Molecular Model Kit Tutorial: How to Use YourModel Kit toDetermineStereochemistryinSN2ReactionMechanisms

BasedonaChemistry14Dextracreditproject,Fall2008

SN2reactionsinvolveabimolecularnucleophilicsubstitutionatansp3carbonwherethebondbetweenthe carbon and the leaving group is broken and a bond between the carbon and the nucleophile isformed.Duetotheelectrondensityoftheleavinggroup,thenucleophile“attacks”thecarbonfromits

“backside,” to formabondwith theσ*orbital that is available. The incomingelectrondensityof thenucleophile also causes the substituents bonded to the carbon to undergo inversion, a complete“umbrellaflip”ofstereochemistry.

Here isanexampleofanSN2 reaction.Abovewehavea cyclohexane ringwithamethylgroupandachlorineatombondedtothering.

Above,wecanseethatthechlorineisfacingawayfromus(red)andthehydrogentowardsus.

Hereisaviewofthemoleculeinchairformation,whichisfavoredduetostabilityandcanmakeiteasiertovisualizeanddrawthetransitionstateofthereaction.

The nucleophile, iodide, approaches from the opposite side of the leaving group, chloride, as can bevisualized by your molecular model. The solvent acetone is ideal for this reaction due to its lowerpolarity,whichstabilizesthepartialchargesofthetransitionstatemorethantheformalchargesofthe

reactantsandaproticity,whichalleviatesthehindranceofhydrogenbondingwiththenucleophile.

Thetransitionstateofthereaction isthehighestenergystructureoftheconcertedmechanism(bondscissionandformationoccurringinthesamestep).Inthetransitionstate,theC‐LGbondbeingbrokenand the C‐Nu: bond being formed simultaneously are drawn as a straight axis, and are dashed lines,

indicatingtheirpartialscissionandformation.Theiodideandchloridebothhaveδ‐charges,theleavinggroup (Cl) becoming more negative as it accepts the electron pair from the C‐LG bond, and thenucleophile(I‐)partiallylosingitsnegativechargeasitdonatesanelectronpairtoformabondwiththe

carbon.

Duetotheelectrondensityofthenucleophile,thehydrogenatomofourmodelisrepelled,andmovesto replace the orientation previously held by the leaving group, which can be seen departing in theimageabove.

Thefinalresultofthisistheinversionofstereochemistryatthecarbon.Inotherwords,RisflippedtoSstereochemistryandviceversa.

Here we can clearly see that inversion of stereochemistry has taken place, when compared to ouroriginalstructure.Iodineisnowfacingtowardsus,andhydrogenawayfromus.Yay!

Here isanotherexample:The leavinggroupof thiscyclopentanemolecule ischlorine,whichbecomeschloride ion, and the nucleophile is CH3S

‐, which is good for this reaction because sulfur has a lowelectronegativity,andcannot formhydrogenbonds in theproticsolventmethanolaseasilydueto its

largeatomicradius.

The nucleophile bonds with the electrophile through backside attack, forming a straight axis in the

transitionstate,asdepictedabove.

TheC‐LGbondisbrokenandtheleavinggroupdepartsaschlorideion.

Aswecanseehere,CH3S‐hasreplacedthechlorine.

Hereisafinalexample.Seeifyoucanidentifytheleavinggroupandimaginewhatthetransitionstatewilllooklike!Black=carbonWhite=hydrogenBlue=iodine

Here is a good picture of our nucleophile. Can you identify where the nucleophile will “attack” thecarbon? (Hint: where is there an excess of electron density? Where is there a negative charge?)

Black=carbonRed=oxygenWhite=hydrogen

Due toanexcessof electrondensityon theoxygenwithonlyonebond, this iswhere thenuleophileattacksthecarbon.Thebondssimultaneouslyformingandbreakingagainformastraightaxis,whichcan

bedrawninthetransitionstate.

The leaving group (iodide) hasdeparted, anddue to theelectrondensity of thenucleophile, and themethylgrouphasshiftedtoreplacetheorientationoftheleavinggroup.

All done! As we can see, the stereochemistry at the carbon has been inverted, the methyl is nowpointingtowardsus,andthehydrogenawayfromus!

Tryotherexampleswithyourownmodelkit,itwillhelpyoutounderstandorganicchemistryinawhole

newlight!Havefun!