Preparation of Ethyl Acetoacetate - Claisen Condensation - Lu Le Laboratory

Ethyl acetoacetate (EAA) is mainly used as a chemical intermediate in the production of a wide variety of compounds, such as amino acids, analgesics, antibiotics, antimalarial Ethyl acetoacetate is mainly used as a chemical intermediate in the production of a wide variety of compounds, such as amino acids, analgesics, antibiotics, antimalarial agents, antipyrine and aminopyrine, and vitamin B1; as well as the manufacture of dyes, inks, lacquers, perfumes, plastics, and yellow paint pigments. Alone, it is used as a flavoring for food.

The Claisen condensation is a carbon–carbon bond forming reaction that occurs between two esters or one ester and another carbonyl compound in the presence of a strong base, resulting in a β-keto ester or a β-diketone. It is named after Rainer Ludwig Claisen, who first published his work on the reaction in 1887.

Claisen Condensation

 

Reaction Equation

 

Mechanism

 

  

Chemicals

1.     Ethyl acetate: 25mL ; FW 88.11g/mole ; m.p. -84℃ ; b.p. 76.5~77.5℃

2.     Xylenes: 12.5mL ; FW 106.17 g/mol ; b.p. 137~140℃

3.     Acetic acid: FM 60.05g/mol ; m.p. 16.2℃ ; b.p.117~117℃

4.     Magnesium sulfate anhydrous

5.     Sodium Metal: 2.0g

 

Procedure

1.     Add 12.5mL xylenes [1] and 2.0g fresh sodium metal in a 50 mL round-bottom bottle.

 

2.     Reflux the mixture until sodium melts.

 

3.     Stir the mixture violently to prepare sodium beads.

 Sodium beads are shining

4.     Pour out xylenes and recycle it.

5.     Add 25 mL ethyl acetate immediately and set up a reflux apparatus.

 The mixture turns into yellow at first

6.     Reflux the mixture for about 1.5 hr until sodium beads are all dissolved.

 Finally, the mixture becomes orange because of the sodium enolate

7.     Cool the solution to about 50 mL and then add 50% acetic acid to acidify the solution [2].

 

 

8.     Transfer the solution into a separatory funnel and add same volume of saturated NaCl solution to wash the mixture.

9.     Drain out the layer of ethyl acetoacetate.

10.  Dry the compound with Mg₂SO₄ anhydrous.

11.  Distill the compound under 1.0atm to remove ethyl acetate.

12.  Distill ethyl acetoacetate under reduced pressure [3] (~0.079atm=7.99kPa=60mmHg).

 

 

Ethyl acetoacetate

Residue in the vessel

Product should look like crystal clean

Notes

[1]  To make sodium beads which make the reaction faster, we have to use a solvent which melting point should higher than sodium and would not react with it. To compare boiling points of benzene(80℃), toluene(110~111℃) and xylenes(137~140℃) with sodium metal(97.8℃), so toluene and xylene may be used as the kind of solvent. But when the temperature is near 100℃(near the m.p. of sodium), the vapor pressure of toluene will raise to 553mmHg while xylenes is only at 342mmHg. So we can prevent the high vapor pressure in the reacting vessel by using xylenes.

[2]  Don’t add too much acetic acid or it would raise the solubility of ethyl acetoacetate then reduce the yield of product.

[3]  The boiling point of ethyl acetoacetate is 189℃ under 1.0atm. But this compound decomposes readily at high temperature and turn into acetic anhydrous. To prevent EAA decomposes, we could distill it under reduced pressure to lower the boiling point EAA.

Experimental Record

Boiling Point of Ethyl Acetate	73.0~76.0 ℃
Boiling Point of Ethyl acetoacetate (under 0.079 atm.)	100.0~101.0 ℃
Theoretical Weight of Ethyl Acetoacetate	11.31 g
Weight of Ethyl Acetoacetate	3.62 g
Yield	32.0 %