Synthesis and Properties of New 4-Oxo-4,5-dihydro-1,3-oxazolium Perchlorates

Article abstract of DOI:10.1134/S1070363218120083

D-Pantoic acid amide obtained by treatment of D-(–)-pantolactone with ammonia reacted with acetic anhydride in the presence of perchloric acid to give 5-[2-(acetoxy)-1,1-dimethylethyl]-2-methyl-4-oxo- 4,5-dihydro-1,3-oxazolium perchlorate. Reaction of the

Full text of DOI:10.1134/S1070363218120083

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 12, pp. 2504–2512. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © D.Yu. Lukina, V.D. Strelkov, L.V. Dyadyuchenko, E.A. Chigorina, V.V. Dotsenko, T.P. Kosulina, 2018, published in Zhurnal
Obshchei Khimii, 2018, Vol. 88, No. 12, pp. 1985–1994.
Synthesis and Properties
of New 4-Oxo-4,5-dihydro-1,3-oxazolium Perchlorates
D. Yu. Lukinaa*, V. D. Strelkova,b, L. V. Dyadyuchenkob, E. A. Chigorinac,
V. V. Dotsenkoa,d, and T. P. Kosulinae
a Kuban State University, ul. Stavropol'skaya 149, Krasnodar, 350040 Russia
*e-mail: kdaryau@yandex.ru
b All-Russian Research Institute of Biological Plant Protection, ul. Vavilova 14, Krasnodar, 350039 Russia
c Research Institute of Chemical Reagents and Ultrapure Chemicals, National Research Center “Kurchatov Institute,”
Bogorodskii val 3, Moscow, 107076 Russia
d North-Caucasus Federal University, ul. Pushkina 1, Stavropol, 355009 Russia
e Kuban State Technological University, ul. Moskovskaya 2, Krasnodar, 350072 Russia
Received May 24, 2018
Revised May 24, 2018
Accepted May 31, 2018
Abstract—D-Pantoic acid amide obtained by treatment of D-(–)-pantolactone with ammonia reacted with
acetic anhydride in the presence of perchloric acid to give 5-[2-(acetoxy)-1,1-dimethylethyl]-2-methyl-4-oxo-
4,5-dihydro-1,3-oxazolium perchlorate. Reaction of the latter with aromatic aldehydes afforded 2-(2-
arylethenyl)-4-oxo-4,5-dihydro-1,3-oxazolium perchlorates which showed no appreciable growth-regulating
activity but clearly exhibited antidotal activity against 2,4-dichlorophenoxyacetic acid (2,4-D herbicide).
Keywords: D-pantoamides, 4-oxo-4,5-dihydro-1,3-oxazolium perchlorates, spirochromenes, antidotal activity,
growth-regulating activity
DOI: 10.1134/S1070363218120083
1,3-Oxazol-4(5H)-ones and 4-oxo-4,5-dihydro-1,3-
oxazolium salts have attracted researchers’ attention
due to broad spectrum of their practically useful
properties [1–4]. A procedure for the synthesis of 4-
oxo-4,5-dihydro-1,3-oxazolium perchlorates starting
from racemic dl-pantolactone has been developed
previously in our laboratory [4–9]. The obtained
oxazolium perchlorates turned out to be promising
intermediate products for the preparation of functional
oxazole derivatives, as well as of various recyclization
products [3, 4, 9, 10]. On the other hand, biological
screening has revealed antiviral, anti-inflammatory,
and fungicidal properties of some oxooxazolium salts
[9], and myocardial activity regulators have bee found
among compounds of this series [4]. These results can
be regarded as promising, which substantiates further
research in this field.
4,5-dihydro-1,3-oxazolium derivatives starting from D-
(–)-pantolactone (1) and studying their condensation
with aldehydes and biological activity of the
condensation products. Initial D-pantoic acid amide (2,
D-2,4-dihydroxy-3,3-dimethylbutanamide) was syn-
thesized according to the modified procedure [11] by
passing gaseous ammonia through a solution of D-(–)-
pantolactone (1) in methylene chloride (Scheme 1).
We failed to obtain N-methylamide 3 from D-(–)-
pantolactone according to the procedure described in
[9]. Instead of the product which should crystallize
from diethyl ether, we isolated a viscous oily material
readily soluble in ether. On the basis of the IR and
NMR spectra and GC/MS data, the oily product was
identified as a mixture of initial D-(–)-pantolactone, N-
methylamide 3, and N-methylbutyrolactam 4 (Scheme 1).
Our attempts to separate this mixture by column
chromatography on silica gel or Al2O3 (eluent acetone–
hexane, 5:2) were unsuccessful. The IR spectrum of
In continuation of our work in this line, we set
ourselves the goal of obtaining new 2-methyl-4-oxo-
2504

SYNTHESIS AND PROPERTIES OF NEW 4-OXO-4,5-DIHYDRO-1,3-OXAZOLIUM
2505
Scheme 1.
Me
Me
Me
Me
Me
Me
OH
H
Me
Me
HO
CH3NH2
H
NH3
HO
H
H
O
+
OH
O
O
N
Me
4
O
OH
OH
HN
O
NH2
Me
1
3
2
Ac2O HClO4
HClO4
Ac2O
Me
Me
Me
−
Me
−
ClO4
CH3
H
ClO4
O
O
H
N+
Me
Me
OAc
NH
R
O
O
O
5a
6
(R = H)
the isolated material contained carbonyl stretching
vibration bands at 1770 (lactone, lactam) and 1651 cm–1
(amide). Increase of the reaction time, i.e., of the
amount of methylamine passed through the mixture,
led to disappearance of the band at 1770 cm–1, but this
band appeared again after the product was stored for a
few hours. These findings suggest that N-methylamide
3 is unstable and that it tends to undergo cyclization.
The chromatogram (GC/MS) of the aminolysis product
displayed two peaks, one of which was assigned to a
mixture of initial pantolactone 1 and butyrolactam 4
(m/z 130 and 143, respectively), and the other, to N-
methylamide 3 (m/z 161).
geminal methyl groups resonated as two singlets at δ
1.04 and 1.25 ppm. It should be noted that the H
1
NMR spectral pattern of 5a is quite sensitive to the
presence of traces of water in the solvent; if water is
present in the solvent, two sets of signals are observed
in the spectrum due to formation of unprotonated
oxazolone impurity.
As shown in [4–10], structural analogs of
perchlorate 5a fairly readily react with aromatic
aldehydes to give condensation products at the
activated methyl group on C2. Under similar condi-
tions, oxazolium perchlorate 5a reacted with aromatic
aldehydes to afford new 2-(2-arylvinyl)oxazolium salts
7 (Scheme 2, a). Compounds 7 can also be synthesized
in slightly lower yields by a one-pot reaction of
D-pantoic acid amide 2 with Ac2O, 70% HClO4, and
the corresponding aromatic aldehyde (b).
Oxazolium perchlorate 5a was synthesized by
heating amide 2 in acetic anhydride in the presence of
70% HClO4. Under analogous conditions, from a
mixture of 3 and 4 obtained by passing gaseous
methylamine through a solution of D-(–)-pantolactone
we isolated crystalline perchlorate 6 in 40% yield; in
this case, no appreciable amount of the corresponding
oxazolium salt 5b (R = Me) was detected. Compound
5a is a colorless crystalline solid which is readily
soluble in acetone, ethyl acetate, and acetic acid and
readily hydrolyzable. The IR spectrum of 5a showed
two carbonyl stretching bands at 1753 (acetate) and
1778 cm–1 (C4=O). The two absorption bands at 1510
and 1600 cm–1 were assigned to stretching vibrations
of the [O···C···N]+ fragment. Stretching vibrations of
the perchlorate counterion were observed at 1092 cm–1.
It is known that aldol condensation of alkyl-
substituted heterocyclic salts (such as indolium, 1,3-
benzoxazinium, and other salts) with ortho-hydroxy-
benzaldehydes leads to the formation of 2-spiro-
chromenes which exhibit photochromic properties and
are therefore promising for the preparation of smart
materials, molecular controllers, nanotransistors, etc.
[12–15]. There are no published data on the synthesis
of spirochromenes from 4-oxo-4,5-dihydro-1,3-
oxazolium perchlorates like 5 or 7.
In order to obtain spirochromenes, 2-methyl-
oxazolium perchlorate 5a was reacted with salicyl-
aldehyde and 5-nitrosalicylaldehyde. However, instead
1
The H NMR spectrum of 5a contained a singlet at
δ 5.83 ppm due to 5-H, and protons of diastereotopic
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 12 2018

2506
LUKIN et al.
Scheme 2.
Ar
O
Me
Me
OAc
O
ClO4−
Me
HO
Ac2O, HClO4
ArCHO
Me
OH
ArCHO,
HN
AcOH
+
ClO4−
O
NH
+
H
а
b
Me
Me
O
O
CH3
5a
R
NH2
AcO
7a_7e
2
OAc
O
Me
Me
CHO
EtOH, H2O
AcOH,
60°C
OH
O
NH
O
Me
Ar
×
Me
O
N
OAc
8
O
9a, 9b, 9d, 9f, 9g
ClO4−
R
R
H
N
+
O
R = H, NO2
OAc
O
Me
Me
HO
7е, 7g
Ar = Ph (а), 4-BrC6H4 (b), 4-Me2NC6H4 (c), 4-MeOC6H4 (d), 4-HOC6H4 (e), 2-HOC6H4 (f), 2-HO-5-NO2C6H3 (g).
of expected spirochromenes 8 we isolated 2-(2-
arylvinyl)oxazolium perchlorates 7f and 7g analogous
to the condensation products with other aromatic
aldehydes (Scheme 2). Attempted cyclization of 7f and
7g to spirochromenes 8 by the action of a base or on
heating (by analogy with known methods [12]) was
unsuccessful.
1750 cm–1 was assigned to the lactam carbonyl
involved in the interaction with the electron-
withdrawing [O···C···N]+ fragment; the latter was
characterized by absorption bands in the region 1510–
1560 cm–1. A strong absorption band at 1100 cm–1
belonged to stretching vibrations of the perchlorate
1
ion. In the H NMR spectra of 7a–7g we observed a
singlet at δ 4.60–5.70 ppm due to proton on C5 of the
oxazole ring, diastereotopic protons of the exocyclic
methylene group resonated as a doublet of doublets at
δ 3.91–4.16 ppm (AB spin system) with a geminal
Perchlorates 7 were readily deprotonated in the
presence of bases (NaHCO3, NH3, Et3N, guanidine) or
under hydrolysis conditions (50% EtOH) to form 2-(2-
arylvinyl)-4-oxo-4,5-dihydro-1,3-oxazoles 9 (Scheme 2).
2-[2-(2-Hydroxyphenyl)ethenyl]oxazolium perchlorates
7f and 7g were also converted to oxazolones 9f and 9g
under similar conditions, but no cyclization occurred.
2
coupling constant J of 11.5–13.9 Hz; and vinylic
protons of the Ar–CH=CH– fragment were represented
by two doublets at δ 6.35–7.56 and 4.41–8.83 ppm
with a vicinal coupling constant 3J of ~16.0 Hz, which
unambiguously indicated E configuration of the
exocyclic C=C double bond.
Compounds 7 were isolated as yellow or red (7c)
crystalline solids with sharp melting points, readily
soluble in ethyl acetate, ethanol, and acetone.
Oxazolones 9 were light yellow crystalline compounds
with sharp melting points. The IR spectra of 7a–7g
displayed two clearly defined bands due to different
carbonyl groups. The high-frequency band at 1810–
The UV spectra of 7a, 7b, and 7d showed only one
absorption maximum at λ 318–326 nm, which
corresponds to the π→π* transition in the entire
conjugation system. The UV spectrum of 7c displayed
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 12 2018

SYNTHESIS AND PROPERTIES OF NEW 4-OXO-4,5-DIHYDRO-1,3-OXAZOLIUM
2507
Scheme 3.
Ar
Ar
.
ClO4−
O
N2H4 H2O
AcOH
N
N
N
Ar
HN
O
×
Me
Me
N
+
Ar
HN
Me
11a−11c
HO
Me
OAc
OAc
7a−7c
10
two absorption maxima at λ 350 and 530 nm due to
π→π* and n→π* transitions, respectively. It is
interesting that the UV spectra of perchlorates 7 are
almost identical to the spectra of their neutral analogs,
oxazol-4(5H)-ones 9, which may be rationalized by
facile hydrolysis of perchlorates 7.
7e–7g were screened for growth-regulating activity in
sunflower seedlings under laboratory conditions. 2,4-
Dichlorophenoxyacetic acid (2,4-D) was used as a
model herbicide at a concentration of 10–3%.
The results of laboratory screening (Table 1)
showed that only one of the compounds tested, 4-oxo-
2-[(E)-2-phenylethenyl]-4,5-dihydro-1,3-oxazolium per-
chlorate (7a), showed a high antidotal effect at a low
concentration (Ae = 150% at a concentration of 10–5%).
Compounds 7b, 7e, and 7f showed a moderate
antidotal effect (Ae = 119–125% at a concentration of
10–2 to 10–4%). Compounds 7 exhibited no growth-
regulating activity or their activity was insignificant.
Moreover, an inhibitory effect of perchlorate 7f at a
low concentration (10–5%) was observed.
The structure of compounds 9 was confirmed by
spectral data. In the IR spectra of 9, the carbonyl
stretching band was located at lower frequencies than
in the spectra of 7. The low-frequency shift can be
rationalized by the lack of electron-withdrawing effect
1
of the [O···C···N]+ fragment. The H NMR spectra of
9f and 9g contained signals typical of the trans-
configured CH=CH bond (3J ~16.0 Hz) and were
generally to the spectra of perchlorates 7f and 7g,
which indicated that there was no cyclization to
spirochromenes 8.
In order to assess prospects of practical application
of 2-(2-arylethenyl)-4-oxo-4,5-dihydro-1,3-oxazolium
perchlorates 7a and 7b, their antidotal activity was
studied under field conditions on Flagman sunflower.
Experiments were carried out in the experimental field
of All-Russian Research Institute of Biological Plant
Protection (Krasnodar). The results are given in Table 2.
It was found that, though 2-(2-arylethenyl)-4-oxo-4,5-
dihydro-1,3-oxazolium perchlorates 7a and 7b showed
antidotal effect, its magnitude was insufficient for
practical purposes.
We then studied the reaction of 2-(2-arylvinyl)oxa-
zolium perchlorates 7 with hydrazine hydrate. Accord-
ing to published data, reactions of analogous oxa-
zolium salts with hydrazines lead to the formation of
1,2,4-triazole derivatives [3]. However, in the reactions
of 7a–7c with hydrazine hydrate in acetic acid at 60°C
we isolated only known aldazines 11 rather than
expected triazoles 10. The structure of 11 was
confirmed by IR, NMR, and GC/MS data (Scheme 3).
In particular, the reaction of perchlorate 7c with
hydrazine hydrate in acetic acid at 60°C afforded 35%
of aldazine 11c.
Thus, we have succeeded in obtaining new 4-oxo-
4,5-dihydro-1,3-oxazolium
salts
starting
from
accessible D-(–)-pantolactone and studying their
properties and some transformations. Contrary to the
expectations, hydrazinolysis of these compounds does
not lead to the formation of 1,2,4-triazoles. We also
failed to accomplish cyclization of 2-[2-(2-hydroxy-
phenyl)ethenyl]oxazolium salts to spirochromene
derivatives. On the other hand, the apparent antidotal
effect of some compounds with respect to 2,4-D
Taking into account fairly food solubility of 2-(2-
arylvinyl)oxazolium perchlorates 7a, 7b, and 7e–7g, it
seemed reasonable to estimate prospects of using them
in agrochemistry. We assessed the antidotal effect of
these compounds toward herbicides according to the
procedure developed by us previously and successfully
tested [16–20]; in addition, oxazolium salts 7a, 7b, and
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 12 2018

2508
LUKIN et al.
Table 1. Antidotal activity of compounds 7a, 7b, and 7e–7g with respect to 2,4-Da
Reference 2,4-D
Concentration, %
10–3 10–4
Compound
no.
Control,
Lc
Organ
10–2
10–5
Le
B
Lo
31
38
38
42
66
88
62
85
63
79
Ae
Lo
33
36
32
39
62
82
57
74
65
87
Ae
Lo
35
40
35
38
68
86
71
76
63
85
Ae
Lo
48
41
25
24
63
87
59
67
63
81
Ae
7a
7b
7e
7f
Stem
Root
Stem
Root
Stem
Root
Stem
Root
Stem
Root
71
121
71
32
38
32
38
57
78
57
78
57
78
55
69
55
69
41
54
41
54
41
54
97
103
95
109
105
109
100
119
110
125
97
150
108
78
100
119
110
116
112
109
109
111
101
100
103
109
105
100
95
125
97
63
111
112
104
86
170
97
170
97
7g
114
112
111
109
111
104
170
а
Lc is the length of an organ (mm) in the control; Le is the length of an organ (mm) in seedlings treated with 2,4-D; Lo is the length of an
organ (mm) in the control group (herbicide + antidote); B is the growth inhibition in percent, herbicide background, B = [(Lk – Le)/
Lk]×100%; Ae is the antidotal effect, %; Ae = (Lo/Le)×100%.
Table 2. Antidotal activity of oxazolium salts 7a and 7b at a dose of 200 g/ha with respect to 2,4-D on Flagman sunflower
(field experiments)
Herbicide + antidote
Com-
Control (not treated
Reference (herbicide)
pound no. with 2,4-D), 102 kg/ha
yield, 102 kg/ha
gain, 102 kg/ha
gain, %
7а
33.6
14.9×102 kg/ha, 56%
inhibition
16.1
15.4
1.2
0.5
8
7b
3.3
suggests that further research in this line may be
promising.
DMSO-d6. The mass spectra (electron impact, 70 eV)
were recorded on a Shimadzu GCMS-QP2010
instrument. The elemental compositions of compounds
9 and 11 were determined using a Vario MicroCube
CHNS analyzer. Elemental analysis of organic
perchlorates 5–7 was not performed because of the
possibility of explosion. The purity of the isolated
compounds and the compositions of product mixtures
were determined by TLC on Sorbfil PTSKh-AF-A
plates using acetone–hexane (5:2), toluene–ethanol
(20:3), ethanol–benzene (1:10) as eluent; spots were
visualized by treatment with iodine vapor or under UV
light. The melting points of crystalline compounds
were measured on a Kofler hot stage and were not
corrected.
EXPERIMENTAL
The IR spectra were recorded in the range 400–
4200 cm–1 on an InfraLyum FT-02 spectrometer with a
resolution of ±1 cm–1. Liquid samples (oils) were
examined as films between KBr plates, and solid
samples, as KBr disks. The electronic absorption
spectra were measured in the range λ 190–900 nm on a
LEKI SS2109 scanning spectrophotometer from
solutions in acetic acid against glacial acetic acid. The
1H NMR spectra were recorded on a JEOL ECA 400
instrument (400 MHz) in DMSO-d6, CDCl3, or acetone-
1
d6 using tetramethylsilane as internal standard. The H
13
and C NMR spectra of 9f were obtained on a Bruker
Initial D-(–)-pantolactone was
product.
a
commercial
1
Avance DPX 300 spectrometer (300.3 MHz for H) in
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 12 2018

SYNTHESIS AND PROPERTIES OF NEW 4-OXO-4,5-DIHYDRO-1,3-OXAZOLIUM
2509
D-Pantoic acid amide (2, D-2,4-dihydroxy-3,3-di-
methylbutanamide). Gaseous ammonia was passed
over a period of 3 h through a mixture of 240 mL of
methylene chloride, 120 g of D-(–)-pantolactone, and
4 mL of water under stirring at 10°C. Large colorless
crystals separated from the mixture during the
subsequent 24 h. Yield 81–86%, mp 98°C. IR
spectrum, ν, cm–1: 3476–3194 (NH, OH), 2976, 2967,
2937, 2924, 2880, 2851 (C–H), 1684 (C=O). 1H NMR
spectrum (400 MHz, acetone-d6), δ, ppm: 0.89 s (3H,
3-Acetoxy-1,4,4-trimethyl-2-oxopyrrolidinium per-
chlorate (6). A 4.8-g portion of the product mixture
obtained by reaction of D-(–)-pantolactone with
methylamine was dissolved in 20 mL of acetic
anhydride, the solution was cooled to 0°C, and 3 mL
(0.03 mol) of 70% HClO4 was slowly added dropwise.
The mixture was heated to the boiling point, refluxed
for 1 min, cooled to room temperature, and diluted
with diethyl ether (20 mL). The crystalline solid was
filtered off and washed with diethyl ether. Yield 40%,
mp 125–127°C. IR spectrum, ν, cm–1: 3295–3120
2
CH3), 0.95 s (3H, CH3), 3.41 d.d (2H, CH2, J =
1
10.9 Hz), 3.91 br.s (1H, CH), 6.77 br.s (2H, NH2), 7.06
br.s (~1.2H, OH, partially exchangeable). Found, %:
C49.30; H 8.51; N 9.09. C6H13NO3. Calculated, %: C
48.97; H 8.90; N 9.52.
(N–H), 1773, 1763 (C=O). NMR spectrum (400
MHz, acetone-d6), δ, ppm: 1.20 s (3H, CH3), 1.31 s
(3H, CH3), 2.05 s (3H, CH3CO), 3.30 s (3H, N+CH3),
3.97 d (2H, CH2, 2J = 11.5), 5.70 s (1H, 3-H).
Reaction of D-(–)-pantolactone with methyl-
amine. D-(–)-Pantolactone, 65 g (0.496 mol), was
dissolved in 120 mL of chloroform, 2 mL of water was
added, the mixture was cooled to 10°C, and gaseous
methylamine was passed through the mixture over a
period of 20 h with stirring. The mixture was kept for
24 h, and the solvent was distilled off under reduced
pressure to leave a viscous oil which, according to the
2-[(E)-2-Arylethenyl)]-5-(1-acetoxy-2-methyl-
propan-2-yl)-4-oxo-4,5-dihydro-1,3-oxazolium per-
chlorates 7a–7g (general procedures). a. A mixture of
3.13 g (0.01 mol) of perchlorate 5a and 0.011 mol of
the corresponding aromatic aldehyde in 4.0 mL of
acetic acid was slowly heated to the boiling point (in
the reactions with 4-methoxybenzaldehyde and
salicylaldehyde derivatives, the mixture was heated for
15–20 min at 60°C). After cooling, the mixture was
diluted with diethyl ether, and the precipitate was
filtered off and washed with diethyl ether.
1
IR, H NMR, and GC/MS data, was a mixture of
unreacted D-(–)-pantolactone, N-methylpantoic acid
amide 3, and N-methylbutyrolactam 4.
5-(1-Acetoxy-2-methylpropan-2-yl)-2-methyl-4-
oxo-4,5-dihydro-1,3-oxazolium perchlorate (5a). A
mixture of 4.42 g (0.03 mol) of amide 2 and 18 mL of
acetic anhydride was cooled in an ice–salt bath, and
3.0 mL (0.03 mol) of 70% aqueous perchloric acid was
added dropwise under continuous stirring. Amide 2
dissolved completely, and the solution turned pale
yellow. The solution was refluxed for 5–10 min until it
acquired saturated straw yellow color, cooled, and
diluted with 20 mL of diethyl ether. An oily material
separated and crystallized on grinding. The crystalline
product was filtered off, washed thrice with diethyl
ether–ethyl acetate (3:1), and dried. Yield 83%, mp
142°C. IR spectrum, ν, cm–1: 3600–3200 (N–H), 2970
(C–H), 1778 (C4=O), 1753 (C=O, ester), 1468 (OCH+),
1092 (ClO4–).1H NMR spectrum (400 MHz, acetone-
d6), δ, ppm: 1.04 s (3H, CH3), 1.25 s (3H, CH3), 2.31 s
(3H, CH3CO), 3.92 s (3H, 2-CH3), 4.13 d.d (2H, CH2,
2J = 10.9 Hz), 5.83 s (1H, 5-H); NH+ signal was not
observed, presumably because of exchange processes. 13C
NMR spectrum (101 MHz, acetone-d6), δ, ppm: 18.4
(Me), 19.9 (Me), 22.0 (Me), 40.4 (Me2C), 75.1 and 75.5
(OCH2, C4), 154.2 (C2), 172.0 (C=O), 176.8 (C=O).
b. A mixture of 1.47 g (0.01 mol) of amide 2,
10 mL of acetic anhydride, and 1 mL of 70%
perchloric acid was cooled to 0°C, 0.011 mol of the
corresponding aromatic aldehyde was added, and the
mixture was heated to the boiling point. The mixture
was cooled and diluted with diethyl ether, and the
precipitate was filtered off and washed first with ethyl
acetate and then with diethyl ether. The purity and
spectral parameters of the products were similar to
those of samples prepared as described in a.
5-(1-Acetoxy-2-methylpropan-2-yl)-4-oxo-2-[(E)-
2-phenylethenyl]-4,5-dihydro-1,3-oxazolium per-
chlorate (7a). Yield 50% (a), 44% (b); yellow crystals,
mp 171°C. IR spectrum, ν, cm–1: 3443 (N–H), 2979
(C–H), 1798, 1739 (C=O), 1633 (C=C), 1550 (O–C+–N),
1114 (ClO4–).1H NMR spectrum (400 MHz, acetone-
d6), δ, ppm: 1.00 s (3H, CH3), 1.16 s (3H, CH3), 1.95 s
(3H, CH3CO), 4.16 br. s (2H, CH2), 5.64 s (1H, 5-H),
6.68 d (1H, CH=, 3J = 16.0 Hz), 7.28–7.40 m (5H, Ph),
3
7.41 d (1H, CH=, J = 16.0 Hz); no NH+ signal was
observed, presumably because of exchange. UV
spectrum (AcOH, c = 10–4 M): λmax 318 nm (logε 2.3).
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LUKIN et al.
3
3
5-(1-Acetoxy-2-methylpropan-2-yl)-2-[(E)-2-(4-
Harom, J = 8.2 Hz), 7.46 d (2H, Harom, J = 8.2 Hz),
7.56 d (1H, CH=, 3J = 16.0 Hz), 7.91 d (1H, CH=, 3J =
16.3 Hz), 10.25 br.s (1H, OH); no NH+ signal was
observed, presumably because of exchange. UV
spectrum (AcOH, c = 10–4 M): λmax 340 nm.
bromophenyl)ethenyl]-4-oxo-4,5-dihydro-1,3-oxazo-
lium perchlorate (7b). Yield 60% (a), 41% (b);
yellow crystals, mp 195–197°C (decomp.). IR
spectrum, ν, cm–1: 3437 (N–H), 2976, 2953 (C–H),
1811, 1736 (C=O), 1618 (C=C), 1560 (O–C+–N), 1118
5-(1-Acetoxy-2-methylpropan-2-yl)-2-[(E)-2-(2-
hydroxyphenyl)ethenyl]-4-oxo-4,5-dihydro-1,3-oxa-
zolium perchlorate (7f). Yield 10% (a), yellow
crystals, mp 170°C (decomp.). IR spectrum, ν, cm–1:
3471 (O–H, N–H), 2945, 2897 (C–H), 1784, 1736
(ClO4–). H NMR spectrum (400 MHz, acetone-d6), δ,
1
ppm: 1.28 s (3H, CH3), 1.35 s (3H, CH3), 2.01 s (3H,
2
CH3CO), 4.11 d.d, AB pattern (2H, CH2, J = 11.5),
5.68 s (1H, 5-H), 7.53 d (1H, CH=, 3J = 16.0 Hz), 7.82
3
3
d (2H, Harom, J = 8.6 Hz), 7.97 d (2H, Harom, J =
(C=O), 1597 (C=C), 1550 (O–C+–N), 1107 (ClO4–). H
1
8.6 Hz), 8.83 d (1H, CH=, J = 16.0 Hz); no NH+
3
NMR spectrum (400 MHz, DMSO-d6), δ, ppm: 0.93 s
(3H, CH3), 1.02 s (3H, CH3), 1.98 s (3H, CH3CO),
3.91 d.d (2H, CH2, J = 11.0), 4.73 s (1H, 5-H), 6.83–
6.87 m (1H, Harom), 6.92 d (1H, Harom, J = 7.5 Hz),
signal was observed, presumably because of exchange.
UV spectrum (AcOH, c = 10–4 M): λmax 326 nm (log ε 1.6).
2
3
5-(1-Acetoxy-2-methylpropan-2-yl)-2-[(E)-2-(4-di-
methylaminophenyl)ethenyl]-4-oxo-4,5-dihydro-1,3-
oxazolium perchlorate (7c). Yield 59% (a), red
crystals. IR spectrum, ν, cm–1: 3443 (N–H), 2964,
2931 (C–H), 1750, 1739 (C=O), 1600 (C=C), 1510
3
7.02 d (1H, CH=, J = 16.0 Hz), 7.19–7.22 m (1H,
3
H
arom), 7.71 d (1H, Harom, J = 7.8 Hz), 8.18 d (1H,
3
CH=, J = 16.3 Hz); neither NH+ nor OH signal was
observed, presumably because of exchange.
–
(O–C+–N), 1108 (ClO4 ). 1H NMR spectrum (400 MHz,
5-(1-Acetoxy-2-methylpropan-2-yl)-2-[(E)-2-(2-
hydroxy-5-nitrophenyl)ethenyl]-4-oxo-4,5-dihydro-
1,3-oxazolium perchlorate (7g). Yield 49% (a), mp
175–176°C (decomp.). IR spectrum, ν, cm–1: 3403,
3116 (O–H, N–H), 3077, 2972, 2941 (C–H), 1726
(C=O), 1594 (C=C), 1518 (O–C+–N), 1095 (ClO4–). 1H
NMR spectrum (400 MHz, acetone-d6), δ, ppm: 0.85 s
(3H, CH3), 1.03 s (3H, CH3), 1.90 s (3H, COCH3),
4.04 d.d (2H, CH2, 2J = 11.0), 4.76 s (1H, 5-H), 6.58 d
acetone-d6), δ, ppm: 1.07 s (3H, CH3), 1.19 s (3H,
CH3), 1.95 s (3H, CH3CO), 3.12 s (6H, NMe2), 4.10
d.d, AB pattern (2H, CH2, 2J = 13.9), 5.49 s (1H, 5-H),
3
6.89 d (2H, Harom, J = 8.9 Hz), 7.48 d (1H, CH=, 3J =
3
16.0 Hz), 7.72 d (2H, Harom, J = 8.9 Hz), 7.84 d (1H,
3
CH=, J = 16.0 Hz); no NH+ signal was observed,
presumably because of exchange. UV spectrum
(AcOH, c = 10–4 M), λmax, nm (logε): 350 (0.3), 530 (0.5).
3
3
5-(1-Acetoxy-2-methylpropan-2-yl)-2-[(E)-2-(4-
methoxyphenyl)ethenyl]-4-oxo-4,5-dihydro-1,3-oxa-
zolium perchlorate (7d). Yield 58% (a), yellow
crystals. IR spectrum, ν, cm–1: 3440 (N–H), 3070 (C–H),
1804, 1732 (C=O), 1600 (C=C), 1531 (O–C+–N), 1116
(ClO4–). 1H NMR spectrum (400 MHz, CDCl3), δ, ppm:
1.12 s (3H, CH3), 1.14 s (3H, CH3), 2.06 s (3H,
CH3CO), 3.84 s (3H, OMe), 4.04 d.d, AB pattern (2H,
CH2, 2J = 13.9), 5.17 s (1H, 5-H), 6.35 d (1H, CH=, 3J =
(1H, CH=, J = 16.0 Hz), 7.46 d (1H, Harom, J =
3
8.7 Hz), 7.63 m (2H, Harom), 7.98 d (1H, CH=, J =
16.0 Hz), 10.20 br.s (1H, OH); no NH+ signal was
observed, presumably because of exchange.
2-[(E)-2-Arylethenyl]-5-(1-acetoxy-2-methyl-
propan-2-yl)-4-oxo-4,5-dihydro-1,3-oxazoles 9a, 9b,
9d, 9f, and 9g (general procedure). a. Perchlorate 7a,
7b, 7d, 7f, or 7g, 0.005 mol, was dissolved in 5 mL of
50% aqueous ethanol. After 3–24 h, a crystalline solid
precipitated and was filtered off and washed with
water.
3
16.0 Hz), 6.91 d (2H, Harom, J = 8.0 Hz), 7.49 d (2H,
Harom, 3J = 8.0 Hz), 7.70 d (1H, CH=, 3J = 16.0 Hz); no NH+
signal was observed, presumably because of exchange.
b. Oxazolium perchlorate 7d (0.002 mol) was
treated with a solution of 0.56 mL (0.004 mol) of
triethylamine in 4 mL of 1,4-dioxane, and the mixture
was heated for 40 min at 60°C. The mixture was
cooled and diluted with 50 mL of ice water, and the
yellow precipitate was filtered off and dried.
5-(1-Acetoxy-2-methylpropan-2-yl)-2-[(E)-2-(4-
hydroxyphenyl)ethenyl]-4-oxo-4,5-dihydro-1,3-oxa-
zolium perchlorate (7e). Yield 54% (a), mp 178°C
(decomp.). IR spectrum, ν, cm–1: 3305, 3133 (O–H, N–H),
2977, 2929 (C–H), 1794, 1739 (C=O), 1623 (C=C),
1569 (O–C+–N), 1121 (ClO4–). H NMR spectrum
1
2-Methyl-2-{2-[(E)-2-Phenylethenyl]-4-oxo-4,5-di-
hydro-1,3-oxazol-5-yl}propyl acetate (9a). Yield
70% (a), light yellow powder, mp 148°C. IR spectrum,
(400 MHz, acetone-d6), δ, ppm: 0.92 s (3H, CH3), 1.01
s (3H, CH3), 1.97 s (3H, CH3CO), 3.94 d.d, AB pattern
2
(2H, CH2, J = 11.0), 4.69 s (1H, 5-H), 6.80 d (2H,
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SYNTHESIS AND PROPERTIES OF NEW 4-OXO-4,5-DIHYDRO-1,3-OXAZOLIUM
2511
ν, cm–1: 2980 (C–H), 1730, 1690 (C=O), 1630 (C=C,
C=N). H NMR spectrum (400 MHz, acetone-d6), δ,
(CH3), 20.5 (CH3CO), 37.8 (CMe2), 67.9 (OCH2), 83.4
(OCH), 112.4, 116.4, 119.6, 120.4, 129.9, 133.3, 143.9,
157.8, 170.1 (C–OH), 186.0 (C=O), 189.8 (C=O). Mass
spectrum, m/z (Irel, %): 317 (10) [M]+, 300 (83) [M –
OH]+, 272 (10) [M – OH – CO]+, 212 (20) [M – 105]+,
212 (11) [M – AcOCH2C(CH3)2]+, 161 (13) [M –
AcOCH2C(CH3)2C=C=O]+, 146 (58) [M – 171]+, 118
(73) [M – 199]+, 55 (16) [C3H3O]+, 43 (100) [CH3C(O)]+.
Found, %: C 64.44; H 6.18; N 4.30. C17H19NO5.
Calculated, %: C 64.34; H 6.03; N 4.41.
1
ppm: 0.90 s (3H, CH3), 1.03 s (3H, CH3), 1.94 s (3H,
2
CH3CO), 4.05 d.d (2H, CH2, J = 11.0), 5.44 s (1H,
5-H), 7.09 d (1H, CH=, 3J = 16.0 Hz), 7.25–7.31 m (5H,
3
Ph), 7.64 d (1H, CH=, J = 16.0 Hz). Mass spectrum,
m/z (Irel, %): 301 (10) [M]+, 228 (10) [M – AcOCH2]+,
187 (30) [M – AcOCH2C(CH3)2]+, 129 (100)
[AcOCH2C·(CH3)2CH2]+, 103 (25) [PhCH=CH]+, 43 (62)
[CH3C(O)]+. Found, %: C 67.80; H 6.48; N 4.57.
C17H19NO4. Calculated, %: C 67.76; H 6.36; N 4.65.
2-{2-[(E)-2-(2-Hydroxy-5-nitrophenyl)ethenyl]-4-
oxo-4,5-dihydro-1,3-oxazol-5-yl}-2-methylpropyl
acetate (9g). Yield 63% (a), yellow crystals, mp 245°C.
IR spectrum, ν, cm–1: 3460 (O–H), 2946, 2927 (C–H),
1724, 1672 (C=O), 1597, 1543 (C=N, C=C). 1H NMR
spectrum (400 MHz, acetone-d6), δ, ppm: 0.84 s (3H,
CH3), 1.02 s (3H, CH3), 2.00 s (3H, CH3CO), 4.03 d.d
2-{2-[(E)-2-(4-Bromophenyl)ethenyl]-4-oxo-4,5-
dihydro-1,3-oxazol-5-yl}-2-methylpropyl acetate (9b).
Yield 80% (a), light yellow crystals, mp 162°C. IR
spectrum, ν, cm–1: 2965, 2932 (C–H), 1728, 1699 (C=O),
1631, 1585 (C=C, C=N). 1H NMR spectrum (400 MHz,
acetone-d6), δ, ppm: 0.88 s (3H, CH3), 1.02 s (3H,
2
2
CH3), 1.92 s (3H, CH3CO), 4.02 d.d (2H, CH2, J =
(2H, CH2, J = 11.0 Hz), 4.61 s (1H, 5-H), 6.92–7.00
3
3
11.5), 5.45 s (1H, 5-H), 7.22 d (1H, CH=, J =
m (2H, Harom, CH=), 7.79 d (1H, Harom, J = 8.0 Hz),
3
15.6 Hz), 7.25 d (2H, Harom, J = 9.0 Hz), 7.56 d (1H,
8.20 m (2H, CH=, Harom), 10.82 br.s (1H, OH).
3
3
CH=, J = 15.6 Hz), 7.58 d (2H, Harom, J = 9.0 Hz).
Found, %: C 53.73; H 4.85; N 3.59. C17H18BrNO4.
Calculated, %: C 53.70; H 4.77; N 3.68.
1,2-Bis(4-methoxybenzylidene)hydrazine (11c).
Perchlorate 7g (0.60 g, 0.0014 mol) and hydrazine
hydrate (0.078 mL, 0.0016 mol) were dissolved in
2 mL of acetic acid, and the solution was heated for 4 h
at 60°C. The mixture was cooled, and the precipitate
was filtered off, washed with diethyl ether, and dried.
Yield 35%, yellow crystals, mp 165°C. IR spectrum, ν,
cm–1: 2968, 2935, 2838 (C–H), 1603 (C=N), 1508
(C=C). 1H NMR spectrum (400 MHz, CDCl3), δ, ppm:
3.86 s (6H, MeO), 6.95 d (4H, Harom, 3J = 8.0 Hz), 7.77
2-{2-[(E)-2-(4-Methoxyphenyl)ethenyl]-4-oxo-4,5-
dihydro-1,3-oxazol-5-yl}-2-methylpropyl acetate (9d).
Yield 77% (a), 47% (b); light yellow crystals, mp 99°C.
1H NMR spectrum (400 MHz, CDCl3), δ, ppm: 1.01 s
(3H, CH3), 1.18 s (3H, CH3), 2.08 s (3H, CH3CO),
3.86 s (3H, MeO), 4.04 br.s (2H, CH2), 4.53 s (1H, 5-H),
6.64 d (1H, CH=, 3J = 16.0 Hz), 6.94 d (2H, Harom, 3J =
3
3
7.9 Hz), 7.57 d (2H, Harom, J = 7.9 Hz), 7.97 d (1H,
d (4H, Harom, J = 8.0 Hz), 8.60 s (2H, HC=N). Mass
3
CH=, J = 16.0 Hz). Mass spectrum, m/z (Irel, %): 300
spectrum, m/z (Irel, %): 268 (80) [M]+, 161 (100) [M –
4-MeOC6H4]+, 134 (30) [4-MeOC6H4CH=N]+, 77 (30)
[C6H5]+. Found, %: C 71.64; H 6.05; N 10.41.
C16H16N2O2. Calculated, %: C 71.62; H 6.01; N 10.44.
(26) [M – MeO]+, 175 (85) [4-MeOC6H4CH=CHNCO]+,
159 (100) [4-MeOC6H4CH=CHCN]+, 43 (60) [CH3C(O)]+.
Found, %: C 65.27; H 6.45; N 4.21. C18H21NO5.
Calculated, %: C 65.24; H 6.39; N 4.23.
Antidotal activity. Sunflower seedlings with a
seminal root length of 2–4 mm were placed for 1 h into
a solution of 2,4-D with a concentration of 10–3% to
attain 40–60% hypocotyl growth inhibition. After
treatment with the herbicide, the seedlings were
washed with water and placed into solutions of com-
pound 7a, 7b, or 7e–7g with concentrations of 10–2, 10–3,
10–4, and 10–5% (herbicide+antidote samples). After
1 h, the seedlings were washed with water and
distributed over filter paper sheets (20 seedlings per
sheet); the sheets were rolled and placed in beakers
charged with 50 mL of water. For further germination,
samples were kept for 3 days at a constant temperature
(28°C). The seedlings treated only with 2,4-D (1 h, 10–3%)
2-{2-[(E)-2-(2-Hydroxyphenyl)ethenyl]-4-oxo-4,5-
dihydro-1,3-oxazol-5-yl}-2-methylpropyl acetate (9f).
Yield 65% (a), light yellow crystals, mp 243°C. IR
spectrum, ν, cm–1: 3471 (O–H), 2976, 2937 (C–H),
1737, 1672 (C=O), 1620, 1523 (C=N, C=C). H NMR
spectrum (300 MHz, DMSO-d6), δ, ppm: 0.96 s (3H,
1
CH3), 1.05 s (3H, CH3), 2.01 s (3H, CH3CO), 3.95 d.d
2
(2H, CH2, J = 10.9), 4.76 s (1H, 5-H), 6.85–6.90 m
3
(1H, Harom), 6.95 d (1H, Harom, J = 8.2 Hz), 7.07 d
3
(1H, CH=, J = 16.3 Hz), 7.29–7.34 m (1H, Har3om),
3
7.76 d (1H, Harom, J = 7.5 Hz), 8.22 d (1H, CH=, J =
16.3 Hz), 10.56 br.s (1H, OH). 13C NMR spectrum
(76 MHz, DMSO-d6), δC, ppm: 19.2 (CH3), 19.7
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 12 2018

2512
LUKIN et al.
4. Kosulina, T.P., Doctoral (Chem.) Dissertation,
and then kept for 1 h in water (herbicide samples) were
used as reference. Each experiment was carried out in
triplicate. The protecting effect was assessed by the
increase of the hypocotyl and root length in
herbicide+antidote samples relative to the reference
samples. The results were statistically processed using
Student’s t-test for a confidence probability p of 0.95
(Table 1). We also assessed the growth-regulating
activity of the same compounds with respect to
sunflower seedlings. For this purpose, solutions of 7a,
7b, or 7e–7g with different concentrations were used
(10–2–10–5%). The growth-regulating effect was
assessed by the elongation of the stem and root of
sunflower seedlings treated with compounds 7a, 7b, or
7e–7g relative to the control. The data were
statistically processed as described above.
Krasnodar, 1999.
5. Kosulina, T.P., Zelikman, Z.I., and Kul’nevich, V.G., Zh.
Org. Khim., 1976, vol. 12, no. 5, p. 2137.
6. Kul’nevich, V.G., Kosulina, T.P., Lyubke, F.-U., and
Zelikman, Z.I., Chem. Heterocycl. Compd., 1980,
vol. 16, no. 1, p. 23. doi 10.1007/BF00475384
7. Kosulina, T.P., Bychenko, N.V., Morenets, I.P.,
Sorotskaya, L.N., Krutosikova, A., Val’ter, N.I., and
Kul’nevich, V.G., Chem. Heterocycl. Compd., 1998,
vol. 34, no. 7, p. 855. doi 10.1007/BF02251697
8. Lyubke, F.-U., Kosulina, T.P., and Kul’nevich, V.G.,
Chem. Heterocycl. Compd., 1981, vol. 17, no. 7, p. 656.
doi 10.1007/BF00506029
9. Lyubke, F.-U., Cand. Sci. (Chem.) Dissertation,
Krasnodar, 1980.
10. Morenets, I.P., Cand. Sci. (Chem.) Dissertation, 2000.
11. Tishchenko, S.G., Chekhun, V.P., Gavrilov, R.S., and
Papanov, V.A., USSR Inventor’s Certificate no. 360340,
1972; Byull. Izobret., 1972, no. 36, p. 66.
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10.1007/s10593-005-0148-x
ACKNOWLEDGMENTS
V.V. Dotsenko thanks the Ministry of Education
and Science of the Russian Federation for financial
support (project no. 4.5547.2017/8.9). The biological
activity of the synthesized compounds was studied in
the framework of the creative collaboration agreement
between the Kuban State University and All-Russian
Research Institute of Biological Plant Protection, as
well as state assignment no. 0686-2014-0024. This
study was performed using the scientific equipment of
the Environmental Analytical Center of the Kuban
State University (unique ID RFMEFI59317Kh0008).
13. Klajn, R., Chem. Soc. Rev., 2014, vol. 43, p. 148. doi
10.1039/c3cs60181a
14. Samat, A., De Keukeleire, D., and Guglielmetti, R.,
Bull. Soc. Chim. Belg., 1991, vol. 100, no. 9, p. 679. doi
10.1002/bscb.19911000908
15. Berkovic, G., Krongauz, V., and Weiss, V., Chem. Rev.,
2000, vol. 100, no. 5, p. 1741. doi 10.1021/cr9800715
16. Dmitrieva, I.G., Dyadyuchenko, L.V., Nazarenko, D.Yu.,
and Strelkov, V.D., Agrokhimiya, 2014, no. 7, p. 33.
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
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