الفهرس 
Synthesis of 5-amino-4-cyano-1H-pyrazoles
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Abstract
The chemistry of pyrazoles has gained increasing attention due to its
diverse pharmacological properties such as antiviral, antagonist,
antimicrobial, anticancer, anti-inflammatory, analgesic, anti-prostate cancer,
herbicidal, acaricidal and insecticidal activities.
The starting material enaminonitriles (1a,b) were prepared according to
a previously reported method.
Treatment of (1a) with acetic anhydride, Ac2O/AcOH mixture, benzoyl
chloride and/or phthalic anhydride afforded N,N-diacetyl pyrazole (2),
pyrazolopyrimidine (3), N-benzoyl pyrazole (4) and 1,3-dioxoisoindolinyl
pyrazole (5) derivatives respectively. (Scheme 1)Scheme 1
N
N
Ar
Ph
N
O
5 O
CN
-C
6H4(OCH3)-4
Ac
2O/AcOH
C
6H5COCl
O
O O
Enaminonitrile (1a) reacted with anisaldehyde in the presence of
catalytic amount of acetic acid afforded Schiff base (6), while reaction of (1a),
(1b) with benzaldehyde in the presence of NaOH, carbon disulfide and/or
carbon disulfide in presence of NaOH afforded the corresponding Scheme 2
9
CH
NH
S
NH
S
N
N
Ar
Ph
NH
NH
S
S
O
-C
6H4(OCH3)-4
AcOH
NaOH
CS
2
CS
2 / NaOH
Ar =
Ar =
a;Ar’=C6H5 b;Ar’=C6H4(Cl)-4
When compound (1a) was allowed to react with cyanoacetic acid and/or
formamide, cyanoacetamide (10) and pyrazolopyrimidine (11) derivatives
were formed respectively, while reaction of 1b with triethyl orthoformate
afforded compound (12). (Scheme 3)Scheme 3
N
N
Ar
Ph
N
CN
CN
CH
O
Ar = -C
6H4(OCH3)-4
N
N
NH
2
CNCH
2COOH
Ac
2O
HCONH
2
CH(OC2H5)3
Ac
2O
Ar =
The study was extended to explore the reactivity of the enaminonitriles
(1a, b) towards some carbon and nitrogen nucleophiles.
Thus, reaction of (1a,b) with malononitrile and/or ethyl acetoacetate in
the presence of a base afforded the acetonitrile and aminoester derivatives
(13a,b) and (14), respectively. While treatment of (1a, b) with hydrazine
hydrate and/or thiourea in the presence of sodium ethoxide afforded the
pyrazolopyrazole (15a,b) and pyrazolopyrimidine (16), respectively.
On the other hand boiling (1a,b) with triethylamine compound (17a,b),
were obtained, respectively. (Scheme 4)Scheme 4
16
Ar = -C
6H4(OCH3)-4
N
N
NH
2
CN
N
N
Ar
Ph
N N
H
2
CO2C2H5
N
N
Ar
Ph
NH
N
NH
2
S
N
N
Ar
Ph
NH
N
NH
2
15a,b
N
N P
h
N
N
NH
2
N
N
H
2N
Ph
Ar
17a,b
N
N
Ar
Ph
N
NH
2
CN
N
(A)
N
N
Ar
Ph
N N
(B)
CO2C2H5
TEA
N
N
Ar
Ph
NH
NH
2
N
(C)
N
N
Ar
Ph
N NH
(D)
NH
2 S
EtONa
N
N
Ar
Ph
N
NH
2
N
N
N
H
2N
Ph
Ar
(E) Ar
TEA
Ar = -C
6H4(OCH3)-4
CH
2(CN)2
EtONa
COCH3
CO
2Et
N
2H4.H2O
H
2NCSNH2
Reaction of (1a,b) with sodium azide in the presence of ammonium
chloride in dimethylformamide gave the tetrazole derivatives (18a, b),
respectively. Reaction of compounds (18a, b) with benzaldehyde, phenacyl
bromide/sodium acetate and/or carbon disulfide/pyridine afforded the
tetrazolopyrimidine, tetrazolodiazepine and tetrazolopyrimidine thione
derivatives (19a,b), (20) and (21), respectively. On the other hand stirring of Scheme 5
21
N
N
Ar
Ph
NH
N
N
S
N
N
Ar
Ph
22
N
N
Ar
Ph
NH
2
N
NH
N N
NH
2
N
N
Ar
Ph
N
N
NH 19
a,b
N
N
Ar
Ph
N
N
N
N
N
Ph
N N
O
NH
2
N N P
h
H
2O2
NH
4OH
NaN
3
Ar =
Ar = -C
Ar = 6H4(OCH3)-4
CS
2/pyridine
PhCOCH
2Br
ACONa
The newly synthesized compounds were characterized by IR, 1H-NMR
and Mass spectral data and also tested against gram positive and gram
negative, fungi and two human tumor cell lines.