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O.A. Ramos Rodríguez et al. / Journal of Molecular Structure 1199 (2020) 127036
antimicrobials [6,7], antivirals [8], antifungals [9], antihistamine
[10] and antioxidant [11]. Derivatives of 4H-1,3-thiazin-4-one have
biological activity and are used as pesticides, herbicides, fungicides
and antituberculosis agents. The compound 2-aryl-2,3-dihydro-
4H- [1,3]thiazino [3,2-a]benzimidazole-4-one under this study and
its crystal was obtained from a different methodology compared to
the one reported by Britsun & Lozinskii [5], to improve the reaction
yield, explore the molecular structure, and determine its antioxi-
dant activity, since it has been described above that this type of
compound presents analgesic, anticonvulsant, antianxiolytic and
antioxidant activity [12].
The importance of antioxidant activity in these compounds lies
in the fact that they offer protection in internal and external
oxidation processes, which results in an excess of reactive mole-
cules that cause cellular aging, cardiovascular alterations and can-
cer [13]. The possible antioxidant activity lies in the structural
characteristic of the system. The presence of thiazine ring allows
conjugation, and the sulphur atom stabilizes the charge. In recent
years, a wide range of spectrophotometric assays has been adopted
to measure antioxidant capacity of foods and compounds, the most
popular being 2,20-azino-bis-3-ethylbenzthiazoline-6-sulphonic
acid (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The
difference between DPPH and ABTS is that the ABTS assay is applied
to a variety of hydrophilic, lipophilic and highly pigmented anti-
oxidant compounds [14].
2. Experimental
2.1. Material and methods
All reagents (Cinnamic acid, 2-mercaptobenzimidazole, 4-
Dimethylaminopyridine
(DMAP)
and
N,N0-Dicyclohex-
ylcarbodiimide (DCC)) were purchased from Sigma Aldrich and
used as received. The solvents used were dried before use by
standard techniques [18]. Analysis of 1H and 13C NMR spectra of
compound III was carried out in CDCl3 as solvent and tetramethyl
silane (TMS) as internal reference, were recorded using Bruker
Ultrashield Plus 400 (1H, 400; 13C, 100.62 MHz) instrument.
Melting point was measured in a Melt-Temp equipment. The most
characteristic functional groups present in the synthesized mole-
cule were identified using a Varian 3100 FT-IR spectrometer of the
Excalibur series in the range 4000e600 cmꢂ1. The elemental
analysis was performed on a Leco TruSpect Micro (C, H, N) analyzer
under standard conditions.
2.1.1. Synthetic procedure 2-aryl-2,3-dihydro-4H- [1,3]thiazino
[3,2-a]benzimidazol-4-one (III)
The compound (III), Scheme 1, was obtained by mixing trans-
In recent years, a wide range of spectrophotometric assays have
been adopted to measure the antioxidant capacity of foods and
compounds, the most popular being 2,20-azino-bis-3-
ethylbenzothiazolin-6-sulfonic acid (ABTS) and the 1,1-diphenyl-
2-picrylhydrazil assay (DPPH). The difference between DPPH and
ABTS is that the ABTS assay applies to a variety of hydrophilic,
lipophilic, and highly pigmented antioxidant compounds [14].
On the other hand, the dizzying development of computation
has allowed theoretical and computational chemistry to flourish.
Under this approach different methodologies have been developed,
such as the density functional theory, which has permitted the
study of chemical systems. One of the problems that has attacked
the theory has been the explanation of the non-classical in-
teractions, specifically with the non-covalent index [15], besides in
solid state the use of Hirshfeld surfaces allows to know the inter
and intramolecular contacts of a crystal [16,17]. Another application
includes the study of chemical reactions, predicting the most
favored reaction mechanisms and the study of the transition state,
being key in the study of antioxidant capacity.
cinnamic
(II)
acid
(1.00 g,
6.7 mmol)
with
2-
mercaptobenzimidazole (I) (1.01 g, 6.7 mmol) and 4-(Dimethyla-
mino)pyridine (DMAP) in catalytic amounts (10%) (0.08 g,
0.67 mmol) in 30 mL of dry CH2Cl2, followed by the slow addition of
N,N0-Dicyclohexylcarbodiimide (DCC) (1.39 g, 6.7 mmol) in 10 mL of
dry CH2Cl2. The reaction mixture was kept in an ice bath with
continue stirring for 1 h, then left at room temperature and con-
stant stirring overnight. Dicyclohexylurea (DCU) was filtered off
and the solvent was removed by evaporation at reduced pressure.
To the dry product 30 mL ethyl acetate was added to perform two
acid washes with HCl (0.05 N) solution, two basic washes with a 5%
solution of K2CO3, and two washes with distilled water. The ethyl
acetate was then dried out with anhydrous magnesium sulphate
and filtered, the solvent was removed by evaporation at reduced
pressure to get the compound.
The resulting compound (III) was a yellow solid crystallizing in a
mixture of dichloromethane-hexane solvents (3:7); (yield 76%,
1.428 g; m. p. 121e122 ꢀC). IR (KBr, nmax, cmꢂ1): 1720.49 (C]O),
1473 (NeCeS), 1451.19 (CeN), 694.52 (CeS); 1H NMR (CDCl3):
d
8.17
ABX 5.41 (1H, m, H12), 3.84
(1H, m, H11), 3.40 (1H, m, H11); 13C NMR:
167.2 (C10), 151.1 (C2),
Here we report the crystalline structure of the compound 2-
aryl-2,3-dihydro4H- [1,3]thiazino [3,2-a]benzimidazole-4-ones,
and its antioxidant activity by experimental and theoretical calcu-
lations, in the search for new compounds with high anti-radical
activity.
(1H, m, H5), 7.63e7.33 (8H, m, Ar),
d
d
142.8 (C8), 137.4 (C13), 132.3 (C9), 129.3 (C15, C17), 128.9 (C14, C18),
127.6 (C5), 125.4 (C6), 124.4 (C4), 118.5 (C7), 42.6 (C12), 41.3 (C11).
Elemental analysis calculated for C16H12N2OS: C 68.55, H 4.31, N
9.99%; found: C 68.57, H 4.47, N 9.95%.
Scheme 1. Schematic representation of the synthesis of (III).