Synthesis of Acetylferocene
Abstract
Introduction
The acylation of the α carbon position of a carbonyl group is one of the greatest breakthroughs that has benefited chemists in organic synthesis particularly when in need of building a carbon skeleton of interest in a molecule.
For one to be able perform this acylation technique, there are two mar approaches which are employable. The first method involves the deprotonation of the α-Carbon atom which has a pKa known to be ̴20 through the use of a strong base for instance, n-butyllithium (n-BuLi) or Lithium diisopropylamide (LDA). The result of this is the production of resonance stabilised enolate ion which perfectly be acylated through treatment with an acyl halide yielding the product of interest.
However, the major limitation of using this type of chemistry in organic synthesis is that if there are other base sensitive functional groups we wish to retain in our starting material, the use of a strong base will lead to the formation of vast amounts of unanticipated acylation reaction products.
In 1954, Gilbert Stork developed another synthesis method that effectively yield the same result as using the enolate approach without necessarily employing a strong base. This method is through enamine synthesis approach where the carbonyl compound to the acylated is first reacted with a secondary amine in an acid-catalysed reaction. Enols and enamines are similar in terms of chemical properties because they are all nucleophilic because of that lone pair of electrons. The mechanism of the enamine formation reaction has some illustration below;
In the presence of an electrophile such as an acyl halide, the enamine the enamine will react at the carbon leading to the formation of iminium ion which can be easily hydrolysed forming the original carbonyl group. in summary the overall acylation reaction of a carbonyl compound follows the route of first synthesising the enamine, the acylation and finally the hydrolysis of the iminium ion to
Introduction
The acylation of the α carbon position of a carbonyl group is one of the greatest breakthroughs that has benefited chemists in organic synthesis particularly when in need of building a carbon skeleton of interest in a molecule.
For one to be able perform this acylation technique, there are two mar approaches which are employable. The first method involves the deprotonation of the α-Carbon atom which has a pKa known to be ̴20 through the use of a strong base for instance, n-butyllithium (n-BuLi) or Lithium diisopropylamide (LDA). The result of this is the production of resonance stabilised enolate ion which perfectly be acylated through treatment with an acyl halide yielding the product of interest.
However, the major limitation of using this type of chemistry in organic synthesis is that if there are other base sensitive functional groups we wish to retain in our starting material, the use of a strong base will lead to the formation of vast amounts of unanticipated acylation reaction products.
In 1954, Gilbert Stork developed another synthesis method that effectively yield the same result as using the enolate approach without necessarily employing a strong base. This method is through enamine synthesis approach where the carbonyl compound to the acylated is first reacted with a secondary amine in an acid-catalysed reaction. Enols and enamines are similar in terms of chemical properties because they are all nucleophilic because of that lone pair of electrons. The mechanism of the enamine formation reaction has some illustration below;
In the presence of an electrophile such as an acyl halide, the enamine the enamine will react at the carbon leading to the formation of iminium ion which can be easily hydrolysed forming the original carbonyl group. in summary the overall acylation reaction of a carbonyl compound follows the route of first synthesising the enamine, the acylation and finally the hydrolysis of the iminium ion to
References: 1. J. S. Nimitz, Experiments in Organic Chemistry, From Microscale to Macroscale, J.S. Prentice Hall, Englewood Cliffs, 1991 2. L.M. Harwood and C>J> Moody, Experimental Organic Chemistry: Principles and Practice, Blackwell Scientific Publications, Oxford, 1989 3. R. Hamilton and S. Hamilton, Thin Layer Chromatography, Willey, Chichester, 1987