Experiment 7: Aldol condensations. Reading assignment: Techniques in Organic
Chemistry 2nd ed pages 56-61, 267-321 (NMR) . 3rd ed pages 24-25, 33, 58-.
Experiment 7: Aldol condensations Reading assignment: Techniques in Organic Chemistry 2nd ed pages 56-61, 267-321 (NMR) . 3rd ed pages 24-25, 33, 5863, 315-365 (NMR). Review the mechanism of the aldol condensation. See, for example, KPC Vollhardt and NE Schore, Organic Chemistry, Ch 18 or any introductory organic chemistry text. Introduction: Condensations are important reactions in organic synthesis, as they are excellent methods for making new carboncarbon bonds. Aldol condensations can be catalyzed by acid or base, the latter being the more common. In many cases the initial condensation is followed by dehydration to form a conjugated enone, as in the example below.
In this example, the condensation begins by deprotonation of the ketone (pKa ≈ 20), followed by attack of the resulting enolate ion on the aldehyde carbonyl, and protonation. The initial condensation product can be deprotonated again, and this enolate ion then expels hydroxide to form the CC π-bond (an "E1cB" reaction; cB = conjugate base). This dehydration step is especially facile in cases where the new double bond becomes part of an extended conjugated π-system. Mixed (or "crossed") aldol condensations — those between two different carbonyl compounds — can often lead to mixtures of products. However, reactions between ketones with only one type of α-H and aldehydes without α-Hs are especially clean, since only one enolate can form, and addition to the aldehyde carbonyl is much more favorable than addition to the ketone carbonyl. In this experiment you will carry out an aldol condensation of the type illustrated above, isolate and purify the product, and establish its structure by NMR and UV-vis spectroscopy. Although the compounds you will be making are known, we're going to pretend they're not. This means you will need to establish your compound's structure from the spectral data alone, rather than by matching your data with known data. Thus, you should not go on a hunting expedition in the S&E Library. Also, don't waste time trying to name your product.
Experimental procedure. You will be assigned a ketone and an aldehyde from the following list. Be sure to look up the relevant data before the lab. Your pre-lab write-up should include the mechanisms of the base-catalyzed condensation and dehydration steps. Ketones and aldehydes cyclopentanone cyclohexanone cycloheptanone benzaldehyde furfural trans-cinnamaldehyde Note: The compounds are all flammable and irritants. Furfural may irritate the skin, eyes, and respiratory tract, and may cause allergic reactions. It's a good idea to wear gloves while handling all the compounds as well as the reaction mixture, and avoid breathing the vapors. Combine 0.25 mmol of ketone with 1.0 mmol of aldehyde, and add 5 ml of 95% ethanol and 4 ml of 2 M aqueous NaOH. Stir the mixture at room temperature for 15 min or until precipitation of solid has stopped. If no precipitate has formed by this time, try heating the solution for a few minutes and then allowing it to cool. If your product is crystalline, collect the crystals and rinse them with a little ethanol and 4% acetic acid in ethanol. If your product is not crystalline at this point, extract it with ether, wash the ether solution with a little 5% aq HCl, dry it, and remove the solvent. If necessary, purify the product by recrystallization. The remainder of this lab will be done collaboratively. Find the other student in your section who used the same aldehyde and ketone. You all presumably have the same product, but you need to be sure. Perhaps by some fluke one of you isolated the 1:1 condensation product or mysteriously got a different stereoisomer, even though all the products look similar. You will have to decide what method(s) to employ to conclusively establish that you all have the same product. Do this without resorting to spectroscopy. (If you have different products, try to figure out what happened — you may want to recheck your procedure or consult your TA.) Once you have done this, decide who has the best sample, and use about 30 mg to make up an NMR sample. Dissolve the compound in 0.35 - 0.5 ml of CDCl3 (Do not use more solvent than this! Only the lowest half inch of the tube goes into the NMR probe.) The person whose product made up the NMR sample should not dissolve it all, but save some to turn in if possible. The NMR tube MUST be labeled with the names of the group members and the proposed structure of the compound. Tubes not properly labeled will be lost. Interpret the NMR spectra as completely as possible. This may be tough for some of the condensation products, but do the best you can. Is the spectrum consistent with the proposed structure of the product? Obtain a UV-vis spectrum of the product. You'll have to make a dilute solution. Weigh small amount of compound (10-20 mg) and dissolved it in "spectrophotometric grade" chloroform. Measure the absorbance of the solution using a spectrophotometer. To get meaningful absorbance values, you'll need to dilute the solution until the absorbance is about 1 or below. Make note of your dilutions so you will be able to calculate the ε of each transition. Report the λmax of each transition you see and assign them as π —> π* or n —> π* as appropriate. Measure the compound's IR spectrum by forming a KBr disk (Zubrick p. 278). Your TA will demonstrate the proper way to form the disk. Are your IR and UV-vis data consistent with your structure? How do the data compare with IR and UV-vis data of related compounds (e.g. non-conjugated ketones and alkenes)?
In your lab report you will have to analyze the IR and UV data of the various compounds that were synthesized in the lab, and comment on the variations in λmax and carbonyl IR stretch. The data will be tabulated on the board as it is acquired by each group. If students in your section write strange-looking data on the board, don't hesitate to challenge them — you need the right numbers for your report! Be sure you record the data from the board before you leave the lab!!!
3 Your report should include the reasoning your group used in determining who had the best product, a thorough analysis of all the spectral data accompanied by a discussion of how it supports the proposed structure, and the original or photocopies of all the spectra. Turn in your product, properly labeled, as always. ________________________________ Based on BA Hathaway, J.Chem.Ed. 1987, 64, 367.
Things to think about before lab — i.
How many stereoisomers of your reaction product are possible? How might you decide which you have?
ii.
Think about all the techniques you've learned so far. There are many ways to tell that two samples are different compounds — if any property is different, they can't be the same compound. Proving that two samples are the same compound is more difficult. They may accidentally have certain physical and chemical properties in common, especially if they are similar in structure. Which techniques provide the strongest support for two samples being identical? For example, if two compounds have the same density, what are the chances that they're different? What if they have the same melting point? The same IR spectrum?
