Nucleophilic Substitution Reactions:

SN2 Mechanism

The SN2 Mechanism of Nucleophilic Substitution

Concerted One Step - Bimolecular Reactions

Many nucleophilic substitutions follow asecond-order rate law.

CH3Br + HO – CH3OH + Br –

rate = k [CH3Br] [HO – ]

What is the reaction order of each starting material?

What can you infer on a molecular level?

What is the overall order of reaction?

Kinetics

HO – CH3Br+ HOCH3 Br –+

one stepconcerted

Bimolecular mechanism

HO – CH3Br+ HOCH3 Br –+

one stepconcerted

Bimolecular mechanism

HO – CH3Br+ HOCH3 Br –+

one stepconcerted

HO CH3 Brd - d -

transition state

Bimolecular mechanism

Question

Assuming the reaction below takes place by a concerted process, which mechanistic scheme is correct?

ClNaCN

CN + NaCl

ClNaCN

ClNaCN

ClNaCN

NC

CN + NaCl

CN + NaCl

CN + NaCl

CN

Cl

CN

CN

A.

B.

C.

Stereochemistry of SN2 Reactions

Generalization

Nucleophilic substitutions that exhibitsecond-order kinetic behavior are

stereospecific and proceed withinversion of configuration.

nucleophile attacks carbonfrom side opposite bondto the leaving group

Inversion of Configuration

nucleophile attacks carbonfrom side opposite bondto the leaving group

three-dimensionalarrangement of bonds inproduct is opposite to that of reactant

Inversion of Configuration

Inversion of configuration (Walden inversion) in an SN2 reaction is due to back side attack

A stereospecific reaction is one in whichstereoisomeric starting materials givestereoisomeric products.

The reaction of 2-bromooctane with NaOH (in ethanol-water) is stereospecific.

(+)-2-Bromooctane (–)-2-Octanol

(–)-2-Bromooctane (+)-2-Octanol

Stereospecific Reaction

C

H

CH3

Br

CH3(CH2)5

C

H

CH3

HO

(CH2)5CH3

NaOH

(S)-(+)-2-Bromooctane (R)-(–)-2-Octanol

Stereospecific Reaction

H Br

CH3

CH2(CH2)4CH3

1) Draw the Fischer projection formula for (+)-S-2-bromooctane.

2) Write the Fischer projection of the (–)-2-octanol formed from it by nucleophilic substitution with inversion of configuration.

HO H

CH3

CH2(CH2)4CH3

A.) R- ? or B.) S- ?

A conceptual view of SN2 reactions

Why does the nucleophile attack from the back side?

Why does the nucleophile attack from the back side?

“Roundabout” SN2 Reaction Mechanism

http://pubs.acs.org/cen/news/86/i02/8602notw1.html

Physicist Roland Wester and his team in Matthias

Weidemüller's group at the University of Freiburg, in Germany,

in collaboration with William L. Hase's group at Texas Tech

University, provide direct evidence for this mechanism in the

gas phase. However, they also detected an additional,

unexpected mechanism. In this new pathway, called the

roundabout mechanism, chloride bumps into the methyl

group and spins the entire methyl iodide molecule 360° before

chloride substitution. Data at lower collision energies support

the traditional SN2 mechanism. However, at higher collision

energies, about 10% of the iodide ions fell outside of the

expected distribution.

"We saw a group of iodide ions with a much slower velocity

than the rest," says Wester. "Since energy is conserved, if

iodide ions are slow, the energy has to be somewhere else."

On the basis of calculations performed by their colleagues at

Texas Tech, the team concluded that the energy missing from

the iodide transfers to the methyl chloride product in the form

of rotational excitation, supporting the proposed roundabout

mechanism.

SN2 Reaction Mechanisms: Gas Phase (2008)

Traditional Roundabout

Roundabout SN2 Mechanism

Traditional SN2 Mechanism

Published by AAAS

J. Mikosch et al., Science 319, 183 -186 (2008)

Fig. 1. Calculated MP2(fc)/ECP/aug-cc-pVDZ Born-Oppenheimer potential energy along the reaction coordinate g = RC-I - RC-Cl for the SN2 reaction Cl- + CH3I and obtained

stationary points

Published by AAAS

J. Mikosch et al., Science 319, 183 -186 (2008)

Fig. 2. (A to D) Center-of-mass images of the I- reaction product velocity from the reaction of Cl- with CH3I at four different relative collision energies

Published by AAAS

J. Mikosch et al., Science 319, 183 -186 (2008)

Fig. 3. View of a typical trajectory for the indirect roundabout reaction mechanism at 1.9 eV that proceeds via CH3 rotation

Steric Effects in SN2 Reactions

The rate of nucleophilic substitutionby the SN2 mechanism is governedby steric effects.

Crowding at the carbon that bears the leaving group slows the rate ofbimolecular nucleophilic substitution.

Crowding at the Reaction Site

RBr + LiI RI + LiBr

Alkyl Class Relativebromide rateCH3Br Methyl 221,000

CH3CH2Br Primary 1,350

(CH3)2CHBr Secondary1

(CH3)3CBr Tertiary too smallto measure

Reactivity toward substitution by the SN2 mechanism

A bulky substituent in the alkyl halide reduces thereactivity of the alkyl halide: steric hindrance

CH3Br

CH3CH2Br

(CH3)2CHBr

(CH3)3CBr

Decreasing SN2 Reactivity

CH3Br

CH3CH2Br

(CH3)2CHBr

(CH3)3CBr

Decreasing SN2 Reactivity

Reaction coordinate diagrams for (a) the SN2 reaction of methyl bromide and (b) an SN2 reaction of a sterically

hindered alkyl bromide

The rate of nucleophilic substitutionby the SN2 mechanism is governedby steric effects.

Crowding at the carbon adjacentto the one that bears the leaving groupalso slows the rate of bimolecularnucleophilic substitution, but the effect is smaller.

Crowding Adjacent to the Reaction Site

RBr + LiI RI + LiBr

Alkyl Structure Relativebromide rateEthyl CH3CH2Br 1.0

Propyl CH3CH2CH2Br 0.8

Isobutyl (CH3)2CHCH2Br 0.036

Neopentyl (CH3)3CCH2Br 0.00002

Effect of chain branching on rate of SN2 substitution

Which reaction will have the fastest rate of reaction?

Question

XNuc:H

HH

XNuc:H3C

HH

XNuc:H3C

HH3C

A) B) C)

Putting things together

IUPAC Nomenclatureof Alkyl Halides

The two that are most widely used are:functional class nomenclaturesubstituent nomenclature

Both types can be applied alkyl halides and to alcohols.

IUPAC Nomenclature

There are several kinds of IUPAC nomenclature.

Name the alkyl group and the halogen asseparate words (alkyl + halide).

Functional Class Nomenclature of Alkyl Halides

CH3F CH3CH2CH2CH2CH2Cl

CH3CH2CHCH2CH2CH3

Br

HI

Name the alkyl group and the halogen asseparate words (alkyl + halide).

Functional Class Nomenclature of Alkyl Halides

CH3F CH3CH2CH2CH2CH2Cl

CH3CH2CHCH2CH2CH3

Br

Methyl fluoride Pentyl chloride

1-Ethylbutyl bromide Cyclohexyl iodide

HI

Name as halo-substituted alkanes.

Number the longest chain containing thehalogen in the direction that gives the lowestnumber to the substituted carbon.

Substituent Nomenclature of Alkyl Halides

CH3CH2CH2CH2CH2F CH3CHCH2CH2CH3

Br

CH3CH2CHCH2CH3

I

Name as halo-substituted alkanes.

Number the longest chain containing thehalogen in the direction that gives the lowestnumber to the substituted carbon.

Substitutive Nomenclature of Alkyl Halides

CH3CH2CH2CH2CH2F CH3CHCH2CH2CH3

Br1-Fluoropentane

3-Iodopentane

2-BromopentaneCH3CH2CHCH2CH3

I

Substitutive Nomenclature of Alkyl Halides

Halogen and alkyl groupsare of equal rank when it comes to numberingthe chain.

Number the chain in thedirection that gives the lowest number to thegroup (halogen or alkyl)that appears first.

CH3

Cl

Cl

CH3

Substitutive Nomenclature of Alkyl Halides

5-Chloro-2-methylheptane

2-Chloro-5-methylheptane

CH3

Cl

Cl

CH3

Question

Name the compound on the right according to the IUPAC system.

A) 4-bromo-5-ethyl-2-methylheptaneB) 4-bromo-3-ethyl-6-methylheptaneC) 4-bromo-5-diethyl-2-methylpentaneD) 4-bromo-3-ethyl-6-dimethylhexane

Question

Cl

Br

A. (3S,4S)-3-bromo-4-chlorohexane B. (3S,4S)-3,4-dibromochloroheptane C. (3R,4R)-3-chloro-4-bromohexane D. (3R,4R)-3-bromo-4-chlorohexane E. (3S,4S)-4-bromo-3-chlorohexane

What is the correct IUPAC name for the ABOVE structure?

Classes of Alkyl Halides

Alkyl halides & alcohols are classified asprimarysecondarytertiary

according to their "degree of substitution."

Degree of substitution is determined by countingthe number of carbon atoms directly attached tothe carbon that bears the halogen or hydroxyl group.

Classification

Different Kinds of Alkyl Halides

CH3CH2CH2CH2CH2F

CH3CHCH2CH2CH3

Br

primary alkyl halide

secondary alkyl halide

Classification

CH3CCH2CH2CH3

OH

CH3

tertiary alcohol

H

OH

secondary alcohol

Question

What type of alcohol is 2-methyl-3-pentanol?

A) primary (1°)

B) secondary (2°)

C) tertiary (3°)

D) quaternary (4°)