Utility of cyano acid hydrazide in heterocyclic chemistry: A new route for the synthesis of new 1,2,4-triazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]isoquinolines

Article abstract of DOI:10.1515/znb-1998-0417

Cyano acid hydrazide 1 was condensed with cyclohexanone in refluxing ethanolic piperidine to yield the hydrazone 4. Compound 4 reacts with arylidines 5a-i to yield the 1,2,4-triazolo[1,5-a]pyridines 7a-i. Compound 4 also reacts with mixtures of aliphatic aldehydes and different active methylene reagents to yield 1,2,4-triazolo[1,5-a]pyridines 8a-d. Similarly reaction of 4 with arylazomalononitrile to yield the triazolopyridines 10a-d. Reaction of 4 with aromatic aldehydes gives 12a-e. Compound 8a reacts with elemental sulfur to yield the thieno-1,2,4-triazolopyridine 13. This underwent cycloaddition with acrylonitrile, ω-nitrostyrene, chalcone, N-phenylmalemide, dimethylacetylenedicarboxylate and tetracyanoethylene yielding the isoquinolines 15-18. All new compounds have been characterized by their IR, ¹H NMR and mass spectra.

Full text of DOI:10.1515/znb-1998-0417

Utility of Cyano Acid Hydrazide in Heterocyclic Chemistry:
A New Route for the Synthesis of New l,2,4-Triazolo[l,5-a]pyridines
and l,2,4-Triazolo[l,5-a]isoquinolines
Abdel Haleem Mostafa Hussein
Chemistry Departm ent, Faculty of Science, Al-Azhar University, Assiut 71524, Egypt
Z. Naturforsch. 53b, 4 8 8 -4 9 4 (1998); received October 27, 1997
l,2,4-Triazolo[l,5-a]pyridines, l,2,4-Triazolo[l,5-a]isoquinolines
Cyano acid hydrazide 1 was condensed with cyclohexanone in refluxing ethanolic piperi-
dine to yield the hydrazone 4. Compound 4 reacts with arylidines 5 a -i to yield the 1,2,4-
triazolo[l,5-a]pyridines 7a-i. Compound 4 also reacts with mixtures of aliphatic aldehydes
and different active m ethylene reagents to yield l,2.4-triazolo[l,5-a]pyridines 8a-d. Similarly
reaction of 4 with arylazomalononitrile to yield the triazolopyridines lOa-d. Reaction of 4
with aromatic aldehydes gives 12a-e. Compound 8a reacts with elem ental sulfur to yield
the thieno-l,2,4-triazolopyridine 13. This underwent cycloaddition with acrylonitrile, a»-nit-
rostyrene. chalcone, N-phenylmalemide, dim ethylacetylenedicarboxylate and tetracyanoethy-
lene yielding the isoquinolines 15-18. All new com pounds have been characterized by their
IR, 'H NM R and mass spectra.
Introduction
N H 2 group and the H NM R spectrum exhibits a
signal at <3 2.8 ppm for a CH2 moiety. Compound
4 reacts with arylidinemalononitrile 5 a -d , arylidi-
necyanoacetate 5 e ,f and arylidinecyanothioace-
tamide 5 g - i to yield product of addition and hy-
drogen elimination which may be formulated as
the oxidized adduct 6 or the 1,2,4-triazolopyridines
7 a -i. Structures 7 a - i were considered to be the
only reaction products based on spectroscopic
data. Thus no NH2 signal can be detected in the
IR spectrum of 7a whereas the 'H NM R spectrum
of 7 a shows two signals at d 2.9 ppm and d 3.2
ppm for two NH groups.
Polyfunctionally substituted heteroaromatics
are interesting as potential biodegradable agro-
chemicals [1,2] interm ediates in dye industry [3,4]
and as pharmaceuticals [5,6]. In spite of enormous
num ber of papers published every year describing
synthesis of such compunds, general inexpensive
routes are rather limited. In recent years we were
involved in programme directed at developing ef-
ficient synthesis of polyfunctionally heteroarom at-
ics from simple and inexpensive starting materials
[7-10]. In previous publications we have shown
that
1
is an excellent adduct for the synthesis of
Recently we have shown that mixture of ali-
phatic aldehyde and malononitrile can be used as
synthetic equivalents to alkylidinemalononitrile
[12]. Thus com pound 4 reacts with mixtures of ac-
etaldehyde/m alononitrile, acetaldehyde/ethyl cya-
noacetate as well as with mixtures of formalde-
heterocyclic systems [11]. In conjunction with this
work we report here the results of our further in-
vestigation on cyano acid hydrazide 1 .
Results and Discussion
It has been found that condensation of 1 with
cyclohexanone in refluxing ethanolic piperidine
yields the hydrazone 4 or 3. The possibility that
the ketone has condensed with the active methy-
lene function in 1 was excluded based on spectral
data IR, 'H NMR and MS. The IR spectrum of
the reaction product reveals the absence of an
hyde/malononitrile
cyanoacetate to yield the l,2,4-triazolo[l,5-a]pyri-
dines 8 a -d . The arylazomalononitriles 9 a - d re-
acts with compound
and
formaldehyde/ethyl
4 to yield the 1,2,4-tria-
zolo[l,5-a]pyridines lO a -d .
A ttem pts were made to cendense 4 with aro-
matic aldehydes to form 11. However under a vari-
ety of conditions only 1 2 a -e were formed. The
structure of compounds 1 2 a -e were confirmed by
spectroscopic data (IR, 'H NM R and MS). It is
interesting to report that compound 12 cannot be
* Reprint requests to A. H. M. Hussein.
N
0932-0776/98/0400-0488 $06.00 © 1998 Verlag der Zeitschrift für Naturforschung. All rights reserved.
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A. H. M. Hussein • Utility of Cyano Acid Hydrazide in Heterocyclic Chemistry
readily obtained by direct condensation of cyclo-
489
CN
hexanonehydrazone and aromatic aldehyde or by
4 +Ar-NH-N
condensation of arylhydrazone with cyclo-
CN
9a-d
Ar = Ph
nhnh2
p-tolyl
P-CIC5 H4
p-anisyl
Scheme 3
NH-N=^
^
4 + ArCHO
11
Ar = Ph
p-CIC6 H4
0-CIC5 H4
p-anisyl
furyl
7a-i
Ar
X
a, Ph
CN
CN
Scheme 4
b, p-anisyl
c, p-CICgH4
CN
CN
COOEt
COOEt
c s n h 2
d. furyl
e, Ph
f, furyl
g, p-tolyl
h, f>CIC6H4
i, furyl
c s n h 2
c s n h 2
Scheme 1
CN
4 + RCHO+
15a-c
a: R = H, R1= CN
b: R = Ph, R1= N 0 2
c: R = Ph, R1= COPh
8a-d
X
CN
R
c h 3
Ph
NH2 O
COOEt
CN
COOEt
c h 3
H
H
Scheme 2
COOMe
In the last few years a new synthesis of benzoa-
zines utilizing alkylazinylcarbonitriles as starting
m aterials has been reported [7,13]. We have found
that com pound 8 a reacts with elemental sulfur in
ethanolic triethylamine to yield thieno-l,2,4-tria-
zolopyridine 13. This underwent, cycloaddition
with acrylonitrile, eo-nitrostyrene, chalcone, N-
phenylmalemide, dimethylacetylenedicarboxylate
and tetracyanoethylene yielding the isoquinolines
1 5 a -c and 16-18. All new compounds have been
Me1O3OC/ =
*
NC
CN
)=K
NC
CN
NC
— NH
NC^ W 'vH 'Ö
KH HN
SH CN
18
Scheme 5
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490
A. H. M. Hussein • Utility of Cyano Acid Hydrazide in Heterocyclic Chemistry
5-Oxo-lH-2,3-dihydro-7-p-anisyl-2-spiro[cyclo-
hexan-1,2,4-triazolo]1,5-a]pyridine]-
6.8-dicarbonitriles (7 b)
characterized by their IR, 'H NMR and mass
spectra. Comound 15 a was produced either from
reaction of 13 with acrylonitrile or from the reac-
tion of 8 a with formaldehyde and malononitrile.
Compound 7 b was obtained as colourless crys-
tals from ethanol (73%); m.p. 265 °C; IR: 3410-
3320 cm “ 1 (2NH); 2222, 2220 c n r 1 (2CN); 1650
cm' 1 (CO); ]H NMR: d 1.2-1.4 (m, 10H, cyclo-
hexyl-H); 3.8 (s, 3H, O C H 3); 5.7 (s, 1H, NH); 7.0-
7.6 (m, 4H, aromatic H); 8.4 (s, 1H. NH); MS: m /
z 361 (M +).
Experimental
All melting points are uncorrected. IR spectra
were recorded on a Shimadzu 470 spectrophoto-
meter, ’H NM R spectra were m easured with a
Varian Em-390 spectrom eter. Microanalyses were
perform ed by the microanalytical data unit at
Cairo University. Mass spectra were recorded with
a mass spectrom eter MS 30 MS 9 (A EI) at 70 ev.
C2 0 H 19N sO 2 (361.40)
Calcd
Found
C 66.47 H 5.30 N 15.38%,
C 6 6 . 6 H 5.4 N 19.5%.
5-Oxo-lH-2,3-dihydro-7-(p-Cl-phenyl)-2-
spiro[cyclohexan-l,2,4-triazolo[l,5-a]pyridine]-
6.8-dicarbonitriles (7 c)
Preparation o f N-cyclohexanomethylidine-
2-cyanoacetohydrazide (4)
To a solution of 1 (0.01 mol) in 30 ml ethanol,
cyclohexanone 2 (0.01 mol) was added. The reac-
tion mixture was treated with few drops of piperi-
dine and refluxed for 3 h. The solid product was
collected by filtration and recrystallized from etha-
nol as colourless crystals from ethanol (85%); m.p.
Compound 7 c was obtained as colourless crys-
tals from ethanol (69%); m.p. 120 °C; IR: 3420-
3300 cm - 1 (2NH); 2225, 2220 cm“ 1 (2CN); 1650
cm“ 1 (CO); !H NMR: (3 1.2-1.4 (m, 10H, cyclo-
hexyl-H); 7 .2 -7 . 6 (m, 4H, aromatic H); 11.3 (s,
2H, 2NH); MS: m/z 265 (M +).
160 °C; IR: 3300-3220 c n r 1 (NH); 2200 cm '
1
C 19H 16N5OCl (265.82)
(CN); 1670 cm - 1 (CO); !H NMR: (3 1.2-1.4 (m,
10H, cyclohexyl-H); 2.8 (s, 2H, CH 2); 11.4 (s, 1H,
NH); MS: m/z 179 (M +).
Calcd
Found C62.5
C 62.38 H4.41 N19.14 Cl 9.96%,
H4.6 N19.3 Cl 9.6%.
C9 H n N ,0
5-Oxo-l H-2,3-dihydro-7-furyl-2-spiro[cyclohexan-
1,2,4-triazolo[1,5-a]pyridine]-6,8-dicarbonitriles
(7d)
Calcd
Found C 60.5
C 60.32 H 7.31 N 23.45%,
H 7.4 N 23.6% .
Compound 7 a was obtained as brown crystals
from ethanol (69%); m.p. 280 °C; IR: 3420-3300
General procedure for the preparation o f l a - i
cm" 1 (2NH); 2224, 2220 cm “ 1 (2CN); 1650 cm "
(CO); 'H NMR: (insoluble); MS: m/z 321 (M +).
1
To a solution of 4 (0.01 mol) in ethanol (50 ml),
the appropriate arylidines reagent (0 . 0 1 mol) were
added. The reaction mixture was treated with few
drops of piperdine, then refluxed for 3 h. The solid
product was collected by filtration and recrystal-
lized from the proper solvent.
C 17H 15N ,0 2 (321.34)
Calcd
Found C 63.8
C 63.54 H 4.71 N 21.79%,
H 4.9 N21.9% .
Ethyl-6-cyano-7-phenyl-5-oxo-1 H-2,3-dihydro-
2-spiro[cyclohexan-1,2,4-triazolo[1,5-a]pyridine]-
8-carboxylate (7e)
5-Oxo-lH-2,3-dihydro-7-phenyl-2-sprio]cyclo-
hexan-1,2,4-triazolo[1,5-a]pyridine]-
6,8-dicarbonitriles (7 a)
Compound 7e was obtained as orange crystals
from diethyl ether (65%); m.p. 110°C; IR: 3390-
3350 cm “ 1 (2NH), 2200cm- 1 (CN); 1720 c ir r 1 (CO
ester); 1650 cm “ 1 (CO); !H NMR: <3 1.2-1.4 (m,
10H, cyclohexyl-H); 1.7 (t, 3H, CH,); 3.2 (s, 2H,
2NH); 4.2 (q, 2H, CH2); 7.20-7.7 (m, 5H. aromatic
CH); MS: m/z 378 (M+).
Compound 7 a was obtained as green crystals
from ethanol (69%); m.p. 310 °C; IR: 3420-3300
cm - 1 (2NH); 2225, 2220 cm - 1 (2CN); 1650 c ir r 1
(CO);
NMR: d 1.2-1.4 (m, 10H, cyclohexyl-
H); 2.9 (s, 1H, NH); 3.2 (s, 1H, NH); 7.0-7.6 (m,
5H, aromatic CH); MS: m/z 331 (M +).
C 19H 17N sO (331.38)
C2 ,H 2 2 N4 0 3 (378.43)
Calcd
Found C 68.9
C 68.87 H 5.17 N 21.13%,
H 5.4 N 21.3% .
Calcd
Found
C 66.65 H 5.86 N 14.81%,
H 6.0 N 15.0%.
C 6 6 . 8
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A. H. M. Hussein • Utility of Cyano Acid Hydrazide in Heterocyclic Chemistry
491
Ethyl-6-cyano-7-furyl-5-oxo-l H-2,3-dihydro-2-
spiro[cyclohexan-1,2,4-triazolo[1,5-a]pyridine]-
8-carboxylate (7f)
priate active methylene reagent (0 . 0 1 mol) were
added. The reaction mixture was treated with few
drops of piperidine, then refluxed for 3 h. The
solid product was collected by filtration and
recrystallized from the proper solvent.
Com pound 7 f was obtained as red crystals from
ethanol (65%); m.p. 280 °C; IR: 3400-3350 cm '
(2NH), 2200 cm " 1 (CN); 1730 cm' 1 (CO ester);
1650 cm - 1 (CO); 'H NMR: (insoluble); MS: m/z
368 (M +).
1
7-Methyl-5-oxo-l H-2,3-dihydro-2-spiro-
[cyclohexan-1 /2,4-triazolo[1,5-a]pyridine]-
6,8-dicarbonitriles ( 8 a)
C 19H 7 0 N4 O 4 (368.39)
Compound 8 a was obtained as colourless crys-
tals from DM F/ethanol (80%); m.p. 310 °C; IR:
3361-3316 cm “ 1 (2NH); 2225 cm “ 1 (CN); 1H
NMR: <5 1.0-1.4 (m, 10H, cyclohexyl-H); 1.8 (s,
3H, C H 3); 3.2 (s, 2H, 2NH); MS: m/z 269 (M+).
Calcd
Found C 62.2
C 61.95 H 5.47 N 15.71%,
H 5.6 N 15.4%.
6-Cyano-7-(p-tolyl)-5-oxo-lH-2,3-dihydro-2-
spiro[cyclohexan-1,2,4-triazolo[1,5-a]pyridine]-
8-thiocarboxamide (7g)
C 14H 1SN ,0 (269.31)
Calcd
Found C 62.6
C 62.44 H 5.61 N 26.01%,
H 5.8 N 26.3%.
Com pound 7g was obtained as gray crystals
from ethanol (70%); m.p. 180 °C; IR: 3400-3350
cm “ 1 (N H 2); 3350-3100 c ir r 1 (2NH); 2200 cm “
1
Ethyl-6-cyano-7-methyl-5-oxo-lH-2,3-dihydro-
(CN); 165Ö cm “ 1 (CO); 'H NMR: (3 1.3-1.5 (m,
10H, cyclohexyl-H); 2.0 (s, 3H, CH3); 3.1 (s, 2H, 2-spiro[cyclohexan-1,2,4-triazolo[1,5-a]pyridine]-
8-carboxylate ( 8 b)
2NH); 1.2-1.1 (m, 4H, aromatic CH); MS: m/z
379 (M +).
Compound 8 b was obtained as buff crystals
from ethanol (75%); m.p. 200 °C; IR: 3422, 3330
C2 0 H 2 1 N5OS (379.48)
Calcd
C 63.3 H 5.58 N 18.46 S 8.45%,
cm “
1 (2NH); 2210 cm “ 1 (CN); 1717 cm “ 1 (CO es-
Found C 63.5 H 5.8 N 18.5
S 8 .6 %.
ter); 1653 cm- 1 (CO); 'H NM R (3 1.0-1.3 (m, 13H.
CH3, cyclohexyl-H); 1.6 (t, 3H, C H 3); 3.2 (s, 2H,
2NH); 4.2 (q, 2H, C H 2); MS: m/z 316 (M+).
6-Cyano-7-(p-Cl-phenyl)-5-oxo-l H-2,3-dihydro-
2-spiro[cyclohexan-1,2,4-trizolo[1,5-a]pyridine]-
8-thiocarboxamide (7h)
C I6 H 2 0 N4 O 3 (316.16)
Calcd
Found C 60.9
C 60.75 H 6.37 N 17.71%,
N 17.9%.
Com pound 7h was obtained as yellow crystals
from diethyl ether (74%); m.p. 130 °C; IR: 3400-
3370 cm ' 1 (N H 2); 3370-3100 cm " 1 (2NH), 2 2 0 0
cm “ 1 (CN); 1650 cm' 1 (CO); MS: m/z 399 (M +).
H
6 . 8
5-Oxo-l H-2,3,7-trihydro-2-spiro[cyclohexan-l,2,4-
triazolo[l,5-a]pyridine]-6,8-dicarbonitriles (8 c)
C 19H 18N,OSCl (399.90)
Com pound 8 c was obtained as yellow crystals
from DM F/ethanol (73%); m.p. 320 °C; IR: 3360-
3330 cm " 1 (2NH); 2222, 2220 c ir r 1 (2CN); 1650
cm “ 1 (CO); MS: m/z 255 (M +).
Calcd
C 57.07 H 4.54 N 17.51 S8.02% ,
N 17.8 S8.3% .
Found C 57.3 H 4.7
6-Cyano-7-furyl-5-oxo-lH-2,3-dihydro-2-
spiro[cyclohexan-1,2,4-triazolo[1,5-a]pyridine]-
8-thiocarboxamide (7i)
C 13H 13N ,0 (255.28)
Calcd
Found C 61.4
C 61.17 H 5.13 N 27.43%,
H 5.3 N 27.6% .
Com pound 7i was obtained as gray crystals
from ethanol (70%); m.p. 278 °C; IR: 3400-3300
cm " 1 (N H 2); 3300-3100 cm “ 1 (2NH), 2200 c ir r 1
(CN); 1650 cm - 1 (CO); MS: m/z 355 (M+).
Ethyl-6-cyano-5-oxo-1 H-2,3,7-trihydro-2-spiro-
[cyclohexan-1,2,4-triazolo[1,5-a]pyridine]-
8-carboxylate (8 d)
C 17H 17N s0 2S (355.41)
Compound 8 d was obtained as red crystals from
ethanol (78%); m.p. 165 °C; IR: 3329-3320 cm - 1
(2NH); 2221 c ir r 1 (CN); 1739 cm “ 1 (CO ester);
1645 cm " 1 (CO); !H NMR: (3 1.0-1.3 (m, 10H.
cyclohexyl-H); 1.5 (t, 3H, C H 3); 3.0 (s, 2H, 2NH);
4.2 (q. 2H, CH ?); 8.0 (s, 1H, pyridine-H); MS: m/z
302 (M +).
Calcd
Found C 57.5
C 57.45 H 4.82 N 19.7 S 9.02%,
H 4.8 N 19.9 S9.3% .
General procedure for the preparation o f 8 a - d
To a solution of 4 (0.01 mol) in ethanol (50 ml),
the appropriate aliphatic aldehyde and the appro-
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492
A. H. M. Hussein • Utility of Cyano Acid Hydrazide in Heterocyclic Chemistry
-Amino-5-oxo-8-p-anisylazo-l H-2,3-dihydro-
C15H 18N4 0 3 (302.33)
7
Calcd
C 59.59 H 6.0 N 18.53%,
2-spiro[cyclohexan-1,2,4-triazolo[1,5-a]pyridine]-
Found C 59.7
H 6.1 N 18.7%.
6-carbonitrile ( 1 0 d)
Compound 10d was obtained as brown crystals
from ethanol (74%); m.p. 255 °C; IR: 3400-3350
General procedure for the preparation o f 10a-d
cm - 1 N H 2; 3350-3320 cm - 1 (2NH); 2220 cm "
1
To a solution of 4 (0.05 mol) in ethanol (50 ml),
arylazomalononitrile 9a-d (0.05 mol) and piperi-
dine (2 drops) were added. The reaction mixture
was heated under reflux for 3 h then left to stand.
The solid product was collected by filtration and
recrystallized from the proper solvent.
(CN); 1650 cm “ 1 (CO); 'H NMR (3 1.0-1.3 (m,
10H, cyclohexyl-H); 3.9 (s, 3H, O CH3); 6,.4 (s, 1H,
NH); 6 . 8 (br, 2H, NH2); 7.0-8.0 (m, 4H, aromatic
CH); 8.0 (s, 1H, NH); MS: m/z 379 (M+).
C 19H 2 1 N7 0 2 (379.42)
Calcd
C 60.5 H 5.58 N 25.84%,
N26.0% .
7-Amino-5-oxo-8-phenylazo-lH-2,3-dihydro-
2-spiro[cyclohexan-1,2,4-triazolo[1,5-a]pyridine]-
6-carbonitrile (1 0 a)
Found C 60.7 H 6.0
General procedure for the preparation o f
3-arylcyclohexano[c[-l H-pyrazole (12a- e)
Compound 10a was obtained as brown crystals
from ethanol (80%); m.p. 260 °C; IR: 3390-3350
cm- 1 (NH2); 3340-3300 cm “ 1 (2NH); 2215 c ir r 1
(CN); 1653 cm “ 1 (CO); 'H NMR: ö 1.0-1.3 (m,
10H, cyclohexyl-H); 3.3 (s, 2H, 2NH); 7.0-7.7 (m,
7H, aromatic CH and N H 2); MS: m/z 349 (M +).
A mixture of 2 (0.01 mol) and benzaldehyde
(0.01 mol) in ethanol (30 ml) was treated with a
little am ount of triethylamine, then refluxed for
3 h. The reaction mixture left to stand and the
solid product was collected by filtration and
recrystallized from the proper solvent.
C 18H 19N70 (349.40)
Calcd
Found C 62.0
C 61.88 H 5.48 N 28.06%,
H 5.6 N 28.3% .
3-Phenylcyclohexano[c]-l H-pyrazole (12a)
Compound 12a was obtained as orange crystals
from ethanol (77%); m.p. 150 °C; IR: 3400-3300
cm “ 1 (NH); 3050 cm“ 1 (aliphatic CH); 1600-1590
c m 1 (arom atic CH); 'H NMR: d 1.4-1.8 (m, 8 H,
cyclohexyl-H); 7.2 -7. 6 (m, 5H, aromatic CH); 8.9
(s, 1H, NH); MS: m/z 198 (M +).
7-Amino-5-oxo-8-p-tolylazo-lH-2,3-dihydro-
2-spiro[cyclohexan-1,2,4-triazolo[1,5-a]pyridine]-
6-carbonitrile ( 1 0 b)
Compound 10b was obtained as brown crystals
from ethanol (80%); m.p. 250 °C; IR: 3400-3370
cm- 1 (NH2); 3370-3310 cm “ 1 (2NH); 2200 cm ” 1
(CN); 1650 cm - 1 (CO); ]H NMR: (3 1.0-1.3 (m,
10H, cyclohexyl-H); 3.0 (s, 2H, 2NH); 3.4 (s, 3H,
CH3); 7.0-7.9 (m, 7H, aromatic CH and NH 2);
MS: m/z 363 (M+).
C n H 14N2 (198.27)
Calcd
Found C 78.9
C 78.75 H 7.12 N 14.13%,
H 7.4 N 14.3%.
3-(p-Cl-Phenyl)cyclohexano[c]-lH-pyrazole (12b)
C19H 2 iN70 (362.42)
Compound 12b was obtained as yellow crystals
from ethanol (75%); m.p. 190 °C; IR: 3400-3100
cm - 1 (NH); 3030 cm “ 1 (aliphtic CH); 1600-1590
cm “ 1 (aromatic CH); *H NMR: Ö 1.3-1.9 (m, 8 H,
cyclohexyl-H); 1.2-7.6 (m, 4H, aromatic H); 8 . 8 (s,
1H, NH); MS: m/z 232 (M +).
Calcd
Found C 62.9
C 62.79 H 5.82 N 26.98%,
H 6.0 N 27.3%.
7-Amino-5-oxo-8-(p-Cl-phenylazo)-lH-2,3-
dihydro-2-spiro[cyclohexan-1,2,4-triazolo-
[l,5-a]pyridine]-6-carbonitrile (10 c)
C 13H 13N2 C1 (232.71)
Compound 10c was obtained as brown crystals
from ethanol (78%); m.p. 262 °C; IR: 3400-3340
cm “ 1 (NH2); 3340-3300 c ir r 1 (2NH); 2210 cm “ 1
(CN); 1655 cm “ 1 (CO); ’H NMR: <3 1.0-1.3 (m,
10H, cyclohexyl-H); 3.2 (s, 2H, 2NH); 7.0-7.5 (m.
6 H, aromatic CH and N H 2); MS: m/z 383 (M +).
Calcd
C 67.1 H 5.63 N 12.04 Cl 15.23%,
Found C 67.3 H 5.8 N 12.3 Cl 15.3%.
3-(o-Cl-Phenyl)cyclohexano[c]-lH-pyrazole (12c)
Compund 12c was obtained as orange crystals
from ethanol (75%); m.p. 200 °C; IR: 3390-3290
cm “ 1 (NH); 3060 cm' 1 (aliphatic CH); 1600-1590
cm' 1 (aromatic CH); 'H NMR: d 1.2-1.6 (m, 8 H,
C 18H 18N7OCl (383.84)
Calcd
Found C 56.6
C 56.32 H 4.73 N 25.54%,
H 4.9 N 25.7% .
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A. H. M. Hussein - Utility of Cyano Acid Hydrazide in Heterocyclic Chemistry
493
cyclohexyl-H); 1.2-1.6 (m, 4H, aromatic H); 9.0 (s,
1H, NH); MS: m/z 232 (M+).
6-Amino-4-oxo-lH-2,3-dihydro-2-spiro-
[cyclohexan-1,2,4-triazolo[l,5-a]isoquinoline]-
7,10-dicarbonitriles (15 a)
C13H 13N2 C1 (232.71)
Calcd
C 67.1 H 5.63 N 12.04 CI 15.24%,
Com pound 15 a was obtained as orange crystals
from ethanol (69%); m.p. 315 °C; IR: 3440-3350
cm - 1 (N H 2); 3317-3191 cm " 1 (2NH); 2222 cm ” 1
(2CN); 1650 cm ' 1 (CO); JH NMR: (3 1.4-1.8 (m,
10H, cyclohexyl-H); 2.8 (s, 2H, 2NH); 7.8-8.0 (m,
4H, aromatic CH and N H 2).
Found C 67.4 H 5.8 N 12.2 CI 15.3%.
3-p-Anisylcyclohexano[c]-lH-pyrazole (12 d)
Com pound 12 d was obtained as yellow crystals
from ethanol (78%); m.p. 188 °C; IR: 3380-3280
cm - 1 (NH); 3040 cm “ 1 (aliphatic CH); 1600-1590
cm - 1 (arom atic CH); *H NMR: (3 1.3-1.7 (m, 8 H,
cyclohexyl-H); 3.8 (s, 3H, O CH 3); 7.0-7.6 (m, 5H,
aromatic CH and NH); MS: m/z 228 (M+).
C 17H 16N60 (320.35)
Calcd
Found C 63.9
C 63.74 H 5.03 N 26.23%,
H 5.3 N 26.4% .
6-Amino-7-nitro-8-phenyl-4-oxo-l H-2,3-dihydro-
2-spiro[cyclohexan-l,2,4-triazolo[l,5-a]-
isoquinoline]-10-carbonitrile (15 b)
Ci4H 16N20 (228.29)
Calcd
C 73.66 H 7.06 N 12.27%,
Found C 73.8
H 7.3 N 13.3%.
Com pound 15 b was obtained as gray crystals
from dioxane (60%); m.p. 250 °C; IR: 3390-3350
cm - 1 (N H 2); 3300-3200 cm ' 1 (2NH); 2200 c rrr1
(CN); 1645 cm “ 1 (CO); MS: m/z 416 (M +).
3-Furylcyclohexano[c]-lH-pyrazole (12 e)
Com pound 12 e was obtained as brown crystals
dioxane (82%); m.p. 300 °C; IR: 3400-3310 cm- 1
(NH); 3050 c rr r 1 (CH); 1600-1590 cm '
1
(aro-
C2 2 H 2 0 N6 O 3 (416.44)
Calcd
Found C 63.6
C 63.45 H 4.84 N 20.18%,
H 5.0 N 20.3% .
matic CH); 'H NMR: (3 1.4—1.8 (m, 8 H, cyclo-
hexyl-H); 2.8 (s, 1H, NH); 6.5-7.0 (m, 3H, furyl
CH); MS: m/z 188 (M+).
6-Amino-7-benzoyl-8-phenyl-4-oxo-l H-2,3-
dihydro-2-spiro[cyclohexan-l,2,4-triazolo-
[1,5-a]isoquinoline]-10-carbonitrile (15 c)
CnH 12N?0 (188.23)
Calcd
C 70.19 H 6.43 N 14.88%,
Found C 70.3
H
6 . 8
N 15.0%.
Com pound 12 c was obtained as yellow crystals
from DM F/ethanol (70%); m.p. 310 °C; IR: 3430
6-Amino-5-oxo-lH-2,3-dihydrothieno]3,4-c]-
2-spiro[cyclohexan-l,2,4-triazolo[l,5-a]pyridine]-
9-carbonitrile (13)
cm - 1 (N H 2); 3300-3200 cm - 1 (2NH); 2200 cm -
1
(CN); 1665 and 1650 cm “ 1 (2CO); 'H NMR: (3
1.4-1.8 (m, 10H, cyclohexyl-H); 2.8 (s, 2H, 2NH);
7.2-8.2 (m, 13H, arom atic CH and NH?); MS:
m/z 427 (M +).
A mixture of 8 a (0.01 mol) and elemental sulfur
(0.01 mol) in 50 ml ethanol was treated with a little
am ount of triethylamine, then refluxed for 3 h.
The solid product formed was collected by filtra-
tion and recrystallized from ethanol as green crys-
tals (70%); m.p. 290 °C; IR: 3450-3380 cm “ 1
(N H 2); 3350-3300 cm -' (2NH); 2200 cm “ 1 (CN);
1655 cm - 1 (CO); MS: m/z 301 (M +).
C2 5 H 25 N ,0 2 (427.51)
Calcd
Found C 70.4
C 70.24 H 5.89 N 16.38%,
H 5.9 N 16.5%.
6-Amino-8-phenyl-5,7,9-trioxo-lH-2,3-dihydro-
2-spiro[cyclohexan-1,2,4-triazolo-
[1,5-a]isoquinoline]-11-carbonitrile (16)
C 14H 15N,OS (301.37)
Calcd
C 55.8 H 5.02 N 23.24 S 10.64%,
S 10.8%.
Found C 55.9 H 5.2 N 23.5
Com pound 16 was obtained as gray crystals
from ethanol (6 6 %); m.p. 270 °C; IR: 3400-3370
General procedure for the preparation of
compounds 15a - c and 16-18
cm " 1 (N H 2); 3300-3200 cm ' 1 (2NH); 2200 cm“
(CN); 1660 and 1650 cm " 1 (CO );‘H NMR: <3 1.4-
1.8 (m, 10H, cyclohexyl-H); 3.0 (s, 2H, 2NH); 7.2-
8.2 (m, 8 H, aromatic CH and N H 2); MS: m/z 440
(M+).
1
To a solution of 13 (0.01 mol) in dry pyridine,
the appropriate dienophils were added. The reac-
tion mixture was refluxed for 3 h. Then poured on
ice-cold water and neutralized with dilute HC1.
The solid product was collected by filtration and
recrystallized from the proper solvent.
C2 4 H 2 0 N6 O 3 (440.46)
Calcd
Found C 65.7
C 65.45 H 4.58 N 19.08%,
H 4.8 N 19.3%.
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494
A. H. M. Hussein ■Utility of Cyano Acid Hydrazide in Heterocyclic Chemistry
Methyl-6-amino-10-cyano-5-oxo-lH-2,3-dihydro-
2-spiro[cyclohexan-1,2,4-triazolo[1,5-a]-
isoquinoline]-7,8-dicarboxlyte (17)
6-Amino-5-oxo-l0-mercapto-l H-2,3-dihydro-2-
spiro[cyclohexan-1,2,4-triazolo[1,5-aJ-
isoquinoline]-7,8,10-pentacarbonitriles (18)
Compound 17 was obtained as gray crystals
from DM F/ethanol (73%); m.p. 310 °C IR: 3400-
3350 cm " 1 (NH,); 3350-3220 cm " 1 (2NH); 2200
cm“ 1 (CN); 1680 and 1650 cm - 1 (2CO); "H NMR:
(3 3.7 (s, 6 H, 2CH3); 4.0-4.5 (m, 10H, cyclohexyl-
H); 8.2 (m, 3H, aromatic CH and N H ,); 8.7 (s, 2H,
2NH); MS: m/z 411 (M +).
Compound 18 was obtained as gray crystals
from DM F/ethanol (6 6 %); m.p. 320 °C; IR: 3410-
3330 cm “ 1 (NH2); 3320-3200 cm' 1 (2NH); 2200
cm - 1 (CN); 1650 cm - 1 (CO); !H NMR: (insolu-
ble); MS: m/z 429 (M+).
C2 ()H ,,N 9OS (429.46)
C2 0H 2 1 N5 O 5 (411.42)
Calcd
Found C 56.2
C 55.94 H 3.52 N 29.35 S7.47% ,
H 3.8 N 29.5 S7.5% .
Calcd
C 58.39 H 5.4 N 17.02%,
H 5.4 N 17.3%.
Found C 58.6
[7] A. H. H. El. Ghandour, A. A. Harb, M. H. Elnagdi,
A. M. Hussein. S. A. Metwelly, J. Prakt. Chem. 334,
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[8] M. H. Elnagdi, A. W. Erian, Liebigs Ann. Chem.
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deir, M. H. Elnagdi. Bull. Chem. Soc. Jpn. 66, 464
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[3] S. M. Fahmy. A. H. Badran, M. H. Elnagdi. J. Chem.
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[4] S. M. Fahmey. M. El-Hosam i. S. Elgamal, M. H. E l-
nagdi, J. Chem. Technol. Biotechnol. 32, 1042
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[5] M. H. Elnagdi. A. W. Erian. Arch. Pharm. 324, 853
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[9] M. H. Elnagdi, F. M. Abdelrazik, N. S. Ibrahim,
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[10] M. H. Elnagdi, A. W. Erian. Bull. Chem. Soc. Jpn.
1845 (1990).
[11] A. M. Hussein, Heteroatom . Chemistry 7, 2 (1996).
[12] M. H. Elnagdi. A. A. Harb. A. H. H. Elghandour,
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[13] M. H. Elnagdi. A. M. Negm . K. U. Sadek. Synlett 1,
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27 (1994).
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