Acetylation of Ferrocene:Electrophilic Aromatic Substitution; Column Chromatography

Ferrocene is a yellow organometallic compound that consists of a complexformed between ferrous ions (Fe2+) and two cyclopentadienyl anions. As you know fromthe organic lecture class, the cyclopentadienyl anion is an unusually stable carbanion,because its π-electr onstructure i s aromatic. Si nce it is aromatic and, in addition, moreelectron-rich t han benzene, the cyclopentadieny l anions i nferroc ene can unde rgo avariet y of electrophilic aromati csubstituti onreactions. T he products of these reactionshave a variety of differen t colors, as a result of c hangesi nthe ener gylevels of their πbonds.

As an example of this type of chemistry, you will reac t ferrocene wit haceticanhydri dein t he pres ence of phosphoric aci dto produce acetyferrocene as the mainproduct, together wit hsom e diacetylferrocene as -a by produc.t You w ill then purify theacetylferrocene by chromatogr aphy on analumina colum ,n i n order to separate it fromunreacted ferrocene, and from the diacetylferrocene and other polymeri cby-products.Finall ,y you will characteri zethe purified acetylferrocene by TLC, IR, andmelti ng point.

H3C O CH3

O O

H3PO4

O

CH3

O

CH3

+O

CH3

Fe2+ Fe2+Fe2+

Mechanism

In your prelab write-up, include a detailed mechanism for (i) formation of theelectrophile in the reaction, and (ii) the electrophilic aromatic substitution reaction.

Pre-Lab Review

This experiment will require you to prepare an alumina column, using the drypacking method, and to perform TLC, IR and melting point analyses. Be sure to reviewall of these procedures before the lab. In particular, review Operations 21 and 22 indetail, focusing on the preparation and operation of a column (pp. 707-720), and theprinciples underlying the separation methods on alumina and silica gel columns and TLCplates (pp. 720-728). Your pre-lab write-up should include a detailed procedure forpacking the column, and a diagram of the column.

Hazards

1. Ferrocene and (especially) acetylferrocene are toxic substances. The maindangers are inhalation and absorption through the skin. Follow standard practice forsafety during all procedures. Wear gloves and work in the hood. Do not lean into thehood and do not rest any part of your body or your lab notebook (or anything else thatyou may later touch with ungloved hands) against hood surfaces.

2. You w ill also work with petroleum ether (pet ether) and diethyl ether, whichare highly flammable. Keep these solvents away from hot surfaces.

3. Alumina (in your column) and silica gel (on the TLC plates) aremicroparticulate and easily become airborne, and are hazardous when inhaled. Keep thealumina in a covered container when you are carrying it through the lab, and only workwith it in the hoods. Work with the TLC plates in the hoods as much as possible, and trynot to scrape the surface material off the TLC plates if you are examining them out of thehoods. Clean up any spills. Dispose of all column materials and TLCs in the solidwaste container when you are finished.

Experimental Procedure

This procedure is adapted from a method described in the Journal of ChemicalEducation. The reference is: Richard E. Bozak, J. Chem. Ed. 43, 73 (1966).

1. Add 1.5 g ferrocene (MW = 186.03) to 5 mL acetic anhydride in a clamped round-bottom flask. Stir using a magnetic stir bar. (Note: the boiling point of acetic anhydrideis 138-140 °C, d = 1.08 g/mL, MW = 102.09)

2. Add approximately 1.0 mL 85% (w/v) phosphoric acid (MW H3PO4 = 98.00)dropwise to the stirring ferrocene solution. Then cap the flask with a rubber septum andattach a drying tube constructed from a syringe and needle, following your TA'sinstructions. Heat the reaction mixture in a boiling water bath (also stirred) for 10 min. atboiling point. Then remove the water bath and cool the reaction mixture for a fewminutes by stirring it in a water bath at RT. Return your hot plate to the cabinet assoon as possible, to avoid having its hot surface around when you prepare and runyour column.

3. Pour the cooled reaction mixture into a 50 mL beaker containing 20 g of crushed ice.Add solid sodium bicarbonate to the resulting mixture until a pH of about 6-7 is attained.Then chill the mixture in an ice bath for a further 30 min. (at least), while you prepareyour alumina column. In your prelab write-up, you should estimate how much sodiumbicarbonate will be needed for this step.

4. Prepare an alumina column using petroleum ether (pet ether) as the solvent, followingthe dry packing method described in the Lehman book (2nd edition, p. 713). Useapproximately 10 g of the neutral alumina provided in the reagents hood (Brockmanactivity I, 60 - 325 mesh). Do not weigh the alumina. Instead, measure it by volume ina small beaker (approx. 10 mL).

5. Once your column is ready for use, return to the reaction mixture. Collect the solidbrown precipitateby vacuum filtration, and wash it with small amounts of chilled water. Then dry the solidfor a further 10-15 min. by leaving it on the filter paper and using continued suction.

Column chromatography works on the same principle as TLC

• The adsorbent (alumina or silica gel) should be packed with a stream of air or nitrogen to drive out air pockets in the column. This leads to better separation.

Selection of the eluting solvent is an important factor in a good separation

• The more polar the eluant, the faster compounds will move through the column. If a solvent is too “fast”, everything will come out with the solvent front.

More polar compounds travel more slowly through the column.

• Compounds with more polar groups will adhere to the adsorbent (alumina or silica gel) more strongly than less polar molecules.

The column should have a level surface so that the bands stay even as they travel through

the column.• The sample should be

applied to the column in a minimum amount of solvent. Wide band widths lead to poor separation.

• Narrow bands traveling through the column prevent overlap.

Isolating the separated compounds

• Run TLC’s of the fractions after the column to decide which ones to combine.

6. Weigh the crude product scraped off the filter paper. Then take a 0.4 g portion of thismaterial and dissolve it in about 1-2 mL of toluene (some material will not dissolve).Load the toluene solution onto the alumina column, including any insoluble material,following the procedure described in your book and by your TA. Then elute your columnusing 20-50 mL aliquots of (a) pet ether only, followed by (b) 20% diethyl ether in petether, and then (c) 50% diethyl ether in pet ether. Never let the column run dry.

Any unreacted ferrocene (yellow) should be eluted in the first or second fractions. Theacetylferrocene product will elute after the ferrocene as an orange-red solution. Collectthis solution as it elutes from the column. (You may also see a second orange-redcomponent at the top of the column that elutes much more slowly than theacetylferrocene. This is the diacetylferrocene by-product, and it can also be eluted andcollected, if you use 100% diethyl ether, if you wish to analyze it later by TLC.)

NOTE: (a) Do not throw any of your column eluate away, until you have identified theacetylferrocene by a TLC comparison with authentic acetylferrocene (see below).(b) If the flow rate of your column is too slow, you can carefully apply air pressure to thetop of the column to increase the flow rate. This should not cause any problems, andoften gives better separations, provided you take care never to let the column run dry.

7. Identify the eluting fraction that contains acetylferrocene, by running a TLC of theeluate (the acetylferrocene should be orange-red, and will probably be in the 50% diethylether fraction). Choose a solvent to elute your TLC that makes sense, based on yourobservations of the column chromatography. The elution characteristics of ferrocene andits derivatives on alumina (your column) and silica gel (your TLC) are very similar. Onthe TLC, compare your eluted product to the crude material you loaded onto the columnand to a sample of authentic acetylferrocene. Use diethyl ether as the solvent for theother two TLC samples. Report your TLCs as diagrams drawn in your notebook,complete with Rf measurements. Do not tape these TLCs in your book, since thecompounds are toxic and the silica gel will flake off the plate.

8. When you have identified the fraction containing your purified acetylferrocene,remove the solvent by rotatory evaporation. Scrape the solid from the flask and weigh it.Then obtain an IR spectrum as a Nujol mull or paste (use a very small drop of "Nujol", ormineral oil). Measure the melting point of your product after drying it in your desiccatorfor a week. Report all of your measurements, and write a conclusion that assesses theevidence for the correct identity of your product, its percent yield (in molar terms), andits purity. When calculating your yield, remember to account for the fact that you onlypurified a fraction of your product.

Exercise Questions

1. (a) What is the molar ratio of acetic anhydride to ferrocene used in your reaction? (b)What is the molar ratio of phosphoric acid to ferrocene used, assuming you added 1.0 mLof the 85% (w/v) acid?

2. Do you expect the acetylated cyclopentadienyl anion to be more reactive or lessreactive towards acetylation, compared to the underivatized cyclopentadienyl anion?Explain.

3. Obtain a copy of the FTIR spectrum of mineral oil (Nujol) from a reliable internetsource, and tape it into your notebook. Label the mineral oil peaks in your IR spectrumof acetylferrocene.

4. Look at the NMR spectra of ferrocene and acetylferrocene in this handout. Note thesingle sharp peak obtained for ferrocene. (a) Based on the proton-NMR spectrum, do youexpect ferrocene to be more reactive towards acetylation than benzene or less reactive?Explain. (b) Suggest an assignment for the four peaks in the proton-NMR spectrum ofacetylferrocene. Explain your assignment.

Expt. 13 – Investigation of a C=O Bond byInfrared Spectroscopy

Goal: To predict the relationship betweenthe vibrational frequencies of C=O bonds inIR spectra and their bond strengths.

Each student will be given one of fivecarbonyl-containing compounds. Recordthe IR spectrum of your assigned compoundand note the frequency of the C=O stretch atthe point of maximum absorption.

O

H

heptanal 2-heptanone

O

O

O

ethyl butyrate

ClO

O

ethyl trichloroacetate

ClCl

H N

O

CH3

CH3

N, N-dimethylformamide

Prelab:Each student should (a) come to the lab witha predicted order of frequencies for thesefive compounds, and an explanation for this,written in your notebooks. (b) convert thedata for each compound into frequencies inHz (s-1). Discuss differences from yourpredictions using the arguments of organicchemistry. (c) Tape your spectrum into yourlab book.

Write your results for the carbonyl stretchfrequency (cm-1) on the board to share thedata. Predict and discuss your experimentalresults and be prepared to modify yourhypothesis about the relationship betweenbond strength and IR vibrational frequency.

The C=O bond has some single bond character.

O O O

δ

δ

If Z is an electron-withdrawing group, then resonance structure 2 becomes less important

R Z

O

R Z

O

R Z

O

δ

δ

1 2

What is the effect on the strength of theC=O bond?

R NH2

O

R NH2

O

1 2 3

R NH2

O

If Z = nitrogen, resonance structure 3 contributes to the overall picture.

If Z = oxygen, resonance structure 3 is considerably less important.

c = λυ c = 3 x108 meters/second = 3 x 1010 centimeters/second

h = Planck’s constant

h = 6.63 x 10-34 Joules . sec

υ = frequenc y λ = wavelength

E = hυ

υ = c/λ

Ε = hc/λ

The wavenumber is the inverse of the wavelength. It is directly proportional to

energy.

Expt. 16 – Separation of an Alkane Clathrate

Urea forms a tunnel-like channel (aclathrate) around straight-chainhydrocarbons with seven or more carbons.

Goal: to see if urea can be used to removehexadecane from a mixture of methanol and2,2,4-trimethylpentane by forming aclathrate with the straight-chainhydrocarbon.

hexadecane

negative octane rating

2,2,4-trimethylpentane

octane rating = 100

CH3OH

octane rating = 107

H2N NH2

O

urea

Expt. 16 – Separation of an Alkane Clathrate

• Preparation: You will add urea dissolved in methanol to a mixture of 2,2,4-trimethylpentane and hexadecane. After a white solid forms, cool with an ice/water bath until crystallization of the clathrate is complete.

Dry and weigh the urea clathrate. Dissolvethe urea in water and extract the hexadecaneinto dichloromethane. Dry the organic layerand then evaporate the solvent. Weigh thehexadecane. Use this equation to estimatethe number of ureas per hexadecane:

Host/guest ratio for urea clathrates = 1.5 +0.65n

n = number of carbons in the guest molecule

Confirm identity of the hydrocarbon by comparison of its IR spectrum to that of hexadecane and 2,2,4-trimethylpentane

Clathrates in the News

• Methane hydrate deposits on the ocean floors are twice the size of the known coal and gas reserves on earth. Could they be tapped as an energy source? Methane is a potent greenhouse gas and could contribute to the global warming phenomenon.

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