Experiment: Acetylation of Ferrocene

Transcription

1 Experiment: Acetylation of Ferrocene Ferrocene is an unusual organometallic compound with a structure now understood to be a "sandwich" of an Fe 2+ cation between two parallel cyclopentadienyl anions. Bonding occurs between the π-m's of the anionic rings and the d-orbitals of the iron. Both the structure and its remarkable bonding pattern were unimagined when Fe(C 5 H 5 ) 2 was first reported in the early 1950's as an accidental result in an experiment intended to examine the properties of a modified Grignard reagent. Fe Ferrocene Although the special qualities of ferrocene were unrecognized in the first report of the synthesis of Fe(C 5 H 5 ) 2, two Harvard chemists, upon reading the original journal article, recognized that there was something unusual about the molecule and set out to prove it. The unusual nature of ferrocene and the cyclopentadienyl anions that it contains can be seen clearly by comparing cyclopentadiene to 1,3-pentadiene. Both contain 5 carbons and two conjugated π bonds. Because of this, at first glance it might be expected that these two molecules would have very similar physical properties and chemical reactivity. However, when we compare the acidity of these two molecules, we see that they are dramatically different. 1,3- pentadiene has a pka of ~ 40, while cyclopentadiene has a pka of 16. This means that cyclopentadiene is ~10 24 times more acidic than 1,3 pentadiene, and can be deprotonated with a base such as KH. Using the relationship between the equilibrium constant and free energy that you learned in CH102, we can calculate that the cyclopentadienyl anion is ~ 130 kcal/mole more stable that the corresponding anion from 1,3-pentadiene. KH - = cyclopentadiene (pka ~16) delocalized aromatic system KH - 1,3-pentadiene (pka~40) Does not form to a measurable extent

2 But what is the nature of the greatly increased stability of the cyclopentadienyl anion and the ferrocene that is formed from it? Both R.B. Woodward and G.. Wilkinson recognized that the stability of ferrocene might stem from the fact that the cylcopentadienyl anion can behave as an aromatic compound, since it is a cyclic compound containing 6 π electrons in a series of uninterrupted overlapping p orbitals. They began immediately, and somewhat independently, to characterize this new material. Woodward's approach was to explore the similarities between the reactions of ferrocene and benzene, expecting ferrocene to exhibit the properties of an aromatic compound like benzene. It was Woodward who coined the term ferrocene, an acknowledgment of the benzene-like aromaticity of Fe(C 5 H 5 ) 2 and the presence of Fe 2+. He found that Friedel- Crafts acylation with acetyl chloride and aluminum chloride yielded diacetylferrocene in which each ring contained an acetyl group. It is now known that ferrocene is not only aromatic but is much more reactive than benzene in electrophilic substitution reactions. The acylation you will be performing uses milder conditions with a weaker acid catalyst and less reactive acylation reagent to achieve monoacetylation of ferrocene. Benzene is not reactive enough to be acetylated under these reactions conditions. Woodward later won a Nobel Prize for his contributions to organic synthesis. Wilkinson won a Nobel Prize for his work elaborating the chemistry of sandwich compounds like ferrocene. In today s experiment, you will be synthesizing acetylferrocene. Note that even though the diacetyl product is also included in the reaction below, we will not be forming it because of the milder conditions that we are using. Because commercial ferrocene is not especially pure, it will have to be purified before the reaction is performed. Sublimation is a particularly convenient method for obtaining small quantities of pure ferrocene. Although the expected product is acetylferrocene, there will quite likely be some unreacted ferrocene left in the reaction mixture. CH 3 CH 3 Fe H 3 C C C CH 3 Fe H 3 P 4 + H 3 C Fe The method of purification we will be using in today s experiment to remove the unreacted ferrocene from our product is different that what we have done so far in this course. In all of the experiments that we have performed so far in CHEM 204, we have purified our products by either distillation or recrystallization. These are very valuable and useful purification methods when they are applicable, but there are many instances when they are not. For instance, distillation is useful for low boiling liquids which are not contaminated with impurities that have a boiling point close to the substance to be purified. In contrast, many organic liquids have quite high boiling points. ften the boiling point of a substance is above the temperature at which the compound would start to decompose. Since these high boiling samples are not solids, they also cannot be recrystallized. In addition, distillation and recrystallization are not useful when working with very small amounts of samples.

3 For these reasons, other methods have been developed for purifying organic compounds. ne of the most widely used and versatile purification methods is column chromatography. In column chromatography, a crude sample is placed on top of a column containing an inert solid material, often referred to as the chromatography support or the chromatography matrix. Two common supports are silica and alumina. The sample to be purified and the impurities to be removed have different affinities for the solid support. A solvent flows through the column, and the desired product and the impurities move through the column at different rates. Molecules that interact strongly with the chromatography support spend most of the time adsorbed on this solid phase and move through the column very slowly. n the other hand, molecules that interact weakly with the solid support spend less time adsorbed on the column and more time dissolved in the solvent that is flowing through the column. These weakly bound samples elute from the column faster. By choosing the appropriate solvent, it is possible to separate the desired product from the impurities present based on their different affinities for the support. In today's experiment we will be separating our desired product (monoacetylated ferrocene) from impurities (unreacted ferrocene and maybe a small amount of diacetylated ferrocene) using alumina as a support in a column chromatography process. Solvent Crude Product mixture Flow solvent through column Product with high affinity for support moves slower More solvent flowed through column Support Product with low affinity for support moves faster Slower moving product still on column Collection tube Faster moving product collected in tube In many ways, a chromatography column behaves like a 3-dimensional TLC plate. In fact TLC is often used to choose a column chromatography solvent and to analyze the effectiveness of purification after column chromatography. We will be determining the effectiveness of our purification in this experiment by analyzing our samples by gc/mass spec. Pre-lab Preparation Before coming to lab, you must do the following in your lab notebook: 1. Write the equation for the reaction that we are performing in this experiment. Underneath each reactant, record the molar mass, the number of grams used, and the number of ml used (if applicable). Also calculate and list the number of moles used. Assume that we are only making the monoacetylated ferrocene. Remember that H 3 P 4 is a catalyst.

4 2. What is the molar ratio of acetic anhydride to ferrocene we are using in this experiment? 3. H 3 P 4 reacts with acetic anhydride to form the electrophile for this reaction, the structure of which is shown below: Draw a mechanism for the formation of this electrophile 4. If the diacetylated product were to form, one acetyl group would be on each ring, instead of both acetyl groups substituting onto the same ring. Using what you know about electrophilic aromatic substitution, explain why this happens. Safety Considerations Experimental Procedure! Phosphoric acid is corrosive if it comes in contact with your skin. Consequently, it is important not to spill any on yourself. If you spill it on yourself, wash it immediately with water. Also clean any lab equipment or surfaces that may have come in contact with phosphoric acid.! Methylene chloride, hexane, ethyl acetate and methanol are toxic solvents. Avoid skin contact, ingestion, and inhalation. If you come in contact with these solvents, wash the affected area with water. nly transport these liquids in closed containers. When evaporating these solvents, work in a fume hood or with equipment specifically designed for trapping organic vapors that have evaporated from a sample (such as a rotary evaporator)! Silica can be an irritant, especially if inhaled. Avoid inhalation or ingestion of silica. 1. In a 25 ml round bottom flask, place, in the order indicated: 280 mg of sublimed ferrocene, 1.0 ml of acetic anhydride, and 0.4 ml of 85% phosphoric acid. Heat the mixture at C for ten minutes using a sand bath. Use a thermometer to monitor the temperature. ccasionally remove the flask from the sand bath and swirl to mix the reaction. If the mixture is not a deep red color, longer heating may be necessary. If the reaction has not occurred within 20 minutes, notify your instructor.

5 2. After the reaction is complete, quench it by transferring the contents of the reaction flask into a beaker containing about 10 ml of ice. Rinse the reaction flask with small volumes of ice water until transfer is complete. Stir the mixture with a glass rod to break up any clumps of crude product. 3. Add 10 ml of 10% sodium hydroxide solution and test the ph of the resulting mixture. If the ph is not basic, and small amounts of the 10% NaH until the sample is slightly basic. 4. Allow the mixture to stand for 5 minutes before isolating the solid product by vacuum filtration using a Hirsch funnel. 5. Dry the product by pressing between two pieces of filter paper to remove as much water as possible 6. Take approximately g of your crude product and dissolve it in a minimum amount of methylene chloride (as little as possible). 7. The columns we will use in today s lab are ~ 10 cm long, and have a removable plastic funnel on one end. Remove the funnel and place a small plug of glass wool into the bottom of the column. Pack this down with a Pasteur pipet. 8. Replace the plastic funnel and clamp this column to the ring stand. Then add silica to a height of ~ 10 cm. (The 10 cm level has been marked on the column with a line). Tap the column to make sure the silica is well packed. If the level goes down upon tapping, add a more to get the appropriate height of silica. 9. Carefully add ~0.5 cm of sand to the top of the column (also marked on the column with a line). Be careful when adding the sand to make sure that the sand sits on top of the silica and does not end up mixing with it. 10. Place a test tube underneath your column, close the stopcock, and fill the top of the column with hexane, being careful not to disturb the sand on top of your column. 11. pen the stopcock, and the liquid should begin to flow through the column. Watch the top of the column closely. When the hexane reaches the level of the sand, close the stop cock. Never let the solvent on your column go below the level of the sand. 12. Using a Pasteur pipette, load the methylene chloride containing your product carefully on to the top of your sand, trying not to get any on the sides of the column. pen the stop cock and let the product flow onto the column. When the liquid level reaches the top of the sand, close the stopcock.

6 13. Add 1.0 ml of hexane to the column, open the stopcock, and let the solvent flow through the column. Close the stopcock when the liquid level reaches the level of the sand. 14. Fill the column with hexane and open the stopcock. If any unreacted ferrocene is left, it will begin to elute in this solvent. bserve the liquid coming out of the bottom of the column. Just before the first drops of colored, ferrocene containing liquid elute from the column, switch to a pre-weighed test tube and collect the liquid. You should flow a total of 10 ml of hexane through your column, although the ferrocene may have completely eluted by then. Collect all of the colored liquid in the pre-weighed tube. nce the liquid is no longer colored, switch to collecting the liquid in a different tube (there is no ferrocene in this liquid, so this liquid is not needed). Again, close the stopcock when the liquid level reaches the level of the sand. Note: You might not have any unreacted ferrocene, in which case you will not see any color moving down the column. If this is the case, move on to the next step. 15. Change to 1:1 ethyl acetate/hexane. Fill the column with this solvent, and allow the solvent to flow through the tube. When the colored acetylferrocene product begins to leave the column, start collecting the liquid in a second pre-weighed test tube. Put a total of 15 ml of this solvent through the column. 16. Switch to a new pre-weighed test tube, and pass 15 ml of ethyl acetate through the column to remove everything else remaining on the column. Note: Eluted solvent samples which are colorless should not be collected to minimize the amount of solvent we have to evaporate at the end of the experiment. 17. Submit a sample of your monoacetylated product for GC/MS analysis. You will use the GC trace to determine the effectiveness of your column purification. 18. Evaporate the solvent from your samples with a stream of nitrogen, or in the rotary evaporator. 19. Determine the number of grams of unreacted ferrocene and acetylferrocene product. Post-Lab and Report Requirements 1. Draw a mechanism for the reaction that we performed in today s lab.

7 2. Assuming all of the material that you loaded onto your column was product, calculate how many moles of crude product were loaded onto your column? 3. From the weight of the product you obtained, calculate the number of moles of acetylferrocene that you isolated 4. Using the information from the two previous questions, calculate the percent yield of acetylferrocene. 5. Was our column chromatography successful in separating our product from the unreacted ferrocene? Explain how you can tell. 6. What could we have done differently in this experiment if we wanted to make the diacetylferrocene product?