Eugenoxyacetic acid (IUPAC name: 2-methoxy-4-(2-propenyl)phenoxyacetic) is an odorless, colorless an — Organic Chemistry Chemistry Question
Synthesis of eugenoxy acetic acid
Eugenoxyacetic acid (IUPAC name: 2-methoxy-4-(2-propenyl)phenoxyacetic) is an odorless, colorless and non-cytotoxic compound. It has shown anti-viral and anti-bacteria properties and is therefore used as antioxidant food preservative in food industry. Recently, eugenoxyactetic acid and its ester derivatives such as methyl and ethyl esters have been found to be the ability to inhibit lipid increasing which leads to their potential application in the treatment of human hyperlipidaemia. In addition, eugenoxyacetic acid acts as a promising plant growth promoter due to their auxin (aryloxyacetic) structural characteristics.
The nature and living organism friendly properties of eugenoxyacetic are the result of the combination of acetic moiety which is present in vinegar and eugenol moiety which is the main constituent of the essential oil obtained from clove oil.
Clove is an aromatic plant in the family Lamiaceae which is native to tropical areas and widespread as a cultivated plant. In Vietnam, there are two species of clove, Ocimum sanctum L. and Ocimum gratissimum L., which have been used in many traditional medicinal purposes without adverse effects.
In this practical problem, eugenoxyacetic acid will be synthesized from eugenol as shown in the scheme below:
[VISUAL]
Chemicals and apparatus:
* Clove essential oil
* Monochloroacetic acid
* NaOH
* Na2CO3
* Aqueous HCl solution
* Distilled water.
Apparatus and glassware:
* Erlenmayer flask, 50 cm3
* Magnetic stirrer with heater
* Magnetic bar
* Beaker, 100 cm3
* Beaker, 250 cm3
* Glass filter, 25 cm3
* Glass filter, 50 cm3
* Vacuum filter set (vacuum pump, Filter flask)
* Dropping funnel
* Spatula
* Glass rod
Experimental procedure:
Step 1:
1. Dissolve 0.6 g NaOH in 3.0 cm3 distilled water in a 50 cm3 Erlenmayer flask and then add 2.0 cm3 clove essential oil. Keep the flask in the water bath at 80 – 90 oC while stirring with the magnetic stirrer.
2. Dissolve carefully 1.0 g monochloroacetic acid in 5.0 cm3 distilled water in a 25 cm3 beaker and stir the solution with the spatula. Add Na2CO3 slowly just to the alkaline reaction (Solution A).
Step 2:
1. Add slowly solution A to an Erlenmayer flask and keep stirring the mixture at 90 – 95 oC for 60 min. Cool the reaction mixture with water to room temperature, and then acidify with HCl solution (1 : 1) to the acidic reaction (test by litmus paper) (Solution B).
2. Add a small amount of crushed ice (5 – 10 g) to the solution B and stir until the yellow oil turns to the solid. Isolate the solid by filtration with suction into a sintered glass crucible. Wash the solid with water to obtain the crude product as pale yellow solid.
Step 3:
1. Purify the product as follows: Transfer the crude product to a 250 cm3 beaker, add 80 - 100 cm3 of hot water (about 90 oC) to the beaker and continue boiling for 5 – 10 min. Cool the solution with water and ice-cold water.
2. Isolate the product by filtering with suction into a sintered glass crucible and wash the solid product several times to obtain white needles. Dry the product in the drying oven for 60 min. Weigh the dried product.
Write down the reactions occurring in steps 1 and 2.
Model Answer
In Step 1, eugenol is deprotonated by NaOH to form sodium eugenolate. Monochloroacetic acid reacts with sodium carbonate (Na2CO3) to form sodium monochloroacetate. In Step 2, sodium eugenolate nucleophilically attacks sodium monochloroacetate to form sodium eugenoxyacetate. Upon acidification with hydrochloric acid (HCl), eugenoxyacetic acid is precipitated.
Calculate the reaction yield.
Model Answer
The reaction yield is calculated by dividing the actual mass of the dried pure eugenoxyacetic acid product by the theoretical yield (calculated from the starting amount of limiting reagent, either eugenol or monochloroacetic acid) and multiplying by 100%.
Propose a mechanism for the reaction in step 2.
Model Answer
The reaction in step 2 follows an SN2 substitution mechanism where the nucleophilic phenoxide/eugenolate oxygen attacks the alpha-carbon of monochloroacetate, displacing the chloride leaving group.
Explain why the reaction must be conducted in alkaline medium? Should an excess amount of alkaline be used in the reaction?
Model Answer
In alkaline media, eugenol is transformed into the eugenolate ion which has adequate nucleophilicity to replace the chlorine atom of monochloroacetic acid. However, an excess amount of alkaline should not be used because hydroxide ions can compete with eugenolate ions to attack monochloroacetic acid, forming the hydroxide derivative of acetic acid (glycolic acid).
Compare the possibilities of the chlorine atom in monochloroacetic acid and those in alkyl chlorides to be substituted.
Model Answer
The carboxyl group in monochloroacetic acid increases the positive charge density at the alpha-carbon through its electron-withdrawing (-I) effect, facilitating the attack of nucleophiles. Additionally, the carbonyl group can help stabilize and delocalize the negative charge appearing in the transition state of the SN2 reaction, making it more reactive towards substitution than standard alkyl chlorides.
If the pure product obtained in the experiment above (m. p. 72 oC) is recrystallized in benzene, its m. p. will rise to 100.5 oC. Suggest an explanation for this observation and propose method to test your explanation.
Model Answer
Crystallized water in the product recrystallized from hot water lowers its melting point. Recrystallization from dry benzene eliminates this crystallized water (producing anhydrous eugenoxyacetic acid), which increases the melting point to 100.5 oC. To test this explanation, one can use titration (to determine acid content/purity) or Thermogravimetric Analysis (TGA) to measure the mass loss corresponding to water crystallization.
When eugenoxyacetic acid is refluxed in KOH solution, and acidified with HCl solution (1 : 1), an isomer of eugenoxyacetic acid, isoeugenoxyacetic acid can be obtained in the form of two stereoisomers. Determine the structures of these two isomers and explain the formation of isoeugenoxyacetic acid with a suitable reaction mechanism.
Model Answer
Under basic conditions (refluxing KOH), eugenoxyacetic acid undergoes base-catalyzed isomerization. The terminal double bond shifts into conjugation with the benzene ring, forming a more stable conjugated system. Isoeugenoxyacetic acid can exist in two stereoisomeric forms: (Z) and (E) configuration isomers.