Lab F: Fischer Esterification

Fischer Esterification Reaction

• Carboxylic acid and alcohol (reagent)

• Acid catalyst (H2SO4)

• Reversible reaction

• Ester and water (product)

Examples of esters

**isoamyl acetate or isopentyl acetate (banana)

• Have pleasant fruity odors

• Used as flavoring agents

General method for preparation of Esters

1. Reflux

2. Extractions

3. Simple distillation

** acid catalyzed reaction, acid is regenerated and is never consumed

Why is it impossible to obtain 100% yield?

The reaction is reversible and will strive to be at equilibrium, need to drive reaction forward:

• Remove water

• Excess reagent (glacial acetic acid)

• Refluxing for 50 min (increase rate)

Glacial acetic acid

• Has little water and looks like ice at room temperature

• Excess amounts because cheaper reagent

• Bp 118

Hazards

Glacial acetic acid: flammable (2), health (3), corrosive

Sulfuric acid: corrosive, health (3)

Fischer esterification reflux schematic

1. Heating mantle on ring stand

   • no stir plate

   • plug into VARIAC on bottom right of hood and cord wrapped around metal bar under white bar

2. RB flask flush on mantle with 2 boiling stones

3. Clamped RB flask cover with foil

4. Condenser

   • CHWS on bottom (water in)

   • CHWR on top (water out)

Scheme 1: synthesis of isopentyl acetate

• 3-methyl-1-butanol (isoamyl alcohol) and glacial acetic acid

• H2SO4

• Isopentyl acetate (isoamyl acetate) and water

Why use boiling stones in Fischer and not Diels Alder?

• boiling stones smoothes boil and avoid bumps - violent boils will spill out of condenser

• Diels Alder product physically similar to boiling stones, inaccurate yield

Flow chart of Fischer Esterification Reaction

1. 15mL 3-methyl butanol and 20mL Glacial acetic acid

2. 2mL conc. H2SO4

3. 50mL cold water and 10mL to rinse

4. 25mL 5% NaHCO3 solution

5. 25mL water and 5mL NaCl solution

6. Anhydrous CaCl2 pellets

7. 125-138

Why use water for the first wash?

1. Cool the reaction

2. Draw out acid catalyst

3. Create an aqueous layer

Why use bicarbonate (NaHCO3) for the second wash?

• Remove excess glacial acetic acid

• COOH can be deprotonated pka~5

• Acetic acid into sodium acetate salt (polar)

• Sodium acetate salt has greater solubility in the aqueous layer (drained)

• Generates CO2, vent to prevent loss in yield

Why use brine (NaCl) and water for third wash?

• Addition of water removes any leftover acetic acid after wash #2 and create an aqueous layer

• Addition of brine initiates the drying process by removing excess water from organic layer

Why transfer the organic layer into a 125mL Erlenmeyer flask?

The sloped slides prevent evaporation of organic layer during gravity filtration with CaCl2

Why collected isopentyl acetate (banana oil) below literature bp?

• Literature bp = 142C

• Thermometers are poorly calibrated at temperatures over 100C, so product distilled from 125-138C

Purification techniques

• Recrystallization

• Thin layer chromatography

• Extraction for immiscible liquids

• Simple distillation for miscible liquids

Why do a simple distillation to purify?

• Separate liquids where bp differ by greater than 100C at 1atm

• Miscible liquids

• Distillation: technique where liquid is vaporized by heating its bp, then recommended back to a liquid

Why do a simple distillation to purify?

• Purifying isopentyl acetate from trace isopentyl alcohol (bp<125)

• Differ by 13C (less than 100C) but fractional distillation will lose a large amount of material to column holdup with sufficient number of theoretical plates

• Small amount left due to driving equilibrium (excess reagent and removing product)

Simple distillation schematic

1. 2 ring stands used

2. Heating mantle supported by ring clamp

3. RB flask flush against heating mantle clamped with 2 boiling stones

4. 3 way distillation adapter with thermometer adapter

   • thermometer bulb position below junction for accurate readings

5. Keck clip between 3 way adapter and condenser

6. Condenser clamped to 2nd ring stand

   • CHWS toward the vacuum adapter (bottom)

   • CHWR toward the RB (top)

7. Keck clip between condenser and vacuum adapter

8. Vacuum adapter to receiving container (vial)

Why do not distill to dryness？

Small amount of residue will prevent overheating and breaking the flask, and the formation of pyrolytic tars that are difficult to wash out

How to minimize loss of material through vaporization if volatile compound is being distilled?

Receiving container can be chilled in an ice water bath

Vacuum Distillation

• For compounds that either boil at too high a temperature or decompose near their bp

• Under vacuum compounds can be distilled at temperatures lower than their atm bp (>200C)

Fractional distillation

• Used to separate liquid mixtures where difference in bp < 100C at 1atm

• Vigreux column: greater surface area for a number of separate liquid equilibria to occur

• Many vaporizations and condensations before distillate is collected

• Efficiency is determined by number of theoretical plates

• Several simple distillation cycles

• Greater loss of product and longer time to distill

Factors affecting Boiling Points

1. Increase in size (MW) = higher bp

2. Increase intramolecular interactions = higher bp

   • hydrogen bond (FON)

   • dipole

   • van der waals

3. Increase stability = higher bp

Factors affecting Boiling Points

1. Increase in size (MW) = higher bp

2. Increase intramolecular interactions = higher bp

   • hydrogen bond (FON)

   • dipole

   • van der waals

3. Increase stability = higher bp

Why should Keck clips at joints be tight?

Loose joints will cause product to escape

Positioning of the thermometer bulb

Below the 3-way junction, if placed too high the temperature readings will be low and inaccurate

Using the VARIAC

• A variable voltage transformer

• Provides voltage adjusted source of alternating current

• Higher bp = greater voltage required (start at ~65)

• Outlet located BELOW fume hood

• Set power = set heat = control reaction rate

Fischer mechanism

1. Protonation of glacial acetic acid with H2SO4

   • protonated = more electrophilic

2. Nucleophile (3-methyl-1-butanol) attacks carbonyl

3. Tetrahedral intermediate O+ deprotonated by HSO4-

4. Neutral addition product OH protonated by H2SO4 to form H2O+

5. Elimination of water and forming of double bond

6. OH+ deprotonated by HSO4-

7. Final product isopentyl acetate and acid catalyst regenerated

General Procedure

1. Add 2 boiling stone to 100mL RB flask

2. Add 15mL 3-methyl-1-butanol, 20mL glacial acetic acid, 2mL H2SO4

3. Reflux set up (no stir plate) and clamp only RB flask

4. VARIAC dial to 65 and insulate with foil until solution comes to a boil

5. Remove foil and reflux for 50 min

6. Raise clamped RB above heating mantle and cool for 10 min

7. Transfer to 250mL sep funnel without boiling stones

8. Add 50mL cold water and rinse RB flask with 10mL

9. Shake and drain aqueous layer into beaker #1

10. Add 25mL 5% NaHCO3

11. Shake and vent, then drain into beaker #2

12. pH of beaker #2 = orange or green

13. Add 25mL water and 5mL NaCl

14. Shake and drain into beaker #1

15. Drain organic layer into 125 Erlenmeyer flask and add CaCl2

16. Gravity filtration into 25mL RB flask with 2 new boiling stones (crude ester)

17. Simple distillation 125-138C

Waste disposal and cleanup

1. Disassemble simple distillation setup starting from the right

2. All aqueous waste disposed in “aqueous waste Fischer lab”

3. CaCl2, gravity paper, boiling stones in biohazard

4. If any, low boiling distillate into “CHO nonhalogenated”

5. MP capillary tubes in sharps

6. Prep glassware for grignard lab by rinsing with acetone

Why is the pH of beaker #2 orange/green (neutral)?

Acid-base neutralizing reaction

OBSERVATION: reflux is deep purple color

OBSERVATION: after extraction the product is yellow

OBSERVATION: final product isopentyl acetate is clear with banana odor

Fischer IR Spectrum