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showed two different conformers; this result may have been due mL) then added and product extracted using ethyl acetate (3 ꢁ 3
to the structural exibilities of 3r–t being relatively high, and mL). The organic layers were collected, washed with an aqueous
greater than those of compounds 3a–q, which have cyclic Na2S2O3 solution and dried over anhydrous Na2SO4. Aer
enaminone moieties. For product 3s, the ratio of its conformers partial vaporization of solvent, the product was precipitated and
was calculated from the 1H-NMR spectrum to be 83 : 17. The the mixture was ltered to give the pure enaminone 1 as a white
methylene protons of the major conformer resonated as two solid.
distinct doublets due to their diastereotopic nature, but they
displayed a simple pattern in the minor conformer (Fig. 1).
General procedure for synthesizing azocine derivatives 3a–t
Surprisingly, the two distinct doublets of methylene protons of
In each case, a mixture of enaminone 3 (1 mmol), Et3N (1
the major conformer of 3s at room temperature converted to
mmol), and acenaphthoquinone 2 (1 mmol) in EtOH (4 mL) was
placed in a ask and the mixture was stirred for 12 hours at
reux conditions. The progress of the reaction was monitored
a sharp singlet when its 1H-NMR spectrum was recorded at 80 ꢀC.
Moreover, the ratio of conformers was determined from the
spectrum recorded at 80 ꢀC to be 94 : 16 (Fig. 1).
by performing TLC using EtOAc/n-hexane as an eluent. Aer
The molecular structures of all products 3a–t were also
completion of the reaction, the reaction mixture was cooled to
elucidated from their IR, 1H-NMR, 13C-NMR and HRMS spectra.
room temperature and H5IO6 (1 mmol) was added to the ask
and the resulting mixture was stirred for an additional 1 hour.
The reaction mixture was ltered and the crude product was
recrystallized from ethanol to afford the pure product 3.
Finally, the structure of product 3c was determined unambig-
uously from an X-ray diffraction study (Fig. 2).
We proposed a general mechanism for the reactions, as
shown in Scheme 2. According to the mechanism, rst enami-
none 1 attacked acenaphthoquinone 2 to form intermediate A,
followed by a rearrangement of A to form intermediate B and
then vicinal diol C. Then reacting C with periodic acid produced
Conflicts of interest
There are no conicts to declare.
intermediate D, which then underwent a rearrangement to form
product 3 with the loss of water and iodic acid molecules.
In summary, we have developed a novel pathway for the
syntheses of new azocine derivatives via the reactions of
enaminones with acenaphthoquinone followed by metal-free
periodic acid-mediated oxidative cleavages of the correspond-
ing vicinal diols. The novelty of the method in combination with
high yields, short reaction times, and mild reaction conditions
makes this procedure an especially attractive method for the
syntheses of the titled compounds.
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Experimental
General information
The chemicals used in this work were purchased from Merck
and Sigma-Aldrich chemical companies and were used without
purication. The progress of the reactions and the purity levels
of the compounds were monitored using thin layer chroma-
tography (TLC) analytical silica gel plates (Merck 60 F250).
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General procedure for preparing enaminones 1a–t
In each case, 1,3-diketone (5 mmol), amine (5 mmol), I2 (0.1
mmol), and CH3CN (5 mL) were added to a reaction tube. The
tube was then sealed and its contents stirred at room temper-
ature for 1 h. In most cases, enaminone 1 precipitated from the
reaction mixture as white crystals, which were collected on lter
paper and further puried by washing them with cool acetoni-
trile (2 ꢁ 2 mL). When the product was soluble in acetonitrile,
the solvent was removed under reduced pressure, with water (10
20556 | RSC Adv., 2020, 10, 20552–20557
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