Enantiotropic Transformation of Carbethoxyhydrazones of Acetophenones

Article abstract of DOI:10.1134/S1070363220020243

Abstract: Hydrazinecarboxylates have been synthesized by reacting substituted acetophenones with carbethoxyhydrazine. One of product is formed as a mixture of E- and Z-isomers. In the process of measuring the melting point of the resulting hydrazinecarbox

Full text of DOI:10.1134/S1070363220020243

ISSN 1070-3632, Russian Journal of General Chemistry, 2020, Vol. 90, No. 2, pp. 311–313. © Pleiades Publishing, Ltd., 2020.
Enantiotropic Transformation of Carbethoxyhydrazones
of Acetophenones
E. A. Popovaa,*, O. V. Stepanovaa, V. V. Bessonova, G. D. Nepochatyia,
L. M. Pevznera, and M. L. Petrova
a St. Petersburg State Institute of Technology (Technical University), St. Petersburg, 190013 Russia
*e-mail: ekaterinaapopova@yandex.ru
Received December 23, 2019; revised January 21, 2020; accepted January 23, 2020
Abstract—Hydrazinecarboxylates have been synthesized by reacting substituted acetophenones with carbethoxy-
hydrazine. One of product is formed as a mixture of E- and Z-isomers. In the process of measuring the melting
point of the resulting hydrazinecarboxylates, a transition of one crystalline form to another has been detected. That
process has been recorded on video in “time-laps” mode for one of the substances.
Keywords: hydrazinecarboxylates, enantiotropic conversion, acetophenone
DOI: 10.1134/S1070363220020243
Carbethoxyhydrazones are well known for a variety
of biological activities that stimulate synthesis of their
derivatives [1, 2]. The specific tendency of carbethoxy-
hydrazones to isomerism with respect to the C=N bond,
results in different physical and chemical properties of
the isomers [3, 4]. Herein, we present synthesis of two
new representatives of this class of compounds.
corresponding acid chlorides 2a, 2b (Scheme 1) with the
yields of 88 and 94%, respectively. The intermediates 2a,
2b were converted into the corresponding esters 2a, 3d
in their reaction with a Grignard reagent derived from
diethyl malonate [yield 56% (3a), yield 65% (3b)] [6].
The following refluxing of compounds 3a, 3b for 6 h in
the presence of hydrochloric acid gave acetophenones
4a (73%) or 4b (81%), respectively [6]. The reaction of
intermediates 4a, 4b with carbethoxyhydrazine in toluene
medium in the presence of p-toluene sulfonic acid led to
hydrazinecarboxylates 5a, 5b (Scheme 1). The product
5b was isolated as a mixture of E- and Z-isomers.
RESULTS AND DISCUSSION
The disubstituted benzoic acids 1a and 1b were
introduced into the reaction with thionyl chloride ac-
cording to the procedure described in [5] to form the
Scheme 1.
COOEt
O
O
Cl
COOH
Br
COOEt
Br
COOEt
COOEt
Br
SOCl2
BrMg
R
R
R
1a, 1b
3a, 3b
2a, 2b
R
O
O
H
N
O
H2N
N
COOEt
Br
N
HCl/H2O
H
OEt
Br
R
4a, 4b
5a, 5b
R = CH (ɚ), OCH (b).
3
3
311

312
POPOVA et al.
Fig. 2. (a) Initial sample 5b before melting, (b) crystallization
from the melt after the first step.
melting and re-crystallization of compounds, the pattern
of the crystals melting did not change. (2) The ratio of
E/Z-isomers in the NMR spectra of 5b (CDCl3 solution)
after isolation from reaction mixture and after melting
procedure remained the same. The similar phenomenon
was observed for carbethoxyhydrazone 5a, characterized
by a single geometric isomer according to 1Н NMR spec-
tra. It exhibited the melting pattern similar to that of 5b.
In addition, this phenomenon could not be attributed to
degradation of a molecular complex of the substance with
the solvent. Recrystallization of carbethoxyhydrazones
from ethyl alcohol after isolation of those from deuterated
chloroform solutions did not influence upon the behavior
of the compounds in the course of their melting.
Fig. 1. Fragment of 1H NMR spectrum of compound 5b that
demonstrates signals of CAr4–H and CAr6–H.
Based on the above, the enantiotropic nature of com-
pounds 5a, 5b was established.
In 1Н NMR spectrum of compound 5b (Fig. 1), dou-
bling of signals of the aromatic and NH groups which
indicated the presence of two geometric isomers was
detected. The ratio of geometric isomers of compound
5b was 4 : 1 (Fig. 1). In the course of measuring melting
point of compound 5b in the range of 81–83°С partial fu-
sion of the sample and its recrystallization at 110°С were
observed (Fig. 2). The second melting point was recorded
in the range of 122–124°С. In the process of melting the
compound 5a, a similar effect was observed, but the first
melting point was measured at higher temperature. A
significant difference between the gaps of melting points
of two enantiomers of the products were determined to
be Δ = 12 (5a) and 46°С (5b). The link to the video of
melting 5b is shown in Fig. 3.
EXPERIMENTAL
1H and 13C NMR spectra were measured on a Bruker
DPX-400 spectrometer at 400.13 and 100.16 MHz, re-
spectively. The signals of residual 1Н and 13С of deuter-
ated chloroform were used as internal standards. Melting
points were measured on a Boetius Cofler instrument.
In a 50 mLround bottom flask equipped with magnetic
stirrer, a Dean-Stark nozzle and condenser, the mixture of
a ketone 4a, 4b (17.6 mmol) with carbethoxyhydrazine
(1.98 g, 19.0 mmol), p-toluene sulfonic acid (0.17 g,
1.0 mmol) and 30 mL of toluene was refluxed for 8 h.
Then the solvent was evaporated under reduced pressure.
The precipitated crystals were stirred with cold ethanol,
filtered off and air dried. The corresponding products 5a,
5b were recrystallized from ethanol.
The process observed in the course of melting of
carbethoxyhydrazones 5a, 5b, attributed initially to the
thermal cis/trans isomerization, appeared to be the con-
version of one polymorphic form into another. This con-
clusion was based on the following facts: (1) Even after
Ethyl-2-[1-(2-bromo-5-methylphenyl)ethylidene]-
hydrazine-1-carboxylate (5a). Yield 78.4%. T1melt
=
110–111°C, T2melt = 122–123°C. Spectral data are pre-
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ENANTIOTROPIC TRANSFORMATION OF CARBETHOXYHYDRAZONES OF ACETOPHENONES
313
133.6 (C3Ph), 134.5 (C1Ph), 141.5 (CH3C=N), 158.9
(C5Ph), 159.7 (C5Ph). HRMS-EI, m/z: 314.0266 [M]+.
C12H15BrN2O3.
ACKNOWLEDGMENTS
This work was proceeding using the equipment of the En-
gineering Center of St. Petersburg State Institute of Technology
(Technical University).
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
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