Recent theoretical and experimental data on the reactions and the mechanisms of imidazole formation under
simultaneous interaction of mono- and dicarbonyl compounds with ammonia and amines in aqueous solutions were reported
in [9, 10]. In [9], a mechanisms of imidazole formation through the interaction of glyoxal, formaldehyde, and methylamine
through a key intermediate diimine was suggested. The authors of [10] considered two variants of imidazole formation:
through the diimine intermediate attacking the aldehyde carbonyl group and through two monoimine intermediates that form
a ring when interacting with each other. However, neither of works [9, 10] provides clear evidences that these intermediates
and mechanisms actually exist.
The analysis of literature devoted to such processes reveals only scattered data on the reactions of imidazole
formation; however, there are currently no confirmed data concerning specific mechanisms and the structures of possible
intermediates and byproducts for these processes. Therefore, the aim of the present work is to study in details the mechanism
of 2-methylimidazole formation through the reaction of acetaldehyde, glyoxal, and ammonia by identifying the structures of
long-living (in experimental conditions) intermediates and byproducts using in situ NMR spectroscopy. Since acetaldehyde
and aqueous ammonia are highly volatile, all these three reactants are difficult to be placed simultaneously into the NMR
tube; therefore, we used an adduct of acetaldehyde and ammonia, 2,4,6-trimethyl-1,3,5-hexahydrotriazine trihydrate
(acetaldehyde ammonia trimer, THT) [11], as a synthetic equivalent of acetaldehyde and ammonia for the reaction with
glyoxal to form 2-MI (Scheme 1).
EXPERIMENTAL
The qualitative composition of the reaction mixture was studied in situ on a 400 MHz Bruker AVANCE III HD
NMR spectrometer. Acetaldehyde ammonia trimer (Sigma Aldrich) was placed in a tube and dissolved in deuterated water.
Then the tube was placed in the NMR spectrometer, the magnetic field was adjusted, then the tube was taken out and filled
with a calculated amount of glyoxal (Sigma Aldrich 40% aqueous solution) according to the molar ratio THT:glyoxal = 1:1.
The moment of glyoxal introduction was assumed to be the reaction starting point. The tube with the reaction mixture was
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first placed into an ultrasonic bath for 20 s and then into the NMR spectrometer to record the spectra. The H, C, DEPT-
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135, HSQC H– C, HMBC H– N NMR spectra were recorded after the reaction termination at a temperature of 294 K.
Liquid ammonia was used as the external reference to determine the chemical shift of nitrogen. Initial and final pH values of
the reaction mixture were 10.67 and 9.65, respectively.
RESULTS AND DISCUSSION
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1D NMR spectroscopy. Fig. 1 shows the H NMR spectrum of the reaction mixture at the final reaction moment;
proton signals of the reagent (THT) and the reaction product (2-MI) are indicated. The chemical shifts of the protons of the
trimer methyl group and that of the quartet of methine protons occur at 1.07 ppm and 3.55 ppm, respectively. The singlet of
protons of the methyl substituent in 2-MI occurs at 2.18 ppm, and the signals of methine protons of the imidazole ring were
recorded in the weak field (6.79 ppm). The overall spectrum of the reaction mixture (Fig. 1) contains the signals of both the
reagent and the reaction product. However, there are additional signals that can be assigned to possible intermediate reaction
products or byproducts. In the region of 1 ppm, there are proton doublets that can be assigned to the formation of structures
close to the one of acetaldehyde ammonia trimer and are its decomposition products (linear trimers, dimers, and monomers).
This assumption is confirmed by the appearance of quartet signals at 3.50-5.20 ppm assigned to the methine protons. Also,
there is an unidentified singlet signal (3.49 ppm) next to the quartet of the CH group of the trimer ring.
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Fig. 2 shows the C NMR spectrum of the reaction mixture. As can be seen, the reaction mixture contains the
signals of the reagent and the reaction product: the signals of methyl groups of 2-MI and THT occur at 12.3 ppm and
20.2 ppm, respectively, while the signals of methine carbons of THT were found at 64.4 ppm, and those of methine groups of
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the imidazole ring at 121.2 ppm. There is a signal of the quaternary carbon of 2-MI at 145.8 ppm. Also, the С NMR
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Bakibaev, A. A.
