Nucleophilic substitution and eliminations

• SN2 reactions use polar aprotic solvents, why?


  Because these solvents wont form hydrogen bonds with molecules, the nucleophiles' abilities aren't hindered and the nucleophile is the most important for SN2 reactions.
• alcohols are a poor leaving group, therefore, the OH group needs to made into a better leaving group in order for a reaction to occur.
• alcohols either be the nucleophillic or electrophilic component of a nucleophilic substitution reaction
• A good leaving group is the conjugate base of a strong acid (more stable product) as the more stable the leaving group is, the more leaving group product is made.
• What makes a good nucleophile?

  
  

  • High electron density
  • Negative charge (anion)
  • Not very electronegative (need to be good electron donors)
  • Large atom as large electron clouds are more polarizable and can deform to favour bond formation
• Nucleophility seek positive charge and are thus electron rich. Nucleophility refers to the ability of a species to act as an electron donor. It's also helpful to think of electron availability and ability to form a new bond as a measure of nucleophillity. Lone pairs have more electron availability than bonded pairs and will be better nucleophiles. With bonded pairs, pi bonds are more nucleophilic because their electrons are more available as pi overlaps are wealer than signma.
• The electrophile center must be sp3 hybridized for nucleophillic substitution to occur
• Which species/functional groups are very good nucleophiles?

  I-,HS-,RS- (anions and large atoms)
• Which species/functional groups are good nucleophiles?

  Br-, HO-, RO-, NC-, N3- (anions, but smaller atoms and more electronegative)
• Which species/functional groups are fair nucleophiles?

  NH3, Cl-, F-, RCO2- (smaller atoms, some are very electronegative, not all are anions, and one is resonance stabilized)
• Which species/functional groups are weak nucleophiles?

  H2O, ROH (neutral and electronegative)
• Which species/functional groups are very weak nucleophiles?

  RCO2H (neutral, resonance stabilized, and 2 electronegative atoms)
• Resonance decreases nucleophility because electrons are less available to donate to the electrophile
• Factors that stabilize leaving groups?


  electronegativity, size, resonance
• If an OH group is converted into H20 as a leaving group by protonation, what conditions are needed for substitution for a water leaving group?


  Acidic conditions
• To avoid acidic conditions needed for H2O substitution reactions, the alcohol can instead be converted into tosylate which does not need a acid to react
• What are polar protic solvents?

  • have dipoles due to polar bonds
  • can have H atoms that can be donated into a H-bond
  • anions will be solvated due to H-bonding, inhibiting their ability to function as Nu
• What are polar aprotic solvents?

  • have dipoles due to polar bonds
  • don't  have H atoms that can be donated into a H-bond
  • examples are acetone, acetonitrile, DMSO, DMF
  • anions are not solvated and are "naked" and reaction is not inhibited (i.e., positive portion of H-bond won't be very attracted to Nu and get in the way of its attack)
• Why do SN1 reactions use polar protic solvents?

  To stabilize carbocation intermediates through hydrogen bonding
• Why do E1 reactions use polar protic solvents?

  to stabilize the carbocation intermediate through hydrogen bonding
• When would an E2 reaction use a polar protic solvent?

  If the polar protic solvent is the conjugate acid of the base, since then even if the compound is solvated and interacts, base would still be produced and an E2 reaction would occur
• What sort of substrate is preferred for each reaction?

  SN1: Tertiary or resonance stabilized

  SN2: primary

  E1: Tertiary or resonance stabilized

  E2: Tertiary
• SN2 involves the simultaneous bonding change of the nucleophile-carbon bond formation and the bond breaking of between the carbon-leaving group bond. Rate of reaction = k[Nu-][R-LG], however having a strong nucleophile is necessary but having a very good leaving group is not.
• Only one transition state in SN2 and 5 groups on central C atom in TS, thus having less substituted groups will lessen steric strain and make SN2 reaction easier.
• Which species/functional groups are excellent leaving groups?

  TsO- (conjugate base of strong acid), NH3 (neutral)
• Which species/functional groups are very good leaving groups?

  I- (conjugate base of strong acid), H2O (neutral)
• Which species/functional groups are good leaving groups?

  Br- (conjugate base of strong acid)
• Which species/functional groups are poor leaving groups?

  F- (conjugate base of weak acid)
• Which species/functional groups are very poor leaving groups?

  OH- (charged and conjugate base of really weak acid), NH2-, RO-
• Rate determining step of SN2 is making C-Nu bond
• Rate determining step of SN1 is breaking C-LG bond
• In SN2, Nu attacks 180 degrees to the LG (backside attack) so they don't get in each other's way. This causes an inversion of configuration known as the Walden Inversion in chiral carbons.
• electrophilic center must be sp3 hybridized in nucleophilic substitution
• Remember that ionic compounds dissociate and thus make anions (strong nucleophiles)
• Rate of reaction of SN1= [R-LG]
• two transition states in SN1
• rate of reaction of SN1 increases in order with a more highly substituted groups (i.e., tertiary vs primary)
• Rate determining step in SN1 is carbocation formation.
• How are carbocation stabillized?

  By electron donors. Alkyl groups are weak electron donors and can donate electrons through inductive effects and hyperconjugation. Carbocations can be further stabilized by resonance.
• • EDG add electron density to the π system making it more nucleophilic