[3197-61-3] · C4H4N2O · N-Formylimidazole · (MW 96.10)
(active agent for formylation1)
Alternate Name: 1H-imidazole-1-carbaldehyde.
Physical Data: mp 53-55 °C; dec 60 °C.2
Solubility: sol THF, acetone, chloroform; partially sol CCl4, diethyl ether.
Preparative Method: a solution of 1.5 g (32 mmol) formic acid (98-100%) in 50 mL dry THF is added over a period of 15 min to a vigorously stirred suspension of 5.0 g (31 mmol) N,N´-Carbonyldiimidazole3 in 80 mL dry THF at rt. N,N-Carbonyldiimidazole dissolves rapidly and CO2 is evolved. After 1 h the solvent is evaporated and the product is sublimed directly from the mixture, 35-40 °C/0.2 mmHg, to give 2.53 g (85%) of N-formylimidazole.2
Handling, Storage, and Precautions: like N,N-carbonyldiimidazole, N-formylimidazole is very sensitive to water. It should be kept sealed under an inert atmosphere.
Like other derivatives of N-carbonyldiimidazole, N-formylimidazole is an activated form of formic acid, which can be used as a reactive intermediate in the synthesis of esters, amides, and isocyanides and for the formylation of Wittig reagents.1 The high reactivity of carboxyimidazoles is due to the aromaticity of the imidazole ring. This exerts an electron-withdrawing effect on the exocyclic carbonyl bond, increasing the rate of nucleophilic attack at the carbonyl carbon. In most cases the freshly prepared reagent is used directly, without isolation. Good yields of products are usually obtained. N,N-Carbonyldiimidazole reacts with an equimolar amount of formic acid in THF or chloroform within a few minutes at rt to form N-formylimidazole (eq 1).
Reaction of this intermediate with a nucleophile leads directly to the desired product. One equivalent of alcohol in the presence of a catalytic amount of alcoholate (formed by addition of a base like Sodium Amide4 or 1,8-Diazabicyclo[5.4.0]undec-7-ene5) yields the ester under mild conditions. Even sterically hindered alcohols like t-butanol react readily at rt (eq 1).2 Under similar conditions, thioesters,6 selenoesters,6 and amides2,7,8 can also be obtained. Triphenylphosphine-alkylidenes are readily C-acylated using 0.5 equiv of N-formylimidazole at rt in benzene or benzene/THF to give a-formyl derivatives.9 Wittig reaction of these triphenylphosphine-a-formylalkylidenes leads to a,b-unsaturated aldehydes10 (eq 2) or, after hydrolysis, to the aldehydes RCH2CHO.
A simple synthesis of isoflavones with yields ranging from 60 to 76% was reported by Krishnamurty (eq 3). This involves the reaction between an O-hydroxydeoxybenzoin and N-formylimidazole whereby C-formylation at the benzylic position is followed by cyclization to the corresponding isoflavone.11
In the synthesis of substituted benz[cd]indoles (eq 4), N-formylimidazole was used to transform an amino group into an isocyanide group after dehydration of the resulting formamide with Phosgene/Triethylamine.12,13
In organometallic chemistry, N-formylimidazole can act as a formylating reagent to produce formyl transition metal complexes. These can react with compounds of the type Na2M(CO)4 (M = Fe, Ru, Os) in THF or HMPA in the presence of a Lewis acid such as Trimethyl Borate to produce a mixture of NaM(CO)4CHO (e.g. sodium tetracarbonylformylferrate, sodium tetracarbonylformylruthenate, sodium tetracarbonylformylosmate) and NaM(CO)4H. NaM(CO)4CRO is the product formed from the reaction with alkyl- and phenyl-N-acylimidazoles.14
University of Neuchâtel, Switzerland