EHOOPrÁHH^ECRAa XHMH3, 2014, moM 40, № 3, c. 377-378
SYNTHESIS OF SOME NEW BISTRIAZOLIDINE DERIVATIVES AND THEIR BIOLOGICAL ACTIVITY © 2014 Amal S. Yanni#
Chemistry Department, Faculty of Science, Assiut University, Assiut, 71526 Egypt Received June 13, 2013; in final form August 29, 2013
Aromatic aldazines with thiocyanates in glacial acetic acid produce corresponding bistriazolidine derivatives via criss-cross cycloaddition reaction. The chemical structure was confirmed by elemental and spectral analysis. Biological activity against some microorganisms was tested.
Keywords: synthesis, bistriazolidine, cycloaddition, antimicrobial activity.
DOI: 10.7868/S0132342314020158
INTRODUCTION
1,2,4-Triazoles are associated with diverse pharmacological activities such as analgesic, antiasthmatic, diuretic, antihypertensive, anticholinergic, antibacterial, antifungal, and anti-inflammatory activities [1—5]. These biological data prompted us to synthesize some new bistriazolidine derivatives.
RESULTS AND DISCUSSION
Cyclic diene systems containing N or O atoms do not appear to undergo normal Diels Alder reactions [6]. Wagner [7] found that heating one mol of benzalazine with 2 mol of maleic anhydride to 100°C in dry benzene for several hours gave an addition compound through simultaneous 1,3- and 2,4-addition of2 moles ofmaleic anhydride to benzalazine, which was designated as criss-cross addition. Moreover, aromatic 1,4-disubsti-tuted 1,4-diazabuta-1,3-dienes with thiocyanates in glacial acetic acid via criss-cross cycloaddition produce the corresponding perhydroimidazo[4,5-d]imidazole-2,5-dithiones [8]. Similarly, as continuation of my previous work [9—12], for the following criss-cross reaction, aromatic aldazines (Ia—c) (such as salicalazine, cinnamalazine, furfuralazine, and/or acetophenona-zine) were in one portion added to a prepared solution of potassium thiocyanate in glacial acetic acid and left to react under stirring for 1 h (Scheme). The solution was poured on water and the precipitate formed was filtered off to produce bistriazolidine derivatives (III) and (IV). Separation by pouring the reaction mixture into water seems to be the best method to isolate the product and get rid of acetic acid and inorganic salts. Therefore, the mentioned working up procedure represents a good way to attain pure compounds. The
* Corresponding author (e-mail: profayanni@yahoo.com).
structure of the synthesized compounds was assigned by elemental and spectral analyses.
R
RCH
NI
-CHR
1 HN.
KNCS/ acetic acid
(I)
or
NH
R (III)
CH3
I 3
,C~ C6H
N
I
N
6H5
V
H3Cv/C6H5
-N NH
H3C-C
C6H5
(II)
HN^/N-H3C C6H5
(IV)
Scheme. R = -C6H4-o-OH(IIIa),-CH=CH-C6H5 (Illb), or C4H3O (IIIc).
Huisgen [13] suggested that criss-cross reaction can best be represented by series of two [3+2]-cycloaddition steps. Azomethine imine [6] (V) was postulated as a key intermediate.
Y
,CHR -N+
HNX ^N-CH I
R (V)
The compounds produced satisfactory results in elemental and spectral analyses. As for their antimicrobial properties, only 1,5-di-o-hydroxysubstituted bis-
S
378
AMAL S. YANNI
triazolidine (IIIa) exhibited moderate activity against Aspergillus niger and A. fumigatus (growth inhibition zone of 7 mm for both), while other compounds showed week or no potency.
EXPERIMENTAL
All melting points are uncorrected. IR spectra were recorded (KBr) with a Perkin-Elmer 1430 spectrophotometer. XH NMR spectra were obtained on a Varian EM 399.65 MHz equipment. MS spectra were recorded with a Jeol the MS route JMS-600H. Aromatic aldazines (I) and/or (II) were prepared according to the known procedures by condensation of aromatic aldehydes and hydrazine sulphate.
1,5-Disubstituted-2^,6ff-perhydrotriazolo-[1,2-a]triazole-3,7-dithiones (IIIa—c) and (IV). Aldazine (I) and/or (II) (1 mmol) was added in one portion to a solution of potassium thiocyanate (0.5 g, 5.15 mmol) in glacial acetic acid (15 mL). After 1 h of stirring, the reaction mixture was poured into water (200 mL). The product was filtered off and washed with water (20 mL) and ethanol (10 mL) and dried. Yield 50-70%.
1,5-Di- 0-hydroxyphenyl-2#,6#-perhydrotriazo-lo[1,2-a]triazole-3,7-dithione (IIIa). Adduct (IIIa), R = -C6H4-o-OH, is obtained from salicalazine and potassium thiocyanate in 48% yield. It is a pale yellow substance, m.p. 210°C. Anal Calcd. for C16H14N4O2S2 (358.46): C, 53.60; H, 3.94; N, 15.63; S, 17.89. Found: C, 53.71; H, 4.0; N, 15.70; S, 17.95. IR (cm-1): v = = 3450 b (OH); 3100 (NH); 1480 and 1270 (C-N), 1190 (C=S). 1H NMR (CDCl3): 8 = 6.93 (2H, 2CH-N); 6.95-7.53 (m, 8Ar-H); 8.9 (s, 2 H, 2 NH); 11.35 (s, 2H, 2-OH). MS m/z(%): [M+] 358.03 (1.3).
1,5-Distyryl-2^,6^-perhydro-triazolo[1,2-a]tria-zole-3,7-dithione (IIIb). Adduct (IIIb), R = -CH=CH-C6H5, is obtained from cinnamalazine and potassium thiocyanate in 68% yield. It is a yellow substance, m.p. 118-120°C. Anal Calcd. for C20H18N4S2 (378.56): C, 63.45; H, 4.80; N, 14.80; S, 16.94. Found: C, 63.50; H, 4.87; N, 14.86; S, 16.99. IR (cm-1): v = 3200 (NH); 3058 (CH st of alkene); 1495 and 1245 (C-N), 1160 (C=S). MS m/z (%): [M+1] 379.0 (0.4).
1,5-Difuryl-2^,6^-perhydrotriazolo-[1,2-a]tria-zole-3,7-dithione (IIIc). Adduct (IIIc), R = -C4H3O, is obtained from furalazine and potassium thiocyanate in 50% yield. It is a buff substance, m.p. 172°C. Anal Calcd. for C12H10N4O2S2 (306.38): C, 47.04; H, 3.30; N, 18.29; S, 20.90. Found: C, 47.35; H, 3.35; N, 18.33; S, 20.95. IR (cm-1): v = 3186 (NH); 1490 and 1230 (C-N), 1170 (C=S). 1H NMR (DMSO): 8 = = 6.48 (4 H, furyl), 6.84 (s, 2 H, 2 CH-N), 7.74 (s, 2H, furyl), 11.35 (s, 2 H, 2 NH), disappeared on addition of D2O. MS m/z (%): [M+2] 308.0 (1.8).
1,5-Dimethyl-1,5-diphenyl-2^,6^-perhydrotria-zolo-[1,2-a]triazole-3,7-dithione (IV). Adduct (IV), is obtained from acetophenonazine and potassium thiocyanate in 15% yield. It is a colorless product,
m.p. 165°C. Anal Calcd. for C18H18N4S2 (354.54): C, 60.97; H, 5.13; N, 15.81; S, 18.09. Found: C, 61.04; H, 5.05; N, 15.93; S, 18.17. IR (cm-1): v= 3170 (NH); 1480 and 1230 (C-N), 1160 (C=S). MS m/z (%): [M+] 354.93 (0.8).
Antimicrobial activity. The fungal species were grown in sterilized 9.0 cm Petri dishes containing potato dextrose agar (PDA) supplemented with 0.05% chloramphenicol to suppress bacterial contamination [14]. From these culture, agar discs (10 mm diameter) containing spores and hyphae were transferred asepti-cally to screw-topped vials containing 20 mL sterile distilled water. After thorough shaking, 1 mL samples of the spore suspension were pipetted into sterile Pertri dishes, followed by the addition of 15 mL liquefied PDA medium which was then left to solidify. The tested compounds (IIIa-c) were dissolved in ethylene glycol to give 2.0% concentration. Antifungal activity was determined according to a method reported by Bauer et al. [15] using 3 mm diameter filter papers discs (Watmann No. 3) loaded with 10 ^L of the solution under investigation (2.0%). The discs were placed on the surface of the fungal culture which were incubated at 30°C. The diameter of the inhibition zone around each disc was measured.
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EHOOPrAHH^ECEAH XHMH3 tom 40 № 3 2014
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