Synthesis of new naphthostyryl derivatives via nucleophilic substitution of methylthio group with C-nucleophiles. Molecular and crystal structure of (Z)-2-{benzo[cd]indol-2(1H)-ylidene}-2-(4-phenythiazol-2-yl)acetonitrile

Article abstract of DOI:10.1134/S1070363214020169

Reactions of 2-(methylthio)benzo[cd]indol-1-inium iodide with C-nucleophiles proceed via substitution of methylthio group to afford new naphthostyryl derivatives. The latter were used in synthesis of the Hantzsch thiazoles. Structure of (Z)-2-{benzo[cd]in

Full text of DOI:10.1134/S1070363214020169

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 2, pp. 259–263. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © V.D. Dyachenko, A.Yu. Kashner, Yu.V. Samusenko, 2014, published in Zhurnal Obshchei Khimii, 2014, Vol. 84, No. 2, pp. 266–
270.
Synthesis of New Naphthostyryl Derivatives via Nucleophilic
Substitution of Methylthio Group with C-Nucleophiles.
Molecular and Crystal Structure of (Z)-2-{Benzo[cd]indol-
2(1Н)-ylidene}-2-(4-phenythiazol-2-yl)acetonitrile
V. D. Dyachenkoa, A. Yu. Kashnera, and Yu. V. Samusenkob
a Shevchenko Lugansk National University, ul. Oboronnaya 2, Lugansk, 91011 Ukraine
e-mail: chem@luguniv.edu.ua
b Korolenko Poltava National Pedagogical University, Poltava, Ukraine
Received March 14, 2013
Abstract―Reactions of 2-(methylthio)benzo[cd]indol-1-inium iodide with C-nucleophiles proceed via sub-
stitution of methylthio group to afford new naphthostyryl derivatives. The latter were used in synthesis of the
Hantzsch thiazoles. Structure of (Z)-2-{benzo[cd]indol-2(1Н)-ylidene}-2-(4-phenylthiazol-2-yl)acetonitrile was
studied by XRD.
DOI: 10.1134/S1070363214020169
Naphthostyryl derivatives (benzo[cd]indoline) are
intermediates in the synthesis of dyes and biologically
active compounds [1]. In particular, highly effective
antineoplastic agents have been found among the
specimens of this class of heterocycles [2].
well as the proton signal of N1H as a broadened singlet
at 11.92–13.54 ppm.
The Hantzsch reaction of III with α-bromoketones
VIa and VIb resulted in the substituted thiazoles VIIa
and VIIb (method a). The latter were readily obtained
by reacting thiazolylacetonitriles VIIIa and VIIIb with
salt I (method b) (see Scheme 1).
Continuing studies of reactions of nucleophilic
substitution in a series of nitrogen-containing hetero-
cycles [3–5], in the present work we investigated the
interaction of 2-(methylthio)benzo[cd]indol-1-inium I
with CH-acids IIa–IId as C-nucleophiles. The reaction
proceeded at reflux of the starting reactants in an-
hydrous ethanol in the presence of an equimolar
amount of triethylamine to give new compounds IIIa–
IIId. Reaction of I with malonodinitrile derivative IV
occurred possibly via an intermediate A formation to
yield new heterocyclic systems, 10-amino-8-imino-
8Н-benzo[cd]pyrido[1,2-a]indol-9,10-dicarbonitrile V.
Characteristic of mass spectra of (Z)-2-{benzo[cd]-
indol-2(1Н)-ylidene}-2-(4-arythiazol-2-yl)acetonitriles
VIIa and VIIb is the presence of molecular ions peaks
of an odd value, confirming an odd number of the
nitrogen atoms in their molecules, and of low-intensity
peaks [M + 2]+ indicating the sulfur atom presence
[10].
An unambiguous assignment to E- or Z-isomer was
not possible to be made on the basis of the spectral
data only. Therefore the structure of 2-{benzo[cd]-
indol-2(1Н)-ylidene}-N-(2-furan-2-ylmethyl)-2-cyano-
acetamide VIIa was studied by XRD analysis (see
figure, Tables 1, 2).
Spectral characteristics and chemical transforma-
tion confirmed the structure of compounds IIIa–IIId
and V. For instance, in their IR spectra characteristic
absorption bands appeared of the stretching vibrations
of the conjugated cyano group (2190–2211 cm–1) and
amide moiety (1668–1691 cm–1). The 1H NMR spectra
contained the signals of the protons of the naphthalene
and amide fragments in their respective regions, as
The phenyl substituent was located in the plane of
the thiazole ring [torsion angle N3C15C17C18 1.8(3)°].
In this position the steric repulsion between the ortho-
hydrogen atoms (short intramolecular contact H22···H16
259

260
DYACHENKO et al.
Scheme 1.
Ar
R
S
N
X
NH
R
HN
X
Ar
O
SMe
CN
I
CN
HN
HN
HN
Br
CN
VIa, VIb
IIa−IId
−HBr, −H2O
method a
−MeSH, −HI
I
IIIa−IIId
VIIa, VIIb
CN
NH2
CN
NC
−MeSH, −HI
method b
I
IV
CN
NC
NH2
CN
NH2
N
C
Ar
N
HN
CN
HN
N
S
CN
VIIIa, VIIIb
A
V
II, III, X = S (а), O (b–d); R = H (а, b), Ph (c), furan-2-ylmethyl (d); VI–VIII, Ar = Ph (а), 2,4,6-(Ме)3С6Н2 (b).
is 2.23 Å while the sum of the van der Waals radii is
2.32 Å [6]) is compensated by the π-conjugation between
the rings, as well as by the attractive contact H18···N3
2.54 Å (sum of the van der Waals radii is 2.66 Å).
There was a small turn around the single С12–С14 bond
[torsion angle C1C12C14N3 6.3(3)°]. Flattened conforma-
tion of the molecule was stabilized by weak hydrogen
bonding N1–H1···N3 (H···N 2.17 Å, N–H···N 125°) [7].
General view of the molecule of VIIa. Thermal ellipsoids of non-hydrogen atoms are shown at the 50% probability.
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SYNTHESIS OF NEW NAPHTHOSTYRYL DERIVATIVES VIA NUCLEOPHILIC SUBSTITUTION
Table 1. Bond lengths in the structure of VIIа Table 2. Bond angles in the structure of VIIа
261
Bond
S1C14
d, Å
Bond
C6C7
C7C8
C8C9
d, Å
Angle
ω, deg
Angle
ω, deg
1.726(2)
1.702(2)
1.366(2)
1.399(3)
1.145(3)
1.316(2)
1.380(3)
1.470(3)
1.371(3)
1.397(3)
1.380(3)
1.399(3)
1.392(3)
1.363(3)
1.418(3)
1.373(4)
1.408(3)
1.410(3)
1.373(3)
1.409(3)
1.426(3)
1.451(3)
1.361(3)
1.473(3)
1.380(3)
1.382(3)
1.379(3)
1.362(3)
1.370(3)
1.369(3)
C16S1C14
C1N1C4
C14N3C15
N1C1C2
N1C1C12
C12C1C2
C3C2C1
C11C2C1
C11C2C3
C2C3C4
C8C3C2
C8C3C4
C3C4N1
C5C4N1
C5C4C3
C4C5C6
C7C6C5
C6C7C8
C3C8C7
C3C8C9
C7C8C9
C10C9C8
89.22(10)
111.57(18)
110.64(18)
106.54(19)
123.86(19)
129.6(2)
105.39(19)
136.4(2)
118.2(2)
110.8(2)
125.7(2)
123.5(2)
105.7(2)
134.0(2)
120.3(2)
117.0(2)
122.9(3)
120.3(3)
116.0(2)
114.8(2)
129.2(3)
120.5(3)
C9C10C11
C2C11C10
C1C12C13
C1C12C14
C13C12C14
N2C13C12
N3C14S1
N3C14C12
C12C14S1
N3C15C17
C16C15N3
C16C15C17
C15C16S1
C18C17C15
C18C17C22
C22C17C15
C19C18C17
C20C19C18
C19C20C21
C22C21C20
C21C22C17
123.2(2)
117.6(2)
119.0(2)
S1C16
N1C1
N1C4
N2C13
N3C14
N3C15
C1C2
C1C12
C2C3
C2C11
C3C4
C3C8
C4C5
C5C6
C9C10
C10C11
C12C13
C12C14
C15C16
C15C17
C17C18
C17C22
C18C19
C19C20
C20C21
C21C22
123.58(19)
117.4(2)
178.4(3)
114.50(16)
123.9(2)
121.63(16)
119.45(19)
114.46(19)
126.1(2)
111.18(17)
121.4(2)
117.2(2)
121.5(2)
121.2(2)
120.6(2)
119.1(2)
120.5(2)
121.6(2)
Among the intermolecular interactions in the
crystal the shortened contacts S1···N2i [i: –x, 1 – y, –z]
3.28 Å and S1···S1i 3.53 Å should noted (sum of the
van der Waals radii are 3.32 and 3.68 Å, respectively),
which can be attributed to the σ-hole interactions.
EXPERIMENTAL
1H NMR spectra were recorded on a Bruker
AVANCE DRX-500 (500.07 MHz) in DMSO-d6
solution, internal reference TMS. Mass spectrum of
IIIa was registered on a Chrommas GC/MS-Hewlett-
Packard 5890/5972 instrument (column HP-5MS,
chemical ionization, 70 eV) in CH2Cl2 solution. Mass
spectra of other compounds were taken on a MKh-
1321 instrument (70 eV) with direct admission of the
sample into the ion source. IR spectra were recorded
on a Perkin-Elmer FIR Spectrum One spectrometer
from KBr pellets. Melting points were measured on a
Koeffler heating block. The reaction progress and
purity of the obtained compounds were monitored by
TLC method [Silufol UV-254 plates, eluent acetone–
hexane (3 : 5), developing with iodine vapor or UV].
Xcalibur 3 (MoKα-irradiation, graphite monochromator,
CCD detector, ω-scanning, 2θmax 57.8°).
The structure was solved by the direct method
using SHELX-97 software [8]. Positions of the
hydrogen atoms were geometrically calculated and
refined in a rider model with Uiso = 1.2Ueq of the
carrier atom. The structure was refined with respect to
F2 using the full-matrix least-square method in aniso-
tropic approximation for non-hydrogen atoms to wR2
0.115 for 3960 reflections [R1 0.057 for 2181 reflec-
tions with F > 4σ(F), S 1.02]. Bond lengths and angles
are given in Tables 1 and 2, respectively.
2-(Methylthio)benzo[cd]indol-1-inium iodide (I)
was prepared by the method of [9].
X-ray diffraction analysis. Crystals of VIIa are
monoclinic, C22H25N3S, at 298 K: a 4.8083(3), b
19.2612(12), c 18.3513(11) Å, β 95.030(5)°, V
1693.05(18) Å3, Mr 363.51, Z 4, space group P21/с,
dcalc 1.426 g cm–3, μ(MoKα) 0.203 mm–1, F(000) 776.
Parameters of the unit cell and intensities of 12091
reflections (3960 independent, Rint 0.047) were
measured on an automatic four-circle diffractometer
(Z)-2-{Benzo[cd]indol-2(1H)-ylidene}-2-cyano-
ethanoamides (IIIa–IIId). A mixture of 3.3 g
(10 mmol) of salt I, 10 mmol of CH-acid IIa–IId, and
1.4 mL (10 mmol) of triethylamine in 15 mL of
anhydrous ethanol was refluxed for 1 h. After 1 day
the formed precipitate was filtered off, washed with
ethanol and hexane.
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DYACHENKO et al.
(Z)-2-{Benzo[cd]indol-2(1Н)-ylidene}-2-cyano-
C19H13N3O2. Calculated, %: С 72.37; Н 4.16; N 13.33.
М 315.335.
ethanethioamide (IIIа). Yield 1.9 g (77%), yellow
powder, mp 247–249°С (ВuOH). IR spectrum, ν, cm–1:
3233–3415 (NH, NH2), 2211 (C≡N). 1Н NMR
spectrum, δ, ppm: 7.49–7.61 m (2Н, НAr), 7.73 d (1Н,
НAr, J 6.8 Hz), 7.91 t (1Н, НAr, J 7.3 Hz), 8.26 t (1Н,
НAr, J 8.0 Hz), 8.44–8.56 m (2Н, НAr, NH2), 9.34 br.s
(1Н, NH2), 13.54 br.s (1Н, N1Н). Mass spectrum, m/z
(Irel, %): 250 (100) [М – 1]+. Found, %: С 66.80; Н
3.55; N 16.69. C14H9N3S. Calculated, %: С 66.91; Н
3.61; N 16.72. М 251.312.
10-Amino-8-imino-8Н-benzo[cd]pyrido[1,2-a]-
indole-9,11-dicarbonitrile (V) was obtained similarly
from 3.3 g (10 mmol) of I and 1.3 g (10 mmol) of IV.
Yield 2.5 g (90%), yellow powder, mp 332–333°С
(DMF). IR spectrum, ν, cm–1: 3290–3415 (NH, NH2),
1
2215 (C≡N), 1649 [δ(NH2)]. Н NMR spectrum, δ,
ppm: 7.15–7.26 m (1Н, НAr), 7.64 br.s (3Н, =NH and
NH2), 7.81–8.06 m (2Н, НAr), 8.35 d (1Н, НAr, J 7.0 Hz),
8.45 d (1Н, НAr, J 7.8 Hz), 8.61 (1Н, НAr, J 8.6 Hz).
Mass spectrum, m/z (Irel, %): 284 (20) [М + 1]+, 283
(100) [М]+, 282 (5) [М – 1]+, 218 (75), 191 (21), 164
(17), 127 (11), 49 (25). Found, %: С 71.99; Н 3.18; N
24.84. C17H9N5. Calculated, %: С 72.08; Н 3.20; N
24.72. М 283.296.
(Z)-2-{Benzo[cd]indol-2(1Н)-ylidene}-2-cyano-
acetamide (IIIb). Yield 1.4 g (60%), yellow powder,
mp 269–270°С (DMF). IR spectrum, ν, cm–1: 3290–
1
3398 (NH, NH2), 2197 (C≡N), 1668 (CONH). Н
NMR spectrum, δ, ppm: 7.14–7.38 m (3Н, 1НAr, NH2),
7.44–7.62 m (2Н, НAr), 7.83 t (1Н, НAr, J 7.8 Hz), 8.15
d (1Н, НAr, J 8.0 Hz), 8.41 d (1Н, НAr, J 7.3 Hz), 11.92
br.s (1Н, N1Н). Mass spectrum, m/z (Irel, %): 237 (4)
[М + 2]+, 236 (18) [М + 1]+, 235 (100) [М]+, 218 (88)
[М – NH3]+, 190 (86), 164 (41), 49 (9). Found, %: С
71.30; Н 3.70; N 17.75. C14H9N3O. Calculated, %: С
71.48; Н 3.86; N 17.86. М 235.248.
(Z)-2-{Benzo[cd]indol-2(1Н)-ylidene}-2-(4-ary-
thiazol-2-yl)acetonitriles (VIIа, VIIb). a. A mixture
of 2.5 g (10 mmol) of amide IIIа and 10 mmol of the
corresponding α-bromoketone VIа or VIb in 15 mL of
DMF was stirred at 20°С for 1 h and incubated for
1 day. Then the reaction mixture was diluted with
equal amount of water and filtered. The precipitate was
washed with water, ethanol and hexane.
(Z)-2-{Benzo[cd]indol-2(1Н)-ylidene}-N-phenyl-
2-cyanoacetamide (IIIc). Yield 2.4 g (76%), yellow
powder, mp 268–269°С (DMF). IR spectrum, ν, cm–1:
(Z)-2-{Benzo[cd]indol-2(1Н)-ylidene}-2-(4-phenyl-
thiazol-2-yl)acetonitrile (VIIа). Yield 3.2 g (92%),
red needles, mp 218–220°С (BuOH). IR spectrum, ν,
1
3240–3398 (NH), 2190 (C≡N), 1671 (CONH). Н
NMR spectrum, δ, ppm: 7.07 t (1Н, 1НAr, J 7.6 Hz),
7.21–7.42 m (3Н, НAr), 7.50–7.68 m (4Н, НAr), 7.87 t
(1Н, НAr, J 7.6 Hz), 8. 19 d (1Н, НAr, J 8.0 Hz), 8. 49 d
(1Н, НAr, J 7.3 Hz), 9.62 br.s (1Н, CONH), 12.02 br.s
(1Н, N1Н). Mass spectrum, m/z (Irel, %): 313 (5)
[М + 2]+, 312 (20) [М + 1]+, 311 (100) [М]+, 219 (88)
[М – PhNH2]+, 191 (49), 164 (46), 93 (52), 65 (18), 51
(7). Found, %: С 77.10; Н 4.13; N 13.35. C20H13N3O.
Calculated, %: С 77.16; Н 4.21; N 13.50. М 311.347.
1
cm–1: 2925 (NH), 2195 (C≡N). Н NMR spectrum, δ,
ppm: 7.32–7.68 m (6Н, НAr), 7.85 t (1Н, НAr, J 7.6 Hz),
8.08 s (1Н, Н5thiazole), 8.11–8.22 m (3Н, НAr), 8. 41 d
(1Н, НAr, J 7.3 Hz), 11.66 br.s (1Н, NН). Mass spec-
trum, m/z (Irel, %): 353 (5) [М + 2]+, 351 (100) [М]+,
350 (19) [М – 1]+, 134 (3). Found, %: С 75.06; Н 3.66;
N 11.80. C22H13N3S. Calculated, %: С 75.19; Н 3.73;
N 11.96. М 351.433.
(Z)-2-{Benzo[cd]indol-2(1Н)-ylidene}-2-(4-mesityl-
thiazol-2-yl)acetonitrile (VIIb). Yield 3.2 g (81%),
red powder, mp 209–211°С (BuOH). IR spectrum, ν,
(Z)-2-{Benzo[cd]indol-2(1Н)-ylidene-N-(furan-2-
ylmethyl)}-2-cyanoacetamide (IIId). Yield 2.0 g
(65%), yellow powder, mp 240–241°С (DMF). IR
spectrum, ν, cm–1: 3283–3402 (NH), 2195 (C≡N),
1691 (CONH). 1Н NMR spectrum, δ, ppm: 4.40 d (2Н,
NCH2, J 5.7 Hz), 6.25 d (1Н, Н3furan, J 3.2 Hz), 6.37 d.
d (1Н, Н4furan, J 3.2, 1.9 Hz), 7.35 d (1Н, НAr, J 6.8 Hz),
7.47–7.66 m (3Н, НAr), 7. 85 t (1Н, НAr, J 7.3 Hz), 8.17
d (1Н, НAr, J 8.2 Hz), 8.35 t (1Н, CONH, J 5.7 Hz),
11.99 br.s (1Н, N1Н). Mass spectrum, m/z (Irel, %): 316
(20) [М + 1]+, 315 (100) [М]+, 314 (6) [М – 1]+, 219
(31), 220 (10), 192 (43), 164 (30), 154 (15), 96 (11),
81 (72), 53 (19). Found, %: С 72.21; Н 4.10; N 13.24.
1
cm–1: 2923 (NH), 2206 (C≡N). Н NMR spectrum, δ,
ppm: 7.32–7.68 m (6Н, НAr), 7.85 t (1Н, НAr, J 7.6 Hz),
8.08 s (1Н, Н5thiazole), 8.11–8.22 m (3Н, НAr), 8. 41 d
(1Н, НAr, J 7.3 Hz), 11.66 br.s (1Н, NН). Mass
spectrum, m/z (Irel, %): 395 (7) [М + 2]+, 394 (26) [М +
1]+, 393 (100) [М]+, 360 (18), 235 (9), 176 (6), 143 (4).
Found, %: С 76.22; Н 4.75; N 10.59. C25H19N3S.
Calculated, %: С 76.31; Н 4.87; N 10.68. М 393.514.
b. Synthesis was performed similarly to the syn-
thesis of III using 3.3 g (10 mmol) of I and 10 mmol
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SYNTHESIS OF NEW NAPHTHOSTYRYL DERIVATIVES VIA NUCLEOPHILIC SUBSTITUTION
263
5. Krivikolysko, S.G., Sharanin, Yu.A., and Dyachenko, V.D.,
of thiazolylacetonitrile VIIIа or VIIIb. Yield 2.9 g
(82%) for VIIа and 3.3 g (85%) for VIIb.
Zh. Obshch. Khim., 1995, vol. 65, no. 5, p. 878.
6. Zefirov, Yu.V. and Zorkii, P.M., Russ. Chem. Rev.,
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