Journal of the Chinese Chemical Society, 2004, 51, 315-319
315
Synthesis of Triazoles, Oxadiazoles and Condensed Heterocyclic
Compounds Containing Cinchopheny and Studies on Biological Activity
of Representative Compounds
Peng-Fei Xua* (
), Zhi-Hui Zhanga (
), Xin-Ping Huia (
),
Zi-Yi Zhanga (
) and Rong-Liang Zhengb (
)
aState Key Laboratory of Applied Organic Chemistry, Lanzhou University,
Lanzhou, 730000, P. R. China
bLife School, Lanzhou University, Lanzhou, 730000, P. R. China
Compounds 2-arylamino-5-cinchophenyl-1,3,4-oxadiazoline (7) and 3-thio-4-amino-5-cinchophenyl-
1,2,4-triazole (3) have been synthesized utilizing cinchophen as the starting material. The compound 3-
cinchopheny-s-triazolo[3,4-b]-1,2,3,4-thiatriazole (4) was prepared from compound 3. Condensation of 3
with aromatic acid in the presence of POCl3 gave 10 new 6-aryl-3-cinchopheny-1,2,4-triazolo[3,4-b]-1,3,4-
thiadiazoles (5). Some of the representative compounds were screened for antibacterial activity. The struc-
tures of these new compounds have been confirmed by means of elemental analysis, IR, 1H NMR and MS.
Keywords: Cinchophen; Synthesis; Triazoles; Oxadiazoles; Condensed heterocyclic compounds;
Biological activity.
INTRODUCTION
tivity.
The derivatives of 1,2,4-s-triazole and 1,3,4-thiadi-
azole possess broad-spectrum biological activities and many
other uses.1-5 There have been more and more reports on these
fused heterocyclic compounds; the studies on them have been
very active since M. Kanaoka6 first condensed these two cy-
clic compounds into one molecule to yield s-triazolo[3,4-b]-
1,3,4-thiadiazole derivatives. These papers indicate that the
triazolothiadiazole 3,6-substituted by aryl, alkyl or hetero-
cyclic radical possesses broad-spectrum biological activities
such as antibacterial,7 anti-inflammatory,8 herbicidal,9 plant
growth regulative activity10 and anti-HIV-1 activities.11
Though a lot of reports on s-triazolo[3,4-b]-1,3,4-thiadiazole
derivatives are available, their derivatives 3,6-substituted by
alkyl, aryl, alkoxyl or 3-substituted by heterocyclic radical
are rarely reported.
RESULTS AND DISCUSSION
The synthesis of compounds: the synthesis of all com-
pounds was accomplished as shown in Scheme I.
After esterification and hydrazinolysis, cinchophen
was converted to 2-phenylquinolyl-4-formylhydratide (1)
which was refluxed with isocyanate in absolute ethanol to
give compound 6 which was changed to compound 7 in
POCl3. Compound 1 reacted with CS2 in KOH absolute etha-
nol solution to give 2-phenylquinolyl-4-potassium formyl-
hydrazino dithioformate (2) which was refluxed in excess
hydrazine hydrate to obtain 3-(2-phenylquinolyl-4-yl)-4-
amino-5-thio-1,2,4-triazole (3). Compound 3 was refluxed
with substituted benzoic acid in POCl3 to yield desired com-
pounds 5a-j.
As is well known, 2-phenlquinolyl-4-carboxylic acid
(cinchophin) displays antifebrile anodyne, antirheumatic and
glucosuria metabolic activities, etc.,12 but it has become ob-
solete in recent years due to its side-effects in clinical use.
With a view to explore other uses of cinchophin, we decided
to use cinchophin as parent material to synthesize some new
derivatives. So, we decided to combine 2-phenyquinolyl to
oxadiazole or condensed heterocycle in order to obtain new
heterocyclic compounds exhibiting promising biological ac-
In order to explore biological properties of cinchophen
we designed such methods that involved diazotization reac-
tion of parent compound 3-(2-phenylquinolyl-4-yl)-4-ami-
no-5-thio-1,2,4-triazole (3). As compound 3 has 5-thio and
4-amino simultaneously, the formed diazonium could cyclize
with thiohydroxy to give triazolothiatriazole. We referred to
the papers on compound 4 and found that A. K. El-Shafei, in
1982, utilized 3-thio-4-amino-5-phenyl-1,2,4-triazole as
Xu, Peng-Fei
