Hydroboration for the Large Organic Laboratory Miles Pickering Princeton University. Princeton, NJ 08544 The important reaction of diborane with olefins followed hv oxidation to form alcohols ( 1 has found its wav into most o&anic textbooks, but there arb few lab experiments based on this reaction. The most important previous student experiment is that of Kabalka and Hedgecock (2) in which are described student procedures for hydroboration of several substrates with the BH3:S(CH3)2 complex, followed by oxidation with trimethylamine N-oxide. The requirement of hood space and inertatmosphere conditions makes this procedure impractical for a large organic lab. Mayo, Pike, and Butcher's classic lab manual describes the hvdroboration of octene with BH3. THF and subsequent oxidation with Hz02 at microscale without inert atmosphere techniques (3). This paper reports an experiment in hydrohoration without large hood space requirements, without special glassware requirements, and without inert atmosphere precautions. Furthermore, rather than having a mere synthetic reaction, we have created true puzzles since each reaction leads to a product whose characterization reveals something about theieaction. This is desirable for many reasons (4,5). Three questions are posed to the student. The first is the product of hydrohoration-oxidation of l-methyl-l-cyclohexene. The possible products are shown below:
The answer to this question establishes the anti-Markovnikov, syn regiospecificity of the reaction sequence. The second problem is the product of the same reaction with indene, that is, will 1-indanol or 2-indanol be formed? (This reaction is described tangentially hy Garrison (6) as part of a larger problem.)
The third problem is the hydroboration-oxidation of norbomene to yield exo- or endo-norborneol:
exo-
endo.
These reactions are run simultaneously in test tubes, at small scale (0.5-1.0 g), but not at true microscale. The standard 1M BH3 THF solution from Aldrich Chemical is used as the source of diborane. Only the dispensing of the dihorane solution and the quenching of the reaction must be done under the hood, so only limited hood space is required. Thus, hydroboration is now a technique suited for the mass organic lab.
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438
Journal of Chemical Education
Experimental This experiment was tested by the 200-student, large introductory organic lab at Princeton. The largest number of students working in the lab on one day was 55, under the direction of six TA's. In all cases, large (15- X 20-mm) clean, dry test tubes were used for reactions. The reaeents were used as received from Aldrich Chemical, exceptUfor the practical-grade indene, which was redistilled bv the technical s u ~ o o ret r o u ~before being dispensed. The indene and 1-metgyl-l&cfohexene are liquids, and 0.5-1.0 mL (5-9 mmol) is used. The norbornene is a waxy solid and is most easily dispensed in individual vials. The student weighs the vial. then transfers the solid to a test tube and weighs the vial again to get the weight by difference. The test tubes are then corked and olaced in ice bath. The diborane solution is stored under the hood and dispensed by a TA using a syringe, directly from the Aldrich Sure-Seal bottles. Compressed nitrogen gas in a line eouiooed with a bubbler and needle was used to eauilibrate the & pressure in the hottles as they became depleted. The test tubeswith olefin should be keot in the ice bath.since the reaction with the diborane is exothermic. The TA should wear gloves for this operation. Three TA's and the instructor dispensed diborane solution, and even on our busiest days there was no serious problem with students waiting. For the liquid olefins it is best to use about 5 mL of diborane solution for each milliliter of olefin. For the norbornene, approximately 5.5 mL of diborane solution is used for each gram of solid. These amounts provide about a 60% mole excess. The mixture is allowed to react at room temperature for an hour in a corked test tube (to exclude water and keep the THF odor under control). To ouench the reaction, the mixtures are aeain cooled. and H 2 0is-added very slowly,dropwise,workingunder the hood, to decompose the excess diborane. Hvdroaen aas should be evolved at this step. After 10-15 drops of water bas been added, then 1.4 mL of 3 M NaOH for each milliliter of liquid olefin, and 1mL of 3 M NaOH for each gram of norbornene is added. Then excess 30% Hz02 is added, using 2 mL for each milliliter of liquid olefin, and 1mL for each gram of norbornene. The temperature should not be allowed to rise above 40 OC for the norbornene mixture. Hydrogen peroxide will cause immediate and painful burns, and it is worth wearing disposable gloves for this operation. The test tubes are then warmed at 5 0 4 0 OC for 30 min to an hour, bv immersina in a warm water bath. It is important to remindstudents to-uncork the test tubes before warming, or they will be heating a closed system. If students run out of time, the reaction will work satisfactorily if it is allowed to stand in the desk for a week. If students try this, they should come back after 24 h, after most of the gases have escaped, and cork the test tube, wrapping the exterior with Parafilm. If the solvent evaporates, a solid mass appears that is difficult to redissolve. There will tvoicallv be a two-ohase mixture at this noint. The alcohol iC;n theLpper laye; with the residual THF. (If the THF has evaporated, the student may add diethyl
.~ ~
ether.) Sodium chloride is added to the water layer to dry the organic layer, which is removed with a dropper and saved. The water laver is extracted once aeain withether. and then . the etherealelayers combined andudried over M ~ S O ~he THF-ether lavers are then allowed to eva~orate.leavine crude products. (1) The cvclohexanol is an oil liauid. A small samnle of this is mad; into the 3,5-dinitrobenzoate derivative, and recwstallized from ethanol. The melting ooints of the derivatives are: l-methylcyclohexanol (128 -oc), (f)-trans-2methylcyclohexanol (114-115 OC), and (5)-cis-2-methylcyclohexanol(98-99 OC). (2) The indanol is frequently contaminated with an oily polymer. If hexane is added, the indanol will dissolve at boiling, leaving the oil at the bottom or on the walls of the test tube. Then. the hexane solution can be noured awav from the oil, A d relatively pure crystals wiliform as tG hexane cools. After another recrystallization, long needleshaped crystals form. The possible substances and their melting points are l-indanol(54 OC for (*). 72 O C for R or S ) and 2-indano1(6E-71 OC). We typically also give the students the melting points of 4indanol(40 OC) and 5-indanol(51-53 OC) to give additional possibilities. (3) The norborneol is almost impossible to crystallize. The crude material is dissolved in a little methylene chloride. dried. and then run throueh a 3-cm column- of ~- silicn.A ~ N in O a~P a s t e pipet ~ to remove any stray olefinic impurity. The eluted solution is allowed to evaporate somewhat and a few drops put on a salt plate. The IR spectra for the exo and endo isomers are strikingly different in the fingerprint region. Hoth spectra are in the Aldrich lndex of IR Spectra. A number of difficulties with the experiment were seen by a minoritv of students. The oreci~itationof a white solid when the borane solution is added br during the hydroboration step indicated the presence of some impurity (acetone or water), but it is a simple matter to restart the reaction mixture. The norborneol is verv volatile. If it is left in an open beaker overnight, it will disappear by sublimation. Many students had difficultv with the3.5-dinitrohenzoate derivative, and in the future-we will replace this with IR characterization (see below) even though the difference in IR spectra between cis- and trans-2-methylcyclohexanolis fairly subtle. Because this was the first small-scale experiment of the semester, there were the difficulties doing the recrystallization. The whole experiment takes about three 3h periods for the average student.
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pure 3.5-dinitrobenzoate derivatives of the methylcyclohexanol, but, of those, most were able to identify their products as the somewhat impure derivative of the trans-2-methylcyclohexanol. Typically students reported melting temperatures as low as 105 OC, but, since the melting range was wide, they either recrystallized or rounded up. Yield was not measured in this exoeriment. since. to solve problems of this sort, purity is essential, andbeginning students seem unable to concentrate on both vield and puritv at the same time. However, the sample size in itself caused no special problems. A separate experiment in which the methylcyclohexanol was worked up in the same way as the norbomeol gave an IR that was definitive for trans-2-methylcyclohexanol.The spectrum showed some stray peaks, notably in the ketone reeion. but the fineemrint region was definitive. For this to - . work, the sample must he scrupulously dry, and, since the alcohol is volatile, the spectrum should be obtained reasonably promptly. The spectra of both cis and trans isomers are in the newer editions of the Aldrich lndex Soectra. Authentic samples are also commercially available.~hisprocedure will be used with students in future years. We deliberately tried "spilling" a milliliter or two of the diborane solution, or of the olefindiborane mixture, in the hood. There was no spontaneous ignition, and a white residue was left behind (presumably boric acid). The reaction therefore appears t o b e at least as safe as the Grignard reaction and other standard student lab procedures. Naturally, however, the usual level of instructor supervision is necessary.
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Conclusion
All the problems encountered in this experiment were at the workup stage. The hydroboration-oxidation went well for the vast maiority . . of students, and there were no fires or other incidents. It is also clear that inert atmosphere techniques are an unnecessary refinement in student work. This experiment used hoods only intermittently, at three steps: the initial dispensing of the diborane solution, the quenching step (to get rid of the Hz gas safely), and perhaps for the evaporation of the solvents. Thus, a large group can get by auite easilv with onlv a few hoods. This experiment also poses real questions for the student ta solve. The reeiochemistrv of the hvdroboration-oxidation sequence is demonstrated ;n the fir& reaction, and the results for the other reactions are not easily predicted. This experiment thus goes beyond the cookbook stage. The student puts a question to nature and receives an answer, and this is what real organic chemistry is about.
Results
Acknowledgment
Virtually all the students correctly identified the norborneol as the exo isomer. The problems based on melting point were less successful. since the students re~ortedlaree melting point ranges and low values. The indanol melting point was tvuicallv renorted around 65-67 OC rather than the 70 OC expectedfor 5-indanol. Those students who did not exert care in recrystallization got large melting ranges and low melting temperature (often as low as 40 OC) and therefore incorrectly identified the products. Only about half the students managed to get reasonably
The help of Henry Gingrich, the TA's of our basic organic lab, and Jerri James in technical support is gratefully acknowledged.
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1. Broun, H . C . Hydroborofion: Benjamin: New York,1962. G.W.:Hedgecmk, H.C . J Chem.Edur. 1957.52.745, 3. M a w D. W.;Pike,R. M.; Buther, S. S. Microseole Orgonk Lobarotory: widey: New 2. Kabslb.
York. 19%. 4. P ~ c L ~ & ~ J. ; MChemEduc. . 1985,62,874
5. Pickering, M.J. Chem. Educ. 1988,65,10. 6. Garrison. J.A. J. Chem.Educ.
1970,47,33W.
Volume 67
Number 5
May 1990
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