Facile, mild and efficient synthesis of azines using phosphonic dihydrazide

Article abstract of DOI:10.1080/10426507.2019.1633531

Several bis(N'-arylpropanehydrazonoyl chlorides) were synthesized in good yields from condensation reactions of hydrazonoyl chlorides and phosphonic dihydrazide. Under the conditions employed, none of the expected phosphorylhydrazines were isolated. Nucle

Full text of DOI:10.1080/10426507.2019.1633531

Phosphorus, Sulfur, and Silicon and the Related Elements
ISSN: 1042-6507 (Print) 1563-5325 (Online) Journal homepage: https://www.tandfonline.com/loi/gpss20
Facile, mild and efficient synthesis of azines using
phosphonic dihydrazide
Rizk E. Khidre, Hanan A. Mohamed, Benson M. Kariuki & Gamal A. El-Hiti
To cite this article: Rizk E. Khidre, Hanan A. Mohamed, Benson M. Kariuki & Gamal A. El-Hiti
(2019): Facile, mild and efficient synthesis of azines using phosphonic dihydrazide, Phosphorus,
Sulfur, and Silicon and the Related Elements
To link to this article: https://doi.org/10.1080/10426507.2019.1633531
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PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
https://doi.org/10.1080/10426507.2019.1633531
Facile, mild and efficient synthesis of azines using phosphonic dihydrazide
a,b
c,d
e
f
Rizk E. Khidre , Hanan A. Mohamed , Benson M. Kariuki , and Gamal A. El-Hiti
a
b
Chemical Industries Division, National Research Centre, Dokki, Giza, Egypt; Chemistry Department, Faculty of Science, Jazan University,
c
d
Jazan, Saudi Arabia; Applied Organic Chemistry Department, National Research Center, Dokki, Giza, Egypt; Department of Chemistry,
e
College of Science and Humanities, Shaqra University, Duwadimi, Saudi Arabia; School of Chemistry, Cardiff University, Cardiff, UK;
f
Department of Optometry, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
ABSTRACT
ARTICLE HISTORY
Several bis(N’-arylpropanehydrazonoyl chlorides) were synthesized in good yields from condensa-
tion reactions of hydrazonoyl chlorides and phosphonic dihydrazide. Under the conditions
employed, none of the expected phosphorylhydrazines were isolated. Nucleophilic substitution of
bis(N’-arylpropanehydrazonoyl chlorides) with thiophenol, sodium phenylsulfinate, hydroxyl amine,
and piperidine afforded the corresponding azines. Similarly, 1,2-bis(heteroaryl)ethylidene)hydra-
zines were produced from reaction of phosphonic dihydrazide and heteroaryl methyl ketones. The
structures of the products were confirmed by NMR and IR spectral data along with X-ray crystal
structure determination and their purities were confirmed by the elemental analyses.
Received 7 February 2019
Accepted 15 June 2019
KEYWORDS
Phosphonic dihydrazide;
azines; nucleophilic
substitution reaction;
heterocycles; bis(N’-
arylpropanehydrazonoyl
chlorides); X-ray
crystallography
GRAPHICAL ABSTRACT
[
24]
Introduction
1,2-bis(arylidene)hydrazines in high yields.
In the current
work, a novel series of azines was produced by simple and
efficient synthetic procedures from phosphonic dihydrazide,
as part of our research program on the synthesis of novel
Azines or 2,3-diaza-1,3-butadienes, (R C ¼ N–N ¼ CR ), are
2
2
important compounds in various synthetic transforma-
[
1–4]
tions.
They have unique chemical structures compared
[
25–29]
heterocycles.
to simple 1,3-butadienes and therefore can produce five-
[
5–8]
membered heterocycles via 1,3-dipolar cycloadditions.
For example, one-pot reaction of azines and benzylidenema-
Results and discussion
lononitriles, via copper-catalyzed tandem cyclization, gave
[
9]
Condensation of a 2:1 mixture of 2-oxo-N’-arylpropanehy-
drazonoyl chlorides 1 and phosphonic dihydrazide (2) in
1
,2,4-triazolo[1,5-a]pyridines.
Azines exhibit various
[
10]
[11]
pharmacological activities
convulsant,
and act as antitumor,
anti-
[
12]
[13]
[14] boiling ethanol for 3 h gave bis(N’-arylpropanehydrazonoyl
antioxidant,
and antimicrobial agents.
chlorides) 3 in good yields rather than the expected prod-
In addition, they have interesting industrial applications and
0 0
(2,2 -phosphoryl)bis(hydrazin-2-yl-1-ylidene))bis(N -
[
15]
[16]
ucts,
arylpropanehydrazonoyl chlorides) 4 (Scheme 1). The
can be used as optical materials,
organic sensors,
c[o1n8]ductive media,
1
[
17]
H
and semiconductors.
NMR spectra of 3 showed exchangeable singlets that reson-
ated within the 10.32–10.47 ppm region corresponding to
The synthesis of azines involves the condensation reac-
tion of carbonyl compounds and hydrazines such as hydra-
13
zine
carboxylate.
per-catalyzed dimerization of imines,
of ketoximes.
hydrate,
hydrazine
sulfate
or
hydrazinium the NH protons. The C NMR spectra of 3 showed all the
[
19]
13
Also, they can be synthesized from the cop- expected carbons. Moreover, IR and C NMR spectra of 3
[
20]
and homo-coupling indicated the absence of a carbonyl group. The X-ray crystal
In addition, azines can be directly synthe- structures of 3c and 3d are shown in Figures 1 and 2,
sized from reaction of alcohols and hydrazine hydrate in the respectively.
[
21]
[
22]
[23]
presence of ruthenium
or nickel complexes.
Recently,
No evidence was found to prove that products 4 were
the reaction of 3-hydrazonobutan-2-one oxime and aromatic formed under the condition attempted. When an equimolar
aldehydes has been reported to produce the corresponding reaction of 1 and 2 was attempted, only products 3 were
CONTACT Gamal A. El-Hiti
gelhiti@ksu.edu.sa
Department of Optometry, College of Applied Medical Sciences, King Saud University, P.O. Box 10219,
Riyadh 11433, Saudi Arabia.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/gpss.
Supplemental data for this article is available online at https://doi.org/10.1080/10426507.2019.1633531.
ß 2019 Taylor & Francis Group, LLC

2
R. E. KHIDRE ET AL.
Scheme 1. Synthesis of azines 3.
Figure 1. Ortep representation of the molecular structure of 3c showing 50%
probability ellipsoids.
Figure 2. Ortep representation of the molecular structure 3d showing 50%
probability ellipsoids.
produced in low yields along with 1. Such results are not in
[
30,31]
agreement with the reported ones.
Two reports, by the
Reaction of methyl ketones 9 and 2 in boiling ethanol for
same author(s), showed that reactions of a 2:1 mixture of 2–3 h furnished the corresponding azines 10a–e (Scheme 4)
compounds of the type of 1 and 2 in EtOH for 1–4 h, in the in good yields. The structures of 10a and 10b were con-
presence or absence of sulfuric acid, gave 4 in 46–91% firmed by X-ray crystallography as shown in Figures 4 and
[
30,31]
yields.
reactions between carbonyl compounds and dihydrazides of ment with those reported.
phosphonothioic acid showed that products either of the
Similarly, reaction of isatin (11) and 2 in ethanol under
type 3 or 4 or a mixture of both could be produced based reflux for 3 h afforded (3Z,3’E)-3,3’-(hydrazine-1,2-diylide-
However, an early report that investigated the 5, respectively. The spectral data for 10a,b were in agree-
[
36,37]
[
32]
on the substituents attached to the carbonyl group.
example, the reaction of 4-methylbenzaldehyde with ray crystal structure of 12 is shown in Figure 6. The spectral
the dihydrazide of phosphonothioic acid gave the corre- data for 12 were in agreement with those reported.
For ne)bis(indolin-2-one) (12) in 85% yield (Scheme 5). The X-
[
38]
For
sponding product of type 3 as the only product in 78% example, the IR spectrum showed a strong absorption peak
[
32]
ꢀ1
yield.
from reaction of 1 (two mole equivalents) and 2 is shown in carbonyl carbon appeared at 164.1 ppm in the C NMR
A proposed mechanism for the formation of 3 at 1725 cm which is attributed to the carbonyl group. The
13
[
32]
1
Scheme 2. Based on an early report,
it is believed that the spectrum. In addition, the H NMR spectrum showed the
nucleophilic attack of the nitrogen of the amino group in 2 presence of exchangeable singlets that appeared at
at the carbonyl carbon of 1 would lead to intermediate A 10.61 ppm due to the two NH protons.
which on reaction with 1 would give cyclic intermediate B.
Hydrolysis of B would give 3 and hydrazinylphosphinic acid
Discussion of molecular structures
as a side product.
The utility of 3 in organic synthesis has been tested on Data refinement parameter, bond lengths and angles obtained
reactions with nucleophiles. Reactions of 3c,d and thiophe- by single crystal diffraction are shown in Tables S1–S12. The
nol, sodium phenylsulfinate, hydroxylamine hydrochloride molecule of 3c has inversion symmetry and, apart from the
and piperidine in boiling ethanol afforded the corresponding methyl hydrogen atoms, is planer with a maximum deviation
azines 5–8 (Scheme 3) in good yields. The reactions pro- of 0.11(1) Å from the least squares plane through the atoms
ceeded via replacement of the two chlorine atoms in com- Figure 1). The molecule of 3d also has inversion symmetry
pounds 3c,d. Similar related reactions have been and is planer apart from the methyl hydrogen atoms with a
[
33–35]
reported.
The X-ray crystal structure of compound 5b maximum deviation of 0.11(1) Å from the least squares plane
(Figure 2). The molecule of 5b has inversion symmetry and,
is shown in Figure 3.

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
3
Scheme 2. Possible pathway for the formation of azines 3.
Scheme 3. Synthesis of azines 5–8.
with the exception of the phenyl group and methyl hydrogen (14) from the least squares plane through the atoms
atoms, is planar with a maximum deviation of 0.105(2) Å (Figure 6).
from the least squares plane (Figure 3).
The planar geometry and inversion symmetry generally
In 10a, the separate dihydrobenzofuranyl ethanimine observed for these materials (except for 10a) is akin to that
0
3,3 -(hydrazine-1,2-diylidenedieth-1-yl-1-
ylidene)bis(1H-pyrazole).
fragments of the molecule are planer (apart from the methyl observed
for
[
39]
hydrogen atoms) with a maximum deviation of 0.192(2) Å
from their least squares planes (Figure 4). The twist angle
ꢁ
between the two fragments of the molecule is 55.66(3) . For
Experimental
10b, the molecule has pseudo-inversion symmetry in the
crystal (Figure 5). In contrast to 10a, the molecule is essen-
tially planar with a maximum deviation of 0.268(2) Å from
General
the least squares plane of the molecule (apart from the Melting points were recorded on a Gallenkamp melting
methyl hydrogen atoms). Molecule 12 has inversion sym- point apparatus. The IR spectra (KBr disks) were obtained
metry and is planer with a maximum deviation of ±0.0706 using PerkinElmer GX Spectrometer. The NMR spectra

4
R. E. KHIDRE ET AL.
Figure 3. Ortep representation of the molecular structure of 5b showing 50% probability ellipsoids.
Scheme 4. Synthesis of azines 10a-e.
Figure 4. Ortep representation of the molecular structure of 10a showing 50%
probability ellipsoids.
Figure 5. Ortep representation of the molecular structure of 10b showing 50%
were carried out on JEOL 500 MHz spectrometer (TMS; d in probability ellipsoids.
1
13
ppm and J in Hz) at 500 MHz for H and 125 MHz for
C
NMR, in DMSO-d unless otherwise indicated. The crystal-
6
0
0
0
0
(
1Z,1 Z,2E,2 E)-2,2 -(Hydrazine-1,2-diylidene)bis(N -phe-
lographic data for compounds 3c, 3d, 5b, 10a, 10b, and 12
were deposited at the Cambridge Crystallographic Data
Center with CCDC reference numbers 1861134–1861139.
Phosphonic dihydrazide 2 was produced based on a litera-
ꢁ
nylpropanehydrazonoyl chloride) (3a): m.p., 197–198 C,
brown, yield, 85%; IR (ꢀmax, cm ): 3319 (NH), 1602
C ¼ N), 1541, 1508 (C ¼ C). H NMR (d , ppm): 2.25 (s,
ꢀ
1
1
(
H
[
40]
ture procedure.
The Supplemental Materials contains 6 H, 2Me), 6.93 (t, J ¼ 8.5 Hz, 2 H, H-4 of 2Ph), 7.30 (t,
1
13
sample H and C NMR spectra for products 3, 5, and 6 J ¼ 8.5 Hz, 4 H, H-3/H-5 of 2Ph), 7.36 (d, 4 H, J ¼ 8.5 Hz, H-
13
(
Figures S1 – S11).
Synthesis of 3a–e: A mixture of 1 (10.0 mmol) and 2 ppm): 14.6 (Me), 114.0, 123.2, 129.2, 143.4, 153.9 (C-Cl),
0.55 g, 5.0 mmol) in EtOH (20 mL) was refluxed for 3 h. 155.7 (C-Me). Anal. Calcd. for C18 (389.28): C,
2/H-6 of 2Ph), 10.32 (s, exch., 2 H, 2NH). C NMR (d ,
C
(
H
18Cl N
2 6
The solid formed on cooling was filtered and recrystallized 55.54; H, 4.66; N, 21.59, Found: C, 55.21; H, 4.42;
from EtOH to give pure 3. N, 21.44%.

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
5
Scheme 5. Synthesis of (3Z,3’E)-3,3’-(hydrazine-1,2-diylidene)bis(indolin-2-one) (12).
(
2
1
d, 4 H, J ¼ 7.9 Hz, H-3/H-5 of 2Ar), 10.47 (s, exch., 2 H,
13
NH). C NMR (d , ppm): 14.6 (Me), 87.0, 116.0, 135.6,
C
43.2, 154.0 (C-Cl), 156.5 (C-Me). Anal. Calcd. for
C H Cl I N (641.08): C, 33.72; H, 2.52; N, 13.11, Found:
18
16 2 2 6
C, 33.64; H, 2.43; N, 13.02%.
Synthesis of 5a,b: A mixture of thiophenol (0.22 g,
2
.0 mmol) and 3c or 3d (1.0 mmol) was added to dry EtOH
(30 mL) containing sodium (46 mg, 2.0 mmol). The mixture
was refluxed for 6 h and the solid formed on cooling was
isolated by filtration, washed with EtOH, dried and recrys-
tallized from EtOH to give 5a or 5 b, respectively.
0
0
0
(
1Z,1 Z,2E,2 E)-Diphenyl
2,2 -(hydrazine-1,2-diylidene)
0
bis(N -4-chlorophenylpropanehydrazono-thioate) (5a): m.p.,
Figure 6. Ortep representation of the molecular structure of 12 showing 50%
probability ellipsoids.
ꢁ
158–159 C, red, yield, 85%; IR (ꢀ , cm ): 3270 (NH), 1590,
max
ꢀ1
1
1
578 (C ¼ N), 1510, 1475 (C ¼ C). H NMR (d , ppm): 1.82 (s,
H
0 0 0
(
1Z,1 Z,2E,2 E)-2,2 -(Hydrazine-1,2-diylidene)bis(N-(4-flu- 6 H, 2Me), 7.32–7.37 (m, 18H, 2Ph and 2Ar), 10.6 (s, exch., 2H,
1
3
orophenyl)propanehydrazonoyl
chloride)
(3b):
m.p., 2NH). C NMR (d , ppm): 13.87 (Me), 112.7, 116.2, 126.0,
C
ꢁ
ꢀ1
1
93–194 C, red, yield, 89%; IR (ꢀmax, cm ): 3329 (NH), 1600 127.5, 129.3, 131.7, 133.9, 135.8, 142.8 (C-S), 155.2 (C-Me). Anal.
1
(
C ¼ N), 1541, 1510 (C ¼ C). H NMR (d , ppm): 2.24 (s, 6 H, Calcd. for C30
H26Cl N S (605.60): C, 59.50; H, 4.33; N, 13.88,
2 6 2
H
2
Me), 7.34 (d, 4 H, J ¼ 8.4 Hz, H-2/H-6 of 2Ar), 7.37 (d, 4 H, Found: C, 59.32; H, 4.15; N, 13.67%.
13
0 0 0
J ¼ 8.4 Hz, H-3/H-5 of 2Ar), 10.34 (s, exch., 2 H, 2NH).
C
(1Z,1 Z,2E,2 E)-Diphenyl 2,2 -(hydrazine-1,2-diylidene)
0
NMR (d , ppm): 14.6 (Me), 114.3, 116.5, 131.8, 143.4, 153.9 bis(N -4-bromophenylpropanehydrazono-thioate)
C-Cl), 156.4 (C-Me). Anal. Calcd. for C H Cl F N (425.26): m.p., 160–161 C, red, yield, 86%; IR (ꢀmax, cm ): 3269
(5 b):
C
ꢁ
ꢀ1
(
18 16 2 2 6
1
C, 50.84; H, 3.79; N, 19.76, Found: C, 50.59; H, 3.57; N, 19.63%. (NH), 1591, 1575 (C ¼ N), 1510, 1475 (C ¼ C). H NMR
0
0
0
0
(
1Z,1 Z,2E,2 E)-2,2 -(Hydrazine-1,2-diylidene)bis(N -(4-
(d , ppm): 1.82 (s, 6 H, 2Me), 7.17–7.28 (m, 10 H, 2Ph),
H
chlorophenyl)propanehydrazonoyl chloride) (3c): m.p., 7.37 (d, 4 H, J ¼ 8.0 Hz, H-2/H-6 of 2Ar), 7.51 (d, 4 H,
ꢁ
ꢀ1
13
2
1
(
(
17–218 C, brown, yield, 90%; IR (ꢀmax, cm ): 3325 (NH), J ¼ 8.0 Hz, H-3/H-5 of 2Ar), 10.60 (s, exch., 2 H, 2NH).
C
1
595 (C ¼ N), 1552, 1500 (C ¼ C). H NMR (d , ppm): 2.26 NMR (d
, ppm): 13.9 (Me), 112.7, 116.2, 126.0, 127.5, 129.3,
H
C
s, 6 H, 2Me), 7.30 (d, 4 H, J ¼ 8.1 Hz, H-2/H-6 of 2Ar), 7.37 131.7, 133.9, 135.8, 142.8 (C-S), 155.2 (C-Me). Anal. Calcd.
d, 4 H, J ¼ 8.1 Hz, H-3/H-5 of 2Ar), 10.45 (s, exch., 2 H, for C H Br N S (694.51): C, 51.88; H, 3.77; N, 12.10,
30
26
2 6 2
1
3
2
NH). C NMR (d , ppm): 14.6 (Me), 115.0, 123.5, 129.8, Found: C, 51.67; H, 3.62; N, 11.92%.
C
1
42.2, 153.4 (C-Cl), 155.9 (C-Me); Anal. Calcd. for
Synthesis of 6a,b: A mixture of 3c or 3d (1.0 mmol) and
C H Cl N (458.17): C, 47.19; H, 3.52; N, 18.34, Found: C, sodium benzenesulfinate dihydrate (0.80 g, 4.0 mmol) in
1
8
16
4 6
4
6.97; H, 3.35; N, 18.19%.
EtOH (30 mL) was heated under reflux for 2 h. The solid
produced on cooling was filtered, washed with EtOH, dried
0
0
0
0
(
1Z,1 Z,2E,2 E)-2,2 -(Hydrazine-1,2-diylidene)bis(N -(4-
bromophenyl)propanehydrazonoyl chloride) (3d): m.p., and recrystallized from EtOH to give 6a or 6 b, respectively.
ꢁ
ꢀ1
2
1
2
7
2
1
27–228 C, brown, yield, 87%; IR (ꢀ , cm ): 3325 (NH),
(1E,2E)-1,2-bis((Z)-1-(2-(4-Chlorophenyl)hydrazono)-1-
max
1
591 (C ¼ N), 1552 s, 1497 s (C ¼ C); H NMR (d , ppm): (phenylsulfonyl)propan-2-ylidene)hydrazine (6a): m.p.,
H
ꢁ
ꢀ1
.21 (s, 6 H, 2Me), 7.36 (d, 4 H, J ¼ 8.0 Hz, H-2/H-6 of 2Ar), 219–220 C, brown, yield, 89%; IR (ꢀmax, cm ): 3325 (NH),
1
.63 (d, 4 H, J ¼ 8.0 Hz, H-3/H-5 of 2Ar), 10.43 (s, exch., 1597 (C ¼ N), 1552, 1500 (C ¼ C). H NMR (d
, ppm): 2.22
H
1
3
H, 2NH); C NMR (d , ppm): 14.6 (Me), 115.0, 116.0, (s, 6 H, 2Me), 7.32–7.37 (m, 18 H, 2Ph and 2Ar), 10.45 (s,
C
13
32.5, 143.2, 153.4 (C-Cl), 156.0 (C-Me); Anal. Calcd. for exch. 2 H, 2NH). C NMR (d , ppm): 14.6 (Me), 115.5,
C
C H Br Cl N (547.08): C, 39.52; H, 2.95; N, 15.36, Found: 116.2, 124.0, 125.0, 129.0, 142.4, 145.8 (C-S), 153.2 (C-Me).
1
8
16
2
2 6
C, 39.37; H, 2.79; N, 15.18%.
Anal. Calcd. for C H Cl N O S (669.60): C, 53.81; H,
30 26 2 6 4 2
3.91; N, 12.55, Found: C, 53.69; H, 3.78; N, 12.39%.
0
0
0
0
(
1Z,1 Z,2E,2 E)-2,2 -(Hydrazine-1,2-diylidene)bis(N -(4-
iodophenyl)propanehydrazonoyl chloride) (3e): m.p.,
(1E,2E)-1,2-bis((Z)-1-(2-(4-Bromophenyl)hydrazono)-1-
ꢁ
ꢀ1
2
1
30–231 C, red, yield, 80%; IR (ꢀmax, cm ): 3323 (NH), (phenylsulfonyl)propan-2-ylidene)hydrazine (6 b): m.p.,
1
ꢁ
ꢀ1
590 (C ¼ N), 1552, 1496 (C ¼ C). H NMR (d , ppm): 2.19 252–253 C, brown, yield, 90%; IR (ꢀmax, cm ): 3325 (NH),
H
1
(
s, 6 H, 2Me), 7.28 (d, 4 H, J ¼ 7.9 Hz, H-2/H-6 of 2Ar), 7.67 1591 (C ¼ N), 1552, 1496 (C ¼ C). H NMR (d , ppm): 1.87
H

6
R. E. KHIDRE ET AL.
(
s, 6 H, 2Me), 7.27–7.32 (m, 10 H, 2Ph), 7.39 (d, 4 H, 4 H, J ¼ 8 Hz, H-2/H-6 of 2Ar), 7.476 (d, 4 H, J ¼ 8.5 Hz, H-
13
J ¼ 8.0 Hz, H-2/H-6 of 2Ar), 7.55 (d, 4 H, J ¼ 8.0 Hz, H-3/H- 3/H-5 of 2Ar), 10.55 (s, exch., 2 H, 2NH). C NMR (d ,
C
13
5
1
1
of 2Ar), 10.63 (s, exch., 2 H, 2NH). C NMR (d , ppm): ppm): 14.6 (Me), 23.0 (C-4 of piperidinyl), 25.5 (C-3/C-5 of
C
3.9 (CH ), 112.7, 116.2, 126.0, 127.5, 129.3, 131.7, 133.9, piperidinyl), 48.7 (C-2/C-6 of piperidinyl), 116.0, 117.0,
3
37.8, 142.8 (C-S), 155.9 (C-Me). Anal. Calcd. for 131.8, 142.2, 153.4 (C-piperidinyl), 154.7 (C-Me). Anal.
C H Br N O S (758.50): C, 47.50; H, 3.46; N, 11.08, Calcd. for C H Br N (644.46): C, 52.18; H, 5.63; N, 17.39,
3
0
26
2
6
4 2
28 36
2 8
Found: C, 47.36; H, 3.29; N, 10.89%.
Found: C, 52.01; H, 5.45; N, 17.21%.
Synthesis of 7a,b: Hydroxylamine hydrochloride (0.14 g,
Synthesis of 10a–e: A mixture of ketones 9 (20 mmol)
2
2
.0 mmol) and anhydrous potassium carbonate (0.28 g, and 2 (1.10 g, 10 mmol) in EtOH (20 mL) was refluxed for
.1 mmol) was added to a solution of 3c or 3d (1.0 mmol) in 2–3 h. The solid produced on cooling was filtered, dried and
dry EtOH (30 mL). The mixture was refluxed for 3 h and recrystallized from EtOH to give 10.
the solid formed on cooling was filtered and recrystallized
(1Z,2Z)-1,2-bis(1-(Benzofuran-2-yl)ethylidene)hydrazine
ꢁ
ꢁ
[36]
from EtOH to give 7a or 7b, respectively.
(10a): m.p., 163–165 C (lit. m.p. 163–164 C ), red, yield,
88%. The spectral data for 10a was in agreement with
0
0
0
0
(
1Z,1 Z,2E,2 E)-2,2 -(Hydrazine-1,2-diylidene)bis(N -(4-
[
36]
chlorophenyl)-N-hydroxypropane-hydrazonamide)
(7a): those reported.
(1Z,2Z)-1,2-bis(1-(1H-Indol-3-yl)ethylidene)hydrazine
ꢁ
ꢀ1
m.p., 235–236 C, red, yield, 83%; IR (ꢀmax, cm1 ): 3392
ꢁ
ꢁ
[37]
(
OH), 3244 (NH), 1597 (C ¼ N), 1496 (C ¼ C). H NMR (10 b): m.p., 280–281 C (lit. m.p. 280–282 C
), red,
(
d , ppm): 2.22 (s, 6 H, 2Me), 7.18 (d, 4 H, J ¼ 8.0 Hz, H-2/ yield, 80%. The spectral data for 10b was in agreement
H
[
37]
H-6 of 2Ar), 7.32 (d, 4 H, J ¼ 8 Hz, H-3/H-5 of 2Ar), 7.70 (s, with those reported.
exch., 2 H, 2OH), 7.80 (s, exch., 2 H, 2NH), 10.46 (s, exch.,
(1Z,2Z)-1,2-bis(1-(5-Methyl-1-phenyl-1H-1,2,3-triazol-4-
H, 2NH). C NMR (d , ppm): 13.9 (Me), 113.6, 116.0, yl)ethylidene)hydrazine (10c): m.p., 260–261 C, yellow,
1
3
ꢁ
2
1
C
ꢀ
1
26.0, 131.9, 143.8 (C-NH), 152.7 (C-Me). Anal. Calcd. for yield, 82%; IR (ꢀmax, cm ): 1614, 1598 (C ¼ N), 1500
1
C H Cl N O (451.31): C, 47.90; H, 4.47; N, 24.83, Found: (C ¼ C). H NMR (CDCl
; d
2.70 (s, 6 H, 2Me), 7.25–7.30 (m, 10 H, 2Ph). C NMR
(CDCl ; d , ppm): 10.5 (Me), 21.34 (Me), 115.0, 125.0,
(7 b): 131.1, 133.1, 139.6, 144.4, 160.0 (C-Me). Anal. Calcd. for
, ppm): 2.47 (s, 6 H, 2Me),
1
8
20
2 8 2
3
H
13
C, 47.76; H, 4.31; N, 24.67%.
0
0
0
0
(
1Z,1 Z,2E,2 E)-2,2 -(Hydrazine-1,2-diylidene)bis(N -(4-
3
C
bromophenyl)-N-hydroxypropane-hydrazonamide)
m.p., 254–255 C, brown, yield, 87%; IR (ꢀmax, cm ): 3400
ꢁ
ꢀ1
C H N (398.47): C, 66.31; H, 5.57; N, 28.12, Found: C,
22 22 8
1
(
OH), 3325 (NH), 1591 (C ¼ N), 1552, 1500 (C ¼ C).
H
66.13; H, 5.39; N, 27.98%.
NMR (d , ppm): 2.22 (s, 6 H, 2Me), 7.30 (d, 4 H, J ¼ 9.0 Hz,
(1Z,2Z)-1,2-bis(1-(1-(4-Fluorophenyl)-5-methyl-1H-1,2,3-
H
ꢁ
H-2/H-6 of 2Ar), 7.45 (d, 4 H, J ¼ 9.0 Hz, H-3/H-5 of 2Ar), triazol-4-yl)ethylidene)hydrazine (10d): m.p., >300 C, pale
ꢀ
1
7
.70 (s, exch., 2 H, 2OH), 7.90 (s, exch., 2 H, 2NH), 10.46 (s, yellow, yield, 81%; IR (ꢀmax, cm ): 1614 (C ¼ N), 1514
13
1
exch., 2 H, 2NH). C NMR (d , ppm): 14.6 (Me), 112.8, (C ¼ C). H NMR (CDCl
; d
3
, ppm): 2.47 (s, 6 H, 2Me), 2.70
H
C
1
16.0, 124.0, 131.9, 142.7 (C-NH), 153.7 (C-Me). Anal. (s, 6 H, 2Me), 7.35 (d, 4 H, J ¼ 8 Hz, H-2/H-6 of 2Ar), 7.38 (d,
13
Calcd. for C H Br N O (540.22): C, 40.02; H, 3.73; N, 4 H, J ¼ 8 Hz, H-3/H-5 of 2Ar). C NMR (CDCl
; d
10.8 (Me), 21.3 (Me), 116.0, 124.7, 132.5, 135.3, 141.5, 145.2,
Synthesis of 8a,b: A mixture of 3c or 3d (1.0 mmol) in dry 161.2 (C-Me). Anal. Calcd. for C22 (434.45): C, 60.82;
EtOH (30 mL) containing piperidine (0.34 g, 4.0 mmol) was H, 4.64; N, 25.79, Found: C, 60.67; H, 4.51; N, 25.57%.
, ppm):
1
8
20
2 8 2
3
C
2
0.74, Found: C, 39.92; H, 3.61; N, 20.56%.
H F N
20 2 8
then refluxed for 6 h. The solid formed on cooling was filtered
and recrystallized from EtOH to yield 8a or 8 b, respectively.
(1Z,2Z)-1,2-bis(1-(5-Methyl-1-(4-tolyl)-1H-1,2,3-triazol-
ꢁ
4-yl)ethylidene)hydrazine (10e): m.p., 285–286 C, yellow,
ꢀ
1
(
1E,2E)-1,2-bis((Z)-1-(2-(4-Chlorophenyl)hydrazono)-1- yield, 86%; IR (ꢀmax, cm ): 1612 (C ¼ N), 1552, 1520
1
(
piperidin-1-yl)propan-2-ylidene)hydrazine (8a): m.p., (C ¼ C). H NMR (CDCl
3
; d
, ppm): 2.47 (s, 6 H, 2Me),
H
ꢁ
ꢀ1
2
1
1
6
28–229 C, red, yield, 82%; IR (ꢀ , cm ): 3310 (NH), 2.68 (s, 6 H, 2Me), 2.75 (s, 6 H, 2Me), 7.26–7.39 (m, 8 H,
max
1
13
601 (C ¼ N), 1562, 1510 (C ¼ C). H NMR (d , ppm): 2Ar). C NMR (CDCl
; (d , ppm): 11.5 (Me), 21.3 (Me),
3 C
H
.58–1.62 (m, 12 H, H-3/H-4/H-5 of 2 piperidinyl), 2.26 (s, 27.9 (Me), 125.0, 125.2, 130.14, 130.2, 140.4, 144.0, 157.0 (C-
H, 2Me), 3.16 (m, 8 H, H-2/H-6 of 2 piperidinyl), 7.28 Me). Anal. Calcd. for C24
H N (426.53): C, 67.58; H, 6.14;
26 8
(
d, 4 H, J ¼ 8 Hz, H-2/H-6 of 2Ar), 7.36 (d, 4 H, J ¼ 7.5 Hz, N, 26.27, Found: C, 67.45; H, 5.97; N, 26.07%.
13
0 0
H-3/H-5 of 2Ar), 10.45 (s, exch., 2 H, 2NH). C NMR
(
Synthesis of (3Z,3 E)-3,3 -(hydrazine-1,2-diylidene)diin-
dC, ppm): 14.6 (Me), 23.7 (C-4 of piperidinyl), 25.3 (C-3/ dolin-2-one (12): A mixture of 11 (1.47 g, 10 mmol) and 2
(0.55 g, 5 mmol) in EtOH (20 mL) was refluxed for 3 h. The
C-5 of piperidinyl), 48.7 (C-2/C-5 of piperidinyl), 115.0,
solid obtained on cooling was filtered, dried and recrystal-
1
24.5, 129.8, 142.21, 153.4 (C-piperidinyl), 155.8 (C-Me).
lized from EtOH to give 12 as red crystals, yield 2.58 g
Anal. Calcd. for C H Cl N (555.55): C, 60.54; H, 6.53;
2
8
36
2
8
ꢁ ꢁ
[38]
(89%), m.p. 293–294 C (lit. m.p. > 300 C ). The spectral
N, 20.17, Found: C, 60.36; H, 6.33; N, 20.02%.
1E,2E)-1,2-bis((Z)-1-(2-(4-Bromophenyl)hydrazono)-1-
piperidin-1-yl)propan-2-ylidene)hydrazine (8 b): m.p.,
(
data was in agreement with those reported.
(
ꢁ
ꢀ1
2
1
1
6
36–237 C, red, yield, 80%; IR (ꢀ , cm ): 3295 (NH),
max
1
Crystal structure determination
597 (C ¼ N), 1560, 1490 (C ¼ C). H NMR (d , ppm):
H
.57–1.63 (m, 12 H, H-3/H-4/H-5 of 2 piperidinyl), 2.26 (s, Single-crystal XRD data were collected on an Agilent
H, 2Me), 3.16 (m, 8 H, H-2/H-6 of 2 piperidinyl), 7.35 (d, SuperNova Dual Atlas diffractometer with
a mirror

PHOSPHORUS, SULFUR, AND SILICON AND THE RELATED ELEMENTS
7
monochromator using either Cu (k ¼ 1.5418 Å) or Mo
[41] [42]
[9] Lv, J.; He, Z.; Zhang, J.; Guo, Y.; Han, Z.; Bao, X. One-Pot
Synthesis of [1,2,4]Triazolo[1,5-a]Pyridines from Azines and
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Cyclization. Tetrahedron 2018, 74, 3996–4004. DOI: 10.1016/j.
tet.2018.06.002.
(
k ¼ 0.7107 Å) radiation. Crystal structures were solved using
SHELXS
and refined using SHELXL.
Non-hydrogen
atoms were refined with anisotropic displacement parameters.
Hydrogen atoms were inserted in idealized positions, and a [10] Kuznetsova, Y. A.; Romakh, V. B. Syringaldazine. Appl.
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Biochem. Biotechnol. 1996, 61, 205–209. DOI: 10.1007/
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iso
value of U (C/N). Data collection and refinement parameters
eq
[
are shown in Tables S1–S12 (Supplemental Materials).
Conclusions
005.
[
12] Gul, H. I.; Calis, U.; Vepsalainen, J. Synthesis of Some Mono-
Mannich Bases and Corresponding Azine Derivatives and
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New, simple and efficient procedures have been developed
for the synthesis of symmetrical azines in high yields from
phosphonic
dihydrazide
and
commercially
avail-
[
able reagents.
Acknowledgements
14756360802218516.
The authors extend their appreciation to the College of Applied [14] Kurteva, V. B.; Simeonov, S. P.; Disheva, M. S. Symmetrical
Medical Sciences Research Center and the Deanship of Scientific
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Disclosure statement
1021/jo802631m.
No potential conflict of interest was reported by the authors.
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