Green chemistry - inherently safer experimentation

Green Chemistry in Practice: Thiamine-Catalyzed Benzoin Condensation

The following experiment provides an illustration of the types of experimentation made possible by a Green curriculum. While simple in practice, it provides exposure to important organic chemical principles and laboratory techniques while at the same time illustrating a number of principles of Green Chemistry.  

The so-called benzoin condensation, discovered serendipitously by Friedrich Wöhler and Justus von Liebig [[i]], converts two equivalents of an aldehyde into an alpha-hydroxyketone. It is a very efficient reaction, incorporating each atom of the reactant into the product. However, the reaction is catalyzed by cyanide ion, requiring the use of cyanide salts which are highly toxic and which if exposed to acidic conditions can generate the volatile and toxic gas, hydrogen cyanide.

More than 100 years after the discovery of the benzoin condensation, it was found that thiamine (vitamin B1) could be used in place of cyanide [[i]]. This represents one of the earliest reports of the use of biologically derived reagents as tools in the synthetic organic chemistry laboratory. Current biologically inspired or assisted synthetic strategies include the use of “cofactors” (such as thiamine), purified single enzymes and mixtures of enzymes, and whole organisms (e.g., yeast, containing a wide range of enzymes and cofactors) to effect chemical transformations.

thiamine hydrochloride

 

In this experiment, furfural is used in place of the traditional starting material, benzaldehyde. The experiment illustrates a number of Green Chemistry principles.

 

  • Use of renewable feed stocks – furfural is obtained from the dry distillation of corn cobs or other agricultural wastes.
  • Design of efficient chemical reactions – each atom of the aldehyde starting material ends up in the product.
  • Use of safer reagents – thiamine is used in place of toxic cyanide.
  • Use of catalysis – thiamine is not consumed in the reaction.
  • Use of safer solvents – water and ethanol are used instead of more hazardous organic solvents.

                                             furfural                              furoin 

1.  With magnetic stirring, dissolve 0.30 g of thiamine hydrochloride in 3 mL of 95% ethanol, and then add 0.45 mL of water.

2.  Drop wise, add 0.90 mL of a 2N aqueous solution of sodium hydroxide (corresponding to 8.0 g NaOH in 100 mL water). This should resemble a titration – addition of each drop should produce a bright yellow color that disappears upon stirring. When all the NaOH solution has been added, the solution should remain pale yellow. If it does not, add more NaOH solution.

3.  Add approximately 0.73 mL of furfural and mix thoroughly, then seal the reaction vessel and let it stand for at least 24 hours.

4.  Cool the reaction mixture in an ice bath and add several mL of water to ensure complete precipitation of the product. Isolate the crude solid product by filtration and, after air drying, determine its mass.

5.  Recrystallize the product from 95% ethanol (melting point 134-138 °C).