Norbert M. Zaczek, James C. Ruff, Albert H. Jackewitz, and David F. Roswell
Loyola College Baltimore, Maryland 21210
1 I
Migratory Aptitudes A n organic chemistry experiment
Molecular rearrangements are discussed in most beginuing organic chemistry courses. One of the more common rearrangements considered is the rearrangement of pinacol to pinacolone, eqn. (1). In the Pinacol Rearrangement
the molecule may have t,wo or more groups which have, geometrically, approximately equal opportunity to migrate, although one is usually more favored electronically. The theory of the relative migratory aptitudes of the various groups is usually discussed in the classroom using the rearrangement of symmetrical pinacols as illustrated in eqn. (2). R = substituted phenyl
However, the only examples of this rearrangement found in laboratory manuals involve either pinacol to pinacolone or benzopinacol to benzopinacolone. In both cases the student can observe that rearrangement occurs but neither case illustrates migratory aptitude. Migratory aptitudes for a number of substituted phenyl groups, aith respect to phenyl, have been measured by a number of wor1cers.l Since the 4-tolyl and 4-chlorophenyl groups show migratory aptitudes (with respect to phenyl) of 15.7 and 0.7, respectively, we decided to develop a laboratoly experiment using 4,4'-dimethylbenzopinacol and 4,4'-dichlorobenzopinacol which would illustrate clearly the concept of migratory aptitude. The reactions involved in this experiment are shown by the follo~vingequations, where R can be either 4chlorophenyl or Ctolyl depending on which substituted benzophenone is used.
0 Ph
The 4-substituted benzophenones used as starting materials in eqn. (3) are both commercially available2 but they may be prepared by a Friedel-Crafts reaction. We have had students synthesize 4-methylbenzophenone since this additional synthesis is helpful in developing student techniques (see Experimental section). The reactions illustrated in eqns. (4) and (5) are carried out in such a way as to prevent selective loss of one of the isomeric pinacolones. When the rearmngement is completed, the acetic acid is removed (in uacuo) and the product mixture completely dissolved in dimethyl sulfoxide. This solution is poured into a potassium t-butoxide-dimethyl sulfoxide slurry to effect the cleavage illustrated in eqn. (5). At the end of the required reaction time the mixture is poured into water and the hydrocarbon products extracted and d i ~ c a r d e d . ~ After acidification and extraction the mixture of acids is analyzed. Starting with 4-methylbenzophenone we have performed the reactions illustrated in eqns. (3), (4), and (5) and analyzed the resulting mixture of benzoic and 4toluic acids in three ways: first, by gas chromatography of the acid mixture on a Chromosorb 101 column; second, by gas chromatography, after conversions of the acid mixture to the corresponding methyl esters with methanolic HCl (see Experimental) on a 20y0 QF-l column; and third by nmr.4 The results are shoxn in Table 1. Standard acid mixtures were used to check all the methods of analysis. In all cases the experimental results were in agreement, with the accuracy indicated For a wllection of this data, see Collins (1).
J. T. Baker Chemical Co. Although we made no attempts to do 80 it should be possible to analyze the mixture of hydrocarbons as well as, or instead of, the mixture of acids. 'Another method of analysis was attempted, i.e., titration, to determine an equivalent weight of the product acid mixture; however, the results obtained were extremely inaccurate. I t proved impossible to remove traces of other (presumably inorganic) acids which caused these inaccuracies.
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Table 1. Results of Analysis of the Mixture of Benzoic and 4-Toluic Acids Obtained from Cleavage of the Rearrangement Products from 4,4'-Dimethylbenzopinacol
Table 2. Results of Analysis of the Mixture of Benzoic and 4-Chlorobenzoic Acids Obtained from Cleavage of the Rearrangement Products from 4.4'-Dichlorobenzopinacol
-Resultsa (mole %)Benzoic 4Taluic acid aoid Gas chromatography of the acid mixture Gas chroms.tography of the resulting ester mixture Nmr of the acid mixture Literatureb
89
11
89 88 94
11 12 6
Method Gas chromatography of the acid
Benaoie acid
benaoic acid
43
57
*I%. T h e literature ( 2 ) method involved oxidation of the acid mixture and isolation of terephthalic acid. I t should also he pointed out that their rearrangement was performed using acetyl chloride in acetic acid.
+If';., Tklritwnture (3~merhodiovolvrddoiogthr rr:trrnligement i n nretyl d>lmde, clcnvina, the rcsultinp; pinndc,nes in alcoholr~. oorn.sium lrwdn,xldc, and isrh~iuga i d n c ~ ~ l i irhr ! . ~4-vhlwobenzoic acidproducd.
in Table 1. Both acids (and their corresponding esters) were shown to give a linear thermal conductivity detector response. For the nmr analysis the ratio of the integral of methyl hydrogen to total aromatic hydrogen absorption was plotted against mole percent toluic acid in the standard mixtures and the mole percent toluic acid from the unlmoxn mixture was then o h r : ~ i n e dd i r c r ~ l yfmm t h i i g r a p l ~ . n t rh?vc ~ ~ i elikewise Stnrtin? w i t l ~I - r h l o r ~ b c n z i ~ ~ ~ h ~w carried out the reactions illustrated in eqns. (3), (4), and ( 5 ) and analyzed the resulting mixture of benzoic and Pchlorobenzoic acids. I n this case nmr analysis is not possible.' The results are shorn in Table 2. In the Cmethyl series the agreement between the analysis of the acids and their esters is excellent; in the Cchloro series the agreement is reasonable. Here again the analytical methods were checked with standard acid mixtures. We have found that this set of reactions and analysis illustrates to students not only a rearrangement reaction but also reinforces the concept of migratory aptitude discussed in the classroom. It is helpful to allow half the class to start with 4-methylbenzophenone and the other half with 4-chlorobenzophenone. At the end of the experiments the students can compare results.
crystallisation of hoth crops from 80% ethanol yields 4.2 g (0.021 mole, 43%) of white needles, mp 5758°C. Lit. mp 59% . .
-
Experimental Preparatin of 4-Methylbenzophenone. Into s 100-ml roundbottom flask, place 7.0 g (0.052 mole) of anhydrous AICb end 30 ml (0.282 mole) of toluene. Through a. condemer, add dropwise, while shaking, 6.0 ml (0.052 mole) of bensoyl chloride. Reflux until no more HCI is evolved. Pour the warm mixture into a flmk containing 50 g of ice and 22 ml of cone. HCI. Swirl vigorously until the toluene layer turns to a yellow or orange color. Pour the contents of the flask into a. separatory funnel and remove the water layer. (If any solid remains in the mixture, filter before separation.) Wash the toluene layer successivelywith 10 ml of 5% NaOH and 10 ml of wster. Trsnsfer the toluene layer to a 50-ml roundhottom flask and remove the solvent by distillstion. When all the toluene has been distilled, drain the water from the condenser and begin collecting the methylbenmphenones in a 25-ml erlenmeyer flask when the temperature begins to rise very rapidly. The product should distill at 312-16°C. Crystallize the distillate by either seeding or scratching. Cool the crystals in ice. Vacuum filter and press the resulting cake to remove the 2-methylbenaophenone. Press the product between several sheets of filter paper to remove more oil. Dissolve the solid in 80% ethanol on a steam bath and seed when the solution reaches room temperature. Allow the product to crystallize slowly. A second crop is collected from the filtrate by heating, adding water, and seeding at room temperature. Allow the product to crystallize slowly. Slow re-
258 / Jourml of Chemical Educafion
b
(4).
Pwparatin of Diastereoisome& 4,$-Dimethylbni.opinaeo1. Into an 8-in. test tube, place 4.0 g (0.020 mole) of 4-methylhenzoph&none, 25 ml of isopropyl alcohol, 2 drops of glacial acetic acid snd heat to effect solution. Expose the solution to a sunlamp (G. E. 275 W) for three days. Cool the mixture in ice and vacuum filter. Add the yellow to white product to 50 ml of n-propyl alcohol and reflux until solution occurs. Add 10 ml of water and allow to crystallize slowly. The yield of white e: .(0.006 mole. 60%). amarohous solid. mD 162-4% was 2.4 Lit. &p 163-4T'(6)' Preparatin q" Diaste~eoisomerie 4,4'-Dichlorobenzopinaeol. Into an eight inch test tube, place 4.0 g (0.018 mole) of 4-chlorobenzophenone, 25 ml of isopropyl a.lwhol, 2 drops of glacial acetic acid and heat to effect solution. Expose the solution to a sunlamp (G. E. 275 W) for two days. Cool the mixtm-e in ice and vacuum filter. The crude yellow to white product is purified by slow crystallization from acetonewater to yield 2.85 g (0.007 mole, 71%) of white amorphous solid, mp 173-4'C (thoroughly dried). Lit. mp 1 6 8 T (dec.) (3); mp 1 7 9 T ( 6 ) ; mp 172-8°C (7). Rearrangement of 4,4'-Dimethylbenzopinacol. Into a 100;ml round-bottom flask, place 1.60 g (0.004 mole) of the 4,4'-dimethvlbenaopinawl, 15 ml of glacial acetic acid and enough 2% iodin; in acetic acid to give the solution a pale, orange color. Reflux the mixture for 10 min. If the solution decolorizes while refluxing, add enough 2% iodine to restore the color to pale yellow. Cool the solution and evaporate to dryness under reduced pressure. The residue is then treated with three 5 m l portions of seetic acid and evaporated to dryness under reduced pressure in each case. Rearrangement of 4,4'-Dichlmobenzopinaeol. The remangement is carried out usine. the above procedure with 1.74 g (0.004 mole) of 4,4'-dichlorohe&opinilcal. Cleavage of the Mizture of Pinaeolones f ~ m 44'-Dimethylbenmpinacol. To the mixture of pinacolones, add 10 ml of dimethyl sulfoxide, warm to effect solution and cool to room temperature. In another 100-ml flssk, add 4.0 g (0.036 mole) of potassium t-butoxide to 0.385 ml (0.021 mole) of wster in 10 ml of dimethyl sulfoxide. Add the solution of pinscolones to this slurry snd swirl the resultant intensely colored mixture for 2 min. Add 50 ml cold water. Extract the white slurry with two 20-ml portions of ether. Discard the ether extracts. Acidify the aqueous solution to pH-1 with cone. HCI and extract with three 15-ml portion? of ether. Extract the combined ether with two 1 0 d portions of water and then with 10 ml of saturated sodium chloride solution. Dry the ether solution with anhydrous magnesium sulfate and evaporate to dryness under reduced pressure and proceed with the analysis. Cleavage of the Mizture of Pinacolmes f r o m 4,4'-Dichlorobenzopinaeol. The cleavage is cltrried out using the above procedure. Analus&. The acid mixture resulting from the cleavage reaction is dissolved in a minimum amount of acetone and injected onto & 4-ft Chromosorb 101 column. The column temperature is held a t 250°C (for the separation of hensoic and toluic acids), or 260°C (for the separation of benzoic and 4chlorohenzoie acids). In hoth cases the flow rate is 55 ml of heliumlmin, and the henaaic acid wmes off the column initially.
The acetone is then evaporated (in vanro), 15 ml of 3% methanolic-HCI is added and the mixture refluxed for 1.5 hr. The condenser is then removed and heating continued to nem dryness. A portion of the remaining solution is injected into a. &ft, 20% QF-1 on Gas Chrom-Q column. Column temperatures between 105 and UO . "C and a. flow rate of 25 ml of heliumhin give good separations in both cases. Methyl benzoate comes off the column. in either case. initiallv. For analysis by'nmr thk acid mixture is dissolved completely in the minimum amount of deuteroehloroform containing 1% tetramethyl silane, the spectrum recorded and integrated. The ratio of the total methyl integral to the total interral is obtained, and, using s graph~ofratios versus percent toluii acid (from standard acid mixtures), the percent toluic acid is calculated.
Acknbwledgment
The authors wish to thank the Division of Chemical Education of the American Chemical Society for a grant under the DuPont Small Grants Program. The authors gratefully acknowledge from ~~~~l~ College in the form of research fellowships. L~~~~~~~~~ cited
,.-"-~
(1) C o ~ ~ mC. s .J., Quort. Rm.. 14, 357 (1960). (2) B*CHM*N. W. E.. A N D MOSER,F. H.. J. A ~ B I Cham. . S.C.. 54, 1124 ,"'*I.
p. J,, R.,. T , ~ .chim.. 26, 253 (1907). (4) V O N AUWERB.K..A N D STRODTER, P., Bm.. so, 533 (1926). (5) HATT.H.H..J. Chen. SOE.,1630 (1929). ( 0 ) C o ~ e a W. , D., Ree. Tlao. Chim., 38, 115 (1919). (3) M....O..,
M.,AND BICRIANN, W. E., J. Amsr. Chsn. Soc., 49. 250 (7) GOMBERO. (1927).
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