ESTERS: SYNTHESIS AND FRAGRANCE Experiment 21: ESTERS: SYNTHESIS AND FRAGRANCE

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.

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.

MECHANISM 1. Protonation of the carbonyl oxygen activates the carboxylic acid… 1 2. …toward nucleophilic attack by the alcohol… 2 3. … yielding a tetrahedral intermediate. 3 4. Transfer of a proton from one oxygen to another yields a second tetrahedral intermediate… 4 5 6 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.

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) 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. CaSO4 tube 25mL

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. 125 mL 50mL 50mL

EXPERIMENTAL PROCEDURE (PRODUCT ISOLATION) 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. 50mL PRODUCT!!! 25mL WASTE SOLVENT

Table 21.1 Theoretical yield (g) Calculated value based on limiting reagent! Actual yield (g) (50mL RB flask + product) – (Empty 50mL RB flask) % yield ACTUAL YIELD X 100 THEORETICAL YIELD Product Appearance PHYSICAL STATE, COLOR

GC Retention Times (min) Table 21.2 Compound GC Retention Times (min) Area Percent Adjusted Standard Sample methanol SOLVENT isoamyl alcohol REACTANT isoamyl acetate PRODUCT

EXPERIMENTAL PROCEDURE (IR ANALYSIS)

Table 21.3 Functional Group Base Values Acetic acid Isoamyl alcohol acetate Frequency (cm-1) sp3 CH stretch 2850-3000 C-O stretch 1000-1300 OH stretch 2400-3600 C=O stretch 1640-1750

EXPERIMENTAL PROCEDURE (NMR ANALYSIS)

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 alcohol Isoamyl acetate Acetic acid Sulfuric acid Diethyl 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.