GC Chemistry Importance of The Solvent Conc Questions

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SYNTHESIS OF T-PENTYL
CHLORIDE (SN1 REACTION)
Chemistry 315
SN1: First Order Nucleophilic Substitution Rxn
■ Class of reactions where an electron-rich nucleophile
selectively bonds or attacks the (partial) positive
charge of an atom(s) to replace a leaving group
Nuc: + R-LG  R-Nuc + LG:
SN1: Reaction Mechanism
■ SN1 reaction mechanism takes place in a two steps
■ The C–L bond breaks first to give a carbocation
intermediate
■ This intermediate can then react with a nucleophile
SN1 Mechanism: Energy Diagram
■ SN1 free energy diagram – maps energy as reaction
progresses
Two ‡s
Highest EA gives
the rate limiting step
Carbocation
intermediate
SN1 Mechanism: Carbocation stability
• Carbocations formed in SN1 processes are sp2 hybridized,
trigonal planar species with an empty p-orbital
• This species has a highly e- deficient carbon and is very
reactive
• When we discuss a ‘stable’ carbocation, it is relative to other
carbocations – all of them are highly reactive!
SN1 Mechanism: Carbocation stability
• Observed
carbocation
stabilities:
• Electrostatic
potential plots
show large
difference in
positive charge
character:
SN1 Mechanism: Carbocation stability
• Carbocation stability is the result of hyperconjugation.
• Hyperconjugation is the spreading out of charge by the
overlap of an empty p orbital with an adjacent  bond.
• This overlap delocalizes the positive charge on the
carbocation over a larger volume, thus stabilizing it.
• Here, (CH3)2CH+ can be stabilized by hyperconjugation, but
CH3+ cannot:
SN1 Mechanism: Carbocation stability
• Hyperconjugation is a similar effect
to the structure of a p-bond.
• A p-bond is the parallel overlap of
two orbitals to make a stable bond
• The overlap of a 2e- σ-bond with
the empty p-orbital is not as
efficient, but stabilizes the empty
orbital
• Note the back lobe of the sp3
orbital is also in position to overlap
and stabilize the empty p-orbital
SN1: Factors that affect the reaction
Six potential influential factors in an SN1 Reaction:
1) Structure of R-X/LG
2) Strength of the Nucleophile
3) Leaving group ability
4) Solvent effect
5) Heat of reaction
6) Stereochemistry
SN1: Factors that affect the reaction
Factor 1: Structure of R-X/LG
• SN1 (top) and SN2
rates have opposite
requirements for the
structure of R-X
• For SN1:
3o >> 2o > 1o
CH3 (essentially never)
SN1: Factors that affect the reaction
Factor 2: Strength of the Nu:
• The nucleophile does not participate in the rate limiting step, the
Nu: has no effect on the rate of the SN1 process
SN1: Factors that affect the reaction
Factor 3: Leaving Group Ability
■ A leaving group must leave in the rate-determining step of
an SN2, SN1, E2, or E1 reaction.
■ The identity of the leaving group has an effect on the rate
of each reaction.
■ A good leaving group is necessary for the reaction to be
exothermic (and spontaneous) via a –∆H
■ Leaving group ability strongly affects SN1 reactions
SN1: Factors that affect the reaction
Factor 3: Leaving Group Ability
■
Overall, SN1 is similar to SN2 as far as leaving group ability:
Are never LGs!
Note that this is a qualitative trend that generally follows the
weakness of the base in water
SN1: Factors that affect the reaction
Factor 4: Solvent Effects
■ Empirical data: Rate of SN1 reactions in various solvents:
SN1: Factors that affect the reaction
Factor 4: Solvent Effects
■ SN1 reactions are most rapid in polar protic solvents
■ Consider the dissolution of NaCl in H2O. The ionic bond in
NaCl is 410 kJ/mole in strength.
■ Water is a strong dielectric and orients to insulate opposing
charges from one another:
■ This allows the Na+ ion to be separated from the Cl- ion at
room temperature
SN1: Factors that affect the reaction
Factor 4: Solvent Effects
■ In an SN1 reaction the Polar Protic solvent has the same
effect
■ This stabilizes both cation and anion and facilitates the rate
limiting step of the SN1 reaction:
SN1: Factors that affect the reaction
Factor 4: Solvent Effects
■ However, there is a limitation with this.
■ Unlike the NaCl example, where no further reaction between
H2O and Na+ or Cl- can occur, the carbocation is highly
reactive in SN1 reactions.
■ With the lone pair of oxygen in proximity to stabilize, it often
becomes the nucleophile!
■ This is called Solvolysis, where the solvent becomes the
nucleophile in SN1 and substitutes for the leaving group.
SN1: Factors that affect the reaction
Factor 4: Solvent Effects
■ In Solvolysis, the reaction requires a third mechanistic step to
deprotonate the Oxygen
SN1: Factors that affect the reaction
Factor 5: Heat
■ When substitution and elimination reactions are
both favored under a specific set of conditions, it is
often possible to influence the outcome by
changing the temperature under which the
reactions take place.
■ All of these reactions have an EA that needs to be
surmounted.
■ Heat will accelerate the rate of all reactions; the
object is not to overheat to allow higher EA reaction
pathways to compete
■ SN1 is accelerated by heat, but competing reactions
like elimination are accelerated more per unit heat!
SN1: Factors that affect the reaction
Factor 5: Heat
• At a particular temperature, only a certain percentage of
molecules possess enough energy to surmount an energy
barrier.
■ As the energy barrier
increases, the percentage
of molecules decreases.
■ As the temperature
increases, the percentage
of molecules increases.
■ In general a 10 oC rise in
temperature will double the
rate of a reaction.
SN1: Factors that affect the reaction
Factor 6: Stereochemistry of SN1
• If an SN1 reaction is carried out on a stereochemically pure
substrate, then a mixture of both the R and S enantiomers
is produced.
• Product is therefore always a Racemic Mixture
SN1: Factors that affect the reaction
Factor 6: Stereochemistry of SN1
■ The mechanism explains why the reaction produces both
configurations of the stereocenter.
■ In the first step of the mechanism, Cl⁻ simply departs,
leaving behind a planar carbocation.
SN1: Factors that affect the reaction
Factor 6: Stereochemistry of SN1
■ If the intermediate
contains a plane of
symmetry, then one side
of the carbocation is the
mirror image of the other
and approach from either
side of the plane is
equally likely.
■ The product of an SN1
reaction is always
racemic at the carbon
center
Lab: Experiment
■ Synthesize tert-pentyl chloride
– Overall RXN (SN1)
■ Practice the new technique: extraction
■ Separation scheme: a flow chart of procedure for
separating a pure product from reaction byproducts
■ Theoretical mole calculation: determine what you
*should* get if 100% of the reactants are
converted to 100% product with 100% recovery of
product
Lab: Reaction Mechanism
The synthesis of t-butyl chloride proceeds by an SN1
mechanism.
CH3
CH3 C OH
H Cl
CH3
CH3
CH3 C
CH3 H
CH3 C O
H
CH3
Cl
CH3
OH2
CH3 C
CH3
CH3
CH3
CH3
CH3 C
CH3
H2O
Cl
CH3 C Cl
CH3
Step 1 is a Bronsted-Lowry
acid/base reaction between
HCl (acid) and alcohol
(base) to form the oxonium
ion.
Step 2 is the dissociation of
the oxonium ion to form
the stable tert-butyl
carbocation and the leaving
group, H2O.
Step 3 is the reaction
(Lewis acid/base) between
the carbocation and the
nucleophile, Cl¯, resulting
in overall substitution of Cl
for OH.
Reaction Mechanism
The SN1 substitution product is often
accompanied by an alkene by-product, produced
by an E1 mechanism.
CH3
CH3CH2 C OH
CH3
H Cl
CH3
CH3
H2O
C C
H
CH3
There is another possible alkene product, but if
it is formed, it would be a minor E1 product.
What is it?
Review the mechanism for formation of the
alkene product shown in your textbook.
H+Cl- (aq.)
Experimental Procedure
■ The reaction takes place within a
separatory funnel.
■ tert-Pentyl alcohol and aq. HCl mix to
form one phase initially, and they
then begin to react when they are
mixed.
■ As the products t-pentyl chloride and
water form, the reaction mixture
separates into two phases (aqueous
and organic).
■ The two phases are the upper organic
phase (with some residual water and
aq. acid) and the lower aqueous phase
with dissolved acid.
Experimental Procedure
1. Obtain vial with t-pentyl alcohol (~5 mL)
– Weigh vial and contents – make sure to use
same balance every time!
2. Pour alcohol into 125 mL separatory funnel –
ensure stopcock is closed!!
– Use glass funnel to avoid contamination
– Re-weigh empty vial
3. Add ~12-13 mL of conc. HCl to the t-pentyl
alcohol in the separatory funnel
– Do not stopper funnel!
– Swirl mixture for ~ 1 – 2 minutes UNSTOPPERED!
■ No shaking necessary yet, just careful
swirling
Experimental Procedure
4. Stopper separatory funnel
and carefully invert
– Quickly open stopcock
to release pressure
5. Close stopcock and gently
shake funnel for ~ 2-3
minutes
– Remember to open the
stopcock and release
the pressure regularly
Experimental Procedure
6. Allow your mixture to stand until two layers have
formed.
– REMOVE the stopper when in neutral, home,
position
– Proceed to separate the two layers – set aside aq.
Layer (make sure to know which layer contains the
alkyl halide)
– Pressure can continue to build and the stopper
may shoot off the funnel. Always remove it when
the funnel is at rest.
7. Wash the organic layer with a 10 mL portion of DI
water
– Gently shake & swirl separatory funnel for ~1
minute venting pressure occasionally
– Allow layers to separate and drain aq. Layer with
the stopper off
Experimental Procedure
8. Wash the organic layer with a 10 mL portion of 5%
aq. NaHCO3
– Swirl the funnel, unstoppered, until mixed then
stopper and invert funnel, release the pressure.
– Gently shake separatory funnel for ~1 minute
venting pressure occasionally
– Allow layers to separate and drain aq. layer
9. Wash organic layer a second time with 10 mL
portion of water to remove any residual
bicarbonate waste
Experimental Procedure
10. Transfer your organic layer into an Erlenmeyer flask
– Pour from the top of the separatory funnel to
prevent contamination with aq. layer
11. Dry crude t-PtCl with anhydrous Na2SO4 until clear
– Add small amount of drying agent to flask with t-
PtCl and swirl for a few minutes
– Allow to sit for ~5 minutes
■ If solution is clear – you’re ready to decant
■ If not, you need more drying agent
12. Decant clear liquid into a small dry distillation flask
using a long stem funnel – again avoiding
contamination
Experimental Procedure
13. Add 2 boiling chips and distill the crude tert-pentyl
chloride using a simple distillation set-up.
– Collect the pure tert-pentyl chloride in a receiver
cooled in ice.
– Collect all the material that distills, changing
receivers if necessary.
14. Weigh a clean empty vial + cap. Pour the tert pentyl chloride product into the vial, screw on the
cap and weigh the vial and contents.
Experimental Procedure
13. After decanting
– weigh the product
– determine the refractive index
– take an IR spectrum
– calculate the percent yield
■ Dispose of aqueous solutions in the sink with plenty
of water.
■ Dispose of t-PtCl product into waste into waste jar in
the hood.
■ Pour organic waste into waste jar in the hood.
Quick Refresh on Stoichiometry
and gmol conversions
■ Stoichiometry
– Make sure you are reacting correctly
■ Na2CO3 can react twice with a simple acid
■ NaHCO3 can react once with a simple
acid/base
– H2CO3 + 2 NaOH  Na2CO3 + 2 H2O
■ Balance the atoms on both sides
■ G mol conversions
– Use unit analysis to cancel out or determine
multiplication/division
– MW: g/mol, MW-1 : mol/g
■ g/MW = mol via g/[g/mol]=mol
Sample Calculations
■ Chemical equation:
C5H11OH + HCl → C5H11Cl + H2O
■ Mass of tert-pentyl alcohol = mass of tert-
pentyl alcohol and its vial – mass of empty
■ Mole of t-pentyl alcohol = mass of t-pentyl
alcohol in grams/ molecular weight
■ Based on the chemical equation of tert-pentyl
alcohol with hydrochloric acid, the ratio is 1:1.
■ The Theoretical yield of tert-Pentyl Chloride =
moles tert-Pentyl Chloride * molecular weight
Additional Resources
■ Review Extraction methods in Mohrig,
Chapter 10
■ Review Drying organic substances in
Mohrig, Chapter 11
1-What is the solvent in this reaction?
2-How is the solvent helping the reaction?
3- Why is solvolysis not an issue?
4-What is the intermediate in this reaction?
5- What modification to the tert-pentyl alcohol 6-molecule could help confirm the nature of this intermediate? (Hint: Think about optical activity of chiral reactants; Talk about the structure of the intermediate)
7-Why is it essential to use HCl instead of NaCl to perform this reaction?
8-Based on the mechanism for this reaction, should we expect the concentration of HCl to affect the reaction rate? Experimentally, its concentration very much affects the rate of reaction. How can this be?
9-Assuming one follows the perfect reaction protocol perfectly and has no loss of product during isolation of 100% pure material, how is it possible that 100% theoretical yield is still not achieved for this reaction?
10-The workup involved multiple washes with different materials. What were the different washes and what materials were likely in each phase during workup? Please answer in the following format:
Wash Step [Wash Step]
[Solution used for the wash]:
Material in the wash solution – [All possible material in detectable amounts expected in the wash solution]
Other phase – [All possible materials in detectable amounts expected in the other phase]
E.g.
Wash Step 2
Water with 5% ethanol and 3M HCl:
Material in the wash solution – benzoic acid, water, ethanol, HCl
Other phase – benzene
11-Did your IR corroborate isolation of the desired product? Please detail what IR peaks give you confidence. Did you have a peak, even if fairly small, in the OH stretch region? If so, what is it most likely from? If not, what would you tell your classmate who did have a peak in the OH stretch region?
12-Did you get a % yield >70%? Please share your theoretical and experimental grams product used in your calculation. If >70%, what was the secret to your success? If not, what would you need to do differently next time to achieve that yield or better?