Synthesis of Benzilic Acid

Transcription

1 E x p e r i m e n t 1 7 Synthesis of Benzilic Acid bjectives To synthesize Benzilic acid usin a solvent free Green Chemistry procedure K. Tanaka and F. Toda, Chem. Rev., 2000, 100, To investiate a carbon skeleton rearranement reaction. To assess the purity of the product by determinin its meltin point. To determine the molar mass of the product via titration with standardized NaH. In the Lab Students work in pairs After Lab Complete the Chem21 assinment Waste Place the fluted filter paper in reular trash. Place the aqueous filtrate down the sink with plenty of water. Place the first three titration solutions (KHP titrations) down the sink with plenty of water. Place the last three titration solutions (Benzilic acid) in the waste container labeled Lab 17 - Aqueous Ethanol Waste located in the Instructor s hood. Safety Students must wear oles for this experiment.

2 Mechanism Benzilic acid, althouh posin no threat itself, is a precursor and deradation product of a chemical warfare aent called BZ. BZ s IUPAC name is -hydroxy- phenylbenzeneacetic acid-1-azabicyclo[2.2.2]oct-3-yl ester (see structure below). This compound is a psychoenic aent that incapacitates H its victim. Approximately 30 minutes after exposure, C C disorientation and visual and auditory hallucinations bein to appear. After four hours and lastin four days, N symptoms can include distended pupils, dry mouth, and increased body temperature. Most of these symptoms are the result of BZ s action on the central and peripheral nervous system via its bindin to muscarinic acetylcholine receptors. Production of BZ bean in the United States in 1962 at Pine Bluff Arsenal in Arkansas. It was later weaponized in bomblets with a pyrotechnic mixture which, when inited, produced a solid aerosol of the hih-meltin BZ. Between 1988 and 1990, the BZ munitions were destroyed and no BZ munitions remain in the US stockpile. The evidence provin that this nerve aent was used in warfare rests upon the detection of benzilic acid (the compound we will make in this lab) in soil and water samples. This can be accomplished usin various instruments/techniques such as GC (as chromatoraphy), MS (mass spectrometry), NMR (nuclear manetic resonance spectroscopy) and LC (liquid chromatoraphy). To date, only one alleation of its use has surfaced this from Bosnian refuees. However, no soil or water samples were available to substantiate their alleations.

3 E x p e r i m e n t 1 7 Benzilic acid Today s lab uses a reen chemistry approach that uses fewer, and less expensive reaents and solvents. Most other procedures use 95% Ethanol as the solvent and its removal requires time and enery. In addition, these procedures use the more expensive KH as the base. Finally, these procedures use decolorizin carbon and celite in their purification schemes. The reen procedure, devised by K. Tanaka and F. Toda, uses only solid NaH, water and conc HCl to accomplish the same reaction in a shorter amount of time with similar yields. Table of Physical Constants Chemical Name Chemical Formula Molecular Weiht Meltin Point Boilin Point Density 20 n D Benzil C 6 H 5 CCC 6 H Conc Hydrochloric Acid Benzilic Acid HCl (C 6 H 5 ) 2 C(H)C H Table

4 E x p e r i m e n t 1 7 Benzilic acid Day 1 Makin Benzilic acid 1. Pack a meltin point tube with the benzil from Lab 16. Leave 0.5 rams of the benzil in the labeled vial. 2. Place the rest of the benzil in a mortar. 3. Wear Gloves!! Add an equivalent mass of NaH to the mortar. 4. Place the mortar on the counter top and use the pestle to thorouhly crush the NaH pellets. nce they are crushed, rind the two solids to make an easy flowin powder (~ 2 minutes). 5. Transfer the powder to a 250 ml Erlenmeyer flask and place the flask in a 600 ml beaker that contains ½ inch of distilled water. 6. Heat the flask at 100 C for 20 minutes. 7. At the end of 20 minutes, place the flask on the counter top and add to it 15 ml of the boilin water from the 600 ml beaker (if yellow crystals are floatin in your solution, notify your instructor for an additional procedure step). 8. Swirl to dissolve the solid. Filter the solution throuh a fluted filter paper and rinse the flask / filter paper with an additional 5 ml of hot distilled water. 9. Cool the solution in an ice / water bath for 10 minutes. 10. Add conc HCl, with stirrin / swirlin, until there is obvious crystal formation. 11. Check the ph with ph paper. If the ph is reater than 1, add conc HCl until the ph is 1 or less. 12. Cool the solution in ice for 5 minutes. 13. Collect the crystals via vacuum filtration and wash twice with 50 ml ice cold water. 14. Spread the crystals out on a ~½ inch of water labeled, weihed watch lass and place them in the dryin oven for 30 minutes. 15. Weih the product, record the mass of the Benzilic Acid [Data Sheet]. 16. Determine the meltin point [Data Sheet] of the crystals and calculate the percent yield [nline Report Sheet]. Standardizin the NaH solution 17. btain ~200 ml of a sodium hydroxide solution that is ~ 0.05 M in a clean beaker. Label the beaker either mark on the beaker or write NaH on a piece of paper and set the beaker on top of the paper. 18. btain a clean buret and buret clamp. Make sure the stopcock on the buret is closed. 19. Add ~ 5 ml of the NaH solution (from Step 17) to the buret (rotate the buret to wash down the sides with this NaH solution) and empty it into a beaker desinated for waste. 20. Repeat Step Fill the buret to the top with the NaH solution. Place the beaker containin the waste NaH under the stopcock and fully open 4

5 E x p e r i m e n t 1 7 Benzilic acid the stopcock allowin ~1 ml of base to exit. Repeat openin and closin the stopcock until no more air bubbles exit the tip of the buret. 22. btain three 200 (or 250 or 300) ml Erlenmeyer flasks. Tare a weihin paper (make sure the balance is not fluctuatin due to air currents). Usin a spatula, place Potassium hydroen phthalate (KHP) on the weihin paper and close the lid to the balance to minimize air currents. Record exactly the mass of KHP [Data Sheet]. 23. Add the KHP, ml of distilled water, and three drops of the phenolphthalein indicator to Flask Place a stir bar in the flask and place the flask on a stirrin plate. 25. Adjust the buret so that it is directly above the flask and the stirrin plate. 26. Record the volume of NaH in the buret [Data Sheet] and bein to slowly add the base to Flask As base drops onto the acid solution, a pink color appears that rapidly disappears with stirrin. As time passes, the color remains loner you should add the base dropwise at this point. Eventually, one drop of Liht pink for 1 minute 5 base will chane the colorless solution to a persistent (for at least 1 minute) liht pink. 28. Record the final volume of base used [Data Sheet]. Remove Air Bubble In Buret Tip. 29. Determine the Molarity of the NaH solution [nline Report Sheet]. 30. Repeat Steps for Flasks 2 & 3 record the data. 31. Determine the averae Molarity of the NaH solution from the 3 Trials [nline Report Sheet]. Titratin Benzilic acid 32. Accurately weih (to three sinificant fiures) approximately 0.2 of Benzilic acid (obtain this from your Instructor while your Benzilic acid is dryin in the oven) usin weihin paper [Data Sheet]. 33. Place the weihed Benzilic acid into three different 125 (or 250) ml Erlenmeyer flasks. 34. Dissolve the acid in each flask with 50 ml of 50% aqueous ethanol (the Benzilic acid does not need to completely dissolve since it will dissolve as it is titrated). 35. Add 3 drops of a phenolphthalein indicator. 36. Record the startin buret volume [Data Sheet]. 37. Titrate the Benzilic acid solution to a liht peach

6 E x p e r i m e n t 1 7 Benzilic acid endpoint - the color chane will be obvious, but not as obvious as a colorless solution turnin pink. Make sure the peach color persists for 1 minute to allow any undissolved acid to dissolve. 38. Record the final buret volume [Data Sheet]. 39. Repeat Steps for Flasks 2 & 3 record the data. 40. Calculate the molar mass of benzilic acid for each titration [nline Lab Sheet]. 41. Determine the averae molar mass of Benzilic acid [nline Lab Sheet]. 42. Turn in the Benzilic acid crystals in a labeled vial with your lab data sheet. Lab Report nce you have turned in your Instructor Data Sheet, lab attendance will be entered and you will have access to enter your lab data online and bein the lab submission process. Enter you lab data before exitin the lab - enter your data accurately to avoid penalty. The lab proram will take you in order to each calculation. Mouse over the orane TL link to see the points and tolerances for each calculation. Name: Mass: Lab 17 Benzilic acid 6

7 Synthesis of Benzilic Acid Student Data Sheet Mass of Benzil used Titration 1 Titration 2 Titration 3 KHP Mass () Initial Volume NaH (ml) Final Volume NaH (ml) Benzilic Acid Titration 4 Mass () Initial Volume NaH (ml) Final Volume NaH (ml) Titration 5 Titration 6 Total mass of Benzilic Acid produced Meltin Point Rane of Benzilic Acid ºC Mass of Benzil used Name: Partner: Synthesis of Benzilic Acid Instructor Data Sheet Titration 1 KHP Mass () Initial Volume NaH (ml) Final Volume NaH (ml) Titration 2 Titration 3 Benzilic Acid Titration 4 Titration 5 Titration 6 Mass () Initial Volume NaH (ml) Final Volume NaH (ml) Total mass of Benzilic Acid produced Meltin Point Rane of Benzilic Acid ºC 7

8 Post Lab Quiz (15pts) At the beinnin of the next lab period, you will have a quiz over the questions below. You will be iven the entire question and any structures on the in-class quiz. You may work toether prior to the in-class quiz to find the correct answers. 1 In this lab, a molecular rearranement, specifically a 1,2-phenyl shift, occurs as shown in the mechanism. While we have studied similar shifts last semester, the intermediate in the reaction performed in this laboratory is different and the mechanism is different. What are the names of the other two shifts and what intermediate is formed in these reactions prior to the shift? Also, what is the drivin force for these latter two reactions (i.e. why does rearranement even occur)? 2 In fact, this benzilic acid rearranement is the oldest known molecular rearranement; discovered by Justus von Liebi in How miht you synthesize benzilic acid startin from benzene oin throuh benzophenone and a cyanohydrin intermediate and finally producin benzilic acid. 3 Assin oxidation numbers to the carbon atoms in Benzil and benzilic acid (see Lab 16 introduction for assinin oxidation numbers). Accordin to your numbers, has an oxidation or reduction (or neither) occurred? C C H H - H H + C C C C - H 4 Bindin studies on stereoisomers of 3-quinuclidinyl esters (BZ bein one such ester) have shown that it is the (R)-stereoisomer that has the reatest affinity for the muscarinic acetylcholine receptors. Usin a dash or wede (the structure will be provided on the quiz), show the R stereoisomer of BZ. 5 BZ s IUPAC name is α-hydroxy-α-phenylbenzeneacetic acid-1-azabicyclo[2.2.2]oct-3-yl ester. To what atom(s) do(es) the term aza refer? To what does the [2.2.2] refer? Explain fully (hint: look up bicyclo" in the McMurray text book). 8

9 6 What aldehyde would you use to prepare the followin compounds (these products are in every way analoous to the benzaldehyde benzoin benzil benzilic acid reactions studied in Experiments 15 17). H a) CH 3 C CH b) H C CH CH 3 7 Give a mechanism for the followin transformations (this mechanism is in every way analoous to the benzil benzilic acid mechanism seen in this very lab). H CH 1) H - 2) H + 8 Alpha hydroxy acids (AHAs) have been marketed and used extensively in the past two decades by older consumers. Use the Internet or resource book to determine why AHA producers have enjoyed widespread financial success. 9 Another AHA that forms in milk as it sours and is produced in muscles and blood after viorous exercise is lactic acid, CH 3 CH(H)CH. The maximum number of stereoisomers of a iven substance is 2 n where n is the # of stereoenic centers. What is the maximum number of stereoisomers possible for lactic acid? Draw all stereoisomers and label all stereoenic centers as R or S. 9