Three Puzzles for Organic Laboratory David Todd Worcester Polytechnic Institute, Worcester, MA 01609 Miles Pickeringl Princeton University, Princeton, NJ 08544 For many years we have advocated that laboratory work be more oriented toward puzzle solving, rather than technique or illustration (1, 2). However, while this has been widely accepted as a goal in freshman chemistry, there has been much less work in organic. T h e impression that organic labs are largely cookbook and illustrative in nature has been confirmed by a detailed scholarly study (3). One of the reasons that so few organic lab courses display any problem orientation is the absence of appropriate exercises. Only two papers giving good problems for this approach seem to have been published (4, 5) although some other organic experiments have some puzzle component (614). Therefore, in this paper, we offer three puzzles, each of which can be solved using melting points alone, and each of which involves work a t the 100-200-mg scale, a scale which still allows the use of conventional glassware, but which has the speed and safety of truly micro work. These puzzles were tried as a special project by two sections (about 20 students) in the mainstream sophomore organic laboratory a t Princeton. These students had no previous experience with micro-scale work, but the challenge did not seem to be overwhelming. Puzzle 1 Suppose one is given the substance 2-chlorotoluene and treats i t with acetyl chloride in the presence of AlC13. This reaction, the Friedel-Crafts acylation, can yield four possible products:
Each possible isomer can then be oxidized via the haloform reaction to a substituted henzoic acid, and these products distinguished by melting point.
& COOH
COOH 209-210 'C
Experlmental for Puzzle 1 A pea-size amount of dry AlCh is added to a test tube containing 2 mL of methylene chloride. Using a calibrated pipet, exactly 0.2 mL of 2-chlorotoluene and 0.15 mL of acetyl chloride are added. The mixture is allowed to react at room temperature for 60-90 min, then poured into a test tube containing cracked ice. About 3-5 mL of eanc. HCI is added to dissolve anv oreei~itatedA1 salts. After shaking, the aqueous layer is disearded,Bnd the methylene chloride layer isshaken vigorously with successive washes of 10mL distilled water and 10 mL of 5% NasC03 solution and then is washed twice more with distilled water. The methylene chloride layer is set aside (or
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placed in the hood) to evaporate, leaving a yellow oil with the characteristic odor of acetophenone. The acetophenone is converted to the correspondingbenzoic acid by treatment with NaClO (15). The yellow oil in the beaker is dissolved in 5 mL of ethanol, and then 10 mL of 5.25% NaClO solution (Clorox or similar) is added. The mixture is heated under the hood to expel chloroform for 2 min, then acetone is added to destroy excess OCI- and the mixture is reheated for 2-3 min. The substituted benzoic acid is precipitated when 2-3 mL of conc. HCl is added. This is collected on agravity filter (suctionfiltration does not work well), and the filtrate discarded. The precipitate is redissolved aqueous 0.1 M NaOH. The solid does not all dissolve-yellow or brown particles of polymeric side product are left on the filter. When the basic solution is neutralized with eonc. HC1 dropwise, extremely pure substituted benzoic acid will he precipitated.This is filtered, and the melting point taken.
This product can then be easily esterified with methanol to
However, there are several possihle isomers, each with a unique melting point, that can be formed (X = COOCH3),
Puzzle 2 There are many student experiments showing examples of electrophilic aromatic substitutions in the literature, but only a few show nucleophilic substitutions (16-18). If 3,4dichloronitrobenzene is treated with sodium metboxide, the methyl ether will be formed. But since there are two chlor i n e ~ will , the replacement be a t the para position or the meta position, or will both be replaced to produce 4-nitroveratrole?
NO2 93 OC
83 'C
I
NO? 96 'C
Experimental for Puzzle 2 Caution: students should be warned that nitroaromatic compounds are skin irritants end poisonous. Ahout 100.200 mg of 3,4-dirhl~~ronitrobenzene is weighed into a small 11O.mLlrefluxfleskand ahout 5 mLofdrv methanol is added. toeether withtwo oea-sized amounts (0.2-0.4 e j of sodium methor: . . -. n ide. l'hia mixture is gently r~fluxedfor ahout an hour. The contents of the reflux flask ere then transferred to a test tube, and enwgh H20to double the volume is added. Then 5 mL of methylene chloride is added, and the tube shaken. The top layer is then discarded, and the methylene chloride layer washed twice more with water. The methylene chloride layer is then allowed to evaporate, and the solid is recrystallized from methanol-water. A second recrystallization is sometimes necessarv . to nurifv . .the .oroduct sufficientlv since the melting points of the various possible products are very ;lose. To distinguish the disnbstituted product from the mono-snbstitnted product of roughly equal melting point, it is best to do a mixed melting point with an authentic sample of 4-nitroveratrole (available from Aldrich). This elegantly uses mixed melting point depression to solve a problem. ~~~
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Puzzle 3 If maleic anhydride is exposed to light, it will photodimerize.
145 'C cis, trans, cis
73-74 'C cis, cis, trans
127 "C trans, trans, trans
Experimental for Puzzle 3 The solution to he exposed to light is prepared by dissolving 4-5 g of maleic anhydride in 30 mL of methylene chloride, warming if necessary, and then filtering off any solid residue of maleie acid using gravity filtration. The solution is placed in a 250-mL conical flask and is sealed with a cork (not a rubber stooner) , , . and a laver , of plastic film on the outside ofthe cork.This is placed on the windowsill in the lab until the following week. At least 6 5 h of bright sunlight seems to he necessary for the reaction. The photoproduct will precipitate from the solution. The excess solutirm is removed by using a dropper pipet, the tip placed firmly against the bottom of the flask to a\,oid sucking up solid. This nolid ir then dissolved in 3-5mLof methanol xith warming, and thpflask rinsed once more with methanol. The rinsings are Eombined with the oriainal solution. four droos of conc. HCI are added. and the mixture refluxed for 1 h. The solution is allowed to evaporate, and the solid product recrystallized from methanol. The melting point will adve the puzzle. ~~~
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I NO?
203 'C cis, cis, cis
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~
~~
Results and Dlscusrlon Most students correctly solved the first puzzle, presumably because the benzoic acid is easy to purify. ~ h e a m w e is r 3-methyl-4-chlorobenzoicacid, melting point 209 OC. About 20% of our students, however, measuredmelting points that were lower due to impurities and ended up attempting to rationalize the 3-chloro-4-methylbenzoicacid. Yields ranged from 30-705, satisfactory considering that students were not used t o workine on a small scale. This somewhat &prising result has been explained by the nartial rate factors of methvl and chloro suhstituents in ~riebel-crafts acylation. T h e methyl group of toluene enhances attack para to it by a factor of about 700 and also enhances attack a t any one ortho and meta position by factors of about 25 and 10, respectively. The chloro u o u p deactivates the position para to it by a-factor of ahou; 1 0 6 and the other positions by very much larger factors-prohably 104or greater. Multiplication of the appropriate partial rate factors leads to the consequence that the position para to the CI of o-chlorutoluene is hv a wide marein the favored position for attack in this reactibn (19,. The second puzzle gave many students problems. About Volume 65
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half obtained the expected product 3-chloro-4-methoxynitrobenzene (mp 92 OC) in good yield (50-70%).The product is easily predictable once the student draws out the resonance forms of the starting material and observes where attack by an anion can be expected. However, a side product formed in some cases, which turned out to be
This is a yellow solid melting at 182 ' C . The e x ~ e c t e d is known'co be product 2-chloro-3-me~hox~nit~obenrene converted into this material under reducinaconditions.This azoxy compound seems to be formed whenever the reaction mixture boils dry. The toxicity of this material is not known; however. unsubstituted azoxvbenzene is not carcinoeenic This side product is k e n according to the latest data tioued for the sake of completeness only, since if procedures are carefully followed, it will not be formed. The maleic anhvdride dimerization vields the cis. trans. cis product with melting point of 142 OC. The deed minimize strain on the central ring necessitates either cis, cis, cis, or cis, trans, cis, assuming no subsequent rearrangement. The crowding of the cis, cis, cis, is probably the reason why i t is not observed. Interestingly, thermodynamic stability favors the most staggered configuration trans, trans, trans, not observed during this experiment.
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The only problem encountered with this puzzle was that some flasks were not exposed to sunlight for enough time. The yield of photoproduct is very low, but can easily be handled with microscale techniques. Acknowledgment We are indebted to Joe LaPrade, in charge of the Princeton organic laboratory, for letting us try out these ideas, and to two TA's, L. C. Dong and D. Cohen, who looked after the students in this experiment. Llterature Cited
7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19.
Gr0enberg.F. H.;Leung,K.K.; Leung,M. J. Chsm.Edu. 1971.48.632 Grob. R. L.: Husk. G. R. J. Cham. Edur. 1969.46.769, Mur0v.S. L.:Pickering,M.J Chem.Educ. 1973,50,74. Silversmith. E. F. J. Cham. Edur. 1919.56127, ~ a n ~ e ~ sM. r kR., R.; KU&, P . L . C);& ~ Edur 1973,50,512. Marchard. A. P. J. Chem. Educ. 1912,49,841. Benaan, B. W.; Obcn, E. S.;Smcltl, L. A. J. Chrm. Edur. 1970.47.220, Garrison, J. A. J. Chem. Edur. 1970.47.3W. Porkins,R.J. Chem.Educ. 1984.61.551. Todd, D.: Larkabsugh, M. J. Chem. Edue. 1912.49,292,850. 8mith.N.H. P. J Chm~Educ.1975,52,238. Farmer. J. L.: Hawa. E. J. J. Chem. Edur. 1970.47.41. Elmwood, T. A,: Flaek, W . R.; Inman. K. J.: Rabideau, P. W. Tetrahedron 575
20. Nat'l Inst. of Occupational Safety aod Health. Registry Substomea;1984 supplement to 1981 ed.: p 362.
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