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11. Reactions of Alkyl Halides: Nucleophilic Substitutions and Eliminations Based on McMurry’s Organic Chemistry, 6 th edition
64

Reaksi sn 1, sn-2, e-1, dan e-2.

Aug 29, 2014

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  • 11. Reactions of Alkyl Halides:Nucleophilic Substitutions andEliminationsBased on McMurrys Organic Chemistry, 6thedition
  • Nucleophiles and Leaving Groups:
  • Alkyl Halides React with Nucleophiles Alkyl halides are polarized at the carbon-halide bond,making the carbon electrophilic Nucleophiles will replace the halide in C-X bonds ofmany alkyl halides(reaction as Lewis base) Nucleophiles that are strong Brnsted bases canproduce elimination
  • Reaction Kinetics The study of rates of reactions is called kinetics The order of a reaction is sum of the exponents of theconcentrations in the rate law the first example is firstorder, the second one second order.NaOH + CCH3CH3CH3 Br NaBr + CCH3CH3CH3 OHv = k[C4H9Br]NaOH + NaBr +v = k[CH3Br][NaOH]CH3Br CH3OH
  • 11.4 The SN1 and SN2 Reactions Follow first or second order reaction kinetics Ingold nomenclature to describe characteristic step: S=substitution N (subscript) = nucleophilic 1 = substrate in characteristic step (unimolecular) 2 = both nucleophile and substrate incharacteristic step (bimolecular)
  • Stereochemical Modes ofSubstitution Substitution with inversion: Substitution with retention: Substitution with racemization: 50% - 50%
  • SN2 Process The reaction involves a transition state in which bothreactants are together
  • Walden Inversion
  • SN2 Transition State The transition state of an SN2 reaction has a planararrangement of the carbon atom and the remainingthree groups
  • Steric Effects on SN2 ReactionsThe carbon atom in (a) bromomethane is readily accessibleresulting in a fast SN2 reaction. The carbon atoms in (b) bromoethane(primary), (c) 2-bromopropane (secondary), and (d) 2-bromo-2-methylpropane(tertiary) are successively more hindered, resulting in successively slower SN2reactions.
  • Steric Hindrance Raises TransitionState Energy Steric effects destabilize transition states Severe steric effects can also destabilize groundstateVery hindered
  • Order of Reactivity in SN2 The more alkyl groups connected to the reactingcarbon, the slower the reaction
  • 11.5 Characteristics of the SN2Reaction Sensitive to steric effects Methyl halides are most reactive Primary are next most reactive Secondary might react Tertiary are unreactive by this path No reaction at C=C (vinyl halides)
  • The SN1 Reaction Tertiary alkyl halides react rapidly in protic solventsby a mechanism that involves departure of theleaving group prior to addition of the nucleophile Called an SN1 reaction occurs in two distinct stepswhile SN2 occurs with both events in same step
  • Stereochemistry of SN1 Reaction The planarintermediateleads to loss ofchirality A freecarbocation isachiral Product isracemic or hassome inversion
  • SN1 in Reality Carbocation is biased to react on sideopposite leaving group Suggests reaction occurs with carbocationloosely associated with leaving group duringnucleophilic addition
  • Effects of Ion Pair Formation If leaving group remainsassociated, thenproduct has moreinversion than retention Product is only partiallyracemic with moreinversion than retention Associated carbocationand leaving group is anion pair
  • SN1 Energy Diagram Rate-determining step isformation of carbocationStep through highest energypoint is rate-limiting (k1 inforward direction)k1 k2k-1V = k[RX]
  • 11.9 Characteristics of the SN1Reaction Tertiary alkyl halide is most reactive bythis mechanism Controlled by stability of carbocation
  • Delocalized Carbocations Delocalization of cationic charge enhances stability Primary allyl is more stable than primary alkyl Primary benzyl is more stable than allyl
  • Comparison: Substitution Mechanisms SN1 Two steps with carbocation intermediate Occurs in 3, allyl, benzyl SN2 Two steps combine - without intermediate Occurs in primary, secondary
  • The Nucleophile Neutral or negatively charged Lewis base Reaction increases coordination at nucleophile Neutral nucleophile acquires positive charge Anionic nucleophile becomes neutral See Table 11-1 for an illustrative list
  • Relative Reactivity of Nucleophiles Depends on reaction and conditions More basic nucleophiles react faster (for similarstructures. See Table 11-2) Better nucleophiles are lower in a column of theperiodic table Anions are usually more reactive than neutrals
  • The Leaving Group A good leaving group reduces the barrier to areaction Stable anions that are weak bases are usuallyexcellent leaving groups and can delocalize charge
  • Super Leaving Groups
  • Poor Leaving Groups If a group is very basic or very small, it is preventsreaction
  • Effect of Leaving Group on SN1 Critically dependent on leaving group Reactivity: the larger halides ions are betterleaving groups In acid, OH of an alcohol is protonated and leavinggroup is H2O, which is still less reactive than halide p-Toluensulfonate (TosO-) is excellent leaving group
  • Allylic and Benzylic Halides Allylic and benzylic intermediates stabilized bydelocalization of charge (See Figure 11-13) Primary allylic and benzylic are also more reactivein the SN2 mechanism
  • The Solvent Solvents that can donate hydrogen bonds (-OH or NH) slow SN2 reactions by associating with reactants Energy is required to break interactions betweenreactant and solvent Polar aprotic solvents (no NH, OH, SH) form weakerinteractions with substrate and permit faster reaction
  • Polar Solvents Promote Ionization Polar, protic and unreactive Lewis base solventsfacilitate formation of R+ Solvent polarity is measured as dielectricpolarization (P)
  • Solvent Is Critical in SN1 Stabilizing carbocation also stabilizesassociated transition state and controls rateSolvation of a carbocation bywater
  • Effects of Solvent on Energies Polar solvent stabilizes transition state andintermediate more than reactant and product
  • Polar aprotic solvents Form dipoles that have well localized negativesides, poorly defined positive sides. Examples: DMSO, HMPA (shown here)+-++OPN N NCH3CH3CH3CH3CH3CH3
  • Common polar aprotic solventsCH3SOCH3OPNNNCH3CH3CH3CH3CH3CH3CHONCH3CH3SO Odimethylsulfoxide (DMSO)hexamethylphosphoramide (HMPA)N,N-dimethylformamide (DMF)sulfolane
  • +-+++-+++-+++-++Na++-+++-+++-+++-++Cl-Polar aprotic solvents solvate cations well, anions poorlygood fit! bad fit!
  • SN1: Carbocation not very encumbered,but needs to be solvated in ratedetermining stepPolar protic solvents are good because they solvate both the leavinggroup and the carbocation in the rate determining step k1!The rate k2 is somewhat reduced if the nucleophile is highly solvated,but this doesnt matter since k2 is inherently fast and not ratedetermining.(slow)
  • SN2: Things get tight if highly solvatednucleophile tries to form pentacoordiantetransition statePolar aprotic solvents favored! There is no carbocation to be solvated.
  • Nucleophiles in SN1 Since nucleophilic addition occurs afterformation of carbocation, reaction rate is notaffected normally affected by nature orconcentration of nucleophile
  • 11.10 Alkyl Halides: Elimination Elimination is an alternative pathway to substitution Opposite of addition Generates an alkene Can compete with substitution and decrease yield,especially for SN1 processes
  • Zaitsevs Rule for EliminationReactions (1875) In the elimination of HX from an alkyl halide, the morehighly substituted alkene product predominates
  • Mechanisms of EliminationReactions Ingold nomenclature: E elimination E1: X-leaves first to generate a carbocation a base abstracts a proton from the carbocation E2: Concerted transfer of a proton to a base anddeparture of leaving group
  • 11.11 The E2 Reaction Mechanism A proton is transferred to base as leaving groupbegins to depart Transition state combines leaving of X and transfer ofH Product alkene forms stereospecifically
  • Geometry of Elimination E2 Antiperiplanar allows orbital overlap and minimizessteric interactions
  • E2 Stereochemistry Overlap of the developing orbital in the transitionstate requires periplanar geometry, anti arrangementAllows orbital overlap
  • Predicting Product E2 is stereospecific Meso-1,2-dibromo-1,2-diphenylethane with basegives cis 1,2-diphenyl RR or SS 1,2-dibromo-1,2-diphenylethane gives trans1,2-diphenyl(E)-1bromo-1,2-diphenylethene
  • 11.12 Elimination From Cyclohexanes Abstracted proton and leaving group should aligntrans-diaxial to be anti periplanar (app) inapproaching transition state (see Figures 11-19 and11-20) Equatorial groups are not in proper alignment
  • 11.14 The E1 Reaction Competes with SN1 and E2 at 3 centers V = k [RX]
  • Stereochemistry of E1 Reactions E1 is not stereospecific and there is no requirementfor alignment Product has Zaitsev orientation because step thatcontrols product is loss of proton after formation ofcarbocation
  • Comparing E1 and E2 Strong base is needed for E2 but not for E1 E2 is stereospecifc, E1 is not E1 gives Zaitsev orientation
  • 11.15 Summary of Reactivity: SN1,SN2, E1, E2 Alkyl halides undergo different reactions incompetition, depending on the reacting molecule andthe conditions Based on patterns, we can predict likely outcomes
  • Special cases, both SN1 and SN2blocked (or exceedingly slow)BrBrBrCH3CH3CH3CH2BrCarbocation highly unstable, attack from behind blockedCarbocation highly unstable, attack from behind blockedCarbocation would be primary, attack frombehind difficult due to steric blockageCarbocation cant flatten out as required by sp2hybridization, attack from behind blockedAlso: elimination not possible, cant place doublebond at bridgehead in small cages (Bredts rule)
  • Kinetic Isotope Effect Substitute deuterium for hydrogen at position Effect on rate is kinetic isotope effect (kH/kD =deuterium isotope effect) Rate is reduced in E2 reaction Heavier isotope bond is slower to break Shows C-H bond is broken in or before rate-limiting step
  • 64 www.ulm.edu/~junk/examkeys/pp230_10_ch11.ppt 31 januari 2010