Chemistry 81 MtSAC Dr. V. Prutyanov Spring 2020 Mechanism of SN2 Reaction Student:______________________ Predicting SN2 reactivity by calculating transition states for RCl + Br - In this exercise you will consider the reactivity of alkyl chlorides towards SN2 reactions. Specifically, you will use Molecular Orbital calculations to explore the relative SN2 reactivity of the following compounds: CH3Cl, EtCl, i-PrCl and PhCH2Cl. The approach you will use is to calculate the energy of the SN2 transition state for the attack of Br - on the alkyl chloride, and subtract the energy of the reactants from it. That should allow to calculate the activation energy, Ea for the following process: RCl + Br- → RBr + Cl- The obtained data analysis should illustrate the impact of the structure of R on the rate of the SN2 reaction as larger activation energy corresponds to a slower reaction. Another variable in this work is the solvent that is going to be introduced later to model the reaction more realistically. Procedure 1. Choose the “5-bonded-carbon” structure from the Inorganic drawing template. This puts the five valences in the desired trigonal bipyramidal geometry, three planar and 120° apart (the equatorial bonds), and the other two at 90° to this plane (called the axial bonds). 2. Add a nucleophile and a LG to the axial valences that are at 180° to each other, and the appropriate groups to the equatorial valences to build each transition structure. Open “Calculations” menu, chose the right charge (-1 for an anion, for example) and run a semi- empirical PM3 “Equilibrium geometry”. This should yield a good starting point for the Transition State search with C-Br distance around 2.2 Å and C-Cl 2.4 Å. If necessary, adjust the bond distances using “Measure distance” option within “Geometry” menu. 3. After the optimization above is complete (you might resubmit “failed” calculations), open the calculations menu and choose “Transition State Geometry”. Check the IR box. Submit the job. 4. If the TS search is successful it should have one and only one negative (or so-called “imaginary”) frequency that could be apparent from the IR spectrum. Click on spectrum icon on the upper panel and chose Calculated IR box in a pop-up window. Clicking on the corresponding frequency on the top of the table will animate the imaginary frequency that leads to collapse of the TS to the products. Hence the name “imaginary” as the common vibrations are reversible and do not collapse a molecule. In this mechanism, the expected movement would be a departure of the leaving group upon an approachment of the nucleophile. 5. Record the energy of the TS in a table below. Safe you file! 6. In a separate file, build the nucleophile and the alkyl chloride together and calculate the energies of the reactants using semi-e.

1. Chemistry 81 MtSAC Dr. V. Prutyanov Spring 2020
Mechanism of SN2 Reaction
Student:______________________
Predicting SN2 reactivity by calculating transition states for
RCl + Br
-
In this exercise you will consider the reactivity of alkyl
chlorides towards SN2 reactions.
Specifically, you will use Molecular Orbital calculations to
explore the relative SN2 reactivity of
the following compounds: CH3Cl, EtCl, i-PrCl and PhCH2Cl.
The approach you will use is to calculate the energy of the SN2
transition state for the attack of
Br - on the alkyl chloride, and subtract the energy of the
reactants from it. That should allow to
calculate the activation energy, Ea for the following process:
RCl + Br- → RBr + Cl-

2. The obtained data analysis should illustrate the impact of the
structure of R on the rate of the SN2
reaction as larger activation energy corresponds to a slower
reaction. Another variable in this
work is the solvent that is going to be introduced later to model
the reaction more realistically.
Procedure
1. Choose the “5-bonded-carbon” structure from the Inorganic
drawing template. This puts
the five valences in the desired trigonal bipyramidal geometry,
three planar and 120°
apart (the equatorial bonds), and the other two at 90° to this
plane (called the axial
bonds).
2. Add a nucleophile and a LG to the axial valences that are at
180° to each other, and the
appropriate groups to the equatorial valences to build each
transition structure. Open
“Calculations” menu, chose the right charge (-1 for an anion,

3. for example) and run a semi-
empirical PM3 “Equilibrium geometry”. This should yield a
good starting point for the
Transition State search with C-Br distance around 2.2 Å and C-
Cl 2.4 Å. If necessary,
adjust the bond distances using “Measure distance” option
within “Geometry” menu.
3. After the optimization above is complete (you might resubmit
“failed” calculations), open
the calculations menu and choose “Transition State Geometry”.
Check the IR box. Submit
the job.
4. If the TS search is successful it should have one and only one
negative (or so-called

4. “imaginary”) frequency that could be apparent from the IR
spectrum. Click on spectrum
icon on the upper panel and chose Calculated IR box in a pop-
up window.
Clicking on the corresponding frequency on the top of the table
will animate the imaginary
frequency that leads to collapse of the TS to the products.
Hence the name “imaginary” as
the common vibrations are reversible and do not collapse a
molecule. In this mechanism,
the expected movement would be a departure of the leaving
group upon an approachment
of the nucleophile.
5. Record the energy of the TS in a table below. Safe you file!
6. In a separate file, build the nucleophile and the alkyl chloride
together and calculate the
energies of the reactants using semi-empirical PM3
calculations. Remember to choose

5. the correct charge in the Calculations menu for this van der
Waals complex where the
nucleophile and RX are bonded by weak intermolecular forces
(London, ion-dipole,
dipole-dipole, etc.)
7. In another separate file, calculate the energy of the complex
of the alkyl bromide with
chloride anion (the product).
8. For each reaction, create a table in your lab notebook like the
one below and work with
your lab partner if you like to run the calculations to fill in each
table. The Eaq calculations
account for the solvation effects and provides an estimate of the
energy profile in an
“aqueous” environment. Running the calculations in water as a
solvent is easy. Open the
saved files with gas phase results and safe as new files with
“aq” suffix. Then change the
state from in “gas” to in “water” as shown below. Run the
calculations, safe your files and
record the energy in the tables below. You also can use Excel
spreadsheet to facilitate the

6. calculations of the Ea.
Data
CH3Cl + Br- TS CH3Br + Cl- Ea, kJ/mol
E,
kJ/mol
Eaq,
kJ/mol
ΔE = E(Product)-E(Reactant) ΔEaq = E(P)aq – E(R)aq
PhCH2Cl + Br- TS PhCH2Br + Cl- Ea, kJ/mol
E

7. Eaq
EtCl + Br- TS EtBr + Cl- Ea, kJ/mol
E
Eaq
i-PrCl + Br- TS i-PrBr + Cl- Ea, kJ/mol
E
Eaq
9. After calculating all of the activation energies, summarize
them in a table like the one
shown below.
MeCl + Br- EtCl + Br- i-PrCl + Br- PhCH2Cl + Br-
Ea
Ea(aq)

8. Discussion Points
1. Briefly discuss your results in terms of consistency with your
expectations for these
reactions. Did you expect the Ea to depend on the structure?
Why?

9. 2. How does solvation affect the activation energies for these
reactions?
3. How does the reactivity of benzyl chloride compare with the
various alkyl chlorides? Can
you find a rational top explain high reactivity of allylic and
benzylic substrates in SN2?

10. 4. Draw the energy diagram for MeCl + Br- reaction including
the reactants, the TS and the
products. Assign the energy of the reactant the zero value.
Repeat for the reaction in
water, using a blue pen or crayon.

11. 5. The benzylic and allylic halides are very reactive in SN1
reaction as well. Why? Draw the
mechanism of the reaction between benzyl chloride and water
and use it to illustrate your
point.