Sn1 Mechanism 2q3125

• The polarity of a carbon-halogen bond leads to the carbon having a partial positive charge – In alkyl halides this polarity causes the carbon to become activated to substitution reactions with nucleophiles

• Carbon-halogen bonds get less polar, longer and weaker in going from fluorine to iodine

•

Nucleophilic Substitution Reactions • In this reaction a nucleophile is a species with an unshared electron pair which reacts with an electron deficient carbon • A leaving group is substituted by a nucleophile

• Examples of nucleophilic substitution

•

Nucleophile • The nucleophile reacts at the electron deficient carbon

• A nucleophile may be any molecule with an unshared electron pair

•

Leaving Group • A leaving group is a substituent that can leave as a relatively stable entity • It can leave as an anion or a neutral species

•

A Mechanism for the SN2 Reaction

• A transition state is the high energy state of the reaction – It is an unstable entity with a very brief existence (10-12 s) • In the transition state of this reaction bonds are partially formed and broken – Both chloromethane and hydroxide are involved in the transition state and this explains why the reaction is second order

•

The Stereochemistry of SN2 Reactions • Backside attack of nucleophile results in an inversion of configuration

• In cyclic systems a cis compound can react and become trans product

•

A Mechanism for the SN1 Reaction • Step 1 is rate determining (slow) because it requires the formation of unstable ionic products • In step 1 water molecules help stabilize the ionic products

III. SN1 Mechanism A. Kinetics

CH3

CH3

RLS: H3C C Br

H3C C

CH3

CH3

CH3 H3C C

+ Br

HOCH3

CH3 CH3 H H3C C O CH3 CH3

-H+

CH3 H H3C C O CH3 CH3 CH3 H3C C O CH3 + HBr CH3

•

Carbocations • A carbocation has only 6 electrons, is sp2 hybridized and has an empty p orbital

• The more highly substituted a carbocation is, the more stable it is – The more stable a carbocation is, the easier it is to form

• Hyperconjugation stabilizes the carbocation by donation of electrons from an adjacent carbon-hydrogen or carbon-carbon s bond into the empty p orbital – More substitution provides more opportunity for hyperconjugation

•

The Stereochemistry of SN1 Reactions • When the leaving group leaves from a stereogenic center of an optically active compound in an SN1 reaction, racemization will occur – This is because an achiral carbocation intermediate is formed • Racemization: transformation of an optically active compound to a racemic mixture

III. SN1 Mechanism A. Kinetics Two-step mechanism:

R+

RBr + CH3OH ROCH3 + HBr

III. SN1 Mechanism C. Carbocation stability R+ stability: 3º > 2º >> 1º > CH3+

R-X reactivity toward SN1: 3º > 2º >> 1º > CH3X

CH3+ 1º R+ 2º R+ 3º R+

•

Solvolysis • A molecule of the solvent is the nucleophile in a substitution reaction – If the solvent is water the reaction is a hydrolysis

III. SN1 Mechanism C. Carbocation stability Rearrangements possible:

EtOH 

CH3CH2O

Br

-H+ H

EtOH Et

O

III. SN1 Mechanism Question. Which of the following compounds will react fastest by SN1? Which by SN2?

A.

Br

Br B.

Br Br

Br Br Check Answer

III. SN1 Mechanism Answer. Which of the following compounds will react fastest by SN1? Which by SN2?

A.

Br fastest by SN2 - 1o

Br B.

Br Br fastest by SN1 - 2o

Br Br

fastest by SN2 - 1o

fastest by SN1 - 3o

IV. SN1 vs SN2 A. Solvent effects nonpolar: moderately polar: polar protic: polar aprotic:

hexane, benzene ether, acetone, ethyl acetate H2O, ROH, RCO2H DMSO DMF O O

CH3

S

CH3

H

C

acetonitrile CH3

C N

N(CH3)2

SN1 mechanism promoted by polar protic solvents stabilize R+, X– relative to RX

R+X– RX

in less polar solvents in more polar solvents

IV. SN1 vs SN2 A. Solvent effects SN2 mechanism promoted by moderately polar & polar aprotic solvents destabilize Nu–, make them more nucleophilic e.g., OH– in H2O: strong H-bonding to water makes OH– less reactive OH– in DMSO: weaker solvation makes OH– more reactive (nucleophilic)

in DMSO in H2O RX + OH– ROH + X–

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Factors Affecting the Rate of SN1 and SN2 Reactions – The Effects of the Structure of the Substrate – SN2 Reactions • In SN2 reactions alkyl halides show the following general order of reactivity • Steric hinderance: the spatial arrangement of the atoms or groups at or near a reacting site hinders or retards a reaction – In tertiary and neopentyl halides, the reacting carbon is too sterically hindered to react

IV. SN1 vs SN2

Rate = k1[RX] + k2[RX][Nu]

B. Summary rate of SN1 increases

RX = CH3X

1º

2º

rate of SN2 increases

(carbocation stability)

3º (steric hindrance)

react may go reacts primarily by either primarily by SN2 mechanism by SN1 (k1 ~ 0, k2 large) (k2 ~ 0, k1 large) SN2 promoted good nucleophile (Rate = k2[RX][Nu]) -usually in polar aprotic solvent SN1 occurs in absence of good nucleophile (Rate = k1[RX]) -usually in polar protic solvent (solvolysis)

IV. SN1 vs SN2 Question 8-4. What would be the predominant mechanism in each of the following reactions? What would be the product?

KCN Br DMSO

Br

H2O 

Br CH3OH 

Br

NaSCH3 DMF

Check Answer

IV. SN1 vs SN2 Answer 8-4. What would be the predominant mechanism in each of the following reactions? What would be the product?

KCN Br DMSO

CN

good nucleophile, 1o RX - SN2

Br

H2O 

poor nucleophile, 3o - SN1

OH

Br CH3OH 

OCH3

poor nucleophile, 2o - SN1 Br

NaSCH3 DMF

good nucleophile, 2o - SN2

SCH3