You are on page 1of 6

55 Hemenway St.

Boston, MA 02115

May 18, 2017

Dr. Brian Fulton
Professor – College of Science
Northeastern University
334 Huntington Ave
Boston, MA, 02115

Dear Professor Fulton,

I am writing to propose an alternative laboratory protocol to be used by upper level
undergraduate students in the Lewis Acid Catalyzed Friedel-Crafts Acetylation of Ferrocene
experiment for the Chemical Synthesis and Characterization 40026 course.
As a current student in this course, I have a personal appreciation of the experience
level held by my classmates and myself. The experiments you created have provided my
peers and I exposure to many new organic chemistry techniques. However, I noticed a
significant portion of the class repeated the second experiment, due to the advanced nature of
the procedure. I believe a supplementary paper, or more exhaustive directions, would be
useful to a large amount of students. Therefore, I have taken the liberty of compiling a
detailed protocol for this experiment that incorporates the original directions by Tappe, K.
and Knochel, P., your modifications to the original protocol, and a detailed description of the
more advanced techniques.
I believe I am qualified to create such a document, as I have successfully completed
the experiment and witnessed first hand the main problems faced by my peers. I think you
will find it follows a clear chronological order and contains detailed descriptions, while still
being challenging enough to maintain the advanced level of the course.
I request you examine and consider the integration of this document for future
students of this seminar. I am happy to meet with either you, or a TA, to perhaps continue
editing the attached document for the increased benefit of the class. You may contact me any
time by email, at, or by telephone, at (832) 523-9336, to discuss
my proposal.
Thank you for your time.

My Regards,

Abigael Gunther

Enc. (1)
Lewis Acid Catalyzed Friedel Crafts
Acetylation of Ferrocene

Original Source – Tappe, K. and Knochel, P. Tetrahedron: Asymmetry 2004, 15

Author – Dr. Brian Fulton

Modified By – Abigael Gunther

Date – May 29, 2017

Friedel-Crafts acylation of an aromatic compound is a specific example of electrophilic
aromatic substitution. Aromatic compounds readily undergo electrophilic substitution as they
exhibit strong resonance stabilization. Simply put, an acyl group can be substituted on an
aromatic ring in the presence of an acid catalyst. More specifically, the acid catalyst converts
the acyl group to an acyl cation that adds to the aromatic ring. In this experiment, ferrocene is
the aromatic compound. It contains two cyclopentadienyl rings connected by an iron ion. The
Lewis acid is aluminum (III) chloride and it treats the alkyl group in acetyl chloride. In micro
scale reactions the acyl group is deactivating, meaning it will stop the reaction after one
group has been added to an aromatic ring. This ensures the major product formed is acetyl
ferrocene with only the minor presence of diacetyl ferrocene.


1 25 mL Round Bottom Flask
1 5 mL Conical Flask
1 Magnetic Stir Bar
Magnetic Stir System
5 Needle + Syringe (never reuse a needle or syringe)
Rubber Band
Thick Walled Plastic Tubing
Separatory Funnel
2 25 mL Beakers
Ice Bath
Rotary Evaporator
TLC Plate
10% Ethyl Acetate: Hexane Solution


300 mg Ferrocene
0.2 mL Acetyl Chloride
70 mL Dichloromethane
250 mg Aluminum (III) Chloride
Saturated K2CO3
Acetyl Ferrocene
Diacetyl Ferrocene

To a 25 mL round bottom flask, add 236 mg (1.77 mmol) of aluminum (III) chloride and a
magnetic stirrer. Cover flask with a plastic stopper to create a closed environment.

To avoid interference from atmospheric water, a nitrogen
environment must be established until the reaction is
quenched. To do so: Fit the plastic body of a syringe into
thick walled rubber tubing. Secure an unfilled balloon
onto the tubing with a rubber band. Connect the syringe
to a nitrogen source and fill the balloon with nitrogen. To
avoid loss of nitrogen, quickly attach a needle to the
syringe then pierce the plastic stopper on top of the round
bottom flask with the needle.

The final set-up should appear similar to the image on the

Note: Most laboratories come equipped with a Schlenk
line connected to an inert gas for the purpose of
separating and managing air-sensitive material. Ask your
professor or TA if unfamiliar with its location in your
specific room.

Add 0.127 mL (1.79 mmol) of acetyl chloride and 2 mL
of dichloromethane (DCM) to the flask with different
syringes. Allow the reaction to stand and stir at room
temperature for 30 minutes.

While waiting, add 291 mg of ferrocene to a 5 mL
conical flask. Setup another balloon filled with nitrogen (following same method as described
above) and attach to the flask. Add 2 mL of DCM via syringe. Submerge the ferrocene/DCM
mixture in an ice bath until the aluminum chloride/acetyl chloride/DCM solution has stirred
for 30 minutes.

Add the cold ferrocene/DCM mixture to the aluminum chloride/acetyl chloride/DCM mixture
in the round bottom flask with a new needle and syringe. Allow the reaction to stir for an
hour at room temperature.

Quench the solution with 5 mL ice-cold water then remove the balloon apparatus.

Note: the absence of water up until the point of quenching is critical. If the balloon method
was performed incorrectly the reaction will not produce the correct product.

The next step is to separate the phases using a separation funnel. To prevent spilling it is
useful to use a funnel to transfer solutions. Set up a standard separation funnel with a clean
beaker underneath the outlet, like the image on the following page. Once the washing liquid
is added, extraction occurs by ensuring the stopcock is closed and the inverted stopper is in
place. Remove from the stand and invert the funnel. Shake the funnel vigorously for a few
seconds and then slowly open the stopcock to vent
pressure buildup. Take care to open the stopcock facing
away from you. Shake and vent a second time.

Note: Separatory funnels separate solution phases
based on density. The lower density liquid is on top and
higher density liquid is on the bottom. Depending on
what is being used to wash the solution, the organic
layer can alternate between being the top or bottom
layer. Since DCM is less dense than the organic
material, which layer is on top?

Pour the solution into the separatory funnel and wash
three times with 10 mL of DCM. DCM is less dense
than the organic layer so it will separate onto the top.
After each wash, filter the organic layer into the beaker
on the bottom and the aqueous layer into another beaker. Pour the organic layer back into the
funnel and repeat, taking care not to mix up the beakers. Keep the organic layer and discard
the aqueous layer in the designated hazardous waste container.

Return the organic layer to the separatory funnel then wash with 10 mL of a saturated K2CO3
solution. The organic layer is now on top. Filter out the K2CO3 solution. Repeat this process
with 10 mL of water. Then repeat with 10 mL of brine.

Collect the organic layer in a small beaker and dry over MgSO4. After a few minutes remove
the magnesium sulfate with vacuum filtration. You should be left with an orange solution that
contains the crude acetyl ferrocene product. Reduce the product in the rotary evaporator and
then leave overnight to fully dry.

The following morning, test the purity of the product by 1H-NMR, IR,
and TLC. Operating the complex 1H-NMR and IR machines is not a part
of this course. Prepare the NMR tube for your professor to test by
dissolving 2 mg of the product with 0.7 mL deuterated chloroform in a
20 mL beaker. Transfer this by Pasteur pipette into an NMR tube.

To run the TLC, dissolve a minimal amount of your product (A), known
acetyl ferrocene (B), and known diacetyl ferrocene (C) into a test tube
with a few mL of DCM. Spot each solution into their corresponding
columns on the plate. Make a tentative identification of the products by
using a mixture of 1:9 ethyl acetate: hexane as the mobile phase. Your
product and the known acetyl ferrocene should elute to the same spot, as
seen in the TLC on the right.

Note: You want to use just enough product to dissolve in the DCM. If
excess product is used the solution will too concentrated and if not
enough is used spotting won’t be visible – either of these options will result in an inaccurate

Confirm the product with your 1H-NMR and IR results.
Expected Results from Original Source

H-NMR (CDCL3, 400 MHz): δ 4.770 (t, 2H), 4.502 (t, 2H), 4.203 (s, 5H), 2.396 (s, 3H)

IR: 1,650 cm-1 (C=O)

TLC (silica gel, 10% ethyl acetate: hexanes): Rf = 0.16

***As my assignment is a technical document relating to chemical synthesis, it is directly
relevant to my current discipline. All laboratory courses I have participated in for college
involve reading the professor’s protocol and then doing additional research to fill in the
blanks. In my experience, protocols are purposefully vague so we have the additional task of
doing research and developing our understanding of the experiment’s theory and techniques.
This document reflects exactly that. I have taken Dr. Fulton’s initial instructions and
conducted additional research in order to complete the procedure successfully. This text fills
in the knowledge gap between instruction and action for future students, while still offering
an academic challenge. My hope is that students have a better understanding of why certain
steps are required. They should feel confidence before undertaking this experiment.***