The Stereochemistry of Additions to trans-Anethole Lawrence McGaheyl Union College, Schenectady, NY 12308 We have designed a series of experiments exploring electrophilic additions to trons-anethole in which product composition and stereochemistry are estahlished by NMR spectroscopy. A basic experiment suitable for the introductory oreanic chemistrv lab is described. as well as modifications adapting the exeicise for advanced courses. hlost introductory organic chemistry texts state that bromine adds exclusively anti to simple alkenes. This result is asxibed to nucleophilic attack by Hr- upon an intermediate cyclic bromonium ion, which maintains the geometry of the startinaalkene. Our textbooks are usually silent about additions t i alkenes conjugated with an aromatic ring; indeed, electron-rich alkenyl benzenes yield significant amounts of the dibromide formed by syn addition ( I ) . Our experiments are presented to students as a mini "research project", which attemots t o answer these anestions: "Does bromine add exclnsivk~yanti to alkenes conjugated with electron-rich aromatic rines? If not. what is the stereochemistrv and composition of &e adduc&? What does the observed &ereoche& try suggest about the reaction mechanism?" In our basic experiment, trans-anethole is brominated with pyridiniurn bromide perbromide ("PyHBrs") in dichloromethane. Since the alkene is unsymmetrical and achiral, four stereoisomeric products are possible; these are the erythro and threo diastereomers and their respective enantiomers:
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limits PvHBra and Br? exhibit about the same oreference for anti addition t o trans:anetho~e.~ Identification of the products is also made more challenaing for advanced students. The chemical shift data for tKe two isomers are provided, but not assigned to either diastereomer; for 2 the shifts are 6.8-7.4,5.0,4.5,3.7, and 2.0 ppm,
andfor3,6.67.4,5.2,4.5,3.7,and1.7ppm(3).Thethreoand erythro diastereomers may be distinguished by their respective coupling constants between the vicinal hydrogens. In general, the magnitude of a coupling constant depends on the angle 6 between the two C-H bonds, the nature of the other substituents on the vicinal carbons, and the relative population of conformers. Compounds of the type Ar-CHXCHY-CH3 are known to have Jerythro > J t h r e o when X,Y = C1,CI or Br,Br; the coupling constants have also been related to the most populated conformer of each diastereomer (3,4). Fahey and Schneider observed J o b = 10 Hz for the erythro dibromide, and for the tbreo isomer, 5.4 Hz (3), while we found Jvalues of 10 and 6 Hz, respectively. These results show that addition of bromine to transanethole occurs with antiselectivity: Students can arrive a t a satisfactory explanation for formation of the syn adduct if some additional data are provided. Bromination of trans-lphenylpropene gives 81-89% of the erythro dibromide, while the ervtbro isomer is obtained exclusivelv in bromination of trans~l-(3,5-di(~~3)-~hen~l~ro~ene (2,i).Thus, preference for anti addition decreasesas suhstituents make the aryl ring a better donor of electrons. Fahey and Schneider (3) suggested that bromination of anethole may occur via the cyclic bromonium ion (4) or a nonbridged,benzylic cation (5) in which charge is stabilized by the metboxy oxygen. Bromide ion then can attack cation 5 syn or anti to the bromine already added.
2
3 An = para-CH30C6Ha erythro, lR2S/lS2R threo, 1S2Sl 1R2R
The anethole dihromides 2 and 3 have similar NMR spectra, but the doublet resonances of the benzylic and methyl hydrogens of the isomers are cleanly separ&ed:
4
5
The final exoeriment in theadvanced exercise centers o n a reaction unfamiliar to most students, the addition of 2,4dinitrohenrenesulfenvl chloride ("ArSCI", to an alkene such as trans-anethole:
6, ppm fromTMS: erythro threo a: 5.0 5.2 c: 2.0 1.7
a b c Thus. once students obtain or are eiven the NMR spectrum of the crude products, the diastereomers in the mixture can be identified by the chemical shift data, and their relative amounts, hy integration over the 2- and 5-ppm regions. In our hands, bromination of anethole with PyHBra gave 73 i fi% ervthro-dihromide. 2. In ;he more advanced version of the experiment, students comoare the stereochemistrv of haloeenation bv PvHBrl a n d L ~ r 2With . molecular biomine we obtained-65-i 5% erythro-anethole dihromide. Thus, within experimental 554
Journal of Chemical Education
Ao2
'
erythro, 1R2ShS2R
Student coauthors: Ray Ashley, Rita Clement, John Cummings. Debbie Hermance. Ed Lln, Robin Miller. Susan Rocker, AR Spalding. Dorothy Taylor, and Ben Wolf. Amine trihalides have been found to add nearly stereospecifically to CIS and transl-phenylpropene, but a satisfactoryexplanation for this observation is lacking (3.
I
threo, lS2SllR2R Based upon the information gained from t h e N M R study of the anethole dibromides and t h e spectrum of t h e crude products of reaction 2, students are invited to propose answers t o these questions: "What is t h e regiochemistry of addition 2? Is t h e mode of addition syn or anti? Is there a bridged intermediate?" Between 1 and 6 ppm t h e N M R spectrum of t h e mixture of adducts 6 a n d 7 is virtually identical to t h a t of t h e anethole d i b r ~ m i d e s When .~ encouraged t o reason by analogy, students can decipher this N M R spectrum by comparing it t o t h a t of 2 and 3. 6, ppm from TMS: erythro threo 5.05 a: 4.95 An-CHH-CHs c: 1.65 1.4 a b c
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I n refluxing CCL we found addition 2 t o he highly stereoselective, giving 85% of the erythro adduct, 6; a t room temperature 6 is 90% or more of the product. Schmid and NowIan reported t h a t t h e erythro adduct accounted for 95% of t h e product when ArSCl added to trans-anethole in 1,1,2,2tetrachloroethane a t 30 OC. Thev also discovered t h a t Dure 6 is isomerized in refluxing benzene t o a mixture conLining 64% 6 and 36% 7, which would account for our results (6). T h e regiochemistry of this addition reaction can be rationalized fairly easily: the electron-withdrawing, deactivated aryl ring polarizes the S-C1 bond, so t h a t sulfur leads t h e Markovnikov addition. Because t h e erythro adduct is t h e major product obtained from a trans-dkene, anti addition must occur. Comparison of reaction 2 with 1 leads t o the conclusion t h a t this addition occurs through a bridged intermediate, 8; indeed, t h e higher stereoselectivity observed in reaction 2 suggests sulfur may be a better bridging atom than bromine.
Experlmental Procedures Bromination of Anethole with Pyridinium Bromide Perbromide (2) A5O-mLflask isrharged with 0.74 g ( 5 mmolJ Irons-anetholeand 15 ml. CH.CI, rwark in hood: roxir uoporr; puwihlp c a r e t n u g m ) and immersed in an rce bath. When the solutim has cooled to about 2 'C. small oortions of finelv oulverized nvridinium bromide nerbromide (1.i3-1.86 e if 90%;ure. 5 mmbi:. corrosioe to skiniare ,~ a d d ~ dso that the mi&al temperature ra held at 0-5 OC; abou; 1520 min are required. Idmlly. the rractim mixture should be stirred ~
~
~~
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magnetically. Once all the PyHBr. has been added, the mixture is stirred a further 5-10 mm if the orange color prrarsts Water (16 mL) is added to the flask and gently mired with the CH2Clzto dissolve the pyridinium bromide. The liquids are transferred to a small separatory funnel. and the h e r urganlc i~ phase retained, it is washed successivel) uuh 10 mL0.2 M sodium throsulfate rNa-S. D .,.).. 10 mL 104 HCI, and 10 mL water. The CH CI, solution is dried over anhvdrous maenesium sulfate ( ~ ..e ~ ~..d. ) . - f i l l tered, and the solvent remv\rd m a ru;ao evaporator. ~lternatively, theCHC1. may bedrstllled at ntmosphrricd~rtillationusing a water hath rtempcrature
