Synthesis and Herbicidal and Antioxidant Activity of a Series of Hetero- and Carbocyclic Derivatives of Monochloroacetic Acid

Article abstract of DOI:10.1134/S1070427220050122

Abstract: Monochloroacetic acid esters and amides containing carbo- and heterocycles and heterocyclic esters and amides derived from commercial aryloxyacetyl chlorides were synthesized. The structures of the compounds were confirmed by ¹Н and ¹³С spectroscopy. The herbicidal activity of the substances was studied with respect to mono- and dicotyledonous plants. The relative antioxidant activity of the compounds was studied by recording the luminol-dependent chemiluminescence. The experimental data, on the whole, confirm that the development of herbicides containing acetal and gem-dichlorocyclopropane fragments is appropriate and promising.

Full text of DOI:10.1134/S1070427220050122

ISSN 1070-4272, Russian Journal of Applied Chemistry, 2020, Vol. 93, No. 5, pp. 712–720. © Pleiades Publishing, Ltd., 2020.
Russian Text © The Author(s), 2020, published in Zhurnal Prikladnoi Khimii, 2020, Vol. 93, No. 5, pp. 705–713.
ORGANIC SYNTHESIS
AND INDUSTRIAL ORGANIC CHEMISTRY
Synthesis and Herbicidal and Antioxidant Activity
of a Series of Hetero- and Carbocyclic
Derivatives of Monochloroacetic Acid
E. A. Yakovenkoa, Yu. L. Baimurzinab, G. Z. Raskil’dinaa,*, and S. S. Zlotskiia
a Ufa State Petroleum Technological University, Ufa, 450064 Russia
b Bashkir State Medical University, Ufa, 450000 Russia
*e-mail: graskildina444@mail.ru
Received October 20, 2018; revised September 4, 2019; accepted February 8, 2020
Abstract—Monochloroacetic acid esters and amides containing carbo- and heterocycles and heterocyclic esters
and amides derived from commercial aryloxyacetyl chlorides were synthesized. The structures of the compounds
were confirmed by 1Н and 13С spectroscopy. The herbicidal activity of the substances was studied with respect to
mono- and dicotyledonous plants. The relative antioxidant activity of the compounds was studied by recording
the luminol-dependent chemiluminescence. The experimental data, on the whole, confirm that the development of
herbicides containing acetal and gem-dichlorocyclopropane fragments is appropriate and promising.
Keywords: amines, monochloroacetic acid esters and amines, cyclic acetal and gem-dichlorocyclopropane
fragments, herbicidal and antioxidant activity
DOI: 10.1134/S1070427220050122
Monochloroacetic acid derivatives, primarily ary-
loxyacetic acid esters and amines, exhibit high herbi-
cidal activity and are widely used as chemical means
for plant protection [1, 2]. Therefore, synthesis of new
hetero- and carbocyclic derivatives of monochloroacetic
acid and evaluation of their herbicidal and biological ac-
tivity is a topical problem.
gas helium, flow rate 30 mL min–1, column length 25
m, column temperature 50–280°С with programmed
heating at a rate of 8 deg min–1, detector temperature
250°С, and vaporizer temperature 300°С. Analysis
by gas chromatography–mass spectrometry was
performed with Fisons (DB 560 50-m quartz capillary
column) and Focus devices using a Finnigan DSQII
mass-spectrometric detector (ion source temperature
200°С, direct inlet temperature 50–270°С, heating
rate 10 deg min–1, Thermo TR-5MS 50 m × 0.25 mm
column, helium flow rate 0.7 mL min–1). The mass
spectra were recorded with electron impact ionization.
The NMR spectra were taken with a Bruker Avance-500
spectrometer (1H 500.13 MHz) in CDCl3.
As shown previously [3], the presence of cyclic
acetal and gem-dichlorocyclopropane fragments in the
structure of the molecules enhances their biological
activity and the ability to control the plant growth [3].
In this study, we prepared monochloroacetic acid
esters and amides containing 1,3-dioxolane and gem-
dichlorocyclopropane fragments and evaluated their
biological and herbicidal activity.
We used freshly distilled acetonitrile, dimethyl
sulfoxide, and pyridine solvents (all chemically pure
grade, OOO Tekhresurs, Russia), monochloroacetyl
chloride (Sigma–Aldrich), freshly calcined K2CO3 and
MgSO4 (both pure grade, OOO Steklopribor, Russia),
EXPERIMENTAL
Chromatographic analysis of reaction products was
performed with an HRGS 5300 Mega Series Carlo
Erba chromatograph equipped with a flame ionization
detector. The analysis conditions were as follows: carrier
2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane as
a
heterocyclic alcohol, and its monochloroacetic acid
ester (1), prepared as described in [4].
712

SYNTHESIS AND HERBICIDAL AND ANTIOXIDANT ACTIVITY
713
Synthesis of (2,2-dimethyl-1,3-dioxolan-4-yl)me-
thyl morpholin-4-ylacetate (2), (2,2-dimethyl-1,3-
dioxolan-4-yl)methyl piperazin-1-ylacetate (3),
(2,2-dimethyl-1,3-dioxolan-4-yl)methyl N,N-dieth-
ylglycinate (4), and bis[(2,2-dimethyl-1,3-dioxolan-
4-yl)methyl] 2,2'-(piperazine-1,4-diyl)diacetate (5)
(general procedure). To a mixture of 20 mL of acetoni-
trile and 0.15 mol (20.7 g) of K2CO3, we added 0.1 mol
of an amine: morpholine (8.7 g), piperazine (8.6 g), or
diethylamine (7.3 g). The mixture was refluxed for 2 h.
Then, 0.12 mol (20.8 g) of compound 1 was added, and
the mixture was refluxed for 7 h. The resulting mixture
was filtered while hot, and the filtrate was evaporated
and vacuum-distilled.
Bis[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]
2,2'-(piperazine-1,4-diyl)diacetate (5). Yield 57%,
1
Тm = 152–154°С. Н NMR spectrum, δ, ppm (J, Hz):
1.30 s (6H, 2C7H3), 1.39 s (6H, C6H3), 2.52 s (4H,
C1'H2, C1''H2), 3.20 s (4H, 2C10H2), 3.75 s (4H, C2'H2,
C2''H2), 3.71 m (1H, C4H1), 4.14 d (1H, C5Ha, 2J = 2.8),
2
4.27 d (1H, C5Hb, J = 2.8). 13C NMR spectrum, δС,
ppm: 25.73 (2C7H3), 26.94 (2C6H3), 52.45 (C2' + C2'',
C1' + C1''), 58.59 (C10), 64.69 (C8), 65.80 (C4), 73.49
(C5), 109.22 (C2), 170.15 (C9).
Synthesis of methyl piperazin-1-ylacetate (6) and
dimethyl 2,2'-(piperazine-1,4-diyl)diacetate (7) (gen-
eral procedure). A three-necked flask equipped with a
reflux condenser, a thermometer, and a mechanical stir-
rer was charged with 0.03 mol (2.58 g) of piperazine,
15 mL of DMSO, and 0.01 mol (2.08 g) of methyl mon-
ochloroacetate. The mixture was stirred for the required
time at 70–75°C. After the reaction completion, the mix-
ture was washed with a 20% NaOH solution and ex-
tracted with ether. The upper organic layer was washed
with water to neutral reaction and dried over anhydrous
potassium carbonate. The solvent was evaporated on a
rotary evaporator, and the residue was distilled under re-
duced pressure in a nitrogen flow.
(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl morpho-
lin-4-ylacetate (2). Yield 37%, Тb = 160°С (2 mmHg).
1Н NMR spectrum, δ, ppm (J, Hz): 1.30 s (3H, C7H3),
1.39 s (3H, C6H3), 2.52 s (4H, C3'H2, C3''H2), 3.20 s
(2H, C10H2), 3.75 s (4H, C2'H2, C2''H2), 3.70–3.74 m
2
(1H, C4H1), 4.14 d (1H, C5Ha, J = 2.8), 4.26 d (1H,
2
C5Hb, J = 2.8). 13C NMR spectrum, δС, ppm: 25.23
(C7), 26.57 (C6), 53.14 (C3' + C3''), 59.21 (C10H2), 64.52
(C8H2), 64.71 (C5H2), 66.10 (C2' + C2''), 73.72 (C4H1)
109.77 (C2), 169.77 (C9). Mass spectrum, m/e (Irel, %):
[M]+ 259 (1), 193 (50), 101 (24), 77 (24), 72 (14), 57
(20), 43 (100).
Methyl piperazin-1-ylacetate (6). Yield 48%, Тm =
1
122–124°С. Н NMR spectrum, δ, ppm (J, Hz): 2.51 s
(1H, NH), 2.63 s (8H, C4H2, C4'H2, C5H2, C5'H2), 3.36 s
(2H, C1H2), 3.69 s (3H, C3H3). 13C NMR spectrum, δС,
ppm: 47.01 (C5 + C5'), 52.13 (C3), 54.10 (C1), 57.32
(C4 + C4'), 176.71 (C2). Mass spectrum, m/e (Irel, %):
[M]+ 158 (8), 116 (20), 99 (100), 88 (8), 70 (18), 56 (34).
(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl
piper-
azin-1-ylacetate (3). Yield 31%, Тm = 135–137°С.
1Н NMR spectrum, δ, ppm (J, Hz): 1.32 s (3H, C7H3),
1.38 s (3H, C6H3), 2.31 s (1H, NH), 2.53 s (4H, C2'H2,
C2''H2), 3.11 s (4H, 2CH2), 3.20 s (2H, C10H2), 3.72 m
Dimethyl 2,2'-(piperazin-1,4-diyl)diacetate (7).
Yield 70%, Тm = 134–136°С. 1Н NMR spectrum, δ, ppm
(J, Hz): 2.65 s (8H, C4H2, C4'H2, C5H2, C5'H2), 3.25 s
(4H, 2C1H2), 3.71 s (6H, 2C3H3). 13C NMR spectrum,
δС, ppm: 51.73 (2C3), 52.76 (C4 + C4', C5 + C5'), 59.33
(2C1), 170.65 (2C2). Mass spectrum, m/e (Irel, %): [M]+
230 (10), 171 (100), 98 (58), 80 (8) 70 (12), 56 (28).
2
(1H, C4H1), 4.02 d (2H, C8H2, J = 4.1), 4.15-4.25 d.d
2
3
13
(2H, C5H2, J = 7.8, J = 4.6). C NMR spectrum, δС,
ppm: 25.41 (C7), 26.35 (C6), 46.91 (C3' + C3''), 55.74
(C2' + C2''), 56.22 (C10), 64.10 (C8), 64.46 (C5), 73.70
(C4), 107.97 (C2), 173.01 (C9).
(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl N,N-di-
ethylglycinate (4). Yield 58%, Тb = 142°С (5 mmHg).
1Н NMR spectrum, δ, ppm (J, Hz): 1.05 t (6H, 2C13H3,
2J = 7.2), 1.31 s (3H, C7H3), 1.39 s (3H, C6H3), 2.61 q
(4H, 2C11H2, 2J = 7.1), 3.32 s (2H, C10H2), 3.71 m (1H,
C4H1), 4.05 d (1H, C5Hb, 2J = 6.0), 4.15 d.d (2H, C8H2,
2J = 4.3, 3J = 7.1), 4.29 d (1H, C5Ha, 2J = 6.0). 13C NMR
spectrum, δС, ppm: 12.08 (2C12), 25.31 (C7), 26.65 (C6),
47.66 (2C11), 53.73 (C10), 64.58 (C8), 65.80 (C5), 73.50
(C4), 109.82 (C2), 171.12 (C9). Mass spectrum, m/e (Irel,
%): [M]+ 245 (2), 230 (6.5), 86 (100), 43 (10).
Synthesis of (2,2-dimethyl-1,3-dioxolan-4-yl)
methyl N-benzyl-N-[(2,2-dichlorocyclopropyl)me-
thyl]glycinate (8) and methyl N-benzyl-N-[(2,2-
dichlorocyclopropyl)methyl]glycinate (9) (general
procedure). To a mixture of 20 mL of acetonitrile and
0.15 mol (20.7 g) of K2CO3, we added 0.1 mol (23 g) of
N-benzyl-1-(2,2-dichlorocyclopropyl)methanamine and
0.12 mol (24.9 g) of (2,2-dimethyl-1,3-dioxolan-4-yl)
methyl chloroacetate (1) or 0.12 mol (12.9 g) of methyl
chloroacetate. The mixture was stirred under microwave
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714
YAKOVENKO et al.
heating for 1 h, after which it was filtered while hot, and
the filtrate was evaporated and vacuum-distilled.
13С NMR spectrum (CDCl3, δC, ppm): 25.24 (C7), 26.61
(C6), 63.14 (C8), 65.45 (C4), 69.77 (C10), 71.12 (C5),
109.88 (C2), 114.56–129.60 (5C, Ph), 157.64 (CPh),
168.79 (C9). Mass spectrum, m/e (Irel, %): [M]+ 266
(18), 251 (68), 117 (17), 107 (100), 101 (32), 79 (14),
77 (50), 72 (12), 59 (10), 51 (9).
(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl N-ben-
zyl-N-[(2,2-dichlorocyclopropyl)methyl]glycinate
(8). Yield 78%, Тb = 270°С (3 mmHg). 1Н NMR spec-
trum, δ, ppm (J, Hz): 1.18 t (1H, C1’Ha, 2J = 7.5), 1.36 s
2
(3H, C7H3), 1.39 s (3H, C6H3), 1.68 t (1H, C1’Hb, J =
(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl (2,4-di-
chlorophenyl)acetate (11). Yield 33%, Тb = 215°С
(3 mmHg). 1Н NMR spectrum (CDCl3, δ, ppm, J, Hz):
1.34 s (3H, C7H3), 1.42 s (3H, C6H3), 3.72 m (1H,
2.8), 1.78–1.84 m (1H, C3’H1), 2.95 d (2Н, С11Н2, 2J =
7.3), 3.45 s (2Н, С10Н2), 3.62 m (1H, C4H1), 3.71 d (2H,
C12H2, 2J = 7.3), 4.01 d.d (2H, C8H2, 2J = 6.9, 3J = 5.6),
3
2
3
4.15 d.d (2H, C5H2, 2J = 4.9, J = 5.6), 7.13–7.65 (5Н,
C4H1), 4.19 d.d (2H, C5H2, J = 7.2, J = 5.7), 4.25 d
(2H, C8H2, 2J = 5.9), 4.75 s (2H, C10H2), 6.75–7.45 (3H,
Ph). 13С NMR spectrum (CDCl3, δC, ppm): 25.25 (C7),
26.62 (C6), 63.13 (C8), 66.02 (C5), 66.26 (C10), 73.22
(C4), 109.99 (C2), 114.70–130.36 (Ph), 152.25 (CPh),
167.88 (C9). Mass spectrum, m/e (Irel, %): M+ not ob-
served, 334/336/338 (10/6/2), 319/321/323 (100/72/8),
Ph). 13C NMR spectrum, δС, ppm: 24.63 (C3’), 25.31
(C7), 26.01 (C6), 26.58 (C2’), 56.74 (C12), 60.29 (C1’),
61.31 (C10), 64.18 (C5), 64.26 (C8), 66.10 (C11), 73.71
(C4), 107.94 (C2), 127.11–130.37 (Ph), 140.21 (CPh),
170.46 (C9).
Methyl
N-benzyl-N-[(2,2-dichlorocyclopropyl)
175/177/179
(66/38/8),
145/147/149
(14/9/2),
methyl]glycinate (9). Yield 88%, Тb = 182°С (2 mmHg).
1Н NMR spectrum, δ, ppm (J, Hz): 1.16 t (1H, C1Ha,
2J = 7.5), 1.66 t (1H, C1Hb, 2J = 2.8), 1.79–1.85 m (1H,
133/135/137 (14/8/2), 109/111/113 (14/8/2), 101 (44),
73 (28), 57 (14), 43 (96).
2
C3H1), 2.95 d (2Н, С4Н2, J = 7.3), 3.45 s (2Н, С6Н2),
Synthesis of 1-[(2,2-dichlorocyclopropyl)methyl]-
4-(phenoxyacetyl)piperazine (12), N-[(2,2-dichloro-
cyclopropyl)methyl]-N-(1,3-dioxolan-4-ylmethyl)-
2-phenoxyacetamide (13), and N-[(2,2-dichlorocy-
clopropyl)methyl]-2-phenoxy-N-(tetrahydrofuran-
2-ylmethyl)acetamide (14) (general procedure). To
a mixture of 0.02 mol of appropriate amine (4.18 g of
[(2,2-dichlorocyclopropyl)methyl]piperazine, 5.21 g
3.65 s (3Н, С8Н3), 3.91 s (2Н, С5Н2), 7.15–7.65 (5Н,
Ph). 13C NMR spectrum, δС, ppm: 25.22 (C3), 29.23
(C1), 51.23 (C8), 53.46 (C4), 57.96 (C6), 60.75 (C5),
127.20–129.27 (Ph), 138.52 (C2), 171.51 (C7). Mass
spectrum, m/e (Irel, %): [M]+ not observed, 242/244/246
(28/20/3), 91 (100), 65 (10).
Synthesis of (2,2-dimethyl-1,3-dioxolan-4-yl)me-
thyl phenoxyacetate (10) and (2,2-dimethyl-1,3-diox-
olan-4-yl)methyl (2,4-dichlorophenoxy)acetate (11)
(general procedure). A mixture of 0.03 mol (3.96 g) of
2,2-dimethyl-4-hydroxymethyl-1,3-dioxolane, 0.03 mol
of phenoxyacetyl (5.1 g) or 2,4-dichlorophenoxyacetyl
(7.17 g) chloride, and 0.03 mol (2.37 g) of freshly dis-
tilled pyridine was stirred for 9 h. The oil that formed
was left to crystallize for 24 h with cooling and intermit-
tent trituration with a glass rod. Then, a mixture of 15 g
of ice and 10 mL of 1 M HCl was added, and the result-
ing mixture was stirred until a suspension was formed.
The crude product was filtered off, washed with ice-cold
water, dried with freshly calcined MgSO4 and the resi-
due was vacuum-distilled.
of
[(2,2-dichlorocyclopropyl)methyl](1,3-dioxolan-
4-ylmethyl)amine, or 5.08 g of [(2,2-dichlorocyclo-
propyl)methyl](tetrahydrofuran-2-ylmethyl)amine)
and 0.02 mol (1.58 g) of freshly distilled pyridine, we
added with stirring and cooling to 0°С 0.02 mol (3.41 g)
of phenoxyacetyl chloride. The mixture was heated at
35°С with continuous stirring for 1 h and left overnight,
after which it was washed with ice-cold water to neu-
tral reaction. The precipitated flakes were filtered off on
a Büchner funnel, washed with water, separated, and
dried in air.
1-[(2,2-Dichlorocyclopropyl)methyl]-4-(phenoxy-
acetyl)piperazine (12). Yield 31%, Тm = 142–144°С.
1Н NMR spectrum (CDCl3, δ, ppm, J, Hz): 1.12 t (2Н,
С1Н2, 2J = 6.8), 1.76 m (1H, C3H1), 2.57 d.d (4H, C5H2,
C5'H2, J = 6.8, J = 5.4), 2.66 d.d (4H, C6H2, C6'H2,
2J = 5.4, J = 6.8), 4.59 s (2H, C8H2), 6.85–7.35 (5H,
Ph). 13С NMR spectrum (CDCl3, δC, м. д.): 25.12 (C1),
28.04 (C3), 41.89 (C5), 45.17 (С5'), 52.31 (C4), 57.61
(C6 + C6'), 60.61 (C1), 67.60 (C8), 114.54–129.60 (Ph),
(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl
phe-
2
3
noxyacetate (10). Yield 67%, Тb = 180°С (4 mmHg).
1Н NMR spectrum (CDCl3, δ, ppm, J, Hz): 1.20 s (3H,
C7H3), 1.50 s (3H, C6H3), 3.65 m (1H, C4H1), 3.95 d.d
(2H, C5H2, 2J = 6.9, 3J = 5.6), 4.20 d.d (2H, C8H2, 2J =
3
3
4.9, J = 5.6), 4.60 s (2H, C10H2), 6.80–7.40 (5H, Ph).
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SYNTHESIS AND HERBICIDAL AND ANTIOXIDANT ACTIVITY
715
Scheme 1.
1
2 4
1
5
(2)
(4)
(3)
157.71 (CPh), 166.38 (C7). Mass spectrum, m/e (Irel,
%): [М]+ 355 (1), 342/344/346 (2/1/0.5), 307/309/311
(18/6.5/0.5), 233/235/237 (26/1/0.5), 205/207/209
(4.5/50/10), 178/180/182 (100/36/5), 123/125/127
(14/10/6.5), 107/109/111 (24/1.5/8), 85/87/89 (4/26/10),
77 (52), 54/56/58 (8/46/4), 42/44 (30/36).
(C4'), 114.58–129.62 (Ph), 157.99 (CPh), 168.85 (C7).
Mass spectrum, m/e (Irel, %): [M]+ 358 (0.3), 322/324
(1/0.4), 274/276/278 (25/20/5), 152/154/156 (5/3/0.8),
123/125/127 (9/6/1), 107 (76), 84 (55), 71 (100), 43
(27).
RESULTS AND DISCUSSION
N-[(2,2-Dichlorocyclopropyl)methyl]-N-(1,3-di-
oxolan-4-ylmethyl)-2-phenoxyacetamide (13). Yield
53%, Тm = 138–140°С. Н NMR spectrum, δ, ppm
(J, Hz): 1.65 t (2H, C1H2, 2J = 7.5), 1.95 m (1H, C3H2),
1
The reaction of monochloroacetyl chloride with
an alcohol, (2,2-dimethyl-1,3-dioxolan-4-yl)carbinol
(isopropylidene derivative of glycerol), gave ester 1
in quantitative yield [4]. Its reactions with secondary
amines yielded the corresponding amino acid esters
2–4. In deep steps of piperazine alkylation at a 3–5-
fold excess of ester 1, dimer 5 was obtained along with
monosubstituted compound 3 (Scheme 1).
2
2
3.11 d (2H, C6H2, J = 5.7), 3.25 d (2H, C4H2, J = 7),
2
2
3.75 d (2H, C5'H2, J = 7.3), 4.10 d.d (1H, C4'H1, J =
4.5, 3J = 7.0), 4.35 d (2H, C2'H2, 2J = 2.1), 4.59 s (2H,
C8H2), 6.85–7.35 (5H, Ph). 13C NMR spectrum, δС, ppm:
25.34 (C1), 25.70 (C3), 29.35 (C4), 29.92 (C6), 47.38
(C2), 51.13 (C8), 60.52 (C5'), 77.72 (C4'), 94.80 (C2'),
114.58–129.62 (Ph), 157.99 (CPh), 168.85 (C7). Mass
spectrum, m/e (Irel, %): [M]+ not observed, 274/276/278
(25/20/5), 152/154/156 (5/3/0.8), 123/125/127 (9/6/1),
107 (76), 84 (55), 73 (100), 43 (27).
To compare the herbicidal activity of “simple” alkyl
and cyclic acetal esters, we prepared from commercial
methyl chloroacetate piperazine derivatives 6 and 7
(product yield 47 and 57%, respectively), which are
“simpler” analogs of compounds 3 and 5 (Scheme 2).
N-[(2,2-Dichlorocyclopropyl)methyl]-2-phenoxy-
By the reaction of chloroacetic acid esters with the
previously described secondary amine [5], we prepared
amino acid esters 8 and 9 in more than 90% yield
(Scheme 3).
N-(tetrahydrofuran-2-ylmethyl)acetamide
(14).
Yield 53%, Тm = 133–135°С. 1Н NMR spectrum, δ, ppm
(J, Hz): 1.25 m (2H, C3'H2), 1.65 d (1H, C1'H1, 2J = 7.5),
1.95 d (2H, C4H2, 2J = 5.7), 2.05 m (1H, C3H1), 3.55 d
(2H, C2'H2, 2J = 7.3), 3.60 d (2H, C6H2, 2J = 7.3), 3.75 d
(2H, C5'H2, 2J = 6.7), 4.10 d (1H, C4'H1, 2J = 4.5), 4.85 s
(2H, C8H2), 6.85–7.35 (5H, Ph). 13C NMR spectrum,
δС, ppm: 25.34 (C1), 25.70 (C3'), 29.35 (C3), 29.92 (C4),
47.38 (C6), 51.13 (C2), 60.52 (C8), 67.72 (C2'), 76.80
From chlorides of commercial aryloxyacetic acids,
we prepared heterocyclic esters 10 and 11 in 75–85%
yield (Scheme 4).
By the reaction of phenoxyacetyl chloride with
secondary amines containing heterocyclic and gem-
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YAKOVENKO et al.
Scheme 2.
Scheme 3.
8, 9
Scheme 4.
dichlorocyclopropane fragments, we prepared the
corresponding amines 12–14 in 30–60% yield
(Scheme 5).
whereas the piperazine detivative containing the gem-
dichlorocyclopropane fragment (12) exerts the strongest
inhibiting effect on monocotyledonous plants (pea).
Compounds 2 and 14 are moderately active with respect
to both wheat and pea.
According to the results of testing monochloroacetic
acid derivatives, compounds 2, 11, 12, and 14 showed
biological activity. Therefore, these compounds were
studied in more detail. We determined the herbicidal and
growth-stimulating activity of compounds 2, 11, 12, and
14 on wheat and pea sprouts by the procedure described
previously [6, 7].
Morpoline derivative 2 containing the dioxolane
fragment inhibited the pea sprout weight to an
approximately the same extent as the reference agent
did. The presence of the gem-dichlorocyclopropyl
fragment in phenoxyacetamides 12 and 14 influences
insignificantly the sprout length for both di- and
monocotyledonous plants.
The performance of the compounds (Table 1) was
determined after 3-day exposure relative to a reference,
Octapon extra (С8), octyl 2,4-dichlorophenoxyacetate
(reg. no. 068(116)-03-605). The dosage of 100 mg L–1
increases the efficiency of inhibiting the wheat sprout
length and weight. Compound 11 inhibits to the greatest
extent the growth of dicotyledonous plants (wheat),
Compounds 2 and 12 showed the best results. They
may be of interest from the viewpoint of the develop-
ment of new polyfunctional chemical agents for plant
protection [8, 9]. We evaluated the effect of these com-
pounds on the in vitro free-radical oxidation in model
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SYNTHESIS AND HERBICIDAL AND ANTIOXIDANT ACTIVITY
717
Scheme 5.
Table 1. Herbicidal activity of compounds (Т = 24–25°С)
Dosage,
mg L–1
Mean sprout
Length
Mean sprout
weight, g
Weight
inhibition, %
Compound
length, mm inhibition, %
Wheat
Control
–
69.7
12.8
71.5
–
14.1
9.6
–
Reference compound
50
50
81.6
+2.6
31.9
4.0
(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl
13.5
morpholin-4-ylacetate (2)
100
50
54.8
11.5
21.4
83.5
11.4
9.9
4.3
(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl
29.8
(2,4-dichlorophenoxy)acetate (11)
100
10.0
85.6
8.7
38.3
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YAKOVENKO et al.
Table 1. (Contd.)
Dosage,
mg L–1
Mean sprout
Length
Mean sprout
weight, g
Weight
inhibition, %
Compound
length, mm inhibition, %
1-[(2,2-Dichlorocyclopropyl)methyl]-4-
50
73.7
31.8
13.2
25.4
(phenoxyacetyl)piperazine (12)
100
50
36.8
65.9
65.9
39.0
10.9
13.3
38.4
24.9
N-[(2,2-Dichlorocyclopropyl)methyl]-2-phenoxy-
N-(tetrahydrofuran-2-ylmethyl)acetamide (14)
100
51.3
52.5
10.7
39.5
P e a
Control
–
5
5
18.4
13.0
18.4
–
72.1
60.0
63.5
–
Reference compound
29.3
0
16.8
11.9
(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl
morpholin-4-ylacetate (2)
(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl
(2,4-dichlorophenoxy)acetate (11)
5
5
5
7.0
36.7
45.9
62.0
34.3
17.9
65.6
9.0
72.2
16.1
1-[(2,2-Dichlorocyclopropyl)methyl]-4-
(phenoxyacetyl)piperazine (12)
6.9
N-[(2,2-Dichlorocyclopropyl)methyl]-2-phenoxy-
N-(tetrahydrofuran-2-ylmethyl)acetamide (14)
28.8
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SYNTHESIS AND HERBICIDAL AND ANTIOXIDANT ACTIVITY
719
Table 2. Variation of the light sum and maximal chemiluminescence intensity in model systems generating active oxygen
species and simulating peroxide oxidation of lipids in the presence of compounds 2 and 12
Model of active oxygen species
Model of peroxide oxidation of lipids
Compound
Imax (maximal
S (light sum), %
Imax (maximal
S (light sum), %
luminance), %
luminance), %
Control (no antioxidant)
100
5
100
7
100
44
100
49
Reference (5-hydroxy-6-methyluracil)
(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl
45
65
113
132
morpholin-4-ylacetate (2)
1-[(2,2-Dichlorocyclopropyl)methyl]-4-
53
66
109
116
(phenoxyacetyl)piperazine (12)
systems generating active oxygen species and in systems
simulating the peroxide oxidation of lipids. The antioxi-
dant activity was studied in dimethyl sulfoxide solution
by measuring the chemiluminescence as described in
[10, 11]. Control experiments were performed without
antioxidant. For comparison, we used as a reference an
inhibitor of free-radical oxidation in biological systems,
5-hydroxy-6-methyluracil [12, 13]. The main character-
istics of the chemiluminescence were the light sum (S)
and maximal flash intensity (Imax) [14]. Reagents 2 and
12 exhibit insignificant anitioxidant effect (Table 2) in a
model system of active oxygen species and prooxidant
effect in peroxide oxidation of lipids.
herbicidal, antimicrobial, and antioxidant activity,
giving grounds to recommend these compounds for
further studies to find fields of their efficient use.
ACKNOWLEDGMENTS
The authors are sincerely grateful to L.V. Spirikhin, head
of Laboratory of Physicochemical Methods of Analysis, Ufa
Federal Research Center, Russian Academy of Sciences,
for the assistance in identification of the structures of the
compounds.
FUNDING
The studies were supported by the Russian Foundation
for Basic Research, mol_ev_a competition (Eureca! Idea),
contract no. 19-33-80002\19 of December 7, 2018.
Importanceofsearchingforcompoundsexhibitingnot
only antioxidant [15, 16] but also prooxidant properties
[17] was noted in the literature. Different directions of
the action of 2 and 12 show that it is promising to search
for new bioactive agents among compounds related to
the carbo- and heterocycles studied.
CONFLICT OF INTEREST
The authors declare that they have no conflict of interest.
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