Synthesis and reactions with N-nucleophiles of 1-(thien-2-yl)- and 1-(4-hydroxyphenyl)-3,4,4-trichloro-3-buten-1-ones

Article abstract of DOI:10.1134/S1070428010090071

Acylation of thiophene and phenol with 3,4,4-trichloro-3-butenoyl chloride afforded the corresponding 1-(thien-2-yl)- and 1-(4-hydroxyphenyl)-3,4,4- trichloro-3-buten-1-ones, whose reaction with amines led to the formation of 3-amino-1-(thien-2-yl, 4-hydr

Full text of DOI:10.1134/S1070428010090071

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 9, pp. 1305−1312. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © V.I. Potkin, S.K. Petkevich, P.V. Kurman, 2010, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 9, pp. 1307−1314.
Synthesis and Reactions
with N-Nucleophiles of 1-(Thien-2-yl)-
and 1-(4-Hydroxyphenyl)-3,4,4-trichloro-3-buten-1-ones
V. I. Potkin, S. K. Petkevich, and P. V. Kurman
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, Minsk, 220072 Belarus
e-mail: potkin@ifoch.bas-net.by
Received December 2, 2009
Abstract—Acylation of thiophene and phenol with 3,4,4-trichloro-3-butenoyl chloride afforded the corresponding
1-(thien-2-yl)- and 1-(4-hydroxyphenyl)-3,4,4-trichloro-3-buten-1-ones, whose reaction with amines led to the
formation of 3-amino-1-(thien-2-yl, 4-hydroxyphenyl)-4,4-dichloro-2-buten-1-ones The heterocyclization of the
initial ketones into pyrazole structure was not observed, and the reaction with hydrazine hydrate provided bispyrazole
products, N,N’-bis(5-thien-2-yl)- and N,N’-bis[5-(4-hydroxyphenyl)-1H-pyrazol-3-ylmethylene]hydrazines.
DOI: 10.1134/S1070428010090071
Chlorine-containing unsaturated ketones possess
a high synthetic potential due to the presence in their
molecules of several reactive sites: C=O, C=C, C–Cl.
They underlie the preparation of various polyfunctional
compounds, in particular, a wide range of heterocyclic
substances frequently exhibiting a high biological action
[1, 2].
phenol and its derivatives are widely used as antiseptic,
antiphlogistic, antihypertensive, antiarrhythmic agents
and adrenoblockaders [8, 9].
The goal of this study consisted in the develop-
ment of preparation methods for 1-(thien-2-yl)- and
1-(4-hydroxyphenyl)-3,4,4-trichloro-3-buten-1-ones I
and II and investigation of their reactions with some
N-nucleophiles.
We formerly developed a convenient procedure for
the preparation of 1-aryl-3,4,4-trichloro-3-buten-1-ones
and their bromo derivatives and showed that they were
successfully applicable to the synthesis of aminoketones,
pyrazoles, isoxazoles, and thiazoles with aryl substitu-
ents in the molecules [3, 4]. The chemical behavior of
the obtained aryltrichloro(bromo)allylketones was in
some events analogous to that of chlorovinylketones for
they were capable to undergo the prototropic allyl rear-
rangement with the formation of conjugated ketovinyl
structures [5].
The preparation of target ketones I and II was
performed by acylation by Friedel–Krafts method of
thiophene and phenol respectively with 3,4,4-trichloro-
3-butenoyl chloride (III), obtained in its turn by a suc-
cession of transformations of the available trichloroeth-
ylene dimer [10]. We formerly successfully applied this
approach to the synthesis of aryltrichloroallylketones [3].
It turned out that the acylation of thiophene and
phenol in the presence of anhydrous aluminum chloride
proceeded with lower yield and less selectively than the
acylation of benzene and its homologs.
The replacement of the aryl fragment by a thienyl
or phenol one increases the synthetic possibilities of
the corresponding trichloroallylketones and extends the
prospects of their application in the directional synthesis
of biologically active compounds. The thiophene hetero-
cycle is present in the molecules of a number of chemi-
cal plant protectors and drugs [6–8]. On the other hand,
We established that the optimum conditions of the
thiophene acylation were at the reagents ratio thio-
phene–AlCl3–acid chloride III 1.5 : 1 : 1 and the reaction
at 20°C in a diluted solution in dichloromethane with the
concentration of acid chloride 0.5 mol l–1 and of thiophene
1305

POTKIN et al.
1306
0.75 mol l–1. In this case the yield of 1-(thien-2-yl)-3,4,4-
trichloro-3-buten-1-one (I) attained 62%. The use of more
concentrated solutions and heating decreased the yield
of the target ketone I due to the increased formation of
tarry products of thiophene polymerization. The increased
amount of the catalyst also favored tarring, and at lesser
quantity of AlCl3 the reaction did not go to completion.
The replacement of aluminum chloride by tin tetrachlo-
ride or boron trifluoride did not provide positive results:
The yield of ketone I in both cases did not exceed 16%.
It was established from the data of 1H NMR spectrum
that the acylation of thiophene occurred in the α-position
with respect to the heteroatom. In the 1H NMR spectrum
of ketone I the methylene group of the aliphatic fragment
gave rise to a singlet at 4.23 ppm. The doublet of dou-
blets at δ 7.18 ppm and doublets at 7.73 and 7.77 ppm
correspond to the CH groups of the heterocycle. In the
13C NMR spectrum of ketone I the signal of the methy-
lene fragment appeared at 46.66 ppm, the signal of the
carbonyl group, at 185.26 ppm, the signals of three CH
groups of the thiophene heterocycle, at 128.54, 132.80,
135.02 ppm, and signals of quaternary carbon atoms
belonging to the thienyl and trichlorovinyl fragments
of the molecule, at δ 121.64, 125.48, and 142.82 ppm.
(IV), and ester IV was the main reaction product (yield
48%), whereas the yield of ketone II did not exceed
12%. We established that ester IV could be converted
into ketone II in 42% yield by Fries rearrangement in
nitrobenzene catalyzed with aluminum chloride [13].
Hence taking into account both stages it was possible to
achieve the 32% yield of ketone II.
However the acylation of phenol with acid chloride
III can be performed more selectively in the process car-
ried out at 50°C in the chlorobenzene at the use of excess
aluminum chloride. It was experimentally established that
the optimum reagents ratio phenol–catalyst–acid chloride
III was 1 : 2.5 : 1. In this event the yield of ketone II was
44%, and the yield of ester IV according to GC-MS data
did not exceed 4–5%. Apparently the excess catalyst
formed a complex of AlCl3 with the hydroxy group of
phenol preventing the esterification. This reasoning ex-
plains the influence on the yield of target ketones I and
II of the order of reagents mixing. In acylation of the
phenol the acid chloride should be added to the complex
of the phenol with the catalyst, whereas the situation in the
thiophene acylation is the opposite: To prevent the cata-
lytic polymerization the thiophen should be added to the
complex of acid chloride with AlCl3, otherwise the yield
of the corresponding ketones significantly decreases.
In the IR spectrum of ketone I the absorption band of
the carbonyl group is observed at 1667 cm–1, of double
bonds C=C of the thiophene ring and of the trichlorovinyl
group at 1613, 1590, and 1515 cm–1. The mass spectrum
contains a group of molecular ion peaks with the ratio
of isotope components 100 : 98 : 32 : 3.5 confirming the
presence in the molecule of three chlorine atoms [11,
12] (Scheme 1).
The composition and the structure of ketone II and
ester IV were established from elemental analyses, IR,
1H and 13C NMR, and mass spectra.
In the IR spectrum of of ketone II the vibrations
of the hydroxy group give rise to the absorption band
at 3275 cm–1, vibrations of C=O bond, to the band at
1657 cm–1. The absorption bands at the wavenumbers
1605, 1572, and 1515 cm–1 correspond to the vibrations
of the C=C bonds. In the 1H NMR spectrum of ketone II
the singlet of the methylene group appears at 4.41 ppm,
and the doublets of the aromatic protons, at δ 6.95 and
The acylation of phenol under the conditions analo-
gous to those used with thiophene led to the formation of
two compounds: 1-(4-hydroxyphenyl)-3,4,4-trichloro-3-
buten-1-one (II) and phenyl 3,4,4-trichloro-3-butenoate
Scheme 1.
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SYNTHESIS AND REACTIONS WITH N-NUCLEOPHILES
1307
7.94 ppm, indicating the location of the acyl residue in
the para-position to the hydroxy group. The 13C NMR
spectrum contains 8 signals among which the signal at
δ 45.74 ppm corresponds to the methylene group, the
joint signals at 115.55 and 130.95 ppm belong to two
pairs of aromatic CH fragments, and the signal of the
carbonyl group appears in the region of 190.38 ppm,
The quaternary carbon atoms of the aromatic ring and of
the trichlorovinyl group give rise to signals at δ 119.86,
127.58, 128.29, 162.62 ppm. The mass spectrum of the
ketone contains a group of molecular ion peaks with the
ratio of isotope components 100:98:32:3.5 confirming the
presence in the molecule of three chlorine atoms [11, 12].
stitution of the internal chlorine atom and resulted in the
corresponding 3-amino-1-(thien-2-yl, 4-hydroxyphenyl)-
4,4-dichloro-2-buten-1-ones V–X. The hydroxy group of
the monoethanolamine was not involved in the process.
The reactions were carried out at the reagents ratio ke-
tone–amine equal ~1 : 2. The excess of amine is required
for binding the evolved hydrogen chloride. The yields of
the reaction products obtained from ketones I and II with
piperidine and morpholine V, VI, VIII, IX were 79–86%.
The reaction of ketones I and II with monoethanolamine
was less selective and was accompanied with tarring
and decomposition of molecules decreasing the yield of
enaminoketones to 48% for compound VII and no more
than 20% for compound X (Scheme 2).
The IR spectrum of ester IV contains the vibrations of
the C=O bond of the ester group at 1763 cm–1, the bands of
C=C vibrations at 1613, 1592, 1493 cm–1. The absorption
bands of the hydroxy group are lacking. In the 1H NMR
spectrum the signals appear belonging to the methylene
fragment of the aliphatic chain and to the protons of the
aromatic ring. In the mass spectrum a group of molecular
ion peak, m/z 264 (35Cl), is observed with the ratio of
isotope components 100:98:32:3.5 also confirming the
presence of three chlorine atoms in the molecule.
The formation of structures of aminoketones V–X with
an internal C=C bond apparently results from the proto-
tropic allyl rearrangement of the ketones and is confirmed
by the presence in their 1H NMR spectra of the signals of
dichloromethyl (6.35–9.26 ppm) and vinyl groups (5.67–
6.25 ppm) and by the lack of the characteristic singlet of
the methylene moiety in the region 4.2–4.4 ppm, However
the positions of the signals of the dichloromethyl groups
and the vinyl fragments in the spectra of the derivatives of
the secondary amines and monoethanolamine VII, X are
considerably different: In the spectra of enaminoketones
V, VI, VIII, IX the singlets of the CHCl2 groups appear in
the range 8.90–9.26 ppm, and the singlets of =CH groups,
in the region 5.67–5.99 ppm, whereas in the spectra of
We studied the reactions of synthesized ketones I and
II with some N-nucleophiles: amines, semicarbazide,
and hydrazine.
The reactions of ketones I and II with morpholine, pi-
peridine, and monoethanolamine proceeded with the sub-
Scheme 2.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 9 2010

POTKIN et al.
1308
compounds VII, X the signal of these moieties appear at
6.35–6.96 and 5.96–6.25 ppm respectively indicating the
different isomeric form of compounds obtained. It follows
from the comparison with the published data on the re-
lated derivatives of the β-amino-γ,γ-dichlorocrotonic acid
that aminoketones V, VI, VIII, IX form as E-isomers in
whose 1H NMR spectra the signal of the dichloromethyl
group is observed in the region 8.90–9.26 ppm, and the
signal of the vinyl proton of the =CH group, in the region
4.35–5.85 ppm. To the derivatives of the monoethanol-
amine VII, X the Z-configuration should be assigned in
whose 1H NMR spectra the singlets of both groups should
be approached and appear in the range 4.4–6.5 ppm [14,
15]. The significant downfield shift of the CHCl2 group
signal in the spectra of E-isomers originates from the for-
mation of an intramolecular hydrogen bond CCl2–H···O=C,
wheras in the Z-isomers exists an intramolecular hydrogen
bond N–H···O=C as confirmed by the downfield shift of
the broadened singlets of the amino groups to the region
of 10.82–11.08 ppm. In the 13C NMR spectra of enamino-
ketones V–X the dichloromethyl group is characterized
by signals in the region 62.74–68.14 ppm, =CH group
of the aliphatic chain, by signals at δ 88.92–94.77 ppm.
pounds: semicarbazones of initial ketones XIa, XIIa, and
the products of their rearrangement, semicarbazones of
1-(4-hydroxyphenyl, thien-2-yl)-3,4,4-trichloro-2-buten-
1-ones XIb, XIIb in the overall yield 37–48%. The
reaction was accompanied with a considerable tarring
(Scheme 3).
The isomeric semicarbazones were separated owing to
significant difference in the solubility in dichloromethane
and were identified by the data of elemental analysis, IR
and 1H NMR spectra. The occurrence of the prototropic
allyl rearrangement was confirmed by the presence in the
1H NMR spectra of semicarbazones XIb, XIIb of one-
proton singlets in the region 6.43–6.86 (=CH–) and 7.79–
7.83 ppm (CHCl2) and the lack of signals of CH2 groups
in the region 4.2–4.4 ppm that appeared in the spectra of
initial ketones I, II and semicarbazones XIa, XIIa. The
vibrations of C=N bonds are observed in the IR spectra of
semicarbazones XIa, XIIa in the region 1589–1606 cm–1,
and of their isomers XIb, XIIb, at 1661 cm–1.
The attempts to carry out the heterocyclization of ob-
tained semicarbazones XIb, XIIb into the corresponding
N-carbamoylpyrazole structure at treating with triethyl-
amine, pyridine, or KOH by the analogy with semicarba-
zones of aryltrichloroallylketones [5] were unsuccessful.
The reactions yielded an intractable mixture of tarry
products. Evidently in the semicarbazones XIb, XIIb
unlike those of aryltrichloroallylketones[5] lacks the Z-s-
cis-syn-configuration favorable for the heterocyclization,
In the IR spectra of compounds V–X the absorption
band of the C=O bond is observed at lower wavenumbers
(1541–1610 cm–1) than in the spectra of the initial ketones
that is characteristic of conjugated enaminoketones [16].
The reaction of ketones I and II with semicarbazide
prceeded unlike the reaction with amines. The process
occurred with the prototropic rearrangement of the allyl
skeleton and led to the formation of two isomeric com-
We succeeded to synthesize the pyrazole structures
from ketones I and II by reacting them with the hydra-
zine hydrate in methanol at 20–25°C and the reagents
Scheme 3.
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SYNTHESIS AND REACTIONS WITH N-NUCLEOPHILES
1309
ratio ketone–hydrazine hydrate ~1 : 4. The excess of the
hydrazine hydrate is used to trap the evolving hydrogen
chloride. The reaction involved the C=O group and the
internal chlorine atom of the ketones, and it led to the
formation 5-(thien-2-yl)- and 5-(4-hydroxyphenyl)-3-
dichloromethylpyrazoles (XIIIb XIVb) which further
reacted with hydrazine at the dichloromethyl group with
the substitution of both chlorine atoms and the formation
of linked bispyrazole derivatives XIIIa, XIVa in 88–90%
yield. We failed to isolate the intermediate pyrazoles with
the dichloromethyl group XIIIb XIVb in the reaction
performed at –20°C, or at smaller amount of hydrazine
and in various solvents.
The chemical shifts of protons were measured relative to
TMS, the carbon signals, relative to the signals of deuter-
ated solvents. Mass spectra were measured on a GC=MS
instrument Hewlett Packard 5890/5972 in the electron
impact mode, ionizing electrons energy 70 eV; capillary
column HP-5MS 30 m × 0.25 mm, stationary phase (5%
PhMe Silicone) 0.25 μm, vaporizer temperature 250°C.
1-(Thien-2-yl)-3,4,4-trichloro-3-buten-1-one (I).
To a complex obtained by mixing 4.16 g (20 mmol) of
3,4,4-trichloro-3-butenoyl chloride and 2.67 g (20 mmol)
of AlCl3 in 50 ml of anhydrous dichloromethane at 20°C
was added dropwise 2.52 g (30 mmol) of thiophene, the
mixture was stirred for 1 h and poured into water with ice
acidified with HCl (pH 3). The organic layer was sepa-
rated, washed with a solution of sodium carbonate, with
water till neutral washings, and dried with CaCl2. The
solvent was distilled off, to the residue 50 ml of hexane
was added, and the mixture was stirred for 10 min at
55°C, the insoluble residue was removed, and the solution
was maintained for 3 h at 0°C. The separated precipitate
was filtered off, washed with cold hexane, and dried in
a vacuum. Yield 3.17 g (62%), mp 48–49°C. IR spectrum,
ν, cm–1: 1667 (C=O), 1613, 1590, 1515 (C=C), 859, 741
The composition and structure of obtained bispyr-
azolylhydrazines XIIIa, XIVa were established from
1
the data of elemental analysis, IR, H and 13C NMR
spectra. In the IR spectra the vibrations of C=N bonds
give rise to absorption bands at 1614–1639 cm–1, of C=C
bonds, to bands in the region 1509–1606 cm–1, of NH
groups, to broad bands in the range 3200–3252 cm–1. In
1
the H NMR spectra the protons of the =CH groups of
the pyrazole rings appear as singlets at δ 7.0–7.05 ppm,
exocyclic =CH groups are characterized by singlets in the
region 8.57–8.60 ppm. The spectrum of compound XIIIa
contains two doublets at δ 7.50 and 7.53 ppm, belonging
to hydrogen atoms in the positions 3, 5 of the thiophene
ring, and a doublet of doublets at 7.11 ppm, corresponding
to C4H fragment. In the 1H NMR spectrum of compound
XIVa the aromatic protons are observed as doublets at
6.82 and 7.62 ppm.
In the 13C NMR spectra of compounds XIIIa, XIVa
the fragments C4H of the pyrazole heterocycle possess the
signals at δ 101.15–103.52 ppm, and the exocyclic =CH
groups, the signals in the region 153.19–155.21 ppm,
The spectra contain also the signals of =CH groups of
the thiophene and phenol residues respectively and the
signals of the quaternary carbon atoms.
1
(C–Cl). H NMR spectrum, δ, ppm: 4.23 s (2H, CH2),
7.18 d.d (1Hthiophene), 7.73 d (1Hthiophene, 3J 5 Hz), 7.77 d
(1Hthiophene, 3J 4 Hz). 13C NMR spectrum, δ, ppm: 46.66
(CH2), 128.54 (CHthiophene), 132.80 (CHthiophene), 135.02
(CHthiophene); 121.64, 125.48, 142.82 (3Cquaternal); 185.26
(C=O). Found, %: C 37.81; H 2.09; Cl 41.30; S 12.37.
[M]+ 254 (35Cl). C8H5Cl3OS. Calculated, %: C 37.60;
H 1.97; Cl 41.62; S 12.55. M 255.55.
Acylation of phenol with 3,4,4-trichloro-3-butenoyl
chloride (III). a. To a complex of 4.16 g (20 mmol) of
3,4,4-trichloro-3-butenoyl chloride (III) and 2.67 g (20
mmol) of AlCl3 in 50 ml of dichloromethane at 10°C
was slowly added dropwise 2.82 g (30 mmol) of phenol
in 10 ml of CH2Cl2, the mixture was boiled for 2 h and
afterwards it was poured into water with ice acidified with
HCl (pH 3). The organic layer was separated, washed with
a solution of sodium carbonate, with water till neutral
washings, and dried with CaCl2. The solvent was distilled
off, to the residue 50 ml of hexane was added, and the
mixture was stirred for 10 min at 50°C, the insoluble
solid product was filtered off while hot, washed with hot
hexane, and dried in a vacuum. We obtained 0.64 g of
1-(4-hydroxyphenyl)-3,4,4-trichloro-3-buten-1-one (II).
Yield 12%, mp 157–159°C. IR spectrum, ν, cm–1: 3275
(OH), 1657 (C=O), 1605, 1572, 1515 (C=C), 838, 761
The compounds obtained are interesting for biotest-
ing for the sybstituted thienylpyrazoles possess high
antiphlogistic, analgesic, and antimicrobial activity [7].
EXPERIMENTAL
IR spectra were recorded on a Fourier spectrophotom-
eter Nikolet Protégé-460 from pellets with KBr. 1H and
13C NMR spectra were registered on a spectrometer
Avance-500 in CDCl3 (I, IV–VII), (CD3)2CO (II, VIII–
X), and (CD3)2SO (XIa, XIb, XIIa, XIIb, XIIIa, XIVa).
1
(C–Cl). H NMR spectrum, δ, ppm: 4.41 s (2H, CH2),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 9 2010

POTKIN et al.
1310
6.95 d (2Harom, 3J 9 Hz), 7.94 d (2Harom, 3J 9 Hz), 9.38 s
(1H, OH). 13C NMR spectrum, δ, ppm: 45.74 (CH2),
115.55 (2CHarom), 130.95 (2CHarom); 119.86, 127.58,
128.29, 162.62 (4Cquaternal); 190.38 (C=O). Found, %:
C 45.40; H 2.46; Cl 39.95. [M]+ 264 (35Cl). C10H7Cl3O2.
Calculated, %: C 45.23; H 2.66; Cl 40.06. M 265.52.
was added, and the mixture was left overnight at 0°C.
The separated precipitate was filtered off, washed with
hexane, and dried in a vacuum.
4,4-Dichloro-3-piperidino-1-(thien-2-yl)-2-buten-
1-one (V). Yield 80%, mp 83–85°C. IR spectrum, ν,
cm–1: 1541 (C=O), 1593, 1517 (C=C), 868, 838 (C–
1
Cl). H NMR spectrum, δ, ppm: 1.71 m (6H, 3CH2C),
The filtrate was evaporated to 10 ml and kept for 20 h
at 0°C. The separated precipitate was filtered off, washed
with cold hexane, and dried in a vacuum. We obtained
2.55 g of phenyl 3,4,4-trichloro-3-butenoate (IV). Yield
48%, mp 42–43°C. IR spectrum, ν, cm–1: 1763 (C=O),
3.60 m (4H, 2CH2N), 5.67 s (1H, =CH), 7.04 d.d
3
(1Hthiophene), 7.47 d (1Hthiophene, J 5 Hz), 7.57 d
3
(1Hthiophene, J 4 Hz), 9.01 s (1H, CHCl2). 13C NMR
spectrum, δ, ppm: 24.07 (CH2), 25.47 (2CH2), 49.84
(2CH2N), 63.01 (CHCl2), 92.24 (=CH), 127.99, 129.06,
131.72 (3CHthiophene), 148.50, 157.90 (2Cquaternal), 180.82
(C=O). Found, %: C 51.44; H 4.78; Cl 23.54; N 4.68;
S 10.69. C13H15Cl2NOS. Calculated, %: C 51.32; H 4.97;
Cl 23.31; N 4.60; S 10.54.
1
1613, 1592, 1493 (C=C), 818, 765 (C–Cl). H NMR
spectrum, δ, ppm: 3.89 s (2H, CH2), 7.30 m (5H, C6H5).
Found, %: C 45.52; H 2.77; Cl 40.22. [M]+ 264 (35Cl).
C10H7Cl3O2. Calculated, %: C 45.23; H 2.66; Cl 40.06.
M 265.52
4,4-Dichloro-3-morpholino-1-(thien-2-yl)-2-buten-
1-one (VI). Yield 86%, mp 113–115°C (Cdecomp). IR
spectrum, ν, cm–1: 1550 (C=O), 1597, 1518 (C=C), 850,
805 (C–Cl). 1H NMR spectrum, δ, ppm: 3.59 m (4H,
2CH2N), 3.81 m (4H, 2CH2O), 5.69 s (1H, =CH),
7.05 d.d (1Hthiophene), 7.51 d (1Hthiophene , 3J 5 Hz), 7.58 d
b. To a dispersion of 10.0 g (75 mmol) of AlCl3 in
30 ml of dry chlorobenzene at stirring was added in
there portions 2.82 g (30 mmol) of phenol, then was
added dropwise 6.24 g (30 mmol) of compound III. The
mixture was stirred at 50°C for 2 h and poured into cold
water acidified with HCl (pH 3), the organic layer was
separated and dried with CaCl2. The reaction product was
precipitated with chloroform, dried in a vacuum, and puri-
fied by recrystallization from a mixture acetone–hexane,
5 : 1. We obtained 3.51 g of compound II. Yield 44%,
mp 158–159°C.
3
(1Hthiophene, J 4 Hz), 8.90 s (1H, CHCl2). 13C NMR
spectrum, δ, ppm: 48.53 (2CH2N), 62.74 (CHCl2),
66.09 (2CH2O), 93.97 (=CH); 128.13, 129.70, 132.46
(3CHthiophene); 147.89, 157.75 (2Cquaternal), 181.08 (C=O).
Found, %: C 47.27; H 4.42; Cl 23.34; N 4.63; S 10.62.
C12H13Cl2NO2S. Calculated, %: C 47.07; H 4.28;
Cl 23.16; N 4.57; S 10.47.
Rearrangement of ester IV into ketone II. To
a solution of 2.66 g (10 mmol) of compound IV in 5 ml
of anhydrous nitrobenzene was added in three portions
1.33 g (10 mmol) ofAlCl3, and the mixture was stirred at
40°C for 1 h. On cooling the mixture was poured into cold
water acidified with HCl (pH 3) and extracted with 50 ml
of chloroform. The extract was washed with a solution of
sodium carbonate ans with water till neutral washings,
and then dried with CaCl2. The solvent was completely
evaporated, to the residue was added 40 ml of hexane,
the mixture was stirred for 30 min, the insoluble product
was filtered off, washed with hot hexane, and dried in
a vacuum. We obtained 1.12 g (42%) of compound II.
4,4-Dichloro-3-(2-hydroxyethylamino)-1-(thien-
2-yl)-2-buten-1-one (VII). Yield 48%, mp 77–79°C
(Cdecomp). IR spectrum, ν, cm–1: 3386 (OH), 3300 (NH),
1610 (C=O), 1556, 1522 (C=C), 773, 732 (C–Cl).
1H NMR spectrum, δ, ppm: 3.08 br.s (1H, OH), 3.74 t
(2H, CH2N, 3J 5 Hz), 3.87 t (2H, CH2O, 3J 5 Hz), 5.96 s
(1H, =CH), 6.35 s (1H, CHCl2), 7.07 d.d (1Hthiophene),
7.49 d (1Hthiophene, 3J 5 Hz), 7.59 d (1Hthiophene, 3J 4 Hz),
10.82 br.s (1H, NH). 13C NMR spectrum, δ, ppm: 45.61
(CH2N), 61.62 (CH2O), 66.87 (CHCl2), 89.82 (=CH);
128.13, 128.94, 131.48 (3CHthiophene), 146.28, 159.53
(2Cquaternal), 183.30 (C=O). Found, %: C 42.90; H 4.12;
Cl 25.57; N 5.15; S 11.63. C10H11Cl2NO2S. Calculated,
%: C 42.87; H 3.96; Cl 25.31; N 5.00; S 11.44.
3-Amino-4,4-dichloro-1-(thien-2-yl)-2-buten-
1-ones V–VII. To a solution of 1.28 g (10 mmol) of
1-(thien-2-yl)-3,4,4-trichloro-3-buten-1-one (I) in 30
ml of ethyl ether at 15°C was added dropwise 21 mmol
of an appropriate amine in 20 ml of ether, the mixture
was heated to boiling and stirred for 4 h. The formed
precipitate of the amine hydrochloride was filtered off,
the filtrate was evaporated to 10 ml, 50 ml of hexane
3-Amino-1-(4-hydroxyphenyl)-4,4-dichloro-2-
buten-1-ones VIII–X. To a mixture of 2.56 g (10 mmol)
of 1-(4-hydroxyphenyl)-3,4,4-trichloro-3-buten-1-one
(II) in 40 ml of ethyl ether at 15°C was added dropwise
21 mmol of an appropriate amine in 20 ml of ether, the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 9 2010

SYNTHESIS AND REACTIONS WITH N-NUCLEOPHILES
1311
mixture was heated to boiling and stirred for 4 h. The
precipitate was filtered off, washed with ether, with water,
and dried in a vacuum.
obtained was added 30 ml of dichloromethane, and the
mixture was stirred for 1 h. The insoluble residue that
was semicarbazone XIa or XIIa was filtered off, washed
with dichloromethane, and dried in a vacuum. The filtrate
was evaporated by half, the reaction product XIb or XIIb
was precipitated with hexane, filtered off, and dried in
a vacuum.
4,4-Dichloro-3-piperidino-1-(4-hydroxy-phenyl)-
2-buten-1-one (VIII). Yield 79%, mp 142–144°C (de-
comp.). IR spectrum, ν, cm–1: 3250 (OH), 1572 (C=O),
1528, 1507 (C=C), 886, 848 (C–Cl). 1H NMR spectrum,
δ, ppm: 1.71 m (6H, 3CH2C), 3.68 m (4H, 2CH2N), 5.96 s
Semicarbazone of 1-(thien-2-yl)-3,4,4-trichloro-
3-buten-1-one (XIa). Yield 29%, mp 153–154°C. IR
spectrum, ν, cm–1: 3402 (NH), 1692 (C=O), 1589 (C=N),
(1H, =CH), 6.88 d (2Harom, 3J 9 Hz), 7.87 d (2Harom
,
3J 9 Hz), 9.01 s (1H, OH), 9.26 s (1H, CHCl2). 13C NMR
spectrum, δ, ppm: 25.15 (CH2), 26.56 (2CH2), 50.65
(2CH2N), 64.53 (CHCl2), 93.92 (=CH), 116.16 (2CHarom),
131.28 (2CHarom), 134.24, 158.14, 162.14 (3Cquaternal),
188.22 (C=O). Found, %: C 57.49; H 5.83; Cl 22.74;
N 4.56. C15H17Cl2NO2. Calculated, %: C 57.34; H 5.45;
Cl 22.57; N 4.46.
1
1600, 1562, 1520 (C=C), 802, 763 (C–Cl). H NMR
spectrum, δ, ppm: 4.30 s (2H, CH2), 6.2 br.s (2H, NH2),
7.10 d.d (1Hthiophene), 7.43 d (1Hthiophene, 3J 5 Hz), 7.96 d
3
(1Hthiophene, J 4 Hz), 9.4 br.s (1H, NH). Found, %:
C 34.69; H 2.38; Cl 34.21; N 13.40, S 10.40. C9H8Cl-
3N3OS. CычandCлe-HO, %: C 34.58; H 2.58; Cl 34.02;
N 13.44; S 10.26.
4,4-Dichloro-3-morpholino-1-(4-hydroxy-phenyl)-
2-buten-1-one (IX). Yield 85%, mp 152–154°C (de-
comp.). IR spectrum, ν, cm–1: 3298 (OH), 1545 (C=O),
1589, 1513 (C=C), 882, 864 (C–Cl). 1H NMR spectrum,
δ, ppm: 3.61 m (4H, 2CH2N), 3.78 m (4H, 2CH2O), 5.99 s
Semicarbazone of 1-(thien-2-yl)-3,4,4-trichloro-2-
buten-1-one (XIb). Yield 8%, mp 246–247°C (decomp.).
IR spectrum, ν, cm–1: 3410, 3204 (NH), 1721 (C=O),
1661 (C=N), 1601, 1513, 1502 (C=C), 800, 761 (C–Cl).
1H NMR spectrum, δ, ppm: 6.60 br.s (2H, NH2), 6.86
(1H, =CH), 6.83 d (2Harom, 3J 9 Hz), 7.84 d (2Harom
,
s (1H, =CH), 7.06 d.d (1Hthiophene), 7.42 d (1Hthiophene
,
3J 9 Hz), 9.10 s (1H, CHCl2). 13C NMR spectrum, δ, ppm:
48.95 (2CH2N), 63.50 (CHCl2), 66.27 (2CH2O), 94.77
(=CH), 115.52 (2CHarom), 130.70 (2CHarom), 134.76,
157.24, 161.88 (3Cquaternal), 187.70 (C=O). Found, %:
C 53.29; H 4.98; Cl 22.81; N 4.67. C14H15Cl2NO3. Cal-
culated, %: C 53.18; H 4.78; Cl 22.43; N 4.43.
3J 5 Hz), 7.52 d (1Hthiophene, 3J 4 Hz), 7.79 s (1H, CHCl2),
10.35 br.s (1H, NH). Found, %: C 34.22; H 2.79; Cl 33.84;
N 13.26; S 10.08. C9H8Cl3N3OS. Calculated, %: C 34.58;
H 2.58; Cl 34.02; N 13.44; S 10.26.
Semicarbazone of 1-(4-hydroxyphenyl)-3,4,4-
trichloro-3-buten-1-one (XIIa). Yield 34%, mp 130–
132°C. IR spectrum, ν, cm–1: 3407 (OH), 3323, 3203
(NH), 1682 (C=O), 1606 (C=N), 1590, 1563, 1514 (C=C).
1H NMR spectrum, δ, ppm: 4.40 s (2H, CH2), 6.44 br.s
(2H, NH2), 6.80 d (2Harom, 3J 9 Hz), 7.54 d (2Harom, 3J 9
Hz), 9.40 s (1H, OH), 10.3 br.s (1H, NH). Found, %: C
40.80; H 3.30; Cl 32.55; N 13.16. C11H10Cl3N3O2. Cal-
culated, %: C 40.96; H 3.13; Cl 32.97; N 13.03.
4,4-Dichloro-3-(2-hydroxyethylamino)-1-(4-
hydroxyphenyl)-2-buten-1-one (X). Yield 20%, mp
107–110°C. IR spectrum, ν, cm–1: 3264 (OH), 3200
(NH), 1592 (C=O), 1537, 1499 (C=C), 786, 778 (C–
1
Cl). H NMR spectrum, δ, ppm: 3.77 t (2H, CH2N,
3
3J 5 Hz), 3.81 t (2H, CH2O, J 5 Hz), 6.25 s (1H,
=CH), 6.89 d (2Harom, 3J 9 Hz), 6.96 s (1H, CHCl2),
3
7.84 d (2Harom, J 9 Hz), 8.96 s (1H, OH), 11.08 (1H,
NH). 13C NMR spectrum, δ, ppm: 46.05 (CH2N), 61.45
(CH2O), 68.14 (CHCl2), 88.92 (=CH), 115.56 (2CHarom),
129.71 (2CHarom), 132.03, 159.34, 161.14 (3Cquaternal),
188.95 (C=O). Found, %: C 49.80; H 4.35; Cl 24.17;
N 4.91. C12H13Cl2NO3. Calculated, %: C 49.68; H 4.52;
Cl 24.44; N 4.83.
Semicarbazone of 1-(4-hydroxyphenyl)-3,4,4-
trichloro-2-buten-1-one (XIIb). Yield 14%, mp 230–
232°C (decomp.). IR spectrum, ν, cm–1: 3403 (OH), 3302,
3203 (NH), 1694 (C=O), 1661 (C=N), 1620, 1604, 1509
(C=C), 841, 762 (C–Cl). 1H NMR spectrum, δ, ppm:
6.20 br.s (2H, NH2), 6.43 s (1H, =CH), 6.81 d (2Harom
,
3J 9 Hz), 7.55 d (2Harom, 3J 9 Hz), 7.83 s (1H, CHCl2),
9.40 s (1H, OH), 11.20 br.s (1H, NH). Found, %: C 41.25;
H 3.01; Cl 33.30; N 12.94. C11H10Cl3N3O2. Calculated,
%: C 40.96; H 3.13; Cl 32.97; N 13.03.
Reaction of ketones I, II with semicarbazide. Amix-
ture of 5 mmol of an appropriate ketone, 7.5 mmol of
semicarbazide hydrochloride, and 7.5 mmol of sodium
acetate in 30 ml of methanol was boiled for 3 h, afterwards
it was poured in water, the precipitate was filtered off,
washed with water, and dried over P2O5.To the product
N,N'-Bis(5-thien-2-yl-1H-pyrazol-3-ylmethylene)-
hydrazine (XIIIa). To a solution of 1.28 g (5 mmol)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 9 2010

POTKIN et al.
1312
2. Kaberdin, R.V., Potkin, V.I., and Petkevich, S.K., Vestsi
Akad Nauk, Ser. Khim., 2006, 2, 99.
3. Potkin, V.I., Kaberdin, R.V., Petkevich, S.K., and Kur-
man, P.V., Zh. Org. Khim., 2002, 38, 1150.
4. Potkin, V.I., Petkevich, S.K., and Kurman, P.V., Zh. Org.
Khim., 2007, 43, 1626.
5. Petkevich, S.K., Potkin, V.I., and Kaberdin, R.V., Zh. Org.
Khim., 2006, 42, 1496.
6. Mel’nikov, N.N., Pestitsidy. Khimiya, tekhnologiya i
primenenie (Pesticides: Chemistry, Technology, and Ap-
plication), Moscow: Khimiya, 1987.
7. Hafez, H.N. and El-Gazzar, A.B.A., Bioorg. Med. Chem.
Lett., 2008, 18, 5222.
8. Mashkovskii, M.D., Lekarstvennye sredstva (Drugs), Mos-
cow: Novaya Volna, 2001, vol. 2, p. 386.
9. Soldatenkov, A.T., Kolyadina, N.M., and Shendrik, I.V.,
Osnovy organicheskoi khimii lekarstvennykh veshchestv
(Fundamentals of Organic Chemistry of Medicines), Mos-
cow: Mir, 2003, p. 62.
of 1-(thien-2-yl)-3,4,4-trichloro-3-buten-1-one (I) in
20 ml of methanol at 25°C was added dropwise 1.1 g
(22 mmol) of hydrazine hydrate in 15 ml of methanol,
the mixture was stirred for 3 h and poured into water.
The separated precipitate was filtered off, washed with
CH2Cl2, and dried in a vacuum. Yield 1.55 g (88%), mp
246–248°C (decomp.). IR spectrum, ν, cm–1: 3200 (N–H),
1639 (C=N), 1597, 1518 (C=C). 1H NMR spectrum, δ,
ppm: 7.05 s (CHpyrazol), 7.11 d.d (=CHthiophene), 7.50 d
(=CHthiophene, J 5 Hz), 7.53 d (=CHthiophene, J 4 Hz),
8.60 s (=CHaliph), 12.50 br.s (NH). 13C NMR spectrum,
δ, ppm: 103.52 (CHpyrazol), 126.41, 128.32, 129.62
(CHthiophene), 132.50, 136.06, 147.07 (Cquaternal), 153.19
(CHaliph). Found, %: C 54.22; H 3.81; N 23.74; S 18.26.
C16H12N6S2. Calculated, %: C 54.53; H 3.43; N 23.85.
S 18.20.
3
3
N,N'-Bis[5-(4-hydroxyphenyl)-1H-pyrazol-3-
ylmethylene]hydrazine (XIV) was similarly obtained
from 1-(4-hydroxyphenyl)-3,4,4-trichloro-3-buten-1-one
(II) and hydrazine. Yield 90%, mp 240–242°C (decomp.).
IR spectrum, ν, cm–1: 3252 (N–H), 1614 (C=N), 1606,
10. Petkevich, S.K., Dikusar, E.A., Potkin, V.I., Kaberdin, R.V.,
Moiseichuk, K.L., Yuvchenko,A.P., and Kurman, P.V., Zh.
Org. Khim., 2004, vol. 74, p. 642.
11. Takhistov, V.V., Prakticheskaya mass-spektrometriya or-
ganicheskikh soedinenii (Practical Spectrometry of Organic
Compounds), Leningrad: Izd. Leningrad. Gos. Univ., 1977,
p. 265.
1
1590, 1509 (C=C). H NMR spectrum, δ, ppm: 6.82 d
(CHarom, 3J 9 Hz), 7.00 s (=CHpyrazol), 7.62 d (CHarom
,
3J 9 Hz), 8.57 (=CHaliph), 9.94 br.s (OH), 13.26 (NH).
13C NMR spectrum, δ, ppm: 101.15 (CHpyrazol), 116.29
(2CHarom), 127.45 (2CHarom), 121.34, 146.40, 146.54,
158.32 (4Cquaternal), 155.21 (CHaliph). Found, %: C 64.37;
H 4.58; N 22.73. C20H16N6O2. Calculated, %: C 64.51;
H 4.33; N 22.57.
12. Takhistov, V.V., Rodin, A.A., and Maksimova, B.N., Usp.
Khim., 1991, vol. 60, p. 2143.
13. Vatsuro, K.V. and Mishchenko, G.L., Imennye reaktsii
v organicheskoi khimii (Personal Reactions in Organic
Chemistry), Moscow: Khimiya, 1976, p. 431.
14. Roedig,A. and Ritschel, W., Lieb. Ann., 1983, vol. 1, p. 13.
15. Roedig, A. and Ritschel, W., Chem. Ber., 1983, vol. 116,
p. 1595.
REFERENCES
16. Bellamy, L.J., The Infra-red Spectra of Complex Molecules,
London: Methuen, 1958.
1. Pohland,A.E. and Benson, W.R., Chem. Rev., 1966, vol. 66,
p. 161.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 9 2010