Reimer-Tiemann Reaction
The Reimer-Tiemann reaction is the formylation of phenols using chloroform in the presence of a strong base, normally an aqueous hydroxide solution.
General features:
1. The reaction is an electrophilic aromatic substitution that occurs under basic conditions in a protic solvent. 2. The substrate is dissolved in 10–40% alkali hydroxide, excess chloroform is added, and the biphasic solution is vigorously stirred at elevated temperatures. 3. The regioselectivity is not high, but ortho-formyl products predominate. But when the reaction is conducted in the presence of cyclodextrins, the p-formyl product is formed predominantly. 4. When the ortho-position is already substituted, para-formyl phenols are generated instead.
Reimer-Tiemann Reaction
Reaction Mechanism
1. Chloroform is deprotonated by the base to generate the chloroform carbanion. 2. Alpha-elimination gives dichlorocarbene. 3. Nucleophilic attack by the phenoxide ion leads to a series of intermediates that provide the desired product upon basic hydrolysis.
Example
Experimental Procedure
The solution of the phenol (30.9 mmol, 1.0 eq) and sodium hydroxide (8.0 eq) in 100 mL ethanol/H2O (2:1) was heated to 70 ºC, chloroform (2.0 eq) was added over 1 h. The resulting mixture was stirred 3 h, cooled to room temperature, evaporated to remove ethanol. The left water solution was adjusted to pH 4~5 and extracted with ethyl acetate. Common work-up and purification gave the desired aldehyde (41% yield).
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