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Chapter 6 al (not complete)

Chapter 6 al (not complete) - Chapter 6 Ionic Reac0ons...

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Unformatted text preview: Chapter 6 Ionic Reac0ons ­ Nucleophilic Subs0tu0on and Elimina0on Reac0ons of Alkyl Halides 1 Polarity •  Alkyl halides (C sp3 hybridized bound to a halogen) are typically polarized towards the halogen, making the carbon atom it is aIached to electron deficient (δ+) •  Carbon ­halogen bonds become less polar, but longer and weaker going down the periodic table 2 Naming •  Vinyl group is CH2=CH ­ •  Vinylic halides are halides bound to an sp2 carbon atom 3 Nucleophilic Subs0tu0on Reac0ons •  A nucleophile replaces a leaving group (bound to an electrophile) •  Nucleophilic subs0tu0on oQen occurs with the leaving group as a halogen (but this is not always the case!) 4 Nucleophiles •  Nucleophile (posi0ve loving): Reagents which seek a posi0ve center, have a lone pair of electrons which can form a bond •  OQen aIack electrophiles in chemical reac0ons •  What makes a GOOD nucleophile? •  Lone pair of electrons (usually charged), but is s0ll quite reac0ve and capable of making a stable new bond •  Isn’t too reac0ve, this will oQen lead it to act like a base instead of a Nucleophile 5 Examples 6 Leaving Groups •  Leaving Group: A group which is capable of accep0ng an electron pair (by heteroly0c bond cleavage) and leaving •  What makes a GOOD Leaving Group? •  Easily accept a pair of electrons and leave on it’s own as a STABLE species (the more stable it is when it leaves, the beIer the LG) •  Forms a weak bond to carbon (easier to break) •  Electron deficient (so it becomes more stable when it leaves) 7 Leaving Groups Cont •  A LG can leave as an anion •  Or a LG can leave to form a neutral species 8 Kine0cs of an SN2 •  The ini0al rate of the following reac0on is found to be directly propor0onal to the ini0al concentra0ons of both methyl chloride and hydroxide 3 •  SN2 reac0on: subs0tu0on, nucleophilic, 2nd order (bimolecular, the rate depends on two things) 9 •  SN2 mechanism occurs in ONE STEP Mechanism of the SN2 Reac0on –  Nucleophile aIacks electrophile and kicks out leaving group •  Proceeds through a TRANSITION STATE (square brackets) •  Transi0on state: VERY short lived species that cannot be isolated (usually has dashed lines) 10 Mechanism of the SN2 Reac0on •  As there is only one step, it is the Rate Limi0ng Step (slowest step of a reac0on) and both the nucleophile and reactant (Electrophile/LeavingGroup) are involved, hence the RATE depends on both the Nu and E/LG 11 Mechanism Cont •  Note the direc0on of Nu aIack –  Backside aIack results in INVERSION of the carbon atoms configura0on –  This really maIers for stereochemistry!!! •  Because bond forma0on and breakage happen simultaneously (one step) this is known as a concerted reac0on 12 Transi0on State Theory: Free Energy Diagrams •  Exergonic reac0on: nega0ve ΔGo (products favored) •  Endergonic reac0on: posi0ve ΔGo (products disfavored) • Example: Reac0on of chloromethane with hydroxide HUGE!! It’s not really an equilibrium 13 Free Energy Diagram for Typical Exergonic SN2 Reac9on •  Must go uphill first(ac0va0on energy), before downhill Monitors progress of reac9on (ex: R ­L bond distance) 14 Free Energy Diagram for Typical Endergonic SN2 Reac9on 15 Rela0onship with Temperature •  The higher the temperature, the faster the rate •  Near room temperature, a 10oC increase in temperature typically causes a doubling of the rate •  Higher temperatures cause more molecules to collide with enough energy to reach the transi0on state and react •  A reac0on with a lower will occur MUCH faster than a reac0on with a higher one Shaded area equals the number of collisions with energies greater than the free energy of activation (reaction occurs) 16 Actual Energy Diagram of Chloromethane with Hydroxide •  In general: A reac0on with a free energy of ac0va0on below 84 kJ/mol will occur readily at room temperature •  If > 84 kJ/mol then heat is required to make the reac0on occur at a reasonable rate EXP4: Substitution reactions that we reflux (require heat to react in a reasonable time) 17 Stereochemistry of SN2 •  Nucleophile approaches electrophiles from the back side (opposite to leaving group) •  This causes a change in configura0on (around the electrophile) NOTE: The reaction on this slide is a MECHANISM (curly arrows) 18 Stereochemistry of SN2 •  In cyclic compounds, SN2 converts a cis compound to trans 19 Stereochemistry •  Inversion at a chiral center by a SN2 mechanism oQen results in change of the R/S designa0on •  As long as the Nu and LG have the same priority then the R/S assignment switches 20 SN1 Reac0on •  SN1 reac0on: subs0tu0on, nucleophilic, 1st order (unimolecular, the rate depends on one thing) The rate of the reac0on DOES NOT depend on the nucleophile!! 21 Mechanism of SN1 NOTE: This third step is not necessary for an SN1 if the nucleophile is negatively charged 22 Carboca9on Reminder •  Because the 1st step of the SN1 mechanism involves carboca0on forma0on, only ter0ary and some0mes secondary substrates can react via SN1 23 Hyperconjuga9on •  Hyperconjuga0on: electron delocaliza0on from a filled bonding orbital to an adjacent unfilled orbital 24 Stability •  Any 0me a charge can be dispersed or delocalized, a system is stabilized 25 Stereochemistry of SN1 •  First step involves carboca0on forma0on (PLANAR INTERMEDIATE) •  This carboca0on can be aIacked from the front or back 26 Stereochemistry •  SN1 reac0on at a chiral center results in a racemic mixture of products 27 Example Mechanism with Cyclohexane Br H2O 28 Solvolysis •  Solvolysis: solvent is also the reagent •  For SN1: Solvolysis is where the solvent acts as a nucleophile •  In the case of water: hydrolysis 29 Factors Affec9ng the Rates of SN1 and SN2 Reac9ons •  The rate of each mechanism pathway determines which mechanism dominates (what products we get!) •  To decide which mechanism dominates, examine: –  Structure of the substrate –  Reac0vity of the nucleophile (and Nu concentra0on for SN2) –  Solvent Effects –  Leaving Group So.... Basically EVERYTHING! 33 Structure Effects (SN1) •  Main factor to determine if a reac0on proceeds by SN1 or SN2 is the nature of the substrate (methyl, 1o, 2o or 3o) •  SN1 can ONLY OCCUR with 3o and rarely 2o •  Reason: Stability of the carboca0on intermediate 34 •  For SN2 reac0ons, the substrate reac0vity is as follows: Why? •  In SN2: Nu and LG are both present in the transi0on state •  The more sterically crowded the electrophile, the less likely it is that a nucleophile could aIack (site is blocked!) this is an example of steric hindrance Structure Effects (SN2) 35 Nucleophile Effects •  The rate of the SN1 does not depend on the iden0ty/strength or the concentra0on of the nucleophile (Nucleophiles must not be BASIC!!) •  SN2 reac0ons: the rate is directly dependent on the concentra0on of the nucleophile •  Nucleophile strength is determined by how quickly it reacts in an SN2 (rela0ve to others) 36 Nucleophile Strength 1.  A nega0vely charged nucleophile is always a more reac0ve nucleophile than its conjugate acid 2.  In a group of nucleophiles in which the atom is the same, nucleophilici0es parallel basici0es But being a good base does NOT necessarily mean it is a good nucleophile!! Nucleophilicity DOES NOT equal basicity Ex: –OH is a beIer base than –CN But –CN is a beIer Nu than –OH I– beIer than Cl– HS– beIer than HO– 37 Solvent Effects •  Pro0c Solvent: Capable of forming hydrogen bonds, contain both δ + and δ ­ par0al charges (H bound to X, O, N) VERY IMPORTANT SN1 •  Pro0c solvents have a strong effect on anionic nucleophiles, they solvate them by forming strong hydrogen bonds that stabilize the nega0ve charge –  Because of this stabiliza0on, pro9c solvents HINDER nucleophiles (reduce their reac0vity) (Which is nucleophile – solvent or nucleophile?) 40 Apro0c Solvent •  Apro0c solvents: Solvents whose molecules do not have a hydrogen that is aIached to an electronega0ve atom –  Cannot hydrogen bond; lousy for SN reac0ons •  Polar apro0c solvent: Solvent whose molecules are polar but are not capable of hydrogen bonding –  Polar apro0c solvents will dissolve ionic compounds and solvate ca0ons very well (usually have strong δ ­) 41 Polar Apro0c Solvents •  Have strong δ ­ but the δ+ is usually well shielded (sterics) •  Polar apro0c solvents are very good at solva0ng (surrounding and stabilizing) ca0ons, but NOT anions •  Therefore these solvents do not hinder nucleophiles •  Good solvents to use for SN2 reac0ons (why?) 42 Size and Stabiliza0on •  What is the order of nucleophilicity of the halides in polar apro0c solvent? •  What is the order of nucleophilicity of the halides in polar pro0c solvent? Relative nucleophilicity in polar protic solvents: 43 Solvent Effects for SN1 •  SN1 reac0ons are best carried out in polar pro0c solvent ­ WHY? •  The rate limi0ng step is the first step (leaving group leaves, carboca0on forms) –  Polar pro0c solvent can stabilize the carboca0on and the leaving group as they form charges in the transi0on state (lowering ΔG‡) 44 •  Best: Stable anion or neutral molecule •  Reason: The LG starts to accept the electrons in the transi0on states for BOTH SN1 and SN2 therefore the beIer it is at stabilizing those electrons, the lower energy the transi0on state and the faster the reac0on Leaving Groups: both SN1 and SN2 •  Which halide would be the best leaving group? 45 Leaving Groups Cont •  Why are the following “super” leaving groups? •  Why is –OH a horrible leaving group? 46 SN1 and SN2 Summary 47 SN2 Reac9ons: Func9onal Group Transforma9ons 48 Stereochemistry SN2 Reminder •  Example •  Vinylic Halide, Phenyl Halides are UNREACTIVE towards standard nucleophilic subs0tu0on (SN1 or SN2) 49 Elimina0on •  Generally COMPETE with subs0tu0on reac0ons •  Forma0on of double bonds through loss of two atoms 50 Elimina0on •  Dehydrohalogena0on: Loss of H and X to form double bond using base (oQen alkoxides) Called β-eliminations or 1,2 eliminations 51 Nucleophiles and Bases Relative nucleophilicity in polar protic solvents: R R X HOH H H R X R R OH H R = Small HO R R R = Small HO H R R = B ig R R + XH R R = B ig + X- + H2O + H2 O •  Me3CO ­ > Me2HCO ­ > MeH2CO ­ > MeO ­ E2 Mechanism •  E2: Elimina0on, second order (rate depends on two things) •  All occurs in one step (concerted) –  Removal of the β hydrogen –  Forma0on of the double bond –  Leaving group leaving 53 •  Orienta0on of groups is important: MUST be in the same plane (an0 ­coplanar) WHY? •  In order for the p orbitals to overlap and form the π bond E2 Mechanism cont How to favor E2:  ­Strong Base  ­Hea0ng  ­ Sterically hindered electrophile (makes SN2 difficult) 54 Cl KOtBu H Cl KOtBu H CH3 Impossible to get anti elimination H Cl H CH3 KOtBu Impossible to get anti elimination 55 E1 •  NOTE: Actually very difficult to occur, need very specific reagents/condi0ons •  To increase the amount of elimina0on product (in general E1 or E2), increase the temperature 56 E1 Mechanism •  Step 1: First step is the same as with SN1 (need 3o carbon) 57 E1 •  Step 2: Remove β proton –  In this case, the orienta0on does not maIer •  OQen results in a mixture of products (if more than one possible β proton) 58 Which occurs? •  You need to be able to predict which reac0on mechanism will occur for a given set of reagents/condi0ons •  Primary substrates: Subs0tu0on occurs preferen0ally if the Nu/B is not strongly hindered 59 Which Occurs? •  Secondary substrates: Elimina0on/ Subs0tu0on is highly dependent on the strength of the Nu/B. A strong base will favor elimina0on due to sterics IN GENERAL: Higher temperature will favor elimination over substitution Bulky bases will favor elimination over substitution 60 Which occurs? •  Ter0ary Substrate: SN2 not possible, so either SN1, E2 or E1 –  Elimina0on is usually favored (due to sterics), especially at higher temperature –  Strong hindered bases will give E2 –  Weak hindered Nu/B will give either E1 or SN1 (elimina0on at higher temperature, SN1 at lower temperature) 61 Size of Base/Nu 62 Stength of Nu/B •  Really strong bases will give elimina0on preferen0ally ( ­ NH2, H ­) •  Weaker bases are more likely to act as nucleophiles (Cl ­, resonance stabilized charges) 63 Summary 64 65 ...
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