Preparation of Benzoin - Synthesis of Dilantin - Lu Le Laboratory

Benzoin is the precursor of the antiepileptic medicine, Dilantin (Phenytoin).

Benzoin is also a white crystal perfumery. The DL-type is a hexagon monoclinic rhombic crystal. Both D-type and L-type are needle-shape crystals.

In this experiment, a benzoin condensation of benzaldehyde is carried out with a biological coenzyme, thiamine hydrochloride, as the catalyst.

Reaction equation

Vitamin B₁ is a coenzyme. It may replace the extremely toxic substance, sodium cyanide, as the catalyst, is benzoin condensation. The structure of Vitamin B₁ is as fallow:

Mechanism

Step 1

Step 2

Step 3

Chemical

1.      Vitamin B₁ hydrochloride: 1.20g

 

2.      Benzaldehyde: ~6.24g

3.      Ethanol 95%: 12mL

4.      Sodium hydroxide solution: 2.5M 4.0mL

Procedure

1.      Dissolve 1.20g thiamine hydrochloride (Vitamin B₁) into 4.0mL water in a 125mL flask.

 

2.      When Vitamin B₁ is dissolved, add 12.0mL 95% ethanol.

3.      Stopper the flask and cool the solution with a ice bath, slowly add 4.0mL of cold 2.5M sodium hydroxide to the flask, and make pH of the solution is about 10~11.

 Vitamin B1 solution turns into yellow after added sodium hydroxide soludtion

4.      Rapidly add ~6.24g benzaldehyde to the reaction mixture and sufficiently mix the solution. Stopper the flask and allow it to stand at room temperature for 24 hours.

 The appearance at the first

The appearance after 6 hours

The appearance after 9 hours

The appearance after 24 hours

 

5.      At the end of the reaction period, the benzoin should have separated as fine while crystals. 

 

6.      When the crystallization is completed, collect the crude product by filtration. And wash is with some cold water and ethanol.

The crude benzoin (still containing some Vitamin B1 and some NaOH)

7.      Recrystallize the product from 95% ethanol.

8.      Air dry the final product.

 The final product should be white crystals

Notes

1.      Vitamin B₁ exists in the form of thiamine hydrochloride. It is stable in the acidic condition, but it absorbs water easily, and it is a heat-sensitive reagent, the thiamine in aqueous solution is oxidated easily by oxygen in the air. The rate of oxidation may be accelerated by light and some ions such as cupric ion, ironic ion and magnesium ion. It should be stored in a refrigerator. Since the thiazole ring is broken easily in basic solution, both the aqueous solutions of thiamine hydrochloride and sodium hydroxide should be cooled thoroughly with an ice bath before use.

2.      The control of the pH value is the key to the benzoin condensation of benzaldehyde. So the benzaldehyde used for this experiment must be free of benzoic acid. The benzaldehyde must be redistilled before use.

Experimental Record

Weight of benzaldehyde	6.11 g
Weight of benzoin after recrystallization and air dried	1.69 g
Yield	27.7 %