Unusual Michael reaction of 3-(4-chlorophenyl)-1-phenylprop-2-en-1-one with 3-amino-N-phenyl-3-thioxopropanamide

Article abstract of DOI:10.1134/S1070428012070111

3-(4-Chlorophenyl)-1-phenylprop-2-en-1-one reacted with 3-amino-N-phenyl-3-thioxopropanamide under basic conditions in ethanol to give a mixture of 3-(4-chlorophenyl)-2-cyano-5-oxo-N,5-diphenylpentanamide and 3-(4-chlorophenyl)-1,5-diphenylpentane-1,5-dione. The structure of the former was determined by X-ray analysis. The reaction of the same compounds in DMSO in the presence of sodium hydroxide produced 4-(4-chlorophenyl)-N,6-diphenyl-2- thioxo-1,2,3,4-tetrahydropyridine-3-carboxamide.

Full text of DOI:10.1134/S1070428012070111

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 7, pp. 953–956. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © V.D. Dyachenko, D.A. Krasnikov, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 7, pp. 958–961.
Unusual Michael Reaction of 3-(4-Chlorophenyl)-1-phenylprop-
2-en-1-one with 3-Amino-N-phenyl-3-thioxopropanamide
V. D. Dyachenko and D. A. Krasnikov
Taras Shevchenko Lugansk National University, ul. Oboronnaya 2, Lugansk, 91011 Ukraine
e-mail: chem@luguniv.edu.ua
Received October 31, 2011
Abstract—3-(4-Chlorophenyl)-1-phenylprop-2-en-1-one reacted with 3-amino-N-phenyl-3-thioxopropanamide
under basic conditions in ethanol to give a mixture of 3-(4-chlorophenyl)-2-cyano-5-oxo-N,5-diphenyl-
pentanamide and 3-(4-chlorophenyl)-1,5-diphenylpentane-1,5-dione. The structure of the former was deter-
mined by X-ray analysis. The reaction of the same compounds in DMSO in the presence of sodium hydroxide
produced 4-(4-chlorophenyl)-N,6-diphenyl-2-thioxo-1,2,3,4-tetrahydropyridine-3-carboxamide.
DOI: 10.1134/S1070428012070111
The phenacyl group on C1 occupies +sc-position
We previously reported on the synthesis of
with respect to the chlorophenyl ring plane [the torsion
angle C2C1C19C24 is 40.9(3)°], despite repulsion be-
tween the methylene group and aromatic ring (short-
ened intramolecular contacts H2A · · · C24 2.86 and
H24···C2 2.72 Å were detected, the sum of the corre-
sponding van der Waals radii being 2.87 Å [3]). As
a result, the C19C1C2 bond angle at the tetrahedral C2
carbon atom increases to 113.6(2)°. The benzoyl group
has antiperiplanar orientation with respect to the
C19–C1 bond [the torsion angle C19C1C2C3 is 156.8(2)°]
and is turned in such a way that orientation of the
carbonyl group is intermediate between sp and –sc
with respect to the C1–C2 bond [the torsion angle
C1C2C3O1 is 29.2(3)°]. Appreciable repulsion between
the methylene group and benzoyl fragment [shortened
intramolecular contacts H2B···C5 2.70 (2.87), H2B···H5
2.18 (2.34), H5···C2 2.67 (2.87) Å] makes the carbonyl
noncoplanar to the aromatic ring [torsion angle
O1C3C4C9 10.0(4)°]. The phenylcarbamoyl(cyano)-
methyl fragment is oriented almost orthogonally to the
plane of the chlorophenyl ring [torsion angle
C10C1C19C24 82.1(3)°]. The cyano group appears in
–sc-conformation with respect to the C19–C1 bond
[torsion angle C19C1C10C11 47.8(3)°]. The phenylcar-
bamoyl group occupies ap-position relative to the
C19–C1 bond, and the carbamoyl group is almost ortho-
gonal to the C1–C10 bond [torsion angles C19C1C10C12
170.9(2)° and C1C10C12O2 75.7(3)°], so that shortened
contacts H2B ···H10 2.32 (2.34) and H10 ···H(N1) 2.11
(2.34) Å are observed. The N-phenyl ring is noncopla-
nar to the carbamoyl group [torsion angle C12N1C13C18
N-phenyl-2-thioxo-1,2,3,4-tetrahydropyridine-3-car-
boxamides from chalcones and 3-amino-N-phenyl-3-
thioxopropanamide (II) [1]. In the present communi-
cation we describe the reaction of 3-(4-chlorophenyl)-
1-phenylprop-2-en-1-one (I) with compound II. The
reaction in ethanol in the presence of sodium hydrox-
ide did not produce the expected product, 4-(4-chloro-
phenyl)-N,6-diphenyl-2-thioxo-1,2,3,4-tetrahydropyri-
dine-3-carboxamide (III) [1], but afforded 3-(4-chloro-
phenyl)-2-cyano-5-oxo-N,5-diphenyl-pentanamide
(IV) (presumably as a result of elimination of hydro-
gen sulfide from hypothetical primary Michael adduct
A) and 3-(4-chlorophenyl)-1,5-diphenylpentane-1,5-di-
one (V) (Scheme 1). The latter is likely to be formed
via exchange of methylene components, which is
known for analogous reactions (see also [2]).
In the reaction of chalcone I with amide II in
DMSO in the presence of sodium hydroxide at room
temperature we isolated only expected 4-(4-chloro-
phenyl)-N,6-diphenyl-2-thioxo-1,2,3,4-tetrahydropyr-
idine-3-carboxamide (III). Addition of methyl iodide
to the reaction mixture, other conditions being equal,
resulted in the formation of substituted pyridine VI.
1
In the H NMR spectrum of IV all proton signals
were doubled. No appreciable change of the spectral
pattern was observed on heating to 70°C (DMSO-d6);
only the amide proton signal was displaced upfield by
0.3 ppm. These findings indicated free rotation of the
amide fragment. The structure of IV was determined
by X-ray analysis (see figure).
953

DYACHENKO, KRASNIKOV
954
Scheme 1.
O
S
Ph
O
N
H
NH2
O
S
O
OH–
+
Ph
Ph
H2N
N
H
Cl
Cl
Ph
I
II
A
O
S
Ph
N
H
NH
DMSO
–H2O
Ph
Cl
III
O
O
NC
Ph
N
H
Ph
EtOH
–H2S
+
Cl
O
IV
Ph
Cl
O
Ph
V
O
SMe
Ph
N
H
N
DMSO, MeI
Ph
Cl
VI
32.1(4)°], presumably due to repulsion between the
carbonyl group and aromatic ring (shortened contact
H18···C12 2.79 Å). The presence of fairly bulky substit-
uents at one carbon atom is likely to be responsible for
extension of the C1–C10 bond to 1.565(3) Å against
standard value 1.542 Å [4].
in the presence of morpholine. However, the authors
1
did not note doubling of signals in the H NMR spec-
trum of IV recorded in CDCl3, whereas proton chem-
ical shifts of homologous compound in DMSO-d6
coincided with those of one set of signals found by us
for compound IV. Taking into account that molecule
IV possesses two neighboring asymmetric carbon
atoms, it is reasonable to presume that two sets of
signals belong to different diastereoisomers present in
equal amounts. They may be represented as two
enantiomer couples IVa and IVb in the most favorable
conformations. Protons in IVa and IVb are charac-
terized by different environments which exert different
shielding effects. The X-ray analysis was performed
for a single crystal of only one diastereoisomer IVb.
Molecules IV in crystal are linked through inter-
molecular hydrogen bonds N1–H(N1) ···O2′ [(x, 0.5 – y,
z – 0.5), H · · · O 2. 04 Å, ∠ NHO 165°] and
C10–H10 ···O2′ [(x, 0.5 – y, z – 0.5), H···O 2.37 Å,
∠CHO 152°] to form infinite chains along the [001]
crystallographic axis. Weak hydrogen bonds C–H···π
[C20–H20 ···C23′ (x, 0.5 – y, z + 0.5), H···π 2.85 Å,
∠CHπ 132°] were also found inside the chains. Neigh-
boring chains are linked through hydrogen bond
C16–H16···Cl1′ (1 + x, 0.5 – y, 0.5 + z), H···Cl 2.80 Å,
∠CHCl 144°. Hydrogen bonding N–H···O also leads
to extension of the O–C12 bond to 1.237(3) Å (against
standard value 1.210 Å).
EXPERIMENTAL
1
The H NMR spectra were recorded on a Bruker
Avance II spectrometer at 400 MHz from solutions in
DMSO-d6 using tetramethylsilane as internal refer-
ence. The mass spectra (electron impact, 70 eV) were
Compound IV was also synthesized previously by
Girgis et al. [5] from chalcone I and cyanoacetanilide
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 7 2012

UNUSUAL MICHAEL REACTION OF 3-(4-CHLOROPHENYL)-1-PHENYLPROP-2-EN-1-ONE
955
Cl
Cl
Cl
Cl
O
O
H
H
H
H
CN
NC
H
PhHN
NHPh
H
H
H
Ph
IVb
O
O
Ph
Ph
IVa
O
O
Ph
CN
CN
O
NHPh
PhHN
O
obtained on a Hewlett–Packard 5890/5972 GC–MS
system using an HP-5MS column; samples were
injected in methylene chloride. The melting points
were determined on a Kofler hot stage. The progress of
reactions and the purity of products were monitored by
TLC on Silufol UV-254 plates using acetone–hexane
(3:5) as eluent; spots were visualized by treatment
with iodine vapor or by UV irradiation.
water, and kept for 16 h on cooling. The precipitate
was filtered off, washed with ethanol, and recrystal-
lized from glacial acetic acid. Yield 1.49 g (71%),
1
mp 198–200°C. H NMR spectrum, δ, ppm: 4.11–
4.15 m (2H, 3-H, 4-H), 5.84 d (1H, 5-H, J = 3.8 Hz),
7.02 t (1H, Harom, J = 7.4 Hz), 7.25–7.43 m (9H, Harom),
7.51 d (2H, Harom, J = 7.9 Hz), 7.55 d (2H, Harom, J =
7.9 Hz), 10.15 s (1H, CONH), 11.93 s (1H, N1H).
Mass spectrum, m/z (Irel, %): 383 (3) [M – Cl]+, 264
(100), 230 (20), 104 (10), 77 (45). Found, %: C 68.77;
H 4.49; N 6.88. C24H19ClN2OS. Calculated, %:
C 68.81; H 4.57; N 6.69. M 418.95.
3-(4-Chlorophenyl)-2-cyano-5-oxo-N,5-diphenyl-
pentanamide (IV). Sodium hydroxide, 0.20 g
(5 mmol), was dissolved in 20 ml of ethanol, 0.97 g
(5 mmol) of compound II and 1.21 g (5 mmol) of
X-Ray duffraction data for compound IV. Mono-
clinic crystals; C24H19ClN2O2, Mr 402.86. Unit cell
parameters (at –173°C): a = 15.761(1), b = 13.907(1),
c = 9.001(1) Å; β = 92.28(1)°; V = 1971.4(3) Å3; Z = 4;
space group P21/c; dcalc = 1.357 g/cm3; μ(MoKα) =
0.217 mm–1; F(000) = 840. The unit cell parameters
and intensities of 11247 reflections (3462 independent
reflections, Rint = 0.106) were measured on
an Xcalibur-3 diffractometer (MoKα irradiation, CCD
detector, graphite monochromator, ω-scanning, 2θmax
=
C6
C5
C4
50°). The structure was solved by the direct method
using SHELXTL software package [6]. The positions
of hydrogen atoms were determined by difference syn-
thesis of electron density and were refined according to
the riding model (Uiso = 1.2Ueq for a non-hydrogen
atom linked to a given hydrogen atom). The NH hy-
drogen atom involved in N–H···O hydrogen bond was
refined in isotropic approximation. The structure was
refined against F2 by the full-matrix least-squares
procedure in anisotropic approximation for non-hydro-
gen atoms; wR2 = 0.064 for 3400 reflections; R1 =
0.045 for 1453 reflections with F > 4σ(F); goodness of
fit 0.667.
C7
C8
C23
C2
C3
Cl1
C9
C22
C24
C1
O1
C10
C14
C19
C20
C21
C15
C16
C13
C12
N1
C11
N2
O3
C17
C18
Structure of the molecule of 3-(4-chlorophenyl)-2-cyano-5-
oxo-N,5-diphenylpentanamide (IV) according to the X-ray
diffraction data. Principal bond lengths and bond angles:
C1–C2 1.522(3), C1–C10 1.565(3), C1–C19 1.517(3), C10–C12
1.547(4), N1–C12 1.346(3), N1–C13 1.419(3), C2–C3 1.520(3),
C3–C4 1.478(3), O1–C3 1.230(3) Å; C12N1C13 126.3(3),
C3C2C1 114.0(2), C19C1C2 113.6(2), C4C3C2 120.9(2),
C19C1C10 109.3(2), C9C4C3 119.4(2), C2C1C10 109.8(2),
C12C10C1 112.5(2), O2C12N1 124.8(3), O2C12C10 120.6(2),
N1C12C10 114.5(2), C14C13N1 118.4(3)°.
4-(4-Chlorophenyl)-N,6-diphenyl-2-thioxo-
1,2,3,4-tetrahydropyridine-3-carboxamide (III).
Sodium hydroxide, 0.20 g (5 mmol), was dissolved in
20 ml of DMSO, 0.97 g (5 mmol) of 3-amino-N-
phenyl-3-thioxopropanamide (II) and 1.21 g (5 mmol)
of chalcone I were added, and the mixture was stirred
for 4 h at room temperature, diluted with 20 ml of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 7 2012

DYACHENKO, KRASNIKOV
956
chalcone I were added, and the mixture was stirred at
50°C until it turned homogeneous, stirred for 2 h at
room temperature, and kept for 16 h at 7°C. The
precipitate was filtered off and recrystallized from
methanol. Yield 0.93 g (46%), mp 161–163°C. 1H NMR
spectrum, δ, ppm: first set of signals: 3.45 d.d (1H,
CH2CH, J = 4.0, 17.6 Hz), 3.81 d.d (1H, CH2CH, J =
9.8, 17.6 Hz), 4.04–4.13 m (1H, CH2CH), 4.36 d (1H,
CH2CHCH, J = 8.5 Hz), 7.07–7.12 m (1H, Harom),
7.28–7.51 m (10H, Harom), 7.59–7.64 m (1H, Harom),
7.93 d (2H, Harom, J = 7.3 Hz), 10.40 s (1H, CONH);
seond set of signals: 3.62 d.d (1H, CH2CH, J = 4.0,
17.6 Hz), 3.87 d.d (1H, CH2CH, J = 9.6, 17.6 Hz),
4.04–4.13 m (1H, CH2CH), 4.25 d (1H, CH2CHCH,
J = 7.8 Hz), 7.07–7.12 m (1H, Harom), 7.28–7.51 m
(10H, Harom), 7.59–7.64 m (1H, Harom), 7.88 d (2H,
4-(4-Chlorophenyl)-2-methylsulfanyl-N,6-di-
phenylpyridine-3-carboxamide (VI). Sodium hy-
droxide, 0.20 g (5 mmol), was dissolved in 20 ml of
DMSO, 0.97 g (5 mmol) of 3-amino-N-phenyl-3-
thioxopropanamide (II) and 1.21 g (5 mmol) of chal-
cone I were added, the mixture was stirred at room
temperature until it turned homogeneous, 0.31 ml
(5 mmol) of methyl iodide was added, and the mixture
was left to stand for 24 h. The mixture was then diluted
with an equal volume of water and was kept for 24 h
on cooling. The precipitate was filtered off and recrys-
tallized from glacial acetic acid. Yield 0.2 g (9%),
1
mp 197–199°C. H NMR spectrum, δ, ppm: 3.34 s
(3H, CH3), 7.11 t (1H, Harom, J = 7.4 Hz), 7.29–7.63 m
(11H, Harom), 7.90 s (1H, 5-H), 8.13 d (2H, Harom, J =
7.3 Hz), 10.70 s (1H, CONH). Mass spectrum: m/z 429
(Irel 100%) [M – 1]+. Found, %: C 69.55; H 4.46;
N 6.57. C25H19ClN2OS. Calculated, %: C 69.68;
H 4.44; N 6.50. M 430.96.
Harom, J = 7.3 Hz), 10.49 s (1H, CONH). Mass spec-
trum: m/z 401 (Irel 100%) [M – 1]+. Found, %: C 71.61;
H 4.79; N 7.19. C24H19ClN2O2. Calculated, %:
C 71.55; H 4.75; N 6.95. M 402.88.
REFERENCES
3-(4-Chlorophenyl)-1,5-diphenylpentane-1,5-di-
one (V). The filtrate obtained after separation of com-
pound IV was diluted with an equal volume of water
and was left to stand for 24 h on cooling. The precip-
itate was filtered off and recrystallized from methanol.
Yield 0.2 g (11%), mp 104–106°C. 1H NMR spectrum,
δ, ppm: 3.47 d (4H, CH2, J = 7.1 Hz), 3.86–3.93 m
(1H, CH), 7.27 d (2H, Harom, J = 8.3 Hz), 7.35 d (2H,
Harom, J = 8.3 Hz), 7.49 t (4H, Harom, J = 7.6 Hz), 7.61 t
(2H, Harom, J = 7.3 Hz), 7.93 d (4H, Harom, J = 7.9 Hz).
Mass spectrum: m/z 361 (Irel 100%) [M – 1]+. Found,
%: C 76.26; H 5.06. C23H19ClO2. Calculated, %:
C 76.13; H 5.28. M 362.86.
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