SN2 Ionic Substitution Reactions Chem 14D Winter 2005 SN2 Ionic Substitution Reactions Substitution can occur in organic compounds that have an electronegative atom or group bonded to an sp3 hybridized carbon S stands for Substitution General Mechanism Nuc Nucleophile R LG Nuc R Nuc LG LG Leaving Group Nucleophile enters as leaving group leaves N stands for Nucleophilic 2 stands for Bimolecular Rate k alkyl halide nucleophile 2nd order reaction Rate k CH3Cl HO for the reaction above Concerted reaction because nucleophile attacks and leaving group leaves simultaneously No intermediates are formed More often molecules collide the faster the reaction Gedunker experiment Example 1 Cars on a freeway The more cars the Kinetics factors that effect reaction rate more accidents 2 Recall throwing molecule balls in HO CH3Cl reaction class collision Chance of collision increases as concentration increases 2 x HO 2 x rate linear relationship CH3O 10 rate 10 Measured rate is related to the mechanism Rate HO CH3O Kinetics can disprove a mechanism Rate k HO CH3O Caution No Trimolecular collisions A B C D Audi Benz More likely Moment of Collision HO CH3 Cl Getting closer Partial bond lone pair beginning to become O C bond Cadillac collision or Audi Benz Cadillac collide altogether HOCH3 CL Lifetime is 10 15s femto second doesn t last very long Transition state studied by Zewail H Bond getting weaker further Cl starting to leave HO C Cl Halogens are more electronegative than H H carbon so they have a larger share of the electrons This polar C halogen bond causes alkyl halides to undergo substitution and elimination reactions Trigonal bipyramidal is the best way to arrange 5 atoms around a central atom Uh oh pentavalent carbon No central C still has 8 e so the rule is not violated In Backside Attack the nucleophile attacks from the backside of the carbon leaving group bond due to o Electrostatics Negative charges on nucleophile and leaving group repel o Sterics steric hindrance Crowding leaving group blocks approach of nucleophile to the front o Hughes Ingold noticed that the stereocenter will change won t happen in front side attack front Retention of Stereochemistry back Inversion of Stereochemistry 99 S R or R S but not always true See virtually 100 Inversion of stereochemistry also called a Walden inversion this is good and bad o When a chiral alkyl halide undergoes an SN2 reaction only one substitution product is formed Bruice p 366 o Good says backside attack is an accurate model o Bad questions the 2 reasons above There must be another factor Real reason for backside attack Greatest stabilization occurs when orbitals overlap end to end The overlap between the orbital containing the pair of donated e by the nucleophile and the carbon leaving group antibonding orbital is maximized Bruice p 364 Practice Problem from Thinkbook 4 Provide the organic product s of this reaction If more than one product is formed indicate which product if any is the major one If no reaction occurs write NR Answer SN2 Energetics o G H T S Gibbs free energy G energy of whole system Enthalpy H differences energy due to bond changes usually tens of kcal mol Entropy S freedom of the system molecules like to be floppy or more molecules entropy is a small factor perhaps only one cal mol and even when multiplied by T temperature in Kelvin it is still smaller than H o At reasonable temperatures G H Products and reactants aren t the only thing that matter the transition state has its own energy really important o Energy Profile CH3Cl HO Energy G TS can go forward or backward matters because need to get over this hill for reaction to occur Example breakfast Bombshelter If you have enough energy you will leave the classroom and eat breakfast G Reaction Coordinate CH3OH Cl G is negative so it wants to spontaneously go to products Transition state TS the highest energy point in the energy reaction profile due to partial bonds Energy of Activation G Energy needed to reach transition state controls the rate of a reaction 2 partial bonds don t make up for 1 full bond 2 partial bonds in is energetically expensive Breakfast metaphor Rate of room emptying is a function of 1 Energy of the students 2 Height of the hill of stairs leading up to the doors G influences the position of the equilibrium but not the rate G influences rate of reaction but not equilibrium Example Cells amino acids Can t wait for years for a reaction to complete so enzymes make the TS more stable This G so reactions go faster A0 constant as fast as reaction can possibly go G energy of activation height of hill R gas constant T temperature in Kelvin Arrhenius Equation figured out before k A0e G RT rate Rate and G are inverses so G rate Exponential factor small changes in G can lead to large rate changes Temperature temp rate Spontaneity If G 0 spontaneous reaction S O2 SO2 H 0 0 72 kcal mol Very spontaneous thermodynamically but in terms of rate kinetics it s extremely slow Block of sulfur isn t going to SO2 If you heat block of sulfur it will convert to SO2 Like a match heating initiates a rxn There are lots of hills in the rxn that convert sulfur G of one of the hills is probably very large So if G 0 then thermodynamically spontaneous If G 25kcal mol then kinetically spontaneous Practice Problem from Thinkbook 5 Consider this reaction a Write the rate expression for this reaction b Write a curved arrow mechanism for this reaction c Draw the transition state Answer SN2 Variables Nucleophile how does the nucleophile influence the rate TS R Nuc C LG R R Role of nucleophile in partial bonds Share electrons it s making the partial bond The more complete the bond is the more stable the TS The single most important factor which controls the nucleophilicity or basicity of any molecule or ion is the ability desire or driving force to share an e pair Nucleophilicity ability to share e pairs with electrophile Basicity ability to share e pair with H Stronger bases are better nucleophiles When comparing molecules with attacking atoms that vary greatly in size the polarizability ability to skew the electron cloud of the atom and the reaction conditions determine whether the greater polarizability of the larger atoms makes up for their decreased basicity The relationship between basicity and nucleophilicity becomes inverted when the reaction is carried out in a protic solvent the solvent molecules have a hydrogen bonded to a nitrogen or oxygen This will be explained in the