Experiment 21:

ESTERS: SYNTHESIS AND FRAGRANCE

+ R'OHRCOH

O

RCOR'

O

+ H2OH+

Objectives:

To synthesize an ester from acetic acid with isoamyl alcohol under reflux.

To purify your product through acid-base extraction and simple distillation.

To identify and analyze the purity of your compound using GC analysis.

To identify your product by analyzing the NMR and IR spectra.

Before coming to lab…

Review these techniques:

Reflux

Acid-Base Extraction

Simple distillation

Drying over MgSO4

GC Analysis

FISCHER ESTERIFICATION Fischer esterification is an acid catalyzed

nucleophilic acyl substitution.

Net effect is the replacement of an –OH of a carboxylic acid with the –OR of an alcohol to produce an ester.

It is an equilibrium reaction with an unfavorable Keq, thus we can improve product yield in several ways: Use an excess of the alcohol reactant. Use an excess of the carboxylic acid reactant. Remove water as it forms.

R O H + H O C R'

O

H+R O C R'

O

+ H O H

FISCHER ESTERIFICATION

• Carboxylic acids are not reactive enough to undergo nucleophilic addition directly.

• By using sulfuric acid as a catalyst, the carbonyl group oxygen is protonated to give the carboxylic acid a positive charge. This makes it more reactive.

+ H OSO3H

H3CC

OH

O

+

H3CC

OH

OH

H C

CH3

CH3

OH

MECHANISM

+ H OSO3H

H3CC

OH

O

+

H3CC

OH

OH

H C

CH3

CH3

OH

CH3C O

OH

HO

C

H3C

CH3

H

H

CH3C O

O

O

C

H3C

CH3

H

H

H

H

CH3C O

O

C

H3C

CH3

H

H

O

H

H2O H2SO4

1. Protonation of the carbonyl oxygen activates the carboxylic acid…

2. …toward nucleophilic attack by the alcohol…

3. … yielding a tetrahedral intermediate.

4. Transfer of a proton from one oxygen to another yields a second tetrahedral intermediate… 5…and converts the OH group into a good leaving group.

6. Loss of a proton and expulsion of H2O regenerates the acid catalyst and gives the ester product.

1

2

3

45

6

OVERVIEW

Synthesize product ester under reflux.

Neutralize acetic acid with 10% NaHCO3.

Extract in ether, then wash with 10% NaHCO3.

Dry organic layer.

Perform simple distillation to remove ether from product.

Obtain final product mass, calculate % yield, prepare GC sample.

EXPERIMENTAL PROCEDURE(SYNTHESIS)

water out

water in

heating mantle

iron ring

to voltage regulator

• Combine acetic acid, isoamyl alcohol and sulfuric acid in a 25 mL round bottom flask.

• Clamp flask to ring stand and add 3 boiling chips.

• Place water cooled condenser on top of flask, with a CaSO4 drying tube in the top.

• Heat to reflux. Reflux 30 minutes.

• Cool to room temp.

• Add 10% NaHCO3 slowly to flask.

25mL

CaSO4 tube

EXPERIMENTAL PROCEDURE(PURIFICATION)

• Transfer liquid to separatory funnel.

• Rinse reaction flask with ether and transfer to separatory funnel.

• Wash the organic layer with 10% NaHCO3.

• Transfer the organic layer to a clean flask.

• Dry over MgSO4.

• Transfer liquid to a preweighed 50 mL round bottom flask.

• Clamp flask to ring stand. 50mL

50mL

125mL

EXPERIMENTAL PROCEDURE(PRODUCT ISOLATION)

Heating Mantle

to voltage regulator

water out

water in

iron ring

• Set up a simple distillation apparatus, using a 25 mL round bottom as the receiving flask.

•Collect all distillate that boils under 40oC.

• Record distillation range, Ti-Tf.

• Allow reaction flask to cool to room temperature.

• Reweigh 50 mL flask to determine final product mass (actual yield) and calculate % yield.

• Prepare GC sample.

25mL WASTE

SOLVENT

50mL PRODUCT!

!!

Table 21.1

Theoretical yield (g)Calculated value based on limiting reagent!

Actual yield (g)(50mL RB flask + product) – (Empty 50mL RB flask)

% yieldACTUAL YIELD X 100THEORETICAL YIELD

Product Appearance

PHYSICAL STATE, COLOR

Table 21.2

CompoundGC Retention Times

(min) Area Percent Adjusted Area PercentStandard

Sample

methanol SOLVENTisoamyl alcohol

REACTANT

isoamyl acetate

PRODUCT

EXPERIMENTAL PROCEDURE

(IR ANALYSIS)

1234

5

CH3CHCH2CH2OH

CH3

1234

5

CH3CHCH2CH2OCCH3

CH3 O

6 7

Table 21.3

FunctionalGroup

Base Values

Acetic acid Isoamylalcohol

Isoamylacetate

Frequency(cm-1)

Frequency (cm-1)

Frequency(cm-1)

Frequency(cm-1)

sp3 CHstretch 2850-3000

C-O stretch1000-1300

OH stretch2400-3600

C=O stretch 1640-1750

EXPERIMENTAL PROCEDURE

(NMR ANALYSIS)

1234

5

CH3CHCH2CH2OH

CH3

1234

5

CH3CHCH2CH2OCCH3

CH3 O

6 7

H3CC

OH

O

1

2

3

SAFETY CONCERNS

CAUTION: H2SO4

is a STRONG ACID!

WASTE MANAGEMENT

• All aqueous washes from the extraction can be flushed down the drain with plenty of water!

• Ester product and distilled ether should be placed in the bottle labeled, “ORGANIC WASTE (Esters)”.

CLEANING

Clean round bottom flasks and distillation glassware with wash acetone only!

Separatory funnel and all other glassware should be cleaned with soap, water, and a brush if necessary, followed by a wash acetone.

DO NOT return any glassware to lab drawer dirty or wet!

LABORATORY NOTEBOOK(Pre-lab)

• OBJECTIVE (Must clearly state…)

• What compounds will be made and how• How the compounds will be purified• How the purity of the product will be determined

• CHEMICAL EQUATION • Include the chemical equation from the top of page 177.

• TABLE OF PHYSICAL DATA (Complete the following table using a site listed on WWW Links ONLY. Wikipedia is unacceptable!)

• REFERENCE TO PROCEDURE (Must include…)

• full title including edition and author names• page numbers where actual procedure can be found

Compound MW (g/mol)

bp(oC)

d (g/mL)

HAZARDS

Isoamyl alcoholIsoamyl acetate

Acetic acidSulfuric acidDiethyl ether

methanol

LABORATORY NOTEBOOK(In-lab)

• DATA/CALCULATIONS • Initial volumes of isoamyl alcohol and acetic acid used• Distillation range • Weight of 50 mL round bottom flask • Weight of 50 mL round bottom flask + product • Final product weight• Physical state and color of product • GC vial slot # • Theoretical yield calculation (not just value!)• % yield calculation (not just value!)• Example of an adjusted area % calculation (not just value!)

• EXPERIMENTAL PROCEDURE• In paragraph form, BRIEFLY describe the procedure that you actually followed

during the lab. • Paragraph must be written in PAST TENSE, PASSIVE VOICE.• Include any volumes or weights of chemicals used during the experiment.• Include any mistakes, accidents or observations if applicable.