The ReimerâÂÂTiemann reaction is a chemical reaction used for the ortho-formylation of phenols. with the simplest example being the conversion of phenol to salicylaldehyde. The reaction was first reported by Karl Reimer and Ferdinand Tiemann.
Chloroform (1) is deprotonated by a strong base (normally hydroxide) to form the chloroform carbanion (2) which will quickly alpha-eliminate to give dichlorocarbene (3); this is the principal reactive species. The hydroxide will also deprotonate the phenol (4) to give a negatively charged phenoxide (5). The negative charge is delocalised into the aromatic ring, making it far more nucleophilic. Nucleophilic attack on the dichlorocarbene gives an intermediate dichloromethyl substituted phenol (7). After basic hydrolysis, the desired product (9) is formed.
By virtue of its two electron-withdrawing chlorine groups, the carbene (3) is highly electron deficient and is attracted to the electron rich phenoxide (5). This interaction favors selective ortho-formylation, consistent with other electrophilic aromatic substitution reactions.
Hydroxides are not readily soluble in chloroform, thus the reaction is generally carried out in a biphasic solvent system. In the simplest sense this consists of an aqueous hydroxide solution and an organic phase containing the chloroform. Therefore, the two reagents are separated and must be brought together for the reaction to take place. This can be achieved by rapid mixing, phase-transfer catalysts, or an emulsifying agent such as 1,4-dioxane as solvent.
The reaction typically needs to be heated to initiate the process; however, once started, the ReimerâÂÂTiemann Reaction can be highly exothermic. This combination of properties makes it prone to thermal runaways.
The ReimerâÂÂTiemann reaction is effective for other hydroxy-aromatic compounds, such as naphthols. Electron rich heterocycles such as pyrroles and indoles are also known to react.
Dichlorocarbenes can react with alkenes and amines to form dichlorocyclopropanes and isocyanides respectively. As such the ReimerâÂÂTiemann reaction may be unsuitable for substrates bearing these functional groups. In addition, many compounds can not withstand being heated with hydroxide.
The direct formylation of aromatic compounds can be accomplished by various methods such as the Gattermann reaction, GattermannâÂÂKoch reaction, VilsmeierâÂÂHaack reaction, or Duff reaction; however, in terms of ease and safety of operations, the ReimerâÂÂTiemann reaction is often the most advantageous route chosen in chemical synthesis. Of the reactions mentioned before, the ReimerâÂÂTiemann reaction is the only route not requiring acidic and/or anhydrous conditions. Additionally the GattermannâÂÂKoch reaction is not applicable to phenol substrates.
Using carbon tetrachloride instead of chloroform gives a carboxylic acid product instead of an aldehyde. For example, this reaction variant with phenol would yield salicylic acid.
Reimer and Tiemann published several papers on the subject. The early work has been reviewed.