1. Lecture 10a Esterification

2. Introduction Esters can be obtained by a broad variety of reactions Acyl chloride Accessibility of SOCl 2 Anhydride Availability of anhydride Methyl iodide CH 3 I is a carcinogen Steglich Esterification DCC is used as reagent 4-Dimethylaminopyridine (DMAP) as catalyst DCU is the thermodynamic sink

3. Esterification I In the lab, acetic acid anhydride will be used as carboxylic acid source and concentrated phosphoric acid as catalyst. In principle, there are several potential outcomes possible: esterification, Friedel- Crafts acylation or the combination of both. Using this particular protocol, it appears that only the acetic acid ester is formed; no acylation product or the combination of esterification and acylation was observed in prior tests. The ester can undergo a Fries arrangement using various catalysts (CH 3 SOOH, Zn, ZnCl 2 ) and solvents leading to a mixture of ortho and para-hydroxyl acetophenones.

4. Esterification II Prior tests also showed that the phenyl ring that is bears the ester function that is considered a weakly activating group does not undergo a Friedel-Crafts reaction afterwards under these conditions. Due to its size, the acylium ion would favor the formation of the para isomer, which is not possible here because of the phenyl substituent in the para position to the acetate group. Previously, it was reported that the acetylation of phenyl acetate (CH 3 COOPh) using acetic acid and polyphosphoric acid (PPA) at 75 o C affords the para-substituted isomer (4-acetyl phenylacetate) in 50 % yield.

5. Experiment I In a RBF, 4-phenylphenol is dissolved in acetic acid anhydride. Concentrated phosphoric acid is added slowly. The reaction mixture is heated to 80-85 o C on a water bath. After cooling the reaction mixture to room temperature, it is poured into water. The solid is isolated by filtration The solid is recrystallized from hot 95 % ethanol. Submit NMR sample (50 mg/mL CDCl 3 ) and GC/MS (1-2 mg/mL ethyl acetate). What is the function of the acetic acid anhydride? What is its function? How is this accomplished? Which observation should be made here? Why is 95 % ethanol used her? The phenol and the ester precipitate while the acids remain in solution The ester is less polar than the phenol and dissolves less in 95 % ethanol It acts as solvent and acid source By placing the flask in a hot water bath It is the catalyst

6. Characterization I Infrared Spectrum (C=O)=1751 cm -1 (COC)=1019 and 1194 cm -1 (oop)=701, 755 cm -1 (mono) and 851 cm -1 (para) (C=O) as (COC) s (COC)

7. Characterization II 1 H-NMR Spectrum (CDCl 3 ) F D C E B A

8. Characterization III 13 C-NMR Spectrum (CDCl 3 ) JHD E F B A/C G K

9. Characterization IV Mass Spectrum (EI) m/z=212 m/z=170