Synthesis of Potential Biologically Active Compounds Based on Aryloxy- and Arylaminopropanehydrazides

Article abstract of DOI:10.1134/S1070363220070014

Abstract: New derivatives of a number of aryloxy and arylaminopropanehydrazides were synthesized. Their heterocyclization under the action of carbon disulfide and potassium hydroxide and subsequent alkylation of the resulting 2-thioxo-1,3,4-oxadiazole rin

Full text of DOI:10.1134/S1070363220070014

ISSN 1070-3632, Russian Journal of General Chemistry, 2020, Vol. 90, No. 7, pp. 1181–1187. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Obshchei Khimii, 2020, Vol. 90, No. 7, pp. 987–993.
Synthesis of Potential Biologically Active Compounds Based
on Aryloxy- and Arylaminopropanehydrazides
T. A. Gomktsyana, R. S. Shainovaa, A. V. Karapetyana, and A. P. Yengoyana,b,*
a Pesticides Synthesis Research Center, National Agrarian University of Armenia, Yerevan, 0009 Armenia
b Russian-Armenian University, Yerevan, 0051 Armenia
*e-mail: ayengoyan@mail.ru
Received March 3, 2020; revised March 3, 2020; accepted March 10, 2020
Abstract—New derivatives of a number of aryloxy and arylaminopropanehydrazides were synthesized. Their
heterocyclization under the action of carbon disulfide and potassium hydroxide and subsequent alkylation of the
resulting 2-thioxo-1,3,4-oxadiazole ring, the corresponding S-substituted products were obtained. The reaction of
the starting hydrazides with arylaldehydes and pentane-2,4-dione afforded their N′-arylidene and N′-(4-oxopentan-
2-ylidene) derivatives. In preliminary laboratory tests, the synthesized compounds showed a pronounced stimulating
effect on plant growth. Their activity was 44–95% compared with heteroauxin.
Keywords: aryloxyhydrazides, arylaminohydrazides, N′-arylidene(4-oxopentane-2-ylidene)-2-aryloxy(amino)-
propanehydrazides, 1,3,4-oxadiazole-2(3H)-thione, plant growth stimulators
DOI: 10.1134/S1070363220070014
Most pharmaceutical preparations that mimic
biologically active natural substances consist of
heterocyclic scaffolds. Hydrazides and their derivatives,
in particular hydrazones, are often used as starting
compounds to obtain new heterocyclic structures.
Hydrazine derivatives occupy a special place in the
chemotherapy of tuberculosis [1]. Isonicotinic acid
hydrazide (isoniazid) has been used in medical practice for
more than half a century and has not lost its significance
to this day. On its basis, ftivazide, saluside, metazide and
other modified analogs with improved pharmacological
properties have been obtained. In medical practice,
antidepressants iproniazid and nialamide (monoamine
oxidase inhibitors) are widely used [1]. Studies of
new hydrazine derivatives are ongoing, among which
compounds with antimicrobial [2–5], anti-tuberculosis
[6], anti-inflammatory [7], antimalarial [8], antitumor
[9], anticonvulsant [10] and antidepressant [11] activities
have been revealed. In agriculture, some hydrazide
derivatives are used, in particular, herbicides (benquinox,
saijunmao, phenoxyaryl hydrazides of nicotinic acid)
[12]. Compounds with growth-stimulating activity have
been found [13–15].
disulfide and KOH in an anhydrous ethanol medium. As
a result, heterocyclization of the hydrazide fragment took
place with the formation of 1,3,4-oxadiazole-2-thione
derivatives 5–8 (Scheme 1, Table 1).
The 13C NMR spectra of compounds 5–8 contain
signals from the sp2-hybridized carbon atom C=S at
177.9 ppm, which indicates the thionic structure. In the
13C NMR spectra of the alkylation products 9–12, these
signals disappear and new ones appear, corresponding
to methylene groups at the S atom. This indicates that
the reaction is proceeding at the exocyclic sulfur atom
of the heterocycle.
The reaction of starting hydrazides 1–4 with various
arylaldehydes in the presence of hydrochloric acid at
room temperature led to the formation of N'-arylidene-
2-aryloxy(amino)propanehydrazides 13–16 (Scheme 1).
Hydrazides 1‒4 reacted with pentane-2,4-dione in acetic
acid in the presence of a catalytic amount of DMF at
room temperature to yield N'-(4-oxopentan-2-ylidene)-
2-aryloxy(amino)propanehydrazides 17‒20 (Scheme 1).
Due to the hindered rotation around the C=N double
bond (or due to inversion at the nitrogen atom), molecules
of compounds 13–20 can exist as E- and Z-isomer forms.
The NMR spectra of compounds 13–16 show two sets
of signals corresponding to the E- and Z-isomers, with
In order to obtain new potential biologically active
compounds, we carried out the reaction of 2-aryloxy-
and 2-(arylamino)propanehydrazides 1–4 with carbon
1181

1182
GOMKTSYAN et al.
Scheme 1.
an intensity ratio from 1 : 1 to 7 : 3. In the latter case, the
spatially more favorable E-form prevails. In the 1H and
13C NMR spectra of compounds 17–19, the signals of
two isomers practically coincide, and only in the NMR
spectra of compound 20 the chemical shifts of signals
with an intensity ratio of 1 : 1 corresponding to E- and
Z-isomers differ only slightly.
EXPERIMENTAL
1H and 13C NMR spectra were recorded at 30°C on
a Varian Mercury-300 NMR spectrometer (300 and
75 MHz, respectively) in a mixture of DMSO-d6‒СCl4
(3 : 1); TMS was used as an internal standard. The
reactions progress and the purity of the obtained
compounds were monitored by TLC on Silufol UV-254
plates; an acetone–hexane 2:1 mixture was used as an
eluent. Elemental analysis was performed on a Eurovector
EA3000 CHNS analyzer. Melting points were determined
by the capillary method and were uncorrected.
During laboratory vegetation tests, almost all of the
compounds obtained showed a stimulating effect on plant
growth. The experiments were carried out on seeds and
seedlings of common beans (Phaseolus vulgaris L.).
The effect of aqueous suspensions of compounds 1–14
at concentrations of 25 and 50 mg/L on seed viability,
germination, and seedling growth was studied. These
data were compared with a similar effect of heteroauxin
solutions of the same concentrations. Activity of
the compounds ranged from 44 to 95% compared to
heteroauxin (see Table). Substances that showed activity
above 70% in the test (5, 7, 11b, 11c, 11d, 14a, 14b, 15d,
15f, 16a, 16b, 16d) were selected for further research.
General procedure for the synthesis of compounds
5–8. To a mixture of 10 mmol of compound 1–4 and
10 mmol of KOH were added 10 mL of absolute ethanol
and 20 mmol of carbon disulfide. The resulting mixture
was stirred for 8–10 h at 75–80°C and then evaporated.
To the residue was added 20–30 mL of water, acidified
with hydrochloric acid to pH = 4. The precipitate was
filtered off, washed with water, and dried.
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SYNTHESIS OF POTENTIAL BIOLOGICALLY ACTIVE COMPOUNDS
1183
Table 1. Physico-chemical characteristics and plant growth stimulating activity of compounds 5‒20
Calculated, %
H
Found, %
H
Activitya, %
50 mg/L 25 mg/L
Comp. Yield,
no.
mp, °C
Formula
12.60 C10H10N2O2S
9.62 C10H8Cl2N2 O2S
%
94
84
80
81
65
63
72
75
92
90
83
68
71
95
90
96
91
87
75
82
77
75
79
76
83
83
62
65
62
63
C
N
C
N
5
6
7
8
9a
9b
80–82
Масло
54.04
41.25
162–164 46.97
108–110 41.39
108–110 56.24
63.14
42.99
120–122 41.39
112–114 57.52
4.54
2.77
3.94
3.13
5.03
5.30
3.33
3.18
4.83
4.31
4.19
3.62
3.48
6.08
5.77
4.83
4.39
4.46
3.43
5.34
5.08
4.66
4.84
4.68
4.73
4.50
6.92
4.87
6.13
5.19
54.11
41.14
46.88
41.44
56.14
63.01
42.85
41.44
57.40
47.71
46.00
43.20
41.42
68.52
64.88
61.21
55.49
53.01
50.17
63.78
60.55
59.00
57.49
55.64
53.12
57.25
64.01
50.67
56.99
50.79
4.40 12.33
2.66 9.41
3.89 16.17
3.20 14.62
5.12
5.22
3.28
3.22 12.28
4.75 11.32
4.40 12.70
4.05 17.73
3.69 11.80
3.44 15.90
6.13
5.71
4.73 13.20
4.28
4.38
3.33 10.74
5.42 13.80
5.17 13.47
4.59 11.89
4.75 14.21
4.60 11.27
4.80 10.71
4.59 12.29
6.83 10.49
74
–
51.4
79
16.43 C10H10ClN3OS
14.48 C10H9Cl2N3OS
76.3
81.1
8.74
8.18
7.71
C15H16N2O4S
C18H18N2O3S
C13H12Cl2N2O4S
8.55
7.88
7.55
62–63
Масло
–
51.3
10c
10d
11b
11c
11d
12c
12d
13a
13b
13c
14a
14b
14c
15d
15e
15f
15g
16a
16b
16d
17
12.07 C12H11Cl2N3O3S
11.18 C18H18ClN3O2S
12.82 C13H14ClN3O3S
17.91 C12H13ClN4O2S
11.60 C13H13Cl2N3O3S
16.14 C12H12Cl2N4O2S
–
44.9
56.2
59.1
74.9
88.1
73.0
59.9
85–86
47.64
120–122 46.08
128–130 43.11
133–135 41.51
147–149 68.44
194–196 64.96
166–168 61.34
169–171 55.60
–
62.0
65.6
44.5
64.2
82.0
76.0
9.39
8.91
C17H18N2O3
C17H18N2O4
9.51
8.73
43.8
56.6
67.2
62.2
63.5
13.41 C16H15N3O4
7.63
7.29
C17H16Cl2N2O3
C17H17Cl2N2O4
7.37
7.05
83–84
88–89
53.14
50.28
10.99 C16H13Cl2N3O4
13.92 C16H16ClN3O
13.22 C16H16ClN3O2
12.15 C17H16ClN3O3
14.40 C14H14ClN3O2
11.47 C17H17Cl2N3O2
10.96 C17H17Cl2N3O3
12.50 C16H15Cl2N3O
10.68 C14H18N2O3
218–220 63.68
223–225 60.48
205–207 59.05
198–200 57.64
187–189 55.75
216–218 53.28
168–170 57.16
152–154 64.11
161–163 50.77
133–135 56.85
136–138 50.92
53.7
–
75.1
51.3
77.6
66.1
76.0
70.7
87.2
56.9
61.2
81.0
94.8
71.1
18
19
20
8.46
C14H16Cl2N2O3
4.79
6.20 14.45
5.11 12.62
8.28
14.21 C14H18ClN3O2
12.73 C14H17Cl2N3O2
a Compared to heteroauxin, the activity of which was taken as 100%.
5-(1-Phenoxyethyl)-1,3,4-oxadiazole-2(3H)-thione
(5). 1Н NMR spectrum, δ, ppm (J, Hz): 1.72 d (3H, CH3,
J = 6.6), 5.52 q (1H, OCH, J = 6.6), 6.94‒7.33 m (5H,
C6H5), 14.30 s (1H, NH).
5-[1-(3,4-Dichlorophenylamino)ethyl]-1,3,4-
1
oxadiazole-2(3H)-thione (8). Н NMR spectrum, δ,
ppm (J, Hz): 1.60 d (3H, CH3, J = 6.8), 4.63 d. q (1H,
NCH, J1 = 6.8, J2 = 8.2), 6.45 d (1H, NHCH, J = 8.2),
6.58‒7.15 m (3H, C6H3), 7.20‒8.50 br. s (2H, 2NH). 13С
NMR spectrum, δС, ppm: 18.1, 44.3, 112.4, 113.8, 118.5,
129.9, 131.6, 146.3, 163.5, 177.9.
5-[1-(3,4-Dichlorophenoxy)ethyl]-1,3,4-oxadiazole-
1
2(3H)-thione (6). Н NMR spectrum, δ, ppm (J, Hz):
1.75 d (3H, CH3, J = 6.5), 5.56 q (1H, OCH, J = 6.5),
7.21‒7.39 m (3H, C6H3), 14.36 br. s (1H, NH). 13С NMR
spectrum, δС, ppm: 17.5, 68.5, 117.7, 124.3, 126.7, 127.5,
129.3, 151.0, 160.7, 177.9.
General procedure for the synthesis of compounds
9a, 10c, 10d, 11c, 11d, 12c, 12d. To 10 mmol of the
potassium salt of compound 5–8 was added 10 mL of
DMF, and then 11 mmol of the corresponding alkyl halide
was slowly added with stirring at 0°C. The resulting
mixture was stirred for 30 min at 0°C, then at room
temperature for 3 h. The next day the reaction mixture
5-[1-(4-Chlorophenylamino)ethyl]-1,3,4-
1
oxadiazole-2(3H)-thione (7). Н NMR spectrum, δ,
ppm (J, Hz): 1.58 d (3H, CH3, J = 6.8), 4.62 d. q (1H,
NCH, J1 = 6.8, J2 = 8.2), 6.22 d (1H, NHCH, J = 8.2),
6.60‒7.05 m (4H, C6H4), 11.10 br. s (1H, NH).
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1184
GOMKTSYAN et al.
was stirred at 65–70°C for 12 h, and then evaporated. The
precipitate was treated with water, filtered off and dried.
18.6, 35.8, 44.2, 112.3, 113.7, 118.3, 129.9, 131.5, 146.5,
163.4, 167.2, 167.7.
3-[5-(1-Phenoxyethyl)-1,3,4-oxadiazol-2-
ylsulfanyl]pentane-2,4-dione (9a). 1Н NMR spectrum,
δ, ppm (J, Hz): 1.77 d (3H, CH3, J = 6.6), 2.39 s (6H,
2CH3), 5.66 q (1H, OCH, J = 6.6), 6.88‒7.28 m (5H,
C6H5), 10.40 s (0.6H, OH-enol).
General procedure for the synthesis of compounds
9b, 10b, 11b, 12b. To a mixture of 10 mmol of the
potassium salt of compound 5–8 and 10 mL of DMF was
added 10 mmol of (2-bromoethoxy)benzene. The reaction
mixture was stirred at 70–75°C for 8–10 h. The solution
was evaporated; the precipitate was washed with water,
filtered off and dried.
Methyl 2-{5-[1-(3,4-dichlorophenoxy)ethyl]-
1
1,3,4-oxadiazol-2-ylsulfanyl}acetate (10c). Н NMR
spectrum, δ, ppm (J, Hz): 1.80 d (3H, CH3, J = 6.6), 3.74 s
(3H, OCH3), 4.12 s (2H, SCH2), 5.72 q (1H, OCH, J =
6.6), 7.21‒7.40 m (3H, C6H3). 13С NMR spectrum, δС,
ppm: 18.0, 33.3, 52.2, 68.4, 117.6, 124.2, 126.6, 127.4,
128.3, 129.3, 151.0, 163.5, 165.3, 166.9.
2-(1-Phenoxyethyl)-5-[(2-phenoxyethyl)sulfanyl]-
1,3,4-oxadiazole (9b). Н NMR spectrum, δ, ppm (J,
Hz): 1.78 d (3H, CH3, J = 6.6), 3.63 t (2H, SCH2, J =
6.8), 4.52 t (2H, OCH2, J = 6.8), 5.65 q (1H, OCH, J =
6.6), 6.82‒7.32 m (10H, C6H5).
1
2-{5-[1-(3,4-Dichlorophenoxy)ethyl]-1,3,4-
oxadiazol-2-ylsulfanyl}acetamide (10d). Н NMR
N-(1-{5-[(2-Phenoxyethyl)sulfanyl]1,3,4-oxadiazol-
2-yl}ethyl)-4-chloroaniline (11b). 1Н NMR spectrum, δ,
ppm (J, Hz): 1.62 d (3H, CH3, J = 6.8), 3.58 t (2H, SCH2,
J = 6.8), 4.28 t (2H, OCH2, J = 6.8), 4.78 d. q (1H, NCH,
J1 = 6.8, J2 = 8.2), 6.17 d (1H, NHCH, J = 8.2), 6.60‒
7.32 m (9H, C6H5 + C6H4).
1
spectrum, δ, ppm (J, Hz): 1.79 d (3H, CH3, J = 6.6), 3.99 s
(2H, SCH2), 5.69 q (1H, OCH, J = 6.6), 7.10 br. s and
7.57 br. s (2H, NH2), 7.20‒7.38 m (3H, C6H3). 13С NMR
spectrum, δС, ppm: 18.1, 35.9, 68.4, 117.7, 124.3, 126.6,
127.4, 128.3, 129.3, 151.1, 164.5, 165.0, 167.0.
General procedure for the synthesis of compounds
13–16. To 10 mmol of compound 1–4 were added 15 mL
of water, 15 mL of 36% hydrochloric acid, and 12 mmol
of the corresponding aldehyde. The mixture was stirred
at room temperature for 6 h and left overnight. The next
day, 10–15 mL of water was added; the precipitate was
filtered off and dried.
Methyl 2-{5-[1-(4-chlorophenylamino)ethyl]1,3,4-
1
oxadiazol-2-ylsulfanyl}acetate (11c). Н NMR
spectrum, δ, ppm (J, Hz): 1.61 d (3H, CH3, J = 6.8), 3.70 s
(3H, OCH3), 4.07 s (2H, SCH2), 4.77 d. q (1H, NCH,
J1 = 6.8, J2 = 8.2), 6.18 d (1H, NHCH, J= 8.2), 6.60‒7.04 m
(4H, C6H4).
2-{5-[1-(4-Chlorophenylamino)ethyl]-1,3,4-
oxadiazol-2-ylsulfanyl}acetamide (11d). Н NMR
spectrum, δ, ppm (J, Hz): 1.61 d (3H, CH3, J = 6.8), 3.97 s
(2H, SCH2), 4.77 d. q (1H, NCH, J1 = 6.8, J2 = 8.2), 6.20 d
(1H, NHCH, J = 8.2), 6.60‒7.04 m (4H, C6H4), 7.08 br. s
and 7.57 br. s (2H, NH2).
N′-(4-Methoxybenzylidene)-2-phenoxy-
propanehydrazide (13a). 1Н NMR spectrum, δ, ppm (J,
Hz): 1.58 d (1.2H, CH3, J = 6.6), 1.60 d (1.8H, CH3, J =
6.6), 4.71 q (0.4H, OCH, J = 6.6), 5.56 q (0.6H, OCH,
J = 6.6), 6.76‒7.63 m (9H, C6H5 + C6H4), 7.94 s (0.6H,
CH), 8.27 s (0.4H, CH), 11.08 s (0.4H, NHCO), 11.31 s
(0.6H, NHCO). 13С NMR spectrum, δС, ppm: 17.5, 18.3,
54.6, 69.1, 73.4, 113.5, 113.6, 114.2, 115.0, 119.9, 120.7,
126.5, 126.7, 127.9, 128.3, 128.7, 128.9, 143.4, 147.5,
157.0, 157.5, 160.4, 166.7, 171.3.
1
1,3,4-Methyl 2-{5-[1-(3,4-dichlorophenylamino)ethyl]-
1
oxadiazol-2-ylsulfanyl}acetate (12c). Н NMR
spectrum, δ, ppm (J, Hz): 1.61 d (3H, CH3, J = 6.9),
3.71 s (3H, OCH3), 4.08 s (2H, SCH2), 4.79 d. q (1H,
NCH, J1 = 6.9, J2 = 8.1), 6.46 d (1H, NHCH, J = 8.1),
6.57‒7.16 m (3H, C6H3). 13С NMR spectrum, δС, ppm:
18.5, 33.3, 44.2, 52.1, 112.2, 113.7, 118.3, 129.8, 131.5,
146.4, 162.3, 167.0, 168.1.
N′-(4-Hydroxy-3-methoxybenzylidene)-2-phenoxy-
propanehydrazide (13b). 1Н NMR spectrum, δ, ppm (J,
Hz): 1.58 d (1.5H, CH3, J = 6.6), 1.60 d (1.5H, CH3, J =
6.6), 3.83 s (1.5H, OCH3), 3.85 s (1.5H, OCH3), 4.72 q
(0.5H, OCH, J = 6.6), 5.57 q (0.5H, OCH, J = 6.6),
6.75‒7.28 m (8H, C6H5 + C6H3), 7.89 s (0.5H, CH),
8.19 s (0.5H, CH), 8.95 s (0.5H, OH), 8.96 s (0.5H, OH),
11.05 s (0.5H, NHCO), 11.24 s (0.5H, NHCO). 13С NMR
spectrum, δС, ppm: 17.4, 18.4, 55.26, 55.28, 69.1, 73.3,
108.7, 109.3, 114.2,114.9, 115.0, 115.1, 120.0, 120.8,
2-{5-[1-(3,4-Dichlorophenylamino)ethyl]1,3,4-
1
oxadiazol-2-ylsulfanyl}acetamide (12d). Н NMR
spectrum, δ, ppm (J, Hz): 1.61 d (3H, CH3, J = 6.9), 3.96 s
(2H, SCH2), 4.79 d. q (1H, NCH, J1 = 6.9, J2 = 8.2), 6.47 d
(1H, NHCH, J = 8.2), 6.56‒7.17 m (3H, C6H3), 7.08 br. s
and 7.56 br. s (2H, NH2). 13С NMR spectrum, δС, ppm:
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SYNTHESIS OF POTENTIAL BIOLOGICALLY ACTIVE COMPOUNDS
1185
121.1, 122.0, 125.2, 125.3, 128.7, 128.9, 144.2, 147.6,
147.7, 148.5, 148.8, 149.0, 157.1, 157.5, 166.8, 171.2.
6.55‒7.52 m (8H, C6H4), 7.90 s (0.6H, CH=N), 8.24 s
(0.4H, CH=N), 9.44 br. s (1H, OH), 10.91 s (0.4H,
NHCO), 11.09 s (0.6H, NHCO). 13С NMR spectrum, δС,
ppm: 17.6, 18.5, 47.8, 51.8, 113.7, 113.9, 115.25, 115.31,
120.0, 120.4, 124.9, 128.0, 128.1, 128.13, 128.4, 144.0,
146.0, 146.1, 147.4, 159.1, 159.3, 169.3, 174.1.
N ′ - ( 3 - N i t r o b e n z y l i d e n e ) - 2 - p h e n o x y -
propanehydrazide (13c). 1Н NMR spectrum, δ, ppm (J,
Hz): 1.60 d (1.5H, CH3, J = 6.6), 1.62 d (1.5H, CH3, J =
6.6), 4.77 q (0.5H, OCH, J = 6.6), 5.60 q (0.5H, OCH,
J = 6.6), 6.78‒8.47 m (9H, C6H5 + C6H4), 8.13 s (0.5H,
CH), 8.49 s (0.5H, CH), 11.54 s (0.5H, NHCO), 11.71 s
(0.5H, NHCO). 13С NMR spectrum, δС, ppm: 17.4, 18.2,
69.2, 73.5, 114.3, 115.1, 120.1, 120.9, 121.2, 123.4, 123.5,
128.7, 128.9, 129.4, 129.5, 131.9, 132.4, 135.8, 136.2,
141.1, 145.1, 148.0, 148.1, 157.0, 157.4, 167.4, 171.7.
N′-(Benzo[d][1,3]dioxol-5-ylmethylidene)-2-(4-
chlorophenylamino)propanehydrazide (15f). 1Н NMR
spectrum, δ, ppm (J, Hz): 1.41 d (3H, CH3, J = 6.8), 3.90 m
(0.3H, NCH), 4.86 m (0.7H, NCH), 5.50 br. s (0.7H,
NHCH), 5.71 br. s (0.3H, NHCH), 6.01 s (2H, OCH2O),
6.57‒7.28 m (7H, C6H3 + C6H4), 7.91 s (0.7H, CH=N),
8.28 s (0.3H, CH=N), 11.05 s (0.3H, NHCO), 11.22 s
(0.7H, NHCO). 13С NMR spectrum, δС, ppm: 17.6, 18.5,
47.8, 51.9, 100.9, 104.8, 105.1, 107.6, 107.7, 113.7, 113.9,
120.0, 120.4, 122.6, 122.8, 128.10, 128.15, 128.5, 128.6,
143.3, 145.9, 146.1, 146.7, 147.7, 147.8, 148.6, 148.7,
169.6, 174.4.
2-(3,4-Dichlorophenoxy)-N′-(4-methoxy-
1
benzylidene)propanehydrazide (14a). Н NMR
spectrum, δ, ppm (J, Hz): 1.65 d (0.9H, CH3, J = 6.6),
1.69 d (2.1H, CH3, J = 6.6), 3.80 s (3H, OCH3), 4.80 q
(0.3H, J = 6.6), 5.58 q (0.7H, OCH, J = 6.6), 6.78‒7.65 m
(7H, C6H3 + C6H4), 7.95 s (0.7H, CH=N), 8.25 s (0.3H,
CH=N), 11.27 s (0.3H, NHCO), 11.42 s (0.7H, NHCO).
N′-(Furan-2-ylmethylidene)-2-(4-chlorophenyl-
amino)propanehydrazide (15g). 1Н NMR spectrum, δ,
ppm (J, Hz): 1.40 d. d and 1.41 d. d (3H, CH3, J = 6.8),
3.89 m (0.3H, NCH), 4.85 m (0.7H, NCH), 5.50 d (0.7H,
NHCH, J=8.2), 5.72d(0.3H, NHCH, J=8.2), 6.47‒7.60m
(7H, 3H-furan + C6H4), 7.90 s (0.7H, CH=N), 8.26 s
(0.3H, CH=N), 11.15 s (0.3H, NHCO), 11.30 s (0.7H,
NHCO). 13С NMR spectrum, δС, ppm: 17.6, 18.4, 47.7,
51.9, 111.27, 111.34, 111.50, 111.53, 113.7, 113.8, 120.0,
120.4, 128.07, 128.10, 133.3, 137.1, 143.5, 143.7, 145.9,
146.0, 149.4, 149.6, 169.8, 174.5.
N′-(4-Hydroxy-3-methoxybenzylidene)-2-
1
(3,4-dichlorophenoxy)propanehydrazide (14b). Н
NMR spectrum, δ, ppm (J, Hz): 1.63 d (1.2H, CH3, J =
6.6), 1.68 d (1.8H, CH3, J = 6.6), 3.82 s (1.8H, OCH3),
3.85 s (1.2H, OCH3), 4.85 q (0.4H, OCH, J = 6.6), 5.58 q
(0.6H, OCH, J = 6.6), 6.75‒7.40 m (6H, 2C6H3), 7.90 s
(0.6H, CH=N), 8.20 s (0.4H, CH=N), 9.00 s (1H, OH),
11.27 s (0.4H, NHCO), 11.42 s (0.6H, NHCO).
2-(3,4-Dichlorophenoxy)-N′-(3-nitrobenzylidene)-
propanehydrazide (14c). 1Н NMR spectrum, δ, ppm (J,
Hz): 1.65 d (1.2H, CH3, J = 6.6), 1.70 d (1.8H, CH3, J =
6.6), 4.80 q (0.4H, OCH, J = 6.6), 5.62 q (0.6H, OCH,
J = 6.6), 6.80‒8.70 m (8H, C6H3, C6H4, CH=N), 11.58 s
(0.4H, NHCO), 11.80 s (0.6H, NHCO).
2-(3,4-Dichlorophenylamino)-N′-(4-methoxy-
1
benzylidene)propanehydrazide (16a). Н NMR
spectrum, δ, ppm (J, Hz): 1.42 d (0.9H, CH3, J = 6.8),
1.43 d (2.1H, CH3, J = 6.8), 3.82 s (0.9H, OCH3), 3.83 s
(2.1H, OCH3), 3.92 m (0.3H, NCH), 4.86 m (0.7H, NCH),
5.91 br. s (0.7H, NHCH), 6.05 br. s (0.3H, NHCH),
6.50‒7.65 m (7H, C6H3 + C6H4), 7.95 s (0.7H, CH=N),
8.20 s (0.3H, CH=N), 11.06 s (0.3H, NHCO), 11.22 s
(0.7H, NHCO). 13С NMR spectrum, δС, ppm: 17.4, 18.3,
47.6, 51.4, 54.59, 54.61, 112.1, 112.4, 113.5, 113.6, 117.4,
117.5, 126.6, 126.7, 127.9, 128.2, 129.7, 129.8, 131.4,
143.4, 146.8, 147.3, 160.4, 160.5, 168.9, 173.8.
N′-Benzylidene-2-(4-chlorophenylamino)pro-
panehydrazide (15d). 1Н NMR spectrum, δ, ppm (J, Hz):
1.43 d (3H, CH3, J = 6.8), 3.90 m (0.3H, NCH), 4.88 m
(0.7H, NCH), 5.52 d (0.7H, NHCH, J = 8.2), 5.73 d (0.3H,
NHCH, J = 8.2), 6.55‒7.70 m (9H, C6H5 + C6H4), 8.01 s
(0.7H, CH=N), 8.28 s (0.3H, CH=N), 11.15 s (0.3H,
NHCO), 11.36 (0.7H, NHCO). 13С NMR spectrum, δС,
ppm: 17.7, 18.5, 47.9, 51.9, 113.7, 113.9, 120.1, 120.5,
126.48, 126.51, 126.8, 128.0, 128.1, 128.2, 129.1, 129.2,
134.1, 134.2, 143.5, 146.0, 146.1, 147.0, 169.8, 174.6.
N′-(4-Hydroxy-3-methoxybenzylidene)2-(3,4-di-
chlorophenylamino)propanehydrazide (16b). 1Н NMR
spectrum, δ, ppm (J, Hz): 1.42 d (0.9H, CH3, J = 6.8),
1.43 d (2.1H, CH3, J = 6.8), 3.86 s (0.9H, OCH3), 3.87 s
(2.1H, OCH3), 3.91 q (0.3H, J = 6.8, NCH), 4.87 q (0.7H,
J = 6.8, NCH), 5.98 br. s (1H, NHCH), 6.50‒7.32 m
(6H, C6H3 + C6H3), 7.88 s (0.7H, CH=N), 8.12 s (0.3H,
N′-(4-Hydroxybenzylidene)-2-(4-chlorophenyl-
amino)propanehydrazide (15e). 1Н NMR spectrum, δ,
ppm (J, Hz): 1.41 d (3H, CH3, J = 6.8), 3.89 m (0.4H,
NCH), 4.86 m (0.6H, NCH), 5.50 br. s (1H, NHCH),
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 90 No. 7 2020

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GOMKTSYAN et al.
CH=N), 8.93 br. s (1H, OH), 11.01 s (0.3H, NHCO),
11.15 s (0.7H, NHCO). 13С NMR spectrum, δС, ppm:
17.4, 18.4, 47.6, 51.5, 55.3, 108.8, 109.5, 112.3, 112.5,
113.5, 113.7, 114.9, 115.2, 117.5, 117.9, 121.1, 122.1,
125.3, 129.8, 129.9, 131.5, 144.3, 147.2, 147.4, 147.6,
147.7, 147.8, 148.8, 149.0, 169.1, 173.8.
ppm (J, Hz): 1.33 d (1.5H, CH3, J = 6.7), 1.34 s (1.5H,
CH3), 1.76 s (1.5H, N=CCH3), 1.78 s (1.5H, N=CCH3),
2.07 s (3H, COCH3), 2.80 d and 2.88 d (2H, CH2, J =
18.4), 4.63 d. q (0.5H, NCH, J1 = 8.7, J2 = 6.7), 4.67 d. q
(0.5H, NCH, J1 = 8.7, J2 = 6.7), 5.84 d (1H, NHCH,
J = 8.7), 5.95 s (0.5H, NHCO), 6.00 s (0.5H, NHCO),
6.47‒7.15 m (3H, C6H3). 13С NMR spectrum, δС, ppm:
15.7, 16.9, 17.5, 25.7, 26.0, 49.1, 49.3, 51.6, 90.5, 112.1,
113.4, 113.7, 129.66, 129.70, 131.36, 131.4, 147.2, 147.3,
153.8, 153.9, 170.4, 170.8.
N′-Benzylidene-2-(3,4-dichlorophenylamino)pro-
1
panehydrazide (16d). Н NMR spectrum, δ, ppm (J,
Hz): 1.42 d (0.9H, CH3, J = 6.8), 1.43 d (2.1H, CH3, J =
6.8), 3.92 q (0.3H, NCH, J = 6.8), 4.88 q (0.7H, NCH, J =
6.8), 5.93 br. s (0.7H, NHCH), 6.07 br. s (0.3H, NHCH),
6.50‒7.98 m (8H, C6H5 + C6H3), 7.98 s (0.7H, CH=N),
8.26 s (0.3H, CH=N), 11.21 s (0.3H, NHCO), 11.38 s
(0.7H, NHCO). 13С NMR spectrum, δС, ppm: 17.5, 18.3,
47.7, 51.5, 112.1, 112.4, 113.6, 113.7, 117.5, 126.5, 126.8,
127.6, 128.0, 128.1, 128.4, 129.08, 129.12, 129.2, 129.7,
129.8, 131.4,131.7, 134.0,134.2, 143.6, 147.0, 147.2,
147.3, 169.3, 174.1.
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
REFERENCES
1. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs),
Moscow: Novaya Volna, 2019.
2. Masunari, A. and Tavaris, L.C., Bioorg. Med. Chem.,
2007, vol. 15, p. 4229.
https://doi.org/10.1016/j.bmc.2007.03.068
General procedure for the synthesis of compounds
17–20. 10 mmol of pentane-2,4-dione and 3 drops of
DMF were added to a solution of 10 mmol of hydrazide
1–4 in 10 mL of acetic acid at 0°C. The reaction mixture
was stirred for 6 h at 80°С, and then left overnight. The
next day, 20–30 mL of ice water was added. The formed
precipitate was filtered off, washed with water, and dried.
3. Loncle, C., Brunel, J., Vidal, N., Dherbomez, M.,
and Letourneux, Y., Eur. J. Med. Chem., 2004,
vol. 39, p. 1067.
https://doi.org/10.1016/j.ejmech.2004.07.005
4. Küҫükgüzel, S.G., Mazi, A., Sahin, F., Öztürk, S., and
Stables, J.P., Eur. J. Med. Chem., 2003, vol. 38, p. 1005.
https://doi.org/10.1016/j.ejmech.2003.08.004
N′-(4-Oxopentan-2-ylidene)-2-phenoxypro-
panehydrazide (17). 1Н NMR spectrum, δ, ppm (J, Hz):
1.50 d (3H, CH3, J = 6.6), 1.80 s (3H, N=CCH3), 2.08 s
(3H, COCH3), 2.80 d and 2.86 d (2H, CH2, J= 18.4), 5.38 q
(1H, OCH, J = 6.6), 6.22 s (1H, NHCO), 6.73‒7.28 m
(5H, C6H5).
5. Vicini, P., Zani, F., Cozzini, P., and Doytchinova, I., Eur.
J. Med. Chem., 2002, vol. 37, p. 553.
https://doi.org/10.1016/S0223-5234(02)01378-8
6. Bijev, A., Lett. Drug Des. Discovery, 2006, vol. 3, p. 506.
7. Todeschini, A.R., Miranda, A.L., Silva, C.M.,
Parrini, S.C., and Barreiro, E.J., Eur. J. Med. Chem.,
1998, vol. 33, p. 189.
2-(3,4-Dichlorophenoxy)-N′-(4-oxopentan-2-
https://doi.org/10.1016/S0223-5234(98)80008-1
1
ylidene)propanehydrazide (18). Н NMR spectrum,
8. Gemma, S., Kukreja, G., Fattorusso, C., Persico, M.,
Romano, M., Altarelli, M., Savini, L., Campiani, G.,
Fattorusso, E., and Basilico, N., Bioorg. Med. Chem.
Lett., 2006, vol. 16, p. 5384.
δ, ppm (J, Hz): 1.47 d (3H, CH3, J = 6.6), 1.79 s (3H,
N=CCH3), 2.08 s (3H, COCH3), 2.80 d and 2.86 d (2H,
CH2, J = 18.4), 5.35 q (1H, OCH, J = 6.6), 6.20 s (1H,
NHCO), 6.62‒7.21 m (3H, C6H3).
https://doi.org/10.1016/j.bmcl.2006.07.060
N′-(4-Oxopentan-2-ylidene)-2-(4-chlorophenyl-
amino)propanehydrazide (19). Н NMR spectrum,
9. Gürsoy, E., and Ulusoy-Güzeldemirci, N., Eur. J. Med.
Chem., 2007, vol. 42, p. 320.
1
δ, ppm (J, Hz): 1.32 d (3H, OCH, J = 6.7), 1.75 s (3H,
N=CCH3), 2.06 s (3H, COCH3), 2.79 d and 2.86 d (2H,
CH2, J = 18.5), 4.65 m (1H, NCH), 5.42 br. s (1H, NH),
5.92 br. s (1H, NHCO), 6.48‒7.05 m (4H, C6H4). 13С
NMR spectrum, δС, ppm: 15.7, 17.1, 26.1, 49.2, 51.5,
90.4, 113.5, 113.7, 119.9, 128.0, 146.0, 153.6, 170.8.
https://doi.org/10.1016/j.ejmech.2006.10.012
10. Ragavendran, J., Sriram, D., Patel, S., Reddy, I., Bharath-
wajan, N., Stables, J., and Yogeeswari, P., Eur. J.
Med. Chem., 2007, vol. 42, p. 146.
https://doi.org/10.1016/j.ejmech.2006.08.010
11. Ergenҫ, N., Günay, N.S., and Demirdamar, R.,
Eur. J. Med. Chem., 1998, vol. 33, p. 143.
2-(3,4-Dichlorophenylamino)-N′-(4-oxopentan-2-
ylidene)propanehydrazide (20). 1Н NMR spectrum, δ,
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SYNTHESIS OF POTENTIAL BIOLOGICALLY ACTIVE COMPOUNDS
1187
https://doi.org/10.1016/S0223-5234(98)80039-1
12. http://www.alanwood.net/pesticides/class_pesticides.html.
13. Gomktsyan, T.A., Karapetyan, A.V., Abrahamyan, L.G.,
and Yengoyan, A.P., Khim. Zh. Arm., 2012, vol. 65,
no. 3, p. 342.
15. Pivazyan, V.A., Ghazaryan, E.A., Azaryan, Zh.A.,
and Yengoyan, A.P., Russ. J. Gen. Chem., 2019, vol. 89,
no. 10, p. 2010.
https://doi.org/10.1134/S1070363219100050
16. Shainova, R.S., Gomktsyan, T.A., Karapetyan, A.V.,
and Yengoyan, A.P., J. Chem. Res., 2019, vol. 43,
nos. 9–10, p. 352.
14. Yengoyan, A.P., Gomktsyan, T.A., Karapetyan, A.V., and
Shainova, R.S., Khim. Zh. Arm., 2017, vol. 70, nos. 1‒2,
p. 199.
https://doi.org/10.1177/1747519819866402
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