Two Step MechanismWhich step is rate determining? A) Step #1 B) Step #2
Solvolysis Reactions Tertiary alkyl halides are very unreactive in substitutions that proceed by the SN2 mechanism. • But they are highly reactive in solvolysis reactions where the solvent is generally one of the reactants.
CH3 CH3 H H CH3 CH3 + .. : : : + O O C : C Br .. H H CH3 CH3 + .. – CH3 : : Br CH3 .. .. .. : + Br H OH C .. .. CH3 Hydrolysis of tert-butyl bromide.
CH3 CH3 H H CH3 CH3 : : O H H CH3 CH3 .. – : : Br .. Hydrolysis of tert-butyl bromide. .. + + : : C Br O C .. + This is the nucleophilic substitutionstage of the reaction; the one withwhich we are concerned.
CH3 CH3 H H CH3 CH3 : : O H H CH3 CH3 .. – : : Br .. Hydrolysis of tert-butyl bromide. .. + + : : C Br O C .. + The reaction rate is independentof the concentration of the nucleophileand follows a first-order rate law. rate = k[(CH3)3CBr]
CH3 CH3 H H CH3 CH3 .. + : : : O : C Br O C .. H H CH3 CH3 .. – : : Br .. Hydrolysis of tert-butyl bromide. + + The mechanism of this step isnot SN2. It is called SN1 and begins with ionization of (CH3)3CBr.
Kinetics and Mechanism rate = k[alkyl halide] First-order kinetics implies a unimolecularrate-determining step. • Proposed mechanism is called SN1, which stands forsubstitution nucleophilic unimolecular
CH3 CH3 .. : Br C .. CH3 unimolecular slow H3C CH3 .. – + : : C Br .. CH3 Mechanism +
H3C CH3 H + C : : O CH3 H bimolecular fast CH3 H CH3 + : O C H CH3 Mechanism
R+ proton transfer RX + ROH2 ROH carbocation formation carbocation capture
Characteristics of the SN1 mechanism • first order kinetics: rate = k[RX] • unimolecular rate-determining step • carbocation intermediate • rate follows carbocation stability • rearrangements sometimes observed • reaction is not stereospecific • racemization occurs in reactions of optically active alkyl halides
Question • What is the rate-determining step in the reaction of cyclobutanol with HCl? • A)protonation of the OH group • B)attack of the bromide on the carbocation • C)simultaneous formation of the C-Br bond and the breaking of the C-OH bond • D)carbocation formation
Question • The species shown below represents _____ of the reaction between isopropyl alcohol and • hydrogen bromide. • A) the alkyloxonium ion intermediate • B) the transition step of the bimolecular proton transfer • C) the transition state of the attack of the nucleophile on the carbocation • D) the transition state of the unimolecular dissociation
Electronic Effects Govern SN1 Rates The rate of nucleophilic substitutionby the SN1 mechanism is governedby electronic effects. Carbocation formation is rate-determining.The more stable the carbocation, the fasterits rate of formation, and the greater the rate of unimolecular nucleophilic substitution.
Reactivity toward substitution by the SN1 mechanism RBr solvolysis in aqueous formic acid • Alkyl bromide Class Relative rate • CH3Br Methyl 1 • CH3CH2Br Primary 2 • (CH3)2CHBr Secondary 43 • (CH3)3CBr Tertiary 100,000,000
Decreasing SN1 Reactivity (CH3)3CBr (CH3)2CHBr CH3CH2Br CH3Br
Question • Select the most stable carbocation. • A) B) • C) D)
Question • Which one of the following reacts with HBr at the fastest rate? • A) B) • C) D)
Generalization • Nucleophilic substitutions that exhibitfirst-order kinetic behavior are not stereospecific.
H CH3 Br C CH3(CH2)5 H CH3 H CH3 H2O OH C C HO CH3(CH2)5 (CH2)5CH3 (R)-(–)-2-Octanol (17%) (S)-(+)-2-Octanol (83%) Stereochemistry of an SN1 Reaction R-(–)-2-Bromooctane
Figure Ionization stepgives carbocation; threebonds to chiralitycenter become coplanar + Leaving group shieldsone face of carbocation;nucleophile attacks faster at opposite face.
CH3 + C H3C CH3 Structure of tert-Butyl Cation • Positively charged carbon is sp2 hybridized. • All four carbons lie in same plane. • Unhybridized p orbital is perpendicular to plane of four carbons.
More than 50% Less than 50% +
H3C CH3 – C + Cl CH3 H3C CH3 Lewis acid Lewis base C Cl Electrophile Nucleophile H3C Carbocation Capture +
Because... • carbocations are intermediatesin SN1 reactions, rearrangementsare possible.
CH3 CH3 H2O C CHCH3 C CH2CH3 CH3 CH3 (93%) H Br OH H2O CH3 CH3 C CHCH3 C CHCH3 CH3 CH3 + + H H Example
In general... • SN1 Reaction Rates Increase in Polar Solvents
Most polar Fastest rate SN1 Reactivity versus Solvent Polarity Solvent Dielectric Relative constant rate acetic acid methanol formic acid water
R X transition state stabilized by polar solvent R+ energy of RX not much affected by polarity of solvent RX
R X transition state stabilized by polar solvent activation energy decreases; rate increases R+ energy of RX not much affected by polarity of solvent RX
In general... • SN2 Reaction Rates Increase inPolar Aprotic Solvents An aprotic solvent is one that doesnot have an —OH group.
SN2 Reactivity versus Type of Solvent CH3CH2CH2CH2Br + N3– • Solvent Type Relative Rate • CH3OH polar protic 1 • H2O polar protic 7 • DMSO polar aprotic 1300 • DMF polar aprotic 2800 • Acetonitrile polar aprotic 5000
When... • primary alkyl halides undergo nucleophilic substitution, they always react by the SN2 mechanism • tertiary alkyl halides undergo nucleophilic substitution, they always react by the SN1 mechanism • secondary alkyl halides undergo nucleophilic substitution, they react by the • SN1 mechanism in the presence of a weak nucleophile (solvolysis) • SN2 mechanism in the presence of a good nucleophile
SN1 vs. SN2 – The Leaving Group • The most commonly used leaving groups are halides and sulfonate ions. • CONCEPTUAL CHECKPOINT 7.28.
SN2 vs. SN1 – Solvent SN2 reaction, use a polar, aprotic solvent • To promote an SN1 reaction, use a polar, protic solvent: The protic solvent will hydrogen bond with the nucleophile, stabilizing it, while the leaving group leaves first.
Calibrated Peer Review / Lab Experimentation http://chemconnections.org/organic/chem226/calendar-f-12