(Z)-3-chloro-3-(2-naphthyl)prop-2-enal in the synthesis of naphthyl-substituted thiophene and quinolines

Article abstract of DOI:10.1134/S1070428006100137

2-(2-Naphthyl)thiophene was synthesized by condensation of 3-chloro-3-(2-naphthyl)prop-2-enal with sulfanylacetic acid. A modified procedure was proposed for the synthesis of 2-(2-naphthyl)-and 2-(2-naphthyl)-6-nitroquinolines from 3-chloro-3-(2-naphthyl)prop-2-enal.

Full text of DOI:10.1134/S1070428006100137

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2006, Vol. 42, No. 10, pp. 1477–1480. © Pleiades Publishing, Inc., 2006.
Original Russian Text © E.V. Vashkevich, V.I. Potkin, N.G. Kozlov, 2006, published in Zhurnal Organicheskoi Khimii, 2006, Vol. 42, No. 10,
pp. 1492–1495.
(Z)-3-Chloro-3-(2-naphthyl)prop-2-enal in the Synthesis
of Naphthyl-Substituted Thiophene and Quinolines
E. V. Vashkevich, V. I. Potkin, and N. G. Kozlov
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus,
ul. Surganova 13, Minsk, 220072 Belarus
e-mail: potkin@ifoch.bas-net.by
Received August 2, 2005
Abstract—2-(2-Naphthyl)thiophene was synthesized by condensation of 3-chloro-3-(2-naphthyl)prop-2-enal
with sulfanylacetic acid. A modified procedure was proposed for the synthesis of 2-(2-naphthyl)- and
2-(2-naphthyl)-6-nitroquinolines from 3-chloro-3-(2-naphthyl)prop-2-enal.
DOI: 10.1134/S1070428006100137
While performing systematic studies on chemical
transformations of (Z)-3-chloro-3-(2-naphthyl)prop-2-
enal, which was synthesized from 2-acetylnaphthalene
by the Vilsmeier–Haak reaction [1], we showed that
the high reactivity of the exocyclic chloropropene
fragment makes this compound a convenient synthon
for the preparation of naphthalene derivatives having
various side-chain functional groups, such as enamino,
iminium, hydroxyimino, peroxy, acetylenic, and nitro-
halodiene moieties, as well as of a large number of
heterocyclic compounds [2–4].
DMF as solvent, an inseparable mixture of products
was obtained; its main component was triethylamine
hydrochloride. The structure of compound II was
confirmed by the analytical and spectral data (IR,
1H NMR, and mass spectra). The IR spectrum of II
contained absorption bands at 1340, 1425, and
1536 cm–1, corresponding to stretching vibrations of
the thiopene ring; these bands are typical of 2-substi-
tuted thiophene derivatives [6]. Compound II showed
in the 1H NMR spectrum a doublet at δ 7.10 ppm (3J =
4 Hz) from 3-H in the thiophene ring and multiplets in
the region δ 7.44–8.00 ppm, the latter belonging to
protons in the naphthalene and thiophene rings. In the
electron-impact mass spectrum of II we observed the
molecular ion peak and fragment ion peaks resulting
from loss of hydrogen atoms and naphthyl residue.
The goal of the present work was to synthesize
a naphthyl-substituted thiophene from (Z)-3-chloro-3-
(2-naphthyl)prop-2-enal and modify the procedure
developed by us previously for the preparation of
quinoline derivatives.
Unlike known methods for the synthesis of
2-(2-naphthyl)thiophene, which are based on palla-
It is known that sulfanylacetic acid reacts with
3-(1-adamantyl)-3-chloropropen-2-al to give a mixture
of adamantyl-substituted thiophene-2-carboxylic acid
and thiophene [5]; it was also shown that the overall
yield of the products increases when the reaction is
performed in DMF rather than in ethanol. We found
that the condensation of 3-chloro-3-(2-naphpthyl)prop-
2-enal (I) with sulfanylacetic acid in boiling ethanol in
the presence of triethylamine is complete in 5 h to give
2-(2-naphthyl)thiophene (II) in 34% yield (Scheme 1).
The process was accompanied by considerable tarring.
The reaction mixture contained no 5-(2-naphthyl)thio-
phene-2-carboxylic acid whose formation could be ex-
pected by analogy with the reaction with adamantyl-
chloropropenal. When the reaction was performed in
Scheme 1.
H
CHO
OH
HS
+
Cl
O
I
Et3N, EtOH
S
II
1477

VASHKEVICH et al.
1478
Scheme 2.
H
CHO
Cl
H
CHO
Ar
H
CHO
OMe
Na2S·9H2O, MeOH
+
H
Ar
Ar
S
Ar
CHO
I
III
IV
dium-catalyzed reactions of thiophene with aryl
bromides [7] or of naphthyl trifluoromethanesulfonate
with tributyl(thienyl)tin [8], the proposed procedure is
simpler from the preparative viewpoint. Moreover,
the yield of II is more than twice as large as that in
the Friedel–Crafts alkylation of naphthalene with
2-chlorothiophene [9]; the latter gives a mixture of
isomeric aryl-substituted thiophenes, and the yield of
2-(2-naphthyl)thiophene (II) does not exceed 13%.
cyclization on heating in boiling glacial acetic acid [3]
(Scheme 3).
We now describe a modified procedure for the
synthesis of 2-(2-naphthyl)quinolines from propenal I.
According to the modified procedure, 2-(2-naphthyl)-
and 2-(2-naphthyl)-6-nitroquinolines VII and VIII
were synthesized in one step without isolation of
intermediate iminium salts V and VI. Compounds VII
and VIII were obtained in 39 and 32% yield, respec-
tively, by heating a mixture of propenal I and the cor-
responding aromatic amine (aniline or p-nitroaniline)
at 200–210°C under solvent-free conditions. The phys-
By analogy with reactions involving β-chlorovinyl
aldehydes [10], we tried to obtain substituted thio-
pyrans by reaction of chloronaphthylpropenal I with
sodium sulfide. However, compound I reacted with
an equimolar amount of sodium sulfide in boiling
methanol to give only acyclic products: 3,3'-thiobis-
[3-(2-naphthyl)prop-2-enal] (III) and 3-methoxy-3-(2-
naphthyl)prop-2-enal (IV) (53 and 22%, respectively;
Scheme 2). No compounds having a thiopyran struc-
ture were detected in the reaction mixture.
1
ical constants and IR, H NMR, and mass spectra of
quinoline VII coincided with those reported in [3].
Previously unknown 2-(2-naphthyl)-6-nitroquinoline
(VIII) was also synthesized in two steps as described
in [3]. The reaction of propenal I with 4 equiv of
p-nitroaniline in diethyl ether gave hydrochloride VI,
and heterocyclization of the latter in boiling glacial
acetic acid led to the formation of naphthylnitro-
quinoline VIII in 38% yield (calculated on the initial
propenal I).
As we showed previously [3, 4], propenal I is also
a convenient starting compound for building up vari-
ous nitrogen-containing heterocyclic systems, in par-
ticular 2-(2-naphthyl)quinolines. The previous proce-
dure for the preparation of 2-(2-naphthyl)quinolines
from prop-2-enal I includes two steps, the first of
which implies the synthesis of N-(3-arylimino-1-(2-
naphthyl)prop-1-en-1-yl)aniline hydrochlorides like V
or VI from propenal I and 4 equiv of the correspond-
ing aromatic amine in diethyl ether; in the second step,
the isolated iminium salts are subjected to hetero-
The structure of compounds VI and VIII was deter-
mined on the basis of their elemental compositions and
1
IR, H NMR, and mass spectra. In the IR spectrum of
VI, stretching vibrations of the C=N bond appeared as
a strong absorption band 1642 cm–1, and bands at
1492–1537 and 1594 cm–1 were assigned to vibrations
of C=C bonds. The NH+ group gave rise to a broad
absorption band with its maximum at 2772 cm–1, and
Scheme 3.
5'
8'
4'
1'
6'
7'
3'
2'
H
12
3
4RC6H4NH2
AcOH, ∆
H
H
13
2
4
CHO
NH HN
Cl
N
1
5
6
Cl
8
R
R
R
7
I
V, VI
VII, VIII
4RC6H4NH2, 200°C
I
VII, VIII
V, VII, R = H; VI, VIII, R = O2N.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 10 2006

(Z)-3-CHLORO-3-(2-NAPHTHYL)PROP-2-ENAL IN THE SYNTHESIS
1479
vibrations of the NH group were characterized by
cooled, and poured into 100 ml of 5% aqueous sodium
hydroxide. The precipitate was filtered off, washed
with water, and recrystallized from ethanol. Yield
0.68 g (34%), mp 101–102°C; published data: mp 102–
103°C [6], 103–108°C [7]. IR spectrum, ν, cm–1: 690,
744 (C–S); 1340, 1425, 1536 (C=C); 3050 (C–H).
1H NMR spectrum, δ, ppm: 7.10 d (1H, 3-H, thio-
1
a frequency of 3300 cm–1. The H NMR spectrum of
salt VI contained multiplet signals in the region
δ 6.35–8.20 ppm due to aromatic protons in the naph-
thalene and benzene rings and olefinic protons in the
=HC12–C13H=N fragment, a broadened singlet at
δ 8.55 ppm from the naphthalene 1-H proton, and
a broadened singlet at δ 12.00 ppm from the NH
groups. In the aromatic region we identified a doublet
at δ 7.7 ppm (3J = 6.4 Hz), which was assigned to
13-H; these data indicate conservation of the s-cis
configuration of the side chain during the reaction [11].
3
phene, J = 4 Hz), 7.44–8.00 m (2H, thiophene, and
6H, naphthalene), 8.16 br.s (1H, 1-H, naphthalene).
Found, %: C 80.42; H 4.35; S 15.43. [M]+ 210. C14H10S.
Calculated, %: C 79.96; H 4.79; S 15.25. M 210.28.
3,3'-Thiobis[3-(2-naphthyl)prop-2-enal] (III) and
3-methoxy-3-(2-naphthyl)prop-2-enal (IV). Com-
pound I, 3.4 g (16 mmol), was added dropwise to
a solution of 3.9 g (16 mmol) of Na2S·9H2O in 25 ml
of methanol under stirring at 30°C. The mixture was
heated for 1 h under reflux, and the precipitate was
filtered off, washed with water and diethyl ether–
hexane (1:2), and dried under reduced pressure. We
thus isolated 2.89 g (53%) of sulfide III, mp 210°C. IR
spectrum, ν, cm–1: 747 (C–S), 1596 (C=C), 1656
(C=O). 1H NMR spectrum, δ, ppm: 6.65 d (1H, C=CH,
3J = 7.7 Hz), 7.48–7.91 m (6H, naphthalene), 8.17 s
In the IR spectrum of quinoline VIII, a strong
absorption band was present at 1636 cm–1; it was
assigned to stretching vibrations of the C=N bond.
Aromatic C=C bonds gave rise to absorption in the
region 1479–1561 cm–1. No NH absorption at about
3300 and 2772 cm–1, which is typical of initial hydro-
chloride VI, was observed in the IR spectrum of quino-
1
line VIII. The H NMR spectrum of VIII contained
multiplet signals from aromatic protons in the region
δ 7.35–8.85 ppm. The molecular ion peak was present
in the mass spectrum of VIII.
3
(1H, 1-H, naphthalene), 9.63 d (1H, CHO, J =
Although the yields of naphthylquinolines VII and
VIII in the two-step procedure were slightly greater
than those in the modified one-step synthesis (48 [3]
and 38% against 39 and 32%, respectively), the latter
seems to be more attractive from the preparative view-
point, for it ensures shorter reaction time and simpler
experiment and requires no solvent.
7.7 Hz). Found, %: C 79.57; H 4.88; S 8.53. [M]+ 394.
C26H18O2S. Calculated, %: C 79.16; H 4.60; S 8.13.
M 394.46.
The filtrate was evaporated on a rotary evaporator,
the residue was treated with 50 ml of water, and the
green precipitate was filtered off and washed with
water and diethyl ether. Yield of compound IV 0.64 g
(22%), mp 93–95°C. IR spectrum, ν, cm–1: 729 (C–S),
EXPERIMENTAL
1
1590 (C=C), 1652 (C=O). H NMR spectrum, δ, ppm:
3
The IR spectra of compounds II–VIII were
recorded in KBr on a Nicolet Protege-460 Fourier-
transform spectrometer. The 1H NMR spectra were ob-
tained on a Tesla BS-567A (100 MHz) instrument from
solutions in acetone-d6 (compound II), DMSO-d6
(V, VI), and CDCl3 (III, IV, VII–VIII); the chemical
shifts were measured relative to tetramethylsilane as
internal reference. The mass spectra were run on
a Hewlett–Packard HP 5890/5972 GC–MS system
(electron impact, 70 eV; HP-5MS capillary column,
30 m × 0.25 mm, film thickness 0.25 µm, 5% of
phenylmethylsilicone; injector temperature 250°C).
3.91 s (3H, OCH3), 5.7 d (1H, C=CH, J = 7.7 Hz),
7.50–7.84 m (6H, naphthalene), 7.85 br.s (1H, 1-H,
3
naphthalene), 9.52 d (1H, CHO, J = 7.7 Hz). Found,
%: C 79.09; H 5.76. [M]+ 211. C14H11O2. Calculated,
%: C 79.59; H 5.26. M 211.25.
N-(1-(2-Naphthyl)-3-(4-nitrophenylamino)prop-
1-en-1-yl)-4-nitroaniline hydrochloride (VI). A solu-
tion of 2.54 g (18.4 mmol) of p-nitroaniline in 3 ml of
diethyl ether was added in portions under stirring to
a solution of 1 g (4.6 mmol) of propenal I in 5 ml of
diethyl ether. After 10–15 min, an intensely colored
solid precipitated and was filtered off, washed with
water and diethyl ether, dried under reduced pressure,
and recrystallized from methanol. Yield 1.75 g (80%),
mp 208–210°C. IR spectrum, cm–1: 1296, 1574 (NO2);
1492, 1514, 1537, 1594 (C=C); 1642 (C=N); 3052
(C–H); 2772 (NH+); 3300 (NH). 1H NMR spectrum, δ,
2-(2-Naphthyl)thiophene (II). Sulfanylacetic acid,
1.1 g (11 mmol), and triethylamine, 2.15 g (21 mmol),
were added dropwise under stirring at 0°C to a solution
of 1.85 g (8.5 mmol) of compound I in 10 ml of
ethanol. The mixture was heated for 5 h under reflux,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 10 2006

VASHKEVICH et al.
1480
2-(2-Naphthyl)-6-nitroquinoline (VIII). Yield
32%. Its melting point and IR, H NMR, and mass
spectra were identical to those of a sample prepared
according to the procedure described in [3].
ppm: 6.35–8.20 m (14H, Harom, and 2H, =CH–CH=N),
8.55 br.s (1H, 1-H), 12.00 br.s (2H, NH). Found, %:
C 63.35; H 4.24; Cl 7.77; N 11.55. [M]+ 474.
C25H19ClN4O4. Calculated, %: C 63.23; H 4.03; Cl 7.47;
N 11.79. M 474.88.
1
REFERENCES
2-(2-Naphthyl)-6-nitroquinoline (VIII). A solu-
tion of 1.19 g (2.5 mmol) of hydrochloride VI in 10 ml
of glacial acetic acid was heated for 3 h under reflux.
The mixture was then treated with a concentrated
aqueous solution of potassium hydroxide to pH 6–7,
and the precipitate was filtered off, washed with water,
dried under reduced pressure, and recrystallized from
methanol. Yield 0.36 g (48%, calculated on VI, or
38%, calculated on initial propenal I), mp 140–142°C
(from methanol). IR spectrum, ν, cm–1: 1224 (C–N);
1258, 1579 (NO2); 1479, 1506, 1561 (C=C); 1636
(C=N); 3058 (C–H). 1H NMR spectrum, δ, ppm: 7.35–
8.60 m (11H, Harom), 8.85 br.s (1H, 1'-H). Found, %:
C 75.49; H 4.24; N 9.28. [M]+ 300. C19H12N2O2. Cal-
culated, %: C 75.98; H 4.03; N 9.33. M 300.31.
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2-(2-Naphthyl)- and 2-(2-naphthyl)-6-nitro-
quinolines VII and VIII (general modified proce-
dure). A mixture of 4.6 mmol of compound I and
18.4 mmol of aniline or p-nitroaniline was heated for
2 h at 200°C (with aniline) or fused for 20 min at 150–
170°C (with p-nitroaniline). The resulting material was
dissolved in 20 ml of hot ethanol, the solution was
cooled, and the precipitate was filtered, washed with
diethyl ether–hexane (1:4), recrystallized from etha-
nol, and dried under reduced pressure.
7. Ohta, A., Akita, Y., Ohkuwa, T., Chiba, M., and Fuku-
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vol. 28, p. 5197.
2-(2-Naphthyl)quinoline (VII). Yield 39%. Its
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1
physical constants and IR, H NMR, and mass spectra
were in agreement with those reported in [3].
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 10 2006