Synthesis of ethyl 5-aryl-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-carboxylates, exhibiting plant growth-regulating properties

Article abstract of DOI:10.1007/s11172-019-2422-6

A convenient method for the synthesis of high-boiling-point α-(trifluoromethyl)styrenes was proposed. The regioselective synthesis of a series of ethyl 5-aryl-5-(trifluoromethyl)-4,5- dihydroisoxazole-3-carboxylates was conducted by the reaction of ethyl

Full text of DOI:10.1007/s11172-019-2422-6

Russian Chemical Bulletin, International Edition, Vol. 68, No. 1, pp. 99—103, January, 2019
99
Synthesis of ethyl 5-aryl-5-(trifluoromethyl)-4,5-dihydroisoxazole-
3-carboxylates, exhibiting plant growth-regulating properties
A. L. Sigan,а A. S. Golubev,a E. V. Belyaeva,a S. M. Gorfinkel,a N. D. Kagramanov,a
Yu. Ya. Spiridonov,b and N. D. Chkanikova
аA. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
28 ul. Vavilova, 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5085. E-mail: asigan@yandex.ru
bAll-Russian Research Institute of Phytopathology,
5 ul. Institut, 143050 Bol´shie Vyazemy, Moscow Region, Russian Federation.
Fax: +7 (498) 694 1124. E-mail: spiridonov@vniif.ru
A convenient method for the synthesis of high-boiling-point -(trifluoromethyl)styrenes
was proposed. The regioselective synthesis of a series of ethyl 5-aryl-5-(trifluoromethyl)-4,5-
dihydroisoxazole-3-carboxylates was conducted by the reaction of ethyl nitroacetate with
-(trifluoromethyl)styrenes in the presence of 1,4-diazabicyclo[2.2.2]octane as a catalyst. The
effect of the resulting compounds on seed germination and root formation was studied.
Key words: -(trifluoromethyl)styrenes, ethyl 5-aryl-5-(trifluoromethyl)-4,5-dihydro-
isoxazole-3-carboxylates, ethyl nitroacetate, 1,3-cycloaddition, nitrile oxide, plant growth
regulator, metsulfuron-methyl.
The synthesis and study of heterocyclic systems based
on 4,5-dihydroisoxazole is one of the rapidly developing
directions of the search for practically useful compounds.
The interest to the representatives of this series is due to
their wide use as building blocks in the total synthesis of
natural compounds1 and to the results of applied bio-
medical and agrochemical studies.2 Numerous 4,5-di-
hydroisoxazole derivatives exhibit antifungal and antiviral
activities,3,4 are promising as anticancer agents,5,6 while
their agrochemical potential was confirmed by patents.7—9
Thus, 5,5-diaryl-substituted ethyl 4,5-dihydroisoxazole-
3-carboxylates (in particular, ethyl 5,5-diphenyl-4,5-di-
hydroisoxazole-3-carboxylate, the trade name Isoxadiphen-
ethyl) is patented by a number of companies as agro-
chemical agents: pesticides, herbicides, or antidotes of the
vegetation period in the composition of disinfectants.10—12
The practical significance of compounds with a 4,5-di-
hydroisoxazole skeleton stimulates the search for new
methods of their synthesis and functionalization, as well
as a productive synthetic application.
5-(trifluoromethyl)-4,5-dihydroisoxazole-3-carboxylates
and the study of their growth-regulating properties on corn
seeds and seedlings.
One of the main strategies in the design of isoxazole
skeleton is a 1,3-dipolar cycloaddition involving alkenes
and generated in situ nitrile oxides15 (Scheme 1).
Scheme 1
i. 1,3-Cycloaddition.
In this work, we used the condensation of 1,1-disub-
stituted alkenes with ethyl nitroacetate in the presence of
1,4-diazabicyclo[2.2.2]octane (DABCO) as a catalyst.16
The starting -(trifluoromethyl)styrenes were obtained
using two synthetic schemes. According to one of them,
the corresponding 1-aryl-1-methyl-1-(trifluoromethyl)-
carbinols (1a,b) were subjected to high-temperature de-
hydration with phosphorus pentoxide (the Tarrant
method17,18) to obtain low-boiling-point and very volatile
styrenes, namely -(trifluoromethyl)-para-methylstyrene
The introduction of fluorine atoms into organic mol-
ecules for several decades has been used as an efficient
strategy for broadening the range of their potential physio-
logical action.13 In the case of 4,5-dihydroisoxazole, the
introduction of polyfluoroalkyl groups at position 5 led
not only to the appearance of specific properties, but also
to the enhancement of the biological effects.14
The purpose of the present work is the development of
an approach to the synthesis of a series of new ethyl 5-aryl-
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 0099—0103, January, 2019.
1066-5285/19/6801-0099 © 2019 Springer Science+Business Media, Inc.

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Russ. Chem. Bull., Int. Ed., Vol. 68, No. 1, January, 2019
Sigan et al.
(2a) and -(trifluoromethyl)styrene (2b) (with a boiling
point below 170 C) (Scheme 2). However, the high-
boiling-point -(trifluoromethyl)styrenes (with a boiling
point above 170 C) cannot be obtained by this method
with a satisfactory yield. Therefore, the high-boiling-point
styrenes were synthesized by the Wittig reaction from the
corresponding 2,2,2-trifluoroacetophenones. We found
that the reflux of 2,2,2-trifluoroacetophenone derivatives
(1с—е) (1 equiv.), methyltriphenylphosphonium bromide
or iodide (1.25 equiv.), and potassium carbonate (1.7 equiv.)
in anhydrous 1,2-dimethoxyethane for 5 h afforded α-(tri-
fluoromethyl)-para-chlorostyrene (2c), α-(trifluorometh-
yl)-para-bromostyrene (2d), and α-(trifluoromethyl)-2,4-
dichlorostyrene (2e) in high yields (Scheme 2). This
version of Wittig reaction is very practical, does not require
strong bases (in particular, organolithium ones) and cryo-
genic temperatures for generation of methylenetriphenyl-
phosphorane (cf. Refs 19 and 20).
The condensation of the obtained α-(trifluoromethyl)-
styrenes (1 equiv.) with ethyl nitroacetate (2 equiv.) was
carried out in anhydrous EtOH at 80 C in the presence
of catalytic amounts of DABCO (0.1 equiv.) for 80 h until
complete conversion of the initial alkene. The reaction
progress was monitored by TLC. The target products, ethyl
5-aryl-5-(trifluoromethyl)-1,2-dihydroisoxazole-3-car-
boxylates (3a—e), were isolated in 65—75% yields after
the removal of the solvent from the reaction mixture and
purification by column chromatography on silica gel. The
compounds were identified by 1Н, 13С, and 19F NMR
spectroscopy, mass spectrometry, and elemental analysis.
The mass spectra were characterized by the low-abundant
peaks of molecular radical cations, which underwent
fragmentation under electron ionization following two
pathways of the 1,2-dihydroisoxazole ring decomposition.
The main direction was the formation of the [RR1C6H3CO]+
ion in all the cases with 100% abundance; the side frag-
mentation pathway gave the [RR1C6H3—C=CH2]+ ions
1
of medium or low abundance. The H NMR spectra, in
addition to the characteristic signals for the aromatic and
ethyl groups of protons, exhibited doublets in the region
of  4.0—3.6 from the diastereotopic protons of the CH2
group of the 1,2-dihydroisoxazole ring forming the AB-
system. As expected, the 19F NMR spectra of 3a—e ex-
hibited the singlets from the (trifluoromethyl) groups in
the region of  –80—81.
Considering the possibility of using the compounds
obtained in agrochemistry, we evaluated their effect on the
germination of corn seeds and studied the antidote effect
against such powerful phytotoxicants as sulfonylureas.
The tests of the antidote activity of ethyl 5,5-diphenyl-
4,5-dihydroisoxazole-3-carboxylate (the Isoxadifen-ethyl
agent) and its fluoro analogs 3a—e were carried out against
the herbicide Zinger, SP (60% metsulfuron-methyl) (see
Experimental and Table 1).
From Table 1, it is seen that none of the compounds
tested in treatment of seed, including the reference
Isoxadifen-ethyl, removed the toxic effect of the herbicide,
i.e., they did not possess the properties of antidotes (safen-
ers). At the same time, they were active as plant growth
regulators, with compounds 3d and 3e significantly exceed-
Scheme 2
Compounds
R
R´
Yield (%)
Compounds
R
R´
Yield (%)
2, 3
2, 3
2
3
2
3
c
d
e
Cl
Br
Cl
H
H
Cl
78
77
73
67
70
75
a
b
Me
H
H
H
75
74
70
65

5-CF3-Isoxazolines as plant growth regulators
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 1, January, 2019
101
Table 1. Comparison of growth-regulating and antidote activity (against herbicide Zinger, SP) of ethyl 5-aryl-5-
(trifluoromethyl)-4,5-dihydroisoxazole-3-carboxylates 3a—e and antidote Isoxadiphen-ethyl (IE)
Agent
Dose of agent,
g t–1 of seeds
Sprouts
Roots
d** (%)
d*/cm
d** (%)
d*/cm
IE
1
3.1
3.4
2.2
2.2
3.8
2.8
2.2
2.0
3.6
3.2
2.0
1.7
2.9
3.7
2.2
2.2
3.8
3.6
2.1
2.1
3.6
2.9
1.9
1.8
1.8
3.5
11.4
2.9
11.3
12.4
2.7
–7.6
–18.1
74.3
10
IE + Zinger, SP
1 + 2.5
10 + 2.5
1
10
1 + 2.5
10 + 2.5
1
10
1 + 2.5
10 + 2.5
37.1
37.1
–8.6
20.0
37.1
42.9
–2.9
8.6
42.9
51.4
17.1
–5.7
37.1
37.1
–8.6
–2.9
40.0
40.0
–2.9
17.1
45.7
48.6
48.6
0
2.6
75.2
3a
11.0
11.4
2.7
–4.8
–8.6
74.3
3a + Zinger, SP
2.8
73.3
3b
11.4
12.1
2.4
–8.6
–15.2
77.1
3b + Zinger, SP
2.6
8.8
12.6
2.4
2.9
75.2
16.2
–20.0
77.1
3c
1
10
3c + Zinger, SP
3d
1 + 2.5
10 + 2.5
72.4
–5.7
–26.7
72.4
72.4
–17.1
–33.3
76.2
76.2
76.2
0
1
11.1
13.3
2.9
10
1 + 2.5
10 + 2.5
1
3d + Zinger, SP
3e
2.9
12.3
14.0
2.5
10
3e + Zinger, SP
1 + 2.5
10 + 2.5
2.5
2.5
2.5
10.5
Zinger, SP
Distilled water (control)
10 L t–1 of seeds
* Average length (d) of 35 measurements.
** Reduction in length (d) is given as a percentage of control, negative values mean stimulation of the maize plant
growth as compared to control.
SiMe4 signal. The 19F chemical shifts were determined using
trifluoroacetic acid as an external standard and recalculated
relative to the signal of CFCl3. Melting points were determined
on a Boetius heating stage and were not corrected. Elemental
analysis was performed on a vario Micro cube CHNS-O analyzer.
Mass spectra were recorded on a Kratos MS-890 spectrometer
with an ionizing potential of 70 eV.
Column chromatography was performed on silica gel with
a particle size of 0.06—0.20 mm (Merck Kieselgel 60). TLC plates
(Merck Kieselgel 60 F254) were used to detect substances and
monitor reaction progress. A 4 : 1 mixture of light petroleum
ether (PE, fraction 40—70)—AcOEt was used as an eluent.
1,1,1-(Trifluoromethyl)-2-phenylpropan-2-ol and 1,1,1-(tri-
fluoromethyl)-2-(para-tolyl)propan-2-ol were obtained by the
Grignard reaction of methylmagnesium iodide with 2,2,2-tri-
fluoroacetophenone and 2,2,2-trifluoro-4´-methylacetophenone,
respectively.21 The reagents were mixed at –15 C, the reaction
was carried out with stirring for 16 h.
ing the reference in this activity. Apparently, it is reason-
able to continue the comparison on vegetative plants.
Thus, we developed a convenient method for the syn-
thesis of previously unknown ethyl 5-aryl-5-(trifluoro-
methyl)-4,5-dihydroisoxazole-3-carboxylates by the
DABCO-catalyzed reaction of -(trifluoromethyl)styrenes
with ethyl nitroacetate. The availability of new heterocycles
is also determined by the feasibility and efficiency of the
method for obtaining high-boiling-point α-(trifluoro-
methyl)styrenes using a modified Wittig reaction. It was
shown that ethyl 5-aryl-5-(trifluoromethyl)-4,5-dihydro-
isoxazole-3-carboxylates can be used as plant growth
regulators.
Experimental
1H and 19F NMR spectra were recorded on a Bruker-
AvanceTM400 spectrometer (400.13 MHz for 1H and 376.50 MHz
with proton decoupling for 19F). The proton chemical shifts were
determined using the residual signal of chloroform and DMSO
( 7.26 and 2.50, respectively) and recalculated relative to the
1-Methyl-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (2a).
1,1,1-(Trifluoromethyl)-2-(para-tolyl)propan-2-ol (8.37 g,
41 mmol) and phosphorus pentoxide (7.52 g, 53 mmol) were
mixed in a distillation apparatus with a 8-cm dephlegmator. The
distillation flask was placed in a Horst heating mantle with a tem-

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Sigan et al.
perature controller and heated to 450 C by an electronic coun-
ter. At first, the liquid with a boiling point of 165 C was distilled
off; at the end of the distillation, the boiling point of the distilled
liquid rose to 180 C. A total of 5.86 g of the liquid was collected,
which was re-distilled to obtain a colorless liquid (5.65 g, 74%)
131.75, 139.77, 151.16 (C(3)), 159.50 (C=O). MS (EI, 70 eV), m/z
(Irel (%)): 301 [M]+ (7), 256 [M – OC2H5]+ (8), 232 [M – CF3]+
(35), 210 [M – C7 H7]+ (13), 186 [C10H9F3]+ (50), 119
[CH3C6H4CO]+ (100), 117 [C9H9]+ (53), 91 [C7H7]+ (29).
Found (%): C, 55.96; H, 4.75; N, 4.72. C14H14F3NO3. Calcul-
ated (%): C, 55.82; H, 4.68; N, 4.65.
1
with b.p. 164—166 C. H NMR (CDCl3), : 7.38 (d, 2 H, Ph,
J = 7.8 Hz); 7.22 (d, 2 H, Ph, J = 7.8 Hz); 5.94 (m, 1 H, CH=);
5.77 (m, 1 H, CH=); 2.40 (s, 3 H, CH3). 19F NMR (CDCl3), :
–64.77 (s, CF3).
Compounds 3b—e were obtained similarly as colorless
powders.
Ethyl 5-phenyl-5-(trifluoromethyl)-4,5-dihydroisoxazole-3-
carboxylate (3b). The yield was 1.95 g (65%), m.p. 32 C (Et2O).
1H NMR (CDCl3), : 7.55 (m, 2 H, Ph); 7.55—7.44 (m, 3 H,
Ph); 4.38 (q, 2 H, CH2, J = 7.1 Hz); 3.97 (d, 1 H, CH2,
АB-system, J = 18.2 Hz); 3.65 (d, 1 Н, СН2, АВ-system,
J = 18.2 Hz); 1.39 (t, 3 H, CH3, J = 7.1 Hz). 19F NMR (CDCl3),
: –80.18 (s, CF3). 13C NMR (CDCl3), : 14.02 (CH3); 42.72
(C(4)); 62.63 (OCH2); 89.9 (q, C(5), J = 30.8 Hz); 123.5 (q, CF3,
J = 283.9 Hz); 126.37, 128.78, 129.68, 134.75, 151.20 (C(3)),
159.43 (C=O). MS (EI, 70 eV), m/z (Irel (%)): 287 [M]+ (14),
242 [M – OC2H5 ]+ (10 ), 218 [M – CF3]+ (31), 214 [M – CO2C2H5
] (29), 190 [M – Ph + HF]+ (29), 172 [C9H7F]+ (49), 164
[M – Ph + OC2H5]+ (7), 105 [PhCO]+ (100), 103 [C8H7]+ (50),
77 [Ph]+ (30 ). Found (%): C, 54.28; H, 4.28; N, 4.91.
C13H12F3NO3. Calculated (%): C, 54.26; H, 4.21; N, 4.87.
Ethyl 5-(4-chlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisox-
azole-3-carboxylate (3c). The yield was 2.1 g (67%), m.p. 51 C
(3,3,3-Trifluoroprop-1-en-2-yl)benzene (2b) was obtained
similarly from 1,1,1-(trifluoromethyl)-2-phenylpropan-2-ol. B.p.
150—152 C. The yield was 75%. 1H NMR (CDCl3), : 7.55—7.47
(m, 2 H, Ph); 7.46—7.38 (m, 3 H, Ph); 5.99 (m, 1 H, CH=);
5.80 (m, 1 H, CH=). 19F NMR (CDCl3), : –64.76 (s, CF3).
1-Chloro-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (2c).
Anhydrous 1,2-dimethoxyethane (45 mL) was added to a mixture
of methyltriphenylphosphonium bromide (6.43 g, 18 mmol) and
anhydrous potassium carbonate (3.45 g, 25 mmol). A solution
of 2,2,2-trifluoro-4´-chloroacetophenone (3.13 g, 15 mmol) in
1,2-dimethoxyethane (5 mL) was added to the resulting suspen-
sion, which was refluxed for 5 h. TLC in the system PE—AcOEt
(10 : 1) showed a complete conversion of the starting ketone. The
reaction mixture was cooled and poured into water (200 mL).
The resulting heterophase system was extracted with light petro-
leum ether (3×40 mL), the organic phases were combined, washed
with brine, and dried with MgSO4. Petroleum ether was distilled
off using a Vigreux column, the residue was distilled to obtain
compound 2c (2.44 g, 78%) as a colorless liquid with b.p.
63—65 C (12 Torr). 1H NMR (CDCl3), : 7.47—7.34 (m, 4 Н,
Ph), 6.00 (m, 1 H, CH=); 5.80 (m, 1 H, CH=). 19F NMR
(CDCl3), : –64.92 (s, CF3).
1
(Et2O). H NMR (CDCl3), : 7.50—7.43 (m, 4 H, Ph); 4.38
(q, 2 H, CH2, J = 7.1 Hz); 3.96 (d, 1 Н, CH2, АB-system,
J = 18.2 Hz); 3.61 (d, 1 Н, СН2, АВ-system, J = 18.2 Hz); 1.39
(t, 3 H, CH3, J = 7.1 Hz). 19F NMR (CDCl3), : –80.19 (s, CF3).
13C NMR (CDCl3), : 14.02 (CH3), 42.75 (C(4)), 62.74 (OCH2),
89.52 (q, C(5), J = 30.8 Hz); 123.48 (q, CF3, J = 283.9 Hz);
127.86, 129.06, 133.20. 135.99. 151.19 (C(3)), 159.27 (C=O). MS
(EI, 70 eV), m/z (Irel (%)): 321 [M]+ (11); 276 [M – OC2H5]+
(8), 252 [M – CF3]+ (26), 248 [M – CO2C2H5]+ (14), 206
[C9H6F3Cl]+(68), 139 [ClC6H4CO]+ (100), 137 [ClC8H6]+ (41),
111 [C6H4Cl]+ (11). Found (%):C, 48.52; H, 3.58; N, 4.44.
C13H11ClF3NO3. Calculated (%): C, 48.54; H, 3.45; N, 4.35.
Ethyl 5-(4-bromophenyl)-5-(trifluoromethyl)-4,5-dihydroisox-
azole-3-carboxylate (3d). The yield was 2.56 g (70%), m.p. 44 C
(Et2O). 1H NMR (CDCl3), : 7.60 (d, 2 H, Ph, J = 8.4 Hz), 7.42
(d, 2 H, Ph, J = 8.4 Hz); 4.38 (q, 2 H, CH2, J = 7.1 Hz); 3.96
(d, 1 H, CH2, АB-system, J = 18.2 Hz); 3.60 (d, 1 Н, СН2,
АВ-system, J = 18.2 Hz); 1.39 (t, 3 H, CH3, J = 7.1 Hz). 19F
NMR (CDCl3), : –80.17 (s, CF3). 13C NMR (CDCl3), : 14.03
(CH3); 42.71 (C(4)); 62.75 (OCH2); 89.6 (q, C(5), J = 30.8 Hz);
123.4 (q, CF3, J = 283.9 Hz); 124.23, 128.1, 132.04, 133.74, 151.18
(C(3)), 159.27 (C=O). MS (EI, 70 eV), m/z (Irel (%)): 365 [M]+
(13), 320 [M – OC2H5]+ (5), 296 [M – CF3]+ (21), 250
[C9H6BrF3]+ (38), 183 [C6H4BrCO]+ (100), 181 [C8H6Br]+ (13).
Found (%): C, 42.71; H, 3.12; N, 3.88. C13H11BrF3NO3.
Calculated (%): C, 42.65; H, 3.03; N, 3.82.
1-Bromo-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (2d) was
obtained similarly from 2,2,2-trifluoro-4´-bromoacetophenone
and methyltriphenylphosphonium iodide. A colorless liquid with
b.p. 75—77 C (12 Torr). The yield was 77%. 1H NMR (CDCl3),
: 7.55 (d, 2 H, Ph, J = 8.6 Hz); 7.35 (d, 2 H, Ph, J = 8.6 Hz);
6.00 (m, 1 H, CH=); 5.80 (m, 1 H, CH=). 19F NMR (CDCl3),
: –64.92 (s, CF3).
2.4-Dichloro-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene (2e)
was obtained similarly from 2,2,2-trifluoro-2´,4´-dichloroaceto-
phenone and methyltriphenylphosphonium iodide. A colorless
liquid purified by column chromatography on silica gel, eluent
1
PE—AcOEt (10 : 1). The yield was 73%. H NMR (CDCl3), :
7.51 (s, 1 H, Ph); 7.35—7.25 (m, 2 H, Ph); 6.25 (s, 1 H, CH=);
5.67 (s, 1 H, CH=). 19F NMR (CDCl3), : –66.85 (s, CF3).
Synthesis of ethyl 5-para-tolyl-5-(trifluoromethyl)-4,5-di-
hydroisoxazole-3-carboxylate (3a) (general procedure). A solution
of styrene (2a) (1.86 g, 10 mmol), ethyl nitroacetate (2.66 g,
20 mmol), and DABCO (0.11 g, 1 mmol) in anhydrous ethanol
(40 mL) was heated for 80 h at 80 C in a sealed tube. Then,
the solvent was removed from the reaction mixture, the residue
was purified by column chromatography on silica gel, eluent
PE—AcOEt (4 : 1) to obtain 3а as a colorless powder. The yield
was 2.1 g (70%), m.p. 49 C (Et2O). 1H NMR (CDCl3), : 7.43
(d, 2 H, Ph, J = 8.0 Hz); 7.26 (d, 2 H, Ph, J = 8.0 Hz); 4.38
(q, 2 H, CH2, J = 7.1 Hz); 3.94 (d, 1 H, CH2, АB-system,
J = 18.2 Hz); 3.63 (d, 1 Н, СН2, АВ-system, J = 18.2 Hz); 2.40
(s, 3 H, CH3); 1.39 (t, 3 H, CH3, J = 7.1 Hz). 19F NMR (CDCl3),
: –80.28 (s, CF3). 13C NMR (CDCl3), : 14.03 (CH3), 21.13
(CH3—Ar), 42.67 (C(4)); 62.60 (OCH2); 90.0 (q, C(5),
J = 30.8 Hz); 123.75 (q, CF3, J = 283.9 Hz); 126.27, 129.43,
Ethyl 5-(2,4-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydro-
isoxazole-3-carboxylate (3e). The yield was 2.67 g (75%), m.p.
74 C (Et2O). 1H NMR (CDCl3), : 7.82 (d, 1 H, Ph, J = 8.7 Hz);
7.51 (d, 1 H, Ph, J = 2.1 Hz); 7.38 (dd, 1 H, Ph, J = 8.7 Hz,
J = 2.1 Hz); 4.40 (q, 2 H, CH2, J = 7.1 Hz); 4.06 (d, 1 H, CH2,
АB-system, J = 18.9 Hz); 3.93 (d, 1 Н, СН2, АВ-system,
J = 18.9 Hz); 1.40 (t, 3 H, CH3, J = 7.1 Hz). 19F NMR (CDCl3),
: –80.02 (s, CF3). 13C NMR (CDCl3), : 14.05 (CH3); 41.62
(C(4)); 62.75 (OCH2); 88.79 (q, C(5), J = 30.8 Hz); 123.63
(q, CF3, J = 283.9 Hz); 127.57, 130.17, 131.23, 132.69, 136.72,

5-CF3-Isoxazolines as plant growth regulators
Russ. Chem. Bull., Int. Ed., Vol. 68, No. 1, January, 2019
103
152.14 (C(3)), 159.22 (C=O). MS (EI, 70 eV), m/z (Irel (%)): 310
[M – OC2H5]+ (3), 286 [M – CF3]+ (11), 240 [C9H5Cl2F3]+
(11), 173 [C7H3Cl2O]+ (100), 171 [Cl2C8H5]+ (15). Found (%):
C, 43.80; H, 2.79; N, 3.89. C13H10Cl2F3NO3. Calculated (%):
C, 43.85; H, 2.83; N, 3.93.
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Biological tests. The seeds of Krasnodar 291 AMB maize were
treated with a mixture of Isoxadifen-ethyl or each of the fluoro
analogs 3a—e (at concentrations of 1 g t–1 and 10 g t–1) with the
herbicide Zinger, SP (at a concentration of 2. 5 g t–1 in all ex-
periments). For comparison, maize seeds were also treated with
a mixture of Isoxadifen-ethyl (at concentrations of 1 g t–1 and
10 g t–1) with Zinger, SP (at a concentration of 2.5 g t–1 in all
experiments). As a control, the seeds were treated with the her-
bicide Zinger, SP at a concentration of 2.5 g t–1. The tests for the
growth-regulating activity of fluoro analogs 3a—e were carried
out in two concentrations: 1 g t–1 and 10 g t–1 of seeds (see Table 1).
For comparison, corn seeds were also treated with Isoxadifen-
ethyl at concentrations of 1 g t–1 and 10 g t–1. Seeds treated with
distilled water were used as a control. The procedure for the
preparation of test compound solutions and their mixtures with
herbicides is described in the work.22
Structural studies were carried out using equipment of
the X-Ray Structural Center of the A. N. Nesmeyanov
Institute of Organoelement Compounds of the Russian
Academy of Sciences.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 15-29-05793).
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Received June 29, 2018;
in revised form September 25, 2018;
accepted October 16, 2018