Formylation refers to any chemical processes in which a compound is functionalized with a formyl group (-CH=O). In organic chemistry, the term is most commonly used with regards to aromatic compounds (for example the conversion of benzene to benzaldehyde in the Gattermann–Koch reaction). In biochemistry the reaction is catalysed by enzymes such as formyltransferases. Formylation generally involves the use of formylation agents, reagents that give rise to the CHO group. Among the many formylation reagents, particulary important are formic acid and carbon monoxide. A formylation reaction in organic chemistry refers to organic reactions in which an organic compound is functionalized with a formyl group (-CH=O). The reaction is a route to aldehydes (C-CH=O), formamides (N-CH=O), and formate esters (O-CH=O). Formylation agents A reagent that delivers the formyl group is called a formylating agent. formic acid Dimethylformamide and phosphorus oxychloride in the Vilsmeier-Haack reaction. Hexamethylenetetramine in the Duff reaction and the Sommelet reaction Carbon monoxide and hydrochloric acid in the Gattermann-Koch reaction Cyanides in the Gattermann reaction. This method synthesizes aromatic aldehydes using hydrogen chloride and hydrogen cyanide (or another metallic cyanide as such zinc cyanide) in the presence of Lewis acid catalysts: Chloroform in the Reimer-Tiemann reaction dichloromethyl methyl ether in Rieche formylation. Formylation of 3-methylamino-1-propanol with formamide (instead of ethyl chloroformate) as a protecting group in the preparation of Protriptyline. Formamide was also used (instead of formic acid) in the synthesis of primidone. A particularly important formylation process is hydroformylation, which converts alkenes to the homologated aldehyde. Aromatic formylation Formylation reactions are a form of electrophilic aromatic substitution and therefore work best when the aromatic starting materials are electron-rich. Phenols are very commonly encountered as they can be readily deprotonated to form phenoxides which are excellent nucleophiles, other electron rich substrates such as mesitylene, pyrrole, or fused aromatic rings can also be expected to react. Benzene will react under aggressive conditions but deactivated rings such as pyridine are difficult to formylate effectively. Phenol would normally be expected to react to give a mixture of ortho and para products, however many formylation reactions will selectively give only the ortho product (e.g. salicylaldehyde). This selectivity can be attributed to an attractive interaction between the phenoxide and the formylating reagent. Ionic interactions have been invoked betwee with cationic nitrogen centres in the Vilsmeier–Haack reaction and Duff reaction or coordination to high oxidation metals in the Casiraghi formylation and Rieche formylation (c.f. Kolbe–Schmitt