Synthesis of some new bistriazolidine derivatives and their biological activity

Article abstract of DOI:10.1134/S1068162014020150

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

Full text of DOI:10.1134/S1068162014020150

ISSN 1068ꢀ1620, Russian Journal of Bioorganic Chemistry, 2014, Vol. 40, No. 3, pp. 350–351. © Pleiades Publishing, Ltd., 2014.
Synthesis of Some New Bistriazolidine Derivatives
and Their Biological Activity1
Amal S. Yanni
Chemistry Department, Faculty of Science, Assiut University, Assiut, 71526 Egypt
Abstract—Aromatic aldazines with thiocyanates in glacial acetic acid produce corresponding bistriazolidine
derivatives via crissꢀcross 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: 10.1134/S1068162014020150
2 1
INTRODUCTION
The structure of the synthesized compounds was assigned
by elemental and spectral analyses.
1,2,4ꢀTriazoles are associated with diverse pharmaꢀ
cological activities such as analgesic, antiasthmatic,
diuretic, antihypertensive, anticholinergic, antibacteꢀ
rial, antifungal, and antiꢀinflammatory activities [1–5].
These biological data prompted us to synthesize some
new bistriazolidine derivatives.
R
S
CHR
N
NH
S
N
N
KNCS/
acetic acid
HN
N
RCH
(I)
(III)
R
or
CH3
C C6H5
RESULTS AND DISCUSSION
H3C C6H5
S
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 benzaꢀ
N
N
N
N
NH
S
HN
H3C C
C6H5
(II)
lazine with 2 mol of maleic anhydride to 100°C in dry
H3C C6H5
benzene for several hours gave an addition compound
through simultaneous 1,3ꢀ and 2,4ꢀaddition of
2 moles of maleic anhydride to benzalazine, which
was designated as crissꢀcross addition. Moreover, aroꢀ
matic 1,4ꢀdisubstituted 1,4ꢀdiazabutaꢀ1,3ꢀdienes
with thiocyanates in glacial acetic acid via crissꢀcross
cycloaddition produce the corresponding perhyꢀ
droimidazo[4,5ꢀd]imidazoleꢀ2,5ꢀdithiones [8]. Simiꢀ
larly, as continuation of my previous work [9–12], for
the following crissꢀcross reaction, aromatic aldazines
(IV)
Scheme.R = –C6H4ꢀ
or –C4H3O (IIIc).
oꢀOH(IIIa),–CH=CHꢀC6H5 (IIIb),
Huisgen [13] suggested that crissꢀcross reaction
can best be represented by series of two [3 + 2]ꢀ
cycloaddition steps. Azomethine imine [6] (
V) was
postulated as a key intermediate.
(Ia–c) (such as salicalazine, cinnamalazine, furfuralaꢀ
S
CHR
N+
zine, and/or acetophenonazine) 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 bistriazoliꢀ
dine 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 inorꢀ
ganic salts. Therefore, the mentioned working up proceꢀ
dure represents a good way to attain pure compounds.
HN
N
–
CH
R
(V)
The compounds produced satisfactory results in
elemental and spectral analyses. As for their antimiꢀ
crobial properties, only 1,5ꢀdiꢀ
bistriazolidine (IIIa) exhibited moderate activity
against Aspergillus niger and A. fumigatus (growth inhiꢀ
oꢀhydroxysubstituted
1
The article is published in the original.
Corresponding author: eꢀmail: profayanni@yahoo.com.
2
350

SYNTHESIS OF SOME NEW BISTRIAZOLIDINE DERIVATIVES
351
bition zone of 7 mm for both), while other compounds 60.97; H, 5.13; N, 15.81; S, 18.09. Found: C, 61.04;
showed week or no potency.
H, 5.05; N, 15.93; S, 18.17. IR (cm–1):
1480 and 1230 (C–N), 1160 (C=S). MS
+] 354.93 (0.8).
Antimicrobial activity. The fungal species were
ν
= 3170 (NH);
(%):
m/z
[M
EXPERIMENTAL
All melting points are uncorrected. IR spectra were
recorded (KBr) with a PerkinꢀElmer 1430 spectroꢀ
photometer. H NMR spectra were obtained on a
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 aseptiꢀ
cally to screwꢀtopped 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
1
Varian EM 399.65 MHz equipment. MS spectra were
recorded with a Jeol the MS route JMS–600H. Aroꢀ
matic aldazines (
ing to the known procedures by condensation of aroꢀ
matic aldehydes and hydrazine sulphate.
1,5ꢀDisubstitutedꢀ2H, ꢀperhydrotriazoloꢀ[1,2ꢀ
triazoleꢀ3,7ꢀdithiones (IIIa–c) and (IV). Aldazine (
I) and/or (II) were prepared accordꢀ
6H
a]
I)
and/or (II) (1 mmol) was added in one portion to a soꢀ
lution of potassium thiocyanate (0.5 g, 5.15 mmol) in
glacial acetic acid (15 mL). After 1 h of stirring, the reꢀ
action 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%.
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
tion under investigation (2.0%). The discs were placed
on the surface of the fungal culture which were incuꢀ
bated at 30 . The diameter of the inhibition zone
µL of the soluꢀ
1,5ꢀDiꢀ
lo[1,2ꢀ ]triazoleꢀ3,7ꢀdithione (IIIa). Adduct (IIIa),
R = –C6H4ꢀ ꢀOH, is obtained from salicalazine and
potassium thiocyanate in 48% yield. It is a pale yellow
substance, mp 210 C. Anal. calcd. for C16H14N4O2S2
oꢀhydroxyphenylꢀ2H,6Hꢀperhydrotriazoꢀ
a
°
C
o
around each disc was measured.
°
REFERENCES
(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):
= 3450 b (OH); 3100 (NH); 1480 and 1270 (C–N),
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ν
1
1190 (C=S). H NMR (CDCl3):
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H
a
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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):
= 3200 (NH);
3058 (CH st of alkene); 1495 and 1245 (C–N), 1160
(C=S). MS (%): [
+1] 379.0 (0.4).
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ν
m/z
M
H
H
a]triaꢀ
zoleꢀ3,7ꢀdithione (IIIc). Adduct (IIIc), R = –C4H3O,
is obtained from furalazine and potassium thiocyanate
in 50% yield. It is a buff substance, mp 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,
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18.33; S, 20.95. IR (cm–1):
ν
= 3186 (NH); 1490 and
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= 6.48 (4 H, furyl), 6.84 (s, 2 H, 2 CH–N), 7.74
(s, 2 H, furyl), 11.35 (s, 2 H, 2 NH), disappeared on
addition of D2O. MS (%): [
+2] 308.0 (1.8).
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zoloꢀ[1,2ꢀ ]triazoleꢀ3,7ꢀdithione (IV). Adduct (IV), is
obtained from acetophenonazine and potassium thioꢀ
cyanate in 15% yield. It is a colorless product,
mp 165 C. Anal. calcd. for C18H18N4S2 (354.54): C,
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δ
.
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M
H
H
a
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°
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 40
No. 3
2014