Reimer Tiemann is a reaction that involves the treatment of phenol with chloroform in aqueous NaoH followed by acid-hydrolysis, where salicylaldehyde is formed. To know more information related to Reimer Tiemann's reaction, the scope, procedure, condition, and mechanism, refer to the full article.
This reaction was discovered by Karl Reimer and Ferdinand Tiemann.
What is Reimer Tiemann Reaction?
On treating phenol with chloroform in the presence of sodium hydroxide, a -CHO group is introduced at the ortho position of the benzene ring leading to the formation of hydroxybenzaldehyde. This ring is known as the Reimer-Tiemann reaction.
The intermediate substituted benzene chloride is hydrolyzed in the presence of alkali to produce salicylaldehyde.
Scope of Reimer-Tiemann Reaction
· The Reimer-Tiemann 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 Reimer-Tiemann reaction may be unsuitable for substrates bearing these functional groups. In addition, many compounds can not withstand being heated in the presence of hydroxide.
Procedure for the Experiment
· Step 1: The solution of the phenol (30.9 mmol, 1.0 eq) and sodium hydroxide (8.0 eq) in 100 ml ethanol/ H20 (2:1) was heated to 70 °C, chloroform (2.0 eq) was added over 1 h.
· Step 2: The resulting mixture was stirred for 3 h, cooled to room temperature, and evaporated to remove ethanol.
· Step 3: The left water solution was adjusted to pH 4~5 and extracted with ethyl acetate.
· Step 4: Common work-up & purification gave the desired aldehyde (41% yield).
Condition for Reimer-Tiemann Reaction
· 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. The two reagents are therefore 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 (the use of 1,4-dioxane as a solvent is an example).
· The reaction typically needs to be heated to initiate the process, however once started the Reimer-Tiemann Reaction can be highly exothermic, this combination makes it prone to thermal runaways.
Mechanism of Reimer-Tiemann Reaction
· 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. (8]
Comparison with other Methods
The direct formylation of aromatic compounds can be accomplished by various methods such as the Gattermann reaction, Gattermann-Koch reaction, Vilsmeier-Haack reaction, or Duff reaction; however, in terms of ease and safety of operations, the Reimer-Tiemann reaction is often the most advantageous route chosen in chemical synthesis. Of the reactions mentioned before, the Reimer-Tiemann reaction is the only route not requiring acidic and/or anhydrous conditions. Additionally, the Gattermann-Koch reaction does not apply to phenol substrates.