<p> Ch. 7 Substitution Reactions of Akyl Halides</p><p> substitution - RCH2CH2Y + X - RCH2CH2X + Y elimination - RHC CH2 + HY + X</p><p>I. Substitution Reactions</p><p>H O CH + Cl H O CH3 Cl 3</p><p>Nucleophile (Nu:): nucleus- loving</p><p>- e- rich </p><p> o (lone pair or π bond): weak Nu:</p><p> o can also have negative (-) charge: strong Nu:-</p><p>- seeks e- deficient species (δ+ or +)</p><p>Electrophile (E+): electron-loving</p><p>- e- poor (δ+ or +)</p><p>- seeks e- rich species</p><p>Leaving group (LG)</p><p>- group leaves and take 2 e- with it</p><p>- stable groups (weak bases) make good LG’s (e.g Cl-, Br-, I-)</p><p>General reaction: R – LG + Nu:  R – Nu + LG:</p><p>Possible mechanism?</p><p>*simultaneous * stepwise</p><p>R Nu: Nu R LG R LG carbocation SN2 SN1</p><p>SN2: Substitution Nucleophilic Biomolecular Reaction CHM 201 Dang 1 H C O + CH Cl E.g 3 3</p><p>Mechanism: one step </p><p>H H H</p><p>C CH3O C Cl C H3C O Cl H H H CO H H H 3 H + Cl-</p><p>*Backside attack Inversion of stereochemistry Increasing steric hindrance, decreasing rate</p><p>- SN2 Kinetic Rate = k [CH3O ] [CH3Cl]</p><p> Rate depends on both Nu:- and E+</p><p> Biomolecular rxn </p><p>Sterics affect rate of SN2</p><p>R Group Abbreviation Carbon type Relative rate MeX H3C X = Cl, Br, I Methyl 30</p><p>EtX 1o CH3CH2 1 H3C o C 2 H IPrX 0.02 H3C</p><p>CH3 TBuX 3o 0.04 H3C C</p><p>CH3</p><p>Relative stabilities of alkyl halides</p><p>(Fastest) Methyl > 1o > 2o > 3o (NR)</p><p>CHM 201 Dang 2 SN2 E vs. POR diagram</p><p>E reactant product + LG</p><p>POR</p><p>*if LG is too sterically hindered (3o)</p><p>- T.S is high energy</p><p>- Ea is high</p><p>- reaction is too slow (N/R)</p><p>Nu H Cl H</p><p>Nu:</p><p>LG is wedge</p><p>SN2 summary</p><p> 1 – step mechanism</p><p> Backside attack</p><p> inversion of stereochemistry</p><p> requires an unhindered LG and good Nu: (-charge or NH3)</p><p> Rate (RX) Methyl > 1o > 2o > 3o (slowest or NR)</p><p>E.g Predict the major product</p><p>CHM 201 Dang 3 NH3</p><p>Cl</p><p>I NaOH</p><p>CH3 NaCN C CH2CH3 Br CH3</p><p>SN1 Substitution Nucleophilic Unimolecular </p><p>CH3 O + Cl H2O + H3C C Cl H O CCH3</p><p>Nu: CH3 E</p><p>Could this be an SN2 ?</p><p>SN1 mechanism (2 key steps but usually 3 steps) (9.4)</p><p>1. Loss of LG </p><p>CHM 201 Dang 4 SLOW CH CH3 3 rate determining step + Cl C break bond --> endothermic H3C Cl requires E H3C CH3 CH3 trigonal planar carbocation</p><p>2. Addition of Nu:</p><p>CH 3 CH3 H H O H H3C C O H3C CH3 O H FAST H CH3 H exothermic bond formed</p><p>CH3</p><p>H3C C O H</p><p>CH3</p><p>SN1 Kinetic </p><p>Rate = k [tBuCl]</p><p> Rate determining step involves E+ only</p><p> Rate is independent of [Nu:]</p><p> A more stable carbocation will be formed faster</p><p> o o o Rate of SN1: benzylic/allylic > 3 > 2 >> 1 , methyl</p><p>Stereochemistry of SN1</p><p>SN1 result in racemization </p><p>CHM 201 Dang 5 CH3 from the front CH3 Nu: Nu H3CH2C CH3 H X H CH C 1:1 3 2 CH3 enantiomers</p><p>(S) from Nu the back CH2CH3</p><p>SN1 Summary</p><p> Stepwise mechanism via carbocation</p><p> More stable carbocation, faster reaction</p><p> Racemization occurs</p><p> Requires no strong Nu (usually with solvent: H2O or ROH)</p><p>E.g Predict the major product(s)</p><p>CH3 OH</p><p>Br</p><p>CH3</p><p>CH3 C OH I H</p><p>Summary</p><p>SN2 SN1</p><p>Alkyl halides (R-X) Methyl, 1o or 2o 2o, 3o</p><p>CHM 201 Dang 6 Nucleophile (Nu) Strong Nu: or Nu:- Weak Nu:</p><p>Mechanism 1 step 2 steps</p><p>Reaction Rate = k [R-X] [Nu:-] = k [R-X]</p><p>Products Typically 1 2 products (enantiomers if chiral)</p><p>Note: If 2o R-X, then the rxn depends on the type of Nu: used</p><p>CHM 201 Dang 7</p>