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)
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°)