH: The
Michael Addition
Possible Missed
Points Points
Date, Name, Desk #, Experiment # & Title(abbreviated after 1
st
pg), Section & TA
Name
4
Summary
8
Goals
8
Reactions, structures, conditions, diagrams
14
Completeness of Chemical Data Table(s)
14
Chromatographic Behavior Comparison
16
Spectral Features Comparison
12
Work-up - Explanation of the product isolation and purification process
12
PreLab Questions
12
TOTAL FOR PRELAB
100
Date Handed in:
General Comments: Total Points:
Synthetic Experiment Final Report Grading Sheet
Name:
TA:
Date:
Final Report For Exp't # 4
The Reaction of Acetophenone with Acrylonitrile in the Presence of KOH: The
Michael Addition
Possible Missed
Points Points
Name, Date, Experiment Title (abbreviated after 1st page) and every page numbered
4
OBSERVATION and DATA - Overall organization, readability, completeness
8
Data: Weighing data, molecular weights, moles, density, volumes, R
f
's, etc.
Product analysis conditions. (Examples: NMR solvent and field strength; MS:
type of ionization, IR: weight of sample and KBr)
12
Yield: Show % yield calculations with limiting reagent clearly stated for 3
possible products.
Purity: Give melting point, color, or other indicators of purity.
12
RESULTS AND DISCUSSION - Overall organization, readability, completeness 8
Results; Achievement of goals
16
Product Analysis Data: Quality and Interpretation Structure(s) drawn on each
Spectrum
Assignment and discussion of all NMR peaks, or major MS or IR peaks and
how they verify product identity.
See Lab Guide Chapter 3, Section 3.4 for guidelines in annotating spectra and
Ch 11 for help with interpretation.
24
POSTLAB QUESTIONS
16
TOTAL POINTS
100
Date Handed in:
General Comments: Total Points: