Experiment 8: Nucleophilic
Substitution Reactions of
Alkyl Halides
Nucleophilic Substitution
• Important reaction of alkyl halides
• Two common mechanistic pathways:
SN1: substitution, nucleophilic, unimolecular
exp 1: Reaction with Sodium Iodide in Acetone
exp 2: Reaction with Silver Nitrate in Ethanol
RDS
Reading: Carey & Guiliano
Ch. 8 pgs 322-350
SN2: substitution, nucleophilic, bimolecular
RDS
Reaction Features
Comparison: SN1 vs. SN2
• SN1 Reactions:
- rate determining step involves ionizaton ! carbocation
- reaction rate governed by cation stability
- RX: 3° > 2° >> 1°
• SN2 Reactions:
SN1
intermediate
carbocation
no formal
intermediate
mechanism
stepwise
concerted
kinetics
1st order
2nd order
weak or strong
strong
polar, protic
various
cation stability
sterics
substrate
3° > 2° > 1°
CH3X > 1° > 2° > 3°
stereochemistry
retention &
inversion
inversion
rearrangements
common
not possible
nucleophile
solvent
rate determined by
- rate determining step involves backside attack of Nu
- reaction rate governed by sterics
- RX: 1° > 2° >> 3°
SN2
Next Week
Substrates
(November 7 - 11)
Experiment 8: Nucleophilic Substitution Reactions of R-X
A. NaI in Acetone
reaction via SN2 mechanism
B. AgNO3 in ethanol
reaction via SN1 mechanism
NOTE: We will not do concentration studies for either part
DUE:
Alkyne Synthesis Lab Report (exp 7)
Lab Reports are due at the beginning of your regular lab session
Reactions
Determine Characteristics of Nu Substitution
• NaI in acetone (SN2)
"
- I- is a very good nucleophile
- acetone is a polar, aprotic solvent
- reaction will result in precipitate formation (NaCl or NaBr)
• Evaluate the reactivity of the alkyl halide substrates considering:
- primary structure (1°, 2°, 3°)
- secondary structure (steric effects, proximity of double bonds)
- nature of the leaving group (Br vs Cl)
- concentration (substrate vs. reagent) - should understand
- solvent (SN1 vs SN2 reaction)
- reaction temperature (will evaluate indirectly)
• AgNO3 in ethanol or ethanol/water (SN1)
"
- Ag+ in protic solvent
- rapidly generates R+ and AgX (ppt)
formation of ppt tells you reaction has occurred
- subsequent reaction of R+ with solvent (ethanol), etc.
• Qualitative evaluation
- be ready to observe and record your results
- watch for ppt formation
- no products will be isolated
- no yield will be determined
Experimental Details - NaI in acetone (SN2)
1.
Obtain microtubes & corks (8-10 each)
- be sure tubes are clean & dry
2. Add 15% NaI/acetone (2 mL) to reaction tubes
- more is not better
3. Add substrates to reaction tubes
- 2 drops of substrate per reaction tube (~ 0.1 mL)
- one substrate per tube
- be sure to label them so you know what is in each one!
- immediately stopper tubes, mix thoroughly, note start time
- watch for ppt formation at room temperature
record the exact time for ppt formation (if any) in each tube
try to quantify how much ppt forms (a lot? just a little?)
also record observations when no ppt forms
Experimental Details - NaI in acetone (SN2)
Specific Experiments:
1. Primary Structure
- substrates:
- expectations?: 1° > 2° >> 3° >>>> aryl
2. Secondary Structure
- substrates:
- expectations?: allylic > 1°
unhindered > hindered
4. If no precipitate forms after ~ 5 minutes, heat to 50°C in hot water bath
- note start time
- watch for reaction (ppt formation) over next 4-5 minutes
- record observations (e.g. reaction time; quantity of precipitate)
Experimental Details - NaI in acetone (SN2)
Specific Experiments (cont):
3. Leaving Group
- substrates:
- expectations?: Br > Cl (Br better able to accommodate negative charge)
4. Concentration (NOTE: we will not do this portion of the experiment)
- substrate:
- variations:
change substrate concentration
change Nu concentration
- expectations?: both situations will result in an increase in reaction rate
specifically, expect rate to double in each case
because the reaction is bimolecular!
k = [RX][I-]
Experimental Details - AgNO3 in ethanol (SN1)
1. Empty microtubes from last set of reactions & wash with ethanol
- DO NOT use acetone!
2. Add 1% AgNO3/ethanol (1 mL) to reaction tubes
- more is not better
3. Add substrates to reaction tubes
- 2 drops of substrate per reaction tube (~ 0.1 mL)
- one substrate per tube (be sure you know what's in each one!)
- immediately stopper tubes, mix thoroughly, note start time
- watch for ppt formation at room temperature
record the exact time for ppt formation (if any) in each tube
try to quantify how much ppt forms (a lot? just a little?)
also record observations when no ppt forms
4. If no precipitate forms after ~ 5 minutes, heat to 50°C in hot water bath
- note start time
- record observations as before
5. When finished, wash tubes (rinse well!), dry, & return
- PLEASE do not put them in your drawer!
Experimental Details - AgNO3 in ethanol (SN1)
Experimental Details - AgNO3 in ethanol (SN1)
Specific Experiments:
Specific Experiments (cont):
1. Primary Structure
- substrates:
3. Leaving Group
- substrates:
- expectations?: 3° > 2° >> 1° >>>> aryl
- expectations?: Br > Cl (Br better able to accommodate negative charge)
2. Secondary Structure
- substrates:
- expectations?: allylic > 1°
4. Concentration (NOTE: we will not do this portion of the experiment)
- substrate:
why??
- variations:
double substrate concentration
double Nu concentration
- expectations?: double [RX], expect reaction rate to double
double [Nu], expect no change
because the reaction is unimolecular! k = [RX]
Experimental Details - AgNO3 in ethanol (SN1)
Specific Experiments (cont):
5. Solvent
- substrate:
Writing the Lab Report: Exp #8 Alkyne Synthesis
! Purpose
- what will you make?
- include a balanced chemical equation for every reaction you did
! Results & Discussion
- Comment on the success of your reaction sequence
- variations:
ethanol
ethanol/water
- expectations?: rxn in ethanol/water will be faster
both are polar, protic solvents (favor SN1)
pure water has a higher dielectric constant = more polar
(really favors SN1)
Did each step work?
How do you know? ! physical appearance, TLC & melting point
don’t forget to discuss the changes in Rf values that you observe
- Were the products pure?
How do you know? ! TLC & mp data
Was your recrystallization successful for step 2?
- Was the reaction sequence efficient?
Calculate the % yield for each step
Calculate the overall yield
Writing the Lab Report: Exp #8 Alkyne Synthesis
! Conclusion
- a brief recap of your findings
- was your reaction sequence successful (did you make it? was it pure?)
- do not include theory
! Appendix A: Calculations
- Table of reagents (for each step)
Calculating Overall Yield:
• Reaction Sequence:
1. Calculate yield for each step (as discussed last week)
- Determine the limiting reagent (for each step)
- Percent Yield calculation (for each step)
for step 2, keep in mind you may not have recrystallized everything
see page 91 of the lab manual for details
- Overall Yield calculation
example follows
- Rf calculation
! Appendix B: Spectra
- none
87%
94%
2. Multiply individual yields together
Overall Yield = (yieldstep 1) x (yieldstep 2)... x 100
= (0.87) x (0.94) x 100
= 82%