The reaction can be simplified by replacing the HCN/AlCl3 combination with zinc cyanide.[4] Although it is also highly toxic, Zn(CN)2 is a solid, making it safer to work with than gaseous HCN.[5] The Zn(CN)2 reacts with the HCl to form the key HCN reactant and Zn(Cl)2 that serves as the Lewis-acid catalyst in-situ. An example of the Zn(CN)2 method is the synthesis of mesitaldehyde from mesitylene.[6]
The Gattermann–Koch reaction, named after the German chemists Ludwig Gattermann and Julius Arnold Koch,[7] is a variant of the Gattermann reaction in which carbon monoxide (CO) is used instead of hydrogen cyanide.[8]
Unlike the Gattermann reaction, this reaction is not applicable to phenol and phenol ether substrates.[5] Although the highly unstable formyl chloride was initially postulated as an intermediate, formyl cation (i.e., protonated carbon monoxide), [HCO]+, is now thought to react directly with the arene without the initial formation of formyl chloride.[9] Additionally, when zinc chloride is used as the Lewis acid instead of aluminum chloride for example, or when the carbon monoxide is not used at high pressure, the presence of traces of copper(I) chlorideornickel(II) chloride co-catalyst is often necessary. The transition metal co-catalyst may server as a "carrier" by first reacting with CO to form a carbonyl complex, which is then transformed into the active electrophile.[10]
^Karrer, P. (1919).『Über Oxycarbonylverbindungen I. Eine neue Synthese von』[Hydroxycarbonyl compounds. I. A new synthesis of hydroxyaldehydes]. Helvetica Chimica Acta (in German). 2 (1): 89–94. doi:10.1002/hlca.19190020109.
